gebhart/patrepeval huggingface dataset:
Cloning, expression and chromosomal localization of a new putative receptor‐like protein tyrosine phosphatase (1991)

We have isolated a mouse cDNA of 5.7 kb, encoding a new member of the family of receptor-like protein tyrosine phosphatases, termed mRPTP mu. The cDNA predicts a protein of 1432 amino acids (not including signal peptide) with a calculated Mr of 161,636. In addition, we have cloned the human homologue, hRPTP mu, which shows 98.7% amino acid identity to mRPTP mu. The predicted mRPTP mu protein consists of a 722 amino acid extracellular region, containing 13 potential N-glycosylation sites, a single transmembrane domain and a 688 amino acid intracellular part containing 2 tandem repeats homologous to the catalytic domains of other tyrosine phosphatases. The N-terminal extracellular part contains a region of about 170 amino acids with no sequence similarities to known proteins, followed by one Ig-like domain and 4 fibronectin type III-like domains. The intracellular part is unique in that the region between the transmembrane domain and the first catalytic domain is about twice as large as in other receptor-like protein tyrosine phosphatases. RNA blot analysis reveals a single transcript, that is most abundant in lung and present in much lower amounts in brain and heart. Transfection of the mRPTP mu cDNA into COS cells results in the synthesis of a protein with an apparent Mr of 195,000, as detected in immunoblots using an antipeptide antibody. The human RPTP mu gene is localized on chromosome 18pter-q11, a region with frequent abnormalities implicated in human cancer.
Gastrointestinal regulation of food intake (2007)

Despite substantial fluctuations in daily food intake, animals maintain a remarkably stable body weight, because overall caloric ingestion and expenditure are exquisitely matched over long periods of time, through the process of energy homeostasis. The brain receives hormonal, neural, and metabolic signals pertaining to body-energy status and, in response to these inputs, coordinates adaptive alterations of energy intake and expenditure. To regulate food consumption, the brain must modulate appetite, and the core of appetite regulation lies in the gut-brain axis. This Review summarizes current knowledge regarding the neuroendocrine regulation of food intake by the gastrointestinal system, focusing on gastric distention, intestinal and pancreatic satiation peptides, and the orexigenic gastric hormone ghrelin. We highlight mechanisms governing nutrient sensing and peptide secretion by enteroendocrine cells, including novel taste-like pathways. The increasingly nuanced understanding of the mechanisms mediating gut-peptide regulation and action provides promising targets for new strategies to combat obesity and diabetes.
Extending Recognition by Peptide Nucleic Acids (PNAs):  Binding to Duplex DNA and Inhibition of Transcription by Tail-Clamp PNA−Peptide Conjugates (2003)

Peptide nucleic acids (PNAs) are a powerful tool for recognition of double-stranded DNA. Strand invasion is most efficient when pyrimidine PNAs are linked to form a bisPNA in which one strand binds by Watson-Crick base pairing while the other binds by Hoogsteen base pairing to the newly formed PNA-DNA duplex. Within many genes, however, polypyrimidine target sequences may not be located in optimal positions relative to transcription factor binding sites, and this deficiency may complicate attempts to identify potent antigene PNAs. To increase the versatility of strand invasion by PNAs, we have synthesized bisPNAs and bisPNA-peptide conjugates containing a mixed base extension of the Watson-Crick polypyrimidine strand. We find that these tail-clamp PNAs (TC-PNAs) bind duplex DNA and inhibit transcription. DNA recognition occurs with single-stranded or TC-bisPNAs and requires attachment of positively charged amino acids. Association rate constants, k(a), for binding to DNA by TC-PNAs are as high as 35000 M(-1) s(-1) and are usually only a fewfold lower than for analogous PNAs that lack mixed base extensions. The ability to bind duplex DNA is not always necessary for inhibition of transcription, possibly because PNAs can bind to accessible DNA within the transcription bubble created by RNA polymerase. These results, together with similar findings independently obtained by Nielsen and colleagues [Bentin, T., Larsen, H. J., and Nielsen, P. E. (2003) Biochemistry 42, 13987-13995], expand the range of sequences within duplex DNA that are accessible to PNAs and suggest that TC-PNA-peptide conjugates are good candidates for further testing as antigene agents.
Is the Property of Being Positively Correlated Transitive? (2001)

Suppose that X, Y, and Z are random variables and that X and Y are positively correlated and that Y and Z are likewise positively correlated. Does it follow that X and Z must be positively correlated? As we shall see by example, the answer is (perhaps surprisingly) “no.” We prove, though, that if the correlations are sufficiently close to 1, thenX and Z must be positively correlated. We also prove a general inequality that relates the three correlations. The ideas should be accessible to students in a first (postcalculus) course in probability and statistics.
PD-L1/B7H-1 Inhibits the Effector Phase of Tumor Rejection by T Cell Receptor (TCR) Transgenic CD8+ T Cells (2004)

Although increased circulating tumor antigen-specific CD8(+) T cells can be achieved by vaccination or adoptive transfer, tumor progression nonetheless often occurs through resistance to effector function. To develop a model for identifying mechanisms of resistance to antigen-specific CTLs, poorly immunogenic B16-F10 melanoma was transduced to express the K(b)-binding peptide SIYRYYGL as a green fluorescent protein fusion protein that should be recognized by high-affinity 2C TCR transgenic T cells. Although B16.SIY cells expressed high levels of antigen and were induced to express K(b) in response to IFN-gamma, they were poorly recognized by primed 2C/RAG2(-/-) T cells. A screen for candidate inhibitory ligands revealed elevated PD-L1/B7H-1 on IFN-gamma-treated B16-F10 cells and also on eight additional mouse tumors and seven human melanoma cell lines. Primed 2C/RAG2(-/-)/PD-1(-/-) T cells showed augmented cytokine production, proliferation, and cytolytic activity against tumor cells compared with wild-type 2C cells. This effect was reproduced with anti-PD-L1 antibody present during the effector phase but not during the priming culture. Adoptive transfer of 2C/RAG2(-/-)/PD-1(-/-) T cells in vivo caused tumor rejection under conditions in which wild-type 2C cells or CTLA-4-deficient 2C cells did not reject. Our results support interfering with PD-L1/PD-1 interactions to augment the effector function of tumor antigen-specific CD8(+) T cells in the tumor microenvironment.
Prevention of phospholipase‐C induced aggregation of low density lipoprotein by amphipathic apolipoproteins (1993)

Phospholipase C (PL-C) digestion of human low density lipoprotein (LDL) results in hydrolytic cleavage of the phosphocholine head group of phosphatidylcholine, thereby generating diacylglycerol. Loss of amphiphillic surface lipids and/or accumulation of diacylglycerol causes LDL samples to develop turbidity. Examination of PL-C treated LDL by electron microscopy revealed a progressive aggregation of LDL as a function of phosphatidylcholine hydrolysis: fused particles, clusters, and multiple stacked aggregates were observed. Lipid analysis of untreated and aggregated LDL confirmed that the phosphatidylcholine content of the latter had decreased with a corresponding increase in diacylglycerol. It is likely that phospholipolysis created hydrophobic gaps within the surface monolayer of LDL, thereby inducing LDL fusion and aggregation. When amphipathic alpha-helix-containing apolipoproteins, such as human apoA-I or Manduca sexta apolipophorin III (apoLp-III) were present, PL-C treated LDL did not aggregate. Compositional analysis of apolipoprotein-containing PL-C LDL showed that phospholipolysis was not affected by the presence of apolipoproteins. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of lipoproteins re-isolated following incubation with PL-C revealed an association of apoA-I or apoLp-III with PL-C digested LDL. Electron microscopy showed no major morphological differences between native LDL and apoprotein stabilized PL-C treated LDL and the average particle diameter of apoA-I stabilized PL-C LDL was 22.5 +/- 2.2 nm versus 22.8 +/- 1.6 nm for control LDL. Incubation of tritium-labeled apoLp-III with LDL and PL-C demonstrated that association of apoLp-III with PL-C LDL correlated with the extent of phospholipid hydrolysis, the apolipoproteins apparently being recruited to compensate for the increased hydrophobic surface created by conversion of phosphatidylcholine into diacylglycerol. The results suggest that transient association of amphipathic apolipoproteins with damaged or unstable LDL may provide a mechanism to obviate formation of atherogenic LDL aggregates in vivo.
271. 1 : 2-Dihydro-2-thianaphthalene derivatives. Part I. Preparation and reactions of 1 : 2-dihydro-1-keto-2-thianaphthalenes (1951)

D. J. Dijksman and G. T. Newbold, J. Chem. Soc., 1951, 1213 DOI: 10.1039/JR9510001213
Deterministic and Probabilistic Q-Ball Tractography: from Diffusion to Sharp Fiber Distribution (2007)

We propose a deterministic and a probabilistic extension of classical diffusion tensor imaging (DTI) tractography algorithms based on a sharp fiber orientation distribution function (ODF) reconstruction from Q-Ball Imaging (QBI). An important contribution of the paper is the integration of some of the latest state-of-the-art high angular resolution diffusion imaging (HARDI) data processing methods to obtain accurate and convincing results of complex fiber bundles with crossing, fanning and branching configurations. First, we develop a new deconvolution \emph{sharpening} transformation from diffusion ODF (dODF) to fiber ODF (fODF). We show that this sharpening transformation improves angular resolution and fiber detection of QBI and thus greatly improves tractography results. The angular resolution of QBI is in fact improved by approximately 20$^\circ$ and the fODF is shown to behave very similarly of the fiber orientation density (FOD) estimated from the spherical deconvolution method of Tournier et al. Another major contribution of the paper is the extensive comparison study on human brain datasets of our new deterministic and probabilistic tracking algorithms. As an application, we show how the reconstruction of transcallosal fiber connections intersecting with the corona radiata and the superior longitudinal fasciculus can be improved with the fODF in a group of 8 subjects. Current DTI based methods neglect these fibers, which might lead to wrong interpretations of the brain functions.
Vocaine the vocoder and applications in speech synthesis (2015)

Vocoders received renewed attention recently as basic components in speech synthesis applications such as voice transformation, voice conversion and statistical parametric speech synthesis. This paper presents a new vocoder synthesizer, referred to as Vocaine, that features a novel Amplitude Modulated-Frequency Modulated (AM-FM) speech model, a new way to synthesize non-stationary sinusoids using quadratic phase splines and a super fast cosine generator. Extensive evaluations are made against several state-of-the-art methods in Copy-Synthesis and Text-To-Speech synthesis experiments. Vocaine matches or outperforms STRAIGHT in Copy-Synthesis experiments and outperforms our baseline real-time optimized Mixed-Excitation vocoder with the same computational cost. We report that Vocaine considerably improves our statistical TTS synthesizers and that our new statistical parametric synthesizer [1] matched the quality of our mature production Unit-Selection system with uncompressed waveforms.
KNOWROB-MAP - knowledge-linked semantic object maps (2010)

Autonomous household robots are supposed to accomplish complex tasks like cleaning the dishes which involve both navigation and manipulation within the environment. For navigation, spatial information is mostly sufficient, but manipulation tasks raise the demand for deeper knowledge about objects, such as their types, their functions, or the way how they can be used. We present KNOWROB-MAP, a system for building environment models for robots by combining spatial information about objects in the environment with encyclopedic knowledge about the types and properties of objects, with common-sense knowledge describing what the objects can be used for, and with knowledge derived from observations of human activities by learning statistical relational models. In this paper, we describe the concept and implementation of KNOWROB-MAP and present several examples demonstrating the range of information the system can provide to autonomous robots.
Analysis of HIV-1 variants by cloning DNA generated with the ViroSeq TM HIV-1 Genotyping System (2003)

10 None Sample 2 Population sequencing K103N, Y181C, G190A Clone 2-1 K103N Clone 2-2 G190A Clone 2-3 Y181C Clone 2-4 G190A Clone 2-5 V106A Clone 2-6 Y181C Clone 2-7 None Clone 2-8 None Clone 2-9 Y181C, G190A Clone 2-10 Y181C NVP, nevirapine. Mutations detected by population sequencing were detected as mixtures of mutant and wild-type amino acids (e.g., Y + C at position 181).
Probing Mechanisms of Photoreceptor Degeneration in a New Mouse Model of the Common Form of Autosomal Dominant Retinitis Pigmentosa due to P23H Opsin Mutations (2011)

Rhodopsin, the visual pigment mediating vision under dim light, is composed of the apoprotein opsin and the chromophore ligand 11-cis-retinal. A P23H mutation in the opsin gene is one of the most prevalent causes of the human blinding disease, autosomal dominant retinitis pigmentosa. Although P23H cultured cell and transgenic animal models have been developed, there remains controversy over whether they fully mimic the human phenotype; and the exact mechanism by which this mutation leads to photoreceptor cell degeneration remains unknown. By generating P23H opsin knock-in mice, we found that the P23H protein was inadequately glycosylated with levels 1-10% that of wild type opsin. Moreover, the P23H protein failed to accumulate in rod photoreceptor cell endoplasmic reticulum but instead disrupted rod photoreceptor disks. Genetically engineered P23H mice lacking the chromophore showed accelerated photoreceptor cell degeneration. These results indicate that most synthesized P23H protein is degraded, and its retinal cytotoxicity is enhanced by lack of the 11-cis-retinal chromophore during rod outer segment development.
Farnesoid X Receptor Deficiency Improves Glucose Homeostasis in Mouse Models of Obesity (2011)

Overall, FXR deficiency in obesity beneficially affects body weight development and glucose homeostasis.
Isolation of Mitochondria from Cells and Tissues (2014)

Mitochondria are complex organelles at the center of cellular metabolism, apoptosis, and signaling. They continue to be the subject of intense basic investigation to understand their composition and function, but they have also captivated the attention of clinical researchers because of the growing knowledge of the (sometimes unexpected) roles of mitochondria in human diseases and aging. A full understanding of these intriguing organelles often requires their purification from cells or tissues under specific physiological or pathological conditions. Here we provide some introductory considerations for those interested in purifying mitochondria for subsequent downstream biophysical, structural, and functional analysis.
Synthetic Spike-in Standards Improve Run-Specific Systematic Error Analysis for DNA and RNA Sequencing (2012)

While the importance of random sequencing errors decreases at higher DNA or RNA sequencing depths, systematic sequencing errors (SSEs) dominate at high sequencing depths and can be difficult to distinguish from biological variants. These SSEs can cause base quality scores to underestimate the probability of error at certain genomic positions, resulting in false positive variant calls, particularly in mixtures such as samples with RNA editing, tumors, circulating tumor cells, bacteria, mitochondrial heteroplasmy, or pooled DNA. Most algorithms proposed for correction of SSEs require a data set used to calculate association of SSEs with various features in the reads and sequence context. This data set is typically either from a part of the data set being "recalibrated" (Genome Analysis ToolKit, or GATK) or from a separate data set with special characteristics (SysCall). Here, we combine the advantages of these approaches by adding synthetic RNA spike-in standards to human RNA, and use GATK to recalibrate base quality scores with reads mapped to the spike-in standards. Compared to conventional GATK recalibration that uses reads mapped to the genome, spike-ins improve the accuracy of Illumina base quality scores by a mean of 5 Phred-scaled quality score units, and by as much as 13 units at CpG sites. In addition, since the spike-in data used for recalibration are independent of the genome being sequenced, our method allows run-specific recalibration even for the many species without a comprehensive and accurate SNP database. We also use GATK with the spike-in standards to demonstrate that the Illumina RNA sequencing runs overestimate quality scores for AC, CC, GC, GG, and TC dinucleotides, while SOLiD has less dinucleotide SSEs but more SSEs for certain cycles. We conclude that using these DNA and RNA spike-in standards with GATK improves base quality score recalibration.
An Animal Model for Small-Diameter Arterial Grafts (1989)

A rabbit model was developed to study small-diameter arterial grafts. A total of 158 2-mm-diameter polytetrafluoroethylene (PTFE) grafts and 35 autogenous carotid artery (AA) grafts were interposed in the carotid arteries of New Zealand white rabbits. A pilot study of 16 PTFE grafts used to develop operative and anesthetic techniques had a 20% mortality and 38% early (less than 2 day) thrombosis rate. Subsequent to the pilot study 177 grafts were placed and a 92% postoperative survival with 100% AA graft patency and 93% PTFE graft patency at 2 weeks was observed. AA grafts followed beyond 16 weeks continued to have 100% patency, while PTFE grafts began to show increased failure. Closure was found to be due to the development of anastomotic myointimal hyperplasia.
Organization and implementation of the register-renaming mapper for out-of-order IBM POWER4 processors (2005)

We present a new nonconventional approach for designing and organizing register rename mappers that can be applied in modern out-of-order processor chips. A content-addressable memory (CAM) configuration optimal for such a register mapper application was developed. The structure of the CAM and search engine, described in this paper, facilitates the implementation of the register mapper as a group of custom arrays. Each array is dedicated to executing a specific function. Among the functions we implemented are allocation of registers, maintaining the register map and status, source lookup, saving a shadow copy of the register map, and freeing up of registers. We made a novel implementation of the register mapper to provide rename resources for the IBM POWER4™ chip, which provides the processing power for the IBM eServer™ p690. Such register renaming allows for a high level of concurrency in the pipeline and contributes to superior machine performance.
Targeted Inflammation During Oncolytic Virus Therapy Severely Compromises Tumor Blood Flow (2007)

Oncolytic viruses (OVs) are selected or designed to eliminate malignancies by direct infection and lysis of cancer cells. In contrast to this concept of direct tumor lysis by viral infection, we observed that a significant portion of the in vivo tumor killing activity of two OVs, vesicular stomatitis virus (VSV) and vaccinia virus is caused by indirect killing of uninfected tumor cells. Shortly after administering the oncolytic virus we observed limited virus infection, coincident with a loss of blood flow to the interior of the tumor that correlated with induction of apoptosis in tumor cells. Transcript profiling of tumors showed that virus infection resulted in a dramatic transcriptional activation of pro-inflammatory genes including the neutrophil chemoattractants CXCL1 and CXCL5. Immunohistochemical examination of infected tumors revealed infiltration by neutrophils correlating with chemokine induction. Depletion of neutrophils in animals prior to VSV administration eliminated uninfected tumor cell apoptosis and permitted more extensive replication and spreading of the virus throughout the tumor. Taken all together, these results indicate that targeted recruitment of neutrophils to infected tumor beds enhances the killing of malignant cells. We propose that activation of inflammatory cells can be used for enhancing the effectiveness of oncolytic virus therapeutics, and that this approach should influence the planning of therapeutic doses.
Growth and properties of nanocrystalline diamond films (2006)

Abstract The aim of this paper is to summarise recent progress in the growth of small grain‐sized Chemical Vapor Deposition (CVD) diamond often called nanocrystalline diamond, i.e., diamond with grains typically smaller than 500 nm. Nanocrystalline (NCD) and Ultrananocrystalline diamond (UNCD) films are new materials offering interesting applications to nanobioelectronics and electrochemistry. However NCD and UNCD thin films comprise of entirely different structures which is highlighted here in this paper. We discuss in detail the main differences in Raman spectra, optical properties and electrical transport properties. Finally we present a simple model of the conductivity mechanism in nitrogenated UNCD (N‐UNCD) and boron doped NCD (B‐NCD) films, and show the possibility of achieving the superconductive transition in B‐NCD films. (© 2006 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Cytokines and immunodeficiency diseases: critical roles of the γc‐dependent cytokines interleukins 2, 4, 7, 9, 15, and 21, and their signaling pathways (2004)

In this review, we discuss the role of cytokines and their signaling pathways in immunodeficiency. We focus primarily on severe combined immunodeficiency (SCID) diseases as the most severe forms of primary immunodeficiencies, reviewing the different genetic causes of these diseases. We focus in particular on the range of forms of SCID that result from defects in cytokine-signaling pathways. The most common form of SCID, X-linked SCID, results from mutations in the common cytokine receptor gamma-chain, which is shared by the receptors for interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21, underscoring that X-linked SCID is indeed a disease of defective cytokine signaling. We also review the signaling pathways used by these cytokines and the phenotypes in humans and mice with defects in the cytokines or signaling pathways. We also briefly discuss other cytokines, such as interferon-gamma and IL-12, where mutations in the ligand or receptor or signaling components also cause clinical disease in humans.
Expression of wild-type p53 is not compatible with continued growth of p53-negative tumor cells. (1991)

Inactivation of the cellular p53 gene is a common feature of Friend virus-induced murine erythroleukemia cell lines and may represent a necessary step in the progression of this disease. As well, frequent loss or mutation of p53 alleles in diverse human tumors is consistent with the view of p53 as a tumor suppressor gene. To examine the significance of p53 gene inactivation in tumorigenesis, we have attempted to express transfected wild-type p53 in three p53-negative tumor cell lines: murine DP16-1 Friend erythroleukemia cells, human K562 cells, and SKOV-3 cells. We found that aberrant p53 proteins, which differ from wild-type p53 by a single amino acid substitution, were expressed stably in these cells, whereas wild-type p53 expression was not tolerated. The inability of p53-negative tumor cell lines to support long-term expression of wild-type p53 protein is consistent with the view that p53 is a tumor suppressor gene.