Miracle-dz/UniFAR-FTUs huggingface dataset:
Developing an integrated biomedical and behavioural theory of functioning and disability: adding models of behaviour to the ICF framework

The International Classification of Functioning Disability and Health (ICF) offers an agreed language on which a scientific model of functional outcomes can be built. The ICF defines functional outcomes as activity and activity limitations (AL) and defines both in behavioural terms. The ICF, therefore, appears to invite explanations of AL as behaviours. Studies of AL find that psychological variables, especially perceptions of control, add to biomedical variables in predicting AL. Therefore, two improved models are proposed, which integrate the ICF with two psychological theories, the theory of planned behaviour (TPB) and social cognitive theory (SCT). These models have a sound evidence base as good predictors of behaviour, include perceived control constructs and are compatible with existing evidence about AL. When directly tested in studies of community and clinic-based populations, both integrated models (ICF/TPB and ICF/SCT) outperform each of the three basic models (ICF, TPB and SCT). However, when predicting activity rather than AL, the biomedical model of the ICF does not improve prediction of activity by TPB and SCT on their own. It is concluded that these models offer a better explanation of functional outcomes than the ICF alone and could form the basis for the development of improved models.
Communication Networks, Externalities and the Price of Information

Information goods (or information for short) play an essential role in modern economies. We consider a trading framework where information has some idiosyncratic value for each consumer, exerts externalities and can be freely replicated and transmitted through links in a communication network. Prices paid for information are determined via the (asymmetric) Nash Bargaining Solution with endogenous disagreement points. This decentralized approach leads to unique prices and payoffs in any exogenous network. We use these payoffs to find connection structures that emerge under different externality regimes in pre-trade network formation stage. An application to citation graphs results in eigenvector-like measures of intellectual influence.
Exploring the Antecedents of Brand Loyalty and Electronic Word of Mouth in Social-Media-Based Brand Communities: Do Gender Differences Matter?

ABSTRACT Recently, social media have emerged as key marketing communication channels. In this context, consumers are increasingly gathering in online communities which have been identified as social-media-based brand communities (SMBBCs). However, notwithstanding scholars' attention towards SMBBCs, the role of consumers' gender in developing brand loyalty intention (BLI) has been scarcely explored by literature. Moreover, scant attention has been given to the analysis of whether gender is related to different propensities towards brand recommendation—identified as a proactive behavior towards a positive electronic word of-mouth diffusion (E-WOM)—in the social media context. Hence, this research aims to explore the antecedents of BLI and E-WOM by focusing on consumers' gender differences. A structural equation model has been created based on 250 surveys collected among SMBBCs of an American sportswear brand. The results showed that male consumers' BLI is influenced by engagement in SMBBCs. Instead, brand trust was the main antecedent of females' BLI.
Phosphorylation of Serine 399 in LKB1 Protein Short Form by Protein Kinase Cζ Is Required for Its Nucleocytoplasmic Transport and Consequent AMP-activated Protein Kinase (AMPK) Activation*

Background: LKB1S activates AMPK despite its lack of Ser-428/431, previously reported as essential for LKB1-mediated activation of AMPK. Results: Ser-399, a novel phosphorylation site in LKB1S, is essential for AMPK activation. Conclusion: Ser-399 is a PKCζ-dependent phosphorylation site similar to Ser-428/431 and likely plays a compensatory role. Significance: This study clarifies paradoxical findings regarding the role of the C terminus in LKB1 signaling. Two splice variants of LKB1 exist: LKB1 long form (LKB1L) and LKB1 short form (LKB1S). In a previous study, we demonstrated that phosphorylation of Ser-428/431 (in LKB1L) by protein kinase Cζ (PKCζ) was essential for LKB1-mediated activation of AMP-activated protein kinase (AMPK) in response to oxidants or metformin. Paradoxically, LKB1S also activates AMPK although it lacks Ser-428/431. Thus, we hypothesized that LKB1S contained additional phosphorylation sites important in AMPK activation. Truncation analysis and site-directed mutagenesis were used to identify putative PKCζ phosphorylation sites in LKB1S. Substitution of Ser-399 to alanine did not alter the activity of LKB1S, but abolished peroxynitrite- and metformin-induced activation of AMPK. Furthermore, the phosphomimetic mutation (S399D) increased the phosphorylation of AMPK and its downstream target phospho-acetyl-coenzyme A carboxylase (ACC). PKCζ-dependent phosphorylation of Ser-399 triggered nucleocytoplasmic translocation of LKB1S in response to metformin or peroxynitrite treatment. This effect was ablated by pharmacological and genetic inhibition of PKCζ, by inhibition of CRM1 activity and by substituting Ser-399 with alanine (S399A). Overexpression of PKCζ up-regulated metformin-mediated phosphorylation of both AMPK (Thr-172) and ACC (Ser-79), but the effect was ablated in the S399A mutant. We conclude that, similar to Ser-428/431 (in LKB1L), Ser-399 (in LKB1S) is a PKCζ-dependent phosphorylation site essential for nucleocytoplasmic export of LKB1S and consequent AMPK activation.
New Approaches to Using Antiretroviral Therapy for the Management of Hiv Infection

Objective To review the changes that have occurred in the past 2 years in the management of HIV infection with antiretroviral agents by contrasting the 1994 with the 1996 Guidelines. Data Sources Conference proceedings, clinical experience of the author and her colleagues, and English-language articles from the body of scientific literature identified via MEDLINE, AIDSLINE, and Current Contents served as data sources. Data Synthesis Current antiretroviral management strategies include movement away from using zidovudine monotherapy, institution of combination antiretroviral therapy earlier in HIV disease, the use of newer agents such as lamivudine, protease inhibitors (i.e., saquinavir, ritonavir, indinavir), and nonnucleoside reverse transcriptase inhibitors (i.e., nevirapine, delavirdine), prevention of vertical transmission with zidovudine, and use of HIV-1 RNA determinations (viral load) to guide the initiation and alteration of antiretroviral therapy. These strategies represent a dramatic change from the 1994 Guideline, which recommended zidovudine monotherapy in nonpregnant and pregnant individuals whose CD4 cell counts were less than 500 cells/mm3, when many of the newer agents were not available and the assays to determine viral load were strictly investigational. Conclusions The difference between the 1994 and 1996 Guidelines is substantial. It is likely that within a year's time, newer information on pathogenesis and antiretroviral agents in development will be known and further management strategies will need to be disseminated. Until then, the International AIDS Society — USA Guidelines for 1996 should be followed as the standard of care.
Is Mortalin a Candidate Gene for T1DM ?

Mortalin has been found to be up-regulated by 2D-protein gel analysis in isolated rodent islets exposed to cytokines. In islets from two rat strains with different sensitivity to the toxic effects of cytokines we observed a significant difference in IL-1β mediated mortalin expression. Constitutive over-expression of rat mortalin in NIH3T3 cells reduced cellular survival in accordance with mortalin being associated to cellular senescence. Hence we consider the gene encoding for mortalin at chromosome 5q31.1 a putative candidate gene in cytokine induced beta-cell destruction. We scanned the human mortalin gene for polymorphisms and identified three novel polymorphisms. Neither the SNPs individually nor as constructed haplotypes showed disease association tested by (E)TDT in a Danish type 1 diabetes (T1DM) population. Furthermore, we tested the D5S500 microsatelite located close to 5q31.1 without finding linkage to (T1DM). In conclusion, the functional data identifying a difference in mortalin expression in IL-1β stimulated islets between two rat strains and over-expression of mortalin in NIH3T3 cells associated with decreased viability suggests a functional role for mortalin in cytokine mediated beta cell destruction; however, the identified polymorphisms did not reveal any association in the presence of linkage disequilibrium of mortalin to T1DM in the Danish population.
Patients’ beliefs about medicine are associated with early thiopurine discontinuation in patients with inflammatory bowel diseases

Background Patients’ beliefs about medicine may either reflect the necessity for treatment or concerns regarding the treatment. We explored the extent to which these beliefs have an effect on thiopurine metabolite levels and premature discontinuation in patients with inflammatory bowel disease (IBD). Patients and methods Patients enrolled in the ‘Thiopurine response Optimization by Pharmacogenetic testing in Inflammatory Bowel Disease Clinics’ (TOPIC) trial were asked to complete the Beliefs about Medicine Questionnaire (BMQ) 4 weeks after thiopurine initiation. The BMQ measures perceptions about treatment necessity and concerns. On the basis of the necessity and concern scores, patients can be categorized as accepting, ambivalent, indifferent, or skeptical. The thiopurine discontinuation rates for these belief subgroups were compared by Kaplan–Meier curves. Furthermore, clinical response and metabolite levels were compared between the belief subgroups. Results A total of 767 patients with IBD started thiopurine treatment, of whom 576 (75%) completed the BMQ. Patients could be classified as accepting (34%), indifferent (17%), ambivalent (34%), or skeptical (15%). Compared with patients in the accepting group (discontinuation rate 22%), patients with an indifferent (35%; P=0.02), ambivalent (37%; P<0.01), or skeptical belief (54%; P<0.01) had higher thiopurine discontinuation rates. No differences were observed in the steady-state thiopurine metabolite levels between the different belief subgroups. Conclusion Patients with a low perceived treatment necessity or high concerns toward IBD treatment were more likely to discontinue thiopurine treatment prematurely. Extra attention toward these patients might prevent premature discontinuation.
Shear Stress Stimulation of p130 cas Tyrosine Phosphorylation Requires Calcium-dependent c-Src Activation*

Fluid shear stress (flow) modulates endothelial cell function via specific intracellular signaling events. Previously we showed that flow activated ERK1/2 in an integrin-dependent manner (Takahashi, M., and Berk, B. C. (1996) J. Clin. Invest. 98, 2623–2631). p130 Crk-associated substrate (Cas), a putative c-Src substrate, was originally identified as a highly phosphorylated protein that is localized to focal adhesions and acts as an adapter protein. Recent reports have shown that Cas is important in cardiovascular development and actin filament assembly. Flow (shear stress = 12 dynes/cm2) stimulated Cas tyrosine phosphorylation within 1 min in human umbilical vein endothelial cells. Phosphorylation peaked at 5 min (3.5 ± 0.7-fold) and was sustained to 20 min. Tyrosine phosphorylation of Cas was functionally important because flow stimulated association of Cas with Crk in a time- and force-dependent manner. Flow-mediated activation of c-Src, phosphorylation of Cas, and association of Cas with Crk were all inhibited by calcium chelation and pretreatment with the Src family-specific tyrosine kinase inhibitor PP1. To determine the role of c-Src in flow-stimulated phosphorylation of Cas, we transduced cells with adenovirus encoding kinase-inactive Src. Expression of kinase-inactive Src prevented flow-induced Cas tyrosine phosphorylation but not ERK1/2 activation. Calcium-dependent activation of c-Src and tyrosine phosphorylation of Cas defines a new flow-stimulated signal pathway, different from ERK1/2 activation. This pathway may be involved in focal adhesion remodeling and actin filament assembly.
GM‐CSF promotes differentiation of a precursor cell of monocytes and Langerhans‐type dendritic cells from CD34+ haemopoietic progenitor cells

Epithelia‐associated dendritic cells (DC) including Langerhans cells in the skin (LC) are precursors of lymph node located interdigitating DC (iDC). CD1a+ LC are known to be derived from CD34+ haemopoietic progenitor cells (HPC); however, cells of an intermediate differentiation state that are CD34− and CD1a− have not been identified. Monitoring the differentiation pathway of HPC in the presence of GM‐CSF + IL‐4, we observed the emergence of a distinct LC precursor population that was CD33+ CD13+ CD4+ CD38+ CD44+ CD34− CD14− CD1a−. The cells could be separated by FACS due to a unique CD44/CD38 expression pattern or by CD44 expression in conjunction with the SSC profile. It was found that they were similarly generated in the presence of GM‐CSF alone and were detectable in culture for at least a week. Irrespective of being generated in the presence of GM‐CSF + IL‐4 or GM‐CSF alone, CD44/SSC‐sorted precursor cells matured to MHC class II compartments (MIIC) and Birbeck granules (BG) expressing LC, when subsequently cultured in the presence of GM‐CSF + IL‐4. When IL‐4 was omitted, however, the same cells matured to phagocytically active adherent macrophages (MΦ). These culture conditions were associated with a > 4‐fold increase in the concentration of IL‐6 when compared to those used for LC differentiation. The identification of a distinct oligopotent precursor cell population that can deliberately be induced to give rise to BG+ MIIC+ CD1a+ CD14− LC or to adherent CD14+ MΦ further substantiates the close relationship of monocytes and DC and may help to identify its in vivo equivalent.
The DNase of Gammaherpesviruses Impairs Recognition by Virus-Specific CD8+ T Cells through an Additional Host Shutoff Function

ABSTRACT The DNase/alkaline exonuclease (AE) genes are well conserved in all herpesvirus families, but recent studies have shown that the AE proteins of gammaherpesviruses such as Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) exhibit an additional function which shuts down host protein synthesis. One correlate of this additional shutoff function is that levels of cell surface HLA molecules are downregulated, raising the possibility that shutoff/AE genes of gammaherpesviruses might contribute to viral immune evasion. In this study, we show that both BGLF5 (EBV) and SOX (KSHV) shutoff/AE proteins do indeed impair the ability of virus-specific CD8+ T-cell clones to recognize endogenous antigen via HLA class I. Random mutagenesis of the BGLF5 gene enabled us to genetically separate the shutoff and AE functions and to demonstrate that the shutoff function was the critical factor determining whether BGLF5 mutants can impair T-cell recognition. These data provide further evidence that EBV has multiple mechanisms to modulate HLA class I-restricted T-cell responses, thus enabling the virus to replicate and persist in the immune-competent host.
Inverse problems in atmospheric constituent transport

Part I. Principles: 1. Introduction 2. Atmospheric transport and transport models 3. Estimation 4. Time series estimation 5. Observations of atmospheric composition 6. The sources and sinks 7. Problem formulation 8. Ill-conditioning 9. Analysis of model error 10. Green's functions and synthesis inversion 11. Time-stepping inversions 12. Non-linear inversion techniques 13. Experimental design Part II. Recent Applications: 14. Global carbon dioxide 15. Global methane 16. Halocarbons and other global-scale studies 17. Regional inversions 18. Constraining atmospheric transport 19. Conclusions References Appendix A. Notation Appendix B. Numerical data Appendix C. Abbreviations and acronyms Appendix D. Glossary Appendix E. Data source acknowledgements Problems.
Discovery of signature genes in gastric cancer associated with prognosis.

Gene expression profiles of gastric cancer (GC) were analyzed with bioinformatics tools to identify signature genes associated with prognosis. Four gene expression data sets (accession number: GSE2685, GSE30727, GSE38932 and GSE26253) were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were screened out using significance analysis of microarrays (SAM) algorithm. P-value 1 were set as the threshold. A co-expression network was constructed for the GC-related genes with package WGCNA of R. Modules were disclosed with WGCNA algorithm. Survival-related signature genes were screened out via COX single-variable regression.A total of 3210 GC-related genes were identified from the 3 data sets. Significantly enriched GO biological process terms included cell death, cell proliferation, apoptosis, response to hormone and phosphorylation. Pathways like viral carcinogenesis, metabolism, EBV viral infection, and PI3K-AKT signaling pathway were significantly over-represented in the DEGs. A gene co-expression network including 2414 genes was constructed, from which 7 modules were revealed. A total of 17 genes were identified as signature genes, such as DAB2, ALDH2, CD58, CITED2, BNIP3L, SLC43A2, FAU and COL5A1.Many signature genes associated with prognosis of GC were identified in present study, some of which have been implicated in the pathogenesis of GC. These findings could not only improve the knowledge about GC, but also provide clues for clinical treatments.
A hybrid encryption model for secure cloud computing

Cloud computing provides a convenient way of content trading and sharing. In this paper, we proposed a secure encryption scheme using advanced encryption standard and fully homomorphic encryption in cloud computing. Firstly, this paper will provide current solutions that are available using encryption technology scheme such as asymmetric and symmetric encryption schemes in cloud computing. The solutions will be analyzed and scrutinized based on their features and limitations. Secondly, from the limitations that are available in current solutions, new algorithm provides comprehensive detail on how encryption method can protect user's confidentiality, integrity and privacy from hackers, malware attack and unauthorized users has proposed. Lastly, the model will be test in the cloud environment, compare the result with previous solutions and evaluate the findings. The analysis and comparison results indicate that the proposed scheme has high efficiency and security.
Willingness to pay for alternative policies for patients with Alzheimer’s Disease

Abstract This paper focuses on eliciting the willingness to pay (WTP) for policy measures aimed at improving the health care offered to patients suffering from Alzheimer’s disease (AD). We utilize a discrete choice experiment (DCE) approach for the elicitation of the preferences of the general population for three alternative policies: home care, day care centres, and medium or long-stay centres. The results show that these policies are significantly valued across the surveyed population. The monthly WTP per hour of home care is estimated as €4 per individual, while the monthly WTP values for full population coverage in day centres and medium–long-stay centres are estimated as €0.43 and €0.42 respectively. We compare the results of classical and Bayesian estimation methods, and conclude that the latter provide a better representation of the heterogeneity in the sample. The results are significant for health care, as they enable policymakers to identify the social demand for such services, as well as the relative economic values placed on the alternative policy measures.
The Impact of the REACH II Intervention on Caregivers’ Perceived Health

The primary goal of the current study was to examine the impact of a caregiving support program on caregivers’ perceived health at 6 months following baseline assessment in the Resources for Enhancing Alzheimer’s Caregiver Health II (REACH II) intervention. A composite measure of perceived health was established and incorporated self-rated health, change in self-rated health, and improvement in physical health. A total of 494 participants receiving the REACH II intervention or an education-only intervention were included in this study. Mixed effect linear regression analysis was performed to examine the effect of the intervention and the factors that mediate this relationship. Findings suggest that the enhanced supportive intervention led to significant improvement in caregivers’ overall perceived health at 6 months. This effect remains significant after controlling for positive satisfaction with caregiving. Improving caregivers’ stress and burden while fostering positive rewards and appraisals may provide indirect health benefits and maintain overall health in dementia caregivers.
Exposure to Interpersonal Violence and Socioemotional Adjustment in Economically Disadvantaged Preschoolers

ABSTRACT Focusing specifically on the experiences of economically disadvantaged preschoolers, the relations between interpersonal violence exposure, behavior problems, and social skills were examined in both the home and school settings. In this racially and ethnically diverse sample of preschoolers from poor, urban households (N = 64; 3–6 years old; 56% female), many children (33%) had been exposed to at least 1 type of interpersonal violence, and even more (70%) had been exposed to any type of potentially traumatic event (PTE). Although exposure to interpersonal violence was not directly associated with parent- or teacher-reported behavior problems or social skills, a significant interaction effect was observed between exposure to interpersonal violence and teacher-reported internalizing problems in predicting teacher-reported social skills; specifically, for children with the highest levels of internalizing problems, a positive relation between interpersonal violence exposure and social skills was observed. This indirect effect was observed only in the school setting, whereas children in this high-risk sample appeared to demonstrate resilience in the home setting. Given these high rates of exposure, additional, clinically relevant research is needed to inform interventions for this vulnerable population.