Miracle-dz/UniFAR-FTUs huggingface dataset:
TRPM8-independent Menthol-induced Ca2+ Release from Endoplasmic Reticulum and Golgi*

Menthol, a secondary alcohol produced by the peppermint herb, Mentha piperita, is widely used in the food and pharmaceutical industries as a cooling/soothing compound and odorant. It induces Ca2+ influx in a subset of sensory neurons from dorsal root and trigeminal ganglia, due to activation of TRPM8, a Ca2+-permeable, cold-activated member of the TRP superfamily of cation channels. Menthol also induces Ca2+ release from intracellular stores in several TRPM8-expressing cell types, which has led to the suggestion that TRPM8 can function as an intracellular Ca2+-release channel. Here we show that menthol induces Ca2+ release from intracellular stores in four widely used cell lines (HEK293, lymph node carcinoma of the prostate (LNCaP), Chinese hamster ovary (CHO), and COS), and provide several lines of evidence indicating that this release pathway is TRPM8-independent: 1) menthol-induced Ca2+ release was potentiated at higher temperatures, which contrasts to the cold activation of TRPM8; 2) overexpression of TRPM8 did not enhance the menthol-induced Ca2+ release; 3) menthol-induced Ca2+ release was mimicked by geraniol and linalool, which are structurally related to menthol, but not by the more potent TRPM8 agonists icilin or eucalyptol; and 4) TRPM8 expression in HEK293 cells was undetectable at the protein and mRNA levels. Moreover, using a novel TRPM8-specific antibody we demonstrate that both heterologously expressed TRPM8 (in HEK293 cells) and endogenous TRPM8 (in LNCaP cells) are mainly localized in the plasma membrane, which contrast to previous localization studies using commercial anti-TRPM8 antibodies. Finally, aequorin-based measurements demonstrate that the TRPM8-independent menthol-induced Ca2+ release originates from both endoplasmic reticulum and Golgi compartments.
Professionals’ views on the roles and needs of family carers of adults with cerebral palsy and complex communication needs in hospital

Abstract Background The aim of this study was to explore the views of hospital and disability service staff on the roles and needs of family carers of adults with cerebral palsy (CP) and complex communication needs (CCN) in hospital. Method We conducted a focus group with six hospital and disability service staff, analysed the content themes of the group discussion, and verified the analysis with participants. Results Participants highlighted the family carers’ expertise and roles in emotional and communication support, advocacy, and providing information. They acknowledged that there is a gap between the ideal of hospital staff being able to provide all necessary care to the patient with CP, and the reality of hospital staff relying upon family carers for their expertise and provision of patient care. Conclusions Hospital and disability staff do not expect family carers to replace the nurse in caring for the patient with CP and CCN in hospital. Nevertheless, family carers provide valuable support in hospital. This includes support with communication, advocacy, protection, information exchange, direct care, and emotional support. Family carers with a high level of expertise in providing care may need support in adapting to the culture of care on the ward and in transferring their roles and expertise in direct care to hospital staff. In addition, they need emotional and practical support through the stressful experience of having a family member hospitalised.
A discrete element 3' of human immunodeficiency virus 1 (HIV-1) and HIV-2 mRNA initiation sites mediates transcriptional activation by an HIV trans activator

An important point of regulation in the reproductive growth and latency of the human and simian immunodeficiency viruses (HIV and SIV, respectively) is provided by virally encoded trans-activators (tat), proteins capable of dramatically increasing viral gene expression. The mechanism of this autostimulatory pathway has remained unclear, however, with substantial effects having been reported at the level of either mRNA accumulation, translational efficiency, or both. Our previous findings indicated that trans-activation results primarily from induction of RNA levels but could not distinguish between the roles of transcriptional rate, RNA stabilization, and RNA transport in this event. In addition, the boundaries of tat-responding elements, which would be valuable in elucidating the mode of tat action, are not precisely known. In this study, HIV-1 and HIV-2 long terminal repeat-directed expression was characterized by using an in vitro nuclear transcription assay to clarify this mechanism, and a detailed mutational analysis was undertaken to localize precisely the sequences participating in this process. Two key findings were revealed: an increased transcription rate was the primary event in tat-mediated activation of HIV-1 and HIV-2, and trans-activation was impaired by mutations in two regions, the TATA box and sequences between +19 to +42, a region lacking enhancer activity. These results implicate a discrete 3' regulatory element in the transcriptional activation of the HIVs.
Changes in perceived pain severity following interdisciplinary treatment for chronic pain.

BACKGROUND There is good support for the effectiveness of interdisciplinary chronic pain management programs in improving functional outcomes; however, relatively little is known about patients who report deterioration following participation in such programs. OBJECTIVES The present retrospective study investigated patients' reports of increased pain severity during participation in a cognitive-behaviourally oriented, outpatient treatment for chronic pain. METHODS Participants (n=280) completed a four-week, group-based, interdisciplinary chronic pain self-management program at a rehabilitation hospital. They completed pre- and post-treatment questionnaires, which included global change ratings of pain severity and clinically-relevant measures, including pain intensity ratings, functional limitations, pain catastrophizing and self-efficacy. RESULTS Statistically significant pre-post improvements were observed for all study variables. Almost all patients reported global improvement overall. Nevertheless, a subset of patients (n=99) reported increased pain severity on global ratings. These individuals were characterized by lower self-efficacy at baseline. CONCLUSIONS Participants endorsed significant pre- and post-treatment improvements in all domains. Nevertheless, some participants reported deterioration. The findings shed light on variables associated with negative treatment outcomes and have practical applications for interdisciplinary chronic pain management programs.
Influence of design on tourists’ recommendation intention: an exploratory study of fjord cruise boats

ABSTRACT In this article we study the influences of esthetic, functional, and symbolic dimensions of design on attitude toward fjord cruise boats and intention to recommend using the product. Also, we argue for the importance of a product to blend in with the surroundings in which it is used – contextually congruent design. In two studies we find that aesthetic, functional and contextually congruent design has positive influences on attitude toward fjord cruise boats. Designers of fjord cruise boats should develop boats with designs that are congruent with the surroundings in which they will be used.
Organizational Forms in Professional Cycling: An Examination of the Efficiency of the UCI Pro Tour

This paper analyzes the changes induced by the newly introduced UCI Pro Tour on the behavior of racing teams. We develop an oligopolistic model starting from the well-known Cournot framework to analyze why the UCI Pro Tour fails to reach its primary aim, namely to increase overall competition among professional cycling teams. In particular we show that the pattern of non-competitive behavior displayed by race teams is the result of a poorly designed Pro Tour licensing assignment procedure. Empirical findings confirm that teams put forth low effort in a high percentage of tour events, reserving their greatest effort for races organized in their home countries. This less-than-optimal performance pattern is the result of an organizational design that focuses solely on financial requirements and does not include incentives related to race performance. The study concludes with the recommendation that the current “closed league” organizational structure be replaced with a relegation system.
Transitions in replication timing in a 340 kb region of human chromosomal R‐Band 1p36.1

DNA replication is initiated within a few chromosomal bands as normal human fibroblasts enter the S phase (Cohen et al. [1998]: Exp Cell Res. 245:321–329). In the present study, we determined the timing of replication of sequences along a 340 kb region in one of these bands, 1p36.13, an R band on chromosome 1. Within this region, we identified a segment of DNA (approximately 140 kb) that is replicated in the first hour of the S phase and is flanked by segments replicated 1–2 h later. Using a quantitative PCR‐based assay to measure sequence abundance in size‐fractionated (900–1,700 nt) nascent DNA (Giacca et al. [1994]: Proc Natl Acad Sci USA. 91:7119), we mapped two functional origins of replication separated by 54 kb and firing 1 h apart. One origin was found to be functional during the first hour of S and was located within a CpG island associated with a predicted gene of unknown function (Genscan NT_004610.2). The second origin was activated in the second hour of S and was mapped to a CpG island near the promoter of the aldehyde dehydrogenase 4A1 (ALDH4A1) gene. At the opposite end of the early replicating segment, a more gradual change in replication timing was observed within the span of approximately 100 kb. These data suggest that DNA replication in adjacent segments of band 1p36.13 is organized differently, perhaps in terms of replicon number and length, or rate of fork progression. In the transition areas that mark the boundaries between different temporal domains, the replication forks initiated in the early replicated region are likely to pause or delay progression before replication of the 340 kb contig is completed. © 2004 Wiley‐Liss, Inc.
Treatment of brain metastases of small-cell lung cancer: comparing teniposide and teniposide with whole-brain radiotherapy--a phase III study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group.

PURPOSE Approximately 60% of patients with small-cell lung cancer (SCLC) develop brain metastases. Whole-brain radiotherapy (WBRT) gives symptomatic improvement in more than 50% of these patients. Because brain metastases are a sign of systemic progression, and chemotherapy was found to be effective as well, it becomes questionable whether WBRT is the only appropriate therapy in this situation. PATIENTS AND METHODS In a phase III study, SCLC patients with brain metastases were randomized to receive teniposide with or without WBRT. Teniposide 120 mg/m(2) was given intravenously three times a week, every 3 weeks. WBRT (10 fractions of 3 Gy) had to start within 3 weeks from the start of chemotherapy. Response was measured clinically and by computed tomography of the brain. RESULTS One hundred twenty eligible patients were randomized. A 57% response rate was seen in the combined-modality arm (95% confidence interval [CI], 43% to 69%), and a 22% response rate was seen in the teniposide-alone arm (95% CI, 12% to 34%) (P<.001). Time to progression in the brain was longer in the combined-modality group (P=.005). Clinical response and response outside the brain were not different. The median survival time was 3.5 months in the combined-modality arm and 3.2 months in the teniposide-alone arm. Overall survival in both groups was not different (P=.087). CONCLUSION Adding WBRT to teniposide results in a much higher response rate of brain metastases and in a longer time to progression of brain metastases than teniposide alone. Survival was poor in both groups and not significantly different.
ATP Induces Protein Arginine Deiminase 2-Dependent Citrullination in Mast Cells through the P2X7 Purinergic Receptor

Posttranslational modifications regulate physiology either by directly modulating protein function or by impacting immune recognition of self-proteins. Citrullination is a posttranslational modification formed by the conversion of arginine residues into the citrulline amino acid by protein arginine deiminase (PAD) family members. We have identified mast cells as a major source of the PAD2 enzyme. Activation of the P2X7 purinergic receptor (P2X7) by the inflammatory “danger” signal ATP induces PAD2 activity and robust protein citrullination. P2X7-mediated activation of PAD2 is sensitive to p38 MAPK and protein kinase C inhibitors, and PAD2 regulates the expression of the TNFR2, Adamts-9, and Rab6b transcripts in mast cells. Further, the PAD2 enzyme and its citrullinated substrate proteins are released from mast cells on activation with ATP. PAD2 expression is closely linked with inflammation in rheumatoid arthritis (RA) synovial tissue, and PAD2 and citrullinated proteins are found in the synovial fluid of RA patients. In addition, RA is associated with the development of autoantibodies to citrullinated self-proteins. Our results suggest that P2X7 activation of mast cells may play a role in inflammation by providing PAD2 and PAD2 substrates access to the extracellular space.
FOOD CHEMISTRY PATENTS INFLUENCE ON PRODUCTIVITY: A CASE STUDY OF A SECTORAL APPROACH IN VARIOUS OECD COUNTRIES

: The effects of Intellectual Property Rights (IPRs) is one of the economic mysteries of the current literature. However, at sectoral-level, it has still failed to provide any obvious empirical evidence regarding any direct link between patents and productivity. The chief contribution of this research paper is to provide empirical evidence on how chemistry patents relate to productivity growth in the case of a low-tech intensive industry (Food, Beverage and Tobacco). In order to support both the theoretical and empirical findings of the literature a dynamic regression model is tested and found a valid representation of the negative relationship between food chemistry patents granted and productivity growth in the long run. Subsequently, some conclusions and policy implications are suggested in order to support the enhanced productivity growth performance of these food industries, highlighting the importance of changes in current property protection systems
Schizophreniform disorder, delusional disorder and psychotic disorder not otherwise specified: clinical features, outcome and familial psychopathology

The relationship between DSM‐III‐R schizophreniform disorder, delusional disorder (DD) and psychotic disorder not otherwise specified (PD‐NOS) and schizophrenia and affective illness (AI) remains uncertain. We explore this question in the Roscommon Family Study by examining symptoms, outcome and patterns of psychopathology in relatives. Probands were selected from a population‐based case registry in the west of Ireland with an ICD‐9 diagnosis of schizophrenia or AI. Personal interviews were conducted with 88% of traceable, living probands, a mean of 16 years after onset, and 86% of traceable, living first‐degree relatives. Best‐estimate diagnoses were made at follow‐up. Schizophreniform disorder, DD and PD‐NOS constituted 6.4%, 2.8% and 7.5%, respectively, of all probands with a registry diagnosis of schizophrenia. Probands with schizophreniform disorder had prominent positive psychotic symptoms, negligible negative symptoms and a good outcome, comparable to that seen in AI probands. Their relatives had an excess risk of schizophrenia spectrum illness but not AI. Probands with DD had prominent delusions but no other psychotic symptoms, few negative symptoms, fair to good outcome and an increased risk in relatives for alcoholism. Probands with PD‐NOS had both moderate positive and negative psychotic symptoms, a poor to fair outcome and a substantially elevated risk in relatives of schizophrenia and schizophrenia spectrum disorders but not AI. These results suggest that i) DSM‐III‐R criteria for schizophreniform disorder define a good outcome disorder with prominent positive psychotic symptoms that probably has a familial relationship to schizophrenia, but not AI; ii) DD is a rare, monosymptomatic psychosis that may have a modest etiologic relationship with alcoholism, but probably not with schizophrenia or AI and iii) PD‐NOS is probably heterogeneous but, of these 3 disorders, most closely resembles schizophrenia with respect to symptoms, outcome and familial psychopathology. These results should be seen as tentative given the small number of probands and relatives evaluated.
Does routine serial computed tomography of the head influence management of traumatic brain injury? A prospective evaluation.

BACKGROUND Computed tomography (CT) of the head is the current standard for diagnosing intracranial pathology following blunt head trauma. It is common practice to repeat the head CT to evaluate any progression of injury. Recent retrospective reviews have challenged the need for serial head CT after traumatic brain injury (TBI). This study intends to prospectively examine the value of routine serial head CT after TBI. METHODS Consecutive adult blunt trauma patients with an abnormal head CT admitted to an urban, Level I trauma center from January 2003 to September 2003 were prospectively studied. Variables collected included: initial head CT results, indication for repeat head CT (routine versus neurologic change), number and results of repeat head CT scans, and clinical interventions following repeat head CT. RESULTS Over the 9-month period, there were 128 patients admitted with an abnormal head CT after sustaining blunt trauma. The 16 patients who died within 24 hours and the 12 patients who went directly to craniotomy were excluded. The remaining 100 patients make up the study population. Abnormal head CT findings were subarachnoid hemorrhage (47%), intraparenchymal hemorrhage (37%), subdural hematoma (28%), contusion (14%), epidural hematoma (11%), intraventricular hemorrhage (3%), and diffuse axonal injury (2%). Overall, 32 patients (32%) had only the admission head CT, while 68 patients (68%) underwent 90 repeat CT scans. Of the repeat head CT scans, 81 (90%) were performed on a routine basis without neurologic change. The remaining 9 (10%) were performed for a change in Glasgow Coma Scale (n = 5), change in intracranial pressure (n = 1), change in Glasgow Coma Scale and intracranial pressure (n = 1), change in pupil size (n = 1), or sudden appearance of a headache (n = 1). Three patients had their care altered after repeat head CT: two underwent craniotomy and one was started on barbiturate therapy. All three patients had their repeat head CT after neurologic change (decrease in Glasgow Coma Scale in 2 and increase in intracranial pressure in 1). CONCLUSIONS Serial head CT is common after TBI. Most repeat head CT scans are performed on a routine basis without neurologic change. Few patients with TBI have their management altered after repeat head CT, and these patients have neurologic deterioration before the repeat head CT. The use of routine serial head CT in patients without neurologic deterioration is not supported by the findings of this study.
Laparoscopic Staging in Gallbladder Cancer

Purpose: Laparoscopy is beneficial in the staging of pancreatic and upper gastrointestinal malignancies but its role in gallbladder cancer has not been investigated. We evaluated the role of laparoscopy in the staging of gallbladder cancer. Methods: From 1989 through 2001, 91 patients with gallbladder cancer, without any evidence of metastatic disease on imaging (ultrasound and/or computed tomographic scan), underwent staging laparoscopy. Peritoneal and surface liver metastases were looked for and assessment of local spread was done if possible. Assessment was based on visual impression and biopsies were not obtained routinely. Results: At laparoscopy, 34 (37%) patients had disseminated disease in the form of liver and/or peritoneal deposits; no further surgery was performed in 29 of these patients while 5 patients underwent surgical bypass procedures. Liver metastases were missed at laparoscopy in 2 patients and were subsequently found at laparotomy. Assessment of the gallbladder mass was possible in 33 (36%) patients, 6 of these were found to have extensive local disease and did not undergo any further surgery. Laparoscopic staging, thus avoided further surgery in 35 (38%) patients. Of the 51 patients without metastatic disease, who underwent laparotomy, 11 were found to have nonresectable locally advanced disease while 1 had liver metastases, which were missed at laparoscopy; 7 underwent bypass procedures only; 21 underwent simple cholecystectomy and extended cholecystectomy was done in 11 patients. The resectability rate (number of resections/operations) in patients undergoing laparoscopic staging was 57% (32/56) as compared with 43% (142/328) in those who did not undergo laparoscopy. Conclusions: Staging laparoscopy in patients with gallbladder cancer detected liver and peritoneal metastases that were missed on imaging. It reduced the number of unnecessary surgical explorations and improved the resectability rate.
Bridging the gap: citizenship diversity and global innovation networks in small and medium size companies

ABSTRACT Recent literature stresses the increasing importance of global innovation networks (GINs) as a mechanism to organize innovation across geographical space. This paper investigates why and to what extent citizenship diversity of the firm's employees relates to the engagement of small and medium size companies in GINs. Citizenship diversity provides knowledge about the institutional context of other countries, increased capabilities to deal with institutional differences, larger social networks to build GINs and a broader search space. Further, the paper examines how the absorptive capacity of firms mediates the relationship between citizenship diversity and GINs. The empirical study is based on a linked employee-employer dataset with 6,771 observations of innovative small and medium size firms in Sweden. It provides strong evidence that the engagement in GINs is positively related to citizenship diversity, depending, however, on the absorptive capacity of firms.
Performance of Decode-and-Forward Cooperative Communications Over Nakagami- Fading Channels

In this paper, we analyze the symbol error rate (SER) performance of decode-and-forward (DF) cooperative communications over Nakagami-m fading channels. For the classical three-node cooperation model, the exact SER expressions for both M phase shift keying (PSK) and M quadrature amplitude modulation (QAM) are derived. For easy usage, we also provide asymptotic approximations for the SER. In the analysis, we first consider the cooperation scenario in which all the channels are uncorrelated. In practice, it may happen that a correlation exists between the source-destination and relay-destination channels, e.g., for user cooperation in the uplink of a cellular network. We then examine the SER in this scenario. In addition, by varying the parameters of the Nakagami-m fading channels in the analytical results, we obtain some perceptions of choosing a good relay for enhancing the cooperation and make clear about how the included Nakagami fading figures and channel variances affect the SER performance. In addition, the optimal power allocation is investigated based on the derived asymptotic SER expressions. Simulations are finally provided to verify the correctness of our analysis.