Miracle-dz/UniFAR-FTUs huggingface dataset:
Escherichia coli mazEF-Mediated Cell Death Is Triggered by Various Stressful Conditions

ABSTRACT mazEF is an Escherichia coli suicide module specific for a stable toxin and a labile antitoxin. Inhibiting mazEF expression appeared to activate the module to cause cell death. Here we show that several stressful conditions, including high temperatures, DNA damage, and oxidative stress, also induce mazEF-mediated cell death. We also show that this process takes place only during logarithmic growth and requires an intact relA gene.
BugBox: A Vulnerability Corpus for PHP Web Applications

Web applications are a rich source of vulnerabilities due to their high exposure, diversity, and popularity. Accordingly, web application vulnerabilities are useful subjects for empirical security research. Although some information on vulnerabilities is publicly available, there are no publicly available datasets that couple vulnerabilities with their source code, metadata, and exploits through an executable test environment. We describe BugBox, a corpus and exploit simulation environment for PHP web application vulnerabilities. BugBox provides a test environment and a packaging mechanism that allows for the distribution and sharing of vulnerability data. The goal is to facilitate empirical vulnerability studies, security tool evaluation, and security metrics research. In addition, the framework promotes developer education by demonstrating exploits and providing a sandbox where they can be run safely. BugBox and its modules are opensource and available online, and new modules may be contributed by community members.
A characterization of locally testable affine-invariant properties via decomposition theorems

Let P be a property of function Fnp → {0, 1} for a fixed prime p. An algorithm is called a tester for P if, given a query access to the input function f, with high probability, it accepts when f satisfies P and rejects when f is "far" from satisfying P. In this paper, we give a characterization of affine-invariant properties that are (two-sided error) testable with a constant number of queries. The characterization is stated in terms of decomposition theorems, which roughly claim that any function can be decomposed into a structured part that is a function of a constant number of polynomials, and a pseudo-random part whose Gowers norm is small. We first give an algorithm that tests whether the structured part of the input function has a specific form. Then we show that an affine-invariant property is testable with a constant number of queries if and only if it can be reduced to the problem of testing whether the structured part of the input function is close to one of a constant number of candidates.
Hypolipidemia in Patients with Amyotrophic Lateral Sclerosis: A Possible Gender Difference?

Background and Purpose We compared the levels of serum lipid, protein, and glucose between patients with amyotrophic lateral sclerosis (ALS) and healthy controls. Methods The serum levels of lipids [including triglycerides, cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL)], protein, and glucose of 95 patients with ALS (60 men) were compared with those of 99 age- and sex-matched healthy controls (64 men). Both groups had normal dietary intakes. Results Total cholesterol (p=0.004), LDL (p=0.040), triglyceride (p=0.025), and protein (p=0.010) levels, and LDL/HDL ratios (p<0.001) in men with ALS were significantly lower than those in their control counterparts. There were no such significant differences in these parameters between female patients with ALS and female controls. Conclusions The serum levels of lipid and protein were significantly lower in male patients with ALS than in the male controls. Since we controlled for the confounding effects of dietary intake, hypolipidemia in ALS might be associated with the pathophysiology of the disease rather than being the result of the decreased dietary intake in ALS patients. Metabolic demand might increase in ALS, and it may be affected by gender.
Association of the rs1346044 Polymorphism of the Werner Syndrome Gene RECQL2 with Increased Risk and Premature Onset of Breast Cancer

Like other RECQ helicases, WRN/RECQL2 plays a crucial role in DNA replication and the maintenance of genome stability. Inactivating mutations in RECQL2 lead to Werner syndrome, a rare autosomal disease associated with premature aging and an increased susceptibility to multiple cancer types. We analyzed the association of two coding single-nucleotide polymorphisms in WRN, Cys1367Arg (rs1346044), and Arg834Cys (rs3087425), with the risk, age at onset, and clinical subclasses of breast cancer in a hospital-based case-control study of an Austrian population of 272 breast cancer patients and 254 controls. Here we report that the rare homozygous CC genotype of rs1346044 was associated with an approximately two-fold elevated breast cancer risk. Moreover, patients with the CC genotype exhibited a significantly increased risk of developing breast cancer under the age of 55 in both recessive and log-additive genetic models. CC patients developed breast cancer at a mean age of 55.2 ± 13.3 years and TT patients at 60.2 ± 14.7 years. Consistently, the risk of breast cancer was increased in pre-menopausal patients in the recessive model. These findings suggest that the CC genotype of WRN rs1346044 may contribute to an increased risk and a premature onset of breast cancer.
The C‐terminal portion of RAG2 protects against transposition in vitro

The assembly of antigen receptor genes by V(D)J recombination is initiated by the RAG1/RAG2 protein complex, which introduces double‐strand breaks between recombination signal sequences and their coding DNA. Truncated forms of RAG1 and RAG2 are functional in vivo and have been used to study V(D)J cleavage, hybrid joint formation and transposition in vitro. Here we have characterized the activities of the full‐length proteins. Unlike core RAG2, which supports robust transposition in vitro, full‐length RAG2 blocks transposition of signal ends following V(D)J cleavage. Thus, one role of this non‐catalytic domain may be to prevent transposition in developing lymphoid cells. Although full‐length RAG1 and RAG2 proteins rarely form hybrid joints in vivo in the absence of non‐homologous end‐joining factors, we show that the full‐length proteins alone can catalyze this reaction in vitro.
Identification and Characterization of Amlexanox as a G Protein-Coupled Receptor Kinase 5 Inhibitor

G protein-coupled receptor kinases (GRKs) have been implicated in human diseases ranging from heart failure to diabetes. Previous studies have identified several compounds that selectively inhibit GRK2, such as paroxetine and balanol. Far fewer selective inhibitors have been reported for GRK5, a target for the treatment of cardiac hypertrophy, and the mechanism of action of reported compounds is unknown. To identify novel scaffolds that selectively inhibit GRK5, a differential scanning fluorometry screen was used to probe a library of 4480 compounds. The best hit was amlexanox, an FDA-approved anti-inflammatory, anti-allergic immunomodulator. The crystal structure of amlexanox in complex with GRK1 demonstrates that its tricyclic aromatic ring system forms ATP-like interactions with the hinge of the kinase domain, which is likely similar to how this drug binds to IκB kinase ε (IKKε), another kinase known to be inhibited by this compound. Amlexanox was also able to inhibit myocyte enhancer factor 2 transcriptional activity in neonatal rat ventricular myocytes in a manner consistent with GRK5 inhibition. The GRK1 amlexanox structure thus serves as a springboard for the rational design of inhibitors with improved potency and selectivity for GRK5 and IKKε.
ALS diagnostic criteria of El Escorial Revisited: do they meet the needs of clinicians as well as researchers?

The El Escorial criteria for diagnosis of amyotrophic lateral sclerosis (ALS) have been in use for almost a decade. A revised set of criteria, meant to supersede the original set, was developed at a 1998 World Federation of Neurology (WFN) ALS meeting at Airlie House in Warrenton, Virginia, USA. This revised document, nicknamed El Escorial Revisited, has been published on the WFN-ALS website. El Escorial has proven useful in standardizing diagnostic criteria for entry into research trials and it is expected that El Escorial Revisited will help to liberalize such entry requirements. However, general neurologists and neuromuscular clinicians have found El Escorial to be unwieldy and generally unhelpful in achieving an earlier, accurate diagnosis of ALS. The El Escorial Revisited document is a step toward lessening these problems, but more ‘user-friendly’ criteria may be necessary for clinicians and those not conducting research. Such ALS criteria would improve categorization of ALS patients, would allow clinicians more latitude in beginning ALS treatment, and would educate practitioners to differentiate ALS from other motor neuron and non-motor neuron diseases. Intensive education of physicians will help improve earlier patient referral and accurate ALS diagnosis. There remains a group of ‘difficult cases’ that will continue to challenge the neuromuscular specialist. Earlier diagnosis in this latter group will require significant advances in the fields of electrodiagnosis, neuroimaging, immunobiochemistry, and neurogenetics. (ALS 2000; 1 (suppl 1): S57–S60).
Mechanism for CARMIL Protein Inhibition of Heterodimeric Actin-capping Protein*

Background: CARMIL inhibits the actin capping action of heterodimeric capping protein. Results: Results argue against a steric blocking model and provide evidence for an allosteric mechanism. Conclusion: The conformations of the actin- and CARMIL-binding sites on capping protein are linked. Significance: Control of capping actin barbed ends is critical for cell motility. Capping protein (CP) controls the polymerization of actin filaments by capping their barbed ends. In lamellipodia, CP dissociates from the actin cytoskeleton rapidly, suggesting the possible existence of an uncapping factor, for which the protein CARMIL (capping protein, Arp2/3 and myosin-I linker) is a candidate. CARMIL binds to CP via two motifs. One, the CP interaction (CPI) motif, is found in a number of unrelated proteins; the other motif is unique to CARMILs, the CARMIL-specific interaction motif. A 115-aa CARMIL fragment of CARMIL with both motifs, termed the CP-binding region (CBR), binds to CP with high affinity, inhibits capping, and causes uncapping. We wanted to understand the structural basis for this function. We used a collection of mutants affecting the actin-binding surface of CP to test the possibility of a steric-blocking model, which remained open because a region of CBR was not resolved in the CBR/CP co-crystal structure. The CP actin-binding mutants bound CBR normally. In addition, a CBR mutant with all residues of the unresolved region changed showed nearly normal binding to CP. Having ruled out a steric blocking model, we tested an allosteric model with molecular dynamics. We found that CBR binding induces changes in the conformation of the actin-binding surface of CP. In addition, ∼30-aa truncations on the actin-binding surface of CP decreased the affinity of CBR for CP. Thus, CARMIL promotes uncapping by binding to a freely accessible site on CP bound to a filament barbed end and inducing a change in the conformation of the actin-binding surface of CP.
A New Look at Framing Effects: Distribution of Effect Sizes, Individual Differences, and Independence of Types of Effects

Abstract Levin, Schneider, and Gaeth (1998) identified three distinct types of framing effects in the literature: attribute framing effects, goal framing effects, risky choice framing effects. While most previous framing studies used between-subjects manipulations of frame, the present study used two sessions, spaced one week apart, to give each of 102 participants both framing conditions and all three types of framing. Using the difference between the score for the positive framing condition and the negative framing condition as the unit of analysis for each type of framing effect, the following were found: (1) reliable framing effects for attribute framing and risky choice framing, but not for goal framing; (2) distributions of individual framing effects showing that the aggregate-level effects were representative of individuals even though some individuals showed no framing effects; (3) no significant interdependencies between the three categories of framing effects; (4) individual differences in reaction to the task scenarios related to various of the “Big Five” personality traits as well as the Faith in Intuition scale. The use of within-subject designs to assess individual differences in decision-making phenomena such as framing effects and other biases and heuristics is recommended for future research.
Intrinsic excitability of CA1 pyramidal neurones from the rat dorsal and ventral hippocampus

• The dorsal (DHC) and ventral (VHC) regions of the rodent hippocampus are anatomically, behaviourally, and biochemically distinct. • The intrinsic electrophysiological properties of CA1 pyramidal neurones from these regions however, have not been fully characterized. • In this study, we found that VHC neurones were intrinsically more excitable than DHC neurones. • The difference in intrinsic excitability stems from a higher input resistance (Rin) and more depolarized resting membrane potential observed in the soma and apical dendrite of VHC neurones. • Morphological analysis of reconstructed neurones revealed significantly more dendritic surface area for DHC than VHC neurones. • Simulations using morphologically realistic passive models indicate that morphological differences could, in principle, underlie somatic but not dendritic differences in Rin.
Lower-Body Torque and Power Declines Across Six Decades in Three Hundred Fifty-Seven Men and Women: A Cross-sectional Study With Normative Values

Abstract Leyva, A, Balachandran, A, and Signorile, JF. Lower-body torque and power declines across six decades in three hundred fifty-seven men and women: a cross-sectional study with normative values. J Strength Cond Res 30(1): 141–158, 2016—This study presents age-specific and gender-specific patterns and normative values for lower-body isokinetic performance in 195 women and 162 men, 18–80 years of age, using data collected from 1991 to 2004. Peak torque (PT) and average power (AP) during knee extension (KE), knee flexion (KF), ankle plantar flexion, and dorsiflexion (DF) at 1.05, 3.14, and 5.24 rad·s−1 were compared by decade. Knee extension and KF at all speeds showed a significant main effect by age group (G). Men's KEPT and KEAP at 60 and 70 G were significantly different than 20, 30, and 40 G at all speeds. Additionally, 50 G differed from all other groups. For women, 50, 60, and 70 G KEPT and KEAP at 5.24 rad·s−1 differed significantly from all other age groups. Men's KFPT and KFAP showed no differences among 20, 30, and 40 G, whereas 50 G differed from all groups except 60 G. For KFPT and KFAP, women 20 and 30 G differed from other age groups at all testing speeds. Plantar flexion and DF performance declines were speed specific mainly occurring at 3.14 rad·s−1. The results reflect declines in strength and power beginning during the fifth decade in men, and earlier in women. The study also provides normative values, which may be used to evaluate neuromuscular performances by gender across decades of life.
How active are we? Levels of routine physical activity in children and adults

The accurate measurement of physical activity is fraught with problems in adults, but more especially in children because they have more complex and multi-dimensional activity patterns. In addition, the results of different studies are often difficult to interpret and compare, because of the diversity of methodological approaches, differences in data analysis and reporting, and the adoption of varying definitions of what constitutes an appropriate level of activity. Furthermore, inactivity is seldom quantified directly. Although there exists an extensive literature documenting the health benefits of regular physical activity in adults, activity-health relationships in children are not clear-cut. Current recommendations reinforce the concept of health-related activity, accumulating 30 min moderate-intensity exercise on at least 5 d/week (adults) and 1 h moderate-intensity exercise/d (children). Evidence suggests a high prevalence of inactivity in adults, but whether or not inactivity is increasing cannot be assessed currently. Similarly, no definite conclusions are justified about either the levels of physical activity of children, or whether these are sufficient to maintain and promote health. Data to support the belief that activity levels in childhood track into adulthood are weak. Inactivity is associated with an increased risk of weight gain and obesity, but causality remains to be established. In children there is strong evidence to demonstrate a dose-response relationship between the prevalence and incidence of obesity and time spent viewing television. Future research should focus on refining methodology for physical activity assessment to make it more sensitive to the different dimensions and contexts of activity in different age-groups.
Nonmedical Use of Prescription Stimulants and Analgesics: Associations with Social and Academic Behaviors among College Students

Nonmedical use of prescription stimulants and analgesics was assessed from personal interviews with a stratified random sample of 1,253 first-year college students ages 17 to 20 attending a large public university (86% response rate). Lifetime and past-year prevalence of nonmedical use of stimulants, analgesics, or both was 19.6%wt and 15.6%wt, respectively. Nonmedical users had significantly lower grade point averages (GPAs) in high school as compared with nonusers; in college they skipped classes more often, spent more time socializing, and spent less time studying. For example, nonmedical users of both stimulants and analgesics skipped 21 % of their college classes whereas nonusers skipped 9%. Controlling for high school GPA and other factors, past-year nonmedical use independently predicted lower college GPA by the end of the first year of college; this effect was partially mediated by skipping more classes. Nonmedical users of prescription drugs comprise a high-risk group for academic problems in college.
From expert generalists to ambiguity masters: using ambiguity tolerance theory to redefine the practice of rural nurses.

AIMS AND OBJECTIVES To redefine the practice of rural nurses and describe a model that conceptualises the capabilities and characteristics required in the rural environment. BACKGROUND The way in which the practice of rural nurses has been conceptualised is problematic. Definitions of rural nursing have been identified primarily through the functional context of rural health service delivery. The expert generalist term has provided a foundation theory for rural nurses with understandings informed by the scope of practice needed to meet service delivery requirements. However, authors exploring intrinsic characteristics of rural nurses have challenged this definition, as it does not adequately address the deeper, intangible complexities of practice required in the rural context. Despite this discourse, an alternative way to articulate the distinctive nature of rural nursing practice has eluded authors in Australia and internationally. DESIGN A theoretical paper based on primary research. METHODS The development of the model was informed by the findings of a study that explored the nursing practice of managing telephone presentations in rural health services in Victoria, Australia. The study involved policy review from State and Federal governments, nursing and medical professional bodies, and five rural health services; semi-structured interviews with eight Directors of Nursing, seven registered nurses and focus group interviews with eight registered nurses. RESULTS An ambiguity tolerance model drawn from corporate global entrepreneurship theory was adapted to explain the findings of the study. The adapted model presents capabilities and characteristics used by nurses to successfully manage the ambiguity of providing care in the rural context. CONCLUSIONS Redefining the practice of rural nurses, through an adapted theory of ambiguity tolerance, highlights nursing characteristics and capabilities required in the rural context. This perspective offers new ways of thinking about the work of rural nurses, rural nurse policy, education, recruitment, retention and clinical governance. RELEVANCE TO CLINICAL PRACTICE A greater understanding of rural nurse practice will assist in achieving positive care outcomes in an environment with competing stakeholder needs, and limited resources and options for care.
Effect of substrate and cellulase concentration on simultaneous saccharification and fermentation of steam-pretreated softwood for ethanol production.

Economic optimization of the production of ethanol by simultaneous saccharification and fermentation (SSF) requires knowledge about the influence of substrate and enzyme concentration on yield and productivity. Although SSF has been investigated extensively, the optimal conditions for SSF of softwoods have yet not been determined. In this study, SO2-impregnated and steam-pretreated spruce was used as substrate for the production of ethanol by SSF. Commercial enzymes were used in combination with the yeast Saccharomyces cerevisiae. The effects of the concentration of substrate (2% to 10% w/w) and of cellulases (5 to 32 FPU/g cellulose) were investigated. SSF was found to be sensitive to contamination because lactic acid was produced. The ethanol yield increased with increasing cellulase loading. The highest ethanol yield, 68% of the theoretical based on the glucose and mannose present in the original wood, was obtained at 5% substrate concentration. This yield corresponds to 82% of the theoretical based on the cellulose and soluble glucose and mannose present at the start of SSF. A higher substrate concentration caused inefficient fermentation, whereas a lower substrate concentration, 2%, resulted in increased formation of lactic acid, which lowered the yield. Compared with separate hydrolysis and fermentation, SSF gave a higher yield and doubled the productivity.
An aroD Ochre Mutation Results in a Staphylococcus aureus Small Colony Variant That Can Undergo Phenotypic Switching via Two Alternative Mechanisms

Staphylococcus aureus can undergo phenotypic switching between a normal colony phenotype (NCP) and a small colony variant (SCV). The SCV phenotype confers increased antibiotic resistance and the capacity to persist within human tissues and cells, and because these cells can revert back to the NCP they cause chronic and/or recurrent infections that are very difficult to treat. A complete picture of the genetic events that can lead to phenotypic switching in S. aureus is currently lacking. We describe the selection of an SCV with a previously unreported genetic alteration leading to an ochre mutation of aroD. In addition to the known mechanisms of phenotypic switching between the SCV and the NCP we describe a previously unreported mechanism involving tRNA ochre suppressors arising. The ochre suppressor strains had wild-type growth rates and restored antibiotic sensitivity, similar to the wild-type strain. However, whilst they had increased virulence compared to the SCV parent strain, their virulence was not restored to that of the NCP parental strain. These findings establish that phenotypic switching between the NCP and SCV states can give rise to strains with different pathogenic potential.