Miracle-dz/UniFAR-FTUs huggingface dataset:
Mixing and matching TREK/TRAAK subunits generate heterodimeric K2P channels with unique properties

Significance Nearly 350 human genes encode ion channels. Posttranscriptional (alternative splicing, editing, and alternative translation initiation) and posttranslational mechanisms (glycosylation, phosphorylation) further increase diversity. For multimeric channels, various heteromeric combinations may raise the number of ion channels to thousands. Here, we show that mixing and matching TWIK1-related K+ (TREK)/Twik-related acid-arachidonic activated K+ channel (TRAAK) subunits generate tens of different channels. Heterodimeric combinations have properties different from those of the corresponding homodimers, including single-channel behavior, regulation by kinases, and sensitivity to pharmacological agents. These results imply that any excitable cell can adjust its response to neurotransmitters by simply modulating the ratio of expressed TREK/TRAAK subunits. These results also imply that heteromerization has to be considered when analyzing in vivo functions of these channels but also when screening new potential therapeutic drugs. The tandem of pore domain in a weak inwardly rectifying K+ channel (Twik)-related acid-arachidonic activated K+ channel (TRAAK) and Twik-related K+ channels (TREK) 1 and TREK2 are active as homodimers gated by stretch, fatty acids, pH, and G protein-coupled receptors. These two-pore domain potassium (K2P) channels are broadly expressed in the nervous system where they control excitability. TREK/TRAAK KO mice display altered phenotypes related to nociception, neuroprotection afforded by polyunsaturated fatty acids, learning and memory, mood control, and sensitivity to general anesthetics. These channels have emerged as promising targets for the development of new classes of anesthetics, analgesics, antidepressants, neuroprotective agents, and drugs against addiction. Here, we show that the TREK1, TREK2, and TRAAK subunits assemble and form active heterodimeric channels with electrophysiological, regulatory, and pharmacological properties different from those of homodimeric channels. Heteromerization occurs between all TREK variants produced by alternative splicing and alternative translation initiation. These results unveil a previously unexpected diversity of K2P channels that will be challenging to analyze in vivo, but which opens new perspectives for the development of clinically relevant drugs.
Integrin-Mediated Signaling Induced by Simian Virus 40 Leads to Transient Uncoupling of Cortical Actin and the Plasma Membrane

Simian Virus 40 (SV40) is a paradigm pathogen with multivalent binding sites for the sphingolipid GM1, via which it induces its endocytosis for infection. Here we report that SV40 also utilizes cell surface integrins to activate signaling networks required for infection, even in the absence of the previously implicated glycosphingolipids. We identify ILK, PDK1, the RhoGAP GRAF1 and RhoA as core nodes of the signaling network activated upon SV40 engagement of integrins. We show that integrin-mediated signaling through host SV40 engagement induces the de-phosphorylation of Ezrin leading to uncoupling of the plasma membrane and cortical actin. Our results provide functional evidence for a mechanism by which SV40 activates signal transduction in human epithelial cells via integrins in the context of clathrin-independent endocytosis.
Energy aware buffer aided cooperative relay selection

In this paper we evaluate an energy-aware relay selection mechanism which exploits channel state information and the availability of buffers at relays to perform flexible relaying based on a backpressure-driven optimization model. This model ensures the maximization of the cell throughput while maintains the stability of backlog queues. Performance evaluation is conducted using a System Level Simulator (SLS) which is fully compliant with IEEE 802.16m and supports various relaying scenarios. The Below Roof Top (BRT) relaying scenario is considered in this work. A holistic and flexible energy framework is implemented to capture the energy consumption of the cellular network nodes. The model maps the RF output power radiated at the antenna elements of each node including relays on the network to the total supply power of the node equipment. Two derivatives of the proposed mechanism, half-duplex and full-duplex are proposed and evaluated. Results of the two derivatives on BRT relaying scenario revealed noticeable increases for both cell throughput and system energy efficiency of the cell-edge users compared to the conventional relaying protocol and the non cooperative scheme.
The Impact of Social Embarrassment on Caregiving Distress in a Multicultural Sample of Caregivers

The purpose of this study was to gauge the impact of social embarrassment on caregivers of Alzheimer's patients. Two hypotheses were tested: First, social embarrassment adds a unique component of distress to caregivers of Alzheimer's patients, controlling for other factors known to cause depression; second, the negativity of the embarrassment varies according to the caregiver's race/ethnicity. Using data from the Alzheimer's Disease Demonstration Grants to States program ( N = 1,183), the caregiver's perceived depression was regressed on culturally situated variables and a set of covariates that included characteristics of both caregiver and care receiver. Results indicate that social embarrassment exerts a substantial effect on caregiver depression, but the effect does not vary meaningfully across cultural groups. In addition to social embarrassment, the health of the caregiver, the certainty of the Alzheimer's diagnosis, and the caregiver's perceived duty to care all uniquely contribute to the caregiver's level of depression.
Dimensions of perceived control: A factor analysis of three measures and an examination of their relation to activity level and mood in a student and cross-cultural patient sample

Abstract This study investigated whether measures of three perceived control (PC) concepts tapped independent dimensions, were invariant to population characteristics of health and culture, were differentially sensitive to health outcomes, and were discriminable from self-report disability. The Multidimensional Health Locus of Control, Generalized Self-efficacy, and Perceived Health Competence (PHC) Scales were administered to 106 Scottish students and 145 Scottish, Spanish and Irish patients, who also completed versions of the Sickness Impact Profile. Principal Components analyses revealed five factors reflecting scale constructions for students and six factors for patients, as PHC items fell on two factors. Disability items fell on a separate factor from all PC items. Results suggest: (a) PC is multidimensional regardless of health and culture; (b) adequate assessment requires multiple PC measures; and (c) it is meaningful to consider PC as a possible influence on disability.
Author ' s personal copy Syntactic processing in the human brain : What we know , what we don ’ t know , and a suggestion for how to proceed

For every claim in the neuroimaging literature about a particular brain region supporting syntactic processing, there exist other claims implicating the target region in different linguistic processes, and, in many cases, in non-linguistic cognitive processes (e.g., Blumstein, 2009). We argue that traditional group analysis methods in neuroimaging may obscure functional specificity because of inter-subject anatomical variability (Fedorenko & Kanwisher, 2009). In Fedorenko, Hsieh, Nieto-Castanon, Whitfield-Gabrieli, and Kanwisher (2010) we presented a functional localizer that allows quick and reliable identification of key language-sensitive regions in each individual brain. This approach enables pooling data from corresponding functional regions across subjects rather than from the same locations in stereotaxic space that may differ functionally due to inter-subject anatomical variability. In the current paper we demonstrate that the individual-subjects functional localization approach is superior to the traditional methods in its ability to distinguish among conditions in a brain region’s response. This ability is at the core of all neuroimaging research and is critical for answering questions of functional specialization (e.g., does a brain region specialize for processing syntactic aspects of the linguistic signal), which is in turn essential for making inferences about the precise computations conducted in each brain region. Based on our results, we argue that supplementing existing methods with an individual-subjects functional localization approach may lead to a clearer picture of the neural basis of syntactic processing, as it has in some other domains, such as high-level vision (e.g., Kanwisher, 2010) and social cognition (e.g., Saxe & Kanwisher, 2003). 2011 Elsevier Inc. All rights reserved.
Filtering of Unnecessary Branch Predictor Lookups for Low-power Processor Architecture

Recently, reducing power consumption for processor has come to constitute one of the defining challenges for processor architecture design. Almost all modern processors are highly pipelined today. To reduce the number of stall cycles due to branches, most processor cores perform dynamic branch prediction at the first pipeline stage. However, since the fetched instruction cannot be identified as a branch at this stage, the dynamic branch predictor, which includes a branch direction predictor and branch target buffer (BTB), is always exercised. Moreover, the dynamic branch predictor is a large array structure. Many works have shown that the dynamic branch predictor dissipates a nontrivial amount of power – averaging to 5-10% of the total processor power [1-4]. The power-hungry nature of the above discourages the portable devices from using the dynamic branch prediction. Nevertheless, dynamic branch prediction is still very attractive to processors for power-miser applications owing to its success in performance improvement. Therefore, low-power issue for dynamic branch prediction becomes a significant research topic. Because branch instructions constitute only a small portion of all executed instructions, most dynamic branch predictor lookups are useless. This work focuses mainly on eliminating these useless branch predictor lookups. The problem of skipping useless branch predictor lookups can be transformed into the problem of locating the next upcoming branch instruction. This work presents a next branch distance collection mechanism to record the number of non-branch instructions between the two adjacent branch
Working Paper Series # 2007-012 The Spatial Hierarchy of Technological Change and Economic Development in Europe

This paper discusses the possibility of a spatial hierarchy of innovation and growth dynamics in Europe. A spatial hierarchy is understood as a geographical clustering of regions, where important differences exist in terms of innovation and growth dynamics between the clusters. The literature on regional growth and innovation is briefly scanned. After this, a database on European regional growth and innovation dynamics is presented. Spatial correlation analysis and spatial principal components analysis are used to explore the possibility of a spatial hierarchy in Europe. The results point to a hierarchy consisting of four groups: South Europe, East Europe, and two groups in West and North Europe. Growth and innovation performance in these clusters is discussed, and some policy conclusions are drawn. UNU-MERIT Working Papers ISSN 1871-9872 Maastricht Economic and social Research and training centre on Innovation and Technology, UNU-MERIT UNU-MERIT Working Papers intend to disseminate preliminary results of research carried out at the Centre to stimulate discussion on the issues raised. This paper was presented at the Kiel workshop Agglomeration and Growth In Knowledge-based Societies, 2021 April 2007, at a seminar at IKE, University of Aalborg, DK, at the Globelics Academy, Lisbon, PT, 2-12 May 2007, and at the EMAEE Conference, 17-19 May 2007 at Manchester Metropolitan University, UK
Compromised trabecular microarchitecture and lower finite element estimates of radius and tibia bone strength in adults with turner syndrome: A cross‐sectional study using high‐resolution–pQCT

Although bone mass appear ample for bone size in Turner syndrome (TS), epidemiological studies have reported an increased risk of fracture in TS. We used high‐resolution peripheral quantitative computed tomography (HR‐pQCT) to measure standard morphological parameters of bone geometry and microarchitecture, as well as estimated bone strength by finite element analysis (FEA) to assess bone characteristics beyond bone mineral density (BMD) that possibly contribute to the increased risk of fracture. Thirty‐two TS patients (median age 35, range 20–61 years) and 32 healthy control subjects (median age 36, range 19–58 years) matched with the TS participants with respect to age and body‐mass index were studied. A full region of interest (ROI) image analysis and a height‐matched ROI analysis adjusting for differences in body height between groups were performed. Mean bone cross‐sectional area was lower in TS patients in radius (−15%) and tibia (−13%) (both p < 0.01) whereas cortical thickness was higher in TS patients in radius (18%, p < 0.01) but not in tibia compared to controls. Cortical porosity was lower in TS patients at both sites (−32% in radius, −36% in tibia, both p < 0.0001). Trabecular integrity was compromised in TS patients with lower bone volume per tissue volume (BV/TV) (−27% in radius, −22% in tibia, both p < 0.0001), trabecular number (−27% in radius, −12% in tibia, both p < 0.05), and higher trabecular spacing (54% in radius, 23% in tibia, both p < 0.01). In the height‐matched ROI analysis, differences remained significant apart from total area at both sites, cortical thickness in radius, and trabecular number in tibia. FEA estimated failure load was lower in TS patients in both radius (−11%) and tibia (−16%) (both p < 0.01) and remained significantly lower in the height‐matched ROI analysis. Conclusively, TS patients had compromised trabecular microarchitecture and lower bone strength at both skeletal sites, which may partly account for the increased risk of fracture observed in these patients. © 2012 American Society for Bone and Mineral Research.
Drug utilization and therapy provision patterns by prescriber types among patients with systemic lupus erythematosus in Korea

Background Systemic lupus erythematosus (SLE) poses a growing challenge for healthcare systems, affecting an increasing number of people in Korea. This study aimed to investigate the prescribing patterns of SLE therapies and to compare common drug regimens prescribed by provider types. Methods Sampled national health insurance claims data in 2015 were used to select eligible SLE patients. Frequency analyses were carried out regarding patient characteristics related to relevant SLE prescriptions. Patient-days were calculated per substance and per drug class and then categorized by provider types. Differences in drug utilization trends among the main types of providers were examined with the chi-square test. Results A total of 2,074 patients with SLE were selected for study inclusion. Systemic corticosteroid therapy was provided for up to 67.9% of patients, frequently in conjunction with other SLE therapies. About 33.2% and 18.7% of steroid users were treated for more than 150 days and 300 days during the study period, respectively. The provider group that most frequently prescribed systemic corticosteroids was dermatologists. Hydroxychloroquine, an antimalarial considered pivotal to SLE management, was prescribed for only 32.4% of patients, predominantly by rheumatologists. Antimalarial therapy was associated with the longest therapy duration (257.7±120.1 days), followed by immunosuppressant therapy (187.0±153.0 days). Prescription rates of antimalarials and immunosuppressants were substantially lower in primary care doctor group and particularly in dermatologist group, compared to rheumatologist group (P-value associated with prescription patterns by provider types was <0.001 for both drug classes). Conclusion The drug utilization patterns among the main provider groups commonly providing care for SLE patients differed significantly depending on their practice areas. The prescription rates of corticosteroids were disproportionately higher among dermatologists. Rheumatologists appeared more cognizant of the importance of providing antimalarial therapy for SLE patients compared to other types of providers.
Craniofacial Variations in a South Dalmatian Population

The aim of the investigation was to determine the mean values of selected craniofacial and gnathometric parameters and to evaluate the distribution of basic craniofacial types and subjects from the south Dalmatian region. The object was to record eventual variations on the basis of comparison with a comparable sample from north Croatia. The investigation was carried out on 100 subjects of both sexes, aged between 18 and 30 years from the south Dalmatian region. The findings for 200 homologous subjects according to sex and age from north Croatia were used for comparison of results. Customary anthropometric procedure was used to measure twelve variables, on the basis of which indexes for the head, face, forehead and palate were calculated. In the examined population, the results showed that according to the head index values mesocephalia predominated, and for the facial index leptoprosopia, while in the north Croatian population, brachycephalia and euriprosopia were most common. The mean value for the head index indicated a lower, wider forehead, and according to palate height index, a high palate was predominate in the subjects from the south Dalmatian region.
A Role of Corazonin Receptor in Larval-Pupal Transition and Pupariation in the Oriental Fruit Fly Bactrocera dorsalis (Hendel) (Diptera: Tephritidae)

Corazonin (Crz) is a neuropeptide hormone, but also a neuropeptide modulator that is internally released within the CNS, and it has a widespread distribution in insects with diverse physiological functions. Here, we identified and cloned the cDNAs of Bactrocera dorsalis that encode Crz and its receptor CrzR. Mature BdCrz has 11 residues with a unique Ser11 substitution (instead of the typical Asn) and a His in the evolutionary variable position 7. The BdCrzR cDNA encodes a putative protein of 608 amino acids with 7 putative transmembrane domains, typical for the structure of G-protein-coupled receptors. When expressed in Chinese hamster ovary (CHO) cells, the BdCrzR exhibited a high sensitivity and selectivity for Crz (EC50 ≈ 52.5 nM). With qPCR, the developmental stage and tissue-specific expression profiles in B. dorsalis demonstrated that both BdCrz and BdCrzR were highly expressed in the larval stage, and BdCrzR peaked in 2-day-old 3rd-instar larvae, suggesting that the BdCrzR may play an important role in the larval-pupal transition behavior. Immunochemical localization confirmed the production of Crz in the central nervous system (CNS), specifically by a group of three neurons in the dorso-lateral protocerebrum and eight pairs of lateral neurons in the ventral nerve cord. qPCR analysis located the BdCrzR in both the CNS and epitracheal gland, containing the Inka cells. Importantly, dsRNA-BdCrzR-mediated gene-silencing caused a delay in larval-pupal transition and pupariation, and this phenomenon agreed with a delayed expression of tyrosine hydroxylase and dopa-decarboxylase genes. We speculate that CrzR-silencing blocked dopamine synthesis, resulting in the inhibition of pupariation and cuticular melanization. Finally, injection of Crz in head-ligated larvae could rescue the effects. These findings provide a new insight into the roles of Crz signaling pathway components in B. dorsalis and support an important role of CrzR in larval-pupal transition and pupariation behavior.
Intragastric and Intranasal Administration of Lactobacillus paracasei NCC2461 Modulates Allergic Airway Inflammation in Mice

Introduction. Preclinical and clinical evidences for a role of oral probiotics in the management of allergic diseases are emerging. Aim. We aimed at testing the immunomodulatory effects of intranasal versus intragastric administration of Lactobacillus paracasei NCC2461 in a mouse model of allergic airway inflammation and the specificity of different probiotics by comparing L. paracasei NCC2461 to Lactobacillus plantarum NCC1107. Methods. L. paracasei NCC2461 or L. plantarum NCC1107 strains were administered either intragastrically (NCC2461) or intranasally (NCC2461 or NCC1107) to OVA-sensitized mice challenged with OVA aerosols. Inflammatory cell recruitment into BALF, eotaxin and IL-5 production in the lungs were measured. Results. Intranasal L. paracasei NCC2461 efficiently protected sensitized mice upon exposure to OVA aerosols in a dose-dependent manner as compared to control mice. Inflammatory cell number, eotaxin and IL-5 were significantly reduced in BALF. Intranasal supplementation of L. paracasei NCC2461 was more potent than intragastric application in limiting the allergic response and possibly linked to an increase in T regulatory cells in the lungs. Finally, intranasal L. plantarum NCC1107 reduced total and eosinophilic lung inflammation, but increased neutrophilia and macrophages infiltration. Conclusion. A concerted selection of intervention schedule, doses, and administration routes (intranasal versus intragastric) may markedly contribute to modulate airway inflammation in a probiotic strain-specific manner.
Toward broader perspectives of young children’s mathematics: Recognizing and comparing Olivia’s beliefs and activity

Little research exists on young children’s beliefs about mathematics, and current research perspectives on early mathematical activity may overlook a great deal of young children’s sophisticated mathematical thinking. We argue this is attributable, in part, to a need for a broader view of what mathematics is, including cultural practices that are mathematical. Thus, this study investigated a young child’s mathematical activity and beliefs prior to school using a framework reflecting a view of mathematics as cultural activity. Through the case study of Olivia, aged 3 and 9 months, we found that her early beliefs about mathematics did not reflect her rich mathematical activity. Although Olivia engaged in a diverse range of mathematical activity (counting, measuring, designing, playing, locating, and explaining), what she believed mathematics to be was constrained to writing numbers and letters. To help young children perceive their own activity as mathematical, we argue there is a need: (a) for researchers, parents, teachers, and teacher educators to recognize the range of mathematics in children’s everyday activities; (b) to explicitly tell children when their activity includes mathematics; and (c) for teacher educators to emphasize the cultural nature of early mathematical experiences and how to capitalize on these experiences.
Hindering Women’s Careers in Academia

This article addresses the role of language abstraction as a means to discriminate female applicants in academic personnel selection. The level of abstraction of 814 judgments, which were drawn from publicly available archival material, was coded. Results reveal that judgments of female applicants were formulated using negative terms at a more abstract level and positive terms at a more concrete level than those of male applicants. Moreover, this gender linguistic discrimination was perpetrated only by male committee members. Further analysis of the use of linguistic category shows that this discrimination was mainly based on the use of negative adjectives. The implications of language abstraction as a subtle means through which women’s academic careers are hindered are discussed.