Miracle-dz/UniFAR-FTUs huggingface dataset:
Kinetic Properties of Mutant Human Thymidine Kinase 2 Suggest a Mechanism for Mitochondrial DNA Depletion Myopathy*

Thymidine kinase 2 (TK2) is a mitochondrial (mt) pyrimidine deoxynucleoside salvage enzyme involved in mtDNA precursor synthesis. The full-length human TK2 cDNA was cloned and sequenced. A discrepancy at amino acid 37 within the mt leader sequence in the DNA compared with the determined peptide sequence was found. Two mutations in the human TK2 gene, His-121 to Asn and Ile-212 to Asn, were recently described in patients with severe mtDNA depletion myopathy (Saada, A., Shaag, A., Mandel, H., Nevo, Y., Eriksson, S., and Elpeleg, O. (2001)Nat. Genet. 29, 342–344). The same mutations in TK2 were introduced, and the mutant enzymes, prepared in recombinant form, were shown to have similar subunit structure to wild type TK2. The I212N mutant showed less than 1% activity as compared with wild type TK2 with all deoxynucleosides. The H121N mutant enzyme had normalK m values for thymidine (dThd) and deoxycytidine (dCyd), 6 and 11 μm, respectively, but 2- and 3-fold lower V max values as compared with wild type TK2 and markedly increased K m values for ATP, leading to decreased enzyme efficiency. Competition experiments revealed that dCyd and dThd interacted differently with the H121N mutant as compared with the wild type enzyme. The consequences of the two point mutations of TK2 and the role of TK2 in mt disorders are discussed.
Antigenic and Genomic Diversity of Human Rotavirus VP4 in Two Consecutive Epidemic Seasons in Mexico

ABSTRACT In the present investigation we characterized the antigenic diversity of the VP4 and VP7 proteins in 309 and 261 human rotavirus strains isolated during two consecutive epidemic seasons, respectively, in three different regions of Mexico. G3 was found to be the prevalent VP7 serotype during the first year, being superseded by serotype G1 strains during the second season. To antigenically characterize the VP4 protein of the strains isolated, we used five neutralizing monoclonal antibodies (MAbs) which showed specificity for VP4 serotypes P1A, P1B, and P2 in earlier studies. Eight different patterns of reactivity with these MAbs were found, and the prevalence of three of these patterns varied from one season to the next. The P genotype of a subset of 52 samples was determined by PCR. Among the strains characterized as genotype P[4] and P[8] there were three and five different VP4 MAb reactivity patterns, respectively, indicating that the diversity of neutralization epitopes in VP4 is greater than that previously appreciated by the genomic typing methods.
Mixing characteristics and structure of a turbulent jet diffusion flame stabilized on a bluff-body

Flow dynamics, scalar mixing, and pollutant formation in a turbulent jet diffusion flame stabilized on a bluff-body are investigated using large-eddy simulation. The density weighted filtered equations for the flow and mixing fields are solved using dynamic models for the subfilter quantities. Subfilter combustion processes are modeled by the conditional filtering method. An integrated formulation that considers only axial variation of conditionally filtered quantities is presented. Results show that vortex shedding from the coflow stream and its interaction with the high speed main jet play an important role in the generation of high dissipation layers in the intense mixing region. The mechanisms that generate the high dissipation layers in the intense mixing region are identified. The relatively uniform composition of combustion products in the recirculation zone helps the flame stabilization by maintaining low scalar dissipation rate and high temperature in the vicinity of the stoichiometric surfaces.
Biij Biomedical Imaging and Intervention Journal Critical Limb Ischaemia in a Diabetic Population from an Asian Centre: Angiographic Pattern of Disease and 3-year Limb Salvage Rate with Percutaneous Angioplasty as First Line of Treatment

Purpose: Lower extremity amputation prevention (LEAP) is an ongoing program in our institution aimed at salvaging limbs in patients with critical limb ischemia (CLI). Patients in the LEAP program with reconstructible anatomy on initial Doppler imaging received either bypass surgery or percutaneous transluminal balloon angioplasty (PTA). We present the 3 year limb salvage rate and angiographic disease patterns in 42 consecutive diabetic patients with CLI who received PTA in 2005. Methods and Material: 26 women and 16 men with diabetes between the ages of 45 and 91 years old (mean age, 70.8 years) received PTA in 2005. Presenting symptoms were rest pain (n = 22), pre-existing gangrene (n = 17), non-healing ulcer (n = 16) and cellulitis (n = 2). The aim of the PTA was to achieve straight-line flow from the abdominal aorta down to the patent dorsalis pedis or plantar arch, with limb salvage as the ultimate outcome. Failure of treatment was defined as any amputation above the level of a Syme's amputation or the need for further surgical bypass. Technical success was achieved in 90% (38 out of 42 patients). Results: Limb salvage rates were 93% at 1 month, 87% at 3 months, 82% at 6 months, 78% at 1 year, 69% at 2 years and 66% at 3 years. Mortality was 17% (n = 7) at 3 years. Of the 13 patients with failed therapy, 3 underwent bypass, 9 had amputations and 1 had bypass followed by amputation. Four of the cases required further intervention due to worsening gangrene and infection, while the remaining was due to persistent rest pain. The rest of the 32 patients had no lower limb related issues at the end of 3 years, with improvement of the presenting symptoms. Patterns of treated segments were aortoiliac occlusions (n = 3), pure infrapopliteal disease (n = 3), femoropopliteal with at least 1 good infrapopliteal runoff vessel (n = 14) and combined femoropopliteal and infrapopliteal disease (n = 25). Conclusion: Involvement of infrapopliteal vessels that needs to be treated is common in Asian diabetics. While early limb salvage rates up to 1 year are similar, the 3 year limb salvage rates in Asian diabetics are lower than the western population.
Accuracy of MicroRNA Discovery Pipelines in Non-Model Organisms Using Closely Related Species Genomes

Mapping small reads to genome reference is an essential and more common approach to identify microRNAs (miRNAs) in an organism. Using closely related species genomes as proxy references can facilitate miRNA expression studies in non-model species that their genomes are not available. However, the level of error this introduces is mostly unknown, as this is the result of evolutionary distance between the proxy reference and the species of interest. To evaluate the accuracy of miRNA discovery pipelines in non-model organisms, small RNA library data from a mosquito, Aedes aegypti, were mapped to three well annotated insect genomes as proxy references using miRanalyzer with two strict and loose mapping criteria. In addition, another web-based miRNA discovery pipeline (DSAP) was used as a control for program performance. Using miRanalyzer, more than 80% reduction was observed in the number of mapped reads using strict criterion when proxy genome references were used; however, only 20% reduction was recorded for mapped reads to other species known mature miRNA datasets. Except a few changes in ranking, mapping criteria did not make any significant differences in the profile of the most abundant miRNAs in A. aegypti when its original or a proxy genome was used as reference. However, more variation was observed in miRNA ranking profile when DSAP was used as analysing tool. Overall, the results also suggested that using a proxy reference did not change the most abundant miRNAs’ differential expression profiles when infected or non-infected libraries were compared. However, usage of a proxy reference could provide about 67% of the original outcome from more extremely up- or down-regulated miRNA profiles. Although using closely related species genome incurred some losses in the number of miRNAs, the most abundant miRNAs along with their differential expression profile would be acceptable based on the sensitivity level of each project.
Dual function of an Arabidopsis transcription factor DREB2A in water-stress-responsive and heat-stress-responsive gene expression

Transcription factor DREB2A interacts with a cis-acting dehydration-responsive element (DRE) sequence and activates expression of downstream genes involved in drought- and salt-stress response in Arabidopsis thaliana. Intact DREB2A expression does not activate downstream genes under normal growth conditions. A negative regulatory domain exists in the central region of DREB2A, and deletion of this region transforms DREB2A to a constitutive active form (DREB2A CA). We carried out microarray analysis of transgenic Arabidopsis-overexpressing DREB2A CA and found that the overexpression of DREB2A CA induces not only drought- and salt-responsive genes but also heat-shock (HS)-related genes. Moreover, we found that transient induction of the DREB2A occurs rapidly by HS stress, and that the sGFP-DREB2A protein accumulates in nuclei of HS-stressed cells. DREB2A up-regulated genes were classified into three groups based on their expression patterns: genes induced by HS, genes induced by drought stress, and genes induced by both HS and drought stress. DREB2A up-regulated genes were down-regulated in DREB2A knockout mutants under stress conditions. Thermotolerance was significantly increased in plants overexpressing DREB2A CA and decreased in DREB2A knockout plants. Collectively, these results indicate that DREB2A functions in both water and HS-stress responses.
The adherence of GPs to guidelines for the diagnosis and treatment of lower urinary tract infections in women is poor.

OBJECTIVES To assess the adherence of GPs to evidence-based guidelines for the diagnosis and management of lower urinary tract infection (UTI) in women. METHODS A cross-sectional study was performed from March to July 2009 in primary care offices. Physicians consecutively registered the first six UTI attended during an 8-week period. Age, days with symptoms, episode of infection, associated morbidity, signs and symptoms, diagnostic procedures performed, antibiotic prescription, allergies and referral or not were registered. The type of antibiotic course (short or long) and first-choice treatments were also taken into account. RESULTS Of 176 physicians invited to participate, 110 (62.5%) included 658 women with lower UTI. Urine dipstick was performed in 550 cases (83.6%) and urine culture was requested in 235 women (35.7%), with criteria for culture in 49.6% and without criteria in 32.8%. Antibiotic treatment was administered in 634 cases (96.4%). Short courses were given to 385 women (60.7%) and 75 of those with complicated UTI were treated with long courses (66.4%). First-choice antibiotics were administered as empiric treatment in only 92 women with uncomplicated UTI (17.7%). CONCLUSIONS These results highlight the poor adherence of GPs to the current recommendations of clinical practice guidelines with a high number of inappropriate urine cultures requested and a low utilization of first-choice antibiotics.
Detection of methylation, acetylation and glycosylation of protein residues by monitoring 13C chemical-shift changes: A quantum-chemical study

Post-translational modifications of proteins expand the diversity of the proteome by several orders of magnitude and have a profound effect on several biological processes. Their detection by experimental methods is not free of limitations such as the amount of sample needed or the use of destructive procedures to obtain the sample. Certainly, new approaches are needed and, therefore, we explore here the feasibility of using 13C chemical shifts of different nuclei to detect methylation, acetylation and glycosylation of protein residues by monitoring the deviation of the 13C chemical shifts from the expected (mean) experimental value of the non-modified residue. As a proof-of-concept, we used 13C chemical shifts, computed at the DFT-level of theory, to test this hypothesis. Moreover, as a validation test of this approach, we compare our theoretical computations of the 13Cε chemical-shift values against existing experimental data, obtained from NMR spectroscopy, for methylated and acetylated lysine residues with good agreement within ∼1 ppm. Then, further use of this approach to select the most suitable 13C-nucleus, with which to determine other modifications commonly seen, such as methylation of arginine and glycosylation of serine, asparagine and threonine, shows encouraging results.
Constitutive Acid Sphingomyelinase Enhances Early and Late Macrophage Killing of Salmonella enterica Serovar Typhimurium

ABSTRACT We have identified acid sphingomyelinase (ASM) as an important player in the early and late anti-Salmonella activity of macrophages. A functional ASM participated in the killing activity of macrophages against wild-type Salmonella enterica serovar Typhimurium. The role of ASM in early macrophage killing of Salmonella appears to be linked to an active NADPH phagocyte oxidase enzymatic complex, since the flavoprotein inhibitor diphenyleneiodonium not only blocked a productive respiratory burst but also abrogated the survival advantage of Salmonella in macrophages lacking ASM. Lack of ASM activity also increased the intracellular survival of an isogenic ΔspiC::FRT Salmonella strain deficient in a translocator and effector of the Salmonella pathogenicity island 2 (SPI2) type III secretion system, suggesting that the antimicrobial activity associated with ASM is manifested regardless of the SPI2 status of the bacteria. Constitutively expressed ASM is responsible for the role that this lipid-metabolizing hydrolase plays in the innate host defense of macrophages against Salmonella. Accordingly, the ASM activity and intracellular concentration and composition of ceramide, gangliosides, and neutral sphingolipids did not increase upon Salmonella infection. Salmonella triggered, nonetheless, a significant increase in the secreted fraction of ASM. Collectively, these findings have elucidated a novel role for constitutive ASM in the anti-Salmonella activity of murine macrophages.
Towards a Theory of Software Diversity for Security

Although many have recognized that software monocultures are a major impediment to improving security, it is currently unclear how much and what kind of diversity is needed to counteract this problem. This thesis provides a framework for investigating software diversity in the context of security. We propose a simple model of a software ecosystem using sets of hosts and vulnerabilities represented as a bipartite graph, and we exhibit a few examples of software security problems formulated precisely enough in this model to admit rigorous analysis. We propose software diversity metrics using entropy, illustrate a calculation using real world data, and analyse six popular defence techniques for their effect on inhibiting large scale attacks. We then employ game theory to understand why computer host owners would choose to diversify and propose a slight variation of the popular security game Capture the Flag to determine users’ underlying utility functions.
How Preservice Teachers' Study Abroad Experiences Lead to Changes in Their Perceptions of English Language Learners.

Introduction Teacher attitudes toward English language learners (ELLs) can affect what these students will learn. It has been noted that teachers with personal multicultural experiences are likelier to have a more positive attitude towards teaching ELLs (Youngs and Youngs, 2001). Thus, preparing future teachers is vital. This cannot be solely accomplished vicariously through textbooks or only from an intellectual perspective (Cushner, 2007). Instead, experiences with others are needed.
Research Paper: Auditing the Unified Medical Language System with Semantic Methods

OBJECTIVE The National Library of Medicine's (NLM) Unified Medical Language System (UMLS) includes a Metathesaurus (Meta), which is a compilation of medical terms drawn from over 30 controlled vocabularies, and a Semantic Net, which contains the semantic types used to categorize Meta concepts and the semantic relations to connect them. Meta has been constructed through lexical matching techniques and human review. The purpose of this study was to audit the Meta using semantic techniques to identify possible inconsistencies. METHODS Five different techniques were applied: (1) detection of ambiguity in Meta concepts with two or more semantic types, (2) detection of interchangeable keyword synonyms, (3) detection of redundant pairs of Meta concepts (using lexical matching combined with keyword synonyms), (4) detection of inconsistent parent-child relationships in Meta (based on the semantic type information), and (5) discovery of pairs of semantic types for which relations could be added to the Semantic Net, based on "other" relationships between Meta concepts. RESULTS Of 57,592 concepts with multiple semantic types, 1817 (3.2%) were judged to be ambiguous. Keyword analysis showed 7121 pairs of interchangeable words. Using the keyword pairs, 5031 pairs of potentially redundant concepts were suggested, of which 3274 (65.1%) were judged to actually be redundant. Review of the 100,586 parent-child relationships revealed 544 (0.54%) that were incorrect. Review of the 219,664 "Other" relationships suggested 1299 places in the Semantic Net where relations between pairs of semantic types could be added. CONCLUSION Semantic techniques, alone or in combination, can be used to audit the UMLS to detect inconsistencies that are not detectable through lexical techniques alone. Use of these methods to augment the UMLS maintenance process will lead to improvement in the UMLS.
An exploratory study on cultural variations in oral health attitudes, behaviour and values of freshman (first-year) dental students.

OBJECTIVE To identify similarities and differences in oral health attitudes, behaviour and values among freshman dental students. DESIGN Cross-cultural survey of dental students. SETTING 18 cultural areas. PARTICIPANTS AND METHODS 904 first-year dental students completed the Hiroshima University-Dental Behavioural Inventory (HU-DBI) translated into their own languages. Individual areas were clustered by similarity in responses to the questions. RESULTS The first group displayed an 'occidental-culture orientation' with the exception of Brazil (Cluster 1 comprised: Australia, United Kingdom, Ireland, Belgium and Brazil, Cluster 2: Germany, Italy, Finland and France). The second group displayed an 'oriental-cultural orientation' with the exception of Greece and Israel (Cluster 3 comprised: China and Indonesia, and Cluster 4: Japan, Korea, Israel, Hong Kong, Malaysia, Thailand and Greece). Australia and United Kingdom were the countries that were most alike. Ireland was the 'neighbour' to these countries. Greece and Malaysia had similar patterns of oral health behaviour although geographic conditions are very different. Although it was considered that in Hong Kong, occidental nations have affected the development of education, it remained in the oriental-culture group. Comparison with the data from the occidentals indicates that a higher percentage of the orientals put off going to the dentist until they have toothache (p < 0.001). Only a small proportion of the occidentals (8%) reported a perception of inevitability in having false teeth, whereas 33% of the orientals held this fatalistic belief (p = 0.001). CONCLUSIONS Grouping the countries into key cultural orientations and international clusters yielded plausible results, using the HU-DBI.
Posterior dorsomedial striatum is critical for both selective instrumental and Pavlovian reward learning

The dorsal striatum (DS) has been implicated in instrumental learning but its role in the acquisition of stimulus‐driven behaviour is not clear. To explore the contribution of the DS to both response‐outcome (R‐O) and stimulus‐outcome (S‐O) associative learning, we pharmacologically inactivated subregions (dorsolateral, anterior dorsomedial and posterior dorsomedial) of the DS during acquisition sessions in which subjects acquired two unique, novel R‐O pairs or two unique, novel S‐O pairs. To test whether specific R‐O or S‐O associations were learned under inactivation, rats were tested following selective‐satiety devaluation of one outcome under drug‐free conditions. In the instrumental task, control rats and rats with dorsolateral striatum (DLS) inactivation during learning responded less on the lever that had earned the devalued outcome than on the alternative lever at test, indicating that the DLS is not critical for the formation of R‐O associations. In contrast, rats with inactivation of the medial DS (DMS) (either anterior or posterior) during learning responded indiscriminately, suggesting failure to acquire the novel R‐O associations. In the Pavlovian task, both controls and rats with anterior DMS inactivation during learning responded less in the presence of the stimulus predicting the devalued outcome, whereas rats with DLS or posterior DMS inactivation during learning responded equally to the stimuli, indicating that they had not acquired the novel S‐O associations. These data confirm that the DLS and anterior region DMS mediate different aspects of reward‐related learning, and suggest that the posterior DMS may mediate a function common to both forms of learning (R‐O and S‐O). Finally, we demonstrate that both S‐O and R‐O associations are required for selective Pavlovian‐instrumental transfer.
Eating when bored: revision of the emotional eating scale with a focus on boredom.

OBJECTIVE The current study explored whether eating when bored is a distinct construct from other negative emotions by revising the emotional eating scale (EES) to include a separate boredom factor. Additionally, the relative endorsement of eating when bored compared to eating in response to other negative emotions was examined. METHOD A convenience sample of 139 undergraduates completed open-ended questions regarding their behaviors when experiencing different levels of emotions. Participants were then given the 25-item EES with 6 additional items designed to measure boredom. RESULTS On the open-ended items, participants more often reported eating in response to boredom than the other emotions. Exploratory factor analysis showed that boredom is a separate construct from other negative emotions. Additionally, the most frequently endorsed item on the EES was "eating when bored". CONCLUSIONS These results suggest that boredom is an important construct, and that it should be considered a separate dimension of emotional eating.
Towards a pervasive computing enabled modeling environment for integrated coevolving energy systems

We present elements of a pervasive computing enabled modeling environment for integrated national energy systems (CI-MINES) to support policy and decision making as it pertains to co-evolving socio-energy systems. Decision support systems built using CI-MINES will provide public policy makers as well as private stakeholders entirely new ways to design and architect next-generation energy systems. When complete, CI-MINES can be used to evaluate the relative merits of competing conceptual architectures for interactive energy grids and markets before substantial investment is made in realizing them. It will also help evaluate new ways to invest in renewable energy sources and assess the reliability and security of the emerging grid architectures. CI-MINES is based on recent computational advances for modeling extremely large, complex, multi-scale socio-technical systems.