Hexagonal Boron Nitride Crystal Growth from Iron, a Single Component Flux.

The highest quality hexagonal boron nitride (hBN) crystals are grown from molten solutions. For hBN crystal growth at atmospheric pressure, typically the solvent is a combination of two metals, one with a high boron solubility and the other to promote nitrogen solubility. In this study, we demonstrate that high-quality hBN crystals can be grown at atmospheric pressure using pure iron as a flux. The ability to produce excellent-quality hBN crystals using pure iron as a solvent is unexpected, given its low solubility for nitrogen. The properties of crystals produced with this flux matched the best values ever reported for hBN: a narrow Raman E2g vibration peak (7.6 cm-1) and strong phonon-assisted peaks in the photoluminescence spectra. To further test their quality, the hBN crytals were used as a substrate for WSe2 epitaxy. WSe2 was deposited with a low nucleation density, indicating the low defect density of the hBN. Lastly, the carrier tunneling through our hBN thin layers (3.5 nm) follows the Fowler-Nordheim model, with a barrier height of 3.7 eV, demonstrating hBN's superior electrical insulating properties. This ability to produce high-quality hBN crystals in such a simple, environmentally friendly and economical process will advance two-dimensional material research by enabling integrated devices.

The Perceived Ability of Gastroenterologists, Hepatologists and Surgeons Can Bias Medical Decision Making.

Medical errors are a troubling issue and physicians should be careful to scrutinize their own decisions, remaining open to the possibility that they may be wrong. Even so, doctors may still be overconfident. A survey was here conducted to test how medical experience and self-confidence can affect physicians working in the specific clinical area. Potential participants were contacted through personalized emails and invited to contribute to the survey. The "risk-intelligence" test consists of 50 statements about general knowledge in which participants were asked to indicate how likely they thought that each statement was true or false. The risk-intelligence quotient (RQ), a measure of self-confidence, varies between 0 and 100. The higher the RQ score, the better the confidence in personal knowledge. To allow for a representation of 1000 physicians, the sample size was calculated as 278 respondents. A total of 1334 individual emails were sent to reach 278 respondents. A control group of 198 medical students were also invited, of them, 54 responded to the survey. The mean RQ (SD)of physicians was 61.1 (11.4) and that of students was 52.6 (9.9). Assuming age as indicator of knowledge, it was observed that physicians ≤34 years had a mean RQ of 59.1 (10.1); those of 35-42 years had 61.0 (11.0); in those of 43-51 years increased to 62.9 (12.2); reached a plateau of 63.0 (11.5) between 52-59 years and decreased to 59.6 (12.1) in respondents ≥60 years (r2:0.992). Doctors overestimate smaller probabilities and under-estimate higher probabilities. Specialists in gastroenterology and hepato-biliary diseases suffer from some degree of self-confidence bias, potentially leading to medical errors. Approaches aimed at ameliorating the self-judgment should be promoted more widely in medical education.

Single-chain antibody-fragment M6P-1 possesses a mannose 6-phosphate monosaccharide-specific binding pocket that distinguishes N-glycan phosphorylation in a branch-specific manner†.

The acquisition of mannose 6-phosphate (Man6P) on N-linked glycans of lysosomal enzymes is a structural requirement for their transport from the Golgi apparatus to lysosomes mediated by the mannose 6-phosphate receptors, 300 kDa cation-independent mannose 6-phosphate receptor (MPR300) and 46 kDa cation-dependent mannose 6-phosphate receptor (MPR46). Here we report that the single-chain variable domain (scFv) M6P-1 is a unique antibody fragment with specificity for Man6P monosaccharide that, through an array-screening approach against a number of phosphorylated N-glycans, is shown to bind mono- and diphosphorylated Man6 and Man7 glycans that contain terminal αMan6P(1 → 2)αMan(1 → 3)αMan. In contrast to MPR300, scFv M6P-1 does not bind phosphodiesters, monophosphorylated Man8 or mono- or diphosphorylated Man9 structures. Single crystal X-ray diffraction analysis to 2.7 Å resolution of Fv M6P-1 in complex with Man6P reveals that specificity and affinity is achieved via multiple hydrogen bonds to the mannose ring and two salt bridges to the phosphate moiety. In common with both MPRs, loss of binding was observed for scFv M6P-1 at pH values below the second pKa of Man6P (pKa = 6.1). The structures of Fv M6P-1 and the MPRs suggest that the change of the ionization state of Man6P is the main driving force for the loss of binding at acidic lysosomal pH (e.g. lysosome pH ∼ 4.6), which provides justification for the evolution of a lysosomal enzyme transport pathway based on Man6P recognition.

Structural insights into parallel strategies for germline antibody recognition of lipopolysaccharide from Chlamydia.

The structure of the antigen-binding fragment from the monoclonal antibody S64-4 in complex with a pentasaccharide bisphosphate fragment from chlamydial lipopolysaccharide has been determined by x-ray diffraction to 2.6 Å resolution. Like the well-characterized antibody S25-2, S64-4 displays a pocket formed by the residues of germline sequence corresponding to the heavy and light chain V gene segments that binds the terminal Kdo residue of the antigen; however, although S64-4 shares the same heavy chain V gene segment as S25-2, it has a different light chain V gene segment. The new light chain V gene segment codes for a combining site that displays greater affinity, different specificity, and allows a novel antigen conformation that brings a greater number of antigen residues into the combining site than possible in S25-2. Further, while antibodies in the S25-2 family use complementarity determining region (CDR) H3 to discriminate among antigens, S64-4 achieves its specificity via the new light chain V gene segment and resulting change in antigen conformation. These structures reveal an intriguing parallel strategy where two different combinations of germline-coded V gene segments can act as starting points for the generation of germline antibodies against chlamydial antigens and show how anti-carbohydrate antibodies can exploit the conformational flexibility of this class of antigens to achieve high affinity and specificity independently of CDR H3.

A common NH53K mutation in the combining site of antibodies raised against chlamydial LPS glycoconjugates significantly increases avidity.

The crystal structures of the antigen-binding fragment of the murine monoclonal antibody (mAb) S25-39 in the presence of several antigens representing chlamydial lipopolysaccharide (LPS) epitopes based on the bacterial sugar 3-deoxy-α-D-manno-oct-2-ulosonic acid (Kdo) have been determined at resolutions from 2.4 to 1.8 Å. The antigen-binding site of this antibody differs from the well-characterized antibody S25-2 by a single mutation away from the germline of asparagine H53 to lysine, yet this one mutation results in a significant increase in avidity across a range of antigens. A comparison of the two antibody structures reveals that the mutated Lys H53 forms additional hydrogen bonds and/or charged-residue interactions with the second Kdo residue of every antigen having two or more carbohydrate residues. Significantly, the NH53K mutation results from a single nucleotide substitution in the germline sequence common among a panel of antibodies raised against glycoconjugates containing carbohydrate epitopes of chlamydial LPS. Like S25-2, S25-39 displays significant induced fit of complementarity determining region (CDR) H3 upon antigen binding, with the unliganded structure possessing a conformation distinct from those reported earlier for S25-2. The four different observed conformations for CDR H3 suggest that this CDR has evolved to exploit the recognition potential of a flexible loop while minimizing the associated entropic penalties of binding by adopting a limited number of ordered conformations in the unliganded state. These observations reveal strategies evolved to balance adaptability and specificity in the germline antibody response to carbohydrate antigens.

The challenge of treating conduct disorder in low-resourced settings: rap music to the rescue.

Conduct disorder is one of the most frequent serious childhood problems that present for treatment in community clinic settings. Evidence-based treatments for conduct disorder are intensive and require considerable resources to implement. In low-resourced contexts it is often not feasible to implement evidence-based treatments in their current form, which poses significant challenges for clinicians attempting to treat children in these settings. This article explores these challenges using a case study of the treatment of a young adolescent boy with a short-term multisystem intervention where rap music was employed as a powerful tool to facilitate an empathic connection in therapy and as a projective technique to explore underlying emotional difficulties.

Mental health problems of men attending district-level clinical psychology services in South Africa.

Over a 1-yr. period, 70 men attended district level clinical psychology services in Msunduzi, South Africa. The mean age was 35.9 yr., and 80% had secondary education. Only 65.7% attended of their own accord. 51% were unemployed, 71.4% had financial problems, 44.3% admitted to substance abuse, 74.3% reported relationship problems, and 14.3% admitted to being violent toward their partners. Suicidal ideation was the commonest referral problem, while mood disorder was the most frequent diagnosis. Clinicians estimated that 75.7% of these men had low self-esteem. 45.8% (34) perceived their partner as disengaged, enmeshed, or oppressive.

Export of dissolved organic matter in relation to land use along a European climatic gradient.

The terrestrial export of dissolved organic matter (DOM) is associated with climate, vegetation and land use, and thus is under the influence of climatic variability and human interference with terrestrial ecosystems, their soils and hydrological cycles. We present a data-set including catchments from four areas covering the major climate and land use gradients within Europe: a forested boreal zone (Finland), a temperate agricultural area (Denmark), a wet and temperate mountain region in Wales, and a warm Mediterranean catchment draining into the Gulf of Lyon. In all study areas, DOC (dissolved organic carbon) was a major fraction of DOM, with much lower proportions of DON (dissolved organic nitrogen) and DOP (dissolved organic phosphorus). A south-north gradient with highest DOC concentrations and export in the northernmost catchments was recorded: DOC concentrations and loads were highest in Finland and lowest in France. These relationships indicate that DOC concentrations/export are controlled by several factors including wetland and forest cover, precipitation and hydrological processes. DON concentrations and loads were highest in the Danish catchments and lowest in the French catchments. In Wales and Finland, DON concentrations increased with the increasing proportion of agricultural land in the catchment, whereas in Denmark and France no such relationship was found. DOP concentrations and loads were low compared to DOC and DON. The highest DOP concentrations and loads were recorded in catchments with a high extent of agricultural land, large urban areas or a high population density, reflecting the influence of human impact on DOP loads.

Suppression of the acute-phase response as a biological mechanism for the placebo effect.

The idea that inert substances such as sugar pills can have powerful therapeutic effects--the so-called 'placebo effect'--has been widely accepted by most medical researchers since the 1950s. Today there is increasing scepticism about the reality of the placebo effect. This debate has been too simplistic; rather than asking whether or not the placebo effect exists, as researchers have done up to now, we should be more precise, and ask which medical conditions (if any) are placebo-responsive. There is evidence that pain, swelling, stomach ulcers, depression, and anxiety are all placebo-responsive. These conditions have all been linked, to a greater or lesser extent, with activation of the acute-phase response (the innate immune response). The placebo effect may therefore be mediated by alteration of one or more components of the acute-phase response. The candidates for such biochemical mediators would need to alter the synthesis, activation, receptor-binding or signalling mechanisms of inflammation, sickness behaviour and other aspects of innate immunity. This hypothesis is consistent with current data suggesting that placebos work by triggering the release of endorphins. The hypothesis would be falsified if it were found that other medical conditions, not involving the activation of the acute-phase response, were nonetheless alleviated by placebos.

How long do the advantages of learning to read a transparent orthography last? An investigation of the reading skills and reading impairment of Welsh children at 10 years of age.

Spencer and Hanley (2003) showed that Welsh-speaking children aged between 5 and 7 years who were learning to read Welsh (a transparent orthography) performed significantly better at reading both real words and nonwords than did English-speaking children living in Wales who were learning to read English (a deep orthography). In this study, the reading skills of these children were reexamined three years later, during their sixth year of formal reading instruction. The children learning to read English continued to perform poorly at reading low- and medium-frequency irregular words but no differences were observed in reading regular words or nonwords. These findings emphasize how long it takes to acquire a large sight vocabulary in English, but indicated that the reading skills of the majority of the English-speaking children had caught up with those of their Welsh-speaking counterparts. However, the poorest 25% of the English readers continued to perform much worse than the lowest performing 25% of Welsh readers on both words and nonwords. An underachieving tail of this kind was not observed in the reading performance of the Welsh-speaking group. Overall, these findings suggest that in the long term the detrimental effects of an opaque orthography are most damaging to the poorest readers.