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Studying latent Mycobacterium tuberculosis (Mtb) infection has been limited by the lack of a suitable mouse model. We discovered that transient depletion of biotin protein ligase (BPL) and thioredoxin reductase (TrxB2) results in latent infections during which Mtb cannot be detected but that relapse in a subset of mice. The immune requirements for Mtb control during latency, and the frequency of relapse, were strikingly different depending on how latency was established. TrxB2 depletion resulted in a latent infection that required adaptive immunity for control and reactivated with high frequency, whereas latent infection after BPL depletion was independent of adaptive immunity and rarely reactivated. We identified immune signatures of T cells indicative of relapse and demonstrated that BCG vaccination failed to protect mice from TB relapse. These reproducible genetic latency models allow investigation of the host immunological determinants that control the latent state and offer opportunities to evaluate therapeutic strategies in settings that mimic aspects of latency and TB relapse in humans.

Studying latent Mycobacterium tuberculosis (Mtb) infection has been limited by the lack of a suitable mouse model. We discovered that transient depletion of protein biotin ligase (BPL) and thioredoxin reductase (TrxB2) results in latent infections during which Mtb cannot be detected but that relapse in a subset of mice. The immune requirements for Mtb control during latency, and the frequency of relapse, were strikingly different depending on how latency was established. TrxB2 depletion resulted in a latent infection that required adaptive immunity for control and reactivated with high frequency, whereas latent infection after BPL depletion was independent of adaptive immunity and rarely reactivated. We identified immune signatures of T cells indicative of relapse and demonstrated that BCG vaccination failed to protect mice from TB relapse. These reproducible genetic latency models allow investigating the host immunological determinants that control the latent state and offer opportunities to evaluate therapeutic strategies in settings that mimic aspects of latency and TB relapse in humans.

Presently maintaining the load is the most challenging issue for a researcher in a cloud environment. In the IT sector, cloud computing is offering a variety of resources and free resources based on robust technology and Internet access in cloud computing. Users can also keep doing, gives a very reliable and inexpensive. Therefore, users of cloud computing are now evolving for every department of the organization, government and education for increased use of cloud services. Then, when they come in a variety of user demand for cloud resources, we can use load balancing technology to meet user needs. The use of the load balancing process is useful for distributing load over load to another node to adjust. The aim of load balancing is to balance virtual machines that should not be under load or overload. In this paper, propose two algorithms for the balance of load balancing algorithm including the workload of cloud system. In our work, there are basically low load systems and virtual machine demand will increase. The minimum finish time would be to put everything on one virtual machine and see the lowest number of high priority virtual machines. Improvements will be made to the importance of our research system, better use of resources and reduced full-time. Propose paper want the ClaudSim cloud platform to use a simulator. Also use unit response time in a VM as a metric, full implementation, and operation. Events demonstrate the features of the proposed algorithm running in a virtual machine to be used on experimental scale and for better application performance as possible.

While the majority of literature on remanufacturing operations examines an end-of-life (EOL) strategy which is both manual and mechanised, authors generally agree that digitalisation of remanufacturing is expected to increase in the next decade. Subsequently, a new research area described as digitally-enabled remanufacturing, remanufacturing 4.0 or smart remanufacturing is emerging. This is an automated, data-driven system of remanufacturing by means of Industry 4.0 (I4.0) paradigms. Insights into smart remanufacturing can be provided through simulation modelling of the remanufacturing process. While the use of simulation modelling in order to predict responses and behaviour is prevalent in remanufacturing, the use of these tools in smart remanufacturing is still limited in literature. The goal of this research is to present, as a first of its kind, a comparative understanding of simulation modelling in remanufacturing in order to suggest the ideal modelling tool for smart remanufacturing. The proposed comparison includes system dynamics, discrete event simulation and agent based modelling techniques. We apply these modelling techniques on a smart remanufacturing space of a sensor-enabled product and use assumptions derived from industry experts. We then proceed to model the remanufacturing operation from sorting and inspection of cores to final inspection of the remanufactured product. Through our analysis of the assumptions utilised and simulation modelling results we conclude that, while individual modelling techniques present important strategic and operational insights, their individual use may not be sufficient to offer comprehensive knowledge to remanufacturers due to the challenge of data complexity that smart remanufacturing offers.

Hospital mortality rates have frequently been improved by identifying diagnostic groups with high mortality and targeting interventions to those specific groups. We found that high residual inpatient mortality persisted after targeted measures had achieved an initial reduction, and that the causes were spread across a wide range of diagnostic groups. Further interventions were put in place consisting of a structured electronic mortality form and systematised mortality scrutiny and reporting (primary intervention) accompanied by a number of quality improvement interventions arising from the mortality analysis (secondary interventions). We found that those interventions were associated with progressive improvements in mortality rates and average lengths of inpatient stay over the 5-year study period. Winter quarter mortality improvements reached a high level of statistical significance but could not be attributed to changes in any particular diagnostic groups. We conclude that progress with mortality improvements is probably best achieved by applying both code-targeted and general interventions simultaneously.

The experiment was conducted to study the effect of supplementation of designer dietary antioxidant micronutrients on udder health, milk yield, and its quality in buffaloes under field conditions. Sixteen healthy multiparous advanced pregnant graded Murrah buffaloes (around the last 3 months of gestation), identical in body weights, parity, and feeding conditions, were selected for the study. Feed offered and residues left of an individual animal were measured and recorded for 7 consecutive days with the sampling of feeds being offered to buffaloes and analyzed for dry matter and trace minerals Zn, Cu, and Se. Carotene and vitamin E content of offered feed samples were calculated based on reported values. The calculation was made to determine the deficiency of above micronutrients, and an antioxidant micronutrient supplement was designed to take care of the deficient micronutrients and supplemented in half of the buffaloes (n = 8) considered to be a treatment, while remaining half (n = 8) is considered to be control, fed as per the existing practice of farmer without additional supplementation. This supplementation study was continued for 2 months during advanced pregnancy and thereafter for 3 months post-calving. Dry matter intake recorded weekly during the pre- and postpartum period of study remained comparable (P > 0.05) between two groups. Udder health monitored fortnightly by modified California mastitis test, milk pH and somatic cell count indicated improvement (P

Protein kinase G (PknG) in Mycobacterium tuberculosis has been shown to modulate phagosome-lysosome fusion. The protein has three distinct domains, an N-terminal Trx domain, a kinase domain, and a C-terminal TPR domain. The present study extensively analyzes the roles of these domains in regulating PknG kinase activity and function. We find that the kinase domain of PknG by itself is inactive, signifying the importance of the flanking domains. Although the deletion of the Trx domain severely impacts the activity of the protein, the C-terminal region also contributes significantly in regulating the activity of the kinase. Apart from this, PknG kinase activity is dependent on the presence of threonine 309 in the p + 1 loop of the activation segment. Mutating the conserved cysteine residues in the Trx motifs makes PknG refractory to changes in the redox environment. In vitro experiments identify threonine 63 as the major phosphorylation site of the protein. Importantly, we find that this is the only site in the protein that is phosphorylated in vivo. Macrophage infection studies reveal that the first 73 residues, the Trx motifs, and the threonine 63 residue are independently essential for modulating PknG-mediated survival of mycobacteria in its host. We have extended these studies to investigate the role of PknG and PknG mutants in the pathogenesis of mycobacteria in mice. Our results reinforce the findings from the macrophage infection experiments, and for the first time demonstrate that the expression of PknG in non-pathogenic mycobacteria allows the continued existence of these bacteria in host tissues.

5′-[N-(d-biotinoyl)sulfamoyl]amino-5′-deoxyadenosine (Bio-AMS, 1) possesses selective activity against Mycobacterium tuberculosis (Mtb) and arrests fatty acid and lipid biosynthesis through inhibition of the Mycobacterium tuberculosis biotin protein ligase (MtBPL). Mtb develops spontaneous resistance to 1 with a frequency of at least 1 × 10–7 by overexpression of Rv3406, a type II sulfatase that enzymatically inactivates 1. In an effort to circumvent this resistance mechanism, we describe herein strategic modification of the nucleoside at the 5′-position to prevent enzymatic inactivation. The new analogues retained subnanomolar potency to MtBPL (KD = 0.66–0.97 nM), and 5′R-C-methyl derivative 6 exhibited identical antimycobacterial activity toward: Mtb H37Rv, MtBPL overexpression, and an isogenic Rv3406 overexpression strain (minimum inhibitory concentration, MIC = 1.56 μM). Moreover, 6 was not metabolized by recombinant Rv3406 and resistant mutants to 6 could not be isolated (frequency of resistance

Cloud is a medium for providing virtual services and resources that can be accessed and utilized easily. Along mechanism in Internet storage content is saved online, retrieved from various distributed and interconnected resources which form a cloud across the network. The prime concern faced by the Internet content system securing, as a result the owner encrypts and utilizes an search technique for accessing the data. When using a cloud storage mechanism, the third party gains the control to import your highly secured and private data to put up in the cloud. The data owners have to deal with various security issues because of entailing intense safety and confidentiality. The present paper outlines the cloud types based on cloud usage and services offered. The focus of the research being to provide secured data sharing by comparing and assessing the functionality of different symmetric encryption algorithms like parallel homomorphic encryption algorithm (PHEA), KUNodes, triple data encryption algorithm (3DEA), Also by implementing PHEA there is flexibility in data sharing, fine-grained access control, improvised average execution time and memory and data size. The research work concludes that PHEA is highly suitable for data sharing compared to other techniques of symmetric encryption.

There exist many prevalent issues in today’s world, many of which seem to have no feasible solution. One such issue is the disparity in the education provided between males and females. Gender equality is an important topic for discussion and reform in the modern world, and yet a full, thorough understanding of the intensity of the issue is yet to be elicited. Using a combination of modern computational statistical analysis and the vast, extensive trough of census data, this paper provides a framework for gaining a better viewpoint on the issues plaguing us currently, thus taking a step closer to eradicating them.

The viability of Mycobacterium tuberculosis (Mtb) depends on energy generated by its respiratory chain. Cytochrome bc1-aa3 oxidase and type-2 NADH dehydrogenase (NDH-2) are respiratory chain components predicted to be essential, and are currently targeted for drug development. Here we demonstrate that an Mtb cytochrome bc1-aa3 oxidase deletion mutant is viable and only partially attenuated in mice. Moreover, treatment of Mtb-infected marmosets with a cytochrome bc1-aa3 oxidase inhibitor controls disease progression and reduces lesion-associated inflammation, but most lesions become cavitary. Deletion of both NDH-2 encoding genes (Δndh-2 mutant) reveals that the essentiality of NDH-2 as shown in standard growth media is due to the presence of fatty acids. The Δndh-2 mutant is only mildly attenuated in mice and not differently susceptible to clofazimine, a drug in clinical use proposed to engage NDH-2. These results demonstrate the intrinsic plasticity of Mtb’s respiratory chain, and highlight the challenges associated with targeting the pathogen’s respiratory enzymes for tuberculosis drug development., New tuberculosis therapies, targeting respiratory chain components of Mycobacterium tuberculosis, are under development. Here the authors show that, contrary to common belief, some of these components are not essential for pathogen viability and/or virulence in animal models of infection.

Background: Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy.Methods: RESTART was a prospective, randomised, open-label, blinded-endpoint, parallel-group trial at 122 hospitals in the UK that assessed whether starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. For this prespecified subgroup analysis, consultant neuroradiologists masked to treatment allocation reviewed brain CT or MRI scans performed before randomisation to confirm participant eligibility and rate features of the intracerebral haemorrhage and surrounding brain. We followed participants for primary (recurrent symptomatic intracerebral haemorrhage) and secondary (ischaemic stroke) outcomes for up to 5 years (reported elsewhere). For this report, we analysed eligible participants with intracerebral haemorrhage according to their treatment allocation in primary subgroup analyses of cerebral microbleeds on MRI and in exploratory subgroup analyses of other features on CT or MRI. The trial is registered with the ISRCTN registry, number ISRCTN71907627.Findings: Between May 22, 2013, and May 31, 2018, 537 participants were enrolled, of whom 525 (98%) had intracerebral haemorrhage: 507 (97%) were diagnosed on CT (252 assigned to start antiplatelet therapy and 255 assigned to avoid antiplatelet therapy, of whom one withdrew and was not analysed) and 254 (48%) underwent the required brain MRI protocol (122 in the start antiplatelet therapy group and 132 in the avoid antiplatelet therapy group). There were no clinically or statistically significant hazards of antiplatelet therapy on recurrent intracerebral haemorrhage in primary subgroup analyses of cerebral microbleed presence (2 or more) versus absence (0 or 1) (adjusted hazard ratio [HR] 0·30 [95% CI 0·08–1·13] vs 0·77 [0·13–4·61]; pinteraction=0·41), cerebral microbleed number 0–1 versus 2–4 versus 5 or more (HR 0·77 [0·13–4·62] vs 0·32 [0·03–3·66] vs 0·33 [0·07–1·60]; pinteraction=0·75), or cerebral microbleed strictly lobar versus other location (HR 0·52 [0·004–6·79] vs 0·37 [0·09–1·28]; pinteraction=0·85). There was no evidence of heterogeneity in the effects of antiplatelet therapy in any exploratory subgroup analyses (all pinteraction>0·05).Interpretation: Our findings exclude all but a very modest harmful effect of antiplatelet therapy on recurrent intracerebral haemorrhage in the presence of cerebral microbleeds. Further randomised trials are needed to replicate these findings and investigate them with greater precision.Funding: British Heart Foundation.

This paper presents an investigation on how simulation informed by the latest advances in digital technologies such as the 4th Industrial Revolution (I4.0) and the Internet of Things (IoT) can provide digital intelligence to accelerate the implementation of more circular approaches in UK manufacturing. Through this research, a remanufacturing process was mapped and simulated using discrete event simulation (DES) to depict the decision-making process at the shop-floor level of a remanufacturing facility. To understand the challenge of using data in remanufacturing, a series of interviews were conducted finding that there was a significant variability in the condition of the returned product. To address this gap, the concept of certainty of product quality (CPQ) was developed and tested through a system dynamics (SD) and DES model to better understand the effects of CPQ on products awaiting remanufacture, including inspection, cleaning and disassembly times. The wider application of CPQ could be used to forecast remanufacturing and production processes, resulting in reduced costs by using an automatised process for inspection, thus allowing more detailed distinction between &ldquo, go&rdquo, or &ldquo, no go&rdquo, for remanufacture. Within the context of a circular economy, CPQ could be replicated to assess interventions in the product lifecycle, and therefore the identification of the optimal CE strategy and the time of intervention for the current life of a product&mdash, that is, when to upgrade, refurbish, remanufacture or recycle. The novelty of this research lies in investigating the application of simulation through the lens of a restorative circular economic model focusing on product life extension and its suitability at a particular point in a product&rsquo, s life cycle.

Background: Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects.Methods: FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762.Findings: Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months.Interpretation: Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function.Funding: UK Stroke Association and NIHR Health Technology Assessment Programme.

The main challenge aerospace industries are facing in recent times has been triggered by the remarkable increase in commercial aircraft demand. To address this challenge, aircraft manufacturers need to explore ways to increase capacity and workflow through process optimisation and automation. This study focusses on the optimisation of component flow and inventory during the assembly of the A320 Family wings’ at Airbus (Broughton, UK) plant through Discrete Event Simulation (DES).

Successful drug treatment for tuberculosis (TB) depends on the unique contributions of its component drugs. Drug resistance poses a threat to the efficacy of individual drugs and the regimens to which they contribute. Biologically and chemically validated targets capable of replacing individual components of current TB chemotherapy are a major unmet need in TB drug development. We demonstrate that chemical inhibition of the bacterial biotin protein ligase (BPL) with the inhibitor Bio-AMS (5′-[N-(d-biotinoyl)sulfamoyl]amino-5′-deoxyadenosine) killed Mycobacterium tuberculosis (Mtb), the bacterial pathogen causing TB. We also show that genetic silencing of BPL eliminated the pathogen efficiently from mice during acute and chronic infection with Mtb. Partial chemical inactivation of BPL increased the potency of two first-line drugs, rifampicin and ethambutol, and genetic interference with protein biotinylation accelerated clearance of Mtb from mouse lungs and spleens by rifampicin. These studies validate BPL as a potential drug target that could serve as an alternate frontline target in the development of new drugs against Mtb.

SummaryEpilepsy is the third most common neurological disorder of older adults, with huge functional and psychological implications. It is often difficult to diagnose in the presence of cognitive impairment and lack of a witness account. The most common identifiable causes of epilepsy in old age are cerebrovascular disease and dementia. New guidelines recommend starting treatment after first unprovoked seizure. If there is any doubt about the diagnosis, electroencephalography (EEG) should be considered, or ‘wait and watch’. The aim of treatment should be to fully control seizure activity with the most effective monotherapy and fewest possible side-effects. Drug compliance is often difficult to achieve in older adults.

Muscarinic acetylcholine receptors (mAChRs) are important therapeutic targets for several diseases of the central nervous system and periphery. However, the lack of subtype-selective ligands for these receptors is a major challenge. A novel approach involving the integration of a natural product framework with a bioactive molecule (iNPBM) by using gephyrotoxin and the isoindoline framework is demonstrated for the discovery of new and selective mAChR modulators. We established a scalable and versatile synthetic scheme to enable the synthesis of various analogues that provided the first structure-activity relationship study of this class of compounds. Pharmacological profiling of these compounds demonstrated several ligands with high affinity and selectivity for mAChRs. Specifically, RG-06 and RG-09 were found to be antagonists of M3-mAChR, whereas RG-02 was found to be an agonist at M2-mAChR. Furthermore, RG-02 exhibited salutary effects in an established pharmacological model of a cognitive deficit in mice.

An efficient and scalable synthesis of various enantiopure 1,3- disubstituted isoindolines is reported. The base catalyzed nucleophilic fragmentation of a rigid overbred template is established with various substrates to afford the corresponding 1,3-disubstituted isoindoline ester, amide, thioate, 1,3-amino alcohol and isoindolylcarboxylic acid. The crucial rigid overbred template is synthesized in an optically pure form in multigram scale by asymmetric desymmetrization of the corresponding meso compound.

The use of optical fibre Bragg gratings (FBGs) to monitor the Interface Pressure Distribution (IPD) on an automotive disc brake pad under a variety of loading conditions is studied. The results demonstrate successful strain transfer from the brake pads to the attached FBG sensors under static loading, with a linear response to increasing pressure, and with the measured IPD showing good agreement with that recorded using pressure sensitive paper. Results are also presented demonstrating that changes in the IPD as a result of torque acting on the brake pads can be monitored by the FBG sensors.

The use of an optical fibre long period grating (LPG) as a soil moisture sensor is reported. Characterization of the device in both clay and sandy soils revealed a sensitivity to moisture levels in the range 10-50%, and the results were compared with the output from a Theta probe, the standard soil moisture sensor, which measures the impedance of the soil. © (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

An investigation on river Pandu in the year 2009-2010 was carried out to explore its current status in terms of physico-chemical and phycological profile. The study revealed that algal spectrum of the river was connected with the intensity of pollution in the river. River, at present is a perturbed ecosystem due to heavy anthropogenic stress on it. Despite abundant nutrients and other factors responsible for propping algal growth, river had a meak algal population and low diversity as compared to other perennial rivers indicating the grossly polluted unhealthy condition of the river. Algae are natural inhabitants of aquatic environment; and act as natural purifiers due to their nutrient gleaning and oxygenating capabilities; they are more sensitive than animals to industrial and municipal wastes. Maximum number of species existed at station-1 followed by stations-4 and 6 and then at station-5. Lowest species representation has been noticed at stations-2 and 3. Species number and algal population too declined sharply at stations-2 and 3 as compared to station-I. Sharp decline in algal population at stations-2 and 3 may be attributed to certain obvious reasons such as low transparency and reduced illumination as a consequence of residual fly ash discharged by PTPP drain at station-2. Except station-1, all downstream stations show grossly polluted condition of the river.DOI: http://dx.doi.org/10.3126/eco.v20i0.11325Ecoprint: An International Journal of EcologyVol. 20, 2013Page : 9-17

In the unreliable newsboy problem, firms sometimes split their orders among multiple suppliers to manage supply risks. In this paper, we discuss how ordering time can be used as a mechanism to mitigate the supply risks of an unreliable newsboy. We consider a situation where a firm has an option of placing a series of sequential orders such that a new order is placed only after the yield from the previous order is known. An optimal order quantity for each ordering stage is derived by assuming a Bernoulli (all or nothing) supply yield distribution. By comparing the expected cost of the sequential orderingbased unreliable newsboy model with the expected cost of the deterministic newsboy, we demonstrate that the adverse effect of supply side risks can be almost completely negated by adopting a sequential ordering policy when the combined purchasing and holding costs for a low cost supplier at an earlier stage are equal to those of a high cost supplier at the next stage. Our computational results suggest that the sequential ordering policy performs better than a simultaneous ordering strategy when customer service level norms become stringent and inventory holding costs decrease.

Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, is the leading cause of bacterial infectious disease mortality. Biotin protein ligase (BirA) globally regulates lipid metabolism in Mtb through the posttranslational biotinylation of acyl coenzyme A carboxylases (ACCs) involved in lipid biosynthesis and is essential for Mtb survival. We previously developed a rationally designed bisubstrate inhibitor of BirA that displays potent enzyme inhibition and whole-cell activity against multidrug resistant and extensively drug resistant Mtb strains. Here we present the design, synthesis, and evaluation of a focused series of inhibitors, which are resistant to cyclonucleoside formation, a key decomposition pathway of our initial analogue. Improved chemical stability is realized through replacement of the adenosyl N-3 nitrogen and C-5′ oxygen atom with carbon as well as incorporation of a bulky group on the nucleobase to prevent the required syn-conformation necessary for proper alignment of N-...

We performed a retrospective cohort comparison study to look at the processes for concentrating geriatric resources in the acute admissions area in a general hospital in the UK and compare key outcomes. The number of consultant geriatricians and other staff working at the 'front door' - acute medical unit (AMU) and short stay ward (SSW) - was increased. We compared 'front door' outcomes with whole department outcomes in 2013 and 2014, looking at the proportion of patients discharged within 3 and 5 days of admission, the proportion discharged from the 'front door', mean lengths of stay (LOS) and readmissions within 28 days of discharge. There were 1,147 and 1,381 discharge episodes in 2013 and 2014, respectively. 'Front door' discharges rose from 36% to 46% (p

The development of an ammonia sensor, formed by the deposition of a functionalised titanium dioxide film onto a tapered optical fibre is presented. The titanium dioxide coating allows the coupling of light from the fundamental core mode to a lossy mode supported by the coating, thus creating lossy mode resonance (LMR) in the transmission spectrum. The porphyrin compound that was used to functionalise the coating was removed from the titanium dioxide coating upon exposure to ammonia, causing a change in the refractive index of the coating and a concomitant shift in the central wavelength of the lossy mode resonance. Concentrations of ammonia as small as 1ppm was detected with a response time of less than 1min. © (2016) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

The study and systematic analysis of protein–protein interaction networks relevant to disease or well-being have become an integral part of systems biology. Recent studies have revealed strong association between the topological properties and biological function of proteins in networks. Hypoxia is a pathophysiological condition which arises due to low oxygen concentration in conditions like prenatal birth, cardiovascular diseases, malignancies, inflammation, ascent to higher altitude, free diving, etc. Conventional techniques of studying a single gene or protein have not been successful in this complex disorder. Considering the complexity and multivariate nature of hypoxic stress, we aimed to identify the key proteins; the central biological regulatory pathways, and their molecular connectivity by the topological analysis of the protein–protein interaction (PPI) network. The study collected proteins whose expressions are altered in response to hypoxia, and calculated an interaction map which is termed as the giant core “hypoxia-responsive PPI network” of 603 nodes connected via 4264 edges. A backbone network of 24 bottleneck proteins with high Betweenness Centrality and large degree was identified. The robustness and accuracy of backbone network was validated by 104 test networks. The giant network was divided into five functional subnetworks, each enriched with important and distinct biological pathways. The study is the first methodological network and pathway enrichment analysis of hypoxia-regulated proteins which sheds light on the important molecular mechanisms operational during hypoxic stress. It also comprehensively describes the global protein–protein interactions, the biological subnetworks, and the backbone network regulating the hypoxic stress response. This helps to identify potential target molecules for therapy or ameliorating the pathophysiology, which could not be found merely through molecular biology methods. In principle, the methodology described may be implemented to understand the molecular mechanisms in other multivariate disorders.

The current salvage therapies for relapsed/refractory acute myeloid leukemia (AML) are unsatisfactory. Over the past 7 years, we have used two salvage regimens: fludarabine, cytarabine, and idarubicin with (FLAG-IM) or without gemtuzumab ozogamicin (GO) (9 mg/m(2) on Day 8) (FLAG-I) in relapsed/refractory AML. Three-quarters of patients also received concurrent G-CSF. Seventy-one patients were treated, 23 with FLAG-I and 48 with FLAG-IM. The median duration of follow-up was 30.6 months. The treatment groups were well balanced with median ages of 48 years (range 18-70) and 47 years (range 20-68), unfavorable cytogenetics in 57% and 35%, prior allogeneic stem cell transplant in 43% and 42%, and CR1 duration

The continued development of ferroelectric materials into more and more consumer led applications has been at the forefront of recent ferroelectric material research. It is, however, possible to view a ferroelectric as a wide band gap semi-conductor that can sustain a surface charge density. This charge density arises from the movement of ions in the crystal lattice and the need to compensate for this charge. When viewing ferroelectrics as polarisable semi-conductors a large number of new interactions are possible. One such is the use of super band gap illumination to generate electron–hole pairs. These photogenerated carriers can then perform local electrochemistry. What is most interesting for ferroelectric materials is that the REDOX chemistry can be chosen by selectively modifying the domain structure of the ferroelectric—we can perform oxidation and reduction on the surface of the same material at spatially separate locations, or use the material to drive photoexcited carriers apart. This means we can separate the REDOX products or produce patterns of photogenerated material in places we have predetermined. This review aims to introduce the background research that has led to the current understanding as well a highlight some of the current areas that require further development.

Protein kinase G (PknG) in Mycobacterium tuberculosis has been shown to modulate phagosome-lysosome fusion. The protein has three distinct domains, an N-terminal Trx domain, a kinase domain, and a C-terminal TPR domain. The present study extensively analyzes the roles of these domains in regulating PknG kinase activity and function. We find that the kinase domain of PknG by itself is inactive, signifying the importance of the flanking domains. Although the deletion of the Trx domain severely impacts the activity of the protein, the C-terminal region also contributes significantly in regulating the activity of the kinase. Apart from this, PknG kinase activity is dependent on the presence of threonine 309 in the p + 1 loop of the activation segment. Mutating the conserved cysteine residues in the Trx motifs makes PknG refractory to changes in the redox environment. In vitro experiments identify threonine 63 as the major phosphorylation site of the protein. Importantly, we find that this is the only site in the protein that is phosphorylated in vivo. Macrophage infection studies reveal that the first 73 residues, the Trx motifs, and the threonine 63 residue are independently essential for modulating PknG-mediated survival of mycobacteria in its host. We have extended these studies to investigate the role of PknG and PknG mutants in the pathogenesis of mycobacteria in mice. Our results reinforce the findings from the macrophage infection experiments, and for the first time demonstrate that the expression of PknG in non-pathogenic mycobacteria allows the continued existence of these bacteria in host tissues.

Silver nanoparticle deposition from an aqueous solution of silver nitrate onto the surface of PZT thin films of stoichiometric compositions PbZr0.3Ti0.7O3 and PbZr0.52Ti0.48O3 has been investigated. The impact of Zr/Ti ratio on the photochemical properties of PZT is shown by the preferential growth of silver nanoparticles onto the surface. Photoreduction of silver occurs on both c+ and c− domains on PbZr0.52Ti0.48O3 whereas it occurs only on c+ domains on a PbZr0.3Ti0.7O3 surface. The difference in deposition pattern is attributed to difference in magnitude of spontaneous polarization, effective hole concentration and band gap of the two samples which impacts shape and width of space charge layer in the two samples resulting in a change in band bending at the surface.

The diagnosis of mixed-type autoimmune haemolytic anaemia (AIHA) is based on demonstrating the presence of "warm" IgG auto-antibody and "low titre" (64 at 4 degrees C), "high thermal amplitude" (reacting at or30 degrees C) "cold" IgM auto-antibody. Mixed-type AIHA is uncommon. Red cell agglutination on the peripheral blood film is a common finding in mixed-type AIHA and can lead, initially, to a mis-diagnosis of cold haemmagglutinin disease (CHAD). Mixed-type AIHA is rare and can be idiopathic or secondary, often associated with systemic lupus erythematosus (SLE) and lymphoma. In general, patients with mixed-type AIHA show a dramatic response to steroid therapy and frequently require few or no transfusions. We report two unusual cases of mixed-type AIHA. Case one was unusual as the patient developed AIHA while on steroid medication. Case two, we believe, is the first reported case of splenic T cell angioimmunoblastic non-Hodgkins lymphoma (NHL) associated with mixed-type AIHA. The patient failed to respond to steroids, intravenous immunoglobulin, chemotherapy and treatment with rituximab. The patient received 33 units of red cells over a 9-week period. She finally underwent splenectomy with resolution of haemolysis. DAT tested with monospecific reagents, and thorough serological investigations is required to reach the diagnosis of mixed-type AIHA. Awareness of this condition is important as management may be different from either treating warm AIHA or CHAD.

The preparation of the asymmetric substrate (I) is elaborated and its KOtBu-catalyzed conversion into enantiopure cis-1,3-disubstituted isoindoline carboxylates.

Two highly sensitive ammonia sensors, formed by depositing coatings composed of titanium dioxide (TiO2) onto the cladding of an optical fibre sensing platform, are evaluated. A long period grating (LPG) of period 111 μm was fabricated in the core of an optical fibre so that the LPG operates at or near the phase matching turning point (PMTP). The first coating that was investigated was composed of TiO2 nanoparticles deposited by liquid phase deposition. The sensor showed high sensitivity and allowed low concentrations of ammonia in water (0.01 ppm) to be detected with a response time of less than 60 sec. The second coating was composed of TiO2 with subsequent layers of poly (allyamine hydrochloride) (PAH), and SiO2 nanospheres infused with a sensitive element composed of porphine. The ammonia adsorption to the porphine compound led to the changes in the LPG’s transmission spectrum and allowed 0.1 ppm of ammonia in water to be detected with a response time of less than 60 sec.

Purpose To analyze the effects of preautografting treatment with rituximab (R) on stem-cell mobilization, post-transplantation complications, engraftment, disease-free survival, and overall survival in patients with non-Hodgkin's lymphoma (NHL). Patients and Methods Single-institution retrospective comparative outcome analysis in a cohort of 273 relapsed chemosensitive NHL patients of whom 127 (47%) received R pretransplantation. Results R was administered a median of 3 months before autologous transplantation. When compared to the nonrituximab group, R patients were older (56 v 50 years; P < .001), and had delays in post-transplantation platelets recovery (39 v 27 days; P = .001). Pretransplantation R did not affect stem-cell mobilization, post-transplantation early complications, duration of hospitalization, or mortality rates at days 30 and 100. In contrast to patients with low-grade NHL, both disease-free and overall survival rates were significantly better when R was included in the pretransplantation salvage therapy for patients with intermediate-grade NHL. Conclusion In this large, single-center retrospective analysis, pretransplantation treatment with R was associated with improved survival in patients with intermediate-grade NHL, at the price, however, of a delay in platelet engraftment.

Here we demonstrate the photochemical reduction of Al 3 + to metallic Al 0 nanoparticles using a ferroelectric material as the photocatalyst, in this case LiNbO 3 . This gives evidence for multi-electron photoreduction reactions and a possible route to the formation of nanostructured metal particles that has high reduction potential cations formed from the dissolution of salts.

Objectives Previous studies suggest an increased incidence of cardiovascular (CV) events after P2Y12 receptor blocker cessation. The aim of this study was to examine the effect of P2Y12 receptor blocker cessation and other risk factors on the risk of CV events and bleeding events after non-cardiac surgery/procedure in patients with drug-eluting stents (DES). Design Retrospective cohort study. Setting Single large healthcare system in the northeast of the USA. Patients All adult patients who had a coronary drug eluting stent (DES) placed between 2002 and 2007 in our institution. Interventions No randomised intervention. The principal exposure was cessation of P2Y12 receptor blocker Methods This was a retrospective study of all adult patients who had a coronary DES placed between 2002 and 2007 in our institution. We considered all non-cardiac procedures up to 1 year after DES placement. Generalised estimating equations were used to identify the independent risk factors. Multiple imputations were used to replace missing values. Main outcome measures The outcomes were CV events including death from any cause and bleeding, occurring within 30 days after the procedure. Results From 2002 to 2007, 6397 patients had DES, 873 (13.6%) had at least one non-cardiac procedure. A total of 3.6% (33/927) of the admissions were complicated by at least one cardiovascular event and 6.9% (55/795) were complicated by bleeding. Urgent procedure (versus elective) was the only independent risk factor for CV events (OR=4.82, 95% CI 1.95 to 11.89). Older age, diabetes, urgent procedures, orthopaedic and vascular surgery compared to unclassified surgery were independent risk factors for bleeding. Conclusions Non-cardiac procedures are common within 1 year after DES placement. Urgent nature of procedure is a risk factor for CV events and bleeding complications. Older age, diabetes, type of surgery, are risk factors associated only with bleeding events.

Background Subarachnoid haemorrhage may result in seizures both acutely and in the longer term. The use of antiepileptic drugs (AEDs) in the primary and secondary prevention of seizures after subarachnoid haemorrhage is uncertain, and there is currently no consensus on treatment. Objectives To assess the effects of AEDs for the primary and secondary prevention of seizures after subarachnoid haemorrhage. Search methods We searched the Cochrane Epilepsy Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 1) in The Cochrane Library, and MEDLINE (1946 to 12th March 2013). We checked the reference lists of articles retrieved from these searches. Selection criteria We considered all randomised and quasi-randomised controlled trials in which patients were assigned to a treatment (one or more AEDs) or placebo. Data collection and analysis Two review authors (RM and JK) independently screened and assessed the methodological quality of the studies. If studies were included, one author extracted the data and the other checked it. Main results No relevant studies were found. Authors' conclusions There was no evidence to support or refute the use of antiepileptic drugs for the primary or secondary prevention of seizures related to subarachnoid haemorrhage. Well-designed randomised controlled trials are urgently needed to guide clinical practice.

Uniformly collated phenological data set is the most important requirement for developing climate change impact models for mango. Consistently collected phenological records directly indicate the effect of change in climatic parameters by depicting shifts in phenological events. Recording of consistent data pertaining to phenophases as a function of time serves as critical input for working out integrated interaction of interannual variability, spatial differences and climate variability impacts. In general, uniform qualitative data recording is difficult in mango due to variations in plant growth and development under diverse climatic fluxes occurring in subtropical to tropical regions. Major observed effects of climate change on mango include early or delayed flowering, multiple reproductive flushes, variations in fruit maturity, abnormal fruit set and transformation of reproductive buds into vegetative ones. These critical phenophase-dependent events require supporting quantitative data representing behaviour of sufficient number of shoots within a tree for objective analysis of factors influencing them. For monitoring the phenophase dynamics, use of extended BBCH (Biologische Bundesanstalt, Bundessortenamt und Chemische Industrie) scale developed for mango helps in monitoring the phenology by employing uniform methodology over same or different locations with the description of each phenophase in mango as distinctly classified by adopting numerical code. A manual to elucidate the methodology for general users has been developed with the help of pictorial representation of phenophases along with corresponding scores, analysis, depiction of results and interpretation for uniform data recording, and this can be downloaded from http://offseasonmango.cishlko.org/phenology.pdf.

Water samples were collected from river Pandu at six stations where human and animal activities were high. Composite samples were analyzed for dissolved oxygen (DO), biochemical oxygen demand (BOD), chemical oxygen demand (COD) , pH values during dry and wet seasons as well as the harmattan period. The total data points were used to establish relationships between the parameters and data were also subjected to statistical analysis and expressed as mean ± standard error of mean (SEM) at a level of significance of p, {"references":["Das D.B. & Nassehl V,\" Development of a new mathematical model for\nsubsurface water quality management\", Water Science & Technology,\n2002,Vol.45, pp. 301-307.","Driver N.E., Tasker G.D, \"Techniques for estimation of storm-runoff\nloads, volumes, and selected constituent concentrations in urban\nwatersheds in the United States\". U.S. Geological Survey Water- Supply\nPaper 2363, 1990, 44 p.","Rene, E.R. and Saidutta, M.B,\" Prediction of Water Quality Indices by\nRegression Analysis and Artificial Neural Networks\". Int. Journal of\nEnvironmental research. 2008, 2(2), pp. 183-188.","Maha I. Al-Ali, Aziz I. Abdullah, Abdulqahar M. Mohammad and\nKutaiba I Al-Ali ,\" Estimating and Modelling the Interrelationships\nbetween Physicochemical Pollutants of Samara Drug Factory\nWastewater\". European Journal of Scientific Research, 2011,61 (2),pp.\n230-241.","American Public Health Association, A.P.H.A., \"Standard methods for\nthe examination of water and wastewater\". 1998, 20th\nEdition.Washington. D.C.","Bala G. and Mukherjee A., \"Statistical Studies on the Surface Water of\nSome Wetlands in Nadia, West Bengal\", International Journal of Lakes\nand Rivers, 2010,3, pp. 87-95.","Agarwal Animesh and Saxena Manish.,\"Assessment of pollution by\nPhysicochemical Water Parameters Using Regression Analysis: A Case\nStudy of Gagan River at Moradabad- India\". Advances in Applied\nScience Research, 2011,2 (2),pp. 185 -189","M. Waziri. and V.O. Ogugbuaja, \"Interrelationships between\nphysicochemical water pollution indicators: A case study of River Yobe-\nNigeria\". Am. J. Sci. Ind. Res., 2010,1(1),pp. 76-80","Verma, S.R., Sharma, P., Tyagi, A., Sarita Rani, Gupta, A.K. and Dalela,\nR.C, \"Pollution and saprobic status of Eastern Kalinadi\". Limnologia\n(Berlin). 1984,15,pp. 69-133.\n[10] Kaur P, \"Effects of combined waste effluents on the ecology of river\nPandu\". 1995, PhD Thesis, Kanpur University, Kanpur.\n[11] Venkateswarlu, V,\" Ecological studies on the rivers of Andhra Pradesh\nwith special reference to water quality and pollution\", Proc. Indian Acad.\nSci. (Plant Sci.) 1986, 96 , pp. 495-508.\n[12] Chakraborty, R.D., Roy, P, and Singh, S.B, \"A quantitative study of the\nplankton and the physicochemical conditions of river Yamuna at\nAllahabod in 1954-55\". Ind. J. Fish. 1959,6 (1),pp. 186-203.\n[13] Venkateswarlu, V.. \"An ecological study of the algae of river Moosi,1\nHyderabad (India) with special reference to water pollution I. Physicochemical\ncomplexes\". Hvdrobioloqia 1969,33,pp. 117-143.\n[14] Tiwari, D. \"Pollution phycology of the Varanasi frontage of river\nGanges\". 1983, Ph.D. Thesis. Banaras Hindu University. Varanasi.\n[15] IS:2296, \"Tolerance limit for Inland Surface Water subjected to\nPollution\". 1982,Indian Standard Institution, New Delhi.\n[16] Campbell, I.C, \"A biological investigation of an organically polluted\nurban stream in Vicrtoria\". Aust. J. Ma_r. Freshwat. Res. 1978, 29 , pp.\n275-291."]}

Recently there has been great interest in using patterned ferroelectric materials for the photochemical growth of metal nanostructures. Variations in surface and sub-surface structure influence the photochemical processes. Here we show that crystallography, and hence remnant polarization, of the ferroelectric affects photo-deposition. The ratio of metal growth on c− and c+ domains varies from 1 : 2 for [100] to 1 : 100 for [111]. This is shown to be dependent on the variations in the band structure.