Miracle-dz/UniFAR-FTUs huggingface dataset:
Essential roles of grp94 in gut homeostasis via chaperoning canonical Wnt pathway

Increasing evidence points to a role for the protein quality control in the endoplasmic reticulum (ER) in maintaining intestinal homeostasis. However, the specific role for general ER chaperones in this process remains unknown. Herein, we report that a major ER heat shock protein grp94 interacts with MesD, a critical chaperone for the Wnt coreceptor low-density lipoprotein receptor-related protein 6 (LRP6). Without grp94, LRP6 fails to export from the ER to the cell surface, resulting in a profound loss of canonical Wnt signaling. The significance of this finding is demonstrated in vivo in that grp94 loss causes a rapid and profound compromise in intestinal homeostasis with gut-intrinsic defect in the proliferation of intestinal crypts, compromise of nuclear β-catenin translocation, loss of crypt-villus structure, and impaired barrier function. Taken together, our work has uncovered the role of grp94 in chaperoning LRP6-MesD in coordinating intestinal homeostasis, placing canonical Wnt-signaling pathway under the direct regulation of the general protein quality control machinery in the ER.
Theoretical Analysis of Sparse Subspace Clustering with Missing Entries

Sparse Subspace Clustering (SSC) is a popular unsupervised machine learning method for clustering data lying close to an unknown union of low-dimensional linear subspaces; a problem with numerous applications in pattern recognition and computer vision. Even though the behavior of SSC for complete data is by now well-understood, little is known about its theoretical properties when applied to data with missing entries. In this paper we give theoretical guarantees for SSC with incomplete data, and analytically establish that projecting the zero-filled data onto the observation pattern of the point being expressed leads to a substantial improvement in performance. The main insight that stems from our analysis is that even though the projection induces additional missing entries, this is counterbalanced by the fact that the projected and zero-filled data are in effect incomplete points associated with the union of the corresponding projected subspaces, with respect to which the point being expressed is complete. The significance of this phenomenon potentially extends to the entire class of self-expressive methods.
Deletion of the GluA1 AMPA receptor subunit alters the expression of short-term memory

Deletion of the GluA1 AMPA receptor subunit selectively impairs short-term memory for spatial locations. We further investigated this deficit by examining memory for discrete nonspatial visual stimuli in an operant chamber. Unconditioned suppression of magazine responding to visual stimuli was measured in wild-type and GluA1 knockout mice. Wild-type mice showed less suppression to a stimulus that had been presented recently than to a stimulus that had not. GluA1 knockout mice, however, showed greater suppression to a recent stimulus than to a nonrecent stimulus. Thus, GluA1 is not necessary for encoding, but affects the way that short-term memory is expressed.
Particulate matter air pollution exposure: role in the development and exacerbation of chronic obstructive pulmonary disease

Due to the rapid urbanization of the world population, a better understanding of the detrimental effects of exposure to urban air pollution on chronic lung disease is necessary. Strong epidemiological evidence suggests that exposure to particulate matter (PM) air pollution causes exacerbations of pre-existing lung conditions, such as, chronic obstructive pulmonary disease (COPD) resulting in increased morbidity and mortality. However, little is known whether a chronic, low-grade exposure to ambient PM can cause the development and progression of COPD. The deposition of PM in the respiratory tract depends predominantly on the size of the particles, with larger particles deposited in the upper and larger airways and smaller particles penetrating deep into the alveolar spaces. Ineffective clearance of this PM from the airways could cause particle retention in lung tissues, resulting in a chronic, low-grade inflammatory response that may be pathogenetically important in both the exacerbation, as well as, the progression of lung disease. This review focuses on the adverse effects of exposure to ambient PM air pollution on the exacerbation, progression, and development of COPD.
Maternal vitamin A supplementation in relation to selected birth defects.

High doses of vitamin A cause birth defects in animals. Concern over vitamin A teratogenicity in humans has been prompted by reports of teratogenic effects of the vitamin A analogue, isotretinoin. The pattern of defects observed among isotretinoin- and vitamin A-exposed infants and animals suggests a possible mechanism involving cranial neural crest cell activity. Data from a case-control study were used to assess maternal use of vitamin A supplements alone and vitamin A-containing multivitamin supplements in relation to the occurrence of certain birth defects involving structures derived, at least in part, from cranial neural crest cells. Cases were 2,658 infants with such defects (primarily craniofacial and cardiac malformations). Controls were 2,609 infants with other malformations. Vitamin A supplementation was defined as daily use for at least 7 days of retinol alone or with vitamin D, or of fish oils. Information on vitamin A dose and nutrition was not available. The mothers of six controls used vitamin A supplements in each of the first three lunar months of pregnancy in comparison to the mothers of 15, 14, and 10 cases in lunar months 1, 2, and 3, respectively. Relative risk estimates and 95% confidence intervals were 2.5(1.0-6.2) for lunar month 1, 2.3(0.9-5.8) for lunar month 2, and 1.6(0.6-4.5) for lunar month 3. These findings should be considered tentative because no dose information was available, small numbers of cases and controls were exposed to vitamin A supplements, and relative risk estimates were not statistically significant. (ABSTRACT TRUNCATED AT 250 WORDS)
2-Line Segment Topology Aggregation Mechanism for QoS Routing

In the distance-vector routing protocols, a node advertises only the best or the most representative path information to its neighbors. Unfortunately, the best path may not be well-defined in a network with two or more constraints. Previous studies have shown that in order not to have any QoS information loss, information of several paths should be advertised. This is not scalable and a line segment representation is developed to aggregate information of several paths. The mechanism solves the scalability problem at the expense of some information accuracy loss. In this paper, we study a variation of the line segment representation aiming at reducing information loss without much increase in advertisement overhead. The performance of our mechanism is justified by extensive simulations
Alarmin S100A8 Activates Alveolar Epithelial Cells in the Context of Acute Lung Injury in a TLR4-Dependent Manner

Alveolar epithelial cells (AECs) are an essential part of the respiratory barrier in lungs for gas exchange and protection against pathogens. Damage to AECs occurs during lung injury and PAMPs/DAMPs have been shown to activate AECs. However, their interplay as well as the mechanism of AECs’ activation especially by the alarmin S100A8/A9 is unknown. Thus, our aim was to study the mechanism of activation of AECs (type I and type II) by S100A8 and/or lipopolysaccharide (LPS) and to understand the role of endogenous S100A8/A9 in neutrophil recruitment in the lung. For our studies, we modified a previous protocol for isolation and culturing of murine AECs. Next, we stimulated the cells with S100A8 and/or LPS and analyzed cytokine/chemokine release. We also analyzed the contribution of the known S100-receptors TLR4 and RAGE in AEC activation. In a murine model of lung injury, we investigated the role of S100A8/A9 in neutrophil recruitment to lungs. S100A8 activates type I and type II cells in a dose- and time-dependent manner which could be quantified by the release of IL-6, KC, and MCP-1. We here clearly demonstrate that AEC s are activated by S100A8 via a TLR4-dependent pathway. Surprisingly, RAGE, albeit mainly expressed in lung tissue, plays no role. Additionally, we show that S100A8/A9 is an essential factor for neutrophil recruitment to lungs. We, therefore, conclude that S100A8 promotes acute lung injury via Toll-like receptor 4-dependent activation of AECs.
Transient responses and adaptation to steady state in a eukaryotic gene regulation system

Understanding the structure and functionality of eukaryotic gene regulation systems is of fundamental importance in many areas of biology. While most recent studies focus on static or short-term properties, measuring the long-term dynamics of these networks under controlled conditions is necessary for their complete characterization. We demonstrate adaptive dynamics in a well-known system of metabolic regulation, the GAL system in the yeast S. cerevisiae. This is a classic model for a eukaryotic genetic switch, induced by galactose and repressed by glucose. We followed the expression of a reporter gfp under a GAL promoter at single-cell resolution in large population of yeast cells. Experiments were conducted for long time scales, several generations, while controlling the environment in continuous culture. This combination enabled us, for the first time, to distinguish between transient responses and steady state. We find that both galactose induction and glucose repression are only transient responses. Over several generations, the system converges to a single robust steady state, independent of external conditions. Thus, at steady state the GAL network loses its hallmark functionality as a sensitive carbon source rheostat. This result suggests that, while short-term dynamics are determined by specific modular responses, over long time scales inter-modular interactions take over and shape a robust steady state response of the regulatory system.
Excalibur: a personalized meta search engine

General purpose Web search engines are becoming ineffective due to the rapid growth and changes in the contents of the World Wide Web. Meta-search engines help a bit by having a better coverage of the WWW. However, users are still overwhelmed by the large amount of irrelevant results returned by a search. A promising approach to tackle the problem is personalized search. Thus the problem of capturing users' personal information need and re-organizing the results has attracted a lot of attention. In this paper, we present a meta-search engine that extracts users' preference implicitly and provides immediate response by re-ranking the results. Re-ranking is done by using the Naive Bayesian classifier and the resemblance measure. Moreover, we show that the users' preference can be succinctly represented by a few keywords.
An Assessment of 30-Day Complications in Primary Cleft Lip Repair: A Review of the 2012 ACS NSQIP Pediatric

Objective The aim of this study is to identify risk factors associated with complications and readmissions following cleft lip repair using the multicenter American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Pediatric. Design Patients undergoing CPT codes 40700, 40701, and 40702 were extracted from the ACS NSQIP Pediatric. Fisher exact, χ2, and rank-sum tests were used to evaluate risk factors. Results Of the 525 patients included, 4.2% had complications, with respiratory complications being the most common. Risk factors included congenital malformations (P = .001), ventilator dependence (P = .002), oxygen support (P = .016), tracheostomy (P = .005), esophageal/gastric/intestinal disease (P = .007), impaired cognitive status (P = .034), acquired central nervous system abnormality (P = .040), nutritional support (P = .001), major and severe cardiac risk factors (P = .011 and P = .005), and an American Society of Anesthesiologists score of 3 (P = .002). In addition, complications were associated with undergoing a one-stage bilateral repair (P = .045) or concomitant ear, nose, and throat procedure (P = .045). The readmission rates for ambulatory patients and inpatients were 2.6% and 4.9% (P = .556), with an overall readmission rate of 4.6%. Ambulatory patients were older (P = .005) and had shorter operative times (P < .001). Conclusions Perioperative complications are low following cleft lip repair, with respiratory complications being the most common. Readmission rates of 4.6% are higher than expected, and insight into predictors of complications will allow surgeons to identify patients who could benefit from additional resources.
Peripheral self-reactivity regulates antigen-specific CD8 T-cell responses and cell division under physiological conditions

T-cell identity is established by the expression of a clonotypic T-cell receptor (TCR), generated by somatic rearrangement of TCRα and β genes. The properties of the TCR determine both the degree of self-reactivity and the repertoire of antigens that can be recognized. For CD8 T cells, the relationship between TCR identity—hence reactivity to self—and effector function(s) remains to be fully understood and has rarely been explored outside of the H-2b haplotype. We measured the affinity of three structurally distinct CD8 T-cell-derived TCRs that recognize the identical H-2 Ld-restricted epitope, derived from the Rop7 protein of Toxoplasma gondii. We used CD8 T cells obtained from mice generated by somatic cell nuclear transfer as the closest approximation of primary T cells with physiological TCR rearrangements and TCR expression levels. First, we demonstrate the common occurrence of secondary rearrangements in endogenously rearranged loci. Furthermore, we characterized and compared the response of Rop7-specific CD8 T-cell clones upon Toxoplasma gondii infection as well as effector function and TCR signalling upon antigenic stimulation in vitro. Antigen-independent TCR cross-linking in vitro uncovered profound intrinsic differences in the effector functions between T-cell clones. Finally, by assessing the degree of self-reactivity and comparing the transcriptomes of naive Rop7 CD8 T cells, we show that lower self-reactivity correlates with lower effector capacity, whereas higher self-reactivity is associated with enhanced effector function as well as cell cycle entry under physiological conditions. Altogether, our data show that potential effector functions and basal proliferation of CD8 T cells are set by self-reactivity thresholds.
Demonstration and Pantomime in the Evolution of Teaching

Donald proposes that early Homo evolved mimesis as a new form of cognition. This article investigates the mimesis hypothesis in relation to the evolution of teaching. The fundamental capacities that distinguish hominin teaching from that of other animals are demonstration and pantomime. A conceptual analysis of the instructional and communicative functions of demonstration and pantomime is presented. Archaeological evidence that demonstration was used for transmitting the Oldowan technology is summarized. It is argued that pantomime develops out of demonstration so that the primary objective of pantomime is that the onlooker learns the motoric patterns shown in the pantomime. The communicative use of pantomime is judged to be secondary. This use of pantomime is also contrasted with other forms of gestures. A key feature of the analysis is that the meaning of a pantomime is characterized by the force patterns of the movements. These force patterns form the core of a model of the cognitive mechanism behind pantomime. Finally, the role of pantomime in the evolution of language is also discussed.
The relationship between depression and quality of life among hemodialysis patients in Chaharmahal and Bakhtiari province in the year 2011

Introduction: Although hemodialysis is therapeutic, it causes numerous physical and psychological tensions, which affect the quality of life of patients. Assessing the quality of life helps to consider clients’ problems; basically, the relationship between depression and quality of life of patients has been observed in this study. Materials and Methods: This was an analytic–descriptive study in which the patients received hemodialysis in Chaharmahal and Bakhtiari province. They were monitored through census method. The data collection instrument was questionnaires consisting of demography, Beck Depression Inventory, and WHO Quality-of-Life Questionnaire. The obtained data was analyzed by SPSS (Version 15) and Mann–Whitney test, Chi-square test, and t-independent test. Results: Ninety-five men and 76 women (171 totally) receiving hemodialysis treatment participated in the study. Chi-square test showed a significant relationship between depression and quality of life of these patients (P < 0.05). Discussion: Considering the present study results, it is essential to take into account depression level and quality of life in planning their care programs.
BRCA1 1675delA and 1135insA Account for One Third of Norwegian Familial Breast-Ovarian Cancer and Are Associated with Later Disease Onset than Less Frequent Mutations

A total of 845 women from breast-ovarian cancer kindreds were enrolled in a clinical follow-up program for early disease diagnosis; 35 women were prospectively identified with cancer. In order to estimate the role of genetic factors for cancer predisposition in this well-defined set of patients, considered as representative for familial breast-ovarian cancer in the Norwegian population, the BRCA1 gene was investigated for germline mutations. The entire coding region of BRCA1 was analysed using a protein truncation test, direct sequencing and a screen for known large genomic deletions and insertions. Twenty one (60%) of the 35 patients were identified as carriers of 11 distinct BRCA1 mutations. Two previously described founder mutations, 1675delA and 1135insA, were found to account for more than half (11/21) of all BRCA1 cases and for almost one third (11/35) of all breast and ovarian cancers. Supported by a previous population-based analysis of these founder mutations in ovarian cancer, our findings suggest that a significant proportion of women at risk for developing inherited breast and ovarian cancer can be identified. This is particularly obvious in certain geographic regions where these founder mutations are prevalent. Women carrying the two founder mutations had a significantly older age of disease onset as compared to women with other BRCA1 mutations. This observation indicates that BRCA mutation penetrance estimates from populations with strong founder effects may be biased. One reason why some deleterious mutations are allowed to prevail in a population may be coupled to penetrance and the fact that they seldom induce disease in women in child-bearing ages. Eleven out of 12 (92%) breast cancers in BRCA1 mutation carriers were estrogen receptor negative, versus 4 out of 9 (44%) in mutation negative patients (p = 0.03). Histopathological characteristics of the prospectively detected cancers indicated an unfavourable prognosis in mutation carriers.
A cross-sectional study on person-centred communication in the care of older people: the COMHOME study protocol

Introduction This paper presents an international cross-sectional study on person-centred communication with older people receiving healthcare (COMHOME). Person-centred care relies on effective communication, but few studies have explored this with a specific focus on older people. The main aim of the COMHOME study is to generate knowledge on person-centred communication with older people (>65 years) in home healthcare services, radiographic and optometric practice. Methods and analysis This study will explore the communication between care providers and older persons in home care services. Home healthcare visits will be audiorecorded (n=500) in Norway, the Netherlands and Sweden. Analyses will be performed with the Verona Coding Definitions for Emotional Sequences (VR-CoDES), the Roter Interaction Analysis System (RIAS) and qualitative methods. The content of the communication, communicative challenging situations as well as empathy, power distance, decision-making, preservation of dignity and respect will be explored. In Norway, an additional 100 encounters, 50 in optometric practice (video recorded) and 50 in radiographic practice (audiorecorded), will be analysed. Furthermore, healthcare providers’ self-reported communication skills, empathy, mindfulness and emotional intelligence in relation to observed person-centred communication skills will be assessed using well-established standardised instruments. Ethics and dissemination Depending on national legislation, approval of either the central ethical committees (eg, nation or university), the national data protection officials or the local ethical committees (eg, units of home healthcare) was obtained. Study findings will be disseminated widely through peer-reviewed publications and conference presentations. The research findings will add knowledge to improve services provided to this vulnerable group of patients. Additionally, the findings will underpin a training programme for healthcare students and care providers focusing on communication with older people.
Canonical correlation to estimate the degree of parkinsonism from local field potential and electroencephalographic signals

In this study, modulation index (MI) features derived from local field potential (LFP) recordings in the sub-thalamic nucleus (STN) and electroencephalographic recordings (EEGs) from the primary motor cortex are shown to correlate with both the overall motor impairment and motor subscores in a monkey model of parkinsonism. The MI features used are measures of phase-amplitude cross frequency coupling (CFC) between frequency sub-bands. We used complex wavelet transforms to extract six spectral sub-bands within the 3-60 Hz range from LFP and EEG signals. Using the method of canonical correlation, we show that weighted combinations of the MI features in LFP or EEG signals correlate significantly with individual and composite scores on a scale for parkinsonian disability.
Genetic Variants of Ehrlichia phagocytophila, Rhode Island and Connecticut

Primers were used to amplify a 561-bp region of the 16S rRNA gene of Ehrlichia phagocytophila from Ixodes scapularis ticks and small mammals collected in Rhode Island and Connecticut. DNA sequences for all 50 E. phagocytophila-positive samples collected from 1996 through 1998 in southwestern Connecticut were identical to the sequence reported for E. phagocytophila DNA from confirmed human cases. In contrast, the sequences from 92 of 123 E. phagocytophila-positive Rhode Island samples collected from 1996 through 1999 included several variants differing by 1-2 nucleotides from that in the agent infecting humans. While 11.9% of 67 E. phagocytophila-positive ticks collected during 1997 in Rhode Island harbored ehrlichiae with sequences identical to that of the human agent, 79.1% had a variant sequence not previously described. The low incidence of human ehrlichiosis in Rhode Island may in part result from interference by these variant ehrlichiae with maintenance and transmission of the true agent of human disease.
The effect of fat on calcium absorption from a mixed meal in normal subjects, patients with malabsorptive disease, and patients with a partial gastrectomy

The absorption of 47Ca Cl2 taken with a milk and porridge meal was measured in normal subjects, patients with a partial gastrectomy, and patients with malabsorption. The addition of palm oil to the meal depressed calcium absorption, whereas the addition of medium-chain triglyceride had no effect. The contrasting effect of the two fats on calcium absorption was most marked in patients with a partial gastrectomy and least marked in patients with malabsorption. In patients with malabsorption, impairment of calcium absorption was most marked in the patients with a significant increase in faecal fat excretion. Absorption of calcium was greater in patients with a partial gastrectomy than in normal subjects.