gebhart/patrepeval huggingface dataset:
Identification of a Novel Cyclic AMP-response Element (CRE-II) and the Role of CREB-1 in the cAMP-induced Expression of the Survival Motor Neuron (SMN) Gene (2004)

Spinal muscular atrophy, an autosomal recessive disorder, is caused by loss of the SMN1 (survival motor neuron) gene while retaining the SMN2 gene. SMN1 produces a majority of full-length SMN transcript, whereas SMN2 generates mostly an isoform lacking exon 7. Here, we demonstrate a novel cAMP-response element, CRE-II, in the SMN promoter that interacts with the cAMP-response element-binding (CREB) family of proteins. In vitro DNase I protection analysis and in vivo genomic footprinting of the SMN promoter using the brain and liver nuclei from SMN2 transgenic mice revealed footprinting at the CRE-II site. Site-directed mutation of the CRE-II element caused a marked reduction in the SMN promoter activity revealed by transient transfection assay. Activation of the cAMP pathway by dibutyryl cAMP (0.5 mm) alone or in combination with forskolin (20 microm) caused a 2-5-fold increase in the SMN promoter activity but had no effect on the CRE-II mutated promoter. Electrophoretic mobility shift assay and a UV-induced DNA-protein cross-linking experiment confirmed that CREB1 binds specifically to the CRE-II site. Transient overexpression of CREB1 protein resulted in a 4-fold increase of the SMN promoter activity. Intraperitoneal injection of epinephrine in mice expressing two copies of the human SMN2 gene resulted in a 2-fold increase in full-length SMN transcript in the liver. Combined treatment with dibutyryl cAMP and forskolin significantly increased the level of both the full-length and exon 7-deleted SMN (exonDelta7SMN) transcript in primary hepatocytes from mice expressing two copies of human SMN2 gene. Similar treatments of type I spinal muscular atrophy mouse and human fibroblasts as well as HeLa cells resulted in an augmented level of SMN transcript. These findings suggest that the CRE-II site in SMN promoter positively regulates the expression of the SMN gene, and treatment with cAMP-elevating agents increases expression of both the full-length and exonDelta7SMN transcript.
Rituximab monoclonal antibody as initial systemic therapy for patients with low-grade non-Hodgkin lymphoma (2000)

Abstract Rituximab, a chimeric antibody that targets CD20+ B cells, produces a 48% response rate in patients with refractory low-grade non-Hodgkin lymphoma. In this phase II trial, patients with low-grade non-Hodgkin lymphoma who had previously received no systemic therapy were treated with rituximab, 375 mg/m2, administered by IV infusion for 4 consecutive weeks. Patients with objective response or stable disease received repeat 4-week courses of rituximab at 6-month intervals. At the time of initial reevaluation at 6 weeks, 21 of 39 patients (54%) had objective response to treatment, and an additional 14 patients (36%) had stable disease or minor response. Response rates were similar in patients with follicular and small lymphocytic (CLL-type) lymphoma (52% versus 57%, respectively). At present, follow-up is short and only 13 patients have undergone a second course of rituximab treatment. However, 4 additional responses were documented either prior to the second course of rituximab (2 patients) or following the second course (2 patients) and 4 patients improved from partial to complete response. The current response rate is 64%, with 6 complete responses (15%). Treatment with rituximab was well tolerated, with only 1 patient experiencing grade 3/4 infusion-related toxicity. Rituximab is well tolerated and highly active in patients with low-grade non-Hodgkin lymphoma previously untreated with systemic therapy. Although further follow-up is required, the demonstration of minimal toxicity and considerable activity of this new biologic agent represents an important beginning of more specific, less toxic treatment for this important group of cancer patients.
GPUWattch (2013)

General-purpose GPUs (GPGPUs) are becoming prevalent in mainstream computing, and performance per watt has emerged as a more crucial evaluation metric than peak performance. As such, GPU architects require robust tools that will enable them to quickly explore new ways to optimize GPGPUs for energy efficiency. We propose a new GPGPU power model that is configurable, capable of cycle-level calculations, and carefully validated against real hardware measurements. To achieve configurability, we use a bottom-up methodology and abstract parameters from the microarchitectural components as the model's inputs. We developed a rigorous suite of 80 microbenchmarks that we use to bound any modeling uncertainties and inaccuracies. The power model is comprehensively validated against measurements of two commercially available GPUs, and the measured error is within 9.9% and 13.4% for the two target GPUs (GTX 480 and Quadro FX5600). The model also accurately tracks the power consumption trend over time. We integrated the power model with the cycle-level simulator GPGPU-Sim and demonstrate the energy savings by utilizing dynamic voltage and frequency scaling (DVFS) and clock gating. Traditional DVFS reduces GPU energy consumption by 14.4% by leveraging within-kernel runtime variations. More finer-grained SM cluster-level DVFS improves the energy savings from 6.6% to 13.6% for those benchmarks that show clustered execution behavior. We also show that clock gating inactive lanes during divergence reduces dynamic power by 11.2%.
Layered Nanocomposite of Close-Packed Gold Nanoparticles and TiO2 Gel Layers (1998)

Nanocomposite films of gold nanoparticles and TiO2 gel have been successfully prepared by combination of a surface sol−gel technique and layer-by-layer assembly. Thanks to surface hydroxyl groups of gold nanoperticles, gold particles were deposited as close-packed monolayers on TiO2 gel layers. The resulting nanocomposite contained ca. 50 wt % of gold. Multilayer films were successfully prepared by alternate assembly of TiO2 gel and gold nanoparticles.
Comparison of the coexpression of cd38, cd33 and hla‐dr antigens on cd34 + purified cells from human cord blood and bone marrow (1995)

Human umbilical cord blood (UCB) cells are currently considered as a potential source of stem cells for transplantation. However, it remains unclear whether a single collection of UCB contains enough progenitors to allow a successful engraftment in adult patients. We were interested in the comparison of the frequency of primitive progenitors in UCB and in human bone marrow (BM). UCB and BM CD34+ cells were purified and compared for their coexpression of CD38, CD33 and HLA-DR. UCB and BM mononuclear fractions were enriched in CD34+ cells using the CEPRATE LC system (CellPro, Bothell, WA). Double-labeling analysis with a flow cytometer showed that 67.9 +/- 7.2% of UCB CD34+ cells are CD38-, while in BM only 10.9 +/- 4.9% of CD34+ are CD38- (p < 0.001). Moreover, our study indicated that a significantly higher percentage of UCB CD34+ is CD33- (97.1 +/- 1.2%) compared to BM (61.8 +/- 8.6%) (p = 0.013). The coexpression of CD34 with HLA-DR was not significantly different in UCB and in BM (respectively, 86.3 +/- 2.7% and 92.7 +/- 5.1%). On the other hand, in vitro assays showed that the number of multipotent (colony-forming units granulocyte-erythroid-macrophage-megakaryocyte [CFU-GEMM]), myeloid (colony-forming units granulocyte-macrophage [CFU-GM]) and erythroid (burst-forming units-erythroid [BFU-E]) progenitors is lower in the CD34+ population from UCB than from BM. In conclusion, in UCB, we have found a significantly higher percentage of CD34+ cells which lacked the expression of CD38 and CD33 antigens suggesting that UCB contains higher proportions of immature progenitor cells (CD34+CD38- and CD34+CD33-) than BM. It seems thus likely that fewer UCB CD34+ cells than BM CD34+ cells would be required for sustained engraftment following transplantation.
Serotypes of <EMPH TYPE="ITAL">Chlamydia trachomatis</EMPH> and Risk for Development of Cervical Squamous Cell Carcinoma (2001)

Chlamydia trachomatis serotype G is most strongly associated with subsequent development of cervical SCC. Increasing numbers of exposures to different C trachomatis serotypes also increases risk. Our results strengthen the evidence that there is a link between past C trachomatis infection and cervical SCC.
Thyroid structure and function in bovine β‐mannosidosis (1990)

In bovine beta-mannosidosis, the thyroid in the affected newborn shows marked cytoplasmic vacuolation. There is an associated reduction in the serum concentrations of thyroxine and tri-iodothyronine.
Clinical Experience with α-Particle–Emitting 211At: Treatment of Recurrent Brain Tumor Patients with 211At-Labeled Chimeric Antitenascin Monoclonal Antibody 81C6 (2007)

This study provides proof of concept for regional targeted radiotherapy with (211)At-labeled molecules in oncology. Specifically, the regional administration of (211)At-ch81C6 is feasible, safe, and associated with a promising antitumor benefit in patients with malignant central nervous system tumors.
Planar strip monopole with a chip‐capacitor‐loaded loop radiating feed for LTE/WWAN slim mobile phone application (2011)

Abstract A small‐size wideband internal mobile phone antenna formed by a planar strip monopole with a chip‐capacitor‐loaded loop radiating feed for achieving eight‐band long term evolution/wireless wide area network operation in the 698–960 and 1710–2690 MHz bands is presented. The antenna is suitable to be disposed on a small no‐ground board space (15 × 45 mm 2 ) of the system circuit board and enclosed by an L‐shaped system ground plane of the mobile phone. On the protruded ground of the L‐shaped system ground plane, a universal series bus connector for the data port of the mobile phone can be accommodated without affecting the antenna performances. The antenna also shows a low profile of 3 mm above the circuit board, which makes it very promising for slim mobile phone applications. The proposed antenna was fabricated and tested. Measured and simulated results are presented. The specific absorption rate results of the antenna are also analyzed. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett 53:952–958, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.25845
Immunologic and genetic studies of diabetes in the BB rat. (1989)

The spontaneous development of diabetes in the Bio-Breeding (BB) rat is an excellent model of human insulin-dependent diabetes mellitus (IDDM). Disease expression is dependent on several genetically determined abnormalities, including specific major histocompatibility complex (MHC) genes. At least one MHC class II locus of the U haplotype is a necessary, but not sufficient, condition for disease expression. The immune system of BB rats is markedly abnormal. There is a striking reduction in the number and function of mature cytotoxic/suppressor T cells, a poor proliferative response to mitogens and in mixed lymphocyte culture, poor interleukin-2 production, and a reduced ability to reject skin allografts. While these immune system abnormalities are closely related to the development of diabetes, the immune recognition and effector mechanisms resulting in islet cell destruction are still poorly understood. The hypothesis that MHC class II induction on pancreatic beta cells serves to target these lymphokines, natural killer (NK) cells, macrophages, etc.) have been implicated in islet cell killing. The incidence of IDDM is reduced by immunosuppressive therapy in both rats and humans, further supporting the role of immune mechanisms in this disease.
A novel hypothesis for the mechanism of action of P-glycoprotein as a multidrug transporter (1999)

For years, P-glycoprotein (P-gp) has been purported to be a membrane transporter capable of selectively transporting many (but not all) lipophilic anticancer drugs with diverse chemical structures. Because the alleged functions of P-gp provide a straightforward, near-perfect explanation for the molecular mechanism of multidrug resistance associated with P-gp overexpression. However, the exact molecular mechanism for P-gp's purported function has never been clearly understood since its initial discovery some 20 yr ago. In this paper, I develop a novel working hypothesis regarding the mechanism of P-gp's action and suggest that P-gp is an energy-dependent efflux pump only for certain conjugated metabolites (probably sulfates) of the lipophilic anticancer drugs but not for the parent compounds, as was always claimed. According to this hypothesis, P-gp overexpression in most cases is not the "culprit" but instead an "accomplice" in P-gp-associated multidrug resistance. The culprit is probably the enhanced function of the metabolizing enzymes for the lipophilic anticancer drugs. This hypothesis also predicts that one of the important physiological functions of P-gp is to be part of an intracellular machinery (together with the phase I and II metabolizing enzymes) for the metabolism, detoxification, and disposition of lipophilic endogenous chemicals as well as xenobiotics, including cytotoxic anticancer drugs. There exists a considerable body of circumstantial evidence in the literature that lends strong support to this mechanistic hypothesis of P-gp's action as well as to the predicted physiological functions of P-gp. It will be of considerable interest to examine this novel hypothesis experimentally.
Sensory and Chemical Characteristics of Selected Gulf of Mexico Coastal Herring Species (1997)

ABSTRACT Gulf of Mexico coastal herrings may become an important alternative fisheries resource for U.S. commercial fisherman. Effects of on board handling on sensory characteristics of chub mackerel ( Scomber japonicus ) and rough scad ( Trachurus lathami ) were investigated. Proximate and fatty acid composition of chub mackerel, rough scad, round scad ( Decapturus punctatus ), round herring ( Etrumeus teres ), and silver rag ( Ariomma bondi ) were determined to provide nutritional and product formulation data. Chub mackerel and rough scad had similar sensory characteristics found in other commercial species, which, with proper on board handling, could be maintained during frozen storage. Proximate and fatty acid compositions of the fish varied by species, season, and year.
Synthesis of Nanocomposite Organic/Inorganic Hybrid Materials Using Controlled/“Living” Radical Polymerization (2001)

The preparation of hybrid organic/inorganic nanocomposites comprised of well-defined polymers was reviewed. In particular, synthetic methods using controlled/“living” radical polymerization techniques, such as stable free-radical/nitroxide-mediated polymerizations, atom transfer radical polymerization, and reversible addition−fragmentation chain-transfer polymerization were described. The various approaches taken to prepare hybrid copolymers, nanoparticles, polymer brushes, dispersed silicate nanocomposites, and nanoporous materials were discussed.
The Area Postrema: A Brain Monitor and Integrator of Systemic Autonomic State (2007)

The area postrema is a medullary structure lying at the base of the fourth ventricle. The area postrema's privileged location outside of the blood-brain barrier make this sensory circumventricular organ a vital player in the control of autonomic functions by the central nervous system. By virtue of its lack of tight junctions between endothelial cells in this densely vascularized structure and the presence of fenestrated capillaries, peptide and other physiological signals borne in the blood have direct access to neurons that project to brain areas with important roles in the autonomic control of many physiological systems, including the cardiovascular system and systems controlling feeding and metabolism. However, the area postrema is not simply a conduit through which signals flow into the brain, but it is now being recognized as the initial site of integration for these signals as they enter the circuitry of the central nervous system. NEUROSCIENTIST 14(2):182—194, 2008. DOI: 10.1177/1073858407311100
Message in a molecule (2016)

Since ancient times, steganography, the art of concealing information, has largely relied on secret inks as a tool for hiding messages. However, as the methods for detecting these inks improved, the use of simple and accessible chemicals as a means to secure communication was practically abolished. Here, we describe a method that enables one to conceal multiple different messages within the emission spectra of a unimolecular fluorescent sensor. Similar to secret inks, this molecular-scale messaging sensor (m-SMS) can be hidden on regular paper and the messages can be encoded or decoded within seconds using common chemicals, including commercial ingredients that can be obtained in grocery stores or pharmacies. Unlike with invisible inks, however, uncovering these messages by an unauthorized user is almost impossible because they are protected by three different defence mechanisms: steganography, cryptography and by entering a password, which are used to hide, encrypt or prevent access to the information, respectively.
Roles for In Vitro Myelotoxicity Tests in Preclinical Drug Development and Clinical Trial Planning (1993)

Myelosuppression is the dose-limiting side effect for most anti-cancer and many anti-human immunodeficiency virus agents, which can be quantitated with optimized colony-forming assays (granulocyte-macrophage, late erythroid, and megakaryocytic [for murine only] colony-forming units and early erythroid burst-forming units (BFUs)). When applied to new drug development, the assays are used for therapeutic index-based screening (e.g., less myelosuppressive analogues, structure-toxicity studies, new drug leads), interpreting efficacy data from xenotransplant models, and selecting the most accurate animal model for human hematopoietic toxicity. However, other types of assays may be required to identify the mechanism underlying myelosuppression. In clinical trial planning, in vitro colony-forming assays can be used to elucidate schedule dependency of myelotoxicity (which in turn provides clues about mechanism of action), to plan cytokine support, and to estimate dose-escalation effects. The inhibition of colony formation can be measured relative to a compound with known clinical myelotoxicity and schedule dependency to provide some idea of the toxicity expected at particular doses, and the degree of heterogeneity between individuals, during clinical trials. The predictive accuracy of the in vitro data has been proven by validation studies with alkylating agents.
Mime: a high performance parallel storage device with strong recovery guarantees (1997)

this paper is organized as follows. We begin with an overview of the kind of recovery properties desirable for a storage system and follow this with a description of related work---one part of which is a key foundation for the Mime architecture. Next, we introduce the functionality and architecture of Mime itself at high level, and follow that with a description of the components of the Mime architecture. We analyze the performance impact of Mime on both existing file systems and new ones that exploit the new functionality, and conclude with a summary of results, and current status.
Ablation of Internalization Signals in the Carboxyl-terminal Tail of the Cystic Fibrosis Transmembrane Conductance Regulator Enhances Cell Surface Expression (2002)

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel that undergoes endocytosis through clathrin-coated pits. Previously, we demonstrated that Y1424A is important for CFTR endocytosis (Prince, L. S., Peter, K., Hatton, S. R., Zaliauskiene, L., Cotlin, L. F., Clancy, J. P., Marchase, R. B., and Collawn, J. F. (1999) J. Biol. Chem. 274, 3602-3609). Here we show that a second substitution in the carboxyl-terminal tail of CFTR, I1427A, on Y1424A background more than doubles CFTR surface expression as monitored by surface biotinylation. Internalization assays indicate that enhanced surface expression of Y1424A,I1427A CFTR is caused by a 76% inhibition of endocytosis. Patch clamp recording of chloride channel activity revealed that there was a corresponding increase in chloride channel activity of Y1424A,I1427A CFTR, consistent with the elevated surface expression, and no change in CFTR channel properties. Y14124A showed an intermediate phenotype compared with the double mutation, both in terms of surface expression and chloride channel activity. Metabolic pulse-chase experiments demonstrated that the two mutations did not affect maturation efficiency or protein half-life. Taken together, our data show that there is an internalization signal in the COOH terminus of CFTR that consists of Tyr(1424)-X-X-Ile(1427) where both the tyrosine and the isoleucine are essential residues. This signal regulates CFTR surface expression but not CFTR biogenesis, degradation, or chloride channel function.
Reduction in Pulmonary Fibrosis in Vivo by Halofuginone (1996)

Pulmonary fibrosis is a disorder causing a high mortality rate for which therapeutic options are limited. Therefore, the effect of halofuginone, a novel inhibitor of collagen type I synthesis, on bleomycin-induced pulmonary fibrosis was studied in rats. Pulmonary fibrosis was induced by intraperitoneal injections of bleomycin for seven consecutive days, and halofuginone was administered intraperitoneally every second day during the entire experimental period of 42 d. Collagen determination in the lungs and the examination of histologic sections showed that halofuginone significantly reduced fibrosis relative to the untreated control rats. We conclude that halofuginone is a potent in vivo inhibitor of bleomycin-induced pulmonary fibrosis, and that it may potentially be used as a novel therapeutic agent for the treatment of this dysfunction.
Methicillin resistantStaphylococcus aureus(MRSA) in the intensive care unit (2002)

Methicillin resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen that causes severe morbidity and mortality worldwide. MRSA strains are endemic in many American and European hospitals and account for 29%-35% of all clinical isolates. Recent studies have documented the increased costs associated with MRSA infection, as well as the importance of colonisation pressure. Surveillance strategies have been proposed especially in high risk areas such as the intensive care unit. Pneumonia and bacteraemia account for the majority of MRSA serious clinical infections, but intra-abdominal infections, osteomyelitis, toxic shock syndrome, food poisoning, and deep tissue infections are also important clinical diseases. The traditional antibiotic therapy for MRSA is a glycopeptide, vancomycin. New antibiotics have been recently released that add to the armamentarium for therapy against MRSA and include linezolid, and quinupristin/dalfopristin, but cost, side effects, and resistance may limit their long term usefulness.