Machine learning enables completely automatic tuning of a quantum device faster than human experts.

Variability is a problem for the scalability of semiconductor quantum devices. The parameter space is large, and the operating range is small. Our statistical tuning algorithm searches for specific electron transport features in gate-defined quantum dot devices with a gate voltage space of up to eight dimensions. Starting from the full range of each gate voltage, our machine learning algorithm can tune each device to optimal performance in a median time of under 70 minutes. This performance surpassed our best human benchmark (although both human and machine performance can be improved). The algorithm is approximately 180 times faster than an automated random search of the parameter space, and is suitable for different material systems and device architectures. Our results yield a quantitative measurement of device variability, from one device to another and after thermal cycling. Our machine learning algorithm can be extended to higher dimensions and other technologies.

Correction: Charge-tunnelling and self-trapping: common origins for blinking, grey-state emission and photoluminescence enhancement in semiconductor quantum dots.

Correction for 'Charge-tunnelling and self-trapping: common origins for blinking, grey-state emission and photoluminescence enhancement in semiconductor quantum dots' by M. A. Osborne, et al., Nanoscale, 2016, 8, 9272-9283.

Charge-tunnelling and self-trapping: common origins for blinking, grey-state emission and photoluminescence enhancement in semiconductor quantum dots.

Understanding instabilities in the photoluminescence (PL) from light emitting materials is crucial to optimizing their performance for different applications. Semiconductor quantum dots (QDs) offer bright, size tunable emission, properties that are now being exploited in a broad range of developing technologies from displays and solar cells to biomaging and optical storage. However, instabilities such as photoluminescence intermittency, enhancement and bleaching of emission in these materials can be detrimental to their utility. Here, we report dielectric dependent blinking, intensity-"spikes" and low-level, "grey"-state emission, as well as PL enhancement in ZnS capped CdSe QDs; observations that we found consistent with a charge-tunnelling and self-trapping (CTST) description of exciton-dynamics on the QD-host system. In particular, modulation of PL in grey-states and PL enhancement are found to have a common origin in the equilibrium between exciton charge carrier core and surface-states within the CTST framework. Parameterized in terms of size and electrostatic properties of the QD and its nanoenvironment, the CTST offers predictive insight into exciton-dynamics in these nanomaterials.

Hydration and endocrine responses to intravenous fluid and oral glycerol.

Athletes use intravenous (IV) saline in an attempt to maximize rehydration. The diuresis from IV rehydration may be circumvented through the concomitant use of oral glycerol. We examined the effects of rehydrating with differing regimes of oral and IV fluid, with or without oral glycerol, on hydration, urine, and endocrine indices. Nine endurance-trained men were dehydrated by 4% bodyweight, then rehydrated with 150% of the fluid lost via four protocols: (a) oral = oral fluid only; (b) oral glycerol = oral fluid with added glycerol (1.5 g/kg); (c) IV = 50% IV fluid, 50% oral fluid; and (d) IV with oral glycerol = 50% IV fluid, 50% oral fluid with added glycerol (1.5 g/kg), using a randomized, crossover design. They then completed a cycling performance test. Plasma volume restoration was highest in IV with oral glycerol > IV > oral glycerol > oral. Urine volume was reduced in both IV trials compared with oral. IV and IV with oral glycerol resulted in lower aldosterone levels during rehydration and performance, and lower cortisol levels during rehydration. IV with oral glycerol resulted in the greatest fluid retention. In summary, the IV conditions resulted in greater fluid retention compared with oral and lower levels of fluid regulatory and stress hormones compared with both oral conditions.

A modern-day solution to a 100-year-old problem: the use of a Bespoke Off-loading Brace in the rehabilitation of 'Deck-Slap' and other high-energy lower limb injuries.

'Deck-Slap' is an injury pattern first described at the Battle of Jutland; it is still relevant today, with anti-vehicle mines a significant threat to Coalition troops. The effect of a device exploding beneath a vehicle produces a wave of high energy that is rapidly transmitted through the steel floor; this causes significant axial loading of lower limbs often resulting in severe fractures (notably of the calcaneum). Recent advancements in orthopaedic surgery have allowed for limbs that were destined for immediate amputation following significant trauma to be salvaged. However, despite intense rehabilitation, many of these salvaged limbs have subsequently gone on to delayed amputation, as functional outcomes are often poor. Technologically advanced prosthetic devices are available that afford good quality of life and allow for increased activity levels; these devices are, however, expensive to procure and maintain. This report describes a United Kingdom (UK) Armed Forces soldier who suffered a typical 'deck-slap' injury in Afghanistan with subsequent limb salvage. The use of the Bespoke Off-loading Brace (BOB) is discussed. The results presented here indicate that the biomechanical function of a patient with this type of injury improves when wearing the BOB. Further studies are needed to assess long-term clinical outcomes and the functional benefit of the device as a viable and cost-effective alternative to delayed limb amputation.

Raphaël Blanchard, parasitology, and the positioning of medical entomology in Paris.

The histories of medical entomology and parasitology are entwined. Raphaël Blanchard (1857-1919), Chair of Medical Natural History and Parasitology at the Faculty of Medicine in Paris, organized the teaching of medical entomology and civilian colonial medicine. He also founded and edited the journal Archives de Parasitologie and started the Institute de Médecine Coloniale where he mentored many foreign students and researchers. Additionally, Blanchard is important for his scientific internationalism and medical historical work on the cultural location of parasitology and for training the future professors of parasitology Jules Guiart, Emile Brumpt, and Charles Joyeux.

Multi-element survey of wild edible fungi and blackberries in the UK.

A survey of 12 metals including lead (Pb), copper (Cu), cadmium (Cd), mercury (Hg), arsenic (As) and platinum (Pt) was carried out using ICP-MS in 34 samples of wild fungi and 48 samples of wild blackberries collected from sites across the UK. On a fresh weight basis (mg/kg) levels of Pb were in the range 0.003-5.990, Cu 0.596-34.800, Cd<0.001-19.6, Hg<0.001-4.150, As 0.001-0.972 and Pt (microg/kg) 0.006-0.200, with higher concentrations found in fungi than in blackberries. The results of the survey showed that the concentrations of the metals were consistent with previous studies, where available. Concentrations in wild fungi of Pt, tin (Sn), and titanium (Ti) were significantly higher at urban sites than at rural sites. Urban blackberries had significantly higher levels of Pb, Ti, and Cd than rural ones, but lower levels of manganese (Mn). Pb, Ti and Sn concentrations were significantly higher in blackberries sampled near main roads rather than in rural areas.

The prevalence of Chlamydia trachomatis infection in male undergraduates: a postal survey.

OBJECTIVES: To determine the prevalence of Chlamydia trachomatis infection in male undergraduates and to investigate whether prevalence increases with time spent at university. To investigate the feasibility of screening men for C trachomatis by self sampling and posting of urine specimens. METHODS: The study design was a postal survey undertaken by the Department of Genito-Urinary Medicine (GUM) and Student University Health Service (SUHS) in SHEFFIELD: 2607 male undergraduates from the SUHS patient list were invited to participate in the study by providing a first void urine specimen and posting it to the laboratory. The main outcome measure was the detection of C trachomatis infection. RESULTS: 758 students participated in the study, a response rate of 29.1%. Nine students (1.2%) tested positive for C trachomatis. The prevalence of infection in the first, second, and third year of study was 0.7%, 1.5%, and 1.6% of participants respectively. There was no statistically significant difference in prevalence of infection between first and third year students (chi(2) test, p = 0.32). However, students with chlamydia had a higher median age (Mann-Whitney U test, p < or = 0.05). Contact tracing identified four further cases of C trachomatis infection. CONCLUSION: Screening for C trachomatis infection by postal survey is feasible. However, the response rate in this study was poor and the estimated sample size was not reached. Therefore, it has not been possible to determine the true prevalence of infection in this population or to accurately assess changes in prevalence with time spent at university.

Single-molecule analysis of DNA immobilized on microspheres.

The formation and analysis of single molecules of fluorescently labeled DNA immobilized on polystyrene microspheres is described. Analysis by confocal fluorescence microscopy revealed single-step photobleaching, characteristic of a single fluorophore. Microspheres provide a means of locating single molecules by bright-field microscopy, prior to single-molecule detection. This allows the interrogation of single molecules without suffering the limitations of premature photobleaching. Statistical analysis of fluorescence intensities for >100 microspheres suggests attachment of DNA to micropsheres to be consistent with Poisson statistics.

Groucho/TLE/R-esp proteins associate with the nuclear matrix and repress RUNX (CBF(alpha)/AML/PEBP2(alpha)) dependent activation of tissue-specific gene transcription.

The Runt related transcription factors RUNX (AML/CBF(alpha)/PEBP2(alpha)) are key regulators of hematopoiesis and osteogenesis. Using co-transfection experiments with four natural promoters, including those of the osteocalcin (OC), multi drug resistance (MDR), Rous Sarcoma Virus long terminal repeat (LTR), and bone sialoprotein (BSP) genes, we show that each of these promoters responds differently to the forced expression of RUNX proteins. However, the three RUNX subtypes (i.e. AML1, AML2, and AML3) regulate each promoter in a similar manner. Although the OC promoter is activated in a C terminus dependent manner, the MDR, LTR and BSP promoters are repressed by three distinct mechanisms, either independent of or involving the AML C terminus, or requiring only the conserved C-terminal pentapeptide VWRPY. Using yeast two hybrid assays we find that the C terminus of AML1 interacts with a Groucho/TLE/R-esp repressor protein. Co-expression assays reveal that TLE proteins repress AML dependent activation of OC gene transcription. Western and northern blot analyses suggest that TLE expression is regulated reciprocally with the levels of OC gene expression during osteoblast differentiation. Digital immunofluorescence microscopy results show that TLE1 and TLE2 are both associated with the nuclear matrix, and that a significant subset of each colocalizes with AML transcription factors. This co-localization of TLE and AML proteins is lost upon removing the C terminus of AML family members. Our findings indicate that suppression of AML-dependent gene activation by TLE proteins involves functional interactions with the C terminus of AML at the nuclear matrix in situ. Our data are consistent with the concept that the C termini of AML proteins support activation or repression of cell-type specific genes depending on the regulatory organization of the target promoter and subnuclear localization.

Acclimatizing the world: a history of the paradigmatic colonial science.

This paper examines the institutions, personages, and the theories that informed acclimatization activities in nineteenth-century France, England, and the two colonies of Algeria and Australia. Treating acclimatization as a scientific concept and activity the essay begins with the conditions of its emergence in Enlightenment France. Subsequent sections trace the growth of the acclimatization movement and its translation to the British context, and consider reasons for its decline in the last third of the nineteenth century. Efforts are made to show why many perceived acclimatization to be the paradigmatic colonial science with applications as diverse as agriculture, settlement schemes, field sports, and human health. Emphasis falls on the French and British cultural spheres, as these were the dual epicenters of both modern colonialism and organized acclimatization activity.

Cardiorespiratory dynamics: sensitivity of the on-transition to endurance-training status.

This project investigated the sensitivity of oxygen uptake (VO(2)) dynamics to training-induced physiological changes, across a broad spectrum of endurance-training histories. Forty subjects participated: sedentary (n = 10), active healthy (n = 10), regular runners (n = 10), and competitive distance runners (n = 10). Subjects completed a cycle step-function protocol, to elicit a steady state at 60% maximal work rate. Breath-by-breath data were collected for VO(2) and cardiac frequency (f(c)), and modelled mathematically, and used to determine the average response times to attain 20%, 40%, 60%, 80% and 100% of the respective steady states. The between-group comparisons for both VO(2) and f(c) revealed significantly faster response times to 40%, 60%, 80% and 100% of the induced response, for the better trained subjects (P < 0.05). In general, this technique permitted differentiation between the VO(2) and f(c) response dynamics of non-elite subjects from a broad range of endurance-training histories, with differences becoming more pronounced as subjects approached the steady state.

Use of fluorescence resonance energy transfer to investigate the conformation of DNA substrates bound to the Klenow fragment.

Fluorescence resonance energy transfer (FRET) has been used to investigate the conformation of the single stranded region for a series of fluorescent DNA template-primers bound to the Klenow fragment (KF) of Escherichia coli DNA polymerase I. Fluorescent derivatives of template-primer DNA, modified with tetramethylrhodamine (TMR), served as energy transfer acceptors to the donor fluorescein fluorophore used to modify cysteine 751 in the double mutant KF (S751C, C907S). Design of the template-primer allowed the probe's position within the DNA-protein complex to be varied by stepwise extension of the primer strand upon addition of the appropriate deoxynucleoside triphosphates (dNTP). The TMR acceptor probe occupied seven different positions in the template-primers, five in the single stranded region and two in the double stranded region. The efficiency of energy transfer was determined at each position by calculating the integrated area of the fluorescein emission peak in the presence and absence of acceptor. Results indicate that the FRET efficiency varied in a sinusoidal fashion with a periodicity of approximately 10 base pairs and that the data could be fitted to an equation derived from a simple model formulated on the basis of helical structure. The data support the conclusion that the single stranded template portion of a DNA template-primer adopts a helical conformation when bound to the KF. The results of this study further support FRET as a useful method for the determination of structure and conformation in protein-DNA complexes.

Nonoperative estimation of the soleus musculotendinous junction using magnetic resonance imaging.

Although it is recognized as the muscle flap of choice for middle-third defects of the lower limb, the capability for even more distal transposition of the soleus muscle remains controversial. Such reach depends directly on the site of insertion of the muscle and previously has not been assessed convincingly without surgical intervention. Magnetic resonance imaging (MRI) may be a noninvasive alternative for determining the distal extent of the musculotendinous junction of the soleus muscle. In our last four patients, preoperative MRI scans were obtained prior to an elective soleus muscle transfer. The distance from the ankle joint to the most distal site of the soleus insertion was measured on the MRI scan and compared with the actual intraoperative measurement, which had a significant correlation (r = 0.98, p = 0.019). A retrospective review of 42 other sagittal ankle MRI scans predicted the mean of this distance to be 1.92 +/- 1.23 cm (range -0.4 to 4.5 cm), compared with gross anatomic dissections in 30 unrelated fresh cadavers, where this was 4.06 +/- 3.11 cm (range -0.7 to 12.5 cm). These additional data are pertinent because they reinforce recognition of the great variation in soleus anatomy, which would limit clinical applications for the distal third of the leg only for those individuals with very distal insertions. The MRI scan can reliably identify the soleus muscle and provides a nonoperative method for evaluation of potential feasibility for its use as a local muscle flap for distal lower extremity defects.

The inositol 5'-phosphatase SHIP binds to immunoreceptor signaling motifs and responds to high affinity IgE receptor aggregation.

Immunoreceptors such as the high affinity IgE receptor, FcepsilonRI, and T-cell receptor-associated proteins share a common motif, the immunoreceptor tyrosine-based activation motif (ITAM). We used the yeast tribrid system to identify downstream effectors of the phosphorylated FcepsilonRI ITAM-containing subunits beta and gamma. One novel cDNA was isolated that encodes a protein that is phosphorylated on tyrosine, contains a Src-homology 2 (SH2) domain, inositolpolyphosphate 5-phosphatase activity, three NXXY motifs, several proline-rich regions, and is called SHIP. Mutation of the conserved tyrosine or leucine residues within the FcepsilonRI beta or gamma ITAMs eliminates SHIP binding and indicates that the SHIP-ITAM interaction is specific. SHIP also binds to ITAMs from the CD3 complex and T cell receptor zeta chain in vitro. SHIP protein possesses both phosphatidylinositol-3,4,5-trisphosphate 5'-phosphatase and inositol-1,3,4,5-tetrakisphosphate 5'-phosphatase activity. Phosphorylation of SHIP by a protein-tyrosine kinase, Lck, results in a reduction in enzyme activity. FcepsilonRI activation induces the association of several tyrosine phosphoproteins with SHIP. SHIP is constitutively tyrosine-phosphorylated and associated with Shc and Grb2. These data suggest that SHIP may serve as a multifunctional linker protein in receptor activation.

Role of magnetic resonance imaging in the diagnosis of osteomyelitis in diabetic foot infections.

PURPOSE: The role of magnetic resonance imaging (MRI) in the diagnosis of osteomyelitis in foot infections in diabetics was investigated. The accuracy, sensitivity, and specificity of MRI, plain radiography, and nuclear scanning were determined for diagnosing osteomyelitis, and a cost comparison was made. METHODS: Twenty-seven patients with diabetic foot infections were studied prospectively. All patients underwent MRI and plain radiography. Twenty-two patients had technetium bone scans, and 19 patients had Indium scans. Nineteen patients had all four tests performed. Patients with obvious gangrene or a fetid foot were excluded. RESULTS: The diagnosis of osteomyelitis was established by pathologic specimen (n = 18), bone culture (n = 3), or successful response to medical management (n = 6). Osteomyelitis was confirmed in nine of the pathologic specimens. The diagnostic sensitivity, specificity, and accuracy for MRI was 88%, 100%, and 95%, respectively, for plain radiography it was 22%, 94%, and 70%, respectively, for technetium bone scanning it was 50%, 50%, and 50%, respectively, and for Indium leukocyte scanning it was 33%, 69%, and 58%, respectively. The data were analyzed statistically with the two-tailed Fisher's exact test. MRI was the only test that was statistically significant (p < 0.01). CONCLUSIONS: MRI appeared to be the single best test for the diagnosis of osteomyelitis associated with diabetic foot infections. It had a better diagnostic accuracy than conventional modalities and appeared to be more cost-effective than the frequently used Indium scan.

Inorganic fluoride concentration after long-term sedation with isoflurane.

We report on five patients in whom long-term sedation with isoflurane for up to 7 days was used successfully. Serum inorganic fluoride concentrations were measured daily. The concentrations ranged from 12 mmol l-1 to 29 mmol l-1. These were well below the described renal toxic level of 50 mmol l-1. There was no deterioration in renal function attributable to the use of isoflurane.