Miracle-dz/UniFAR-FTUs huggingface dataset:
A 65k-neuron 73-Mevents/s 22-pJ/event asynchronous micro-pipelined integrate-and-fire array transceiver

We present a 65k-neuron integrate-and-fire array transceiver (IFAT) for spike-based neural computation with low-power, high-throughput connectivity. The internally analog, externally digital chip is fabricated on a 4×4 mm2 die in 90 nm CMOS and arranged in 4 quadrants of 16k parallel addressable neurons. Each neuron circuit serves input spike events by dynamically instantiating conductance-based synapses onto four local synapse circuits over two membrane compartments, and produces output spike events upon reaching a threshold in integration over one of the membrane compartments. Fully asynchronous input and output spike event data streams are mediated over the standard address event representation (AER) protocol. To support full event throughput at large synaptic fan-in, a two-tier micro-pipelining scheme parallelizes input events along neural array cores, and along rows of each core. Measured results show sustained peak synaptic event throughput of 18.2 Mevents/s per quadrant, at 22 pJ average energy per synaptic input event and 25 μW standby power.
Immunophenotyping does not improve predictivity of the local lymph node assay in mice

The local lymph node assay (LLNA) is a regulatory accepted test for the identification of skin sensitizing substances by measuring radioactive thymidine incorporation into the lymph node. However, there is evidence that LLNA is overestimating the sensitization potential of certain substance classes in particular those exerting skin irritation. Some reports describe the additional use of flow cytometry‐based immunophenotyping to better discriminate irritants from sensitizing irritants in LLNA. In the present study, the 22 performance standards plus 8 surfactants were assessed using the radioactive LLNA method. In addition, lymph node cells were immunophenotyped to evaluate the specificity of the lymph node response using cell surface markers such as B220 or CD19, CD3, CD4, CD8, I‐Aκ and CD69 with the aim to allow a better discrimination above all between irritants and sensitizers, but also non‐irritating sensitizers and non‐sensitizers. However, the markers assessed in this study do not sufficiently differentiate between irritants and irritant sensitizers and therefore did not improve the predictive capacity of the LLNA. Copyright © 2014 John Wiley & Sons, Ltd.
Recognition of Bisecting N-Acetylglucosamine

Background: Mouse dendritic cell inhibitory receptor 2 (DCIR2) specifically binds to bisecting GlcNAc-containing N-glycans. Results: The crystal structure of DCIR2 carbohydrate recognition domain in complex with bisected glycan was elucidated. Conclusion: The lectin asymmetrically interacts with the α1-3 arm (GlcNAcβ1–2Man) of the biantennary oligosaccharide including bisecting GlcNAc. Significance: Mouse DCIR2 is the first bisecting GlcNAc-specific lectin to be structurally characterized. Dendritic cell inhibitory receptor 2 (DCIR2) is a C-type lectin expressed on classical dendritic cells. We recently identified the unique ligand specificity of mouse DCIR2 (mDCIR2) toward biantennary complex-type glycans containing bisecting N-acetylglucosamine (GlcNAc). Here, we report the crystal structures of the mDCIR2 carbohydrate recognition domain in unliganded form as well as in complex with an agalactosylated complex-type N-glycan unit carrying a bisecting GlcNAc residue. Bisecting GlcNAc and the α1-3 branch of the biantennary oligosaccharide asymmetrically interact with canonical and non-canonical mDCIR2 residues. Ligand-protein interactions occur directly through mDCIR2-characteristic amino acid residues as well as via a calcium ion and water molecule. Our structural and biochemical data elucidate for the first time the unique binding mode of mDCIR2 for bisecting GlcNAc-containing glycans, a mode that contrasts sharply with that of other immune C-type lectin receptors such as DC-SIGN.
Development and characterization of microsatellite markers in two agarophyte species Gracilaria birdiae and G. caudata (Gracilariaceae, Rhodophyta) using next-generation sequencing

The two species Gracilaria birdiae Plastino and E.C. Oliveira and G. caudata J.Agardh are the most important natural sources of agar in Brazil. Using the 454 sequencing system, we identified 464 and 487 perfect microsatellite loci in G. birdiae and G. caudata , respectively. After a conservative removal of potentially problematic loci, 144 loci were tested (72 from each species). A total of 25 polymorphic microsatellite loci were defined (13 loci for G. birdiae and 17 loci for G. caudata , including five loci common to both species). The five microsatellite loci that cross-amplified in both species showed species-specific differences in allele size. Polymorphic microsatellite loci were used to assess the genetic diversity of both species in their main harvest and cultivation areas on the Brazilian coast. Gene diversity was similar in G. birdiae and G. caudata . However, significant heterozygote deficiency was observed in G. birdiae , whereas heterozygote excess occurred in G. caudata , suggesting that these two related species differ in their mating system. These results also raised new questions on their biology in the field and on their patterns of genetic structure across their geographical ranges. In addition, the 20 loci developed in this study proved successful in identifying each individual in the field as a unique multilocus genotype, and will be useful for studying lineage sorting, breeding programs or conservation issues.
Processing of a Membrane Protein Required for Cell-to-Cell Signaling during Endospore Formation in Bacillus subtilis

ABSTRACT Activation of the late prespore-specific RNA polymerase sigma factor σG during Bacillus subtilis sporulation coincides with completion of the engulfment process, when the prespore becomes a protoplast fully surrounded by the mother cell cytoplasm and separated from it by a double membrane system. Activation of σG also requires expression of spoIIIJ, coding for a membrane protein translocase of the YidC/Oxa1p/Alb3 family, and of the mother cell-specific spoIIIA operon. Here we present genetic and biochemical evidence indicating that SpoIIIAE, the product of one of the spoIIIA cistrons, and SpoIIIJ interact in the membrane, thereby linking the function of the spoIIIJ and spoIIIA loci in the activation of σG. We also show that SpoIIIAE has a functional Sec-type signal peptide, which is cleaved during sporulation. Furthermore, mutations that reduce or eliminate processing of the SpoIIIAE signal peptide arrest sporulation following engulfment completion and prevent activation of σG. SpoIIIJ-type proteins can function in cooperation with or independently of the Sec system. In one model, SpoIIIJ interacts with SpoIIIAE in the context of the Sec translocon to promote its correct localization and/or topology in the membrane, so that it can signal the activation of σG following engulfment completion.
Building a realistic neuronal model that simulates multi‐joint arm and hand movements in 3D space

The question as to how the brain controls voluntary movements of the arm and hand still remains largely unsolved despite much research focused on behavioral studies, neurophysiological investigations, and neuronal modeling in computer science. This is because behavioral studies are usually performed without detailed knowledge of the underlying neuronal networks, neurophysiological studies often lack an understanding of the function, and neuronal models are frequently focused on a particular control problem with restricted knowledge of the underlying neuronal networks involved. Therefore, it seems appropriate to start by trying to integrate knowledge of neuronal networks with known function and computer based neuronal models to seek more realistic models that can better control robots or artificial limbs and hands. We propose to combine knowledge of a behavioral model for reaching with the hand toward an object, which is based on detailed knowledge of the underlying neuronal network, and a neuronal model that includes several functional levels, from the planning level via intermediate levels to the final level of control of motoneurons and muscles.
Roles of the jejunum and ileum in the first-pass effect as absorptive barriers for orally administered tacrolimus.

BACKGROUND The immunosuppressant tacrolimus shows poor and variable bioavailability following oral administration in clinical use. Recently, the hepatic and intestinal metabolisms, or first-pass effect, of tacrolimus have been suggested to be responsible for its bioavailability. In the present study, we investigated the respective contribution of the jejunum and ileum to the first-pass effect of tacrolimus in rats. METHODS The metabolism of tacrolimus in everted sacs of the duodenum, jejunum, and ileum was examined. Tacrolimus was administered intravenously or intraintestinally to sham-operated, jejunum-resected, or ileum-resected rats. Blood samples were collected over a 240-min period, and whole-blood tacrolimus concentrations were measured by semiautomated microparticle enzyme immunoassay. The pharmacokinetic parameters of tacrolimus in each group were estimated. RESULTS The metabolic activity of tacrolimus appeared to be the highest in the everted sacs of the duodenum. The bioavailability of tacrolimus in the jejunum- or ileum-resected rats was higher than that in sham-operated controls. On the other hand, the time to peak concentration in the jejunum-resected rats was about twofold slower than those in ileum-resected and sham-operated rats. CONCLUSIONS These results suggested that the first-pass effect of tacrolimus in the small intestine shows regional differences and the extraction of tacrolimus in the small intestine consists of the amount of extraction in the jejunum and ileum. In addition, the ileum rather than the jejunum as a graft of segmental small bowel transplantation would be useful to avoid the adverse effects of tacrolimus.
An Electron Paramagnetic Resonance Spin-Probe Study of Membrane-Permeability Changes with Seed Aging

We developed an electron paramagnetic resonance spin-probe technique to study changes in the barrier properties of plasma membranes in wheat (Triticum aestivum L.) seeds during aging under dry storage. The estimation of these barrier properties was based on the differential permeability of membranes for the stable free radical 4-oxo-2,2,6,6-tetramethyl-1-piperidinyloxy and the broadening agent ferricyanide. The line-height ratio between the water and lipid components in the electron paramagnetic resonance spectra of 4-oxo-2,2,6,6-tetramethyl-1-piperidinyloxy (R value) allowed for the quantitative assessment of the plasma membrane permeability in small samples, enabling separate studies of the axis, scutellum, aleurone layer, and starchy endosperm tissue. High R values corresponded to low permeability and vice versa. Starchy endosperm cells had completely permeable plasma membranes even in mature, viable seeds. The loss of germinability with aging coincided with a considerably increased plasma membrane permeability of the embryo axis cells, but not of the scutellum and aleurone layer cells. The threshold R value for the individual axes associated with viability loss was established at 5 to 6, with the total ranging from 0 to more than 12. We suggest that the R value of an individual axis is the result of contributions from all individual cells, each of them characterized by a different permeability. The loss of viability, therefore, corresponds to the accumulation of cells having permeability above a critical level.
A retrospective analysis of antimicrobial resistance in bacterial pathogens in an equine hospital (2012-2015).

INTRODUCTION Antimicrobial resistance has become an important concern in veterinary medicine. The aim of this study was to describe the rate of antimicrobial resistance in common equine pathogens and to determine the occurrence of multidrug-resistant isolates. A retrospective analysis of all susceptibility testing results from bacterial pathogens cultured from horses at the University of Zurich Equine Hospital (2012-2015) was performed. Strains exhibiting resistance to 3 or more antimicrobial categories were defined as multidrug-resistant. Susceptibility results from 303 bacterial pathogens were analyzed, most commonly Escherichia coli (60/303, 20%) and Staphylococcus aureus (40/303, 13%). High rates of acquired resistance against commonly used antimicrobials were found in most of the frequently isolated equine pathogens. The highest rate of multidrug resistance was found in isolates of Acinetobacter baumannii (23/24, 96%), followed by Enterobacter cloacae complex (24/28, 86%) and Escherichia coli (48/60, 80%). Overall, 60% of Escherichia coli isolates were phenotypically ESBL-producing and 68% of Staphylococcus spp. were phenotypically methicillin-resistant. High rates of acquired antimicrobial resistance towards commonly used antibiotics are concerning and underline the importance of individual bacteriological and antimicrobial susceptibility testing to guide antimicrobial therapy. Minimizing and optimizing antimicrobial therapy in horses is needed.
25-year trends in gender disparity for obesity and overweight by using WHO and IOTF definitions among Chinese school-aged children: a multiple cross-sectional study

Objectives We sought to explore 25-year trends of gender disparity in the prevalence of obesity and overweight both in urban and rural areas among Chinese children from 1985 to 2010. Methods Data included 1 280 239 children aged 7–18 years enrolled in the Chinese National Survey on Students's Constitution and Health (CNSSCH), which is the largest nationally representative sample of school-aged children in China. Obesity and overweight were defined according to both WHO and the International Obesity Task Force (IOTF) definitions. Logistic regression was used to estimate the prevalence OR (POR) of gender for obesity and overweight prevalence in different surveys. Results The prevalence of obesity increased (WHO definition: from 0.10% to 4.3%; IOTF definition: from 0.03% to 2.2%) over the past 25 years in urban and rural areas among Chinese children and it was much higher among boys than girls at each survey point (p<0.01). The increasing trend was significant in all age subgroups (p<0.01). Although the prevalence of obesity continuously increased in boys and girls, the changing pace was more rapid in boys than in girls. PORs of boys versus girls for obesity also increased over time, and the estimates of PORs were higher in urban areas than in rural areas at each survey point. Conclusions The gradually increasing gender disparity in urban and rural areas suggests that the prevalence of obesity and overweight in boys, and especially in urban boys, contributes to a large and growing proportion of obese and overweight children.
Sensation Seeking and Cocaine Dependence in Adults With Reported Childhood ADHD

Objective: To compare measures of sensation seeking in a clinical group of cocaine-dependent (CD) patients with and without a history of probable childhood ADHD and in non-cocaine-dependent (NCD) healthy volunteers. Method: Patients (n = 75; 42 with and 33 without probable childhood ADHD) and comparisons (n = 84) were assessed with the Diagnostic Interview for Genetic Studies, the Wender Utah Rating Scale for childhood ADHD, and the Zuckerman Seeking Sensation Scale. Results: We found significantly higher prevalence rates of probable childhood ADHD in CD versus NCD (p < .001). The mean total scores of sensation seeking were significantly higher in CD versus NCD participants (p < .001) as well as in CD patients with versus those without a probable history of childhood ADHD (p < .001). Conclusion: Our study sets the basis for longitudinal investigation assessing whether the persistence of high level of sensation seeking in adults with childhood ADHD contributes to the transition to cocaine dependence.
IT-enabled value co-creation process for product design

Value co-creation is a modern approach to innovation, in which all stakeholders can play roles in organizational processes; this concept can be studied and implemented in various aspects of management science such as marketing, strategic management, innovation management, etc. This study explores the process of value co-creation in new product design in IT concept. The research method is quantitative; the statistical populations are academic experts and senior managers of the interactive software developers (product) companies. Sampling was continued until theoretical saturation. Interviews data were analyzed by open coding. Findings showed that the process of value co-creation in the organization is a reciprocal process and consists of four stages of thinking, planning, designing, testing and evaluation with the customer, which requires, at each stage, review of the prior steps. The innovation of the article is the presentation of a process and reciprocating model for value co-creation in product design and its components that are introduced at the end.
1.1-kV Vertical GaN p-n Diodes With p-GaN Regrown by Molecular Beam Epitaxy

High-voltage vertical regrown p-n junction diodes on bulk GaN substrates are reported in this letter with molecular-beam-epitaxy regrown p-GaN on metalorganic-chemical-vapor-deposition grown n-GaN drift region. The highest breakdown voltage is measured at 1135 V, and the differential on-resistance is 3.9 mOhm.cm2 at room temperature. The forward I–V show a turn-ON voltage near 3.9 V and an ideality factor of 2.5. Electroluminescence measurement of regrown p-n junctions shows ~30 times reduced emission intensity compared with as-grown p-n junctions, indicating presence of excessive non-radiative recombination centers introduced by the regrowth process. Temperature dependent reverse I–V measurements suggest that variable range hopping inside the depleted regrown p-GaN layer is likely the mechanism of the reverse leakage. This is the first high-voltage vertical regrown p-n junction ever reported in the GaN system.
Using systematic change management to improve emergency patients' access to specialist care: the Big Squeeze

Background Delayed access to specialist care for emergency patients is associated with increased risk of morbidity and mortality, and increased patient anxiety. Objectives (1) To provide timelier access to inpatient and urgent outpatient specialist care for emergency patients. (2) To influence multiple stakeholders to modify their traditional practices and sustain changes. Setting National University Hospital of Singapore, an academic medical centre with 997 beds in Singapore and over 34 sub-specialties. Methods A set of six interventions was implemented to meet three goals: (1) provide timely access to urgent outpatient specialist care requested by the emergency department ED; (2) increase early inpatient discharges (in order to better match timing of emergency admissions); and (3) provide earlier defined care by inpatient specialists at the ED. An eight-step organisational change management plan was implemented to ensure all specialties complied with the changes. Results The goals were achieved. (1) Specialist outpatient appointments given within the timeframe requested by the ED doctor increased from 51.7% to 80.8%. (2) Early discharges increased from 11.9% to 26.6% and were sustained at 27.2%. (3) 84% of eligible patients received earlier defined specialist care at the ED. The change management achieved excellent clinician compliance rates ranging from 84% to 100%. However the median wait for admission remained unchanged. Conclusion The interventions reduced the time for ED patients to access specialist outpatient and inpatient care. The systematic organisational change management approach resulted in sustained compliance.
Hormone Therapy for Relieving Postmenopausal Vasomotor Symptoms: A Systematic Review.

BACKGROUND Menopause is a critical phenomenon in women's life. After cardiac diseases, menopause is the second major cause of living with a disability in 45-60 year old women. The majority of women will experience bothersome vasomotor symptoms (VMS). Menopausal hormone therapy (MHT) is the most effective treatment for these symptoms. The objective of this review is to focus on hormone therapy for relieving postmenopausal vasomotor symptoms. METHODS For this systematic review, we primarily explored 125 papers published about hormone therapy for VMS from 2001 to 2015 by searching with combinations of the keywords in various databases. Among those, 59 papers met the initial search criteria and among them, 9 papers were potentially retrievable and reviewed. All included studies used estrogen formulations in the management of VMS. RESULTS Nine studies met all inclusion criteria. All studies assessed the effects of hormone replacement therapy on VSM. The results showed that low-dose oral and transdermal estrogen in all dose ranges were more likely than placebo to decrease the frequency of VMS. Indeed, the nanostructured formulation was safe and effective in relieving the symptoms of menopause. The mean daily decrease in the number of hot flashes from baseline was found in the studies. CONCLUSION MHT has a complex pattern. Understanding the natural history of VMS, and the risks and benefits of both hormonal therapies, helps to individualize management plans. Low-dose estrogen-based therapies can be the most effective regimens to relieve VMS. These medications can be used by different administration routes and formulations.
Fasting Serum Ghrelin Level is Associated with Metabolic Syndrome in Peritoneal Dialysis Patients

⋄ Background Serum ghrelin levels are elevated in uremic patients. However, no data are available on the relationship between metabolic syndrome and serum ghrelin levels in peritoneal dialysis (PD) patients. ⋄ Methods Metabolic syndrome and its components were defined using diagnostic criteria recommended by the International Diabetes Federation. Fasting serum samples were taken from 30 PD patients. Serum ghrelin levels were measured by using a commercial enzyme-linked immunosorbent assay kit. ⋄ Results Of the 30 PD patients, 53.3% (16/30) had metabolic syndrome. Fasting serum ghrelin corrected inversely with metabolic syndrome among these PDs patients (p = 0.002). By odds ratio (OR) analysis of metabolic syndrome and metabolic syndrome diagnostic criteria, the predictors for metabolic syndrome are fasting glucose [OR: 39.00; 95% confidence interval (CI): 3.80 to 399.85; p < 0.001], triglycerides (OR: 37.50; 95% CI: 3.64 to 386.51; p < 0.001), and waist circumference (OR: 4.20; 95% CI: 1.95 to 9.03; p < 0.001). Univariate linear regression analysis showed that body weight (r = –0.461, p = 0.010), waist circumference (r = –0.390, p = 0.033), and body mass index (r = –0.438, p = 0.016) were negatively correlated with serum ghrelin, and serum high density lipoprotein [HDL (r = 0.626, p < 0.001)] was positively correlated with serum ghrelin. Multivariate forward stepwise linear regression analysis of the significant variables showed that HDL (R2 change = 0.392; p < 0.001) was the independent predictor of serum ghrelin in PD patients and explained 39.2% of the variance. ⋄ Conclusions These results indicate an inverse association between circulating fasting ghrelin and metabolic syndrome in PD patients. Serum HDL was associated with serum ghrelin among PD patients.