Miracle-dz/UniFAR-FTUs huggingface dataset:
A genome-wide association study in multiple system atrophy

Objective: To identify genetic variants that play a role in the pathogenesis of multiple system atrophy (MSA), we undertook a genome-wide association study (GWAS). Methods: We performed a GWAS with >5 million genotyped and imputed single nucleotide polymorphisms (SNPs) in 918 patients with MSA of European ancestry and 3,864 controls. MSA cases were collected from North American and European centers, one third of which were neuropathologically confirmed. Results: We found no significant loci after stringent multiple testing correction. A number of regions emerged as potentially interesting for follow-up at p < 1 × 10−6, including SNPs in the genes FBXO47, ELOVL7, EDN1, and MAPT. Contrary to previous reports, we found no association of the genes SNCA and COQ2 with MSA. Conclusions: We present a GWAS in MSA. We have identified several potentially interesting gene loci, including the MAPT locus, whose significance will have to be evaluated in a larger sample set. Common genetic variation in SNCA and COQ2 does not seem to be associated with MSA. In the future, additional samples of well-characterized patients with MSA will need to be collected to perform a larger MSA GWAS, but this initial study forms the basis for these next steps.
Ventral subicular interaction with the hypothalamic paraventricular nucleus: Evidence for a relay in the bed nucleus of the stria terminalis

The axonal projections of the ventral subiculum to the bed nucleus of the stria terminalis (BST) were examined in the rat with the anterograde neuronal tracer Phaseolus vulgaris‐ leucoagglutinin (PHA‐L). Axons originating in the ventral subiculum coursed to the BST through either the fimbria‐fornix, or a pathway involving the stria terminalis via the amygdala. Ventral subicular axons gave rise to dense terminal networks that were preferentially distributed in medial and ventral subregions of the BST. The distribution of subicular fibers and terminals was examined in relation to BST neurons that project to the hypothalamic paraventricular nucleus (PVN). In these cases, discrete iontophoretic injections of the retrograde tracer Fluoro‐gold were made in the PVN, with PHA‐L delivered to the ipsilateral ventral subiculum. An immunocytochemical double‐labeling protocol was then employed for the simultaneous detection of PHA‐L and Fluoro‐gold, and provided light microscopic evidence for subicular input to PVN‐projecting cells located within the BST.
Physical Properties of Liquid Crystalline Materials

W H de Jeu 1980 New York: Gordon and Breach ix + 133 pp price $32 It is to be regretted that the practice is growing, even among those knowledgeable in the field, of writing about liquid crystals as though a single type existed and the two processes for their formation produced similar molecular distributions. The distinction between thermotropic and lyotropic liquid crystals is not made in the title of this book.
The role of natural killer cells in murine cytomegalovirus eye infection.

PURPOSE To study the role of natural killer cells in the dissemination of virus to the eye and virus growth as well as the production of lesions in the eye during primary infection of murine cytomegalovirus. METHODS Virus activity and lesion production by murine cytomegalovirus in various organs of natural killer cell-depleted BALB/c strain of inbred mice were compared with those of immunocompetent normal BALB/c mice. RESULTS In mice injected intraperitoneally with murine cytomegalovirus, virus could be isolated from 50% of eyes in the natural killer cell-depleted group whereas no virus was detected from any eye in the control group. In natural killer cell-depleted mice with positive virus isolation from eyes, no murine cytomegalovirus was isolated from either optic nerves or trigeminal ganglia whereas virus was detected from blood lymphocytes, macrophages, granulocytes, and plasma. After intravitreal injection of murine cytomegalovirus, virus titers in eyes of natural killer cell-depleted mice were significantly higher than those in the control group. Derangement of retinal cell layer and inflammatory cells as well as cytomegalic cells in iris and ciliary body were noted in natural killer cell-depleted group, whereas no such changes were observed in the eyes of the control mice. CONCLUSION Natural killer cell depletion enhances the dissemination of murine cytomegalovirus to the eye through the hematogenous route, and increases virus multiplication as well as lesion production in the eye.
Towards a mental representation of vowel height in SSBE speakers

Vigorous debate in phonetics and phonology has focused on the structure and cognitive foundation of distinctive feature theory, as well as on the definition and representation of features themselves. In particular, we show in Section 1 that, although vowel height has long been the object of close scrutiny, research on the three- or more- tiered height representation of vowels in the phonology of English remains inconclusive. Section 2 reports on the rationale and methodology of a sound-symbolism experiment designed to evaluate the implicit phonological knowledge that English native speakers have of vowel height differences. In Section 3 we tabulate results and argue in Section 4 that their intuitive understanding of such differences is best accounted for in terms of a three- tiered height axis.
Recruitment of E‐cadherin associated with α‐ and β‐catenins and p120ctn to the nectin‐based cell‐cell adhesion sites by the action of 12‐O‐tetradecanoylphorbol‐13‐acetate in MDCK cells

The formation of tight junctions (TJs) is dependent on the formation of adherens junctions (AJs) in MDCK cells. E‐Cadherin and nectin are major cell‐cell adhesion molecules (CAMs) at AJs, whereas claudin, occludin and junctional adhesion molecule (JAM) are major CAMs at TJs. When MDCK cells precultured at 2 µm Ca2+ are cultured at 2 mm Ca2+, nectin first forms cell‐cell adhesion and recruits E‐cadherin to the nectin‐based cell‐cell adhesion sites to form AJs. Thereafter, nectin recruits first JAM‐A and then claudin‐1 and occludin to the apical side of AJs to form TJs. In contrast, when MDCK cells precultured at 2 µm Ca2+ are cultured at 2 µm Ca2+ in the presence of a phorbol ester, 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), a TJ‐like structure is formed without the formation of the E‐cadherin‐based AJs. We showed here that GFP‐E‐cadherin, which did not trans‐interact due to 2 µm Ca2+ but associated with α‐ and β‐catenins and p120ctn, was recruited to the nectin‐based cell‐cell adhesion sites by the action of TPA. The nectin inhibitors, which inhibited the trans‐interaction of nectin, inhibited the recruitment of GFP‐E‐cadherin and their associating catenins by the action of TPA. Microbeads coated with the extracellular fragment of nectin recruited not only cellular nectin but also GFP‐E‐cadherin and their associating catenins by the action of TPA. These results indicate that when the TJ‐like structure is formed by the action of TPA, non‐trans‐interacting E‐cadherin and its associating catenins are recruited to the nectin‐based cell‐cell adhesion sites and that the trans‐interaction of E‐cadherin is not essential for the formation of TJs.
Pelvic collection drainage by Heald anal stent

TECHNIQUE The Heald anal stent (Fig 1) can be used to drain pelvic collections on the ward after any surgery that leaves a short rectal stump. The stent is inserted through the rectal cross-staples after the instillation of local anaesthetic gel. After several days, once drainage is complete, the stent is removed painlessly. We have used this technique successfully on patients with pelvic collections (Fig 2) who have failed Foley catheter drainage. The stent may be left for a few days until drainage is complete. (Pelvic magnetic resonance imaging may be used to confirm this [Fig 3].) The stent can then be removed on the ward.
L-Type Ca2+ Channel Function Is Linked to Dystrophin Expression in Mammalian Muscle

Background In dystrophic mdx skeletal muscle, aberrant Ca2+ homeostasis and fibre degeneration are found. The absence of dystrophin in models of Duchenne muscular dystrophy (DMD) has been connected to altered ion channel properties e.g. impaired L-type Ca2+ currents. In regenerating mdx muscle, ‘revertant’ fibres restore dystrophin expression. Their functionality involving DHPR-Ca2+-channels is elusive. Methods and Results We developed a novel ‘in-situ’ confocal immuno-fluorescence and imaging technique that allows, for the first time, quantitative subcellular dystrophin-DHPR colocalization in individual, non-fixed, muscle fibres. Tubular DHPR signals alternated with second harmonic generation signals originating from myosin. Dystrophin-DHPR colocalization was substantial in wt fibres, but diminished in most mdx fibres. Mini-dystrophin (MinD) expressing fibres successfully restored colocalization. Interestingly, in some aged mdx fibres, colocalization was similar to wt fibres. Most mdx fibres showed very weak membrane dystrophin staining and were classified ‘mdx-like’. Some mdx fibres, however, had strong ‘wt-like’ dystrophin signals and were identified as ‘revertants’. Split mdx fibres were mostly ‘mdx-like’ and are not generally ‘revertants’. Correlations between membrane dystrophin and DHPR colocalization suggest a restored putative link in ‘revertants’. Using the two-micro-electrode-voltage clamp technique, Ca2+-current amplitudes (imax) showed very similar behaviours: reduced amplitudes in most aged mdx fibres (as seen exclusively in young mdx mice) and a few mdx fibres, most likely ‘revertants’, with amplitudes similar to wt or MinD fibres. Ca2+ current activation curves were similar in ‘wt-like’ and ‘mdx-like’ aged mdx fibres and are not the cause for the differences in current amplitudes. imax amplitudes were fully restored in MinD fibres. Conclusions We present evidence for a direct/indirect DHPR-dystrophin interaction present in wt, MinD and ‘revertant’ mdx fibres but absent in remaining mdx fibres. Our imaging technique reliably detects single isolated ‘revertant’ fibres that could be used for subsequent physiological experiments to study mechanisms and therapy concepts in DMD.
Pre-eclampsia disrupts the normal relationship between serum leptin concentrations and adiposity in pregnant women.

The adipocyte hormone, leptin, is secreted in proportion to adipose mass and is implicated in the regulation of energy balance via its central actions on food intake and sympathetic nervous system activity. The placenta was also shown recently to be a possible source of leptin in pregnant women, raising the possibility that the normal relationship between leptin and adiposity may be altered in pre-eclampsia. We therefore sought to assess the extent to which maternal second trimester serum leptin concentrations differed for women who would subsequently develop pre-eclampsia and those who would remain normotensive. This nested case-control study population comprised 38 women with pregnancy-induced hypertension and proteinuria (pre-eclampsia) and 192 normotensive women. Multiple least-squares regression procedures were used to assess the independent relationship between leptin concentrations and risk of pre-eclampsia. Serum leptin concentrations, measured by radioimmunoassay, were highly correlated with maternal pre-pregnancy and second trimester body mass index (r = 0.71 and r = 0.74 respectively; P < 0.001 for both) among normotensive women, and to a lesser extent among women who developed pre-eclampsia (r = 0.29 and r = 0.42; P = 0.09 and 0.02 respectively). Among women with a pre-pregnancy body mass index of < or = 25 kg/m2, pre-eclampsia cases compared with controls had higher mean second trimester leptin concentrations after adjustment for confounding factors. In contrast, pre-eclampsia cases had lower mean leptin concentrations than controls for those women with a pre-pregnancy body mass index above 25 kg/m2. Other factors in addition to the level of adiposity may therefore influence serum leptin concentrations in pre-eclamptic pregnant women. Our results suggest the possibility that leptin, like several other placentally derived substances (e.g. steroid hormones, eicosanoids and cytokines), may be involved in the pathogenesis of pre-eclampsia. Further work is needed to confirm our findings and to assess the metabolic importance and determinants of leptin concentrations in uncomplicated and pre-eclamptic pregnancies.
Binary Alkali-Metal Silicon Clathrates by Spark Plasma Sintering: Preparation and Characterization

The binary intermetallic clathrates K8-xSi46 (x = 0.4; 1.2), Rb6.2Si46, Rb11.5Si136 and Cs7.8Si136 were prepared from M4Si4 (M = K, Rb, Cs) precursors by spark-plasma route (SPS) and structurally characterized by Rietveld refinement of PXRD data. The clathrate-II phase Rb11.5Si136 was synthesized for the first time. Partial crystallographic site occupancy of the alkali metals, particularly for the smaller Si20 dodecahedra, was found in all compounds. SPS preparation of Na24Si136 with different SPS current polarities and tooling were performed in order to investigate the role of the electric field on clathrate formation. The electrical and thermal transport properties of K7.6Si46 and K6.8Si46 in the temperature range 4–700 K were investigated. Our findings demonstrate that SPS is a novel tool for the synthesis of intermetallic clathrate phases that are not easily accessible by conventional synthesis techniques.
Studying the Effects of Stereo, Head Tracking, and Field of Regard on a Small-Scale Spatial Judgment Task

Spatial judgments are important for many real-world tasks in engineering and scientific visualization. While existing research provides evidence that higher levels of display and interaction fidelity in virtual reality systems offer advantages for spatial understanding, few investigations have focused on small-scale spatial judgments or employed experimental tasks similar to those used in real-world applications. After an earlier study that considered a broad analysis of various spatial understanding tasks, we present the results of a follow-up study focusing on small-scale spatial judgments. In this research, we independently controlled field of regard, stereoscopy, and head-tracked rendering to study their effects on the performance of a task involving precise spatial inspections of complex 3D structures. Measuring time and errors, we asked participants to distinguish between structural gaps and intersections between components of 3D models designed to be similar to real underground cave systems. The overall results suggest that the addition of the higher fidelity system features support performance improvements in making small-scale spatial judgments. Through analyses of the effects of individual system components, the experiment shows that participants made significantly fewer errors with either an increased field of regard or with the addition of head-tracked rendering. The results also indicate that participants performed significantly faster when the system provided the combination of stereo and head-tracked rendering.
Beliefs about Alzheimer's disease in Britain

Objectives: Alzheimer's disease (AD) represents one of the most debilitating conditions affecting the elderly. Despite the prevalence and consequences of AD, surveys have revealed that the general public in North America and Australia hold numerous misconceptions of the disease. The aim of this study was to examine whether misconceptions of AD are also endorsed by adults in Britain. Method: The Alzheimer's disease knowledge scale (ADKS) was completed by 312 adults residing in Lincolnshire, UK. The ADKS contains 30 true or false statements pertaining to risk factors, assessment and diagnosis, symptoms, course, life impact, caregiving, and treatment and management of AD. Results: Regardless of age, education, and familiarity with AD, respondents in this survey demonstrated a good understanding (≥80% mean correct) of some items from all categories. However, knowledge gaps exist about the course of the disease, and of conditions that can exacerbate (inadequate nutrition) or simulate (depression) the symptoms of AD. Moreover, a large proportion of respondents (∼75%) are unaware that hypertension or hypercholesterolemia may increase ones predisposition to developing AD. Conclusion: Respondents revealed knowledge gaps pertaining to conditions that masquerade as AD, increase ones vulnerability to AD, and exacerbate AD symtomatology. Educational campaigns that specifically target these issues may help reduce the impact of AD.
In Vitro Effect of Ultrasound on Bacteria and Suggested Protocol for Sonication and Diagnosis of Prosthetic Infections

ABSTRACT Sonication of implants has been shown to be a promising method for diagnosis of prosthetic infections due to its improved sensitivity, simplicity, and low cost. The aim of the present study was to evaluate the effects of ultrasound performed under different conditions regarding temperature, duration, and composition of sonication tubes on bacterial species often associated with prosthetic infections. We found that ultrasound had an inhibitory effect on bacteria, of which gram-negative bacteria, in particular Escherichia coli, were almost eradicated after 5 min of sonication at 35°C. Gram-positive bacteria were found to be resistant to the effect of ultrasound. Four factors were important for the inhibitory effect of sonication: the type of microorganism, the temperature of the sonication buffer, the duration of exposure to ultrasound (minutes), and the material and composition of the sonication tube in which sonication is performed. On the basis of the results from the present study, we propose a protocol for sonication and recovery of bacteria associated with biofilm on infected implants prior to conventional culture. From the present protocol, we recommend sonication for 7 min at 22°C at the maximum effect which permits survival of gram-negative bacteria.
KRAS Mutation Test in Korean Patients with Colorectal Carcinomas: A Methodological Comparison between Sanger Sequencing and a Real-Time PCR-Based Assay

Background Mutations in the KRAS gene have been identified in approximately 50% of colorectal cancers (CRCs). KRAS mutations are well established biomarkers in anti–epidermal growth factor receptor therapy. Therefore, assessment of KRAS mutations is needed in CRC patients to ensure appropriate treatment. Methods We compared the analytical performance of the cobas test to Sanger sequencing in 264 CRC cases. In addition, discordant specimens were evaluated by 454 pyrosequencing. Results KRAS mutations for codons 12/13 were detected in 43.2% of cases (114/264) by Sanger sequencing. Of 257 evaluable specimens for comparison, KRAS mutations were detected in 112 cases (43.6%) by Sanger sequencing and 118 cases (45.9%) by the cobas test. Concordance between the cobas test and Sanger sequencing for each lot was 93.8% positive percent agreement (PPA) and 91.0% negative percent agreement (NPA) for codons 12/13. Results from the cobas test and Sanger sequencing were discordant for 20 cases (7.8%). Twenty discrepant cases were subsequently subjected to 454 pyrosequencing. After comprehensive analysis of the results from combined Sanger sequencing–454 pyrosequencing and the cobas test, PPA was 97.5% and NPA was 100%. Conclusions The cobas test is an accurate and sensitive test for detecting KRAS-activating mutations and has analytical power equivalent to Sanger sequencing. Prescreening using the cobas test with subsequent application of Sanger sequencing is the best strategy for routine detection of KRAS mutations in CRC.
The inflammatory component in progressive renal disease--are interventions possible?

The pathogenesis of progressive renal diseases leading to end-stage renal failure is still largely unknown and is therefore the subject of intense investigation. Some features have been well recognized such as the development of glomerulosclerosis, tubulointerstital injury, and the accumulation of extracellular matrix leading to fibrosis and scarring of the renal structures. It is now clear that major events, which determine the outcome of progressive renal disease, regardless of the initial insult, are related to the tubulointerstitial compartment. Even in primary glomerulonephritis the degree of tubulointerstitial damage correlates more closely with the long-term outcome than to the extent of glomerular involvement w1,2x. Although mechanical factors such as glomerular hypertension and hypertrophy are likely to contribute to the initiation of some forms of progressive renal disease, tubulointerstitial lesions cannot be simply interpreted as an ischaemic sequela of glomerular sclerosis. There is growing evidence that the participation of cellular and inflammatory mechanisms play a critical role in the progression of renal disease. Tubulointerstitial inflammation comprises an influx and proliferation of inflammatory cells capable of producing a variety of local inflammatory mediators and activation of tubular as well as other intrinsic renal cells. The development of progressive renal damage occurs even after resolution of the initial insult suggesting that this cascade of events occurring in the tubulointerstitium, once triggered, has an autonomic and progressive pattern. Thus, the recognition of these events is of crucial importance not only in understanding the steps involved in the development of chronic inflammatory lesions but also in defining targets of therapies. Cellular and molecular events involved in the progression of renal disease
Comprehensive and Interactive Temporal Query Processing with SAP HANA

In this demo, we present a prototype of a main memory database system which provides a wide range of temporal operators featuring predictable and interactive response times. Much of real-life data is temporal in nature, and there is an increasing application demand for temporal models and operations in databases. Nevertheless, SQL:2011 has only recently overcome a decade-long standstill on standardizing temporal features. As a result, few database systems provide any temporal support, and even those only have limited expressiveness and poor performance. Our prototype combines an in-memory column store and a novel, generic temporal index structure named Timeline Index. As we will show on a workload based on real customer use cases, it achieves predictable and interactive query performance for a wide range of temporal query types and data sizes.