Integrins as therapeutic targets: lessons and opportunities.

The integrins are a large family of cell adhesion molecules that are essential for the regulation of cell growth and function. The identification of key roles for integrins in a diverse range of diseases, including cancer, infection, thrombosis and autoimmune disorders, has revealed their substantial potential as therapeutic targets. However, so far, pharmacological inhibitors for only three integrins have received marketing approval. This article discusses the structure and function of integrins, their roles in disease and the chequered history of the approved integrin antagonists. Recent advances in the understanding of integrin function, ligand interaction and signalling pathways suggest novel strategies for inhibiting integrin function that could help harness their full potential as therapeutic targets

CSR, co-optation and resistance: the emergence of new agnostic relations between business and civil society

This article examines the theoretical implications of the changing relationships between NGOs and businesses that have emerged as a response to the evolving agenda around CSR and sustainable development. In particular, it focuses upon examining whether greater engagement from non-governmental organisations (NGOs) in this area reflects a process of appropriation and co-optation of protest by the business community. To examine this process, the article considers two forms of appropriation—appropriation of language and appropriation via participation—as a basis for discussion. While co-optation pressures are identified within both areas, the article argues that co-optation is identified almost as an inevitable outcome of engagement without significant consideration of the ability of movements to identify and respond to these processes. In identifying an alternative approach, the article utilises Mouffe’s framework of agonistic pluralism. Mouffe’s framework, it is argued, provides an understanding of the way in which agonistic relationships are emerging between NGOs and businesses while highlighting the continuance of conflict between parties struggling to influence the contested interpretations of responsible business

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Towards neuro-inspired symbolic models of cognition: linking neural dynamics to behaviors through asynchronous communications

A computational architecture modeling the relation between perception and action is proposed. Basic brain processes representing synaptic plasticity are first abstracted through asynchronous communication protocols and implemented as virtual microcircuits. These are used in turn to build mesoscale circuits embodying parallel cognitive processes. Encoding these circuits into symbolic expressions gives finally rise to neuro-inspired programs that are compiled into pseudo-code to be interpreted by a virtual machine. Quantitative evaluation measures are given by the modification of synapse weights over time. This approach is illustrated by models of simple forms of behaviors exhibiting cognition up to the third level of animal awareness. As a potential benefit, symbolic models of emergent psychological mechanisms could lead to the discovery of the learning processes involved in the development of cognition. The executable specifications of an experimental platform allowing for the reproduction of simulated experiments are given in “Appendix”

Parasites and immunotherapy: with or against?

Immunotherapy is a sort of therapy in which antibody or antigen administrates to the patient in order to treat or reduce the severity of complications of disease. This kind of treatment practiced in a wide variety of diseases including infectious diseases, autoimmune disorders, cancers and allergy. Successful and unsuccessful immunotherapeutic strategies have been practiced in variety of parasitic infections. On the other hand parasites or parasite antigens have also been considered for immunotherapy against other diseases such as cancer, asthma and multiple sclerosis. In this paper immunotherapy against common parasitic infections, and also immunotherapy of cancer, asthma and multiple sclerosis with parasites or parasite antigens have been reviewe

Sloan Digital Sky Survey IV: Mapping the Milky Way, Nearby Galaxies, and the Distant Universe

We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

A Systems Biology Approach to Drug Targets in Pseudomonas aeruginosa Biofilm

Antibiotic resistance is an increasing problem in the health care system and we are in a constant race with evolving bacteria. Biofilm-associated growth is thought to play a key role in bacterial adaptability and antibiotic resistance. We employed a systems biology approach to identify candidate drug targets for biofilm-associated bacteria by imitating specific microenvironments found in microbial communities associated with biofilm formation. A previously reconstructed metabolic model of Pseudomonas aeruginosa (PA) was used to study the effect of gene deletion on bacterial growth in planktonic and biofilm-like environmental conditions. A set of 26 genes essential in both conditions was identified. Moreover, these genes have no homology with any human gene. While none of these genes were essential in only one of the conditions, we found condition-dependent genes, which could be used to slow growth specifically in biofilm-associated PA. Furthermore, we performed a double gene deletion study and obtained 17 combinations consisting of 21 different genes, which were conditionally essential. While most of the difference in double essential gene sets could be explained by different medium composition found in biofilm-like and planktonic conditions, we observed a clear effect of changes in oxygen availability on the growth performance. Eight gene pairs were found to be synthetic lethal in oxygen-limited conditions. These gene sets may serve as novel metabolic drug targets to combat particularly biofilm-associated PA. Taken together, this study demonstrates that metabolic modeling of human pathogens can be used to identify oxygen-sensitive drug targets and thus, that this systems biology approach represents a powerful tool to identify novel candidate antibiotic targets

Validity of the Clock Drawing Test in predicting reports of driving problems in the elderly

BACKGROUND: This study examined the use of the Folstein Mini Mental Status Exam (MMSE) and the Clock Drawing Test (CDT) in predicting retrospective reports of driving problems among the elderly. The utility of existing scoring systems for the CDT was also examined. METHODS: Archival chart records of 325 patients of a geriatric outpatient clinic were reviewed, of which 162 had CDT results (including original clock drawings). T-test, correlation, and regression procedures were used to analyze the data. RESULTS: Both CDT and MMSE scores were significantly worse among non-drivers than individuals who were currently or recently driving. Among current or recent drivers, scores on both instruments correlated significantly with the total number of reported accidents or near misses, although the magnitude of the respective correlations was small. Only MMSE scores, however, significantly predicted whether or not any accidents or near misses were reported at all. Neither MMSE nor CDT scores predicted unique variance in the regressions. CONCLUSIONS: The overall results suggest that both the MMSE and CDT have limited utility as potential indicators of driving problems in the elderly. The demonstrated predictive power for these instruments appears to be redundant, such that both appear to assess general cognitive function versus more specific abilities. Furthermore, the lack of robust prediction suggests that neither are sufficient to serve as stand-alone instruments on which to solely base decisions of driving capacity. Rather, individuals who evidence impairment should be provided a more thorough and comprehensive assessment than can be obtained through screening tools

Rheumatoid arthritis, gold therapy, contact allergy and blood cytokines

OBJECTIVE: To study the clinical and biochemical effects of a low starting dose for gold therapy in rheumatoid arthritis patients with a contact allergy to gold. METHODS: Serum cytokines were assayed before and 24 h after the first injection of gold sodium thiomalate (GSTM). RESULTS: Contact allergy to gold was found in 4 of 19 patients. Compared to gold-negative patients (starting dose: 10 mg GSTM), there was a larger increase in serum TNFalpha (p < 0.05), sTNF-R1 (NS), and IL-1 ra (p < 0.05) in gold-allergic patients. CONCLUSIONS: Cytokines are released in blood by GSTM in RA patients with gold allergy. To minimize the risk of acute adverse reactions the starting dose of GSTM should be lowered to 5 mg. Alternatively, patients should be patch-tested before gold therapy; in test-positive cases, 5 mg is recommended as the first dose