gebhart/patrepeval huggingface dataset:
Molecular regulation of pancreatic stellate cell function. (2004)

Until now, no specific therapies are available to inhibit pancreatic fibrosis, a constant pathological feature of chronic pancreatitis and pancreatic cancer. One major reason is the incomplete knowledge of the molecular principles underlying fibrogenesis in the pancreas. In the past few years, evidence has been accumulated that activated pancreatic stellate cells (PSCs) are the predominant source of extracellular matrix (ECM) proteins in the diseased organ. PSCs are vitamin A-storing, fibroblast-like cells with close morphological and biochemical similarities to hepatic stellate cells (also known as Ito-cells). In response to profibrogenic mediators such as various cytokines, PSCs undergo an activation process that involves proliferation, exhibition of a myofibroblastic phenotype and enhanced production of ECM proteins. The intracellular mediators of activation signals, and their antagonists, are only partially known so far. Recent data suggest an important role of enzymes of the mitogen-activated protein kinase family in PSC activation. On the other hand, ligands of the nuclear receptor PPARgamma (peroxisome proliferator-activated receptor gamma) stimulate maintenance of a quiescent PSC phenotype. In the future, targeting regulators of the PSC activation process might become a promising approach for the treatment of pancreatic fibrosis.
Effects of transcutaneous electrical nerve stimulation (TENS) on arterial stiffness and blood pressure in resistant hypertensive individuals: study protocol for a randomized controlled trial (2016)

Clinical Trials NCT02365974.
Classification of unit types in the anteroventral cochlear nucleus: PST histograms and regularity analysis (1989)

1. The responses of neurons in the anteroventral cochlear nucleus (AVCN) of barbiturate-anesthetized cats are characterized with regard to features of their responses to short tone bursts (STBs; 25 ms). A "decision tree" is presented to partition AVCN units on the basis of post-stimulus time histogram (PSTH) shape, first spike latency, and discharge rate and regularity calculated as functions of time during responses to STBs. The major classes of AVCN units (primary-like, primary-like-with-notch, chopper, and onset) have been described previously; in this paper, special attention is given to clarifying and systematizing boundaries between classes. Certain types of "unusual" units that may be confused with units in one of the major classes are also examined. 2. When STBs are presented synchronously (constant phase at onset), PSTHs of responses to very-low-frequency (less than 1.0 kHz) tones are difficult if not impossible to resolve into the classes listed above because all unit types phase-lock to low-frequency tones. However, when STBs are presented asynchronously, the responses of units with low best frequencies can be categorized on the basis of PSTH shape and first spike latency. 3. Primary-like, primary-like-with-notch, and onset units are distinguished primarily on the basis of PSTH shape. These three unit types have comparable minimum first spke latencies and synchronization to tones. One type of "unusual" response poses a particular hazard with respect to the generation of uncontaminated primary-like populations. Such "unusual" units have PSTHs that appear primary-like; these units are, however, distinguished by their unusually long first spike latencies. Unlike primary-like units, these "unusual" units show extremely poor synchronization to tones. 4. Chopper units are defined as having an initial response that is highly regular, resulting in the characteristic multimodal PSTH. "Unusual" units with multimodal PSTHs but whose initial responses are not highly regular (measured by the reproducibility of the initial firing pattern in response to multiple repetitions of a STB) are eliminated from the chopper populations. 5. In barbiturate-anesthetized cats, at least three patterns of chopper response can be distinguished on the basis of temporal patterns of rate and regularity adaptation. "Sustained" choppers show no adaptation of instantaneous rate (measured by the inverse of the mean interspike interval), and their discharge remains highly regular throughout the response. "Transiently adapting" choppers undergo a very rapid (less than 10 ms) decrease in instantaneous rate accompanied by a sharp increase in discharge irregularity.(ABSTRACT TRUNCATED AT 400 WORDS)
Intrinsic B cell hypo‐responsiveness in mice prematurely expressing human CR2/CD21 during B cell development (2007)

We previously reported that human CR2 (hCR2) prematurely expressed under a murine Vlambda2 promoter/Vlambda2-4 enhancer minigene during the CD43+ CD25- late pro-B cell stage of development results in peripheral B cells with impaired responses to immunization with T-dependent antigens. Herein, we show that hCR2 transgenic (Tg) mice also demonstrate a severe defect in T-independent antigen responses and are substantially protected from clinical arthritis, synovitis and cartilage/bone destruction in a collagen-induced arthritis model. This outcome is found despite the apparently normal development of autoreactive T cells with equivalent cytokine and proliferative responses to antigen when compared to non-Tg control mice. These data suggest the presence of an intrinsic B cell defect in the hCR2 Tg mice. We also show that an hCR2-dependent Ca2+ influx can be generated in both developing and mature Tg B cells, but with different rates of decay as compared to control wild-type (WT) mice. In addition, although analysis of tyrosine-phosphorylated proteins in WT and Tg B cells following B cell receptor (BCR)-induced activation revealed the presence of distinctly different phosphorylation patterns, no differences were identified in several candidate protein targets. Overall, these data suggest that premature hCR2 expression and the consequences thereof during B cell development intrinsically alters the way mature B cells develop and subsequently respond to antigen through the BCR signaling complex.
Integrated CMOS-selenium x-ray detector for digital mammography (1998)

This paper describes a novel area detector for direct conversion and readout of the x-ray energy that eliminates multiple conversions and coupling stages which degrade performance. The pixel array and readout electronics are fabricated on the same piece of silicon. The detector consists of a uniform layer (approximately 300 micrometers) of amorphous selenium alloy vapor-deposited on an electronic readout array fabricated using conventional complementary metal oxide semiconductor (CMOS). The CMOS array features 66 micrometer pixels in a 1024 X 832 array providing a 5.5 X 6.75 cm image area. Each pixel has active circuitry including signal amplification, pixel selection and reset, while peripheral circuitry on one end of the array provides shift registers, sample and hold and multiplexing. The CMOS readout array was fabricated at a standard facility on a 10-cm diameter silicon wafer using 2 micrometer CMOS process. Fifteen separate image sensors were assembled for evaluation in a 3 X 5 format to provide a 20 X 27 cm composite field of view. Missing data between sensors is recovered by acquiring three sub-exposures, between which the array is translated diagonally approximately 2 mm. Total exposure time for an average breast is less than one second. Conversion efficiency was found to be approximately 120 electrons per absorbed x-ray (19 keV average). Electronic readout noise was measured to be 2.4 ADU corresponding to approximately 500 electrons. Detective quantum efficiency was found to be 0.65 at low spatial frequency (0.25 lp/mm) and at 0.2 at high spatial frequency (8 lp/mm) for x-ray fluence ranging from 5 - 35 mR. Images of an ACR phantom show visualization of all of the fibers, specks and masses when displayed with a linear lookup table on a high-resolution monitor. These studies demonstrated that there is a slight but measurable image retention evident as 'ghost' images. The two most effective means to reduce this effect are flushing the sensors with infrared light or x-rays between exposures and reversing the applied voltage on the selenium layer. A number of improvements designed to increase sensitivity and reduce noise also have been identified and are being implemented. Sample images were acquired from four volunteer human subjects at exposure factors identical to their film-screen mammograms. The results suggest that the detector performance is suitable for further clinical investigation.
An interactive out-of-core rendering framework for visualizing massively complex models (2005)

With the tremendous advances in both hardware capabilities and rendering algorithms, rendering performance is steadily increasing. Even consumer graphics hardware can render many million triangles per second. However, scene complexity seems to be rising even faster than rendering performance, with no end to even more complex models in sight.In this paper, we are targeting the interactive visualization of the "Boeing 777" model, a highly complex model of 350 million individual triangles, which - due to its sheer size and complex internal structure - simply cannot be handled satisfactorily by today's techniques. To render this model, we use a combination of real-time ray tracing, a low-level out of core caching and demand loading strategy, and a hierarchical, hybrid volumetric/lightfield-like approximation scheme for representing not-yet-loaded geometry. With this approach, we are able to render the full 777 model at several frames per second even on a single commodity desktop PC.
Molecular genetics of bipolar disorder (2001)

Background A robust body of evidence from family, twin and adoption studies demonstrates the importance of genes in the pathogenesis of bipolar disorder. Recent advances in molecular genetics have made it possible to identify these susceptibility genes. Aims To present an overview for clinical psychiatrists. Method Review of current molecular genetics approaches and emerging findings. Results Occasional families may exist in which a single gene plays a major role in determining susceptibility, but the majority of bipolar disorder involves more complex genetic mechanisms such as the interaction of multiple genes and environmental factors. Molecular genetic positional and candidate gene approaches are being used for the genetic dissection of bipolar disorder. No gene has yet been identified but promising findings are emerging. Regions of interest include chromosomes 4p16, 12q23-q24, 16p13, 21q22, and Xq24-q26. Candidate gene association studies are in progress but no robust positive findings have yet emerged. Conclusion It is almost certain that over the next few years the identification of bipolar susceptiblity genes will have a major impact on our understanding of disease pathophysiology. This is likely to lead to major improvements and treatment in patient care, but will also raise important ethical issues.
Salivary Secretory Leukocyte Protease Inhibitor Is Associated with Reduced Transmission of Human Immunodeficiency Virus Type 1 through Breast Milk (2002)

Secretory leukocyte protease inhibitor (SLPI), a protein found in saliva, breast milk, and genital secretions, is capable of inhibiting human immunodeficiency virus (HIV) type 1 in vitro. The aim of this study was to determine whether SLPI in infant saliva provides protection against mother-to-child HIV-1 transmission. In total, 602 saliva specimens were collected from 188 infants at birth and at ages 1, 3, and 6 months. Infants' median salivary SLPI concentrations were higher at birth than at 6 months (341 vs. 219 ng/mL; P=.001). There was no association between SLPI concentration and HIV-1 transmission overall. However, among 122 breast-fed infants who were HIV-1 uninfected at 1 month, higher salivary SLPI levels were associated with a decreased risk of HIV-1 transmission through breast milk (hazard ratio, 0.5; 95% confidence interval, 0.3-0.9; P=.03). These results suggest that SLPI plays an important role in reducing HIV-1 transmission through breast milk.
Identification of the thymidine kinase gene of feline herpesvirus: use of degenerate oligonucleotides in the polymerase chain reaction to isolate herpesvirus gene homologs (1989)

Feline herpesvirus 1 (FHV) is the causative agent of viral rhinotracheitis in cats. Current vaccination programs employing attenuated live and killed FHV vaccines have been effective in reducing the incidence of this disease. As an initial step in the development of recombinant FHVs for use in the vaccination of cats, we have identified the thymidine kinase (TK) gene of this feline-specific alphaherpesvirus. Comparisons of the amino acid sequences of other herpesvirus TK proteins have shown that these proteins are highly divergent, sharing only short regions of imperfect amino acid identity. We have used the polymerase chain reaction method of DNA amplification to increase the specificity associated with the use of short, highly degenerate oligonucleotide probes derived from regions of imperfect amino acid conservation. These methods were used to isolate the TK gene of FHV and should prove to be useful in the identification of new members of other viral and cellular gene families. A recombinant FHV bearing a deletion in the identified TK gene was constructed and shown to possess the expected TK- phenotype. The FHV TK gene is located at a position of approximately 40% in the long unique component of the FHV genome. The location of the TK gene and the location and orientation of flanking FHV genes, homologs of herpes simplex virus type 1 UL24 and UL22, are conserved among alphaherpesviruses.
Global Expression Profiling of Acetate-grown Escherichia coli (2002)

This study characterized the transcript profile of Escherichia coli in acetate cultures using DNA microarray on glass slides. Glucose-grown cultures were used as a reference. At the 95% confidence level, 354 genes were up-regulated in acetate, while 370 genes were down-regulated compared with the glucose-grown culture. Generally, more metabolic genes were up-regulated in acetate than other gene groups, while genes involved in cell replication, transcription, and translation machinery tended to be down-regulated. It appears that E. coli commits more resources to metabolism at the expense of growth when cultured in the poor carbon source. The expression profile confirms many known features in acetate metabolism such as the induction of the glyoxylate pathway, tricarboxylic acid cycle, and gluconeogenic genes. It also provided many previously unknown features, including induction of malic enzymes, ppsA, and the glycolate pathway and repression of glycolytic and glucose phosphotransferase genes in acetate. The carbon flux delivered from the malic enzymes and PpsA in acetate was further confirmed by deletion mutations. In general, the gene expression profiles qualitatively agree with the metabolic flux changes and may serve as a predictor for gene function and metabolic flux distribution.
Ki-1 -Positive Non-Hodgkin's Lymphomas: An Immunophenotypic, Ultrastructural, and Morphometric Study (1990)

The authors studied four cases of diffuse, large cell non-Hodgkin's lymphomas with strong Ki-1 expression to determine if they shared characteristic ultrastructural or morphometric features in common. The tumor cells in these lymphomas all had very abundant cytoplasm, which often showed a concentration of organelles, especially mitochondria and Golgi apparatus, in regions next to nuclear concavities. One case had very complex cytoplasmic membrane projections resembling a "microvillous" lymphoma. These ultrastructural features combined with the frequent reniform nuclei and scattered lysosomes suggested histiocyte differentiation. However the immunophenotype was variable, more often showing "activation" markers and abnormal T-cell marker patterns. The mean nuclear area for all cases was between 38.3 +/- 12.7 to 42.3 +/- 16.2 microns2, roughly twice the size of the small lymphocyte population. The nuclear contour index, a measure of irregularity of the nuclear membrane, ranged from 4.75 +/- 0.86 to 6.36 +/- 1.89 (a circle is 3.54). These nuclear parameters are comparable in size to those of previously measured large cell lymphomas but exhibit more nuclear irregularity than most. Ki-1 lymphomas appear to represent a somewhat diverse group of tumors of lymphoid origin that exhibit some hybrid features of histiocytes.
The optimal distance measure for nearest neighbor classification (1981)

A local distance measure is shown to optimize the performance of the nearest neighbor two-class classifier for a finite number of samples. The difference between the finite sample error and the asymptotic error is used as the criterion of improvement. This new distance measure is compared to the well-known Euclidean distance. An algorithm for practical implementation is introduced. This algorithm is shown to be computationally competitive with the present nearest neighbor procedures and is illustrated experimentally. A closed form for the corresponding second-order moment of this criterion is found. Finally, the above results are extended to
Anagram: A Content Anomaly Detector Resistant to Mimicry Attack (2006)

In this paper, we present Anagram, a content anomaly detector that models a mixture of high-order n-grams (n &gt; 1) designed to detect anomalous and "suspicious" network packet payloads. By using higher-order n-grams, Anagram can detect significant anomalous byte sequences and generate robust signatures of validated malicious packet content. The Anagram content models are implemented using highly efficient Bloom filters, reducing space requirements and enabling privacy-preserving cross-site correlation. The sensor models the distinct content flow of a network or host using a semi-supervised training regimen. Previously known exploits, extracted from the signatures of an IDS, are likewise modeled in a Bloom filter and are used during training as well as detection time. We demonstrate that Anagram can identify anomalous traffic with high accuracy and low false positive rates. Anagram's high-order n-gram analysis technique is also resilient against simple mimicry attacks that blend exploits with "normal" appearing byte padding, such as the blended polymorphic attack recently demonstrated in [1]. We discuss randomized n-gram models, which further raises the bar and makes it more difficult for attackers to build precise packet structures to evade Anagram even if they know the distribution of the local site content flow. Finally, Anagram's speed and high detection rate makes it valuable not only as a standalone sensor, but also as a network anomaly flow classifier in an instrumented fault-tolerant host-based environment; this enables significant cost amortization and the possibility of a "symbiotic" feedback loop that can improve accuracy and reduce false positive rates over time.
DC-SIGNR, a DC-SIGN homologue expressed in endothelial cells, binds to human and simian immunodeficiency viruses and activates infection in trans (2001)

DC-SIGN, a C-type lectin expressed on the surface of dendritic cells (DCs), efficiently binds and transmits HIVs and simian immunodeficiency viruses to susceptible cells in trans. A DC-SIGN homologue, termed DC-SIGNR, has recently been described. Herein we show that DC-SIGNR, like DC-SIGN, can bind to multiple strains of HIV-1, HIV-2, and simian immunodeficiency virus and transmit these viruses to both T cell lines and human peripheral blood mononuclear cells. Binding of virus to DC-SIGNR was dependent on carbohydrate recognition. Immunostaining with a DC-SIGNR-specific antiserum showed that DC-SIGNR was expressed on sinusoidal endothelial cells in the liver and on endothelial cells in lymph node sinuses and placental villi. The presence of this efficient virus attachment factor on multiple endothelial cell types indicates that DC-SIGNR could play a role in the vertical transmission of primate lentiviruses, in the enabling of HIV to traverse the capillary endothelium in some organs, and in the presentation of virus to CD4-positive cells in multiple locations including lymph nodes.
Clinical Development of a Cytomegalovirus DNA Vaccine: From Product Concept to Pivotal Phase 3 Trial (2013)

2013 marks a milestone year for plasmid DNA vaccine development as a first-in-class cytomegalovirus (CMV) DNA vaccine enters pivotal phase 3 testing. This vaccine consists of two plasmids expressing CMV antigens glycoprotein B (gB) and phosphoprotein 65 (pp65) formulated with a CRL1005 poloxamer and benzalkonium chloride (BAK) delivery system designed to enhance plasmid expression. The vaccine's planned initial indication under investigation is for prevention of CMV reactivation in CMV-seropositive (CMV⁺) recipients of an allogeneic hematopoietic stem cell transplant (HCT). A randomized, double-blind placebo-controlled phase 2 proof-of-concept study provided initial evidence of the safety of this product in CMV⁺ HCT recipients who underwent immune ablation conditioning regimens. This study revealed a significant reduction in viral load endpoints and increased frequencies of pp65-specific interferon-γ-producing T cells in vaccine recipients compared to placebo recipients. The results of this endpoint-defining trial provided the basis for defining the primary and secondary endpoints of a global phase 3 trial in HCT recipients. A case study is presented here describing the development history of this vaccine from product concept to initiation of the phase 3 trial.
Novel Small Molecule Inhibitors of 3-Phosphoinositide-dependent Kinase-1 (2005)

The phosphoinositide 3-kinase/3-phosphoinositide-dependent kinase 1 (PDK1)/Akt signaling pathway plays a key role in cancer cell growth, survival, and tumor angiogenesis and represents a promising target for anticancer drugs. Here, we describe three potent PDK1 inhibitors, BX-795, BX-912, and BX-320 (IC(50) = 11-30 nm) and their initial biological characterization. The inhibitors blocked PDK1/Akt signaling in tumor cells and inhibited the anchorage-dependent growth of a variety of tumor cell lines in culture or induced apoptosis. A number of cancer cell lines with elevated Akt activity were >30-fold more sensitive to growth inhibition by PDK1 inhibitors in soft agar than on tissue culture plastic, consistent with the cell survival function of the PDK1/Akt signaling pathway, which is particularly important for unattached cells. BX-320 inhibited the growth of LOX melanoma tumors in the lungs of nude mice after injection of tumor cells into the tail vein. The effect of BX-320 on cancer cell growth in vitro and in vivo indicates that PDK1 inhibitors may have clinical utility as anticancer agents.
A novel strategy for converting recombinant viral protein into high immunogenic antigen (1991)

Interleukin 2 (IL-2) is a lymphokine promoting immune response and therefore has been investigated as an immunological adjuvant. In order to enhance the immunogenicity of recombinant viral protein, herpes simplex virus type 1 (HSV-1) glycoprotein D (gD), we genetically created a fusion protein consisting of gD and human IL-2. The fusion protein, without any other adjuvants, induced high antibody responses and cell-mediated immunity to HSV-1 in mice. Mice immunized with the fusion protein were protected against HSV-1 infection. The results indicate that IL-2-fusing can provide a means for converting a weak immunogenic protein into a high immunogenic antigen, and the strategy would be widely applicable to the other antigens for pathogens.
Feature-Based Textures (2004)

This paper introduces feature-based textures, a new image representation that combines features and samples for high-quality texture mapping. Features identify boundaries within an image where samples change discontinuously. They can be extracted from vector graphics representations, or explicitly added to raster images to improve sharpness. Texture lookups are then interpolated from samples while respecting these boundaries. We present results from a software implementation of this technique demonstrating quality, efficiency and low memory overhead.