Miracle-dz/UniFAR-FTUs huggingface dataset:
A New Class of Phosphotransferases Phosphorylated on an Aspartate Residue in an Amino-terminal DXDX(T/V) Motif*

When incubated with their substrates, human phosphomannomutase and l-3-phosphoserine phosphatase are known to form phosphoenzymes with chemical characteristics of an acyl-phosphate. The phosphorylated residue in phosphomannomutase has now been identified by mass spectrometry after reduction of the phosphoenzyme with tritiated borohydride and trypsin digestion. It is the first aspartate in a conserved DVDGT motif. Replacement of either aspartate of this motif by asparagine or glutamate resulted in complete inactivation of the enzyme. The same mutations performed in the DXDST motif of l-3-phosphoserine phosphatase also resulted in complete inactivation of the enzyme, except for the replacement of the second aspartate by glutamate, which reduced the activity by only about 40%. This suggests that the first aspartate of the motif is also the phosphorylated residue inl-3-phosphoserine phosphatase. Data banks contained seven other phosphomutases or phosphatases sharing a similar, totally conserved DXDX(T/V) motif at their amino terminus. One of these (β-phosphoglucomutase) is shown to form a phosphoenzyme with the characteristics of an acyl-phosphate. In conclusion, phosphomannomutase and l-3-phosphoserine phosphatase belong to a new phosphotransferase family with an amino-terminal DXDX(T/V) motif that serves as an intermediate phosphoryl acceptor.
Ecological dynamics of emerging bat virus spillover

Viruses that originate in bats may be the most notorious emerging zoonoses that spill over from wildlife into domestic animals and humans. Understanding how these infections filter through ecological systems to cause disease in humans is of profound importance to public health. Transmission of viruses from bats to humans requires a hierarchy of enabling conditions that connect the distribution of reservoir hosts, viral infection within these hosts, and exposure and susceptibility of recipient hosts. For many emerging bat viruses, spillover also requires viral shedding from bats, and survival of the virus in the environment. Focusing on Hendra virus, but also addressing Nipah virus, Ebola virus, Marburg virus and coronaviruses, we delineate this cross-species spillover dynamic from the within-host processes that drive virus excretion to land-use changes that increase interaction among species. We describe how land-use changes may affect co-occurrence and contact between bats and recipient hosts. Two hypotheses may explain temporal and spatial pulses of virus shedding in bat populations: episodic shedding from persistently infected bats or transient epidemics that occur as virus is transmitted among bat populations. Management of livestock also may affect the probability of exposure and disease. Interventions to decrease the probability of virus spillover can be implemented at multiple levels from targeting the reservoir host to managing recipient host exposure and susceptibility.
Financial Markets and Firm Dynamics

Recent studies have shown that the dynamics of firms (growth, job relocation and exit) are negatively associated with the firm's size. In this paper we analyze whether financial factors are important in generating this negative relation. We develop a model in which, at each point in time, firms are heterogeneous in the amount of equity, and the equity affects their financing decision. The production and investment behavior of small and large firms differs substantially, and the model replicates many of the key features of industry evolution: smaller firms experience faster growth, higher rates of job creation and destruction and lower survival rates. *We have received helpful comments and suggestions from Jeff Campbell, David Chapman, Hal Cole, Tom Cosimano, Joao Gomes, Hugo Hopenhayn, Jose-Victor Rios-Rull, and Harald Uhlig. This research is supported in part by NSF Grant SBR 9617396.
Neuroleptic malignant syndrome

Three cases of the neuroleptic malignant syndrome, which complicated treatment with haloperidol, fluphenazine and, in one case, with several drugs, are described. All three patients recovered and, in two, levodopa appeared to modify the course of the condition. In one patient, myoclonus was present and has persisted. The pharmacological mechanisms involved in this syndrome are discussed.
Cochlear implantation in the world's largest medical device market: Utilization and awareness of cochlear implants in the United States

Abstract Provision of cochlear implants (CIs) for those within the criteria for implantation remains lower in the United States than in some other developed nations. When adults and children are grouped together, the rate of utilization/provision remains low at around 6%. For children, the provision rate is about 50% of those who could benefit from an implant, compared with figures of about 90% for the Flanders part of Belgium, the United Kingdom and other European countries. The probable reasons for this underprovision include: low awareness of the benefits of CIs among the population; low awareness among health-care professionals; the lack of specific referral pathways; some political issues relating to the Deaf Community; and financial issues related to health provision. Such financial issues result in situations which either fail to provide for access to implants or provide too low a level of the necessary funding, especially for low-income individuals covered by public health-care programs such as Medicaid. These issues might be mitigated by adoption and publication of standards for best clinical practices for CI provision, availability of current cost-effectiveness data, and the existence of an organization dedicated to cochlear implantation. Such an organization, the American Cochlear Implant Alliance (ACI Alliance), was recently organized and is described in the paper by Niparko et al. in this Supplement.
Solar cycle modulation of the North Atlantic Oscillation: Implication in the spatial structure of the NAO

The spatial extent of the North Atlantic Oscillation (NAO) is investigated. The results suggest that the spatial structure of the NAO differs significantly according to the phase of the solar cycle. During the solar maximum phases, the NAO has a hemispherical structure extending into the stratosphere, which is similar to the Arctic Oscillation (AO) except for the Pacific sector. However, during the minimum phase, the NAO is confined to the eastern Atlantic sector in the troposphere. Whether or not the NAO is modulated by the solar cycle, these results may shed new light on the controversy of the physical reality of the two modes of variability, the NAO and the AO.
THE INTRODUCTION OF THE EXOTIC Q BIOTYPE OF BEMISIA TABACI FROM THE MEDITERRANEAN REGION INTO CHINA ON ORNAMENTAL CROPS

Abstract The Q biotype of Bemisia tabaci (Gennadius), which has been described from the Mediterranean/North African region, was identified for the first time infesting ornamental crop species in several locations in China. Identification and partial distributions of the exotic B biotype and the recently introduced Q biotype in China were established by using the mitochondrial cytochrome oxidase I gene (mtCOI) as a molecular marker. Collections of B. tabaci were made from representative geographical locations and plant hosts in different provinces of China. MtCOI sequence analysis revealed that collections from Beijing [AY582872, AY589499], Yunnan [AY518189, AY587516], and Henan [AY587514] shared >99.6% sequence identity with the Q biotype from Spain [AY587513, AY562216, AY596950]. The Q type from China shared 98.9-99.4% nucleotide sequence identity with Q-like relatives of B. tabaci described from Israel [AY518191, AY582869]. Phylogenetic analyses indicated that certain B. tabaci populations that are present in China are the Q biotype, and that the Q biotype now in China may have originated from Spain or other nearby locations where the Q biotype has been identified. This is the first report of the introduction of the Q biotype from the Mediterranean region into China. The specific outcomes of the Q biotype as an invasive species in Asia are presently unknown. Certain Q biotype populations from Spain have been reported to exhibit resistant to neonicotinoid insecticides, which are commonly used for controlling this pest and virus vector in ornamental and field crops. Thus, the close monitoring of the Q biotype in China and elsewhere, particularly where commercial plants are grown for export or received for importation, respectively, is essential to avoid the further geographical expansion of the habitat of the Q biotype.
Non-Hematopoietic MLKL Protects Against Salmonella Mucosal Infection by Enhancing Inflammasome Activation

The intestinal mucosal barrier is critical for host defense against pathogens infection. Here, we demonstrate that the mixed lineage kinase-like protein (MLKL), a necroptosis effector, promotes intestinal epithelial barrier function by enhancing inflammasome activation. MLKL−/− mice were more susceptible to Salmonella infection compared with wild-type counterparts, with higher mortality rates, increased body weight loss, exacerbated intestinal inflammation, more bacterial colonization, and severe epithelial barrier disruption. MLKL deficiency promoted early epithelial colonization of Salmonella prior to developing apparent intestinal pathology. Active MLKL was predominantly expressed in crypt epithelial cells, and experiments using bone marrow chimeras found that the protective effects of MLKL were dependent on its expression in non-hematopoietic cells. Intestinal mucosa of MLKL−/− mice had impaired caspase-1 and gasdermin D cleavages and decreased interleukin (IL)-18 release. Moreover, administration of exogenous recombinant IL-18 rescued the phenotype of increased bacterial colonization in MLKL−/− mice. Thus, our results uncover the role of MLKL in enhancing inflammasome activation in intestinal epithelial cells to inhibit early bacterial colonization.
Changes in arm morbidities and health-related quality of life after breast cancer surgery – a five-year follow-up study

Background and purpose. Many breast cancer survivors (BCS) suffer from long-term upper limb morbidities after axillary node dissection. The purpose of this five-year follow-up study was to describe changes in long-term upper limb morbidities, physical activity level, and Health-Related Quality of Life (HRQoL) and to find factors that predict HRQoL five years after surgery. Patients and methods. This study included 204 women aged 55±10 years who had primary breast cancer surgery with axillary node dissection. The subjects were examined for arm volumes and arm lymphedema, arm pain, sensation of heaviness, shoulder function, physical activity level, and HRQoL, prior to surgery, and six months and five years after surgery. The statistical analyses used included ANOVA for repeated measures and multivariate linear regression. Results. ALE (13%), pain (36%), and sensation of heaviness (21%) in the upper limbs were present five years after surgery. ALE was the only morbidity that continued to increase over time. Several dimensions of HRQoL temporarily declined after surgery, but significantly improved in the period from six months to five years after surgery. The significant predictive factors of HRQoL five years after surgery included HRQoL prior to surgery, physical activity level at leisure time (both prior to and at six months after surgery), and duration of sick leave after surgery (in weeks). Conclusions. The overall HRQoL improved significantly from baseline to five years, despite the chronic arm pain and increase in ALE. Three independent predictive factors of HRQoL were identified.
A comparison of actual versus predicted emergency ambulance journey times using generic Geographic Information System software

Study objective The planning of regional emergency medical services is aided by accurate prediction of urgent ambulance journey times, but it is unclear whether it is appropriate to use Geographical Information System (GIS) products designed for general traffic. We examined the accuracy of a commercially available generic GIS package when predicting emergency ambulance journey times under different population and temporal conditions. Methods We undertook a retrospective cohort study of emergency ambulance admissions to three emergency departments (ED) serving differing population distributions in northeast England (urban/suburban/rural). The transport time from scene to ED for all the highest priority dispatches between 1 October 2009 and 30 September 2010 was compared with predictions made by generic GIS software. Results For 10 156 emergency ambulance journeys, the mean prediction discrepancy between actual and predicted journey times across all EDs was an underprediction of 1.6 min (SD 4.9). Underprediction was statistically significant at all population densities, but unlikely to be of clinical significance. Ambulances in urban areas were able to exceed general traffic speed, whereas, the opposite effect was seen in suburban and rural road networks. There were minor effects due to travel outside the busiest traffic times (mean overprediction 0.8 min) and during winter months (mean underprediction 0.4 min). Conclusions It is reasonable to estimate emergency ambulance journey times using generic GIS software, but in order to avoid insufficient regional ambulance provision it would be necessary to make small adjustments because of the tendency towards systematic underprediction.
Experience-Specific Functional Modification of the Dentate Gyrus through Adult Neurogenesis: A Critical Period during an Immature Stage

Neural circuits in the dentate gyrus are continuously modified by adult neurogenesis, whose level is affected by the animal's experience. However, it is not known whether this experience-dependent anatomical modification alters the functional properties of the dentate gyrus. Here, using the expression of immediate early gene products, c-fos and Zif268, as indicators of recently activated neurons, we show that previous exposure to an enriched environment increases the total number of new neurons and the number of new neurons responding to reexposure to the same environment. The increase in the density of activated new neurons occurred specifically in response to exposure to the same environment but not to a different experience. Furthermore, we found that these experience-specific modifications are affected exclusively by previous exposure around the second week after neuronal birth but not later than 3 weeks. Thus, the animal's experience within a critical period during an immature stage of new neurons determines the survival and population response of the new neurons and may affect later neural representation of the experience in the dentate gyrus. This experience-specific functional modification through adult neurogenesis could be a mechanism by which new neurons exert a long-term influence on the function of the dentate gyrus related to learning and memory.
Application of regression-discontinuity analysis in pharmaceutical health services research.

OBJECTIVE To demonstrate how a relatively underused design, regression-discontinuity (RD), can provide robust estimates of intervention effects when stronger designs are impossible to implement. DATA SOURCES/STUDY SETTING Administrative claims from a Mid-Atlantic state Medicaid program were used to evaluate the effectiveness of an educational drug utilization review intervention. STUDY DESIGN Quasi-experimental design. DATA COLLECTION/EXTRACTION METHODS A drug utilization review study was conducted to evaluate a letter intervention to physicians treating Medicaid children with potentially excessive use of short-acting beta(2)-agonist inhalers (SAB). The outcome measure is change in seasonally-adjusted SAB use 5 months pre- and postintervention. To determine if the intervention reduced monthly SAB utilization, results from an RD analysis are compared to findings from a pretest-posttest design using repeated-measure ANOVA. PRINCIPAL FINDINGS Both analyses indicated that the intervention significantly reduced SAB use among the high users. Average monthly SAB use declined by 0.9 canisters per month (p<.001) according to the repeated-measure ANOVA and by 0.2 canisters per month (p<.001) from RD analysis. CONCLUSIONS Regression-discontinuity design is a useful quasi-experimental methodology that has significant advantages in internal validity compared to other pre-post designs when assessing interventions in which subjects' assignment is based on cutoff scores for a critical variable.
Expression analysis for genes involved in arachidonic acid biosynthesis in Mortierella alpina CBS 754.68

The time courses for production of fungal biomass, lipid, phenolic and arachidonic acid (ARA) as well as expression of the genes involved in biosynthesis of ARA and lipid were examined in Mortierella alpina CBS 754.68. A significant increase in the arachidonic acid content in lipids that coincided with reduced levels of lipid was obtained. Reduced gene expression occurred presumably due to the steady reduction of carbon and nitrogen resources. However, these energy resources were inefficiently compensated by the breakdown of the accumulated lipids that in turn, induced up-regulated expression of the candidate genes. The results further indicated that the expression of the GLELO encoding gene is a rate-limiting step in the biosynthesis of ARA in the early growth phase.
Automata Techniques for Epistemic Protocol Synthesis

In this work we aim at applying automata techniques to problems studied in Dynamic Epistemic Logic, such as epistemic planning. To do so, we first remark that repeatedly executing ad infinitum a propositional event model from an initial epistemic model yields a relational structure that can be finitely represented with automata. This correspondence, together with recent results on uniform strategies, allows us to give an alternative decidability proof of the epistemic planning problem for propositional events, with as by-products accurate upper-bounds on its time complexity, and the possibility to synthesize a finite word automaton that describes the set of all solution plans. In fact, using automata techniques enables us to solve a much more general problem, that we introduce and call epistemic protocol synthesis.
Is Vancomycine Still a Choice for Chronic Osteomyelitis Empirical Therapy in Iran?

Background Pyogenic bacteria and especially Staphylococcus aurous (S. aurous) are the most common cause of chronic osteomyelitis. Not only treatment protocol of chronic osteomyelitis occasionally is amiss but also this malady responds to treatment difficultly. Objectives This study investigates antibiotic resistance pattern of S. aurous isolated from Iranian patients who suffer from chronic osteomyelitis by two methods: disk diffusion (Kirby bauyer) and E-test (Epsilometer test) to find Vancomycin susceptibility and MIC (Minimum inhibitory concentration). Patients and Methods One hundred and thirty one patients who suffer from chronic osteomyelitis which have been referred to both governmental and private hospitals at 2010 were tried out for culturing of osteomyelitis site (sites). Antibiotic susceptibility and MIC of isolated bacteria were investigated by Kirby bauyer and E-test respectively. Results Samples were collected from bone (73.4%), surrounding tissue (14.6%) and wound discharge (12%). S. aureus was isolated from 49.6% of the samples. According to disc diffusion, methicillin resistance S. aureus (MRSA) was 75% and Vancomycin resistance S. aurous (VRSA) was 0% and based on MIC, MRSA was 68.5% and VRSA was 0%. According to MIC experiments, maximum sensitivity was against to Vancomycin (90.2%) and ciprofloxacin (54.4%) respectively but based on disc diffusion, maximum sensitivity was against to Vancomycin (97.7%) and ciprofloxacin (43.2%), respectively (P = 0.001). E-test (9.8%) in comparison with Disc diffusion (2.3%) showed higher percent of intermediate susceptibility to Vancomycin (P = 0.017). Conclusions Comparison of antibiograms and MICs showed that Kirby bauyer technique especially for detection of VISA strains is not reliable comparison with E-test. Already VRSA strains have not detected in Iranian chronic osteomyelitis, Thus Vancomycin is the first choice for chronic osteomyelitis empirical therapy in Iran yet.
An Overview of Feature-Oriented Software Development

Feature-oriented software development (FOSD) is a paradigm for the construction, customization, and synthesis of large-scale software systems. In this survey, we give an overview and a personal perspective on the roots of FOSD, connections to other software development paradigms, and recent developments in this field. Our aim is to point to connections between different lines of research and to identify open issues.
Methylenetetrahydrofolate Reductase Genotype Affects Risk of Relapse after Hematopoietic Cell Transplantation for Chronic Myelogenous Leukemia

Purpose: Methylenetetrahydrofolate reductase (MTHFR) directs intracellular folate toward homocysteine metabolism and away from nucleotide synthesis. Two common MTHFR polymorphisms, C677T and A1298C, are associated with reduced enzyme activity. We evaluated the association of these polymorphisms with risk of relapse and bcr-abl mRNA transcript detection among 336 Caucasian patients who underwent allogeneic hematopoietic cell transplantation for chronic myelogenous leukemia. Experimental Design: Data on the transplant course and folate-related exposures were abstracted from medical records. MTHFR C677T and A1298C genotypes were determined using polymerase chain reaction/restriction fragment length polymorphism and TaqMan assays. Qualitative bcr-abl mRNA testing was conducted using a two-step reverse transcription-polymerase chain reaction assay. Cox regression analysis was used to assess the association between MTHFR genotypes and time to relapse and bcr-abl mRNA detection. Results: A statistically significant decreased risk of relapse was observed in patients with the variant A1298C genotype [1298AC, hazard ratio (HR) = 0.48 and 95% confidence interval (CI) = 0.26–0.88; 1298CC, HR = 0.28 and 95% CI = 0.09–0.84; P-trend < 0.01). For the joint C677T/A1298C genotype, variant genotypes were associated with a decreased risk of relapse when compared with the wild-type 677CC/1298AA genotype. This risk was lowest for the 677CC/1298CC genotype (HR, 0.23; 95% CI, 0.08–0.72). MTHFR genotypes were not associated with bcr-abl transcript detection. Conclusions: These findings suggest that individuals with the 677CC/1298AA genotype are at higher risk of relapse after hematopoietic cell transplantation and that the balance of intracellular folate metabolites available for nucleotide synthesis (regulated by the relative activity of the MTHFR enzyme) may affect the progression from bcr-abl positivity to clinical relapse.
Mathematical Modeling of the Relation between Myosin Phosphorylation and Stress Development in Smooth Muscles

In this paper the 4-state latch bridge model proposed by Rembold and Murphy is expanded; first by incorporation of the analytical expression of Ca2+ dependent MLCK activation from the work of Kato et al. and second, by inclusion of the myosin dephosphorylation based on the Michaelis-Menten kinetics. The analysis of the proposed model and the comparison with the original model results as well as with the experimental data is presented. The model is able to predict the steady-state isometric stress and the myosin phosphorylation in dependence on steady cytosolic [Ca2+] as well as the temporal evolution of the system in dependence on the input Ca2+ signal in the form of biphasic transient, whereby our model results are in several aspects in better agreement with experimental observations.