Miracle-dz/UniFAR-FTUs huggingface dataset:
Compartmentalization of Distinct cAMP Signaling Pathways in Mammalian Sperm*♦

Background: cAMP is essential for the acquisition of sperm fertilizing capacity. The presence of transmembrane adenylyl cyclases (tmACs) in sperm remains controversial. Results: tmAC activity and its activator Gs are detected in the sperm head. Conclusion: Two cAMP synthesis pathways coexist in sperm and lead to capacitation. Significance: Understanding capacitation is essential for improvement of assisted fertilization and for finding novel contraceptive targets. Fertilization competence is acquired in the female tract in a process known as capacitation. Capacitation is needed for the activation of motility (e.g. hyperactivation) and to prepare the sperm for an exocytotic process known as acrosome reaction. Although the HCO3−-dependent soluble adenylyl cyclase Adcy10 plays a role in motility, less is known about the source of cAMP in the sperm head. Transmembrane adenylyl cyclases (tmACs) are another possible source of cAMP. These enzymes are regulated by stimulatory heterotrimeric Gs proteins; however, the presence of Gs or tmACs in mammalian sperm has been controversial. In this study, we used Western blotting and cholera toxin-dependent ADP-ribosylation to show the Gs presence in the sperm head. Also, we showed that forskolin, a tmAC-specific activator, induces cAMP accumulation in sperm from both WT and Adcy10-null mice. This increase is blocked by the tmAC inhibitor SQ22536 but not by the Adcy10 inhibitor KH7. Although Gs immunoreactivity and tmAC activity are detected in the sperm head, PKA is only found in the tail, where Adcy10 was previously shown to reside. Consistent with an acrosomal localization, Gs reactivity is lost in acrosome-reacted sperm, and forskolin is able to increase intracellular Ca2+ and induce the acrosome reaction. Altogether, these data suggest that cAMP pathways are compartmentalized in sperm, with Gs and tmAC in the head and Adcy10 and PKA in the flagellum.
On Automated Discovery of Models Using Genetic Programming: Bargaining in a Three-Agent Coalitions Game

The creation of mathematical, as well as qualitative (or rule-based), models is difficult, time-consuming, and expensive. Recent developments in evolutionary computation hold out the prospect that, for many problems of practical import, machine learning techniques can be used to discover useful models automatically. The prospects are particularly bright, we believe, for such automated discoveries in the context of game theory. This paper reports on a series of successful experiments in which we used a genetic programming regime to discover high-quality negotiation policies. The game-theoretic context in which we conducted these experiments-- a three-player coalitions game with sidepayments--is considerably more complex and subtle than any reported in the previous literature on machine learning applied to game theory.
Investment‐Based Expected Stock Returns

We derive and test q‐theory implications for cross‐sectional stock returns. Under constant returns to scale, stock returns equal levered investment returns, which are tied directly to firm characteristics. When we use generalized method of moments to match average levered investment returns to average observed stock returns, the model captures the average stock returns of portfolios sorted by earnings surprises, book‐to‐market equity, and capital investment. When we try to match expected returns and return variances simultaneously, the variances predicted in the model are largely comparable to those observed in the data. However, the resulting expected return errors are large.
Proactive interventions for smoking cessation in general medical practice: a quasi-randomized controlled trial to examine the efficacy of computer-tailored letters and physician-delivered brief advice*

Aims To test the efficacy of (i) computer-generated tailored letters and (ii) practitioner-delivered brief advice for smoking cessation against an assessment-only condition; and to compare both interventions directly. Design Quasi-randomized controlled trial. Setting A total of 34 randomly selected general practices from a German region (participation rate 87%). Participants A total of 1499 consecutive patients aged 18–70 years with daily cigarette smoking (participation rate 80%). Interventions The tailored letters intervention group received up to three individualized personal letters. Brief advice was delivered during routine consultation by the practitioner after an onsite training session. Both interventions were based on the Transtheoretical Model of behaviour change. Measurements Self-reported point prevalence and prolonged abstinence at 6-, 12-, 18- and 24-month follow-ups. Findings Among participants completing the last follow-up, 6-month prolonged abstinence was 18.3% in the tailored letters intervention group, 14.8% in the brief advice intervention group and 10.5% in the assessment-only control group. Assuming those lost to follow-up to be smokers, the rates were 10.2%, 9.7% and 6.7%, respectively. Analyses including all follow-ups confirmed statistically significant effects of both interventions compared to assessment only. Using complete case analysis, the tailored letters intervention was significantly more effective than brief advice for 24-hour [odds ratio (OR) = 1.4; P = 0.047] but not for 7-day point prevalence abstinence (OR = 1.4; P = 0.068) for prolonged abstinence, or for alternative assumptions about participants lost to follow-up. Conclusions The study demonstrated long-term efficacy of low-cost interventions for smoking cessation in general practice. The interventions are suitable to reach entire populations of general practices and smoking patients. Computer-generated letters are a promising option to overcome barriers to provide smoking cessation counselling routinely.
Impact of symptomatic hypoglycemia on medication adherence, patient satisfaction with treatment, and glycemic control in patients with type 2 diabetes

Background The purpose of this study was to evaluate the impact of symptomatic hypoglycemia on medication adherence, satisfaction with treatment, and glycemic control in patients with type 2 diabetes based on the treatment goals stated in the Swedish national guidelines. Methods This cross-sectional, multicenter study was carried out between January and August 2009 in 430 consecutive primary health care patients on stable doses of metformin and sulfonylureas for at least 6 months. The patients completed questionnaires covering their experiences of low blood glucose and adherence, as well as barriers to and satisfaction with drug treatment (using the Treatment Satisfaction Questionnaire for Medication). Physicians collected the data from medical records. Results Patients who experienced moderate or worse symptoms of hypoglycemia reported poorer adherence to medication (46% versus 67%; P<0.01) and were more likely to perceive barriers such as “bothered by medication side effects” (36% versus 14%; P<0.001) compared with patients with no or mild symptoms. Patients with moderate or worse symptoms of hypoglycemia were less satisfied with their treatment than those with no or mild symptoms as determined by the Treatment Satisfaction Questionnaire for Medication-Global satisfaction (67.0 versus 71.2; P<0.05). Overall, achievement of target glycated hemoglobin (HbA1c) based on the treatment goals stated in the Swedish national guidelines was 40%. Despite poorer adherence, patients who experienced moderate or worse symptoms of hypoglycemia had lower mean HbA1c values than patients with no or mild symptoms (7.0% versus 7.3% [Diabetes Control and Complications Trial standard]; P<0.05). Conclusion Symptomatic hypoglycemia in patients with type 2 diabetes on metformin and sulfonylureas was associated with nonadherence and decreased treatment satisfaction despite lower mean HbA1c values. A broader understanding of patient preferences and self-reported outcomes could improve the management of patients with type 2 diabetes.
Race, Party, and American Voting Rights

Abstract There are few advanced democracies that simultaneously make voting as easy and as difficult as the US. This essay outlines some of the recent changes in voting rights and election law, with a particular attention to the causes and consequences of restrictive changes. I argue that both historically and today this pattern has been driven by strategic partisan calculation, which in the American context almost necessarily results in patterns of access and exclusion that fall sharply on lines of race, class, and civic status. The recent skirmishes in the “voting wars” are a continuation of this historical dynamic, enabled by the unique institutional context in which American elections take place, in which parties retain control over the parameters and administration of a highly fragmented electoral system. So long as this remains the case, and so long as there are relatively few institutions capable of checking the incentive to engage in partisan manipulation, the “voting wars” will continue and are likely even to intensify.
Examining the Average and Local Effects of a Standardized Treatment for Fourth Graders With Reading Difficulties

ABSTRACT The present study used a randomized control trial to examine the effects of a widely used multicomponent Tier 2-type intervention, Passport to Literacy, on the reading ability of 221 fourth graders who initially scored at or below the 30th percentile in reading comprehension. Intervention was provided by research staff to groups of 4–7 students for 30 min, 4 days a week throughout the school year (M = 90.45 lessons). Tier 1 instruction was observed to be of generally high quality and intervention fidelity was strong. Findings revealed small, average effects (ES = .14–.28) in favor of intervention students on standardized measures of comprehension, but no effects on word reading or fluency measures. Exploratory analyses indicated that intervention effects may differ by students’ comprehension abilities. Implications for intervention implementation and directions for future research are discussed.
The Propanediol Utilization (pdu) Operon ofSalmonella enterica Serovar Typhimurium LT2 Includes Genes Necessary for Formation of Polyhedral Organelles Involved in Coenzyme B12-Dependent 1,2-Propanediol Degradation

ABSTRACT The propanediol utilization (pdu) operon ofSalmonella enterica serovar Typhimurium LT2 contains genes needed for the coenzyme B12-dependent catabolism of 1,2-propanediol. Here the completed DNA sequence of the pduoperon is presented. Analyses of previously unpublished pduDNA sequence substantiated previous studies indicating that thepdu operon was acquired by horizontal gene transfer and allowed the identification of 16 hypothetical genes. This brings the total number of genes in the pdu operon to 21 and the total number of genes at the pdu locus to 23. Of these, six encode proteins of unknown function and are not closely related to sequences of known function found in GenBank. Two encode proteins involved in transport and regulation. Six probably encode enzymes needed for the pathway of 1,2-propanediol degradation. Two encode proteins related to those used for the reactivation of adenosylcobalamin (AdoCbl)-dependent diol dehydratase. Five encode proteins related to those involved in the formation of polyhedral organelles known as carboxysomes, and two encode proteins that appear distantly related to those involved in carboxysome formation. In addition, it is shown that S. enterica forms polyhedral bodies that are involved in the degradation of 1,2-propanediol. Polyhedra are formed during either aerobic or anaerobic growth on propanediol, but not during growth on other carbon sources. Genetic tests demonstrate that genes of the pdu operon are required for polyhedral body formation, and immunoelectron microscopy shows that AdoCbl-dependent diol dehydratase is associated with these polyhedra. This is the first evidence for a B12-dependent enzyme associated with a polyhedral body. It is proposed that the polyhedra consist of AdoCbl-dependent diol dehydratase (and perhaps other proteins) encased within a protein shell that is related to the shell of carboxysomes. The specific function of these unusual polyhedral bodies was not determined, but some possibilities are discussed.
Overexpression of the Maize psbA Gene Enhances Drought Tolerance Through Regulating Antioxidant System, Photosynthetic Capability, and Stress Defense Gene Expression in Tobacco

The psbA (encoding D1 protein) plays an important role in protecting photosystem II (PSII) from oxidative damage in higher plants. In our previous study, the role of the psbA from maize (Zea mays. L) in response to SO2 stress was characterized. To date, information about the involvement of the psbA gene in drought response is scarce. Here we found that overexpression (OE) of ZmpsbA showed increased D1 protein abundance and enhanced drought stress tolerance in tobacco. The drought-tolerant phenotypes of the OE lines were accompanied by increases of key antioxidant enzymes SOD, CAT, and POD activities, but decreases of hydrogen peroxide, malondialdehyde, and ion leakage. Further investigation showed that the OE plants had much less reductions than the wild-type in the net photosynthesis rate (Pn), stomatal conductance (Gs), and the maximal photochemical efficiency of PSII (Fv/Fm) during drought stress; indicating that OE of ZmpsbA may alleviate photosynthesis inhibition during drought. qRT-PCR analysis revealed that there was significantly increased expression of NtLEA5, NtERD10C, NtAREB, and NtCDPK2 in ZmpsbA-OE lines. Together, our results indicate that ZmpsbA improves drought tolerance in tobacco possibly by alleviating photosynthesis reduction, reducing reactive oxygen species accumulation and membrane damage, and modulating stress defense gene expression. ZmpsbA could be exploited for engineering drought-tolerant plants in molecular breeding of crops.
Birds of the Same Feather Tweet Together: Bayesian Ideal Point Estimation Using Twitter Data

Politicians and citizens increasingly engage in political conversations on social media outlets such as Twitter. In this article, I show that the structure of the social networks in which they are embedded can be a source of information about their ideological positions. Under the assumption that social networks are homophilic, I develop a Bayesian Spatial Following model that considers ideology as a latent variable, whose value can be inferred by examining which politics actors each user is following. This method allows us to estimate ideology for more actors than any existing alternative, at any point in time and across many polities. I apply this method to estimate ideal points for a large sample of both elite and mass public Twitter users in the United States and five European countries. The estimated positions of legislators and political parties replicate conventional measures of ideology. The method is also able to successfully classify individuals who state their political preferences publicly and a sample of users matched with their party registration records. To illustrate the potential contribution of these estimates, I examine the extent to which online behavior during the 2012 US presidential election campaign is clustered along ideological lines.
Venous Stasis Retinopathy in Symptomatic Carotid Artery Occlusion: Prevalence, Cause, and Outcome

Background and Purpose— Chronic ocular ischemia is a rare form of ischemia of the eye in patients with carotid artery occlusion (CAO). The early and often asymptomatic stage of chronic ocular ischemia is referred to as venous stasis retinopathy (VSR). The aim of this study was to gain insight into the prevalence, cause, and outcome of VSR in patients with symptomatic CAO. Methods— In 110 patients with symptomatic CAO, we prospectively investigated the frequency of VSR, the association between the presence of VSR and impaired cerebral blood flow, and the proportion of patients who developed clinically manifest chronic ocular ischemia with ischemia of the anterior eye segment or blindness. Results— At study entry, VSR was found in 32 patients (29%; 95% CI, 21 to 38), particularly in those with symptoms classically associated with a hemodynamic cause, such as limb shaking (relative risk, 2.4; 95% CI, 1.0 to 5.9). Patients with VSR had lower pulsatility indexes in the ophthalmic artery in case of reversed flow, lower cerebral CO2 reactivity, and lower cerebropetal blood flow than patients without VSR. On follow-up (mean, 29 months), clinically manifest chronic ocular ischemia developed in 4 patients (annual rate, 1.5%; 95% CI, 0.4 to 3.8); it tended to occur more often in patients in whom VSR was present at study entry (relative risk, 7.3; 95% CI, 0.8 to 68). Conclusions— One third of patients with symptomatic CAO has VSR on ophthalmoscopy. VSR is associated with an impaired flow state of the brain. Development of clinically manifest chronic ocular ischemia is rare.
A Comprehensive Framework for the Application of Process Mining in Risk Management and Compliance Checking

As process-aware information systems are becoming omnipresent in contemporary organizations, the requirements for risk management and compliance checking have evolved and demand a more process-centered approach. The business events recorded by these information systems are systematically and securely logged, which results in a wide variety of opportunities to evaluate dynamic or multi-state process properties. Process mining research has proposed a spectrum of techniques for analyzing the functional, control-flow, organizational and data perspective of the business processes. The framework presented in this paper structures the relationship between the process mining techniques, the organization's stakeholders with a control function and their activities. Focus will be placed on proposing a process-oriented approach that enables a timely analysis of large amount of event data and provides a high process deviation detection effectiveness. Additionally, in this contribution we analyze the optimal settings for the process mining techniques and provide suggestions for further adapting the techniques to the specific needs of risk management and compliance checking. The applicability of the framework is tested and evaluated.
HPL-PD Architecture Specification:Version 1.1

instruction-level parallelism, parametric architecture, EPIC, VLIW, superscalar, speculative execution, predicated execution, programmatic cache control, run-time memory disambiguation, branch architecture HPL-PD is a parametric processor architecture conceived for research in instruction-level parallelism (ILP). Its main purpose is to serve as a vehicle to investigate processor architectures having significant parallelism and to investigate the compiler technology needed to effectively exploit such architectures. The architecture is parametric in that it admits machines of different composition and scale, especially with respect to the nature and amount of parallelism offered. The architecture admits EPIC, VLIW and superscalar implementations so as to provide a basis for understanding the merits and demerits of these different styles of implementation. This report describes those parts of the architecture that are common to all machines in the family. It introduces the basic concepts such as the structure of an instruction, instruction execution semantics, the types of register files, etc. and describes the semantics of the operation repertoire.
Large deviation inequalities for sums of indicator variables

A survey is given of some Chernoff type bounds for the tail probabilities P(X-EX > a) and P(X-EX < a) when X is a random variable that can be written as a sum of indicator variables that are either independent or negatively related. Most bounds are previously known and some comparisons are made. This paper was written in 1994, but was never published because I had overlooked some existing papers containing some of the inequalities. Because of some recent interest in one of the inequalities, which does not seem to be published anywhere else, it has now been lightly edited and made available here.
“I Like My Peeps”: Diversifying the Net Generation's Digital Leisure

ABSTRACT The current generation of adolescents is the first to have grown up with the widespread use of the internet as part of their everyday lives; they are the Net Generation. To diversify existing research on this generation's digital practices, this study explored the intersectional experiences of diverse immigrant adolescent girls' digital leisure. Conversational interviews with nine girls revealed that they encountered numerous interpersonal leisure constraints following their immigration to Canada. Within their digital leisure, girls were able to negotiate these constraints through online connections with family and friends back home, Canadian friends, and the global village. These online connections facilitated an expansion of social boundaries and communication with both familiar and broad networks to maintain and develop relationships, pursue interests, share culture, and resist limiting gendered norms with the unparalleled interactivity and sociability of digital leisure.
Reducing salt in bread: a quasi-experimental feasibility study in a bakery in Lima, Peru

Abstract Objectives To explore salt content in bread and to evaluate the feasibility of reducing salt contained in ‘pan francés’ bread. Design The study had two phases. Phase 1, an exploratory phase, involved the estimation of salt contained in bread as well as a triangle taste test to establish the amount of salt to be reduced in ‘pan francés’ bread without detection by consumers. In Phase 2, a quasi-experimental, pre–post intervention study assessed the effects of the introduction of low-salt bread on bakery sales. Setting A municipal bakery in Miraflores, Lima, Peru. Subjects Sixty-five clients of the bakery in Phase 1 of the study; sales to usual costumers in Phase 2. Results On average, there was 1·25 g of salt per 100 g of bread. Sixty-five consumers were enrolled in the triangle taste test: fifty-four (83·1 %) females, mean age 58·9 (sd 13·7) years. Based on taste, bread samples prepared with salt reductions of 10 % (P=0·82) and 20 % (P=0·37) were not discernible from regular bread. The introduction of bread with 20 % of salt reduction, which contained 1 g of salt per 100 g of bread, did not change sales of ‘pan francés’ (P=0·70) or other types of bread (P=0·36). Results were consistent when using different statistical techniques. Conclusions The introduction of bread with a 20 % reduction in salt is feasible without affecting taste or bakery sales. Results suggest that these interventions are easily implementable, with the potential to contribute to larger sodium reduction strategies impacting the population’s cardiovascular health.
Robust con fi dence intervals for autoregressive coe ffi cients near one

We construct outlier robust confidence sets for autoregressive roots near unity. There are a few difficulties in doing this the asymptotics for robust methods generally involve several poorly estimated nuisance parameters, and robust procedures are more difficult to compute than least squares based methods. We propose a family of “aligned” robust procedures that eliminate the need to estimate some of the nuisance parameters. The procedures are computationally no more burdensome than least squares. In thick-tailed data the robust sets outperform those based on normality.