gebhart/patrepeval huggingface dataset:
Signal Transduction From the Endoplasmic Reticulum to the Cell Nucleus (1999)

The endoplasmic reticulum (ER) serves several important functions. Cholesterol, an essential component of cellular membranes, is synthesized on the ER surface. Inside the organelle, proteins destined for secretion or transport to the cell surface are folded and become glycosylated. Because these processes are essential for cell viability, a disturbance in ER function presents significant stress to the cell. In response to ER stress, three distinct signal transduction pathways can be activated. Two of these, the unfolded protein response and the ER-overload response, respond to disturbances in protein processing. The third, the sterol regulatory cascade, is activated by depletion of cholesterol. This review summarizes the recent advances in our understanding of these ER-nuclear signal transduction pathways. In addition, it points to novel regulatory mechanisms discovered in these pathways, which may be widely used in other systems.
The ash2 gene is involved in Drosophila wing development (2002)

The absent small and homeotic (ash2) gene is a member of the trithorax group of positive transcriptional regulators of the homeotic genes. In this work we present evidence that loss-of-function of ash2 results in patterning alterations in the developing wing. Homozygous adults of the weak allele ash2(112411) develop extra cross-veins. However, clonal analysis of a stronger allele, ash2(11), shows that this allele results in reduction of intervein tissue and increase of longitudinal veins and cross-vein tissue in the wing except the region between vein L3 and L4. These results suggest that ash2 function is required for both activation of intervein tissue and repression of vein tissue. Moreover, we have found that cross-vein development can be rescued in the absence of crossveinless-2 when the levels of ash2 were reduced.
Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double‐Blind, Placebo‐Controlled, Crossover Study in Healthy Subjects (2021)

The psychedelic psilocybin is being investigated for the treatment of depression and anxiety. Unclear is whether antidepressant treatments interact with psilocybin. The present study used a double-blind, placebo-controlled, crossover design with two experimental test sessions to investigate the response to psilocybin (25 mg) in healthy subjects after pretreatment with escitalopram or placebo. The treatment order was random and counterbalanced. Pretreatment consisted of 10 mg escitalopram daily for 7 days, followed by 20 mg daily for 7 days, including the day of psilocybin administration, or 14 days of placebo pretreatment before psilocybin administration. Psilocybin treatments were separated by at least 16 days. The outcome measures included self-rating scales that evaluated subjective effects, autonomic effects, adverse effects, plasma brain-derived neurotrophic factor (BDNF) levels, electrocardiogram QTc time, whole-blood HTR2A and SCL6A4 gene expression, and pharmacokinetics. Escitalopram pretreatment had no relevant effect on positive mood effects of psilocybin but significantly reduced bad drug effects, anxiety, adverse cardiovascular effects, and other adverse effects of psilocybin compared with placebo pretreatment. Escitalopram did not alter the pharmacokinetics of psilocin. The half-life of psychoactive free (unconjugated) psilocin was 1.8 hours (range 1.1-2.2 hours), consistent with the short duration of action of psilocybin. Escitalopram did not alter HTR2A or SCL6A4 gene expression before psilocybin administration, QTc intervals, or circulating BDNF levels before or after psilocybin administration. Further studies are needed with a longer antidepressant pretreatment time and patients with psychiatric disorders to further define interactions between antidepressants and psilocybin.
Interrelationships of interleukin-8 with interleukin-1beta and neutrophils in vaginal fluid of healthy and bacterial vaginosis positive women (2003)

Vaginal innate immunity in response to microbial perturbation is still poorly understood and could be crucial for protection from adverse outcomes. We investigated the relationship between interleukin (IL)-8, IL-1beta and neutrophils in vaginal fluid obtained from 60 healthy women and 51 women who were bacterial vaginosis (BV) positive. Concentrations of IL-8 and IL-1beta were highly correlated with counts of neutrophils in vaginal fluid of the entire population examined (111 subjects). Vaginal IL-1beta concentrations were significantly higher (P < 0.001) in BV positive women. There was no significant difference in IL-8 levels or number of neutrophils between healthy controls and BV positive women. None of the healthy controls with high neutrophil counts (> or =75th percentile, 14 average count per field) had high concentrations of IL-1beta (> or =75th percentile, 220 pg/ml), whereas 84% of BV positive women with high neutrophil counts had high IL-1beta concentrations (P < 0.001). On the contrary, no difference in the percentage of subjects with elevated concentrations of IL-8 (> or =75th percentile, 2842 pg/ml) was found between healthy and BV positive women with high numbers of neutrophils (55.5% of healthy versus 53% of BV positive women). Our findings show that BV causes a large increase in IL-1beta concentrations which is not paralleled by an increase in IL-8 concentrations in vaginal fluid, suggesting that BV-associated factors more specifically dampen IL-8 rather than IL-1beta. The lack of an increase in IL-8 may explain the absence of an increase in neutrophil numbers in most women exposed to abnormal vaginal colonization (BV).
Solid-Phase Microextraction Coupled to Gas Chromatography-Mass Spectrometry for the Analysis of Famoxadone in Wines, Fruits, and Vegetables (2009)

ABSTRACT A sensitive, selective, and solvent-free method based on direct immersion solid-phase microextraction (DI-SPME) followed by gas chromatography with mass spectrometry (GC-MS) is proposed for the determination of trace amounts of famoxadone in wines, fruits, and vegetables. Parameters affecting the sample enrichment step, such as sample mass, ionic strength, adsorption and desorption times, and temperatures were carefully optimized. A polar 85 µm polyacrylate fiber was found to be suitable for extraction at 60°C in 20 min under continuous stirring. Desorption was carried out at 270°C for 5 min. Undiluted wine samples and diluted extracts obtained from the solid samples submitted to an ultrasound treatment in the presence of ethanol were quantified against external aqueous standards prepared in 12% ethanol (v/v). Under the optimized conditions, detection limits of 5 ng L−1 and 10 pg g−1 were obtained for liquid and solid samples, respectively. SPME-GC-MS analysis yielded good repeatability (RSD under 10% in all cases). The method provided recoveries of 91.6–110.9% from spiked samples. The method was applied to different samples, and none of them was found to contain famoxadone at concentrations above the corresponding detection limits.
Activation of T Cells by Bispecific Single-Chain Construct MT103 (MEDI-538) Is Strictly Target Cell-Dependent. (2006)

Abstract Background: Bispecific antibodies have been extensively studied in vitro and in vivo for their use in redirected tumor cell lysis. A particular challenge of bispecific antibody constructs recognizing the CD3 signaling complex is to achieve a controlled polyclonal activation of T-cells that, ideally, is entirely dependent on the presence of target cells. If this is not the case, systemic production of inflammatory cytokines and secondary endothelial reactions may occur as side effects, as are observed with the murine anti-human CD3e antibody OKT-3 (muromab, Orthoclone®). Here we present evidence that MT103 (or MEDI-538), a bispecific single chain antibody of the BiTE class that targets CD19 and CD3, induces T-cell activation exclusively in the presence of target cells. Material and methods: Peripheral blood mononuclear cells from healthy donors were prepared by Ficoll density centrifugation. PBMC were incubated for 24 hours with MT103 in presence or absence of specific target cells. Target cell lysis was determined by measurement of adenylate kinase activity released from lysed cells. De novo expression of activation markers CD69 and CD25 on T-cells was assessed by flow cytometry using directly conjugated monoclonal antibodies, and the concentration of cytokines in the supernatant was determined by a commercial FACS-based bead array. Results: MT103 was analyzed for conditional T-cell activation. In the presence of target-expressing cell lines, low picomolar concentrations of MT103 were sufficient to stimulate a high percentage of peripheral human T-cells to express cytokines and surface activation markers, to enter into the cell cycle and to induce redirected lysis of target cells. However, in the absence of target cells, the BiTE molecules no longer detectably activated human T-cells even at concentrations exceeding the ED50 for redirected lysis and conditional T-cell activation by more than five orders of magnitude. Conclusion: Our data show that T-cell activation by MT103 is highly conditional in that it is strictly dependent on the presence.
Taking advantage of semantic-social information in recommendation systems (2013)

With the rapid growth of Web 2.0 and the consequent success of different social network Web sites such Amazon, and MovieLens, recommender systems have recently been extensively studied by both academia and industry. In this article we combine social network analysis and semantic user profile to provide a new semantic-social recommendation, featuring a two-stage process that relies on a simple formalization of semantic user preferences that contains the user's main interests, and heuristically explores the social graph. Given a recommendation request concerning a product, the semantic-social recommendation algorithm compares the user preferences, which are found in the exploration path, with the product preferences by referencing them to domain ontology. Experiments on real-world data from Amazon, examine the quality of our recommendation method as well as the efficiency of our recommendation algorithms.
Marketing's contribution to the implementation of business strategy: an empirical analysis (2001)

Abstract This paper describes a study that assesses the performance implications of matching marketing strategy to business strategy. In order to conduct this study we first reviewed the literature on marketing strategy to identify its key dimensions. We then conducted a survey of 1000 senior marketing executives about the strategic marketing practices adopted in their respective firms or business units, and developed scales to describe 11 strategic marketing activities. We next performed a K‐means cluster analysis using these scales to develop a taxonomy of marketing strategy types consisting of: Aggressive Marketers, Mass Marketers, Marketing Minimizers, and Value Marketers. We then observed that superior performance at the firm or SBU level was achieved when specific marketing strategy types were matched with appropriate Miles and Snow (1978) business strategy types. Copyright © 2001 John Wiley &amp; Sons, Ltd.
The Effect of Carboxyl-terminal Mutagenesis of Gtα on Rhodopsin and Guanine Nucleotide Binding (1995)

The carboxyl terminus of G protein alpha subunits plays an important role in receptor recognition. To identify the amino acids that participate in this interaction, COOH-terminal mutants of alpha t (the transducin alpha subunit) were expressed in vitro and analyzed for their ability to interact with rhodopsin and to bind guanine nucleotide. Gly-348, the reported site of a beta turn, was replaced with other neutral amino acids without severely affecting rhodopsin binding. However, proline substitution abolished rhodopsin interaction, suggesting that flexibility is important at this site. A comparison between C347Y, which lost both rhodopsin and guanine nucleotide binding, and a mutant substituted with alpha q sequence (D346E/C347Y/G348N/F350V), in which guanine nucleotide binding was restored, implies that distinct motifs maintain the structure of the alpha subunit and are necessary for selective interaction with receptors. Surprisingly, mutants L344A, L349A, F350stop, and stop351A demonstrated a parallel loss of rhodopsin and guanine nucleotide binding. Altered profiles of L344A and F350stop on sucrose density gradients indicate that these mutants may undergo denaturation. The equivalent of alpha tL344A generated in alpha s and alpha i did not show such a severe loss of guanine nucleotide binding, revealing that the alpha t carboxyl terminus is unique in its susceptibility to changes in amino acid sequence.
Scanning whole cells with phage‐display libraries: Identification of peptide ligands that modulate cell function (1994)

Abstract A general strategy has been developed for rapidly identifying peptides that alter cellular function, which has revealed a series of peptides that inhibit platelet aggregation. First whole cells—platelets in this case—were used as an affinity matrix to isolate cell‐binding phage from a phage‐display, random‐peptide library. In this step 3 × 10 7 different filamentous phage, each encoding and displaying a different random peptide, were screened as a single pool. Since it is the peptide displayed on the surface of the phage that presumably causes a particular phage to bind specifically to a cell, synthetic peptides were then made based on the predicted sequences of the displayed peptides. Because the initial affinity selection step had focused attention on a handful of peptides, each of the 17 synthetic peptides could be individually tested in an appropriate functional assay, such as platelet aggregation. The majority of the 17 different peptides that we analyzed inhibited platelet aggregation; these peptides could be grouped into at least five different motifs including the expected RGD motif. It is believed that this strategy, which requires neither purification nor prior knowledge of a particular target receptor, will prove to be generally useful for identifying peptide ligands that influence cellular function. © 1994 Wiley‐Less, Inc.
Near-Field Optical Recording without Low-Flying Heads: Integral Near-Field Optical (INFO) Media (2002)

The promise of near-field (NF) optics to increase the density in optical data storage, whether solid immersion lenses (SILs), apertures, or their variants, has not yet been fulfilled, largely because of the difficulties with the head-media interface at near-field dimensions, especially if removable media is a design goal. We introduce a new approach to NF optical storage, in which integral near-field optics (INFO), in the form of nano-cylinders, are formed in the media upon manufacture. Combining the advantages of near- and far-field optical data storage, we obtain double the track density of digital versatile discs (DVD) in removable rewritable (RW) phase change media. Potential for in-track density increase is also demonstrated. We briefly report on the modeling, manufacture, and performance of INFO media.
The Functional Effects of Physical Interactions among Toll-like Receptors 7, 8, and 9 (2006)

Toll-like receptors (TLRs) TLR1, TLR2, TLR4, and TLR6 are evolutionarily conserved, highly homologous, and localized to plasma membranes of host cells and recognize pathogen-associated molecular patterns (PAMPs) derived from bacterial membranes. These receptors cooperate in a pairwise combination to elicit or inhibit the inflammatory signals in response to certain PAMPs. The other TLRs that are evolutionarily closely related and highly homologous are TLR7, TLR8, and TLR9. They are all confined to the membranes of endosomes and recognize similar molecular structures, the oligonucleotide-based PAMPs. However, the cooperative interactions among these receptors that may modulate the inflammatory signaling in response to their cognate agonists are not reported. We report here for the first time the functional effects of one TLR on the other among TLR7, TLR8, and TLR9. The results indicate that TLR8 inhibits TLR7 and TLR9, and TLR9 inhibits TLR7 but not vice versa in HEK293 cells transfected with TLRs in a pairwise combination. This is concluded by selectively activating one TLR over the other by using small molecule TLR agonists. We also show that these inhibitory interactions are the result of direct or indirect physical interactions between the TLRs. The murine TLR8 that does not respond to any known human TLR8 agonists also inhibits both murine and human TLR7. The implications of the inhibitory interactions among these TLRs in host-pathogen recognition and subsequent inflammatory responses are not obvious. However, given the complexity in expression pattern in a particular cell type and the variation in distribution and response to different pathogens and stress signals in different cell types, the inhibitory physical interactions among these TLRs may play a role in balancing the inflammatory outcome from a given cell type to a specific challenge.
Hormone Replacement Therapy and Interrelation between Serum Interleukin-6 and Body Mass Index in Postmenopausal Women: A Population-Based Study (2000)

Postmenopausal women are at increased risk to develop osteoporosis, coronary artery disease, heart failure, and hypertension. Interleukin-6 (IL-6) may be a pathogenetic element in these disorders. Serum IL-6 levels increase during aging and seem to be related to increased body fat mass. In the present retrospective study we aimed to investigate the role of hormone replacement therapy (HRT) on serum IL-6 levels and the interrelation of IL-6 and body fat mass. Parameters were assessed in a population-based sample of postmenopausal women (n = 302) and, for comparison, 245 men of the same age. Women with HRT (n = 92) had significantly lower serum IL-6 levels compared to subjects without HRT, which was independent of age, antihypertensive therapy, smoking habits, and blood pressure (1.5 +/- 0.1 vs. 2.9 +/- 0.6 pg/mL; P = 0.017). In women without HRT, the body mass index (BMI) was correlated with serum IL-6 levels (P < 0.001). Multivariate analysis controlling simultaneously for the effects of blood pressure and heart rate confirmed the positive correlation (P = 0.001). However, in subjects with HRT no such correlation between IL-6 and BMI was demonstrated, which was confirmed after controlling covariates. In male subjects, BMI correlated with serum IL-6 (P = 0.009), which was, however, blunted after controlling for blood pressure and heart rate, probably indicating an influence of the sympathetic nervous system on this interrelation. In conclusion, women receiving HRT display lower serum IL-6 levels and a blunted interrelation of IL-6 and BMI. As IL-6 may be a pathogenetic factor in age-related diseases, HRT-related inhibition of IL-6 secretion could be an important element for the favorable effects of HRT in postmenopausal women.
bag-of-marbles and benign gonial cell neoplasm act in the germline to restrict proliferation during Drosophila spermatogenesis (1997)

Stem cells divide asymmetrically, regenerating a parental stem cell and giving rise to a daughter cell with a distinct fate. In many stem cell lineages, this daughter cell undergoes several amplificatory mitoses, thus generating more cells that embark on the differentiation program specific for the given lineage. Spermatogenesis in Drosophila is a model system to identify molecules regulating stem cell lineages. Mutations at two previously identified loci, bag-of-marbles (bam) and benign gonial cell neoplasm (bgcn), prevent progression through spermatogenesis and oogenesis, resulting in the overproliferation of undifferentiated germ cells. Here we investigate how bam and bgcn regulate the male germline stem cell lineage. By generating FLP-mediated clones, we demonstrate that both bam and bgcn act autonomously in the germline to restrict proliferation during spermatogenesis. By using enhancer trap lines, we find that the overproliferating germ cells express markers specific to amplifying germ cells, while at the same time retaining the expression of some markers of stem cell and primary spermatogonial cell fate. However, we find that germ cells accumulating in bam or bgcn mutant testes most resemble amplifying germ cells, because they undergo incomplete cytokinesis and progress through the cell cycle in synchrony within a cyst, which are two characteristics of amplifying germ cells, but not of stem cells. Taken together, our results suggest that bam and bgcn regulate progression through the male germline stem cell lineage by cell-intrinsically restricting the proliferation of amplifying germ cells.
Morphology and Charge Transport in Conjugated Polymers (2006)

Determining the relationship between charge transport and morphology is key to increasing the charge carrier mobility of conjugated polymers. This review details a fundamental study of the charge transport and morphology of regioregular poly(3‐hexylthiophene) and sets out general principles for obtaining high charge carrier mobilities. The basis for this study was the finding that despite being more crystalline, low molecular weight films have a substantially lower mobility than high‐MW films. An examination of this apparent contradiction is used to provide insight into how the charge carriers move through a conjugated polymer film and provide a model for charge transport.
The Drosophila segmentation gene runt encodes a novel nuclear regulatory protein that is also expressed in the developing nervous system. (1990)

Generation of the anterior-posterior body pattern in the Drosophila embryo requires the activity of the segmentation genes. The segmentation gene runt has been classified as one of the primary pair-rule genes because of the pivotal role it plays in regulating the expression of other pair-rule genes. Here, we present the structure of this gene and describe the pattern of runt protein expression during embryogenesis. The deduced protein sequence shows no obvious overall homology with any sequences in the data base. The absence of an identifiable transcription factor motif (e.g., homeo box, zinc finger, leucine zipper, or helix-loop-helix) makes runt different from the other early-acting segmentation proteins. A runt-specific polyclonal antibody was generated and used to demonstrate that the subcellular location of the protein is in the nucleus. Double-staining immunolocalization experiments were used to determine the overlap of the runt protein pattern with the patterns of the pair-rule genes hairy (h), even-skipped (eve), and fushi tarazu (ftz). We found that the patterns of runt and hairy are complementary. Their phasing is shifted anteriorly by two cell diameters with respect to the complementary eve and ftz patterns. Experiments with the runt antibody also indicated that the protein is present throughout embryogenesis and is expressed extensively in the developing central and peripheral nervous system.
Impact of the Lipophilicity of Desferrithiocin Analogues on Iron Clearance (2005)

Increasing chelator lipophilicity can substantially augment iron clearing efficiency in Cebus apella primates. The impact of altering the lipophilicity, i.e., octanol—water partition properties (log P), of analogues of desazadesferrithiocin, (S)-4,5-dihydro-2-(2-hydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid, on the ligands' iron clearing properties is described. The complications of iron overload are often associated with the metal's interaction with hydrogen peroxide, generating hydroxyl radicals (Fenton chemistry) and, ultimately, other related deleterious species. In fact, some iron chelators actually promote this chemistry. A number of the title compounds synthesized and tested in our laboratory are shown to be both inhibitors of the iron-mediated oxidation of ascorbate as well as effective radical scavengers.