bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stress-Inducible Alternative Translation Initiation of Human Cytomegalovirus Latency Protein pUL138
Authors: Grainger Lora , Cicchini Louis , Rak Michael , Petrucelli Alex , Fitzgerald Kerry D. , Semler Bert L. , Goodrum Felicia 
Published: July 2010

ABSTRACTWe have previously characterized a 21-kDa protein encoded byUL138(pUL138) as a viral factor inherent to low-passage strains of human cytomegalovirus (HCMV) that is required for latent infectionin vitro. pUL138 is encoded on 3.6-, 2.7-, and 1.4-kb 3′ coterminal transcripts that are produced during productive and latent infections. pUL138 is encoded at the 3′ end of each transcript and is preceded by an extensive 5′ sequence (∼0.5 to 2.5 kb) containing several putative open reading frames (ORFs). We determined that three putative ORFs upstream ofUL138(UL133,UL135, andUL136) encode proteins. TheUL138transcripts are polycistronic, such that each transcript expresses pUL138 in addition to the most-5′ ORF. The upstream coding sequences (CDS) present a significant challenge for the translation of pUL138 in mammalian cells. We hypothesized that sequences 5′ ofUL138mediate translation initiation of pUL138 by alternative strategies. Accordingly, a 663-nucloetide (nt) sequence overlapping theUL136CDS supported expression of a downstream cistron in a bicistronic reporter system. We did not detect cryptic promoter activity or RNA splicing events that could account for downstream cistron expression. These data are consistent with the sequence element functioning as an internal ribosome entry site (IRES). Interestingly, pUL138 expression from the 3.6- and 2.7-kb transcripts was induced by serum stress, which concomitantly inhibited normal cap-dependent translation. Our work suggests that an alternative and stress-inducible strategy of translation initiation ensures expression of pUL138 under a variety of cellular contexts. TheUL138polycistronic transcripts serve to coordinate the expression of multiple proteins, including a viral determinant of HCMV latency.
Genetic and Phenotypic Characterization of GII-4 Noroviruses That Circulated during 1987 to 2008
Authors: Yang Yang , Xia Ming , Tan Ming , Huang Pengwei , Zhong Weiming , Pang Xiao Li , Lee Bonita E. , Meller Jarek , Wang Tao , Jiang Xi 
Published: July 2010

ABSTRACT
The predominance and continual emergence of new variants in GII-4 noroviruses (NVs) in recent years have raised questions about the role of host immunity and histo-blood group antigens (HBGAs) in NV evolution. To address these questions, we performed a genetic and phenotypic characterization of GII-4 variants circulating in the past decade (1998 to 2008). Ninety-three GII-4 sequences were analyzed, and of them, 16 strains representing 6 genetic clusters were selected for further characterization. The HBGA binding properties were determined by both saliva- and oligosaccharide-binding assays using P particles as a model of NV capsid. The antigenic properties were also examined by enzyme immunoassay (EIA), Western blot analysis, and receptor blocking assay, using P-particle-specific antibodies from immunized mice and GII-4 virus-infected patients. Our results showed that 15 of the 16 GII-4 viruses bound to saliva of all A, B, and O secretors. Oligosaccharide binding assays yielded largely consistent results, although the binding affinities to some oligosaccharides varied among some strains. The only nonbinder had a mutation in the binding site. While antigenic variations were detected among the 16 strains, significant cross-blocking on the HBGA binding was also noted. Sequence alignment revealed high conservation of HBGA binding interfaces with some variations in adjacent regions. Taken together, our data suggested that the ability of GII-4 to recognize different secretor HBGAs persisted over the past decade, which may explain the predominance of GII-4 over other genotypes. Our data also indicated that both the host immunity and HBGAs play a role in NV evolution. While host immunity may continue driving NV for antigenic change, the functional selection by the HBGAs tends to lock the architecture of the capsid/HBGA interfaces and allows only limited variations outside the HBGA binding sites. A potential outcome of such counterselection between theses two factors in NV evolution is discussed.
LEAVING AN UNKNOWN MAZE USING AN ERROR-PRONE COMPASS
Authors: KAMPHANS TOM , LANGETEPE ELMAR 
Published: July 2010

Imagine you are trapped in a maze of caves. All you have is an old rusty compass and barely enough light to read it. How much inaccuracy can you allow to ensure that you can leave the maze? Or you are walking in a maze of hedgerows that are on the whole orthogonal. Can you find the exit by counting left and right turns?We consider the problem of escaping from an unknown polygonal maze under limited resources and errors in inputs and motion. It is well known that the Pledge algorithm always finds a path out of an unknown maze without any means of orientation—provided that such a path exists—but it relies on fact that inputs and motions are correct.
GUARDING A POLYGON FROM TWO NEARLY-OPPOSITE DIRECTIONS
Authors: BRASS PETER , NA HYEON-SUK , SHIN CHAN-SU 
Published: July 2010

In this paper, we study a variant of the classical art-gallery problem, in which we require that each point of the art gallery is observed by two guards from nearly-opposite directions, ideally from front and back. We call a polygon P α-guarded by a set G of guards if every point p in P is visible from two guards g1,g2 in G satisfying α ≤ ∠g1pg2 ≤ π. We show that any simple n-gon is ⅔π-guarded by its n vertex guards, and there are simple n-gons that require at least n guards. Any simple n-gon can be (π – δ)-guarded by [Formula: see text] guards, and there are simple n-gons that require at least [Formula: see text] guards in any guard placement. We prove that the region of a simple n-gon that is α-guarded by k guards can have Θ(nk + k4) complexity in the worst case. Given simple n-gon P and k guard positions, we can decide for a fixed 0 < α < π whether P is α-guarded in O((nk2 + k4) log 2 nk) time and find the largest α < π for which P is α-guarded in O((nk2 + k4) log 6 nk) time.
Molecular Analysis of Plasma DNA for the Early Detection of Lung Cancer by Quantitative Methylation-Specific PCR
Authors: Ostrow Kimberly Laskie , Hoque Mohammad O. , Loyo Myriam , Brait Marianna , Greenberg Alissa , Siegfried Jill M. , Grandis Jennifer R. , Gaither Davis Autumn , Bigbee William L. , Rom William , Sidransky David 
Published: July 2010

Abstract
Purpose: Aberrant promoter hypermethylation of tumor suppressor genes is a promising marker for lung cancer detection. We investigated the likelihood of detecting aberrant DNA methylation of tumor suppressor genes in plasma samples of patients with abnormalities of the lung detected upon computed tomography (CT) scan.
Experimental Design: In a small evaluation cohort, four gene promoters (DCC, Kif1a, NISCH, and Rarb) were found to be methylated with increased frequency in samples from cancer patients specifically. We then examined DNA from 93 plasma samples from patients with abnormal findings in the lung detected upon CT scan for aberrant methylation of these four gene promoters by quantitative fluorogenic real-time PCR. The patients were divided into two groups, ground glass opacity (n = 23) and cancerous tumors (n = 70). Plasma DNA from age-matched nodule-free individuals were used as controls (n = 80).
Results: In plasma, 73% of patients with cancerous tumors showed methylation of at least one gene with a specificity of 71% (P = 0.0001). Only 22% patients with ground glass opacity exhibited methylation of at least one gene. When smoking history was taken into account, 72% of cancer patients with no smoking history or those who smoked &lt;20 pack-years showed methylation of at least one gene with 100% specificity (P = 0.05) when compared with matched controls. Among heavy smokers with 20+ pack-years of smoking history, 30% of the control group and 73% of the patients with cancerous tumors showed methylation (P = 0.0001).
Conclusions: These biomarkers can distinguish between cancerous and noncancerous abnormal CT findings. Clin Cancer Res; 16(13); 3463–72. ©2010 AACR.
BRCA1 Loss Preexisting in Small Subpopulations of Prostate Cancer Is Associated with Advanced Disease and Metastatic Spread to Lymph Nodes and Peripheral Blood
Authors: Bednarz Natalia , Eltze Elke , Semjonow Axel , Rink Michael , Andreas Antje , Mulder Lennart , Hannemann Juliane , Fisch Margit , Pantel Klaus , Weier Heinz-Ulrich G. , Bielawski Krzysztof P. , Brandt Burkhard 
Published: July 2010

Abstract
Purpose: A preliminary study performed on a small cohort of multifocal prostate cancer (PCa) detected BRCA1 allelic imbalances among circulating tumor cells (CTC). The present analysis was aimed to elucidate the biological and clinical roles of BRCA1 losses in metastatic spread and tumor progression in PCa patients.
Experimental Design: To map molecular progression in PCa outgrowth, we used fluorescence in situ hybridization analysis of primary tumors and lymph node sections, and CTCs from peripheral blood.
Results: We found that 14% of 133 tested patients carried monoallelic BRCA1 loss in at least one tumor focus. Extended molecular analysis of chr17q revealed that this aberration was often a part of larger cytogenetic rearrangement involving chr17q21 accompanied by allelic imbalance of the tumor suppressor gene PTEN and lack of BRCA1 promoter methylation. The BRCA1 losses correlated with advanced T stage (P &lt; 0.05), invasion to pelvic lymph nodes (P &lt; 0.05), as well as biochemical recurrence (P &lt; 0.01). Their prevalence was twice as high within 62 lymph node metastases (LNM) as in primary tumors (27%, P &lt; 0.01). The analysis of 11 matched primary PCa-LNM pairs confirmed the suspected transmission of genetic abnormalities between these two sites. In four of seven patients with metastatic disease, BRCA1 losses appeared in a minute fraction of cytokeratin- and vimentin-positive CTCs.
Conclusions: Small subpopulations of PCa cells bearing BRCA1 losses might be one confounding factor initiating tumor dissemination and might provide an early indicator of shortened disease-free survival. Clin Cancer Res; 16(13); 3340–8. ©2010 AACR.
Mutation of SDHB is a Cause of Hypoxia-Related High-Altitude Paraganglioma
Authors: Cerecer-Gil Nidia Y. , Figuera Luis E. , Llamas Francisco J. , Lara Mauricio , Escamilla José G. , Ramos Ruben , Estrada Gerardo , Hussain A. Karim , Gaal José , Korpershoek Esther , de Krijger Ronald R. , Dinjens Winand N.M. , Devilee Peter , Bayley Jean Pierre 
Published: July 2010

Abstract
Purpose: Paragangliomas of the head and neck are neuroendocrine tumors and are associated with germ line mutations of the tricarboxylic acid cycle–related genes SDHB, SDHC, SDHD, and SDHAF2. Hypoxia is important in most solid tumors, and was directly implicated in tumorigenesis over 40 years ago when it was shown that dwelling at high altitudes increases the incidence of carotid body hyperplasia and paragangliomas. Although recent research has now elucidated several pathways of hypoxia in paragangliomas, nothing is currently known of the genetics or of gene-environment interactions in high-altitude paraganglioma. We postulated that SDH mutations might play a role in these tumors.
Experimental Design: Patients from a Mexican family, originating and resident in Guadalajara, were tested for mutations of SDHD, and subsequently, for mutations of SDHB followed by immunohistochemical confirmation of SDHB loss.
Results: Two patients, born and resident at altitudes of between 1,560 and 2,240 m, were found to have head and neck paragangliomas, including a remarkably aggressive recurrent tumor. Mutation analysis identified a pathogenic missense mutation in exon 7 of SDHB, c.689G&gt;A, p.Arg230His, and loss of the SDHB protein was confirmed by immunohistochemistry.
Conclusions: This is the first report of a SDH gene mutation in paraganglioma at high altitude. A rapidly recurrent head and neck paraganglioma is a very rare finding in an SDH mutation carrier, suggesting a gene-environment interaction. Neither patient showed evidence of sympathetic paraganglioma. Clin Cancer Res; 16(16); 4148–54. ©2010 AACR.
Multimodality Imaging Reveals a Gradual Increase in Matrix Metalloproteinase Activity at Aneurysmal Lesions in Live Fibulin-4 Mice
Authors: Kaijzel Eric L. , van Heijningen Paula M. , Wielopolski Piotr A. , Vermeij Marcel , Koning Gerben A. , van Cappellen Wiggert A. , Que Ivo , Chan Alan , Dijkstra Jouke , Ramnath Natasja W.M. , Hawinkels Lukas J.A.C. , Bernsen Monique R. , Löwik Clemens W.G.M. , Essers Jeroen 
Published: July 2010

Background—

We imaged the protease activity of matrix metalloproteinases (MMPs) upregulated during aneurysm formation, using protease-activatable near-infrared fluorescence probes. We tested whether these protease-activatable sensors can directly report the in vivo activity of the key biomarkers in aneurysm, using our genetically modified fibulin-4 mouse models for aneurysm formation. Mice homozygous for the fibulin-4 reduced-expression allele (fibulin-4
R/R
) show dilatation of the ascending aorta and a tortuous, stiffened aorta resulting from disorganized elastic fiber networks. Strikingly, even a moderate reduction in expression of fibulin-4 in the heterozygous fibulin-4
+/R
mice occasionally results in modest aneurysm formation.

Methods and Results—

Aorta transcriptome and protein expression analysis of fibulin-4
+/R
and fibulin-4
R/R
animals identified excessive transforming growth factor-β signaling as the critical event in the pathogenesis of aneurysm formation. To determine whether a perturbed elastin lamellar structure arose from induction of transforming growth factor-β-regulated MMPs, we performed gelatin zymography and used a protease-activatable near-infrared fluorescence probe to monitor and quantify MMP upregulation in animals, using various in vivo optical imaging modules and coregistration of the fluorescence signal with CT images of the same animals. Gelatin zymography demonstrated a significant increase in the presence of the active form of MMP-9 in the aortic arch of fibulin-4
R/R
mice. In vivo analysis of MMP upregulation using the near-infrared fluorescence probe and subsequent isosurface concentration mapping from reconstructed tomographic images from fibulin-4
+/R
and fibulin-4
R/R
mice revealed a graded increase in activation of MMPs within the aneurysmal lesions.

Conclusions—
We aimed to develop molecular imaging procedures for faster, earlier, and easier recognition of aortic aneurysms. We show that in vivo coregistration of MMP activity by noninvasive tomographic imaging methods allows the detection of increased MMP activity, even before the aneurysm has actually formed.
Rembrandt, de verwarde bruidegom
Authors: Groeneweg Irene 
Published: July 2010

AbstractThe signature on Rembrandt's little sketch of Saskia in silver point on parchment, bearing the date '8 juni 1633', has long been a source of puzzlement. For how can Rembrandt's remarks - that Saskia was his wife and that on June 8 of that year the couple had been married for three days - be reconciled with the true date of their wedding, June 22 1634, recorded in the register of marriages of Sint-Annaparochie in Friesland? There is however an explanation for the mystifying caption. First, Rembrandt had written that Saskia was 21 years old. Her baptism was registered on August 2 1612, so that she was still only 20 in June 1633. Furthermore, it was compulsory by law to give notice of a marriage, after registration at the town hall and prior to the actual ceremony, by means of a public announcement in the next three weeks. The banns were usually called in church on three successive Sundays. Rembrandt's and Saskia's first bann was called in the church at Sint-Annaparochie on Sunday June 8 1634 - according to the Julian calendar still used in Friesland at that time, which was ten days behind the Gregorian calendar adhered to in Holland. On June 22, the Sunday of the third announcement, their marriage was solemnized. In the seventeenth century, however, many people regarded the day on which the banns were first called as the actual wedding-day, for the betrothed couple could no longer change their minds. Rembrandt and Saskia, then, regarded their wedding-day as June 8 1634 - according to the Frisian calendar. The caption to the sketch thus correctly reads: This is my 21-year-old wife, drawn three days after our wedding-day, and that was on June 8.
Knabe im Atelier und Bücherstilleben, zwei frühe Gemälde von Jan Lievens und ihr Leidener Kontext: Rembrandt, Jan Davidz. de Heem, Pieter Codde
Authors: Schnackenburg Bernhard 
Published: July 2010

AbstractA painting entitled Le jeune Dessinateur (the young draughtsman), identified in 1932 by Hans Schneider as an early work by Jan Lievens and hung in the Louvre together with Rembrandt, should still, according to prevailing scholarly opinion, be attributed to the much younger Wallerent Vaillant on the basis of a reproduction engraving with his address. It was made after Vaillant and Michael Sweerts had come across the more than 30-year old Lievens painting in about 1660 which inspired them to make variants of their own in the style of their times - variants which Vaillant also published as engravings. This important consequence underlines the status of an unrecognised major work by the young Jan Lievens, a work which in terms of content and form has much to tell us about painting in Leiden around 1628. The curious iconography (the boy is not drawing, but studying drawings, in keeping with Schneider's understanding of the title, Knabe in Atelier (Boy in the Studio), is found only in Pieter Codde's work of that period. Codde owned many works by Leiden painters, prompting Abraham Bredius to suggest as early as 1888 that this Amsterdam painter worked in Leiden for a while. A studio prop in the form of a plaster cast of the infant Jesus from Michelangelo's Bruges Madonna casts a new light on Lievens' interest in the great exemplars of classical art, an interest which Constantijn Huygens failed to perceive when he visited the studio. Lievens had depicted the figure before, in oblique perspective ; it was evidently important for the training of his ability to render three-dimensionality. The group of studio plaster casts is related to a hitherto anonymous Leiden Still Life with Books dating from about 1628, in the Alte Pinakothek, Munich. Discussed earlier in connection with Lievens, this still life is now assigned to Lievens himself, an attribution which is supported by additional arguments. The choice of motif and monochrome colouring has aspects in common with the Vanitas and still lifes with books painted by Jan Davidz. de Heem during the same period and endorsing, with new arguments, his connection with Lievens' and Rembrandt's circle. Lievens' Boy in the Studio, finally, is of significance for the interpretation of Rembrandt's Young Painter in the Studio in Boston, painted at the same time. The two pictures would appear to be linked by antithetical basic statements and art education.
Rembrandts eerste reis naar Friesland
Authors: Broos Ben 
Published: July 2010

AbstractOn at least three occasions (in 1633, 1634 and in 1635) Rembrandt visited the village of Sint Annaparochie in Het Bildt, where Saskia Uylenburgh lived from her fourteenth to her twentieth year. Biographies of the artist discuss only the days surrounding his marriage to Saskia in the Frisian village on 22 June 1634. The present report concerns Rembrandt's very first visit to Friesland, in 1633. His last visit to Het Bildt can be dated to 12 July 1635, when Saskia served as witness at the baptism of her young niece Antje van Loo, the fourth child of her sister Hiskia Uylenburgh, who was married to Gerrit van Loo, Het Bildt's municipal secretary. Saskia was presumably also present with Rembrandt at the baptism of Hiskia's third child, Sophia, on 2 June 1633. On 8 June he drew his famous portrait of Saskia in silverpoint on parchment. In 1853, A. Wassenbergh, pastor of Sint Annaparochie, published the details on the baptisms of the Van Loo children in the church register, including the presence of Titia Uylenburgh as witness in 1633. The importance of this document has been underestimated. Titia had married François Coopal of Flushing. He turns out to have registered at Franeker's university (a veritable Uylenburgh bastion), which explains his marriage around 1628 to Saskia's sister Titia. Titia and/or her husband were also witnesses at the baptism of every one of Rembrandt and Saskia's children. The document that indirectly establishes Rem-brandt's presence in Sint Annaparochie from 2 to 8 June 1633 is important. Rembrandt carried with him a kind of sketchbook, of which three parchment leaves have survived. One of them shows his engagement portrait of Saskia. The two other sheets, drawn on both sides, feature three landscapes. The stylistic connection between these sheets and the then uncommon subject matter, the landscape, has been noted by Schatborn, Schneider and Van de Wetering. The type of farm depicted is not Dutch but more likely Frisian. The date on the portrait, 8 June 1633, is a sound benchmark for the dating of the landscapes. The second sheet was later substantially cropped to turn the studies of the heads on the back into the main depiction. The third sheet, a view of some farm's still has its original format. The back of this sheet shows a panorama with a view of a village. Until recently a matt obscured the correspondence in format with Saskia's portrait. The panoramic landscape deserves closer consideration because it must have been done in Sint Annaparochie and could therefore depict the surroundings of the village. 'Het Bildt' is depicted on a map in Schotanus' 1664 Beschryvinge ... van Frieslandt. The situation in Rembrandt's drawing corresponds closely with the plan of the area as reproduced on Schotanus' map: from left to right we see Sint Annaparochie, a copse of trees to the north of what the map calls 'Vogel', and, probably, Vrouwenparochie, with summarily indicated spire. In June of 1633, in my opinion, Rembrandt drew the surroundings of the village in which he was to marry Saskia in July of 1634.
Selbstdarstellung und Spezialistentum in der niederländischen Malerei des I7. Jahrhunderts - ein neuer Fund zur Biographie Hendrick van Steenwijcks d.J
Authors: Nicolaisen Jan 
Published: July 2010

AbstractAn inscription in a painting of I636 depicting a church interior by the painter Hendrick van Steenwijck the Younger in the Museum der bildenden Künste Leipzig (Maximilian Speck von Stern-burg Foundation, Inv.No. I62I) has not been read correctly until today. It deserves attention, since it turns out to be the artist's signature and the only surviving source of information about the place and date of Steenwijck the Younger's birth. It reads: H.V.S. nat(us). Ant(werpen).// Ao MDLXXX M(ens). Sept(embris). The inscription is part of an epitaph in which there is also a portrait of Steenwijck the Younger, resembling his portrait by Anton van Dyck in the portrait series of the "Iconographie" published around the same date. The article links this rare case of an artist's self-representation in a painting with the biographical situation of Steenwijck, who probably returned from London to The Hague in I638. An analysis of the painting shows how Steenwijck the Younger integrated this monumental self-representation with the painting and its decoration with altarpieces. The artist himself looks out of the painting, stimulating a direct contact with the viewer, who is furthermore encouraged by numerous minute and delicately painted details to look closely at the painting.