gebhart/patrepeval huggingface dataset:
The urban psychology of Stanley Milgram (2005)

Although his obedience research will always remain Stanley Milgram's most important work, his involvement with the social psychology of the city occupied a much larger portion of his professional career. This article traces the evolution and intensification of Milgram's interest in cities, starting with his pre-professional years, through his early research at Harvard, culminating in his multifaceted engagement with urban psychology at the Graduate Center of CUNY. There, as head of the social psychology program, he was able to infuse it with an urban emphasis. He created and taught a variety of courses on urban psychology and got his students involved in a potpourri of experiments comparing behavior in cities and towns. Those experiments provided much of the substance for Milgram's seminal article in Science, "The experience of living in cities," in which he also introduced the theoretical concept of stimulus overload to help account for the city-small town differences he and his students found. This article evaluates the overload concept and concludes with Milgram's overarching legacy for the study of city life.
No nursing homes': General Practitioner attitudes to residential aged care facility visiting (2015)

Abstract of a poster presentation at the 2015 PHC Research Conference, Adelaide, 29-31 July, 2015. Disciplines Medicine and Health Sciences | Social and Behavioral Sciences Publication Details Pearson, R., Uvary, E., Bonney, A., Mullan, J. & Dijkmans-Hadley, B. (2015). No nursing homes': General Practitioner attitudes to residential aged care facility visiting. 2015 Primary Health Care Research Conference: Abstracts and Presentations (pp. 1-1). Australia: Primary Health Care Research & Information Service. This conference paper is available at Research Online: http://ro.uow.edu.au/smhpapers/2975 2015 PHC Research Conference: Poster abstract Adelaide, 29‐31 July, 2015 No nursing homes': General Practitioner Attitudes to Residential Aged Care Facility Visiting Author(s) Russell Pearson*, Eniko Uvary, Andrew Bonney, Judy Mullan, Bridget Dijkmans‐Hadley Organisation University of Wolloongong Aims & rationale Demographic trends suggest that the sustainability of the GP Residential Aged Care Facility (RACF) workforce is under threat, compromising the ongoing care of chronically ill RACF residents. It is therefore important to ascertain current GP attitudes towards this work, in order to help reduce the inequity this cohort of elderly Australians currently experience and improve their access to quality health care. Methods The views of a purposive sample of 26 GPs and GP Registrars working in rural and regional NSW were captured as part of focus group discussions and one‐on‐one interviews. Data were analysed by two independent coders, underlying themes were synthesised and ratified by the research team. Findings Thematic analysis of the qualitative data revealed that GP attitudes towards RACF visiting fell into five key themes: pleasure, duty, charity, hesitation and frustration. The data also revealed that the overriding emotion GPs felt about RACF visitation was frustration with the avoidable delays and inefficiencies associated with the work. Relevance to policy, research and/or practice needs This research provides insight into the barriers and enablers of efficient RACF health care provision. Its findings may assist RACF and general practice managers better understand how GPs and GP registrars feel about RACF visits, and how they may be able to better address the identified barriers in order to improve future access to quality health care for the elderly. Presentation type Paper Session theme Population ageing Session details 2015 PHC Research Conference: Poster abstract Adelaide, 29‐31 July, 2015 11:15am Thursday 30 July 2015, Adelaide Convention Centre ‐ Riverbank 7 Citation Pearson R, Uvary E, Bonney A, Mullan J, Dijkmans‐Hadley B. (2015). No nursing homes': General Practitioner Attitudes to Residential Aged Care Facility Visiting. In: 2015 Primary Health Care Research Conference: Program & Abstracts. Primary Health Care Research and Information Service, Australia. phcris.org.au/conference/abstract/8226
The role of the membrane-bound hydrogenase in the energy-conserving oxidation of molecular hydrogen by <i>Escherichia coli</i> (1980)

H2-dependent reduction of fumarate and nitrate by spheroplasts from Escherichia coli is coupled to the translocation of protons across the cytoplasmic membrane. The leads to H+/2e- stoicheiometry (g-ions of H+ translocated divided by mol of H2 added) is approx. 2 with fumarate and approx. 4 with nitrate as electron acceptor. This proton translocation is dependent on H2 and a terminal electron acceptor and is not observed in the presence of the protonophore carbonyl cyanide m-chlorophenylhydrazone and the respiratory inhibitor 2-n-heptyl-4-hydroxyquinoline N-oxide. H2-dependent reduction of menadione and ubiquinone-1 is coupled to a protonophore-sensitive, but 2-n-heptyl-4-hydroxy-quinoline N-oxide-insensitive, proton translocation with leads to H+/2e- stoicheiometry of approx. 2. H2-dependent reduction of Benzyl Viologen (BV++) to its radical (BV+) liberates protons at the periplasmic aspect of the cytoplasmic membrane according to the reaction: H2 + 2BV++ leads to 2H+ + 2BV+. It is concluded that the effective proton translocation observed in the H2-oxidizing segment of the anaerobic respiratory chain of Escherichia coli arises as a direct and inevitable consequence of transmembranous electron transfer between protolytic reactions that are spatially separated by a membrane of low proton-permeability.
Epithelial transformation by KLF4 requires Notch1 but not canonical Notch1 signaling (2009)

The transcription factors Notch1 and KLF4 specify epithelial cell fates and confer stem cell properties. Suggesting a functional relationship, each gene can act to promote or suppress tumorigenesis in a context-dependent manner, and alteration of KLF4 or Notch pathway genes in mice gives rise to similar phenotypes. Activation of a conditional allele of KLF4 in RK3E epithelial cells rapidly induces expression of Notch1 mRNA and the active, intracellular form of Notch1. KLF4-induced transformation was suppressed by knockdown of endogenous Notch1 using siRNA or an inhibitor of gamma-secretase. Chromatin immunoprecipitation assay shows that KLF4 binds to the proximal Notch1 promoter in human mammary epithelial cells, and siRNA-mediated suppression of KLF4 in human mammary cancer cells results in reduced expression of Notch1. Furthermore, KLF4 and Notch1 expression are correlated in primary human breast tumors (N = 89; Pearson analysis, r > 0.5, p < 0.0001). Like KLF4, Notch1 was previously shown to induce transformation of rat cells immortalized with adenovirus E1A, similar to RK3E cells. We therefore compared the signaling requirements for Notch1- or KLF4-induced malignant transformation of RK3E. As expected, transformation by Notch1 was suppressed by dominant-negative CSL or MAML1, inhibitors of canonical Notch1 signaling. However, these inhibitors did not suppress transformation by KLF4. Therefore, while KLF4-induced transformation requires Notch1, canonical Notch1 signaling is not required, and Notch1 may signal through a distinct pathway in cells with increased KLF4 activity. These results suggest that KLF4 could contribute to breast tumor progression by activating synthesis of Notch1 and by promoting signaling through a non-canonical Notch1 pathway.
Pathway for the Thermal Unfolding of Wild Type and Mutant Forms of the Thermostable P22 Tailspike Endorhamnosidase (1991)

Increasing the stabilities of proteins under realistic conditions requires understanding the mechanisms of protein denaturation far from equilibrium. A protein displaying very high thermal stability, resistance to proteases and resistance to detergents is the tailspike endorhamnosidase of bacteriophage P22. The folding pathway for the tailspike is well defined both in vivo and in vitro. Kinetic analysis of the thermal and detergent unfolding pathway reveals a relatively slow process which passes through a long-lived partially folded trimeric intermediate. This species has its N-termini unfolded with the remaining regions of the polypeptide chains in a compact native-like form. The intermediate can refold back to the native on cooling. Further unfolding of the intermediate at high temperature generates an aggregating species which renders the process kinetically irreversible. In the presence of SDS the unfolding intermediate is quantitatively converted to an unfolded monomer/SDS complex. Thus denaturation initiates via the melting of sites at the N-terminus, but the rate limiting step for the overall process is the melting of the intermediate species. Examining the thermal unfolding kinetics of more than ten temperature sensitive for folding (tsf) mutant proteins shows they have small effects on the transition from the native to the intermediate, but large effects on the transition from the intermediate to the fully unfolded form. The genetic modification of unfolding intermediates may provide an avenue for increasing the stability of proteins to irreversible denaturation.
Cinnoline chemistry XIII. 4‐aziridinocinnolines (1978)

Abstract Nine substituted 4‐aziridinoeinnolines have been prepared and subjected to anticancer screening. J. Heterocyclic Chem. , 15 , 1039 (1978)
Dashboard Reports for Predictive Model Management (2009)

Dashboard applications enable users to get big pictures on very complicated sets of data and information quickly. Traditionally, dashboard tools are applied on top of rather descriptive variables. This article, however, describes how SAS
EVIDENCE FOR A COMPLEX CLASS OF NONADENYLATED mRNA IN DROSOPHILA (1980)

The amount, by mass, of poly(A+) mRNA present in the polyribosomes of third-instar larvae of Drosophila melanogaster, and the relative contribution of the poly(A+) mRNA to the sequence complexity of total polysomal RNA, has been determined. Selective removal of poly(A+) mRNA from total polysomal RNA by use of either oligo-dT-cellulose, or poly(U)-sepharose affinity chromatography, revealed that only 0.15% of the mass of the polysomal RNA was present as poly(A+) mRNA. The present study shows that this RNA hybridized at saturation with 3.3% of the single-copy DNA in the Drosophila genome. After correction for asymmetric transcription and reactability of the DNA, 7.4% of the single-copy DNA in the Drosophila genome is represented in larval poly(A+) mRNA. This corresponds to 6.73 X 10(6) nucleotides of mRNA coding sequences, or approximately 5,384 diverse RNA sequences of average size 1,250 nucleotides. However, total polysomal RNA hybridizes at saturation to 10.9% of the single-copy DNA sequences. After correcting this value for asymmetric transcription and tracer DNA reactability, 24% of the single-copy DNA in Drosophila is represented in total polysomal RNA. This corresponds to 2.18 X 10(7) nucleotides of RNA coding sequences or 17,440 diverse RNA molecules of size 1,250 nucleotides. This value is 3.2 times greater than that boserved for poly(A+) mRNA, and indicates that congruent to 69% of the polysomal RNA sequence complexity is contributed by nonadenylated RNA. Futhermore, if the number of different structural genes represented in total polysomal RNA is congruent to 1.7 X 10(4), then the number of genes expressed in third-instar larvae exceeds the number of chromomeres in Drosophila by about a factor of three. This numbeology indicates that the number of chromomeres observed in polytene chromosomes does not reflect the number of structural gene sequences in the Drosophila genome.
Hybrid designs generating maximum-length sequences (1988)

Two hybrid schemes for the design of maximum-length sequence generators (MLSGs) are presented. Compared to an n-stage maximum-length LFSR (for generating 2/sup n/-1 nonzero distinct states) that uses m exclusive-or (XOR) gates, this hybrid MLSG will use exactly (m+1)/2 XOR gates if its characteristic polynomial meets certain requirements. For applications such as exhaustive testing, this hybrid MLSG is then reconfigured to include the all-zero state. It is shown that the reconfiguration is very simple and the hardware overhead is low.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
A Comparison of Valving Strategies Appropriate for Multi-Mode Combustion Within a Downsized Boosted Automotive Engine: Part B — Mid Load Operation Within the SACI Combustion Regime (2013)

Spark Assisted Compression Ignition (SACI) is a combustion mode that may offer significant efficiency improvements compared to conventional spark-ignited combustion systems. Unfortunately, SACI is constrained to a relatively narrow range of dilution levels and top dead center temperatures. Both positive valve overlap (PVO) and negative valve overlap (NVO) strategies may be utilized to attain these conditions at low and intermediate engine loads. The current work compares 1D thermodynamic simulations of PVO valving strategies and a baseline NVO strategy in a downsized boosted automotive engine with variable valve timing capability. As future downsized boosted engines may employ multiple combustion modes, the goal of this work is the definition of valving strategies appropriate for SACI combustion at low to moderate loads and SI combustion at moderate to high loads for an engine with fixed camshaft profiles. PVO durations, valve opening timings and peak lifts are investigated at low to moderate loads and are compared to a baseline NVO configuration in order to assess valving strategies appropriate for multi-mode combustion operation. A valvetrain kinematic model is used to translate the desired valve lift profiles into camshaft profiles, while a kinematic analysis is used to calculate piston to valve clearances and to define the practical limits of the PVO strategies. The NVO and PVO strategies are also compared to throttled SI operation at part load to assess the overall efficiency benefit of operating under the thermodynamic conditions of the SACI combustion regime. While the results of this study are engine specific, there are several camshaft profiles that are appropriate for the use of PVO rebreathing type valve events. For the range of PVO valve events examined and taking into consideration piston to valve interference, the use of high exhaust and low intake lifts with early exhaust valve opening timing and long PVO durations enables high levels of internal EGR with relatively low pumping losses.
Transcriptional profiling of interleukin-2-primed human adipose derived mesenchymal stem cells revealed dramatic changes in stem cells response imposed by replicative senescence (2015)

Inflammation is a double-edged sword with both detrimental and beneficial consequences. Understanding of the mechanisms of crosstalk between the inflammatory milieu and human adult mesenchymal stem cells is an important basis for clinical efforts. Here, we investigate changes in the transcriptional response of human adipose-derived stem cells to physiologically relevant levels of IL-2 (IL-2 priming) upon replicative senescence. Our data suggest that replicative senescence might dramatically impede human mesenchymal stem cell (MSC) function via global transcriptional deregulation in response to IL-2. We uncovered a novel senescence-associated transcriptional signature in human adipose-derived MSCs hADSCs after exposure to pro-inflammatory environment: significant enhancement of the expression of the genes encoding potent growth factors and cytokines with anti-inflammatory and migration-promoting properties, as well as genes encoding angiogenic and anti-apoptotic promoting factors, all of which could participate in the establishment of a unique microenvironment. We observed transcriptional up-regulation of critical components of the nitric oxide synthase pathway (iNOS) in hADSCs upon replicative senescence suggesting, that senescent stem cells can acquire metastasis-promoting properties via stem cell-mediated immunosuppression. Our study highlights the importance of age as a factor when designing cell-based or pharmacological therapies for older patients and predicts measurable biomarkers characteristic of an environment that is conducive to cancer cells invasiveness and metastasis.
Comparative effects of L-methionine, S-adenosyl-L-methionine and 5'-methylthioadenosine on the growth of preneoplastic lesions and DNA methylation in rat liver during the early stages of hepatocarcinogenesis. (1992)

Male Wistar rats, initiated with diethylnitrosamine (DENA), were subjected to a selection treatment, according to the "resistant hepatocyte" model, followed or not followed by phenobarbital (PB). Rats received, for 3 weeks after selection, 4 i.m. doses (96 mmol/kg) of L-methionine, S-adenosyl-L-methionine (SAM), or 5'-methylthioadenosine (MTA), a SAM catabolite formed during polyamine synthesis or by spontaneous splitting of SAM at physiologic temperature and pH. They were then killed. In some rats, SAM and MTA treatments were started 20 weeks after initiation. The animals were killed 3 weeks later and persistent (neoplastic) nodules (PN) were collected. Some rat groups received 1/2 and 1/4 of the above SAM and MTA doses, or 1/8 of the above MTA dose. SAM and MTA, but not methionine, caused a dose-dependent decrease in number and surface area of gamma-glutamyltranspeptidase (GGT)-positive foci, and in labeling index (LI) of focal cells, coupled with remodeling. SAM and MTA liver contents, SAM/S-adenosylhomocysteine (SAH) ratio and overall methylation of liver DNA were low during the development of GGT-positive foci. SAM, but not methionine, caused a dose-dependent recovery of SAM content and DNA methylation, and a partial reconstitution of liver MTA pool. Exogenous MTA only induced the reconstitution of MTA pool, without affecting SAM level and DNA methylation. Recovery of SAM and MTA pool and DNA methylation was found in the rats subjected to SAM plus MTA, indicating the absence of inhibition of DNA methyltransferases in vivo by MTA. MTA also inhibited liver reparative growth in partially hepatectomized rats, without modifying SAM content and DNA methylation of regenerating liver (RL). A high activity of ornithine decarboxylase (ODC) was found in the liver, during the development of preneoplastic foci, and in PN. This activity was inhibited by SAM and MTA treatments. Although MTA was more effective than SAM, the decrease in ODC activity was coupled with a larger fall in DNA synthesis in SAM-treated than in MTA-treated rats. Thus the antipromotion effect of SAM could not merely depend on its (spontaneous) transformation into MTA. Although MTA production may play a role in the SAM antipromotion effect, other mechanisms could be involved. A role of DNA methylation in the inhibition of growth by SAM is suggested. MTA is a potential chemopreventive agent for liver carcinogenesis.
Protease/inhibitor mechanisms involved in ATP-dependent proteolysis. (1989)

ATP-dependent proteolytic activities constitute a family of distinct enzymes and enzyme complexes which function in the selective degradation of proteins in the cytosol and possibly other non-lysosomal cellular compartments. In reticulocytes as well as other eukaryotic cells, conjugation of the polypeptide ubiquitin to proteins, an ATP-requiring process, is important for proteolysis. However, the popular view that ubiquitin functions by tagging substrates for recognition by conjugate-specific proteases should be viewed with caution. Evidence is reviewed implicating an ATP-independent high molecular weight protease (HMP) which can degrade non-ubiquitinated proteins in the ATP-dependent pathway. This protease consists of several related subunits based upon monoclonal antibody studies. HMP by itself, can account for effects of substrate amino group blockage on ATP-dependent proteolysis. Endogenous inhibitors (40 kDa and 50 kDa) have been isolated and shown to block HMP non-competitively. Unlike the soluble system in reticulocytes, the major ATP-dependent activity in mouse erythroleukemia cells is particulate in aqueous media but soluble in the presence of sucrose. Despite such differences, evidence suggests analogous inhibitory components in this system. The possibility that protease/inhibitor interaction is regulated by ATP and ubiquitin in different systems is discussed.
SEVENS: Comprehensive Collection of Human Seven Transmembrane Helix Receptors (2002)

Recent progress in determination of human draft sequences [6, 8] and tertiary structure of seven-transmembrane-helix receptors (7-TMR) accelerates the comprehensive sequence analysis of 7-TMRin whole human genome. Despite the enormous amount of available data on genome sequences [6, 8],theoverviewedfamiliesof7-TMRhavenotyetbeenwellcharacterized. OurSEVENSdatabaseintendsto cover all \7-TMR universe with not only the known sequences but also to use newly discoveredsequence by computational gene nding program.
Chemical Site-Specific Conjugation Platform to Improve the Pharmacokinetics and Therapeutic Index of Antibody–Drug Conjugates (2021)

To overcome a lack of selectivity during the chemical modification of native non-engineered antibodies, we have developed a technology platform termed "AJICAP" for the site-specific chemical conjugation of antibodies through the use of a class of IgG Fc-affinity reagents. To date, a limited number of antibody-drug conjugates (ADCs) have been synthesized via this approach, and no toxicological study was reported. Herein, we describe the compatibility and robustness of AJICAP technology, which enabled the synthesis of a wide variety of ADCs. A stability assessment of a thiol-modified antibody synthesized by AJICAP technology indicated no appreciable increase in aggregation or decomposition upon prolonged storage, indicating that the unexpectedly stable thiol intermediate has a great potential intermediate for payload or linker screening or large-scale manufacturing. Payload conjugation with this stable thiol intermediate generated several AJICAP-ADCs. <i>In vivo</i> xenograft studies indicated that the AJICAP-ADCs displayed significant tumor inhibition comparable to benchmark ADC Kadcyla. Furthermore, a rat pharmacokinetic analysis and toxicology study indicated an increase in the maximum tolerated dose, demonstrating an expansion of the AJICAP-ADC therapeutic index, compared with stochastic conjugation technology. This is the first report of the therapeutic index estimation of site-specific ADCs produced by utilizing Fc affinity reagent conjugation. The described site-specific conjugation technology is a powerful platform to enable next-generation ADCs through reduced heterogeneity and enhanced therapeutic index.