Miracle-dz/UniFAR-FTUs huggingface dataset:
Conus Venom Peptide Pharmacology

Conopeptides are a diverse group of recently evolved venom peptides used for prey capture and/or defense. Each species of cone snails produces in excess of 1000 conopeptides, with those pharmacologically characterized (∼0.1%) targeting a diverse range of membrane proteins typically with high potency and specificity. The majority of conopeptides inhibit voltage- or ligand-gated ion channels, providing valuable research tools for the dissection of the role played by specific ion channels in excitable cells. It is noteworthy that many of these targets are found to be expressed in pain pathways, with several conopeptides having entered the clinic as potential treatments for pain [e.g., pyroglutamate1-MrIA (Xen2174)] and one now marketed for intrathecal treatment of severe pain [ziconotide (Prialt)]. This review discusses the diversity, pharmacology, structure-activity relationships, and therapeutic potential of cone snail venom peptide families acting at voltage-gated ion channels (ω-, μ-, μO-, δ-, ι-, and κ-conotoxins), ligand-gated ion channels (α-conotoxins, σ-conotoxin, ikot-ikot, and conantokins), G-protein-coupled receptors (ρ-conopeptides, conopressins, and contulakins), and neurotransmitter transporters (χ-conopeptides), with expanded discussion on the clinical potential of sodium and calcium channel inhibitors and α-conotoxins. Expanding the discovery of new bioactives using proteomic/transcriptomic approaches combined with high-throughput platforms and better defining conopeptide structure-activity relationships using relevant membrane protein crystal structures are expected to grow the already significant impact conopeptides have had as both research probes and leads to new therapies.
Plasma and Recombinant Thrombin-activable Fibrinolysis Inhibitor (TAFI) and Activated TAFI Compared with Respect to Glycosylation, Thrombin/Thrombomodulin-dependent Activation, Thermal Stability, and Enzymatic Properties*

Thrombin-activable fibrinolysis inhibitor (TAFI) is a human plasma zymogen similar to pancreatic pro-carboxypeptidase B. Cleavage of the zymogen by thrombin/thrombomodulin generates the enzyme, activated TAFI (TAFIa), which retards fibrin clot lysis in vitro and likely modulates fibrinolysis in vivo. In the present work we stably expressed recombinant TAFI in baby hamster kidney cells, purified it to homogeneity from conditioned serum-free medium, and compared it to plasma TAFI (pTAFI) with respect to glycosylation and kinetics of activation by thrombin/thrombomodulin. Although rTAFI is glycosylated somewhat differently than pTAFI, cleavage products with thrombin/thrombomodulin are indistinguishable, and parameters of activation kinetics are very similar with k cat= 0.55 s−1, K m = 0.54 μm, and K d = 6.0 nm for rTAFI and k cat = 0.61 s−1,K m = 0.55 μm, andK d = 6.6 nm for pTAFI. The respective TAFIa species also were prepared and compared with respect to thermal stability and enzymatic properties, including inhibition of fibrinolysis. The half-life of both enzymes at 37 °C is about 10 min, and the decay of enzymatic activity is associated with a quenching (to ∼62% of the initial value at 60 min) of the intrinsic fluorescence of the enzyme. Stability was highly temperature-dependent, which, according to transition state theory, indicates both high enthalpy and entropy changes associated with inactivation (ΔH o ‡ ≅ 45 kcal/mol and ΔS o ‡ ≅ 80 cal/mol/K). Both species of TAFIa are stabilized by the competitive inhibitors 2-guanidinoethylmercaptosuccinic acid and ε-aminocaproic acid. rTAFIa and pTAFIa are very similar with respect to kinetics of cleavage of small substrates, susceptibility to inhibitors, and ability to retard both tPA-induced and plasmin-mediated fibrinolysis. These studies provide new insights into the thermal instability of TAFIa, a property which could be a significant regulator of its activity in vivo; in addition, they show that rTAFI and rTAFIa are excellent surrogates for the natural plasma-derived species, a necessary prerequisite for future studies of structure and function by site-specific mutagenesis.
Substance abuse among patients presenting at an inner-city psychiatric emergency room.

This study showed a high prevalence of cocaine abuse among patients presenting to a psychiatric emergency service. We strongly recommend routine toxicological screening in addition to systematic questioning about past drug use for all patients aged 18 to 50 presenting at innercity psychiatric emergency rooms who have not admitted to recent drug use. Toxicological screening of patients outside this age range may also provide important information.
To persevere is to save the world: exploring expertise in gaming

This paper applies a psychological theory of motivation (Self-determination theory) to gamer motivation and persistence. By comparing three different expertise groups (casual gamers, heavy gamers, hardcore gamers) we found that the more experienced gamers not surprisingly exhibit the highest levels of persistence, need satisfaction and motivation, where intrinsic motivation is more important than extrinsic motivation. A similar structure is found for the less experienced gamers, even if their general levels of need fulfillment and motivation are lower. When comparing the motivational structure of the three groups with use of structural equation modeling we found that the difference between the more and less experienced gamers becomes more apparent. While casual and heavy gamers exhibit identical structures in their motivational mechanism, hardcore gamers differ significantly regarding the importance of relatedness when trying to explain their heightened levels of persistence.
Fractional Urinary Fluoride Excretion of Young Female Adults during the Diurnal and Nocturnal Periods

Objectives: This study aimed to confirm a previously obtained value for the fractional urinary fluoride excretion (FUFE) over a 24-hour period in adults and to assess whether there are significant differences between FUFE measured during the diurnal (7 a.m. and 6 p.m.) and the subsequent nocturnal (6 p.m. until 7 a.m. of the following day) periods. Methods: Urine was collected over 24 h from 60 healthy female volunteers residing in Santiago, Chile. The individuals’ fluoride intakes over the diurnal and nocturnal periods were calculated from their corresponding F ingestion, measured by dietary analysis. Separate urine collections during both periods were obtained from each volunteer. The fluoride concentrations were measured with a fluoride-ion-selective electrode either directly (urine, water and beverages) or after sample treatment with the microdiffusion technique (food). Results: The average 24-hour FUFE value was 0.69, with a 95% CI of 0.65–0.72, while the average FUFE for the diurnal period was 0.46 (95% CI: 0.42–0.50), and the corresponding result for the nocturnal period showed a significantly higher (paired t test, p < 0.0001) amount of 1.09 (95% CI: 0.97–1.22). Conclusions: A recently published result for the daily FUFE value (0.71) in adults was confirmed. The diurnal average FUFE value is significantly lower than the average nocturnal one. Accepting that approximately 10% of the fluoride intake is not absorbed, the daily fluoride retention can be preliminarily estimated as 20% of the ingested fluoride.
Anti-nutritional effects of a moderate dose of soybean agglutinin in the rat

This study was conducted to investigate the effects of a moderate dose of purified soybean agglutinin on performance and nitrogen digestibility in rats as well as to determine its effects on the protein, DNA and RNA content of the small intestine and pancreas. Twenty-four Sprague - Dawley rats were randomly allotted into one of four groups for a 10-day nitrogen balance experiment. The four groups of rats were fed 7 g of a casein-cornstarch based diet or a similar diet supplemented with 0.1, 0.2 or 0.4 mg/g purified soybean agglutinin. All experimental diets were adjusted to an identical nutrient level. Dose of soybean agglutinin had no significant effect on rat performance. Incorporation of soybean agglutinin in the diet reduced apparent protein digestibility and the utilization of dietary protein by increasing nitrogen loss from the faeces and urine. Fresh pancreatic weight increased in rats fed soybean agglutinin at a level of 0.4 mg/g in the diet compared to the control, but the dry pancreatic weight and the protein content of the pancreas did not differ among the four groups. However the DNA and RNA content of the pancreas had a tendency to increase with a higher level of soybean agglutinin. The weight of the jejunum and its protein, DNA and RNA content were not significantly affected by soybean agglutinin, but the dry weight and the RNA of the jejunum tended to increase with higher levels of soybean agglutinin in the diet. In conclusion, purified soybean agglutinin, at moderate levels in the rats diet, had negative effects on digestive function, such as nitrogen digestibility, nitrogen retention and nitrogen balance. As the level of soybean agglutinin increased, the effects became more pronounced. Meanwhile, hypertrophy of the pancreas was observed with higher doses of soybean agglutinin incorporation in the diets.
Hierarchical Heteroclinics in Dynamical Model of Cognitive Processes: Chunking

Combining the results of brain imaging and nonlinear dynamics provides a new hierarchical vision of brain network functionality that is helpful in understanding the relationship of the network to different mental tasks. Using these ideas it is possible to build adequate models for the description and prediction of different cognitive activities in which the number of variables is usually small enough for analysis. The dynamical images of different mental processes depend on their temporal organization and, as a rule, cannot be just simple attractors since cognition is characterized by transient dynamics. The mathematical image for a robust transient is a stable heteroclinic channel consisting of a chain of saddles connected by unstable separatrices. We focus here on hierarchical chunking dynamics that can represent several cognitive activities. Chunking is the dynamical phenomenon that means dividing a long information chain into shorter items. Chunking is known to be important in many processes of perception, learning, memory and cognition. We prove that in the phase space of the model that describes chunking there exists a new mathematical object — heteroclinic sequence of heteroclinic cycles — using the technique of slow–fast approximations. This new object serves as a skeleton of motions reflecting sequential features of hierarchical chunking dynamics and is an adequate image of the chunking processing.
Pikachurin Protein Required for Increase of Cone Electroretinogram B-Wave during Light Adaptation

In normal eyes, the amplitude of the b-wave of the photopic ERGs increases during light adaptation, but the mechanism causing this increase has not been fully determined. The purpose of this study was to evaluate the contribution of receptoral and post-receptoral components of the retina to this phenomenon. To accomplish this, we examined the ERGs during light adaptation in Pikachurin null-mutant (Pika -/-) mice, which have a misalignment of the bipolar cell dendritic tips to the photoreceptor ribbon synapses. After dark-adaptation, photopic ERGs were recorded from Pika -/- and wild type (WT) mice during the first 9 minutes of light adaptation. In some of the mice, post-receptoral components were blocked pharmacologically. The photopic b-waves of WT mice increased by 50% during the 9 min of light adaptation as previously reported. On the other hand, the b-waves of the Pika -/- mice decreased by 20% during the same time period. After blocking post-receptoral components, the b-waves were abolished from the WT mice, and the ERGs resembled those of the Pika -/- mice. The extracted post-receptoral component increased during light adaptation in the WT mice, but decreased for the first 3 minutes to a plateau in Pika -/- mice. We conclude that the normal synaptic connection between photoreceptor and retinal ON bipolar cells, which is controlled by pikachurin, is required for the ERGs to increase during light-adaptation. The contributions of post-receptoral components are essential for the photopic b-wave increase during the light adaptation.
DRAM errors in the wild: a large-scale field study

Errors in dynamic random access memory (DRAM) are a common form of hardware failure in modern compute clusters. Failures are costly both in terms of hardware replacement costs and service disruption. While a large body of work exists on DRAM in laboratory conditions, little has been reported on real DRAM failures in large production clusters. In this paper, we analyze measurements of memory errors in a large fleet of commodity servers over a period of 2.5 years. The collected data covers multiple vendors, DRAM capacities and technologies, and comprises many millions of DIMM days. The goal of this paper is to answer questions such as the following: How common are memory errors in practice? What are their statistical properties? How are they affected by external factors, such as temperature and utilization, and by chip-specific factors, such as chip density, memory technology and DIMM age? We find that DRAM error behavior in the field differs in many key aspects from commonly held assumptions. For example, we observe DRAM error rates that are orders of magnitude higher than previously reported, with 25,000 to 70,000 errors per billion device hours per Mbit and more than 8% of DIMMs affected by errors per year. We provide strong evidence that memory errors are dominated by hard errors, rather than soft errors, which previous work suspects to be the dominant error mode. We find that temperature, known to strongly impact DIMM error rates in lab conditions, has a surprisingly small effect on error behavior in the field, when taking all other factors into account. Finally, unlike commonly feared, we don't observe any indication that newer generations of DIMMs have worse error behavior.
Depot Medroxyprogesterone Acetate Use Is Associated With Elevated Innate Immune Effector Molecules in Cervicovaginal Secretions of HIV-1–Uninfected Women

Objective:The effects of sex hormones on the immune defenses of the female genital mucosa and its susceptibility to infections are poorly understood. The injectable hormonal contraceptive depot medroxyprogesterone acetate (DMPA) may increase the risk for HIV-1 acquisition. We assessed the local concentration in the female genital mucosa of cationic polypeptides with reported antiviral activity in relation to DMPA use. Methods:HIV-1–uninfected women were recruited from among couples testing for HIV in Nairobi, Kenya. Cervicovaginal secretion samples were collected, and the concentrations of HNP1–3, LL-37, lactoferrin, HBD-2, and SLPI were measured by enzyme-linked immunosorbent assays. Levels of cationic polypeptides in cervicovaginal secretions were compared between women who were not using hormonal contraception and those using DMPA, oral, or implantable contraception. Results:Among 228 women, 165 (72%) reported not using hormonal contraception at enrollment, 41 (18%) used DMPA, 16 (7%) used an oral contraceptive, and 6 (3%) used a contraceptive implant. Compared with nonusers of hormonal contraception, DMPA users had significantly higher mean levels of HNP1–3 (2.38 vs. 2.04 log10 ng/mL; P = 0.024), LL-37 (0.81 vs. 0.40 log10 ng/mL; P = 0.027), and lactoferrin (3.03 vs. 2.60 log10 ng/mL; P = 0.002), whereas SLPI and HBD-2 were similar. Conclusions:Although all analyzed cationic polypeptides have intrinsic antiviral capacity, their interaction and cumulative effect on female genital mucosa susceptibility to infections in vivo has yet to be unraveled. This study suggests a potential mechanism underlying the effect of DMPA on the innate immune defenses, providing a rationale to investigate its effect on HIV-1 acquisition risk.
Psychometric Properties of the Croatian Version of Pavlov’s Temperament Survey for Preschool Children

Croatian version of Pavlov’s Temperament survey for children was created and validated in this study. N = 245 pre-school teachers (all female) provided estimates on this scale for a total of N = 4256 children (2121 girls and 2135 boys) with mean age M = 4.59 (SD = 1.289). As it was expected, factor analysis on principal components with Varimax rotation revealed that three-factor solution is the most interpretable. Overall, three components explained 36.84% of the total variance. Reliability levels Cronbach alpha for Strength of excitation, Strength of inhibition and Mobility are very satisfying. Descriptive for subscales, their intercorrelations and gender differences have mostly confirmed earlier findings on adults. Results indicate the scale can be considered a useful and reliable tool for measuring Pavlovian temperament characteristics of children, however, future verifications on different samples of raters should be conducted.
TESTING THE EFFECTS OF ELEVATED PCO2 ON COCCOLITHOPHORES (PRYMNESIOPHYCEAE): COMPARISON BETWEEN HAPLOID AND DIPLOID LIFE STAGES 1

The response of Emiliania huxleyi (Lohmann) W. W. Hay et H. Mohler, Calcidiscus leptoporus (G. Murray et V. H. Blackman) J. Schiller, and Syracosphaera pulchra Lohmann to elevated partial pressure of carbon dioxide (pCO2) was investigated in batch cultures. We reported on the response of both haploid and diploid life stages of these three species. Growth rate, cell size, particulate inorganic carbon (PIC), and particulate organic carbon (POC) of both life stages were measured at two different pCO2 (400 and 760 parts per million [ppm]), and their organic and inorganic carbon production were calculated. The two life stages within the same species generally exhibited a similar response to elevated pCO2, the response of the haploid stage being often more pronounced than that of the diploid stage. The growth rate was consistently higher at elevated pCO2, but the response of other processes varied among species. Calcification rate of C. leptoporus and of S. pulchra did not change at elevated pCO2, whereas it increased in E. huxleyi. POC production and cell size of both life stages of S. pulchra and of the haploid stage of E. huxleyi markedly decreased at elevated pCO2. It remained unaltered in the diploid stage of E. huxleyi and C. leptoporus and increased in the haploid stage of the latter. The PIC:POC ratio increased in E. huxleyi and was constant in C. leptoporus and S. pulchra. Elevated pCO2 has a significant effect on these three coccolithophore species, the haploid stage being more sensitive. This effect must be taken into account when predicting the fate of coccolithophores in the future ocean.
Feature Selection for Microarray Gene Expression Data using Simulated Annealing guided by the Multivariate Joint Entropy

In this work a new way to calculate the multivariate joint entropy is presented. This measure is the basis for a fast information-theoretic based evaluation of gene relevance in a Microarray Gene Expression data context. Its low complexity is based on the reuse of previous computations to calculate current feature relevance. The mu-TAFS algorithm --named as such to differentiate it from previous TAFS algorithms-- implements a simulated annealing technique specially designed for feature subset selection. The algorithm is applied to the maximization of gene subset relevance in several public-domain microarray data sets. The experimental results show a notoriously high classification performance and low size subsets formed by biologically meaningful genes.
300x Matlab

The true costs of high performance computing are currently dominated by software. Addressing these costs requires shifting to high productivity languages such as Matlab. MatlabMPI is a Matlab implementation of the Message Passing Interface (MPI) standard and allows any Matlab program to exploit multiple processors. The performance has been tested on both shared and distributed memory parallel computers (Sun, SGI, HP, IBM and Linux). A test image filtering application using MatlabMPI achieved a speedup of 300 using 304 CPUs and 15% of the theoretical peak (450 Gigaflops) on an IBM SP2 at the Maui High Performance Computing Center. In addition, this entire parallel benchmark application was implemented in 70 software-lines-of-code (SLOC) yielding 0.85 Gigaflop/SLOC or 4.4 CPUs/SLOC. The MatlabMPI software will be available for download at hpcmo.hpc. mil.
Therapeutic options in treatment-resistant depression

Abstract The phenomenon of treatment-resistant depression (TRD), described as the occurrence of an inadequate response after an adequate treatment with antidepressant agents (in terms of dose, duration, and adherence), is very common in clinical practice. It has been broadly defined in the context of unipolar major depression, but alternative definitions for bipolar depression have also been suggested. In both cases, there is a remarkable lack of consensus amongst professionals concerning its operative definition. A relatively wide variety of treatment options for unipolar TRD are available, whilst the evidence is very scanty for bipolar TRD. TRD is associated to poor clinical, functional, and social outcomes. Several novel therapeutic options are currently being investigated as promising alternatives, targeting the neurotransmitter system outside of the standard monoamine hypothesis. Augmentation or combination with lithium or atypical antipsychotics appears as a valid option for both conditions, and the same occurs with electroconvulsive therapy. Other non-pharmacological strategies such as deep brain stimulation may be promising alternatives for the future. The use of cognitive behaviour therapy is recommended for unipolar TRD, but there is no evidence supporting its use in bipolar TRD.
MCMI-II borderline personality disorder in anorexia and bulimia nervosa. 'Trastorno límite de personalidad según el MCMI-II en la anorexia y bulimia nerviosas'

The aim of the present study is to explore the MCMI-II personality style and MCMI-II possible disorder of borderline personality (BPD) in various groups of women. 93 patients-31 anorexia nervosa restricting subtype (ANr), 31 anorexia nervosa binge-eating/purging subtype (ANp), and 31 bulimia nervosa purging subtype (BNp); 31 women at high risk for eating disorder or symptomatic control group (SCG) and 31 without known pathology or not symptomatic control group (NS-CG)-completed the Spanish version of the MCMI-II. The results revealed: (1) clinically significant borderline personality traits [74>Base Rate (BR) 84): 29% ANr, 41.9% ANp and 29% BNp. According to the MCM-II, women with BNp displayed more BPD traits than possible disorder (though these were more severe). However, the probability of a possible disorder was higher in ANp (more disorders than traits).