gebhart/patrepeval huggingface dataset:
Aberrantly Methylated CDKN2A, MGMT, and MLH1 in Colon Polyps and in Fecal DNA from Patients with Colorectal Polyps (2005)

Colon cancer is the third leading cause of cancer-related death in the United States, affecting approximately 147,000 people each year. Most colon cancers arise from benign neoplasms and evolve into adenocarcinomas through a stepwise histologic progression sequence that starts from adenomas or hyperplastic polyps/serrated adenomas. Genetic alterations and, more recently, epigenetic alterations have been associated with specific steps in this polyp-adenocarcinoma sequence and likely drive the histologic progression of colon cancer. Consequently, we have assessed in colon adenomas and hyperplastic polyps the methylation status of MGMT, CDKN2A, and MLH1 to determine the timing and frequency of these events in the polyp-carcinoma progression sequence and subsequently to analyze the potential for these methylated genes to be molecular markers for adenomas and hyperplastic polyps. We have found that methylated MGMT, CDKN2A, and MLH1 occur in 49%, 34%, and 7% of adenomas and in 5%, 10%, and 7% of hyperplastic polyps, respectively, and that they are more common in histologically advanced adenomas. Furthermore, analysis of fecal DNA from persons who have undergone colonoscopic exams revealed methylated CDKN2A, MGMT, and MLH1 in fecal DNA from 31%, 48%, and 0% of individuals with adenomas and from 16%, 27%, and 10% of individuals with no detectable polyps, respectively. These results show that aberrant methylated genes can be detected frequently in sporadic colon polyps and that they can be detected in fecal DNA. Notably, improvements in the specificity and sensitivity of the fecal DNA-based assays will be needed to make them clinically useful diagnostic tests for polyps.
Object-level vertical search (2007)

Current web search engines essentially conduct document-level ranking and retrieval. However, structured information about realworld objects embedded in static webpages and online databases exists in huge amounts. We explore a new paradigm to enable web search at the object level in this paper, extracting and integrating web information for objects relevant to a specific application domain. We then rank these objects in terms of their relevance and popularity in answering user queries. In this paper, we introduce the overview and core technologies of object-level vertical search engines that have been implemented in two working systems: Libra Academic Search (http://libra.msra.cn) and Windows Live Product Search (http://products.live.com).
Autologous antitumor activity by NK cells expanded from myeloma patients using GMP-compliant components (2008)

Multiple myeloma (MM) is an incurable plasma cell malignancy with poor outcome. The most promising therapeutic options currently available are combinations of transplantation, targeted pharmacotherapy, and immunotherapy. Cell-based immunotherapy after hematopoietic stem-cell transplantation has been attempted, but with limited efficacy. Natural killer (NK) cells are interesting candidates for new means of immunotherapy; however, their potential clinical use in MM has not been extensively studied. Here, we explored the possibility of expanding NK cells from the peripheral blood of 7 newly diagnosed, untreated MM patients, using good manufacturing practice (GMP)-compliant components. After 20 days of culture, the number of NK cells from these patients had expanded on average 1600-fold. Moreover, expanded NK cells showed significant cytotoxicity against primary autologous MM cells, yet retained their tolerance against nonmalignant cells. Based on these findings, we propose that autologous NK cells expanded ex vivo deserve further attention as a possible new treatment modality for MM.
Compact directional coupler switches using quantum well electrorefraction (1989)

We have utilized excitonic electrorefraction in reverse-biased InGaAsP/InP quantum well heterostructures to produce directional coupler switches with active lengths under 600 μm operating at 1.3 and 1.55 μm wavelengths.
Gene therapeutic strategies for neurodegenerative diseases. (2000)

Gene transfer into the central nervous system by ex vivo or in vivo techniques is a rapidly emerging field in neuroscience. Potential applications of gene therapy for the nervous system include not only congenital single gene disorders, but also brain tumors and acquired chronic diseases. Considerable progress has been made in the understanding of neurodegenerative diseases such as Parkinson's and Alzheimer's disease. As a result, gene therapy for Parkinson's, and possibly Alzheimer's disease could be regarded as a realistic alternative to the limited treatment options currently available. In this review, we highlight the most important developments in gene transfer techniques as well as the newest insights in the mechanisms of some neurodegenerative disorders and put these into the perspective of gene therapeutic strategies for the central nervous system.
Id1 cooperates with oncogenic Ras to induce metastatic mammary carcinoma by subversion of the cellular senescence response (2008)

Recent evidence demonstrates that senescence acts as a barrier to tumorigenesis in response to oncogene activation. Using a mouse model of breast cancer, we tested the importance of the senescence response in solid cancer and identified genetic pathways regulating this response. Mammary expression of activated Ras led to the formation of senescent cellular foci in a majority of mice. Deletion of the p19(ARF), p53, or p21(WAF1) tumor suppressors but not p16(INK4a) prevented senescence and permitted tumorigenesis. Id1 has been implicated in the control of senescence in vitro, and elevated expression of Id1 is found in a number of solid cancers, so we tested whether overexpression of Id1 regulates senescence in vivo. Although overexpression of Id1 in the mammary epithelium was not sufficient for tumorigenesis, mice with expression of both Id1 and activated Ras developed metastatic cancer. These tumors expressed high levels of p19(Arf), p53, and p21(Waf1), demonstrating that Id1 acts to make cells refractory to p21(Waf1)-dependent cell cycle arrest. Inactivation of the conditional Id1 allele in established tumors led to widespread senescence within 10 days, tumor growth arrest, and tumor regression in 40% of mice. Mice in which Id1 expression was inactivated also exhibited greatly reduced pulmonary metastatic load. These data demonstrate that established tumors remain sensitive to senescence and that Id1 may be a valuable target for therapy.
LUNG PATHOLOGY IN PLATELET-DERIVED GROWTH FACTOR TRANSGENIC MICE: EFFECTS OF GENETIC BACKGROUND AND FIBROGENIC AGENTS (2002)

We previously developed transgenic mice expressing human platelet-derived growth factor B chain (PDGF-B) from the lung-specific surfactant protein C (SPC) promoter. These mice developed enlarged airspaces, inflammation, and fibrosis of varying severity. In the present study we examined potential causes of this phenotypic variation and tested whether constitutive PDGF-B expression exacerbated fibrosis induced by bleomycin and silica. The SPC-PDGFB transgene construct was modified by replacement of the PDGF-B 3' UTR, which contains motifs known to mediate instability in other cytokine genes, with SV40 sequences containing an intron and polyadenylation signal. This modification resulted in an increase in the efficiency with which the construct was expressed, but no difference in lung pathology was observed compared to the original construct. Backcrossing of mice carrying the original SPC-PDGFB construct to C57BL/6 and SJL inbred strains resulted in a more severe phenotype in SJL-bred mice compared to C57BL/6-bred mice after 4 generations. To determine whether SPC-PDGFB transgenic mice had increased susceptibility to fibrogenic agents, the mice were treated with bleomycin or silica. No significant differences were detected in lung weight, hydroxyproline content, or histopathologic changes between transgenic and wild-type mice after bleomycin or silica treatment. These results demonstrate that the amount of PDGF-BB produced in wild-type mice is not a limiting factor in the development of bleomycin- or silica-induced pulmonary fibrosis.
Chromosome painting using repetitive DNA sequences as probes for somatic chromosome identification in maize (2004)

Study of the maize (Zea mays L.) somatic chromosomes (2n = 20) has been difficult because of a lack of distinguishing characteristics. To identify all maize chromosomes, a multicolor fluorescence in situ hybridization procedure was developed. The procedure uses tandemly repeated DNA sequences to generate a distinctive banding pattern for each of the 10 chromosomes. Fluorescence in situ hybridization screening trials of nonsubtracted or subtracted PCR libraries resulted in the isolation of microsatellite 1-26-2, subtelomeric 4-12-1, and 5S rRNA 2-3-3 clones. These three probes, plus centromeric satellite 4 (Cent4), centromeric satellite C (CentC), knob, nucleolus-organizing region (NOR), pMTY9ER telomere-associated sequence, and tandemly repeated DNA sequence 1 (TR-1) were used as a mixture for hybridization to root-tip chromosomes. All 10 chromosomes were identified by the banding and color patterns in the 14 examined lines. There was significant quantitative variation among lines for the knob, microsatellite, TR-1, and CentC signals. The same probe mixture identifies meiotic pachytene, late prophase I, and metaphase I chromosomes. The procedure could facilitate the study of chromosomal structure and behavior and be adapted for other plant species.
Drug discovery for alopecia: gone today, hair tomorrow (2015)

The desire to treat alopecia with an easy topical preparation is expected to grow with time, particularly with an increasing aging population. The discovery of epidermal stem cells in the HF has given new life to the search for a cure for baldness. Drug discovery efforts are being increasingly centered on these stem cells, boosting the hair cycle and reversing miniaturization of HF. Better understanding of the molecular mechanisms underlying the immune attack in AA will yield new drugs. New discoveries in HF neogenesis and low-level light therapy will undoubtedly have a role to play.
Mutations and common polymorphisms in ADAMTS13 gene responsible for von Willebrand factor-cleaving protease activity (2002)

von Willebrand factor (VWF) is synthesized primarily in vascular endothelial cells and secreted into the plasma as unusually large VWF multimers. Normally, these multimers are quickly degraded into smaller forms by a plasma metalloproteinase, VWF-cleaving protease (VWF-CP). Decreases in the activity of this enzyme result in congenital and acquired thrombotic thrombocytopenic purpura (TTP). The human VWF-CP has recently been purified. Cloning of the corresponding cDNA revealed that the 1,427-aa polypeptide is a member of the ADAMTS gene family, termed ADAMTS13. Twelve rare mutations in this gene have been identified in patients with congenital TTP. Here, we report missense and nonsense mutations in two Japanese families with Upshaw-Schulman syndrome, congenital TTP with neonatal onset and frequent relapses. The comparison of individual ADAMTS13 genotypes and plasma VWF-CP activities indicated that the R268P, Q449stop, and C508Y mutations abrogated activity of the enzyme, whereas the P475S mutant retained low but significant activity. The effects of these mutations were further confirmed by expression analysis in HeLa cells. Recombinant VWF-CP containing either the R268P or C508Y mutations was not secreted from cells. In contrast, Q449stop and P475S mutants were normally secreted but demonstrated minimal activity. Genotype analysis of 364 Japanese subjects revealed that P475S is heterozygous in 9.6% of individuals, suggesting that approximately 10% of the Japanese population possesses reduced VWF-CP activity. We report on a single-nucleotide polymorphism associated with alterations in VWF-CP activity; it will be important to assess this single-nucleotide polymorphism as a risk factor for thrombotic disorders.
Bayesian inference of protein–protein interactions from biological literature (2009)

Supplementary data are available at Bioinformatics online.
Charcot–Marie–Tooth disease and pathways to molecular based therapies (2014)

The discovery in 1991 that chromosome 17p12 duplication is associated with Charcot-Marie-Tooth (CMT) disease marked the beginning of an era of molecular insight into this disorder, which encompasses the peripheral motor and sensory neuropathies. A mere two decades later, over 40 subtypes of CMT have been molecularly defined and many have been extensively studied in vitro and in animal models, providing the framework for a more comprehensive understanding of the biological pathways dictating myelination, axonal dynamics, and axon-glia interactions. The advent of next-generation sequencing technologies offers opportunities in both research and clinical settings for gene discovery, further molecular understanding and diagnosis, and calls for modifications of the existing algorithms guiding genetic testing. Although treatment is mainly supportive at this time, advances in this field are anticipated as the molecular basis of CMT is unraveled.
SpikeProp: backpropagation for networks of spiking neurons. (2000)

For a network of spiking neurons with reasonable postsynaptic potentials, we derive a supervised learning rule akin to traditional error-back-propagation, SpikeProp and show how to overcome the discontinuities introduced by thresholding. Using this learning algorithm, we demonstrate how networks of spiking neurons with biologically plausible time-constants can perform complex non-linear classi cation in fast temporal coding just as well as rate-coded networks. When comparing the (implicit) number of neurons required for the respective encodings, it is empirically demonstrated that temporal coding potentially requires signi cantly less neurons.
Memory CD8+ T Cells Provide an Early Source of IFN-γ (2003)

During the non-Ag-specific early phase of infection, IFN-gamma is believed to be primarily provided by NK and NKT cells in response to pathogen-derived inflammatory mediators. To test whether other cell types were involved in early IFN-gamma release, IFN-gamma-producing cells were visualized in spleens and lymph nodes of LPS-injected mice. In addition to NK and NKT cells, IFN-gamma was also detected in a significant fraction of CD8(+) T cells. CD8(+) T cells represented the second major population of IFN-gamma-producing cells in the spleen ( approximately 30%) and the majority of IFN-gamma(+) cells in the lymph nodes ( approximately 70%). LPS-induced IFN-gamma production by CD8(+) T cells was MHC class I independent and was restricted to CD44(high) (memory phenotype) cells. Experiments performed with C3H/HeJ (LPS-nonresponder) mice suggested that CD8(+) T cells responded to LPS indirectly through macrophage/dendritic cell-derived IFN-alpha/beta, IL-12, and IL-18. IFN-gamma was also detected in memory CD8(+) T cells from mice injected with type I IFN or with poly(I:C), a synthetic dsRNA that mimics early activation by RNA viruses. Taken together, these results suggest that in response to bacterial and viral products, memory T cells may contribute to innate immunity by providing an early non-Ag-specific source of IFN-gamma.
Cloning of a cDNA for a T Cell-Specific Serine Protease from a Cytotoxic T Lymphocyte (1986)

A new serine protease was encoded by a clone isolated from a murine cytotoxic T-lymphocyte complementary DNA library by an RNA-hybridization competition protocol. Complementary transcripts were detected in cytotoxic T lymphocytes, spleen cells from nude mice, a rat natural killer cell leukemia, and in two of eight T-helper clones (both cytotoxic), but not in normal mouse kidney, liver, spleen, or thymus, nor in several tested T- and B-cell tumors. T-cell activation with concanavalin A plus interleukin-2 induced spleen cells to express this gene with kinetics correlating with the acquisition of cytolytic capacity. The nucleotide sequence of this gene encoded an amino acid sequence of approximately 25,700 daltons, with 25 to 35 percent identity to members of the serine protease family. The active site "charge-relay" residues (His57, Asp102, and Ser195 of the chymotrypsin numbering system) are conserved, as well as the trypsin-specific Asp (position 189 in trypsin). A Southern blot analysis indicated that this gene is conserved in humans, mouse, and chicken. This serine protease may have a role in lymphocyte lysis and a "lytic cascade."
Receptor-mediated gene delivery in vivo. Partial correction of genetic analbuminemia in Nagase rats (1991)

A plasmid (palb3) was constructed containing the structural gene for human serum albumin driven by mouse albumin enhancer-rat albumin promoter elements. Using an asialoglycoprotein-polycation conjugate consisting of asialoorosomucoid coupled to poly-L-lysine, a soluble DNA complex was formed that was capable of targeting specifically to hepatocytes via asialoglycoprotein receptors present on these cells. Groups of Nagase analbuminemic rats were injected with complexed DNA or controls, followed by two-thirds partial hepatectomy to stimulate hepatocyte replication. Using a cDNA probe for the human albumin structural gene, hybridizable sequences were detected in analbuminemic rats treated with complex as determined by Southern blot analysis. Two weeks post-injection, the targeted DNA was found to exist primarily in plasmid form with an average copy number of 1000/diploid cell. Human albumin mRNA was detected by dot-blot hybridization with a specific oligonucleotide cDNA probe and confirmed by RNase protection assay using a vector-specific probe. Circulating human albumin was detected in the serum of palb3-treated Nagase analbuminemic rats by Western blots using an antibody specific for human serum albumin. A time course demonstrated that circulating human albumin was not detectable 24 h after injection, but became measurable at a level of 0.05 micrograms/ml within 48 h and increased in concentration to a maximum of 34 micrograms/ml by 2 weeks post-injection. This level of expression remained stable through 4 weeks after injection and partial hepatectomy.
Synthesis of large-scale undoped and nitrogen-doped amorphous graphene on MgO substrate by chemical vapor deposition (2012)

Despite amorphous graphene (a-graphene) domains having been created and observed within crystalline graphene, large-area synthesis is still in its infancy. Here, using MgO single crystals as a catalytic substrate, large-area (10 × 5 mm) undoped and nitrogen-doped a-graphene were synthesized by chemical vapor deposition with benzene and pyridine as precursors, respectively. The dependence of the number of layers and the crystallinity of a-graphene on the growth temperature was observed by transmission electron microscopy, selected area electron diffraction and Raman spectroscopy. Few-layer (2–5 layers) a-graphene films are demonstrated to have high transmittance (>85% at 550 nm) and low conductivity (<1 × 10−3 S cm−1). When doped with nitrogen (N/C ratio = ∼0.09), the conductivity of the a-graphene film could be increased. The preparation of large-area a-graphene films not only extends to two-dimensional carbon materials but also might provide building blocks for future all-carbon devices.
Brd4 Recruits P-TEFb to Chromosomes at Late Mitosis To Promote G 1 Gene Expression and Cell Cycle Progression (2007)

Brd4, a bromodomain protein capable of interacting with acetylated histones, is implicated in transmitting epigenetic memory through mitosis. It also functions as an associated factor and positive regulator of P-TEFb, a Cdk9-cyclin T1 heterodimer that stimulates transcriptional elongation by phosphorylating RNA polymerase II. In the present study, experiments were performed to determine whether these two functions of Brd4 are interrelated and, if so, how they may impact cell cycle progression. Our data demonstrate that while the P-TEFb level remains constant, the Brd4-P-TEFb interaction increases dramatically in cells progressing from late mitosis to early G(1). Concurrently, P-TEFb is recruited to chromosomes, beginning around mid- to late anaphase and before nuclear envelope/lamina formation and nuclear import of other general transcription factors. Importantly, the recruitment of P-TEFb depends on Brd4. Abrogation of this process through Brd4 knockdown reduces the binding of P-TEFb to and expression of key G(1) and growth-associated genes, leading to G(1) cell cycle arrest and apoptosis. Because P-TEFb is synonymous with productive elongation, its recruitment by Brd4 to chromosomes at late mitosis may indicate those genes whose active transcription status must be preserved across cell division.
ClusterGAN: Latent Space Clustering in Generative Adversarial Networks (2019)

Generative Adversarial networks (GANs) have obtained remarkable success in many unsupervised learning tasks and unarguably, clustering is an important unsupervised learning problem. While one can potentially exploit the latent-space back-projection in GANs to cluster, we demonstrate that the cluster structure is not retained in the GAN latent space. In this paper, we propose ClusterGAN as a new mechanism for clustering using GANs. By sampling latent variables from a mixture of one-hot encoded variables and continuous latent variables, coupled with an inverse network (which projects the data to the latent space) trained jointly with a clustering specific loss, we are able to achieve clustering in the latent space. Our results show a remarkable phenomenon that GANs can preserve latent space interpolation across categories, even though the discriminator is never exposed to such vectors. We compare our results with various clustering baselines and demonstrate superior performance on both synthetic and real datasets.
Attenuation of fructose-induced hypertension in rats by exercise training. (1988)

This study was initiated to see if the insulin resistance, hyperinsulinemia, and hypertension that follow feeding normotensive Sprague-Dawley rats a fructose-rich diet could be prevented by letting rats run spontaneously in exercise wheel cages. Blood pressure in sedentary rats increased from (mean +/- SEM) 125 +/- 2 to 148 +/- 3 mm Hg in response to 2 weeks of a high fructose diet, and this increment was significantly (p less than 0.001) attenuated in exercising rats (from 121 +/- 1 to 131 +/- 2 mm Hg). In addition, mean (+/- SEM) plasma insulin concentration was lower in fructose-fed rats allowed to run spontaneously (44 +/- 2 vs 62 +/- 5 microU/ml; p less than 0.01). Finally, resistance to insulin-stimulated glucose uptake was assessed by determining the steady state plasma glucose response to a continuous glucose and exogenous insulin infusion during a period in which endogenous insulin secretion was suppressed. The results of these studies indicated that the mean (+/- SEM) steady state plasma glucose concentration was significantly lower in the exercise-trained rats (127 +/- 5 vs 168 +/- 6 mg/dl; p less than 0.001), despite the fact that the steady state plasma insulin levels were also lower in rats allowed to run spontaneously (75 +/- 4 vs 90 +/- 5 microU/ml; p less than 0.05). Thus, the ability of exercise-trained rats to stimulate glucose disposal was enhanced as compared with that of sedentary rats fed the same fructose-rich diet. These data demonstrate that the insulin resistance, hyperinsulinemia, and hypertension produced in normotensive rats by feeding them a high fructose diet can be attenuated if rats are allowed to run spontaneously.(ABSTRACT TRUNCATED AT 250 WORDS)