gebhart/patrepeval huggingface dataset:
Inhibition of SF3B1 by molecules targeting the spliceosome results in massive aberrant exon skipping (2018)

The recent identification of compounds that interact with the spliceosome (sudemycins, spliceostatin A, and meayamycin) indicates that these molecules modulate aberrant splicing via SF3B1 inhibition. Through whole transcriptome sequencing, we have demonstrated that treatment of Rh18 cells with sudemycin leads to exon skipping as the predominant aberrant splicing event. This was also observed following reanalysis of published RNA-seq data sets derived from HeLa cells after spliceostatin A exposure. These results are in contrast to previous reports that indicate that intron retention was the major consequence of SF3B1 inhibition. Analysis of the exon junctions up-regulated by these small molecules indicated that these sequences were absent in annotated human genes, suggesting that aberrant splicing events yielded novel RNA transcripts. Interestingly, the length of preferred downstream exons was significantly longer than the skipped exons, although there was no difference between the lengths of introns flanking skipped exons. The reading frame of the aberrantly skipped exons maintained a ratio of 2:1:1, close to that of the cassette exons (3:1:1) present in naturally occurring isoforms, suggesting negative selection by the nonsense-mediated decay (NMD) machinery for out-of-frame transcripts. Accordingly, genes involved in NMD and RNAs encoding proteins involved in the splicing process were enriched in both data sets. Our findings, therefore, further elucidate the mechanisms by which SF3B1 inhibition modulates pre-mRNA splicing.
Epigenetic Silencing of Novel Tumor Suppressors in Malignant Melanoma (2006)

Malignant melanoma is a common and frequently lethal disease. Current therapeutic interventions have little effect on survival, emphasizing the need for a better understanding of the genetic, epigenetic, and phenotypic changes in melanoma formation and progression. We identified 17 genes that were not previously known to be silenced by methylation in melanoma using a microarray-based screen following treatment of melanoma cell lines with the DNA methylation inhibitor 5-Aza-2'-deoxycytidine. Eight of these genes have not been previously shown to undergo DNA methylation in any form of cancer. Three of the genes, QPCT, CYP1B1, and LXN, are densely methylated in >95% of uncultured melanoma tumor samples. Reexpression of either of two of the silenced genes, HOXB13 and SYK, resulted in reduced colony formation in vitro and diminished tumor formation in vivo, indicating that these genes function as tumor suppressors in melanoma.
Prevalence, Incidence, and Persistence or Recurrence of Trichomoniasis among Human Immunodeficiency Virus (HIV)–Positive Women and among HIV‐Negative Women at High Risk for HIV Infection (2002)

Trichomoniasis has been implicated in the acquisition and transmission of human immunodeficiency virus (HIV) infection. The prevalence, incidence, and persistence or recurrence of trichomoniasis were assessed among HIV-positive women and among HIV-negative women at high risk for HIV infection. A total of 871 HIV-seropositive women and 439 HIV-seronegative women enrolled in the HIV Epidemiology Study (HERS) were seen biannually. The prevalence of trichomoniasis was 9.4%-29.5% among HIV-seropositive women and 8.2%-23.4% among HIV-seronegative women. Prevalence decreased over time, did not vary according to HIV status or CD4 cell count, and was higher among women who reported crack use (P=.02) or cigarette use (P=.02), women who had bacterial vaginosis (P=.02), and those who were black (compared with white women, P<.001). There were no differences, according to HIV status or CD4 cell count, in the adjusted incidence, unadjusted incidence, or persistence or recurrence of trichomoniasis. HIV infection does not make a woman more likely to have prevalent, incident, or persistent or recurrent trichomoniasis.
Interleukin 1: a mitogen for human vascular smooth muscle cells that induces the release of growth-inhibitory prostanoids. (1988)

There is much interest in defining the signals that initiate abnormal proliferation of cells in a variety of states characterized by the presence of mononuclear phagocytes. Since IL-1 is a major secretory product of activated human monocytes we examined whether this cytokine can stimulate the growth of human vascular smooth muscle cells (SMC). Neither recombinant IL-1 (rIL-1) alpha (less than or equal to 5.0 ng/ml) nor beta (less than or equal to 100 ng/ml) stimulated SMC growth during 2-d incubations under usual conditions. IL-1 did stimulate SMC to produce prostanoids such as PGE1 or PGE2 that can inhibit SMC proliferation. When prostaglandin synthesis was inhibited by indomethacin or aspirin both rIL-1 alpha and beta (greater than or equal to 1 ng/ml) markedly increased SMC growth. In longer-term experiments (7-28 d) rIL-1 stimulated the growth of SMC even in the absence of cyclooxygenase inhibitors. The addition of exogenous PGE1 or PGE2 (but not PGF1 alpha, PGF2 alpha, PGI2) to indomethacin-treated SMC blocked their mitogenic response to rIL-1. Antibody to IL-1 (but not to platelet-derived growth factor [PDGF]) abolished the mitogenic response of SMC to rIL-1. Exposure of SMC to rIL-1 or PDGF caused rapid (maximal at 1 h) and transient (baseline by 3 h) expression of the c-fos proto-oncogene, determined by Northern analysis. We conclude that IL-1 is a potent mitogen for human SMC. Endogenous prostanoid production simultaneously induced by IL-1 appears to antagonize this growth-promoting effect in the short term (2 d) but not during more prolonged exposures. IL-1 produced by activated monocytes at sites of tissue inflammation or injury may thus mediate both positive and negative effects on SMC proliferation that are temporally distinct.
NC/Nga Mice: A Mouse Model for Atopic Dermatitis (1999)

Atopic dermatitis (AD) is a common pruritic disease that occurs primarily in infancy and childhood. AD is characterized by itching and the patient having an individual or family history of atopic diseases. Although AD is also frequently associated with elevated serum IgE levels and with common environmental factors contributing to its pathogenesis, the etiology of AD is still unknown. We examined NC/Nga mice (NC mice) that showed AD-like skin lesions with aging as a possible mouse model for AD. NC mice were maintained under conventional (Conv) or specific pathogen-free (SPF) conditions. Clinical symptoms, serum IgE levels and histopathology of the skin were compared between these 2 groups, and we explored their application as a model of human AD. It was found that the skin lesions of inbred NC mice were clinically and histologically very similar to human AD when the mice were raised under Conv conditions, but not under SPF conditions, and we assumed that some kinds of environmental factors might trigger AD-like signs and symptoms in NC mice. To further investigate the pathophysiology and treatment of AD, a suitable animal model is absolutely required, and NC mice are very useful for this purpose.
Measuring the Chemosensory Irritability of Human Skin (1995)

Contact with environmental chemicals can cause cutaneous sensations of irritation, such as burning, stinging, and itching, that are not always correlated with physical signs of irritation. This paper describes the development and evaluation of a psychophysical methodology that allows for measurement of this form of chemical irritation in humans. In the first experiment a labeled magnitude scale (LMS) was used to assess the chemosensory irritation produced when single concentrations of lactic acid, capsaicin, and ethanol were repeatedly applied to the skin of the face. The chemicals were applied on filter paper disks, occluded, and alternated at 3 min intervals with a water vehicle. The results revealed large differences in reactivity to the three chemicals within and between individuals. A second experiment assessed the reliability of the method and found good reproducibility in a subgroup of subjects from experiment 1. The final experiment tested a modification of the method that employed an ascending concentration series to estimate the minimal concentration necessary for detection of irritation. The results showed a wide range of sensitivities to ethanol and lactic acid, and indicated that for a given subject, sensitivity to one chemical did not always predict sensitivity to the other chemical. Overall, the data demonstrate that chemosensory irritation varies significantly across both individuals and chemicals, and that this variability can be quantified by combining rigorous methods of stimulus control with modern methods of psychophysical scaling.
Projecting the demographic consequences of adult HIV prevalence trends: the Spectrum Projection Package (2004)

This paper describes the software package Spectrum, which is a modular program that is used to examine the consequences of current trends and future program interventions in reproductive health. It is used to determine the consequences of the HIV/AIDS epidemic, including the number of people living with HIV/AIDS by age and sex, the number of AIDS deaths, and the number of orphans as a result of AIDS, as well as other demographic indicators of interest, such as life expectancy and <5 mortality. The core of Spectrum is a demographic projection model called DemProj, which projects the population by age and sex. Other modules interact with the demographic projection. The HIV/AIDS projections are added to the demographic projections using a module called AIDS Impact Model. This module uses the projection of adult HIV prevalence over time, which is prepared using the Estimation and Projection Package model or the projection workbook. It also requires assumptions about the epidemiology of HIV, including the ratio of female:male prevalence, the distribution of infection by age, the distribution of the time from infection until AIDS death, and the effect of HIV on fertility.
Characterization of aBorrelia burgdorferiVlsE Invariable Region Useful in Canine Lyme Disease Serodiagnosis by Enzyme-Linked Immunosorbent Assay (2000)

Sera collected from dogs experimentally infected with Borrelia burgdorferi by tick inoculation were analyzed for an antibody response to each of the six invariable regions (IRs; i.e., IR(1) to IR(6)) of VlsE, the variable surface antigen of B. burgdorferi. Six synthetic peptides (C(1) to C(6)), which reproduced the six IR sequences were used as peptide-based, enzyme-linked immunosorbent assay (ELISA) antigens. Two IRs, IR(2) and IR(6), were found to be immunodominant. Studies with serially collected serum samples from experimentally infected dogs revealed that the antibody response to IR(6) appears earlier and is stronger than that to IR(2). Thus, the IR(6) sequence alone appeared to be sufficient for serodiagnosis. When C(6) alone was used as antigen, the peptide-based ELISA was positive in 7 of 23 dogs (30%) as early as 3 weeks postinfection. All dogs (n = 33) became strongly positive 1 or 2 weeks later, and this response persisted for the entire study, which lasted for 69 weeks. Of 55 sera submitted by veterinarians from dogs suspected of having Lyme disease, 19 were also positive by the C(6) ELISA, compared to 20 positives detected by immunoblot analysis using cultured B. burgdorferi lysates as antigen. The sensitivity of using C(2) and C(6) together for detecting specific antibody in both experimentally infected and clinically diagnosed dogs was not better than sensitivity with C(6) alone, confirming that C(6) suffices as a diagnostic probe. Moreover, the C(6) ELISA yielded 100% specificity with serum samples collected from 70 healthy dogs, 14 dogs with infections other than B. burgdorferi, and 15 animals vaccinated with either outer surface protein A, whole-spirochete vaccines, or the common puppy-vaccines. Therefore, this C(6) ELISA was both sensitive and specific for the serodiagnosis of canine Lyme disease and could be used with vaccinated dogs.
A 3D Dynamic Scene Analysis Framework for Development of Intelligent Transportation Systems (2018)

Holistic driving scene understanding is a critical step toward intelligent transportation systems. It involves different levels of analysis, interpretation, reasoning and decision making. In this paper, we propose a 3D dynamic scene analysis framework as the first step toward driving scene understanding. Specifically, given a sequence of synchronized 2D and 3D sensory data, the framework systematically integrates different perception modules to obtain 3D position, orientation, velocity and category of traffic participants and the ego car in a reconstructed 3D semantically labeled traffic scene. We implement this framework and demonstrate the effectiveness in challenging urban driving scenarios. The proposed framework builds a foundation for higher level driving scene understanding problems such as intention and motion prediction of surrounding entities, ego motion planning, and decision making.
Shielding properties of laser-induced breakdown in water for pulse durations from 5 ns to 125 fs (1997)

The shielding effectiveness of laser-induced breakdown from focused, visible laser pulses from 5 ns to 125 fs is determined from measurements of transmission of energy through the focal volume. The shielding efficiency decreases as a function of pulse duration from 5 ns to 300 fs and increases from 300 fs to 125 fs. The results are compared with past studies at similar pulse durations. The results of the measurements support laser-induced breakdown models and may lead to an optimization of laser-induced breakdown in ophthalmic surgery by reduction of collateral effects.
Interactions of synthetic peptide analogs of the class A amphipathic helix with lipids. Evidence for the snorkel hypothesis. (1994)

Class A amphipathic helixes present in exchangeable plasma apolipoproteins are characterized by the location of positively charged amino acid residues at the non-polar-polar interface and negatively charged amino acid residues at the center of the polar face. The objectives of the present study were: (i) to investigate the role of hydrocarbon side chain length of the interfacial positively charged amino acid residues in the lipid affinity of class A amphipathic helixes, and (ii) to investigate the importance of the nature of interfacial charge in the lipid affinity of class A amphipathic helixes. Toward this end, lipid interactions of the following two analogs of the class A amphipathic helix, Ac-18A-NH2 (acetyl-Asp-Trp-Leu-Lys-Ala-Phe-Tyr- Asp-Lys-Val-Ala-Glu-Lys-Leu-Lys-Glu-Ala-Phe-NH2), and Ac-18A(Lys > Haa)-NH2 (acetyl-Asp-Trp-Leu-Haa-Ala-Phe-Tyr-Asp-Haa-Val-Ala-Glu-Haa-Leu-Haa-Glu- Ala-Phe-NH2) (Haa = homoaminoalanine), were studied. The side chain of Haa has two CH2 groups less than that of lysine. The lipid affinities of these two peptide analogs were compared with that of Ac-18R-NH2, an analog of Ac-18A-NH2 with positions of the charged amino acid residues reversed. The techniques used in these studies were circular dichroism, fluorescence spectroscopy, right-angle light scattering measurements, and differential scanning calorimetry. The results of these studies indicated the following rank order of lipid affinity: Ac-18A-NH2 > Ac-18A(Lys > Haa)-NH2 > Ac-18R-NH2. These results are in agreement with the "snorkel" model proposed earlier to explain the higher lipid affinity of class A amphipathic helixes (Segrest, J. P., Loof, H. D., Dohlman, J. G., Brouillette, C. G., and Anantharamaiah, G. M. (1990) Proteins Struct. Funct. Genetics 8, 103-117). In addition, it was observed from the differential scanning calorimetry studies that Ac-18A-NH2 and Ac-18A(Lys > Haa)-NH2 interact more strongly than Ac-18R-NH2 with negatively charged dimyristoyl phosphatidylglycerol. The weaker interaction of Ac-18R-NH2 with dimyristoyl phosphatidylglycerol is suggested to be due to electrostatic repulsion between the negatively charged lipid and the interfacial negative charges of the peptide.
Identification of human melanoma peptides recognized by class I restricted tumor infiltrating T lymphocytes. (1993)

Using a newly described pH 3.3 acid elution technique, peptides were extracted by denaturation of class I molecules on the surface of human melanomas. HPLC fractionation of this material revealed six T cell epitopes (termed P1-P6) recognized by HLA-A2-restricted, melanoma-specific tumor infiltrating lymphocyte (TIL) lines. Three of these fractions (P1, P2, and P4) appeared to represent shared/immunodominant melanoma Ag recognized in the context of HLA-A2 because they were expressed by 4/4 HLA-A2+ melanoma cell lines and were each recognized by all four oligoclonal HLA-A2-restricted TIL lines examined. Interestingly, P1 and P2 (but not P3-P6) could also be recognized by these same TIL when presented by the HLA-Aw69 class I molecule, which is closely related to HLA-A2. P3, P5, and P6 displayed more restricted expression and were differentially recognized by the four oligoclonal TIL lines. These results suggest that synthetic peptide derived from P1, P2, and P4 sequences (when deduced) may form the basis of effective prophylactic or therapeutic melanoma vaccines by stimulating CD8+ CTL in HLA-A2+ individuals. This approach of identifying T cell epitopes presented by class I molecules should prove generally applicable to the study of other tumors recognized by class I-restricted CTL.
Relationship of aortic annular eccentricity and paravalvular regurgitation post transcatheter aortic valve implantation with CoreValve. (2013)

Eccentricity index is related to significant PAR after TAVI with Medtronic CoreValve. Further larger studies are required to determine the utility of this novel index in screening suitable patients for this procedure.
Index assignment for progressive transmission of full-search vector quantization (1994)

The authors study codeword index assignment to allow for progressive image transmission of fixed rate full-search vector quantization (VQ). They develop three new methods of assigning indices to a vector quantization codebook and formulate these assignments as labels of nodes of a full-search progressive transmission tree. The tree is used to design intermediate codewords for the decoder so that full-search VQ has a successive approximation character. The binary representation for the path through the tree represents the progressive transmission code. The methods of designing the tree that they apply are the generalized Lloyd algorithm, minimum cost perfect matching from optimization theory, and a method of principal component partitioning. Their empirical results show that the final method gives intermediate signal-to-noise ratios (SNRs) that are close to those obtained with tree-structured vector quantization, yet they have higher final SNRs.
Gene Expression Profiling Identifies Genes Predictive of Oral Squamous Cell Carcinoma (2008)

Oral squamous cell carcinoma (OSCC) is associated with substantial mortality and morbidity. To identify potential biomarkers for the early detection of invasive OSCC, we compared the gene expressions of incident primary OSCC, oral dysplasia, and clinically normal oral tissue from surgical patients without head and neck cancer or preneoplastic oral lesions (controls), using Affymetrix U133 2.0 Plus arrays. We identified 131 differentially expressed probe sets using a training set of 119 OSCC patients and 35 controls. Forward and stepwise logistic regression analyses identified 10 successive combinations of genes which expression differentiated OSCC from controls. The best model included LAMC2, encoding laminin-gamma2 chain, and COL4A1, encoding collagen, type IV alpha1 chain. Subsequent modeling without these two markers showed that COL1A1, encoding collagen, type I alpha1 chain, and PADI1, encoding peptidyl arginine deiminase, type 1, could also distinguish OSCC from controls. We validated these two models using an internal independent testing set of 48 invasive OSCC and 10 controls and an external testing set of 42 head and neck squamous cell carcinoma cases and 14 controls (GEO GSE6791), with sensitivity and specificity above 95%. These two models were also able to distinguish dysplasia (n = 17) from control (n = 35) tissue. Differential expression of these four genes was confirmed by quantitative reverse transcription-PCR. If confirmed in larger studies, the proposed models may hold promise for monitoring local recurrence at surgical margins and the development of second primary oral cancer in patients with OSCC.
Direct Synthesis and Stimulus-Responsive Micellization of Y-Shaped Hydrophilic Block Copolymers (2004)

Two bifunctional atom transfer radical polymerization (ATRP) macroinitiators were synthesized via Michael addition of 2 equivalents of 2-hydroxyethyl acrylate to two commercial monoamine-capped poly(alkylene oxides), Jeffamine XTJ-506 and Jeffamine XTJ-507, followed by esterification using excess 2-bromoisobutyryl bromide. 1H NMR and MALDI−TOF mass spectra (MALDI−TOF MS) were consistent with the expected structures for these two ATRP macroinitiators. A range of well-defined, Y-shaped, pH-responsive or thermoresponsive block copolymers was synthesized using these macroinitiators by polymerizing various hydrophilic methacrylic monomers via ATRP in methanol at 20 °C. The stimulus-responsive micellization of selected Y-shaped block copolymers in aqueous solution was investigated by 1H NMR, dynamic light scattering (DLS), and surface tensiometry. For comparative purposes, their linear diblock copolymer counterparts were also synthesized, and their micellization properties in aqueous solution were investigated. DLS studies indicated that the nonlinear architectures of selected Y-shaped block copolymers usually resulted in micelles with differing dimensions to those formed by the corresponding linear diblock copolymers. DLS studies also confirmed that one of these new Y-shaped block copolymers exhibited "schizophrenic" thermoresponsive behavior in aqueous solution. Near-monodisperse spherical micelles were obtained at higher temperatures (above 45 °C), whereas polydisperse nonspherical micelles appear to be formed at lower temperatures (below 12 °C).
The Presence of Airway Reactivity before the Development of Asthma (1990)

Exaggerated airway reactivity is an essential component of the current asthmatic. It is not clear, however, if airway reactivity is genetically determined or acquired. To examine the possibility that increased bronchial reactivity exists prior to the development of asthma, we report on 20 subjects who were studied before and after the onset of clinical asthma. Subjects were part of a larger on-going study of the Natural History of Asthma. Thirteen subjects indicated by their answers to the National Heart, Lung, and Blood Institute respiratory questionnaire that they were not asthmatic at their initial visit. Seven subjects had pulmonary symptoms on their initial visit, but had not been diagnosed as asthmatic. Bronchial reactivity was assessed using a standardized methacholine challenge. For the 20 subjects, there was a mean interval of 3.5 yr between the initial visit and the diagnosis of asthma. Ten of 13 nonasthmatic subjects had moderate or strongly positive responses (208 breath units or less) to methacholine prior to onset of asthma. These 13 subjects were compared to age- and sex-matched controls, from both asthmatic and nonasthmatic families, who had not become asthmatic. There was a difference in bronchial responses at the initial visit between the 13 study subjects and their control subjects from nonasthmatic families, but not between the subjects and their controls from asthmatic families. Five of 7 subjects with pulmonary symptoms had responses of 100 breath units or less. Overall, 19 of 20 subjects had strongly positive responses to methacholine after the diagnosis of asthma was established. The results show that enhanced airway reactivity usually precedes the development of asthma, which could support a genetic basis for it.