Raman scattering studies of order parameters in liquid crystalline dimers exhibiting the nematic and twist-bend nematic phases

Polarized Raman Spectroscopy (PRS) is used to quantify the orientational order in the conventional (N) and twist-bend (NTB) nematic phases of a homologous series of liquid crystalline dimers. The dimers investigated have 7, 8, 9 and 11 methylene groups connecting two cyanobiphenyl mesogens and data for 4-pentyl-4'-cyanobiphenyl (5CB) and 4-octyl-4'-cyanobiphenyl (8CB) are included for comparison. Simulated and measured Raman spectra for the materials are compared. PRS is used to determine both (P2) and (P4) order parameters across the nematic temperature range and immediately below the NTB–N phase transition using a model that takes into account the molecular bend of the odd dimers, which is described in detail. In the nematic phase, the odd dimers are found to exhibit rather low order parameters with hP2i taking values between 0.3 and 0.5 and (P4) about 0.25. In contrast, the even dimer shows extremely high values of the order parameters with (P2) taking values between 0.7 and 0.8 and (P4) between 0.4 and 0.45. For the odd dimers, the values of (P2) in the NTB phase are similar to those of the N phase, whereas (P4) jumps by approximately 5–10% and then decreases with temperature. On comparing the experimental data with the theoretical predictions, we find reasonable qualitative agreement for all materials with molecular field theory. The odd dimers, however, show higher (P4) values than obtained from theoretical models, a factor attributed to the neglect of molecular flexibility and biaxiality in the PRS analysis

The broad phenotypic spectrum of 17α-hydroxylase/17,20-lyase (CYP17A1) deficiency: a case series

CONTEXT: 17α-Hydroxylase/17,20-lyase deficiency (17OHD) caused by mutations in the CYP17A1 gene is a rare form of congenital adrenal hyperplasia typically characterised by cortisol deficiency, mineralocorticoid excess and sex steroid deficiency. OBJECTIVE: To examine the phenotypic spectrum of 17OHD by clinical and biochemical assessment and corresponding in silico and in vitro functional analysis. DESIGN: Case series. PATIENTS AND RESULTS: We assessed eight patients with 17OHD, including four with extreme 17OHD phenotypes: two siblings presented with failure to thrive in early infancy and two with isolated sex steroid deficiency and normal cortisol reserve. Diagnosis was established by mass spectrometry-based urinary steroid profiling and confirmed by genetic CYP17A1 analysis, revealing homozygous and compound heterozygous sequence variants. We found novel (p.Gly111Val, p.Ala398Glu, p.Ile371Thr) and previously described sequence variants (p.Pro409Leu, p.Arg347His, p.Gly436Arg, p.Phe53/54del, p.Tyr60IlefsLys88X). In vitro functional studies employing an overexpression system in HEK293 cells showed that 17,20-lyase activity was invariably decreased while mutant 17α-hydroxylase activity retained up to 14% of WT activity in the two patients with intact cortisol reserve. A ratio of urinary corticosterone over cortisol metabolites reflective of 17α-hydroxylase activity correlated well with clinical phenotype severity. CONCLUSION: Our findings illustrate the broad phenotypic spectrum of 17OHD. Isolated sex steroid deficiency with normal stimulated cortisol has not been reported before. Attenuation of 17α-hydroxylase activity is readily detected by urinary steroid profiling and predicts phenotype severity. SIGNIFICANCE STATEMENT: Here we report, supported by careful phenotyping, genotyping and functional analysis, a prismatic case series of patients with congenital adrenal hyperplasia due to 17α-hydroxylase (CYP17A1) deficiency (17OHD). These range in severity from the abolition of function, presenting in early infancy, and unusually mild with isolated sex steroid deficiency but normal ACTH-stimulated cortisol in adult patients. These findings will guide improved diagnostic detection of CYP17A1 deficiency

General Analysis of Antideuteron Searches for Dark Matter

Low energy cosmic ray antideuterons provide a unique low background channel for indirect detection of dark matter. We compute the cosmic ray flux of antideuterons from hadronic annihilations of dark matter for various Standard Model final states and determine the mass reach of two future experiments (AMS-02 and GAPS) designed to greatly increase the sensitivity of antideuteron detection over current bounds. We consider generic models of scalar, fermion, and massive vector bosons as thermal dark matter, describe their basic features relevant to direct and indirect detection, and discuss the implications of direct detection bounds on models of dark matter as a thermal relic. We also consider specific dark matter candidates and assess their potential for detection via antideuterons from their hadronic annihilation channels. Since the dark matter mass reach of the GAPS experiment can be well above 100 GeV, we find that antideuterons can be a good indirect detection channel for a variety of thermal relic electroweak scale dark matter candidates, even when the rate for direct detection is highly suppressed.Comment: 44 pages, 15 Figure

Effect of pre-milking teat preparation procedures on the microbial count on teats prior to cluster application

A study was carried out to investigate the effect of six pre-milking teat preparation procedures on lowering the staphylococal, streptococcal and coliform microbial count on teat skin prior to cluster application. The teat preparations included 'Iodine', 'Chlorhexidine' teat foam, 'Washing and drying' with paper, 'No preparation', 'Chlorine' teat foam, and disinfectant 'Wipes'. Teat preparations were applied for five days to 10 cows for each treatment during two herd management periods (indoors and outdoors). Teats were swabbed on day four and five before teat preparation and repeated after teat preparation. The swabs were plated on three selective agars: Baird Parker (Staphylococcus spp.), Edwards (Streptococcus spp.), and MacConkey (coliform). Following incubation, microbial counts for each pathogen type were manually counted and assigned to one of six categories depending on the microbial counts measured. The results were analysed by logistic regression using SAS [28]. The main analysis was conducted on binary improvement scores for the swabbing outcomes. There were no differences for staphylococcal, streptococcal and coliform bacterial counts between treatments, measured 'before' teat preparation. Treatments containing 'Chlorhexidine' teat foam (OR = 4.46) and 'Wipes' (OR = 4.46) resulted in a significant reduction (P < 0.01) in the staphylococcal count on teats compared to 'Washing and drying' or 'No preparation'. 'Chlorine' teat foam (OR = 3.45) and 'Wipes' (3.45) had the highest probability (P < 0.01) of reducing streptococcal counts compared to 'Washing and drying' or 'No preparation'. There was no statistical difference between any of the disinfectant treatments applied in reducing coliforms. Thus, the use of some disinfectant products for pre-milking teat preparation can have beneficial effects on reducing the levels of staphylococcal and streptococcal pathogens on teat skin

Magnetic resonance imaging in patients with meningitis induced hearing loss

The aim of this multicentre study was to compare T1 with T2 weighted MRI scans of the labyrinth after meningitis and to investigate whether waiting with scanning improved the reliability of diagnosing an ongoing process such as cochlear osteogenesis. Forty-five patients were included who suffered from meningitis induced hearing loss (radiological imaging <1 year after meningitis). Twenty-one gadolinium enhanced T1 and 45 T2 weighted MRI scans were scored by two radiologists regarding the condition of the labyrinth. These radiological observations were compared with the condition of the cochlea as described during cochlear implantation. A higher percentage of agreement with surgery was found for T2 (both radiologists 73%) than for T1 weighted MRI scans (radiologist 1: 62%, radiologist 2: 67%), but this difference is not significant. There was no significant difference between early (0–3 months) and late (>3 months) scanning, showing that radiological imaging soon after meningitis allows early diagnosis without suffering from a lower agreement with surgical findings

Calf health from birth to weaning. I. General aspects of disease prevention

Calfhood diseases have a major impact on the economic viability of cattle operations. This is the first in a three part review series on calf health from birth to weaning, focusing on preventive measures. The review considers both pre- and periparturient management factors influencing calf health, colostrum management in beef and dairy calves and further nutrition and weaning in dairy calves

Exhaustive exercise training enhances aerobic capacity in American alligator (Alligator mississippiensis)

The oxygen transport system in mammals is extensively remodelled in response to repeated bouts of activity, but many reptiles appear to be ‘metabolically inflexible’ in response to exercise training. A recent report showed that estuarine crocodiles (Crocodylus porosus) increase their maximum metabolic rate in response to exhaustive treadmill training, and in the present study, we confirm this response in another crocodilian, American alligator (Alligator mississippiensis). We further specify the nature of the crocodilian training response by analysing effects of training on aerobic [citrate synthase (CS)] and anaerobic [lactate dehydrogenase (LDH)] enzyme activities in selected skeletal muscles, ventricular and skeletal muscle masses and haematocrit. Compared to sedentary control animals, alligators regularly trained for 15 months on a treadmill (run group) or in a flume (swim group) exhibited peak oxygen consumption rates higher by 27 and 16%, respectively. Run and swim exercise training significantly increased ventricular mass (~11%) and haematocrit (~11%), but not the mass of skeletal muscles. However, exercise training did not alter CS or LDH activities of skeletal muscles. Similar to mammals, alligators respond to exercise training by increasing convective oxygen transport mechanisms, specifically heart size (potentially greater stroke volume) and haematocrit (increased oxygen carrying-capacity of the blood). Unlike mammals, but similar to squamate reptiles, alligators do not also increase citrate synthase activity of the skeletal muscles in response to exercise

Copy Number and Loss of Heterozygosity Detected by SNP Array of Formalin-Fixed Tissues Using Whole-Genome Amplification

The requirement for large amounts of good quality DNA for whole-genome applications prohibits their use for small, laser capture micro-dissected (LCM), and/or rare clinical samples, which are also often formalin-fixed and paraffin-embedded (FFPE). Whole-genome amplification of DNA from these samples could, potentially, overcome these limitations. However, little is known about the artefacts introduced by amplification of FFPE-derived DNA with regard to genotyping, and subsequent copy number and loss of heterozygosity (LOH) analyses. Using a ligation adaptor amplification method, we present data from a total of 22 Affymetrix SNP 6.0 experiments, using matched paired amplified and non-amplified DNA from 10 LCM FFPE normal and dysplastic oral epithelial tissues, and an internal method control. An average of 76.5% of SNPs were called in both matched amplified and non-amplified DNA samples, and concordance was a promising 82.4%. Paired analysis for copy number, LOH, and both combined, showed that copy number changes were reduced in amplified DNA, but were 99.5% concordant when detected, amplifications were the changes most likely to be ‘missed’, only 30% of non-amplified LOH changes were identified in amplified pairs, and when copy number and LOH are combined ∼50% of gene changes detected in the unamplified DNA were also detected in the amplified DNA and within these changes, 86.5% were concordant for both copy number and LOH status. However, there are also changes introduced as ∼20% of changes in the amplified DNA are not detected in the non-amplified DNA. An integrative network biology approach revealed that changes in amplified DNA of dysplastic oral epithelium localize to topologically critical regions of the human protein-protein interaction network, suggesting their functional implication in the pathobiology of this disease. Taken together, our results support the use of amplification of FFPE-derived DNA, provided sufficient samples are used to increase power and compensate for increased error rates

Protein and Overtraining: Potential Applications for Free-Living Athletes

Despite a more than adequate protein intake in the general population, athletes have special needs and situations that bring it to the forefront. Overtraining is one example. Hard-training athletes are different from sedentary persons from the sub-cellular to whole-organism level. Moreover, competitive, "free-living" (less-monitored) athletes often encounter negative energy balance, sub-optimal dietary variety, injuries, endocrine exacerbations and immune depression. These factors, coupled with "two-a-day" practices and in-season demands require that protein not be dismissed as automatically adequate or worse, deleterious to health. When applying research to practice settings, one should consider methodological aspects such as population specificity and control variables such as energy balance. This review will address data pertinent to the topic of athletic protein needs, particularly from a standpoint of overtraining and soft tissue recovery. Research-driven strategies for adjusting nutrition and exercise assessments will be offered for consideration. Potentially helpful nutrition interventions for preventing and treating training complications will also be presented