gebhart/patrepeval huggingface dataset:
Rab5 Mediates Caspase-8–promoted Cell Motility and Metastasis (2009)

Caspase-8 is a key apical sensory protein that governs cell responses to environmental cues, alternatively promoting apoptosis, proliferation, and cell migration. The proteins responsible for integration of these pathways, however, have remained elusive. Here, we reveal that Rab5 regulates caspase-8-dependent signaling from integrins. Integrin ligation leads to Rab5 activation, association with integrins, and activation of Rac, in a caspase-8-dependent manner. Rab5 activation promotes colocalization and coprecipitation of integrins with caspase-8, concomitant with Rab5 recruitment to integrin-rich regions such as focal adhesions and membrane ruffles. Moreover, caspase-8 expression promotes Rab5-mediated internalization and the recycling of beta1 integrins, increasing cell migration independently of caspase catalytic activity. Conversely, Rab5 knockdown prevented caspase-8-mediated integrin signaling for Rac activation, cell migration, and apoptotic signaling, respectively. Similarly, Rab5 was critical for caspase-8-driven cell migration in vivo, because knockdown of Rab5 compromised the ability of caspase-8 to promote metastasis under nonapoptotic conditions. These studies identify Rab5 as a key integrator of caspase-8-mediated signal transduction downstream of integrins, regulating cell survival and migration in vivo and in vitro.
Constitutive Activity of Dopamine D1-Receptor Subtypes (1995)

Dopamine (DA) mediates brain functions through its interaction with membrane-bound receptors belonging to the superfamily of G-proteincoupled receptors. The DA receptors are divided into two groups: the D1 family (D1A and D1B/D5) and the D2 family (D2, D3, and D4). Biochemical characterization of the D1-like receptor subtypes has revealed that compared with the D1A receptor, the D1B/D5 receptor subtype displays properties that resemble those of adrenergic receptors in which mutagenesis of intracellular regions yields constitutively active phenotypes. In other G-protein-coupled receptor systems, such as the rhodopsin and thyroid-stimulating hormone receptors systems, naturally occurring activating mutations lead to pathophysiological manifestations such as retinitis pigmentosa, night blindness, and hyperthyroidism. It is not known if the constitutive activity of the D1B/D5 receptor has physiological significance, but the high agonist-independent activity, as well as the increased affinity of this receptor subtype for DA, suggests that this receptor might respond to the endogenous neurotransmitter with intrinsic properties different than those of the related D1A receptor.
Sequestering of the 3′ Splice Site in a Theophylline-Responsive Riboswitch Allows Ligand-Dependent Control of Alternative Splicing (2008)

Despite the important role of alternative splicing in various aspects of biological processes, our ability to regulate this process at will remains a challenge. In this report, we asked whether a theophylline-responsive riboswitch could be adapted to manipulate alternative splicing. We constructed a pre-mRNA containing a single upstream 5' splice site and two 3' splice sites, of which the proximal 3' splice site is embedded in theophylline-responsive riboswitch. We show that this pre-mRNA spliced with preferential utilization of proximal 3' splice site in vitro. However, addition of theophylline to the splicing reaction promoted splicing at distal 3' splice site thereby changing the ratio of distal-to-proximal 3' splice site usage by more than twofold. Our data suggest that theophylline influenced 3' splice site choice without affecting the kinetics of the splicing reaction. We conclude that an in vitro selected riboswitch can be adapted to control alternative splicing, which may find many applications in basic, biotechnological, and biomedical research.
A Review of Ground Coupled Heat Pump Models Used in Whole-Building Computer Simulation Programs (2010)

Energy Systems Laboratory, Department of Architecture Texas A&M University College Station, TX
An Analysis of Online Marketing in the Sport Industry: User Activity, Communication Objectives, and Perceived Benefits (2003)

The purpose of this study was to analyze marketing on the Internet in the sport industry. The rational for the study was based upon the industry's need to understand this technology as an effective marketing tool. Seven hundred and fifty sport organizations in the performance segment of the industry were randomly selected and surveyed. Three hundred and twenty-eight usable surveys were returned for a 44% response rate. The online marketing communications objective of most organizations was to provide information about the organization to the visitor or to generate awareness of the organization. Very little emphasis was placed on interactive marketing. In the opinion of the author, most sport marketers need to emphasize the online consumer/seller relationship to continue developing this medium as an effective marketing tool. Without this focus, business will be lost to organizations effectively implementing their interactive marketing plans.
Flight craft Patent (1966)

Designing spacecraft for flight into space, atmospheric reentry, and landing at selected sites
A Technology-Agnostic Simulation Environment (TASE) for iterative custom IC design across processes (2009)

A designer's intent and knowledge about the critical issues and trade-offs underlying a custom circuit design are implicit in the simulations she sets up for design creation and verification. However, this knowledge is tightly conjoined with technology-specific features and decoupled from the final schematic in traditional design flows. As a result, this knowledge is easily lost when the technology specifics change. This paper presents a technology agnostic simulation environment (TASE), which is a tool that uses simulation templates to capture the designer's knowledge and separate it from the technology-specific components of a simulation. TASE also allows the designer to form groups of related simulations and port them as a unit to a new technology. This allows an actual design schematic to remain tied to the analyses that illuminate the underlying trade-offs and design issues, unlike the case where schematics are ported alone. Giving the designer immediate access to the trade-offs, which are likely to change in new technologies, accelerates the re-design that often must accompany porting of complicated custom circuits. We demonstrate the usefulness of TASE by investigating Read and Write noise margins for a 6T SRAM in predictive technologies down to 16 nm.
Power to peep-all: Inference Attacks by Malicious Batteries on Mobile Devices (2018)

Abstract Mobile devices are equipped with increasingly smart batteries designed to provide responsiveness and extended lifetime. However, such smart batteries may present a threat to users’ privacy. We demonstrate that the phone’s power trace sampled from the battery at 1KHz holds enough information to recover a variety of sensitive information. We show techniques to infer characters typed on a touchscreen; to accurately recover browsing history in an open-world setup; and to reliably detect incoming calls, and the photo shots including their lighting conditions. Combined with a novel exfiltration technique that establishes a covert channel from the battery to a remote server via a web browser, these attacks turn the malicious battery into a stealthy surveillance device. We deconstruct the attack by analyzing its robustness to sampling rate and execution conditions. To find mitigations we identify the sources of the information leakage exploited by the attack. We discover that the GPU or DRAM power traces alone are sufficient to distinguish between different websites. However, the CPU and power-hungry peripherals such as a touchscreen are the primary sources of fine-grain information leakage. We consider and evaluate possible mitigation mechanisms, highlighting the challenges to defend against the attacks. In summary, our work shows the feasibility of the malicious battery and motivates further research into system and application-level defenses to fully mitigate this emerging threat.
Somatic Mutations of<i>EGFR</i>in Colorectal Cancers and Glioblastomas (2004)

To the Editor: Recent reports suggest that mutations in the epidermal growth factor receptor (EGFR) gene predict sensitivity to EGFR kinase inhibitors. In particular, patients with lung cancers containing mutations in the EGFR kinase domain have had responses to gefitinib.1,2 Are similar EGFR mutations present in a significant fraction of other tumor types for which gefitinib might be suitable therapy? To answer this question, we screened DNA from 293 colorectal tumors and 59 glioblastomas for alterations in the EGFR kinase domain (exons 17 to 24). These tumors were chosen for analysis because they have been linked to . . .
Simultaneous assay of every <i>Salmonella</i> Typhi gene using one million transposon mutants (2009)

Very high-throughput sequencing technologies need to be matched by high-throughput functional studies if we are to make full use of the current explosion in genome sequences. We have generated a very large bacterial mutant pool, consisting of an estimated 1.1 million transposon mutants and we have used genomic DNA from this mutant pool, and Illumina nucleotide sequencing to prime from the transposon and sequence into the adjacent target DNA. With this method, which we have called TraDIS (transposon directed insertion-site sequencing), we have been able to map 370,000 unique transposon insertion sites to the Salmonella enterica serovar Typhi chromosome. The unprecedented density and resolution of mapped insertion sites, an average of one every 13 base pairs, has allowed us to assay simultaneously every gene in the genome for essentiality and generate a genome-wide list of candidate essential genes. In addition, the semiquantitative nature of the assay allowed us to identify genes that are advantageous and those that are disadvantageous for growth under standard laboratory conditions. Comparison of the mutant pool following growth in the presence or absence of ox bile enabled every gene to be assayed for its contribution toward bile tolerance, a trait required of any enteric bacterium and for carriage of S. Typhi in the gall bladder. This screen validated our hypothesis that we can simultaneously assay every gene in the genome to identify niche-specific essential genes.
Interleukin-10 Functions <i>In Vitro</i> and <i>In Vivo</i> to Inhibit Bacterial DNA-Induced Secretion of Interleukin-12 (1997)

Bacterial DNA (bDNA) has a number of biologic properties, including the ability to induce interleukin-12 (IL-12) production by macrophages. We studied the role of the regulatory cytokine IL-10 as a potential inhibitor of bDNA-induced IL-12 production. IL-10 concentrations as low as 0.3 ng/ml profoundly inhibited bDNA-induced macrophage IL-12 production as measured by Elispot analysis of IL-12 p40-secreting cells. Additionally, we found that IL-10 inhibited bDNA-induced IL-12 secretion by the macrophage cell lines J774 and RAW 264. Preincubation of splenic adherent cells with IL-10 markedly reduced bDNA-induced transcription of IL-12 p40 mRNA. Interestingly, after 2 h of exposure, bDNA also induces transcription of IL-10 mRNA by splenic adherent cells. The importance of IL-10 in the in vivo regulation of bDNA-induced cytokine secretion was illustrated by the response of mice with disrupted IL-10 genes (IL-10 ko mice) to i.v. bDNA challenge. Compared to +/+ mice, IL-10 knockout (ko) mice exhibited increased numbers of IL-12 and interferon-gamma (IFN-gamma)-secreting cells following either single or repeated challenge with bDNA. These findings indicate that IL-10 plays a key role in regulating bDNA-induced production of inflammatory cytokines.
Kinetics of N-formyl peptide receptor up-regulation during stimulation in human neutrophils (1991)

The kinetics of receptor up-regulation was examined in isolated neutrophils and in whole blood by flow cytometry during cell activation. Stimulation of neutrophils prepared without exposure to LPS with chemoattractants induced fast up-regulation of N-formyl peptide receptors and C receptor type 3 (CR3). Biphasic N-formyl peptide binding curves were detected for saturating concentrations of N-formyl peptide at 37 degrees C. The bulk of the rapid binding during the first 30 to 60 s is attributed to already expressed binding sites whereas the slow binding over the next 3 to 4 min represents a time course of receptor up-regulation. Support for this interpretation comes from conditions under which the number of binding sites and the progress of the binding curves were affected. Cells treated with LPS, which caused expression of internal N-formyl peptide receptors, exhibited rapid, monophasic binding curves with increased total binding. In LPS-untreated, calcium-depleted cells, N-formyl peptide receptor up-regulation was inhibited and rapid, monophasic binding to a smaller total number of expressed sites was observed. Cytochalasin B enhanced the total number of available N-formyl peptide receptors in LPS-untreated but not LPS-treated cells. In both cases binding was rapid and monophasic suggesting that receptors were either fully or rapidly up-regulated. Although not studied in real-time, C receptor type 3 up-regulation was similar to N-formyl peptide receptor up-regulation in response to LPS, or stimulation by N-formyl peptide, C product C5a, leukotriene B4, and platelet-activating factor in isolated cells and in whole blood. After stimulation with formyl peptide, LPS, or C product 5a, the release of vitamin B12-binding protein paralleled up-regulation of receptors. These data indicate that untreated cells up-regulate N-formyl peptide receptors during cell response at a rate of approximately 10,000/min in a calcium-dependent manner whereas LPS-treated cells already express the bulk of their receptors. In cytochalasin B-treated, degranulating cells 30,000 to 50,000 receptors were up-regulated within a minute.
Factors affecting movement of F-actin filaments propelled by skeletal muscle heavy meromyosin (1992)

The measurement of fluorescent-labeled actin filament movement driven by mechanoenzymes (e.g., myosin) is an important methodology for the study of molecular motors. It is assumed that the filament velocity (Vf) is analogous to the unloaded shortening velocity (Vu) seen in muscle fibers. Methods are described to reproducibly quantitate the movement of these filaments and to select uniformly moving filaments and specify their Vf. Use of these techniques allowed comparison of Vf to literature values for Vu with regard to [ATP], [ADP], [Pi], pH, ionic strength (10-150 mM), and temperature (15-30 degrees C). Vf and Vu are quantitatively similar with respect to the effects of substrate and product concentrations and temperatures greater than 20 degrees C. However, Vf is more sensitive to decreases in pH and temperatures less than 20 degrees C than Vu. At ionic strengths of 50-150 mM, Vf and Vu exhibit similar ionic strength dependencies (decreasing with ionic strength). At ionic strengths less than 50 mM, Vf is markedly reduced. Results of experiments using adenosine 5'-O-(3-thiotriphosphate) suggest that increasing the number of weakly bound cross bridges does not seriously affect Vf. Thus, although Vf is a good analogue for Vu under certain conditions (elevated ionic strength and temperatures greater than 20 degrees C), under others it is not. The results of motility assays must be cautiously interpreted.
A fluorogenic assay using pressure-driven flow on a microchip (2001)

A fluorogenic assay for human T-cell phosphatase (TCPTP) was conducted on an etched glass microchip using pressure driven flow. The TCPTP enzyme catalyzes the removal of a phosphate group from 6,8-difluoro-4-methylumbelliferyl/phosphate (DiFMUP) to produce the fluorogenic product 6,8-difluoro-4-methylumbelliferone (DiFMU). Enzyme assays with real-time on-chip dilution were performed in both low-viscosity (1 cP) buffer and an enzyme solution containing 50% glycerol (6 cP). Single side channels connect a series of reagent wells to a main channel where the fluorescent product of the enzyme reaction passes the detector region. Flow regulation of mixed viscosity fluids requires a pressure control on each arm of the chip contributing to the overall flow. An 8-channel pressure controller was built to regulate the air pressure above all wells feeding channels of the chip, thereby controlling the dilution ratios of buffer, substrate and enzyme. Well pressures maintained a constant concentration of enzyme in the detector channel while adjusting the flow contribution of substrate and buffer. The substrate concentration was stepped over two orders of magnitude while verifying fluid dilutions using marker dyes. The kinetic parameters, Km, Vmax, and Kcat, showed good agreement with the values determined using a standard well plate and fluorometer.
Hemolysis and free hemoglobin revisited: exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins (2012)

Hemolysis occurs in many hematologic and nonhematologic diseases. Extracellular hemoglobin (Hb) has been found to trigger specific pathophysiologies that are associated with adverse clinical outcomes in patients with hemolysis, such as acute and chronic vascular disease, inflammation, thrombosis, and renal impairment. Among the molecular characteristics of extracellular Hb, translocation of the molecule into the extravascular space, oxidative and nitric oxide reactions, hemin release, and molecular signaling effects of hemin appear to be the most critical. Limited clinical experience with a plasma-derived haptoglobin (Hp) product in Japan and more recent preclinical animal studies suggest that the natural Hb and the hemin-scavenger proteins Hp and hemopexin have a strong potential to neutralize the adverse physiologic effects of Hb and hemin. This includes conditions that are as diverse as RBC transfusion, sickle cell disease, sepsis, and extracorporeal circulation. This perspective reviews the principal mechanisms of Hb and hemin toxicity in different disease states, updates how the natural scavengers efficiently control these toxic moieties, and explores critical issues in the development of human plasma-derived Hp and hemopexin as therapeutics for patients with excessive intravascular hemolysis.
PRESSURES GENERATED BY A BUBBLE CLOUD COLLAPSE (1984)

Abstract The collapse of a low density cloud of bubbles is studied using matched asymptotic expansions. Equations describing the motion and deformation of an individual bubble accounting for its interaction with the other bubbles in the cloud are derived. Numerical results for the case of a symmetrical cloud configuration show a dramatic increase of the pressure generated at the end of the collapse due to collective effects. This explains the observed high erosion associated with cloud cavitation. KEYWORDS: Cloud cavitationBubble interactionBubble dynamicsBubble collapseBubble cloud
Biochemical and functional effects of prenatal and postnatal omega 3 fatty acid deficiency on retina and brain in rhesus monkeys. (1986)

Docosahexaenoic acid [22:6 omega 3; 22:6-(4,7,10,13,16,19)] is the major polyunsaturated fatty acid in the photoreceptor membranes of the retina and in cerebral gray matter. It must be obtained either from the diet or by synthesis from other omega 3 fatty acids, chiefly alpha-linolenic acid (18:3 omega 3). We tested the effect of dietary omega 3 fatty acid deprivation during gestation and postnatal development upon the fatty acid composition of the retina and cerebral cortex and upon visual function. Rhesus monkeys (Macaca mulatta) were fed semipurified diets very low in 18:3 omega 3 throughout pregnancy, and their infants received a similar diet from birth. A control group of females and their infants received a semipurified diet supplying ample 18:3 omega 3. In near-term fetuses and newborn infants of the deficient group, the 22:6 omega 3 content of phosphatidylethanolamine was one-half of control values in the retina and one-fourth in cerebral cortex. By 22 months of age, the content of 22:6 omega 3 in these tissues approximately doubled in control monkeys, but it failed to increase in the deficient group. Low levels of 22:6 omega 3 in the deficient animals' tissues were accompanied by a compensatory increase in longer-chain omega 6 fatty acids, particularly 22:5 omega 6. Functionally, the deficient animals had subnormal visual acuity at 4-12 weeks of age and prolonged recovery time of the dark-adapted electroretinogram after a saturating flash. Abnormally low levels of 22:6 omega 3 may produce alterations in the biophysical properties of photoreceptor and neural membranes that may underlie these functional impairments. The results of this study suggest that dietary omega 3 fatty acids are retina and brain.
The long-period motion of the plane of a distant circular orbit (1964)

Abstract We consider Earth satellites in the region where the perturbing effects due to Earth’s oblateness and luni-solar gravitational forces are comparable. A general solution is obtained for simultaneous precession about any number of fixed axes; this is an extension of Laplace’s treatment for the motion of Iapetus about Saturn. Results are given for general orbits on the assumption that the lunar orbit lies in the ecliptic. Synchronous orbits are considered in greater detail.
Effect of Puromycin Analogues and Other Agents on Peptidyl-Puromycin Synthesis on Polyribosomes (1973)

The incorporation of [(3)H]puromycin into nascent polypeptide chains of polyribosomes has proved to be a sensitive method of evaluating effects of inhibitors on peptide bond synthesis. Several analogues of puromycin were found to react with polyribosomes from both bacteria and rat liver. The K(m) for puromycin is 4 muM with bacterial polyribosomes; under the same conditions, the K(i) for psi-hydroxy-puromycin (6-dimethylamino-9-[3-(l-beta-phenyllactylamino)-3-deoxy-beta- d-ribofuranosyl] purine) is 240 muM and for a carbocyclic analogue of puromycin (6-dimethylamino-9- {R- [2R-hydroxy-3R- (p-methoxyphenyl-l-alanylamino)]-cyclopentyl}purine) is 1 muM. Both were found to be competitive inhibitors of puromycin. The K(m) for C-A-C-C-A(Phe) is 250 muM. In addition, the dissociation constant for C-A-C-C-A(Phe) binding to washed ribosomes was found to be 1 and 0.03 muM in the absence and presence, respectively, of 20% (vol/vol) ethanol. The results with these analogues lead to the following conclusions. Substitution of a hydroxyl group for the alpha-amino group of puromycin results in an active analogue with about one-sixtieth the affinity of puromycin in the reaction. Omission of the 5'-hydroxymethyl group or substitution of the furanosyl ring oxygen by a carbon atom in the carbocyclic analogue reduces its activity compared with puromycin only slightly. Additionally, the relatively high K(m) for C-A-C-C-A(Phe) as an acceptor compared with puromycin suggests the existence of a protective mechanism on polyribosomes, which prevents aminoacyl-transfer ribonucleic acid (tRNA) free in solution from stripping nascent chains from polyribosomes so that only aminoacyl-tRNA bound to ribosomes through the appropriate coding mechanism can form a peptide bond.