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Introduction: Variants of the APOL1 gene are associated with chronic kidney disease (CKD) in people of African ancestry, although evidence for their impact in people with HIV are sparse. Methods: We conducted a cross-sectional study investigating the association between APOL1 renal risk alleles and kidney disease in people of African ancestry with HIV in the UK. The primary outcome was end-stage kidney disease (ESKD; estimated glomerular filtration rate [eGFR] of 2, chronic dialysis, or having received a kidney transplant). The secondary outcomes included renal impairment (eGFR 2), albuminuria (albumin-to-creatinine ratio [ACR] >30 mg/mmol), and biopsy-proven HIV-associated nephropathy (HIVAN). Multivariable logistic regression was used to estimate the associations between APOL1 high-risk genotypes (G1/G1, G1/G2, G2/G2) and kidney disease outcomes. Results: A total of 2864 participants (mean age 48.1 [SD 10.3], 57.3% female) were genotyped, of whom, 354 (12.4%) had APOL1 high-risk genotypes, and 99 (3.5%) had ESKD. After adjusting for demographic, HIV, and renal risk factors, individuals with APOL1 high-risk genotypes were at increased odds of ESKD (odds ratio [OR] 10.58, 95% CI 6.22–17.99), renal impairment (OR 5.50, 95% CI 3.81–7.95), albuminuria (OR 3.34, 95% CI 2.00–5.56), and HIVAN (OR 30.16, 95% CI 12.48–72.88). An estimated 49% of ESKD was attributable to APOL1 high-risk genotypes. Conclusion: APOL1 high-risk genotypes were strongly associated with kidney disease in people of African ancestry with HIV and accounted for approximately half of ESKD cases in this cohort.

Excavation in advance of housing development at Basing View, Basingstoke, revealed the remains of an Early Roman enclosed settlement that possibly originated in the Late Iron Age and was occupied to the early 2nd century. The settlement was fairly low status, focussed on mixed farming practices, but was notable for the presence of a possible sunken- featured building with a baby burial. The site adds to current knowledge of the Late Iron Age/Early Roman settlement archaeology of the area south of Silchester (Calleva Atrebatum).

Rapid nucleic-acid based tests that can be performed by non-professionals outside laboratory settings could help the containment of the pandemic SARS-CoV-2 virus and may potentially prevent further widespread lockdowns. Here, we present a novel compact portable detection instrument (the Egoo Health System) for extraction-free detection of SARS-CoV-2 using isothermal Reverse Transcription Strand Invasion Based Amplification (RT-SIBA). The SARS-CoV-2 RT-SIBA assay can be performed directly on crude oropharyngeal swabs without nucleic acid extraction with a reaction time of 30 minutes. The Egoo health system uses a capsule system, which is automatically sealed tight in the Egoo instrument after applying the sample, resulting in a closed system optimal for molecular isothermal amplification. The performance of the Egoo Health System is comparable to the PCR instrument with an analytical sensitivity of 25 viral RNA copies per SARS-CoV-2 RT-SIBA reaction and a clinical sensitivity and specificity between 87.0-98.4% and 96.6-98.2% respectively.

Sickle cell trait (SCT) has been associated with chronic kidney disease (CKD) in African Americans, although evidence for its impact in Africans and people with HIV is currently lacking. We conducted a cross-sectional study investigating the association between SCT and kidney disease in people of African ancestry with HIV in the UK.The primary outcome was estimated glomerular filtration rate (eGFR) 60 ml/min per 1.73 mA total of 2895 participants (mean age 48.1 [SD 10.3], 57.2% female) were included, of whom 335 (11.6%) had SCT and 352 (12.2%) had eGFR 60 ml/min per 1.73 mOur results extend previously reported associations between SCT and kidney disease to people with HIV. In people of African ancestry with HIV, these associations were largely restricted to those with

Purpose The purpose of this study was to understand the experiences and perspectives of clients who stutter who are receiving telepractice treatment. Method Five adult participants (19–68 years old...

In the marine environment agar degradation is assured by bacteria that contain large agarolytic systems with enzymes acting in various endo- and exo-modes. Agarase A (AgaA) is an endo-glycoside hydrolase of family 16 considered to initiate degradation of agarose. Agaro-oligosaccharide binding at a unique surface binding site (SBS) in AgaA from Zobellia galactanivorans was investigated by computational methods in conjunction with a structure/sequence guided approach of site-directed mutagenesis probed by surface plasmon resonance binding analysis of agaro-oligosaccharides of DP 4-10. The crystal structure has shown that agaro-octaose interacts via H-bonds and aromatic stacking along 7 subsites (L through R) of the SBS in the inactive catalytic nucleophile mutant AgaA-E147S. D271 is centrally located in the extended SBS where it forms H-bonds to galactose and 3,6-anhydrogalactose residues of agaro-octaose at subsites O and P. We propose D271 is a key residue in ligand binding to the SBS. Thus AgaA-E147S/D271A gave slightly decreasing KD values from 625 ± 118 to 468 ± 13 μM for agaro-hexaose, -octaose and -decaose, which represent 3-4-fold reduced affinity compared to AgaA-E147S. Molecular dynamics simulations and interaction analyses of AgaA-E147S/D271A indicated disruption of an extended H-bond network supporting that D271 is critical for the functional SBS. Notably, neither AgaA-E147S/W87A nor AgaA-E147S/W277A, designed to eliminate stacking with galactose residues at subsites O and Q, respectively, were produced in soluble form. W87 and W277 may thus control correct folding and structural integrity of AgaA. This article is protected by copyright. All rights reserved.

In vision-aided navigation, several challenges affect algorithm performance in different ways. These challenges include terrain type, sensor technology, cloud coverage, sensor malfunction, and environmental conditions such as illumination. Currently, ordinance such as precision-guided munitions, may experience any of these challenges over the course of the mission. Each challenge has an associated probability-of-occurrence, e.g. probability that clouds will obscure the field-of-view, or that sensor hardware will induce image blurring or other artifacts that impede scene imaging ability. Different navigation algorithms respond differently to each challenge. By capturing these outcomes for a given algorithm and understanding the likelihood that such challenges occur during a mission, we can derive the overall mission-reliability and performance ranking of that algorithm. In this context, reliability refers to the ability of an algorithm to maintain a required Circle of Equal Probability at the target location that ensures mission success. Moreover, in multi-vendor system development efforts, critical algorithms such as navigation are frequently provided as a proprietary “black-box,” with no visibility into internal functioning. The absence of internal visibility makes performance evaluation more challenging. In this paper we present our novel analysis approach, and results from application to a black-box state-of-the-art navigation algorithm developed for navigation in GPS-denied environments. Our approach identifies possible technologies used, and delineates hypothesized challenges affecting algorithm performance. It identifies all algorithm inputs and develops an evaluation framework where all challenges can be applied individually and successively to evaluate mission worthiness, i.e., mission reliability. Challenges refer to realistic, confounding stressors, arising in-mission, such as terrain type differences, attitude errors, imager faults, cloud coverage, and timing errors.

Effective infantry training requires accurate pointing direction knowledge of soldier-carried weapons to determine hit or miss scores. Infantry training solutions, which transition seamlessly to operational use, enables soldiers to train with what they use in combat, thereby increasing training efficacy and soldier lethality. To meet these dual needs, BAE Systems is developing the High-precision Infantry Training System (HITS). HITS provides a day/night, weapon-mounted ballistics point-of-impact detection system, to be used for live force-on-force training at Combat Training Centers (CTCs). HITS is hardware agnostic, but presently leverages BAE Systems’ fielded FWSI (Family-of-Weapons Sights-Individual) IR camera optic system to provide a ruggedized, low-SWaP, weapon-mounted platform for high-precision gun barrel pointing angle determination. The magnetometer and Inertial Measurement Unit (IMU) sensors, housed in the FWS-I gunsight, provide approximate pointing direction information while the FWS-I IR camera produces IR imagery with a field-of-view centered on the pointing direction of the gun. HITS uses innovative computer-vision processing to calculate the gun’s correct pointing angles. HITS performs geometric alignment of the FWS-I acquired IR image to a reference image of the view. The reference image is created by projecting a pre-generated reference model of the training site, consisting of geo-located 3-D LIDAR point-cloud data, onto the image plane. Using the gunsight location information, obtained from a GPS-RTK, the correct pointing angles are calculated from the image alignment. The system has an initial pointing accuracy goal of two milliradians. In this paper, we provide an overview of the HITS algorithm components including reference image generation, image registration, and pointing angle determination.

Here we present a water-in-air droplet platform for micro-compartmentalization for single molecule guided synthesis and analysis consisting of a flow-system hosting dense arrays of aqueous microdroplets on a glass surface surrounded by air. The droplets are formed in a few seconds by passing a waterfront over the array of hydrophilic spots surrounded by a hydrophobic coating, thus forming a micro-droplet array (MDA). The droplet volumes are tunable from approximately 50 femtoliter to 20 picoliter by adjusting the size of the hydrophilic spots. MDAs consisting of femtoliter volume droplets were stable for more than 24 hours in air at 37 °C in a reversibly sealed flow-system, thus allowing us to perform assays that require long incubations in the droplets. Using differently fluorescing liquids, it was further shown that droplets can be reformed on the same MDA several times by passing a new liquid plug over the surface, and that fluorescence from one reaction can be washed away with little to no carry-over, hence allowing for multistep reactions to be carried out on the system. The MDA created by an air/water interface supported digital immunoassays as was demonstrated by measuring the Aβ42 peptide in cerebrospinal fluid of Alzheimers patients and control patients. To demonstrate a two step droplet assay, first, histidine tagged peptides were expressed in the droplets and bound to the droplet-enclosed surface. Subsequently, the his-tagged peptides were detected using enzyme-conjugated antibodies in a second droplet generation step. As such, the chip demonstrates features necessary for library preparations for high throughput screening applications.

Drawing upon the literature and her experience as a professional coach, Helen Webb discusses the importance of effective contracting for in-school coaching programmes, including return on investment, goal-setting, confidentiality and demonstrating impact

While Machine Learning (ML) Automatic Target Recognition (ATR) represents the state-of-the art in target recognition, model-based ATR plays a valuable role. Model-based ATR complements machine learning ATR approaches by filling a near-term niche. While explainable Artificial Intelligence (AI) is not yet fully realized, model-based ATR serves to validate machine learning recognition decisions, and thus instills confidence in ML target calls. Alternatively, model-based ATR can act as a stand-alone ATR component, particularly in scenarios in which a small number of targets are of interest, e.g., “target-of-the-day” engagements. Model-based ATR approaches need no training data, and thus provide an alternative to machine learning approaches in the absence of sufficient quantities of real, or sufficiently high-fidelity synthetic, training data. In this paper, we present an approach to model-based ATR, called Shape-Based ATR (SB-ATR), which captures salient target shape information for recognizing targets in wide-area satellite imagery. SB-ATR finds the right blend of coarse 3-D target shape abstraction and target realism to provide robustness against target variations and environmental operating conditions, while simultaneously providing high-performance target recognition. The approach uses newer, robust forms of image correlation for matching a predicted target shape against the image. Shape prediction searches over target pose, and uses satellite metadata and solar geometry to generate realistic target shape and shadow predictions. The correlation matchers provide tolerance to illumination variations, moderate occlusions, image distortions and noise, and geometric differences between models and real targets. We present technical details of the shape-based approach, and provide numerical target recognition results on real-world satellite imagery demonstrating performance.

Accurate and successful image registration is a key enabling technology in applications such as image fusion, matching and pattern recognition. Knowledge of registration solution quality and accuracy can help prevent an inaccurate registration from degrading or corrupting performance of downstream image processing applications. However, estimating the spatial accuracy of image registration solutions can be difficult in the absence of ground-truth information on feature content or fiducial marker correspondences. This paper presents an automated spatial registration accuracy measurement for estimating and quantifying the spatial accuracy of correlation-based image registration in the absence of ground-truth information. For correlation surfaces exhibiting a single dominant peak, the approach consists of fitting an appropriate region of the correlation surface, about the peak coefficient, with a two-dimensional Gaussian. It then uses the covariance of the Gaussian to model the registration spatial error covariance. Use of a fitted Gaussian provides an intuitive probabilistic interpretation to the registration solution; the Gaussian function value at a spatial offset from the Gaussian peak gives the likelihood of that offset value. For more complicated regions containing multiple correlation local peak values, we extend the approach to fit a Gaussian mixture model to the region and use the mixture model covariance for the spatial accuracy metric. We describe an energy-based method for choosing the model region of the correlation surface. We discuss implementation subtleties and provide perturbation methods for handling numerically illconditioned matrices. We present numerical spatial error estimation results generated from registration of real video imagery acquired from a UAV platform.

Summary Background Since the 1918 influenza pandemic, non-randomised studies and small clinical trials have suggested that convalescent plasma or anti-influenza hyperimmune intravenous immunoglobulin (hIVIG) might have clinical benefit for patients with influenza infection, but definitive data do not exist. We aimed to evaluate the safety and efficacy of hIVIG in a randomised controlled trial. Methods This randomised, double-blind, placebo-controlled trial was planned for 45 hospitals in Argentina, Australia, Denmark, Greece, Mexico, Spain, Thailand, UK, and the USA over five influenza seasons from 2013–14 to 2017–18. Adults (≥18 years of age) were admitted for hospital treatment with laboratory-confirmed influenza A or B infection and were randomly assigned (1:1) to receive standard care plus either a single 500-mL infusion of high-titre hIVIG (0·25 g/kg bodyweight, 24·75 g maximum; hIVIG group) or saline placebo (placebo group). Eligible patients had a National Early Warning score of 2 points or greater at the time of screening and their symptoms began no more than 7 days before randomisation. Pregnant and breastfeeding women were excluded, as well as any patients for whom the treatment would present a health risk. Separate randomisation schedules were generated for each participating clinical site using permuted block randomisation. Treatment assignments were obtained using a web-based application by the site pharmacist who then masked the solution for infusion. Patients and investigators were masked to study treatment. The primary endpoint was a six-category ordinal outcome of clinical status at day 7, ranging in severity from death to resumption of normal activities after discharge. The choice of day 7 was based on haemagglutination inhibition titres from a pilot study. It was analysed with a proportional odds model, using all six categories to estimate a common odds ratio (OR). An OR greater than 1 indicated that, for a given category, patients in the hIVIG group were more likely to be in a better category than those in the placebo group. Prespecified primary analyses for safety and efficacy were based on patients who received an infusion and for whom eligibility could be confirmed. This trial is registered with ClinicalTrials.gov , NCT02287467 . Findings 313 patients were enrolled in 34 sites between Dec 11, 2014, and May 28, 2018. We also used data from 16 patients enrolled at seven of the 34 sites during the pilot study between Jan 15, 2014, and April 10, 2014. 168 patients were randomly assigned to the hIVIG group and 161 to the placebo group. 21 patients were excluded (12 from the hIVIG group and 9 from the placebo group) because they did not receive an infusion or their eligibility could not be confirmed. Thus, 308 were included in the primary analysis. hIVIG treatment produced a robust rise in haemagglutination inhibition titres against influenza A and smaller rises in influenza B titres. Based on the proportional odds model, the OR on day 7 was 1·25 (95% CI 0·79–1·97; p=0·33). In subgroup analyses for the primary outcome, the OR in patients with influenza A was 0·94 (0·55–1·59) and was 3·19 (1·21–8·42) for those with influenza B (interaction p=0·023). Through 28 days of follow-up, 47 (30%) of 156 patients in the hIVIG group and in 45 (30%) of 152 patients in the placebo group had the composite safety outcome of death, a serious adverse event, or a grade 3 or 4 adverse event (hazard ratio [HR] 1·06, 95% CI 0·70–1·60; p=0·79). Six (4%) patients in the hIVIG group and five (3%) in the placebo group died, but these deaths were not necessarily related to treatment. Interpretation When administered alongside standard care (most commonly oseltamivir), hIVIG was not superior to placebo for adults hospitalised with influenza infection. By contrast with our prespecified subgroup hypothesis that hIVIG would result in more favourable responses in patients with influenza A than B, we found the opposite effect. The clinical benefit of hIVIG for patients with influenza B is supported by antibody affinity analyses, but confirmation is warranted. Funding NIAID and NIH. Partial support was provided by the Medical Research Council (MRC_UU_12023/23) and the Danish National Research Foundation.

The pervasiveness of small Unmanned Aerial Vehicles (UAVs), due to low cost, ease of control, and portability, opens the possibility of their use in urban environments for illegal or adversarial purposes. Such use includes unauthorized surveillance, reconnaissance, and weaponization. Detecting adversarial UAVs in urban environments is difficult. Urban canyons provide shielding from visibility. The small size of quadcopter-type UAVs limits the number of object pixels available for processing, which reduces standoff detection performance. UAVs fly against a background of ground motion clutter which can mask their motion. One possible solution to small UAV detection in urban environments uses low-cost UAV surveillance platforms, equipped with optical sensors, together with computer vision algorithms to detect adversarial UAVs in video data. In this paper we adapt the astronomical technique of transit photometry to detect small UAVs, operating in urban environments, in video data. Transit photometry, typically used for exo-planet discovery, detects small changes in background brightness due to a transiting object. As the UAV traverses across a bright background region, for example, the vehicle occludes the background and reduces the perceived brightness. This brightness dip may be used to infer the existence of a potential UAV passing across the background. The transit photometry curve, resulting from this brightness dip, reveals information about the traversing vehicle. We investigate mathematical properties of the transit photometry curve and derive a closed-form expression for it. We present numerical results demonstrating the technique on real video data acquired from a small UAV operating in an urban environment.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection.METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants.FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005).INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia.FUNDING: UK National Institute for Health Research Health Technology Assessment.

‘Spacing’ refers to revision throughout the course of study, while ‘interleaving’ means switching between ideas while you learn. Both techniques can help boost students' long-term memories and retrieval of key information. Helen Webb explains

Modern satellites tag their images with geolocation information using GPS and star tracking systems. Depending on the quality of the geopositioning equipment, errors may range from a few meters to tens of meters on the ground. At the current state of art, there is no established method to automatically correct these errors limiting the large-scale joint utilization of cross-platform satellite images. In this paper, an automatic geolocation correction framework that corrects images from multiple satellites simultaneously is presented. As a result of the proposed correction process, all the images are effectively registered to the same absolute geodetic coordinate frame. The usability and the quality of the correction framework are demonstrated through a 3-D surface reconstruction application. The 3-D surface models given by original satellite geopositioning metadata, and the corrected metadata, are compared. The quality difference is measured through an entropy-based metric applied to the orthographic height maps given by the 3-D surface models. Measuring the absolute accuracy of the framework is harder due to lack of publicly available high-precision ground surveys. However, the geolocation of images of exemplar satellites from different parts of the globe are corrected, and the road networks given by OpenStreetMap are projected onto the images using original and corrected metadata to demonstrate the improved quality of alignment.

Supporting and challenging more able students and students with high prior attainment is essential. With a focus on science – but with some ideas that all subjects can adapt – Helen Webb offers a range of strategies

Teachers working together in-school to improve their classroom practice is an effective and inexpensive form of CPD. With a focus on the curriculum reforms, Helen Webb discusses her school's approach

How do you teach a mixed-ability class effectively? Helen Webb offers some practical advice and ideas to help achieve effective differentiation in your classroom

As part of her work on improving feedback to students, Helen Webb focused on improving performance in GCSE science extended writing questions. She discusses her findings

How can you judge whether all your students are learning something in your lessons and making the progress they are capable of? Teacher Helen Webb discusses what learning looks like…

There is a clear gap between GCSE and A Level study and supporting students to make the leap is important. Teacher Helen Webb discusses her work to develop students’ independent study skills

What makes an outstanding teacher? This age-old question is the bane of any in-school teacher development programme. Helen Webb discusses the challenges, successes and failures of her school's outstanding teacher programme

The study of anatomy in England during the 18th and 19th century has become infamous for bodysnatching from graveyards to provide a sufficient supply of cadavers. However, recent discoveries have improved our understanding of how and why anatomy was studied during the enlightenment, and allow us to see the context in which dissection of the human body took place. Excavations of infirmary burial grounds and medical school cemeteries, study of hospital archives, and analysis of the content of surviving anatomical collections in medical museums enables us to re-evaluate the field from a fresh perspective. The pathway from a death in poverty, sale of the corpse to body dealer, dissection by anatomist or medical student, and either the disposal and burial of the remains or preservation of teaching specimens that survive today in medical museums is a complex and fascinating one.

Site-specific pKa values measured by NMR spectroscopy provide essential information on protein electrostatics, the pH-dependence of protein structure, dynamics and function, and constitute an important benchmark for protein pKa calculation algorithms. Titration curves can be measured by tracking the NMR chemical shifts of several reporter nuclei versus sample pH. However, careful analysis of these curves is needed to extract residue-specific pKa values since pH-dependent chemical shift changes can arise from many sources, including through-bond inductive effects, through-space electric field effects, and conformational changes. We have re-measured titration curves for all carboxylates and His 15 in Hen Egg White Lysozyme (HEWL) by recording the pH-dependent chemical shifts of all backbone amide nitrogens and protons, Asp/Glu side chain protons and carboxyl carbons, and imidazole protonated carbons and protons in this protein. We extracted pKa values from the resulting titration curves using standard fitting methods, and compared these values to each other, and with those measured previously by 1H NMR (Bartik et al., Biophys J 1994;66:1180–1184). This analysis gives insights into the true accuracy associated with experimentally measured pKa values. We find that apparent pKa values frequently differ by 0.5–1.0 units depending upon the nuclei monitored, and that larger differences occasionally can be observed. The variation in measured pKa values, which reflects the difficulty in fitting and assigning pH-dependent chemical shifts to specific ionization equilibria, has significant implications for the experimental procedures used for measuring protein pKa values, for the benchmarking of protein pKa calculation algorithms, and for the understanding of protein electrostatics in general. Proteins 2011. © 2010 Wiley-Liss, Inc.

What makes an outstanding teacher? Last year, Helen Webb wrote about her work developing an in-school teacher development programme. She now updates us on this work, the challenges she has encountered and how the programme has evolved

The lesson is a key part of any teaching job interview and often causes the most stress for applicants. Helen Webb looks at how to plan your job interview lessons

When considering effective learning strategies, Helen Webb suggests creating online, automatically marked quizzes to improve your tracking and students' learning

NMR-monitored pH titration experiments are routinely used to measure site-specific protein pKa values. Accurate experimental pKa values are essential in dissecting enzyme catalysis, in studying the pH-dependence of protein stability and ligand binding, in benchmarking pKa prediction algorithms, and ultimately in understanding electrostatic effects in proteins. However, due to the complex ways in which pH-dependent electrostatic and structural changes manifest themselves in NMR spectra, reported apparent pKa values are often dependent on the way that NMR pH-titration curves are analyzed. It is therefore important to retain the raw NMR spectroscopic data to allow for documentation and possible re-interpretation. We have constructed a database of primary NMR pH-titration data, which is accessible via a web interface. Here, we report statistics of the database contents and analyze the data with a global perspective to provide guidelines on best practice for fitting NMR titration curves. Titration_DB is available at http://enzyme.ucd.ie/Titration_DB. Proteins 2010. (c) 2009 Wiley-Liss, Inc.

High-resolution and accurate Digital Elevation Model (DEM) generation from satellite imagery is a challenging problem. In this work, a stereo 3-D reconstruction framework is outlined that is applicable to nonstereoscopic satellite image pairs that may be captured by different satellites. The orthographic height maps given by stereo reconstruction are compared to height maps given by a multiview approach based on Probabilistic Volumetric Representation (PVR). Height map qualities are measured in comparison to manually prepared ground-truth height maps in three sites from different parts of the world with urban, semi-urban and rural features. The results along with strengths and weaknesses of the two techniques are summarized.

Ubiquitin-conjugating enzymes (E2s or Ubcs) are essential components in the ubiquitination apparatus. These enzymes accept ubiquitin from an E1 enzyme and then, usually with the aid of an E3 enzyme, donate the ubiquitin to the target protein. The function of E2 relies critically on the chemistry of its active site cysteine residue since this residue must form a thioester bond with the carboxyl terminus of ubiquitin. Despite the plethora of structural information that is available, there has been a notable dearth of information regarding the chemical basis of E2 function. Toward filling this large void in our understanding of E2 function, we have examined the pK(a) of the active site cysteine using a combination of experimental and theoretical approaches. We find, remarkably, that the pK(a) of the active site cysteine residue is elevated by approximately 2 pH units above that of a free cysteine. We have identified residues that contribute to the increase in this pK(a). On the basis of experimental values obtained with three different E2 proteins, we believe this to be a general and important characteristic of E2 protein chemistry. Sequence comparison suggests that the electrostatic environment is maintained not through strict residue conservation but through different combinations of residues near the active site. We propose that the elevated pK(a) is a regulatory mechanism that prevents the highly exposed cysteine residue in free E2 from reacting promiscuously with electron deficient chemical moieties in the cell.

Post-exposure prophylaxis after sexual exposure (PEPSE) awareness was audited in an HIV-positive cohort. A total of 403 out of 828 (48.7%) patients were PEPSE aware. Patients diagnosed post-2006 were more PEPSE aware; 57.2% vs. 44.2% ( p = 0.0004). Men who have sex with men (MSM) were more PEPSE aware; 65.8% vs. 39.1% in heterosexuals ( p 35 years ( p 400 copies/mL), awareness was 64.1%. Overall, PEPSE awareness was unexpectedly low. MSM, younger patients, and those diagnosed after 2006 were significantly more likely to be PEPSE aware. More than one in three patients with detectable viraemia were PEPSE unaware.

Continuing her series on effective pupil feedback, Helen Webb looks now at using comment banks to provide students with better quality feedback while also reducing teacher workload

Good feedback can have a significant impact on student progress. In the second part of this two-part article, teacher Helen Webb continues her research review on effective feedback, looking at assessment for learning, peer and self-assessment, the role of marking and the views of Ofsted

Australia's commercial fisheries are relatively small by world standards yet have disproportionately large ecological, social and political footprints. A large proportion of the catch is high-value species that are mostly exported. For example, in Australia marine fisheries account for 0.2 per cent of global marine fisheries landed tonnage but 2 per cent of marine fisheries landed value. Australian fisheries are generally regarded as well managed by global standards. The country is seen as a leader in the implementation of ecosystem-based fisheries management; an approach that considers the broader ecosystem impacts of fishing as well as those on the target species.