Miracle-dz/UniFAR-FTUs huggingface dataset:
Where are bottlenecks in NK fitness landscapes?

Usually the offspring-parent fitness correlations is used to visualize and analyze some characteristics of fitness landscapes such as evolvability. In this paper, we introduce a more general representation of this correlation, the fitness cloud (FC). We use the bottleneck metaphor to emphasis fitness levels in landscape that cause local search process to slow down. For a local search heuristic such as hill-climbing or simulated annealing, FC allows one to visualize the bottleneck and neutrality of landscapes. To confirm the relevance of the FC representation we show where the bottlenecks are in the well-known NK fitness landscape and also how to use neutrality information from the FC to combine some neutral operator with local search heuristic.
The Clinical Utility of Doppler Ultrasound Prior to Arteriovenous Fistula Creation

Arteriovenous fistula (AVF) is the preferred access for long‐term hemodialysis, with superior long‐term patency rates; however, early failure rates are significant. Recent evidence has brought into question the preferred site of AVF creation in many patient groups. A preoperative test that could reliably predict the outcome of a proposed AVF would be of great benefit. Doppler ultrasound has been the most extensively studied and widely used test to guide access creation. Accurate and validated measurements of internal vessel diameter, both arterial and venous, and blood flow in the upper extremity are obtainable by Doppler ultrasound. Studies evaluating the utility of Doppler ultrasound prior to AVF creation suggest that vessel size and blood flow are predictive of AVF outcome. An AVF created using a cephalic vein and/or radial artery smaller than 1.5–2.0 mm is likely to fail; such preoperative data may indicate that an upper arm AVF should be the primary access attempted. Further prospective studies are needed to evaluate the utility of Doppler ultrasound.
Effects of Carbon Fillers on Rheology of Polypropylene-based Resins

Varying amounts of three different carbons (carbon black, synthetic graphite particles, and carbon nanotubes) are added to polypropylene and the resulting single filler composites are tested for viscosity. In addition, the effects of single fillers and combinations of different carbon fillers are studied via a factorial design. Each single filler and all the combinations of different fillers cause a statistically significant increase in composite viscosity. For synthetic graphite/polypropylene composites, the viscosity increase is due to a volume filling effect. Composites containing carbon black and/or carbon nanotubes show viscosity increases above those containing only synthetic graphite.
Association of molecular markers with cold tolerance and green period in zoysiagrass (Zoysia Willd.)

Cold tolerance and the green period are key traits in the breeding of zoysiagrass (Zoysia Willd.). Identification of molecular markers associated with cold tolerance and the green period of zoysiagrass will contribute to efficient selection of elite cultivars. These two traits were measured in 96 zoysiagrass accessions in 2004 and 2005–2006, respectively. The mapping population was screened with 29 pairs of simple sequence repeat (SSR) primers and 54 pairs of sequence-related amplified polymorphism (SRAP) primers. A multi-loci in silico mapping approach implemented with an empirical Bayes method was applied for association mapping of cold tolerance and green period. We detected 254 SSR polymorphic loci and 338 SRAP polymorphic loci, among which three SSR loci (Xgwm131-3B-187, Xgwm469-6D-194 and Xgwm234-5B-244) and one SRAP locus (Me11Em7-406) were significantly associated with cold tolerance with effect values of 57.83%, 38.05%, 36.92% and 37%, respectively. Three SSR loci (Xgwm132-6B-225, Xgwm111-7D-34 and Xgwm102-2D-97) and two SRAP loci (Me19Em5-359 and Me16Em8-483) were significantly associated with the green period with effect values of 79.54%, 62.59%, 99.04%, 49.01% and 82.57%. These markers will be useful for genetic improvement of the cold tolerance and green period of zoysiagrass by marker-assisted breeding.
Dacarbazine with or without oblimersen (a Bcl-2 antisense oligonucleotide) in chemotherapy-naive patients with advanced melanoma and low–normal serum lactate dehydrogenase: ‘The AGENDA trial’

In a previous large randomized, open-label study, retrospective subset analysis revealed that the addition of the Bcl-2 antisense oligonucleotide oblimersen to dacarbazine (Dac) significantly improved overall survival, progression-free survival, and the response rate in chemotherapy-naive patients with advanced melanoma and normal baseline serum lactate dehydrogenase (LDH) levels. To confirm and expand on this observation, we conducted a prospective double-blind, placebo-controlled study to determine whether oblimersen augmented the efficacy of Dac in advanced melanoma patients with low–normal baseline LDH levels. A total of 314 chemotherapy-naive patients were randomly assigned to receive Dac (1000 mg/m2) preceded by a 5-day continuous intravenous infusion of either oblimersen sodium (7 mg/kg/day) or placebo every 21 days for less than eight cycles. Co-primary efficacy endpoints were overall survival and progression-free survival. Response and progression of the disease were assessed by independent blinded review of computed tomography scan images. No difference in overall nor progression-free survival was observed between the Dac–oblimersen and Dac–placebo groups. Although the overall (17.2 vs. 12.1%) and durable (10.8 vs. 7.6%) response rates numerically favored Dac–oblimersen over Dac–placebo, they did not differ significantly (P=0.19 and 0.32, respectively). The incidence of hematologic adverse events, particularly thrombocytopenia and neutropenia, was higher in the Dac–oblimersen group than in the Dac–placebo group. Withdrawals from the study because of treatment-related adverse events were low (i.e. <2.5%) in both groups. The addition of oblimersen to Dac did not significantly improve overall survival nor progression-free survival in patients with advanced melanoma and low–normal levels of LDH at baseline.
Dislocation-mobility-controlled cracking in gaas caused by constantrate indentation

Abstract The presence of a brittle to ductile transition (BDT) controlled by dislocation mobility previously found in Si has been observed for n-GaAs in the present study employing a novel type of dynamic fracture test (constant-rate indentation cracking test). This is a modification of the indentation-induced fracturing method for measuring the transition temperature, which is the critical temperature above which cracking ceases to occur as a function of loading rate. The BDT temperature thus measured was found to depend on the loading rate according to an Arrhhenius-type kinetic equation. Activation energies characterizing the equation varied with the geometrical type of crack formed by indentations on polar {111} planes of GaAs. The magnitudes of the activation energies for the BDT were found to be very close to those for motion of the dislocations that emanate from the respective types of crack tips. This result probably indicates that the BDT is caused by dislocation emission from crack tips, i.e. by.
Circulating Blood Endothelial Nitric Oxide Synthase Contributes to the Regulation of Systemic Blood Pressure and Nitrite Homeostasis

Objective—Mice genetically deficient in endothelial nitric oxide synthase (eNOS−/−) are hypertensive with lower circulating nitrite levels, indicating the importance of constitutively produced nitric oxide (NO•) to blood pressure regulation and vascular homeostasis. Although the current paradigm holds that this bioactivity derives specifically from the expression of eNOS in endothelium, circulating blood cells also express eNOS protein. A functional red cell eNOS that modulates vascular NO• signaling has been proposed. Approach and Results—To test the hypothesis that blood cells contribute to mammalian blood pressure regulation via eNOS-dependent NO• generation, we cross-transplanted wild-type and eNOS−/− mice, producing chimeras competent or deficient for eNOS expression in circulating blood cells. Surprisingly, we observed a significant contribution of both endothelial and circulating blood cell eNOS to blood pressure and systemic nitrite levels, the latter being a major component of the circulating NO• reservoir. These effects were abolished by the NOS inhibitor L-NG-nitroarginine methyl ester and repristinated by the NOS substrate L-arginine and were independent of platelet or leukocyte depletion. Mouse erythrocytes were also found to carry an eNOS protein and convert 14C-arginine into 14C-citrulline in NOS-dependent fashion. Conclusions—These are the first studies to definitively establish a role for a blood-borne eNOS, using cross-transplant chimera models, that contributes to the regulation of blood pressure and nitrite homeostasis. This work provides evidence suggesting that erythrocyte eNOS may mediate this effect.
Global Estimates of Prevalent and Incident Herpes Simplex Virus Type 2 Infections in 2012

Background Herpes simplex virus type 2 (HSV-2) infection causes significant disease globally. Adolescent and adult infection may present as painful genital ulcers. Neonatal infection has high morbidity and mortality. Additionally, HSV-2 likely contributes substantially to the spread of HIV infection. The global burden of HSV-2 infection was last estimated for 2003. Here we present new global estimates for 2012 of the burden of prevalent (existing) and incident (new) HSV-2 infection among females and males aged 15–49 years, using updated methodology to adjust for test performance and estimate by World Health Organization (WHO) region. Methods and Findings We conducted a literature review of HSV-2 prevalence studies world-wide since 2000. We then fitted a model with constant HSV-2 incidence by age to pooled HSV-2 prevalence values by age and sex. Prevalence values were adjusted for test sensitivity and specificity. The model estimated prevalence and incidence by sex for each WHO region to obtain global burden estimates. Uncertainty bounds were computed by refitting the model to reflect the variation in the underlying prevalence data. In 2012, we estimate that there were 417 million people aged 15–49 years (range: 274–678 million) living with HSV-2 infection world-wide (11.3% global prevalence), of whom 267 million were women. We also estimate that in 2012, 19.2 million (range: 13.0–28.6 million) individuals aged 15–49 years were newly-infected (0.5% of all individuals globally). The highest burden was in Africa. However, despite lower prevalence, South-East Asia and Western Pacific regions also contributed large numbers to the global totals because of large population sizes. Conclusions The global burden of HSV-2 infection is large, leaving over 400 million people at increased risk of genital ulcer disease, HIV acquisition, and transmission of HSV-2 to partners or neonates. These estimates highlight the critical need for development of vaccines, microbicides, and other new HSV prevention strategies.
Assessing TLI as a Predictor of Treatment Seeking for SUD among Youth Transitioning to Young Adulthood.

BACKGROUND To date, few studies have been conducted evaluating predictors of treatment seeking for substance use disorders as persons make the transition from preadolescence (a period of very low substance use) to young adulthood (a period of peak substance use). The few studies of this area which have been conducted to date have generally been limited by their use of a cross-sectional rather than a longitudinal study design. We have conducted a longitudinal etiology study (CEDAR) to assess whether an index of behavioral undercontrol called the Transmissible Liability Index (TLI) measured during preadolescence serves as a predictor of the development of substance use disorders (SUD) and of treatment utilization during young adulthood. Our recent work has focuses on subjects with cannabis use disorders (CUD), since CUD are the most common SUD. In recent analyses, we found that TLI serves as a predictor of the development of cannabis use disorder (CUD) among young adults (Kirisci et al., 2009). OBJECTIVE In the current study, we hypothesized that TLI as assessed during preadolescence would predict treatment seeking a decade later when the subjects were young adults. METHOD The 375 participants in this study were initially recruited when they were 10-12 years of age. TLI status was determined at baseline, and subsequent assessments were conducted at 12-14, 16, 19, and 22 years of age. Variables examined included TLI as well as demographic variables. Path analyses were conducted. RESULTS Of the 375 subjects recruited at age 10-12, 92 subjects (24.5%) were diagnosed with a CUD by the age of 22. TLI as assessed during pre-adolescence (at age 10 to 12) was found to be associated with substance-related treatment during young adulthood (age 19 and at age 22). CONCLUSIONS These findings confirmed our hypothesis that TLI assessed during preadolescent years serves as a predictor of treatment at age 19 and at age 22.
Deception detection in Russian texts

Humans are known to detect deception in speech randomly and it is therefore important to develop tools to enable them to detect deception. The problem of deception detection has been studied for a significant amount of time, however the last 10-15 years have seen methods of computational linguistics being employed. Texts are processed using different NLP tools and then classified as deceptive/truthful using machine learning methods. While most research has been performed for English, Slavic languages have never been a focus of detection deception studies. The paper deals with deception detection in Russian narratives. It employs a specially designed corpus of truthful and deceptive texts on the same topic from each respondent, N = 113. The texts were processed using Linguistic Inquiry and Word Count software that is used in most studies of text-based deception detection. The list of parameters computed using the software was expanded due to the designed users’ dictionaries. A variety of text classification methods was employed. The accuracy of the model was found to depend on the author’s gender and text type (deceptive/truthful).
Kinetic Mechanism of Activation of the Cdk2/Cyclin A Complex

Eukaryotic cell cycle progression is controlled by the ordered action of cyclin-dependent kinases, activation of which occurs through the binding of the cyclin to the Cdk followed by phosphorylation of a conserved threonine in the T-loop of the Cdk by Cdk-activating kinase (CAK). Despite our understanding of the structural changes, which occur upon Cdk/cyclin formation and activation, little is known about the dynamics of the molecular events involved. We have characterized the mechanism of Cdk2/cyclin A complex formation and activation at the molecular and dynamic level by rapid kinetics and demonstrate here that it is a two-step process. The first step involves the rapid association between the PSTAIRE helix of Cdk2 and helices 3 and 5 of the cyclin to yield an intermediate complex in which the threonine in the T-loop is not accessible for phosphorylation. Additional contacts between the C-lobe of the Cdk and the N-terminal helix of the cyclin then induce the isomerization of the Cdk into a fully mature form by promoting the exposure of the T-loop for phosphorylation by CAK and the formation of the substrate binding site. This conformational change is selective for the cyclin partner.
A meta-analysis of relationships between polychlorinated biphenyl exposure and performance across studies of free-ranging tree swallows (Tachycineta bicolor)

Habitats worldwide are increasingly being degraded by human activities, with environmental pollution representing a significant threat to species and ecosystems. The presence of persistent organic chemicals, such as polychlorinated biphenyls (PCBs), has generated concern. Captive experiments and field studies have reported some evidence for detrimental effects of PCB exposure, but also significant variation across studies and species. Here, I use a meta-analytical approach to combine findings across 10 studies investigating effects of PCBs on performance (e.g. reproductive success, offspring growth) in free-ranging tree swallows, a common bioindicator species that accumulates high levels of PCBs at some contaminated sites. Contrary to predictions, five complementary analyses revealed no significant negative association between PCB exposure and performance in tree swallows. In fact, in one analysis, increased PCB exposure was associated with improved reproductive success. Possible explanations for these findings include several limitations of field studies, variation in the toxicity of different PCB congener mixtures found across sites included in the analysis, and variation in the degree of tolerance of PCB exposure among species (with high tolerance found in tree swallows). At this point, the available evidence from field studies does not demonstrate negative impacts of PCB exposure on tree swallow performance.
Thrombosis and Prognosis Following ST-Elevation Myocardial Infarction: Left Ventricular Thrombus Assessment by Cardiac Magnetic Resonance.

Acute ST-segment–elevation myocardial infarction (STEMI) is estimated to occur in over 3 million patients each year.1 Left ventricular (LV) thrombus is a serious complication of STEMI, which has been attributed to blood stasis resulting from LV contractile dysfunction and altered geometry (aneurysm). Advances in STEMI management bear particular relevance to LV thrombus: improved coronary reperfusion has augmented myocardial salvage, resulting in improved LV function and remodeling. Newly adopted standard of care therapies, such as thienopyridines, inhibit platelet aggregation, thereby potentially decreasing risk for thrombus. However, despite widespread changes in post-STEMI care, limited data exists concerning LV thrombus in the current era. Given that LV thrombus provides a substrate for embolic events and a rationale for anticoagulation, better understanding of prevalence, predictors, and prognostic significance of post-STEMI LV thrombus is of substantial importance. See Article by Poss et al Beyond changes in clinical management, advances in noninvasive imaging provide a strong rationale for revisiting post-STEMI LV thrombus. Echocardiography (echo) has traditionally been used as the primary modality for evaluating STEMI patients because it is widely available, inexpensive, and supported by ample data demonstrating that echo-based quantification of LV structure and function stratifies post-STEMI prognosis.2,3 However, echo can be limited with respect to LV thrombus. Image quality can be compromised by near field artifacts that obscure the LV apex, a location in which thrombus is often suspected. More broadly, echo limitations may stem from the approach by which thrombus is diagnosed. Echo identifies thrombus based on morphology. This approach can be straightforward when thrombus is large or protuberant, but challenging when thrombus is small or flat (mural). Consistent with these concepts, echo studies have reported marked variability in thrombus prevalence and prognostic significance4,5 and reported substantial inter-reader variability concerning diagnosis of LV thrombus.6 Given …
Non-stationary condition torsional vibration monitoring using induction machine electromagnetic torque estimation

Mechanical anomalies like load troubles, great torque dynamic variations and torsional oscillations, result in the fatigue of the shaft driving electrical machine and other mechanical parts as bearings and gearboxes of complex electromechanical systems. Particularly in non-stationary condition, torsional vibration can reach important levels at resonant frequencies by producing weaknesses in the mechanical part and lifetime consumption during an event. In this way, this paper proposes electromagnetic torque estimation using noninvasive measuring as a means for mechanical torsional stresses monitoring in an induction machine driving system at non-stationary operating condition. A test-bed based on a 5.5 kW squirrel-cage induction machine connected to one-stage gearbox has been used to validate the proposed method.
The Wnt antagonist Dickkopf-1 and its receptors are coordinately regulated during early human adipogenesis

Secretion of Wnts by adipose cells has an important role in the control of murine adipogenesis. We present the first evidence that a Wnt antagonist, Dickkopf 1 (Dkk1), is secreted by human preadipocytes and promotes adipogenesis. DKK1 mRNA increases six hours after onset of human adipogenesis and this is followed by an increase in Dkk1 protein. With further differentiation, the mRNA and protein levels progressively decline such that they are undetectable in mature adipocytes. The transient induction in DKK1 correlates with downregulation of cytoplasmic and nuclear β-catenin levels, this being a surrogate marker of canonical Wnt signalling, and Wnt/β-catenin transcriptional activity. In addition, constitutive expression of Dkk1 in 3T3-L1 preadipocytes promotes their differentiation, further supporting the functional significance of increased Dkk1 levels during human adipogenesis. Concomitant downregulation of the Dkk1 receptors LRP5 and LRP6 is likely to potentiate the ability of Dkk1 to inhibit Wnt signalling and promote differentiation. Notably, Dkk1 is not expressed in primary murine preadipocytes or cell lines. The involvement of Dkk1 in human but not murine adipogenesis indicates that inter-species differences exist in the molecular control of this process. Given the public health importance of disorders of adipose mass, further knowledge of the pathways involved specifically in human adipocyte differentiation might ultimately be of clinical relevance.
Structural evidence for recognition of a single epitope by two distinct antibodies

The structure of a complex between the hemagglutinin of influenza virus and the Fab of a neutralizing antibody was determined by X‐ray crystallography at 2.8 Å resolution. This antibody and another which has only 56% sequence identity bind to the same epitope with very similar affinities and in the same orientation. One third of the interactions is conserved in the two complexes; a significant proportion of the interactions that differ are established by residues of the H3 complementarity‐determining regions (CDR) which adopt distinct conformations in the two antibodies. This demonstrates that there is a definite flexibility in the selection of antibodies that bind to a given epitope, despite the high affinity of their complexes. This flexibility allows the humoral immune response to be redundant, a feature that may be useful in achieving longer lasting protection against evolving viral pathogens. Proteins 2000;40:572–578. © 2000 Wiley‐Liss, Inc.
An N-Myristoylated Globin with a Redox-Sensing Function That Regulates the Defecation Cycle in Caenorhabditis elegans

Globins occur in all kingdoms of life where they fulfill a wide variety of functions. In the past they used to be primarily characterized as oxygen transport/storage proteins, but since the discovery of new members of the globin family like neuroglobin and cytoglobin, more diverse and complex functions have been assigned to this heterogeneous family. Here we propose a function for a membrane-bound globin of C. elegans, GLB-26. This globin was predicted to be myristoylated at its N-terminus, a post-translational modification only recently described in the globin family. In vivo, this globin is found in the membrane of the head mesodermal cell and in the tail stomato-intestinal and anal depressor muscle cells. Since GLB-26 is almost directly oxidized when exposed to oxygen, we postulate a possible function as electron transfer protein. Phenotypical studies show that GLB-26 takes part in regulating the length of the defecation cycle in C. elegans under oxidative stress conditions.