Miracle-dz/UniFAR-FTUs huggingface dataset:
Banting lecture 1988. Role of insulin resistance in human disease.

Resistance to insulin-stimulated glucose uptake is present in the majority of patients with impaired glucose tolerance (IGT) or non-insulin-dependent diabetes mellitus (NIDDM) and in approximately 25% of nonobese individuals with normal oral glucose tolerance. In these conditions, deterioration of glucose tolerance can only be prevented if the beta-cell is able to increase its insulin secretory response and maintain a state of chronic hyperinsulinemia. When this goal cannot be achieved, gross decompensation of glucose homeostasis occurs. The relationship between insulin resistance, plasma insulin level, and glucose intolerance is mediated to a significant degree by changes in ambient plasma free-fatty acid (FFA) concentration. Patients with NIDDM are also resistant to insulin suppression of plasma FFA concentration, but plasma FFA concentrations can be reduced by relatively small increments in insulin concentration. Consequently, elevations of circulating plasma FFA concentration can be prevented if large amounts of insulin can be secreted. If hyperinsulinemia cannot be maintained, plasma FFA concentration will not be suppressed normally, and the resulting increase in plasma FFA concentration will lead to increased hepatic glucose production. Because these events take place in individuals who are quite resistant to insulin-stimulated glucose uptake, it is apparent that even small increases in hepatic glucose production are likely to lead to significant fasting hyperglycemia under these conditions. Although hyperinsulinemia may prevent frank decompensation of glucose homeostasis in insulin-resistant individuals, this compensatory response of the endocrine pancreas is not without its price. Patients with hypertension, treated or untreated, are insulin resistant, hyperglycemic, and hyperinsulinemic. In addition, a direct relationship between plasma insulin concentration and blood pressure has been noted. Hypertension can also be produced in normal rats when they are fed a fructose-enriched diet, an intervention that also leads to the development of insulin resistance and hyperinsulinemia. The development of hypertension in normal rats by an experimental manipulation known to induce insulin resistance and hyperinsulinemia provides further support for the view that the relationship between the three variables may be a causal one. (ABSTRACT TRUNCATED AT 400 WORDS)
Distinct Mechanism of Cysteine Oxidation-Dependent Activation and Cold Sensitization of Human Transient Receptor Potential Ankyrin 1 Channel by High and Low Oxaliplatin

Oxaliplatin, a third-generation platinum-based chemotherapeutic agent, displays unique acute peripheral neuropathy triggered or enhanced by cold, and accumulating evidence suggests that transient receptor potential ankyrin 1 (TRPA1) is responsible. TRPA1 is activated by oxaliplatin via a glutathione-sensitive mechanism. However, oxaliplatin interrupts hydroxylation of a proline residue located in the N-terminal region of TRPA1 via inhibition of prolyl hydroxylase (PHD), which causes sensitization of TRPA1 to reactive oxygen species (ROS). Furthermore, PHD inhibition endows cold-insensitive human TRPA1 (hTRPA1) with ROS-dependent cold sensitivity. Since cysteine oxidation and proline hydroxylation regulate its activity, their association with oxaliplatin-induced TRPA1 activation and acquirement of cold sensitivity were investigated in the present study. A high concentration of oxaliplatin (1 mM) induced outward-rectifier whole-cell currents and increased the intracellular Ca2+ concentration in hTRPA1-expressing HEK293 cells, but did not increase the probability of hTRPA1 channel opening in the inside-out configuration. Oxaliplatin also induced the rapid generation of hydrogen peroxide, and the resultant Ca2+ influx was prevented in the presence of glutathione and in cysteine-mutated hTRPA1 (Cys641Ser)-expressing cells, whereas proline-mutated hTRPA1 (Pro394Ala)-expressing cells showed similar whole-cell currents and Ca2+ influx. By contrast, a lower concentration of oxaliplatin (100 μM) did not increase the intracellular Ca2+ concentration but did confer cold sensitivity on hTRPA1-expressing cells, and this was inhibited by PHD2 co-overexpression. Cold sensitivity was abolished by the mitochondria-targeting ROS scavenger mitoTEMPO and was minimal in cysteine-mutated hTRPA1 (Cys641Ser or Cys665Ser)-expressing cells. Thus, high oxaliplatin evokes ROS-mediated cysteine oxidation-dependent hTRPA1 activation independent of PHD activity, while a lower concentration induces cold-induced cysteine oxidation-dependent opening of hTRPA1 via PHD inhibition.
Unified fusion rules for multisensor multihypothesis network decision systems

In this paper, we present a fusion rule for distributed multihypothesis decision systems where communication patterns among sensors are given and the fusion center may also observe data. It is a specific form of the most general fusion rule, independent of statistical characteristics of observations and decision criteria, and thus, is called a unified fusion rule of the decision system. To achieve globally optimum performance, only sensor rules need to be optimized under the proposed fusion rule for the given conditional distributions of observations and decision criterion. Following this idea, we present a systematic and efficient scheme for generating optimum sensor rules and hence, optimum fusion rules, which reduce computation tremendously as compared with the commonly used exhaustive search. Numerical examples are given, which support the above results and provide a guideline on how to assign sensors to nodes in a signal detection networks with a given communication pattern. In addition, performance of parallel and tandem networks is compared.
Psychobiological models of adolescent risk: implications for prevention and intervention.

Psychobiological models of risk have much to contribute to the prevention of and intervention with risky behavior among adolescents. Emerging research is beginning to provide better information about mechanisms underlying individual differences in risky behavior (e.g., differences in self-regulation) and providing insight into unique vulnerabilities that occur during adolescence (e.g., increases in reward seeking). This work suggests ways in which prevention programming can be designed to be sensitive to both individual differences and developmental timing. Psychobiological models of risk also have practical implications for the manner and methods of conducting prevention and intervention work. Future work in both the etiology and prevention of risky behavior can benefit from ongoing dialogue and has the potential to result in a more sophisticated understanding of the mechanisms of change related to risky behavior.
Incidence of Parasitic Diarrhea in Patients with Common Variable Immune Deficiency.

OBJECTIVE Parasites might cause atypical and severe infections in immunocompromised hosts. The prevalence of diarrhea among common variable immune deficiency (CVID) syndrome patients varies between 20% and 94%, which indicates that diarrhea and gastrointestinal system (GIS) complaints could be the second leading cause of morbidity in CVID patients after respiratory tract infections. This study aimed to assess the prevalence of intestinal parasites in CVID patients with GIS complaints and diarrhea. METHODS In this study, all cases followed up in the Immunology and Allergy Clinic of Ege University School of Medicine from July 2008 to August 2015 with the diagnosis of CVID were reviewed retrospectively. The stool samples of patients with diarrhea were identified using direct microscopy of native (0.09% NaCl) and Lugol's iodine preparations followed by formol-ethyl acetate concentration to apply modified Kinyoun, trichrome, acid-fast trichrome, and modified trichrome stains for the presence of intestinal parasites. RESULTS Overall, 26 of 37 CVID patients had diarrhea; white and red blood cells (WBCs and RBCs, respectively) were identified in 11 and 10 of these 26 samples, respectively. Intestinal parasites were found to be present in 7 of the 11 patients with WBCs and 3 of the 10 patients with RBCs. With the addition of patients who neither had WBCs nor RBCs in their stool, a parasitic agent was detected in 13 (50%) of the 26 patients with diarrhea. There was no significant difference between the diarrheic patients with or without intestinal parasites with respect to cramps, fever, nausea and vomiting, tenesmus, bloody feces, and presence of mucus in the stool. Only one patient had malabsorption, which was not associated with intestinal parasites. The most common parasites detected in this study were Cryptosporidium spp. (n=9; 69.2%), Giardia spp. (n=7; 53.8%), and Blastocystis spp. (n=3; 23.1%). We also identified that parasitic diarrhea in CVID patients tended to last longer (M (mean): 16.2 days) than other causes of infectious diarrhea; this is in accordance with previous studies. CONCLUSION Cryptosporidium spp. was found be the major cause of parasitic intestinal infection in this patient population. It was concluded that parasitic infections may cause chronic diarrhea, which are major causes of morbidity in CVID patients. Therefore, special attention is necessary for the identification of intestinal parasites in CVID patients with diarrhea.
Sense of meaning in context: A study of meaning for past events in relation to future goals, and in relation to intrusions and personality over time.

Meaning making is a common response to many types of important life events, which individuals use to try to make sense of and gain benefits from difficult experiences. It has been traditionally associated with positive psychological and physiological outcomes (Affleck & Tennen, 1996). Nevertheless, the circumstances and mechanisms by which it becomes beneficial are less well understood. This thesis consists of three studies. The goal of Study 1 was to establish whether meaning and affect for a specific event reflect unique constructs and are independent of more global individual characteristics such as purpose and meaning in life. Study 2 then sought to identify the possible mechanisms by which sense of meaning for self-defining memories is associated with positive outcomes. This was accomplished by specifically focusing on the mediating effect of positive affect on self-efficacy and importance of goals. Lastly, to expand on the current understanding of the role of meaning making, Study 3 examined how sense of meaning changes over time, its relation to intrusions and avoidance, and its relation to personality factors. Individuals reported a self-defining event, the affect and sense of meaning associated with that event, as well as general indices of purpose and affectivity (Study 1). In addition, individuals rated a number of current goals and their sense of self-efficacy and importance for those goals (Study 2). Finally, individuals reported a traumatic event, their sense of meaning for that event as well as their affect, and their experience of intrusions and avoidance at three different points in time (Study 3). Individuals also completed a personality questionnaire. Positive affect and meaning for self-defining events were correlated with one another, but not with more general indices of affectivity and purposefulness. Sense of meaning for memories was associated with more positive affect, which, in turn, was associated with more self-efficacy and importance of current life goals. Finally, sense of meaning tended to be stable over time and was associated both with more intrusions, and extraversion and conscientiousness. Intrusions and avoidance tended to decrease over time and were associated with neuroticism. This thesis clarifies some of the functions of having a sense of meaning with regard to self-defining or negative life events, in a broader context than previously considered.
Changes in endolysosomal enzyme activities in cerebrospinal fluid of patients with Parkinson's disease

Parkinson's disease (PD) is characterized neuropathologically by the cytoplasmic accumulation of misfolded α‐synuclein in specific brain regions. The endolysosomal pathway appears to be involved in α‐synuclein degradation and, thus, may be relevant to PD pathogenesis. This assumption is further strengthened by the association between PD and mutations in the gene encoding for the lysosomal hydrolase glucocerebrosidase. The objective of the present study was to determine whether endolysosomal enzyme activities in cerebrospinal fluid (CSF) differ between PD patients and healthy controls. Activity levels of 6 lysosomal enzymes (β‐hexosaminidase, α‐fucosidase, β‐mannosidase, β‐galactosidase, β‐glucocerebrosidase, and cathepsin D) and 1 endosomal enzyme (cathepsin E) were measured in CSF from 58 patients with PD (Hoehn and Yahr stages 1–3) and 52 age‐matched healthy controls. Enzyme activity levels were normalized against total protein levels. Normalized cathepsin E and β‐galactosidase activity levels were significantly higher in PD patients compared with controls, whereas normalized α‐fucosidase activity was reduced. Other endolysosomal enzyme activity levels, including β‐glucocerebrosidase activity, did not differ significantly between PD patients and controls. A combination of normalized α‐fucosidase and β‐galactosidase discriminated best between PD patients and controls with sensitivity and specificity values of 63%. In conclusion, the activity of a number of endolysosomal enzymes is changed in CSF from PD patients compared with healthy controls, supporting the alleged role of the endolysosomal pathway in PD pathogenesis. The usefulness of CSF endolysosomal enzyme activity levels as PD biomarkers, either alone or in combination with other markers, remains to be established in future studies. © 2013 Movement Disorder Society
How Good Are My Predictions? Efficiently Approximating Precision-Recall Curves for Massive Datasets

Large scale machine learning produces massive datasets whose items are often associated with a conﬁdence level and can thus be ranked. However, computing the precision of these resources requires human annotation, which is often prohibitively expensive and is therefore skipped. We consider the problem of cost-effectively approximating precision-recall (PR) or ROC curves for such systems. Our novel approach, called PAULA, provides theoretically guaranteed lower and upper bounds on the underlying precision function while relying on only O(log N ) annotations for a resource with N items. This contrasts favorably with Θ( √ N log N ) annotations needed by commonly used sampling based methods. Our key insight is to capitalize on a natural monotonicity property of the underlying conﬁdence-based ranking. PAULA provides tight bounds for PR curves using, e.g., only 17K annotations for resources with 200K items and 48K annotations for resources with 2B items. We use PAULA to evaluate a subset of the much utilized PPDB paraphrase database and a recent Science knowledge base.
EPIDURAL ANALGESIA FOR PARTIAL GASTRECTOMY.

Summary A technique of epidural analgesia for partial gastrectomy is described, using 1.5 per cent lignocaine with adrenaline. Satisfactory operating conditions were provided in 234 of the 250 patients reviewed. No serious complications occurred that with certainty could be attributed to the anaesthetic technique. One patient died 10 days after operation. The results confirm that the method is practical and safe and has advantages in patients with some pulmonary disorders. Lack of bleeding and contraction of the gut during operation are advantageous to the surgeon.
Leadership Tendencies of Pakistanis: Exploring Similarities and Differences based on Age and Gender

The management styles of people are influenced by their cultural contexts and urgency of completing tasks. For example, it is expected that people will get things done in a speedy manner when their jobs are on the line, but they will still try to minimize the negative impact to their relationships. To explore the leadership tendencies of working adults in the Pakistani workplace, this paper focused on comparing the leadership orientation of 232 respondents based on their age and gender. Pakistanis have a significantly higher score on task orientation. Their relationship orientation score is also on the moderately high range. The high score on both leadership dimensions reflects on their cultural orientation. Practical suggestions for expatriates and implications for future studies are presented.
Past water flow beneath Pine Island and Thwaites glaciers, West Antarctica

Abstract. Outburst floods from subglacial lakes beneath the Antarctic Ice Sheet modulate ice-flow velocities over periods of months to years. Although subglacial lake drainage events have been observed from satellite-altimetric data, little is known about their role in the long-term evolution of ice-sheet basal hydrology. Here, we systematically map and model past water flow through an extensive area containing over 1000 subglacial channels and 19 former lake basins exposed on over 19 000 km2 of seafloor by the retreat of Pine Island and Thwaites glaciers, West Antarctica. At 507 m wide and 43 m deep on average, the channels offshore of present-day Pine Island and Thwaites glaciers are approximately twice as deep, 3 times as wide, and cover an area over 400 times larger than the terrestrial meltwater channels comprising the Labyrinth in the Antarctic Dry Valleys. The channels incised into bedrock offshore of contemporary Pine Island and Thwaites glaciers would have been capable of accommodating discharges of up to 8.8×106 m3 s−1. We suggest that the channels were formed by episodic discharges from subglacial lakes trapped during ice-sheet advance and retreat over multiple glacial periods. Our results document the widespread influence of episodic subglacial drainage events during past glacial periods, in particular beneath large ice streams similar to those that continue to dominate contemporary ice-sheet discharge.
The Influence of Fatty Acids on the GpA Dimer Interface by Coarse-Grained Molecular Dynamics Simulation

The hydrophobic thickness of membranes, which is manly defined by fatty acids, influences the packing of transmembrane domains of proteins and thus can modulate the activity of these proteins. We analyzed the dynamics of the dimerization of Glycophorin A (GpA) by molecular dynamics simulations to describe the fatty acid dependence of the transmembrane region assembly. GpA represents a well-established model for dimerization of single transmembrane helices containing a GxxxG motif in vitro and in silico. We performed simulations of the dynamics of the NMR-derived dimer as well as self-assembly simulations of monomers in membranes composed of different fatty acid chains and monitored the formed interfaces and their transitions. The observed dimeric interfaces, which also include the one known from NMR, are highly dynamic and converted into each other. The frequency of interface formation and the preferred transitions between interfaces similar to the interface observed by NMR analysis strongly depend on the fatty acid used to build the membrane. Molecular dynamic simulations after adaptation of the helix topology parameters to better represent NMR derived structures of single transmembrane helices yielded an enhanced occurrence of the interface determined by NMR in molecular dynamics simulations. Taken together we give insights into the influence of fatty acids and helix conformation on the dynamics of the transmembrane domain of GpA.
Role of polynucleotide kinase/phosphatase in mitochondrial DNA repair

Mutations in mitochondrial DNA (mtDNA) are implicated in a broad range of human diseases and in aging. Compared to nuclear DNA, mtDNA is more highly exposed to oxidative damage due to its proximity to the respiratory chain and the lack of protection afforded by chromatin-associated proteins. While repair of oxidative damage to the bases in mtDNA through the base excision repair pathway has been well studied, the repair of oxidatively induced strand breaks in mtDNA has been less thoroughly examined. Polynucleotide kinase/phosphatase (PNKP) processes strand-break termini to render them chemically compatible for the subsequent action of DNA polymerases and ligases. Here, we demonstrate that functionally active full-length PNKP is present in mitochondria as well as nuclei. Downregulation of PNKP results in an accumulation of strand breaks in mtDNA of hydrogen peroxide-treated cells. Full restoration of repair of the H2O2-induced strand breaks in mitochondria requires both the kinase and phosphatase activities of PNKP. We also demonstrate that PNKP contains a mitochondrial-targeting signal close to the C-terminus of the protein. We further show that PNKP associates with the mitochondrial protein mitofilin. Interaction with mitofilin may serve to translocate PNKP into mitochondria.
Family or Future in the Academy?

This article critically reviews recent literature on the relationship between family formation and academic-career progression, emphasizing obstacles women face seeking a tenured position and beyond. Evidence indicates that the pipeline model is dominated by “ideal worker” norms. These norms impose rigid, tightly coupled, sequential, time-bound requirements on aspiring academics, making the raising of young children and advancing an academic career incompatible. Studies indicate that women with PhDs and young children are disproportionately more likely to leak out of the tenure-track pipeline. Lack of family friendliness is one of the chief reasons why women opt out of tenure-track careers. One way to increase the proportion of tenured women is to adapt the pipeline model by bolstering institutional work–family policies and providing child care centers. Departmental leaders can ensure that making use of work–family policies does not negatively affect tenure decisions. Collecting longitudinal data to evaluate how well policies are working is critical.
ENSO Bimodality and Extremes

Tropical sea surface temperature (SST) and winds vary on a wide range of timescales and have a substantial impact on weather and climate across the globe. Here we study the variability of SST and zonal wind during El Niño‐Southern Oscillation (ENSO) between 1982 and 2014. We focus on changes in extreme statistics using higher‐order moments of SST and zonal winds. We find that ENSO characteristics exhibit bimodal distributions and fat tails with extreme warm and cold temperatures in 1982–1999, but not during 2000–2014. The changes in the distributions coincide with changes in the intensity of ENSO events and the phase of the Interdecadal Pacific Oscillation. We also find that the strongest Easterly Wind Bursts occur during extreme El Niños and not during La Niñas. Maps of SST kurtosis can serve as a diagnostic for the thermocline feedback mechanism responsible for the differences in ENSO diversity between the two periods.
On the stability of the information carried by traffic flow features at the packet level

This paper presents a statistical analysis of the amount of information that the features of traffic flows observed at the packet-level carry, with respect to the protocol that generated them. We show that the amount of information of the majority of such features remain constant irrespective of the point of observation (Internet core vs. Internet edge) and to the capture time (year 2000/01 vs. year 2008). We also describe a comparative analysis of how four statistical classifiers fare using the features we studied.