Miracle-dz/UniFAR-FTUs huggingface dataset:
Sex differences in the prevalence of genetic mutations in FTD and ALS

Objective: To conduct a meta-analysis that investigates sex differences in the prevalence of mutations in the 3 most common genes that cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)—chromosome 9 open reading frame 72 (C9orf72), progranulin (GRN), or microtubule-associated protein tau (MAPT)—in patients clinically diagnosed with these conditions. Methods: MEDLINE, EMBASE, and PsycINFO databases were searched (inception to June 30, 2016). Studies of patients with FTD or ALS that reported the number of men and women with and without mutations of interest were selected. Female to male pooled risk ratios (RR) and 95% confidence intervals (CI) for each mutation were calculated using random-effects models. Results: Thirty-two articles reporting 12,784 patients with ALS (including 1,244 C9orf72 mutation carriers) revealed a higher prevalence of female patients with C9orf72-related ALS (RR 1.16, 95% CI 1.04–1.29). Twenty-three articles reporting 5,320 patients with FTD (including 488 C9orf72 mutation carriers) revealed no sex differences in C9orf72-related FTD (RR 0.95, 95% CI 0.81–1.12). Thirty-six articles reporting 3,857 patients with FTD (including 369 GRN mutation carriers) revealed a higher prevalence of female patients with GRN-related FTD (RR 1.33, 95% CI 1.09–1.62). Finally, 21 articles reporting 2,377 patients with FTD (including 215 MAPT mutation carriers) revealed no sex difference in MAPT-related FTD (RR 1.21, 95% CI 0.95–1.55). Conclusions: Higher female prevalence of C9orf72 hexanucleotide repeat expansions in ALS and GRN mutations in FTD suggest that sex-related risk factors might moderate C9orf72 and GRN-mediated phenotypic expression.
Near-term memory in programming: a simulation-based analysis

Near-term memory (NTM) is proposed as a construct for analysing the memory that experts build up and use as they solve a problem in their domain of expertise. Large amounts of information are processed in such situations, and any particular detail could become important later, so performance is facilitated by maintaining long-term memory access to as much detail as possible. Precise analysis of such memory is difficult to achieve with experimentation or observation alone, so computational simulation is used as the analytical method. A computational process model grounded in cognitive theory (Soar) is constructed to fit extensive fine-grained behavioral data from an expert programmer. The model's structures and processes are then inspected for insights into NTM. Structurally, the model's NTM consists of fine-grain perceptual, semantic, and episodic items whose availability is tied to cues from the encoding context. Quantitatively, much more detail enters NTM than is ever retrieved, but when retrieval does occur it can change the course of behavior. To illustrate applications of the construct, the model is used to examine how a cluttered interface might impose cognitive costs by increasing retrieval demands on memory.
Current incidence and clinical outcomes of bivalirudin administration among patients undergoing primary coronary intervention for stent thrombosis elevation acute myocardial infarction

BackgroundMultiple antithrombotic options are available for patients undergoing primary percutaneous coronary interventions for stent thrombosis elevation acute myocardial infarction. Current utilization and outcomes of antithrombotic agents for primary percutaneous coronary intervention, including bivalirudin, have not been defined. MethodsA total of 84 471 patients were reported from 439 hospitals to the National Registry of Myocardial Infarction-5 registry between April 2004 and June 2005. Consecutive patients undergoing primary percutaneous coronary interventions for stent thrombosis elevation acute myocardial infarction (n=7629 at 231 United States percutaneous coronary intervention capable hospitals) comprised the population analyzed. We examined antithrombotic strategies and the occurrence of adverse cardiac events stratified according to the use of bivalirudin. Logistic regression was performed to control for differences between three antithrombotic therapy treatment groups. ResultsGlycoprotein IIbIIIa inhibitors were used nearly ubiquitously, but given prior to percutaneous coronary interventions in only 36% of patients. Less than one-quarter of patients received clopidogrel prior to percutaneous coronary interventions. Bivalirudin was used in 4.2% of patients (n=320) undergoing primary percutaneous coronary intervention during this time period. Patients treated with bivalirudin were more likely to be elderly (P=0.03), have a history of prior bleeding (P=0.003) and stroke (P=0.06). Major adverse events and bleeding complications were similar in antithrombotic therapy groups (bleeding: bivalirudin 7.8% versus nonbivalirudin 7.5%, P=0.85). The adjusted outcomes were also similar after confining the analysis to bivalirudin patients who had not received any glycoprotein IIbIIIa inhibitors (n=143). ConclusionsContemporary primary percutaneous coronary intervention includes mainly clopidogrel and eptifibatide initiated at the time of percutaneous coronary intervention. Patients who received bivalirudin were at higher risk and had similar adjusted outcomes as patients in the nonbivalirudin group. Optimization of primary percutaneous coronary intervention pharmacology requires future randomized clinical trials, examining the timing and type of adjunctive antithrombotic agents.
FUNCTIONAL CHARACTERIZATION OF FIVE NOVEL CYP 2 C 8 VARIANTS , G 171 S , R 186 X , R 186 G , K 247 R , AND K 383 N , FOUND IN A JAPANESE POPULATION

Cytochrome P450 2C8 is one of the primary enzymes responsible for the metabolism of a wide range of drugs such as paclitaxel, cerivastatin, and amiodarone. We have sequenced the CYP2C8 gene from 201 Japanese subjects and found five novel nonsynonymous single nucleotide polymorphisms (SNPs): 511G>A (G171S), 556C>T (R186X; X represents the translational stop codon), 556C>G (R186G), 740A>G (K247R), and 1149G>T (K383N), with the allele frequency of 0.0025. The CYP2C8 variants were heterologously expressed in COS-1 cells and functionally characterized in terms of expression level, paclitaxel 6 -hydroxylase activity, and intracellular localization. The prematurely terminated R186X variant was undetectable by Western blotting and inactive toward paclitaxel 6 -hydroxylation. The G171S, K247R, and K383N variants exhibited properties similar to those of the wild-type CYP2C8. Paclitaxel 6 -hydroxylase activity of the R186G transfectant was only 10 to 20% that of wild-type CYP2C8. Furthermore, the R186G variant displayed a lower level of protein expression in comparison to the wild type, which was restored by the addition of a proteasome inhibitor (MG-132; Z-Leu-Leu-Leu-aldehyde). The reduced CO-difference spectral analysis using recombinant proteins from an insect cell/baculovirus system revealed that the R186G variant has a minor peak at 420 nm in addition to the characteristic Soret peak at 450 nm, suggesting the existence of improperly folded protein. These results indicate that the novel CYP2C8 SNPs, 556C>T (R186X) and 556C>G (R186G), could influence the metabolism of CYP2C8 substrates such as paclitaxel and cerivastatin. Cytochrome P450 (P450) 2C8 plays an important role in the metabolism of xenobiotics and endogenous compounds in the human liver. CYP2C8 is also found in the extrahepatic tissues, including kidney, adrenal gland, brain, uterus, mammary gland, ovary, and duodenum (Klose et al., 1999). A wide range of drugs of clinical importance have been reported to be metabolized by CYP2C8. For instance, CYP2C8 catalyzes paclitaxel 6 -hydroxylation (Rahman et al., 1994), amiodarone N-deethylation (Ohyama et al., 2000), demethylation and hydroxylation of cerivastatin (Mück, 1998), repaglinide hydroxylation on the piperidine ring (Bidstrup et al., 2003), and chloroquine N-deethylation (Projean et al., 2003). Endogenous retinoids and arachidonic acid are also metabolized by CYP2C8 (Zeldin et al., 1996; Nadin and Murray 1999). Thus, genetic defects in the CYP2C8 gene could lead to the altered metabolism/disposition of
On composite laminates with extensional anisotropy

*The definite list of extensionally (membrane) anisotropic composite laminates with up to 21 plies is presented. The listings comprise of individual stacking sequences of entirely nonsymmetric laminates, which are characterized in terms of angle- and cross-ply sub-sequence relationships as well as the blend-ratio of unbalanced angle-plies. Dimensionless parameters, including lamination parameters, are provided, from which the extensional and bending stiffness terms are readily calculated and an assessment of the bending stiffness efficiency made for angle- and cross-ply sub-sequences. Comparisons are made between the structural response of extensionally-anisotropic laminates and laminates with both extensional- and bending-anisotropy, which can often be achieved in practice using symmetric configurations. This new class of coupled non-symmetric laminate can also be manufactured flat under a standard elevated temperature curing process, which is contrary to current understanding.
Adding motivational interviewing and thought mapping to cognitive-behavioral group therapy: results from a randomized clinical trial.

OBJECTIVE Recent factor-analytic studies of obsessive-compulsive disorder identified consistent symptom dimensions. This study was designed in order to observe which obsessive compulsive symptom dimensions could be changed by adding two individual sessions of motivational interviewing and thought mapping of cognitive-behavioral group therapy using a randomized clinical trial. METHOD Forty outpatients with a primary diagnosis of obsessive-compulsive disorder were randomly assigned to receive cognitive-behavioral group therapy (control group) or motivational interviewing+thought mapping plus cognitive-behavioral group therapy. To evaluate changes in symptom dimensions, the Dimensional Yale-Brown Obsessive-Compulsive Scale was administered at baseline and after treatment. RESULTS At post-treatment, there were statistically significant differences between cognitive-behavioral group therapy and motivational interviewing+thought mapping+cognitive behavioral group therapy groups in the mean total Dimensional Yale-Brown Obsessive-Compulsive Scale score, and in the contamination and aggression dimension score. Hoarding showed a statistical trend towards improvement. CONCLUSION These findings suggest that adding motivational interviewing+thought mapping to cognitive-behavioral group therapy can facilitate changes and bring about a decrease in the scores in different obsessive-compulsive disorder symptom dimensions, as measured by the Dimensional Yale-Brown Obsessive-Compulsive Scale. Nonetheless, additional trials are needed to confirm these results.
A Digital Smoking Cessation Program Delivered Through Internet and Cell Phone Without Nicotine Replacement (Happy Ending): Randomized Controlled Trial

Background Happy Ending (HE) is an intense 1-year smoking cessation program delivered via the Internet and cell phone. HE consists of more than 400 contacts by email, Web pages, interactive voice response, and short message service technology. HE includes a craving helpline and a relapse prevention system, providing just-in-time therapy. All the components of the program are fully automated. Objective The objectives were to describe the rationale for the design of HE, to assess the 12-month efficacy of HE in a sample of smokers willing to attempt to quit without the use of nicotine replacement therapy, and to explore the potential effect of HE on coping planning and self-efficacy (prior to quitting) and whether coping planning and self-efficacy mediate treatment effect. Methods A two-arm randomized controlled trial was used. Subjects were recruited via Internet advertisements and randomly assigned to condition. Inclusion criteria were willingness to quit on a prescribed day without using nicotine replacement and being aged 18 years or older. The intervention group received HE, and the control group received a 44-page self-help booklet. Abstinence was defined as “not even a puff of smoke, for the last seven days” and was assessed by means of Internet surveys or telephone interviews 1, 3, 6, and 12 months postcessation. The main outcome was repeated point abstinence (ie, abstinence at all four time points). Coping planning and self-efficacy were measured at baseline and at the end of the preparation phase (ie, after 2 weeks of treatment, but prior to cessation day). Results A total of 290 participants received either the HE intervention (n=144) or the control booklet (n=146). Using intent-to-treat analysis, participants in the intervention group reported clinically and statistically significantly higher repeated point abstinence rates than control participants (20% versus 7%, odds ratio [OR] = 3.43, 95% CI = 1.60-7.34, P = .002). Although no differences were observed at baseline, by the end of the preparation phase, significantly higher levels of coping planning (t 261 = 3.07, P = .002) and precessation self-efficacy (t 261 = 2.63, P = .01) were observed in the intervention group compared with the control group. However, neither coping planning nor self-efficacy mediated long-term treatment effect. For point abstinence 1 month after quitting, however, coping planning and self-efficacy showed a partial mediation of the treatment effect. Conclusions This 12-month trial documents a long-term treatment effect of a fully automated smoking cessation intervention without the use of nicotine replacement therapy. The study adds to the promise of using digital media in supporting behavior change.
Microarray study of gene expression in uterine leiomyoma.

UNLABELLED Uterine leiomyoma is a most common benign neoplasm in women of reproductive age. It arises from the myometrial compartment of the uterus and may transform in some cases to a malignant phenotype. AIM To identify the genes involved in pathogenesis of uterine leiomyoma. METHODS We have studied differential gene expression in matched tissue samples of leiomyoma and normal myometrium from the very same people utilizing a cDNA microarray screening method. We also compared our results with previously published microarray data to identify the overlapping gene alterations. RESULTS Based on this comparison we can divide genes deregulated in our study into two groups. The first group comprises genes that to our knowledge have not been previously reported as deregulated in fibroids: CLDN1, FGF7 (KGF), HNRPM, ISOC1, MAGEC1 (CT7), MAPK12, RFC, TIE1, TNFRSF21 (DR6). The second group consists of genes identified also in previous studies: CCND1 (BCL1), CDKN1A (P21), CRABP2, FN1 and SOX4 (EVI16). In our study FN1 was the most up-regulated gene, occupying the place between the myometrium and fibroids ranging from 2.07 to 3.64, depending of the probe molecule used for detection. CONCLUSIONS Newly identified genes may be regarded as potential diagnostic or prognostic markers of uterine leiomyoma and thus may be very useful as new therapeutic candidates.
The dynamics of sperm cooperation in a competitive environment

Sperm cooperation has evolved in a variety of taxa and is often considered a response to sperm competition, yet the benefit of this form of collective movement remains unclear. Here we use fine-scale imaging and a minimal mathematical model to study sperm aggregation in the rodent genus Peromyscus. We demonstrate that as the number of sperm cells in an aggregate increase, the group moves with more persistent linearity but without increasing speed; this benefit, however, is offset in larger aggregates as the geometry of the group forces sperm to swim against one another. The result is a non-monotonic relationship between aggregate size and average velocity with both a theoretically predicted and empirically observed optimum of 6-7 sperm/aggregate. To understand the role of sexual selection in driving these sperm group dynamics, we compared two sister-species with divergent mating systems and find that sperm of P. maniculatus (highly promiscuous), which have evolved under intense competition, form optimal-sized aggregates more often than sperm of P. polionotus (strictly monogamous), which lack competition. Our combined mathematical and experimental study of coordinated sperm movement reveals the importance of geometry, motion and group size on sperm velocity and suggests how these physical variables interact with evolutionary selective pressures to regulate cooperation in competitive environments.
Row-Based Power-Gating: A Novel Sleep Transistor Insertion Methodology for Leakage Power Optimization in Nanometer CMOS Circuits

Leakage power has become a serious concern in nanometer CMOS technologies, and power-gating has shown to offer a viable solution to the problem with a small penalty in performance. This paper focuses on leakage power reduction through automatic insertion of sleep transistors for power-gating. In particular, we propose a novel, layout-aware methodology that facilitates sleep transistor insertion and virtual-ground routing on row-based layouts. We also introduce a clustering algorithm that is able to handle simultaneously timing and area constraints, and we extend it to the case of multi- Vt sleep transistors to increase leakage savings. The results we have obtained on a set of benchmark circuits show that the leakage savings we can achieve are, by far, superior to those obtained using existing power-gating solutions and with much tighter timing and area constraints.
Separation of Presynaptic and Postsynaptic Contributions to Depression by Covariance Analysis of Successive EPSCs at the Calyx of Held Synapse

Synaptic short-term plasticity is considered to result from multiple cellular mechanisms, which may include presynaptic and postsynaptic contributions. We have recently developed a nonstationary EPSC fluctuation analysis (Scheuss and Neher, 2001) to estimate synaptic parameters and their transient changes during short-term synaptic plasticity. Extending the classical variance–mean approach, a short train of stimuli is applied repetitively, and the resulting EPSCs are analyzed for means, variances, and covariances. This provides estimates of the quantal size and quantal content for each EPSC in the train, and furthermore, an estimate of the number of release sites. The latter is less sensitive to heterogeneity in the release probability than that of the variance–mean approach. Here, we applied this analysis to the calyx of Held synapse in brainstem slices of young rats (postnatal day 8–10). We found significant negative covariance in the amplitude of successive EPSCs in a train. The analysis showed that the 10-fold depression in the EPSC amplitude during 100 Hz trains at elevated extracellular Ca2+ concentration resulted from a 2.5-fold reduction in quantal size caused by postsynaptic AMPA receptor desensitization and saturation, and a fourfold reduction in quantal content, which was partially relieved by application of cyclothiazide. The number of release sites estimated by covariance analysis was ≈2000 and significantly larger than estimates from variance–mean parabolas.
To branch or not to branch: the role of pre-patterning in lateral root formation

The establishment of a pre-pattern or competence to form new organs is a key feature of the postembryonic plasticity of plant development, and the elaboration of such pre-patterns leads to remarkable heterogeneity in plant form. In root systems, many of the differences in architecture can be directly attributed to the outgrowth of lateral roots. In recent years, efforts have focused on understanding how the pattern of lateral roots is established. Here, we review recent findings that point to a periodic mechanism for establishing this pattern, as well as roles for plant hormones, particularly auxin, in the earliest steps leading up to lateral root primordium development. In addition, we compare the development of lateral root primordia with in vitro plant regeneration and discuss possible common molecular mechanisms.
A Novel Socioeconomic Measure Using Individual Housing Data in Cardiovascular Outcome Research

Background: To assess whether the individual housing-based socioeconomic status (SES) measure termed HOUSES was associated with post-myocardial infarction (MI) mortality. Methods: The study was designed as a population-based cohort study, which compared post-MI mortality among Olmsted County, Minnesota, USA, residents with different SES as measured by HOUSES using Cox proportional hazards models. Subjects’ addresses at index date of MI were geocoded to real property data to formulate HOUSES (a z-score for housing value, square footage, and numbers of bedrooms and bathrooms). Educational levels were used as a comparison for the HOUSES index. Results: 637 of the 696 eligible patients with MI (92%) were successfully geocoded to real property data. Post-MI survival rates were 60% (50–72), 78% (71–85), 72% (60–87), and 87% (81–93) at 2 years for patients in the first (the lowest SES), second, third, and fourth quartiles of HOUSES, respectively (p < 0.001). HOUSES was associated with post-MI all-cause mortality, controlling for all variables except age and comorbidity (p = 0.036) but was not significant after adjusting for age and comorbidity (p = 0.24). Conclusions: Although HOUSES is associated with post-MI mortality, the differential mortality rates by HOUSES were primarily accounted for by age and comorbid conditions. HOUSES may be useful for health disparities research concerning cardiovascular outcomes, especially in overcoming the paucity of conventional SES measures in commonly used datasets.
Characteristics of fatigue crack propagation behaviour as identified by hysteresis loop at the crack tip

Fatigue crack propagation tests have been carried out under various load conditions. Hysteresis loops denoting the relationship between load and strain at the crack tip are obtained by using local compliance measurement. Crack growth acceleration, delayed retardation and non-propagation phenomena are investigated by considering the variation of hysteresis loop expansion and hysteresis loop tail. Based on the physical meaning of hysteresis loops, two types of crack closure are ascertained and the effect of crack closure on fatigue crack propagation is studied. Results show that change of the effective amplitude of the stress intensity factor at the crack tip is the reason that crack propagation rates vary.
Rare earth doped fiber lasers and amplifiers

Rare earth doped fibre fabrication - techniques and physical properties, Jay R. Simpson optical and electronic properties of rare earth ions in glasses, Wiliam J. Miniscalco devices and configurations for fibre laser sources and amplifiers, Paul Urquhart theory of operation of laser fibre devices, Michael J.F. Digonnet Nd3+- and Er3+-doped silica fibre lasers, Michael J.F. Digonnet and E. Snitzer narrow line width and tunable fibre lasers, P.R. Morkel broadband operation of erbium- and neodymium-doped fibre sources, Paul F. Wysocki Q-switched fibre lasers, W.L. Barnes mode-locked fibre lasers, Mark W. Phillips rare earth doped heavy-metal fluoride glass fibres, J.S. Sanghera and I.D. Aggarwal erbium-doped fibre amplifiers - basic physics and characteristics, E. Desurvire applications of fibre amplifiers to telecommunications systems, Noboru Edagawa.