gebhart/patrepeval huggingface dataset:
Novel Three-Pronged Strategy to Enhance Cancer Cell Killing in Glioblastoma Cell Lines: Histone Deacetylase Inhibitor, Chemotherapy, and Oncolytic Adenovirus dl520 (2006)

Resistance to radiation and chemotherapy remains an obstacle to the treatment of brain tumors. We have demonstrated that the replication-deficient adenovirus d1520, which lacks the E1A 13S protein, replicates efficiently and exhibits oncolytic potential in multidrug-resistant cells with nuclear localization of the human transcription factor YB-1. However, besides others, key factors regarding oncolytic virotherapy are limited tumor transduction rate and low replication efficiency. The objective of this study was to determine whether the chemotherapeutic agent irinotecan, by enhancing nuclear localization of YB-1, and the histone deacetylase inhibitor trichostatin A, by upregulating coxsackievirus-adenovirus receptor (CAR) expression, could augment replication of and cell lysis by adenovirus dl520 in glioblastomas in vitro. We found that trichostatin A upregulated CAR expression and that irinotecan caused increased nuclear localization of YB-1 in both glioblastoma cell lines. Irinotecan alone, and trichostatin A alone, enhanced replication of and cell lysis by dl520. Importantly, when combining both agents, the replication efficiency (maximum, 27-fold) and induction of cytopathic effect (maximum, 3.8-fold) of dl520 were further augmented significantly. These results support the hypothesis that the enhanced oncolytic effect of dl520, after incubation with chemotherapeutic agents, is mediated by an increased accumulation of YB-1 in the nucleus (due to irinotecan) and by upregulation of CAR (due to trichostatin A). Thus, therapy combining virotherapy, chemotherapy, and histone deacetylase inhibitor treatment is a novel approach to enhance the oncolytic efficacy of dl520.
The role of nuclear imaging in the failing heart: myocardial blood flow, sympathetic innervation, and future applications (2010)

Heart failure represents a common disease affecting approximately 5 million patients in the United States. Several conditions play an important role in the development and progression of heart failure, including abnormalities in myocardial blood flow and sympathetic innervation. Nuclear imaging represents the only imaging modality with sufficient sensitivity to assess myocardial blood flow and sympathetic innervation of the failing heart. Although nuclear imaging with single-photon emission computed tomography (SPECT) is most commonly used for the evaluation of myocardial perfusion, positron emission tomography (PET) allows absolute quantification of myocardial blood flow beyond the assessment of relative myocardial perfusion. Both techniques can be used for evaluation of diagnosis, treatment options, and prognosis in heart failure patients. Besides myocardial blood flow, cardiac sympathetic innervation represents another important parameter in patients with heart failure. Currently, sympathetic nerve imaging with 123-iodine metaiodobenzylguanidine (123-I MIBG) is often used for the assessment of cardiac innervation. A large number of studies have shown that an abnormal myocardial sympathetic innervation, as assessed with 123-I MIBG imaging, is associated with increased mortality and morbidity rates in patients with heart failure. Also, cardiac 123-I MIBG imaging can be used to risk stratify patients for ventricular arrhythmias or sudden cardiac death. Furthermore, novel nuclear imaging techniques are being developed that may provide more detailed information for the detection of heart failure in an early phase as well as for monitoring the effects of new therapeutic interventions in patients with heart failure.
Sleep and mental disorders: A meta-analysis of polysomnographic research. (2016)

Investigating sleep in mental disorders has the potential to reveal both disorder-specific and transdiagnostic psychophysiological mechanisms. This meta-analysis aimed at determining the polysomnographic (PSG) characteristics of several mental disorders. Relevant studies were searched through standard strategies. Controlled PSG studies evaluating sleep in affective, anxiety, eating, pervasive developmental, borderline and antisocial personality disorders, attention-deficit-hyperactivity disorder (ADHD), and schizophrenia were included. PSG variables of sleep continuity, depth, and architecture, as well as rapid-eye movement (REM) sleep were considered. Calculations were performed with the "Comprehensive Meta-Analysis" and "R" software. Using random effects modeling, for each disorder and each variable, a separate meta-analysis was conducted if at least 3 studies were available for calculation of effect sizes as standardized means (Hedges' g). Sources of variability, that is, sex, age, and mental disorders comorbidity, were evaluated in subgroup analyses. Sleep alterations were evidenced in all disorders, with the exception of ADHD and seasonal affective disorders. Sleep continuity problems were observed in most mental disorders. Sleep depth and REM pressure alterations were associated with affective, anxiety, autism and schizophrenia disorders. Comorbidity was associated with enhanced REM sleep pressure and more inhibition of sleep depth. No sleep parameter was exclusively altered in 1 condition; however, no 2 conditions shared the same PSG profile. Sleep continuity disturbances imply a transdiagnostic imbalance in the arousal system likely representing a basic dimension of mental health. Sleep depth and REM variables might play a key role in psychiatric comorbidity processes. Constellations of sleep alterations may define distinct disorders better than alterations in 1 single variable. (PsycINFO Database Record
[After ten years of AIDS, a vision emanating from feminism]. (1994)

AIDS and the economic crisis in Mexico are threatening the epidemiologic transition in which infectious diseases ceased to be the only major cause of death and chronic degenerative diseases began to account for a growing proportion of deaths. Many factors combined to produce the sexual, gay, and women's liberation movements beginning in the 1970s. At the beginning of the feminist movement, women proposed different kinds of interpersonal relations both between women and with men. Women together realized their rights to control their own bodies, to sexual enjoyment, to abortion, and to free themselves of feelings of shame and guilt. The weight of moral pressures was lessened and the personal desires of the woman assumed a greater role in selection of sexual partners. Conservative forces grew stronger in the 1980s, and the proliferation of sexually transmitted diseases began to imperil the sexual revolution. But these setbacks were minor compared to AIDS. Now, 10 years after its appearance, it is clear that AIDS is not limited to homosexual men. The number of cases in Mexico increased from none 10 years ago to some 10,000 estimated cases reported and unreported today. 1/6 of the cases are in women. Many women and heterosexuals felt immune from AIDS in the beginning, and some still do, but many more have become aware of the danger. Women now fear contracting AIDS, but they also fear confronting their partners to suggest that they use condoms. Denial may play a role, but deeply rooted cultural factors that women may recognize but fee powerless to change may also be at play. Many women over 30 have difficulty taking the initiative in sexual matters. They are embarrassed to buy condoms and even more embarrassed to propose their use. They imagine that men will consider them "loose" if they carry condoms. Mexican women are poorly prepared to tell their men explicitly what they want sexually, and Mexican men are also poorly equipped to ask what women want, accustomed as they are to exercising sexuality exclusively to satisfy their own needs. The entire problem of condom use is related to ethical-moral and ideological factors and to broader attitudes toward knowledge. Those with more rational orientations see AIDS as a disease rather than a divine punishment and can more easily accept condom use as a preventive.
Model-based object characterization with active infrared sensor array (2007)

The paper presents a low-cost solution based on reflected infrared light intensity measurements for the determination of characteristic properties of moving objects like form, size, location, trajectory, velocity and surface reflectivity. Two arrays of several infrared (IR) emitter-receiver pairs, working on a reflection light principle and driven alternately, are mounted on opposite sides of the area of observation. In order to model the reflecting surface properly, it is considered to be composed of a number of so called elementary reflectors (ER), effectively decoupling the three components of the received intensity: distance, azimuth and surface reflection angle. Results from measurements with basic object forms are shown proving its potential. The model parameters (number of ERs involved, their position and direction towards the IR sensor) are obtained by an optimization procedure, enabling to recognize virtually every object form by decomposition into ERs.
Perspective:  A Program to Improve Protein Biomarker Discovery for Cancer (2005)

Biomarkers for cancer risk, early detection, prognosis, and therapeutic response promise to revolutionize cancer management. Protein biomarkers offer tremendous potential in this regard due to their great diversity and intimate involvement in physiology. An effective program to discover protein biomarkers using existing technology will require team science, an integrated informatics platform, identification and quantitation of candidate biomarkers in disease tissue, mouse models of disease, standardized reagents for analyzing candidate biomarkers in bodily fluids, and implementation of automation. Technology improvements for better fractionation of the proteome, selection of specific biomarkers from complex mixtures, and multiplexed assay of biomarkers would greatly enhance progress.
Towards Synthetic Molecular Muscles: Contraction and Stretching of a Linear Rotaxane Dimer (2000)

Copper(I)-induced template synthesis produces a linear rotaxane dimer capable of undergoing contraction and stretching motions of large amplitude under the action of a chemical stimulus (see scheme). The process is reminiscent of those observed in natural muscles.
Molecular pathogenesis of pulmonary arterial hypertension (2012)

Recent clinical and experimental studies are redefining the cellular and molecular bases of pulmonary arterial hypertension (PAH). The genetic abnormalities first identified in association with the idiopathic form of PAH -together with a vast increase in our understanding of cell signaling, cell transformation, and cell-cell interactions; gene expression; microRNA processing; and mitochondrial and ion channel function -have helped explain the abnormal response of vascular cells to injury. Experimental and clinical studies now converge on the intersection and interactions between a genetic predisposition involving the BMPR2 signaling pathway and an impaired metabolic and chronic inflammatory state in the vessel wall. These deranged processes culminate in an exuberant proliferative response that occludes the pulmonary arterial (PA) lumen and obliterates the most distal intraacinar vessels. Here, we describe emerging therapies based on preclinical studies that address these converging pathways.
Improved Algebraic Cryptanalysis of QUAD, Bivium and Trivium via Graph Partitioning on Equation Systems. (2010)

Abstract. We present a novel approach for solving systems of polynomial equations via graph partitioning. The concept of a variable-sharing graph of a system of polynomial equations is defined. If such graph is disconnected, then the corresponding system of equations can be split into smaller ones that can be solved individually. This can provide a significant speed-up in computing the solution to the system, but is unlikely to occur either randomly or in applications. However, by deleting a certain vertices on the graph, the variable-sharing graph could be disconnected in a balanced fashion, and in turn the system of polynomial equations are separated into smaller ones of similar sizes. In graph theory terms, this process is equivalent to finding balanced vertex partitions with minimum-weight vertex separators. The techniques of finding these vertex partitions are discussed, and experiments are performed to evaluate its practicality for general graphs and systems of polynomial equations. Applications of this approach in algebraic cryptanalysis on symmetric ciphers are presented. For the QUAD family of stream ciphers, we show how a malicious party can manufacture conforming systems that can be easily broken. For the stream cipher Trivium and its variants, we achieve significant speedups in algebraic attacks launched against them. In each of these cases, the systems of polynomial equations involved are well-suited to our graph partitioning method. These results may open a new avenue for evaluating the security of symmetric ciphers against algebraic attacks. 1
Vaccination with NY-ESO-1 protein and CpG in Montanide induces integrated antibody/Th1 responses and CD8 T cells through cross-priming (2007)

The use of recombinant tumor antigen proteins is a realistic approach for the development of generic cancer vaccines, but the potential of this type of vaccines to induce specific CD8(+) T cell responses, through in vivo cross-priming, has remained unclear. In this article, we report that repeated vaccination of cancer patients with recombinant NY-ESO-1 protein, Montanide ISA-51, and CpG ODN 7909, a potent stimulator of B cells and T helper type 1 (Th1)-type immunity, resulted in the early induction of specific integrated CD4(+) Th cells and antibody responses in most vaccinated patients, followed by the development of later CD8(+) T cell responses in a fraction of them. The correlation between antibody and T cell responses, together with the ability of vaccine-induced antibodies to promote in vitro cross-presentation of NY-ESO-1 by dendritic cells to vaccine-induced CD8(+) T cells, indicated that elicitation of NY-ESO-1-specific CD8(+) T cell responses by cross-priming in vivo was associated with the induction of adequate levels of specific antibodies. Together, our data provide clear evidence of in vivo cross-priming of specific cytotoxic T lymphocytes by a recombinant tumor antigen vaccine, underline the importance of specific antibody induction for the cross-priming to occur, and support the use of this type of formulation for the further development of efficient cancer vaccines.
Disruption of a gene encoding glycerol 3-phosphatase fromCandida albicansimpairs intracellular glycerol accumulation-mediated salt-tolerance (2005)

Intracellular glycerol accumulation is critical for Candida albicans to maintain osmolarity, and therefore defects in glycerol homeostasis can have severe effects on the morphogenetic plasticity and pathogenicity of this fungus. The final step of glycerol synthesis involves the dephosphorylation of glycerol 3-phosphate by glycerol 3-phosphatase (GPP1). We have identified a single copy of the GPP orthologous gene (GPP1) in the C. albicans haploid genome, as well as the paralogous gene 2-deoxyglucose-6-phosphate phosphatase (DOG1); both belong to a family of low molecular weight phosphatases. A knockout of the GPP1 gene in C. albicans caused increased susceptibility to high salt concentrations, indicating a deficiency in osmoregulation. Reintroduction of the GPP1 gene complemented the impairment of salt-tolerance in the gpp1/gpp1 mutant. Northern blot analysis showed that the GPP1 gene was strongly responsive to osmotic stress, and its transcriptional expression was positively correlated with intracellular glycerol accumulation. These results demonstrate that the GPP1 gene plays an important role in the osmoregulation in C. albicans.
Advances in the discovery and development of heat-shock protein 90 inhibitors for cancer treatment (2011)

INTRODUCTION: Over the last 15 - 20 years, targeted anticancer strategies have focused on therapies aimed at abrogating a single malignant protein. Agents that are directed towards the inhibition of a single oncoprotein have resulted in a number of useful drugs in the treatment of cancers (i.e., Gleevec, BCR-ABL; Tarceva and Iressa, EGFR). However, such a strategy relies on the notion that a cancer cell is dependent on a single signaling pathway for its survival. The possibility that a cancer cell may mutate or switch its dependence to another signaling pathway can result in the ineffectiveness of such agents. Recent advances in the biology of heat-shock protein 90 (Hsp90) have revealed intimate details into the complexity of the chaperoning process that Hsp90 is engaged in and, at the same time, have offered those involved in drug discovery several unique ways to interfere in this process. AREAS COVERED: This review provides the current understanding of the chaperone cycle of Hsp90 and presents the multifaceted approaches used by researchers in the discovery of potential Hsp90 drugs. It discusses the phenotypic outcomes in cancer cells on Hsp90 inhibition by these several approaches and also addresses several distinctions observed among direct Hsp90 ATP-pocket competitors providing commentary on the potential biological outcomes as well as the clinical relevance of such features. EXPERT OPINION: The significantly different phenotypic outcomes observed from Hsp90 inhibition by the many inhibitors developed suggest that the clinical development of Hsp90 inhibitors would be better served by careful consideration of the pharmacokinetic/pharmacodynamic properties of individual candidates rather than a generic approach directed towards the target.
p53 is mutated in a subset of advanced-stage prostate cancers. (1993)

Inactivation of p53, a tumor suppressor gene, contributes to the genesis and/or progression of a substantial fraction of all human cancers, including > or = 50% of breast, lung, and colon carcinomas. Mutated p53 alleles typically contain missense single-base substitutions within exons 5-8 and encode abnormally stable p53 proteins that accumulate to high levels in tumor cell nuclei. To evaluate the frequency, type, and clinical significance of p53 mutation in human prostate cancer, archival tumor material from 150 prostate cancer patients was examined by immunohistochemistry (IHC) with anti-p53 antibodies. Abnormal nuclear p53 accumulation (IHC) was observed in 19 tumors (12.7%) and was strongly related to disease stage (23% of 69 stage III or IV tumors were IHC+ versus 4% of 74 stage 0-II tumors; P < 0.001, Fisher's exact test). The methods of polymerase chain reaction, single-strand conformational polymorphism, and direct sequencing were used to identify mutations, predominantly missense single-base substitutions in exons 5, 7, or 8 in 9 of 14 IHC+ cases but in none of 20 IHC- cases; 5 of these mutations were G:C-->A:T transitions at CpG dinucleotides. These data indicate that mutated p53 alleles are quite uncommon in early prostate cancers but are found in 20-25% of advanced cancers, suggesting a role for p53 mutation in the progression of at least a subset of prostate cancers.
Enantiospecific synthesis of shikimic acid from D-mannose: formation of a chiral cyclohexene by intramolecular olefination of a carbohydrate-derived intermediate (1984)

An enantiospecific synthesis of (–)-shikimic acid from D-mannose in an overall yield of 39% is described, in which the key step is an intramolecular Wadsworth–Emmons olefination reaction of a phosphonate. Nucleophilic displacement of triflate from benzyl 2,3-O-isopropylidene-5-O-trifluoro-methylsulphonyl-α-D-lyxofuranoside by the sodium salt of t-butyl dimethoxyphosphorylacetate provides a rare example of substitution at the C-5 position of a furanose derivative by a carbanion.
Regulation of Glucagon-Like Peptide-1 Synthesis and Secretion in the GLUTag Enteroendocrine Cell Line1 (1998)

Glucagon-like peptide-1 (GLP-1) released from the intestine is a potent stimulator of glucose-dependent insulin secretion. To elucidate the factors regulating GLP-1 secretion, we have studied the enteroendocrine GLUTag cell line. GLP-1 secretion was stimulated in a dose-dependent fashion by activation of protein kinase A or C with forskolin or phorbol 12,13-dibutyrate, respectively (by 2.3 +/- 0.5-fold at 100 microM and 4.3 +/- 0.6-fold at 0.3 microM, respectively; P < 0.01-0.001). Of the regulatory peptides tested, only glucose-dependent insulinotropic peptide stimulated the release of GLP-1 (by 2.3 +/- 0.2-fold at 0.1 microM; P < 0.001); glucagon was without effect, and paradoxically, the inhibitory neuropeptide somatostatin-14 increased secretion slightly (by 1.6 +/- 0.3-fold at 0.01 microM; P < 0.05). In tests of several neurotransmitters, only the cholinergic agonists carbachol and bethanechol stimulated peptide secretion in a dose-dependent fashion (by 2.3 +/- 0.5- and 1.7 +/- 0.3-fold at 1000 microM; P < 0.05-0.001); the beta-adrenergic agonist isoproterenol and the chloride channel inhibitor gamma-aminobutyric acid did not affect release of GLP-1. Long chain monounsaturated fatty acids (18:1), but not saturated fatty acids (16:0), also stimulated the release of GLP-1 (by 1.7 +/- 0.1-fold at 150 microM; P < 0.001). Consistent with the presence of a cAMP response element in the proglucagon gene, activation of the protein kinase A-dependent pathway with forskolin increased proglucagon messenger RNA transcript levels by 2-fold (P < 0.05); glucose-dependent insulinotropic peptide and phorbol 12,13-dibutyrate were without effect. Therefore, by comparison with results obtained using primary L cell cultures or in vivo models, GLUTag cells appear to respond appropriately to the regulatory mechanisms controlling intestinal GLP-1 secretion.
Proposal of new postural positions for infants’ oral cleaning (2019)

The aim of this study was to propose to mothers two new postural positions to assist in the oral cleaning of infants up to 8 months of age and to verify their acceptance. The sample consisted of 38 mothers and their infants who participated in a program to promote oral health for children. The study consisted of 2 residential visits. In the first, a questionnaire was filled out by the mothers in order to know the habitual position in which the mother performed the hygiene of the baby's oral cavity and there was orientation with the new proposals for oral cleaning (Positions 1 and 2) . After 30 days, there was the return to verify which of the positions the mother preferred. Although the mothers received information about the baby's oral health, they weren’t told about an ideal postural position to perform oral cleaning. The diaper (86.8%) was the most used instrument, 31.5% found it difficult to clean the child's mouth, in which the majority of mothers reported being afraid of hurting the child during hygiene (91.6%). Position 1 was preferred for oral hygiene (p = 0.01), and of the reasons pointed out, proposal 1 was the easiest one (p = 0.04). All mothers adopted one of the new positions presented and position 1 was the most selected for oral hygiene in children.