Miracle-dz/UniFAR-FTUs huggingface dataset:
F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase

Significance New antifungal drugs that act via novel mechanisms are urgently needed to combat the high mortality of invasive fungal disease and the emergence of resistance to existing therapies. We describe the discovery, structure, activity, and mechanism of action of F901318, a new antifungal agent. A member of a novel class of antifungals, the orotomides, F901318 acts via inhibition of dihydroorotate dehydrogenase, an enzyme of de novo pyrimidine biosynthesis. F901318 is currently in clinical development for the treatment of invasive aspergillosis. There is an important medical need for new antifungal agents with novel mechanisms of action to treat the increasing number of patients with life-threatening systemic fungal disease and to overcome the growing problem of resistance to current therapies. F901318, the leading representative of a novel class of drug, the orotomides, is an antifungal drug in clinical development that demonstrates excellent potency against a broad range of dimorphic and filamentous fungi. In vitro susceptibility testing of F901318 against more than 100 strains from the four main pathogenic Aspergillus spp. revealed minimal inhibitory concentrations of ≤0.06 µg/mL—greater potency than the leading antifungal classes. An investigation into the mechanism of action of F901318 found that it acts via inhibition of the pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH) in a fungal-specific manner. Homology modeling of Aspergillus fumigatus DHODH has identified a predicted binding mode of the inhibitor and important interacting amino acid residues. In a murine pulmonary model of aspergillosis, F901318 displays in vivo efficacy against a strain of A. fumigatus sensitive to the azole class of antifungals and a strain displaying an azole-resistant phenotype. F901318 is currently in late Phase 1 clinical trials, offering hope that the antifungal armamentarium can be expanded to include a class of agent with a mechanism of action distinct from currently marketed antifungals.
Clinical islet transplant: current and future directions towards tolerance

Summary: The ultimate goal of islet transplantation is to completely correct the diabetic state from an unlimited donor source, without the need for chronic immunosuppressive drug therapy. Although islet transplantation provides an opportunity to develop innovative strategies for tolerance in the clinic, both alloimmune and autoimmune barriers must be controlled, if stable graft function is to be maintained long‐term. After islet extraction from the pancreas, the cellular graft may be stored in tissue culture or cryopreserved for banking, providing an opportunity not only to optimally condition the recipient but also to allow in vitro immunologic manipulation of the graft before transplantation, unlike solid organ grafts. As such, islets may be considered a ‘special case. ’ Remarkable progress has occurred in the last three years, with dramatic improvements in outcomes after clinical islet transplantation. The introduction of a steroid‐free, sirolimus‐based, anti‐rejection protocol and islets prepared from two (or rarely three) donors led to high rates of insulin independence. The ‘Edmonton Protocol’ has been successfully replicated by other centers in an international multicenter trial. A number of key refinements in pancreas transportation, processing, purification on non‐ficoll‐based media, storage of islets in culture for two days and newer immunological conditioning and induction therapies have led to continued advancement through extensive collaboration between key centers. This review outlines the historical development of islet transplantation over the past 30 years, provides an update on current clinical outcomes, and summarizes a series of unique opportunities for development and early testing of tolerance protocols in patients.
Susceptibility to skin stinging, non‐immunologic contact urticaria and acute skin irritation; is there a relationship?

Adverse skin reactions cover many types of response: toxic, irritant, allergic, urticarial, sensory, etc. The relationships between an individual's tendency to develop different types of skin response are not well‐described. We examined whether those who perceive stinging might be more likely to experience urticarial, sensory and irritation reactions in skin. A panel of 86 volunteers was tested with 10% lactic acid in the nasolabial fold to assess their ability to perceive stinging. At the same time, their capacity to develop non‐immunologic contact urticaria was evaluated using chemicals of different structural type and urticant ability: methyl nicotinate, benzoic acid, cinnamic acid, cinnamaldehyde and dimethyl sulfoxide (DMSO). DMSO was also used to assess sensory effects and skin irritation. 44 were classed as “stingers” and 42 as “non‐stingers”. The pattern of urticant reactivity in the stingers and non‐stingers was essentially the same, with neat DMSO generating the strongest reactions in both groups. Sensory reactions to DMSO (stinging, itching, tingling or burning) were similar in stingers and non‐stingers; although the former may have reacted more quickly, a smaller proportion reacted (64% versus 76%). The skin irritation response to DMSO was also identical in stingers and non‐stingers and the intensity of the urticant response in an individual did not correlate with the intensity of their subsequent irritant reaction. In conclusion, this study demonstrated that an individual's ability to perceive skin stinging does not give a general indication of their susceptibility to other types of non‐immunologic skin response. Indeed, there appeared to be little evidence of correlations between any of the skin effects studied.
Integral Resonant Control of a Piezoelectric Tube Actuator for Fast Nanoscale Positioning

There is a need, in the wide ranging scientific community, to perform fast scans using scanning tunneling microscopes (STMs) and atomic force microscopes (AFMs) with nanoscale precision. In this paper, a piezoelectric tube of the type typically used in STMs and AFMs is considered. The resonant mode that hampers the fast scanning is identified and damped using a feedback control technique known as integral resonant control (IRC). The piezoelectric tube is then actuated to perform fast and accurate scans. IRC is a new feedback control technique suitable for damping highly resonant structures. Here, the IRC control technique is suitably modified to damp the resonance of a piezoelectric tube and achieve fast tracking of a wideband set point.
A comparison of illumination algorithms in unbounded spaces

Illumination algorithms are a new class of evolutionary algorithms capable of producing large archives of diverse and high-performing solutions. Examples of such algorithms include Novelty Search with Local Competition (NSLC), the Multi-dimensional Archive of Phenotypic Elites (MAP-Elites) and the newly introduced Centroidal Voronoi Tessellation (CVT) MAP-Elites. While NSLC can be used in unbounded behavioral spaces, MAP-Elites and CVT-MAP-Elites require the user to manually specify the bounds. In this study, we introduce variants of these algorithms that expand their bounds based on the discovered solutions. In addition, we introduce a novel algorithm called "Cluster-Elites" that can adapt its bounds to non-convex spaces. We compare all algorithms in a maze navigation problem and illustrate that Cluster-Elites and the expansive variants of MAP-Elites and CVT-MAP-Elites have comparable or better performance than NSLC, MAP-Elites and CVT-MAP-Elites.
Mechanical air drying of hands following preoperative scrubbing.

THERE ARE several possibilities of bacterial contamination inherent in the drying of the hands and forearms following preoperative scrubbing. Contamination by dustcarried airborne bacteria is one of these. The degree of such contamination will vary with the amount of circulating dust, duration of exposure, and moisture content of the air. Since most operating room layouts are similar, these factors will probably be fairly constant among different hospitals. Scrubbing techniques differ somewhat, but the differences are not great enaough to allow much variation in the elimination of bacteria. It is in the drying of the hands that the greatest possible opportunities for contamination exist. In the use of sterile towels for drying, these opportunities are the greatest. Improper rotation of the towel during drying, the touching of the scrub suit or of the unscrubbed portions of the upper extremities, all offer great probabilities of gross contamination. It would seem that simple air drying of the hands would eliminate these probabilities of contamination. Such a method further has the advantage of elimination of more costly methods of drying. However, it is slow, physically uncomfortable, and may cause chapping of the skin. It could be followed by dust-laden air contamination in relatively dry operating
Patients' perceptions of the benefits and problems of using the ActiGait implanted drop-foot stimulator.

OBJECTIVE To evaluate patients' perceptions of the benefits and problems associated with using the ActiGait implanted drop-foot stimulator. METHOD Thirteen participants who had suffered a stroke at least 6 months prior to recruitment, had a drop-foot that affected walking and had taken part in a trial in which an ActiGait drop-foot stimulator had been implanted, completed a postal questionnaire. RESULTS Users agreed that the ActiGait had a positive effect on walking; they used it regularly and had little difficulty with putting it on and taking it off. Reliability was a greater problem at 90 days than at the final assessment. Ten of the 13 responders either agreed or strongly agreed with the statement that the ActiGait improved their quality of life at 90 days and 9 out of 12 at the final assessment: 11 of the 12 respondents would recommend the ActiGait to others. DISCUSSION AND CONCLUSION From the users' perspective the ActiGait improved walking, it was reported to be used regularly and it appeared to be easier to use than a surface system. Users were equivocal about the reliability of the system at 90 days, but at the final assessment reliability had improved.
Somatosensory evoked potentials following lesions of the claustrum.

Ipsi- and contralateral cortical somatosensory evoked potentials (SEP) were recorded following median nerve stimulation in 12 patients with unilateral brain lesions and in 5 healthy subjects. Computed tomographic scans of brain were performed on admission. In all patients with lesions of the claustrum there was absence of SEP contralateral to the side of the lesion and ipsilateral to the stimulated nerve. This phenomenon did not appear in our material following lesions involving other structures e.g. thalamus or somatosensory cortex. Our observations suggest that the claustrum may influence deeply the contralateral somatosensory cortex. This may be due to the fact that a large part of the claustrum is involved in transmission of the sensory information from receptors to the somatosensory cortex.
The Role of Attention in Sexual Arousal: Implications for Treatment of Sexual Dysfunction

The literature on the role of attention in sexual arousal is reviewed, especially that which has implications for noninvasive treatment of sexual dysfunction. Findings suggest that voluntary control of sexual arousal can be achieved through attentional focus on nonsexual cognitions or sexual fantasy. Cognitive biases may direct attention and thus facilitate or impede sexual arousal. Sexual arousal may be influenced by directed attentional focus, and preliminary evidence suggests that mindfulness techniques may result in longer-term changes in attentional focus; these changes, in turn, may improve sexual response. Information-processing models of sexual arousal developed in light of such findings are discussed. This research establishes the central role of attentional processes in facilitating physiological and, especially, subjective sexual arousal. Implementing approaches that capitalize on attentional processes could advance noninvasive treatment of sexual dysfunction. Future avenues of research might investigate how play, mammalian play circuits, and flow states are relevant to sexual response and satisfaction.
An acoustic typology of apraxic speech - toward reliable diagnosis

Differential diagnosis of apraxia of speech (AOS) is complicated by frequently co-occurring speech and language disorders. Auditory-perceptual measures may not adequately differentiate between disorders. This study adapted an acoustic analysis protocol developed for Parkinson’s disease (PD). Preliminary results are positive, showing differences between individuals with AOS, PD, and healthy controls (HC).
Overview of SNS Cryomodule Performance

Thomas Jefferson National Accelerating Facility (Jefferson Lab) has completed production of 24 Superconducting Radio Frequency (SRF) cryomodules for the Spallation Neutron Source (SNS) superconducting linac. This includes one medium-β (0.61) prototype, eleven medium-β and twelve high-β (0.81) production cryomodules. Nine medium-β cryomodules as well as two high-β cryomodules have undergone complete operational performance testing in the Cryomodule Test Facility at Jefferson Lab. The set of tests includes measurements of maximum gradient, unloaded Q (Q0), microphonics, and response to Lorentz forces. The Qext’s of the various couplers are measured and the behavior of the higher order mode couplers is examined. The mechanical and piezo tuners are also characterized. The results of these performance tests will be discussed in this paper.
Prevalence of orthostatic hypotension among patients presenting with syncope in the ED.

We sought to determine the prevalence of orthostatic hypotension as a cause of syncope in the emergency setting, and describe the characteristics of patients diagnosed with this condition. Blood pressure orthostatic changes were measured prospectively in a standardized fashion up to 10 minutes, or until symptoms occurred, in all consecutive patients with syncope as a chief complaint presenting in the emergency department (ED) of a primary and tertiary care hospital. Patients unable to stand-up were excluded. Hypotension was considered to be the cause of syncope when there was: (1) a decrease in systolic blood pressure (SBP) >or= 20 mm Hg with simultaneous symptoms; (2) a decrease in SBP between 10 and 20 mm Hg, but a SBP <or= 90 mm Hg with or without symptoms; and (3) a nonsignificant decrease in SBP in the ED, but a prehospital value <or= 80 mm Hg was documented that prompted fluid therapy before standardized measurements. Among 788 patients with syncope seen in the ED during a 20-month period, 650 were included in the study, and 579 (89%) had standardized measurements of SBP. According to diagnostic criteria, orthostatic hypotension was considered to be the cause of syncope in 156 of them (24%). Fifty-eight patients (37%) had drug-induced hypotension, 33 (21%) hypovolemia, 19 (12%) postprandial hypotension, and 46 (29%) idiopathic hypotension. Asymptomatic SBP changes >or= 20 mm Hg were found in 10% of patients with syncope attributed to other causes. Compared with patients with vasovagal disorder, those with orthostatic hypotension were older; had more comorbid conditions including hypertension, organic heart disease, and abnormal electrocardiogram; were taking more hypotensive medications; and required more frequently hospitalization (P <.01). We concluded that standardized blood pressure measurement in the ED enabled to strongly implicate orthostatic hypotension as a cause of syncope in 24% of patients with this symptom. Drug-related hypotension was the most frequent cause for this disorder.
On Bipolar Reduction and Splintered Pieces

Objects variously called bipolar cores, pièces esquillées and other things are abundant in the record. Some interpret them as the exhausted remnants of bipolar reduction, others as wedges used with antler or bone. I propose that we call them “splintered pieces” to avoid functional connotations. Splintered pieces illustrate the problem of equifinality, different causes producing like consequences. A growing but uncertain consensus regards most splintered pieces as cores. Reviewing the latest expression of a different interpretation, I conclude that experimental, ethnographic, and archaeological data continue to support the view that most—not all—splintered pieces are cores. Nevertheless, the need remains urgent to search ethnographic accounts for support of the wedge view, to conduct further experiments, and to seek conclusive archaeological association of splintered pieces with wedging.
Expression of a Bacillus Phytase C Gene in Pichia pastoris and Properties of the Recombinant Enzyme

ABSTRACT The cloning and expression of a native gene encoding a Bacillus subtilis phytase using Pichia pastoris as the host is described. In addition, the influence of N-glycosylation on the biochemical properties of the B. subtilis phytase, the influence of pH on the thermostability of the recombinant and native B. subtilis phytases, and the resistance of both phytases to shrimp digestive enzymes and porcine trypsin are also described. After 48 h of methanol induction in shake flasks, a selected recombinant strain produced and secreted 0.82 U/ml (71 mg/liter) recombinant phytase. This phytase was N-glycosylated, had a molecular mass of 39 kDa after N-deglycosylation, exhibited activity within a pH range of 2.5 to 9 and at temperatures of 25 to 70°C, had high residual activity (85% ± 2%) after 10 min of heat treatment at 80°C and pH 5.5 in the presence of 5 mM CaCl2, and was resistant to shrimp digestive enzymes and porcine trypsin. Although the recombinant Bacillus phytase had pH and temperature activity profiles that were similar to those of the corresponding nonglycosylated native phytase, the thermal stabilities of the recombinant and native phytases were different, although both were calcium concentration and pH dependent.
Exploring the quality of life after denture-wearing within elders in Kaohsiung.

OBJECTIVE The objective of the research is to investigate whether the elderly people's quality of life get improved after denture wearing. MATERIAL AND METHODS About 1600 elderly persons, over 65 years old, were sampled as the research target. The overall response rate was 71.62%. The tool of research is a structural questionnaire Oral Health Impact Profile (OHIP) that was used to measure the oral health-related quality of life. Individual's satisfaction of denture wearing divides into three groups: edentulous individuals who are satisfied with denture wearing, edentulous individuals who are not satisfied with denture wearing and dentulous individuals. RESULTS The result shows the eight variables, which are oral health condition, frequency of snacks-eating, age, frequency in participation in social activities, instrumental activities of daily living (IADL), vision, satisfaction with life and physical functions, have significant influence on total OHIP score. CONCLUSIONS Although being edentulous, if the elderly are satisfied with their denture, the quality of life can be maintained and not affected by oral health problems. It is suggested that the further researches can include more relevant factors when in a discussion on the oral health-related quality of life, especially, the subjective perception of individual's feeling.
Quantifying Microvascular Abnormalities With Increasing Severity of Diabetic Retinopathy Using Optical Coherence Tomography Angiography

Purpose We quantified retinal and choriocapillaris microvascular changes in healthy control eyes and different stages of diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA). Methods This retrospective cross-sectional study included 137 eyes of 86 patients with different stages of DR and 44 eyes of 26 healthy age-matched controls. Participants were imaged with a commercial OCTA device (RTVue-XR Avanti). We analyzed the superficial (SCP) and deep (DCP) retinal capillary plexus, the full retina, and choriocapillaris for the following OCTA parameters: foveal avascular zone, vessel density, percent area of nonperfusion (PAN), and adjusted flow index (AFI). We adjusted for age, sex, and the correlation between eyes of the same study participant in our statistical models. Results All OCTA parameters showed a significant linear correlation with DR severity (P < 0.05) in the univariate models except for AFI measured in the SCP and these correlations remained significant after correcting for covariates. Compared to the other capillary layers, the AFI at the DCP decreased significantly with DR severity. When comparing individual disease severity groups as categories, eyes of subjects with diabetes without DR had significantly increased PAN and AFI in the SCP compared to healthy subjects (P < 0.05). Conclusions Retinal and choriocapillaris vascular nonperfusion in OCTA is correlated significantly with disease severity in eyes with DR. Higher flow in the SCP may be an early marker of diabetic microvascular changes before clinical signs of DR. The steep decline of blood flow in the DCP with increasing DR severity suggests that alterations at the DCP warrant further investigation.
Antigenic and genetic variation in the hemagglutinins of H1N1 and H3N2 human influenza a viruses in the Shanghai area from 2005 to 2008

Continued rapid evolution of the influenza A virus is responsible for annual epidemics and occasional pandemics in the Shanghai area. In the present study, the representative strains of A/H1N1 and A/H3N2 influenza viruses isolated in the Shanghai area from 2005 to 2008 were antigenically and genetically characterized. The antigenic cartography method was carried out to visualize the hemagglutination‐inhibition data. Antigenic differences were detected between circulating A/H1N1 strains isolated from 2005 to 2006 and the epidemic A/H1N1 strains isolated in 2008, which were found to be associated with the amino acid substitution K140E in HA1. The present vaccine strain A/Brisbane/59/2007 is considered to be capable of providing sufficient immunity against most of the circulating A/H1N1 viruses isolated in 2008 from the Shanghai population. The study showed that there were significant antigenic differences between the epidemic A/H3N2 strains isolated in 2007 and 2008, suggesting that antigenic drift had occurred in the A/H3N2 strains isolated in 2008. The P194L mutation was thought to be responsible for the antigenic evolution of influenza A/H3N2 viruses isolated from Shanghai in 2008. Evidence of antigenic drift suggests that the influenza A/H3N2 vaccine component needs to be updated. J. Med. Virol. 83:1113–1120, 2011. © 2011 Wiley‐Liss, Inc.
CLOUD SERVICE BROKER: SELECTION OF PROVIDERS USING DTRFV EVALUATION

Multicloud environment possess new challenges to the Cloud Service Requesters. Cloud Service Requesters are not aware of the quality of service offered by Cloud Service Providers. To select the suitable provider for a service the requester meets the Cloud Service Broker. Broker finds the best suitable provider for every request. Broker identifies the previous service ratings to evaluate the Reputation Factor Value of provider. In this paper, we present Dynamic True Reputation Factor Value Evaluation algorithm to find the best providers. By using this algorithm Broker can identify the unfair ratings and reduce the effect of unfair ratings in the calculation of True Reputation Factor Value of provider. Results are presented to appraise the success of the proposed model.