gebhart/patrepeval huggingface dataset:
MiR-21 is an EGFR-regulated anti-apoptotic factor in lung cancer in never-smokers (2009)

Fifteen percent of lung cancer cases occur in never-smokers and show characteristics that are molecularly and clinically distinct from those in smokers. Epidermal growth factor receptor (EGFR) gene mutations, which are correlated with sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKIs), are more frequent in never-smoker lung cancers. In this study, microRNA (miRNA) expression profiling of 28 cases of never-smoker lung cancer identified aberrantly expressed miRNAs, which were much fewer than in lung cancers of smokers and included miRNAs previously identified (e.g., up-regulated miR-21) and unidentified (e.g., down-regulated miR-138) in those smoker cases. The changes in expression of some of these miRNAs, including miR-21, were more remarkable in cases with EGFR mutations than in those without these mutations. A significant correlation between phosphorylated-EGFR (p-EGFR) and miR-21 levels in lung carcinoma cell lines and the suppression of miR-21 by an EGFR-TKI, AG1478, suggest that the EGFR signaling is a pathway positively regulating miR-21 expression. In the never-smoker-derived lung adenocarcinoma cell line H3255 with mutant EGFR and high levels of p-EGFR and miR-21, antisense inhibition of miR-21 enhanced AG1478-induced apoptosis. In a never-smoker-derived adenocarcinoma cell line H441 with wild-type EGFR, the antisense miR-21 not only showed the additive effect with AG1478 but also induced apoptosis by itself. These results suggest that aberrantly increased expression of miR-21, which is enhanced further by the activated EGFR signaling pathway, plays a significant role in lung carcinogenesis in never-smokers, as well as in smokers, and is a potential therapeutic target in both EGFR-mutant and wild-type cases.
Mechanism of the development of nonalcoholic steatohepatitis after pancreaticoduodenectomy (2015)

These results provide a basis for understanding the pathogenesis of NAFLD/NASH following PD.
Face detection with the modified census transform (2004)

Illumination variation is a big problem in object recognition, which usually requires a costly compensation prior to classification. It would be desirable to have an image-to-image transform, which uncovers only the structure of an object for an efficient matching. In this context the contribution of our work is two-fold. First, we introduce illumination invariant local structure features for object detection. For an efficient computation we propose a modified census transform which enhances the original work of Zabih and Woodfill. We show some shortcomings and how to get over them with the modified version. S6econdly, we introduce an efficient four-stage classifier for rapid detection. Each single stage classifier is a linear classifier, which consists of a set of feature lookup-tables. We show that the first stage, which evaluates only 20 features filters out more than 99% of all background positions. Thus, the classifier structure is much simpler than previous described multi-stage approaches, while having similar capabilities. The combination of illumination invariant features together with a simple classifier leads to a real-time system on standard computers (60 msec, image size: 288/spl times/384, 2GHi Pentium). Detection results are presented on two commonly used databases in this field namely the MIT+CMU set of 130 images and the BioID set of 1526 images. We are achieving detection rates of more than 90% with a very low false positive rate of 10/sup -7/%. We also provide a demo program that can be found on the Internet http://www.iis.fraunhofer.de/bv/biometrie/download/.
De Novo Design of Saccharide−Peptide Hydrogels as Synthetic Scaffolds for Tailored Cell Responses (2009)

A new class of functional saccharide-peptide copolymer-based hydrogels was synthesized and investigated as synthetic extracellular matrices for regenerative medicine applications. The polymer was composed entirely of natural building blocks, namely, galactaric acid and lysine on the backbone, with tyrosine grafted onto the side chain as a handle for enzyme-catalyzed hydrogelation. The resulting hydrogels are degradable under simulated physiological conditions and exhibit minimal cytotoxicity on dermal fibroblast and PC-12 cells. As a demonstration of the versatility of the system, the mechanical properties of the gels can be independently controlled without changing the polymer chemical composition. Using an identical copolymer solution, by simply allowing different lengths of cross-linking time, a series of hydrogels was obtained with different mechanical moduli at constant chemical structure. The moduli of the resulting hydrogels varied stepwise from 1.7, 4.1, 6.9, and 12.5 kPa to allow for systematic studies on the effects of modulus on cell behavior. It was exciting to observe that a simple change in hydrogel physical properties could induce a direct phenotypic change in cell adhesion and proliferation. Depending on the substrate mechanical modulus, the cell morphology changed and proliferation rate differed by an order of magnitude for different cell lines. These data suggest our saccharide-peptide hydrogels as promising synthetic extracellular matrices for cell culture and tissue regeneration.
CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS (2008)

Neuroinflammation, marked by gliosis and infiltrating T cells, is a prominent pathological feature in diverse models of dominantly inherited neurodegenerative diseases. Recent evidence derived from transgenic mice ubiquitously overexpressing mutant Cu(2+)/Zn(2+) superoxide dismutase (mSOD1), a chronic neurodegenerative model of inherited amyotrophic lateral sclerosis (ALS), indicates that glia with either a lack of or reduction in mSOD1 expression enhance motoneuron protection and slow disease progression. However, the contribution of T cells that are present at sites of motoneuron injury in mSOD1 transgenic mice is not known. Here we show that when mSOD1 mice were bred with mice lacking functional T cells or CD4+ T cells, motoneuron disease was accelerated, accompanied by unexpected attenuated morphological markers of gliosis, increased mRNA levels for proinflammatory cytokines and NOX2, and decreased levels of trophic factors and glial glutamate transporters. Bone marrow transplants reconstituted mice with T cells, prolonged survival, suppressed cytotoxicity, and restored glial activation. These results demonstrate for the first time in a model of chronic neurodegeneration that morphological activation of microglia and astroglia does not predict glial function, and that the presence of CD4+ T cells provides supportive neuroprotection by modulating the trophic/cytotoxic balance of glia. These glial/T-cell interactions establish a novel target for therapeutic intervention in ALS and possibly other neurodegenerative diseases.
Targeting RET in Patients With RET-Rearranged Lung Cancers: Results From the Global, Multicenter RET Registry (2017)

Purpose In addition to prospective trials for non-small-cell lung cancers (NSCLCs) that are driven by less common genomic alterations, registries provide complementary information on patient response to targeted therapies. Here, we present the results of an international registry of patients with RET-rearranged NSCLCs, providing the largest data set, to our knowledge, on outcomes of RET-directed therapy thus far. Methods A global, multicenter network of thoracic oncologists identified patients with pathologically confirmed NSCLC that harbored a RET rearrangement. Molecular profiling was performed locally by reverse transcriptase polymerase chain reaction, fluorescence in situ hybridization, or next-generation sequencing. Anonymized data-clinical, pathologic, and molecular features-were collected centrally and analyzed by an independent statistician. Best response to RET tyrosine kinase inhibition administered outside of a clinical trial was determined by RECIST v1.1. Results By April 2016, 165 patients with RET-rearranged NSCLC from 29 centers across Europe, Asia, and the United States were accrued. Median age was 61 years (range, 29 to 89 years). The majority of patients were never smokers (63%) with lung adenocarcinomas (98%) and advanced disease (91%). The most frequent rearrangement was KIF5B-RET (72%). Of those patients, 53 received one or more RET tyrosine kinase inhibitors in sequence: cabozantinib (21 patients), vandetanib (11 patients), sunitinib (10 patients), sorafenib (two patients), alectinib (two patients), lenvatinib (two patients), nintedanib (two patients), ponatinib (two patients), and regorafenib (one patient). The rate of any complete or partial response to cabozantinib, vandetanib, and sunitinib was 37%, 18%, and 22%, respectively. Further responses were observed with lenvantinib and nintedanib. Median progression-free survival was 2.3 months (95% CI, 1.6 to 5.0 months), and median overall survival was 6.8 months (95% CI, 3.9 to 14.3 months). Conclusion Available multikinase inhibitors had limited activity in patients with RET-rearranged NSCLC in this retrospective study. Further investigation of the biology of RET-rearranged lung cancers and identification of new targeted therapeutics will be required to improve outcomes for these patients.
Transcriptional Profiling of Human Endogenous Retrovirus Group HERV-K(HML-2) Loci in Melanoma (2013)

Recent studies suggested a role for the human endogenous retrovirus (HERV) group HERV-K(HML-2) in melanoma because of upregulated transcription and expression of HERV-K(HML-2)-encoded proteins. Very little is known about which HML-2 loci are transcribed in melanoma. We assigned >1,400 HML-2 cDNA sequences generated from various melanoma and related samples to genomic HML-2 loci, identifying a total of 23 loci as transcribed. Transcription profiles of loci differed significantly between samples. One locus was found transcribed only in melanoma-derived samples but not in melanocytes and might represent a marker for melanoma. Several of the transcribed loci harbor ORFs for retroviral Gag and/or Env proteins. Env-encoding loci were transcribed only in melanoma. Specific investigation of rec and np9 transcripts indicated transcription of protein encoding loci in melanoma and melanocytes hinting at the relevance of Rec and Np9 in melanoma. UVB irradiation changed transcription profiles of loci and overall transcript levels decreased in melanoma and melanocytes. We further identified transcribed HML-2 loci formed by reverse transcription of spliced HML-2 transcripts by L1 machinery or in a retroviral fashion, with loci potentially encoding HML-2-like proteins. We reveal complex, sample-specific transcription of HML-2 loci in melanoma and related samples. Identified HML-2 loci and proteins encoded by those loci are particularly relevant for further studying the role of HML-2 in melanoma. Transcription of HERVs appears as a complex mechanism requiring specific studies to elucidate which HERV loci are transcribed and how transcribed HERVs may be involved in disease.
Generation and manipulation of droplets in an optoelectrofluidic device integrated with microfluidic channels (2009)

This letter describes an optoelectrofluidic platform integrated with microfluidic channels for continuous generation and programmable manipulation of water-in-oil droplet emulsions. A microchannel was integrated into a film-based optoelectrofluidic device by selective perforation of poly(dimethylsiloxane) layer for simultaneously performing microfluidic generation and optoelectrofluidic manipulation of droplets in a single device. By using this device, we could continuously generate, interactively transport, and merge multiple droplets using optically induced virtual electrodes.
Adipocyte-derived collagen VI affects early mammary tumor progression in vivo, demonstrating a critical interaction in the tumor/stroma microenvironment (2005)

The interactions of transformed cells with the surrounding stromal cells are of importance for tumor progression and metastasis. The relevance of adipocyte-derived factors to breast cancer cell survival and growth is well established. However, it remains unknown which specific adipocyte-derived factors are most critical in this process. Collagen VI is abundantly expressed in adipocytes. Collagen(-/-) mice in the background of the mouse mammary tumor virus/polyoma virus middle T oncogene (MMTV-PyMT) mammary cancer model demonstrate dramatically reduced rates of early hyperplasia and primary tumor growth. Collagen VI promotes its growth-stimulatory and pro-survival effects in part by signaling through the NG2/chondroitin sulfate proteoglycan receptor expressed on the surface of malignant ductal epithelial cells to sequentially activate Akt and beta-catenin and stabilize cyclin D1. Levels of the carboxyterminal domain of collagen VIalpha3, a proteolytic product of the full-length molecule, are dramatically upregulated in murine and human breast cancer lesions. The same fragment exerts potent growth-stimulatory effects on MCF-7 cells in vitro. Therefore, adipocytes play a vital role in defining the ECM environment for normal and tumor-derived ductal epithelial cells and contribute significantly to tumor growth at early stages through secretion and processing of collagen VI.
A comparative evaluation of combination therapy of fluconazole 1% and urea 40% compared with fluconazole 1% alone in a nail lacquer for treatment of onychomycosis: therapeutic trial (2011)

This is a randomized, double-blind study enrolling 70 patients with onychomycosis of the finger and toenails. Clinical and mycological efficacies as well as measures of safety were assessed monthly for a maximum of 6 months of treatment. The treatment regimens were: fluconazole 1% and fluconazole 1% with urea 40%. These results indicated topical treatment of onychomycosis with a combination of fluconazole 1% and urea 40% was more effective (82.8%) than fluconazole 1% (62.8%) nail lacquer alone in treatment of dermatophytic onychomycosis. Fluconazole was well tolerated and side effects were negligible. At the end of therapy and the end of the 6-month follow-up, fluconazole 1% and urea 40% demonstrated statistically significant superiority in clinical and mycological responses compared with fluconazole 1% alone.
Metalloenediynes:  Ligand Field Control of Thermal Bergman Cyclization Reactions  [J. Am. Chem. Soc. 2000, 122, 7208−7217]. (2000)

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionMetalloenediynes: Ligand Field Control of Thermal Bergman Cyclization Reactions [J. Am. Chem. Soc.2000, 122, 7208−7217]. Pedro J. Benites, , and Jeffrey M. ZaleskiCite this: J. Am. Chem. Soc. 2000, 122, 40, 9882Publication Date (Web):September 21, 2000Publication History Published online21 September 2000Published inissue 1 October 2000https://pubs.acs.org/doi/10.1021/ja004659ghttps://doi.org/10.1021/ja004659gcorrectionACS PublicationsCopyright © 2000 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views380Altmetric-Citations1LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (8 KB) Get e-Alertsclose Get e-Alerts
Preventing bots from playing online games (2005)

As multiplayer online gaming gains in economic and social importance, an increasingly large number of players is beginning to rely on bots (automated player agents) to gain unfair advantages in games. In this article we study the problem of restricting participation in online games to human players so they can enjoy the game without interference from the bots. We propose two broad approaches to prevent bots from playing online games. The first consists of seamlessly integrating software-based tests (known as reverse Turing tests or CAPTCHA tests) into online games to tell humans and computers apart. Our second contribution is to propose hardware instantiations of CAPTCHA tests. Our techniques are applicable in a wide variety of online games, from poker to "shoot'em ups." They are cost-effective, immune to cheating, and preserve the human players' enjoyment of each game. We conclude with a discussion of how approaches to deter the use of bots may complement our techniques to detect bots.
Functional dissection of the murine lck distal promoter (1995)

The lymphocyte-specific proto-oncogene lck is transcribed from two developmentally regulated, independently functioning promoters. The proximal promoter is used in thymocytes, but not in peripheral T lymphocytes. The distal promoter operates in all stages of T cell development, but predominates in more mature cells. Both promoters lack a TATAA element and they share little sequence similarity with each other. Using transgenic mice to locate in vivo functional cis-acting regions of the murine distal promoter, we defined a region from -1786 to -2913 that is essential for consistent insertion site-independent expression of a heterologous cDNA reporter. The transgene is lymphoid specific and expressed predominantly in T cells. One of four transgenic mice bearing a shortened distal promoter (-886 to +41) expressed the reporter in the expected developmental pattern, suggesting that important regulatory elements that require favorable flanking sequences for expression are present nearer the transcription start site. The DNA sequence from -4032 to +623 contains few consensus binding sites for previously described T lymphocyte-specific trans-acting factors, and their locations do not correlate well with the functional data. However, the locations of tissue-specific modifications of chromatin structure in the promoter region, manifest as sites of DNase hypersensitivity, correlated with these two functional regions in normal mice. The identification of lck distal promoter regulatory regions provides a useful control element for deliberate expression of transgenes in mature T lymphocytes. In addition, these regulatory regions should assist in defining T cell-specific trans-acting factors.
AN EFFICIENT SYNTHESIS OF (2S,3R)- AND (2S,3S)-SPHINGOSINE (1985)

Abstract A straightforward sequence of reactions allows the conversion of D(+)-Mannose and D(+)-ribono-1,4-lactone into “erythro”-(2S,3R)-and “threo”-(2S,3S)-sphingosine, respectively.
Three different mRNAs encoding human granulocyte colony-stimulating factor receptor. (1990)

Three cDNAs for the human granulocyte colony-stimulating factor (G-CSF) receptor were isolated from the cDNA libraries of human U937 leukemia cells and placenta by using a murine G-CSF receptor cDNA as the probe. The human G-CSF receptor containing 813 amino acids had a marked homology (62.5%) with its murine counterpart and consisted of extracellular, transmembrane, and cytoplasmic domains. The WSXWS motif found in members of the newly identified growth factor receptor family was also present in the extracellular domain of the human G-CSF receptor. Expression of the cloned cDNA in monkey COS cells gave rise to a protein that could specifically bind G-CSF with a high affinity (Kd, 550 pM). Two other classes of the human G-CSF receptor were also identified, one of which had a deletion of the transmembrane domain and seemed to encode a secreted, soluble receptor. The third class of the G-CSF receptor contained a 27-amino acid insertion in the cytoplasmic domain and was highly expressed in placenta.
Viral dynamics in hepatitis B virus infection. (1996)

Treatment of chronic hepatitis B virus (HBV) infections with the reverse transcriptase inhibitor lamivudine leads to a rapid decline in plasma viremia and provides estimates for crucial kinetic constants of HBV replication. We find that in persistently infected patients, HBV particles are cleared from the plasma with a half-life of approximately 1.0 day, which implies a 50% daily turnover of the free virus population. Total viral release into the periphery is approximately 10(11) virus particles per day. Although we have no direct measurement of the infected cell mass, we can estimate the turnover rate of these cells in two ways: (i) by comparing the rate of viral production before and after therapy or (ii) from the decline of hepatitis B antigen during treatment. These two independent methods give equivalent results: we find a wide distribution of half-lives for virus-producing cells, ranging from 10 to 100 days in different patients, which may reflect differences in rates of lysis of infected cells by immune responses. Our analysis provides a quantitative understanding of HBV replication dynamics in vivo and has implications for the optimal timing of drug treatment and immunotherapy in chronic HBV infection. This study also represents a comparison for recent findings on the dynamics of human immunodeficiency virus (HIV) infection. The total daily production of plasma virus is, on average, higher in chronic HBV carriers than in HIV-infected patients, but the half-life of virus-producing cells is much shorter in HIV. Most strikingly, there is no indication of drug resistance in HBV-infected patients treated for up to 24 weeks.
Seed Treatment Evaluated for Greenbug Control in Sorghum, 1994 (1995)

Abstract Seed of three sorghum hybrids treated with 0, 2 or 4 oz AI of Gaucho per cwt were furnished by Gustafson, Inc. The hybrids used in the study were NC+ 271 (greenbug susceptible), DK 56 (biotype- E resistant), and Cargill 607E, (biotype-I resistant). All three hybrids were pretreated with Captan and Concept and the DK 56 was also pretreated with Apron. The seed was planted on 24 May in a modified Latin square design with three replications. Each plot was two rows wide (5 ft) and 22 ft long. The seed was planted at the rate of 5 g per row using a cone planter. On 23 Jul corn leaf aphid and greenbug populations were monitored by cutting off two plants per plot and counting the number of aphids on the plant and removing the whorl and counting the number of aphids observed as the leaves were unrolled. On 4-5 Aug, two plants were cut off at the base and visually examined to estimate greenbug numbers. Yield data were collected by machine harvesting the plots on 27 Oct.
Protein chemical synthesis by serine and threonine ligation (2013)

An efficient method has been developed for the salicylaldehyde ester-mediated ligation of unprotected peptides at serine (Ser) or threonine (Thr) residues. The utility of this peptide ligation approach has been demonstrated through the convergent syntheses of two therapeutic peptides--ovine-corticoliberin and Forteo--and the human erythrocyte acylphosphatase protein (∼11 kDa). The requisite peptide salicylaldehyde ester precursor is prepared in an epimerization-free manner via Fmoc-solid-phase peptide synthesis.