Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterizing the Role of Thr352 in the Inhibition of the Large Conductance Ca2+-Activated K+ Channels by 1-[1-Hexyl-6-(methyloxy)-1H-indazol-3-yl]-2-methyl-1-propanone

Large conductance Ca2+-activated K+ (BK) channels are known to be regulated by both intracellular Ca2+ and voltage. Although BK channel modulators have been identified, there is a paucity of information regarding the molecular entities of this channel that govern interaction with blockers and activators. Using both whole-cell and single-channel electrophysiological studies we have characterized the possible role that a threonine residue in the pore region of the channel has on function and interaction with BK channel modulators. A threonine-to-serine substitution at position 352 (T352S) resulted in a 59-mV leftward shift in the voltage-dependent activation curve. Single-channel conductance was 236 pS for the wild-type channel and 100 pS for the T352S mutant, measured over the range −80 mV to +80 mV. In addition, there was an almost 10-fold reduction in the potency of the BK channel inhibitor 1-[1-hexyl-6-(methyloxy)-1H-indazol-3-yl]-2-methyl-1-propanone (HMIMP), the IC50 values being 4.3 ± 0.3 and 38.2 ± 3.3 nM for wild-type and mutant channel, respectively. There was no significant difference between wild type and the mutant channel in response to inhibition by iberiotoxin. The IC50 was 8.1 ± 0.3 nM for the wild type and 7.7 ± 0.3 nM for the mutant channel. Here, we have identified a residue in the pore region of the BK channel that alters voltage sensitivity and reduces the potency of the blocker HMIMP.
A Predictive Model for Life-Threatening Neutropenia and Febrile Neutropenia after the First Course of CHOP Chemotherapy in Patients with Aggressive Non-Hodgkin's Lymphoma

The purpose of this study was to develop a model for predicting the occurrence of life-threatening neutropenia (LN, ANC ≤ 0.5 × 109/1) and febrile neutropenia (FN, an ANC ≤ 0.5×l09/l in association with a body temperature of ≥ 38.3°C) after the first cycle of CHOP therapy in patients newly diagnosed with aggressive NHL. One hundred and forty-five patients, aged ≥ 15 years, with newly diagnosed diffuse mixed, diffuse large-cell or large-cell immunoblastic lymphoma (IWF categories, F, G, H), who had been treated with CHOP at King Chulalongkorn Memorial Hospital between June 1994 and December 1998, were entered into the study. The criteria for eligibilty included complete work-up for baseline evaluation, treatment with standard CHOP chemotherapy, at least one complete blood count performed during days 8-14 post-treatment or if at any time the patients experienced a BT of ≥ 38.3°C and were not treated with any colony-stimulating factors (CSFs). The median age of the patients was 47 years (range, 17-78). Forty-eight percent of the patients were in stage III/IV, 36% had ECOG performance status (PS) II-IV, 30% had ≥ 2 extranodal diseases, 59% had serum LDH > 1 × normal and 23% had bone marrow involvement. The frequencies of patients in the low-, low-intermediate, high-intermediate and high risk groups according to the international index were 29%, 28%, 17% and 26%, respectively. Thirty-nine percent of the patients had LN at nadir and 33% developed FN after the first course of CHOP. By using stepwise logistic regression analysis, the pretreatment variables independently predictive of the LN at nadir and the FN were serum albumin concentration of ≤ 3.5 g/dl, serum LDH > 1 × normal and whether there was bone marrow involvement of lymphoma at presentation. The model, based on the incorporation of these three factors, identified three risk groups of patients with a predicted probability of developing LN at nadir of 81.5% (95% CI, 68.5 - 90.7)(high risk), 23.9% (95% CI, 12.6 - 38.8)(intermediate risk) and 4.4% (95% CI, 0.5- 15.1)(low risk). The predicted rate of FN in the three groups were 72.2% (95% CI, 58.4 - 83.5), 17.4% (95% CI, 7.8 - 31.4) and 2.2% (95% CI, 0.05 - 11.8), respectively. In conclusion, our model could be used as a means to identify patients with newly diagnosed aggressive NHL, treated with CHOP, who are at high risk (≥ 50% probability) of developing post-first course LN and FN, in whom CSF and/or antibiotic prophylaxis might be indicated.
Haemoglobin concentration and the risk of death in older adults: differences by race/ethnicity in the NHANES III follow‐up

Mildly low haemoglobin concentration is associated with increased mortality in older adults. However, this relationship has not been well characterized in racial/ethnic minorities. Therefore, this study determined the haemoglobin threshold below which risk of death is significantly increased in older non‐Hispanic whites, non‐Hispanic blacks, and Mexican Americans. Data on 4089 participants of the 1988–94 US National Health and Nutrition Examination Survey who were ≥65 years of age were analyzed with mortality follow‐up through December 31, 2000. Mean haemoglobin in non‐Hispanic whites (n = 2686) and Mexican Americans (n = 663) was 140 g/l, while in non‐Hispanic blacks (n = 740) the mean was 10 g/l lower. A total of 1944 (47·5%) participants died. Among non‐Hispanic whites and Mexican Americans, age‐ and sex‐adjusted models showed that the haemoglobin thresholds below which mortality risk was significantly increased were 4 and 2 g/l respectively, above the World Health Organization (WHO) cut‐off points for anaemia. In contrast, the threshold for non‐Hispanic blacks was 7 g/l below the WHO criteria. Similar threshold effects were observed when analyzing haemoglobin in categories and adjusting for multiple confounders. In conclusion, the haemoglobin threshold below which mortality rises significantly is a full g/dl lower in non‐Hispanic blacks than in non‐Hispanic whites and Mexican Americans.
Activation of human synovial mast cells from rheumatoid arthritis or osteoarthritis patients in response to aggregated IgG through Fcγ receptor I and Fcγ receptor II.

OBJECTIVE Substantial evidence suggests that human synovial mast cells (MCs) are involved in the pathogenesis of rheumatoid arthritis (RA). A plausible pathway for the activation of synovial MCs is through IgG receptors, given the prevalence of circulating IgG isotype autoantibodies and synovial immune complexes in patients with RA. However, IgG receptor expression on human synovial MCs remains uncharacterized. The aim of this study was to identify which IgG receptor(s) on synovial MCs are responsible for MC activation in immune complexes. METHODS Synovial tissue specimens were obtained from patients with RA or patients with osteoarthritis (OA) who were undergoing joint replacement surgery, and synovial MCs were enzymatically dispersed. Cultured synovium-derived MCs were generated by culturing synovial cells with stem cell factor, and receptor expression was analyzed using fluorescence-activated cell sorting. Mediators released from MCs were measured using enzyme immunoassays or enzyme-linked immunosorbent assays. RESULTS Primary synovial MCs and cultured synovium-derived MCs obtained from both patients with RA and patients with OA expressed Fcε receptor I (FcεRI), FcγRI, and FcγRII but not FcγRIII. Cultured synovium-derived MCs induced degranulation and the production of prostaglandin D2 and tumor necrosis factor α (TNFα) through FcγRI. The aggregation of FcγRII caused histamine release from cultured MCs but not from primary MCs. Histamine release induced by aggregated IgG was significantly inhibited by neutralizing anti-FcγRI monoclonal antibody and anti-FcγRII monoclonal antibody. CONCLUSION With regard to the FcR expression profile, synovial MCs from patients with RA and patients with OA were similar. FcγRI was responsible for producing abundant TNFα from synovial MCs in response to aggregated IgG. Immune complexes may activate synovial MCs through FcγRI and FcγRII.
Aggression between peers in early childhood: individual continuity and developmental change.

43 children were observed in play with "best available friends" at 2 and again at 5 years of age. An arousing stimulus, an angry interaction between adults, was introduced during play sessions to increase the likelihood of elicitation of aggressive patterns. Dimensions of physical aggression at age 2 (e.g., object-related aggression, bodily aggression) predicted dimensions of children's physical aggression at age 5. However, substantial sex differences in the stability of aggression were found. Among boys, the disposition to engage in physical aggression was highly stable, with correlations ranging as high as r = . 76. Certain dimensions of physical aggression at age 2 were also positively associated with verbal aggression at age 5. Fewer and more modest correlations were found among girls. The frequency of aggression, particularly bodily aggression (e.g., hitting, pushing), initiations of aggression, and the average length of aggression episodes, decreased between 2 and 5 years of age. These results indicate that relative aggressiveness tends to remain stable despite declines in the frequency of aggressive behavior between 2 and 5 years of age.
UBP43 (USP18) Specifically Removes ISG15 from Conjugated Proteins*

UBP43 shows significant homology to well characterized ubiquitin-specific proteases and previously was shown to hydrolyze ubiquitin-β-galactosidase fusions in Escherichia coli. In our assays, the activity of UBP43 toward Ub fusions was undetectable in vitro directing us to investigate the possibility of Ub-like proteins such as SUMO, Nedd8, and ISG15 as probable substrates. We consequently demonstrate that UBP43 can efficiently cleave only ISG15 fusions including native ISG15 conjugates linked via isopeptide bonds. In addition to commonly used methods we introduce a new experimental design featuring ISG15-UBP43 fusion self-processing. Deletion of the UBP43 gene in mouse leads to a massive increase of ISG15 conjugates in tissues indicating that UBP43 is a major ISG15-specific protease. UBP43 is the first bona fide ISG15-specific protease reported. Both ISG15 andUBP43 genes are known to be strongly induced by interferon, genotoxic stress, and viral infection. We postulate that UBP43 is necessary to maintain a critical cellular balance of ISG15-conjugated proteins in both healthy and stressed organisms.
Oral administration of fumonisin B1 and T-2 individually and in combination affects hepatic total and mitochondrial membrane lipid profile of rabbits.

Weaned rabbits were fed diets contaminated with 2 mg/kg diet T-2 toxin alone, or 10 mg/kg diet fumonisin B1 (FB1) alone, and both toxins in combination (2 + 10 mg/kg, respectively) compared to a toxin-free control diet. Samplings were performed after 4 weeks (blood and liver). Bodyweight of T-2-fed group was lower after 4 weeks; the liver weight was increased dramatically (threefold of control). Liver total phospholipids (PLs) provided slight alterations in the fatty acid (FA) composition; all three toxin-treated groups showed a decrease in palmitoleic acid (C16:1 n7) proportion. In the liver mitochondrial PL FA composition, margaric acid (C17:0) proportion decreased in the separated toxin treatments compared to the combined setting. Oleic acid (C18:1 n9) proportion was increased and arachidonic acid (C20:4 n6) was decreased in the FB1-treated group, while docosapentaenoic acid (C22:5 n3) was decreased in the separated treatments. The total monounsaturation was significantly higher in the FB1 group's mitochondrial PL FA profile. After 4 weeks, all toxin treatments decreased the blood plasma reduced glutathione and glutathione peroxidase activity, and FB1 increased the plasma sphinganine/sphingosine ratio. Both mycotoxins seem to cross the hepatocellular and the hepatic mitochondrial membrane, without drastic membrane disruption, as assessed from the PL FA composition, but inducing detectable lipid peroxidation.
Operative Environment

Liaisons: Pouya Alijanipour MD, Joseph Karam MD Leaders: Adolfo Llinás MD (International), Kelly G Vince MD (International), Charalampos Zalavras MD (US) Delegates: Matthew Austin MD, Grant Garrigues MD, Snir Heller MD, James Huddleston MD, Brian Klatt MD, Viktor Krebs MD, Christoph Lohmann MD, Edward J McPherson MD, Robert Molloy MD, Ali Oliashirazi MD, Mitchell Schwaber MD, Eoin Sheehan MD, Eric Smith MD, Robert Sterling MD, Gregory Stocks MD, Shrinand Vaidya MD
Institutionalized adolescents in therapy: narratives of psychotherapy and healing from sexual abuse

Adolescent sexual abuse is a pressing social issue worldwide, specifically for institutionalized population that lack access to alternative care such as family-based options. This study examines narratives associated with healing from sexual abuse among teenagers in long-term residential care programs who have successfully completed specialized psychotherapy. Using a qualitative research methodology and multiple case analysis, in-depth interviews were conducted with five adolescents and then analyzed using thematic narrative analysis. Results show two different narrative positions regarding the meanings of healing after an experience of sexual abuse: narratives of healing and in complete healing. In addition, factors that influence the healing process are observed, of which psychotherapy and therapeutic relationships are key. Study participants’ own voices show the possibilities for generating recovery narratives among adolescents in residential care who have been sexually assaulted, highlighting aspects of therapeutic intervention that may better orientate psychotherapy for this specific group.
On the duality of Gaussian multiple-access and broadcast channels

We show that the Gaussian multiple-access channel (MAC) and broadcast channel (BC) are duals. The dual channels we consider have the same channel gains and the same noise power at all receivers. We find an expression for the capacity region of the BC in terms of the capacity region of the dual MAC, and vice versa. Duality applies to many different channel models and capacity definitions.
Attenuation of neointima formation through the inhibition of DNA repair enzyme PARP-1 in balloon-injured rat carotid artery.

Increased oxidative stress is a major characteristic of restenosis after angioplasty. The oxidative stress is mainly created by oxidants such as reactive oxygen species (ROS), which are assumed to play an important role in neointima formation after angioplasty. DNA is a sensitive target for oxidants; however, oxidative DNA damage remains a poorly examined field in the pathogenesis of restenosis. In the present study, we demonstrated that the expression of the oxidative DNA damage marker 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) was quickly increased in rat carotid arteries after balloon injury. It reached its peak at 14 days after injury and still kept high expression at 28 days after injury. The immunostaining of 8-oxo-dG was present predominantly in the neointima. In response to oxidative DNA damage, the DNA repair enzyme poly(ADP-ribose) polymerase-1 (PARP-1) was significantly increased after balloon injury. The time course change and location of PARP-1 is similar to that of 8-oxo-dG. Daily injections of the PARP-1 inhibitor PJ34 (5 mg.kg(-1). day(-1) ip) attenuated neointima formation by approximately 40% at 7, 14, and 28 days after balloon injury. Treatment with PJ34 inhibited leukocyte infiltration and improved both anatomic (reendothelialization) and functional (endothelial function) recovery of endothelial cells after balloon injury. In conclusion, levels of oxidative DNA damage and the DNA repair enzyme PARP-1 are increased in vessels after balloon injury. Inhibition of PARP-1 attenuates neointima formation through inhibition of leukocyte infiltration and improvement of endothelial cell recovery after balloon injury. Targeting of the DNA repair enzyme might be a therapeutic strategy for restenosis.
Coeducational or single‐sex school: does it make a difference on high school girls’ academic motivation?

The aim of the present study was to further examine the impact over time of single‐sex and coeducational school environments on girls’ motivation in language arts and mathematics. Two cohorts comprising 340 girls (7th to 9th grade; 9th to 11th grade) from eight coeducational and two single‐sex schools were followed during a period of three academic years in a longitudinal research scheme. Data were collected with a self‐reported questionnaire including several scales: parental and teachers’ support, competence beliefs, utility‐value and achievement goals. In general, mixed‐design repeated measures analyses of variance indicated no effect of the environment or of the interaction between environment and time of measurement. Significant time effects on several variables indicated a general decline of achievement motivation over time. Consequently, the multiplication of non‐mixed high schools, as proposed by some, would constitute an expensive and inefficient social policy, as far as girls’ motivation is concerned.
The life and death of online groups: predicting group growth and longevity

We pose a fundamental question in understanding how to identify and design successful communities: What factors predict whether a community will grow and survive in the long term? Social scientists have addressed this question extensively by analyzing offline groups which endeavor to attract new members, such as social movements, finding that new individuals are influenced strongly by their ties to members of the group. As a result, prior work on the growth of communities has treated growth primarily as a diffusion processes, leading to findings about group evolution which can be difficult to explain. The proliferation of online social networks and communities, however, has created new opportunities to study, at a large scale and with very fine resolution, the mechanisms which lead to the formation, growth, and demise of online groups. In this paper, we analyze data from several thousand online social networks built on the Ning platform with the goal of understanding the factors contributing to the growth and longevity of groups within these networks. Specifically, we investigate the role that two types of growth (growth through diffusion and growth by other means) play during a group's formative stages from the perspectives of both the individual member and the group. Applying these insights to a population of groups of different ages and sizes, we build a model to classify groups which will grow rapidly over the short-term and long-term. Our model achieves over 79% accuracy in predicting group growth over the following two months and over 78% accuracy in predictions over the following two years. We utilize a similar approach to predict which groups will die within a year. The results of our combined analysis provide insight into how both early non-diffusion growth and a complex set of network constraints appear to contribute to the initial and continued growth and success of groups within social networks. Finally we discuss implications of this work for the design, maintenance, and analysis of online communities.
Relations between psychophysical measures of spatial hearing and self-reported spatial-hearing abilities

Abstract Objective: The aim of the present study was to investigate how well the virtual psychophysical measures of spatial hearing from the preliminary auditory profile predict self-reported spatial-hearing abilities. Design: Virtual spatial-hearings tests (conducted unaided, via headphones) and a questionnaire were administered in five centres in Germany, the Netherlands, Sweden, and the UK. Correlations and stepwise linear regression models were calculated among a group of hearing-impaired listeners. Study sample: Thirty normal-hearing listeners aged 19–39 years, and 72 hearing-impaired listeners aged 22–91 years with a broad range of hearing losses, including asymmetrical and mixed hearing losses. Results: Several significant correlations (between 0.24 and 0.54) were found between results of virtual psychophysical spatial-hearing tests and self-reported localization abilities. Stepwise linear regression analyses showed that the minimum audible angle (MAA) test was a significant predictor for self-reported localization abilities (5% extra explained variance), and the spatial speech reception threshold (SRT) benefit test for self-reported listening to speech in spatial situations (6% extra explained variance). Conclusions: The MAA test and spatial SRT benefit test are indicative measures of everyday binaural functioning. The binaural SRT benefit test was not found to predict self-reported spatial-hearing abilities.
The Politics of Peoplehood

Contemporary political theory has made the question of the “people” a topic of sustained analysis. This article identifies two broad approaches taken—norm-based and contestation-based—and, noting some problems left outstanding, goes on to advance a complementary account centred on partisan practice. It suggests the definition of “the people” is closely bound up in the analysis of political conflict, and that partisans engaged in such conflict play an essential role in constructing and contesting different principled conceptions. The article goes on to show how such an account does not lead to a normatively hollow, purely historical conception of “the people,” but rather highlights the normative importance of practices that, at the minimum, de-naturalise undesirable conceptions of the people and, at their best, give political legitimacy and a representative basis to those one might wish to see prosper.
Evaluating the relationship between physical education, sport and social inclusion

Focusing upon the recent policy context within the UK, this paper offers a review of the evidence related to the outcomes of the participation of children and young people in curricular physical education and sport. Particular attention is paid to potential contributions that such activities can make towards social inclusion and the development of social capital. The review suggests that there are some areas for which there is a considerable amount of evidence in favour of a positive relationship with participation in these activities (such as physical and mental health), and others for which further research remains necessary (such as cognitive and academic development, crime reduction, truancy and disaffection). In general, however, it is evident that much more empirical research is necessary if the benefits of sporting participation for young people and society are to become much more than a theoretical aspiration.
The Impact of Mood on Affect Regulation Effects on Film Preferences

Drawing on the mood-behavior model (Gendolla, 2000), I predicted that both negative and positive moods evoke a stronger need for hedonic affect regulation than a so-called neutral mood. To test this hypothesis, participants were induced into a positive, neutral, or negative mood by autobiographical recollection and then selected which of three films they wanted to watch. The films varied in the extent of their potential for hedonic affect regulation. As expected, preferences for a pleasant film were higher in both positive and negative moods than in a neutral mood and the positive and negative mood conditions did not differ. Furthermore, a regression analysis found that the preference for a pleasant film was related to mood intensity. Implications for other models of affect regulation are discussed.