Miracle-dz/UniFAR-FTUs huggingface dataset:
Revealing a shortened version of SecA (SecAN) that conceivably functions as a protein-conducting channel in the bacterial cytoplasmic membrane

During biogenesis, nascent polypeptides of many proteins have to be translocated across biological membranes by relying on specific protein-conducting channels. It remains a great challenge to unequivocally identify the specific membrane-integrated channel proteins that translocate particular client proteins in living cells. In Gram-negative bacteria, proteins destined to the periplasmic compartment or outer membrane are all synthesized in the cytoplasm and have to be translocated across the inner (i.e., the cytoplasmic) membrane. The currently prevailing perception is that all these transmembrane translocations occur by using the same SecY channel on the inner membrane. Nevertheless, this perception, formed largely based on genetic and in vitro studies, has not yet been proved by direct analysis in living cells. Here, mainly via a systematic in vivo protein photo-crosslinking analyses mediated by a genetically incorporated unnatural amino acid, we revealed that, in contrary to the long-held view, nascent polypeptides of β-barrel OMPs are not translocated across the inner membrane via the SecY channel, but through a shortened version of SecA, designated as SecAN, which exists as a membrane-integrated homo-oligomers. Furthermore, we demonstrated that SecAN is most likely part of the supercomplex that we revealed earlier as one which is responsible for the biogenesis of β-barrel OMPs in living cells and spans the cytoplasm, the inner membrane, the periplasm and the outer membrane.
Acute effects of power and resistance exercises on hemodynamic measurements of older women

Purpose The purpose of this study was to compare the acute effects of resistance training (RT) and power training (PT) on the hemodynamic parameters and nitric oxide (NO) bioavailability of older women. Materials and methods A randomized experimental design was used in this study. Twenty-one older women (age: 67.1±4.6 years; body mass index: 28.03±4.9 kg/m2; systolic blood pressure: 135.1±21.1 mmHg) were recruited to participate in this study. Volunteers were randomly allocated into PT, RT, and control session (CS) groups. The PT and RT groups underwent a single session of physical exercise equalized by training volume, characterized by 3 sets of 8–10 repetitions in 8 different exercises. However, RT group performed exercise at a higher intensity (difficult) than PT (moderate) group. On the other hand, concentric contractions were faster in PT group than in RT group. Hemodynamic parameters and saliva samples (for NO quantification) were collected before and during an hour after exercise completion. Results Results demonstrated post-exercise hypotension during 35 minutes in the PT when compared to rest period (P=0.001). In turn, RT showed decreased heart rate and double product (P<0.001) during the whole evaluation period after exercise completion compared with the rest period. NO levels increased in the PT and RT during the whole evaluation period in relation to rest period. However, there were no differences between PT, RT, and CS regarding hemodynamic and NO evaluations. Conclusion Data indicate that an acute session of power and resistance exercise can be effective to cause beneficial changes on hemodynamic parameters and NO levels in older women.
Genetic Determinants of Trabecular and Cortical Volumetric Bone Mineral Densities and Bone Microstructure

Most previous genetic epidemiology studies within the field of osteoporosis have focused on the genetics of the complex trait areal bone mineral density (aBMD), not being able to differentiate genetic determinants of cortical volumetric BMD (vBMD), trabecular vBMD, and bone microstructural traits. The objective of this study was to separately identify genetic determinants of these bone traits as analysed by peripheral quantitative computed tomography (pQCT). Separate GWA meta-analyses for cortical and trabecular vBMDs were performed. The cortical vBMD GWA meta-analysis (n = 5,878) followed by replication (n = 1,052) identified genetic variants in four separate loci reaching genome-wide significance (RANKL, rs1021188, p = 3.6×10−14; LOC285735, rs271170, p = 2.7×10−12; OPG, rs7839059, p = 1.2×10−10; and ESR1/C6orf97, rs6909279, p = 1.1×10−9). The trabecular vBMD GWA meta-analysis (n = 2,500) followed by replication (n = 1,022) identified one locus reaching genome-wide significance (FMN2/GREM2, rs9287237, p = 1.9×10−9). High-resolution pQCT analyses, giving information about bone microstructure, were available in a subset of the GOOD cohort (n = 729). rs1021188 was significantly associated with cortical porosity while rs9287237 was significantly associated with trabecular bone fraction. The genetic variant in the FMN2/GREM2 locus was associated with fracture risk in the MrOS Sweden cohort (HR per extra T allele 0.75, 95% confidence interval 0.60–0.93) and GREM2 expression in human osteoblasts. In conclusion, five genetic loci associated with trabecular or cortical vBMD were identified. Two of these (FMN2/GREM2 and LOC285735) are novel bone-related loci, while the other three have previously been reported to be associated with aBMD. The genetic variants associated with cortical and trabecular bone parameters differed, underscoring the complexity of the genetics of bone parameters. We propose that a genetic variant in the RANKL locus influences cortical vBMD, at least partly, via effects on cortical porosity, and that a genetic variant in the FMN2/GREM2 locus influences GREM2 expression in osteoblasts and thereby trabecular number and thickness as well as fracture risk.
Tests of Analytic Bias in Native Mandarin Speakers and Native Southern Min Speakers

In this study, I did the experiment in two language groups. Groups 1 were the speakers whose first language is Mandarin and Group 2 were speakers whose first language is Southern Min. In the experiment, the subjects had to learn two artificial languages, HH (a vowel agrees with another vowel in height) such as [titi], and HV (a high vowel is followed by a voiced consonant, or a low vowel is followed by a voiceless consonant) such as [tidi]. My goal is twofold. The first goal is to figure out whether HH is learned better than HV due to typological asymmetry. The second goal is to find out whether language-specific phonology such as Mandarin and Southern Min help subjects to learn HH and HV. Mandarin generally has no voicing contrast, but Southern Min has voicing contrast. Both languages have no vowel harmony. The findings showed that Group 1 and 2 learned HH better than HV. However, Group 2 did not learn HV better than Group 1 did. Two implications could be inferred. First, L1 phonology plays no role in learning HH and HV, because Group 2 did not learn HV better than Group 1 did. Second, both groups learned HH better than HV.
Mechanism and regulation of the nonsense-mediated decay pathway

The Nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs harboring premature termination codons (PTCs) but also regulates the abundance of a large number of cellular RNAs. The central role of NMD in the control of gene expression requires the existence of buffering mechanisms that tightly regulate the magnitude of this pathway. Here, we will focus on the mechanism of NMD with an emphasis on the role of RNA helicases in the transition from NMD complexes that recognize a PTC to those that promote mRNA decay. We will also review recent strategies aimed at uncovering novel trans-acting factors and their functional role in the NMD pathway. Finally, we will describe recent progress in the study of the physiological role of the NMD response.
Functional connectivity in the basal ganglia network differentiates PD patients from controls

Objective: To examine functional connectivity within the basal ganglia network (BGN) in a group of cognitively normal patients with early Parkinson disease (PD) on and off medication compared to age- and sex-matched healthy controls (HC), and to validate the findings in a separate cohort of participants with PD. Methods: Participants were scanned with resting-state fMRI (RS-fMRI) at 3T field strength. Resting-state networks were isolated using independent component analysis. A BGN template was derived from 80 elderly HC participants. BGN maps were compared between 19 patients with PD on and off medication in the discovery group and 19 age- and sex-matched controls to identify a threshold for optimal group separation. The threshold was applied to 13 patients with PD (including 5 drug-naive) in the validation group to establish reproducibility of findings. Results: Participants with PD showed reduced functional connectivity with the BGN in a wide range of areas. Administration of medication significantly improved connectivity. Average BGN connectivity differentiated participants with PD from controls with 100% sensitivity and 89.5% specificity. The connectivity threshold was tested on the validation cohort and achieved 85% accuracy. Conclusions: We demonstrate that resting functional connectivity, measured with MRI using an observer-independent method, is reproducibly reduced in the BGN in cognitively intact patients with PD, and increases upon administration of dopaminergic medication. Our results hold promise for RS-fMRI connectivity as a biomarker in early PD. Classification of evidence: This study provides Class III evidence that average connectivity in the BGN as measured by RS-fMRI distinguishes patients with PD from age- and sex-matched controls.
Assembling oppositely charged lock and key responsive colloids: A mesoscale analog of adaptive chemistry

Oppositely charged thermoresponsive particles with complementary geometries are assembled into adaptive colloidal molecules. We have seen a considerable effort in colloid sciences to copy Nature’s successful strategies to fabricate complex functional structures through self-assembly. This includes attempts to design colloidal building blocks and their intermolecular interactions, such as creating the colloidal analogs of directional molecular interactions, molecular recognition, host-guest systems, and specific binding. We show that we can use oppositely charged thermoresponsive particles with complementary shapes, such as spherical and bowl-shaped particles, to implement an externally controllable lock-and-key self-assembly mechanism. The use of tunable electrostatic interactions combined with the temperature-dependent size and shape and van der Waals interactions of these building blocks provides an exquisite control over the selectivity and specificity of the interactions and self-assembly process. The dynamic nature of the mechanism allows for reversibly cycling through various structures that range from weakly structured dense liquids to well-defined molecule-shaped clusters with different configurations through variations in temperature and ionic strength. We link this complex and dynamic self-assembly behavior to the relevant molecular interactions, such as screened Coulomb and van der Waals forces and the geometrical complementarity of the two building blocks, and discuss our findings in the context of the concepts of adaptive chemistry recently introduced to molecular systems.
Racial discrimination and health-promoting vs damaging behaviors among African-American adults

Studies have found relationships between racial discrimination and increased health-damaging behaviors among African-Americans, but have not examined possible concomitant decreased health-promoting behaviors. We explored the role of discrimination in two health-promoting behaviors, consuming ≥ 5 fruits/vegetables daily (FVC) and physical activity (PA), for the first time, and likewise examined discrimination’s contribution to cigarette smoking, among a sample of N = 2118 African-American adults. Results revealed that discrimination contributed positively to smoking and to PA but was unrelated to FVC. These findings suggest that both adaptive and maladaptive health behaviors might be used to cope with the stress of discrimination.
Cognitive prosthetics: an overview to a method of treatment

This paper is the first survey of the cognitive prosthetics field. Neurorehabilitation based on cognitive prosthetics is now reimbursed as a conventional therapy by many national insurance companies. The need for cognitive prosthetics is described in terms of gaps in rehabilitation methods, and a response to managed care limitations on duration of services. A definition is developed from work in the field, and a cognitive prosthesis is distinguished from both electronic aids as well as from conventional computer software. Some key concepts from computer science are reviewed, along with their significance to cognitive prosthetics. Key studies are reviewed, and show the accomplishments of researchers, differences in their orientation, as well as the impact of computer and communications advances over the past decade. There is a discussion of future research. A key problem is the need to make cognitive prosthetics rehabilitation more user friendly to the therapist. This will be necessary if cognitive prosthetics is to gain widespread use in rehabilitation facilities. 1. The need for cognitive prosthetics
Open-label Study of Initial and Repeat Treatment Cycles of Hylan G-F 20 in Patients with Symptomatic Knee Osteoarthritis

Objective: To evaluate the efficacy and safety of initial and repeat treatment with hylan G-F 20 in patients with symptomatic osteoarthritis (OA) of the knee. Methods: A prospective, multicenter, open-label study in adult patients with symptomatic knee OA (Kellgren-Lawrence grades I-III) undergoing repeat (SC group) or initial (IC group) treatment courses (3 x 2 mL of hylan G-F 20 at weekly intervals) was conducted with a maximum follow-up of 26 weeks. Reduction of pain using the Verbal Pain Questionnaire (VPQ) and Patient Global Assessment (PTGA) scores, concomitant pain medications use, and adverse events (AEs) were evaluated. Results: A total of 842 patients were included (SC group, n=314; IC group, n=528), of whom 616 formed the intent-to-treat (ITT) population (SC group, n=235; IC group, n=381). Of the 462 patients with follow-up at week 26, 311 (67.3%) were defined as responders. In the ITT population, VPQ scores decreased significantly at 26 weeks (p<0.001) compared with baseline. VPQ and PTGA scores decreased significantly (p<0.001) from baseline at all time points, without any significant changes in concomitant medication use. Twenty-four treatment-related AEs (TEAEs) were reported in 2.9% of patients, with most being mild or moderate in intensity and resolving without sequelae. Conclusion: Initial and repeat courses of hylan G-F 20 were effective with a favorable safety profile for knee OA. The large patient population and the study’s pragmatic design suggest that these results could be replicated in routine clinical practice.
Information is not a Virus, and Other Consequences of Human Cognitive Limits

The many decisions that people make about what to pay attention to online shape the spread of information in online social networks. Due to the constraints of available time and cognitive resources, the ease of discovery strongly impacts how people allocate their attention to social media content. As a consequence, the position of information in an individual’s social feed, as well as explicit social signals about its popularity, determine whether it will be seen, and the likelihood that it will be shared with followers. Accounting for these cognitive limits simplifies mechanics of information diffusion in online social networks and explains puzzling empirical observations: (i) information generally fails to spread in social media and (ii) highly connected people are less likely to re-share information. Studies of information diffusion on different social media platforms reviewed here suggest that the interplay between human cognitive limits and network structure differentiates the spread of information from other social contagions, such as the spread of a virus through a population.
Word Sense Induction with Closed Frequent Termsets

The article is devoted to the problem of word sense induction. We propose a method for inducing senses from a raw text corpus. The proposed sense induction algorithm (called SenseSearcher, or SnS) is based on closed frequent sets, and as a result, it provides a multilevel sense representation. To a large extent, it is a knowledge‐poor approach, as it does not need any kind of structured knowledge base about senses and there is no deep language knowledge embedded. By discovering a hierarchy of senses, the algorithm enables identifying subsenses (fine‐grained senses). SnS discovers not only frequent (dominating) senses but also infrequent ones (dominated). The method was evaluated in two main areas: lexicography and information retrieval. With the use of the SnS algorithm, we provide a tool able to induce from a textual corpus a structure of senses, with a varying number of granularity levels. In the area of information retrieval, SnS can be used for clustering search result, according to the discovered senses. The experiments have shown that SnS performs better than the methods participating in the SemEval2013 WSI Task 11 competition, and most of the known search result clustering methods.
Resource Legacies of Organic and Conventional Management Differentiate Soil Microbial Carbon Use

Long-term contrasts in agricultural management can shift soil resource availability with potential consequences to microbial carbon (C) use efficiency (CUE) and the fate of C in soils. Isothermal calorimetry was combined with 13C-labeled glucose stable isotope probing (SIP) of 16S rRNA genes to test the hypothesis that organically managed soils would support microbial communities with greater thermodynamic efficiency compared to conventional soils due to a legacy of lower resource availability and a resultant shift toward communities supportive of more oligotrophic taxa. Resource availability was greater in conventionally managed soils, with 3.5 times higher available phosphorus, 5% more nitrate, and 36% more dissolved organic C. The two management systems harbored distinct glucose-utilizing populations of Proteobacteria and Actinobacteria, with a higher Proteobacteria:Actinobacteria ratio (2.4 vs. 0.7) in conventional soils. Organically managed soils also harbored notable activity of Firmicutes. Thermodynamic efficiency indices were similar between soils, indicating that glucose was metabolized at similar energetic cost. However, differentially abundant glucose utilizers in organically managed soils were positively correlated with soil organic matter (SOM) priming and negatively correlated to soil nutrient and carbon availability, respiration, and heat production. These correlation patterns were strongly reversed in the conventionally managed soils indicating clear differentiation of microbial functioning related to soil resource availability. Fresh C addition caused proportionally more priming of SOM decomposition (57 vs. 51%) in organically managed soils likely due to mineralization of organic nutrients to satisfy microbial demands during glucose utilization in these more resource deprived soils. The additional heat released from SOM oxidation may explain the similar community level thermodynamic efficiencies between management systems. Restoring fertility to soils with a legacy of nutrient limitation requires a balanced supply of both nutrients and energy to protect stable SOM from microbial degradation. These results highlight the need to consider managing C for the energy it provides to ıcritical biological processes that underpin soil health.
Experimental and Analytical Evaluation of Available Bandwidth Estimation Tools

In this paper, we present a low cost and flexible testbed to evaluate the performance of available bandwidth estimation tools in a common and controlled environment. In addition, we include a model based on a network of M/M/I queues to have an analytical reference to compare the experiments with. We then utilize the proposed testbed and model to evaluate the performance of Pathload, IGI, and Spruce, three well-known bandwidth estimation tools. Our main results indicate that Pathload is the most accurate tool but the slowest to converge. IGI, on the other hand, is the fastest tool but the least accurate. Spruce is the least intrusive tool with intermediate accuracy and convergence time
Quality and Safety in the Italian Donor Evaluation Process

Background. The shortage of available organs, has increasingly prompted the use of elderly donors, with a consequent growth of possible risk factors. In this context the risk of donor-recipient transmission of infectious or neoplastic pathologies may be considered as a major issue; in each case for each organ potentially available, acceptable quality must be provided and unacceptable risks must be avoided. Methods. We are presenting here the process of risk management followed by the Italian centers. In 2001, the Italian National Transplant Centre created a national commission of experts, with the mission of defining guidelines for the evaluation process of the potential organ donor. As a supplement to these measures, the Italian National Transplant Centre has supported transplant network health workers through ad hoc developed information tools and an expert task force (second opinion) for evaluation of doubtful cases. Results. Starting from the date of guidelines application and second opinion start up, 9519 potential cadaveric donors were reported in Italy. Of these, 1611 presented a neoplastic or infectious risk. Over this period, 4861 donors were used for transplantation, equal to 48.5% of reported donors. Among the 1611 donors, who had been diagnosed at risk, 674 were neoplastic-disease affected donors and 937 infection-disease affected donors. Conclusions. At the European level, several new activities have been recently implemented to increase organ safety. In Italy, new guidelines and actions to ensure organ safety have been implemented. The evaluation of the impact of these actions will be performed in the near future.
A Geometric Perspective on Sparse Filtrations

We present a geometric perspective on sparse filtrations used in topological data analysis. This new perspective leads to much simpler proofs, while also being more general, applying equally to Rips filtrations and Cech filtrations for any convex metric. We also give an algorithm for finding the simplices in such a filtration and prove that the vertex removal can be implemented as a sequence of elementary edge collapses.
Combination Therapy Reduces Self-injurious Behavior in a Chimpanzee (Pan Troglodytes Troglodytes): A Case Report

Self-injurious behavior (SIB) remains a severe and intractable abnormal behavior for nonhuman primates in diverse settings and is a significant concern for veterinarians and behavioral scientists. To date, no single pharmacological, behavioral, social, or environmental intervention method has emerged as a reliable permanent cure for treating SIB in all, or even most, individuals. Implementation and evaluation of a combination therapeutic approach to treating SIB for nonhuman primates is rare. In May 2004, a 25-year-old male chimpanzee with severe SIB (M = 2.09 episodes/day, range = 1–4 episodes/day) underwent intensive behavioral intervention that utilized a combination of techniques. The combination therapy approach entailed the following: (a) pharmacological intervention with a gamma-aminobutyric acid (GABA) analogue to treat suspected HIV-related sensory neuropathic pain, (b) positive reinforcement training, and (c) environmental enrichment, as well as social and environmental modification. The severity of SIB warranted immediate implementation of intensive combination therapy rather than a systematic evaluation of the individual treatment options. The individually tailored, multifaceted combination therapy resulted in the virtual elimination of SIB in this chimpanzee over a 2-year period.