Data collection with a tailored X-ray beam size at 2.69 angstrom wavelength (4.6 keV):sulfur SAD phasing of Cdc23(Nterm)

The capability to reach wavelengths of up to 3.1 Å at the newly established EMBL P13 beamline at PETRA III, the new third-generation synchrotron at DESY in Hamburg, provides the opportunity to explore very long wavelengths to harness the sulfur anomalous signal for phase determination. Data collection at $\lambda$ = 2.69 Å (4.6 keV) allowed the crystal structure determination by sulfur SAD phasing of Cdc23$^{Nterm}$, a subunit of the multimeric anaphase-promoting complex (APC/C). At this energy, Cdc23$^{Nterm}$ has an expected Bijvoet ratio <|F$_{anom}$|>/<F> of 2.2%, with 282 residues, including six cysteines and five methionine residues, and two molecules in the asymmetric unit (65.4 kDa; 12 Cys and ten Met residues). Selectively illuminating two separate portions of the same crystal with an X-ray beam of 50 µm in diameter allowed crystal twinning to be overcome. The crystals diffracted to 3.1 Å resolution, with unit-cell parameters a = b = 61.2, c = 151.5 Å, and belonged to space group $P4_3$. The refined structure to 3.1 Å resolution has an R factor of 18.7% and an R$_{free}$ of 25.9%. This paper reports the structure solution, related methods and a discussion of the instrumentation

Tutoring in problem-based learning medical curricula: the influence of tutor background and style on effectiveness

BACKGROUND: Evidence for the superiority of particular characteristics in PBL tutors in medical curricula is generally inconclusive. Most studies have investigated the effectiveness of content experts compared with that of non-experts as measured either by student satisfaction or academic achievement. A few have compared academic staff tutors with student tutors. The purpose of this study was to investigate the relationship between students' perception of overall tutor effectiveness, particular tutor behaviours, clinical qualifications and academic appointment. METHOD: A questionnaire designed to evaluate particular aspects of PBL tutoring technique, related either to subject-matter knowledge or to process-facilitation skill, as well as overall effectiveness, was distributed to students in first year of a PBL medical program at the end of each of three tutor terms. A total of 76 tutor terms were included in the study. Data analysis compared clinical with non-clinical tutors, and staff with non-staff tutors. RESULTS: Clinically qualified tutors used their subject-matter knowledge significantly more than non-clinical tutors and were seen as being more empathic with their students. Staff tutors placed more emphasis on assessment than non-staff tutors and were seen as having greater skill in establishing and maintaining an environment of cooperation within their PBL groups than non-staff tutors. CONCLUSION: These results suggest that both subject-matter knowledge and process-facilitation skills are necessary but not individually sufficient characteristics of effective tutors

Gemini GMOS and WHT SAURON integral-field spectrograph observations of the AGN driven outflow in NGC 1266

We use the SAURON and GMOS integral field spectrographs to observe the active galactic nucleus (AGN) powered outflow in NGC 1266. This unusual galaxy is relatively nearby (D=30 Mpc), allowing us to investigate the process of AGN feedback in action. We present maps of the kinematics and line strengths of the ionised gas emission lines Halpha, Hbeta, [OIII], [OI], [NII] and [SII], and report on the detection of Sodium D absorption. We use these tracers to explore the structure of the source, derive the ionised and atomic gas kinematics and investigate the gas excitation and physical conditions. NGC 1266 contains two ionised gas components along most lines of sight, tracing the ongoing outflow and a component closer to the galaxy systemic, the origin of which is unclear. This gas appears to be disturbed by a nascent AGN jet. We confirm that the outflow in NGC 1266 is truly multiphase, containing radio plasma, atomic, molecular and ionised gas and X-ray emitting plasma. The outflow has velocities up to \pm900 km/s away from the systemic velocity, and is very likely to be removing significant amounts of cold gas from the galaxy. The LINER-like line-emission in NGC 1266 is extended, and likely arises from fast shocks caused by the interaction of the radio jet with the ISM. These shocks have velocities of up to 800 km/s, which match well with the observed velocity of the outflow. Sodium D equivalent width profiles are used to set constraints on the size and orientation of the outflow. The ionised gas morphology correlates with the nascent radio jets observed in 1.4 GHz and 5 GHz continuum emission, supporting the suggestion that an AGN jet is providing the energy required to drive the outflow.Comment: Contains 18 figures. Accepted to MNRA

Current Directions in the Auricular

Electrical stimulation of the auricular vagus nerve (aVNS) is an emerging electroceutical technology in the field of bioelectronic medicine with applications in therapy. Artificial modulation of the afferent vagus nerve – a powerful entrance to the brain – affects a large number of physiological processes implicating interactions between the brain and body. Engineering aspects of aVNS determine its efficiency in application. The relevant safety and regulatory issues need to be appropriately addressed. In particular, in silico modeling acts as a tool for aVNS optimization. The evolution of personalized electroceuticals using novel architectures of the closed-loop aVNS paradigms with biofeedback can be expected to optimally meet therapy needs. For the first time, two international workshops on aVNS have been held in Warsaw and Vienna in 2017 within the scope of EU COST Action “European network for innovative uses of EMFs in biomedical applications (BM1309).” Both workshops focused critically on the driving physiological mechanisms of aVNS, its experimental and clinical studies in animals and humans, in silico aVNS studies, technological advancements, and regulatory barriers. The results of the workshops are covered in two reviews, covering physiological and engineering aspects. The present review summarizes on engineering aspects – a discussion of physiological aspects is provided by our accompanying article (Kaniusas et al., 2019). Both reviews build a reasonable bridge from the rationale of aVNS as a therapeutic tool to current research lines, all of them being highly relevant for the promising aVNS technology to reach the patient.European Cooperation in Science and TechnologyThe Austrian Research Promotion Agenc

Community Violence and Youth: Affect, Behavior, Substance Use, and Academics

Community violence is recognized as a major public health problem (WHO, World Report on Violence and Health,2002) that Americans increasingly understand has adverse implications beyond inner-cities. However, the majority of research on chronic community violence exposure focuses on ethnic minority, impoverished, and/or crime-ridden communities while treatment and prevention focuses on the perpetrators of the violence, not on the youth who are its direct or indirect victims. School-based treatment and preventive interventions are needed for children at elevated risk for exposure to community violence. In preparation, a longitudinal, community epidemiological study, The Multiple Opportunities to Reach Excellence (MORE) Project, is being fielded to address some of the methodological weaknesses presented in previous studies. This study was designed to better understand the impact of children’s chronic exposure to community violence on their emotional, behavioral, substance use, and academic functioning with an overarching goal to identify malleable risk and protective factors which can be targeted in preventive and intervention programs. This paper describes the MORE Project, its conceptual underpinnings, goals, and methodology, as well as implications for treatment and preventive interventions and future research

A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations