gebhart/patrepeval huggingface dataset:
High‐Mobility Ambipolar Near‐Infrared Light‐Emitting Polymer Field‐Effect Transistors (2008)

A polymer semiconductor with ambipolar charge transport properties, BBTDPP1, is presented. Solution-processed ambipolar field-effect transistors based on this material exhibit hole and electron mobilities of 0.1 cm2 V−1 s−1 and up to 0.09 cm2 V−1 s−1, respectively. Near-infrared light emission from top-gate as well as bottom-gate ambipolar field-effect transistors based on BBTDPP1 is also reported.
A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression (2010)

In patients with treatment-resistant bipolar depression, robust and rapid antidepressant effects resulted from a single intravenous dose of an N-methyl-D-aspartate antagonist.
Angiotensin II Receptor Blockade After Myocardial Infarction in Rats (1992)

Angiotensin-converting enzyme (ACE) inhibitors are widely used for treatment of heart failure after myocardial infarction (MI). The beneficial effects consist of a combination of hemodynamic effects and interference with cardiac structural alterations. These effects are believed to depend on inhibition of angiotensin II (AII) formation and thus diminished angiotensin receptor stimulation. We administered the angiotensin II-1 (AT-1) receptor antagonist losartan during and after completion of the repair phase of an MI to investigate involvement of the AT-1 receptor in the above described effects of captopril. MI reduced cardiac output (CO) (sham 94 +/- 4 ml/min, MI 78 +/- 5 ml/min) and maximal CO (sham 154 +/- 4, MI 107 +/- 5 ml/min, respectively). Losartan (15 mg/kg/day) resulted in a rightward shift of the AII pressor dose-response curve by a factor of 32-40. Neither CO nor COVL,max was affected by losartan treatment in either phase (late treatment CO = 78 +/- 5, COVL,max = 118 +/- 9 ml/min). Although early treatment with losartan reduced cardiac hypertrophy measured as heart weight, DNA synthesis was reduced only slightly. In contrast, collagen deposition was inhibited completely. The results suggest that the effects of captopril in rats after MI are not dependent on AT-1 receptor-mediated mechanisms.
Engineering therapeutic antibodies targeting G-protein–coupled receptors (2016)

G-protein-coupled receptors (GPCRs) are one of the most attractive therapeutic target classes because of their critical roles in intracellular signaling and their clinical relevance to a variety of diseases, including cancer, infection and inflammation. However, high conformational variability, the small exposed area of extracellular epitopes and difficulty in the preparation of GPCR antigens have delayed both the isolation of therapeutic anti-GPCR antibodies as well as studies on the structure, function and biochemical mechanisms of GPCRs. To overcome the challenges in generating highly specific anti-GPCR antibodies with enhanced efficacy and safety, various forms of antigens have been successfully designed and employed for screening with newly emerged systems based on laboratory animal immunization and high-throughput-directed evolution.
Cloning and functional characterisation of a peptide transporter expressed in the scutellum of barley grain during the early stages of germination (1998)

A peptide transport gene (HvPTR1) expressed in the scutella of germinating barley grain has been cloned by an RT-PCR approach. Sequence analysis of the full length cDNA (2260 bp) revealed an open reading frame encoding a 579 amino acid protein of predicted molecular mass 63 kDa, which displayed 58% identity to the Arabidopsis thaliana peptide transporter AtPTR2-B. Expression of HvPTR1 in Xenopus laevis oocytes conferred a 48-fold increase in alanyl-[14C]phenylalanine uptake relative to water injected oocytes, confirming the function of HvPTR1 as a peptide transporter. HvPTR1 expression was detectable only in the scutellum of the germinating barley grain, with no transcript found in roots, shoots or the embryo axis. Transcript levels increased rapidly from 6 to 24 h imbibition, correlating with the development of peptide transport activity in the barley scutellum. Peptide transport provides a significant source of organic nitrogen to the barley embryo for use in germination and growth processes associated with the early stages of seedling development. The temporal and spatial pattern of HvPTR1 expression is consistent with a central role for HvPTR1 in the transport of peptides in the germinating barley grain.
Selective Growth of Cubic GaN in Small Areas on Patterned GaAs(100) Substrates by Metalorganic Vapor Phase Epitaxy (1994)

The metalorganic vapor phase epitaxy growth of cubic GaN in small areas on SiO 2 -patterned GaAs substrates has been performed. We have succeeded in selective growth without deposition on the SiO 2 mask at temperatures between 620 and 675° C. The crystal quality of cubic GaN has been improved through growth in small areas on patterned GaAs substrates. It is found that the grain size becomes larger and the full width at half maximum of the X-ray diffraction peak of cubic GaN becomes narrower on patterned substrates than on unpatterned ones.
Germ line deletion of the CD1 locus exacerbates diabetes in the NOD mouse (2001)

Quantitative and qualitative defects in CD1-restricted natural killer T cells have been reported in several autoimmune-prone strains of mice, including the nonobese diabetic (NOD) mouse. These defects are believed to be associated with the emergence of spontaneous autoimmunity. Here we demonstrate that both CD1d-null NOD and CD1d-null NOD/BDC2.5 T cell receptor transgenic mice have an accelerated onset and increased incidence of diabetes when compared with CD1d(+/-) and CD1d(+/+) littermates. The acceleration of disease did not seem to result from changes in the T helper (Th)1/Th2 balance because lymphocytes purified from lymphoid organs and pancreatic islets of wild-type and CD1d-null mice secreted equivalent amounts of IFN-gamma and IL-4 after stimulation. In contrast, the pancreata of CD1d-null mice harbored significantly higher numbers of activated memory T cells expressing the chemokine receptor CCR4. Notably, the presence of these T cells was associated with immunohistochemical evidence of increased destructive insulitis. Thus, CD1d-restricted T cells are critically important for regulation of the spontaneous disease process in NOD mice.
The Tol2kit: A multisite gateway‐based construction kit for Tol2 transposon transgenesis constructs (2007)

Transgenesis is an important tool for assessing gene function. In zebrafish, transgenesis has suffered from three problems: the labor of building complex expression constructs using conventional subcloning; low transgenesis efficiency, leading to mosaicism in transient transgenics and infrequent germline incorporation; and difficulty in identifying germline integrations unless using a fluorescent marker transgene. The Tol2kit system uses site-specific recombination-based cloning (multisite Gateway technology) to allow quick, modular assembly of [promoter]-[coding sequence]-[3' tag] constructs in a Tol2 transposon backbone. It includes a destination vector with a cmlc2:EGFP (enhanced green fluorescent protein) transgenesis marker and a variety of widely useful entry clones, including hsp70 and beta-actin promoters; cytoplasmic, nuclear, and membrane-localized fluorescent proteins; and internal ribosome entry sequence-driven EGFP cassettes for bicistronic expression. The Tol2kit greatly facilitates zebrafish transgenesis, simplifies the sharing of clones, and enables large-scale projects testing the functions of libraries of regulatory or coding sequences.
The Total Synthesis of Psymberin (2007)

The total synthesis of a new member of the pederin family of natural products, psymberin 1, was accomplished. Using a recently reported novel and efficient PhI(OAc)2 mediated oxidative entry to 2-(N-acylaminal)-substituted tetrahydropyrans as the key step, this total synthesis was executed in a convergent and efficient manner. The longest linear sequence of this synthesis was 22 steps starting from known 6.
Repair of Articular Cartilage Defects One Year After Treatment with Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2)* (2000)

The problems associated with operative repair of cartilage include the formation of fibrocartilage rather than normal articular cartilage and the degeneration of that repair tissue over time. Our results demonstrate that the addition of rhBMP-2 to the operative site after creation of a full-thickness defect results in an improvement in the histological appearance and composition of the extracellular matrix at one year postoperatively. If these experimental results translate directly to the clinical situation, it is possible that the addition of rhBMP-2 to existing operative treatments for the repair of cartilage may improve the repair process and may help to maintain the integrity of the repair tissue.
Administration of angiotensin II in refractory septic shock (1991)

In septic shock, hypotension is often due to peripheral vasodilation with a normal or increased cardiac output (1). In such situations, the use of vasoconstrictors to increase systemic vascular resistance may increase systemic arterial pressure and improve perfusion of the heart and other essential organs. Norepinephrine is often used in this situation for its a-adrenergic effects, but these effects often decrease with time (2). Angiotensin II is a potent vasoconstrictor whose actions are not mediated by adrenergic receptors. It has a half-life time of <2 mins. Tachyphylaxis is reportedly not a problem. The following case report describes the use of angiotensin II to increase mean arterial pressure in an adult with severe sepsis who was hypotensive despite rapid infusion rates of norepinephrine and other adrenergic drugs. We found no previous reports of the use of angiotensin II in a hemodynamically monitored patient with refractory septic shock.
Phase III Evaluation of 4 Doses of Megestrol Acetate as Therapy for Patients with Cancer Anorexia and/or Cachexia (1994)

Several randomized, placebo-controlled clinical trials have demonstrated that megestrol acetate therapy can result in appetite stimulation and nonfluid weight gain in patients with cancer anorexia/cachexia. The present trial was designed to compare megestrol acetate doses ranging from 160 to 1,280 mg/day. day. This trial randomly assigned 342 evaluable patients with cancer anorexia/cachexia to receive oral megestrol acetate at doses of 160, 480, 800 and 1,280 mg/day. Patients were evaluated monthly by history, examination and patient-completed questionnaires, as well as by serum albumin levels. The data demonstrate a positive dose-response effect for megestrol acetate on appetite stimulation (p = 0.02). there was a trend for more nonfluid weight gain with higher drug doses. Megestrol acetate was well tolerated in this group of patients with advanced malignant disease. The positive dose-response effect observed for megestrol acetate on appetite stimulation supports both the prestudy hypothesis and findings in the literature. The optimal dose in this study seemed to be 800 mg/day; no further benefit was derived from using the higher dose. Nonetheless, it may be reasonable to start with lower initial doses in routine clinical practice, taking into account dosage form, availability and cost of therapy.
The role of small cells, coordinated multipoint, and massive MIMO in 5G (2014)

5G will have to support a multitude of new applications with a wide variety of requirements, including higher peak and user data rates, reduced latency, enhanced indoor coverage, increased number of devices, and so on. The expected traffic growth in 10 or more years from now can be satisfied by the combined use of more spectrum, higher spectral efficiency, and densification of cells. The focus of the present article is on advanced techniques for higher spectral efficiency and improved coverage for cell edge users. We propose a smart combination of small cells, joint transmission coordinated multipoint (JT CoMP), and massive MIMO to enhance the spectral efficiency with affordable complexity. We review recent achievements in the transition from theoretical to practical concepts and note future research directions. We show in measurements with macro-plus-smallcell scenarios that spectral efficiency can be improved by flexible clustering and efficient user selection, and that adaptive feedback compression is beneficial to reduce the overhead significantly. Moreover, we show in measurements that fast feedback reporting combined with advanced channel prediction are able to mitigate the impairment effects of JT CoMP.
Specific correlation between the major chromosome 10q26 haplotype conferring risk for age-related macular degeneration and the expression of HTRA1. (2017)

SNPs in chromosome 10q26 that influence the expression of only <i>PLEKHA1</i> or <i>ARMS2</i> are not associated with risk for AMD, while most SNPs that influence the expression of <i>HTRA1</i> are associated with risk for AMD. Two of the AMD-risk SNPs affect transcription factor binding sites that may control expression of one of the linked genes in the RPE. These findings suggest that the variation in the risk for AMD associated with chromosome 10q26 is likely due to variation in <i>HTRA1</i> expression. Modulating <i>HTRA1</i> activity might be a potential therapy for AMD.
Evaluation of the antioxidant peptide SS31 for treatment of burn-induced insulin resistance (2011)

After severe burn injury and other major traumas, glucose tolerance tests demonstrate delayed glucose disposal. This 'diabetes of injury' could be explained by insulin deficiency, and several studies have shown that soon after trauma (ebb phase) insulin concentrations are reduced in the face of hyperglycemia. After resuscitation of trauma patients (flow phase), β-cell responsiveness normalizes and plasma insulin levels are appropriate or even higher than expected, however, glucose intolerance and hyperglycemia persist. In the acute care setting, several approaches have been used for treating insulin resistance, including insulin infusion, propranolol and glucagon-like-peptide-1 (GLP-1). Recently, it was demonstrated that a tetrapeptide with antioxidant properties D-Arg-Dmt-Lys-Phe-NH2 (SS31), but not its inactive analogue Phe-D-Arg-Phe-Lys-NH2 (SS20) attenuates insulin resistance in mice maintained on a high fat diet. In this report the effects of SS31 and SS20 on burn-induced insulin resistance was studied in mice. Oral glucose tolerance tests (OGTT) were performed in 4 groups of 6 mice with thermal injury with or without pre-treatment with SS31 or SS20 and sham controls. In addition, biodistribution of 18FDG was measured in burned mice with and without SS31 treatment and shams (subsets of these animals were also studied by µPET). For comparison purposes, groups of 6 cold-stressed mice with and without SS31 treatment were also studied. The results of these studies demonstrate that SS31 but not SS20 ameliorated burn-induced insulin resistance. In addition, SS31 treatment resulted in marked reduction in the increased 18FDG uptake by brown adipose tissue (BAT) in burned but not cold-stressed animals; suggesting that the stressors act by different mechanisms. Overall, these studies confirmed that SS31 can be used to reverse burn-induced insulin resistance and provide a firm pre-clinical basis for future clinical trials of SS31 for the treatment of insulin resistance in patients with burn injury.
The 3′ Untranslated Region of Sindbis Virus Represses Deadenylation of Viral Transcripts in Mosquito and Mammalian Cells (2007)

The positive-sense transcripts of Sindbis virus (SINV) resemble cellular mRNAs in that they possess a 5' cap and a 3' poly(A) tail. It is likely, therefore, that SINV RNAs must successfully overcome the cytoplasmic mRNA decay machinery of the cell in order to establish an efficient, productive infection. In this study, we have taken advantage of a temperature-sensitive polymerase to shut off viral transcription, and we demonstrate that SINV RNAs are subject to decay during a viral infection in both C6/36 (Aedes albopictus) and baby hamster kidney cells. Interestingly, in contrast to most cellular mRNAs, the decay of SINV RNAs was not initiated by poly(A) tail shortening in either cell line except when most of the 3' untranslated region (UTR) was deleted from the virus. This block in deadenylation of viral transcripts was recapitulated in vitro using C6/36 mosquito cell cytoplasmic extracts. Two distinct regions of the 319-base SINV 3' UTR, the repeat sequence elements and a U-rich domain, were shown to be responsible for mediating the repression of deadenylation of viral mRNAs. Through competition studies performed in parallel with UV cross-linking and functional assays, mosquito cell factors-including a 38-kDa protein-were implicated in the repression of deadenylation mediated by the SINV 3' UTR. This same 38-kDa protein was also implicated in mediating the repression of deadenylation by the 3' UTR of another alphavirus, Venezuelan equine encephalitis virus. In summary, these data provide clear evidence that SINV transcripts do indeed interface with the cellular mRNA decay machinery during an infection and that the virus has evolved a way to avoid the major deadenylation-dependent pathway of mRNA decay.
Human homologue of a candidate for the Mom1 locus, the secretory type II phospholipase A2 (PLA2S-II), maps to 1p35-36.1/D1S199. (1995)

Mice heterozygous for the dominant Min mutation in their Apc gene develop multiple intestinal neoplasia. Analogously, family members from familial adenomatous polyposis kindreds inheriting mutations in their human APC homologue develop a similar phenotype. Quantitative trait loci studies have identified the Mom1 locus (for modifier of Min-1), which is responsible for part of the genetic variability in polyp number found among inbred mouse strains. The secretory type II phospholipase [nonpancreatic Pla2s (type II Pla2s or Pla2s-II)] has been demonstrated to be a candidate for Mom1, and a mutation in Pla2s-II in mice carrying the Min mutation has been proposed to account for an increased polyp number compared to mice without the Pla2s-II mutation. In this study, we have mapped the chromosomal position of the human homologue of Pla2s-II. We have identified 3 mega-yeast artificial chromosomes that carry PLA2S-II and localized one of them by fluorescence in situ hybridization to the border between 1p35 and 1p36.1. The presence of the microsatellite marker D1S199 in all three clones integrates PLA2S-II into different genetic maps. This highly polymorphic CA repeat D1S199 has previously been shown by us to identify loss of heterozygosity in 48% of sporadic colorectal tumors, indicating that the human homologue of the Pla2s-II/Mom1 locus might be related to human colorectal cancer.
Androgen receptor in human normal and malignant pancreatic tissue and cell lines (1986)

Estrogen and progestogen receptors have been demonstrated in human pancreatic adenocarcinoma tissue. Tumor growth as xenografts in nude mice is promoted by testosterone and retarded by cyproterone acetate but is not influenced by estrogens, progestogens, or their antagonists, although estrogen receptors were demonstrated in xenograft cytosol. A new sensitive microassay technique for sex steroid receptors which relies on affinity chromatography was used in this study. With this assay, androgen receptors were detected in five fresh human pancreatic adenocarcinoma specimens (three male), two pancreatic cancer cell lines (Mia PaCa 2 and Ger), one xenograft tumor which responded to androgens, five specimens of normal adult pancreas (two male), and a pool of fetal pancreatic tissue. The similarity of the androgen receptor in pancreatic carcinoma to that of classical androgen target organs was demonstrated by sedimentation behavior and competitive binding studies. The improved sensitivity of the microassay allowed low levels of estrogen, androgen, and progesterone receptors to be detected in normal adult pancreatic tissue.
Strong antigenic selection shaping the immunoglobulin heavy chain repertoire of B-1a lymphocytes in λ2315 transgenic mice (2002)

The B lymphocyte compartment of the recombinant mouse line L2 consists predominantly of CD5(+) B-1 cells that exclusively express the transgenic (Tg) lambda 2 L chain of the plasmacytoma MOPC315. Using such Tg mice as a simplified model to study positive selection processes, we show that restriction to a single L chain results in a strongly oligoclonal IgH chain repertoire in fetal and neonatal liver-derived B cells, as well as in peritoneal CD5(+) B-1 lymphocytes from adult mice. In contrast, in vitro differentiated fetal liver Pro/PreB-I cells from L2 embryos show a clear increase of complementarity determining region three (CDR3) diversity. These data suggest that the antibody repertoire of B-1a cells is strongly selected by antigen during fetal as well as adult peritoneal phase.
ERK and Akt signaling pathways function through parallel mechanisms to promote mTORC1 signaling (2011)

The mammalian target of rapamycin (mTOR) is a protein kinase that, when present in a complex referred to as mTOR complex 1 (mTORC1), acts as an important regulator of growth and metabolism. The activity of the complex is regulated through multiple upstream signaling pathways, including those involving Akt and the extracellular-regulated kinase (ERK). Previous studies have shown that, in part, Akt and ERK promote mTORC1 signaling through phosphorylation of a GTPase activator protein (GAP), referred to as tuberous sclerosis complex 2 (TSC2), that acts as an upstream inhibitor of mTORC1. In the present study we extend the earlier studies to show that activation of the Akt and ERK pathways acts in a synergistic manner to promote mTORC1 signaling. Moreover, we provide evidence that the Akt and ERK signaling pathways converge on TSC2, and that Akt phosphorylates residues on TSC2 distinct from those phosphorylated by ERK. The results also suggest that leucine-induced stimulation of mTORC1 signaling occurs through a mechanism distinct from TSC2 and the Akt and ERK signaling pathways. Overall, the results are consistent with a model in which Akt and ERK phosphorylate distinct sites on TSC2, leading to greater repression of its GAP activity, and consequently a magnified stimulation of mTORC1 signaling, when compared with either input alone. The results further suggest that leucine acts through a mechanism distinct from TSC2 to stimulate mTORC1 signaling.
Specific Targeting, Biodistribution, and Lack of Immunogenicity of Chimeric Anti-GD3 Monoclonal Antibody KM871 in Patients With Metastatic Melanoma: Results of a Phase I Trial (2001)

This study is the first to demonstrate the biodistribution and specific targeting of an anti-GD3 antibody to metastatic melanoma in patients. The long half-life and lack of immunogenicity of KM871 makes this antibody an attractive potential therapy for patients with metastatic melanoma.
Discovery of a Potent and Selective Prostaglandin D2 Receptor Antagonist, [(3R)-4-(4-Chloro- benzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]-acetic Acid (MK-0524) (2007)

The discovery of the potent and selective prostaglandin D2 (PGD2) receptor (DP) antagonist [(3R)-4-(4-chlorobenzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]-acetic acid (13) is presented. Initial lead antagonists 6 and 7 were found to be potent and selective DP antagonists (DP Ki = 2.0 nM for each); however, they both suffered from poor pharmacokinetic profiles, short half-lives and high clearance rates in rats. Rat bile duct cannulation studies revealed that high concentrations of parent drug were present in the biliary fluid (Cmax = 1100 microM for 6 and 3900 microM for 7). This pharmacokinetic liability was circumvented by replacing the 7-methylsulfone substituent present in 6 and 7 with a fluorine atom resulting in antagonists with diminished propensity for biliary excretion and with superior pharmacokinetic profiles. Further optimization led to the discovery of the potent and selective DP antagonist 13.