gebhart/patrepeval huggingface dataset:
Bexarotene Plus Erlotinib Suppress Lung Carcinogenesis Independent of KRAS Mutations in Two Clinical Trials and Transgenic Models (2011)

The rexinoid bexarotene represses cyclin D1 by causing its proteasomal degradation. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib represses cyclin D1 via different mechanisms. We conducted a preclinical study and 2 clinical/translational trials (a window-of-opportunity and phase II) of bexarotene plus erlotinib. The combination repressed growth and cyclin D1 expression in cyclin-E- and KRAS/p53-driven transgenic lung cancer cells. The window-of-opportunity trial in early-stage non-small-cell lung cancer (NSCLC) patients (10 evaluable), including cases with KRAS mutations, repressed cyclin D1 (in tumor biopsies and buccal swabs) and induced necrosis and inflammatory responses. The phase II trial in heavily pretreated, advanced NSCLC patients (40 evaluable; a median of two prior relapses per patient (range, 0-5); 21% with prior EGFR-inhibitor therapy) produced three major clinical responses in patients with prolonged progression-free survival (583-, 665-, and 1,460-plus days). Median overall survival was 22 weeks. Hypertriglyceridemia was associated with an increased median overall survival (P = 0.001). Early PET (positron emission tomographic) response did not reliably predict clinical response. The combination was generally well tolerated, with toxicities similar to those of the single agents. In conclusion, bexarotene plus erlotinib was active in KRAS-driven lung cancer cells, was biologically active in early-stage mutant KRAS NSCLC, and was clinically active in advanced, chemotherapy-refractory mutant KRAS tumors in this study and previous trials. Additional lung cancer therapy or prevention trials with this oral regimen are warranted.
Defective Fas expression exacerbates neurotoxicity in a model of Parkinson's disease (2005)

Fas (CD95), a member of the tumor necrosis factor-receptor superfamily, has been studied extensively as a death-inducing receptor in the immune system. However, Fas is also widely expressed in a number of other tissues, including in neurons. Here, we report that defects in the Fas/Fas ligand system unexpectedly render mice highly susceptible to neural degeneration in a model of Parkinson's disease. We found that Fas-deficient lymphoproliferative mice develop a dramatic phenotype resembling clinical Parkinson's disease, characterized by extensive nigrostriatal degeneration accompanied by tremor, hypokinesia, and loss of motor coordination, when treated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at a dose that causes no neural degeneration or behavioral impairment in WT mice. Mice with generalized lymphoproliferative disease, which express a mutated Fas ligand, display an intermediate phenotype between that of lymphoproliferative and WT mice. Moreover, Fas engagement directly protects neuronal cells from MPTP/1-methyl-4-phenylpyridinium ion toxicity in vitro. Our data show that decreased Fas expression renders dopaminergic neurons highly susceptible to degeneration in response to a Parkinson-causing neurotoxin. These findings constitute the first evidence for a neuroprotective role for Fas in vivo.
Periodontal Disease in Non‐Insulin‐Dependent Diabetes Mellitus (1991)

The relationship between diabetes mellitus and oral health status was determined in Pima Indians from the Gila River Indian Community in Arizona. This tribe of native Americans has the world's highest reported incidence and prevalence of non-insulin-dependent (type 2) diabetes mellitus. The probing attachment level, alveolar bone loss, age, sex, Calculus Index, Plaque Index, Gingival Index, fluorosis, and DMFT as well as the diabetic status was assessed in 1,342 Pima Indians who were at least partially dentate. The prevalence and severity of destructive periodontal disease was determined by measuring probing attachment loss and radiographically apparent interproximal crestal alveolar bone loss, two independent but correlated indicators of periodontal destruction. Only diabetic status, age, and the presence of subgingival calculus were significantly associated with both increased prevalence and greater severity of destructive periodontal disease in this population. Diabetic status was significantly and strongly related to both the prevalence and severity of disease after adjusting for the effects of demographic variables and several indices of oral health including the Plaque Index. Subjects with type 2 diabetes have an increased risk of destructive periodontitis with an odds ratio of 2.81 (95% confidence interval 1.91 to 4.13) when attachment loss is used to measure the disease. The odds ratio for diabetic subjects was 3.43 (95% confidence interval 2.28 to 5.16) where bone loss was used to measure periodontal destruction. These findings demonstrate tht diabetes increases the risk of developing destructive periodontal disease about threefold. Furthermore, diabetes increases the risk of developing periodontal disease in a manner which cannot be explained on the basis of age, sex, and hygiene or other dental measures.(ABSTRACT TRUNCATED AT 250 WORDS)
Demyelinating neuropathies (2003)

Demyelinating neuropathies, even those due to abnormalities in intrinsic Schwann cell or myelin proteins, can have clinical manifestations due to distally predominant axonal degeneration.
A Direct Method of Nonparametric Measurement Selection (1971)

A direct method of measurement selection is proposed to determine the best subset of d measurements out of a set of D total measurements. The measurement subset evaluation procedure directly employs a nonparametric estimate of the probability of error given a finite design sample set. A suboptimum measurement subset search procedure is employed to reduce the number of subsets to be evaluated. Teh primary advantage of the approach is the direct but nonparametric evaluation of measurement subsets, for the M class problem.
How Computers Work with CD-ROM (1998)

From the Publisher:
Take a trip through the neural pathways and vital organs of your personal computer with the newest edition of this long-standing bestseller. Glorious full color illustrations make even the most complex subjects easy to understand. Follow PC/Computing senior editor and computer expert Ron White as he shows you the cutting edge technologies, including the Internet, multimedia sound and video, Pentium processors, local bus architecture, Plug and Play, CD-ROM, digital cameras, color printing, and more in new chapters on the hottest, and coolest, PC components.
Modified technique of stent fenestration of the atrial septum (2003)

This new technique allows placement of a diabolo shaped stent with a predefined diameter across the atrial septum. The diabolo shape increases stent stability, facilitates recrossing of the stent during future catheter interventions, and ensures medium term stent patency.
Recent Trends in Deep Learning Based Natural Language Processing [Review Article] (2018)

Deep learning methods employ multiple processing layers to learn hierarchical representations of data, and have produced state-of-the-art results in many domains. Recently, a variety of model designs and methods have blossomed in the context of natural language processing (NLP). In this paper, we review significant deep learning related models and methods that have been employed for numerous NLP tasks and provide a walk-through of their evolution. We also summarize, compare and contrast the various models and put forward a detailed understanding of the past, present and future of deep learning in NLP.
Isolation of tyrosinase-specific CD8+ and CD4+ T cell clones from the peripheral blood of melanoma patients following in vitro stimulation with recombinant vaccinia virus (1996)

The identification of Ags expressed by tumor cells and recognized by autologous T cells has led to the prospect of treating cancer by adoptive transfer of tumor-reactive T cells selected for Ag specificity. Tyrosinase is an Ag expressed by normal melanocytes as well as melanoma cells for which responses by autologous T cells have been detected. To evaluate the frequency with which tyrosinase-specific T cells can be isolated from melanoma patients for potential use in therapy, a recombinant vaccinia virus expressing tyrosinase was constructed for infection of autologous APCs that could be used to stimulate T cells reactive with this protein. Eight patients were studied, with peripheral blood serving as the source of both responder T cells and autologous APCs. Tyrosinase-specific CD8+ CTL clones were isolated from five of the eight patients with melanoma. The tyrosinase-specific CTL generated in this manner recognized autologous tumor cells as well as targets expressing the recombinant virus vector. CTL clones from three of the individuals were restricted to HLA-A28, -B8, and -B60, which have not previously been identified as alleles that can present immunogenic tyrosinase peptides. Tyrosinase-specific CD4+ T cell clones were isolated from six of the eight patients by stimulation with autologous APCs infected with recombinant vaccinia virus, and all these CD4+ clones were capable of recognizing autologous tumor cells. These studies demonstrate a high prevalence of CD4+ and CD8+ tyrosinase-specific responses in peripheral blood and support the feasibility of using peripheral blood to generate T cells for tumor therapy without the requirement for isolating T cells that have infiltrated tumor sites.
P16 and HPV discordance in metastatic carcinoma of cervical lymph nodes of unknown primary (2015)

The prognostic utility of HPV in oropharyngeal squamous cell carcinoma (OPSCC) and non-OPSCC as has been well documented. Currently, a standardized IHC scoring system does not exist and is needed to define HPV positivity. We have recently seen a patient that provides a caution in using p16 status as a diagnostic aid.
DNS extensions to Network Address Translators (DNS_ALG) (1999)

Domain Name Service (DNS) provides name to address mapping within a routing class (ex: IP). Network Address Translators (NATs) attempt to provide transparent routing between hosts in disparate address realms of the same routing class. Typically, NATs exist at the border of a stub domain, hiding private addresses from external addresses. This document identifies the need for DNS extensions to NATs and outlines how a DNS Application Level Gateway (DNS_ALG) can meet the need. DNS_ALG modifies payload transparently to alter address mapping of hosts as DNS packets cross one address realm into another. The document also illustrates the operation of DNS_ALG with specific examples.
Cutting Edge: CD28 Controls Peripheral Homeostasis of CD4+CD25+ Regulatory T Cells (2003)

CD28/B7 blockade leads to exacerbated autoimmune disease in the nonobese diabetic mouse strain as a result of a marked reduction in the number of CD4(+)CD25(+) regulatory T cells (Tregs). Herein, we demonstrate that CD28 controls both thymic development and peripheral homeostasis of Tregs. CD28 maintains a stable pool of peripheral Tregs by both supporting their survival and promoting their self-renewal. CD28 engagement promotes survival by regulating IL-2 production by conventional T cells and CD25 expression on Tregs.
DeepStory: Video Story QA by Deep Embedded Memory Networks (2017)

Question-answering (QA) on video contents is a significant challenge for achieving human-level intelligence as it involves both vision and language in real-world settings. Here we demonstrate the possibility of an AI agent performing video story QA by learning from a large amount of cartoon videos. We develop a video-story learning model, i.e. Deep Embedded Memory Networks (DEMN), to reconstruct stories from a joint scene-dialogue video stream using a latent embedding space of observed data. The video stories are stored in a long-term memory component. For a given question, an LSTM-based attention model uses the long-term memory to recall the best question-story-answer triplet by focusing on specific words containing key information. We trained the DEMN on a novel QA dataset of children's cartoon video series, Pororo. The dataset contains 16,066 scene-dialogue pairs of 20.5-hour videos, 27,328 fine-grained sentences for scene description, and 8,913 story-related QA pairs. Our experimental results show that the DEMN outperforms other QA models. This is mainly due to 1) the reconstruction of video stories in a scene-dialogue combined form that utilize the latent embedding and 2) attention. DEMN also achieved state-of-the-art results on the MovieQA benchmark.
Piezoelectric cantilever array for multiprobe scanning force microscopy (2002)

This paper attempts to describe a newly conceived multiprobe scanning force microscope (SFM) using a microfabricated piezoelectric cantilever. An array of piezoelectric microcantilevers with a piezoelectric ZnO layer on a SiO/sub 2/ film makes it possible to build the multiprobe SFM system. The piezoelectric cantilever is suitable for each cantilever of the array in the multiprobe SFM, because it can be utilized for both dynamic force sensing and controlling the tip-sample spacing. We have verified die applicability of the piezoelectric cantilever to each cantilever of the multiprobe array by characterizing tile sensitivities of the deflection sensing and actuation in z-direction. The 125-/spl mu/m-long cantilever could be statically driven by applying dc voltages to the piezoelectric layer, where the sensitivity of static drive was 20 nm/V. We have also fabricated an experimental piezoelectric microcantilever arrays with ten cantilevers. The mechanical resonance property of the cantilevers of the array has been studied.
Breadth of Human Immunodeficiency Virus-Specific Neutralizing Activity in Sera: Clustering Analysis and Association with Clinical Variables (2009)

Induction of antibodies that neutralize a broad range of human immunodeficiency virus type 1 (HIV-1) isolates is a major goal of vaccine development. To study natural examples of broad neutralization, we analyzed sera from 103 HIV-1-infected subjects. Among progressor patients, 20% of sera neutralized more than 75% of a panel of 20 diverse viral isolates. Little activity was observed in sera from long-term nonprogressors (elite controllers). Breadth of neutralization was correlated with viral load, but not with CD4 count, history of past antiretroviral use, age, gender, race/ethnicity, or route of exposure. Clustering analysis of sera by a novel method identified a statistically robust subgrouping of sera that demonstrated broad and potent neutralization activity.
Backbone Amide Linker (BAL) Strategy for Solid-Phase Synthesis of C-Terminal-Modified and Cyclic Peptides1,2,3 (1998)

Peptide targets for synthesis are often desired with C-terminal end groups other than the more usual acid and amide functionalities. Relatively few routes exist for synthesis of C-terminal-modified peptidesincluding cyclic peptidesby either solution or solid-phase methods, and known routes are often limited in terms of ease and generality. We describe here a novel Backbone Amide Linker (BAL) approach, whereby the growing peptide is anchored through a backbone nitrogen, thus allowing considerable flexibility in management of the termini. Initial efforts on BAL have adapted the chemistry of the tris(alkoxy)benzylamide system exploited previously with PAL anchors. Aldehyde precursors to PAL, e.g. 5-(4-formyl-3,5-dimethoxyphenoxy)valeric acid, were reductively coupled to the α-amine of the prospective C-terminal amino acid, which was blocked as a tert-butyl, allyl, or methyl ester, or to the appropriately protected C-terminal-modified amino acid derivative. These reductive aminations were carried out either in solution or on the solid phase, and occurred without racemization. The secondary amine intermediates resulting from solution amination were converted to the 9-fluorenylmethoxycarbonyl (Fmoc)-protected preformed handle derivatives, which were then attached to poly(ethylene glycol)−polystyrene (PEG-PS) graft or copoly(styrene−1% divinylbenzene) (PS) supports and used to assemble peptides by standard Fmoc solid-phase chemistry. Alternatively, BAL anchors formed by on-resin reductive amination were applied directly. Conditions were optimized to achieve near-quantitative acylation at the difficult step to introduce the penultimate residue, and a side reaction involving diketopiperazine formation under some circumstances was prevented by a modified protocol for Nα-protection of the second residue/introduction of the third residue. Examples are provided for the syntheses in high yields and purities of representative peptide acids, alcohols, N,N-dialkylamides, aldehydes, esters, and head-to-tail cyclic peptides. These methodologies avoid postsynthetic solution-phase transformations and are ripe for further extension.
Human Steroid Receptors and erbA Proto-oncogene Products: Members of a New Superfamily of Enhancer Binding Proteins (1986)

The activation and execution of animal developmental programs are ultimately based on precise temporal and spatial patterns of differential gene expression. Regulation of gene transcription in eukaryotes requires the coordinate action of both general and specific transcription factors that interact with DNA control elements to modulate the transcription rate of a particular gene. Several DNA sequences involved in the initiation of transcription by RNA polymerase II have been identified. Among them, enhancer elements have been shown to increase dramatically the transcriptional activity of many genes (Khoury and Gruss 1983). They can exert their action at great distances and independently of their orientation with respect to the coding region of the gene. The presence of cellular factors that are in limited quantity within a cell are absolutely required for this enhancer function (Scholer and Gruss 1984). Analysis of the molecular basis of transcription activation by positive regulatory factors will be greatly...
Regions of human papillomavirus type 16 E7 oncoprotein required for immortalization of human keratinocytes (1992)

Binding of the retinoblastoma gene product (pRB) by viral oncoproteins, including the E7 of human papillomavirus type 16 (HPV 16), is thought to be important in transformation of cells. One of the steps in transformation is the immortalization process. Here we show that mutations in E7 within the full-length genome which inhibit binding of pRB do not abrogate the ability of the HPV 16 DNA to immortalize primary human epithelial (keratinocyte) cells. A mutation in one of the cysteines of a Cys-X-X-Cys motif which is contained in the carboxy half of the E7 and is part of a zinc finger arrangement completely eliminates the ability of HPV 16 DNA to immortalize cells. The results indicate the importance of E7 in the immortalization of primary keratinocytes but suggest that the binding of pRB is not essential.
Hypoxia enhances vascular cell proliferation and angiogenesis in vitro via rapamycin (mTOR) ‐dependent signaling (2002)

Angiogenesis and vascular cell proliferation are pivotal in physiological and pathological processes including atherogenesis, restenosis, wound healing, and cancer development. Here we show that mammalian target of rapamycin (mTOR) signaling plays a key role in hypoxia-triggered smooth muscle and endothelial proliferation and angiogenesis in vitro. Hypoxia significantly increased DNA synthesis and proliferative responses to platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) in rat and human smooth muscle and endothelial cells. In an in vitro 3-dimensional model of angiogenesis, hypoxia increased PDGF- and FGF-stimulated sprout formation from rat and mouse aortas. Hypoxia did not modulate PDGF receptor mRNA, protein, or phosphorylation. PI3K activity was essential for cell proliferation under normoxic and hypoxic conditions. Activities of PI3K-downstream target PKB under hypoxia and normoxia were comparable. However, mTOR inhibition by rapamycin specifically abrogated hypoxia-mediated amplification of proliferation and angiogenesis, but was without effect on proliferation under normoxia. Accordingly, hypoxia-mediated amplification of proliferation was further augmented in mTOR-overexpressing endothelial cells. Thus, signaling via mTOR may represent a novel mechanism whereby hypoxia augments mitogen-stimulated vascular cell proliferation and angiogenesis.
Identification and molecular-genetic characterization of a LAMP/CD68-like protein from Caenorhabditis elegans (2000)

Lysosome associated membrane proteins (LAMPs) constitute a family of vertebrate proteins located predominantly in lysosomes, with lesser amounts present in endosomes and at the cell surface. Macrosialin/CD68s are similar to LAMPs in their subcellular distribution and amino acid sequence and presumed structure across the carboxyl terminal two thirds of their length. The functions of LAMPs and CD68s are not known. In the present study, a bioinformatics approach was used to identify a Caenorhabditis elegans protein (LMP-1) with sequence and presumed structural similarity to LAMPs and CD68s. LMP-1 appears to be the only membrane protein in C. elegans that carries a GYXX(phi) vertebrate lysosomal targeting sequence at its C terminus (where (phi) is a large, hydrophobic residue). LMP-1 was found to be present from early embryonic stages through adulthood and to be predominantly localized at the periphery of a population of large, membrane-bound organelles, called granules, that are seen throughout the early embryo but in later stages are restricted to the cells of the intestine. Analysis of an LMP-1 deficient C. elegans mutant revealed that LMP-1 is not required for viability under laboratory conditions, but the absence of LMP-1 leads to an alteration in intestinal granule populations, with apparent loss of one type of granule.
Presentation of endogenous peptides to MHC class I-restricted cytotoxic T lymphocytes in transport deletion mutant T2 cells (1993)

The ability of minigene-encoded viral peptide epitopes to be presented by class I molecules in the absence of MHC-encoded transporters has been evaluated in mutant T2 cells. These cells have a large deletion in the class II MHC region that includes the known transporter protein for antigenic peptides and proteasome genes and they are defective in presenting viral epitopes to CTL. T2 cells that express minigenes encoding the influenza virus matrix peptide 58-66 (GILGFVFTL) and two HTLV 1 Tax peptides 11-19 (LLFGYPVYV) and 12-19 were lysed by HLA-A2-restricted peptide-specific CTL. Minigene expression of a HLA-A2-restricted HIV reverse transcriptase peptide 476-484 (ILKEPVHGV) with three charged residues sensitized T2 cells poorly for lysis by HIV-specific CTL unless the peptide was preceded by an endoplasmic reticulum translocation signal sequence. Expression of an influenza virus nucleoprotein peptide 383-391 (SRYWAIRTR) with three charged arginine residues did sensitize HLA-B27+ T2 cells for lysis by peptide-specific CTL. These and other results with endogenously expressed peptide analogs in which hydrophobic and charged amino acids were interchanged demonstrate that antigenic peptides can be translocated from the cytoplasm into the class I Ag presentation pathway independent of MHC-encoded transporters; and that peptide hydrophobicity appears not to be a major determinant in selecting peptides for this alternate pathway.