Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of the Ocular Hypotensive Response of Serotonin 5-HT1A and 5-HT2 Receptor Ligands in Conscious Ocular Hypertensive Cynomolgus Monkeys

Published investigations of serotonin-1A (5-hydroxytryptamine1A; 5-HT1A) receptor agonists and serotonin-2A (5-hydroxytryptamine2A; 5-HT2A) receptor antagonists in nonprimate species provide conflicting results with regard to their intraocular pressure-lowering efficacy. Thus, their therapeutic utility in the treatment of human glaucoma has been confusing. We evaluated the effect of selected 5-HT1A agonists and 5-HT2A receptor antagonists on intraocular pressure in a nonhuman primate model, the conscious cynomolgus monkey with laser-induced ocular hypertension. Neither selective 5-HT1A agonists [e.g., R-8-hydroxy-2-(di-n-propylamino)tetralin and flesinoxan] nor selective 5-HT2 receptor antagonists [e.g., R-(+)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol (M-100907) and 6-chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxamide (SB-242084)] lowered intraocular pressure in the primate model following topical ocular administration. However, compounds that function as agonists at both the 5-HT1A and 5-HT2 receptors were found to effectively lower intraocular pressure in the model: 5-hydroxy-α-methyltryptamine, 5-methoxy-α-methyltryptamine, 5-hydroxy-N,N-dimethyltryptamine (bufotenine), and 5-methoxy-N,N-dimethyltryptamine. Furthermore, the selective 5-HT2 receptor agonist R-(–)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane lowered intraocular pressure in the primate model, demonstrating a pharmacological response associated with activation of the 5-HT2 receptor. These observations suggest that compounds that function as efficient agonists at 5-HT2 receptors should be considered as potential agents for the control of intraocular pressure in the treatment of ocular hypertension and glaucoma in humans.
Systematic Identification of Cyclic-di-GMP Binding Proteins in Vibrio cholerae Reveals a Novel Class of Cyclic-di-GMP-Binding ATPases Associated with Type II Secretion Systems

Cyclic-di-GMP (c-di-GMP) is a ubiquitous bacterial signaling molecule that regulates a variety of complex processes through a diverse set of c-di-GMP receptor proteins. We have utilized a systematic approach to identify c-di-GMP receptors from the pathogen Vibrio cholerae using the Differential Radial Capillary Action of Ligand Assay (DRaCALA). The DRaCALA screen identified a majority of known c-di-GMP binding proteins in V. cholerae and revealed a novel c-di-GMP binding protein, MshE (VC0405), an ATPase associated with the mannose sensitive hemagglutinin (MSHA) type IV pilus. The known c-di-GMP binding proteins identified by DRaCALA include diguanylate cyclases, phosphodiesterases, PilZ domain proteins and transcription factors VpsT and VpsR, indicating that the DRaCALA-based screen of open reading frame libraries is a feasible approach to uncover novel receptors of small molecule ligands. Since MshE lacks the canonical c-di-GMP-binding motifs, a truncation analysis was utilized to locate the c-di-GMP binding activity to the N-terminal T2SSE_N domain. Alignment of MshE homologs revealed candidate conserved residues responsible for c-di-GMP binding. Site-directed mutagenesis of these candidate residues revealed that the Arg9 residue is required for c-di-GMP binding. The ability of c-di-GMP binding to MshE to regulate MSHA dependent processes was evaluated. The R9A allele, in contrast to the wild type MshE, was unable to complement the ΔmshE mutant for the production of extracellular MshA to the cell surface, reduction in flagella swimming motility, attachment to surfaces and formation of biofilms. Testing homologs of MshE for binding to c-di-GMP identified the type II secretion ATPase of Pseudomonas aeruginosa (PA14_29490) as a c-di-GMP receptor, indicating that type II secretion and type IV pili are both regulated by c-di-GMP.
A highly parallel Turbo Product Code decoder without interleaving resource

This article presents an innovative turbo product code (TPC) decoder architecture without any interleaving resource. This architecture includes a full-parallel SISO decoder able to process n symbols in one clock period. Syntheses show the better efficiency of such an architecture compared with existing previous solutions. Considering a 6-iteration turbo decoder of a (32,26)2 BCH product code, synthetized in a 90 nm CMOS technology, the resulting information throughput is 2.5 Gb/s with an area of 233 Kgates. Finally a second architecture enhancing parallelism rate is described. The information throughput is 33.7 Gb/s while an area estimation gives A=10 mum2.
Lactate utilization by brain cells and its role in CNS development

We studied the role played by lactate as an important substrate for the brain during the perinatal period. Under these circumstances, lactate is the main substrate for brain development and is used as a source of energy and carbon skeletons. In fact, lactate is used actively by brain cells in culture. Neurons, astrocytes, and oligodendrocytes use lactate as a preferential substrate for both energy purposes and as precursor of lipids. Astrocytes use lactate and other metabolic substrates for the synthesis of oleic acid, a new neurotrophic factor. Oligodendrocytes mainly use lactate as precursor of lipids, presumably those used to synthesize myelin. Neurons use lactate as a source of energy and as precursor of lipids. During the perinatal period, neurons may use blood lactate directly to meet the need for the energy and carbon skeletons required for proliferation and differentiation. During adult life, however, the lactate used by neurons may come from astrocytes, in which lactate is the final product of glycogen breakdown. It may be concluded that lactate plays an important role in brain development. © 2004 Wiley‐Liss, Inc.
Active and latent forms of transforming growth factor beta activity in synovial effusions

We have evaluated the possible involvement of TGF-beta in rheumatoid arthritis by assay of 16 cell-free synovial fluids for the presence of its active and "latent" forms. Evidence has been obtained for TGF-beta- like activity in synovial effusions by four criteria: (a) TGF-beta receptor competition, (b) soft-agar colony formation of AKR-2B and NRK- 49F indicator cells, (c) immunological neutralization of the biological activity, and (d) biochemical activation of a latent form.
Neurotensin receptors in human meningiomas

We have investigated the presence of neurotensin receptors in human meningiomas by in vitro binding autoradiography. Ten of the 12 meningiomas tested displayed specific {3H}neurotensin binding. All meningothelial (n = 3) and transitional (n = 5) meningiomas were positive, whereas only 2 of the 4 fibroblastic meningiomas showed measurable concentrations of neurotensin binding sites. Within the tumors, {3H}neurotensin binding was preferentially observed in syncytial areas. Saturation experiments showed that the maximal binding capacity (Bmax) greatly varied among tumors, ranging from low values to more than 290 fmol/mg of protein. All positive tumors had neurotensin binding sites with a dissociation constant (kd) within the nanomolar range and a pharmacological specificity for {3H}neurotensin similar to neurotensin receptors.
Extending position/phase-shift tuning to motion energy neurons improves velocity discrimination

We extend position and phase-shift tuning, concepts already well established in the disparity energy neuron literature, to motion energy neurons. We show that Reichardt-like detectors can be considered examples of position tuning, and that motion energy filters whose complex valued spatio-temporal receptive fields are space-time separable can be considered examples of phase tuning. By combining these two types of detectors, we obtain an architecture for constructing motion energy neurons whose center frequencies can be adjusted by both phase and position shifts. Similar to recently described neurons in the primary visual cortex, these new motion energy neurons exhibit tuning that is between purely space-time separable and purely speed tuned. We propose a functional role for this intermediate level of tuning by demonstrating that comparisons between pairs of these motion energy neurons can reliably discriminate between inputs whose velocities lie above or below a given reference velocity.
Controversial issues in a disabling society

At its best Disability Studies is an arena of critical debate addressing controversial issues concerning, not just the meaning of disability, but the nature of society, dominant values, quality of life, and even the right to live. Indeed, Disability Studies is itself the subject of controversy, in terms of its theoretical basis and who controls courses and research and whether it should be shaped and controlled by disabled academics or grassroots activists. Within these debates, generated by the social model of disability, are fundamental challenges to policy, provision and professional practice that are directly relevant to all who work with disabled people, whether in the field of social work, health or education. Controversial Issues in a Disabling Society has been written specifically to raise questions and stimulate debate. It has been designed for use with students in group discussion, and to support in-depth study on a variety of professional courses. It covers a wide range of specific, substantive issues within Disability Studies in a series of succinct chapters. Each chapter sets a question for debate, places the key issues in context and presents a particular argument. This is an accessible and engaging book which challenges dominant positions and ideologies from a social model viewpoint of disability.
An exploration of the interrelationship between intimacy resolution, coping styles, and suicidal attitudes among a sample of university students.

Whilst much has been written about the determinants of suicidal behaviour within a South African context, few studies have investigated suicidal behaviour from a developmental context. This study explored the relationship between suicidal tendencies, coping styles, and Intimacy vs. Isolation. There were 175 participants between the ages of 18 to 24 years. Scales measuring coping, suicidal attitudes, and intimacy resolution were administered. The data was analysed quantitatively. Most significant in the findings is the relationship that exists between intimacy resolution, suicidal attitudes and active coping styles. These and other findings provide an initial but empirically important platform for future research endeavours that aim to understand the incidence of suicide amongst one of the most at-risk groups in South
Spinal cord injury in the pediatric population: a systematic review of the literature.

Spinal Cord Injury (SCI) in the pediatric population is relatively rare but carries significant psychological and physiological consequences. An interdisciplinary group of experts composed of medical and surgical specialists treating patients with SCI formulated the following questions: 1) What is the epidemiology of pediatric spinal cord injury and fractures? ; 2) Are there unique features of pediatric SCI which distinguish the pediatric SCI population from adult SCI? ; 3) Is there evidence to support the use of neuroprotective approaches, including hypothermia and steroids, in the treatment of pediatric SCI? A systematic review of the literature using multiple databases was undertaken to evaluate these three specific questions. A search strategy composed of specific search terms (Spinal Cord Injury, Paraplegia, Quadriplegia, tetraplegia, lapbelt injuries, seatbelt injuries, cervical spine injuries and Pediatrics) returned over 220 abstracts that were evaluated and by two observers. Relevant abstracts were then evaluated and papers were graded using the Downs and Black method. A table of evidence was then presented to a panel of experts using a modified Delphi approach and the following recommendation was then formulated using a consensus approach: Pediatric patients with traumatic SCI have different mechanisms of injury and have a better neurological recovery potential when compared to adults. Patients with SCI before their adolescent growth spurt have a high likelihood of developing scoliosis. Because of these differences, traumatic SCI should be highly suspected in the presence of abnormal neck or neurological exam, a high-risk mechanism of injury or a distracting injury even in the absence of radiological anomaly.
Explorer The influence of viral coding sequences on pestivirus IRES activity reveals further parallels with translation initiation in prokaryotes

Classical swine fever virus (CSFV) is a member of the pestivirus family, which shares many features in common with hepatitis C virus (HCV). It is shown here that CSFV has an exceptionally efficient cis-acting internal ribosome entry segment (IRES), which, like that of HCV, is strongly influenced by the sequences immediately downstream of the initiation codon, and is optimal with viral coding sequences in this position. Constructs that retained 17 or more codons of viral coding sequence exhibited full IRES activity, but with only 12 codons, activity was ; 66% of maximum in vitro (though close to maximum in transfected BHK cells), whereas with just 3 codons or fewer, the activity was only ; 15% of maximum. The minimal coding region elements required for high activity were exchanged between HCV and CSFV. Although maximum activity was observed in each case with the homologous combination of coding region and 5 9 UTR, the heterologous combinations were sufficiently active to rule out a highly specific functional interplay between the 5 9 UTR and coding sequences. On the other hand, inversion of the coding sequences resulted in low IRES activity, particularly with the HCV coding sequences. RNA structure probing showed that the efficiency of internal initiation of these chimeric constructs correlated most closely with the degree of single-strandedness of the region around and immediately downstream of the initiation codon. The low activity IRESs could not be rescued by addition of supplementary eIF4A (the initiation factor with ATP-dependent RNA helicase activity). The extreme sensitivity to secondary structure around the initiation codon is likely to be due to the fact that the eIF4F complex (which has eIF4A as one of its subunits) is not required for and does not participate in initiation on these IRESs.
Seasonal Changes in a Maize-Based Polyculture of Central Mexico Reshape the Co-occurrence Networks of Soil Bacterial Communities

The milpa is a traditional maize-based polyculture in Mexico that is typically practiced as rainfed agriculture. Because milpa cultivation has been practiced over a vast range of environmental and cultural conditions, this agroecosystem is recognized as an important repository of biological and cultural diversity. As for any agroecosystem, the relationship between plant development and the biogeochemical processes of the soil is critical. Although the milpa has been studied from different perspectives, the diversity and structure of microbial communities within milpa soils remain largely unexplored. In this study, we surveyed a milpa system in Central Mexico across cropping season: before planting (dry season; t1), during the early growth of plants (onset of the rainy season; t2), and before harvest (end of the rainy season; t3). In order to examine changes in community structure through time, we characterized bacterial diversity through high-throughput sequencing of 16S rRNA gene amplicons and recorded the nutrient status of multiple (5–10) soil samples from our milpa plots. We estimated microbial diversity from a total of 90 samples and constructed co-occurrence networks. Although we did not find significant changes in diversity or composition of bacterial communities across time, we identified significant rearrangements in their co-occurrence network structure. We found particularly drastic changes between the first and second time points. Co-occurrence analyses showed that the bacterial community changed from a less structured network at (t1) into modules with a non-random composition of taxonomic groups at (t2). We conclude that changes in bacterial communities undetected by standard diversity analyses can become evident when performing co-occurrence network analyses. We also postulate possible functional associations among keystone groups suggested by biogeochemical processes. This study represents the first contribution on soil microbial diversity of a maize-based polyculture and shows its dynamic nature in short-term scales.
“It Is Me Who Endures but My Family That Suffers”: Social Isolation as a Consequence of the Household Cost Burden of Buruli Ulcer Free of Charge Hospital Treatment

Despite free of charge biomedical treatment, the cost burden of Buruli ulcer disease (Bu) hospitalisation in Central Cameroon accounts for 25% of households' yearly earnings, surpassing the threshold of 10%, which is generally considered catastrophic for the household economy, and calling into question the sustainability of current Bu programmes. The high non-medical costs and productivity loss for Bu patients and their households make household involvement in the healing process unsustainable. 63% of households cease providing social and financial support for patients as a coping strategy, resulting in the patient's isolation at the hospital. Social isolation itself was cited by in-patients as the principal cause for abandonment of biomedical treatment. These findings demonstrate that further research and investment in Bu are urgently needed to evaluate new intervention strategies that are socially acceptable and appropriate in the local context.
Distributed under Creative Commons Cc-by 4.0 the Hsp70-like Stka Functions between T4p and Dif Signaling Proteins as a Negative Regulator of Exopolysaccharide in Myxococcus Xanthus

Myxococcus xanthus displays a form of surface motility known as social (S) gliding. It is mediated by the type IV pilus (T4P) and requires the exopolysaccharide (EPS) to function. It is clear that T4P retraction powers S motility. EPS on a neighboring cell or deposited on a gliding surface is proposed to anchor the distal end of a pilus and trigger T4P retraction at its proximal end. Inversely, T4P has been shown to regulate EPS production upstream of the Dif signaling pathway. Here we describe the isolation of two Tn insertions at the stk locus which had been known to play roles in cellular cohesion and formation of cell groups. An insertion in stkA (MXAN 3474) was identified based on its ability to restore EPS to a pilA deletion mutant. The stkA encodes a DnaK or Hsp70 homolog and it is upstream of stkB (MXAN 3475) and stkC (MXAN 3476). A stkB insertion was identified in a separate genetic screen because it eliminated EPS production of an EPS + parental strain. Our results with in-frame deletions of these three stk genes indicated that the stkA mutant produced increased level of EPS while stkB and stkC mutants produced less EPS relative to the wild type. S motility and developmental aggregation were affected by deletions of stkA and stkB but only minimally by the deletion of stkC. Genetic epistasis indicated that StkA functions downstream of T4P but upstream of the Dif proteins as a negative regulator of EPS production in M. xanthus.
Exploring the impact of a pre-service interprofessional educational intervention for school mental health trainees

Abstract With collaborative interprofessional teams integral to school mental health (SMH) service delivery, pre-service educational strategies are needed to promote interprofessional collaboration among SMH trainees. The current study evaluated the effectiveness, feasibility, and acceptability of a pre-service, interprofessional SMH educational intervention focused on promoting the cross-disciplinary competencies essential for SMH practice. Eight SMH trainees participated in the study. Using a mixed-method design, quantitative pre/post competency data were collected via trainee self-report. Qualitative data were collected through a focus group and reflection journals. Results indicate that the intervention promoted competency in all areas, with significant growth in the provision of learning supports to youth. Key factors influencing intervention feasibility included time/scheduling, changing school team composition, and project coordination. Trainees’ perceptions of the educational intervention were related to buy-in, clinical experience, and role flexibility. Implications for the design of pre-service interprofessional SMH education strategies are discussed.
Parkinson Disease Classification using Data Mining Algorithms

discovery in databases has established its success rate in various prominent fields such as e-business, marketing, retail and medical. Medical data mining has great potency for exploring the out of sight patterns in the respective medical data sets. This paper intends to provide a survey of current techniques of knowledge discovery in databases using data mining techniques that are in use today for the classification of Parkinson Disease. Parkinson Disease is a chronic malady of the central nervous system where the key indications can be captivated from the Mentation, Activities of Daily Life (ADL), Motor Examination and Complications of Therapy. The speech symptom which is an ADL is a common ground for the progress of the disease. The dataset for the disease is acquired from UCI, an online repository of large data sets. A comparative study on different classification methods is carried out to this dataset by applying the feature relevance analysis and the Accuracy Analysis to come up with the best classification rule. Also the intention is to sieve the data such that the healthy and people with Parkinson will be correctly classified.
Efficient filterbank channelizers for software radio receivers

For cellular software radio receivers, this paper presents a computationally efficient algorithm for extracting individual radio channels from the output of the wideband A/D converter. In a software radio, the extraction of individual channels from the output of the wideband A/D converter is by far the most computationally demanding task; hence, it is very important to devise computationally efficient algorithms for this task. Our algorithm is obtained by modifying the DFT filter bank structure that is well known in the multi-rate signal processing literature. We show that the complexity of the proposed algorithm is significantly less (2X-50X) than the complexity of the conventional channelizers.