gebhart/patrepeval huggingface dataset:
Internalization of caveolin-1 scaffolding domain facilitated by Antennapedia homeodomain attenuates PAF-induced increase in microvessel permeability (2004)

We demonstrated previously that inhibition of endothelial nitric oxide synthase (NOS), using pharmacological inhibitors, attenuated the ionomycin- and ATP-induced increases in microvessel permeability (Am J Physiol Heart Circ Physiol 272: H176-H185, 1997). Recently, the scaffolding domain of caveolin-1 (CAV) has been implicated as a negative regulator of endothelial NOS (eNOS). To examine the role of CAV-eNOS interaction in regulation of permeability in intact microvessels, the effect of internalized CAV on the platelet-activating factor (PAF)-induced permeability increase was investigated in rat mesenteric venular microvessels. Internalization of CAV was achieved by perfusion of individual vessels using a fusion peptide of CAV with Antennapedia homeodomain (AP-CAV) and visualized by fluorescence imaging and electron microscopy. Changes in microvessel permeability were evaluated by measuring hydraulic conductivity (Lp) in individually perfused microvessels. We found that the PAF (10 nM)-induced Lp increase was significantly attenuated from 6.0 +/- 0.9 (n = 7) to 2.0 +/- 0.3 (n = 5) times control after microvessels were perfused with 10 microM AP-CAV for 2 h. The magnitude of this reduction is comparable with that of the inhibitory effect of Nomega-monomethyl-l-arginine on the PAF-induced Lp increase. In contrast, perfusion with 10 microM AP alone for 2 h modified neither basal Lp nor the vessel response to PAF. These results indicate that CAV plays an important role in regulation of microvessel permeability. The inhibitory action of CAV on permeability increase might be attributed to its direct inactivation of eNOS. In addition, this study established a method for studying protein-protein interaction-induced functional changes in intact microvessels and demonstrated AP as an efficient vector for translocation of peptide across the cell membrane in vivo.
The molecular basis of the Rhesus antigen Ew (2004)

The single-point mutation T500A in exon 4 of the RHCE gene is a molecular basis of the rare Rhesus antigen Ew.
ASPRO-216: a standard-cell Q.D.I. 16-bit RISC asynchronous microprocessor (2002)

The design of a CMOS standard-cell Quasi-Delay-Insensitive (QDI) 16-bit asynchronous microprocessor is presented. ASPRO-216 is being developed for embedded applications. It is a scalar processor which issues instructions in-order and completes their execution out-of-order, and it can be customized both at the hardware and software levels to fit specific application requirements. Its architecture extensively uses an overlapping pipelined execution scheme involving desynchronized units. The design flow and circuit style are an original application of A. Martin's method. The expected performance is 200 peak MIPS, 0.5 Watt using a 0.25 /spl mu/m technology.
Hospital Management of Hyperglycemia (2004)

For decades, a precept was passed down by academic physicians to trainees and staff as a guideline for inpatient care of patients with diabetes. That bit of wisdom held that it is best to “keep the patient a little sweet.” The Diabetes Control and Complications Trial1 and the U.K. Prospective Diabetes Study2 showed the ability of intensified control to reduce microvascular complications of diabetes. Despite the increased risk of hypoglycemia, these trials changed practice patterns in ambulatory settings in favor of intensification of diabetes therapy. Among hospitalized patients, a relationship of adverse outcomes to hyperglycemia was suggested by many observational studies that reported on mortality,3–7 infectious complications,8–11 length of stay,12 and other findings. Nevertheless, hospitalization continued to be seen by many practitioners as just a brief interlude during which tight glycemic control was risky and also irrelevant to the long-term well-being of patients with diabetes.

Two randomized, prospective trials using intravenous insulin therapy now have revolutionized our thinking about inpatient care of diabetes and hyperglycemia by showing the ability of intensive insulin treatment of critically ill hospitalized patients to reduce mortality without increasing morbidity due to hypoglycemia.13,14 The first study called for initiation of an infusion of glucose and insulin in the setting of myocardial infarction and aimed at a target glucose of 126–180 mg/dl.13,15,16 The second used intravenous insulin infusion in the surgical intensive care unit to achieve a target glucose of 80–110 mg/dl.14,17 Control of hyperglycemia or insulin therapy per se hypothetically might reduce risks for hospitalized patients by correcting mechanisms of injury such as neutrophil dysfunction, abnormal activation of cytokines and the inflammatory pathway, cardiac reperfusion injury, endothelial dysfunction, thrombotic tendency, catabolism, and hyperglycemia-induced oxidative stress with …
Structure and Mechanistic Analysis of the Anti-Human Immunodeficiency Virus Type 1 Antibody 2F5 in Complex with Its gp41 Epitope (2004)

The membrane-proximal region of the ectodomain of the gp41 envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) is the target of three of the five broadly neutralizing anti-HIV-1 antibodies thus far isolated. We have determined crystal structures of the antigen-binding fragment for one of these antibodies, 2F5, in complex with 7-mer, 11-mer, and 17-mer peptides of the gp41 membrane-proximal region, at 2.0-, 2.1-, and 2.2-A resolutions, respectively. The structures reveal an extended gp41 conformation, which stretches over 30 A in length. Contacts are made with five complementarity-determining regions of the antibody as well as with nonpolymorphic regions. Only one exclusive charged face of the gp41 epitope is bound by 2F5, while the nonbound face, which is hydrophobic, may be hidden due to occlusion by other portions of the ectodomain. The structures reveal that the 2F5 antibody is uniquely built to bind to an epitope that is proximal to a membrane surface and in a manner mostly unaffected by large-scale steric hindrance. Biochemical studies with proteoliposomes confirm the importance of lipid membrane and hydrophobic context in the binding of 2F5 as well as in the binding of 4E10, another broadly neutralizing antibody that recognizes the membrane-proximal region of gp41. Based on these structural and biochemical results, immunization strategies for eliciting 2F5- and 4E10-like broadly neutralizing anti-HIV-1 antibodies are proposed.
Energy management in mobile devices with the cinder operating system (2011)

We argue that controlling energy allocation is an increasingly useful and important feature for operating systems, especially on mobile devices. We present two new low-level abstractions in the Cinder operating system, reserves and taps, which store and distribute energy for application use. We identify three key properties of control -- isolation, delegation, and subdivision -- and show how using these abstractions can achieve them. We also show how the architecture of the HiStar information-flow control kernel lends itself well to energy control. We prototype and evaluate Cinder on a popular smartphone, the Android G1.
Mechanism of DNA strand nicking at apurinic/apyrimidinic sites by Escherichia coli [formamidopyrimidine]DNA glycosylase (1989)

Escherichia coli [formamidopyrimidine]DNA glycosylase catalyses the nicking of both the phosphodiester bonds 3' and 5' of apurinic or apyrimidinic sites in DNA so that the base-free deoxyribose is replaced by a gap limited by 3'-phosphate and 5'-phosphate ends. The two nickings are not the results of hydrolytic processes; the [formamidopyrimidine]DNA glycosylase rather catalyses a beta-elimination reaction that is immediately followed by a delta-elimination. The enzyme is without action on a 3'-terminal base-free deoxyribose or on a 3'-terminal base-free unsaturated sugar produced by a beta-elimination reaction nicking the DNA strand 3' to an apurinic or apyrimidinic site.
Dissection of human humoral immune response against hepatitis C virus E2 glycoprotein by repertoire cloning and generation of recombinant fab fragments (1998)

Demonstration of antibodies inhibiting key viral functions is the basis for the design of an effective vaccine. Dissection of the human antibody response by repertoire cloning may be a powerful means to address this issue. In this study, a panel of human monoclonal recombinant Fab fragments specific for hepatitis C virus (HCV) E2 envelope protein was generated. The selection procedure was designed to select for cross-genotype reactive antibodies. Sequences coding five different human recombinant Fabs specific for the HCV/E2 protein were cloned and characterized. The ability of the cloned antibody fragments to inhibit adhesion of recombinant envelope E2 protein to target cells was assayed. While affinity of the different antibody fragments appeared similar, activity in inhibiting E2 binding to target cells varied considerably from one Fab fragment to another. Two Fabs were not able to inhibit E2 binding at high concentration (40 microg/mL), while three other Fab clones were active in neutralizing 50% of the E2 binding at concentrations ranging from 3 to 0.35 microg/mL.
Pd Supported on Titanium Nitride for Efficient Ethanol Oxidation (2010)

The excellent metal−support interaction between palladium (Pd) and titanium nitride (TiN) is exploited in designing an efficient anode material, Pd-TiN, that could be useful for direct ethanol fuel cell in alkaline media. The physicochemical and electrochemical characterization of the Pd-TiN/electrolyte interface reveals an efficient oxidation of ethanol coupled with excellent stability of the catalyst under electrochemical conditions. Characterization of the interface using in situ Fourier transform infrared spectroscopy (in situ FTIR) shows the production of CO2 at low overvoltages revealing an efficient cleaving of the C−C bond. The performance comparison of Pd supported on TiN (Pd-TiN) with that supported on carbon (Pd-C) clearly demonstrates the advantages of TiN support over carbon. A positive chemical shift of Pd (3d) binding energy confirms the existence of metal−support interaction between Pd and TiN, which in turn helps weaken the Pd−CO synergetic bonding interaction. The remarkable ability of TiN to accumulate −OH species on its surface coupled with the strong adhesion of Pd makes TiN an active support material for electrocatalysts.
Glucagon-like peptide-1 (GLP-1): A gut hormone of potential interest in the treatment of diabetes (1998)

GLP-1 (glucagon-like peptide-1) is a gut hormone which is released into the blood stream after feeding. Its main action is to stimulate insulin secretion through potentiating the insulinotropic action of glucose. The peptide is encoded in the glucagon gene and expressed mainly in the gut L cells. It exerts its actions through activating specific receptors of the seven transmembraneous domain-G-protein-coupled type with 463 amino acids. Its main signalling mechanism is activation of adenylate cyclase and formation of cyclic AMP. The peptide also increases the cytoplasmic concentration of Ca2 which is thought to be executed both through a Na(+)-dependent uptake of extracellular Ca2+ and through release of Ca2+ from intracellular Ca2+ stores. GLP-1 also inhibits glucagon secretion and inhibits gastric emptying and gastric acid and pancreatic exocrine secretion. Its integrated action on carbohydrate metabolism results in reduction of circulating glucose, and GLP-1 has therefore been suggested as a therapeutic alternative in diabetes. Finally, GLP-1 is also expressed in neurons in the hypothalamus, and may be involved in the regulation of feeding behaviour, since it inhibits food intake.
Localization of a Domain in Apolipoprotein E with both Cytostatic and Cytotoxic Activity (1995)

Apoliprotein E (apoE) is a potent suppressor of interleukin 2- (IL2-) dependent T lymphocyte proliferation. In this study, we have used a range of monomeric and dimeric peptides encompassing amino acids 130-169 in human apoE to locate a region with both cytostatic and cytotoxic effects on IL2-dependent T lymphocytes. Monomeric peptides representing residues 130-149 or 130-155 inhibited the proliferation of the cells without causing loss of cell viability. However, cytostasis by a peptide representing the extended 130-169 domain or dimeric peptides of amino acids 141-155 or 141-149 was accompanied by potent cytotoxic activity. These results suggest that residues 141-149, which include the overlap between the functional peptides, are responsible for cytostasis and cytotoxicity. Complete ablation of both activities by the polyanionic agent heparin highlighted the important contribution of the positively charged amino acids in the 141-149 region to peptide bioactivity. Furthermore, the bioactive apoE peptides also had a relatively high helical content, suggesting that alpha-helical content is necessary for bioactivity. Cytotoxic apoE peptides were characterized by a high density of polar face positively charged residues together with a high nonpolar face hydrophobicity. This conclusion is supported by the reduced hydrophobicity and polar face positive charge density of the significantly less active E2(130-169) peptide. The cytotoxic apoE peptides are structurally similar to previously characterized class L lytic peptides. They do not, however, exert their cytotoxic activity by destabilizing membrane bilayers as is the case with the class L peptides, as evidenced by their minimal hemolytic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
MMSE-Based MDL Method for Robust Estimation of Number of Sources Without Eigendecomposition (2009)

It is well known that the conventional eigenvalue-based minimum description length (MDL) approach for source number estimation suffers from high computational load and performs optimally only in the presence of spatially and temporally white noise. To improve the robustness of the MDL methodology, we propose to utilize the minimum mean square error (MMSE) of the multistage Wiener filter to calculate the required description length for encoding the observed data, instead of relying on the eigenvalues of the data covariance matrix. As there is no need to calculate the covariance matrix and its eigenvalue decomposition, our derived MMSE-based MDL (mMDL) method is also more computationally efficient than the traditional counterparts. Numerical examples are included to demonstrate the robustness of the mMDL detector in nonuniform noise.
Molecular genetic anatomy of inter- and intraserotype variation in the human bacterial pathogen group A Streptococcus (2006)

In recent years we have studied the relationship between strain genotypes and patient phenotypes in group A Streptococcus (GAS), a model human bacterial pathogen that causes extensive morbidity and mortality worldwide. We have concentrated our efforts on serotype M3 organisms because these strains are common causes of pharyngeal and invasive infections, produce unusually severe invasive infections, and can exhibit epidemic behavior. Our studies have been hindered by the lack of genome-scale phylogenies of multiple GAS strains and whole-genome sequences of multiple serotype M3 strains recovered from individuals with defined clinical phenotypes. To remove some of these impediments, we sequenced to closure the genome of four additional GAS strains and conducted comparative genomic resequencing of 12 contemporary serotype M3 strains representing distinct genotypes and phenotypes. Serotype M3 strains are a single phylogenetic lineage. Strains from asymptomatic throat carriers were significantly less virulent for mice than sterile-site isolates and evolved to a less virulent phenotype by multiple genetic pathways. Strain persistence or extinction between epidemics was strongly associated with presence or absence, respectively, of the prophage encoding streptococcal pyrogenic exotoxin A. A serotype M3 clone significantly underrepresented among necrotizing fasciitis cases has a unique frameshift mutation that truncates MtsR, a transcriptional regulator controlling expression of genes encoding iron-acquisition proteins. Expression microarray analysis of this clone confirmed significant alteration in expression of genes encoding iron metabolism proteins. Our analysis provided unprecedented detail about the molecular anatomy of bacterial strain genotype-patient phenotype relationships.
Fast Assessment of Resistance to Carbapenems and Ciprofloxacin of Clinical Strains of Acinetobacter baumannii (2012)

Infections caused by multidrug-resistant Acinetobacter baumannii constitute a major life-threatening problem worldwide, and early adequate antibiotic therapy is decisive for success. For these reasons, rapid detection of antibiotic susceptibility in this pathogen is a clinical challenge. Two variants of the Micromax kit were evaluated for a rapid detection in situ of susceptibility or resistance to meropenem or ciprofloxacin, separately, in 322 clinical isolates. Release of the nucleoid is the criterion of susceptibility to the beta-lactams (carbapenems), whereas diffusion of DNA fragments emerging from the nucleoid characterizes the quinolone activity. All the susceptible and resistant strains were correctly categorized in 100 min according to the MIC results and CLSI criteria. Thus, our technology is a promising tool for rapid identification of carbapenem and quinolone resistance of A. baumannii strains in hospital settings.
Inhibitory effects of caffeic acid phenethyl ester (CAPE) on 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion in mouse skin and the synthesis of DNA, RNA and protein in HeLa cells (1996)

Topical application of caffeic acid phenethyl ester (CAPE), a constituent of the propolis of honeybee hives, to the backs of CD-1 mice previously initiated with 7, 12-dimethylbenz[α]anthracene (DMBA) inhibited 12-O-tetra-decanoylphorbol-13-acetate (TPA)-induced tumor promotion and the formation of 5-hydroxymethyl-2'-deoxyuridine (HMdU) in epidermal DNA. Topical application of 5 nmol TPA twice weekly for 20 weeks to mice previously initiated with 200 nmol ofDMBA resulted in 18.8 skin papillomas per mouse. Topical application of 1, 10, 100 or 3000 nmol of CAPE together with 5 nmol of TPA twice a week for 20 weeks inhibited the number of skin papillomas per mouse by 24, 30, 45 or 70%, respectively, and tumor size per mouse was decreased by 42, 66, 53 or 74%, respectively. Topical application of 5 nmol of TPA twice weekly for 20 weeks to mice previously initiated with DMBA produced an average of 12.6 HMdU residues per 104 normal bases in epidermal DNA. Topical application of 1, 10, 100 or 3000 nmol of CAPE with 5 nmol of TPA twice weekly for 20 weeks to DMBA-initiated mice decreased the level of HMdU in epidermal DNA by 40-93%. The in vitro addition of 1.25, 2.5, 5, 10 or 20 μM CAPE to cultured HeLa cells inhibited the synthesis of DNA by 32, 44, 66, 79 or 95%, respectively, the synthesis of RNA was inhibited by 39, 43, 58, 64 or 75%, respectively, and the synthesis of protein was inhibited by 29, 30, 37, 32 or 47%, respectively. The results indicate a potent inhibitory effect of CAPE on TPA-induced tumor promotion and TPA-induced formation of HMdU in DNA of mouse skin as well as an inhibitory effect of CAPE on the synthesis of DNA, RNA and protein in cultured HeLa cells.
Compression and Aggregation-Resistant Particles of Crumpled Soft Sheets (2011)

Unlike flat sheets, crumpled paper balls have both high free volume and high compressive strength, and can tightly pack without significantly reducing the area of accessible surface. Such properties would be highly desirable for sheet-like materials such as graphene, since they tend to aggregate in solution and restack in the solid state, making their properties highly dependent on the material processing history. Here we report the synthesis of crumpled graphene balls by capillary compression in rapidly evaporating aerosol droplets. The crumpled particles are stabilized by locally folded, π-π stacked ridges as a result of plastic deformation, and do not unfold or collapse during common processing steps. In addition, they are remarkably aggregation-resistant in either solution or solid state, and remain largely intact and redispersible after chemical treatments, wet processing, annealing, and even pelletizing at high pressure. For example, upon compression at 55 MPa, the regular flat graphene sheets turn into nondispersible chunks with drastically reduced surface area by 84%, while the crumpled graphene particles can still maintain 45% of their original surface area and remain readily dispersible in common solvents. Therefore, crumpled particles could help to standardize graphene-based materials by delivering more stable properties such as high surface area and solution processability regardless of material processing history. This should greatly benefit applications using bulk quantities of graphene, such as in energy storage or conversion devices. As a proof of concept, we demonstrate that microbial fuel electrodes modified by the crumpled particles indeed outperform those modified with their flat counterparts.
Cyclic adenosine monophosphate signal pathway in targeted therapy of lymphoma. (2010)

cAMP signal pathway has different effects on various lymphoma cells. cAMP analogues and phosphodiesterase 4B (PDE4B) inhibitors have potential clinical significance. However, many challenges remain in understanding the various roles of such agents.
In Vitro Release of Hydrophobic Drugs From Polyanhydride Disks (1991)

We have evaluated the feasibility of using polyanhydride disks containing hydrophobic antiproliferative agents for controlled drug release after glaucoma filtration surgery. Taxol and VP-16 were the most potent inhibitors of fibroblast proliferation tested, with ID50s of 3 ng/mL and 200 ng/mL, respectively. In vitro release of taxol occurred at concentrations exceeding its ID50 for at least 100 days; VP-16 was released for 31 days. The media into which the drugs were released were able to inhibit fibroblast proliferation in vitro, indicating that the bioactivity of the drugs withstood incorporation into, and release from, the polyanhydride. Polyanhydride disks containing taxol and VP-16 merit testing in animal models of glaucoma filtration surgery.
Materials for Fluorescence Resonance Energy Transfer Analysis: Beyond Traditional Donor–Acceptor Combinations (2006)

The use of Förster or fluorescence resonance energy transfer (FRET) as a spectroscopic technique has been in practice for over 50 years. A search of ISI Web of Science with just the acronym "FRET" returns more than 2300 citations from various areas such as structural elucidation of biological molecules and their interactions, in vitro assays, in vivo monitoring in cellular research, nucleic acid analysis, signal transduction, light harvesting and metallic nanomaterials. The advent of new classes of fluorophores including nanocrystals, nanoparticles, polymers, and genetically encoded proteins, in conjunction with ever more sophisticated equipment, has been vital in this development. This review gives a critical overview of the major classes of fluorophore materials that may act as donor, acceptor, or both in a FRET configuration. We focus in particular on the benefits and limitations of these materials and their combinations, as well as the available methods of bioconjugation.