Miracle-dz/UniFAR-FTUs huggingface dataset:
Presence and structure of innervated myotendinous cylinders in rabbit extraocular muscle.

Innervated myotendinous cylinders (IMCs) in rabbit extraocular muscles (EOMs) were identified for the first time. The nature of IMC nerve terminals was demonstrated by means of electron microscopy and double fluorescent staining. The distal EOM portions of four rabbits of different age and sex were prepared for transmission electron microscopy and for double-fluorescent labelling. Antibody against neurofilament H and alpha-bungarotoxin were applied on longitudinal cryostat sections of distal myotendinous junction. IMCs were consistently and frequently observed at the distal myotendons of each EOM. More than 30 IMCs were counted in two medial recti of a 6 month and 3 year old rabbit. IMCs were enveloped by two to three layered capsules of fibrocytes. Each IMC contained the terminal portion of one multiply-innervated muscle fibre and its corresponding tendon. The tendon compartment of an IMC was entered by a single myelinated nerve fibre (2-3 microm in diameter). Inside the IMC, this nerve fibre ramified into up to four preterminal branches. Nerve terminals exclusively established contacts with the muscle fibre at its junction with the tendon fibrils. Nerve terminals contained mitochondria and a multitude of clear vesicles. Within the synaptic cleft a basal lamina was always present. alpha-Bungarotoxin labelled the muscle side of these myoneural contacts. Nerve terminals exhibited neither age nor sex differences. Among all species so far investigated, rabbit IMCs are unique by exhibiting exclusively myoneural terminal contacts. Based on fine structure and alpha-bungarotoxin binding, myoneural contacts in rabbit IMCs are almost certainly motor, as previously observed only in human IMCs. Thus, rabbit IMCs are supposed to have a predominant effector function.
Induced chromosome deletions cause hypersociability and other features of Williams–Beuren syndrome in mice

The neurodevelopmental disorder Williams–Beuren syndrome is caused by spontaneous ∼1.5 Mb deletions comprising 25 genes on human chromosome 7q11.23. To functionally dissect the deletion and identify dosage‐sensitive genes, we created two half‐deletions of the conserved syntenic region on mouse chromosome 5G2. Proximal deletion (PD) mice lack Gtf2i to Limk1, distal deletion (DD) mice lack Limk1 to Fkbp6, and the double heterozygotes (D/P) model the complete human deletion. Gene transcript levels in brain are generally consistent with gene dosage. Increased sociability and acoustic startle response are associated with PD, and cognitive defects with DD. Both PD and D/P males are growth‐retarded, while skulls are shortened and brains are smaller in DD and D/P. Lateral ventricle (LV) volumes are reduced, and neuronal cell density in the somatosensory cortex is increased, in PD and D/P. Motor skills are most impaired in D/P. Together, these partial deletion mice replicate crucial aspects of the human disorder and serve to identify genes and gene networks contributing to the neural substrates of complex behaviours and behavioural disorders.
Genome‐Wide Association Mapping With Longitudinal Data

Many genome‐wide association studies have been performed on population cohorts that contain phenotype measurements at multiple time points. However, standard association methodologies only consider one time point. In this paper, we propose a mixed‐model‐based approach for performing association mapping which utilizes multiple phenotype measurements for each individual. We introduce an analytical approach to calculate statistical power and show that this model leads to increased power when compared to traditional approaches. Moreover, we show that by using this model we are able to differentiate the genetic, environmental, and residual error contributions to the phenotype. Using predictions of these components, we show how the proportion of the phenotype due to environment and genetics can be predicted and show that the ranking of individuals based on these predictions is very accurate. The software implementing this method may be found at http://genetics.cs. ucla.edu/longGWAS/. Genet. Epidemiol. 36:463‐471, 2012. © 2012 Wiley Periodicals, Inc.
Fast Local Search Algorithm for Weighted Feedback Arc Set in Tournaments

We present a fast local search algorithm that finds an improved solution (if there is any) in the k-exchange neighborhood of the given solutionto an instance of Weighted Feedback Arc Set in Tournaments. More precisely,given an arc weighted tournament T on n vertices and a feedback arc set F (a set of arcs whose deletion from T turns it into a directed acyclic graph), our algorithm decides in time O(2o(k) n log n) if there is a feedback arc set of smaller weight and that differs from F in at most k arcs. To our knowledge this is the first algorithm searching the k-exchange neighborhood of an NP-complete problem that runs in (parameterized) subexponential time. Using this local search algorithm for Weighted Feedback Arc Set in Tournaments, we obtain subexponential time algorithms for a local search variant of Kemeny Ranking — a problem in social choice theory and of One-Sided Cross Minimization — a problem in graph drawing.
Nurses attitudes and beliefs to attempted suicide in Southern India

Abstract Background: There is growing global interest into the attitudes and clinical management of persons who have attempted suicide. Aims: The principal purpose was to determine senior nursing staff attitudes towards patients who had attempted suicide from a professional and cultural perspective, which might influence care following hospital admission. The focus concerned nursing staff interactions at a psychological level that compete with physical tasks on general hospital wards. Methods: A qualitative methodology was employed with audio-taped interviews utilising four level data coding. This article reports on a group of 15 nursing staff from a large general hospital in Mysore, Southern India. Results: Findings suggested that patient care and treatment is directly influenced by the nurse’s religious beliefs within a general hospital setting with physical duties prioritised over psychological support, which was underdeveloped throughout the participant group. Conclusion: The results allow a series of recommendations for educational and skills initiatives before progressing to patient assessment and treatment projects and cross-cultural comparison studies. In addition, interventions must focus on current resources and context to move the evidence-based suicide prevention forward.
Progression of Subclinical Coronary Atherosclerosis: Does Obesity Make a Difference?

Background—Obesity is associated with coronary artery calcification (CAC), a marker of the presence and extent of subclinical coronary atherosclerosis. Obesity adds incremental information in identifying those at higher risk of coronary heart disease to traditional risk factor assessment. The present study examined associations between obesity measures and progression of CAC in those at higher (≥10%) and lower (<10%) 10-year coronary heart disease risk according to the Framingham risk equation. Methods and Results—In this study, 443 asymptomatic white individuals >30 years of age (243 men) had baseline and follow-up CAC measurements an average of 8.9 years apart. Multivariable linear regression models were fit to determine associations of obesity measures at baseline with progression of CAC defined as loge of the difference between follow-up and baseline CAC area plus 1 divided by time (in years) between examinations, adjusting for baseline CAC quantity, age, sex, baseline hypertension status, and baseline cholesterol level. Among 329 participants (74.3%) in the lower-risk group, waist circumference (P=0.024), waist-to-hip ratio (P<0.001), body mass index (P=0.036), and being overweight compared with being underweight or of normal weight (P=0.008) were each significantly positively associated with progression of CAC. Among those at higher coronary heart disease risk, no baseline obesity measures were associated with CAC progression. Conclusions—Various measures of obesity were associated with increased progression of CAC in those at lower risk of coronary heart disease. Future studies examining the effectiveness of weight reduction strategies in reducing CAC progression among those with an otherwise favorable risk factor profile may be warranted.
Refector: heuristic header error recovery for error-tolerant transmissions

High bit error rates reduce the performance of wireless networks. This is exacerbated by the enforcement of bit-by-bit correct transmissions and the resulting retransmission overhead. Recently, research has focused on more efficient link layer mechanisms and on tolerating payload errors. Header errors, however, still cause today's network and transport protocols to drop the erroneous packets. Instead of retransmitting such packets, we investigate a novel concept (called Refector) of heuristically repairing header bit errors. Refector accepts erroneous packets on end hosts and exploits protocol knowledge and protocol state to assign packets to their correct destination applications. It operates on layers 3 and 4, is independent of the underlying MAC and PHY, and requires no changes to hardware, firmware, and communication behavior. We evaluate the Refector concept via a prototype implementation deployed in an 802.11 network. Our results show that Refector reduces packet loss in the network by more than 25% when compared to payload-error-tolerant protocols such as UDP-Lite.
Use of Cryopreserved Human Hepatocytes in Sandwich Culture to Measure Hepatobiliary Transport

Fresh hepatocytes cultured in a sandwich configuration allow for the development of intact bile canaliculi and the ability to measure hepatic uptake and biliary clearance. A disadvantage of this model is its dependence upon hepatocytes from fresh tissue. Therefore, the ability to use cryopreserved human hepatocytes in this model would be a great advantage. Multiple variables were tested, and the recommended conditions for culturing cryopreserved human hepatocytes in a sandwich configuration in 24-well plates are as follows: BioCoat plates, a cell density of 0.35 × 106 cells/well in 500 μl, an overlay of Matrigel and InVitroGRO media. These conditions resulted in good hepatocyte morphology and the formation of distinct bile canaliculi. The function of multiple uptake and efflux transporters was tested in multiple lots of cryopreserved and fresh human hepatocytes. For taurocholate [Na+ taurocholate cotransporting polypeptide/organic anion transporting polypeptide (OATP) uptake/bile salt export pump efflux], the average apparent uptake, apparent intrinsic biliary clearance, and biliary excretion index among five cryopreserved hepatocyte lots was high, ranging from 11 to 17 pmol/min/mg protein, 5.8 to 10 μl/min/mg protein, and 41 to 63%, respectively. The corresponding values for digoxin (OATP-8 uptake/multidrug resistance protein 1 efflux) were 0.69 to 1.5 pmol/min/mg protein, 0.60 to 1.5 μl/min/mg protein, and 37 to 63%. Both substrates exhibited similar results when fresh human hepatocytes were used. In addition, substrates of breast cancer resistance protein and multidrug resistance-associated protein 2 were also tested in this model, and all cryopreserved lots showed functional transport of these substrates. The use of cryopreserved human hepatocytes in 24-well sandwich culture to form intact bile canaliculi and to exhibit functional uptake and efflux transport has been successfully demonstrated.
Forkhead box N4 (Foxn4) activates Dll4-Notch signaling to suppress photoreceptor cell fates of early retinal progenitors

The generation of diverse neuronal types and subtypes from multipotent progenitors during development is crucial for assembling functional neural circuits in the adult central nervous system. During mouse retinogenesis, early retinal progenitors give rise to several cell types, including ganglion, amacrine, horizontal, cone, and rod cells. It is unknown at present how each of these fates is selected from the multiple neuronal fates available to the early progenitor. By using a combination of bioinformatic, genetic, and biochemical approaches, we investigated the mechanism by which Foxn4 selects the amacrine and horizontal cell fates from multipotential retinal progenitors. These studies indicate that Foxn4 has an intrinsic activity to suppress the alternative photoreceptor cell fates of early retinal progenitors by selectively activating Dll4-Notch signaling. Gene expression and conditional ablation analyses reveal that Dll4 is directly activated by Foxn4 via phylogenetically conserved enhancers and that Dll4 can partly mediate the Foxn4 function by serving as a major Notch ligand to expand the progenitor pool and limit photoreceptor production. Our data together define a Foxn4-mediated molecular and signaling pathway that underlies the suppression of alternative cell fates of early retinal progenitors.
Effect of Hyperthermia on the ImmuÃ ± ocompete nee of VX 2 Tumor-bearing Rabbits 1 SudhirA

Nonspecific Â¡mmunocompetencein VX2 tumor-bearing rabbits was assessed by skin response to dinitrochlorobenzene and development of antibody titer to bovine serum albumin. Skin reactivity to a 3 M KCI extract of the VX2 and antitumor antibody titer were used to monitor host immunocompetence against the tumor. Rabbits bearing a 15to 20-ml i.m. VX2 tumor in the hind limb were treated by local and total-body heating after established mÃ©tastaseswere present in regional and aor tic lymph nodes and lungs. Following local heating of the VX2 (intratumor tempera ture, 47-50/30 min) achieved by radiofrequency current at 13.56 MHz, there was tumor regression and host cure in 9 of 13 (70%) rabbits. Tumor regression was accompanied by a marked and sustained increase in skin reactivity to both tumor extract and dinitrochlorobenzene, and there was a 100-fold increase in serum levels of antitumor and anti-bovine serum albumin antibody. The animals are alive 2 years after heating and are immune to inoculation of 30 x 10" VX2 cells; 1 x 106 tumor cells led to a 100% death rate in 72 Â±7 (S.D.) days in untreated rabbits. In the 4 rabbits that did not respond to heating, unrestrained tumor growth was accompanied by a progressive de crease in host response to skin tests and antibody titers of 1:10 or less, findings similar to those in untreated tumor-bearing hosts. Eight rabbits were subjected to total-body hyperthermia (42/60 min on 3 successive days) 7 days after radiofre quency treatment. In 7 of the animals (88%), temporary restraint of tumor growth was followed by return to expo nential increase in tumor volume and rapid death. This was accompanied by abrogation of the enhanced cellular and humoral immune responsiveness that followed local heating; in the single animal that was cured there was a sustained increase in skin response to dinitrochloroben zene and tumor extract and in serum levels of antitumor and anti-bovine serum albumin antibody. Necrotic material removed from regressing VX2 carci nomas up to 17 days after radiofrequency heating pro duced tumors on inoculation into rabbits. It is concluded that the immune response generated following curative local heating of the VX2 carcinoma is involved in regression of the primary tumor as well as in the destruction of mÃ©tastases.The abrogation of such enhanced immunocompetence by total-body heating sup1 Work was supported by the North of England Council of the Cancer Research Campaign. Received January 18, 1978; accepted July 11, 1978. ports the concept that in this animal tumor system wholebody hyperthermia is hazardous for the host.
Neurochemical dissociation of memory systems

The administration of scopolamine, an anticholinergic drug, reduced the ability to recall and recognize stimuli presented previously—abilities thought to require declarative memory. In contrast, measures of procedural memory were unaffected by scopolamine: performance on a serial reaction time task incorporating a repeating stimulus and response sequence showed no difference in acquisition and retention of the sequence after scopolamine or saline. These results suggest that the cholinergic system is required for declarative but not procedural memory.
Plant polyploidy and non-uniform effects on insect herbivores

Genomic duplication through polyploidy has played a central role in generating the biodiversity of flowering plants. Nonetheless, how polyploidy shapes species interactions or the ecological dynamics of communities remains largely unknown. Here we provide evidence from a 4 year study demonstrating that the evolution of polyploidy has reshaped the interactions between a widespread plant and three species of phytophagous moths. Our results show that polyploidy has produced non–uniform effects, with polyploids less attacked by one insect species, but significantly more attacked by two other species. These results suggest that the evolution of plant polyploidy may not generally confer uniform resistance to multiple species of insect herbivores. In the absence of such a uniform release, the extreme evolutionary success of polyploid plants is probably due to factors other than escape from herbivory. Together, these results suggest that a primary consequence of plant polyploidy may be to shape the ecological structure of plant–insect interactions, thereby providing opportunities for diversification in both plant and insect taxa.
A cloned pathogenicity island from enteropathogenic Escherichia coli confers the attaching and effacing phenotype on E. coli K‐12

Attaching and effacing (AE) bacteria are a diverse group of gastrointestinal pathogens, comprising members of four genera, that cause the intestinal epithelial microvilli to be replaced with raised clusters of filamentous actin that conform to the surface of attached bacteria. We have cloned a 35.4 kb ‘pathogenicity island’ from the prototype AE bacterium, enteropathogenic Escherichia coli, containing all previously described AE genes. Transfer of this pathogenicity island to avirulent E. coli converts the recipients into strains that secrete virulence proteins, induce host signal‐transduction pathways, and cause AE lesions on cultured epithelial cells. These results demonstrate that this pathogenicity island contains all pathogen‐specific genes necessary for inducing AE lesions, and that the defining feature of this class of pathogens can be acquired by an avirulent bacterium in a single genetic step.
Increased Proportion of HLA-Class-I-Specific Natural Killer Cell Receptors (CD94) on Peripheral Blood Mononuclear Cells after Allogeneic Bone Marrow Transplantation

In the present study, we investigated the inhibitory natural killer cell receptor (NKR) expression of CD94/NKG2A on PBMC after allogeneic bone marrow transplantation (BMT). The proportion of CD94 expression on PBMC was higher in patients without chronic graft-versus-host disease (cGVHD) and also in cGVHD patients with good response to conventional immunosuppressive therapy than in cGVHD patients with poor response. Also, the proportions of CD94+/CD3+ cells and CD94+/CD8+ cells were higher in cGVHD patients showing good response. In addition, the proportion of NKG2A-expressing cells was higher in patients without cGVHD than in patients with cGVHD. Therefore, chronic allostimulation after allo-BMT may augment the proportion of CD94/NKG2A-positive cells, and these cells may play some role in the regulation of alloresponse in some patients.
Religious and/or Spiritual Practices: Extending Spiritual Freedom to People with Schizophrenia

Background. It continues to be a challenge to define and utilize spirituality in client-centred occupational therapy practice. Dialogue about spirituality is especially problematic for occupational therapists working with people with schizophrenia. Purpose. To explore the meaning of religion and/or spirituality for people living with a diagnosis of schizophrenia. Methods. Nine community-based individuals with schizophrenia engaged in interviews about the meaning of religion and/or spirituality and demonstrated self-defined spiritual practices. Phenomenology, hermeneutic theory, and a symbolic interactionism framework provided methodological and analytic guidance. Findings. Participants employed religious and/or spiritual practices to cope with schizophrenia symptoms and make meaning of their lives. Individuals used multiple systems of meaning to explain their experiences. Religious and/or spiritual agency, an individual's sense of freedom to choose among the spiritual options, renewed their sense of empowerment. Implications. Therapists can engage in spiritual negotiation with clients by using well-worded empowering questions toward a common goal of life enhancement.
Severe hypoglycaemia and cardiovascular disease: systematic review and meta-analysis with bias analysis

Objectives To provide a systematic and quantitative summary of the association between severe hypoglycaemia and risk of cardiovascular disease in people with type 2 diabetes and to examine the sensitivity of the association to possible uncontrolled confounding by unmeasured comorbid severe illness using a bias analysis. Design Meta-analysis of observational studies. Data sources Medline, Embase, the Cochrane Library, and Web of Science databases were searched to February 2013, without any language restrictions. Eligibility criteria Two independent reviewers selected cohort studies that evaluated the association of severe hypoglycaemia with cardiovascular events in people with type 2 diabetes; we excluded studies from acute hospital settings. We extracted descriptive and quantitative data. Results Of 3443 citations screened, six eligible studies with 903 510 participants were identified. In the conventional random effects meta-analysis, severe hypoglycaemia was strongly associated with a higher risk of cardiovascular disease (relative risk 2.05, 95% confidence interval 1.74 to 2.42; P<0.001). The excess fraction of cardiovascular disease incidence that was attributable to severe hypoglycaemia (the population attributable fraction) was 1.56% (95% confidence interval 1.32% to 1.81%; P<0.001). Although moderate heterogeneity across the studies was suggested (I2=73.1%; P=0.002 for heterogeneity), most subgroups showed similar results in stratified analyses. The bias analysis indicated that comorbid severe illness alone may not explain the association between hypoglycaemia and cardiovascular disease; to explain this association, comorbid severe illness would have had to be extremely strongly associated with both severe hypoglycaemia and cardiovascular disease. Conclusion Our findings suggest that severe hypoglycaemia is associated with a higher risk of cardiovascular disease; they also support the notion that avoiding severe hypoglycaemia may be important to prevent cardiovascular disease in people with type 2 diabetes.