gebhart/patrepeval huggingface dataset:
Kinetic Investigation of the a‐Chymotrypsin‐Catalyzed Hydrolysis of Peptide Substrates (1982)

Peptide substrates of the general structure Ac‐Tyr‐L y1 ‐L y2 …‐L ym ‐NH 2 and Ac‐Phe‐L y1 ‐NH 2 have been synthesized and subjected to α‐chymotrypsin‐catalyzed hydrolysis to collect information on the interactions between the enzyme active site and the amino‐acid residues L yl , L y2 , etc., C‐terminal to the susceptible bond of the peptide. For this purpose changes in the dissociation constants of the enzyme‐substrate complexes and in the rate constants of acylation have been related to the structural variations of the substrates. The results indicate that interactions occur with the two residues next to the scissible bond, L y1 and L y2 , but not with residue L y3 . Structural description of individual interactions was carried out with the aid of skeletal models of the active site. From such combination of kinetic and structural data a plausible interaction scheme for the substrate side C‐terminal to the scissible bond has been deduced. This interaction scheme, which defines conformation and orientation of this part of the substrate within the active site, is characterized by the presence of a single hydrogen bond occurring between NH(L y2 ) and O(Phe‐41). No donor interacting with the back‐bone carbonyl groups of residues L y1 and L y2 could be detected in the model of α‐chymotrypsin. The effect of modification of the side chains of residues L yl and L y2 on the kinetic constants was shown to be consistent with the interactions assumed to occur between the side chains of these residues and the active site. The interpretation of the results obtained from these specificity studies have led to refined concepts concerning the relative importance of different sets of enzyme‐substrate interactions in determining reactivity.
Individual differences in anterior brain asymmetry and fundamental dimensions of emotion. (1992)

This research assessed whether individual differences in anterior brain asymmetry are linked to differences in basic dimensions of emotion. In each of 2 experimental sessions, separated by 3 weeks, resting electroencephalogram (EEG) activity was recorded from female adults during 8 60-s baselines. Mean alpha power asymmetry across both sessions was extracted in mid-frontal and anterior temporal sites. Across both regions, groups demonstrating stable and extreme relative left anterior activation reported increased generalized positive affect (PA) and decreased generalized negative affect (NA) compared with groups demonstrating stable and extreme relative right anterior activation. Additional correlational analyses revealed robust relations between anterior asymmetry and PA and NA, particularly among subjects who demonstrated stable patterns of EEG activation over time. Anterior asymmetry was unrelated to individual differences in generalized reactivity.
Pti4 Is Induced by Ethylene and Salicylic Acid, and Its Product Is Phosphorylated by the Pto Kinase (2000)

Yong-Qiang Gu, Caimei Yang, Venkatappa K. Thara, Jianmin Zhou, Gregory B. Martin, Pti4 Is Induced by Ethylene and Salicylic Acid, and Its Product Is Phosphorylated by the Pto Kinase, The Plant Cell, Vol. 12, No. 5 (May, 2000), pp. 771-785
Blocked element compensation in phased array imaging (1993)

In clinical applications using large apertures, a significant number of phased array elements may be blocked due to discontinuous acoustic windows into the body. These blocked elements produce undesired beamforming artifacts, degrading spatial and contrast resolution. To minimize these artifacts, an algorithm using multiple receive beams and the total-least-squares method is proposed. Simulations and experimental results show that this algorithm can effectively reduce imperfections in the point spread function of the imager. Combined with first-and second-order scatterer statistics derived from multiple receive beams, the algorithm is modified for blocked element compensation on distributed scattering sources. Results also indicate that compensated images are comparable to full array images, and that even full array images can be improved by removing undesired sidelobe contributions. This method, therefore, can enhance detection of low contrast lesions using large phased-array apertures.
ASAP7: A 7-nm finFET predictive process design kit (2016)

We describe a 7-nm predictive process design kit (PDK) called the ASAP7 PDK, developed in collaboration with ARM Ltd. for academic use. The PDK is realistic, based on current assumptions for the 7-nm technology node, but is not tied to any specific foundry. The initial version assumes EUV lithography for key layers, a decision based on its present near cost-effectiveness and resulting simpler layout rules. Non-EUV layers assume appropriate multiple patterning schemes, i.e., self-aligned quadruple patterning (SAQP), self-aligned double patterning (SADP) or litho-etch litho-etch (LELE), based on 193-nm optical immersion lithography. The specific design rule derivation is explained for key layers at the front end of line (FEOL), middle of line (MOL), and back end of line (BEOL) of the predictive process modeled. The MOL and BEOL DRC rules rely on estimation of time dependent dielectric breakdown requirements using layer alignments determined with projected machine to machine overlay assumptions, with significant guard-bands where possible. A high density, low-power standard cell architecture, developed using design/technology co-optimization (DTCO), as well as example SRAM cells are shown. The PDK transistor electrical assumptions are also explained, as are the FEOL design rules, and the models include basic design corners. The transistor models support four threshold voltage (Vth) levels for both NMOS and PMOS transistors. Cadence Virtuoso technology files and associated schematic and layout editing, as well as netlisting are supported. DRC, LVS, and full parasitic extraction is enabled through Mentor Calibre decks.
Expression of Biologically Active Human TRAIL in Transgenic Pigs (2005)

Ubiquitous expression of human TRAIL was achieved in transgenic pigs without detrimental side effects. Pigs expressing biologically active human TRAIL will be used for future xenotransplantation experiments to modulate primate anti-pig cellular immune responses.
Regenerative Engineering (2012)

The future of tissue regeneration lies in “regenerative engineering,” with biomaterials playing a key role.
Nucleation and growth of carbon nanotubes by microwave plasma chemical vapor deposition (2000)

The nucleation and growth of aligned multiwall carbon nanotubes by microwave plasma-enhanced chemical vapor deposition have been studied. The nanotubes nucleate and grow from catalytic cobalt islands on a silicon substrate surface, with both their diameter and length dependent on the size of the cobalt islands. Electron microscopy reveals that the nanotubes grow via a “base growth” mechanism. The nanotubes grow initially at a very rapid and constant rate (∼100 nm/s) that decreases sharply after the catalyst Co particles become fully encapsulated by the nanotubes. We propose a detailed model to explain these experimental observations on nucleation and growth of nanotubes.
An Electrochemical Method for Making Enzyme Microsensors. Application to the Detection of Dopamine and Glutamate (1997)

A novel method of microbiosensor fabrication is described. It is based on the electrochemical polymerization of an enzyme-amphiphilic pyrroleammonium solution on the surface of a microelectrode in the absence of supporting electrolyte. By trapping glutamate oxidase (GMO) or polyphenol oxidase (PPO) in such polypyrrole films, we made microbiosensors for the amperometric determination of glutamate or dopamine, respectively. The response of the GMO microelectrode to glutamate was based on the amperometric detection of the enzymically generated hydrogen peroxide at 0.6 V vs SCE. The detection limit and sensitivity of this microbiosensor were 1 μM and 32 mA M(-1) cm(-2), respectively. The response of the PPO microelectrode to dopamine was based on the amperometric detection of the enzymically generated quinoid product at -0.2 V. The calibration range for dopamine measurement was 5 × 10(-8)-8 × 10(-5) M and the detection limit and sensitivity were 5 × 10(-8) M and 59 mA M(-1) cm(-2), respectively.
Impact of naproxen sodium at over-the-counter doses on cyclooxygenase isoforms in human volunteers (2008)

Administration of naproxen sodium at OTC doses was associated with a profound inhibition of both COX enzymes. Although low-dose naproxen may elicit a virtually complete COX-1 inhibition in some individuals, it does not mimic the reliable, sustained and complete COX-1 blockade produced by aspirin. In conclusion, prolonged treatment with 220 mg naproxen sodium b.i.d. is not expected to provide sufficient cardioprotection in all patients, but may influence platelet function in some.
Repetitive Bilateral Arm Training With Rhythmic Auditory Cueing Improves Motor Function in Chronic Hemiparetic Stroke (2000)

-Six weeks of BATRAC improves functional motor performance of the paretic upper extremity as well as a few changes in isometric strength and range of motion. These benefits are largely sustained at 8 weeks after training cessation.
A non-invasive method of measuring concentrations of rubidium in rat skeletal muscle in vivo by 87Rb nuclear magnetic resonance spectroscopy: implications for the measurement of cation transport activity in vivo (1990)

1. We have used n.m.r. spectroscopy to measure rubidium concentrations in the skeletal muscle of live intact rats. Using a 1.9 T superconducting magnet and an ear-phone coil tuned to both protons (1H) and rubidium (87Rb), it was possible to make measurements of both tissue rubidium content and water content, and from these measurements to obtain the rubidium concentration. 2. The n.m.r. estimate of rubidium concentration in muscle in vivo was found to be a constant 31% (SEM 4%) of that estimated by flame atomic absorption spectroscopy in an extract of excised muscle. This is close to the predicted theoretical n.m.r. visibility of 33%. The visibility was constant for muscle rubidium concentrations ranging between 10 and 34 mmol/l. 3. Rubidium concentration measurement by this method is unaffected by variations in sample geometry, sample volume, tissue conductivity, coil tuning and amplifier gain. 4. By using this method to measure changes in tissue rubidium concentration with time in the same animal, it should now be possible to assess the activity of ion transport systems, such as sodium- and potassium-activated adenosine triphosphatase in vivo, by measuring the rates of change of tissue rubidium concentrations during the administration of rubidium salts. 5. This method could also be used to measure the absolute concentration of any n.m.r.-visible nucleus and could be applied to man.
Getting StartED with Windows 7 (2010)

To my Mom, who set the ball rolling by buying me my first computer many years ago, and to my wife, for all her love and support.
User Profiling for Energy Optimisation in Mobile Cloud Computing (2015)

Both mobile and cloud computing are two areas which are rapidly expanding in terms of use case and functionality.Both mobile and cloud computing are two areas which are rapidly expanding in terms of use case and functionality. This paper reviews current work in energy consumption of mobile cloud computing and then proposes a system whereby user applications may be profiled for their resource consumption locally and then if augmentation is required, they may negotiate with an external cloud for optimum energy consumption. Such a system is particularly useful for cloudlets which contain constrained resources so may need to choose between a number of clients. Whilst mobile computing enables a variety of feature rich functionality for users in a non-fixed location, cloud computing is revolutionising the way in which computing resources are being provisioned, used and optimised for both service providers and end users. These two fields are being combined in order to provide greater functionality for mobile devices in a number of different ways. Augmentation of mobile resources from the cloud has been shown as one way in which the energy consumption and power of mobile devices may be considerably enhanced. However, due to the resource constrained nature of the devices, in particular their power source and communication interfaces, there is often a fine line where offloading of these resources is economical.
Chimeric Antigen Receptor T Cells with Dissociated Signaling Domains Exhibit Focused Antitumor Activity with Reduced Potential for Toxicity In Vivo (2013)

Adoptive immunotherapy using T lymphocytes genetically modified to express a chimeric antigen receptor (CAR-T) holds considerable promise for the treatment of cancer. However, CAR-based therapies may involve on-target toxicity against normal tissues expressing low amounts of the targeted tumor-associated antigen (TAA). To specify T cells for robust effector function that is selective for tumor but not normal tissue, we developed a trans-signaling CAR strategy, whereby T-cell activation signal 1 (CD3z) is physically dissociated from costimulatory signal 2 (CD28) in two CARs of differing antigen specificity: mesothelin and a-folate receptor (FRa). Human T cells were genetically modified to coexpress signal 1 (anti-Meso scFv-CD3z) and signal 2 (anti-FRa scFv-CD28) CARs in trans. Trans-signaling CAR-T cells showed weak cytokine secretion against target cells expressing only one TAA in vitro, similar to first-generation CAR-T cells bearing CD3z only, but showed enhanced cytokine secretion upon encountering natural or engineered tumor cells coexpressing both antigens, equivalent to that of second-generation CAR-T cells with dual signaling in cis. CAR-T cells with dual specificity also showed potent anticancer activity and persistence in vivo, which was superior to first-generation CAR-T cells and equivalent to second-generation CARs. Importantly, second-generation CAR-T cells exhibited potent activity against cells expressing mesothelin alone, recapitulating normal tissue, whereas trans-signaling CAR-T cells did not. Thus, a dual specificity, trans-signaling CAR approach can potentiate the therapeutic efficacy of CAR-T cells against cancer while minimizing parallel reactivity against normal tissues bearing single antigen.
Marker gene expression driven by the maize ubiquitin promoter in transgenic wheat (2000)

Summary Selecting a promoter for driving transgene expression is one of the most important factors to consider in a transformation project. Information about the native regulation of the promoter activity is important, but it is also necessary to consider how that activity will be affected when integrated into the genome of the transformed plants. Study of a promoter performance in individually transformed lines provides useful information in this area. The maize ubiquitin 1 (Ubi‐1) promoter has been widely used to drive constitutive transgene expression in monocotyledonous plants. However, lack of data on its activity in individual transformed wheat lines constitutes a gap in the understanding and predictability of this promoter's performance. In this paper, we began addressing this problem by examining the expression of the marker gene uid A, coding for β‐glucuronidase (GUS), under the control of the maize Ubi‐1 promoter in individual transgenic wheat ( Triticum aestivum L.) lines from different wheat varieties. The expression of uid A driven by this promoter depended to a great extent on the specific transformation event. Whilst expression was strong and constitutive in all tissues in some of the lines analysed, there were also transgenic lines in which GUS activity was restricted to only a few tissues. In general the maize Ubi‐1 promoter had strong activity in young, metabolically active tissues and in pollen grains.
Hepatoprotective effects of the dual peroxisome proliferator-activated receptor alpha/delta agonist, GFT505, in rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (2013)

The dual PPAR-α/δ agonist, GFT505, is a promising liver-targeted drug for treatment of NAFLD/NASH. In animals, its protective effects are mediated by both PPAR-α-dependent and -independent mechanisms.
Masitinib mesylate in imatinib-resistant advanced GIST: A randomized phase II trial. (2012)

10007 Background: Masitinib is an oral tyrosine kinase inhibitor with greater in vitro activity and selectivity than imatinib against wild-type and juxtamembrane mutations of KIT (Dubreuil, 2009, PLoSONE). This trial studied efficacy and safety of masitinib at 12 mg/kg/day and sunitinib at 50 mg/day for the treatment of imatinib-resistant GIST. Methods: Patients with inoperable, locally advanced or metastatic GIST and showing disease progression while treated with imatinib 400 mg/day received either masitinib or sunitinib until progression. Primary endpoint was PFS evaluated with RECIST with OS as a secondary endpoint. Based upon an 80% power to detect with a Fleming design a median PFS ≥3 months (alpha 10%, unilateral), a population of 44 patients (22 per arm) was required. Stratification was applied based on mutation status. Results: 44 patients (exon 11 [66%], exon 9 [11%], wild-type or other [5%], not done at baseline [18%]) were randomized into masitinib (n=23) or sunitinib (n=21) treatment-arms from 9 centers between 02/2009 and 09/2011. After a median follow-up of 14 months, median PFS was 3.9 months (95%CI [2.6;8.1]) for masitinib vs 3.8 months [1.9;11] for sunitinib. Of those patients progressing under masitinib, 88% received sunitinib in third line. Median OS was not reached (NR) (95%CI [21;NR]) for masitinib vs 15 months [9.4;22] for sunitinib. The 18-month and 24-month OS rates for masitinib vs sunitinib were 79% (95%CI [53;92]) vs 20% [1.5;55], and 53% (95%CI [9.5;84]) vs 0%, respectively. Similar results were seen in the exon 11 subpopulation with median OS for masitinib NR (95%CI [NR;NR]) vs 15 months [9.6;22] for sunitinib. The safety profile of masitinib was better than sunitinib with a lower occurrence of severe related adverse events (AEs) (17% vs 52%) and related AEs leading to discontinuation (0% vs 9.5%). In masitinib treated patients, nausea, diarrhea and asthenia were the most common related AEs. Conclusions: Although PFS curves looked similar, this study apparently showed a longer survival in the masitinib treatment-arm with a better safety profile than sunitinib. Masitinib may potentially offer patients a new active compound for advanced GIST in the second-line setting.
Dissection of the Inflammatory Bowel Disease Transcriptome Using Genome-Wide cDNA Microarrays (2005)

A comprehensive set of candidate genes not previously associated with IBD was revealed, which underlines the polygenic and complex nature of the disease. It points out substantial differences in pathophysiology between CD and UC. The multiple unknown genes identified may stimulate new research in the fields of barrier mechanisms and cell signalling in the context of IBD, and ultimately new therapeutic approaches.
The interaction of eIF4E with 4E‐BP1 is an induced fit to a completely disordered protein (1998)

4E binding protein 1 (4E-BP1) inhibits translation by binding to the initiation factor eIF4E and is mostly or completely unstructured in both free and bound states. We wished to determine whether the free protein has local structure that could be involved in eIF4E binding. Assignments were obtained using double and triple resonance NMR methods. Residues 4-10, 43-46, and 56-65 could not be assigned, primarily because of a high degree of 1H and 15N chemical shift overlap. Steady-state ¿1H¿-15N NOEs were measured for 45 residues in the assigned regions. Except for the two C-terminal residues, the NOEs were between -0.77 and - 1.14, indicating a high level of flexibility. Furthermore, the ¿1H¿-15N NOE spectrum recorded with presaturation contained no strong positive signals, making it likely that no other residues have positive or smaller negative NOEs. This implies that 4E-BP1 has no regions of local order in the absence of eIF4E. The interaction therefore appears to be an induced fit to a completely disordered protein molecule.
Evaluation of analgesic agents in rats with adjuvant arthritis. (1975)

Rats with adjuvant arthritis were used for an analgesic test in which flection stimuli were applied to the arthritic joints. TAI-284, indomethacin, phenylbutazone, mefenamic acid, ibufenac, aspirin and aminopyrine were effective at the relatively low doses in this method. Oral ED50s of these compounds run parallel to their clinical doses. The method detects not only the analgesic action of morphine, pethidine and codeine, but also that of nalorphine, pentazocine and amphetamine. Prednisolone was mildly effective dose-independently. In spite of the high sensitivities, the method was specific in the sense that CNS-depressant, anti-depressant, anti-epileptic, naloxone, anti-serotonin and anti-histamine drugs were inactive or slightly active at toxic doses. The arthritic flection pain test was concluded to be a sensitive and specific test.
Vitamin A storage in hepatic stellate cells in the regenerating rat liver: With special reference to zonal heterogeneity (2005)

Under physiological conditions, hepatic stellate cells (HSCs) within liver lobules store about 80% of the total body vitamin A in lipid droplets in their cytoplasm, and these cells show zonal heterogeneity in terms of vitamin A-storing capacity. Vitamin A is essential for the growth and differentiation of cells, and it is well known that liver cells including HSCs show a remarkable growth capacity after partial hepatectomy (PHx). However, the status of vitamin A storage in HSCs in the liver regeneration is not yet known. Therefore, we conducted the present study to examine vitamin A storage in these cells during liver regeneration. Morphometry at the electron microscopic level, fluorescence microscopy for vitamin A autofluorescence, and immunofluorescence microscopy for desmin and alpha-smooth muscle actin (alpha-SMA) were performed on sections of liver from male Wistar strain rats at various times after the animal had been subjected to 70% PHx. The mean area of vitamin A-storing lipid droplets per HSC gradually decreased toward 3 days after PHx, and then returned to normal within 14 days after it. However, the heterogeneity of vitamin A-storing lipid droplet area per HSC within the hepatic lobule disappeared after PHx and did not return to normal by 14 days thereafter, even though the liver volume had returned to normal. These results suggest that HSCs alter their vitamin A-storing capacity during liver regeneration and that the recovery of vitamin A homeostasis requires a much longer time than that for liver volume.
Regulation of the Human Immune Response to Hbsag: Effects of Antibodies and Antigen Conformation in the Stimulation of Helper T Cells by Hbsag (1985)

The role of accessory cells (antigen-presenting cells) in binding HBsAg in the response of human T cells to this antigen was studied. Antibodies to HBsAg of IgG class increased significantly the amount of HBsAg that was captured and internalized by accessory cells in vitro. On the other hand, antibodies to HBsAg of IgM class or the F(ab')2 and Fab fragments of antibodies to HBsAg of IgG class did not modify the amount of HBsAg associated to these cells. HBsAg that was subjected to various denaturing treatments (acid, organic solvents, urea and heat) was compared for its capacity to react with antibody to HBsAg and stimulate the response of helper T lymphocytes. Results presented here indicate that HBsAg denatured by treatment with formic acid was captured by accessory cells and presented to the T cells much more efficiently than the native HBsAg. These results suggest that the response of helper T lymphocytes to some antigens such as HBsAg can be affected greatly by the presence of antibodies or the antigens' conformation.