gebhart/patrepeval huggingface dataset:
Adaptive Garbage Collection for Battery-Operated Environments (2002)

Energy is an important constraint for battery-operated embedded Java environments. In this work, we show how the garbage collector (GC) can be tuned to reduce the energy consumption of Java applications. In particular, we show the importance of tuning the frequency of invoking GC based on object allocation and garbage creation rates to optimize leakage energy consumption. We reduce the leakage energy by exploiting the supplygated leakage power optimization that is controlled by the GC. In this mechanism, power supply to memory banks that do not hold any useful data can be shut down. We implement a new adaptive GC mechanism within Sun&amp;apos;s KVM that optimizes the ability to shut down more banks. An evaluation of our approach using various embedded applications shows that the adaptive garbage collection scheme is effective in reducing the system energy consumption across different hardware configurations.
Characterization of a recombinant type II 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Helicobacter pylori (2005)

DAH7P (3-Deoxy-D-arabino-heptulosonate 7-phosphate) synthase catalyses the condensation reaction between phosphoenolpyruvate (PEP) and D-erythrose 4-phosphate (E4P) as the first committed step in the biosynthesis of aromatic compounds in plants and micro-organisms. Previous work has identified two families of DAH7P synthases based on sequence similarity and molecular mass, with the majority of the mechanistic and structural studies being carried out on the type I paralogues from Escherichia coli. Whereas a number of organisms possess genes encoding both type I and type II DAH7P synthases, the pathogen Helicobacter pylori has only a single, type II, enzyme. Recombinant DAH7P synthase from H. pylori was partially solubilized by co-expression with chaperonins GroEL/GroES in E. coli, and purified to homogeneity. The enzyme reaction follows an ordered sequential mechanism with the following kinetic parameters: K(m) (PEP), 3 microM; K(m) (E4P), 6 microM; and kcat, 3.3 s(-1). The enzyme reaction involves interaction of the si face of PEP with the re face of E4P. H. pylori DAH7P synthase is not inhibited by phenylalanine, tyrosine, tryptophan or chorismate. EDTA inactivates the enzyme, and activity is restored by a range of bivalent metal ions, including (in order of decreasing effectiveness) Co2+, Mn2+, Ca2+, Mg2+, Cu2+ and Zn2+. Analysis of type II DAH7P synthase sequences reveals several highly conserved motifs, and comparison with the type I enzymes suggests that catalysis by these two enzyme types occurs on a similar active-site scaffold and that the two DAH7P synthase families may indeed be distantly related.
Pharmacokinetics and in vivo stability of intraperitoneally administered therapeutic antibody catumaxomab (2008)

14006 Background: The EpCAM-specific trifunctional rat/mouse hybrid antibody catumaxomab simultaneously activates T cells and Fcγ-receptor positive immune cells redirecting them against the tumor. In a phase II/III randomized study catumaxomab significantly prolonged puncture free survival and time to progression in cancer patients (pts) with symptomatic ascites. Here, the results of the corresponding pharmacokinetic trial are presented. Methods: The pharmacokinetics of catumaxomab were evaluated in a phase II, open- label, multi-centre study in 13 pts with malignant ascites requiring paracentesis. Four intraperitoneal (i.p.) infusions of 10, 20, 50 and 150 μg catumaxomab were administered within 11 days. Antibody concentrations were quantified by a high-sensitivity ELISA in ascites and plasma to determine local and systemic exposure. Immunological activity of catumaxomab was measured using a potency assay. Anti-drug antibody (ADA) development was monitored applying a bridging ELISA. Results: 10 pts receiving all four infusions were evaluable. Increasing concentrations (C) of free catumaxomab were detected in ascites fluid during the course of the treatment. Median Cascites before the last infusion was 6121 pg/ml. Systemic exposure was observed in 9 pts with median Cmax of 403 pg/ml. High inter-individual variability was demonstrated by Area Under the Curve AUC0-tlast values ranging between 0 and 10,020 day*pg/ml (median = 2,045). There was no correlation between safety parameters and systemic C. Elimination half life t1/2 was 2.13 days in mean. The therapeutic antibody exhibited remarkable in vivo stability remaining almost fully immunologically active (80–100%) even after three days of circulation in ascites. Also systemic catumaxomab in plasma still revealed 50–60% bioactivity. None of the pts developed significant ADA responses (> 100 ng/ml) until the time of last infusion. Conclusions: The relatively long t1/2 of 2.13 days and the high in vivo stability of immunologically active catumaxomab support its observed clinical efficacy. High local C, minor systemic exposure with an acceptable safety profile and ADA onset not until the last i.p. infusion confirm the appropriateness of the chosen dosing scheme. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Fresenius Biotech, Trion Pharma, Trion Research Trion Pharma, Trion Research
Human Hand Function (2006)

1. Historical Overview and general introduction 2. Evolutionary development and anatomy of the hand 3. Sensory neurophysiology 4. Tactile sensing 5. Active haptic sensing 6. Prehension 7. Non-prehensile skilled movements 8. End-effector constraints 9. Hand function across the lifespan 10. Applications 11. Summary, conclusions and future directions
The Cationic Cell-Penetrating Peptide CPPTAT Derived from the HIV-1 Protein TAT Is Rapidly Transported into Living Fibroblasts:  Optical, Biophysical, and Metabolic Evidence (2004)

Cell-penetrating peptides (CPPs) are cationic peptides which, when linked to genes, proteins, or nanoparticles, facilitate the transport of these entities across the cell membrane. Despite their potential use for gene transfer and drug delivery, the mode of action of CPPs is still mysterious. It has even been argued that the observed transport across the cell membrane is an artifact caused by chemical fixation of the cells, a common preparation method for microscopic observation. Here we have synthesized a fluorescent derivative of the HIV-1 TAT protein transduction domain [Fg-CPP(TAT(PTD))] and have observed its uptake into nonfixated living fibroblasts with time-lapse confocal microscopy, eliminating the need for fixation. We observe that Fg-CPP(TAT(PTD)) enters the cytoplasm and nucleus of nonfixated fibroblasts within seconds, arguing against the suggested artifact of cell fixation. Using differential interference contrast microscopy, dense aggregates are detected on the cell surface. Several observations suggest that these aggregates consist of Fg-CPP(TAT(PTD)) bound to membrane-associated heparan sulfate (HS). The aggregates grow in parallel with Fg-CPP(TAT(PTD)) uptake and are detected only on fibroblasts showing Fg-CPP(TAT(PTD)) uptake. These observations resemble earlier reports of "capping" of cell surface molecules combined with a polarized endocytotic flow. Enzymatic removal of extracellular HS reduced the rate of both Fg-CPP(TAT(PTD)) uptake and aggregate formation, demonstrating that HS is involved in the uptake mechanism. The functionality of the fibroblasts during the CPP uptake was investigated with a cytosensor microphysiometer measuring the extracellular acidification rate (ECAR). Short exposures (2.5 min) to the CPP reduced the ECAR which was, however, reversible upon reperfusion with buffer only. In contrast, no recovery to baseline values was observed after repeated exposures to the CPP, suggesting that the CPP is toxic in long-term applications.
RNA Stable Isotope Probing, a Novel Means of Linking Microbial Community Function to Phylogeny (2002)

Identifying microorganisms responsible for recognized environmental processes remains a great challenge in contemporary microbial ecology. Only in the last few years have methodological innovations provided access to the relationship between the function of a microbial community and the phylogeny of the organisms accountable for it. In this study stable-isotope-labeled [13C]phenol was fed into a phenol-degrading community from an aerobic industrial bioreactor, and the 13C-labeled RNA produced was used to identify the bacteria responsible for the process. Stable-isotope-labeled RNA was analyzed by equilibrium density centrifugation in concert with reverse transcription-PCR and denaturing gradient gel electrophoresis. In contradiction with findings from conventional methodologies, this unique approach revealed that phenol degradation in the microbial community under investigation is dominated by a member of the Thauera genus. Our results suggest that this organism is important for the function of this bioreactor.
Phosphorylation of connexin43 in cells containing mutant src oncogenes. (1992)

Disruption of gap junctional communication (measured by intercellular dye transfer) in cultured fibroblasts by pp60v-src is correlated with phosphorylation of the gap junction protein, connexin43 (cx43), on tyrosine. In this report, we examine the functional relevance of these observations by studying cx43 phosphorylation in cells containing kinase-active, non-myristylated pp60(2A527F) or pp60v-src temperature sensitive (ts) for transformation. Non-transformed cells expressing pp60(2A527F) transferred fluorescent dye at high levels and contained cx43 that was phosphorylated predominately on serine. In contrast, cells transformed by kinase-active, myristylated pp60(527F) did not transfer dye and contained cx43 proteins which were phosphorylated on serine and tyrosine. Additionally, activation of ts pp60v-src tyrosine kinase activity upon shift of cells to the permissive temperature was correlated with a rapid increase in the phosphorylated tyrosine content of cx43 proteins and loss of gap junctional communication. These combined results suggested that cx43 is a substrate of pp60v-src whose phosphorylation on tyrosine may be involved in the disruption of gap junctional communication observed in Rous sarcoma virus (RSV)-transformed cells.
Food nanotechnology &ndash; an overview (2010)

Food nanotechnology is an area of emerging interest and opens up a whole universe of new possibilities for the food industry. The basic categories of nanotechnology applications and functionalities currently in the development of food packaging include: the improvement of plastic materials barriers, the incorporation of active components that can deliver functional attributes beyond those of conventional active packaging, and the sensing and signaling of relevant information. Nano food packaging materials may extend food life, improve food safety, alert consumers that food is contaminated or spoiled, repair tears in packaging, and even release preservatives to extend the life of the food in the package. Nanotechnology applications in the food industry can be utilized to detect bacteria in packaging, or produce stronger flavors and color quality, and safety by increasing the barrier properties. Nanotechnology holds great promise to provide benefits not just within food products but also around food products. In fact, nanotechnology introduces new chances for innovation in the food industry at immense speed, but uncertainty and health concerns are also emerging. EU/WE/global legislation for the regulation of nanotechnology in food are meager. Moreover, current legislation appears unsuitable to nanotechnology specificity.
The 5'-terminal sequence of the hepatitis C virus genome. (1990)

The 5'-terminal sequence of the genome of hepatitis C virus (HCV) was determined for two distinct HCV strains in human and chimpanzee carriers. It had a 5'-noncoding region of at least 324 nucleotides, well preserved by the two strains with a high homology (99.1%), followed by 1348 nucleotides that continued to the documented sequence of prototype HCV spanning 7310 nucleotides (European Patent Application #88310922.5). Based on these results, HCV is considered to possess an uninterrupted open reading frame encoding at least 2886 amino acid residues. Two structural genes were postulated on the 5'-terminal sequence of the HCV genome. One gene in the upstream region, highly conserved by the two strains at the amino acid level and rich in basic amino acids such as arginine, appeared to encode the viral capsid protein. The other gene in the downstream region was divergent between the two strains at both nucleotide and amino acid levels. It coded for nine potential N-glycosylation sites, and was considered to encode the viral envelope protein. Disclosure of the 5'-terminal sequence of the HCV genome would facilitate its taxonomic classification, and contribute toward immunological diagnosis of infection and development of vaccines.
Protein flexibility and rigidity predicted from sequence (2005)

Structural flexibility has been associated with various biological processes such as molecular recognition and catalytic activity. In silico studies of protein flexibility have attempted to characterize and predict flexible regions based on simple principles. B-values derived from experimental data are widely used to measure residue flexibility. Here, we present the most comprehensive large-scale analysis of B-values. We used this analysis to develop a neural network-based method that predicts flexible-rigid residues from amino acid sequence. The system uses both global and local information (i.e., features from the entire protein such as secondary structure composition, protein length, and fraction of surface residues, and features from a local window of sequence-consecutive residues). The most important local feature was the evolutionary exchange profile reflecting sequence conservation in a family of related proteins. To illustrate its potential, we applied our method to 4 different case studies, each of which related our predictions to aspects of function. The first 2 were the prediction of regions that undergo conformational switches upon environmental changes (switch II region in Ras) and the prediction of surface regions, the rigidity of which is crucial for their function (tunnel in propeller folds). Both were correctly captured by our method. The third study established that residues in active sites of enzymes are predicted by our method to have unexpectedly low B-values. The final study demonstrated how well our predictions correlated with NMR order parameters to reflect motion. Our method had not been set up to address any of the tasks in those 4 case studies. Therefore, we expect that this method will assist in many attempts at inferring aspects of function.
Unique Structure−Activity Relationship for 4-Isoxazolyl-1,4-dihydropyridines (2002)

A series of 4-isoxazolyl-1,4-dihydropyridines (IDs) were prepared and characterized, and their interaction with the calcium channel was studied by patch clamp analysis. The structure-activity relationship (SAR) that emerges is distinct from the 4-aryldihydropyridines (DHPs), and affinity increases dramatically at higher holding potentials. Thus, among the 3'-arylisoxazolyl analogues p-Br > p-Cl >> p-F, and p-Cl > m-Cl > o-Cl >> o-MeO. Four of the analogues were examined by single-crystal X-ray diffractometry, and all were found to adopt an O-exo conformation in the solid state. The calculated barrier to rotation, however, suggests that rotation about the juncture between the heterocyclic rings is plausible under physiological conditions. A variable-temperature NMR study confirmed the computation. With Striessnig's computational sequence homologation procedure, a working hypothesis was derived from the data that explains the unique SAR for IDs.
Modulation of murine radiation-induced fibrosarcoma-1 tumor metabolism and blood flow in situ via glucose and mannitol administration monitored by 31P and 2H nuclear magnetic resonance spectroscopy. (1991)

The hyperglycemia-induced in situ metabolism and blood flow changes produced in s.c. implanted murine radiation-induced fibrosarcoma-1 tumors, grown on the flanks of female C3H/HeJ mice, were examined with 31P and 2H nuclear magnetic resonance. Initial experiments verified a hyperglycemic tumor acidification similar to that reported earlier with a different substrain of mice, C3H/AnF (J.L. Evelhoch et al., Proc. Natl. Acad. Sci. USA, 81: 6496-6500, 1984). Changes in the tumor pH, phosphorus metabolites, and blood flow were then compared after administration of saline, glucose, or mannitol (a nonmetabolizable glucose analogue) using a mole-equivalent dose of the sugars (i.e., 0.8 mmol/20g mouse). Neither saline (n = 8) nor mannitol (n = 6) administration had any marked effect upon tumor pH, whereas glucose administration produced a mean maximum tumor pH reduction of 0.74 +/- 0.09 (SE; n = 9) during the 2.5 h post-glucose injection. No significant changes in high energy phosphate concentrations were observed during the same period after saline injection. After glucose injection, the [phosphocreatine] gradually decreased by 64% (P = 0.0001). After the initial 1 h post-glucose injection, the [inorganic phosphate] increased by 58% (P = 0.0001), and the [nucleoside triphosphates] decreased by 29% (P = 0.0001) during the following 1.5 h. After mannitol injection, while there was no change in [inorganic phosphate] over time (P = 0.37), the [phosphocreatine] decreased by 33% (P = 0.0001) and the [nucleoside triphosphates] decreased by 21% (P = 0.0015) within 20 min, then both the [phosphocreatine] and [nucleoside triphosphates] remained at constant levels during the following 2 h. In parallel experiments, the volumetric rate of tumor blood flow and perfusion was measured by 2H nuclear magnetic resonance monitoring of 2H2O washout kinetics (S-G. Kim and J. J. H. Ackerman, Cancer Res., 48: 3449-3453, 1988); tumor blood flow decreased by 80% (P = 0.0001, n = 11), 60% (P = 0.0031, n = 4), and 20% (P = 0.058, n = 10) at 2 h after glucose, mannitol, or saline injections, respectively. These results suggest that anaerobic glycolysis is a requirement for hyperglycemic tumor acidification. However, the decrease in tumor blood flow accompanying hyperglycemic acidification suggests that flow reduction also may be a contributing or a required cofactor for acidification via inhibition of lactic acid egress.(ABSTRACT TRUNCATED AT 400 WORDS)
Pericardial heterografts: a comparative study of suture pull-out and tissue strength (1989)

The force required to pull sutures out of glutaraldehyde fixed bovine pericardium, for four different suture bites: 0.5 mm, 1 mm, 1.5 mm and 2.0 mm, was compared with the tissue strength. The mean suture pull-out force was significantly lower than the tissue strength for all bites, with a minimum value of 2.86 +/- 1.02 N for the 0.5 mm bite and a maximum value of 6.32 +/- 0.77 N for the 2.0 mm bite. The mean force which produced failure of the chemically modified pericardium was 15.49 +/- 8.48 N. The mean force at pull-out of the sutures lay on a regression line: force at failure = 1.68 + 2.25 x Bite. A video film of the experiments showed that the suture does not cut through the pericardium. It pulls a V-shaped band of collagen fibre bundles through the stationary pericardium. Eventually this band breaks away from the free edge of the tissue specimen. The specimens under uniaxial load failed by laminate debonding of two layers of tissue, rupture of the serosal surface layer followed by shear and fibre slippage. These results indicate that any suture which bears load, during the normal functioning of a heart valve substitute, will be a source of weakness, compared to the overall tissue strength. As a consequence the alignment/holding suture of the Standard Ionescu-Shiley valve and the modified stitch of the low profile valve are likely to be potential sites of fatigue failure.
Connective tissue growth factor: a mediator of TGF-β action on fibroblasts (1997)

Connective tissue growth factor (CTGF) is a cysteine-rich mitogenic peptide that binds heparin and is secreted by fibroblasts after activation with transforming growth factor beta (TGF-beta). CTGF is a member of a highly conserved family of peptides that include immediate early gene products cef10, cyr61, fisp12; a putative avian proto-oncogene, nov; and a drosophila gene, twisted gastrulation, tsg, that controls medial mesoderm induction during dorsal-ventral axis pattern formation, a process also controlled by TGF-beta related peptides (dpp, scw). In the adult mammal, CTGF functions as a downstream mediator of TGF-beta action on connective tissue cells, where it stimulates cell proliferation and extracellular matrix synthesis. CTGF does not appear to act on epithelial cells or immune cells. Because the biological actions of TGF-beta are complex and affect many different cell types, CTGF may serve as a more specific target for selective intervention in processes involving connective tissue formation during wound repair or fibrotic disorders. Northern blot and in situ hybridization studies have demonstrated that CTGF is coordinately expressed with TGF-beta in every fibrotic disorder examined to date. Agents that inhibit CTGF production or action could lead to the development of new therapeutic approaches for the control of fibrotic disorders in humans.
Structure-activity relationships of dimeric Catharanthus alkaloids. 2. Experimental antitumor activities of N-substituted deacetylvinblastine amide (vindesine) sulfates (1979)

While structure-activity relationships for vinblastine (VLB), vincristine, deacetyl-VLB, and deacetyl-VLB amide (vindesine, VDS) in several tumor and leukemia models have been reported previously, the present study explores these relationships for a series of N-substituted vindesine analogues. These compounds were prepared from the reaction of deacetyl-VLB acid azide with the appropriate amines and were characterized by mass spectral analysis, 1H and 13C NMR spectra, electrometric titration, and infrared spectra. N-Alkylvindesines have reduced activity compared to that of VDS against the Gardner lymphosarcoma (GLS). N-beta-Hydroxyethyl-VDS surpasses vindesine in its activity against the Ridgway osteogenic sarcoma and the GLS, whereas against the B16 melanoma it is less active than VDS. N-beta-(4-Hydroxyphenethyl)-VDS, envisaged as a substrate for the enzyme tryosinase, was shown to be more active than VDS against the B16 melanoma but has only marginal activity against the GLS. In terms of collective antitumor activity against the model systems used, vindesine emerges as the congener with optimum qualities. Bis(N-ethylidenevindesine) disulfide, the first example of a bridged bisvindesine and comparable to VDS in its antitumor profile, shows evidence of activity against a P388/VCR leukemia strain known to be resistant to maytansine as well as to vincristine.
Sketching interfaces: toward more human interface design (2001)

Researchers at University of California, Berkeley and Carnegie Mellon University have designed, implemented, and evaluated SILK (Sketching Interfaces Like Krazy), an informal sketching tool that combines many of the benefits of paper-based sketching with the merits of current electronic tools. With SILK, designers can quickly sketch an interface using an electronic pad and stylus, and SILK recognizes widgets and other interface elements as the designer draws them. Unlike paper-based sketching, however, designers can exercise these elements in their sketchy state. For example, a sketched scroll-bar is likely to contain an elevator or thumbnail, the small rectangle a user drags with a mouse. In a paper sketch, the elevator would just sit there, but in a SILK sketch, designers can drag it up and down, which lets them test component or widget behavior. SILK also supports the creation of storyboards-the arrangement of sketches to show how design elements behave, such as how a dialog box appears when the user activates a button. Storyboards are important because they give designers a way to show colleagues, customers, or end users early on how an interface will behave.