gebhart/patrepeval huggingface dataset:
Genome-Wide Analyses of Exonic Copy Number Variants in a Family-Based Study Point to Novel Autism Susceptibility Genes (2009)

The genetics underlying the autism spectrum disorders (ASDs) is complex and remains poorly understood. Previous work has demonstrated an important role for structural variation in a subset of cases, but has lacked the resolution necessary to move beyond detection of large regions of potential interest to identification of individual genes. To pinpoint genes likely to contribute to ASD etiology, we performed high density genotyping in 912 multiplex families from the Autism Genetics Resource Exchange (AGRE) collection and contrasted results to those obtained for 1,488 healthy controls. Through prioritization of exonic deletions (eDels), exonic duplications (eDups), and whole gene duplication events (gDups), we identified more than 150 loci harboring rare variants in multiple unrelated probands, but no controls. Importantly, 27 of these were confirmed on examination of an independent replication cohort comprised of 859 cases and an additional 1,051 controls. Rare variants at known loci, including exonic deletions at NRXN1 and whole gene duplications encompassing UBE3A and several other genes in the 15q11-q13 region, were observed in the course of these analyses. Strong support was likewise observed for previously unreported genes such as BZRAP1, an adaptor molecule known to regulate synaptic transmission, with eDels or eDups observed in twelve unrelated cases but no controls (p = 2.3x10(-5)). Less is known about MDGA2, likewise observed to be case-specific (p = 1.3x10(-4)). But, it is notable that the encoded protein shows an unexpectedly high similarity to Contactin 4 (BLAST E-value = 3x10(-39)), which has also been linked to disease. That hundreds of distinct rare variants were each seen only once further highlights complexity in the ASDs and points to the continued need for larger cohorts.
How Does Indoleamine 2,3-Dioxygenase Contribute to HIV-Mediated Immune Dysregulation (2007)

Infection with the human immunodeficiency virus type 1 (HIV) results in a chronic infection that progressively cripples the host immune defenses. HIV infection is associated with increased tryptophan (trp) catabolism by the cytokine-inducible enzyme indoleamine 2,3-dioxygenase (IDO). IDO has powerful immune suppressive activity, which could contribute to the immune dysfunction observed in HIV-infected patients. In this review we discuss the immune mechanisms that could mediate the HIV-induced increase of IDO activity (such as IFN-gamma, IFN-alpha, CTLA-4/B7 and direct viral exposure). We then consider the current knowledge of IDO-mediated immune suppressive mechanisms with regard to different cell types (CD4(+) T cells, CD8(+) T cells, natural killer cells, B cells and regulatory T cells), from the perspective of their potential consequences for the HIV-infected host. HIV-induced, IDO-mediated trp catabolism may contribute to the perpetuation of HIV infection into its chronic phase by dampening efficient immune anti-viral responses. Therapeutic approaches aimed at manipulating this powerful immune suppressive mechanism might be considered in the setting of HIV infection.
A Survey of Affect Recognition Methods: Audio, Visual, and Spontaneous Expressions (2008)

Automated analysis of human affective behavior has attracted increasing attention from researchers in psychology, computer science, linguistics, neuroscience, and related disciplines. However, the existing methods typically handle only deliberately displayed and exaggerated expressions of prototypical emotions despite the fact that deliberate behaviour differs in visual appearance, audio profile, and timing from spontaneously occurring behaviour. To address this problem, efforts to develop algorithms that can process naturally occurring human affective behaviour have recently emerged. Moreover, an increasing number of efforts are reported toward multimodal fusion for human affect analysis including audiovisual fusion, linguistic and paralinguistic fusion, and multi-cue visual fusion based on facial expressions, head movements, and body gestures. This paper introduces and surveys these recent advances. We first discuss human emotion perception from a psychological perspective. Next we examine available approaches to solving the problem of machine understanding of human affective behavior, and discuss important issues like the collection and availability of training and test data. We finally outline some of the scientific and engineering challenges to advancing human affect sensing technology.
Thermal Plasmas: Fundamentals and Applications (1994)

The Plasma State. Basic Atomic and Molecular Theory. Kinetic Theory. Fundamental Concepts in Gaseous Electronics. Derivation of the Plasma Equations. Thermodynamic Properties. Transport Properties. Radiation Transport. Index.
1-Adrenergic receptors prevent a maladaptive cardiac response to pressure overload (2006)

An alpha1-adrenergic receptor (alpha1-AR) antagonist increased heart failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), but it is unknown whether this adverse result was due to alpha1-AR inhibition or a nonspecific drug effect. We studied cardiac pressure overload in mice with double KO of the 2 main alpha1-AR subtypes in the heart, alpha 1A (Adra1a) and alpha 1B (Adra1b). At 2 weeks after transverse aortic constriction (TAC), KO mouse survival was only 60% of WT, and surviving KO mice had lower ejection fractions and larger end-diastolic volumes than WT mice. Mechanistically, final heart weight and myocyte cross-sectional area were the same after TAC in KO and WT mice. However, KO hearts after TAC had increased interstitial fibrosis, increased apoptosis, and failed induction of the fetal hypertrophic genes. Before TAC, isolated KO myocytes were more susceptible to apoptosis after oxidative and beta-AR stimulation, and beta-ARs were desensitized. Thus, alpha1-AR deletion worsens dilated cardiomyopathy after pressure overload, by multiple mechanisms, indicating that alpha1-signaling is required for cardiac adaptation. These results suggest that the adverse cardiac effects of alpha1-antagonists in clinical trials are due to loss of alpha1-signaling in myocytes, emphasizing concern about clinical use of alpha1-antagonists, and point to a revised perspective on sympathetic activation in heart failure.
An initial operational problem oriented medical record system (1971)

The ultimate role of the computer in the delivery of health services has yet to be defined. There may be profound implications in terms of quality of medical care, efficiency, economics of care, and medical research. Final judgments as to advisability and economic feasibility await the implementation of prototype total medical information systems and further technical developments directed toward lowering the high cost of currently developing systems. Development of less expensive hardware and real-time application of the present hardware and software must go on in parallel. We have been involved in the latter, and an experimental time-shared medical information system has been developed for storing and retrieving the total medical record, including both the narrative and the numeric data. This development has integrated the Problem Oriented Medical Record, a means of organizing medical data around a patient's problems, with a touch sensitive cathode ray tube terminal that allows structured input (with additional keyboard entry capability) by directly interfaced medical users (in particular the physician and the nurse).
An anti–glypican 3/CD3 bispecific T cell–redirecting antibody for treatment of solid tumors (2017)

Cancer care is being revolutionized by immunotherapies such as immune checkpoint inhibitors, engineered T cell transfer, and cell vaccines. The bispecific T cell-redirecting antibody (TRAB) is one such promising immunotherapy, which can redirect T cells to tumor cells by engaging CD3 on a T cell and an antigen on a tumor cell. Because T cells can be redirected to tumor cells regardless of the specificity of T cell receptors, TRAB is considered efficacious for less immunogenic tumors lacking enough neoantigens. Its clinical efficacy has been exemplified by blinatumomab, a bispecific T cell engager targeting CD19 and CD3, which has shown marked clinical responses against hematological malignancies. However, the success of TRAB in solid tumors has been hampered by the lack of a target molecule with sufficient tumor selectivity to avoid "on-target off-tumor" toxicity. Glypican 3 (GPC3) is a highly tumor-specific antigen that is expressed during fetal development but is strictly suppressed in normal adult tissues. We developed ERY974, a whole humanized immunoglobulin G-structured TRAB harboring a common light chain, which bispecifically binds to GPC3 and CD3. Using a mouse model with reconstituted human immune cells, we revealed that ERY974 is highly effective in killing various types of tumors that have GPC3 expression comparable to that in clinical tumors. ERY974 also induced a robust antitumor efficacy even against tumors with nonimmunogenic features, which are difficult to treat by inhibiting immune checkpoints such as PD-1 (programmed cell death protein-1) and CTLA-4 (cytotoxic T lymphocyte-associated protein-4). Immune monitoring revealed that ERY974 converted the poorly inflamed tumor microenvironment to a highly inflamed microenvironment. Toxicology studies in cynomolgus monkeys showed transient cytokine elevation, but this was manageable and reversible. No organ toxicity was evident. These data provide a rationale for clinical testing of ERY974 for the treatment of patients with GPC3-positive solid tumors.
Lipid peroxidation in experimental uveitis: Sequential studies (1992)

Previously we have detected the occurrence of retinal lipid peroxidation initiated by phagocyte-derived oxygen radicals in experimental autoimmune uveitis (EAU). In the current studies, the confirmation of inflammation-mediated lipid peroxidation was proceeded further to include measurement of multiple parameters, including conjugated dienes, ketodienes, thiobarbituric acid reactive substances and fluorescent chromolipids. The assay for myeloperoxidase, a measure for the number of polymorphonuclear leukocytes in the inflammatory sites was also carried out. The levels of all these parameters were followed through the course of EAU development. The sequential evaluation of histologic changes using both light and electron microscopy was also carried out and the results were correlated with lipid peroxidation indices. These data suggest that the retinal lipid peroxidation plays a causative role in the subsequent retinal degeneration.
Degradation of Pesticides in a Continuous‐Flow Two‐Phase Microemulsion Reactor (1994)

Biocatalytic processes in reversed micelles are limited by the need for continuous reactors in which reaction and separation are feasible. In this paper, we report the design and testing of a continuous-flow centrifugal bioreactor for the enzyme-catalyzed hydrolysis of the common pesticide paraoxon in reverse micelles of Tween 85. In this system, organophosphorus hydrolase catalyzes hydrolysis of the pesticide in an organic-organic two-phase system. The enzyme is retained in one of the phases by encapsulation in reversed micelles, while the other phase is under a continuous flow. This liquid-liquid plug-flow reactor does not leach enzyme because the enzyme is not soluble in the flowing organic phase that contains the paraoxon.
<title>Bulk and surface light scattering from transparent silica aerogel</title> (1992)

Elastic light scattering has been used to study structural properties of different transparent aerogels, which may be used as filling materials in super-windows. With a goniometer having an angular resolution better than 0.6 degree(s) and a He-Ne laser as the light source we investigated the angular distribution of scattered intensity from transparent silica aerogels and one xerogel. The densities ranged between 0.11 and 0.60 gcm<SUP>-3</SUP>. An exponential correlation function for the density fluctuations of a random porous medium has been utilized to analyze the large-angle scattering, which is dominated by bulk scattering, for different polarization of the incident light. The determination of correlation lengths in the nanometer range was possible, because the absolute scattering intensities were determined. For relative angular dependence measurements, this range would have been accessible only to small angle x-ray scattering (SAXS). The resulting mean pore sizes between 8 nm and 50 nm and specific surface areas between 500 and 700 m<SUP>2</SUP>/g agree well with nitrogen-porosimetry data from the literature. The data compare quite well with correlation lengths calculated from specular transmittance data from an ordinary spectrophotometer. This method, which is not sensitive to the angular distribution of superposed forward scattering with large correlation lengths, has also been applied to a series of base-catalyzed TMOS aerogels with different catalyst concentrations. The forward scattering peak of the signal may be attributed to correlation lengths in the micrometer range. Experimental results for aerogel surfaces with evaporated aluminum indicate that this might be due to the surface properties. A quantitative analysis, however, is not possible yet.
The PD-1/PD-L1 axis contributes to T-cell dysfunction in chronic lymphocytic leukemia (2013)

Chronic lymphocytic leukemia is marked by profound defects in T-cell function. Programmed death-1 is a receptor involved in tumor-mediated immunosuppression through binding of the PD-L1 ligand. Multiparametric flow cytometry and immunohistochemistry were used to study PD-1/PD-L1 expression. Functional assays were used to determine the involvement of the PD-1/PD-L1 axis in T-cell responses. PD-1 expression by CD4(+) and CD8(+) T lymphocytes was significantly higher in 117 chronic lymphocytic leukemia patients than in 33 donors of a comparable age. CD4(+) and CD8(+) T lymphocytes from chronic lymphocytic leukemia patients displayed increased numbers of effector memory and terminally differentiated cells, respectively, when compared to controls. The number of effector memory CD4(+) and terminally differentiated CD8(+) lymphocytes positively associated with a more advanced stage of disease, treatment requirements and unfavorable genomic aberrations. Furthermore, leukemic lymphocytes expressed higher levels of PD-L1 than circulating B lymphocytes from normal donors. PD-1 and PD-L1 surface expression spiked in proliferating T and B lymphocytes, suggesting that this interaction works efficiently in activated environments. Within chronic lymphocytic leukemia proliferation centers in the lymph node, CD4(+)/PD-1(+) T lymphocytes were found to be in close contact with PD-L1(+) chronic lymphocytic leukemia cells. Lastly, functional experiments using recombinant soluble PD-L1 and blocking antibodies indicated that this axis contributes to the inhibition of IFN-γ production by CD8(+) T cells. These observations suggest that pharmacological manipulation of the PD-1/PD-L1 axis may contribute to restoring T-cell functions in the chronic lymphocytic leukemia microenvironment.
Effective ribozyme delivery in plant cells. (1995)

Hammerhead ribozyme sequences were incorporated into a tyrosine tRNA (tRNA(Tyr)) and compared with nonembedded molecules. To increase the levels of ribozyme and control antisense in vivo, sequences were expressed from an autonomously replicating vector derived from African cassava mosaic geminivirus. In vitro, the nonembedded ribozyme cleaved more target RNA, encoding chloramphenicol acetyltransferase (CAT), than the tRNA(Tyr) ribozyme. In contrast, the tRNA(Tyr) ribozyme was considerably more effective in vivo than either the nonembedded ribozyme or antisense sequences, reducing CAT activity to < 20% of the control level. A target sequence (CM2), mutated to be noncleavable, showed no reduction in CAT activity in the presence of the tRNA(Tyr) ribozyme beyond that for the antisense construct. The reduction in full-length CAT mRNA and the presence of specific cleavage products demonstrated in vivo cleavage of the target mRNA by the tRNA(Tyr) ribozyme. The high titer of tRNA(Tyr) ribozyme was a result of transcription from the RNA polymerase III promoter and led to the high ribozyme/substrate ratio essential for ribozyme efficiency.
Megakaryocytic Progenitors Can Be Generated Ex Vivo and Safely Administered to Autologous Peripheral Blood Progenitor Cell Transplant Recipients (1997)

We evaluated different culture conditions to obtain a lineage-selected proliferation of clonogenic megakaryocytic progenitors (MP). In low-density (LD) or CD34+ cell cultures, the best results were obtained in serum-free medium in the presence of megakaryocyte growth and development factor, stem cell factor, interleukin-3 (IL-3), IL-6, IL-11, FLT-ligand, and macrophage inflammatory protein-1alpha. In paired studies, expansion of LD cells was less effective than expansion of CD34+ cells, and pre-enrichment of CD34+ cells using negative depletion of lineage-positive cells produced significantly larger quantities of MP than pre-enrichment using positive selection. MP proliferation peaked on day 7 in culture, and an 8- +/- 5-fold expansion of CD34+/CD61+ cells, a 17- +/- 5-fold expansion of colony-forming units-megakaryocytes, and a 58- +/- 14-fold expansion of the total number of CD61+ cells was obtained. In a feasibility clinical study, 10 cancer patients (8 with breast cancer and 2 with non-Hodgkin's lymphoma) undergoing autologous peripheral blood progenitor cell (PBPC) transplant received MP generated ex vivo (range, 1 to 21 x 10(5)/kg CD61 cells) together with unmanipulated PBPC. Eight patients received a single allogeneic platelet transfusion, whereas platelet transfusion support was not needed in 2 of the 4 patients receiving the highest doses of cultured MP. This result compares favorably with a retrospective control group of 14 patients, all requiring platelet transfusion support. Adverse reactions or bacterial contamination of cell cultures have not been observed. In conclusion, MP can be expanded ex vivo and safely administered to autologous transplant recipients. Further clinical trials will indicate the reinfusion schedule able to consistently abrogate the need for allogeneic platelet transfusion support in autologous transplantation.
Microleakage of IRM® used to restore endodontic access preparations (1990)

The effect on microleakage of varying the powder-to-liquid ratio (P/L) of IRM used to restore endodontic access preparations was evaluated. Crowns of noncarious, nonrestored extracted human teeth were used in this study. Microleakage was measured using a fluid filtration technique prior to access preparation to obtain control measurements. After access preparation, IRM restorations were placed using P/L of 2, 3, 4, 5, and 6 g/ml, using the manufacturer's recommended dispensing scoop and dropper, and using 2 P/L in a new capsulated IRM delivery system (IRM CAPS). Microleakage measurements were made after various time intervals and after thermal stress. The results indicated that the lower P/L provided the best seals. All groups demonstrated significant microleakage measurements after thermal stress. Significantly greater microleakage measurements were obtained with the P/L of 6 g/ml and the manufacturer's recommended dispensing scoop and dropper. A P/L of 2 g/ml demonstrated less microleakage than the other groups tested.
The multifocality of bronchioloalveolar lung carcinoma: evidence and implications of a multiclonal origin. (1994)

Bronchioloalveolar lung carcinoma (BAC) is a unique type of lung cancer with distinguishing pathologic, biologic, epidemiologic, and perhaps etiologic features that set it apart from all other forms of lung cancer, including general adenocarcinoma, into which it is traditionally grouped. Recent studies at our institution have demonstrated a near exponential increase in BAC cases with 25% showing evidence of multifocality. Although some theories suggest that this multifocality is caused by intrapulmonary aerosol/aspiration or lymphatic spread, this study provides evidence for multiclonality as the basis for some cases of multifocal BAC by exploiting a novel strategy for clonality determinations that involves polymerase chain reaction amplification of a 511-base pair region located within the first intron of the human hypoxanthine phosphoribosyltransferase gene, a site that contains inactive X chromosomal obligately methylated HpaII/MspI sites and single-base allelic polymorphisms in 5 to 10% of females. BAC cells, obtained by enzymatic dissociation of different fresh/paraffin-embedded tumoral foci from polymorphic individuals with multilobar or bilateral BAC, were sorted to homogeneity with a fluorescein-conjugated anticarcinoembryonic antigen and then subjected to genomic DNA extraction and HpaII digestion before polymerase chain reaction amplification and subsequent analysis of the product on denaturing gradient gel electrophoresis. The differing migrations of the single homoduplexes generated were indicative of BAC clonal nonidentity or multiclonality in three separate cases. The demonstration of multiclonality in some cases of BAC provides an alternate explanation for multifocality.
Peroxide‐initiated grafting of acrylamide on to polyethylene surfaces (1992)

Abstract Acrylamide has been grafted onto the surface of a polyethlene film with the aid of a peroxide initiator ( tert ‐butyl peroxyneodecanoate). The peroxide was first swollen into the film from cyclohexane solution; the film was then dried under reduced pressure at room temperature. Excess initiator, adsorbed on the surface, was washed off with acetone. The grafting reaction was carried out by placing the film in a boiling solution of the monomer in water. After grafting, the film was extracted with water to remove monomers and homopolymer. The grafted films were characterized by infrared spectroscopy, X‐ray photoelectron spectroscopy (XPS), gravimetric measurements, and contact angle measurements. The graft yield was found to increase with reaction time up to about 5–15 min and thereafter level off. The presence of air was found to retard the grafting reaction. Increase in monomer concentration gave an almost continuous increase in graft yield, but high concentrations were not necessary to cover the surface of the film with polyacrylamide. This grafting has been found to function, but the process requires further development to reduce the total grafting time before it can be used commercially.
Geometrical inversion of methoxymethyl cations (1979)

The barrier for geometrical isomerization of the title ion [ΔH‡= 11·9 kcal mol–1, ΔS‡=–4 cal mol–1 K–1(1 cal = 4·184 J), variable temperature n.m.r. spectrum 270 MHz] agrees with ab initio(4-31G) calculations for an inversion process (ΔEcalc= 12·0 kcal mol–1); the values computed for a rotation around the C+–O bond (20·8 kcal mol–1) or at the STO-3G level (25·2 and 32·8 kcal mol–1, respectively) are too high.
Best Subsets Logistic Regression (1989)

Selection of covariates is an important step in any regression modeling situation. An effective strategy when the model is a linear regression with normal errors is to use a software package that implements a best subsets selection algorithm. A number of years ago Lawless and Singhal (1978) proposed a method for efficiently screening nonnormal regression models, thus providing the basis for best subsets nonlinear regression. Recently Lawless and Singhal (1987a, 1987b) have made available a software package that implements their method. The purpose of this note is to illustrate that for one of the more frequently used nonnormal regression models, logistic regression, we may perform the Lawless-Singhal analysis with any best subsets linear regression program that allows for case weights. The methods presented may also be obtained from the general method for model selection proposed by Gilks (1986). We also discuss the use and interpretation of Mallows's measure of predictive squared error as a statistic for comparing models with different subsets of variables.