gebhart/patrepeval huggingface dataset:
Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target (2004)

Expression of B7-H1, a costimulating glycoprotein in the B7 family, is normally restricted to macrophage-lineage cells, providing a potential costimulatory signal source for regulation of T cell activation. In contrast, aberrant expression of B7-H1 by tumor cells has been implicated in impairment of T cell function and survival, resulting in defective host antitumoral immunity. The relationship between tumor-associated B7-H1 and clinical cancer progression is unknown. Herein, we report B7-H1 expression by both renal cell carcinoma (RCC) tumors of the kidney and RCC tumor-infiltrating lymphocytes. In addition, our analysis of 196 clinical specimens reveals that patients harboring high intratumoral expression levels of B7-H1, contributed by tumor cells alone, lymphocytes alone, or tumor and/or lymphocytes combined, exhibit aggressive tumors and are at markedly increased risk of death from RCC. In fact, patients with high tumor and/or lymphocyte B7-H1 levels are 4.5 times more likely to die from their cancer than patients exhibiting low levels of B7-H1 expression (risk ratio 4.53; 95% confidence interval 1.94-10.56; P < 0.001.) Thus, our study suggests a previously undescribed mechanism whereby RCC may impair host immunity to foster tumor progression. B7-H1 may prove useful as a prognostic variable for RCC patients both pre- and posttreatment. In addition, B7-H1 may represent a promising target to facilitate more favorable responses in patients who require immunotherapy for treatment of advanced RCC.
Genome-wide transcriptome analysis identifies novel gene signatures implicated in human chronic liver disease (2013)

The molecular mechanisms behind human liver disease progression to cirrhosis remain elusive. Nuclear receptor small heterodimer partner (SHP/Nr0b2) is a hepatic tumor suppressor and a critical regulator of liver function. SHP expression is diminished in human cirrhotic livers, suggesting a regulatory role in human liver diseases. The goal of this study was to identify novel SHP-regulated genes that are involved in the development and progression of chronic liver disease. To achieve this, we conducted the first comprehensive RNA sequencing (RNA-seq) analysis of Shp(-/-) mice, compared the results with human hepatitis C cirrhosis RNA-seq and nonalcoholic steatohepatitis (NASH) microarray datasets, and verified novel results in human liver biospecimens. This approach revealed new gene signatures associated with chronic liver disease and regulated by SHP. Several genes were selected for validation of physiological relevance based on their marked upregulation, novelty with regard to liver function, and involvement in gene pathways related to liver disease. These genes include peptidoglycan recognition protein 2, dual specific phosphatase-4, tetraspanin 4, thrombospondin 1, and SPARC-related modular calcium binding protein-2, which were validated by qPCR analysis of 126 human liver specimens, including steatosis, fibrosis, and NASH, alcohol and hepatitis C cirrhosis, and in mouse models of liver inflammation and injury. This RNA-seq analysis identifies new genes that are regulated by the nuclear receptor SHP and implicated in the molecular pathogenesis of human chronic liver diseases. The results provide valuable transcriptome information for characterizing mechanisms of these diseases.
Detection of Antisense and Ribozyme Accessible Sites on Native mRNAs: Application to NCOA3 mRNA (2001)

The efficacies of antisense oligonucleotides and ribozymes are greatly dependent on the accessibility of their mRNA targets. Target site accessibility is affected by both RNA structure and the proteins associated along the length of the RNA. To mimic the native state of mRNA for site identification, we have previously used endogenous mRNAs in cellular extracts as targets for defined sequence oligodeoxynucleotides (ODNs) designed to identify both antisense pairing and potential ribozyme cleavage sites. The rationale for this approach is that the specific pairing of an ODN with a mRNA forms a DNA:RNA hybrid that is cleaved by the endogenous RNaseH in the cell extract. To extend the usefulness of this basic approach, we report here the use of semi-random ODN libraries to identify hammerhead ribozyme cleavage sites. Thus, the most accessible sites for antisense and ribozyme base pairing are selected by this approach. A novel feature of the approach described here is the use of terminal transferase-dependent PCR (TDPCR) after reverse transcription to estimate the cleavage efficiency and to precisely determine the RNaseH and ribozyme cleavage sites on mRNAs in cell extracts following treatment with ODN or ribozyme libraries. As a model system, we have targeted the NCOA3 (also known as AIB-1) mRNA in cell extracts. The NCOA3 mRNA encodes a nuclear receptor co-activator that is amplified and over-expressed in a high proportion of breast and ovarian cancers. A highly accessible site on this mRNA was identified, and a ribozyme targeted to this site was demonstrated to effectively downregulate NCOA3 function in cells.
Signal Transduction and the Control of Gene Expression (2002)

More than 2000 transcription factors are encoded in the human genome. Such proteins have often been classified according to common structural elements. But because transcription factors evolved in the service of biologic function, we propose an alternative grouping of eukaryotic transcription factors on the basis of characteristics that describe their roles within cellular regulatory circuits.
One-Step Selection of Artificial Transcription Factors Using an In Vivo Screening System (2006)

Gene expression is regulated in large part at the level of transcription under the control of sequence-specific transcriptional regulatory proteins. Therefore, the ability to affect gene expression at will using sequence-specific artificial transcription factors would provide researchers with a powerful tool for biotechnology research and drug discovery. Previously, we isolated 56 novel sequence-specific DNA-binding domains from the human genome by in vivo selection. We hypothesized that these domains might be more useful for regulating gene expression in higher eukaryotic cells than those selected in vitro using phage display. However, an unpredictable factor, termed the "context effect", is associated with the construction of novel zinc finger transcription factors--- DNA-binding proteins that bind specifically to 9-base pair target sequences. In this study, we directly selected active artificial zinc finger proteins from a zinc finger protein library. Direct in vivo selection of constituents of a zinc finger protein library may be an efficient method for isolating multi-finger DNA binding proteins while avoiding the context effect.
Attachment of the soluble complement regulator factor H to cell and tissue surfaces: relevance for pathology. (2004)

Complement is a central element of innate immunity and this vital defense system initiates and coordinates immediate immune reactions which attack and eliminate microbes, foreign particles and altered self cells. Newly generated activation products are extremely toxic and consequently, activation is highly restricted in terms of time and space. The initial activation of the alternative complement pathway occurs continuously and the early phase acts indiscriminatoryl and forms on any surface. However, the system discriminates between self and foreign, and therefore allows activation on foreign surfaces e.g. microbes, and restricts activation on host cells. Consequently, self cells and tissues are protected from the harmful activation products. This protection is mediated by specific regulators or inhibitors, which exist in the fluid phase and/or in membrane-bound forms. Here we review a novel mechanism, i.e. the attachment of the soluble complement regulator factor H to the surface of self cells. This attachment, which is demonstrated experimentally by means of immunofluorescense microscopy and by flow cytometry, increases the inhibitory potential at the cell surface and mediates protection by reducing the local formation of toxic inflammatory products. This attachment is highly relevant and has pathophysiological consequences in several human diseases, including Factor H-associated hemolytic uremic syndrome (FH-HUS), membrano-proliferative glomerulonephritis type II, recurrent microbial infections and chronic inflammation, e.g. rheumatoid arthritis and immune evasion of tumor cells. Defects of this safeguard activity have been recently understood in patients with FH-HUS. Point mutations in the Factor H gene occurring in the C-terminus of the protein result in impaired cell binding capacity of Factor H and, consequently, during an inflammatory insult endothelial cells are not properly protected and are damaged.
A new powerful inhibitor specific for the TPN binding site of 6‐phosphogluconate dehydrogenase (1975)

It has been recently reported that, treating TPN&#13;\nwith periodate, there is the oxidation to aldehydic&#13;\ngroups of the two alcoholic groups present at carbons&#13;\n2’ and 3’ of the ribose ring bound to the nicotinamide;&#13;\nthis periodate oxidized TPN can be bound covalently&#13;\nto a resin to obtain a resin derivative useful for affinity&#13;\nchromatography of dehydrogenases [2] .&#13;\nWe have now found that periodate oxidized TPN&#13;\ncan be used efficiently as a powerful inhibitor specific&#13;\nfor the TPN binding site of 6-phosphogluconate&#13;\ndehydrogenase from Candida utilis.
Model-based learning of segmentations (1996)

A method for integrating image segmentation information into geometric models is presented. The resulting object representation has advantages of both model-based and view-based representations, in that model geometry plus learned appearance information is used to improve the prediction of object appearance over purely geometric methods. The combined models are constructed over a training set of imagery using prior geometric models. Segmentation features are matched to the geometric models, and an evidential framework is used to characterize the segmentations of model features. To test the validity of the models, a pose adjustment system was modified to incorporate the prior segmentation information. Results indicate that the inclusion of the segmentation information significantly improves pose adjustment accuracy over using purely geometric information for model appearance.
Molecular Characterization of Two Novel Antibacterial Peptides Inducible upon Bacterial Challenge in an Annelid, the Leech Theromyzon tessulatum (2004)

Two novel antimicrobial peptides named theromacin and theromyzin were isolated and characterized from the coelomic liquid of the leech Theromyzon tessulatum. Theromacin is a 75-amino acid cationic peptide containing 10 cysteine residues arranged in a disulfide array showing no similarities with other known antimicrobial peptides. Theromyzin is an 86-amino acid linear peptide and constitutes the first anionic antimicrobial peptide observed in invertebrates. Both peptides exhibit activity directed against Gram-positive bacteria. Theromacin and theromyzin cDNAs code precursor molecules containing a putative signal sequence directly followed by the mature peptide. The enhancement of theromacin and theromyzin mRNA levels has been observed after blood meal ingestion and upon bacterial challenge. In situ hybridization revealed that both genes are expressed in large fat cells in contact with coelomic cavities. Gene products were immunodetected in large fat cells, in intestinal epithelia, and at the epidermis level. In addition, a rapid release of the peptides into the coelomic liquid was observed after bacterial challenge. The presence of antimicrobial peptide genes in leeches and their expression in a specific tissue functionally resembling the insect fat body provide evidence for the first time of an antibacterial response in a lophotrochozoan comparable to that of holometabola insects.
High Resolution Genome Wide Binding Event Finding and Motif Discovery Reveals Transcription Factor Spatial Binding Constraints (2012)

An essential component of genome function is the syntax of genomic regulatory elements that determine how diverse transcription factors interact to orchestrate a program of regulatory control. A precise characterization of in vivo spacing constraints between key transcription factors would reveal key aspects of this genomic regulatory language. To discover novel transcription factor spatial binding constraints in vivo, we developed a new integrative computational method, genome wide event finding and motif discovery (GEM). GEM resolves ChIP data into explanatory motifs and binding events at high spatial resolution by linking binding event discovery and motif discovery with positional priors in the context of a generative probabilistic model of ChIP data and genome sequence. GEM analysis of 63 transcription factors in 214 ENCODE human ChIP-Seq experiments recovers more known factor motifs than other contemporary methods, and discovers six new motifs for factors with unknown binding specificity. GEM's adaptive learning of binding-event read distributions allows it to further improve upon previous methods for processing ChIP-Seq and ChIP-exo data to yield unsurpassed spatial resolution and discovery of closely spaced binding events of the same factor. In a systematic analysis of in vivo sequence-specific transcription factor binding using GEM, we have found hundreds of spatial binding constraints between factors. GEM found 37 examples of factor binding constraints in mouse ES cells, including strong distance-specific constraints between Klf4 and other key regulatory factors. In human ENCODE data, GEM found 390 examples of spatially constrained pair-wise binding, including such novel pairs as c-Fos:c-Jun/USF1, CTCF/Egr1, and HNF4A/FOXA1. The discovery of new factor-factor spatial constraints in ChIP data is significant because it proposes testable models for regulatory factor interactions that will help elucidate genome function and the implementation of combinatorial control.
Electrical detection of kidney injury molecule-1 with AlGaN∕GaN high electron mobility transistors (2007)

Al Ga N ∕ Ga N high electron mobility transistors (HEMTs) were used to detect kidney injury molecule-1 (KIM-1), an important biomarker for early kidney injury detection. The gate region consisted of 5nm gold deposited onto the AlGaN surface. The gold was conjugated to highly specific KIM-1 antibodies through a self-assembled monolayer of thioglycolic acid. The HEMT source-drain current showed a clear dependence on the KIM-1 concentration in phosphate-buffered saline solution. The limit of detection was 1ng∕ml using a 20×50μm2 gate sensing area. This approach shows potential for both preclinical and clinical kidney injury diagnosis with accurate, rapid, noninvasive, and high throughput capabilities.
Towards nanocomputer architecture (2002)

At the nanometer scale, the focus of micro-architecture will move from processing to communication. Most general computer architectures to date have been based on a stored program paradigm that differentiates between memory and processing and relies on communication over busses and other (relatively) long distance mechanisms. Nanometer-scale electronics --- nanoelectronics - promises to fundamentally change the ground-rules. Processing will be cheap and plentiful, interconnection expensive but pervasive. This will tend to move computer architecture in the direction of locally-connected, reconfigurable hardware meshes that merge processing and memory. If the overheads associated with reconfigurability can be reduced or even eliminated, architectures based on non-volatile, reconfigurable, fine-grained meshes with rich, local interconnect offer a better match to the expected characteristics of future nanoelectronic devices.
Structural Characteristics and Swelling Behavior of Poly(ethylene glycol) Diacrylate Hydrogels (1996)

Poly(ethylene glycol)s (PEGs) in the molecular weight range 200−3400 were derivatized at both ends with acryloyl chloride. These poly(ethylene glycol) diacrylates (PEGDAs) on homopolymerization yield cross-linked networks whose Mc values should correspond to the molecular weight of the PEGDA macromer. Mc values calculated according to the Flory−Rehner equation compare very well with the theoretical values for low concentrations of low molecular weight monomers. Those at high concentrations and higher molecular weights are always lower than the expected values. Attempts to resolve the equilibrium swelling and elastic components indicate that the phantom model gives a better fit.
Requirement for terminal cytochromes in generation of the aerobic signal for the arc regulatory system in Escherichia coli: study utilizing deletions and lac fusions of cyo and cyd (1990)

Escherichia coli has two terminal oxidases for its respiratory chain: cytochrome o (low O2 affinity) and cytochrome d (high O2 affinity). Expression of the cyo operon, encoding cytochrome o, is decreased by anaerobic growth, whereas expression of the cyd operon, encoding cytochrome d, is increased by anaerobic growth. We show by the use of lac gene fusion that the expressions of cyo and cyd are under the control of the two-component arc system. In a cyo+ cyd+ background, expression of phi(cyo-lac) is higher when the organism is grown aerobically than when it is grown anaerobically. A mutation in either the sensor gene arcB or the pleiotropic regulator gene arcA almost abolishes the anaerobic repression. In the same background, expression of phi(cyd-lac) is higher under anaerobic growth conditions than under aerobic growth conditions. A mutation in arcA or arcB lowers both the aerobic and anaerobic expressions, suggesting that ArcA plays an activating role instead of the typical repressing role. Under aerobic growth conditions, double deletions of cyo and cyd lower phi(cyo-lac) expression but enhance phi(cyd-lac) expression. The double deletions also prevent elevated aerobic induction of the lct operon (encoding L-lactate dehydrogenase), another target operon of the arc system. In contrast, these deletions do not circumvent aerobic repression of the nar operon (encoding the anaerobic respiratory enzyme nitrate reductase) under the control of the pleiotropic fnr gene product. It thus appears that ArcB senses the presence of O2 by level of an electron transport component in reduced form or that of an nonautoxidizable compound linked to the process by a redox reaction, whereas Fnr senses O2 by a different mechanism.
In vitroActivation of Mononuclear Cells by Two Probiotics:Lactobacillus paracaseiI 1688,Lactobacillus salivariusI 1794, and their Mixture (PSMIX) (2007)

This study provides the first evidence that Lactobacillus paracasei and Lactobacillus salivarius are capable of inducing a specific immune response that may be useful in the clinical setting for improving innate and adaptive immune responses.
Narrowband and broadband ISDN CPE directions (1990)

Noting that ISDN customer premises equipment (CPE) is critical to the successful deployment of ISDN whatever the bandwidth, the author examines the market for narrowband and wideband integrated services digital network (NISDN and BISDN) CPE. He establishes the basic requirements for NISDN terminals and discusses terminal adaptors, digital telephone sets, screen-based telephony, workstations, customer premises networks, and CPE maintenance and upgrades. He examines the BISDN market and discusses the features and architecture of the terminals.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Technology constraints on VLSI processor implementation (2003)

It is shown that the critical path for the machine cycle time is determined by signals crossing the chip boundaries. The microarchitecture and logic design of processors integrated on VLSI must work within the technological constraints to perform optimal functionality with a machine cycle. With efficient pipeline control techniques the optimal pipeline depth can be chose to balance the maximum function per pipeline segment with the penalty of crossing the chip boundaries. The gate-density provided by automated ASICs (application-specific integrated circuits) is rapidly approaching what has so far been possible with extensive customization, but for the near future the highest gate-density still requires a full-custom approach. Advances in cost-effective integration have to extend to multichip packaging and board assembly. Efficient methods of cooling that can allow the VLSI chips to operate at lower temperatures can also give gains that are frequently ignored.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Phase I study of nanoliposomal irinotecan (PEP02) in advanced solid tumor patients (2015)

PEP02 apparently modified the PK parameters of irinotecan and SN-38 by liposome encapsulation. The MTD of PEP02 monotherapy at 3-week interval is 120 mg/m(2), which will be the recommended dose for future studies.
A More Accurate Method To Estimate Glomerular Filtration Rate from Serum Creatinine: A New Prediction Equation (1999)

The equation developed from the MDRD Study provided a more accurate estimate of GFR in our study group than measured creatinine clearance or other commonly used equations.
Acoustofluidics 23: acoustic manipulation combined with other force fields (2013)

In this, the final paper of the Acoustofluidics series of tutorial articles, we discuss applications in which acoustic radiation forces are used in conjunction with competing or complementary force-fields. This may be in order to enable manipulation operations that would not be easily performed by either force-field alone, or may be used to effect separation based on the different physical principals underlying competing fields. Examples are given of a number of different applications in which acoustic forces are combined with gravitational fields, hydrodynamic forces, electric fields (including dielectrophoresis), magnetic forces and optical forces.
TM-wave radiation from grooves in a dielectric-covered ground plane (2001)

This article describes the radiation characteristics from multiple rectangular grooves in a dielectric-covered ground plane. The theoretical far-zone radiation pattern is compared with the measured data at 10 and 11 GHz using a wavenumber conversion procedure.