Miracle-dz/UniFAR-FTUs huggingface dataset:
L . monocytogenes renders cells inert to Ca 2 + signalling via LLO induced depletion of intracellular Ca 2 + stores

Listeriolysin O (LLO), the pore-forming toxin of L. monocytogenes (L.m), is a prototype of the cholesterol dependent cytolysins secreted by several pathogenic and non-pathogenic Gram-positive bacteria. In addition to mediating escape of the bacterium into the cytosol, this toxin is generally believed to be a central player in host-pathogen interactions during L.m infection. LLO triggers influx of Ca into host cells as well as release from intracellular stores. Thus, many of the cellular responses induced by LLO are related to calcium signalling. Interestingly, in this study, we report that prolonged exposure to LLO renders cells resistant to the induction of Ca mobilization upon subsequent stimulations. Cells pre-exposed to LLO, L.m but not to the LLO deficient mutant L.m∆hly were found to be highly refractory to Ca induction in response to receptor mediated stimulation. Such cells also exhibit diminished Ca signals in responses to LLO and thapsigargin. The presented results suggest that this phenomenon is due to depletion of intracellular Ca stores.
GnRH agonists and add‐back therapy: is there a perfect combination?

Gonadotrophin-releasing hormone (GnRH) is a decapeptide, secreted by hypothalamic neurones in a pulsatile fashion. Other hypothalamic neurotransmitters influence its secretion; catecholamines enhance and endogenous opioid peptides inhibit it. GnRH controls the release of luteinising hormone (LH) and follicle stimulating hormone (FSH) fiom the gonadotroph cells of the anterior lobe of the pituitary gland. The pituitary response depends to some extent on the fkquency of the GnRH pulses; pulsatile administration causes a sustained secretion, while continuous infusion inhibits it. GnRH was isolated and characterised in 19711,2; it has a short half-life and is rapidly degraded by endopeptidases. The synthesis of the first GnRH agonist (GnRH-a) in 1 9723 was followed by the development of a whole new class of drugs. GnRH-a are produced by altering the amino acids in positions 6 and/or 10, resulting in compounds with high affinity for the GnRH receptof'~~ and a long half-life due to their resistance to cleavage by endopeptidases6. There is no doubt about the major impact on reproductive endocrinology that followed the introduction of GnRH-a. Their short term use is of proven benefit in assisted reproduction and prior to endometrial resection or ablation. Long term applications range from shrinking fibroids before surgery, to the management of endometriosis, ovarian hyperandrogenism, the premenstrual syndrome, precocious puberty and dysfunctional uterine bleeding. Their use is also reported in the treatment of women with such diverse conditions as hidradenitis suppurativa7, catamenial pneumothorax*, functional bowel disease9, menstrual asthmalo and migraine' I . Many different GnRH-a are available, but there is no evidence that any one is superior. They are rapidly degraded by the gastrointestinal tract and therefore are administered nasally, subcutaneously (daily), or as intramuscular or subcutaneous depot injections (monthly). Many clinicians favour the depot preparations because of the consistency of the endocrine response and greater compliance. The main disadvantages of GnRH-a are secondary to the induced hypo-oestrogenic state, affecting the cardiovascular, skeletal, and urogenital systems while producing vasomotor symptoms. These symptoms and concerns about bone loss initiated the search for additional therapeutic agents to combine with GnRH-a to negate their harmful effects. Hence the evolution of add-back therapy using oestrogens, progestogens or both. Addback therapy aims to counteract the hypo-oestrogenic side effects of GnRH-a without exacerbating the condition for which they are being used, thus introducing the possibility of extended or repeat treatment courses. Despite many trials involving add-back therapy, no regimen has found universal acceptance for the adequate treatment of all gynaecological conditions treated by GnRH-a, which protects against the deleterious effects induced by the pseudo-menopausal state. Similarly, most of the trials have been for a maximum of six months, so that little is known about the effects of prolonged GnRH-a administration.
Implementing cancer pain education for medical students.

PURPOSE The purpose of this study was to develop and pilot a cancer pain education course for medical students, using a structured home hospice visit. DESCRIPTION OF STUDY A 1-hour home hospice visit was presented to 57 senior medical students. The content and objective criteria for the structured home hospice visit were developed by a multidisciplinary group of experts. During a 1-hour interview, students completed a cancer pain history, performed a focused physical examination, and received feedback and teaching regarding the essentials of cancer pain management from the hospice nurse. All students and hospice patients completed a multi-item evaluation questionnaire with a 5-point Likert scale (1=strongly disagree; 5=strongly agree) regarding the structured home hospice visit. RESULTS Most students agreed strongly that the home hospice visit was a positive experience (mean +/- SD 4.8 +/- 0.44) that helped them to understand the management of cancer pain (mean 4.7 +/- 0.46) and opioid-related side effects (mean 4.5 +/- 0.57). Most patients enjoyed visiting with the students (mean 4.90 +/- 0.30), agreed that the visit was not tiring (mean 4.81 +/- 0.51), and felt that they benefited from participating (mean 4.76 +/- 0.54). CLINICAL IMPLICATIONS The authors concluded the following: 1) that medical students benefited from learning about cancer pain assessment and management through the use of a structured home hospice visit; 2) that a structured home hospice visit helped the students to learn the basics of cancer pain management; 3) that patients enjoyed their role as teacher for medical students; and 4) that senior hospice nurses provided excellent instruction for medical students in the management of cancer pain.
A novel immunohistochemical method to estimate cell‐cycle phase distribution in archival tissue: implications for the prediction of outcome in colorectal cancer

An immunohistochemical method for assessing cell‐cycle phase distribution in colorectal resection specimens would enable phase data to be incorporated into diagnostic algorithms for the estimation of prognosis and response to adjuvant chemotherapy in colorectal cancer. In contrast to flow cytometry, an immunohistochemical method would also allow the phase distribution to be examined within morphologically heterogeneous regions of neoplasms. Paraffin sections of normal colon (n = 25), colonic adenoma (n = 15), and colonic adenocarcinoma (n = 30) were analysed by immunohistochemistry using antibodies against markers of cell‐cycle entry, Mcm‐2 and Ki67, and putative markers of the cell‐cycle phase, cyclins D1 and E (putative markers of G1 phase), cyclin A (S phase), cytoplasmic cyclin B1 (G2 phase), and phosphohistone H3 (M phase). The phase specificity of each marker was assessed by examining the degree of co‐expression of adjacent phase markers using double‐antibody fluorescence confocal microscopy and by comparison with flow cytometric analysis performed on adjacent tissue sections. The S‐phase specificity of detectable cyclin A was also assessed in combination with in situ DNA replication using fluorescence confocal microscopy. All cells expressing phase markers co‐expressed Mcm‐2. Adjacent phase markers were not significantly co‐expressed, confirming the relative specificity of these markers in tissue sections of colon. Cell‐cycle phase distribution, calculated by immunohistochemistry, compared well with phase analyses obtained by flow cytometry. No cells expressed cyclin A in the absence of active DNA replication. The S‐phase labelling index, as defined by detectable cyclin A expression, showed a positive correlation with the Mcm‐2 labelling index and increased in the progression from normal colon to adenocarcinoma. In conclusion, a combination of these cell‐cycle phase markers can be used to calculate the distribution of cells throughout each phase of the cell cycle in colorectal tissue sections. Detectable cyclin A can be used as a surrogate marker of S phase and may be of value in predicting prognosis and response to adjuvant therapy. Copyright © 2003 John Wiley & Sons, Ltd.
Complementary Roles of Multiple Nuclear Targeting Signals in the Capsid Proteins of the Parvovirus Minute Virus of Mice during Assembly and Onset of Infection

ABSTRACT This report describes the distribution of conventional nuclear localization sequences (NLS) and of a beta-stranded so-called nuclear localization motif (NLM) in the two proteins (VP1, 82 kDa; VP2, 63 kDa) forming the T=1 icosahedral capsid of the parvovirus minute virus of mice (MVM) and their functions in viral biogenesis and the onset of infection. The approximately 10 VP1 molecules assembled in the MVM particle harbor in its 142-amino-acid (aa) N-terminal-specific region four clusters of basic amino acids, here called BC1 (aa 6 to 10), BC2 (aa 87 to 90), BC3 (aa 109 to 115), and BC4 (aa 126 to 130), that fit consensus NLS and an NLM placed toward the opposite end of the polypeptide (aa 670 to 680) found to be necessary for VP2 nuclear uptake. Deletions and site-directed mutations constructed in an infectious MVM plasmid showed that BC1, BC2, and NLM are cooperative nuclear transport sequences in singly expressed VP1 subunits and that they conferred nuclear targeting competence on the VP1/VP2 oligomers arising in normal infection, while BC3 and BC4 did not display nuclear transport activity. Notably, VP1 proteins mutated at BC1 and -2, and particularly with BC1 to -4 sequences deleted, induced nuclear and cytoplasmic foci of colocalizing conjugated ubiquitin that could be rescued from the ubiquitin-proteasome degradation pathway by the coexpression of VP2 and NS2 isoforms. These results suggest a role for VP2 in viral morphogenesis by assisting cytoplasmic folding of VP1/VP2 subviral complexes, which is further supported by the capacity of NLM-bearing transport-competent VP2 subunits to recruit VP1 into the nuclear capsid assembly pathway regardless of the BC composition. Instead, all four BC sequences, which are located in the interior of the capsid, were absolutely required by the incoming infectious MVM particle for the onset of infection, suggesting either an important conformational change or a disassembly of the coat for nuclear entry of a VP1-associated viral genome. Therefore, the evolutionarily conserved BC sequences and NLM domains provide complementary nuclear transport functions to distinct supramolecular complexes of capsid proteins during the autonomous parvovirus life cycle.
Horizon 2020 and Beyond: On the 5G Operating System for a True Digital Society

The advanced fifth-generation (5G) infrastructure will not only be a sheer evolution of the current network generations but, more significantly, a revolution in the information and communication technology (ICT) field. The 5G technology will efficiently enable new secure, dependable, ultrareliable, and delay-critical services to everyone and everything, such as cognitive objects and cyberphysical systems (CPSs). A fully immersive experience and anything as a service are the primary drivers for a global adoption and market uptake of new technology components, beyond today's client-server model, where the network has been reduced to a mere pipe of bits. The network will become the nervous system of the true digital society and economy. This article gives fundamental insight into how the 5G mobile communications system is being designed to be powerful and, especially, flexible enough, thus meeting the foreseen and unknown traffic scenarios and services requirements. We also present how a massive adoption and exploitation of mobile-edge computing (MEC), software-defined networking (SDN), network functions virtualization (NFV), and services virtualization will make the 5G operating system (OS) feasible and business viable.
Genetic and morphological evidence reveals the existence of a new family, genus and species of Echinorhynchida (Acanthocephala).

Gymnorhadinorhynchus gen. n. is proposed to accommodate its type species, G. decapteri sp. n. , a parasite of the marine fish Decapterus punctatus (Cuvier), caught from the coastal waters of Brazil. Gymnorhadinorhynchus decapteri sp. n. was morphologically most similar to species of two echinorhynchid families, the Rhadinorhynchidae and the Cavisomidae, particularly in the structure of the proboscis and the absence of somatic spines, respectively. This combination of morphological features made it difficult to assign our specimen to an extant family of the Acanthocephala. Therefore, in order to clarify the systematic placement of G. decapteri, a molecular phylogenetic analysis was performed based on the SSU and LSU rDNA and the mitochondrial cox1 gene sequences obtained for the new taxon and other 26 acanthocephalan species. The results of parsimony and maximum likelihood analyses, using individual, combined and concatenated sequence data, consistently indicate that the specimens do not belong to any known family of the Echinorhynchida. Rather, G. decapteri represents a distinct lineage that is closely related to the Transvenidae, but distantly related to both the Rhadinorhynchidae and the Cavisomidae. Gymnorhadinorhynchidae fam. n. is therefore erected. This newly described family can be distinguished from other families of Echinorhynchida by the combination of the following morphological characters: a proboscis cylindrical with 10 rows of 22-26 hooks, dorsoventral differences in proboscis hooks, basal hooks forming a ring and being abruptly larger than anterior hooks, absence of trunk spines and presence of four tubular cement glands. This combination, in addition to several molecular autapomorphies, justifies the erection of a new genus, Gymnorhadinorhynchus gen. n. , in order to accommodate this new species.
Expansion of Antigen-Specific Regulatory T Cells with the Topical Vitamin D Analog Calcipotriol1

1,25-Dihydroxyvitamin D3 is immunosuppressive both in vivo and in vitro. Topical vitamin D analogs such as calcipotriol alter keratinocyte function, but their effects on cutaneous immune responses are less well understood. We demonstrate that exposure of the skin to calcipotriol before transcutaneous immunization with OVA protein and CpG adjuvant prevents Ag-specific CD8+ T cell priming coincident with Langerhans cell depletion in the skin. Immunization through calcipotriol-treated skin induces CD4+CD25+ regulatory T cells (Treg) that prevent subsequent Ag-specific CD8+ T cell proliferation and IFN-γ production. Treg induced by calcipotriol are able to inhibit the induction and the elicitation of protein contact hypersensitivity. Topical calcipotriol treatment also induces RANKL (receptor activator of NF-κB ligand) expression by keratinocytes, a TNF family member involved in modulation of skin dendritic cells. UV light B induces Ag-specific tolerance when it is applied before transcutaneous immunization. We suggest that UV light B-induced tolerance is induced via a vitamin D receptor-dependent mechanism as vitamin D receptor (VDR) knockout mice fail to increase FoxP3+ Treg in their peripheral draining lymph node following irradiation. Additionally, keratinocytes of VDR−/− mice fail to induce RANKL upon UV irradiation or calcipotriol treatment. The in vivo expansion of Ag-specific Treg with the topical application of the vitamin D analog calcipotriol followed by transcutaneous immunization is a simple method to augment functional Ag-specific CD4+CD25+Foxp3+ Treg populations and mimics Ag-specific UV-induced tolerance.
Generic Human Action Recognition from a Single Example

We present a novel human action recognition method based on s pace-time locally adaptive regression kernels and the matrix cosine similari ty measure. The proposed method operates using a singleexample (e.g., short video clip) of an action of interest to fi nd similar matches. It does not require prior knowledge (learning) abo ut actions being sought; and does not require foreground/background segmentation, or any mo tion estimation or tracking. Our method is based on the computation of the so-called local ste ering kernels as space-time descriptors from a query video, which measure the likeness o f a v xel to its surroundings. Salient features are extracted from said descriptors and co mpared against analogous features from the target video. This comparison is done using a matrix generalization of the cosine similarity measure. The algorithm yields a scalar resembla nce volume with each voxel here, indicating the likelihood of similarity between the query v ideo and all cubes in the target video. By employing nonparametric significance tests and no n-maxima suppression, we detect the presence and location of actions similar to the give n query video. High performance is demonstrated on the challenging set of action data (Shech tman and Irani 2007b) indicating successful detection of actions in the presence of fast m otion, different contexts and even when multiple complex actions occur simultaneously within t e field of view of the camera. Further experiments on the Weizmann dataset (Gorelick et al . 2007) and the KTH dataset (Schuldt et al. 2004) for action categorization task demons trate that the proposed method achieves improvement over other (state-of-the-art) algor ithms.
Measure of Clinical Information Technology Adoption

Objectives The objective of this study was to create a new measure for clinical information technology (IT) adoption as a proxy variable of clinical IT use. Methods Healthcare Information and Management Systems Society (HIMSS) data for 2004 were used. The 18 clinical IT applications were analyzed across 3,637 acute care hospitals in the United States. After factor analysis was conducted, the clinical IT adoption score was created and evaluated. Results Basic clinical IT systems, such as laboratory, order communication/results, pharmacy, radiology, and surgery information systems had different adoption patterns from advanced IT systems, such as cardiology, radio picture archiving, and communication, as well as computerized practitioner order-entry. This clinical IT score varied across hospital characteristics. Conclusions Different IT applications have different adoption patterns. In creating a measure of IT use among various IT components in hospitals, the characteristics of each type of system should be reflected. Aggregated IT adoption should be used to explain technology acquisition and utilization in hospitals.
Effect of probiotics on lipid profiles and blood pressure in patients with type 2 diabetes

Background: This meta-analysis aimed to systematically evaluate the effects of probiotics on blood lipid and blood pressure among patients with type 2 diabetes mellitus (T2DM) based on the randomized controlled studies. Methods: PubMed, Cochrane, Embase, Wanfang, China National Knowledge Infrastructure, and VIP database were searched by the index words to identify the qualified randomized control trial. The latest research was done in the January 2017. Mean difference (MD) along with 95% confidence interval (CI) was used to analyze the included outcomes. Results: Ten trials were included at last with 297 patients in the treatment group and 294 patients in the control group. Probiotics significantly decreased the value of total cholesterol (SMD −0.57, 95% CI −0.92 to 0.21), triglyceride (SMD −0.66, 95% CI −0.93 to 0.39), low-density lipoprotein (SMD −0.40, 95% CI −0.79 to 0.01), systolic blood pressure (WMD −5.04, 95% CI −8.8 to 1.20), diastolic blood pressure (SMD −0.39, 95% CI −0.62 to 0.17), fasting blood glucose (FBG) (SMD 3.54, 95% CI 1.94–5.15) compared with the placebo treatment. Apart from this, probiotics could significantly improve the value of high-density lipoprotein (SMD 0.38, 95% CI 0.03–0.73). Conclusion: Probiotics may decrease the indexes of lipid profile, blood pressure, and FBG in patients with T2DM; application of probiotics might be a new method for lipid profiles and blood pressure management in T2DM.
Perceived Information Security Risk as a Function of Probability and Severity

Information security risks are frequently assessed in terms of the probability that a threat will be realized and the severity of the consequences of a realized threat. In methods and manuals, the product of this probability and severity is often thought of as the risk to consider and manage. However, studies of human behavior and intentions in the field of information security suggest that in general, this is not the way security is perceived. In fact, few studies have found an interaction (i.e., a multiplicative relationship) between probability and severity. This paper describes a study where the ratings of risk and the two variables probability and severity were collected on 105 security threats from ten individuals together with information about the respondents’ expertise and cognitive style. These ten individuals do not assess risk as the product of probability and severity, regardless of expertise and cognitive style. Depending on how risk is measured, an additive model explains 54.0% or 38.4% of the variance in risk. If a multiplicative term is added, the mean increased variance is only 1.5% or 2.4%, and for most of the individuals the contribution of the multiplicative term is statistically insignificant.
ANALYZING DUCTILE FRACTURE USING DUAL DILATIONAL CONSTITUTIVE EQUATIONS

— By adopting a suggestion made by Thomason, a new failure criterion for the Gurson-Tvergaard model has been recently introduced by the authors. In this study, a method based on the Gurson-Tvergaard constitutive model and the new failure criterion is applied to the analysis of ductile fracture. The main features of the method are that the material failure is a natural process of the development of Thomason's dual dilational constitutive responses, and the void volume fraction corresponding to the failure by void coalescence is not necessarily a material constant and is not needed to be fitted beforehand. Furthermore, void nucleation parameter(s) can be numerically fitted from experimental tension results. This method has been implemented into the ABAQUS finite element program via a user material subroutine and is applied to the prediction of tension problems conducted by the authors. In the analyses, two strain-controlled void nucleation models have been studied and compared. The void nucleation parameters corresponding to the two models have been calibrated. The crack initiation of both smooth and notched axisymmetric tensile specimens are well predicted by the method. Finally, several critical issues in the analysis of ductile fracture are discussed.