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Vice President Biden will head to New Hampshire next week for an event on the economy that is certain to intensify speculation that he is readying a bid for the presidential nomination in 2016.
Biden will be joined at the Wednesday event in Portsmouth by members of Congress, the White House said in a statement.
The attendees at the event could include Sen. Jeanne Shaheen Jeanne ShaheenDem senator asks for 'top to bottom' review of Syria policy A guide to the committees: Senate Mattis on rise in Trump administration MORE (D-N.H.), who is locked in a tough reelection fight against former Sen. Scott Brown (R-Mass.). Shaheen did not meet with Biden during his last trip to the state, a fact that was highlighted by the state's GOP.
The vice president's trip comes as other possible presidential contenders also announced their intention to head to the early-voting state.
Maryland Gov. Martin O'Malley (D) will also visit Portsmouth for a Democratic fundraiser next month, his fourth visit to New Hampshire. And Sen. Ted CruzTed CruzConquering Trump returns to conservative summit The Hill's 12:30 Report Cruz predicts another Supreme Court vacancy this year MORE (R-Texas) announced Friday his third visit to the state this year, appearing alongside Louisiana Gov. Bobby Jindal at a GOP fundraiser.
During the vice president's last trip to the state — a visit to a Nashua job training site in March — he made reference to speculation about his possible run.
"The reason we're here, notwithstanding what others may think, is because you run the best outfit in the country," Biden told New Hampshire Gov. Maggie Hassan (D) at the event.
At an early stop at a local business that hires workers who have completed the state's job training initiative, the vice president told reporters he was "here about jobs, not mine."


text:
Giotto's Pro II ball head series features a light and extra large ball with ball hollowed structure designed and manufactured to precisely position the camera both easily and securely.
Each has a stable and smooth base allowing fluid effect pans. Pro II features a slim and light body structure yet it is hardness strengthened, strong enough to support the heaviest of professional SLR's.
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Giotto's has designed various camera mounts and sliding plates to fit these socket bases.
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subset: commoncrawl


text:
The Rights of Minorities
A Commentary on the European Framework Convention for the Protection of National Minorities
Edited by Marc Weller
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Rights of Minorities by Marc Weller
Book DescriptionThe rights of minorities are becoming increasingly important, especially in the context of enlargement of the European Union, yet there are remarkably few treaties dealing with minority rights under international law. One of these is the Council of Europe's Framework Convention for the Protection of National Minorities. This volume provides the first expert commentary on the Convention, which is the principal international document establishing minority rights in a legally binding way. Many minority rights such as those to political participation, non-assimilation, and the use of native languages are not incorporated in other major Human Rights agreements. The Convention is therefore often taken to be the leading standard in the international law of minority rights. This commentary offers a detailed article-by-article analysis of the Convention, by a group of international legal experts in minority rights. Their commentary draws upon the Convention's negotiating history and implementation practice, in addition to examining the pronouncements of the Advisory Committee, which is the implementation body attached to the treaty. It offers a clear sense of the concrete meaning of the provisions of the Convention to scholars, students, and members of minority rights groups.
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Book DetailsISBN: 9780199207626
(233mm x 157mm x 41mm)
Pages: 752
Imprint: Oxford University Press
Publisher: Oxford University Press
Publish Date: 3-Aug-2006
Country of Publication: United Kingdom
Other Editions...
Books By Author Marc Weller
Protection of Civilians, Hardback (April 2016)
The protection of civilians which has been at the forefront of international discourse during recent years is explored through harnessing perspective from international law and international relations. Presenting the realities of diplomacy and mandate implementation in academic discourse.
UN Declaration on the Rights of Indigenous Peoples, Hardback (February 2015)
The Declaration on the Rights of Indigenous Peoples set key standards for the treatment of indigenous people, and has significantly developed how indigenous rights are viewed and enforced. This commentary thematically assesses all aspects of the Declaration's provisions, providing an overview of its impact.
Oxford Handbook of the Use of Force in International Law, Hardback (January 2015)» View all books by Marc Weller
This Oxford Handbook provides an authoritative and comprehensive analysis of one of the most controversial areas of international law. Over seventy contributors assess the current state of the international law prohibiting the use of force, assessing its development and analysing the many recent controversies that have arisen in this field.
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Author Biography - Marc Weller
Marc Weller is Director of the European Centre for Minority Issues and an Assistant Director of Studies in the Centre of International Studies at the University of Cambridge where he lectures on international law. He is a Fellow of the Lauterpacht Research Centre for International Law and of Hughes Hall, Cambridge.
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Good Technology Expands EMM Platform to Windows
Good Access for Windows provides a secure environment for deployment of HTML5 apps, securing corporate Web apps in containers.Good Technology announced the launch of a secure solution for Web apps for Windows and has expanded its enterprise mobility management (EMM) solution to Windows. Good Access for Windows provides a secure environment for deployment of HTML5 apps, securing corporate Web apps in containers to ensure that data never leaves enterprise control. It also provides a rich user experience, including HTML5 offline access in a secure browser for Windows. This gives IT pros access to a range of Web apps and the ability to more quickly develop additional apps knowing that corporate data will be secure. "With the rise of BYOD in the workplace, mobile devices are becoming an increasingly attractive access point for attackers," Phil Barnett, vice president and general manager of EMEA at Good Technology, told eWEEK. "Windows devices, like any phone or tablet, are susceptible to these security vulnerabilities and flaws. Additionally, there will always be a learning curve with IT to effectively secure devices when a new operating system is introduced, so our support for Windows streamlines this process."
Good Access for Windows is available in beta immediately, while Good Work for Windows will be available in beta later this year.
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14:24 if the way is too long. Travel was not easy, and the transportation of agricultural products was harder still. A practical solution was allowed—they could convert the goods to money and carry the money (v. 25).
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- Author: Jim Clark
- Format:Mixed media product
- Publisher:Pearson Education Limited
- Published:18 June 2009
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Product description
- Total Pages: 240
- Genre: Educational: Chemistry
Written specifically for Edexcel's new International GCSE Chemistry qualification in a clear and engaging style that students will find easy to understand, this book includes a wide range of activities and exercises for self-study, as well as examination style questions and summaries to aid revision. Full answers to the Student Book questions are available to teachers and parents by emailing firstname.lastname@example.com (for UK teachers and parents) or firstname.lastname@example.com (for all other teachers and parents).


text:
Lovely blog you 2 and is a great ad for our area. Weather is still "roasting" here but looks as though finally it cools down a bit from Wednesday.
We are now following you so await your next entry.
Ricky and Jan
Portugal-Week 17
Trip Start Jan 02, 2014
118Trip End Dec 31, 2014
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During the week, Liz and I managed to do some walking and sight seeing, most of it with Ron. As there is still daylight until after 8:30pm, it has been possible to combine the golf (played either in the morning or afternoons) with sight seeing and then when the temperature drops, end each day on a different beach.
On Tuesday this week we visited Silves, a town north of Carvoeira, which has the biggest and finest castle in the Algarve. It was built in the Islamic period, on the sight of Roman or Visigothic fortifications (4th or 5th century) with modifications made during reconstruction in the 14th/15th centuries. It is a stunning red sandstone castle built up high, overlooking the rest of the old town
On Wednesday, Liz and I did some long walks, first along the beach from the lovely fishing town of Ferragudo,
Thursday 1st May, labour day, was a public holiday and all residents of the Algarve had planned family picnics. We headed out to Sitio das Fontes, a park in Estombar village, as we had picked up a brochure about the park, its tidal mill, water wheel and springs. Families had arrived early to set up picnic spots and children were already kicking about in the spring pools. Several men were playing a game of 'Chincalhao'
On Friday after a drive to Lagos and a walk around the marina,
After enjoying a great 10 days with Liz, we returned her, very brown, to Faro airport. We then meandered back to Carvoeira along the scenic route, stopping for walks along the promenades and beaches at Quarteira, Vilamoura and Albufeira.
On Sunday afternoon we headed out to Loule, to witness the biggest religious festival in Southern Portugal, Festa da Mae Soberana (Sovereign Mother Festival). I'm not sure whether it was a coincidence that Sunday was mothers day here, or whether the festival always happens on mothers day, but the brochures indicated that it was the 2nd and largest of two festivals, the first one being on Easter Sunday. I think I read somewhere that Mary is the patron saint of Loule. I think we have now completed our religious preparation for our camino walk, we stood through a 1.5 hour outdoor mass, before following the procession of the statue of Mary being carried through the streets, back to her church, Igreja de S. Francisco. I have no idea how many people were there, but it could have been 10 or 20 thousand. They lined the streets and then fell in behind the procession as it passed......Mounted police, scouts, school bands, marching and philharmonic bands, all escorting the statue, which was carried on the shoulders of about 8 men. A great spectacle.
I think Ron could quite happily move here, he loves the golf and the beaches, doesn't mind the heat and likes the idea that the European ski fields are only a few hours on a plane away. People certainly enjoy a great life style here, but I think I prefer to live in a country where I can still drink water straight from the tap.


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Alice + Olivia Blayne Sleeveless Cut Back Top
Sold Out
Details Launched in 2002, alice + olivia by Stacey Bendet is a sophisticated brand with a playful sensibility, which epitomizes the personality and style of its founder, Stacey Bendet. The brand was born from Staceys personal quest to create a flattering pair of pants, and has since grown into a full womens ready to wear collection, including outerwear, dresses, and the perfect pants that started it all. Now a full lifestyle collection, the brand has become a Hollywood favorite with fans including Gwyneth Paltrow, Fergie, Anne Hathaway, Jennifer Lopez, Blake Lively, and Taylor Swift.
- Self: 93% silk , 7% spandex Combo: 100% silk
- Dry clean only
- Button front closure
- Front breast pocket
- Back cut out with drape detail
- Sheer fabric


text:
replaced Water pump on the car because it had been leaking and could have possibly overheated, but nofor long. There is no no coolant mixed with the oil, in the engine. Also what should compression be the car won't start now seems it lost compression.
Asked by for the 1996 Mercedes-Benz C220


text:
To better understand the meaning of HONORED, certain examples of its usage are presented.Examples from famous English prose on the use of the word HONORED
"I'm honored, said harry darkly"
"When azkaban is broken open, the lestranges will be honored beyond their dreams"
"I will be honored beyond all other death eaters"
"But was honored to have served his country and he lies and dies" - This term honored was used by Shay Norman in the Poem The silent hills.
"For i am honored to know the beauty i have found" - This term honored was used by Harry Boslem in the Poem Let me - poem.
"I feel humbly honored by her acquaintance" - This term honored was used by Harry Boslem in the Poem She brings me warmth - poem.
"Time-honored institutions"
"He was honored posthumously"
"Time-honored customs"
हिंदी मे अर्थ[+]
अंग्रेजी मे अर्थ[+]
उदाहरण और उपयोग[+]


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Firecracker Grilled Mahi Mahi
|Mahi mahi fillets
|4 (4 ounce each)
|Peanut oil
|1 Teaspoon
|Soy sauce
|2 Tablespoon
|Balsamic vinegar
|3 Tablespoon
|2 Tablespoon, chopped
|Brown sugar
|1 1⁄2 Teaspoon
|1 Clove (5 gm), minced
|1⁄4 Teaspoon, grated
|Red chili flakes
|1⁄2 Teaspoon
|1⁄2 Teaspoon
Place fillets in glass dish.
Whisk together remaining ingredients and pour over Mahi Mahi.
Cover with plastic wrap and marinate in refrigerator 4-6 hours.
Remove fish from marinade and place on grill, five inches from coals.
Grill 10 minutes per inch of thickness, or until fish flakes when tested with a fork.
Turn halfway through cooking.
Rate It
Nutrition Rank
Nutrition Facts
Serving size: Complete recipe
Calories 760 Calories from Fat 104
% Daily Value*
Total Fat 12 g17.9%
Saturated Fat 0.91 g4.6%
Trans Fat 0 g
Cholesterol 484.2 mg161.4%
Sodium 3351.5 mg139.6%
Total Carbohydrates 22 g7.4%
Dietary Fiber 1.9 g7.6%
Sugars 15.5 g
Protein 131 g261.2%
Vitamin A 8% Vitamin C 15%
Calcium 4.9% Iron 8.1%
*Based on a 2000 Calorie diet


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Ilse Jurriën : February 7th 2013 - 09:50 CET
Olympus VG-180
Olympus VG-180 digital camera :
Olympus introduces a new easy-to-use camera, the VG-180. Small enough to fit in your pocket, the Olympus VG-180 is an ideal camera to take with you wherever you go. Incorporating a 16 megapixel CCD sensor and a 5x optical zoom lens this Olympus camera shoots great pictures every time. The 26-130mm wide-angle lens lets you capture anything, from breath-taking landscapes to indoor group shots. In addition, the Olympus VG-180 incorporates 9 Magic Filters for still photos, users can choose from the following photo effects; punk, pop art, pinhole, fish eye, soft focus, sparkle, watercolour, reflection and miniature. Besides taking photos, the Olympus VG-180 records videos with sound in VGA movie quality.
Olympus VG-180 camera
If you buy a chic-looking, lightweight camera for well under €100, picture quality is usually the first disappointment. In fact, make that quality full stop. The Olympus VG-180 is different. This camera has such a good lens that you can shoot great pictures and videos with sound every time - in 16 Megapixel clarity. You get a high-precision 5x optical zoom for razor-sharp close-ups and a nice wide lens that can zoom out to 26mm for group shots, buildings and landscapes. The Olympus VG-180 takes care of all the settings itself with i-Auto. If you really need to, you can also boost magnification digitally from 5x to 20x. When you're done shooting photos, it's a cinch to add special effects using one of nine Magic Filters. The new Miniature filter turns a regular scene into an enchanting miniature world - by enhancing contrast and colour and narrowing the depth of field - at the touch of a button. Like everything else on our Smart cameras, it's that simple.
Olympus VG-180 price & availability
The Olympus VG-180 comes in two different colors, black and red. The Olympus VG-180 sales box includes a Lithium-Ion battery, an AC adapter, an USB cable and a worldwide warranty card. The camera is scheduled to be available from April 2013, the Olympus VG-180 price has been set at $99 USD / €90 Euro. Availability of colors, optional accessories and suggested retail prices may vary from country to country. For more information about this new compact camera download the
Olympus VG-180
specification sheet.
Olympus Stylus VG-180 review
As soon as we got our hands on a test sample, we will publish a sample picture gallery with high-res images and Full HD movies, followed by an in-depth Olympus VG-180 review. In the mean time you may want to read another
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Continental Competition
European Championship
Held every four years since 1960. Officially, the European Football Championship. Winners receive the Henri Delaunay trophy, named for the Frenchman who first proposed the idea of a European Soccer Championship in 1927. The first one would not be played until five years after his death in 1955.
Multiple winners: Germany/West Germany (3); France (2).
Copa America
Held irregularly since 1916. Unofficially, the Championship of South America.
Multiple winners: Argentina and Uruguay (14); Brazil (7); Paraguay and Peru (2).
African Nations Cup
Contested since 1957 and held every two years since 1968.
Multiple winners: Cameroon, Egypt and Ghana (4); Congo/Zaire (3); Nigeria (2).
CONCACAF Gold Cup
The Confederation of North, Central American and Caribbean Football Championship. Contested irregularly from 1963-81 and revived as CONCACAF Gold Cup in 1991.
Multiple winners: Mexico (7); Costa Rica (2).


text:
An oestrogen-dependent model of breast cancer created by transformation of normal human mammary epithelial cells
DOI: 10.1186/bcr1734
© Duss et al.; licensee BioMed Central Ltd. 2007
Received: 26 January 2007
Accepted: 15 June 2007
Published: 15 June 2007
About 70% of breast cancers express oestrogen receptor α (ESR1/ERα) and are oestrogen-dependent for growth. In contrast with the highly proliferative nature of ERα-positive tumour cells, ERα-positive cells in normal breast tissue rarely proliferate. Because ERα expression is rapidly lost when normal human mammary epithelial cells (HMECs) are grown in vitro, breast cancer models derived from HMECs are ERα-negative. Currently only tumour cell lines are available to model ERα-positive disease. To create an ERα-positive breast cancer model, we have forced normal HMECs derived from reduction mammoplasty tissue to express ERα in combination with other relevant breast cancer genes.
Candidate genes were selected based on breast cancer microarray data and cloned into lentiviral vectors. Primary HMECs prepared from reduction mammoplasty tissue were infected with lentiviral particles. Infected HMECs were characterised by Western blotting, immunofluorescence microscopy, microarray analysis, growth curves, karyotyping and SNP chip analysis. The tumorigenicity of the modified HMECs was tested after orthotopic injection into the inguinal mammary glands of NOD/SCID mice. Cells were marked with a fluorescent protein to allow visualisation in the fat pad. The growth of the graft was analysed by fluorescence microscopy of the mammary glands and pathological analysis of stained tissue sections. Oestrogen dependence of tumour growth was assessed by treatment with the oestrogen antagonist fulvestrant.
Microarray analysis of ERα-positive tumours reveals that they commonly overexpress the Polycomb-group gene BMI1. Lentiviral transduction with ERα, BMI1, TERT and MYC allows primary HMECs to be expanded in vitro in an oestrogen-dependent manner. Orthotopic xenografting of these cells into the mammary glands of NOD/SCID mice results in the formation of ERα-positive tumours that metastasise to multiple organs. The cells remain wild type for TP53, diploid and genetically stable. In vivo tumour growth and in vitro proliferation of cells explanted from tumours are dependent on oestrogen.
We have created a genetically defined model of ERα-positive human breast cancer based on normal HMECs that has the potential to model human oestrogen-dependent breast cancer in a mouse and enables the study of mechanisms involved in tumorigenesis and metastasis.
Classic epidemiological studies on the increase in cancer incidence with age predicted that from three to six independent events would be required to convert a normal cell into a tumour cell [1]. Experimental studies have now proven that it is indeed possible to transform a cell in culture by modifying the activity of only a few critical genes. Cell lines quantitatively transformed by expressing oncogenes or inactivating tumour suppressor genes have been produced from normal fibroblasts, embryonic kidney cells and human mammary epithelial cells (HMECs) [2, 3]. The genes initially chosen for these studies were those encoding simian virus 40 large T and small t antigen, activated Ras and telomerase. Subsequently it was shown that viral oncogenes can be replaced by activated MYC and genes targeting the retinoblastoma pathway [4]. This combination will transform HMECs, but the resulting tumours do not express oestrogen receptor α (ERα); this is an important weakness of current models, because about 70% of human breast tumours are ERα-positive.
ERα behaves quite differently in ERα-positive cell lines derived from human breast cancer and in normal human mammary epithelium in vivo. Oestradiol is a direct mitogen for ERα-positive cancer cell lines, but in normal human breast tissue the ERα-positive cells do not themselves divide in response to oestrogen [5]. Instead, they relay a proliferative signal to neighbouring ERα-negative cells. The barrier to proliferation of ERα-positive normal cells may explain why HMECs rapidly lose ERα expression in culture and why the transformation studies performed so far have produced ERα-negative tumour cell lines.
The target cell of oncogenic mutations in the breast is probably a stem cell or bipotent progenitor cell [6, 7]. It is possible to enrich for these cells by growing primary HMECs in the non-adherent conditions previously developed for culture of neural stem cells, leading to the formation of so-called floating mammospheres [8]. The Polycomb-group gene BMI1 can suppress activation of the p53 and Rb pathways by silencing the expression of p14ARF and p16CDKN2A [9] and it has been shown to increase the rate of self-renewal of mammospheres in response to Wnt, Hedgehog and Notch signals [10]. Since Polycomb-group genes are overexpressed in breast cancer [11, 12], BMI1 is a relevant candidate to test in HMEC transformation assays. BMI1 was originally identified as an oncogene that cooperates with MYC to induce lymphomas in mice [13], and MYC is commonly amplified in breast cancer, so it is reasonable to use MYC in a transformation protocol that includes BMI1. We show here that lentiviral transduction of HMECs with ERα, BMI1, MYC and TERT leads to the formation of ERα-positive tumours whose growth is dependent on oestrogen.
Materials and methods
Cell culture
Approval for culture of reduction mammoplasty tissue was granted by the Lausanne University Hospital ethics committee, and patients gave informed consent. The patients were healthy women with no previous history of breast cancer. All samples were confirmed by histopathological examination to be free of malignancy. Primary HMECs and human mammary fibroblasts (HMFs) were prepared by standard techniques [8, 14]. HMECs were cultured in human mammosphere medium (HMM): Hepes-buffered DMEM/F12 without phenol red (Gibco, Basel, Switzerland) supplemented with 20 ng/ml EGF (Invitrogen, Basel, Switzerland), 1 × B-27 (Gibco) and 1 nM 17-β-oestradiol (Sigma, Buchs, Switzerland). B27 is a serum-free medium supplement containing antioxidants, vitamins, growth factors and hormones including progesterone [15]. HMM was used for suspension and adherent culture of HMECs; tissue culture plastic was not coated with collagen for adherent culture. HMFs and MCF7 cells were grown in DMEM containing 10% fetal calf serum. For the proliferation assays, 20,000 cells were seeded per well in six-well plates in duplicate and stained with crystal violet (Sigma) after 10 days of culture in HMM containing 1 nM 17-β-oestradiol or 1 μM fulvestrant (ICI 182,780; Torcis Pharmaceuticals, Bristol, UK). The area covered with cells was quantified with ImageJ software (NIH, Bethesda, MD, USA). For the growth curves, 20,000 cells per well were seeded in 12-well plates in duplicate in HMM containing 1 nM 17-β-oestradiol or 1 μM fulvestrant. A separate plate was used for each time point and cells were counted in a Neubauer chamber. For colony formation and SNP assays from tumours, explanted cells were grown briefly in puromycin to eliminate murine cells.
Lentiviral vectors
The pSD-69 plasmid contains the human phosphoglycerate kinase (PGK) promoter, a Gateway attR cassette (Invitrogen), the mouse PGK promoter and the puromycin acetyltransferase gene cloned into pRRLhPGK.GFP.SIN18 [16]. Preliminary studies showed that the human PGK promoter is active in mammospheres and differentiated HMECs. Gateway BMI1 and ESR1 clones were obtained from Flexgene (Boston, MA, USA). The MYC (c-Myc) and TERT (hTERT) clones were provided by J Lingner and A Trumpp, respectively, and cloned into pENTR1A (Invitrogen). The BMI1, ESR1, MYC and TERT cDNAs were transferred to pSD-69 by LR recombination (Invitrogen) to give pSD-84, 82, 94 and 83. The MYC clone was wild-type in sequence. The β-glucuronidase gene (gusA) was transferred from pENTR-GUS (Invitrogen) into pSD-69 by LR recombination to give the control vector pSD-86. The cyan fluorescent protein gene (CFP) was cloned into pRRLhPGK.GFP.SIN18 from pECFP (Clontech, Saint-Germain-en-Laye, France) by standard techniques to give pSD-25. Lentivirus was produced by calcium phosphate transfection of 293T cells [16]. To transduce HMECs with multiple genes, infections were performed simultaneously with different viruses: cells were infected in suspension with the ERα and BMI1 vectors 24 hours after harvest from the patient (that is, after digestion with collagenase and dissociation of organoids to single cells), grown in suspension for 6 days in ultra-low-attachment dishes (Corning, New York, NY, USA), then dissociated, plated and infected with the MYC, TERT and CFP vectors. HMFs were infected with the CFP-expressing lentivirus in the initial experiment to facilitate identification in mice but were not transduced with TERT or transforming genes. The titre of each lentiviral batch was determined on primary HMECs. All infections were performed at a multiplicity of infection of 50 viral particles per cell.
The following antibodies were used: antibodies against p14 (FL-132), p16 (M-156), MYC (9E10) (Santa Cruz Biotechnologies, Santa Cruz, USA); keratin 14 (RB-9020), keratin 18 (MS-142), progesterone receptor (PGR; Ab1), ERα (SP1), high molecular weight keratins (AB-3; Neomarkers, Stehelin, Basel, Switzerland); BMI1 (F6; Upstate, Lucerna-Chem AG, Lucerne, Switzerland); β-tubulin (Sigma); GFP (A11122) (Molecular Probes, Invitrogen); Ki67 (Novocastra, Newcastle, UK) and hTERT (R484) [17]. For Western blotting, goat anti-mouse or goat anti-rabbit antibodies coupled to horseradish peroxidase (Jackson ImmunoResearch, Newmarket, UK) were used, followed by chemiluminescent detection (Amersham, Little Chalfont, Bucks., UK). For immunofluorescent staining of tissue culture cells, samples were fixed with cold methanol. For staining of tissue, samples were fixed for 2 hours at 4°C in 4% paraformaldehyde and embedded in paraffin. Antigens were retrieved by boiling sections for 20 minutes in trisodium citrate buffer pH 6. Goat anti-mouse or goat anti-rabbit antibodies coupled to Alexa 488 or Alexa 568 (Jackson ImmunoResearch) were used for detection and the slides were mounted with 1,4-diazabicyclo [2.2.2]octane (DABCO; Sigma).
Microarray analysis
RNA was extracted with an RNeasy kit (Qiagen, Hombrechtikon, Switzerland), amplified as described previously [18] and hybridised to U133Plus 2.0 gene chips (Affymetrix, CA, USA). CEL files were normalised with RMA [19]. The CEL files have been deposited in the GEO database under accession number GSE6548. DNA was extracted with a DNeasy kit (Qiagen), and 250 ng per chip was processed and hybridised to 50K HindIII SNP chips in accordance with the manufacturer's instructions (Affymetrix). The CEL files were analysed with CNAG 2.0 [20].
Cells were grown for 8 hours in HMM plus 100 ng/ml colcemid (Sigma). Metaphase spreads were prepared and stained with Giemsa (Sigma) essentially as described [21]. Fifty-five metaphase spreads of HMEC strains established from different donors were photographed and the chromosomes were counted.
p53 assay
RNA was extracted from HMECs before injection into mice and from tumours in the fat pad with the use of an RNeasy kit (Qiagen). p53 status was determined by yeast functional assay with total RNA [22].
Orthotopic xenograft
Animal experiments were authorised by the Veterinary Office of the Canton de Vaud, Switzerland. One million HMECs and 200,000 normal human mammary fibroblasts from separate cultures were mixed with 12.5% Matrigel (BD Biosciences) and injected into the fourth mammary gland of 8-week-old female NOD/SCID mice (NOD.CB17-Prkdc scid /J; Jackson Laboratory, Bar Harbor, ME, USA). Either the HMECs or the HMFs expressed CFP but never both: only one cell type in a single experiment was ever CFP-positive. The total time in tissue culture ex vivo before the epithelial cells were injected into the mammary fat pad was 28 days. Silicon pellets containing 1.5 mg of oestradiol [23] were inserted subcutaneously into the neck region of the experimental animals at the time that the cells were injected. For fulvestrant treatment, 5 mg of Faslodex (AstraZeneca AG, Zug, Switzerland) was injected subcutaneously at weekly intervals. The oestrogen pellets were not removed from fulvestrant-treated animals.
BMI1 allows expansion of HMECs that express ERα
The medium used for both suspension and adherent culture was HMM [8]. Because it is based on neurosphere medium and the microarray showed the expression of some neural genes, such as NEFL, we sought to confirm the epithelial nature of the cells by staining for keratins. Control cells plated after one round of mammosphere culture formed three types of colony: pure keratin 18 (K18)-positive luminal colonies, pure keratin 14 (K14)-positive myoepithelial colonies, and mixed colonies containing both luminal and myoepithelial cells (Figure 1g, top panels). This is the same pattern as that reported by Dontu and colleagues [8] after mammosphere culture; similar observations have been made by other groups using different HMEC culture conditions [28–30]. At later passages, luminal cells were lost from the control cultures, resulting in the formation of increasingly pure K14-positive myoepithelial cell cultures (Figure 1g, middle panels). This is the expected result when HMECs are put into culture (reviewed in [31]). In contrast with the single-positive staining pattern of the controls, cells transduced with ERα and BMI1 were double-positive, staining for both K14 and K18 (Figure 1g, bottom panels). We conclude that the transduced cells are HMECs, the ERα and BMI1 proteins are correctly expressed and biologically active, and that BMI1 expression permits the outgrowth of ERα-positive colonies.
Growth of ERα-transduced cells is dependent on oestrogen
Creation of an ERα-positive tumour model
Tumour formation in NOD/SCID mice.
HMEC strain
No treatment
E2 + fulvestrant
The physiological level of oestradiol is higher in women than in mice, and it is frequently necessary to administer exogenous oestradiol to study human oestrogen-dependent phenotypes in mice [23]. The xenografts were therefore repeated in mice given slow-release oestradiol pellets. In these experiments, the HMECs were tagged with CFP. All except one of the 32 injected mammary glands developed tumours; the tumorigenicity of the transgene-expressing cells was confirmed by using HMECs from three different patients (Table 1, 'E2'). The process of engraftment and tumour formation was followed by killing mice at different time points (Figure 4d–f, day 5; then Figure 4g–i, days 14, 21 and 35, respectively). Five days after injection there was a large necrotic mass of tumour cells at the site of injection, accompanied by a vigorous vascular response (Figure 4e). On the surface of the mass, patches of brightly fluorescent CFP-positive epithelial cells were visible (Figure 4d). Histological examination confirmed that the main mass was necrotic (Figure 4f, the asterisked region bounded by the dotted line), presumably because it was insufficiently vascularised, but the brightly staining patches on the surface contained viable cells that were forming invasive tumour even at this early time point (Figure 4f, open arrowheads; closed arrowheads show mouse ducts). The absence of any lag suggests that the cells are quantitatively transformed. Every subsequent time point showed the presence of invasive tumour cells with a similar histological pattern: dense islands of squamous carcinoma adjacent to diffuse regions of invasive ductal carcinoma. We conclude that HMECs transduced with ERα, BMI1, MYC and TERT readily form oestrogen-dependent tumours in mice.
ERα is active in the tumours
ERα-transduced cells are genetically stable
Response to anti-oestrogen therapy
Metastasis of tumour cells
We have developed a model for ERα-positive breast cancer by transformation of normal HMECs with ERα, BMI1, MYC and TERT. Metastasis occurred in 38% of the mice after 90 days. Previous attempts to make an ERα-positive model probably failed because ERα induces growth arrest and differentiation. We have not addressed the mechanism in this study, but transforming growth factor-β is known to restrain the proliferation of ERα-positive murine mammary epithelial cells [34]. Expression of BMI1 prevents differentiation and relieves the growth arrest, allowing the expansion of oestrogen-dependent HMECs in culture.
There are several differences between our culture system and those used previously. We grew the cells in floating mammosphere conditions before the first passage for several reasons. At a practical level, the final step after tissue digestion is a single-cell straining step; this facilitates efficient infection of the cells with lentiviral vectors less than 24 hours after the cells are removed from the patient. A second practical advantage is that fibroblasts do not survive in suspension, so floating mammosphere culture is an efficient way to eliminate fibroblasts. More importantly, it is based on techniques developed initially for propagation of neural stem cells [35] and later adapted for culture of HMECs [8]. The mammosphere approach enriches for bipotent progenitor cells that are capable of differentiating to myoepithelial and luminal cells, with production of milk proteins by the latter after treatment with prolactin in three-dimensional Matrigel culture [8]. The main difference between our approach and that of Dontu and colleagues [8] is that we used the same medium for suspension and adherent cell culture, and we omitted basic fibroblast growth factor. The medium is based on B27 [15], a serum-free medium supplement that is known to preserve the phenotype of human tumour cells in culture better than serum-containing media [36]. In our study, the relative importance of the medium versus the suspension culture is unclear but we have preliminary evidence that suspension culture may not be strictly necessary.
In the absence of a stem cell assay for HMECs it is not possible to state definitively whether mammospheres contain true human mammary epithelial stem cells (MaSCs). It is possible that the mammosphere approach enriches for mammary colony-forming cells (Ma-CFCs) rather than mammary repopulating units (MRUs) [37, 38]. The nature of the cell initially infected with lentiviruses in our protocol is unknown because the infections were performed on the mixed population of cells present in reduction mammoplasty tissue. An intriguing question is whether cells expressing the recently identified murine MaSC markers would be more sensitive to transformation. Given the uncertainty surrounding the identity of human MaSCs, our main aim was to reduce the duration of growth in vitro to limit the potential for selection of adaptations to culture in vitro. The present study used 106 cells per fat pad injection, for which we needed to expand the cultures in vitro for a total of 28 days. We have preliminary results indicating that 5,000 cells are sufficient to form tumours, so it should be possible to greatly reduce the duration of culture in vitro.
Polycomb-group genes such as BMI1, EZH2 and SUZ12 have repeatedly been identified as adverse prognostic factors in breast cancer [11, 12]. BMI1 is required for proliferation and renewal of stem cells in the brain and hematopoietic system. In mammospheres, BMI1 is thought to act as a point of convergence of the Wnt, Notch and Hedgehog signals that promote stem cell renewal [10]. BMI1 probably has at least a dual role, allowing cell proliferation by suppressing p14ARF and p16CDKN2A expression, and preventing differentiation through a more complex mechanism. Both processes are clearly visible in the microarray data reported here (Figure 2). ERα-positive tumours typically contain wild-type p53 and have fewer genomic changes than ERα-negative tumours [39]. The ERα-positive tumour model we have produced matches the human disease in this respect. The most likely explanation for the tumours to have retained wild-type p53 is that BMI1 suppresses p14ARF expression [9]. Previous quantitative transformation models included genes such as those encoding simian virus 40 T antigen and p53DD to inactivate p53 [3, 4]. The MCF10A and MCF15 HMEC-derived cell lines show large differences in their DNA damage response despite both retaining wild-type p53 [40], and ERα-positive human breast tumours respond poorly to chemotherapy despite having wild-type p53. It is therefore important to note that although we have shown that the p53 cDNA is wild type, we have not shown that the p53 pathway is functional in our cells. The genes suppressed by BMI1 in ERα-expressing cells include many associated with neural and squamous differentiation. Suppression of these genes presumably favours proliferation by avoiding entry into a terminal differentiation program. We found that BMI1 itself was one of the genes suppressed by exogenous BMI1 expression. Bracken and colleagues showed by chromatin immunoprecipitation (ChIP) that the Polycomb-repressive complex 1 (PRC1) component CDX8 and the PRC2 component SUZ12 were present at the BMI1 promoter [27]. Suppression of PRC function by RNA-mediated interference (RNAi) led to derepression of genes with PRC proteins at the promoter [27]. On the basis of the ChIP data and the transcriptional response to RNAi against BMI1, EED, SUZ12 and EZH2, Bracken and colleagues suggested that PcG proteins autoregulate their own synthesis [27]. Autoregulation of BMI1 itself would by definition not have been detectable in their RNAi experiment, but when taken together with our results it is plausible that BMI1 suppresses its own expression through binding to its own promoter.
Wild-type ERα is not normally considered to be an oncogene, but behaves like one in our protocol. It is well known that ERα expression is rapidly lost from HMECs in culture. This is not solely a consequence of growth inhibition by ERα, because expression is still lost when cells are forced to express exogenous BMI1. In comparison with previous studies, the combination of genes we used to transform the cells seems rather gentle. In particular, we see no need to activate Ras signalling [2–4, 41]. TERT was essential for successful transformation of HMECs in previous studies [3], but BMI1 and MYC can both activate TERT expression [42, 43], so it is possible that TERT may not be required in our protocol. We included MYC in the protocol because BMI1 was originally identified as an oncogene that cooperates with MYC in lymphoma production in mice [13], MYC is commonly amplified in human breast cancer, and several groups have reported that MYC is required for HMEC transformation. Indeed, when Elenbaas and colleagues [3] used an HMEC transformation protocol lacking MYC, the cells spontaneously amplified MYC during culture in vitro. We used a wild-type MYC (c-myc) clone for our studies, rather than the activated form of MYC (T58A) used by Kendall and colleagues [4]. Despite the strong evidence that MYC is important, the requirements may differ when the selection conditions are changed, and we have preliminary evidence that MYC may not be required in ERα/BMI/TERT-transduced HMECs, at least for the initial stages of tumour formation.
It is intriguing that the transformed HMECs in our model can form polarised epithelial structures in vivo that express the correct luminal and basal keratins (Figure 6). This indicates that the double-positive keratin staining pattern in vitro is more likely to reflect a specific progenitor state than a loss of control of lineage-specific gene expression. Unlike the primary tumours in the mammary gland, the metastases were K18-negative. This suggests that the cells differentiate in response to signals from their local environment and that the mammary fat pad supplies specific signals that promote luminal keratin expression. Although the tumours contained regions of invasive adenocarcinoma, the predominant pathology was squamous carcinoma. Squamous differentiation is uncommon in human breast tumours. The squamous differentiation we observed in the NOD/SCID mice may reflect a general property of the mouse mammary fat pad model, a specific property of the target cell of the in vitro transformation protocol, or a defect in the transactivation of critical ERα target genes in the transformed cells. In comparison with the human breast, the mouse mammary gland contains much less fibrous connective tissue [44]. To promote engraftment of HMECs in the mouse mammary gland, human fibroblasts are commonly injected either at the same time as the HMECs or a few days earlier, to 'humanise' the stroma [32]. Human cancer-associated fibroblasts (CAFs) are similarly used to promote engraftment of human tumour cells in mice [45]. It is possible that the HMFs we injected together with the HMECs may have contributed to the squamous phenotype, but injection of our HMECs without HMFs led to the formation of tumours with similar kinetics and histology (data not shown). As mentioned above, we do not know the identity of the target cell of the transformation protocol. The mammosphere protocol enriches for mammary epithelial progenitor cells, but it is possible that expression of BMI1 promotes the survival of more differentiated cells or, conversely, forces progenitors to adopt a more stem-cell-like phenotype. HMEC protocols commonly give rise to squamous tumours in mice [3, 46, 47], so we consider it unlikely that the mammosphere protocol has led to the expansion of cells that are unrelated to mammary epithelium. Another possibility is that, despite expressing ERα, the cells are unable to respond appropriately to it. The gene expression profile of breast tumours is dominated by genes that are tightly associated with ERα status [48]. Many of these genes are direct targets of ERα but others are thought to represent markers of cell type. Some classic ERα target genes, such as the progesterone and prolactin receptor genes, were induced by oestradiol in the ERα/BMI1 HMECs, but others, such as TFF1 and XBP1, were not (Figure 2; the full data set is available in the GEO database under accession number GSE6548). The uninduced group includes many of the genes shown by RNA interference to require co-activation by FOXA1 [49]. Because FOXA1 is expressed only weakly in the transformed cells, transduction with a FOXA1 vector might lead to the activation of a broader range of ERα target genes and suppression of the squamous phenotype. More generally, there may be regulators of the differentiation programme of mammary epithelial cells, such as GATA3 or TP73L, that are not correctly expressed in the xenografts. We are currently testing these models to develop a transformation protocol that more faithfully reproduces the histology of human breast tumours.
It has long been known that ERα-positive breast tumours metastasise early, leading to distant relapse many years after excision of the primary tumour. In comparison with ERα-negative tumours, they have a better initial prognosis but this is followed by a relentless increase in breast cancer-specific mortality that continues even 15 years after treatment of the primary tumour [50]. It is tempting to speculate that the correct paradigm for these tumours is a low-grade lymphoma: a systemic disease characterised by few genetic changes and poor response to therapy. Intriguingly, there is a class of ERα-positive breast tumours that have only a single change on genomic profiling: an unbalanced translocation leading to gain of chromosome 1q and loss of chromosome 16q [51]. For this model to be correct, metastasis would have to occur early. Metastasis has not previously been reported in studies with HMECs transformed with defined oncogenes [3]. At early time points the transformed HMECs reported here invaded the fat pad rapidly, forming a prominent duct-like structure that arose either from cells deposited in the needle track or by the migration of cells out from the main mass (Figure 4g–i). We have not tested the invasive properties of the cells in vitro, but the specific combination of genes used to transform the cells certainly triggers an invasive and metastatic program in vivo. Because the key difference between this model and previous HMEC models is ERα expression, it is tempting to speculate that ERα itself has a critical role in the early metastasis of ERα-positive human breast tumours.
We have created a new model for ERα-positive breast cancer by transduction of normal HMECs with lentiviruses expressing ERα, BMI1, MYC and TERT. The transformed cells are oestrogen-dependent for growth, wild-type for p53, diploid, and genetically normal as judged by hybridisation of tumour-cell DNA to SNP chips. The lack of secondary genetic changes and the high efficiency of tumour formation suggest that the cells are quantitatively transformed by the transgenes. The cells form disseminated peritoneal and liver metastases, a feature not previously seen with genetically defined, ERα-negative breast cancer models.
cyan fluorescent protein
Dulbecco's modified Eagle's medium
- ERα:
oestrogen receptor alpha
green fluorescent protein
human mammary epithelial cell
human mammary fibroblast
human mammosphere medium
keratin 14
keratin 18
- MaSC:
mammary epithelial stem cell
phosphoglycerate kinase
progesterone receptor
Polycomb-repressive complex
- RNAi:
RNA-mediated interference
single nucleotide polymorphism.
We thank V Sechet, A Cottilard and W Raffoul for providing reduction mammoplasty samples, S Mallepell and RD Rajaram for breeding mice, C Pythoud, C Morel and N Mueller for expert technical assistance, X Schmidt for analysing p53 responses, J Huelsken, D Trono, L Naldini, J Lingner and A Trumpp for providing reagents, F Paulin and A Thompson for help with microarrays, CS Herrington and V Becette for advice on pathology, and P Gonczy for critical reading of the manuscript. We acknowledge financial support from Oncosuisse, the Swiss National Science Foundation NCCR Molecular Oncology program, Breast Cancer Research Scotland, EU Active p53 project and ISREC.
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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.


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But the good news was tempered by a fresh round of cutbacks in the oil industry with Shell announcing 750 more job losses than expected and Texaco axing 1,000 jobs in exploration and production.
Universal Scientific Industrial Company of Taiwan is to build a pounds 15m plant at Irvine in Ayrshire - Silicon Glen - to produce components for the computer, telecoms and automotive industry.
The announcement was seen an important boost for the Government's drive to attract more inward investors following high-profile factory closures by Siemens and Fujitsu in the North East.
Barbara Roche, the DTI minister responsible for inward investment, said: "This investment represents an important vote of confidence in the UK electronics industry."
The Taiwanese investment was secured with support from the Invest in Britain Bureau, Locate in Scotland and local enterprise agencies who fought off strong European competition.
There are now nine Taiwanese electronics companies in Scotland who will employ more than 4,000 by the turn of the century.
Shell is cutting a total of 3,000 jobs in its European oil products businesses. This is equivalent to 20 per cent of the workforce, not the 15 per cent reduction initially announced.
A spokesman said that the job losses would be achieved by a combination of redeployment, natural wastage and redundancies.
Texaco blamed its 1,000 job losses - 12 per cent of its exploration and production workforce - on weak oil prices and said the move would save it $200m a year.
Meanwhile, a pounds 10m bid for Crabtree, specialist maker of machinery for colour printing drink and food cans, has saved 380 jobs at the group's Gateshead headquarters which faced an uncertain future.
The board is recommending a rescue bid worth 50p a share from LTG Technologies, a wholly owned subsidiary of LTG Holding, based in Stuttgart. LTG Technologies, which secured an AIM listing six weeks ago, has been talking to Crabtree since August and has already underwritten an overdraft for the company.
Crabtree's business has been hard hit by the global downturn in demand for capital equipment.
- More about:
- Energy
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Back to Don's Maps
Back to Venus figures from the Stone Age
Kostenki on the Don River is a very important Paleolithic site. It was a settlement which contained venus figures, dwellings made of mammoth bones, and many flint tools and bone implements.
Venus figures from the Kostenki - Borshevo region on the Don River
Photomontage of an important Kostenki Venus, diadem, and the Don River in the Kostenki region
Photo: Vladimir Gorodnjanski
Kostenki is a very important Paleolithic site on the Don River in Russia. It was a settlement which contained venus figures, dwellings made of mammoth bones, and many flint tools and bone implements. Kostenki / Kostienki is not actually a single site but really an area on the right bank of the Don River in the regions of the villages of Kostenki and Borshevo, consisting of more than twenty site locations, all dating to the Paleolithic.
Distribution of mobile art in Eastern Europe.
1 Staryé Duruitory, 2 Brynzeny, 3 Kosseoutzy, 4 Klimaoutzy, 5 Suren' 1, 6 Chan-Koba, 7 Apiantcha, 8 grotte d'Uvarov, 9 Sakagia, 10 Sagvardgilé, 11 Gvardgilas-Kldé, 12 Devis-Khvreli, 13 Taro-Kldé, 14 Molodova V, 15 Lissitchniki, 16 Lipa VI, 17 Klinetz, 18 Ossokorovka, 19 Dubovaya Balka, 20 Kaïstrovaya Balka, 21 Mejiritch (Mezhirich), 22 Kievo-Kirillovskaya, 23 Mézine (Mezin), 24 Novgorod Severskyi, 25 Puchkari I, 26 Dobranitchevka, 27 Gontzy, 28, Rogalik, 29 Amvrossievka, 30 Eliseevitchi I, 31 Eliseevitchi II, 32 Yudinovo, 33 Khoylevo II, 34 Timonovka, 35 Suponevo, 36 Avdeevo, 37 Sungir', 38 Gagarino, 39 Kostienki 19, 40 Kostienki 21, 41 Kostienki 13, 42 Kostienki 1, 43 Kostienki 14, 44 Kostienki 12, 45 Kostienki 17, 46 Kostienki 2, 47 Kostienki 11, 48 Kostienki 4, 49 Kostienki 15, 50 Kostienki 9, 51 Kostienki 8, 52 Borchtchevo 1, 53 Borchtchevo 2, 54 Ilskaya, 55 Murakovka, 56 Ostrovskaya, 57 Bez'imyannyi, 58 Smelobskaya, 59 Kapova, 60 Ignatievskaya.
Photo: Abramova (1995)
The Kostienki limestone venus.
Found at the Russian site of Kostenki in 1988, this is by far the biggest such object known from the ice age. The height of the surviving fragment is 13.5 cm (5.5 inches) It is noteworthy not only for its massive size and the prominent navel, but also for the bracelets on the wrists, which appear to be joined together at the front like a pair of handcuffs.
Photo: P. Bahn, 'Prehistoric Art'
The Kostienki limestone venus.
Photo: Cohen (2003)
This Venus figure from Kostienki 1, catalogued as number 3 by Abramova (1962), made of mammoth bone, shows the characteristic pregnancy, well developed buttocks and pendulous breasts of many such statues. In the rear view she can be seen to be wearing a fringe or girdle.
The Venus of Kostienki 1, catalogue number 3, is one of the most well-known Venuses of the world, created 24 500 - 21 500 BP
It has never been seen outside of Russia. This is a very high quality facsimile.
Photo: LWL/Egbert.
Source and text: http://www.lwl.org/pressemitteilungen/mitteilung.php?urlID=16067#.Us96qmQyFO0
Venus figure, another version of the one above.
Note that the head, apparently found separately, has been attached at a different angle.
Photo: Vladimir Gorodnjanski 2008
Source: Facsimile, Voronezh Museum.
This photo of the original is catalogued as Kostenki 1, Venus figure number 3 by Abramova (1962)
(Note the hole between the ankles which could have been used to thread a cord through to make a pendant - Don )
Photo: Abramova (1962)
This photo of the original as seen in the upper drawing in the image below, is catalogued as Kostenki 1, Venus figure number 4 by Abramova (1962)
Photo: Abramova (1962)
Venus figure as shown in the lower drawings above of two venus figurines from Jelinek.
Photo: Vladimir Gorodnjanski 2008
Source: Facsimile, Voronezh Museum.
Venus figure as shown above.
The venus does not seem to be in a very good condition, the ivory is apparently delaminating.
Catalogued as Venus figure number 2 by Abramova (1962)
Photo: Abramova (1962)
Statuette féminine de Kostienki 1, vue de face. Collection MAE. Photo
L. Iakovleva.
Venus from Kostienki 1, frontal view. Collection MAE. This is the same as the venus above.
Photo and French text: "les mammouths - Dossiers Archéologie - n° 291 - Mars 2004"
Photograph L Iakovleva.
My thanks to Anya for access to this resource.
This is quite a heavy looking venus figurine. It may not have been completely finished.
Photo: Vladimir Gorodnjanski 2008
Source: Facsimile, Voronezh Museum.
Black and white photos of the original of the venus above.
This is catalogued as Venus figure number 5 by Abramova (1962)
Photo: Abramova (1962)
Venus figure from Kostenki 1, and a fragment of a venus figure, both facsimiles.
Photo: Vladimir Gorodnjanski 2008
Source: Facsimile, Voronezh Museum.
Apparently the original of the venus on the left, above.
Catalogued as Kostenki 1 Venus figure number 1 by Abramova (1962)
Photo: Abramova (1962)
Venus figure, another version of the one on the left, above.
Photo: Vladimir Gorodnjanski 2008
Source: Facsimile, Voronezh Museum.
Venus figure, another version of the one on the left, above. The venus is from Kostenki 1 and is 9 cm high.
This is apparently of the original. Note the cross hatching across the top of the breasts, possibly a decorative band of some kind.
Photo: http://www.istmira.com/foto-i-video-pervobytnoe-obschestvo/3924-iskusstvo-predystorii-pervobytnost-2.html
The Venus statuette above.
Photo: © MAE (Kunstkamera) RAS, St. Petersburg, Russia, MAE # 4464-1
Source: http://eiszeiten-hamburg.de/2016/05/11/die-kunst-der-mammutjaeger/
Venus figure from Kostenki.
Figure of a naked woman. Her head is covered with rows of shallow teeth cuts, depicting, according to Z. A. Abramova, hair or a closely fitting head-dress. Engraved and relief lines on the chest and on the back. Mammoth's tusk. Height 114 mm. Found in 1936, excavation made by P.P. Efimenko, who thought it to be 'one of the best creations of that period, known to us'.
Photo: Cohen (2003)
Text above: http://vm.kemsu.ru/en/palaeolith/plastic/costenki.html
бивень мамонта Костенки 1,1 слой (22 тыс. лет), муляж
Одна из самых совершенных женских статуэток эпохи палеолита поражает мастерством исполнения и гармонией внутреннего содержания образа. Пред нами много рожавшая женщина, которая вновь готовится стать матерью. Маленькие ручки вытянуты вдоль живота, голова наклонена, как будто она прислушивается к находящейся внутри ее новой жизни, вся фигурка производит ощущение умиротворения и покоя. Это древнейший женский образ на Земле и символ красоты той эпохи.
Made of mammoth tusk, Kostenki 1, layer 1 (22 000 BP)
One of the most perfect female figurines of the Palaeolithic, with striking craftsmanship and harmony of the inner content of the image. We have before us a woman who already has children, and is preparing to become a mother again. Little hands stretched along the abdomen, head tilted as if she listens to the new life inside her, the whole figure produces a feeling of peace and tranquility. It is a symbol of the beauty of that era.
Additional text: Display, Kostenki Museum
Another photo of the venus above.
This image shows both front and back views.
Photo: Rau et al. (2009)
Venus figure from Kostenki 1.
Photo: (left) N.D. Praslov
Photo: (right) Cohen (2003)
Scientific examination of the Venus statuette above in the Kunstkamera St. Petersburg
Photo: © Archaeological Museum Hamburg
Source: http://eiszeiten-hamburg.de/2016/05/11/die-kunst-der-mammutjaeger/
Female figurine carved from mammoth tusk. Kostenki 1, layer 1
Plaster cast.
Photo: Vladimir Gorodnjanski 2011, 2014
Venus figure, same as above, plaster cast.
Photo: Vladimir Gorodnjanski, 2006
Female figurine carved from marl. Kostenki 1, layer 1
Plaster cast.
Photo: Vladimir Gorodnjanski 2011
мергель Костенки 1,1 слой (22 тыс. лет), муляж
Некоторые женские статуэтки из мергеля в Костенках представляют собой сознательно разбитые фигурки. У данной статуэтки не хватает нижней части ног и верхней части туловища: они были отбиты еще в каменном веке. Возможно, это был ритуал, смысл которого уже не ясен.
Female figurine.
Kostenky 1, layer 1 (22 000 BP), made of marl.
Some female figurines of marl in Kostenki present as deliberately broken figurines. In this statuette the lower part of the legs and the upper body are missing: they were broken off in the Stone Age. Perhaps it was a ritual, the meaning of which is not clear.
Photo: Vladimir Gorodnjanski 2014
Source: Facsimile, Kostenki Museum
Another version of the venus figure above.
Photo: Vladimir Gorodnjanski, 2006
The upper horizon of Kostenki 4 yielded some interesting finds.
1 and 2 are venus figures, 3 and 4 are fragments of anthropomorphic pieces, and 5 and 6 are engraved plaques of marl (clayey limestone).
Photo: Abramova (1962)
Kostenki 1 venus figures.
1 - A rod with a globular head.
2 - a point with a hat like head.
3 - Rod with a rounded head.
Photo: Abramova (1962)
This is described as a male venus from Kostenki.
Photo: Abramova (1995)
A photograph of the male venus figure above.
Photo: Vladimir Gorodnjanski 2007
Source: The Hermitage Museum, Saint Petersburg
Vulve sculptée de Kostienki 1. Collection MAE. Photo L. Iakovleva.
Vulva sculpture from Kostienki 1. Collection MAE.
Photo and French text: "les mammouths - Dossiers Archéologie - n° 291 - Mars 2004"
Photograph L Iakovleva.
My thanks to Anya for access to this resource.
23 000 - 21 000 BC Limestone
H 10.2 cm
This figurine represents the Palaeolithic 'Venus', with overlarge breasts and belly. The faceless head bends towards the chest while the arms are pressed to the body with hands on the belly. Covering the surface of the head are rows of incisions indicating a hair style or cap. Relief work in the form of a tight plait convey a breast ornament tied up at the back. There are bracelets on the arms.
(right images) http://exn.ca/stories/2000/02/03/53.asp
Venus figure above, but minus the head.
This has the classic and famous beaded decoration around the neck and above the breasts.
Photo: Vladimir Gorodnjanski, 2006
This is a much better photograph of the original in the Hermitage Museum at St Petersburg, Russia.
Photo: Vladimir Gorodnjanski 2007
Various views of the original.
Photo: Vladimir Gorodnjanski 2014
Source: The Hermitage Museum, Saint Petersburg
This facsimile of the figurine above is missing the head, but the very small hands and lower arms are clear in this view.
Photo: Vladimir Gorodnjanski 2014
Source: Facsimile, Kostenki Museum
Facsimile of the venus figure above.
Photo: Don Hitchcock 2008
Source: Vienna Natural History Museum
Venus figurines from Kostenki
Photo: http://vantit.ru/antiquities/908-venera-iz-kostenok.html
Venus figurine from Kostenki
Photo (left): http://vantit.ru/antiquities/908-venera-iz-kostenok.html
Photo (right): http://old.national-geographic.ru/ngm/200903/article_269/
Venus figurine from Kostenki
Photo: Cohen (2003)
Kostenki Venus figure, with a good view of the back of the venus.
Photo: http://shamans-storytellers.wikispaces.com/9E+Look,+Ma,+No+Feet!++Paleolithic+Goddess+Figures
Venus figurine made of marl from Kostenki 1, apparently a facsimile.
Photo: Soffer et al. (2000)
Venus figurine from Kostenki
Photo: http://vantit.ru/antiquities/908-venera-iz-kostenok.html
Venus figurine from Kostenki 1.
Abramova (1962) identifies this as Number 6 from Kostenki 1.
Photo: Abramova (1962)
Head of a venus known popularly as the golf ball. From the Kostenki I site in Russia. The real basket headware was made of plaited starts and coiled basketry, copied here in stone.
Photo: http://www.unl.edu/rhames/212/venus/venus_string.html
Dr. Olga Soffer examining the "golf ball" head of the Venus of the Kostenki I site in Russia.
"Because they have emotionally charged thingies like breasts and buttocks, the Venus figurines have been the subject of more spilled ink than anything I know of," Dr. Soffer said.
"There are as many opinions on them as there are people in field."
Text and Photo: http://www.hort.purdue.edu/newcrop/history/lecture02/r_2-1.html
These are photographs of the original in the Hermitage Museum at St Petersburg, Russia.
Photo: Vladimir Gorodnjanski 2007
The golf ball venus.
Photo: Vladimir Gorodnjanski 2014
Source: The Hermitage Museum, Saint Petersburg
Large head made of marl from Kostenki I.
Left, right profile; centre, left profile; right, superior view.
Photo: Soffer et al. (2000)
Animal head (possibly a cave lion head), and two bison figurines from Kostenki 4.
Photo: Abramova (1995)
- Abramova Z., 1962: Paleolitičeskoe iskusstvo na territorii SSSR, Moskva : Akad. Nauk SSSR, Inst. Archeologii, 1962
- Abramova Z., 1995: L'Art paléolithique d'Europe orientale et de Sibérie., Grenoble: Jérôme Millon.
- Cohen C., 2003: La femme des origines. Images de la femme dans la préhistoire occidentale,, Paris, Belin-Herscher, 2003, 191 pages.
- Soffer O., Adovasio J., Hyland D., 2000: The 'Venus' Figurines - Textiles, Basketry, Gender, and Status in the Upper Paleolithic, Current Anthropology Volume 41, Number 4, August–October 2000
- Rau, S., Naumann D., Barth M., Mühleis Y., Bleckmann C., 2009: Eiszeit: Kunst und Kultur, Thorbecke, 2009, 396p. ISBN: 978-3-7995-0833-9


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Focus 2013
L2: Business Intelligence for Digital
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L2: Business Intelligence for Digital
L2 is a subscription business intelligence ("BI") firm focused on digital innovation. L2 was founded on the notion that digital competence is inextricably linked to shareholder value and that ongoing BI can replace episodic consulting engagements with actionable insights at a fraction of the cost.
The L2 Digital IQ Index is the globally recognized benchmark for digital performance of consumer brands. L2 collects more than 850 data points across four dimentions (Site & E-Commerce, Digital Marketing Social Media, and Mobile) and has assembled the largest data set to-date to diagnose brands' digital strengths and weaknesses relative to peers.
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In order to vote in any election in Virginia, a person must be a U.S. citizen, a resident of Virginia, 18 years old by General Election day and registered to vote in the precinct in which he or she resides.
You may register to vote year round with the exception of 22 days prior to a general or primary election or 13 days prior to any special election. Voter registrations are available at the County Government Center, the Department of Motor Vehicles, all post offices, all libraries, on the Virginia State Board of Elections website and on our forms and publications age.
Overseas voters--both civilian and military--should visit the Virginia Department of Elections website for more information.
Please inform the Registrar of any changes to your address or name in writing:
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I was vaccinated as a child. Then when I was 15, I was in the Hospital for two and a half weeks, every day they drew lots and lots of blood, finally I was sent home, and after I was home for 2 months, I got a letter in the mail, from the State, it read, " you have the measles".In England now, the fools who didn't vaccinate are watching their children get hospitalized with measles right now. It's an epidemic. As they watch their children suffer in pain, they see teenagers who were vaccinated skateboarding past the hospital, healthy, smart, and happy with not a trace of autism. Is that justice? Oh yeah, some of the measles patients will die. Call it survival of the fittest, if you must.
Parents who refuse to vaccinate should sign a "I you so" agreement with the government that says the hospital can seize their house and bank accounts to pay for future measles treatment. Let the parents assume the risk! Not the taxpayers who are not superstitious. Those parents should lose very penny to reimburse doctors.
Pass a "PARENT REIMBURSEMENT ACT" in every state. All parents who refuse to vaccinate who get sick kids have to pay for everyone they infect and the doctors. It could be millions. Let them put up or shut up. Screw them!!
Long story short, the vaccine did not work for me.


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... good tour today. We drove outside of the city to Goshogawara City. It was an hour's drive through rice fields which were heavy with the ripened grain. Some fields were being harvested. Then we came to the apple orchards. Aomori is the apple capital of Japan. They go several varieties of apples, but the most famous is the Fuji apple. Warning, this ...
... sanshin, that apparently is sometimes covered in dog skin (according to our guide…a pamphlet said that they're covered in snakeskin). They use a large pic to play the sanshin (think small ice scraper size and shape), using it to pluck the 3 strings and to tap the body of the instrument. They had examples of lanterns and floats used during the Hirosaki Neputa and Aormori Nebuta festivals (which ...
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... from Hirosaki. The garden is separated into 2 parts by a 13m cliff. There is a western house which is now a tea house, a Japanese house and an Archeology Museum. We have morning tea in the tea house. Glenn has Apple Pie and coffee and I had a pot of apple tea and although we don't have to sit on the floor in true Japanese style, we do have to remove our shoes to go inside. The gardens are beautiful. The philosophy of making a garden in a Japan is to ...
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IFSC Code of STATE BANK OF INDIA (SBI) Qutubullapur branch - Ranga Reddy. Contact phone number and address
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IFSC Code Details and Qutubullapur Branch Information
STATE BANK OF INDIA - QUTUBULLAPUR is located at ANDHRA PRADESH state, RANGA REDDY district, RANGAREDDY city and the bank branch's address is [NEAR GODAVARI HOMES,RAGHAVENDRA NAGAR,QUTUBULLAPUR,HYDERABAD]. Contact phone number / numbers - BM 9652345707. The IFSC Code is SBIN0012947. Branch code is the last six characters of the IFSC Code - 012947. Individual bank branch's details are listed below.
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012947 (Last 6 Characters of the IFSC Code)
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Indian Financial System Code, Magnetic Ink Character Recognition, SWIFT Code, Address and Contact number of STATE BANK OF INDIA (SBI) - Qutubullapur branch. Branch office / ATM location : Near Godavari Homes,raghavendra Nagar,qutubullapur,hyderabad
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Cloth Covered Spool Wire - PANACEA PRODUCTS-Cloth Wire. Use this to wrap up and secure floral arrangements and decorations. This package contains 10yd of white cloth wire. Imported.View Product Specs
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Lip syncing, dancing, music: Aliso Viejo films Lip Dub
Residents of Aliso Viejo were singing and dancing through the streets Sunday as part of the city's Lip Dub, a video that combines lip syncing and audio dubbing.
More than 1,300 local businesses and residents participated in the four-hour production that ended at the Town Center fountain. Video crews drove a cart along the designated streets filming one group after another in choreographed routines to Kool and the Gang's song "Celebration" played from a speaker.
Olympic gold medalist Kyla Ross was also on hand to participate and celebrate the video's production.
The song will be combined with "Party Rock Anthem" by LMFAO to make a video for the city and You Tube that organizers hope will go viral.
Most participants were promoting their local business in an effort to draw attention to the city, bring in new business and eventually improve the economy.
"I love Aliso Viejo," said Cindy Nielsen just before a 10-second dance at the start of the video. "It's a great way to get the city on the map."
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Dr Rosemary Isaacs, Medical Director Sexual Assault and Clinical Forensic Medicine, Sydney & South West Sydney LHDs, Royal Prince Alfred & Liverpool Hospitals, Secretary, Australasian Association of Forensic Physicians presented this at the 2nd Annual Forensic Nursing Conference.
This is the only national even of its kind promoting research and leadership for Australia's Forensic Nursing Community. The program addresses future training of forensic nursing examiners, forensic mental health consmers, homicide and its aftermath, ethical dilemmas in clinical forensic medicine, child sexual abuse, providing health care to indigenous patients in the forensic arena and more.
To find out more about this conference, please visit http://www.healthcareconferences.com.au/forensicnursing


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In Touch Moblie Media
business, marketing, clients
There are many reasons to use mobile marketing to promote your business from its low cost to the ease of communicating your message global through a powerful marketing medium. SMS provides guaranteed results for business because it is a form of permission-based marketing meaning subscribers want to receive your messages as well as these reasons:
SMS is a powerful marketing channel for business providing a reach around 95% of mobile phone subscribers. (MobileProfile)
Mobile phone users have their phones with them almost 24 hours day. (Braj Mohan Chaturvedi)
90% of text messages are read within 3 minutes of being delivered. (MobileProfile)
79% of smartphone users use their phone to assist whilst shopping, with 74% making a purchase as a result. (Search Engine Land)
4.0 billion out of 6.8 Billion people own a mobile phone, making this a great communication tool for business. (60secondmarketer)
4 billion text messages are sent daily, compared to 2.9 billion daily Google searches. (60secondmarketer)
According to Marketingcharts.com, 54% of respondents had received text messages with special offers.
With more than half of those purchasing because of a marketing message received to their smartphone, made on the device itself. (Exact Target)
Mobile coupons achieve 10 times the redemption rate of traditional (print) coupons (60secondmarketer)
Half of smartphone owners have scanned QR codes causing 1 in 5 people to make a subsequent purchase. (Consumer Pulse)
The average amount of time smartphone and tablet users spend with mobile applications reached 94 minutes in December 2011, more than the 72 minutes they spend on the Web. (Flurry)
40% of smartphone users report using their device while watching TV on a daily basis. (Nielsen)
Think Local with your mobile marketing activities as 95% of smartphone users looked up local information, and of those, 61% called and 59% visited the business. (Google IPSOS)
Businesses using SMS Text messaging to market their products are confident that their messages are received instantly. (Braj Mohan Chaturvedi)
Braj Mohan Chaturvedi states that on average 94% of messages received are read immediately.
The growth rate of the iPhone was 10 times faster than AOL (60secondmarketer)
By 2013, mobile phones will overtake PCs as the most common Web access device worldwide. (Gartner)
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