gebhart/patrepeval huggingface dataset:
Lymphokine Control of In Vivo Immunoglobulin Isotype Selection (1990)

Several specific conclusions can be drawn from these studies: 1. IL-4 is required for the generation of both primary polyclonal and secondary antigen-specific IgE responses in vivo. 2. IL-4 is required to maintain established, ongoing, antigen-specific and polyclonal IgE responses. 3. Most, but not all, polyclonal IgE production during a secondary immune response is IL-4-dependent. Memory B cells that have already switched to IgE at the DNA level may no longer require stimulation with IL-4 to be induced to secrete IgE. 4. The generation of a secondary IgE response is not dependent upon the presence of IL-4 during primary immunization. However, if IL-4 is not present during primary immunization, it is required during secondary immunization for the generation of an IgE response. 5. IL-4 does not appear to be required for the generation of in vivo IgG1 responses, and in at least some instances, does not contribute significantly to the generation of IgG1 responses in vivo. 6. A late-acting form of T-cell help other than IL-4 appears to be required for the generation of an IgE, but not an IgG1 response. 7. An antibody that inhibits IL-4 binding to IL-4 receptors affects Ig isotype selection in the same way as an antibody that neutralizes IL-4. 8. IFN-gamma can act in both spontaneous and induced immune responses to suppress IgE production. 9. IFN-gamma can also suppress IgG1 production and stimulate IgG2a production. However, IFN-gamma appears to suppress polyclonal IgG1 responses more than antigen-specific IgG1 responses, and it enhances, but is not required for, the generation of IgG2a responses. 10. IFN-alpha appears to resemble IFN-gamma in its ability to inhibit IgE and enhance IgG2a responses in GaM delta-injected mice, but it requires the presence of IFN-gamma to suppress IgG1 production in these mice. 11. Both IFN-alpha and IFN-gamma appear to be able to decrease IgE production in some human patients. 12. There is no direct evidence that IL-5 contributes to the generation of in vivo antibody responses. Two general conclusions may also be drawn.(ABSTRACT TRUNCATED AT 400 WORDS)
Vaginal Wall Sling (1989)

We describe a new technique for the treatment of urinary incontinence due to intrinsic sphincteric damage in which a sling constructed from vaginal wall is used to provide compression and support of the urethra. A rectangular island of in situ anterior vaginal wall underlying the urethra and bladder neck is developed, the 4 corners are anchored with polypropylene sutures and a ligature carrier is used to transfer the sutures to a suprapubic location. An anterior vaginal wall flap proximal to the island is advanced to cover the island. When the sutures are tied the resulting sling will support the urethra and increase urethral resistance by compression, restoring continence. The advantages are its simplicity, need for only a small incision, short operative time and hospital stay, and reliance on healthy, well vascularized, in situ tissue. Continence has been achieved in 29 of 32 cases. All patients voided spontaneously except for those with neuropathic urethral incompetence who required self-catheterization.
Biomechanical Analysis of a Chondrocyte-Based Repair Model of Articular Cartilage (1999)

The objective of this study was to evaluate the biomechanical properties of newly formed cartilaginous tissue synthesized from isolated chondrocytes. Cartilage from articular joints of lambs was either digested in collagenase to isolated chondrocytes or cut into discs that were devitalized by multiple freeze-thaw cycles. Isolated cells were incubated in suspension culture in the presence of devitalized cartilage matrix for 3 weeks. Multiple chondrocyte/matrix constructs were assembled with fibrin glue and implanted subcutaneously in nude mice for up to 6 weeks. Testing methods were devised to quantify integration of cartilage pieces and mechanical properties of constructs. These studies showed monotonic increase with time in tensile strength, fracture strain, fracture energy, and tensile modulus to values 5-10% of normal articular cartilage by 6 weeks in vivo. Histological analysis indicated that chondrocytes grown on dead cartilage matrix produced new matrix that integrated individual cartilage pieces with mechanically functional tissue.
Epidermal growth factor receptor inhibition by a monoclonal antibody as anticancer therapy. (1997)

Monoclonal antibody (mAb) 225 against the human epidermal growth factor receptor blocks activation of receptor tyrosine kinase. This retards or arrests cell cycle progression, with accumulation of cells in G1 phase. The mechanism of growth inhibition involves increased levels of p27KIP1 and inhibition of cyclin-dependent kinase-2 activity. mAb in combination with chemotherapy exhibits a synergistic antitumor activity, with successful eradication of well-established tumor xenografts that resist treatment with either mAb or drug alone. A Phase I clinical trial has established the safety of repeated administration of human:mouse chimeric mAb 225 at concentrations that maintain receptor-saturating blood levels for up to 3 months. Phase I trials exploring mAb 225 treatment in combination with doxorubicin, cisplatin, or paclitaxel are ongoing.
RESEARCH ON VEHICLE-BASED DRIVER STATUS/PERFORMANCE MONITORING; DEVELOPMENT, VALIDATION, AND REFINEMENT OF ALGORITHMS FOR DETECTION OF DRIVER DROWSINESS. FINAL REPORT (1994)

This report summarizes the results of a 3-year research project to develop reliable algorithms for the detection of motor vehicle driver impairment due to drowsiness. These algorithms are based on driving performance measures that can potentially be computed on-board a vehicle during highway driving, such as measures of steering wheel movements and lane tracking. A principal objective of such algorithms is that they correlate highly with, and thus are indicative of, psychophysiological measures of driver alertness/fatigue. Additional objectives are that developed algorithms produce low false alarm rates, that there should be minimal encumbering of (interference with) the driver, and that the algorithms should be suitable for later field testing. This report describes driving simulation and other studies performed to develop, validate, and refine such algorithms.
Anti-Epithelial Cell Adhesion Molecule Antibodies and the Detection of Circulating Normal-Like Breast Tumor Cells (2008)

Identification of specific subtypes of circulating tumor cells in peripheral blood of cancer patients can provide information about the biology of metastasis and improve patient management. However, to be effective, the method used to identify circulating tumor cells must detect all tumor cell types. We investigated whether the five subtypes of human breast cancer cells that have been defined by global gene expression profiling-normal-like, basal, HER2-positive, and luminal A and B-were identified by CellSearch, a US Food and Drug Administration-approved test that uses antibodies against the cell surface-expressed epithelial cell adhesion molecule (EpCAM) to isolate circulating tumor cells. We used global gene expression profiling to determine the subtypes of a well-defined panel of 34 human breast cancer cell lines (15 luminal, nine normal-like, five basal-like, and five Her2-positive). We mixed 50-150 cells from 10 of these cell lines with 7.5 mL of blood from a single healthy human donor, and the mixtures were subjected to the CellSearch test to isolate the breast cancer cells. We found that the CellSearch isolation method, which uses EpCAM on the surface of circulating tumor cells for cell isolation, did not recognize, in particular, normal-like breast cancer cells, which in general have aggressive features. New tests that include antibodies that specifically recognize normal-like breast tumor cells but not cells of hematopoietic origin are needed.
A SNP in a let-7 microRNA Complementary Site in the KRAS 3′ Untranslated Region Increases Non–Small Cell Lung Cancer Risk (2008)

Lung cancer is the leading cause of cancer deaths worldwide, yet few genetic markers of lung cancer risk useful for screening exist. The let-7 family-of-microRNAs (miRNA) are global genetic regulators important in controlling lung cancer oncogene expression by binding to the 3' untranslated regions of their target mRNAs. The purpose of this study was to identify single nucleotide polymorphisms (SNP) that could modify let-7 binding and to assess the effect of such SNPs on target gene regulation and risk for non-small cell lung cancer (NSCLC). let-7 complementary sites (LCS) were sequenced in the KRAS 3' untranslated region from 74 NSCLC cases to identify mutations and SNPs that correlated with NSCLC. The allele frequency of a previously unidentified SNP at LCS6 was characterized in 2,433 people (representing 46 human populations). The frequency of the variant allele is 18.1% to 20.3% in NSCLC patients and 5.8% in world populations. The association between the SNP and the risk for NSCLC was defined in two independent case-control studies. A case-control study of lung cancer from New Mexico showed a 2.3-fold increased risk (confidence interval, 1.1-4.6; P = 0.02) for NSCLC cancer in patients who smoked <40 pack-years. This association was validated in a second independent case-control study. Functionally, the variant allele results in KRAS overexpression in vitro. The LCS6 variant allele in a KRAS miRANA complementary site is significantly associated with increased risk for NSCLC among moderate smokers and represents a new paradigm for let-7 miRNAs in lung cancer susceptibility.
Pattern analysis for machine olfaction: a review (2002)

Pattern analysis constitutes a critical building block in the development of gas sensor array instruments capable of detecting, identifying, and measuring volatile compounds, a technology that has been proposed as an artificial substitute for the human olfactory system. The successful design of a pattern analysis system for machine olfaction requires a careful consideration of the various issues involved in processing multivariate data: signal-preprocessing, feature extraction, feature selection, classification, regression, clustering, and validation. A considerable number of methods from statistical pattern recognition, neural networks, chemometrics, machine learning, and biological cybernetics have been used to process electronic nose data. The objective of this review paper is to provide a summary and guidelines for using the most widely used pattern analysis techniques, as well as to identify research directions that are at the frontier of sensor-based machine olfaction.
Acute and Chronic Changes in the Microcirculation of the Liver in Inbred Strains of Mice Following Infection With Mouse Hepatitis Virus Type 3 (1985)

The acute and chronic effects of mouse hepatitis virus type 3 on the microcirculation of the liver in both semisusceptible C3HeB/FeJ and fully resistant A/J mice were studied. In the C3HeB/FeJ mice, abnormalities of microcirculatory flow were noted as early as 12 hr after infection and by 24 hr, localized avascular foci appeared. Disturbances were characterized by granular blood flow, sinusoidal microthrombi, distortion of sinusoids by edematous hepatocytes and necrotic lesions. Following the acute infection, Day 10, two patterns of chronic disease were observed. Eighty percent of the mice developed chronic granulomatous hepatitis whereas in the remaining 20% a more severe chronic aggressive hepatitis was observed which was characterized by ongoing hepatocellular necrosis and a marked mononuclear cell infiltrate. In both cases, in vivo microcirculatory abnormalities were found predominantly around visible lesions. Onset of the microcirculatory abnormalities was found to be concomitant with a rise in monocyte related procoagulant activity. Procoagulant activity rose acutely and remained elevated throughout the chronic phase but was higher in animals with severe disease. In contrast to the above, normal blood flow and histology were seen in the resistant A/J mice at all times following infection, and procoagulant activity remained at basal levels despite active viral replication as demonstrated by immunofluorescence studies and recovery of infectious virus. These observations suggest a role for monocyte procoagulant activity in the development of microcirculatory abnormalities following mouse hepatitis virus type 3 infection which may be important in the pathogenesis of the disease.
Native oxide-embedded AlyGa1−yAs-GaAs-InxGa1−xAs quantum well heterostructure lasers (1993)

Data are presented on the photopumped laser operation of an AlAs-AlyGa1−yAs-GaAs-InxGa1−xAs quantum well heterostructure in which the GaAs-InxGa1−xAs active region is embedded, top and bottom, in native oxide. The upper and lower wider gap confining regions of the laser are selectively converted to oxide, leaving the active region intact. The oxidation (H2O+N2, 425 °C) proceeds laterally (perpendicular to the crystal growth direction) from a chemically etched mesa edge. The photopumped oxide-embedded heterostructure operates as a laser continuously at 77 K and pulsed at 300 K. In comparison with the as-grown crystal, the oxidized sample shows no significant laser threshold degradation.
Making VR work (2014)

Building a real-world immersive 3D modeling application is hard. In spite of the many supposed advantages of working in the virtual world, users quickly tire of waving their arms about and the resulting models remain simplistic at best. The dream of creation at the speed of thought has largely remained unfulfilled due to numerous factors such as the lack of suitable menu and system controls, inability to perform precise manipulations, lack of numeric input, challenges with ergonomics, and difficulties with maintaining user focus and preserving immersion. The focus of our research is on the building of virtual world applications that can go beyond the demo and can be used to do real-world work. The goal is to develop interaction techniques that support the richness and complexity required to build complex 3D models, yet minimize expenditure of user energy and maximize user comfort. We present an approach that combines the natural and intuitive power of VR interaction, the precision and control of 2D touch surfaces, and the richness of a commercial modeling package. We also discuss the benefits of collocating 2D touch with 3D bimanual spatial input, the challenges in designing a custom controller targeted at achieving the same, and the new avenues that this collocation creates.
Safinamide (2006)

Ideal treatment in Parkinson's disease (PD) aims at relieving symptoms and slowing disease progression. Of all remedies, levodopa remains the most effective for symptomatic relief, but the medical need for neuroprotectant drugs is still unfulfilled. Safinamide, currently in phase III clinical trials for the treatment of PD, is a unique molecule with multiple mechanisms of action and a very high therapeutic index. It combines potent, selective, and reversible inhibition of MAO-B with blockade of voltage-dependent Na+ and Ca2+ channels and inhibition of glutamate release. Safinamide has neuroprotective and neurorescuing effects in MPTP-treated mice, in the rat kainic acid, and in the gerbil ischemia model. Safinamide potentiates levodopa-mediated increase of DA levels in DA-depleted mice and reverses the waning motor response after prolonged levodopa treatment in 6-OHDA-lesioned rats. Safinamide has excellent bioavailability, linear kinetics, and is suitable for once-a-day administration. Therefore, safinamide may be used in PD to reduce l-dopa dosage and also represents a valuable therapeutic drug to test disease-modifying potential.
Area Postrema Neurons Are Modulated by the Adipocyte Hormone Adiponectin (2006)

Adiponectin is an adipocyte-derived peptide hormone involved in energy homeostasis and the pathogenesis of obesity, including hypertension. Area postrema (AP) lacks a blood-brain barrier and is a critical homeostatic integration center for humoral and neural signals. Here we investigate the role of AP in adiponectin signaling. We show that rat AP expresses AdipoR1 and AdipoR2 adiponectin receptor mRNA. We used current-clamp electrophysiology to investigate whether adiponectin influenced membrane properties of AP neurons and found that approximately 60% of rat AP neurons tested were sensitive to adiponectin. Additional electrophysiology experiments coupled with single-cell reverse transcription-PCR indicated that all neurons that expressed both subtypes of receptor were sensitive to adiponectin, whereas neurons expressing only one subtype were predominantly insensitive. Last, microinjection of adiponectin into AP caused significant increases in arterial blood pressure, with no change in heart rate, suggesting that adiponectin acts at AP to provide a possible link between control of energy homeostasis and cardiovascular function.
Conditional Knock-Out of Kir4.1 Leads to Glial Membrane Depolarization, Inhibition of Potassium and Glutamate Uptake, and Enhanced Short-Term Synaptic Potentiation (2007)

During neuronal activity, extracellular potassium concentration ([K+]out) becomes elevated and, if uncorrected, causes neuronal depolarization, hyperexcitability, and seizures. Clearance of K+ from the extracellular space, termed K+ spatial buffering, is considered to be an important function of astrocytes. Results from a number of studies suggest that maintenance of [K+]out by astrocytes is mediated by K+ uptake through the inward-rectifying Kir4.1 channels. To study the role of this channel in astrocyte physiology and neuronal excitability, we generated a conditional knock-out (cKO) of Kir4.1 directed to astrocytes via the human glial fibrillary acidic protein promoter gfa2. Kir4.1 cKO mice die prematurely and display severe ataxia and stress-induced seizures. Electrophysiological recordings revealed severe depolarization of both passive astrocytes and complex glia in Kir4.1 cKO hippocampal slices. Complex cell depolarization appears to be a direct consequence of Kir4.1 removal, whereas passive astrocyte depolarization seems to arise from an indirect developmental process. Furthermore, we observed a significant loss of complex glia, suggestive of a role for Kir4.1 in astrocyte development. Kir4.1 cKO passive astrocytes displayed a marked impairment of both K+ and glutamate uptake. Surprisingly, membrane and action potential properties of CA1 pyramidal neurons, as well as basal synaptic transmission in the CA1 stratum radiatum appeared unaffected, whereas spontaneous neuronal activity was reduced in the Kir4.1 cKO. However, high-frequency stimulation revealed greatly elevated posttetanic potentiation and short-term potentiation in Kir4.1 cKO hippocampus. Our findings implicate a role for glial Kir4.1 channel subunit in the modulation of synaptic strength.
Impaired inhibitory Fcγ receptor IIB expression on B cells in chronic inflammatory demyelinating polyneuropathy (2009)

The inhibitory Fc-gamma receptor FcgammaRIIB, expressed on myeloid and B cells, has a critical role in the balance of tolerance and autoimmunity, and is required for the antiinflammatory activity of intravenous Ig (IVIG) in various murine disease models. However, the function of FcgammaRIIB and its regulation by IVIG in human autoimmune diseases are less well understood. Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common treatable acquired chronic polyneuropathy, and IVIG is widely used as a first-line initial and maintenance treatment. We found that untreated patients with CIDP, compared with demographically matched healthy controls, showed consistently lower FcgammaRIIB expression levels on naive B cells, and failed to up-regulate or to maintain up-regulation of FcgammaRIIB as B cells progressed from the naive to the memory compartment. Concomitantly, the rare -386C/-120A FcgammaRIIB promoter polymorphism resulting in reduced promoter activity previously associated with autoimmune phenotypes was overrepresented in CIDP. Also, FcgammaRIIB protein expression was up-regulated on monocytes and B cells after clinically effective IVIG therapy. Thus, our results suggest that the inhibitory FcgammaRIIB is impaired at a critical B cell differentiation checkpoint in CIDP, and that modulating FcgammaRIIB expression might be a promising approach to efficiently limit antibody-mediated immunopathology in CIDP.
Companion Biomarkers: Paving the Pathway to Personalized Treatment for Cancer (2013)

The availability of companion biomarkers should improve drug efficacy, decrease toxicity, and lead to a more individualized approach to cancer treatment.
On-line CORDIC algorithms (1990)

A number of new algorithms to make an online CORDIC implementation are introduced. The online CORDIC algorithm takes n+6 clock cycles to compute a CORDIC function. It is estimated that an implementation of the proposed algorithm is six to seven times as fast as the traditional CORDIC approach for Given's rotation, and seven to eight times as fast for SVD computation.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Site-specific mutagenesis defines the intracellular role of the asparagine-linked oligosaccharides of chorionic gonadotropin beta subunit. (1988)

The beta subunit of human chorionic gonadotropin contains two asparagine (N)-linked oligosaccharides. To examine the structural and functional roles of these oligosaccharide units in vivo, we constructed mutant genes containing alterations in either the asparagine or threonine codons of the two glycosylation consensus sequences and inserted them into a eukaryotic expression vector. Wild-type and mutant CG beta proteins were expressed in Chinese hamster ovary cells alone or in the presence of native alpha subunit. Pulse-chase analysis of the beta-expressing clones showed that absence of the second N-linked sugar but not the first slows secretion 1.6-1.8-fold; absence of both N-linked units slows secretion 2-2.4-fold. Analysis of dimer clones reveals that greater than 80% of the native and glycosylation mutant CG beta subunits are secreted as dimer. However, pulse-chase analysis of these clones also reveals that the mutants completely devoid of N-linked sugars but not the single site mutants are slow to assemble with the alpha subunit. Thus, in vivo the two N-linked oligosaccharides of CG beta are critical for efficient secretion and assembly with the alpha subunit and are likely important for proper folding of the CG beta subunit.
Subtilisin BPN' (1967)

In attempts to complete the amino acid sequence of subtilisin BPN', the diisopropylphosphoryl derivative was cleaved with cyanogen bromide, and the peptides were separated by gel filtration on Sephadex G-75. Four of the expected six fragments were isolated in pure form; the other two were purified together but could not be separated from each other. Tryptic digestion of the mixture of the two cyanogen bromide fragments produced six of the expected seven peptides. The remaining peptide was obtained by tryptic digestion of the diisopropylphosphoryl derivative of subtilisin BPN' followed by BrCN cleavage of the tryptic peptides. This procedure permitted the isolation of the peptide missing from the former procedure as well as the other expected peptides. This information combined with that previously obtained from the tryptic, chymotryptic, and peptic digests has provided the evidence to construct a unique amino acid sequence for the 275 residues in subtilisin BPN'. Proof of this structure is provided along with a discussion of some of the features of the sequence.