gebhart/patrepeval huggingface dataset:
Renin-angiotensin system-related highlights from the High Blood Pressure Research Conference annual meeting (2008)

The High Blood Pressure Research Conference of the American Heart Association is a theoretical meeting for hypertension researchers who direct their attention to hypertension-related basic disease mechanisms. The items that I have selected for this brief review are molecular intracellular receptor function, novel angiotensin (Ang)-related pathways, including Ang-(1-7), the Mas receptor, and angiotensin-converting enzyme 2, oxidative stress, immunity, the (pro)renin receptor, and until now unappreciated signalling pathways, such as the tonicity element binding protein.
Conformational Energy Studies andin Vitroandin VivoActivity Data on Growth Hormone-Releasing Peptides* (1984)

A series of growth hormone-releasing peptides have been designed and tested for both in vitro and in vivo activity. In vitro activity at 1-10 ng/ml was obtained for the pentapeptide, His-DTrp-Ala-Trp-DPhe-NH2 (I) and the hexapeptide, His-DTrp-Ala-Trp-DPhe-Lys-NH2 (II). These peptides, as well as others to be described, are active in releasing GH in vivo at low microgram dosages. In this manuscript, the conformational properties and in vitro and in vivo activity of a series of small peptides are reported. Results of the biological studies are reported in an accompanying paper.
2,3,7,8-Tetrachlorodibenzo-p-dioxin Toxicity in the Zebrafish Embryo: Local Circulation Failure in the Dorsal Midbrain Is Associated with Increased Apoptosis (2002)

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on local circulation and apoptosis in the midbrain were investigated in zebrafish (Danio rerio) embryos during early development. Embryos were exposed to TCDD from 24 h post fertilization (hpf) until observation, in water maintained at 28.5 degrees C. TCDD decreased blood flow in the mesencephalic vein, the only vessel perfusing the dorsal midbrain of the embryo. At 50 hpf, blood flow was maximally reduced in this vessel and gradually returned to the control level at 60 hpf. In contrast, blood flows in the trunk and in other vessels of the head of the embryo did not significantly change until 72 hpf. Furthermore, TCDD exposure caused apoptosis in the midbrain at 60 hpf, and the TCDD dose response relationship for this effect was similar to that for reduced blood flow in the mesencephalic vein at 50 hpf. The effects of TCDD on apoptosis in the midbrain, but not on blood flow, were abolished by Z-VAD-FMK, a general caspase inhibitor. TCDD effects on both endpoints were mimicked by beta-naphthoflavone (BNF), an aryl hydrocarbon receptor (AHR) agonist, and almost abolished by concomitant exposure to TCDD and alpha-naphthoflavone (ANF), an AHR antagonist. Concomitant exposure to TCDD and either an inhibitor of cytochrome P450 (CYP) (SKF525A or miconazole) or an antioxidant (N-acetylcysteine or ascorbic acid) inhibited these effects of TCDD. The incidence of apoptosis in the midbrain was inversely related to blood flow in this brain region following these various treatments and graded TCDD exposure concentrations (r = -0.91). The same range of TCDD exposure concentrations that reduced blood flow and increased apoptosis in the midbrain greatly enhanced CYP1A mRNA expression and immunoreactivity at 50 hpf in endothelial cells of blood vessels including the mesencephalic vein and the heart, but not the brain parenchyma. Taken together, these results suggest that TCDD induces apoptosis in the midbrain of the zebrafish embryo secondary to local circulation failure, which could be related to AHR activation, induction of CYP1A, and oxidative stress.
Treatment decisions in axillary node-negative breast cancer patients. (1992)

Treatment decisions must be made on 9000 axillary node-negative breast cancer patients each month in the United States. Which of these patients will benefit from adjuvant therapy is a major question. Valid methods are needed to distinguish those patients who are "cured" from those who will suffer a cancer recurrence. A complex network of prognostic variables enters into the treatment decision, together with a risk-versus-benefit assessment. We are using a neural-network-based form of artificial intelligence that, once "trained" with data representing an event and its outcome, can identify subsets of patients with low recurrence risks. Larger data sets are being evaluated with the hope of introducing the neural-network technique to routine clinical practice.
Choline, an essential nutrient for humans (1991)

Choline is required to make essential membrane phospholipids. It is a precursor for the biosynthesis of the neurotransmitter acetylcholine and also is an important source of labile methyl groups. Mammals fed a choline-deficient diet develop liver dysfunction; however, choline is not considered an essential nutrient in humans. Healthy male volunteers were hospitalized and fed a semisynthetic diet devoid of choline supplemented with 500 mg/day choline for 1 wk. Subjects were randomly divided into two groups, one that continued to receive choline (control), and the other that received no choline (deficient) for three additional wk. During the 5th wk of the study all subjects received choline. The semisynthetic diet contained adequate, but no excess, methionine. In the choline-deficient group, plasma choline and phosphatidylcholine concentrations decreased an average of 30% during the 3-wk period when a choline-deficient diet was ingested; plasma and erthrocyte phosphatidylcholine decreased 15%; no such changes occurred in the control group. In the choline-deficient group, serum alanine aminotransferase activity increased steadily from a mean of 0.42 mukat/liter to a mean of 0.62 mukat/liter during the 3-wk period when a choline-deficient diet was ingested; no such change occurred in the control group. Other tests of liver and renal function were unchanged in both groups during the study. Serum cholesterol decreased an average of 15% in the deficient group and did not change in the control group. Healthy humans consuming a choline-deficient diet for 3 wk had depleted stores of choline in tissues and developed signs of incipient liver dysfunction. Our observations support the conclusion and choline is an essential nutrient for humans when excess methionine and folate are not available in the diet.
Computational RNA secondary structure design: empirical complexity and improved methods (2007)

Our analysis helps to better understand the strengths and limitations of both the RNA-SSD and RNAinverse algorithms, and suggests ways in which the performance of these algorithms can be further improved.
Identification of the NF-E2-related Factor-2-dependent Genes Conferring Protection against Oxidative Stress in Primary Cortical Astrocytes Using Oligonucleotide Microarray Analysis (2003)

The antioxidant responsive element (ARE) mediates transcriptional regulation of phase II detoxification enzymes and antioxidant proteins such as NAD(P)H:quinone oxidoreductase (NQO1), glutathione S-transferases, and glutamate-cysteine ligase. In this study, we demonstrate that NF-E2-related factor-2 (Nrf2) plays a major role in transcriptional activation of ARE-driven genes and identify Nrf2-dependent genes by oligonucleotide microarray analysis using primary cortical astrocytes from Nrf2(+/+) and Nrf2(-/-) mice. Nrf2(-/-) astrocytes had decreased basal NQO1 activity and no induction by tert-butylhydroquinone compared with Nrf2(+/+) astrocytes. Similarly, both basal and induced levels of human NQO1-ARE-luciferase expression in Nrf2(-/-) astrocytes were significantly lower than in Nrf2(+/+) astrocytes. Furthermore, human NQO1-ARE-luciferase expression in Nrf2(-/-) astrocytes was restored by overexpression of Nrf2, whereas ARE activation in Nrf2(+/+) astrocytes was completely blocked by dominant-negative Nrf2. In addition, we observed that Nrf2-dependent genes protected primary astrocytes from H(2)O(2)- or platelet-activating factor-induced apoptosis. In support of these observations, we identified Nrf2-dependent genes encoding detoxification enzymes, glutathione-related proteins, antioxidant proteins, NADPH-producing enzymes, and anti-inflammatory genes using oligonucleotide microarrays. Proteins within these functional categories are vital to the maintenance and responsiveness of a cell defense system, suggesting that an orchestrated change in gene expression via Nrf2 and the ARE gives a synergistic protective effect against oxidative stress.
Nonlinear Optics of Semiconductor‐Doped Glasses (1988)

Abstract Nonlinear optical properties of semiconductor‐doped glasses are reviewed. A growth technique enabling to obtain semiconductor microcrystals with controlled sizes grown in a glassy matrix is described. It is shown that the optical properties of such systems are determined by the energy spectrum of the electron–hole pairs confined in the small‐size microcrystals. The dependences of these spectra on the microcrystal size are analysed. The effect of the blue‐shift of the spectra occurring at high excitation levels is discussed. At excitation with light of photon energy below the energy gap of the glass photoionization is discovered. In this process the electron is ejected from the microcrystal to the glass where it is captured by the long‐lived centers. The latter process is likely to explain the effect of the glass darkening and the formation of permanent volume grating.
Association of increased CCL5 and CXCL7 chemokine expression with neutrophil activation in severe stable COPD (2009)

The increased expression of CCL5 and CXCL7 in the bronchial mucosa of patients with stable COPD, together with an increased expression of extracellular matrix-binding receptors on neutrophils, may be involved in the pathogenesis of COPD.
The OB Protein (Leptin) Pathway - A Link Between Adipose Tissue Mass and Central Neural Networks (1996)

OB protein (also known as leptin), a previously unknown protein signal, is secreted from adipose tissue, circulates in the blood, probably bound to a family of binding proteins, and acts on central neural networks that regulate ingestive behavior and energy balance. OB protein provides a communication link from fat tissue and the brain. Rapidly accumulating evidence suggests that OB protein appears to play a major role in the control of body fat stores through coordinated regulation of feeding behavior, metabolism, autonomic nervous system and body energy balance in rodents, primates and humans. The field has rapidly moved from cloning of the ob gene to demonstration of complex regulation of ob gene expression in adipose tissue in rats and humans, and then the demonstration of potent biological activity of OB protein in ob/ob, diet-induced, and lean mice as well as obese and lean rats but not in db/db obese mice. A significant milestone was our demonstration that central administration of OB protein lead to reductions in food intake, body weight and alterations in metabolism consistent with activation of the autonomic nervous system. These findings were followed by the identification of a central binding site for labelled OB protein in the choroid plexus in ob/ob, db/db and lean mice as well as lean and obese Zucker rats. The expression cloning of a central receptor, OB-R, from the mouse choroid plexus soon followed. The OB-R receptor was found to be expressed in the choroid plexus, the hypothalamus as well as several peripheral tissues. OB-R exists in multiple forms; the two major forms are a short form (with a truncated intracellular domain) and long form (with the complete intracellular domain). The long form is thought to be the form that signals and mediates the biological effects of OB protein. Initial in situ hybridization studies have demonstrated the mRNA for the long form OB-R receptor to be localized to the hypothalamus as well as peripheral sites. Recently, it was demonstrated that the db gene encodes the OB-R receptor. Evidence has been provided for a specific transport system for OB protein to cross the blood-brain-barrier and enter the brain of mice, rats and humans. The rate of transport can be decreased by high plasma concentrations of OB protein. Thus, reduced entry of OB protein to the brain may be one of the mechanisms of reduced sensitivity of the OB protein pathway in obese individuals. OB protein appears to also play a role in the important neuroendocrine adaptive responses to fasting and in the control of reproduction. Therapeutic approaches to the treatment of obesity based on OB protein ranging from OB protein by injection to OB-R receptor agonists and to upregulation of OB signalling pathways are under intense investigation.
High charge mobility in two-dimensional percolative networks of PbSe quantum dots connected by atomic bonds (2015)

Two-dimensional networks of quantum dots connected by atomic bonds have an electronic structure that is distinct from that of arrays of quantum dots coupled by ligand molecules. We prepared atomically coherent two-dimensional percolative networks of PbSe quantum dots connected via atomic bonds. Here, we show that photoexcitation leads to generation of free charges that eventually decay via trapping. The charge mobility probed with an AC electric field increases with frequency from 150 ± 15 cm(2) V(-1) s(-1) at 0.2 terahertz to 260 ± 15 cm(2) V(-1) s(-1) at 0.6 terahertz. Gated four-probe measurements yield a DC electron mobility of 13 ± 2 cm(2) V(-1) s(-1). The terahertz mobilities are much higher than for arrays of quantum dots coupled via surface ligands and are similar to the highest DC mobilities reported for PbSe nanowires. The terahertz mobility increases only slightly with temperature in the range of 15-290 K. The extent of straight segments in the two-dimensional percolative networks limits the mobility, rather than charge scattering by phonons.
Transcriptional mapping of human respiratory syncytial virus. (2020)

A transcriptional map for human respiratory syncytial virus was determined by measuring the kinetics of viral gene inactivation in response to UV irradiation. Monolayer cell cultures of respiratory syncytial virus-infected HEp-2 cells were exposed to UV light, and residual viral RNA synthesis was monitored both by gel electrophoresis and by hybridization to dot blots of cloned cDNAs of the 10 known viral genes. Target sizes for the 10 individual viral genes were calculated relative to the UV sensitivity of intracellular viral genome replication. Target size analysis indicated that the 10 viral genes were transcribed as a single transcriptional unit and that the transcription of an individual gene was dependent on the prior transcription of all the preceding genes. The order of gene transcription (with nomenclature according to encoded proteins) was determined to proceed from the promoter as follows: 14K, 11K, N, P, M, 9.5K, 36K, F, 24K, L.
Construction of a human Ig combinatorial library from genomic V segments and synthetic CDR3 fragments. (1993)

A naive combinatorial Ig library was constructed from semi-synthetic V genes consisting of human genomic V segments and synthetic CDR3 fragments. VH and V kappa segments were amplified from human genomic DNA by polymerase chain reaction using V subgroup-specific primers. The amplified VH and V kappa segments were combined with synthetic oligonucleotides containing a J region and CDR3 with amino acid sequence variations, resulting in complete V genes. These V genes were cloned into a phagemid expression vector in a single-chain form fused to the carboxyl-terminus of the M13 minor coat protein III. Phagemid particles displaying the single chain hybrid proteins on their surface were screened with Con A as Ag. Several clones showing specific binding to Con A were obtained after four rounds of selection and were further analyzed for their binding properties and DNA sequences. This method provides a novel way to create a naive combinatorial library without using mRNA from B lymphocytes as template. The method should be useful to isolate human antibodies that react with self-Ag.
The Risk for Preterm Labor in Women Receiving 17 Alpha-Hydroxyprogesterone Caproate Prophylaxis for Preterm Birth Prevention (2009)

We sought to identify maternal or clinical characteristics of women likely to develop preterm labor (PTL) at <34 weeks' gestation while receiving 17 alpha-hydroxyprogesterone caproate (17P) prophylaxis. Current singleton gestations with prior preterm delivery enrolled for outpatient 17P administration at <27 weeks' gestation were identified ( N = 1177). Maternal and clinical characteristics were compared between women hospitalized and diagnosed with PTL at <34 weeks' gestation (PTL group, N = 270) and those without PTL (No PTL group, N = 660). PTL at <34 weeks' gestation occurred in 270/1177 (22.9%) of patients receiving 17P prophylaxis (mean gestational age at diagnosis was 28.3 +/- 4.0 weeks). Recurrent preterm delivery occurred in 73.3% of women with PTL at <34 weeks. Maternal age, marital status, race, tobacco use, cerclage, gestational age at start of 17P, and Medicaid status were similar between the groups. Women developing PTL at <34 weeks were more likely to have >1 prior preterm delivery than those without PTL (35.2% versus 25.9%, P = 0.006, odds ratio [95% confidence interval] 1.5 [1.1, 2.1]). Women receiving 17P prophylaxis remain at increased risk for PTL and preterm birth. Patient education and surveillance for PTL symptoms may be warranted in women with a history of more than one prior preterm delivery.
3-Ethoxycarbonylmethylenequinoxalin-2-one in heterocyclic synthesis. Part 1 : Synthesis of new substituted and condensed quioxalines (2005)

Se usa 6,7-dimetil-3-etoxicarbonilmetilen-2-oxo-1,2,3,4-tetrahidroquinoxalina (1) como producto de partida para la sintesis de varios nuevos derivados de 2-quinoxalinona, pirrolo[2,3-b]quinoxalina y furo[2,3-b]quinoxalina
Serial Changes of Cerebral Glucose Metabolism and Caudate Size in Persons at Risk for Huntington's Disease (1992)

The results suggest that a reduction in caudate glucose metabolism and atrophy develop rapidly in Huntington's disease. The findings establish a strategy for using serial positron emission tomographic imaging to monitor experimental pharmacologic interventions in presymptomatic individuals who have developed caudate hypometabolism.
An Adenovirus Mutant That Replicates Selectively in p53- Deficient Human Tumor Cells (1996)

The human adenovirus E1B gene encodes a 55-kilodalton protein that inactivates the cellular tumor suppressor protein p53. Here it is shown that a mutant adenovirus that does not express this viral protein can replicate in and lyse p53-deficient human tumor cells but not cells with functional p53. Ectopic expression of the 55-kilodalton EIB protein in the latter cells rendered them sensitive to infection with the mutant virus. Injection of the mutant virus into p53-deficient human cervical carcinomas grown in nude mice caused a significant reduction in tumor size and caused complete regression of 60 percent of the tumors. These data raise the possibility that mutant adenoviruses can be used to treat certain human tumors.
A High-Resolution Anatomical Atlas of the Transcriptome in the Mouse Embryo (2011)

Ascertaining when and where genes are expressed is of crucial importance to understanding or predicting the physiological role of genes and proteins and how they interact to form the complex networks that underlie organ development and function. It is, therefore, crucial to determine on a genome-wide level, the spatio-temporal gene expression profiles at cellular resolution. This information is provided by colorimetric RNA in situ hybridization that can elucidate expression of genes in their native context and does so at cellular resolution. We generated what is to our knowledge the first genome-wide transcriptome atlas by RNA in situ hybridization of an entire mammalian organism, the developing mouse at embryonic day 14.5. This digital transcriptome atlas, the Eurexpress atlas (http://www.eurexpress.org), consists of a searchable database of annotated images that can be interactively viewed. We generated anatomy-based expression profiles for over 18,000 coding genes and over 400 microRNAs. We identified 1,002 tissue-specific genes that are a source of novel tissue-specific markers for 37 different anatomical structures. The quality and the resolution of the data revealed novel molecular domains for several developing structures, such as the telencephalon, a novel organization for the hypothalamus, and insight on the Wnt network involved in renal epithelial differentiation during kidney development. The digital transcriptome atlas is a powerful resource to determine co-expression of genes, to identify cell populations and lineages, and to identify functional associations between genes relevant to development and disease.
A Genetic Approach to Mammalian Glycan Function (2003)

The four essential building blocks of cells are proteins, nucleic acids, lipids, and glycans. Also referred to as carbohydrates, glycans are composed of saccharides that are typically linked to lipids and proteins in the secretory pathway. Glycans are highly abundant and diverse biopolymers, yet their functions have remained relatively obscure. This is changing with the advent of genetic reagents and techniques that in the past decade have uncovered many essential roles of specific glycan linkages in living organisms. Glycans appear to modulate biological processes in the development and function of multiple physiologic systems, in part by regulating protein-protein and cell-cell interactions. Moreover, dysregulation of glycan synthesis represents the etiology for a growing number of human genetic diseases. The study of glycans, known as glycobiology, has entered an era of renaissance that coincides with the acquisition of complete genome sequences for multiple organisms and an increased focus upon how posttranslational modifications to protein contribute to the complexity of events mediating normal and disease physiology. Glycan production and modification comprise an estimated 1% of genes in the mammalian genome. Many of these genes encode enzymes termed glycosyltransferases and glycosidases that reside in the Golgi apparatus where they play the major role in constructing the glycan repertoire that is found at the cell surface and among extracellular compartments. We present a review of the recently established functions of glycan structures in the context of mammalian genetic studies focused upon the mouse and human species. Nothing tends so much to the advancement of knowledge as the application of a new instrument. The native intellectual powers of men in different times are not so much the causes of the different success of their labours, as the peculiar nature of the means and artificial resources in their possession. T. Hager: Force of Nature (1)