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- CFCS, cardio-facio-cutaneous syndrome
- LEOPARD, multiple lentigines, ECG conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth and sensorineural deafness
- ML/LS, multiple lentigines/LEOPARD syndrome
- SSCP, single strand conformation polymorphism
Noonan syndrome (MIM 163950), an autosomal dominant disorder with an estimated prevalence of 1/1000–2500 at birth, is characterised by short stature, facial anomalies, pterygium colli, and congenital heart disease.1,2 Although pulmonary valve stenosis with dysplastic leaflets, hypertrophic cardiomyopathy, and atrial septal defects (ASD) are the most common congenital heart defects in Noonan syndrome,3 a broad spectrum of cardiac phenotypes has been recognised.2–6 About half the affected individuals have PTPN11 gene mutations.7–9 This gene, which maps to chromosome 12q22-qter,10 encodes for the human SH2 domain containing protein tyrosine phosphatase (SHP2).11PTPN11 gene mutations have also been detected in multiple lentigines/LEOPARD syndrome (multiple lentigines, ECG conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth and sensorineural deafness; ML/LS, MIM 151100),12,13 in Noonan-like/multiple giant cell lesion syndrome (MIM 163955),8 in two families presumably affected by cardio-facio-cutaneous syndrome (CFCS, MIM 115150),14 but not in sporadic CFCS.15 The clinical and genetic heterogeneity of these disorders suggests a possible relation between different PTPN11 gene mutations and distinct clinical features. A genotype–phenotype correlation study in Noonan syndrome found an association between pulmonary stenosis and PTPN11 mutations.8 Our aim in this study was to screen a large cohort of patients with Noonan syndrome and ML/LS in order to expand the genotype–phenotype correlation analysis, with particular emphasis on cardiac diseases.
Key points
Noonan syndrome and multiple lentigines/LEOPARD syndrome (ML/LS) are associated with a broad spectrum of congenital heart defects in 50–80% of patients. Many patients with Noonan syndrome and most with ML/LS harbour mutations in the PTPN11 gene.
The occurrence of PTPN11 gene mutations was investigated in 71 patients with Noonan syndrome and 13 with ML/LS, including 73 with congenital heart defects. A genotype-phenotype correlation analysis was undertaken, with major emphasis on the occurrence of congenital heart defects.
Fourteen different PTPN11 mutations were detected in 23 patients with Noonan syndrome and 11 with ML/LS.
The distribution of congenital heart defects was markedly different between the two groups. Pulmonary valve stenosis, the most common congenital heart defect in Noonan syndrome, was related to an exon 8 mutation hot spot, while hypertrophic cardiomyopathy, predominant in patients with ML/LS, was associated with mutations in exon 7 and 12. Atrial septal defects were related to exon 3 mutations, while atrioventricular canal defects and mitral valve anomalies were found in association with different exon mutations.
Among extracardiac features, only short stature in Noonan syndrome showed a definite relation to PTPN11 gene mutations.
Eighty four white Italian patients were recruited. Informed consent and family history were obtained from all subjects and their parents. Patients were ascertained by clinical geneticists and paediatric cardiologists. Noonan syndrome was diagnosed on the basis of the cardinal features delineated by Allanson1 —in particular short stature, congenital heart defects, broad or webbed neck, chest deformity, developmental delay of variable degree, cryptorchidism, and characteristic facies. For diagnosis of ML/LS, the presence of lentiginosis and café au lait spots was required, in combination with at least three of the cardinal features outlined by Voron et al.16 Clinical assessment included family history, complete physical evaluation of dysmorphisms and malformations, anthropometric measurements, renal ultrasonography, and radiological studies. Standard karyotyping was normal in all patients.
Cardiac evaluation in all patients included preoperative chest x ray, ECG, and cross sectional and colour Doppler echocardiography. Pulmonary stenosis, pulmonary valve leaflet dysplasia, and hypertrophic cardiomyopathy were assessed using classical echocardiographic criteria.2 Cardiac catheterisation with angiocardiography was undertaken in 51 patients as an aid to preoperative assessment, to attempt pulmonary valve dilatation, or to demonstrate left ventricular shape. The cardiac diagnoses were confirmed during cardiac surgery in 32 subjects.
The patients' parents were examined for major or minor dysmorphisms and cardiac or extracardiac anomalies.
Noonan syndrome was diagnosed in 71 subjects, including one with pigmented villonodular arthrosynovitis, and ML/LS in 13. The study group included 44 females (52%) and 40 males (48%), ranging between 0.1 and 26 years (mean (SD), 8.4 (5.7) years). Seventy four patients were sporadic and 10 familial. One member from each family, presenting with the full blown phenotype, was included in the mutation screening and correlation analysis. Affected and unaffected parents and relatives were screened only after the identification of a PTPN11 gene mutation in the index case.
Mutation screening
PTPN11 gene coding regions and exon-intron boundaries, including about 50 base pairs (bp) upstream and downstream of the exons (GenBank Accession Number: NM_002834), were amplified by polymerase chain reaction (PCR) and analysed by single strand conformation polymorphism (SSCP; Genephor Unit; Amersham Pharmacia Biotech, Uppsala, Sweden). Anomalous fragments were sequenced by the Big Dye Terminator Abi Prism sequencing kit (Applied Biosystems, Foster City, California, USA), and run on an ABI PRISM 3100 genetic analyser automated sequencer (Applied Biosystems). Mutation hot spots were analysed by direct sequencing in patients with Noonan syndrome affected by pulmonary stenosis and in patients with ML/LS not associated with any anomalous mobility shifts on SSCP analysis of exon 8 and exons 7 and 12, respectively, before screening the rest of the gene.
Statistical analysis
All continuous variables were expressed as the mean (SD) for each measurement. Comparisons between patient groups were done using Fisher's exact test, with a significance threshold of p≤0.05.
PTPN11 mutation analysis
Fourteen different missense mutations, including four novel changes, were detected in 34 patients, including 29 sporadic and five unrelated familial cases (fig 1, table 1). None of these mutations was found in 200 control chromosomes or in unaffected parents (fig 2). In detail, 23 of 71 patients with Noonan syndrome had 12 different PTPN11 mutations, 10 of which were located in the N-SH2 and PTP domains. Codon 308 was a mutation hot spot, while two sporadic mutations were found in exons 1 and 14, at the NH2 and COOH termini, respectively (table 1). Two PTPN11 mutations were found in 11 of 13 ML/LS patients in exon 7 or 12. These mutations were not detected in any of the Noonan syndrome patients.
Genotype–phenotype correlation analysis
Twenty seven patients with congenital heart defects (27/73, 37%) had a PTPN11 mutation. The most common congenital heart defects in patients with mutations were pulmonary stenosis (52%) and hypertrophic cardiomyopathy (30%) (table 2). Partial atrioventricular canal defect (AVCD; 11%), ASD (11%), and mitral valve anomalies (MVA; 4%) were also found in association with PTPN11 mutations, while aortic coarctation, tetralogy of Fallot, and ventricular septal defect did not occur in patients with PTPN11 mutations (table 2). Both mutated and non-mutated patients presented a similar spectrum of congenital heart defects. With respect to all 27 patients with congenital heart defects and PTPN11 mutations, pulmonary stenosis showed a significant correlation with mutations in codon 308 (p=0.002), which was a mutation hot spot only in patients with Noonan syndrome. Conversely, hypertrophic cardiomyopathy was more strictly associated with mutations in exons 7 and 12 (p=0.01), a hot spot in ML/LS. The three patients with ASD had mutations in exon 3 (p=0.013) within the N-SH2 domain. Although not statistically significant (p=0.07), a positive trend was noted between mutations in the N-SH2 domain and congenital heart defects. In fact, congenital heart disease occurred in all patients with N-SH2 mutations (11/11), and in only 70% of those with PTP domain mutations (16/23) (table 1). No association was found between AVCD, MVA, and different domain mutations (table 1). Seven of 11 patients without congenital heart defects presented PTPN11 mutations, all within the PTP domain.
No significant difference was found in the prevalence of congenital heart defects between Noonan syndrome and ML/LS with PTPN11 mutations (87% (20/23) in Noonan syndrome; 64% (7/11) in ML/LS; p=0.1). Among the Noonan syndrome patients with mutations, pulmonary stenosis was the most common congenital heart defect (65%) and was associated with a codon 308 mutation hot spot (p=0.03), while hypertrophic cardiomyopathy was detected only in the 15% of the individuals with congenital heart defects. Two of three Noonan syndrome patients without congenital heart defects harboured exon 13 mutations. Among the ML/LS patients with mutations, the prevailing congenital heart defect was hypertrophic cardiomyopathy (71%), in association with mutation hot spots in exon 7 and 12, while pulmonary stenosis and AVCD occurred in single patients. Two of four ML/LS patients without structural congenital heart defects had atrioventricular conduction defects (fig 1, table 1).
Among the extracardiac features, only short stature in the Noonan syndrome patients was significantly related to PTPN11 mutations (p=0.04) (table 3). No mutation was found in the only patient with Noonan syndrome who had villonodular arthrosynovitis in the present study.
Family analysis
Screening of the PTPN11 gene in 10 familial cases showed mutations co-segregated with the disease in all affected family members in one ML/LS and four Noonan syndrome pedigrees. A concordant congenital heart defect (pulmonary stenosis) was found in a mother and her son with Noonan syndrome carrying the A923G mutation (fig 2, family C). Discordant phenotypes were observed in two Noonan syndrome families (fig 2, families A and B). In family A, the affected mother without congenital heart disease had transmitted the A923G mutation to her affected child with pulmonary stenosis (fig 2, family A). In family B, only one of five affected relatives—all with the A188G mutation—had congenital heart disease (pulmonary stenosis) (fig 2, family B). Two additional families had no congenital heart defects, including a Noonan syndrome father and son pair with the exon 13 G1508C mutation (fig 2, family D), and an ML/LS mother and her daughter pair with the exon 12 C1403T mutation (fig 2, family E).
PTPN11 mutations are associated with a broad spectrum of congenital heart defects, both in Noonan syndrome and in ML/LS. This is consistent with animal models, which have suggested a pathogenic role of the SHP2 protein in semilunar valve and myocardial development.17 In the present study we have investigated possible correlations between PTPN11 mutations and clinical features, in particular cardiac defects.
Pulmonary stenosis was the most common congenital heart defect in patients with Noonan syndrome and PTPN11 mutations. However, in contrast to a previous study,8 pulmonary stenosis had a similar frequency in patients with and without mutations. The association between pulmonary stenosis and codon 308 mutations could reflect the presence of a Noonan syndrome mutation hot spot in this position. However, previous genotype–phenotype correlation studies, which recognised the mutation hot spot, did not establish such a correlation. Interestingly, in this cohort of patients, pulmonary stenosis was the only congenital heart defect associated with mutations in codon 308. In patients with PTPN11 mutations, pulmonary stenosis showed a distinct valve leaflet dysplasia (table 2), in agreement with evidence in mice.17 On the other hand, non-syndromic pulmonary stenosis without leaflet dysplasia is not related to PTPN11 mutations,18 suggesting that a different genetic background causes distinct pulmonary stenosis subtypes.19
PTPN11 mutations occurred in eight of 12 patients with hypertrophic cardiomyopathy, without any obvious difference between individuals with and without mutations. The hypertrophic cardiomyopathy rate among ML/LS patients with mutations was higher than previously recognised16 and was clearly related to exon 7 and 12 mutations in the group of patients with mutations as a whole. Interestingly, all ML/LS individuals with hypertrophic cardiomyopathy who have been screened so far harboured a PTPN11 mutation.12,13 Hence, PTPN11 mutations are a major cause of hypertrophic cardiomyopathy in paediatric patients, mainly in the setting of ML/LS. However, the histological features of syndromic and non-syndromic hypertrophic cardiomyopathy are similar,20 and therefore PTPN11 could also be a candidate gene for isolated hypertrophic cardiomyopathy.
ASDs often occur in association with different malformation syndromes.21 Although our cohort of patients with Noonan syndrome and ASD was small, this defect was noticeably correlated with exon 3 mutations.
PTPN11 mutations were associated with partial AVCD in three patients, suggesting that mutations of this gene are responsible of a specific type of syndromic AVCD, similarly to chromosomal aneuploidies (that is, Down's syndrome and deletion 8p syndrome)22,23 and other gene mutations (EVC gene in Ellis-van Creveld syndrome, DHCR7 in Smith-Lemli-Opitz syndrome, MKS gene in McKusick-Kaufman syndrome, and ZIC3 gene in X linked heterotaxia).24–27 As with ASD, MVA was also associated with an exon 3 mutation. It has been suggested that MVA in Noonan syndrome may be secondary to cardiac jelly and extracellular matrix defects, which are also likely to account for AVCD.3–5,28–30 Hence, myocardial and atrioventricular valve involvement suggests a role for the PTPN11 gene in left ventricular differentiation and mesenchyme development of the atrioventricular cushion.
None of patients harbouring PTPN11 gene mutations had coarctation of the aorta or other common congenital heart defects such as Fallot's tetralogy or ventricular septal defects. Two ML/LS patients with PTPN11 mutations had conduction defects, which have also been detected in PTPN11 animal models.17 Even if the figure of 87% congenital heart defects in our present series was biased by cardiological recruitment criteria, only 37% of them had PTPN11 mutations. Other gene mutations could account for the heterogeneous cardiac phenotype in Noonan syndrome and ML/LS. Our study has shown that N-SH2 domain mutations are strictly associated with congenital heart defects, although in two Noonan syndrome families not all the affected family members had congenital heart disease. Intrafamilial variability of the cardiac phenotype related to the A188G and A922G mutations points to a reduced penetrance, with a likely regulatory effect of other unknown genes and environmental agents.
The overall PTPN11 mutation detection rate was 40% (39% in sporadic and 50% in familial cases). This figure, which is reduced to 33% if only patients with Noonan syndrome are considered, is slightly lower than previously reported (45%).8 This difference could be explained by assuming that both deletions and missense mutations could have been overlooked by SSCP screening. However, Musante et al have also reported a superimposable rate of mutation in a wide cohort of patients with Noonan syndrome screened by DHPLC analysis.9 On the other hand, 85% of ML/LS patients had PTPN11 gene mutations, with two specific hot spots in the PTP domain. Thus PTPN11 can be considered the major gene of ML/LS.12,13 As previously reported,12 the differential diagnosis between these two syndromes may sometimes be difficult on clinical grounds alone, as specific ML/LS features can appear over the years in subjects diagnosed as having Noonan syndrome. In this respect, it would be of interest to follow up the Noonan patient reported by Tartaglia et al,8 who carried the A836G mutation that was found only in ML/LS individuals in the present and previous cohorts of patients.12,13
In contrast to other reports,8,9 we also found that short stature in Noonan syndrome was significantly associated with PTPN11 mutations, supporting a role of SHP2 in linear growth, as shown by studies in murine models.31
Pulmonary stenosis and hypertrophic cardiomyopathy are the prevailing congenital heart defects in Noonan syndrome and ML/LS associated with PTPN11 mutations. Different heart defects show correlations with the location of mutations within the PTPN11 gene, with statistically significant associations for pulmonary stenosis, hypertrophic cardiomyopathy, and ASD, which appear to cluster to distinct gene domains.
This study was supported in part by grants from the Italian Ministry of Health (RC 2002) and from the Italian Ministry of Instruction, University and Research (40% grant to BD). We thank Tania Dottorini and Giorgia Esposito for assistance.


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Many times a user came across a situation when he or she accidentally deleted an important file. In such a situation there is no need to panic as there are many ways to get back your lost data. Today I am going to describe the various ways to recover deleted files from Windows 10 OS easily.
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subset: commoncrawl


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Off-trail trekking home | Pack Food | Alaska Treks | Trekking Gear
6/21/04 - day 13
There's something very homey and comforting about these clothes I only wear away from home. The feeling grows on me with all my gear and its associated daily rituals. The dry bag into which I stuff the sleeping bag, a pair of socks, and the extra camera batteries; the food going into the Ursacks and the dry bags, and into the perfect spot in the hatch; the stove and the fuel and the carefully folded map in my deck bag. I feel it with everything, but most strongly with my clothes. My fleece suit and rain gear may stink of 13 unwashed days in the wilderness, but so do I. And they are my home here, where my location is continually changing.
And camping locations have gotten difficult of late. Rudyerd Bay is a long, beautiful and scenic cliff-lined fjord, which happens to be home to a sizeable bear population. And bears don't like cliffs. They can climb reasonably well, and can swim back and forth across the channel, but they don't live on cliffs. Unfortunately, kayakers don't like cliffs either.
Today we had planned to camp at the northern tip of Rudyerd Bay, where the map showed a flatter and shallower area near the river mouth. It seemed the most likely spot to have a campable beach. The tip of the bay was a lovely spot in the evening sun, with snowy peaks surrounding it, huge cliffs, waterfalls, a snowbridge, a yacht in the middle of the bay, and a bear swimming across a channel on the river flats.
And there lay our problem. Needless to say, after last night we were a bit spooked about camping with bears. I woke up to the memory of the crashing, the sight of my bear-shifted kayak, and a slight lingering whiff of bear that was quite possibly imaginary. We didn't want a repeat of last night's visitation.
For all my bear-country camping, that was the first time I've been visited at night, and I don't intend to make a habit of it. But we hopped out of the boats at the edge of the river flats, and hopefully poked around. We found a well-used bear trail all along the beach, piles of bear scat, and a flattened down spot that looked suspiciously like a bear bed. There lay our problem, indeed.
Of course we didn't camp there. We got back in and paddled the way we came, envious of the yacht-goers for their ability too camp in the middle of the bay. We were thankful for the summer solstice and the many hours of light remaining. At the next beach, it was the same story. The river was smaller, but the trails were beaten all along the beach, complete with bear scat, a flattened resting spot, and huge bear footprints in a muddy hole. The bears are funneled here. Everywhere they can go, they do go. My hiking instincts told me not to camp there, stupid. The rest of me wondered what normal boat campers in Rudyerd Bay must do? Live with nighttime bear visitations? But Niki wasn't comfortable their either.
We seriously considered paddling 8 miles back to a floating deck we'd seen earlier in the day and camping there. But just across the bay from our second bear beach we found a bit of beach on a point. There are rocks to either side, a steep cliffy band of alder above us, and jumping fish below. I don't think a bear would have much reason to come here, though I still harbor vague suspicions about some of the flattened grass on our knob. Hopefully we're right.
Rudyerd Bay is purportedly the most popular place in Misty Fjords. What that seems to mean is that on a sunny morning, the place is just a giant glorified runway. Float planes take off, float planes land, float planes zoom about overhead. We couldn't keep track of them all, but between 11:30 and 12:30 I counted 12 separate float planes leaving the bay. And then they were gone. We saw them as we set off at about 9 this morning, but by lunch time they had all cleared away.
There is also boat traffic here. We saw one giant tourist boat zoom past us on its way into and out of the bay. There was a boat in our cove last night, and a different one at the tip of Rudyerd tonight. What we have not seen is a single other crazy soul in a kayak. But I know that people come. The animals here seem more used to humans. Seals stayed on their rocks as we passed, a muskrat scrambled along the bank next to us, peering at me inquisitively and letting me keep taking his picture, and the bear at last night's campsite didn't seem at all inclined to run away when we yelled at it.
Today is summer solstice and my first wedding anniversary. Hig is not here, but I ate a Snickers bar in his honor, and am surely having good adventures for him as well.
6/22/04 - day 14
We were right or we were lucky. No bears visited last night, and we had only the sounds of seals to sleep to. And we had planes to wake up to. I heard the first one as I was struggling out of sleep at 7:30, and they were zooming about all morning. I got to the point where I'd glance up at birds out of the corner of my eye and half expect them to be float planes too.
As the heat continues, the haze settles more and more thickly on the land, until even a slope a mile or two away is blue with distance. Industrial pollution seems unlikely in this air, and I wonder if the haze is all from the evaporating ocean? Or maybe some distant fire, blown here and settled in our still air.
The ocean returned today. It had been glassy calm for days, like an overly large pond. When we crossed the channel two days ago the wakes of our kayaks were the largest waves on the sea. Even in Rudyerd Bay we had a little wind today. There was a small chop in the middle of the bay, waves to rock the boats and slap them into the rocks as they sat on the beach, and some wind to fight with our paddles. But when we rounded Point Louise into Behm Canal proper, there we had ocean.
It started with a headwind, gusting and railing at us, and making every push of the paddle (even a feathered paddle) an all out effort. We were only inching along, and quickly abandoned our plans o visit New Eddystone Rock in the middle of the channel.
Just then, as we were struggling and concentrating to make any headway at all, we ran into the first people we've talked to since the kayaker at Blind Pass on our fourth day out. Four kayak rangers were headed the opposite direction, being pushed by the wind up the coast. One was quite friendly, and we chatted with him a few minutes as he hung back and we tried not to be swept too far the wrong direction. I wish we'd had longer. But we did pick up one interesting piece of information, which is that Sunday, the day we hiked to Manzanita Lake, was the hottest day ever on record in Ketchikan. 88 degrees. I feel justified for feeling baked. We have certainly come for an unusual spell of weather.
After we left the rangers the wind slacked off a bit but the waves grew larger. They came up the channel and bounced off the rock wall of the shore, and they came at us from every direction at once. The tallest were maybe four feet high. They slapped under the boats and splashed on top of them, and rolled under us in swells, moving the boat up, down and sideways in the helter skelter mess of waves. It was fun, and much preferable to the slog against the wind. Each time I take the kayak into choppier seas I am amazed at its natural stability. It seems that all it wants to do is to sit happily upright in the water, and it asks of me only to avoid doing anything stupid.
6/23/04 - day 15
As a kayaker, perhaps it would be best to wake up early. When we woke up the channel was glassy cam, the sky was a clear pale blue, and all the hills and islands were cloaked in a thick blue haze. The haze is growing with each day of sun, but the heat has thankfully lessened.
We paddled out to New Eddystone Rock, and odd-looking volcanic protuberance in the center of the channel. The seaplanes zoomed by on their way to Rudyerd Bay, and large cruise boats of tourists speed through the channel. New Eddystone Rock had a sizeable beach, where we were surprised to see and a small group of kayakers on the beach, which we were even more surprised to see. As we paddled around the rock, one of them came down to give us a survey. They were more rangers, doing surveys of intrusion and traffic in the area, and waylaying passing kayakers.
Most of the traffic they're watching is seaplanes and boats of course, particularly since 7 of the 9 kayakers I've seen on this trip are working for the forest service. But they did catch us, and they also caught the Asian kayaker, who we saw once again this morning. Apparently he's on a 6-month trip. That seem s a long way to go alone.
We left the rangers and crossed back to the shore. The dead calm turned into a pleasant breeze. The day grew hotter. We passed a forest service cabin. We stopped for lunch. And then the wind came.
It came up suddenly, rushing northward through our pass, rippling he water into small choppy waves. We could still move forward. But it was a slog. Each stroke fought the wind more than it pushed the water, and the boats inched slowly along the shore. Gusts blew through even more strongly, roughening the surface of the little waves and wrenching the paddle blades backwards. We kept paddling. Around a point. Across a little channel. Pushing. Around another little point...
And then we gave it up. With so much time, why paddle in the worst of the day? We parked in the lee of a little peninsula, hoping the wind would die down in the early evening. It hasn't. So now we hope for a morning calm and plan to sleep and rise early. Such a plan is always more easily made at 5PM than executed at 5AM, but we will try. The wind will either die down or it won't. Either way we'll be moving, but I'm hoping for the faster alternative.
Off-trail trekking home | Alaska Treks | Pack Food | Trekking Gear
Contact me with comments or questions at mckittre at yahoo.com
Last modified: 10/20/2004


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In the new and revised edition of Retire Secure!, James Lange supplements his tried and true tax saving strategies for getting the most out of your IRA and retirement plans with updated information and his latest recommendations for the new Roth vehicles. Always a strong proponent of contributing as much as you can to all the tax-deferred retirement plans available to you, Jim makes a convincing case for adding a slight modification to his pay taxes later adage—pay taxes later, except for the Roth.
On the accumulation side of the equation, when individuals are working to save money for retirement, he delves into great detail on the differences between traditional 401(k)s and 403(b)s and Roth 401(k)s and 403(b)s. When it comes time to tap into your retirement savings, Jim revisits determining the appropriate spending order for the different classes of retirement assets, IRS minimum distribution rules, and annuities—all with updated information. But he has also written a whole new chapter on Roth IRA conversions. A significant portion of the new chapter is a discussion of the opportunity in the year 2010 for higher income taxpayers to move into the Roth environment.
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Comment for a chance to win a copy of Protecting Amy, SEAL Undercover or Desperate Deception
SEALs use handguns such as the 9mm SIG Sauer P226 and the MK23 MOD 0 45-caliber offensive handgun with a suppressor and laser-aiming module.
They use rifles such as the carbine automatic M4A1 5.56 mm and the AK-47. They also use shotguns, machine guns (MK43 and M2HB), and the HK MP5 9mm submachine gun series, among others. Add to that list sniper rifles such as the M88 .50 PIP and the M-14 sniper rifle, along with grenade launchers, mortars and AT4 anti-tank rockets, and SEALs can choose a weapon to fit the specific task at hand.
Each vehicle that Navy SEALs use to transport teams and units to their destination has a specific benefit and utility.
One type of vehicle is the SEAL Delivery Vehicle. These are vehicles that operate below the surface of the water to deliver Navy SEALs and their equipment to their mission area. The crew uses underwater breathing apparatus for life support while navigating the submerged SDV to the destination. Remaining completely submerged the entire time, some models of SDVs can deliver several SEALs with their gear to their mission area, remain in the area while they complete the mission, and then return them to their ship.
There are several primary surface watercraft. They include the CRRC, the SOC-R, the 11-meter RHIB, and the MK V.
The MK V Special Operations Craft (SOC) is the most versatile, high-performance combatant craft in the Naval Special Warfare inventory. It is used primarily in medium-range ocean transport of SEAL combat swimmers in environments where the threat is low-to-medium. It is also used for some coastal patrol and maritime interdiction operations, such as destroying an enemy supply line. The MK V can operate from shore facilities or from specially equipped ships.
The NSW Rigid-hull Inflatable Boat (RHIB) is an 11-meter, high-speed, high-buoyancy, extreme-weather craft used for moving SEAL tactical elements to and from the ship and beaches. It is large enough to transport an entire SEAL squad.
The Special Operations Craft-Riverine (SOC-R) is Naval Special Warfare's newest surface craft. It is used in river environments and has a top speed of 42 knots. It holds up to 20,500 lbs (9,300 kg) of personnel and cargo and is well-suited to inland waterways. The SOC-R can be transported by U.S. Air Force cargo aircraft and by helicopter.
The Combat Rubber Raiding Craft (CRRC) is a 15-foot, heavily reinforced, inflatable rubber boat that is useful on many missions. This is the one trainees are carrying overhead during BUD/S training (it's often called a Zodiac — Zodiac manufactures the CRRC). In deployment, it is used for over-the-horizon transportation and dropping and retrieving lightly armed SEALS on beaches and in rivers.
This boat is easy for the SEALS to move around and can even be launched from the air as a rubber duck, which is a CRRC bound on top of a wooden platform with a parachute attached.
Come back tomorrow for the nest installment


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8503 Greenbelt Rd, Suite T4
Greenbelt, MD 20770
Would you like your smile to be a bit brighter than it is right now? We can make it happen at Zebrowski Dental Care, with professional tooth whitening for brighter natural looking teeth. Dr. Robert Zebrowski's Greenbelt, MD area office can effectively lighten your stained or discolored tooth enamel. Whiter teeth not only look great, they improve your self-confidence.
If you're looking for dentures that look great and last, look no further than Zebrowski Dental Care located in the Greenbelt, MD area. Robert Zebrowski, D.D.S. will assess your needs and fit you with durable, comfortable, natural-looking dentures - at a price you can afford.
Greenbelt area restorative dentistry at Zebrowski Dental Care can produce natural-looking results. If you have a damaged or missing tooth, we can help.
Our highly skilled team will assess your need for a crown, bridge, implant or other procedure to restore or improve your smile. Our goal is to provide quality dental care for your life-long oral health.
If you're interested in natural-looking bridges and dentures, look no further than Robert Zebrowski, D.D.S. who practices in the Greenbelt, Maryland area. Using modern materials and techniques, Dr. Zebrowski can achieve the natural look you seek. You will be very pleased with the comfortable, long-lasting results.
Dr. Robert Zebrowski has a gentle touch and provides comfortable cleaning for a whiter smile. Offering cosmetic dentistry in the Greenbelt, Maryland area, Dr. Zebrowski assures you that a bright, healthy smile is the result of regular, preventative, professional dental cleanings.
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Horizon Dental Care
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7905 Malcolm Rd # 300
Clinton, MD, 20735-1708
People of a certain age sometimes find themselves in need of dental care involving dental crowns instead of a filling, or dental bridges to replace missing teeth. Understandably, in light of the present economy, many patients think first of the expense. But the fact remains that postponed care costs more in the long run, both financially and physically.
In the case of broken teeth, extensive decay or an old filling, a crown is intended to hold the remaining tooth structure together. After a root canal, enamel becomes especially brittle - another candidate for a crown.
A badly damaged tooth, left untreated, causes changes in the mouth that disrupt how the teeth work, chewing patterns, and jaw function. Normal eating habits may be inhibited. Tenderness forces the bite away from one side of the mouth and exerts undue pressure elsewhere. Why not just extract this troublesome tooth?
A missing tooth eventually spells oral disaster, meaning permanent changes to your bite. Because the mouth is dynamic, teeth on either side of an empty space will shift. The teeth next to them move, too. With all this movement, periodontal disease could invade soft tissues. Jaw misalignment, and the pain that goes with it, is likely. So tooth restoration to bolster neighboring teeth and keep the "architecture" of the mouth in good shape is the best course of treatment.
After fillings, crown and bridge work is our first line of defense against oral deterioration. This kind of dentistry brings a lot of satisfaction to both patient and dentist. A transformation happens. With the mouth functioning again, people feel better about themselves.
So call your cosmetic dentist today to find out how you can restore your mouth to total dental health. You'll look and feel better.
Choice is a wonderful thing. It can mean the opportunity to look a dozen years younger than your actual age. Which, in this youth-obsessed culture, gives you extra advantages, whether you're thirty-something or a grandparent.
These choices include your teeth. Not just movie stars, but adults in all walks of life, are opting for cosmetic dental care that restore youthful vitality to their skin and faces. You might be surprised by the role fresh "young" teeth play in creating that overall first impression.
Your cosmetic dentist can bring you up to date on the incredible and youth-restoring dental options, like dental crowns and veneers, that are available to you. Options available at a fraction of the cost of risky and invasive surgery such as, say, a face-lift.
Whichever restorative dentistry procedure you agree to, or decline, is your personal choice. For example, suppose you're missing teeth. Maybe the gap doesn't show, and you've lived with it for awhile. Replacement with dental crowns or dental bridges might be recommended. The consequences of living with missing teeth are important, but the choice to replace that missing tooth and get one step closer to a beautiful smile is yours.
Just the same, it's your mouth and your decision. Whenever you have questions about your care, ask your local dentist and together you can do what's right for you.


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I am particularly fascinated by how the properties of host pollen affect bees. I discuss this topic a bit in my paper "Convergent evolution of pollen transport mode in two distantly related bee genera (Hymenoptera: Andrenidae and Melittidae)." In that paper, I suggest that the properties of pollen could influence how it is carried. In particular, it seems that very sticky pollen types are often carried in a dry state, even in bee groups where most species moisten the pollen in order to carry it.
The plant family Onagraceae is particularly well-known for having sticky pollen. It has been well-documented that Onagraceae pollen has "viscin threads" which make the pollen sticky and difficult to handle (Linsley and MacSwain 1958, Roberts and Vallespir 1978, Hesse 1981). In fact, many Onagraceae-specialist bees have evolved specialized pollen-transporting hairs in order to effectively manipulate the pollen (Linsley 1958, Thorp 1979).
However, it's hard to get a sense of what exactly is meant by "viscin threads," especially since if you look up "viscin" in the dictionary, it refers to the mucous-like substance in Mistletoe fruits.
I believe the term "cobwebby" is the most accurate synonym for "viscin threads." I feel like it captures the sticky, but not too sticky, nature of the threads. In my experience, these viscin threads adhere in a very similar manner to cobwebs, since their adherence feels more like it is due to static cling of the filamentous threads rather than to any inherent stickiness in the threads themselves.
One last thing I want to mention about Onagraceae pollen is that I commonly see two distinct size-classes in the pollen, big grains and small grains. I have never seen this mentioned before in the literature and I don't know why this happens, but it seems to be fairly consistent in different individual plants and even different species. I had noticed different-sized Onagraceae pollen in the scopa of bees previously, and had initially chalked it up to them visiting multiple species of Onagraceae. However, now it's not clear whether that is the case.
Hesse M (1981) Pollenkitt and viscin threads: their role in cementing pollen grains. Grana 20: 37–41.
Linsley E (1958) The ecology of solitary bees. Hilgardia 27: 543–585.
Linsley EG, MacSwain JW (1958) The significance of floral constancy among bees of the genus Diadasia (Hymenoptera, Anthophoridae). Evolution 12: 219–223.
Roberts RB, Vallespir SR (1978) Specialization of hairs bearing pollen and oil on the legs of bees (Apoidea: Hymenoptera). Annals of the Entomological Society of America 71: 619–627.
Thorp RW (1979) Structural, behavioral, and physiological adaptations of bees (Apoidea) for collecting pollen. Annals of the Missouri Botanical Garden 66: 788–812.
Michelle Boone
9/28/2018 06:12:19 pm
You are quite the accomplished scientist! Thank you so much for sharing your NSF fellowship application!
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Art Books
Nights on Prose Mountain
A new collection that captures the enigmatic prose of poet and interdisciplinary figure bpNichol
Nights on Prose Mountain
(Coach House Books, 2018)
Canadian literary figure bpNichol (1944–1988) is known for his experimental writings: concrete poetry, typewriter and computer experiments, and sound poetry. He's included in numerous anthologies covering this type of work from the 1960s–80s, often cited as a seminal figure. His long poems with intensely personal subject matter, and his visual-verbal approach, evoke his contemporary Joe Brainard. Nichol's tragically short life and immense output of printed materials also recalls the mysterious Ray Johnson—who, like Nichol, inspired a film about his life and work. Last year, Coach House Books, where Nichol was an editor, published a collection of his fiction. As a collected book of writings, Nights on Prose Mountain (2018) is not an easy read. 320 pages that are a mix of dense paragraphs without traditional line spacing and sparse pages with just a word or letter, his "fiction" is not linear storytelling. After trying (and failing) to read the book from front to back, I embraced what caught my eye. Flipping through the pages, drawn to certain spacing or images. For example, "Two Novels" (1971) is illustrated throughout with hand-drawn pictures, while in many other stories the text presents itself visually, a central principle of concrete poetry that remains in his fiction.
For a literary figure whose output was so varied—during his lifetime Nichol wrote poetry and scripts for kids' television shows, and was a member of a performance group, among other activities—this collection poses questions about genre and form. What distinguishes fiction from poetry and what is the value in a segregated collection as such? In his afterward (which I skimmed first to aid in my navigation of the text), editor and poet Derek Beaulieu notes that Nichol was interested in "'borderblur,' the exploration of the textual possibilities between genre." He explored "how hand-drawn letters, visuals, comic strips, and other forms of storytelling could challenge his writing process and the limits of genre." With this in mind, the collection appears not like a traditional collected stories, but rather a book grouped thematically by time and subject matter more so than genre or form. Beaulieu explains that much of Nichol's fiction was written while we was working as a therapist, "The pages of Nights on Prose Mountain are populated with Oedipal nightmares, violent sexual and emotional tension and abuse, relationships in crisis, menages a trois, murder—much of which is described in a way that may be shocking to a twenty-first-century readership. This is the stuff of crisis."
"Extreme Positions" (190–272), subtitled a "murmur mystery," drew my attention for its unique layout. It includes sparse pages with the lone letter "s" and others filled completely with the repeated letter, creating a visual sea of curves. The story sketches out a setting in nature, "moon / owl / tree" and the body's relation to it, "wave / hand / wave/ boat". Is this the wave of a hand or the ocean against a boat? These fragments become motifs throughout the six chapter story in which something tragic repeatedly occurs: "crying / laughs" precedes the disturbing:
will SHOUT
didn't SHOUT
should SHOUT
can't SHOUT
Beaulieu quotes some of Nichol's explanation of this story, "This guy has two wives and he murders both of them. It's quite linear." While I am not sure I would qualify these bursts of sentiment as linear storytelling, the trauma and violence certainly comes through, heightened by the slow progress and Nichol's choice to draw out the action, to the level of breaking down individual words like, "vio / lent / let". This story also includes, as Beaulieu points out, the smaller poem: "a / lake / a / lane / a / line / a / lone" which appears as an illustration on the cover of this book and is one of Nichol's most famous poems. His dismantling of language forces the reader to experience each piece of the word, showing how language itself can be forceful and violent.
His writing plays with repetition, sound, and layout, often requiring the words to be both seen on the page but also read aloud to fully grasp the meaning that comes from the subtle wordplay. The titular story, which includes various repeated phrases recalling the modernist styling of Gertrude Stein, reads like an ode or obituary to poetry, "NOW THIS IS THE DEATH OF POETRY." It also demonstrates Nichol's awareness not just of words on the page, but sound as well. In an early paragraph he writes, "Insect. Incest. C'est in. Infant. In font." The linguistic play here requires the knowledge of French pronunciation to read the rhyming phrases, and a little wordplay on the French word for child (enfant) that reads similarly to the English word infant. The words on the page require a performance of sound, reading them aloud or saying them to oneself.
Some even go farther, instructing readers to perform an action as part of the reading, as with "Craft Dinner" (1978), which includes a few chapters with instructions like "Cautious Diary" that begins with the note, "cut two holes for eyes in a brown paper bag & place it over your head now read the following piece" and "Lipstick on my Watchband" that opens with the instruction, "lounge in the doorway of a crowded room humming & read this to yourself". These instructional works seem tied so much to performance art of the 70s and 80s, and even later works by artists like Adrian Piper, particularly her 2012 work The Humming Room, which required visitors to hum while passing through a space.
The performative aspect of the work also extends to presentation on the page—it creates a visual, verbal, and auditory experience unique to each story. How then, do we collect it into a single bound book? "The editorial and design changes necessitated in the creation of this collection present these texts in a way that suggest but don't precisely echo the original editions," Beaulieu writes. With it, he calls for readers to "seek out the original editions" in order to fully grasp Nichol's "sensory new fiction." Luckily for readers of the collected issue, Nichol has an extensive archive online with fully digitized materials of his chapbooks, comics, and other visually stimulating works. This collection adds to this archive through thoughtful reinterpretation of form—in many ways it is a new performance of Nichol's original sound, language, and visual play.


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Reggie Ragland entered the Buffalo Bills' preseason opener against the Minnesota Vikings with something to prove.
The linebacker, who was selected by the team in the second round of the 2016 NFL Draft, had struggled in camp in the days leading up to the game. Once believed to be in contention for the Bills' starting middle linebacker job, Ragland practiced exclusively with the second-team in camp before being demoted to the third-team in last Tuesday's practice.
An offer for Bills fans
Ragland was undoubtedly eager to show Buffalo's front office what he is capable of on Thursday night, as his job potentially depended on it.
Did Ragland have a stellar outing against the Vikings? He wasn't stellar, but he also wasn't bad.
Ragland finished the game with six combined tackles, leading the team in that statistic. He also recorded one tackle for loss, an impressive play in which he burst past Minnesota's offensive line to take their running back down in the backfield.
However, Ragland's game wasn't without its flaws. It took the former Alabama linebacker some time to get his feet back under him, and there were even some plays in which he stumbled when trying to adjust.
Perhaps surprisingly, Ragland didn't see any time with the second-team defense on Thursday night. The first time he took the field was with the third defensive unit, perhaps suggesting that he will still be with the third-team when practices once again commence.
However, when talking to the media after Thursday night's game, Ragland said that his demotion to the third-team is not "a setback," as he's still playing football.
"It's never a setback," Ragland said. "I'm out there playing. Still getting reps, still getting better. I mean it's been a year since I got done playing but I got to do whatever the coaches need me to do. For me, I got to keep getting better and I think about that."
Ragland, of course, is coming off of an ACL injury, an ailment that prevented him from playing a single down in his rookie season.
While Ragland is likely no-longer in contention to win a starting job in the team's linebacking corps, he could still fight his way up the depth chart. He's an extremely talented player who is adjusting to a new system after tearing an ACL – a situation that most players would struggle in.
Ragland needed a decent outing against the Vikings to silence critics. A decent outing is exactly what Ragland delivered, and he can perhaps use this performance as the foundation for his comeback.


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Wear your love of a certain Japanese scent on your sleeve.
Beautiful series of artistic wristwatches is also part of celebration of the Studio Ghibli classic.
New product comes with special features to recreate the friendly lamp character from the hit anime film.
Adulting just got a lot more fun with this stylish accessory.
Laputa: Castle in the Sky timepiece will be available worldwide in very limited numbers.
Out of all the motifs to come out in this collab, there was one which completely blindsided us.
A new collaboration appears, and we want to catch 'em all.
Six different limited-edition models could be yours for just 51,700 yen (US$488.37) each!
What's the time, you ask? Time for destruction.
Aside from the attractive design, we love the fact that the face of the watch features none other than … "No Face"!
Fans of Kiki's Delivery Service will also want to check these out.
Our roundup of the country's craziest April Fool's Day products and services we actually wish were real.
The Japanese watchmaker's dazzling new timepiece has an incredible price to match.
Because what better way to showcase an eye for precision than to build a miniature obstacle course for marbles?
There's no denying that Pokémon and the series' adorable Pikachu are loved around the world. The international franchise has been around long enough that there are now several generations of former kids who grew up infatuated with the fantastic monsters but who may feel they can no longer openly show their affection for Pokémon, on account of supposedly being all "grown up".
Well, you may be a grown-up in age, but if you still have a tiny bit of that Pokémon Master left in you, you might be delighted by the newest collaborative item being offered by fashion and culture brand BEAMS and the Pokémon Company. Check out these Pokémon×BEAMS watches that combine fashionable design and accurate time-keeping with your love of the Pokémon world!


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Sometimes heroes fall.
Colonel Michael Cedars is a decorated war hero returning home from Afghanistan. Wounded, unsure if he'll walk again, he's not sure how he fits in civilian life, and he definitely questions if he wants to remain married to the feisty redhead, Hope Shane.
Hope's never been one to play it safe. She met the Colonel while working as a war correspondent, fell in love with the man in uniform, watched him get blown up, and isn't willing to give up on him now.
Back in Denver, Colorado, she's working as an investigative reporter who becomes entangled in a human trafficking story. As the danger of her story intensifies, Hope and Michael are tested more than they ever imagined. Will Michael be able to see beyond what he's lost to embrace what remains? Is he still the man she married or has he become a liability that could get her killed? Is he still the hero she claims him to be? Will her reckless pursuit of justice endanger the life they've pieced together?
Review Time:
Amber Lea Easton is a multi-published cross genre author of romantic suspense, action adventure, mystery thrillers and new adult (coming in summer 2013). Her current releases cross all boundaries and appeal to a wide audience. If you love a clever plot, action that will leave you breathless, riveting characters and sexy love scenes, her books will appeal to you. "Smart is sexy," Easton says, which is why she focuses on smart heroines who always have a lot to lose yet find the courage to face their fears to overcome adversity. She's an avid reader of all genres or "whatever turns her on in the moment".


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Article Title
Indigenous Geographies: Research as Reconciliation
Employing a reflexive and co-constructed narrative analysis, this article explores our experiences as a non-Indigenous doctoral student and a First Nations research assistant working together within the context of a community-based participatory Indigenous geography research project. Our findings revealed that within the research process there were experiences of conflict, and opportunities to reflect upon our identity and create meaningful relationships. While these experiences contributed to an improved research process, at a broader level, we suggest that they also represented our personal stories of reconciliation. In this article, we share these stories, specifically as they relate to reconciliatory processes of re-education and cultural regeneration. We conclude by proposing several policy recommendations to support research as a pathway to reconciliation in Canada.
We wish to acknowledge Dr. Chantelle Richmond's Early Researcher Award from the Ontario Ministry of Research and Innovation, and Canadian Institutes of Health Research New Investigator Award.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Recommended Citation
Smithers Graeme, C.
Mandawe, E.
Indigenous Geographies: Research as Reconciliation. The International Indigenous Policy Journal, 8(2)
. Retrieved from: https://ir.lib.uwo.ca/iipj/vol8/iss2/2
DOI: 10.18584/iipj.2017.8.2.2


text: 2012 will likely go down as the year when LTE became a standard smartphone feature rather than a luxury. Strategy Analytics has put out new research this week showing that the fourth quarter of 2012 "witnessed phenomenal +1100% annual growth for LTE handset volumes, led by Apple (AAPL) and Samsung (005930) in developed markets." 2012 was certainly a banner year for LTE in the United States after Sprint (S) finally got around to launching its own LTE services and both Verizon (VZ) and AT&T (T) continued expanding their LTE networks to cover the majority of major markets throughout the country. With much of the U.S. now covered, carriers' next big milestone will be deploying Voice over LTE (VoLTE) services that will let users make calls over LTE and thus potentially end the need for separate voice and data plans.


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Loose Incense Bowl with Handle Pomegranate
Free Shipping on All EU Orders €85+
IN STOCK - Ready For Shipping
With their striking combination of shapes and colors, these Loose Incense Bowls with Handle will be a welcome addition to your cleansing or meditation rituals. Add a touch of sand, a charcoal disk, and your favorite loose incense to create a welcoming and cleansing space anywhere in your home. With the added handle, cleansing your home while moving form room to room has never been easier!
Comes in 10 stunning colors!
Size & Fit
10 cm x 8 cm x 5 cm
Material & Care


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Program Type:Arts & Music, Enrichment, Environment & Sustainability, Library & Community, STEAM & Maker
Age Group:Children (Grades K-6) , All Ages
Program Description
It's a Seeds and Reads takeover! This year Sonoma County Library's Take & Make kits will focus on the environment and sustainability. The mission of the library's Seeds and Reads program is to explore nature and better the environment through science, books, art, play, and community engagement. We hope you join us as we explore different topics about our Sonoma County ecosystems.
Check out the instructional video featuring children's librarian Jen Ryder! https://youtu.be/WYuak5_qd2M
Available at all 14 library branch locations!
Take the fun home and make a new craft with one of SCL's Take & Make Kits! Kits are available on a first come, first served basis. While supplies last. Limit one per patron.
For ages 5 & up w/ adult supervision.
Kits limited availability
Kits are available on a first come, first served basis. While supplies last. Limit one per patron.


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Flag of England
First international: Scotland 0-0 England (1872)
Biggest win: Ireland 0-13 England (1882)
Biggest loss: Hungary 7-1 England (1954)
Most capped: Peter Shilton (125 caps)
Top scorer: Bobby Charlton (49 goals)
Star player: Wayne Rooney (Manchester United FC)
This is my favourite English shirt. It is different to have a shirt that isn't red or blue for England. I orginally ordered a Soccer Aid Rest of the World shirt but when it arrived from JJB it was just a plain Umbro shirt. I emailed them and they say it should take 1 day to get a reply but 5 days later I now get a reply saying they will refund me for the shirt. Unknown to them I had already gone into the shop and got a refund and bought this shirt with the refunded money. So now they have given me two refunds which basically means I got this shirt for free. Now to wear this when Carroll heads in the winner to gift England the European trophy.


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We each have a natural set point, a place we feel most comfortable.
We might be seers who can imagine, out of whole cloth, a future.
We might be doers who need to be neck-deep in the work to come to conclusions that mean anything to us.
We might be analyzers who see the whole field of play and can visualize which pieces need to be moved in what ways to tilt the field.
We might be movers who just need to make something happen to feel any sense of accomplishment.
The point is, each of us starts somewhere, and like any good journey the first step is to figure out where that "where" is.
For example, I remember back in college the terror of each paper I had to write.
Inevitably, days before a paper was due I'd stumble across one classmate or another whose answer to a perfunctory "so…what are you writing about?" came back in fully-formed, immaculate, intimidating paragraphs. I'd nod, mutter something in response, and walk away, even more stressed that I was still just reading, and reading, and reading some more, taking tons of notes but struggling to come up with any sort of well-formed ideas of my own.
Over time I discovered that my own process required me to read and sit and write and struggle and read some more until, finally, my perspective would emerge. Not an easy process, but once I'd done it enough times I noticed that I like starting from the middle and working my way up (big picture) and down (specific proof points or tactics). No coincidence, then, that having a daily practice of capturing and developing ideas—in this blog and in my daily work—is part of how I structure my time. It's a system that allows me to produce my best ideas.
So, if, irrespective of where we like to start, we must eventually build out everything from vision to tactics and all that lies in between, we must ask ourselves questions like:
How do I process information?
Where do I feel most comfortable along the chain?
More often than not, what are the moments, contexts, or situations in which my new ideas arise?
Once I've got a new perspective, or insight, or even just an inkling, what steps do I then need to take to fill out the other pieces of the puzzle?
And, finally, given all of this, how can I structure my day, my time, my conversations (or lack thereof) to give myself more opportunity both to develop the nuggets that come most easily to me, and to then turn these into flushed-out ideas that I'm ready to start putting out into the world?


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Male pattern baldness is the most common form of hair loss among aging men. New research sheds light on hair growth mechanisms that could pave the way for new treatments for male baldness.
Male pattern baldness, also known as male alopecia, is the most widespread form of hair loss in men. Some studies have estimated that between 30 and 50 percent of men are affected by alopecia by the time they reach 50 years of age.
A team of researchers from the University of California, Irvine (UCI) set out to explore hair growth across the skin surface of the entire body. Their findings - which are published in the journal eLife - may help us to understand and treat male baldness, as well as excessive hair growth, differently.
The researchers were jointly led by Maksim Plikus, an assistant professor of developmental and cell biology, and Qing Nie, a professor of mathematics, both of UCI.
Using a combination of mathematical modeling and biological data, the researchers were able to map hair growth patterns across the entire skin.
As the authors explain, mathematical modeling is a valuable tool for understanding how hair follicles grow across the entire body.
"Our new mathematical model predicted details of signaling communications between hairs, otherwise difficult to reveal with standard biological experiments alone," says Prof. Nie.
Wnt and BMP signaling pathways
For the first time, scientists engineered a mouse model of "baldness" in an attempt to understand how poor hair growth occurs in humans.
They examined the Wnt proteins and bone morphogenetic proteins (BMPs) signaling pathways, as previous research on dorsal skin has shown that these play an important role in the "hair cycle clock." Specifically, previous studies referenced by the authors have shown that defects in either one of these pathways may disrupt hair growth patterns.
Wnt proteins regulate cell proliferation, at first during the development of embryos, and then in the growth and regeneration of other tissues. BMPs are also growth factors that drive development in the embryo and play a key role in the functioning of cells.
Previous research referenced by the authors has indicated how these signaling pathways control hair growth across the body, but what the new study shows is that hair growth is a coordinated process, with different skin areas "communicating" with one another.
Wnt-BMP pathway regulation facilitates this communication, as it was found to occur across the entire surface of the skin.
Communication may prevent baldness
Male pattern baldness tends to occur in the frontal and upper back, or crown, areas of the skull, but not at the lower back. The "communication" between the different hair follicles across the different areas of the head is thought to be interrupted, and hair follicles are believed to grow independently.
"If communication between nonbalding and balding regions can be reactivated, hair growth signals can then start spreading across the entire head skin, preventing regional baldness," says Prof. Plikus.
He also adds that Wnt and BMP signaling can be controlled pharmacologically - in other words, we can come up with drugs that may inhibit or activate these pathways, as needed.
By manipulating these pathways, researchers may, in the future, not only be able to stimulate hair growth, but also stop hair from growing in undesired areas.
"Our study identified the types of Wnt-BMP signaling levels that are very favorable for hair growth and the types that prevent it," Prof. Plikus adds. "It provides the road map for optimizing Wnt-BMP levels to achieve enhanced hair growth."
Finally, in addition to the Wnt and BMPs signaling pathways, the new study found more signaling factors that were associated with hair growth. In the future, the researchers plan to further explore these newly discovered factors.
Ana Sandoiu - Medical News Today


text: The town of Mirto is located high in the Nebrodi mountains approx. 12km from the north coast beaches. Mirto means 'myrtle in Italian and it is from this plant that the town gets its name. It was founded by the Saracens who it seems have long been forgotten unless you can disregard the Catholic buildings and churches that otherwise characterize this town. We don't offer accommodation in the town itself but on the hillsides surrounding Mirto there are a number of properties available for vacations that offer spectacular views down the mountainside and across the bay to the Aeolian Islands.


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How to Knit a Yarn Over Increase Stitch
Do you have a YO in your pattern and you need to know how to knit the Yarn Over stitch? This is an increase knitting technique used commonly to make eyelets in lace patterns. Multiple yarn overs create drop stitch patterns.
My tutorial shows you exactly how to Yarn Over with both written and close-up video instructions to power up your knitting skills.
Table of Contents
Knit, Yarn Over, Knit
When your pattern has the Knit stitch both before and after your Yarn Over: K, YO, K. Your yarn will be wrapping counter-clockwise for Yarn Overs.
- After your Knit Stitch, prepare your Yarn Over by bringing your yarn to the front of your work between your two knitting needles.
- Next, insert your right needle into the left and knit your stitch though.
- You will see that by starting with your yarn in the front of your work, it creates the Yarn Over when knitting that next stitch.
Purl, Yarn Over, Knit
When your pattern has the Purl stitch before your Yarn Over, then a Knit stitch: P, YO, K. Remember, your yarn will be wrapping counter-clockwise for Yarn Overs.
- After your Purl Stitch, your yarn is in the front of your work, so you are already in position for the Yarn Over.
- Next, insert your right needle into the left and knit your stitch though.
- You will see that by starting with your yarn in the front of your work after that first Purl stitch, your Yarn Over is created while knitting through your last stitch.
How to Knit a Yarn Over on the First Stitch of Your Work
Does your knitting pattern have a YO as the first stitch of your work? The first time I encountered it, I was totally confused. How do you yarn over when you haven't even begun to knit on your needle? It's actually a lot easier than you think! Yay!
Pattern with a Yarn Over, then Knit stitch: YO, K. Begin with the yarn in the front of your right needle, insert the right needle as if to knit, and knit through. Because you began with your yarn in the front of your needle, it wrapped around once prior to the Knit Stitch and created the first stitch as a Yarn Over.
Pattern with a Yarn Over, then Purl stitch: YO, P. Begin with the yarn in the front of your right needle and wrap it once around your right needle in a counter-clockwise direction, bringing the yarn around to the front. Insert the right needle as if to purl, and purl through. Because you wrapped your yarn around your needle prior to purling, it created the first stitch as a Yarn Over.
Knitting Yarn Overs on the Wrong Side of Your Work
When you turn your work, you will be knitting or purling those YO stitches. Make sure that the stitches are straight on your needle and not twisted. If they are twisted, just straighten them up before knitting the wrong side.
Helpful tip! If you get confused about where that YO stitch is supposed to be placed on your knitting needle, refer to your knitting pattern to see where they are placed among your stitches.
Again, my video is very helpful to see how I straighten up my stitches before I knit or purl the wrong side of my work.
Want to see the Yarn Over in action? Watch my video to fully understand just how easy this technique is to accomplish!
I hope you are inspired to knit yarn overs with confidence in your next knitting project. Find more knitting help with all of my technique tutorials. If you would like to practice Yarn Overs in a new project, please check out my Lace Heart Knit Stitch Pattern, as well as my Sea Foam Wave Drop Knit Stitch Pattern.
If you'd like even more great knitting ideas, please make sure you join my mailing list. Subscribing to my YouTube channel Studio Knit is another free and easy way for us to stay connected and help support my work.
Happy Knitting to You!


text:
We Save Stockings For New Year's Day to Keep the Holiday Magic Going
When I was growing up, Christmas Eve was my favorite night of the holiday season. It's when my family would open gifts, which felt extra special with the twinkling lights of our Christmas tree dancing against the backdrop of darkness outside. While the excitement of tearing open packages was over by morning, the magic stretched into Christmas Day when I awoke to find a big red stocking stuffed with a host of small treasures. But Christmas never seemed to last long enough, and I always felt sad when it was over.
That's why I tried something new once I was married and starting a family of my own. In an effort to prolong the magic of the season, I decided to save our stockings for New Year's Day. With piles of presents to open at Christmas, I didn't see a reason to open stockings at the same time. Instead, I thought it'd be nice to start off the new year with something, well, new. So in my first year of marriage, Christmas stockings became New Year's stockings. And it's been that way ever since.
Just like we did in those early years, my husband and I still stuff one another's stocking on New Year's Eve when the other isn't looking. And on New Year's Day, we unload them, delighting in the surprise. Much of the time, we awake to find our stockings bulging with small, inexpensive gifts, like candy, coffee, gift cards, or socks. But occasionally, we've saved the best gifts of the season for the first day of the year, like the latest iPhone or a sparkling piece of jewelry.
Having kids has made this tradition even better. Christmas stockings are a foreign concept to my kids, who have only ever known New Year's stockings. Though I'll admit that when they excitedly bring up the topic in social situations, it can be awkward responding to strange looks and explaining how and why we carry out this tradition differently than most.
As a family, we hang our stockings along with the rest of our Christmas decor. But when the gifts are all unwrapped and cleanup has begun, my kids know they still have surprises ahead as they anticipate opening their stockings on New Year's Day. It keeps the sparkle of Christmas from fading for just a little bit longer. And even though the gifts in their stockings are smaller and sometimes more practical than the gifts they tear open on Christmas, they still wake up on New Year's Day and race to their stockings with excitement comparable to that of Christmas. Plus, they love getting a few final gifts to enjoy when their friends have been done opening presents for a week.
Over the years, the tradition has evolved just a bit. While we still stuff stockings with goodies like candy, lip gloss, fancy coffee, or small toys, we also focus on items or experiences that serve a real purpose. As a family, during the week between Christmas and New Year's, we discuss goals and resolutions for the coming year. Then we use those discussion points as inspiration for stocking stuffers. So when my daughter tells me she'd like to improve her drawing skills, I might register her for an art class and place a receipt for the registration in her stocking. Or when my husband says he'd like to complete a 5K, he might get a gift card to our local running store so he can purchase the gear needed to reach his goal. One year, I told my husband I wanted to keep better track of the silly things my kids say and do, so he stuffed my stocking with pens and a small, take-anywhere journal to make it easy for me to record anecdotes from the day-to-day of family life.
Try as we might, there's no easing into the holiday season. We rush, rush, rush in the weeks prior to Christmas, and it's all over in a matter of hours. But saving our stockings for New Year's Day has been a fun way for our family to ease out of it, because after the big event is over, there's still something special to look forward to even as the season ends. And with the added focus of choosing stocking stuffers that can be used throughout the year, it truly is a way to enjoy the magic of Christmas all year long.


text:
See also: IRC log
previous minutes 2007-05-14 are approved.
Bob: interop test in Ottawa, co-located with WSP. MS and IBM did the testing.
David: we got interop across the board.
ms<->ms, ms<->ibm, ibm<->ibm.
... it's all green.
Bob: section 2 hasn't been tested however...
David: some of it were tested last year during
interop with Sun.
... we intended to test it with them, but didn't have time. I wonder if Sun would be willing to achieve the testing.
Bob: section 2 is related to WSDL on the EPR.
... section 2.1 is described as required in the conformance section of the addressing specification.
... but the conformance section indicates only that any child element must conform structurally with the specification. is it intended that way?
David: my reading of section 2.1 and conformance simply requires that an EPR processesor to read the metadata section. I don't believe that the conformance requirement imposes to dereference the WSDL.
Bob: so any processor that doesn't reference
is conformant.
... we now have a choice to make: CR call for implementation with marking some section at risk, or go directly to PR.
... looking at the test matrix, going to PR today, we would need to trim out those sections that do not meet the exit criteria of the charter (2 impls), the only features are those in section 2.1 and 2.2.
... so, what should we do?
Ram: section 2.1 and 2.2 are optional imho. any objections to that?
Bob: are you looking for rephrasing in conformance section?
Ram: yes, we should make it clear if section 2 is optional.
Bob: if it's not clear to Ram, we should clarify the spec.
Ram: we could remove the first statement of section 6.
<Ram> 6. Conformance
<Ram> An endpoint reference whose wsa:Metadata element has among its children the elements defined in 2.1 Referencing WSDL Metadata from an EPR conforms to this specification if it obeys the structural constraints defined in that section.
Katy: if the point of that section isn't there to indicate that the elements should be syntactically correct?
Anish: why would we not want the implementations to behave the way we specified?
Ram: is that a required feature or not?
Anish: there are certain things that you have to do to conform to the spec, but if you do that optional normative stuff, you are required to do what it says.
David: my take is that nothing in the
specification defines solution to the potential problem of embedding
metadata. Those could be out of date, etc.
... we're not going to solve that issue.
... I don't believe that the spec should require any processing of the metadata.
... those metadata can be expensive processing for example. that's why you don't want to require processing.
... regarding the conformance section, it simply says that the multiplicity is right.
Bob: choices are to produce 2 interoperable impls for each of those features, or to drop one or both.
Anish: even section 3 is optional, but it still part of the specification.
plh: [...]
Philippe: do we expect an implementation to reject an EPR with 2 serviceName?
Anish: yes, we do.
Tom: one minimal test would be to make sure
that one can accept an EPR that contains those metadata.
... that might be enough of a test.
Katy: two issues here. are those sections optional? the sentence is really about when the EPR has among its children elements from section 2.1.
<anish> agree with katy
Katy: it doesn't say anything about the optionality of 2.1
Ram: don't disagree with Katy's statement, but when the tooling sees the data in there, can it barf? Does an implementation have to parse and understand the semantics of section 2.1?
<TRutt__> understanding semantics is untestable
Ram: if the tooling doesn't have to do anything with it, we should make it clear in the spec
Bob: how would you modify that sentence?
<David_Illsley> how about at the end of section 2: NOTE: This specification does not override Core section 2.1, in particular, because the specification does not specify how to deal with the problems mentions, EPR users are free to decide whether or not to use this embedded metadata.
Ram: need to think about it
Anish: if the tooling treats it as any, then it's not checking the syntax that we define and shouldn't be claiming conformance to the spec.
Ram: then the tooling is required to
understand the syntactic part.
... it cannot be treated as any, there are some expected behaviors.
Anish: there are some syntactic constraints. the sentence is quite clear as it is.
Ram: so the implementation has to do something...
Bob: yes and schema validation would be enough
Ram: from our point of view, we don't think
that section 2 is the right approach from our product point of view.
... we don't expect to implement it.
plh: you have to do schema validation, that's what the spec says.
Bob: on section 2.1 and 2.2, what are our chances to get implementations?
David: given the late requirement, I'm willing to implement both.
Bob: so IBM is willing to implement section
2.1 and 2.2. Do we have another?
... MSFT does not intent to implement 2.1 and 2.2. Correct?
Ram: I believe we support 2.2 already but we are not planning to carry that forward.
Bob: ok, anyone else?
Tom: speaking of MSFT, we are just saying that they should do the conformance. correct?
Bob: specifically, the rule calls for interop
implementations. they are expectations that those implementations turn into
products. Although, it would be odd to participate in the CR phase and not
conforming to it in the product.
... unless we are able to come up with 2 implementations, we cannot progress these features.
... Sun has done some earlier interop.
Rama: we're not currently implementing the metadata spec. we're trying to understand the use case. I do think that section 2.1 is important. I do need to talk more internally.
Bob: so, do we go through the CR path or the
PR path?
... for CR, we need interop. We could wait for it.
... how long does Sun need?
Rama: I don't have an answer right now.
Bob: how much time for the internal discussion?
Rama: within a day or two.
Tom: WS-Policy is now expecting to have a PR something in July or August. For a practical point of view, late July/early August would be acceptable for me.
5 to 6 weeks.
for PR
Bob: there is no constraints for CR phase.
... we could have a 5 minutes CR phase.
... we do have another item on our way, the IP exclusion running until mid-July.
... the only way to go to PR earlier than July 15 is for all companies to agree to clause the exclusion interval early.
... so it may very well that we can't go to PR earlier than mid-July.
Katy: doing interop on 2.1 and forgetting 2.2
would be ok for us.
... if we go to CR and mark those 2 sections at risk, then proceed quickly through CR (one to two weeks0.
Bob: I would propose to end the CR period
around July 15 and if we don't get impls by then, those sections will be
... the conclusion of the CR interval would be end of June. (3 weeks CR)
Katy: this would be acceptable to us.
Ram: given where we are today, I'm wondering our chances to meet those deadlines?
Bob: depends on how quickly we can resolve this issue.
Ram: an other issue with section 2.1: it's
using the wsdli namespace, which only occurs on wsdl 2.0.
... could wsdl 1.1 implementations compose with this spec?
David: yes, it could simply ignore it.
Anish: I queued to answer the question: can you use wsdli with wsdl 1.1? the answer is yes.
Ram: wsdli namespace is not defined in wsdl 1.1
Anish: you don't need to understand wsdl 2.0 to understand wsdli.
Ram: we do agree that a addressing implementation has to understand the namespace
Anish: yes, you have to understand the qname.
Ram: I'm trying to point out a problem here. should a wsdl 1.1 implementation support this new namespace?
David: the wsdli is trivial to implement.
... I don't think it has to implement.
<Ram> Introduction: WS-Addressing is designed to be able to work with WS-Policy 1.5 [WS Policy 1.5], WSDL 2.0 [WSDL 2.0] and also (for backwards compatibility) with WSDL 1.1 [WSDL 1.1] described services.
Anish: agreed. Ram, are you arguing against the spec, or are we talking about interop implementations?
Ram: it's not clear to me that section 2.1 has it stands really composes.
Anish: if you have existing wsdl 1.1 artifacts, you may recognize other qnames. that separate from being able to reuse existing artifacts.
Ram: for us, it doesn't seem to be the right approach.
Bob: do you have a concrete issue to raise?
Ram: I do not want to push forward with any issue at this point.
Bob: proposed resolution: we try to close the remaining issues that we have, then we start a CR interval and try to conclude at the end of June, marking section 2.1 and 2.2 at risk.
[no objection]
Resolution: short CR, with 2.1 and 2.2 marked at risk.
Katy: trying to find the dependency with the
policies specifications.
... they are all moving towards being policy framework independent.
... I wonder if it's good idea to follow the example of RM
... we should modify the document to make the namespace generic.
Anish: this would be a bad idea. RM, etc are
going to charter clarifications to only use Policy 1.5.
... the reason why it was done like that in OASIS is that the policy specification was not ready.
<TRutt__> +1 to anish
Anish: my company would like to see the specification based on W3C technologies.
Katy: I didn't realize that the intention was
to move towards to 1.5
... are all the specs going to move to 1.5
Bob: RX and TX do intent to do this.
Anish: SX as well
Katy: are there going to be usable with policy 1.2?
Bob: I don't hear much sympathy for that.
Tom: one could claim conformance with the older spec if they want to.
Resolution: issue is dropped, withdrawn by submitter
<bob> http://lists.w3.org/Archives/Public/public-ws-addressing-comments/2007May/0003.html
Bob: in section 4.4, we talk about best
practices regarding the action property.
... but [[Unfortunately, the default action pattern for a WSDL 2.0 fault message does
NOT "fulfill that best practice.]]
David: always assumed that the best practice is about input messages, and not output messages.
For each Interface Operation component in the {interface operations} property of an Interface component, the {name} property MUST be unique.
<anish> Despite having a {name} property, Interface Operation components cannot be identified solely by their QName. Indeed, two Interface components whose {name} property value has the same namespace name, but different local names, can contain Interface Operation components with the same {name} property value. Thus, the {name} property of Interface Operation components is not sufficient to form the unique identity of an Interface Operation component. A method f
Gil: example 4.4 shows that the operation name doesn't appear in the wsa:Action.
Tom: a fault is returned in response to a
message, you should already be correlating the two.
... I think this is a misunderstanding. the action is for message in, not for message out.
David: I don't think that the potential benefit of uniquely identifying faults is worth breaking compatibility with existing implementations.
Bob: any editorial clarification?
<anish> it seems that either we should remove the reference to wsdl best practice or add operation name to the fault action algo
Anish: either we remove the best practices comment, or we change the fault algorithm.
Bob: changing the algorithm would be a breaking change.
David: I'm not sure it is really a best practice we can refer to.
Anish: this was at the time why we needed
... we pointed to the wsdl best practice because we needed it.
Bob: would it be enough to remove the comment about best practice?
Gil: I don't think that solves the problem
... two choices: a. you have a point but we don't think the point is serious enough to disrupt the spec, or we try to address it.
David: option a sounds reasonable. it isn't serious enough to fix the specification.
<dhull> +1
Resolution: issue is closed with no action
<scribe> ACTION: Gil to answer the comment on action property to the commenter [recorded in http://www.w3.org/2007/06/04-ws-addr-minutes.html#action01]
Bob: any more issues?
Ram: Is there is one issue from David Hull?
David_Hull: which one is that?
... I thought we nailed the issue of composability before
Bob: I received an ack to cr33. so it's
... move to CR for the end of June, marking 2.1 and 2.2 at risk?
... if we don't reach the CR criteria at the end of June (2 impls), 2.1 and 2.2 would be removed.
<gpilz> easier just to list it as "Section 2"
<gpilz> since "Section 2" is made up entirely of 2.1 and 2.2
Resolution: move to CR as soon as possible target completion for the end of June, marking 2.1 and 2.2 at risk
Ram: how does this decision intersect with the exclusion period?
Bob: on the 15 of July, we would request to
move to PR.
... this means end of august for the REC.
... I'm assuming that during the CR, nothing major will happen. I'll ask the group to vote to accept new issues.
Bob: I was thinking to have it on July 2.
David: this doesn't leave any meeting for the
group to approve the testing
... I'm ok with it. otherwise, we should have an early meeting.
Bob: So, the interval will be June 29.
Next meeting will be June 18, to discuss testing
and then July 2 to act on the result of the CR period.
Prepare final text for distribution to the director for review, then try to have the meeting with the Director on July 16.
<bob> thanks philippe for scribing