Miracle-dz/UniFAR-FTUs huggingface dataset:
Parental Feeding Attitudes and Styles and Child Body Mass Index: Prospective Analysis of a Gene-Environment Interaction

Background. Parental feeding styles were linked to child weight in cross-sectional studies, which were unable to test the direction of effect. Prospective studies can best establish causal relationships among such variables. Objective. We tested the 2-year stability of parental feeding attitudes and styles and investigated whether these variables predict child body mass index (BMI) z scores 2 years later. We evaluated whether these associations were dependent on children’s predisposition to obesity. Methods. Participants were 57 families enrolled in an Infant Growth Study of children born at high risk or low risk for obesity, on the basis of maternal prepregnancy overweight or leanness. Children were evaluated for weight and height at 3, 5, and 7 years of age. Measures of parental feeding attitudes and styles were ascertained with the Child Feeding Questionnaire at 5 and 7 years of age. Correlation and multiple regression analyses tested whether parental feeding styles at age 5 predicted increased child BMI z scores 2 years later. Results. Parental feeding attitudes and styles were stable for child ages of 5 to 7 years. With respect to feeding attitudes, perceived responsibility at age 5 predicted reduced child BMI z scores at age 7 among low-risk families, whereas child weight concern and perceived child weight predicted increased child BMI z scores among high-risk families. With respect to feeding styles, monitoring predicted reduced child BMI z scores at age 7 among low-risk children. In contrast, restriction predicted higher BMI z scores and pressure to eat predicted reduced BMI z scores among high-risk children. These associations remained significant after controlling for child weight status at age 3. Conclusions. The relationship between parental feeding styles and child BMI z scores depends on child obesity predisposition, suggesting a gene-environment interaction. Among children predisposed to obesity, elevated child weight appears to elicit restrictive feeding practices, which in turn may produce additional weight gain. Parenting guidelines for overweight prevention may benefit from consideration of child characteristics such as vulnerability to obesity and current weight status.
Fast Prolog with an extended general purpose architecture

Most Prolog machines have been based on specialized architectures. The authors' goal is to start with a general-purpose architecture and determine a minimal set of extensions for high-performance Prolog execution. They have developed both the architecture and optimizing compiler simultaneously, drawing on results of previous implementations. They find that most Prolog-specific operations can be done satisfactorily in software; however, there is a crucial set of features that the architecture must support to achieve the best Prolog performance. The emphasis in this study is on the authors' architecture and instruction set. The costs and benefits of the special architectural features and instructions are analyzed. Simulated performance results are presented and indicate a peak compiled Prolog performance of 3.68 million logical inferences per second. <<ETX>>
Loss of Mfn2 results in progressive, retrograde degeneration of dopaminergic neurons in the nigrostriatal circuit

Mitochondria continually undergo fusion and fission, and these dynamic processes play a major role in regulating mitochondrial function. Studies of several genes associated with familial Parkinson's disease (PD) have implicated aberrant mitochondrial dynamics in the disease pathology, but the importance of these processes in dopaminergic neurons remains poorly understood. Because the mitofusins Mfn1 and Mfn2 are essential for mitochondrial fusion, we deleted these genes from a subset of dopaminergic neurons in mice. Loss of Mfn2 results in a movement defect characterized by reduced activity and rearing. In open field tests, Mfn2 mutants show severe, age-dependent motor deficits that can be rescued with L-3,4 dihydroxyphenylalanine. These motor deficits are preceded by the loss of dopaminergic terminals in the striatum. However, the loss of dopaminergic neurons in the midbrain occurs weeks after the onset of these motor and striatal deficits, suggesting a retrograde mode of neurodegeneration. In our conditional knockout strategy, we incorporated a mitochondrially targeted fluorescent reporter to facilitate tracking of mitochondria in the affected neurons. Using an organotypic slice culture system, we detected fragmented mitochondria in the soma and proximal processes of these neurons. In addition, we found markedly reduced mitochondrial mass and transport, which may contribute to the neuronal loss. These effects are specific for Mfn2, as the loss of Mfn1 yielded no corresponding defects in the nigrostriatal circuit. Our findings indicate that perturbations of mitochondrial dynamics can cause nigrostriatal defects and may be a risk factor for the neurodegeneration in PD.
Distinct implications of different BRCA mutations: efficacy of cytotoxic chemotherapy, PARP inhibition and clinical outcome in ovarian cancer

Approximately a fifth of ovarian carcinoma (OC) is associated with inherited germline mutations, most commonly in the DNA repair genes BRCA1 or BRCA2 (BRCA). BRCA1- and BRCA2-associated OCs have historically been described as a single subgroup of OC that displays a distinct set of characteristics termed the “BRCAness” phenotype. The hallmarks of this phenotype are superior clinical outcome and hypersensitivity to platinum-based chemotherapy and poly-(ADP-ribose) polymerase (PARP) inhibitors. However, growing evidence suggests that BRCA1- and BRCA2-associated OCs display distinct characteristics, most notably in long-term patient survival. Furthermore, recent data indicate that the site of BRCA1 mutation is important with regard to platinum and PARP inhibitor sensitivity. Here, we summarize the body of research describing the BRCAness phenotype and highlight the differential implications of different BRCA mutations with regard to clinicopathologic features, therapy sensitivity and clinical outcome in OC.
The role of chemokines in severe malaria: more than meets the eye

SUMMARY Plasmodium falciparum malaria is responsible for over 250 million clinical cases every year worldwide. Severe malaria cases might present with a range of disease syndromes including acute respiratory distress, metabolic acidosis, hypoglycaemia, renal failure, anaemia, pulmonary oedema, cerebral malaria (CM) and placental malaria (PM) in pregnant women. Two main determinants of severe malaria have been identified: sequestration of parasitized red blood cells and strong pro-inflammatory responses. Increasing evidence from human studies and malaria infection animal models revealed the presence of host leucocytes at the site of parasite sequestration in brain blood vessels as well as placental tissue in complicated malaria cases. These observations suggested that apart from secreting cytokines, leucocytes might also contribute to disease by migrating to the site of parasite sequestration thereby exacerbating organ-specific inflammation. This evidence attracted substantial interest in identifying trafficking pathways by which inflammatory leucocytes are recruited to target organs during severe malaria syndromes. Chemo-attractant cytokines or chemokines are the key regulators of leucocyte trafficking and their potential contribution to disease has recently received considerable attention. This review summarizes the main findings to date, investigating the role of chemokines in severe malaria and the implication of these responses for the induction of pathogenesis and immunity to infection.
Adherens junctions: new insight into assembly, modulation and function.

Adherens junctions play pivotal roles in cell and tissue organization and patterning by mediating cell adhesion and cell signaling. These junctions consist of large multiprotein complexes that join the actin cytoskeleton to the plasma membrane to form adhesive contacts between cells or between cells and extracellular matrix. The best-known adherens junction is the zonula adherens (ZA) that forms a belt surrounding the apical pole of epithelial cells. Recent studies in Drosophila have further illuminated the structure of adherens junctions. Scaffolding proteins encoded by the stardust gene are novel components of the Crumbs complex, which plays a critical role in ZA assembly.1-3 The small GTPase Rap1 controls the symmetric re-assembly of the ZA after cell division.4 Finally, the asymmetric distribution of adherens junction material regulates spindle orientation during asymmetric cell division in the sensory organ lineage.
WhoWas: A Platform for Measuring Web Deployments on IaaS Clouds

Public infrastructure-as-a-service (IaaS) clouds such as Amazon EC2 and Microsoft Azure host an increasing number of web services. The dynamic, pay-as-you-go nature of modern IaaS systems enable web services to scale up or down with demand, and only pay for the resources they need. We are unaware, however, of any studies reporting on measurements of the patterns of usage over time in IaaS clouds as seen in practice. We fill this gap, offering a measurement platform that we call WhoWas. Using active, but lightweight, probing, it enables associating web content to public IP addresses on a day-by-day basis. We exercise WhoWas to provide the first measurement study of churn rates in EC2 and Azure, the efficacy of IP blacklists for malicious activity in clouds, the rate of adoption of new web software by public cloud customers, and more.
A MMSE Vector Precoding with Block Diagonalization for Multiuser MIMO Downlink

Block diagonalization (BD) algorithm is a generalization of the channel inversion that converts multiuser multi-input multi-output (MIMO) broadcast channel into single-user MIMO channel without inter-user interference. In this paper, we combine the BD technique with a minimum mean square error vector precoding (MMSE-VP) for achieving further gain in performance with minimal computational overhead. Two key ingredients to make our approach effective are the QR decomposition based block diagonalization and joint optimization of transmitter and receiver parameters in the MMSE sense. In fact, by optimizing precoded signal vector and perturbation vector in the transmitter and receiver jointly, we pursue an optimal balance between the residual interference mitigation and the noise enhancement suppression. From the sum rate analysis as well as the bit error rate simulations (both uncoded and coded cases) in realistic multiuser MIMO downlink, we show that the proposed BD-MVP brings substantial performance gain over existing multiuser MIMO algorithms.
Software reliability analysis with optimal release problems based on hazard rate model for an embedded OSS

An OSS (open source software) system is frequently applied as server use, instead of client use. Especially, embedded OSS systems have been gaining a lot of attention in the embedded system area, i.e., Android, BusyBox, TRON, etc. However, the poor handling of quality problem and customer support prohibit the progress of embedded OSS. Also, it is difficult for developers to assess the reliability and portability of embedded OSS on a single-board computer. We focus on software quality/reliability problems that can prohibit the progress of embedded OSS. In this paper, we propose a method of software reliability assessment based on a hazard rate model for the embedded OSS. In particular, we derive several assessment measures from the model. Also, we analyze actual software failure-occurrence time-interval data to show numerical examples of software reliability assessment for the embedded OSS. Moreover, we discuss the optimal software release problem for the porting-phase based on the total expected software maintenance cost.
Influence of Self‐Efficacy on the Functional Relationship Between Ratings of Perceived Exertion and Exercise Intensity

PURPOSE Rating of perceived exertion (RPE) has been consistently used as a subjective index of exercise intensity for both exercise testing and prescription. Little empirical efforts have been made to determine how psychological factors influence changes in RPE. This study examined the influence of self-efficacy expectations on changes in RPE as a function of exercise intensity. METHODS Participants were 193 sedentary older adults (mean age = 66.7 years) who completed an assessment of exercise self-efficacy and aerobic capacity. RESULTS Analyses indicated that RPE during exercise changed in both a linear and a quadratic manner as intensity increased and that self-efficacy was a predictor of both patterns of change. Those high in self-efficacy maintained a constant rate of change in RPE as exercise intensity increased, whereas less efficacious participants exhibited a slower rate of change in RPE as a function of exercise intensity, with an initial gradual curve at lower intensity and a more dramatic trajectory at higher intensity. CONCLUSIONS Results have important implications for using RPE for exercise prescription in older adults and suggest that exercise self-efficacy is implicated in patterns of RPE change.
Adjuvant modulation of immune responses to tuberculosis subunit vaccines

Mice were immunized with experimental subunit vaccines based on secreted antigens from Mycobacterium tuberculosis in a series of adjuvants, comprising incomplete Freund's adjuvant (IFA), dimethyl dioctadecyl ammoniumbromide (DDA), RIBI adjuvant, Quil-A saponin, and aluminum hydroxide. Immune responses induced by these vaccines were characterized by in vitro culture of primed cells, PCR analysis for cytokine mRNA, detection of specific immunoglobulin G isotypes induced, and monitoring of protective immunity to tuberculosis (TB). The study demonstrated marked differences in the immune responses induced by the different adjuvants and identified both IFA and DDA as efficient adjuvants for a TB subunit vaccine. Aluminum hydroxide, on the other hand, induced a Th2 response which increased the susceptibility of the animals to a subsequent TB challenge. DDA was further coadjuvanted with either the Th1-stimulating polymer poly(I-C) or the cytokines gamma interferon, interleukin 2 (IL-2), and IL-12. The addition of IL-12 was found to amplify a Th1 response in a dose-dependent manner and promoted a protective immune response against a virulent challenge. However, if the initial priming in the presence of IL-12 was followed by two booster injections of vaccine without IL-12, no improvement in long-term efficacy was found. This demonstrates the efficacy of DDA to promote an efficient immune response and suggests that IL-12 may accelerate this development, but not change the final outcome of a full vaccination regime.
An Extract of Pomegranate Fruit and Galangal Rhizome Increases the Numbers of Motile Sperm: A Prospective, Randomised, Controlled, Double-Blinded Trial

Pomegranate fruit (Punica granatum) and galangal (Alpinia galanga) have separately been shown to stimulate spermatogenesis and to increase sperm counts and motility in rodents. Within traditional medicine, pomegranate fruit has long been used to increase fertility, however studies on the effect on spermatogenesis in humans have never been published. With this study we investigated whether oral intake of tablets containing standardised amounts of extract of pomegranate fruit and powder of greater galangal rhizome (Punalpin) would increase the total number of motile spermatozoa. The study was designed as a prospective, randomized, controlled, double-blinded trial. Enrolment was based on the mean total number of motile spermatozoa of two ejaculates. The participants delivered an ejaculate after 4–8 days of tablet intake and two ejaculates just before they stopped taking the tablets. Seventy adult men with a semen quality not meeting the standards for commercial application at Nordic Cryobank, but without azoospermia, were included in the study. Participants were randomized to take tablets containing extract of pomegranate fruit (standardised with respect to punicalagin A+B, punicalin and ellagic acid) and freeze-dried rhizome of greater galangal (standardised with respect to 1′S-1′-acetoxychavicol acetate) or placebo on a daily basis for three months. Sixty-six participants completed the intervention (active treatment: n = 34; placebo: n = 32). After the intervention the total number of motile spermatozoa was increased in participants treated with plant extracts compared with the placebo group (p = 0.026). After three months of active treatment, the average total number of motile sperm increased by 62% (from 23.4 to 37.8 millions), while for the placebo group, the number of motile sperm increased by 20%. Sperm morphology was not affected by the treatment. Our findings may help subfertile men to gain an improved amount of motile ejaculated sperm by taking tablets containing preparations of pomegranate fruit extract and rhizome of greater galangal. Trial Registration ClinicalTrials.gov NCT01357044
Shrinking the Lymphatic Filariasis Map of Ethiopia: Reassessing the Population at Risk through Nationwide Mapping

Background Mapping of lymphatic filariasis (LF) is essential for the delineation of endemic implementation units and determining the population at risk that will be targeted for mass drug administration (MDA). Prior to the current study, only 116 of the 832 woredas (districts) in Ethiopia had been mapped for LF. The aim of this study was to perform a nationwide mapping exercise to determine the number of people that should be targeted for MDA in 2016 when national coverage was anticipated. Methodology/Principal Finding A two-stage cluster purposive sampling was used to conduct a community-based cross-sectional survey for an integrated mapping of LF and podoconiosis, in seven regional states and two city administrations. Two communities in each woreda were purposely selected using the World Health Organization (WHO) mapping strategy for LF based on sampling 100 individuals per community and two purposely selected communities per woreda. Overall, 130 166 people were examined in 1315 communities in 658 woredas. In total, 140 people were found to be positive for circulating LF antigen by immunochromatographic card test (ICT) in 89 communities. Based on WHO guidelines, 75 of the 658 woredas surveyed in the nine regions were found to be endemic for LF with a 2016 projected population of 9 267 410 residing in areas of active disease transmission. Combining these results with other data it is estimated that 11 580 010 people in 112 woredas will be exposed to infection in 2016. Conclusions We have conducted nationwide mapping of LF in Ethiopia and demonstrated that the number of people living in LF endemic areas is 60% lower than current estimates. We also showed that integrated mapping of multiple NTDs is feasible and cost effective and if properly planned, can be quickly achieved at national scale.
Interaction between residues in the Mg2+-binding site regulates BK channel activation

As a unique member of the voltage-gated potassium channel family, a large conductance, voltage- and Ca2+-activated K+ (BK) channel has a large cytosolic domain that serves as the Ca2+ sensor, in addition to a membrane-spanning domain that contains the voltage-sensing (VSD) and pore-gate domains. The conformational changes of the cytosolic domain induced by Ca2+ binding and the conformational changes of the VSD induced by membrane voltage changes trigger the opening of the pore-gate domain. Although some structural information of these individual functional domains is available, how the interactions among these domains, especially the noncovalent interactions, control the dynamic gating process of BK channels is still not clear. Previous studies discovered that intracellular Mg2+ binds to an interdomain binding site consisting of D99 and N172 from the membrane-spanning domain and E374 and E399 from the cytosolic domain. The bound Mg2+ at this narrow interdomain interface activates the BK channel through an electrostatic interaction with a positively charged residue in the VSD. In this study, we investigated the potential interdomain interactions between the Mg2+-coordination residues and their effects on channel gating. By introducing different charges to these residues, we discovered a native interdomain interaction between D99 and E374 that can affect BK channel activation. To understand the underlying mechanism of the interdomain interactions between the Mg2+-coordination residues, we introduced artificial electrostatic interactions between residues 172 and 399 from two different domains. We found that the interdomain interactions between these two positions not only alter the local conformations near the Mg2+-binding site but also change distant conformations including the pore-gate domain, thereby affecting the voltage- and Ca2+-dependent activation of the BK channel. These results illustrate the importance of interdomain interactions to the allosteric gating mechanisms of BK channels.
Protein conformational dynamics in the mechanism of HIV-1 protease catalysis

We have used chemical protein synthesis and advanced physical methods to probe dynamics-function correlations for the HIV-1 protease, an enzyme that has received considerable attention as a target for the treatment of AIDS. Chemical synthesis was used to prepare a series of unique analogues of the HIV-1 protease in which the flexibility of the “flap” structures (residues 37–61 in each monomer of the homodimeric protein molecule) was systematically varied. These analogue enzymes were further studied by X-ray crystallography, NMR relaxation, and pulse-EPR methods, in conjunction with molecular dynamics simulations. We show that conformational isomerization in the flaps is correlated with structural reorganization of residues in the active site, and that it is preorganization of the active site that is a rate-limiting factor in catalysis.
The role of interventional therapy for pleural diseases

Pleural diseases encompass a vast and heterogeneous group of diseases that have traditionally received relatively little attention from researchers, resulting in empiric approaches to patient management based largely on expert opinions and anecdotal evidence. Yet, paradoxically, pleural diseases represent a considerable burden for patients, providers, and the healthcare system as a whole, with a rising incidence of malignant pleural effusions and pleural space infections, in increasingly complex patients. Fortunately, the last decade has witnessed unprecedented research efforts from the pleural community, which have resulted in substantial advances in risk-stratification, patient selection, treatment efficacy and the development of evidence-based recommendations ultimately leading to improved patient care. In this review, we will present a summary of the current evidence for the management of pleural diseases with an emphasis on interventional procedures, and highlight the need for future research efforts in the field of malignant pleural effusions, pleural space infections and pneumothorax.