Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Na(+)HCO(3)(-) cotransporter NBC1, Na(+)/H(+) exchanger NHE1, and carbonic anhydrase in rabbit duodenal bicarbonate secretion.

BACKGROUND & AIMS HCO(3)(-) supply to the enterocyte is rate limiting for duodenal HCO(3)(-) secretion (J(HCO3-)). This study defines the molecular nature of the major HCO(3)(-) uptake pathways in rabbit duodenocytes and investigates their physiologic significance and regulation during basal and stimulated J(HCO3-). METHODS & RESULTS pH gradient-driven (22)Na(+) uptake into duodenal basolateral membrane vesicles was partly HCO(3)(-) dependent, stilbene sensitive, and therefore mediated by Na(+)HCO(3)(-) cotransport, and partly HCO(3)(-) independent, Hoechst 642 sensitive, and therefore mediated by the Na(+)/H(+) exchanger isoform NHE1. Semiquantitative polymerase chain reaction (PCR) revealed high duodenal expression levels for the NBC1 isoform of the Na(+)HCO(3)(-) cotransporter gene family and NHE1. Cloning and comparison of full-length rabbit with human gastrointestinal and kidney NBC1 subtype revealed a conserved protein kinase A consensus sequence in the cytoplasmic N-terminus of the gastrointestinal NBC1. Inhibition of either Na(+)HCO(3)(-) cotransport or carbonic anhydrase reduced ouabain-sensitive J(HCO3-) in in vitro rabbit duodenal mucosae by approximately 50%, but did not affect 8-Br-cAMP-induced DeltaJ(HCO3-), suggesting cAMP-mediated up-regulation of the alternative pathway. However, inhibition of both Na(+)HCO(3)(-) cotransport and either carbonic anhydrase or NHE1 strongly reduced DeltaJ(HCO3-). CONCLUSIONS NBC1 and NHE1 are the major base importers in rabbit duodenocytes. Na(+)HCO(3)(-) cotransport and CO(2) hydration/Na(+)/H(+) exchange are equally important pathways for duodenal HCO(3)(-) supply and are up-regulated during cAMP-mediated stimulation.
Macrophage IKK&agr; Deficiency Suppresses Akt Phosphorylation, Reduces Cell Survival, and Decreases Early Atherosclerosis

Objective— The I&kgr;B kinase (IKK) is an enzyme complex that initiates the nuclear factor &kgr;B transcription factor cascade, which is important in regulating multiple cellular responses. IKK&agr; is directly associated with 2 major prosurvival pathways, PI3K/Akt and nuclear factor &kgr;B, but its role in cell survival is not clear. Macrophages play critical roles in the pathogenesis of atherosclerosis, yet the impact of IKK&agr; signaling on macrophage survival and atherogenesis remains unclear. Approach and Results— Here, we demonstrate that genetic IKK&agr; deficiency, as well as pharmacological inhibition of IKK, in mouse macrophages significantly reduces Akt S473 phosphorylation, which is accompanied by suppression of mTOR complex 2 signaling. Moreover, IKK&agr; null macrophages treated with lipotoxic palmitic acid exhibited early exhaustion of Akt signaling compared with wild-type cells. This was accompanied by a dramatic decrease in the resistance of IKK&agr;−/− monocytes and macrophages to different proapoptotic stimuli compared with wild-type cells. In vivo, IKK&agr; deficiency increased macrophage apoptosis in atherosclerotic lesions and decreased early atherosclerosis in both female and male low-density lipoprotein receptor (LDLR)−/− mice reconstituted with IKK&agr;−/− hematopoietic cells and fed with the Western diet for 8 weeks compared with control LDLR−/− mice transplanted with wild-type cells. Conclusions— Hematopoietic IKK&agr; deficiency in mouse suppresses Akt signaling, compromising monocyte/macrophage survival and this decreases early atherosclerosis.
Myogenin Induces a Shift of Enzyme Activity from Glycolytic to Oxidative Metabolism in Muscles of Transgenic Mice

Physical training regulates muscle metabolic and contractile properties by altering gene expression. Electrical activity evoked in muscle fiber membrane during physical activity is crucial for such regulation, but the subsequent intracellular pathway is virtually unmapped. Here we investigate the ability of myogenin, a muscle-specific transcription factor strongly regulated by electrical activity, to alter muscle phenotype. Myogenin was overexpressed in transgenic mice using regulatory elements that confer strong expression confined to differentiated post-mitotic fast muscle fibers. In fast muscles from such mice, the activity levels of oxidative mitochondrial enzymes were elevated two- to threefold, whereas levels of glycolytic enzymes were reduced to levels 0.3–0.6 times those found in wild-type mice. Histochemical analysis shows widespread increases in mitochondrial components and glycogen accumulation. The changes in enzyme content were accompanied by a reduction in fiber size, such that many fibers acquired a size typical of oxidative fibers. No change in fiber type-specific myosin heavy chain isoform expression was observed. Changes in metabolic properties without changes in myosins are observed after moderate endurance training in mammals, including humans. Our data suggest that myogenin regulated by electrical activity may mediate effects of physical training on metabolic capacity in muscle.
Genetics of Unilateral and Bilateral Age-Related Macular Degeneration Severity Stages

Background Age-related macular degeneration (AMD) is a common disease causing visual impairment and blindness. Various gene variants are strongly associated with late stage AMD, but little is known about the genetics of early forms of the disease. This study evaluated associations of genetic factors and different AMD stages depending on unilateral and bilateral disease severity. Methods In this case-control study, participants were assigned to nine AMD severity stages based on the characteristics of each eye. 18 single nucleotide polymorphisms (SNPs) were genotyped and attempted to correlate with AMD severity stages by uni- and multivariate logistic regression analyses and trend analyses. Area under the receiver operating characteristic curves (AUC) were calculated. Results Of 3444 individuals 1673 were controls, 379 had early AMD, 333 had intermediate AMD and 989 showed late AMD stages. With increasing severity of disease and bilateralism more SNPs with significant associations were found. Odds ratios, especially for the main risk polymorphisms in ARMS2 (rs10490924) and CFH (rs1061170), gained with increasing disease severity and bilateralism (exemplarily: rs1061170: unilateral early AMD: OR = 1.18; bilateral early AMD: OR = 1.20; unilateral intermediate AMD: OR = 1.28; bilateral intermediate AMD: OR = 1.39, unilateral geographic atrophy (GA): OR = 1.50; bilateral GA: OR = 1.71). Trend analyses showed p<0.0001 for ARMS2 (rs10490924) and for CFH (rs1061170), respectively. AUC of risk models for various AMD severity stages was lowest for unilateral early AMD (AUC = 0.629) and showed higher values in more severely and bilaterally affected individuals being highest for late AMD with GA in one eye and neovascular AMD in the other eye (AUC = 0.957). Conclusion The association of known genetic risk factors with AMD became stronger with increasing disease severity, which also led to an increasing discriminative ability of AMD cases and controls. Genetic predisposition was also associated with the disease severity of the fellow-eye, highlighting the importance of both eyes in AMD patients.
Perplexed Messengers from the Cloud: Automated Security Analysis of Push-Messaging Integrations

In this paper, we report the first large-scale, systematic study on the security qualities of emerging push-messaging services, focusing on their app-side service integrations. We identified a set of security properties different push-messaging services (e.g., Google Cloud Messaging) need to have, and automatically verified them in different integrations using a new technique, called Seminal. Seminal is designed to extract semantic information from a service's sample code, and leverage the information to evaluate the security qualities of the service's SDKs and its integrations within different apps. Using this tool, we studied 30 leading services around the world, and scanned 35,173 apps. Our findings are astonishing: over 20% apps in Google Play and 50% apps in mainstream Chinese app markets are riddled with security-critical loopholes, putting a huge amount of sensitive user data at risk. Also, our research brought to light new types of security flaws never known before, which can be exploited to cause serious confusions among popular apps and services (e.g., Facebook, Skype, Yelp, Baidu Push). Taking advantage of such confusions, the adversary can post his content to the victim's apps in the name of trusted parties and intercept her private messages. The study highlights the serious challenges in securing push-messaging services and an urgent need for improving their security qualities.
Transcranial Alternating Current Stimulation Increases Risk-Taking Behavior in the Balloon Analog Risk Task

The process of evaluating risks and benefits involves a complex neural network that includes the dorsolateral prefrontal cortex (DLPFC). It has been proposed that in conflict and reward situations, theta-band (4–8 Hz) oscillatory activity in the frontal cortex may reflect an electrophysiological mechanism for coordinating neural networks monitoring behavior, as well as facilitating task-specific adaptive changes. The goal of the present study was to investigate the hypothesis that theta-band oscillatory balance between right and left frontal and prefrontal regions, with a predominance role to the right hemisphere (RH), is crucial for regulatory control during decision-making under risk. In order to explore this hypothesis, we used transcranial alternating current stimulation, a novel technique that provides the opportunity to explore the functional role of neuronal oscillatory activities and to establish a causal link between specific oscillations and functional lateralization in risky decision-making situations. For this aim, healthy participants were randomly allocated to one of three stimulation groups (LH stimulation/RH stimulation/Sham stimulation), with active AC stimulation delivered in a frequency-dependent manner (at 6.5 Hz; 1 mA peak-to-peak). During the AC stimulation, participants performed the Balloon Analog Risk Task. This experiment revealed that participants receiving LH stimulation displayed riskier decision-making style compared to sham and RH stimulation groups. However, there was no difference in decision-making behaviors between sham and RH stimulation groups. The current study extends the notion that DLPFC activity is critical for adaptive decision-making in the context of risk-taking and emphasis the role of theta-band oscillatory activity during risky decision-making situations.
Impairment of nonverbal recognition in Alzheimer disease

Objective: To characterize deficits in nonverbal recognition memory and functional brain changes associated with these deficits in Alzheimer disease (AD). Methods: Using O-15 PET, we studied 11 patients with AD and 17 cognitively intact elders during the combined encoding and retrieval periods of a nonverbal recognition task. Both task conditions involved recognition of line drawings of abstract shapes. In both conditions, subjects were first presented a list of shapes as study items, and then a list as test items, containing items from the study list and foils. In the titrated demand condition, the shape study list size (SLS) was adjusted prior to imaging so that each subject performed at approximately 75% recognition accuracy; difficulty during PET scanning in this condition was approximately matched across subjects. A control task was used in which SLS = 1 shape. Results: During performance of the titrated demand condition, SLS averaged 4.55 (±1.86) shapes for patients with AD and 7.53 (±4.81) for healthy elderly subjects (p = 0.031). However, both groups of subjects were closely matched on performance in the titrated demand condition during PET scanning with 72.17% (±7.98%) correct for patients with AD and 72.25% (±7.03%) for elders (p = 0.979). PET results demonstrated that patients with AD showed greater mean differences between the titrated demand condition and control in areas including the left fusiform and inferior frontal regions (Brodmann areas 19 and 45). Conclusions: Relative fusiform and inferior frontal differences may reflect the Alzheimer disease (AD) patients' compensatory engagement of alternate brain regions. The strategy used by patients with AD is likely to be a general mechanism of compensation, rather than task-specific.
Justifying Spam and E-mail Virus Security Investments: A Case Study

Justifying Spam and E-mail Virus Security Investments: A Case Study Hemantha Herath and Tejaswini Herath Abstract: Our paper investigates the problem of justifying security investments concerning spam and email virus using real life data from a midsize North American university. We formulate the spam and email virus security problem as a capital budgeting problem using operating characteristic (ROC) curves in a decision theoretic framework. Prior research has investigated the optimal configuration in a detection system focusing on hacking. In a corporate setting when making the case for information security not only the technology specific detection costs but other costs (capital expenditures, operating costs and opportunity costs) have to be considered. We contribute to the current literature by investigating the spam email and virus problem and demonstrating how theoretical research can really be applied in practice through a real life case study.
Does Fish Ecology Predict Dispersal Across a River Drainage Divide?

Abstract Obligate freshwater taxa are frequently distributed among catchments isolated by marine and terrestrial barriers. Such distributions can arise through vicariant changes in drainage geometry, or dispersal via intermittent freshwater connections. We employed two adjacent rivers in southern New Zealand to test for interdrainage dispersal while controlling for historical drainage geometry, and analyzed four ecologically distinct freshwater-limited fish taxa to assess any relationship with habitat preference. Individuals from the Mararoa and Oreti catchments (n >100 per species) were sequenced for a minimum of 1297 bp of mitochondrial DNA (cytochrome b and control region). Phylogeographic relationships were consistent with ecological expectations of interdrainage dispersal capability, with the two obligate riverine taxa each exhibiting reciprocal monophyly between catchments, whereas the two facultative swamp dwellers revealed paraphyletic relationships, one of which shared a haplotype between catchments. Statistical phylogeography, accommodating taxon-specific mutation rates and the known age of the last major riverine connection between these catchments, rejected complete isolation of populations for one of the swamp dwellers. Therefore, dispersal across a young (145–240 kyr) drainage divide is inferred for one species, and can be predicted to some extent by species ecology. Moreover, our study highlights the importance of historical drainage geometry when assessing the causes of contemporary genetic structuring in freshwater taxa.
Outcome of surgically treated Lisfranc injury: a review of 34 cases.

BACKGROUND We reviewed cases with Lisfranc injuries who presented to our center in order to study the adequacy of the treatment method and their final functional outcome. METHODS This is a retrospective review of 34 cases diagnosed with Lisfranc injuries treated at our center from 2000 to 2006. This review is aimed to determine the demography and functional outcome of all patients with Lisfranc injury treated during this period. RESULTS The injury was classified based on the "Hardcastle and Associates Classification". In our review, we found that the commonest Lisfranc injury was type B2 (41%). These injuries are mostly fixed with K-wires (76.5%). All patients assessed with Bristol Foot Score (BFS) had a good score in all categories, with a total score ranging from 16 to 25. CONCLUSION We concluded that all Lisfranc injuries, whether treated with closed or open fixation methods, demonstrated a good long-term functional outcome.
Cytokines as Biomarkers of Treatment Response to IFNβ in Relapsing-Remitting Multiple Sclerosis

Background. MS patients show a remarkable heterogeneity in their response to disease modifying treatments. Given the need for early treatment initiation and the diversity of available options, a predictive marker that indicates good or poor response to treatment is highly desirable. Objective. To find a biomarker for treatment response to IFNβ among pro- and anti-inflammatory cytokines. Materials and Methods. IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, IL-17A, and TGF-β1 levels were measured in serum and CSF of 43 patients with RR-MS who were followed up for a mean period of 5.3 years. Thirty-five patients received IFNβ treatment and were divided into good responders (GR, n = 19) and poor responders (PR, n = 16). The remaining 8 patients showed a very favorable outcome and remained untreated (noRx). Results. GR had significantly higher serum baseline levels of IL-17A than PR and significantly higher serum levels of IL-17A, IFN-γ, TNF-α, and IL-2 than noRx. PR had significantly higher IFN-γ serum levels than noRx. No significant differences were observed in serum levels of IL-6, IL-4, IL-10, and TGF-β1 or the levels of all cytokines measured in CSF between the 3 groups of patients. Conclusions. Baseline serum levels of IL-17A can be used as a biomarker of IFNβ treatment response.
Analysis and Diagnosis of SLA Violations in a Production SaaS Cloud

A software-as-a-service (SaaS) needs to provide its intended service as per its stated service-level agreements (SLAs). While SLA violations in a SaaS platform have been reported, not much work has been done to empirically characterize failures of SaaS. In this paper, we study SLA violations of a production SaaS platform, diagnose the causes, unearth several critical failure modes, and then, suggest various solution approaches to increase the availability of the platform as perceived by the end user. Our approach combines field failure data analysis (FFDA) and fault injection. Our study is based on 283 days of operational logs of the platform. During this time, the platform received business workload from 42 customers spread over 22 countries. We have first developed a set of home-grown FFDA tools to analyze the log, and second implemented a fault injector to automatically inject several runtime errors in the application code written in . NET/C#, and then, collate the injection results. We summarize our finding as: first, system failures have caused 93% of all SLA violations; second, our fault injector has been able to recreate a few cases of bursts of SLA violations that could not be diagnosed from the logs; and third, the fault injection mechanism could recreate several error propagation paths leading to data corruptions that the failure data analysis could not reveal. Finally, the paper presents some system-level implication of this study and how the joint use of fault injection and log analysis may help in improving the reliability of the measured platform.
Numerical Conservation Properties of H(div)-Conforming Least-Squares Finite Element Methods for the Burgers Equation

Least-squares finite element methods (LSFEMs) for the inviscid Burgers equation are studied. The scalar nonlinear hyperbolic conservation law is reformulated by introducing the flux vector, or the associated flux potential, explicitly as additional dependent variables. This reformulation highlights the smoothness of the flux vector for weak solutions, namely, $\bff(u) \in H({\rm div},\Omega)$. The standard least-squares (LS) finite element (FE) procedure is applied to the reformulated equations using H(div)-conforming FE spaces and a Gauss--Newton nonlinear solution technique. Numerical results are presented for the one-dimensional Burgers equation on adaptively refined space-time domains, indicating that the H(div)-conforming FE methods converge to the entropy weak solution of the conservation law. The H(div)-conforming LSFEMs do not satisfy a discrete exact conservation property in the sense of Lax and Wendroff. However, weak conservation theorems that are analogous to the Lax--Wendroff theorem for conservative finite difference methods are proved for the H(div)-conforming LSFEMs. These results illustrate that discrete exact conservation in the sense of Lax and Wendroff is not a necessary condition for numerical conservation but can be replaced by minimization in a suitable continuous norm.
Migraine, suicidal ideation, and suicide attempts

We examined the risk of suicide attempts and suicidal ideation separately in persons with (1) migraine with aura alone, (2) migraine with aura and coexisting major depression, (3) migraine without aura alone, and (4) migraine without aura and coexisting major depression. Persons with migraine with aura alone and migraine with aura and coexisting major depression had significantly higher rates of suicide attempts and suicidal ideation compared with persons with neither migraine nor major depression. The rates of suicide attempts and suicidal ideation in persons with migraine with aura and major depression were higher than the combined rates in persons with major depression alone and migraine with aura alone. In contrast, migraine without aura was not associated with an increased risk for suicide attempts and suicidal ideation.
Myotomal slow muscle function of rainbow trout Oncorhynchus mykiss during steady swimming.

Strain and activity patterns were determined during slow steady swimming (tailbeat frequency 1.5-2.5 Hz) at three locations on the body in the slow myotomal muscle of rainbow trout Oncorhynchus mykiss using sonomicrometry and electromyography. Strain was independent of tailbeat frequency over the range studied and increased significantly from +/-3.3 % l0 at 0.35BL to +/-6 % at 0.65BL, where l0 is muscle resting length and BL is total body length. Muscle activation occurred significantly later in the strain cycle at 0.35BL (phase shift 59 degrees) than at 0.65BL (30 degrees), and the duration of activity was significantly longer (211 degrees at 0.35BL and 181 degrees at 0.65BL). These results differ from those of previous studies. The results have been used to simulate in vivo activity in isolated muscle preparations using the work loop technique. Preparations from all three locations generated net positive power under in vivo conditions, but the negative power component increased from head to tail. Both kinematically, and in the way its muscle functions to generate hydrodynamic thrust, the rainbow trout appears to be intermediate between anguilliform swimmers such as the eel, which generate thrust along their entire body length, and carangiform fish (e.g. saithe Pollachius virens), which generate thrust primarily at the tail blade.