gebhart/patrepeval huggingface dataset:
Engineering stability of the insulin monomer fold with application to the structure-activity relationship (1993)

To evaluate the possible relationship between biological activity and structural stability in selected regions of the insulin molecule, we have analyzed the guanidine hydrochloride induced reversible unfolding of a series of mutant insulins using a combination of near- and far-UV circular dichroism (CD). The unfolding curves are reasonably described on the basis of a two-state denaturation scheme; however, the observation of subtle differences between near- and far-UV CD detected unfolding indicates that intermediates may be present. Three regions of the insulin molecule are analyzed in detail with respect to their contribution to folding stability, i.e., the central B-chain helix, the NH2-terminal A-chain helix, and the B25-B30 extended chain region. Considerable enhancement of folding stability is engineered by mutations at the N-cap of the central B-chain helix and at the C-cap of the NH2-terminal A-chain helix. Mutations that confer increased stability in these regions are identical to those that lead to enhanced biological activity. In contrast, for insulin species modified in the B25-B30 region of the molecule, we observe no correlation between global folding stability and bioactivity. Mutations in the three regions examined are found to affect stability in a nearly independent fashion, and stabilizing mutations are generally found to enhance the cooperativity of the unfolding transition. We conclude that highly potent insulins (i.e., HisA8, ArgA8, GluB10, and AspB10) elicit enhanced activity because these mutations stabilize structural motifs of critical importance for receptor recognition.
A comparison of the inactive urinary kallikrein:creatinine ratio and the angiotensin sensitivity test for the prediction of pre‐eclampsia (1996)

There appears to be some relation between the IUK:Cr and AST tests in pregnancy. However, in this population, the IUK:Cr ratio was a better screening test for pre-eclampsia than the AST, but overall neither test was a powerful predictor for the syndrome.
D-Lactate oxidation and generation of the proton electrochemical gradient in membrane vesicles from Escherichia coli GR19N and in proteoliposomes reconstituted with purified D-lactate dehydrogenase and cytochrome o oxidase (1986)

The respiratory chain in the cytochrome d deficient mutant Escherichia coli GR19N is a relatively simple, linear system consisting of primary dehydrogenases, ubiquinone 8, cytochrome b-556, and cytochrome o oxidase. By use of right-side-out and inside-out membrane vesicles from this strain, various oxidase activities and the generation of the H+ electrochemical gradient were studied. Oxidation of ubiquinol 1 or N,N,-N',N'-tetramethyl-p-phenylenediamine, which donate electrons directly to the terminal oxidase, generates a H+ electrochemical gradient comparable to that observed during D-lactate oxidation. In contrast, D-lactate/ubiquinone 1 or D-lactate/ferricyanide oxidoreductase activity does not appear to generate a membrane potential, suggesting that electron flow from D-lactate dehydrogenase to ubiquinone is not electrogenic. Moreover, proteoliposomes reconstituted with purified D-lactate dehydrogenase, ubiquinone 8, and purified cytochrome o catalyze D-lactate and ubiquinol 1 oxidation and generate a H+ electrochemical gradient similar to that observed in membrane vesicles. Strikingly, in inside-out vesicles, NADH oxidation generates a H+ electrochemical gradient that is very significantly greater than that produced by either D-lactate or ubiquinol 1; furthermore, NADH/ubiquinone 1 and NADH/ferricyanide oxidoreductase activities are electrogenic. It is suggested that the only component between D-lactate dehydrogenase or ubiquinol and oxygen in GR19N membranes that is directly involved in the generation of the H+ electrochemical gradient is cytochrome o, which functions as a "half-loop" (i.e., the oxidase catalyzes the scalar release of 2 H+ from ubiquinol on the outer surface of the membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
IHARP: a multiple instruction issue processor (1992)

Recently, multiple instruction issue architectures have attempted to improve processor performance by fetching and dispatching more than one instruction in each processor cycle. This paper describes iHARP, a multiple instruction issue processor chip, which is currently being developed at Hatfield Polytechnic. The objective of the HARP project is to develop a processor which will execute nonnumeric programs at a sustained rate in excess of two instructions per processor cycle. This paper emphasises the distinctive hardware features which have been incorporated into the iHARP chip to achieve this goal.
Application of Normal Avian Gut Flora by Prolonged Aerosolization onto Turkey Hatching Eggs Naturally Exposed to Salmonella (1997)

A commercial preparation of normal avian gut flora (NAGF) was aerosolized for an extended period over turkey hatching eggs during pipping and hatching to examine any protective effects against natural exposure to salmonellae. Turkey hatching eggs, produced by salmonellae-infected breeder flocks and hatched in a commercial hatchery with a history of salmonellae contamination, were used in two trials. In Trial 1, four doses of NAGF inoculum per hatching egg were aerosolized through an automated hatcher fogging system during the final 48 hr of the pipping and hatching process. In Trial 2, two doses of NAGF inoculum were aerosolized in a like manner. In both trials, poults were exposed to Salmonella montevideo during hatching, as indicated by samples collected at the time of pull. At day 7, treated poults in both trials were culture negative for salmonellae and control poults were culture positive for salmonellae. In Trial 1, control poults were infected with Salmonella brandenburg, and in Trial 2, control poults were infected with S. montevideo. These studies justify further critical evaluation of the protective effects of prolonged aerosolization of normal avian gut flora during pipping and hatching against salmonellae colonization in turkey poults.
AVPR1a and SLC6A4 Gene Polymorphisms Are Associated with Creative Dance Performance (2005)

Dancing, which is integrally related to music, likely has its origins close to the birth of Homo sapiens, and throughout our history, dancing has been universally practiced in all societies. We hypothesized that there are differences among individuals in aptitude, propensity, and need for dancing that may partially be based on differences in common genetic polymorphisms. Identifying such differences may lead to an understanding of the neurobiological basis of one of mankind's most universal and appealing behavioral traits--dancing. In the current study, 85 current performing dancers and their parents were genotyped for the serotonin transporter (SLC6A4: promoter region HTTLPR and intron 2 VNTR) and the arginine vasopressin receptor 1a (AVPR1a: promoter microsatellites RS1 and RS3). We also genotyped 91 competitive athletes and a group of nondancers/nonathletes (n = 872 subjects from 414 families). Dancers scored higher on the Tellegen Absorption Scale, a questionnaire that correlates positively with spirituality and altered states of consciousness, as well as the Reward Dependence factor in Cloninger's Tridimensional Personality Questionnaire, a measure of need for social contact and openness to communication. Highly significant differences in AVPR1a haplotype frequencies (RS1 and RS3), especially when conditional on both SLC6A4 polymorphisms (HTTLPR and VNTR), were observed between dancers and athletes using the UNPHASED program package (Cocaphase: likelihood ratio test [LRS] = 89.23, p = 0.000044). Similar results were obtained when dancers were compared to nondancers/nonathletes (Cocaphase: LRS = 92.76, p = 0.000024). These results were confirmed using a robust family-based test (Tdtphase: LRS = 46.64, p = 0.010). Association was also observed between Tellegen Absorption Scale scores and AVPR1a (Qtdtphase: global chi-square = 26.53, p = 0.047), SLC6A4 haplotypes (Qtdtphase: chi-square = 2.363, p = 0.018), and AVPR1a conditional on SCL6A4 (Tdtphase: LRS = 250.44, p = 0.011). Similarly, significant association was observed between Tridimensional Personality Questionnaire Reward Dependence scores and AVPR1a RS1 (chi-square = 20.16, p = 0.01). Two-locus analysis (RS1 and RS3 conditional on HTTLPR and VNTR) was highly significant (LRS = 162.95, p = 0.001). Promoter repeat regions in the AVPR1a gene have been robustly demonstrated to play a role in molding a range of social behaviors in many vertebrates and, more recently, in humans. Additionally, serotonergic neurotransmission in some human studies appears to mediate human religious and spiritual experiences. We therefore hypothesize that the association between AVPR1a and SLC6A4 reflects the social communication, courtship, and spiritual facets of the dancing phenotype rather than other aspects of this complex phenotype, such as sensorimotor integration.
Memory Effect and Redistribution of Mg into Sequentially Regrown GaN Layer by Metalorganic Chemical Vapor Deposition (2003)

Mg redistribution into a subsequently regrown GaN epilayer by metalorganic chemical vapor deposition (MOCVD) is studied. Dopant profiles from secondary ion mass spectrometry (SIMS) on n–p–n GaN samples have been analyzed. The regrowth study in a Mg-free reactor reveals that a Mg-rich film is present on MOCVD as-grown GaN:Mg base layers and can be removed by an acid etch, and that a slow Mg decay into the sequentially regrown GaN results from this Mg-rich surface film. We believe the commonly seen Mg memory effect in MOCVD causes the accumulation of Mg on the surface. From a MOCVD regrowth on n–p–n GaN grown by molecular beam epitaxy (MBE), the Mg diffusion constant is calculated to be about 3 ×10-15 cm2/s at 1160°C for Mg concentrations between 5 ×1017 cm-3 and 1 ×1019 cm-3. The roles of memory effect, surface segregation, and diffusion associated with Mg are addressed.
Identification of a novel macrophage population in the normal mouse corneal stroma. (2002)

The normal murine corneal stroma contains a significant number of CD45(+) leukocytes. Most these cells express the CD11b marker, but not other dendrite, granulocyte, T-cell, or NK markers, placing them in the monocyte/macrophage lineage.
Scutellaria baicalensis decreases ritonavir-induced nausea (2005)

Scutellaria baicalensis significantly attenuated ritonavir-induced pica, and demonstrated a potential in treating ritonavir-induced nausea.
Inhibition of IFN-γ-Induced Class II Transactivator Expression by a 19-kDa Lipoprotein from Mycobacterium tuberculosis : A Potential Mechanism for Immune Evasion (2003)

Mycobacterium tuberculosis (MTB) persists inside macrophages despite vigorous immune responses. MTB and MTB 19-kDa lipoprotein inhibit class II MHC (MHC-II) expression and Ag processing by a Toll-like receptor 2-dependent mechanism that is shown in this study to involve a defect in IFN-gamma induction of class II transactivator (CIITA). Exposure of macrophages to MTB or MTB 19-kDa lipoprotein inhibited IFN-gamma-induced MHC-II expression, but not IL-4-induced MHC-II expression, by preventing induction of mRNA for CIITA (total, type I, and type IV), IFN regulatory factor-1, and MHC-II. MTB 19-kDa lipoprotein induced mRNA for suppressor of cytokine signaling (SOCS)1 but did not inhibit IFN-gamma-induced Stat1 phosphorylation. Furthermore, the lipoprotein inhibited MHC-II Ag processing in SOCS1(-/-) macrophages. MTB 19-kDa lipoprotein did not inhibit translocation of phosphorylated Stat1 to the nucleus or Stat1 binding to and transactivation of IFN-gamma-sensitive promoter constructs. Thus, MTB 19-kDa lipoprotein inhibited IFN-gamma signaling independent of SOCS1 and without interfering with the activation of Stat1. Inhibition of IFN-gamma-induced CIITA by MTB 19-kDa lipoprotein may allow MTB to evade detection by CD4(+) T cells.
Neurogenesis of subpopulations of rat lumbar dorsal root ganglion neurons including neurons projecting to the dorsal column nuclei (1996)

The time of birth of subpopulations of dorsal root ganglion (DRG) neurons was studied with immunohistochemistry for 5-bromodeoxyuridine (BrdU). Pregnant rats were injected with BrdU i.p. to label the neurons on one of the embryonic days (E) E11-E16. When they were adults, the rats were given injections of Fluoro-Gold (FG) into the gracile nucleus to identify DRG neurons projecting to this structure. Following a 5 day survival period, the animals were perfused with aldehyde fixative. Sections from the L3-L5 DRGs were processed for BrdU immunohistochemistry followed by either immunostaining for the antineurofilament antibody RT97, as marker of the light neuronal subpopulation, or histochemical staining for the B4 isolectin from Griffonia simplicifolia I, as marker of the small dark subpopulation. The results indicated that the DRG neurons were generated between E12 and E16. The RT97+ neurons were generated on E12-E15, with a peak at E13. FG+ neurons, the majority of which were RT97+, were also generated on E12-E15. The B4+ neurons were generated on E13-E16, with a peak around E14. The overall pattern of neurogenesis of the DRG neurons showed that the RT97+ neurons were produced prior to the B4+ neurons. These findings are in agreement with earlier observations that the large DRG neurons are generated earlier than the small dark neurons. Our findings also suggest the existence of a third neuronal subpopulation that might be produced at the latest period of DRG neurogenesis at E15-E16.
Genetic Dissection of Immunity to Mycobacteria: The Human Model (2002)

Humans are exposed to a variety of environmental mycobacteria (EM), and most children are inoculated with live Bacille Calmette-Guérin (BCG) vaccine. In addition, most of the world's population is occasionally exposed to human-borne mycobacterial species, which are less abundant but more virulent. Although rarely pathogenic, mildly virulent mycobacteria, including BCG and most EM, may cause a variety of clinical diseases. Mycobacterium tuberculosis, M. leprae, and EM M. ulcerans are more virulent, causing tuberculosis, leprosy, and Buruli ulcer, respectively. Remarkably, only a minority of individuals develop clinical disease, even if infected with virulent mycobacteria. The interindividual variability of clinical outcome is thought to result in part from variability in the human genes that control host defense. In this well-defined microbiological and clinical context, the principles of mouse immunology and the methods of human genetics can be combined to facilitate the genetic dissection of immunity to mycobacteria. The natural infections are unique to the human model, not being found in any of the animal models of experimental infection. We review current genetic knowledge concerning the simple and complex inheritance of predisposition to mycobacterial diseases in humans. Rare patients with Mendelian disorders have been found to be vulnerable to BCG, a few EM, and M. tuberculosis. Most cases of presumed Mendelian susceptibility to these and other mycobacterial species remain unexplained. In the general population leprosy and tuberculosis have been shown to be associated with certain human genetic polymorphisms and linked to certain chromosomal regions. The causal vulnerability genes themselves have yet to be identified and their pathogenic alleles immunologically validated. The studies carried out to date have been fruitful, initiating the genetic dissection of protective immunity against a variety of mycobacterial species in natural conditions of infection. The human model has potential uses beyond the study of mycobacterial infections and may well become a model of choice for the investigation of immunity to infectious agents.
Low energy ion-assisted deposition of titanium nitride ohmic contacts on alpha (6H)-silicon carbide (1991)

Low energy (100 eV) ion-assisted reactive evaporation was used to deposit titanium nitride (TiN) onto single crystal α(6H)-silicon carbide (SiC) wafers to investigate the potential of the former for electrical contacts. Theoretical considerations indicate that TiN (work function of 3.74 eV) should form an ohmic contact with SiC [work function of 4.8 eV for the (0001) face] provided an oxide-free interface can be obtained. Activated nitrogen was used to clean the SiC surface prior to deposition, while Auger spectroscopy and current-voltage (I-V) measurements were used to assess oxygen concentration at the interface and contact character, respectively. The contacts were ohmic after deposition. Little change was observed after annealing at 450 and 550 °C for 15 min.
Noise robust feature extraction for ASR using the Aurora 2 database (2001)

Four front-end processing techniques developed for noise robust speech recognition are tested with the Aurora 2 database. These techniques include three previously published algorithms: variable frame rate analysis [Zhu and Alwan, 2000], peak isolation [Strope and Alwan, 1997], and harmonic demodulation [Zhu and Alwan, 2000], and a new technique for peak-to-valley ratio locking. Our previous work has focused on isolated digit recognition. In this paper, these algorithms are modified for recognition of connected digits. Recognition results with the Aurora 2 database show that a combination of these four techniques results in 40% error rate reduction when compared to the baseline MFCC front-end for the clean training condition, with no significant increase in computational complexity.
Electromagnetic Navigation Diagnostic Bronchoscopy (2006)

Electromagnetic navigation bronchoscopy is a safe method for sampling peripheral and mediastinal lesions with high diagnostic yield independent of lesion size and location.
Fast breakpoints: design and implementation (1990)

We have designed and implemented a fast breakpoint facility. Breakpoints are usually thought of as a feature of an interactive debugger, in which case the breakpoints need not be particularly fast. In our environment breakpoints are often used for non-interactive information gathering; for example, procedure call count and statement execution count profiling [Swinehart, et al.]. When used non-interactively, breakpoints should be as fast as possible, so as to perturb the execution of the program as little as possible. Even in interactive debuggers, a conditional breakpoint facility would benefit from breakpoints that could transfer to the evaluation of the condition rapidly, and continue expeditiously if the condition were not satisfied. Such conditional breakpoints could be used to check assertions, etc. Program advising could also make use of fast breakpoints [Teitelman]. Examples of advising include tracing, timing, and even animation, all of which should be part of an advanced programming environment. We have ported the Cedar environment from a machine with microcode support for breakpoints [Lampson and Pier] to commercial platforms running C code [Atkinson, et al.]. Most of our ports run under the Unix * operating system, so one choice for implementing breakpoints for Cedar was to use the breakpoint facility provided by that system. The breakpoints provided by the Unix operating system are several orders of magnitude too slow (and also several process switches too complicated) for the applications we have in mind. So we designed a breakpoint system that was fast enough for our purposes. Breakpoints for uni-processors running single threads of control used to be fast and simple to implement. This paper shows that breakpoints can still be fast, even with multiple threads of control on multi-processors. This paper describes problems in the design of a breakpoint package for modern computer architectures and programming styles, and our solutions to them for a particular architecture.
A simulation-based approach for solving the flowshop problem (2010)

A simulation-based algorithm for the Permutation Flowshop Sequencing Problem (PFSP) is presented. The algorithm uses Monte Carlo Simulation and a discrete version of the triangular distribution to incorporate a randomness criterion in the classical Nawaz, Enscore, and Ham (NEH) heuristic and starts an iterative process in order to obtain a set of alternative to the PFSP. Thus, a random but biased local search of the space of is performed, and a list of good alternative solutions is obtained. We can then consider several properties per solution other than the makespan, such as balanced idle times among machines, number of completed jobs at a given target time, etc. This allows the decision-maker to consider multiple solution characteristics apart from those defined by the aprioristic objective function. Therefore, our methodology provides flexibility during the sequence selection process, which may help to improve the scheduling process. Several tests have been performed to discuss the effectiveness of this approach. The results obtained so far are promising enough to encourage further developments and improvements on the algorithm and its applications in real-life scenarios. In particular, Multi-Agent Simulation is proposed as a promising technique to be explored in future works.
Expression of Presenilin 1 and 2 (PS1 and PS2) in Human and Murine Tissues (1996)

Mutations in genes encoding related proteins, termed presenilin 1 (PS1) and presenilin 2 (PS2), are linked to the majority of cases with early-onset familial Alzheimer's disease (FAD). To clarify potential function(s) of presenilins and relationships of presenilin expression to pathogenesis of AD, we examined the expression of PS1 and PS2 mRNA and PS1 protein in human and mouse. Semi-quantitative PCR of reverse-transcribed RNA (RT-PCR) analysis revealed that PS1 and PS2 mRNA are expressed ubiquitously and at comparable levels in most human and mouse tissues, including adult brain. However, PS1 mRNA is expressed at significantly higher levels in developing brain. In situ hybridization studies of mouse embryos revealed widespread expression of PS1 mRNA with a neural expression pattern that, in part, overlaps that reported for mRNA encoding specific Notch homologs. In situ hybridization analysis in adult mouse brain revealed that PS1 and PS2 mRNAs are enriched in neurons of the hippocampal formation and entorhinal cortex. Although PS1 and PS2 mRNA are expressed most prominently in neurons, lower but significant levels of PS1 and PS2 transcripts are also detected in white matter glial cells. Moreover, cultured neurons and astrocytes express PS1 and PS2 mRNAs. Using PS1-specific antibodies in immunoblot analysis, we demonstrate that PS1 accumulates as approximately 28 kDa N-terminal and approximately 18 kDa C-terminal fragments in brain. Immunocytochemical studies of mouse brain reveal that PS1 protein accumulates in a variety of neuronal populations with enrichment in somatodendritic and neuropil compartments.
Use of fMRI to Predict Recovery From Unipolar Depression With Cognitive Behavior Therapy (2006)

Objective: In controlled treatment trials, 40%–60% of unmedicated depressed individuals respond to cognitive behavior therapy (CBT). The authors examined whether pretreatment neural reactivity to emotional stimuli accounted for this variation. Method: Unmedicated depressed individuals (N=14) and never depressed comparison subjects (N=21) underwent fMRI during performance of a task sensitive to sustained emotional information processing. Afterward, depressed participants completed 16 sessions of CBT. Results: Participants whose sustained reactivity to emotional stimuli was low in the subgenual cingulate cortex (Brodmann’s area 25) and high in the amygdala displayed the strongest improvement with CBT. Conclusions: The presence of emotion regulation disruptions, which are targeted in CBT, may be the key to recovery with this intervention.