Miracle-dz/UniFAR-FTUs huggingface dataset:
The “Albumin Effect” and Drug Glucuronidation: Bovine Serum Albumin and Fatty Acid-Free Human Serum Albumin Enhance the Glucuronidation of UDP-Glucuronosyltransferase (UGT) 1A9 Substrates but Not UGT1A1 and UGT1A6 Activities

Bovine serum albumin (BSA) and fatty acid-free human serum albumin (HSAFAF) reduce the Km values for UGT2B7 substrates by sequestering inhibitory long-chain fatty acids released by incubations of human liver microsomes (HLM) and HEK293 cells expressing this enzyme. However, the scope of the “albumin effect” is unknown. In this investigation we characterized the effects of albumin on the kinetics of 4-methylumbelliferone (4MU) glucuronidation by UDP-glucuronosyltransferase (UGT) 1A1, 1A6, and 1A9, and propofol (PRO) glucuronidation by UGT1A9 and HLM. BSA and HSAFAF, but not human serum albumin, reduced the Km values for 4MU and PRO glucuronidation by UGT1A9. For example, HSAFAF (2%) reduced the Km values for 4MU and PRO glucuronidation from 13.4 to 2.9 and 41 to 7.2 μM, respectively. Similarly, HSAFAF (2%) reduced the Km for PRO glucuronidation by HLM from 127 to 10.6 μM. Arachidonic, linoleic, and oleic acids and a mixture of these decreased the rates of 4MU and PRO glucuronidation by UGT1A9. Km values for these reactions were increased 3- to 6-fold by the fatty acid mixture. Inhibition was reversed by the addition of BSA (2%). Extrapolation of kinetic constants for PRO glucuronidation by HLM in the presence of HSAFAF predicted in vivo hepatic clearance within 15%. Fatty acids had no effect on 4MU glucuronidation by UGT1A1 and UGT1A6 but, paradoxically, all forms of albumin altered the kinetic model for 4MU glucuronidation by UGT1A6 (from Michaelis-Menten to two-site). Only BSA caused a similar effect on 4MU glucuronidation by UGT1A1. It is concluded that BSA and HSAFAF reduce the Km values of only those enzymes inhibited by long-chain unsaturated fatty acids.
Tecemotide in unresectable stage III non-small-cell lung cancer in the phase III START study: updated overall survival and biomarker analyses.

BACKGROUND Tecemotide is a MUC1-antigen-specific cancer immunotherapy. The phase III START study did not meet its primary end point but reported notable survival benefit with tecemotide versus placebo in an exploratory analysis of the predefined patient subgroup treated with concurrent chemoradiotherapy. Here, we attempted to gain further insight into the effects of tecemotide in START. PATIENTS AND METHODS START recruited patients who did not progress following frontline chemoradiotherapy for unresectable stage III non-small-cell lung cancer. We present updated overall survival (OS) data and exploratory analyses of OS for baseline biomarkers: soluble MUC1 (sMUC1), antinuclear antibodies (ANA), neutrophil/lymphocyte ratio (NLR), lymphocyte count, and HLA type. RESULTS Updated OS data are consistent with the primary analysis: median 25.8 months (tecemotide) versus 22.4 months (placebo) (HR 0.89, 95% CI 0.77-1.03, P = 0.111), with ∼20 months additional median follow-up time compared with the primary analysis. Exploratory analysis of the predefined subgroup treated with concurrent chemoradiotherapy revealed clinically relevant prolonged OS with tecemotide versus placebo (29.4 versus 20.8 months; HR 0.81, 95% CI 0.68-0.98, P = 0.026). No improvement was seen with sequential chemoradiotherapy. High sMUC1 and ANA correlated with a possible survival benefit with tecemotide (interaction P = 0.0085 and 0.0022) and might have future value as biomarkers. Interactions between lymphocyte count, NLR, or prespecified HLA alleles and treatment effect were not observed. CONCLUSION Updated OS data support potential treatment benefit with tecemotide in patients treated with concurrent chemoradiotherapy. Exploratory biomarker analyses suggest that elevated sMUC1 or ANA levels correlate with tecemotide benefit. CLINICALTRIALSGOV NUMBER NCT00409188.
The identification problem for the attenuated X-ray transform

We study the problem of recovery both the attenuation $a$ and the source $f$ in the attenuated X-ray transform in the plane. We study the linearization as well. It turns out that there is a natural Hamiltonian flow that determines which singularities we can recover. If the perturbation $\delta a$ is supported in a compact set that is non-trapping for that flow, then the problem is well posed. Otherwise, it may not be, and least in the case of radial $a$, $f$, it is not. We present uniqueness and non-uniqueness results for both the linearized and the non-linear problem; as well as a H\"older stability estimate.
A 1.5GHz 1.35mW −112dBc/Hz in-band noise digital phase-locked loop with 50fs/mV supply-noise sensitivity

A highly digital PLL employs a 1b TDC and a low power regulator to reduce output jitter in the presence of large amount of supply-noise. Fabricated in a 0. 13μm CMOS process, the ring-oscillator based DPLL consumes 1.35mW at 1.5GHz output frequency and achieves better than 50fs/mV worst-case noise sensitivity (≡10pspp jitter degradation with 200mVpp noise).
Social citizenship formation at university: a South African case study

The paper considers citizenship formation at universities, drawing on the example of a student leadership project at the University of the Free State, a formerly White South African university, in a higher education context and society where racialised difference continues to influence peer relationships. The paper proposes a multi-dimensional conceptualisation of social citizenship, as described by T.H. Marshall, enriched by the capabilities approach, which adds specific citizenship dimensions of deliberation, acknowledgment of heterogeneity, and agency goals and activities as core elements of being able to be and to do as citizens. This is operationalised by investigating the student development intervention, based on biographical interview data from 50 of the 71 students who participated in the first iteration of the programme. The data is analysed for the three capability dimensions and for student criticisms of the programme, before an overall judgment is made of the programme’s contribution to democratic values and citizenship formation.
‘Rowing against the current’: the policy process and effects of removing user fees for caesarean sections in Benin

Background In 2009, the Benin government introduced a user fee exemption policy for caesarean sections. We analyse this policy with regard to how the existing ideas and institutions related to user fees influenced key steps of the policy cycle and draw lessons that could inform the policy dialogue for universal health coverage in the West African region. Methods Following the policy stages model, we analyse the agenda setting, policy formulation and legitimation phase, and assess the implementation fidelity and policy results. We adopted an embedded case study design, using quantitative and qualitative data collected with 13 tools at the national level and in seven hospitals implementing the policy. Results We found that the initial political goal of the policy was not to reduce maternal mortality but to eliminate the detention in hospitals of mothers and newborns who cannot pay the user fees by exempting a comprehensive package of maternal health services. We found that the policy development process suffered from inadequate uptake of evidence and that the policy content and process were not completely in harmony with political and public health goals. The initial policy intention clashed with the neoliberal orientation of the political system, the fee recovery principles institutionalised since the Bamako Initiative and the prevailing ideas in favour of user fees. The policymakers did not take these entrenched factors into account. The resulting tension contributed to a benefit package covering only caesarean sections and to the variable implementation and effectiveness of the policy. Conclusion The influence of organisational culture in the decision-making processes in the health sector is often ignored but must be considered in the design and implementation of any policy aimed at achieving universal health coverage in West African countries.
Diagnostic and Prognostic Value of ProEx C and GLUT1 in Melanocytic Lesions.

BACKGROUND Melanoma is one of the most aggressive types of skin cancer. The purpose of this study was to evaluate the use of two biomarkers, ProEx C and glucose transporter isoform 1 (GLUT1), in the diagnosis and prognostication of melanoma. MATERIALS AND METHODS We analyzed 129 melanomas and 59 benign nevi in a tissue microarray using immunohistochemical method with antibodies to topoisomerase IIα (TOP2A) and minichromosome maintenance complex component 2 (MCM2) using ProEx C and to GLUT1. RESULTS The average proliferative index by ProEx C immunostain was significantly higher in melanomas (37.5%) compared to benign nevi (1.9%) as was the expression of GLUT1 (p<0.0001 respectively). Dermal mitosis was found to correlate positively with both ProEx C and GLUT1 (p=0.003 and p<0.001, respectively). Ulceration and tumor thickness positively correlated with GLUT1 expression (p=0.013 and p=0.033, respectively), but not with ProEx C staining. There was a significant association between increasing ProEx C index and stronger expression of GLUT1 (p<0.001). Kaplan-Meier disease-specific survival analyses indicated that patients whose melanoma exhibited expression of GLUT1 had a significantly lower rate of disease-specific survival than patients whose melanoma did not (p=0.039). However, staining by ProEx C did not show a prognostic significance in disease-specific survival. CONCLUSION ProEx C and GLUT1 are potentially useful markers in differentiation of melanoma from nevi. Absence of GLUT1 expression in patients with primary melanoma predicts better survival.
Contemporary psychotherapists: A national survey of characteristics, practices, orientations, and attitudes.

A representative sample of American psychologists engaged in psychotherapy were surveyed concerning their characteristics, activities, affiliations, theories, and selected attitudes. 410 members ofAPA Division 29 (Psychotherapy) returned a mailed questionnaire, providing a current and comprehensive assessment of the profession. Survey results are described in detail and compared to the findings of a similar survey of American clinical psychologists (Division 12 members). Among the most salient findings were that: 1) over 80% of therapists have had personal therapy and highly value these experiences as preparation for providing therapy; 2) individual therapy is the most popular therapeutic modality, but over one-half of the sample engage in marital and family therapy; 3) while therapists spend relatively small percentages of their time doing research, they do as a group publish and present papers; 4) private practice is the modal affiliation of the sample and may be the most equitable employment setting; and 5) psychodynamic orientations have experienced renewed preference with eclecticism declining, suggesting a need for more integrative models of therapy.
The Ripple Effect of the Matthew Shepard Murder

This research investigated the psychological impact of the Shepard murder, a widely publicized antigay hate crime in 1998, on nonvictims who were members of the targeted group, through the lens of assumptive world theory. Nine people with minority sexual identities who indicated that they were deeply affected by this murder participated in semistructured interviews of 60 to 90 minutes, and verbatim transcripts were coded and analyzed using qualitative data analysis software. Participants were five men and four women ranging in age from 17 to 51. Results illustrate a vicarious traumatization effect; that is, this event challenged participant fundamental assumptions of benevolence and meaningfulness of the world and worthiness of self. Findings also reflect positive aftereffects. Strengths and limitations of the study, as well as future research possibilities, are discussed.
GUN4-Porphyrin Complexes Bind the ChlH/GUN5 Subunit of Mg-Chelatase and Promote Chlorophyll Biosynthesis in Arabidopsis[W]

We show that GUN4-porphyrin complexes help to channel protoporphyrin IX into chlorophyll biosynthesis by binding to the ChlH subunit of Mg-chelatase with a higher affinity than unliganded GUN4 on Arabidopsis chloroplast membranes. GUN4 and ChlH used distinct mechanisms to associate with chloroplast membranes, and mutant alleles of GUN4 and Mg-chelatase subunit genes cause sensitivity to intense light. The GENOMES UNCOUPLED4 (GUN4) protein stimulates chlorophyll biosynthesis by activating Mg-chelatase, the enzyme that commits protoporphyrin IX to chlorophyll biosynthesis. This stimulation depends on GUN4 binding the ChlH subunit of Mg-chelatase and the porphyrin substrate and product of Mg-chelatase. After binding porphyrins, GUN4 associates more stably with chloroplast membranes and was proposed to promote interactions between ChlH and chloroplast membranes—the site of Mg-chelatase activity. GUN4 was also proposed to attenuate the production of reactive oxygen species (ROS) by binding and shielding light-exposed porphyrins from collisions with O2. To test these proposals, we first engineered Arabidopsis thaliana plants that express only porphyrin binding–deficient forms of GUN4. Using these transgenic plants and particular mutants, we found that the porphyrin binding activity of GUN4 and Mg-chelatase contribute to the accumulation of chlorophyll, GUN4, and Mg-chelatase subunits. Also, we found that the porphyrin binding activity of GUN4 and Mg-chelatase affect the associations of GUN4 and ChlH with chloroplast membranes and have various effects on the expression of ROS-inducible genes. Based on our findings, we conclude that ChlH and GUN4 use distinct mechanisms to associate with chloroplast membranes and that mutant alleles of GUN4 and Mg-chelatase genes cause sensitivity to intense light by a mechanism that is potentially complex.
Work–family policies, participation, and practices: fathers and childcare in Europe

This paper asks about social policies for fathers’ participation in childcare in Europe, and fathers’ work–family reconciliation practices and ideals, with special reference to the UK. In some European countries, especially Sweden, reform has given fathers non-transferable rights to parental leave. Might such innovations enhance UK men's contribution to childcare? In the UK, gender inequalities in policy are stark: parental leave systems assume – through maternity leaves – mothers’ responsibility for care, while seeing fathers’ care as a question of individual choice. Our qualitative research asked how fathers managed reconciliation between work and family, and how alternative social policy strategies would fit with their practices and ideals. The paper concludes that social policies supporting men's care – particularly parental leave dedicated to fathers – are needed to enhance gender equality and work–family reconciliation for men and for women.
A wearable skin stretch haptic feedback device: Towards improving balance control in lower limb amputees

Haptic feedback to lower limb amputees is essential to maximize the functionality of a prosthetic device by providing information to the user about the interaction with the environment and the position of the prostheses in space. Severed sensory pathway and the absence of connection between the prosthesis and the Central Nervous System (CNS) after lower limb amputation reduces balance control, increases visual dependency and increases risk of falls among amputees. This work describes the design of a wearable haptic feedback device for lower limb amputees using lateral skin-stretch modality intended to serve as a feedback cue during ambulation. A feedback scheme was proposed based on gait event detection for possible real-time postural adjustment. Preliminary perceptual test with healthy subjects in static condition was carried out and the results indicated over 98% accuracy in determining stimuli location around the upper leg region, suggesting good perceptibility of the delivered stimuli.
Exploring the Potential Disadvantages of High Cohesion in Sports Teams

In the present study, a heterogeneous sample of 105 athletes (mean age = 21.4 years) was used to gain insight into the potential negative consequences of high team cohesion. Athletes were asked open-ended questions relating to the potential disadvantages of high task and high social cohesion. It was found that 56% of athletes reported possible disadvantages to high social cohesion, whereas 31% of athletes reported possible disadvantages to high task cohesion. Furthermore, data analyses revealed multiple dimensions of negative consequences for both high task and social cohesion. More specifically, analysis of responses revealed both group- and personal-level consequences. The findings contrast with the popularly held view that high cohesion is always beneficial for teams and team members. It was suggested that future research assess the prevalence and importance of the disadvantages of high cohesion.
Duplicate Bug Report Detection Using Clustering

Bug reporting and fixing the reported bugs play a critical part in the development and maintenance of software systems. The software developers and end users can collaborate in this process to improve the reliability of software systems. Various end users report the defects they have found in the software and how these bugs affect them. However, the same defect may be reported independently by several users leading to a significant number of duplicate bug reports. There are a number of existing methods for detecting duplicate bug reports, but the best results so far account for only 24% of actual duplicates. In this paper, we propose a new method based on clustering to identify a larger proportion of duplicate bug reports while keeping the false positives of misidentified non-duplicates low. The proposed approach is experimentally evaluated on a large sample of bug reports from three public domain data sets. The results show that this approach achieves better performance in terms of a harmonic measure that combines true positive and true negative rates when compared to the existing methods.
Citizenship in Practice: Poverty Reduction and Self-Help Groups

Citizenship is essentially about membership in society which enables citizens to participate in the affairs of their community on roughly equal terms and culturally enjoins upon them to collectively surmount their commonly felt problems, such as poverty. The role of Self-Help Groups (SHGs) should be understood in this context. Through observation and conversation-analysis methods, this paper studies two SHGs in India: the successful one practiced citizenship, envisaged a sense of community and made progress towards capacity building and empowerment, especially pertaining to education, health and sanitation. It concludes that in developing countries, citizens acquire the appropriate virtues through participation in the programmes linked with their vision of well-being and thus strengthen the cause of citizenship.
A sociocultural functional analysis of fragmentation in Japanese

The purpose of this paper is to suggest that a functional analysis of such a language-related phenomenon as listener cues may lead to more useful insights about language in use than a formal, structural-driven approach. An available analysis of listener cues in Japanese concerning the co-occurrence of relatively frequent back channel cues and particular syntactic environments is contrasted with a pragmatic analysis which includes a consideration of cognitive, psychological, and sociocultural factors to generate an approach with more explanatory power regarding the role human communicative needs play in language development and the use of language in everyday life.
The Recaptured Scale Technique: A Method for Testing the Structural Robustness of Personality Scales

ABSTRACT Tellegen and Waller advocated a complex and time-consuming scale construction method that they called “exploratory test construction. ” Scales that are constructed by this method—such as the Multidimensional Personality Questionnaire (MPQ)—are presumed to be more “psychologically coherent” and “robust” than scales constructed by other means. Using a novel procedure that we call the “recaptured scale technique,” we tested this conjecture by conducting a megafactor analysis on data from the 411 adult participants of the Minnesota Study of Twins Reared Apart who completed the MPQ, the MMPI, and the CPI. We extracted and obliquely rotated 21 factors from a matrix of gender-corrected tetrachoric correlations for the 1,102 nonredundant items of the three omnibus inventories. Robustness of the 11 MPQ scales was assessed by the degree to which these factors recaptured the MPQ item groupings. Our results showed that nine factors were clearly recognizable as MPQ scales and two additional factors represented a bifurcation of an MPQ scale. A higher-order factor analysis of all 21 factor scales yielded five factors that clearly resembled the Big Five. Our results provide strong support for (a) the method of exploratory test construction, (b) the structural robustness of most MPQ scales, and (c) the utility of the recaptured scale technique.
Measurement of IgG antibodies to Chlamydia trachomatis by commercial enzyme immunoassays and immunofluorescence in sera from pregnant women and patients with infertility, pelvic inflammatory disease, ectopic pregnancy, and laboratory diagnosed Chlamydia psittaci/Chlamydia pneumoniae infection

Background: Screening for Chlamydia trachomatis specific antibodies is valuable in diagnosing asymptomatic pelvic inflammatory disease (PID) and tubal damage following repeated episodes of PID. The assays in current use are unsuitable for screening large numbers of samples so there is a need to develop more suitable assays. Aims: To compare the performance of several commercial C trachomatis enzyme immunoassays (EIAs) (SeroCT, C trachopep, Medac p-EIA, Vircell and Labsystems C trachomatis IgG EIAs) using major outer membrane protein (MOMP), an inactivated organism EIA (Genzyme Virotech EIA), and a genus specific EIA (Platelia Chlamydia IgG) with the whole cell inclusion immunofluorescence (WIF) assay. In addition, to adapt, using time resolved fluorescence technology, the assay showing the highest correlation with WIF. Methods: Ninety sera from patients presenting with ectopic pregnancies, 187 sera from those with a variety of types of infertility, 33 sera from cases of PID where a fourfold rise in WIF titre occurred, and 90 sera from antenatal clinic attenders were tested. A panel of 36 sera from laboratory diagnosed cases of Chlamydia psittaci/Chlamydia pneumoniae infection was also tested. Results: The Genzyme Virotech EIA showed the highest rank correlation coefficient (0.82) with WIF, particularly at high WIF titres. The MOMP specific assays varied in their correlation with WIF, with rank correlation coefficients ranging from 0.70 (Medac p-EIA) to 0.80 (Vircell EIA). The Genzyme Virotech assay showed poor specificity (5.6%; 95% confidence interval (CI), 0.68% to 18.7%)—it was reactive with 34 of the panel of 36 C psittaci/C pneumoniae positive sera. The MOMP based EIAs showed high specificity, particularly the Medac p-ELISA (97.2%; 95% CI, 85.5% to 99.9%)—only one serum was reactive. In view of the good correlation between WIF and the Genzyme Virotech EIA, a time resolved fluorescence immunoassay (TRFIA) was developed using the Genzyme Virotech antigen. Using an appropriate cut off the TRFIA assay showed excellent correlation with WIF. Conclusions: The TRFIA assay may be useful as a screening assay, possibly in conjunction with one of the highly specific EIAs studied (for example, Medac p-EIA) to confirm the antibody specificity of sera selected by the screening assay.