text:
Mayor Bloomberg today unleashed an attack on The New York Times, accusing the paper of hypocrisy for publishing an editorial against the NYPD's stop and frisk policy days after the "paper of record" didn't bother covering of the murder of a black teenager.
"Last week, a Bronx resident named Alphonza Bryant was shot and killed while standing with friends near his home. He was 17. Like most murder victims in our city, he was a minority," a frustrated Bloomberg told NYPD brass during an address at 1 Police Plaza.
"He was just a victim of too many guns on our streets. But after his murder … there was not even a mention of his murder in our paper of record, the New York Times. All the news that's fit to print did not include the murder of a 17-year-old Alphonza Bryant."
Bryant was gunned down near his home in Foxhurst April 22, weeks before his senior prom and graduation from Urban Assembly Bronx Studio for Writers and Artists in exactly the kind of violent crime stop and frisk aims to prevent by taking guns off the street.
"Four days after Alphonza Bryant's murder went unreported by the Times, the paper published another editorial attacking stop, question, and frisk. They called it a wildly loathed practice, even though a growing number of mothers and fathers who have had their children murdered with guns have been speaking out in support of stop, question, and frisk," the mayor said.
"Let me tell you now what I loathe. I loathe that 17-year-old minority children can be senselessly murdered in the Bronx and some of the media doesn't even consider it news."
Bloomberg pointedly accused the paper of a double standard in its crime coverage, saying the paper ignores gun violence in minority neighborhoods – but would play it differently if the victim were wealthy and white.
"Do you think that a white 17-year-old prep student from Manhattan had been murdered, the Times would have ignored it?" Hizzoner asked. "I believe the life of every 17 year old and every child and every adult is precious, and I wake up every morning thinking about what we can do to protect the lives of innocent New Yorkers and spare more people the pain and heartbreak that we've seen far too much," Bloomberg said.
The story was covered by several media outlets, including The Post.
Bryant was hanging out with pals on Fox Street about 8:15 p.m. when two thugs walked by, cops said.
The pair returned a short time later and one opened fire, squeezing off nine shots, fatally wounding Bryant in the torso.
Cops said it wasn't even clear if the teen was the intended target.
"After his murder, there was no outrage from the Center for Constitutional Rights, or the NYCLU," Bloomberg noted, citing frequent critics of the policy who are also plaintiffs in a suit against the city claiming it discriminates against minorities. "He was just a victim of too many guns on our streets."
The NYCLU said today in a statement, ""It's a lot easier to trash the NYCLU than to acknowledge the widespread dissatisfaction the community feels with an NYPD that acts like it's above the law and accountable to no one."
Bloomberg insisted that stop and frisk saves lives – and that the majority of those saved are minorities.
"About 90 percent of our murder victims in our city are black or Latino.
The fact of the matter is that when police stop and ask a 17 year old a question based on a reasonable suspicion of a crime there is outrage. Yet when a 17-year-old is standing on the street corner near his home at 8:15 in the evening and gets shot and killed, there is silence," Bloomberg said in remarks that prompted a thunderous standing ovation from the police chiefs and other brass present.
A Times spokeswoman did not immediately return a call for comment.


text:
Lastly came Person of Interest, starring Jim Caviezel and Michael Emerson. (In all of the official info for this show, Caviezel is only ever noted as having been in The Thin Red Line – never his more recent role in The Passion of the Christ. Not surprising, just an observation.) In it, Caviezel is a former soldier and CIA agent who – after losing the woman he loved – now's just a crazy hobo, beating the crap out of not-very-tough-looking toughs on the subway. Early in the show he's approached by Emerson, who plays a character disappointingly similar to the one he played on Lost (he knows everything about you, but you don't get to know too much about him), "Dr. Finch". Dr. Finch has a job offer for the lost, directionless badass: come to work for him preventing future crime.
It seems Finch wrote a software program meant to sort through and make sense of all the data the government collects in the post-Patriot Act world (cell phone records, e-mails, images, everything); somehow, it started occasionally spitting out social security numbers of people who will be involved in a crime in the future. They might be the victim, they might be the perpetrator – there's no way to know, only that they will be a
part of something ugly if someone doesn't intervene first.
From the first episode, it was hard to tell what to make of the series, or what the typical show would look like. Presumably, each episode would be Caviezel and Emerson working to either save or cap the next person on their list – but the pilot is burdened with also laying the groundwork for the show's somewhat complicated concept, making the entire first episode feel a little hurried and superficial, with too much to do in an hour. And with no big mystery to tease an audience with for years and years, ultimately the show is going to rest on how interesting they can make each week's new victim/perp. Can they do it? This remains to be seen.http://www.deadline.com/2011/07/2011-comic-con-warner-bros-tv-pilots/

subset: commoncrawl


text:
- Research article
- Open Access
Global analysis of X-chromosome dosage compensation
© Gupta et al.; licensee BioMed Central Ltd. 2006
- Received: 20 June 2005
- Accepted: 7 December 2005
- Published: 16 February 2006
Drosophila melanogaster females have two X chromosomes and two autosome sets (XX;AA), while males have a single X chromosome and two autosome sets (X;AA). Drosophila male somatic cells compensate for a single copy of the X chromosome by deploying male-specific-lethal (MSL) complexes that increase transcription from the X chromosome. Male germ cells lack MSL complexes, indicating that either germline X-chromosome dosage compensation is MSL-independent, or that germ cells do not carry out dosage compensation.
To investigate whether dosage compensation occurs in germ cells, we directly assayed X-chromosome transcripts using DNA microarrays and show equivalent expression in XX;AA and X;AA germline tissues. In X;AA germ cells, expression from the single X chromosome is about twice that of a single autosome. This mechanism ensures balanced X-chromosome expression between the sexes and, more importantly, it ensures balanced expression between the single X chromosome and the autosome set. Oddly, the inactivation of an X chromosome in mammalian females reduces the effective X-chromosome dose and means that females face the same X-chromosome transcript deficiency as males. Contrary to most current dosage-compensation models, we also show increased X-chromosome expression in X;AA and XX;AA somatic cells of Caenorhabditis elegans and mice.
Drosophila germ cells compensate for X-chromosome dose. This occurs by equilibrating X-chromosome and autosome expression in X;AA cells. Increased expression of the X chromosome in X;AA individuals appears to be phylogenetically conserved.
- Additional Data File
- Dosage Compensation
- Gene Expression Omnibus Accession Number
- Altered Gene Dose
- Photon Multiplier Tube
In most organisms, copy number at any given locus has little effect on proper organismal function. Very few genes are deleterious if present in only one copy (haploinsufficiency) or are overtly deleterious in three copies. Having more or fewer copies (aneuploidy) of a large fraction of the genome is, however, invariably incompatible with viability. For example, over 10% of human oocytes are aneuploid, but with a few exceptions none of these aneuploid oocytes gives rise to viable offspring [1]. The most common aneuploid genotypes in a wide range of species involve the deletion or duplication of a chromosome or chromosome segment. Deletions are the most deleterious.
In Drosophila melanogaster, a systematic study of aneuploids with deletions of different segments of chromosomes indicates that having only a single copy of 1% of the genome reduces viability (and often fertility) and having only a single copy of 3% or more of the genome is lethal [2]. From current estimates of gene content in Drosophila, 3% represents about 500 genes [3]. Therefore, having only a single copy of 500 genes or more usually results in the collapse of a major part of the genetic network. That genetic networks do indeed collapse because of minor differences in the expression levels of a few connected nodes is evident from genetic interaction studies. In the female germline, for example, the dose of the gene ovarian tumor (otu) strongly modifies the sterility phenotype of flies heterozygous for ovo D [4]. (The gene ovo encodes a transcription factor that acts on otu [5]). Similarly, in the male germline, heterozygosity for haywire or β-tubulin mutations are tolerated, but heterozygosity for both results in failed spermatogenesis [6].
The sex chromosomes represent an extraordinary exception to the genetic imbalance rule. Drosophila males have one copy of the X chromosome per diploid set of autosomes (X;AA) and females have two (XX;AA) [7]. As the Drosophila X chromosome bears about 20% of the genome [3], Drosophila males vastly exceed the usual 3% single-copy threshold for viability. This is not due to an underrepresentation of dosage-sensitive genes on the X chromosome, as females are sensitive to X-chromosome deletions [2]. Therefore, males have a special mechanism(s) to compensate for X-chromosome dose (for reviews see [8, 9]). An extensive set of autoradiographic experiments on the giant polytene chromosomes of the salivary gland showed that the X chromosome in X;AA flies is expressed at roughly twice the level as an X chromosome in XX;AA flies. Hypertranscription of the X chromosome in karyotypic males is dependent on a complex of at least five proteins and two non-coding RNAs. The genes encoding the proteins in the complex are referred to as the male specific lethal (msl) loci (msl). Males lacking any of the msl activities show reduced X-chromosome transcription and die as larvae. At the molecular level, these genes encode a histone-modifying MSL complex, which acetylates histone 4 on lysine 16 (H4 K16). The modification is thought to relieve the general repressive action of histones and result in increased transcription.
Interestingly, the MSLs do not function in the germline. The X chromosomes of male germ cells are not decorated with MSL complexes and are not hyperacetylated at H4 K16 [10]. Furthermore, neither the genes encoding the MSL complex nor the obligate somatic regulators of the MSLs are required for germline viability [11, 12]. There is similar lack of evidence of dosage compensation in the germline of other organisms [13, 14], leading to the hypothesis that germ cells are dosage-tolerant. Alternatively, dosage compensation in germ cells may be MSL-independent. Whether the germline X chromosome of Drosophila, or indeed of any organism, is dosage compensated is one of the major unresolved issues in the study of sex chromosomes. Our array results indicate that Drosophila germ cells do, in fact, dosage compensate.
Equally enigmatic are the dosage-compensation systems in Caenorhabditis elegans and mammals, which are based on reducing X-chromosome expression in XX;AA cells [15, 16]. This is seen most clearly in mammals, where one of the X chromosomes in XX;AA females is inactivated. In C. elegans, both the X chromosomes in XX;AA hermaphrodites show reduced expression. In both cases, the dosage-compensation model equilibrates X-chromosome expression between the sexes but it also makes both sexes functionally aneuploid with respect to the autosomes. Both males and females (or hermaphrodites) become functionally X;AA. It has been suggested that this is counterintuitive, as within each diploid X;AA organism, gene expression from a single X chromosome should be equilibrated and balanced to the autosomes [17–20]. Therefore, it is more useful to think of X-chromosome dosage as a mechanism for equilibrating X chromosome and autosome expression, rather than as only a mechanism for equilibrating expression between the sexes. This predicts, for example, that in mammals both the single X chromosome of males and the single active X chromosome in females are hypertranscribed [17, 18]. While there is an overwhelming literature supporting X-chromosome inactivation, there has been very little experimental evidence to support hypertranscription of the active X chromosome [21]. Our examination of array results in C. elegans and the mouse suggests that such X-chromosome hypertranscription does occur.
Comparing XX;AA and X;AA expression ratios
To determine how genes with housekeeping function respond to dose in the germline, we examined in more detail the expression levels of nuclear genes encoding cytoplasmic or mitochondrial ribosomal subunits [26]. The X chromosome and autosomal genes show strikingly similar distributions (p > 0.1 by regression analysis of slopes and intercepts), despite a twofold difference in X-chromosome dose (Figure 5b). We also identified a de facto set of housekeeping genes by investigating array elements showing reduced hybridization variance and high intensity hybridization across all our experiments (Figure 5c). In the absence of dosage compensation, we would expect a deficit of X chromosome genes in this subset, as they would show increased variance due to the dose difference. We found no deficit of X-chromosome encoded genes showing low-variance expression. Both these analyses indicate that at least some X-chromosome genes are dosage compensated in the wild-type germline.
Transcriptional response to altered autosomal gene dose
To understand the precision of X-chromosome dosage compensation, we first need to understand the general response of the biological system to altered gene dose. What should we expect if there is no X-chromosome dosage compensation? A twofold difference in gene dose is unlikely to always result in a twofold difference in steady-state transcript levels, as many genes are regulated by elegant feedback mechanisms that would dampen the effect of gene dose. Similarly, we need to prove that the entire data-handling pipeline allows us to see gene-expression differences associated with altered gene dose.
To determine whether differences in genetic dose result in detectable differences in gene expression, we have directly measured gene-expression changes resulting from altered gene dose due to deficiency (deletion) and duplication of an autosomal segment of the genome. The duplication that we used overlaps the deletion region, but covers more genes. Flies heterozygous for the duplication Dp(2:2)Cam3/+ (Dp/+) have three copies of around 330 genes, while flies heterozygous for the deletion Df(2L)J-H/+ (Df/+) are hemizygous for a subset of around 70 of those duplicated genes [27]. By directly comparing gene expression in flies bearing these aberrations, we assayed the consequences for gene expression of 1-fold, 1.5-fold, and 3-fold differences in gene dose along chromosome arm 2L.
The differences in gene-expression ratios corresponding to 1-, 1.5- and 3-fold dose changes on chromosome 2L are highly significant (p <<10-4 by ANOVA followed by Tukey HSD, Hodges-Lehmann, and Kolmogorov-Smirnov tests; see Materials and methods). No other similar large blocks of genes elsewhere in the genome show significantly greater expression in Dp/+ flies than in Df/+ flies. There were, however, smaller two-copy regions that showed expression ratios mimicking the 1.5- to 3-fold gene dose effect or the inverse effect. These regions could be due to unrecognized aberrations or could be secondary transcriptional effects.
We also used these 1-, 1.5- and 3-fold dose-change data to tune our data handling. The on-spot background correction method gave the greatest discrimination power (see Materials and methods and Additional data file 1), and was used for all subsequent distribution analyses. This method maximizes our ability to detect the absence of dosage compensation.
The salient feature of the above analyses is that expression changes due to altered gene dose changes on autosomes are readily detectable. This provides us with a metric for the analysis of the similar X-chromosome gene-expression ratios when comparing XX;AA with X;AA tissues. We performed 48 hybridizations using 96 biological samples (see Materials and methods). Matched XX;AA and X;AA tissues were compared in direct hybridizations and were linked through the loop design to other XX;AA and X;AA samples hybridized on other arrays. This allowed for even greater numbers of comparisons. In all of our global comparisons of XX;AA with X;AA expression in the soma (72 comparisons), a 1.5-fold dose difference on an autosome gave a greater difference in gene-expression profiles than did a twofold difference in X-chromosome dose (p << 10-4). The same was found in all of our global comparisons of XX;AA to X;AA expression in transformed gonads (119 comparisons). These data conclusively demonstrate that germ cells carry out dosage compensation.
Mechanism of X-chromosome dosage compensation
Balancing X-chromosome expression between XX;AA and X;AA germ cells in Drosophila is likely to require either hypertranscription of the X in males (as occurs in the soma) or hypotranscription of the X chromosome in females compared with an autosomal reference. Determining which mechanism of dosage compensation operates in the germline requires measuring the absolute expression levels of the X chromosome genes relative to those of autosomal genes. Gene expression varies by orders of magnitude, but in a large representative population of genes on a chromosome arm we expect that those represented by two copies will have higher transcript abundance than those represented by a single copy.
Escape from dosage compensation
Scattered genes along the X chromosome that fail to become dosage compensated in either the soma or the germline are more difficult to detect because there are X chromosome and autosomal genes that are differentially expressed between XX;AA and X;AA tissues even following sex transformation of those tissues. If some autosomal genes are expressed at higher levels in XX;AA flies than in X;AA flies, then some X-chromosome genes are expected to do the same. To test for isolated genes that have escaped dosage compensation, we extracted all the genes that were at least 1.5-fold overexpressed in either XX;AA or X;AA flies, normalized them to gene content per arm, and looked for departure from a normal distribution (Figure 8). If there are a significant number of genes on the X chromosome that escape dosage compensation, then there should be more expression outliers mapping to the X chromosome relative to similarly sized autosomal segments. Furthermore, the outliers from the X chromosome should show XX-biased expression if they escape dosage compensation. In the sex-transformed soma, even though there are X-chromosome genes that always show higher expression in XX;AA than X;AA soma, we observed no significant enrichment (Figure 8) of such genes. About twice as many X-chromosome genes as expected, however, show higher expression in XX;AA transformed germline (p <10-3, by the χ2 test). At face value, we can calculate that approximately 2% of X-chromosome genes escape dosage compensation in the germline. In the soma, sex determination and dosage compensation are linked pathways, however, and this could conceivably be true for the germline [7, 22]. We cannot rule out the possibility that reduced X-chromosome expression in X;AA, hs-tra/+ ovaries relative to XX;AA otu or Sxl ovaries is due to a slight defect in germline dosage compensation concurrent with a germline sex transformation.
Dosage-compensation mechanisms in C. elegansand the mouse
Although X-chromosome dosage compensation equilibrates X-chromosome expression between the sexes, the X;AA individuals are the ones to face an unbalanced karyotype. This makes the increased X-chromosome expression in the X;AA male Drosophila a logical mechanism of dosage compensation. In contrast, X-chromosome transcription is reduced from both X chromosomes in C. elegans hermaphrodites, and one X chromosome is inactivated in mammalian females [15, 16]. In both cases, this dosage compensation equilibrates X-chromosome expression between the sexes, but also makes both sexes functionally aneuploid with respect to the autosomes. This conundrum is solved if X chromosomes are generally hypertranscribed and if X-chromosome inactivation or hypotranscription in XX;AA females or hermaphrodites is a mechanism to prevent overexpression of the X chromosome. Otherwise, hypertranscription of the X chromosome in XX;AA individuals would result in functional tetraploidy.
To determine whether per-copy transcription from the X chromosome is reduced in XX;AA somas, we measured the average hybridization intensity for the X and all autosomes in both X;AA and XX;AA animals (Figure 9). Transcripts from the single X chromosome in X:AA C. elegans male soma hybridize as well as those of two-copy autosomes. Indeed, the X chromosomes of both X;AA and XX;AA C. elegans appear to be overexpressed relative to autosomes (p << 10-4). Similarly, X-chromosome transcripts from X;AA and XX;AA mouse soma (average of hypothalamus, kidney and liver) are detected well within the range of those of the autosomes. Many mouse tissues have been examined, and we find evidence of elevated X-chromosome expression in all cases (data not shown). A study concurrent with this one has extensively cataloged mammalian X-chromosome dosage compensation, and confirms our observation that the single X chromosome in males and the single active X chromosome in females are compensated [30]. These findings suggest that the single X chromosomes of X;AA C. elegans and mice are expressed at levels comparable to two autosomes, as we observed in Drosophila. Perhaps this is a universal phenomenon.
Polytene salivary gland chromosomes have greatly facilitated the analysis of dosage compensation in Drosophila [8], but global analysis of dosage compensation in the other tissues has not been conclusive. A recent reverse transcriptase (RT)-PCR study showed a wide range of states of compensation of X-chromosome genes [31]. Sex-biased expression potentially distorts such dosage-compensation analysis, however. There is extensive sex-biased expression in Drosophila [24, 32–34] and, furthermore, these genes are not equally distributed between the X chromosome and autosomes [25, 35]. Studies directed at subsets of genes have revealed complex relationships between X chromosome and autosome expression. It is, however, difficult to interpret a subtle difference in X-chromosome expression between XX;AA and X;AA individuals if effects of a similar magnitude are seen for autosomal genes [36]. Global analysis of transcription in non-polytene tissues could help resolve the nature of X-chromosome dosage compensation in the understudied tissues that make up the bulk of the fly.
Microarray analysis is ideally suited to the study of dosage compensation. Our results suggest that remarkably tight X-chromosome dosage compensation occurs in a wide range of adult tissues. Most importantly, we also provide the first evidence for germline dosage compensation in any organism. The compensation mechanism in both the soma and germline is the equilibration of X chromosome expression with autosomal expression. This is likely to be due to increased expression from the single X chromosome in X;AA, although decreased expression from all the autosomes could also ensure that X chromosome expression is equilibrated with the autosomes [37].
MSL-independent germline dosage compensation
Germline X-chromosome dosage compensation has been a black box for decades [22]. As the well-known somatic dosage-compensation mechanisms in the major genetic model organisms clearly do not function in the germline, the idea has gradually emerged that germ cells are dosage-tolerant. This is due not to evidence of absence, but to absence of evidence. Although our results show that dosage compensation in the soma and germline are thematically similar, the mechanisms in the germline must be distinct.
The MSL complexes required for dosage compensation in the soma are dispensable in the germline [10, 12]. This might appear to be non-parsimonious, but germline and somatic gene expression also appear to be distinct. The male and female germline express different types of basal transcription machinery, such as male-germline-specific TATA-box-binding associated factors (TAFs), which might require a different chromatin structure [38, 39], and germline-restricted factors bind the germline-restricted core promoter of the ovo gene [40]. In addition, even though somatic dosage compensation is highly conserved, proteins mediating dosage compensation are not. For example, in some other species of flies the MSL complex associates with all chromosomes, not just the X chromosome [41–43], suggesting that the complex plays no role in dosage compensation in those organisms. In yeast, which lack well differentiated sex chromosomes, one of the main MSL complex components is required for viability [44]. These observations indicate that MSL complexes play markedly different roles in different species. Given the differences in gene expression between the germline and the soma, it is perhaps unsurprising that different proteins might be involved in Drosophila germline dosage compensation.
It is also unclear whether the MSL complex accounts for all somatic dosage compensation. For example, XX;AA flies lacking Sex-lethal (Sxl) protein in the soma die, presumably because of a failure to repress MSL complex formation [45]. But mutations in the MSL-encoding genes fail to rescue the lethality of XX;AA flies without Sxl, suggesting that Sxl represses additional dosage-compensation functions [46]. Similarly, in polytene salivary glands, large blocks of the X chromosome do not associate with MSL complexes [47]. We find no evidence to support extensive escape from X-chromosome dosage compensation in somatic tissues. These results are consistent with either selective deployment of MSLs at active genes [47] or MSL-independent dosage compensation at a subset of genes.
Mutations in genes regulating germline dosage compensation would be expected to show karyotype-specific phenotypes. Interestingly, there are at least two genes that appear to be required for the viability of XX;AA but not X;AA germ cells; ovo and stand still (stil) [48, 49]. Negative and positive Ovo protein isoforms act at the transcription start site of at least some promoters [5, 40, 50] and Stil protein decorates active chromatin when overexpressed in the soma [49]. Perhaps one or both of these proteins serve to block the upregulation of the X chromosome that normally occurs in the male germline. This could be analogous to the situation in the Drosophila soma, where dosage compensation is actively repressed in XX;AA females [7]. There are also a number of genes that are required for the viability of male germ cells [51]. Some of these genes may encode dosage-compensation functions. If such dosage-compensation genes exist, they might encode chromatin-modifying complexes, as in the Drosophila soma. Given that our data show that steady-state transcripts from the X chromosome are compensated, however, there are a host of post-transcriptional mechanisms, such as preferential mRNA stability, that could conceivably mediate germline dosage compensation.
X-chromosome dosage-compensation mechanisms might arise from dosage control mechanisms that are active at many or all genes. Indeed, we have detected transcriptional buffering in our control experiments on the effects of autosome gene dose. We found that the magnitude of the transcriptional effect was less than expected from a simple calculation of gene dose. This inverse effect on transcription relative to gene dose has been known for decades [52–54], and has recently been observed in expression profiling and RT-PCR studies [31, 55–57]. It seems likely that many genes have a self-contained dosage-compensation system, albeit an imperfect one. The MSL components have general transcriptional activity in yeast and appear to have been co-opted in Drosophila to regulate somatic dosage compensation. Germline dosage compensation might be mediated by other co-opted cis- or trans-acting components that serve to buffer gene expression.
Escape from dosage compensation
There are X-chromosome genes, such as LSP1-α, that escape dosage compensation in Drosophila [58], but it is not known how common this might be. Similarly, in mammals, many X-chromosome genes escape inactivation in females (escape from dosage compensation in X;AA males has not been examined). In theory, this is expected, as not all genes need to be dosage compensated in the course of X-chromosome evolution [59]. Although we can confidently analyze populations of X-chromosome genes, it is quite difficult to determine whether a given gene escapes dosage compensation. Indeed, in the absence of a detailed, gene-by-gene mechanistic study, it might be impossible. There are many autosomal genes that are more highly expressed in XX;AA than X;AA tissues, even after controlling for sex-biased expression. These gene-expression differences are clearly not directly related to X-chromosome dosage compensation. Many of the X-chromosome genes expressed at higher levels in XX;AA than X;AA tissues will be similarly unrelated to dosage compensation per se. In studies of escape from dosage compensation in Drosophila, C. elegans, or mammals where sex-bias is uncontrolled, reports of genes escaping dosage compensation could well be spurious.
On a global level, we find no evidence for escape from dosage compensation in the Drosophila soma. In the germline, however, there are clearly more genes with XX-biased expression than expected. There are several different interpretations of this finding. It is possible that escape from dosage compensation is more common in the germline (about 2% of genes). Alternatively, there may be slight under-compensation in the germline. The X chromosomes in both XX;AA and X;AA gonads appear to be overexpressed relative to autosomes, however. It is therefore possible that the slight excess of XX-biased expression is due to failure to fully dampen X-chromosome hypertranscription in XX;AA females.
Towards a unified model of dosage compensation
Dosage compensation has been under study for a nearly a century. Examination of chromatin structure, rather than direct assay of gene transcription, dominates the recent dosage-compensation literature. Microarray analysis allows us direct access to the transcript accumulation of all X-chromosome genes. The Drosophila array data provide the first demonstration in any organism that germ cells dosage compensate. These data also add a significant twist to our understanding of dosage compensation in mammals and C. elegans. Microarray analysis will be a vital tool for directly assaying this intriguing whole-chromosome regulation of gene expression.
Materials and methods
Flies were grown at 25°C, aged for 5–6 days, dissected, flash-frozen, and prepared for RNA extraction as described previously [24] (see the Flybase compendium of information on genes, alleles, and phenotypes for additional descriptions [27]). Flies used to test for the effect of chromosomal aberrations were Dp(2;2)Cam3/+ and Df(2L)J-H/+ that were generated from outcrossing the stocks to y 1 w 67 c to remove the balancer chromosomes. In addition to using XX;AA females (y 1 w 67 c ), we transformed XX;AA flies into males using null mutations of transformer2 (tra2 B /Df(2R)trix) and by using a dsx mutation encoding a pre-mRNA that is constitutively spliced into the male-specific form (dsx swe ). Flies bearing dsx swe trans to a deletion produce DsxM protein and no DsxF protein (dsx swe /Df(3R)dsxM+15). Similarly, flies null for tra2 produce only DsxM. To obtain X;AA flies that are sex transformed from males into females, we crossed female flies bearing female-specific tra cDNA transgenes (w; P{w+ hs-tra 83 }/CyO or Gla) or (Df(3L)st j 7 Ki roe p p P{hs-tra}/TM3 or TM6) to B s Y males. The hs-tra transgenes are sufficiently active at 25°C to transform males into phenotypic females. We did not utilize a heat-shock regimen.
In order to study the expression changes resulting from a twofold change in the dose of the X chromosome between the XX;AA and X;AA germlines, we utilized genetic mutations that we show remove most sex-biased germline expression from the analysis. The activation of female rather than male sexual differentiation in the soma with hs-tra in X;AA flies results in gonads with vast numbers of poorly differentiated germ cells. Mutations in Sxl (y Sxl fs 3 /y cm Sxl 7 BO ) or otu (ct otu1 v 24 /y w otu 17 ) result in a similar germline phenotype. Occasionally, a few ovaries from X;AA hs-tra flies and germline-transformed Sxl or otu flies bear eggs. These ovaries were not included in the samples. Similarly, very small ovaries that are essentially germlineless were not included in any of our samples.
To remove germline expression from the analysis of somatic X-chromosome dosage compensation, we took advantage of the fact that XX;AA flies transformed from females to males usually have no germline, but rarely have a few germ cells showing either oogenic or spermatogenic phenotypes. These germline-atrophic XX;AA females transformed into males were compared with both gonadectomized X;AA males or sham-dissected X;AA males with a genetically ablated germline as a result of the absence of maternal Tud+ (progeny of tud 1 bw 1 sp 1 mothers).
We have used an extensively tested microarray platform designed to detect transcription from 94% of D. melanogaster release 1 genes [61]. Unlike most array studies, where the object is to determine which genes are altered between tissues, life stages or treatments, we focus here on non-differential expression. In dozens of homotypic hybridization experiments (where an mRNA sample is split, labeled with either Cy3 or Cy5, mixed, and hybridized to the array) performed as part of this (data not shown) and previous studies, we find that the expression ratio is 1 and that there are very few outliers [24, 25, 61]. In the most extensive set of such homotypic hybridizations, the 99.5% confidence intervals were always between 1.4 and 1.5-fold [61]. Given that only a handful of genes are expected to show artifactually a greater than 1.5-fold expression difference, we easily had the sensitivity to detect changes in expression owing to a twofold difference in the 2,245 X-chromosome genes represented on the array.
We have further shown that twofold differences in mRNA concentrations can be readily detected by adding known concentrations of mRNA to hybridization mixes in 'spike-in' experiments [61]. Analysis of spike-in control data (a twofold change in input results in a twofold difference in expression ratios) and a comparison of sex-biased expression determined by FlyGEM and northern blotting reveal no evidence of compression of expression ratios in our data [24, 61].
Sample preparation and labeling
We used 96 biological samples in this study. Careful sample preparation ensures minimum adjustment in subsequent data handling. Dissections, flash freezing and RNA extractions were performed as described [24, 61]. Briefly, total RNA was extracted using Trizol (Life Technologies, Carlsbad, USA), followed by mRNA isolation using an Oligotex poly(A) extraction kit (Qiagen, Valencia, USA). RNA concentration was determined using RiboGreen dye (Molecular Probes, Oak Ridge, USA) in a fluorescent assay using a Luminescence Spectrometer LS-50B (PerkinElmer, Fremont, USA) fitted with 485 nm (excitation) and 520 nm (emission) filters. RNA quality was determined by capillary electrophoresis on a Bioanalyzer 2100 (Agilent, Palo Alto, USA), using the 6000 Nano Assay kit (Agilent) according to the manufacturer's instructions.
Samples were labeled with Cy3- or Cy5-labeled random nonamers (Trilink Biosciences, San Diego, USA). To ensure that each of the nonamer sets was in fact equally 'random', we ordered a single batch of random oligonucleotides that was split into half at the penultimate synthetic step with Cy3 or Cy5 nucleotides added at the end. To verify performance of these oligonucleotides, we performed an experiment in which RNA was labeled using both Cy3 and Cy5 nonamers in the same tube, followed by hybridization, scanning and analysis. There was no dye bias evident. Hybridizations of samples to the microarrays were performed at 60°C, followed by washes exactly as described [24, 61].
Arrays were scanned using an Axon GenePix 3000A fluorescence reader (Molecular Devices Corporation, Union City, USA) in which the photon multiplier tube (PMT) settings were first adjusted using calibration slides. GenePix v.4.1 image acquisition software (Molecular Devices Corporation) was used to extract signal for each target element. Calibration slides were Ultra GAPS (Corning, Acton, USA) spotted with 10-3 to 10-6 dilutions of a 0.33 nM each stock of Cy3 and Cy5 dyes (Amersham Biosciences, Pittsburgh, USA) using GMS 417 Arrayer (Affymetrix, Santa Clara, USA). The PMT voltages, in the linear range, were balanced using these slides. With each new batch of labeling and hybridization, we included a homotypic hybridization [61], in which the same RNA preparation from y1 w 67 c whole males was split into two tubes, labeled with Cy3 or Cy5 nonamers, mixed and hybridized. Slight adjustments of PMT voltages were sometimes made on these control slides. No elements were saturated. Once PMT settings were determined, all arrays in the same hybridization batch were scanned at the same voltage settings. Hybridization and labeling quality was determined by confirming that the channels were close to global balance in the absence of PMT adjustment (no 'on-the-fly' adjustments were made). No arrays were discarded because of failed labeling reactions in one of the two channels. In addition, all elements were printed in duplicate. Regression analysis of plots of duplicate elements was also used as a quality-control step for gradients and severe speckling. No arrays were discarded following duplicate element evaluation. Finally, we determined the fraction of elements that returned signal above on-spot background (see Data handling). Three arrays were discarded from the study because less than 50% of elements exhibited above-background signal.
Loop design for microarray pairings
Samples used for measuring X chromosome dosage compensation
Somatic phenotype
Germline phenotype
Wild type (whole fly)
y 1 w 67 c /+; Dp(2;2)Cam3/+
Wild type (whole fly)
y 1 w 67 c /+; Df(2L)J-H/+
Wild type (ovary)
y 1 w 67 c /+; Dp(2;2)Cam3/+
Wild type (ovary)
y 1 w 67 c /+; Df(2L)J-H/+
Wild type (whole fly)
y 1 w 67 c /Y; Dp(2;2)Cam3/+
Wild type (whole fly)
y 1 w 67 c /Y; Df(2L)J-H/+
Wild type (whole fly)
y 1 w 67 c
Ovaries removed
Wild type (carcass)
y 1 w 67 c
Wild type (ovary)
y 1 w 67 c
tud 1 progeny (whole fly)
tud 1 bw 1 sp 1
Transformed to male
dsx swe /Df (whole fly)
dsx swe /Df(3R)dsxM+15
Transformed to male
tra2 B /Df (whole fly)
tra2 B /Df(2R)trix
Non-differentiated 'ovarian tumor'
otu 17 /otu 1 (ovary)
ct otu 1 v 24 /y w otu17
Non-differentiated 'ovarian tumor'
Sxl fs 3 /Df (ovary)
y Sxl fs 3 /y cm Sxl 7 BO
Wild type (whole fly)
y 1 w 67 c
Testes removed
Wild type (carcass)
y 1 w 67 c
tud 1 progeny (whole fly)
tud 1 bw 1 sp 1
Transformed to female
Ovaries removed
hs-tra (carcass)
y 1 w 67 c /Y; Df(3L)st j 7 Ki roe p p P{hs-tra}/+)
Transformed to female
Ovaries removed
hs-tra (carcass)
w/B s Y; P{w+ hs-tra 83 }/+
Wild type (testis)
y 1 w 67 c
Non-differentiated 'ovarian tumor'
hs-tra (ovary)
y 1 w 67 c /Y; Df(3L)st j 7 Ki roe p p P{hs-tra}/+)
Non-differentiated 'ovarian tumor'
hs-tra (ovary)
w/B s Y; P{w+ hs-tra83}/+
Data handling
Drosophila data were processed using the Bioconductor [63] package limma (Linear Models for Microarray Analysis) v. 1.7.6, to adjust for effects that arise from variations in microarray technology rather than biological differences. Because of the care taken in using identical RNA concentrations in labeling reactions and scanner settings, data handling resulted in minimal adjustments to the raw data. We did not average duplicate array elements as this would reduce statistical power in later steps. At the individual array level, the raw intensity data were normalized using print-tip loess (locally weighted scatter plot smooth) [64]. This corrects for tip biases and for minor hybridization gradients. This was followed by one of three different background corrections. For background elimination, intensities less than the average intensities of the barcode elements (designed against DNA corresponding to an intron that were included in printing plates for tracking purposes, but are also quite useful for background correction [61]) were classified as background and excluded from calculations. For on-spot background correction, the average intensity of the barcoding elements in the array were subtracted from the spot intensity for every array element. For the no-correction option, we used quantile normalization to compare across arrays [64]. Experiments with the Df/+ and Dp/+ flies confirm that on-spot background correction maximizes expression differences within aneuploid segments, but the effect of the copy number was evident with both background elimination and no background correction (see Additional data file 1).
Array data from C. elegans and mouse were extracted directly from the Gene Expression Omnibus (GEO) website [65]. We performed no additional normalization or background correction. The C. elegans experiments were two-channel hybridizations on spotted arrays [28]. Test samples were hybridized with a reference sample. The reference channels cancel in our comparison of XX;AA vs X;AA gene expression. The mouse experiments were performed on Affymetrix arrays [29].
Data sources
All array data are available at GEO. An extensive platform description of FlyGEM is available at GEO under accession number GPL20 [61]. Data are available under GEO accessions GSM37438-GSM37451, GSM2464-2467, GSM16582-GSM16583, GSM16570-GSM16581, and GSM77749-GSM77752. Expression data from mouse hypothalamus, kidney and liver were obtained from GEO accession number GSE1148 [29]. C. elegans data were from GEO accession number GSE715 and GSE724 [28].
Exploratory data visualization
Data were clustered and visualized using Cluster 3.0/Tree-View 1.6 [66]. A self-organizing map (SOM) was calculated to organize normalized hybridization intensities (on-spot background subtraction followed by quantile normalization across arrays) of array elements at 100,000 iterations, followed by k-means clustering of genes with 10 nodes using the correlation (uncentered) similarity metric. Genes, but not experiments, were clustered. We averaged duplicate elements for this analysis to avoid crashing the application.
For scatterplots and moving average plots, we used data processed by background elimination followed by quantile normalization across all experiments. We used on-spot background corrected data for histograms of Drosophila expression data. Chi-squared tests were performed in Excel (Microsoft, Redmond, USA).
Array elements encoding Drosophila ribosomal subunits were identified using the Gene Ontology identifier 'structural constituent of ribosomes' as assigned in GEO accession GPL20. The de facto housekeeping elements were identified as follows. Following background elimination and quantile normalization across all experiments, we selected the elements with hybridization intensities greater than two standard deviations above the median intensity of all array elements, from all experiments. From the above, we selected the de facto housekeeping elements as those elements with standard deviations for the expression ratios as ± 0.1. Regressions for the X-encoded and the autosome-encoded elements were calculated separately in Bioconductor. Slopes and intercepts were compared at the 95% confidence limit.
Moving averages of expression ratios for every 40 consecutive elements (two elements per predicted transcript) were plotted against the corresponding gene positions on chromosome arm 2L or X. The predicted cytological break points [27] were used to define the boundaries of aneuploid segments on chromosome arm 2L, in the Dp/+ versus Df/+ experiments. Moving averages were calculated in Bioconductor.
Analysis of distributions
The distribution statistics cited in the text were obtained using data processed with print-tip loess and on-spot background correction on individual arrays, and quantile normalization between arrays. We can unequivocally show that a modest 1.5-fold difference in gene dose has a detectable effect on gene expression using precisely the same data-handling methods that we apply to the study of the X. In addition, the data-handling method used is the least favorable method vis-a-vis the conclusions we report. Differences in gene expression in autosomal aneuploid segments were always significantly greater than those observed between the X chromosomes from XX;AA and X;AA samples.
We performed a one-way analyses of variance (ANOVA) followed by the Tukey HSD method for protection in multiple comparisons using Matlab (The MathWorks, Natick, USA). All cells were filled ten times. One-way ANOVA was used to compare three different sets of expression ratios or hybridization intensities. The single blocking factor for one-way ANOVA was gene dose. We used bootstrap sampling of pooled array data to fill each of the three ANOVA cells of the one-way design. For ratiometric data, those cells were (Dp/+)/(+/+), AA/AA, and XX/X (see Additional data files 3, Tables 1-3). To fill the (Dp/+)/(+/+) cell, we pooled expression ratios associated with a 1.5-fold difference in gene dose from the replicate samples from whole males, whole females and ovaries, and sampled 600 ratios. There are fewer genes in the Dp region than on all autosomes or on the X chromosome. Therefore, the stability of this inference was verified by filling this cell with 200 ratios from each of the tissue types separately (data not shown). To fill the AA/AA cell we pooled all array data reported in this article where the gene dose was 1 and sampled 600 ratios. To fill the XX/X cells we sampled 600 X-chromosome ratios for each of three different gonad comparisons separately. Those are (otu1/otu17)/(hs-tra/+), (Sxlfs3/Sxl7BO)/(hs-tra/+) and ovary/testis (see Additional data file 3, Tables 1-3). For analysis of Drosophila intensity data, the cells were Df/+, AA, and X (see Additional data files 3, Tables 4,5). As with ratiometric data, intensity data were bootstrap sampled 600 times and the procedure was repeated ten times. Stability for the Df/+ cell was also verified. The inferences were similar in all ten samplings of 200 intensity values from each tissue type (data not shown). For C. elegans and mouse data the cells were AA and X (see Additional data file 3, Table 6). These cells were filled as for Drosophila. For mouse, we ran ANOVA on pooled intensities from liver, kidney and hypothalamus. We also analyzed each tissue separately. The Tukey HSD procedure was performed in Matlab and generated a confidence interval for each pair of comparisons that has a family-wise error rate of, at most, α = 0.05 (see Additional data file 3).
For the Drosophila data, we applied a bootstrapped Hodges-Lehmann (HL) estimate of median differences to determine if X-chromosome expression was more similar to autosomal expression or to expression from autosomal aberrations (see Additional data files 4,5). Additional data file 6 shows a cartoon depicting bootstrap HL estimates of median differences followed by the Kolmogorov-Smirnov (KS) test. HL estimates and KS tests were performed in Bioconductor. For ratiometric data (see Additional data file 4), the HL estimate was calculated for every drawing of 600 bootstrap samples from the (Dp/+)/(+/+) and AA/AA distributions to generate a new distribution of differences. Next, the same bootstrap sampling was used for the XX/X and AA/AA distribution to generate a second distribution of differences. Intensity data were treated similarly (see Additional data file 5). The two distributions of differences were then compared using the KS test. The differences in the medians and associated D and p-values for the KS tests then permitted inference concerning the proximity of expression ratios or intensities. In practical terms, a significant p-value allows us to accept (not reject) the assumption that expression ratios AA/AA are closer to XX/X than to Dp/+. This procedure of bootstrap sampling, HL estimation and KS evaluation was repeated ten times to check the stability and robustness of the inferences. In all cases, replicate evaluations resulted in the same inference.
Additional data files
The following files are available. Additional data file 1 is a figure showing the effect of different data handling techniques on differential expression resulting from altered gene dose on the autosomes. Additional data file 2 is a figure showing the experimental design in detail. Additional data files 3,4and 5 are tables showing the results of statistical analysis of gene expression ratios and absolute intensities for whole chromosome arms and for autosomal aneuploid segments: Additional data file 3 shows one-way ANOVA comparisons and Additional data file 4 shows estimation of Hodges-Lehmann (HL) median differences between expression ratios in various experiments and Additional data file 5 shows estimation of Hodges-Lehmann (HL) median differences between signal intensities. Additional data file 6 is a figure showing a simple picture depicting bootstrap HL estimates of median differences followed by the Kolmogorov-Smirnov (KS) test.
This research was supported in part by the Intramural Research Program of the NIH, NIDDK and CIT. We acknowledge our colleagues Mathias Beller, Jurrien Dean, Sandra Farkas, Leonie Hempel, Jamileh Jemison, Rasika Kalamegham, Alan Kimmel, James Minor, John E. Smith, Charles Vinson, and Yu Zhang for discussions and technical assistance. We are grateful to Christine Disteche for providing a preprint of work from her laboratory and to Jim Birchler for discussions on autosomal aneuploidy and dosage compensation.
Authors' Affiliations
- Rosenbusch B: The incidence of aneuploidy in human oocytes assessed by conventional cytogenetic analysis. Hereditas. 2004, 141: 97-105. 10.1111/j.1601-5223.2004.01803.x.View ArticlePubMedGoogle Scholar
- Lindsley DL, Sandler L, Baker BS, Carpenter AT, Denell RE, Hall JC, Jacobs PA, Miklos GL, Davis BK, Gethmann RC, et al: Segmental aneuploidy and the genetic gross structure of the Drosophila genome. Genetics. 1972, 71: 157-184.PubMed CentralPubMedGoogle Scholar
- Celniker SE, Wheeler DA, Kronmiller B, Carlson JW, Halpern A, Patel S, Adams M, Champe M, Dugan SP, Frise E, et al: Finishing a whole-genome shotgun: release 3 of the Drosophila melanogaster euchromatic genome sequence. Genome Biol. 2002, 3: research0079-0079.14. 10.1186/gb-2002-3-12-research0079.PubMed CentralView ArticlePubMedGoogle Scholar
- Pauli D, Oliver B, Mahowald AP: The role of the ovarian tumor locus in Drosophila melanogaster germ line sex determination. Development. 1993, 119: 123-134.PubMedGoogle Scholar
- Lu J, Oliver B: Drosophila OVO regulates ovarian tumor transcription by binding unusually near the transcription start site. Development. 2001, 128: 1671-1686.PubMedGoogle Scholar
- Regan CL, Fuller MT: Interacting genes that affect microtubule function: the nc2 allele of the haywire locus fails to complement mutations in the testis-specific β-tubulin gene of Drosophila. Genes Dev. 1988, 2: 82-92.View ArticlePubMedGoogle Scholar
- Cline TW, Meyer BJ: Vive la difference: males vs females in flies vs worms. Annu Rev Genet. 1996, 30: 637-702. 10.1146/annurev.genet.30.1.637.View ArticlePubMedGoogle Scholar
- Baker BS, Gorman M, Marin I: Dosage compensation in Drosophila. Annu Rev Genet. 1994, 28: 491-521. 10.1146/annurev.ge.28.120194.002423.View ArticlePubMedGoogle Scholar
- Meller V, Kuroda M: Sex and the single chromosome. Adv Genet. 2002, 46: 1-24.View ArticlePubMedGoogle Scholar
- Rastelli L, Kuroda MI: An analysis of maleless and histone H4 acetylation in Drosophila melanogaster spermatogenesis. Mech Dev. 1998, 71: 107-117. 10.1016/S0925-4773(98)00009-4.View ArticlePubMedGoogle Scholar
- Schüpbach T: Normal female germ cell differentiation requires the female X chromosome to autosome ratio and expression of Sex-lethal in Drosophila melanogaster. Genetics. 1985, 109: 529-548.PubMed CentralPubMedGoogle Scholar
- Bachiller D, Sanchez L: Mutations affecting dosage compensation in Drosophila melanogaster: effects in the germline. Dev Biol. 1986, 118: 379-384. 10.1016/0012-1606(86)90007-2.View ArticlePubMedGoogle Scholar
- Gartler SM, Liskay RM, Campbell BK, Sparkes R, Gant N: Evidence for two functional X chromosomes in human oocytes. Cell Differ. 1972, 1: 215-218. 10.1016/0045-6039(72)90039-5.View ArticlePubMedGoogle Scholar
- Kelly WG, Schaner CE, Dernburg AF, Lee MH, Kim SK, Villeneuve AM, Reinke V: X-chromosome silencing in the germline of C. elegans. Development. 2002, 129: 479-492.PubMed CentralPubMedGoogle Scholar
- Heard E, Clerc P, Avner P: X-chromosome inactivation in mammals. Annu Rev Genet. 1997, 31: 571-610. 10.1146/annurev.genet.31.1.571.View ArticlePubMedGoogle Scholar
- Meyer BJ: Sex in the worm: counting and compensating X chromosome dose. Trends Genet. 2000, 16: 247-253. 10.1016/S0168-9525(00)02004-7.View ArticlePubMedGoogle Scholar
- Ohno S: Sex Chromosomes and Sex-linked Genes. 1967, Berlin: Springer-VerlagView ArticleGoogle Scholar
- Charlesworth B: The evolution of chromosomal sex determination and dosage compensation. Curr Biol. 1996, 6: 149-162. 10.1016/S0960-9822(02)00448-7.View ArticlePubMedGoogle Scholar
- Charlesworth B: The evolution of sex chromosomes. Science. 1991, 251: 1030-1033.View ArticlePubMedGoogle Scholar
- Charlesworth B: Model for evolution of Y chromosomes and dosage compensation. Proc Natl Acad Sci USA. 1978, 75: 5618-5622.PubMed CentralView ArticlePubMedGoogle Scholar
- Adler DA, Rugarli EI, Lingenfelter PA, Tsuchiya K, Poslinski D, Liggitt HD, Chapman VM, Elliott RW, Ballabio A, Disteche CM: Evidence of evolutionary up-regulation of the single active X chromosome in mammals based on Clc4 expression levels in Mus spretus and Mus musculus. Proc Natl Acad Sci USA. 1997, 94: 9244-9248. 10.1073/pnas.94.17.9244.PubMed CentralView ArticlePubMedGoogle Scholar
- Oliver B: Genetic control of germline sexual dimorphism in Drosophila. Int Rev Cytol. 2002, 219: 1-60.View ArticlePubMedGoogle Scholar
- Steinmann-Zwicky M, Schmid H, Nothiger R: Cell-autonomous and inductive signals can determine the sex of the germ line of Drosophila by regulating the gene Sxl. Cell. 1989, 57: 157-166. 10.1016/0092-8674(89)90181-5.View ArticlePubMedGoogle Scholar
- Parisi M, Nuttall R, Edwards P, Minor J, Naiman D, Lu J, Doctolero M, Vainer M, Chan C, Malley J, et al: A survey of ovary-, testis-, and soma-biased gene expression in Drosophila melanogaster adults. Genome Biol. 2004, 5: R40-10.1186/gb-2004-5-6-r40.PubMed CentralView ArticlePubMedGoogle Scholar
- Parisi M, Nuttall R, Naiman D, Bouffard G, Malley J, Andrews J, Eastman S, Oliver B: Paucity of genes on the Drosophila X chromosome showing male-biased expression. Science. 2003, 299: 697-700. 10.1126/science.1079190.PubMed CentralView ArticlePubMedGoogle Scholar
- Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, et al: Gene Ontology: tool for the unification of biology. Nat Genet. 2000, 25: 25-29. 10.1038/75556.PubMed CentralView ArticlePubMedGoogle Scholar
- FlyBase: The FlyBase database of the Drosophila: genome projects and community literature. Nucleic Acids Res. 2003, 31: 172-175. 10.1093/nar/gkg094.View ArticleGoogle Scholar
- Reinke V, Gil IS, Ward S, Kazmer K: Genome-wide germline-enriched and sex-biased expression profiles in Caenorhabditis elegans. Development. 2004, 131: 311-323. 10.1242/dev.00914.View ArticlePubMedGoogle Scholar
- Rinn JL, Rozowsky JS, Laurenzi IJ, Petersen PH, Zou K, Zhong W, Gerstein M, Snyder M: Major molecular differences between mammalian sexes are involved in drug metabolism and renal function. Dev Cell. 2004, 6: 791-800. 10.1016/j.devcel.2004.05.005.View ArticlePubMedGoogle Scholar
- Nguyen DK, Disteche CM: Dosage compensation of the active X chromosome in mammals. Nat Genet. 2006, 38: 47-53.View ArticlePubMedGoogle Scholar
- Chiang PW, Kurnit DM: Study of dosage compensation in Drosophila. Genetics. 2003, 165: 1167-1181.PubMed CentralPubMedGoogle Scholar
- Jin W, Riley RM, Wolfinger RD, White KP, Passador-Gurgel G, Gibson G: The contributions of sex, genotype and age to transcriptional variance in Drosophila melanogaster. Nat Genet. 2001, 29: 389-395. 10.1038/ng766.View ArticlePubMedGoogle Scholar
- Arbeitman MN, Furlong EE, Imam F, Johnson E, Null BH, Baker BS, Krasnow MA, Scott MP, Davis RW, White KP: Gene expression during the life cycle of Drosophila melanogaster. Science. 2002, 297: 2270-2275. 10.1126/science.1072152.View ArticlePubMedGoogle Scholar
- Andrews J, Bouffard GG, Cheadle C, Lu J, Becker KG, Oliver B: Gene discovery using computational and microarray analysis of transcription in the Drosophila melanogaster testis. Genome Res. 2000, 10: 2030-2043. 10.1101/gr.10.12.2030.PubMed CentralView ArticlePubMedGoogle Scholar
- Ranz JM, Castillo-Davis CI, Meiklejohn CD, Hartl DL: Sex-dependent gene expression and evolution of the Drosophila transcriptome. Science. 2003, 300: 1742-1745. 10.1126/science.1085881.View ArticlePubMedGoogle Scholar
- Birchler JA, Pal-Bhadra M, Bhadra U: Dosage dependent gene regulation and the compensation of the X chromosome in Drosophila males. Genetica. 2003, 117: 179-190. 10.1023/A:1022935927763.View ArticlePubMedGoogle Scholar
- Pal Bhadra M, Bhadra U, Kundu J, Birchler JA: Gene expression analysis of the function of the male-specific lethal complex in Drosophila. Genetics. 2005, 169: 2061-2074. 10.1534/genetics.104.036020.PubMed CentralView ArticleGoogle Scholar
- Kai T, Williams D, Spradling AC: The expression profile of purified Drosophila germline stem cells. Dev Biol. 2005, 283: 486-502. 10.1016/j.ydbio.2005.04.018.View ArticlePubMedGoogle Scholar
- Hiller M, Chen X, Pringle MJ, Suchorolski M, Sancak Y, Viswanathan S, Bolival B, Lin TY, Marino S, Fuller MT: Testis-specific TAF homologs collaborate to control a tissue-specific transcription program. Development. 2004, 131: 5297-5308. 10.1242/dev.01314.View ArticlePubMedGoogle Scholar
- Bielinska B, Lu J, Sturgill D, Oliver B: Core promoter sequences contribute to ovo-B regulation in the Drosophila melanogaster germline. Genetics. 2005, 169: 161-172. 10.1534/genetics.104.033118.PubMed CentralView ArticlePubMedGoogle Scholar
- Ruiz MF, Esteban MR, Donoro C, Goday C, Sanchez L: Evolution of dosage compensation in Diptera: the gene maleless implements dosage compensation in Drosophila (Brachycera suborder) but its homolog in Sciara (Nematocera suborder) appears to play no role in dosage compensation. Genetics. 2000, 156: 1853-1865.PubMed CentralPubMedGoogle Scholar
- da Cunha PR, Granadino B, Perondini AL, Sanchez L: Dosage compensation in sciarids is achieved by hypertranscription of the single X chromosome in males. Genetics. 1994, 138: 787-790.PubMed CentralPubMedGoogle Scholar
- Serna E, Gorab E, Ruiz MF, Goday C, Eirin-Lopez JM, Sanchez L: The gene Sex-lethal of the Sciaridae family (order Diptera, suborder Nematocera) and its phylogeny in dipteran insects. Genetics. 2004, 168: 907-921. 10.1534/genetics.104.031278.PubMed CentralView ArticlePubMedGoogle Scholar
- Hilfiker A, Hilfiker-Kleiner D, Pannuti A, Lucchesi JC: mof, a putative acetyl transferase gene related to the Tip60 and MOZ human genes and to the SAS genes of yeast, is required for dosage compensation in Drosophila. EMBO J. 1997, 16: 2054-2060. 10.1093/emboj/16.8.2054.PubMed CentralView ArticlePubMedGoogle Scholar
- Kelley RL, Wang J, Bell L, Kuroda MI: Sex lethal controls dosage compensation in Drosophila by a non-splicing mechanism. Nature. 1997, 387: 195-199. 10.1038/387195a0.View ArticlePubMedGoogle Scholar
- Cline TW: Autoregulation functioning of a Drosophila gene product that establishes and maintains the sexually determined state. Genetics. 1984, 107: 231-277.PubMed CentralPubMedGoogle Scholar
- Smith ER, Allis CD, Lucchesi JC: Linking global histone acetylation to the transcription enhancement of X-chromosomal genes in Drosophila males. J Biol Chem. 2001, 276: 31483-31486. 10.1074/jbc.C100351200.View ArticlePubMedGoogle Scholar
- Oliver B, Singer J, Laget V, Pennetta G, Pauli D: Function of Drosophila ovo+ in germ-line sex determination depends on X-chromosome number. Development. 1994, 120: 3185-3195.PubMedGoogle Scholar
- Sahut-Barnola I, Pauli D: The Drosophila gene stand still encodes a germline chromatin-associated protein that controls the transcription of the ovarian tumor gene. Development. 1999, 126: 1917-1926.PubMedGoogle Scholar
- Andrews J, Garcia-Estefania D, Delon I, Lu J, Mevel-Ninio M, Spierer A, Payre F, Pauli D, Oliver B: OVO transcription factors function antagonistically in the Drosophila female germline. Development. 2000, 127: 881-892.PubMedGoogle Scholar
- Wakimoto BT, Lindsley DL, Herrera C: Toward a comprehensive genetic analysis of male fertility in Drosophila melanogaster. Genetics. 2004, 167: 207-216. 10.1534/genetics.167.1.207.PubMed CentralView ArticlePubMedGoogle Scholar
- Birchler JA: A study of enzyme activities in a dosage series of the long arm of chromosome one in maize. Genetics. 1979, 92: 1211-1229.PubMed CentralPubMedGoogle Scholar
- Birchler JA, Riddle NC, Auger DL, Veitia RA: Dosage balance in gene regulation: biological implications. Trends Genet. 2005, 21: 219-226. 10.1016/j.tig.2005.02.010.View ArticlePubMedGoogle Scholar
- Devlin RH, Holm DG, Grigliatti TA: Autosomal dosage compensation Drosophila melanogaster strains trisomic for the left arm of chromosome 2. Proc Natl Acad Sci USA. 1982, 79: 1200-1204.PubMed CentralView ArticlePubMedGoogle Scholar
- Kahlem P, Sultan M, Herwig R, Steinfath M, Balzereit D, Eppens B, Saran NG, Pletcher MT, South ST, Stetten G, et al: Transcript level alterations reflect gene dosage effects across multiple tissues in a mouse model of Down syndrome. Genome Res. 2004, 14: 1258-1267. 10.1101/gr.1951304.PubMed CentralView ArticlePubMedGoogle Scholar
- Bond U, Neal C, Donnelly D, James TC: Aneuploidy and copy number breakpoints in the genome of lager yeasts mapped by microarray hybridisation. Curr Genet. 2004, 45: 360-370. 10.1007/s00294-004-0504-x.View ArticlePubMedGoogle Scholar
- Phillips JL, Hayward SW, Wang Y, Vasselli J, Pavlovich C, Padilla-Nash H, Pezullo JR, Ghadimi BM, Grossfeld GD, Rivera A, et al: The consequences of chromosomal aneuploidy on gene expression profiles in a cell line model for prostate carcinogenesis. Cancer Res. 2001, 61: 8143-8149.PubMedGoogle Scholar
- Ghosh S, Lucchesi JC, Manning JE: The non-dosage compensated LSP1-α gene of Drosophila melanogaster lies immediately downstream of the dosage compensated L12 gene. Mol Gen Genet. 1992, 233: 49-52. 10.1007/BF00587560.View ArticlePubMedGoogle Scholar
- Marin I, Siegal ML, Baker BS: The evolution of dosage-compensation mechanisms. BioEssays. 2000, 22: 1106-1114. 10.1002/1521-1878(200012)22:12<1106::AID-BIES8>3.0.CO;2-W.View ArticlePubMedGoogle Scholar
- de Wit E, Greil F, van Steensel B: Genome-wide HP1 binding in Drosophila : developmental plasticity and genomic targeting signals. Genome Res. 2005, 15: 1265-1273. 10.1101/gr.3198905.PubMed CentralView ArticlePubMedGoogle Scholar
- Johnston R, Wang B, Nuttall R, Doctolero M, Edwards P, Lü J, Vainer M, Yue H, Wang X, Minor J, et al: FlyGEM, a full transcriptome array platform for the Drosophila community. Genome Biol. 2004, 5: R19-10.1186/gb-2004-5-3-r19.PubMed CentralView ArticlePubMedGoogle Scholar
- Churchill GA: Fundamentals of experimental design for cDNA microarrays. Nat Genet. 2002, 32 (Suppl): 490-495. 10.1038/ng1031.View ArticlePubMedGoogle Scholar
- Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, et al: Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 2004, 5: R80-10.1186/gb-2004-5-10-r80.PubMed CentralView ArticlePubMedGoogle Scholar
- Yang YH, Dudoit S, Luu P, Lin DM, Peng V, Ngai J, Speed TP: Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation. Nucleic Acids Res. 2002, 30: e15-10.1093/nar/30.4.e15.PubMed CentralView ArticlePubMedGoogle Scholar
- Edgar R, Domrachev M, Lash AE: Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 2002, 30: 207-210. 10.1093/nar/30.1.207.PubMed CentralView ArticlePubMedGoogle Scholar
- de Hoon MJ, Imoto S, Nolan J, Miyano S: Open source clustering software. Bioinformatics. 2004, 20: 1453-1454. 10.1093/bioinformatics/bth078.View ArticlePubMedGoogle Scholar
- Deng W, Lin H: Asymmetric germ cell division and oocyte determination during Drosophila oogenesis. Int Rev Cytol. 2001, 203: 93-138.View ArticlePubMedGoogle Scholar
- Mahowald AP: Assembly of the Drosophila germ plasm. Int Rev Cytol. 2001, 203: 187-213.View ArticlePubMedGoogle Scholar
- Nagoshi RN, Patton JS, Bae E, Geyer PK: The somatic sex determines the requirement for ovarian tumor gene activity in the proliferation of the Drosophila germline. Development. 1995, 121: 579-587.PubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


text:
Thursday, March 10, 2016
Auction Watch: 1970 Ford Mustang Fastback
Take a look at this 1970 Ford Mustang Fastback here on eBay bidding for $20,100 with auction ending Thursday around 3PM PST.
Posted by DailyTurismo at 6:00 AM
Labels: Auction Watch, Fastback, Ford, Mustang
1 comment:
Commenting Commandments:
I. Thou Shalt Not write anything your mother would not appreciate reading.
II. Thou Shalt Not post as anonymous unless you are posting from mobile and have technical issues. Use name/url when posting and pick something Urazmus B Jokin, Ben Dover. Sir Edmund Hillary Clint Eastwood...it don't matter. Just pick a nom de plume and stick with it.
III. Honor thy own links by using  description of your link
IV. Remember the formatting tricks italics and  bold
V. Thou Shalt Not commit spam.
VI. To embed images: use [image src="http://www.IMAGE_LINK.com" width="400px"/]. Limit images to no wider than 400 pixels in width. No more than one image per comment please.
Subscribe to: Post Comments (Atom)


text:
Aus to top this group. Windies to sh*t on their tails unless Gayle shows why he loves t/20 so much.
Aus to top this group. Windies to sh*t on their tails unless Gayle shows why he loves t/20 so much.
Oh Holy Mary Mother of God! Thank goodness Aus v WI is on a Saturday!
What really should be Australia starting XI?. Still a big mystery i guess.
Presuming Watson can bowl, im leaning towards this XI:
M Hussey
D Hussey
- Would pick Siddle over Bracken unfortunately because i reckon having 3, 145K bowlers will be a massive plus againts batting line-ups like India & SA - if Australia get far in the tournament.
- Not fully behind starting Warner, he is too hit & miss for me - more so the latter.
- Hopes could open if they want to save Haddin for the death & he can give useful overs, although batsmen will obviously want to target him. Plus
- Clark... well just stick him @ 6.
- No need for Hauritz, Hussey, Symonds & Clarke to sweak it.
The opening batsmen combination will prove the most crucial decision for Australian selectors. Vital they get it right, as the IPL and previous international games have shown that a decent opening combination is the difference between a 120 score and a 160+ score. Very difficult for teams to make a comeback from 2/20 after 4.
Any bat out of Haddin, Clarke, Hopes, Watson and Warner may be used for the position.
Watson is the most suited to open. Most likely to score a 50+ score at better than a run a ball. More adaptable than all the other candidates, is actually capable of mixing defence with ability to hit over the top.
Warner is the gamble. If he comes off, 180+ is possible. Has actually shown remarkable consistency over T20 games with Australia, NSW and in the IPL. Not always scoring a big innings, but providing a quick start.
Haddin, Clarke and Hopes all suffer from similar issues. Each batsmen can get tied down at one end early on. They all find it a struggle to pierce the in-field early, totally reliant on a big shot to get out of trouble. Which is not the natural game of any of the three batsmen. I would back Haddin and Hopes over Clarke to actually compile a decent innings.
My preferred combination is:
Watson and Warner
But depending on team selection, the combination may prove anything.
I feel a bit sorry for the West Indies.
They're crap but are better than Bangladesh and should've been given their spot in India's group imo.
All-Time Test XI:
Gavaskar, Boycott, Tendulkar, G.Pollock, V.Richards, Sobers, Gilchrist (wk), Warne (c), Waqar/Wasim, Lillee, Ambrose.
I think a very competitive group with lost of excitement. I will go for Sri Lanka and West Indies. Since Australians are not focussing on twenty20 world cup, their main aim is to retain Ashes. So i will go with Sri Lanka and West Indies to qualify for the Super Eight Stage.
Exactly, our shocking performance in the last 20/20 World Cup is the reason we are in this group.
Our decent 20-20 performances since that event have been completely ignored even though we have won matches against England, South Africa, Australia and New Zealand.
I'm not convinced that is the right system because it basically means 20/20 internationals outside of this event are exhibition matches only.
You can't decide how good a team someone is on 1 game.
If Everton were to beat Chelsea in the FA Cup final- would they be a better team, or just better on that day?
Bangladesh are just a hopeless team and India have been dealt an easy group.
And since then we have been pretty damn good at 20-20. Certainly far better than England, Bangladesh etc, and probably on a par with NZ.
Does just one team from each group go forward? Or is there a second round of 8 teams? Can't remember. If it's 2 I'd pick Aus and SL, but Windies could easily upset either side. Seems silly to have such a strong group when you have India, Bangladesh & Ireland in another.
There are currently 1 users browsing this thread. (0 members and 1 guests)


text:
Lyle Gash was born with only half his heart. It was his heart for which people are remembering him after he died this week at 24.
KINGSTOWN � Lyle Gash was born with only half his heart.
But he used that heart, his family and friends said, to love people every day of his life.
�You hear people talking about loving people to death. Lyle�s family, they loved him to life,� said James L. Smith, pastor of Palmer Grove Baptist Church. �He beat the odds, and he did it because his mom, dad and the rest of his family showed him how to overcome his struggles.�
Lyle had Downs Syndrome, a critical heart condition and suffered from kidney failure. He died this week at 24.
�He had such a kindred spirit. He loved people,� his mother Ramona Gash said. �The unique thing about Lyle, even from being a baby, he never liked toys. He never liked candy and cookies or any of that. From day one, Lyle liked people. That was his joy.�
Lyle was known and supported by people around the world through a ministry that collected thousands of greeting cards for him. The Star first reported on the ministry in December, at a time when he had already received thousands of special messages from supporters near and far.
�Always there to support us�
Lyle�s friends and family say he supported them his whole life, even as he needed support, too.
�Sometimes you knew he was in pain, but he never complained,� his cousin Angela Bowden said. �He didn�t let his condition slow him down at all. He lived beyond his own limitations. Lyle was happy with who he was. I don�t think he ever questioned that.�
Cousin Jermica Walker said she would take Lyle places and he would interact with people.
�Everywhere he went, he changed the atmosphere,� she said. �He�d brighten up every situation.�
His aunt Lynn Lynch said she remembers when Lyle comforted her when he was only 4 years old. Her mother had died and she was having a hard time dealing with the loss.
�Lyle went over and got a picture of her and laid it on my heart and told me I would be all right,� Lynch said. �He was always there to support us in our tough times and good times.�
�Lyle dunked�
Lyle was a big supporter of his brother, Chris, who played basketball at Burns High School and Gardner-Webb University.
And the university supported him.
In the days before Lyle�s death, new GWU basketball coach Tim Craft and the Runnin� Bulldogs visited the Gash home. They took him a jersey with the No. 5 and it was signed by the team.
�They helped him to his feet,� his mother said, �and draped him in the jersey. They stood up and raised their hands. Lyle�s hand was around their elbows. Then one, two, three, Lyle!�
Lyle loved to cheer on his family and his sports teams, his mother said.
His aunt Sharon Diann McCullough said she remembers Lyle coaching alongside his father, Paul, with the Palmer Grove church team at Holly Oak Park in Shelby.
Lyle sported a black T-shirt with the word "coach" and would give players a "good job" for their performance, she said.
"And whether they won or not, Lyle would give them a victory dance," she said.
Lyle was also an athlete himself, his mother said, recalling one story in particular.
�We had two basketball goals on our paved court out here. His father and brother played, so Lyle naturally took a strong liking to basketball. One day, he decided he wanted to do something spectacular,� she said. �He pushed a chair up to the goal where he wanted to dunk the basketball because the goal was not at his height. He jumped up in the chair and thought he could dunk the basketball. He would later show people a scar he had and say �Lyle dunked.� He had about a two-inch vertical. In his mind, he dunked that basketball. He was an athlete, and he loved basketball.�
Thousands of greetings
Lyle also loved getting mail. And he received more than 20,000 cards in the past year alone.
Last year, his mother posted a letter to Facebook explaining his condition and requesting cards because Lyle loved seeing his name on mail.
Cards poured in � from the local community, from Michelle Obama, from Russia and Saudi Arabia, and from every U.S. state.
�He was actually getting cards and letters on the day he died,� Ramona said. �We stopped counting in the early summer when we needed to be by Lyle most.�
Lyle's cousin Sarah Gerald said the card ministry shares its own message to the world.
"Thousands of people were given hope and felt true love," Gerald said. "To know Lyle is to know the hand of God on our lives. God created us all in His image and for His purpose. Lyle was created to show people how to worship God in times of sheer turmoil, to love those who society deemed unworthy, and to show that all life, no matter what form, is valuable."
Lyle also liked to share greetings with his family and friends. He visited the home of each family member on his street in the days before he died.
�We just pulled up in the yards,� Ramona said. �He ended his journey by saying �Lyle drive.� He could never drive, but I scooted him under the wheel and let him drive me home in the golf cart.�
�He encouraged others�
Lyle was also strong in his faith, his pastor, Smith, said.
�Because he was loved, he knew how to exhibit love,� Smith said. �He was an honorary junior deacon. He encouraged others by the way he conducted himself.�
His mother said the day before Lyle died, he took the hands of his brother and his father and said �let�s pray.�
�When he got to the point where he couldn�t eat, hadn�t eaten in weeks, he was living off sips,� his mother said. �We filled up a shot glass and filled it half full. Before he would take that sip of juice, he bowed his head and prayed. He loved his family, he loved his God, and he loved to praise and worship. I don�t think Lyle did anything in his life that measured up to those.�
His aunt Janet Lynch Gerald likened him to an angel.
�Lyle�s touched a lot of lives,� aunt Shirley Ann Lewis said. �He was very precious to all of us.�
�Unique in everything�
For his 19th birthday, Lyle�s family gathered hundreds of people in a local gym.
He was presented with a No. 5 basketball jersey, the same number he received in his final days.
�Number 5 in the Bible is the number of grace,� Ramona said. �How ironic. Five years ago, he got the same number.
�Lyle was not a normal child. Every year he lived was a gamble against time. He was unique in everything he did. His life was a life lived through leaving a legacy of love all around the world.�
Reach Matthew Tessnear at 704-669-3331, at email@example.com or on Twitter @MatthewTessnear.


text:
Koenigseggs are not for children. They're for hairy chested adults (men or women, doesn't matter, just need hair on the old chest) who don't get terrified easily. The new One:1 will make a lumberjack out of anyone.
Set to debut at the Geneva Motor Show next month, the One:1 is named for its power to weight ratio. It'll have 1,340 horsepower and weigh 1,340 kilograms. One to one.
Get it? (We originally heard 1,400/1,400. That was incorrect as about 630 people have pointed out. Sorry.)
The teaser that Koenigsegg released today show a car that looks much like the Agera, but with a wing that you could eat Thanksgiving dinner off of. It's gigantic. There are also rumors that Koenigsegg will remove the 258 MPH speed limiter that was on the old car in favor of trying to beat the Bugatti Veyron Super Sport's top speed. With a top speed that could go past 280 MPH in theory, this might be the ultra terrifying way to do it.
Godspeed Koenigsegg. Godspeed.


text:
Barliman Butterbur
Barliman Butterbur (late Third Age – early Fourth Age) was the owner of the Inn known as The Prancing Pony in Bree.
Barliman appears to have had a rather bad memory, "One thing drives out another" he says. He forgot to send Gandalf's letter to Frodo, leaving Frodo uncertain as to Gandalf's fate and causing him to start his journey much later than the letter indicated. He did not remember it until Frodo and his companions arrived to stay at the inn, and even then it was long before the connection was made. He did, however, remember to produce Strider's credentials.
When Gandalf finally arrives at The Prancing Pony, he's furious with Barliman's forgetfulness, but quickly forgives him when he finds out the Hobbits are alive. He even goes so far as to put a blessing on his beer.
In The Return of the King, Barliman was amazed to learn that Strider, a former patron of the Prancing Pony, had become king of Gondor and Arnor.
Barliman was a Man, but as Bree was inhabited by both Men and Hobbits, he had two hobbit employees: Bob, who worked in the stables, and Nob, a servant.
Portrayal in Adaptations
- Ralph Bakshi's Barliman Butterbur.jpg
Barliman as portrayed in Ralph Bakshi's The Lord of the Rings
- Peter Jackson's Barliman Butterbur.jpg
David Weatherley played Barliman in Peter Jackson's The Fellowship of the Ring
In Ralph Bakshi's The Lord of the Rings, Barliman was voiced by Alan Tilvern.
In Peter Jackson's The Fellowship of the Ring, he is played by David Weatherley, although the character is not named and most of his scenes from the book (including the reference to Gandalf's letter) are not in the film.


text:
Archive for the 'Solar System' Category
Solar Therm – a 5.0 star rated pro. (ServiceMagic.com)
Solar Contractors Therm has been providing excellent customer service and superior workmanship for over 25 yrs
GEOSCAPE SOLAR – $500 OFF SOLAR SYSTEM INSTALLED – Expires 2012-02-02 (Valpak.com)
Free, On-Site Estimates with Sunshine Solar Technologies! (eBay Classifieds)
Sunshine Solar Contractors Technologies is pleased to provide free estimates and site analysis. If you


text:
|TidBITS#188 19930809
by Mark H. Anbinder, News Editor -- email@example.com
Turnabout is Fair Play -- There have been several products to let Mac users read DOS-formatted disks over the years, from the DaynaFile drives to the collection of software taking advantage of the SuperDrive. Rumor has it that there have been shareware solutions for DOS users who wish to read Mac disks, but finally there's a high-profile commercial product - from the DOS experts at Insignia Solutions. MacDisk, shipping soon, is a simple, straightforward product that allows Mac disks and their contents to be accessed within DOS and Windows; DOS 6.0 is supported (but its compression won't work on the Mac volumes), and the developers expect to be able to claim official support for OS/2 and DR-DOS after some extra tests are completed.
Insignia Solutions -- 800/848-7677 -- 415/694-7600
Most Worthwhile "Me Too" -- Usually the second company to market with a comparable product finds itself at a disadvantage. Not so with Stac Electronics, whose Stacker driver-level disk compression software goes up against Times Two from Golden Triangle (which we mentioned in last August's Macworld Superlatives list, in TidBITS #137). Stacker uses the same compression engine as Times Two; Stac licensed their LZS engine, also used in their DOS version of Stacker, to Golden Triangle last year. The innards may be the same, but Stac points out a number of interface and implementation differences that they feel put them in the lead. Initial examination suggests there are plenty of differences; we'll examine them in depth at a later time.
Stac Electronics -- 800/522-7822 -- 619/431-7474 -- 619/431-0880 (fax)
Welcome to the 1980s -- Aldus has finally shipped PageMaker 5.0, the long-awaited version that includes an ability perfected in most applications the better part of a decade ago: handling multiple open documents at once. Don't get the idea, though, that we don't applaud Aldus's achievement. We do! In the process of modifying this old application to handle multiple documents, Aldus software engineers played leapfrog with much of the rest of the market. PageMaker 5.0 allows any object to be moved or copied from one document to another in the most intuitive way imaginable - by dragging. Kudos to PageMaker for extending the desktop metaphor.
Aldus -- 206/622-5500 -- 206/233-7404 (fax)
2 + 2 = 4 -- PSI Integration wins the award for most intelligent combination of existing technologies with the introduction of its FAXcilitate Broadcast product/service. PSI has combined its newly-revamped fax-sending software with US Sprint's fax broadcasting service to produce a product that makes it easy to send faxes to as many as thousands of fax recipients with a single toll-free call. According to literature distributed at the PSI booth, it would cost about $140 and take just a few minutes to send a two-page fax to 200 recipients through the FAXcilitate Broadcast service, whereas the same fax sent directly to each recipient would take hours.
PSI Integration -- 800/622-1722 -- 408/559-8544 -- 408/559-8548 (fax)
Best Revival -- This close contender for Best PowerBook Product actually deserves its own category, since it's the best use of old technology in a new way. Back in 1985, I bought the first scanner available for Macintosh, and ThunderScan's creators, ThunderWare, have done it again with the first scanner (that I know of) designed specifically for PowerBook users. Their handheld, battery-powered scanner uses a similar design to the popular LightningScan, and since it sports a serial interface, it should work with literally any PowerBook (including the Duos) or, presumably, any other Mac.
ThunderWare, Inc. -- 415/254-6581 -- 415/254-3047 (fax)
Best Battery -- There must have been a dozen vendors showing or selling replacement batteries or add-on batteries for PowerBooks, but the ThinPack from VST deserves special recognition. It's neither almost as big nor almost as heavy as your PowerBook (as some add-on batteries are), and you can put it under the PowerBook as you use it, or leave it connected via the included cord while it sits out of the way, perhaps in your briefcase or carry-on bag. If you want to use your PowerBook for several more hours than you dreamed possible, give these folks a call. (Note that there's no Duo battery yet, and color PowerBook owners can expect a less-dramatic extension on battery life.)
VST -- 508/287-4600 -- 508/287-4068 (fax)
Worst Congestion -- After attending several Macworld Expos, I've grown accustomed to wending my way through crowds of impressed folks trying to look at the wares at one booth or another. Badly-designed booths can cause quite a bit of blockage in the aisles. The award goes to Adobe, though, since at several points when I tried to get by, their demonstrations were literally blocking the entire aisle. A novice could be excused for putting a visually-interesting display at the corner of a booth, with no place for onlookers to stand other than in the aisle, but veterans like Adobe should know better. Please, folks, when planning your next booth, if you want show attendees to be able to stand and watch, provide for some space within your booth. Don't use all the space out to the edge of the booth so there will be no place to stand other than the aisle. If you're hoping that the congestion will get more people to stop and see what you have, grow up and let your product stand on its own two feet. [I'd like to give Apple an honorable mention for this as well - I couldn't even get close the AV Macs every time I tried. -Adam]
Unfair Competition -- It used to be that Global Village Communications offered one of the strongest fax/modem products, but at a premium price. Competitors could smugly say, "Yes, theirs is better, but ours is cheaper." No more, thanks to Global Village's introduction this week of the TelePort/Bronze II, a redesigned version of the company's low-end modem without some of the bells and whistles. Global Village's customer surveys concluded that most people never use many of the fancy features, so this new $109 modem leaves out the data compression and error correction from the 2400 bps data modem, draws power from the Mac's ADB instead of from an expensive, clumsy power adapter, has no voice/fax switch, and doesn't include the company's fancy OCR (optical character recognition) software for turning received faxes into editable documents. But with a basic product that does everything most people need, and does it with Global Village's award-winning fax software, other companies will find they can no longer compete on price alone.
Global Village Communications -- 800/736-4821 -- 415/329-0700
Best Newton Vaporware -- While we're at it, there were lots of almost-ready add-on products for the Newton MessagePad being shown, both on the show floor and at the Newton Showcase at Boston's Symphonic Hall. The most impressive-looking (given our biases toward universal email access, of course) was CE Software's QuickAccess prototype. QuickAccess (invoked on the MessagePad through the use of the action word "qac," pronounced "quack") will enable roaming Newton users to access their QuickMail, Novell MHS, or PowerTalk (AOCE) compliant mail servers. To CE's credit, the prototype sported not a Newtonized QuickMail interface, but a new approach to mail access that seemed much better integrated with Newton's overall design.
CE Software, Inc. -- 515/224-1995
Best Old Idea -- SuperMac did this years ago with their DataStream tape drive, and I've been wondering why no one else has. Optima Technology has just released a new version of its DeskTape software, which will now be available separately from the company's storage devices. DeskTape uses the familiar desktop interface for high-capacity tape storage, allowing DAT cartridges to appear on the Finder desktop. You can drag files to and from your tape drive, and even open and use applications or documents that are stored on tape. The advantages for graphic designers and service bureaus are obvious, even though the access time for such devices can be as long as 26 seconds. DeskTape can't work with tape archives created with backup software like Retrospect, but once you create a DeskTape volume on a DAT cartridge, you can use just about any backup software to back up or archive files to that volume.
Optima Technology Corp. -- 714/476-0515 -- 714/476-0613 (fax)
Hungriest -- We mentioned Focus Enhancements as being "Most Evident" at last August's Macworld Expo. They had a slightly lower-key presence outside the World Trade Center this year (only a few local youngsters handing out bags and buttons) but an even bigger booth at Bayside Expo Center. Focus operates by finding good technology and acquiring it, then selling and supporting it directly. This month we learned that Focus has just acquired ETC, the mail-order company seen in the pages of many a Mac magazine. According to Focus, they're most excited about having acquired ETC's European distribution channel, since there's a large European market just waiting to buy high quality products at mail-order prices.
Focus Enhancements -- 617/938-8088 -- 617/938-1098 (fax) -- email@example.com
Long-Lost Cousin Award -- While Apple introduced its Newton MessagePad with lots of noise and commotion, Apple's Newton manufacturing partner Sharp Electronics quietly released its own version, the Sharp Newton ExpertPad. The ExpertPad is identical to the MessagePad except for the name, a hinged door to cover the screen, and (as a result of the door) a slightly different pen-holder. Newton enhancements should work equally well on either unit. If past performance is any guide, Apple's version is likely to be hard to find for a few weeks (supplies were artificially abundant at Macworld) and the ExpertPad is likely to be available at just about any Sharp consumer electronics dealer.
Sharp Electronics -- 800/237-4277 -- 201/529-8200


text:
Published on
This zip-archive contains two Matlab functions for the recursive solution of the partial matrix inversion and partial 3-matrix multiplication used in the non-equilibrium Green's function (NEGF) method.
- works for 3-diagonal matrices
- works for 3-block-diagonal matrices
The explanations of the arguments and the calling sequence are in file headers. To display, use the Matlab commands
>> help recuresealg3d
>> help recuresealgblock3d
Co-authored by Siyu Koswatta (Purdue University) and Dmitri Nikonov (Intel).
See attached license which governs distribution, copying and modification.
For the explanations of the algorithm see the article "Modeling of Nanoscale Devices" by
M. P. Anantram, M. S. Lundstrom, and D. E. Nikonov available e.g. from
Please cite this publication when using the code to obtain any results you intend to publish.
Please report bugs to Dmitri Nikonov
Cite this work
Researchers should cite this work as follows:


text:
Federal Government Won't Let Californians Smoke Pot in Peace
Don't get that excited about California Prop 19 — a state ballot measure to legalize small possessions of marijuana — passing, kids. Because mean old Attorney General Eric Holder says his department will still "vigorously enforce" superseding federal anti-pot laws.
The Associated Press has obtained a letter Eric Holder wrote to former heads of the Drug Enforcement Administration, who apparently still give a shit about any of this. Holder explains that while Californian pot-smokers might get their precious little "state law" changed, the federal government will still enforce its famously futile anti-pot laws, to protect our communities from the reefer:
"We will vigorously enforce the CSA [Controlled Substance Act] against those individuals and organizations that possess, manufacture or distribute marijuana for recreational use, even if such activities are permitted under state law," Holder wrote.
The attorney general also said that legalizing recreational marijuana in California would be a "significant impediment" to the government's joint efforts with state and local law enforcement to target drug traffickers, who often distribute marijuana alongside cocaine and other drugs.
He said the ballot measure's passage would "significantly undermine" efforts to keep California communities safe.
What an old fart. But he may not really mean it. It might just be an official position he needs to set for his department, knowing all the while that he doesn't have the means to "vigorously enforce" this ambitious War on Fun. Fewer than one percent of arrests for marijuana crimes are carried out on the federal level right now, and DEA agents probably don't want to pick up the slack, since it's just dumb marijuana. Then again, some local police — like Los Angeles County's — have said they'll help the federal government out.
This could be a mess to watch. It's best to get high beforehand.


text:
My latest lunch from Sonny Bowl -
$5. BBQ Soy Curls. Green Beans. Brown Rice. Sauce.
Comforty, wholesomey, lunchy. adorable.
SW 3rd and Stark.
Oh, Hey! PDX!:
- Try Vegan Week starts this weekend! I'm going to go to as many events as possible, and will definitely be at Vegan BBQ at 5pm tomorrow - Tofurkey and veggie bonanza!
- The U Can't Touch This! Vegan Prom is next Saturday night, the 22nd. I'm going nuts listening to 90s classics at work.
- Buy your tickets online or this weekend, late night, at the 12th and Hawthorne food carts - or at the Hawthorne Street Fair (old Daily Grind parking lot at 41st) or Sunday Parkways at Laurelhurst. $10 advance price! We'll have free cookies at the carts tonight! I'm going to try and make something from Isa's upcoming cookie book, of course. Stop by and say hi!


text:
What's another word or phrase for "true to himself"?
He remains true to himself even when his friend is murdered.
In this case, let's say 'He' is some sort of activist whose friend is murdered by a gang wanting 'He' to shut up. However, 'He' does not shut up and continues to raise awareness for whatever it is the gang members do not want to draw attention to.
Basically, 'He' keeps doing what he knows is morally correct, despite something bad happening to him as a consequence.


text:
Flavorpill's 10 Most Anticipated Summer Reads
We are on the cusp of summer, and it's time for a preview of the books and novels worth reading in the months to come. June marks the release of a slew of good books, from a collection of Kurt Vonnegut's work to offerings from the acclaimed 33 1/3 series, while July and August give us heists, holes, and hackers, so get ready to while away the lazy summer days with a book by one of the authors below. We are indebted to The Millions for much of this list, so check out their 2011 book preview if you're curious about what's going to be popular in the fall.
Kurt Vonnegut: Novels & Stories 1963-1973 (June 2)
Kurt Vonnegut (1922-2007) has finally received Library of America fame. This is the first of a projected three-volume edition, so you may as well immerse yourself in the world of darkly comedic sci-fi this summer. In the meantime, here's some sage advice from Mother Night: "We are what we pretend to be, so we must be careful about what we pretend to be."