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Protein interactions with surfaces are key to understanding the behavior of implantable medical devices. The optical technique of reflection anisotropy spectroscopy (RAS) has considerable potential for the study of interactions between important biological molecules and surfaces. This study used RAS to investigate the adsorption of S amino acids onto Au(110) in a liquid environment under different conditions of potential and pH. Certain spectral features can be associated with the Au(110), as reported previously, while other features are assigned to bonds between the amino acids and the Au surface. The RA spectra are shown to be influenced by the structure of the amino acid, the solution pH, and the applied electrode potential. This work has assigned the negative feature at 2.5 eV to the Au-thiolate, bond while the positive feature at 2.5 eV is assigned to the disulfide bond. The broad spectral feature at 3.5 eV is attributed to the Au-amino interaction, while the sharper feature at slightly higher energy is associated with the Au-carboxylate interaction. Sulfur-containing amino acids are frequently found on the outside of protein molecules and could be used to anchor the protein to the surface.

Many recombinant poxviral vaccines are currently in clinical trials for cancer and infectious diseases. However, these agents have failed to generate T cell responses specific for recombinant gene products at levels comparable with T cell responses associated with natural viral infections. The recent identification of vaccinia-encoded CTL epitopes, including a new epitope described in this study, allows the simultaneous comparison of CTL responses specific for poxviral and recombinant epitopes. We performed detailed kinetic analyses of CTL responses in HLA-A*0201 patients receiving repeated injections of recombinant modified vaccinia Ankara encoding a string of melanoma tumor Ag epitopes. The vaccine-driven CTL hierarchy was dominated by modified vaccinia Ankara epitope-specific responses, even in patients who had not received previous smallpox vaccination. The only recombinant epitope that was able to impact on the CTL hierarchy was the melan-A26–35 analog epitope, whereas responses specific for the weaker affinity epitope NY-ESO-1157–165 failed to be expanded above the level detected in prevaccination samples. Our results demonstrate that immunodominant vaccinia-specific CTL responses limit the effectiveness of poxviruses in recombinant vaccination strategies and that more powerful priming strategies are required to overcome immunodominance of poxvirus-specific T cell responses.

We have investigated the adsorption of L-cysteine (L-Cys) onto Au(110) in an electrochemical cell and under ultra-high vacuum (UHV) conditions using reflection anisotropy spectroscopy (RAS). The L-Cys saturated surfaces created by both deposition methods exhibit similar RA profiles which indicates a similar adsorption process. Our results are consistent with L-Cys binding to the Au(110) surface through a goldthiolate (Au-S) linkage. Heating the L-Cys saturated surface in UHV to 580 K results in the decomposition of the adsorbate and leaves behind a sulphur/Au surface composed of different structural domains. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Asymmetric dimethylarginine (ADMA) is an endogenously occurring methylarginine that inhibits nitric oxide synthesis. Plasma levels of methylarginines increase in renal failure and certain cardiovascular pathologies, and in patients with end stage renal failure the level of ADMA predicts the risk of cardiovascular events and overall mortality. The object of this review is to describe the mechanisms of ADMA synthesis, metabolism and uptake and to outline techniques for measuring ADMA and the pathological states in which ADMA levels are altered.

The reflection anisotropy spectra of 2,-bipyridine and 4,-bipyridine adsorbed onto an Au(110) surface in an electrochemical cell demonstrate that both systems form ordered structures. It is shown that reflection anisotropy spectroscopy can be used to distinguish between structural isomers adsorbed on the Au(110) surface.

Objectives: To evaluate the diet of 16–18-y-old boys and girls with particular reference to intakes of nutrients believed to affect bone health and dietary acid–base balance. Design: A 7-day food diary was completed between the months of October and December. Setting: Cambridge, UK Subjects: A total of 111 boys and 101 girls aged 16–18 y who were recruited into the Cambridge Bone Studies. Main outcome measures: Mean daily intakes of foods and selected nutrients (protein, calcium, phosphorus, magnesium, potassium, vitamins C and K) were calculated. Two estimates of acid–base balance were calculated from the diet using the formulae of Remer (net acid excretion, estimated indirectly; NAEind) and Frassetto (protein/potassium ratio). Results: Mean calcium and phosphorus intakes were above the UK Reference Nutrient intake (RNI). In all, 39% of the boys and 36% of the girls had vitamin K intakes lower than 1 μg/kg body weight/day. Calcium intake was positively correlated with all other nutrients except vitamins C and K. Boys had a significantly higher estimated net acid excretion (NAEind) than girls (P

The linguistic structure of an utterance is known to affect the durational prosody of sounds, words and phrases. There has been increasing interest in how discourse-level organization affects prosody, in part because modeling discourse-level effects could improve the comprehensibility of longer passages of synthesized text. The approach taken here is to look at how topics are sequenced in a text, and how this affects durational prosody when that text is read aloud. Two speakers of American English were recorded reading a set of text materials on 10 separate occasions. Measurements of these recordings indicated that the type of transition in topic between two successive sentences had a significant effect on the amount of sentence-final lengthening, the duration of the pause between sentences, and the speech rate at the end of a sentence and the beginning of the following sentence. These measurements were then used to create a mathematical model of one speaker, and to generate several versions of one of this speaker's original recordings, with each version incorporating different manipulations of the durational patterns and their variability. These versions were played to listeners, who preferred those where the manipulations included durational patterns reflecting the organization of topics in the text.

The compounds 4-ROC6F4CCPh (4) where R = Me (a), Et (b), Prn (c), Pri (d), Bun (e), n-C5H11 (f), PhCH2 (g), PhCH2CH2 (h), 4-MeC6H4 (i), 4-EtC6H4 (j) and menthyl (k), have been prepared by reaction of C6F5CCPh (3) with ROH in the presence of KOH, and characterised by NMR (1H, 13C, 19F) and mass spectroscopy. The single-crystal structures of PhCCPh·C6F5CCC6F5 (1∶2), 3 and 4a,c,d,f,g,i have been determined by X-ray diffraction at 120–160 K, and that of 3 also calculated by an ab initio pseudo-potential DFT method. The tolan moiety is nearly planar in each molecule except 4a, which has a Ph/C6F5 dihedral angle of 25.8°. The R group adopts an out-of-plane orientation except in 4f, where the n-pentyl chain is nearly coplanar with the C6F5 group at the cost of severe distortion of the C(ar)–C(ar)–O angles (which differ by 13.5°). The structures of 1∶2, 3 (pseudo-isomorphous with 1∶2), 4a, 4g (disordered) and 4i contain stacks of alternating arene and perfluoroarene moieties; 4c and 4d form discrete centrosymmetric dimers with arene/perfluoroarene overlap, while 4f forms infinite stacks without such overlap. Differential thermal analysis and transmitted polarised light microscopy revealed no liquid-crystalline behaviour of 3 and 4.

Body sweat mapping Of male athletes following acclimation to a hot-dry environment: 660 June 1, 2: 30 PM - 2: 45 PM.

Key Clinical Message Lingual tonsillar hypertrophy is an unusual presentation of voice change. If managed incorrectly this group of patients has the potential to deteriorate significantly causing airway obstruction and potentially death.

Department of Physics, University of Aberystwyth, Ceredigion SY23 3BZ, Wales, UK Received 30 May 2003, revised 4 August 2003, accepted 11 August 2003 Published online 10 November 2003 PACS 07.60.Fs, 78.20.Ci, 78.40.Kc We report measurements of the optical constants of single crystal Au(110) in the range of 1.5 to 5.0 eV using Spectroscopic Ellipsometry. The results are compared with previously published data. In addition we have used the data to carry out a fit to RAS data obtained from the same crystal.

Fagyal and Moisset (1999) suggested that vowel devoicing in standard French occurs most often in phrase-final high vowels. An experiment testing the effect of both immediate segmental context and sentence-level contextual factors was conducted to further identify the linguistic features involved. Six French speakers were recorded reading test sentences. Devoicing only occurred in sentence-final vowels, but in more contexts than expected. From a cross-linguistic perspective the distribution of devoicing in French is unusual. Final position is prosodically prominent in French, whereas in many languages devoicing is a form of vowel reduction associated with lack of prominence. Different physical mechanisms may therefore be responsible.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and is metabolised by dimethylarginine dimethylaminohydrolase (DDAH). Elevated levels of circulating ADMA correlate with various cardiovascular pathologies less is known about the cellular effects of altered DDAH activity. We modified DDAH activity in cells and measured the changes in ADMA levels, morphological phenotypes on Matrigel, and expression of vascular endothelial growth factor (VEGF). DDAH over-expressing ECV304 cells secreted less ADMA and when grown on Matrigel had enhanced tube formation compared to untransfected cells. VEGF mRNA levels were 2.1-fold higher in both ECV304 and murine endothelial cells (sEnd.1) over-expressing DDAH. In addition the DDAH inhibitor, S-2-amino-4(3-methylguanidino)butanoic acid (4124W 1mM), markedly reduced human umbilical vein endothelial cell tube formation in vitro. We have found that upregulating DDAH activity lowers ADMA levels, increases the levels of VEGF mRNA in endothelial cells, and enhances tube formation in an in vitro model, whilst blockade of DDAH reduces tube formation.

The IR and resonance Raman spectra of the nickel(II) complexes of dibenzo[b,i][1,4,8,11]tetraaza[14]annulene (TAA) and 5,7,12,14-tetramethyldibenzo[b,i][1,4,8,11]tetraaza[14]annulene (TMTAA) have been measured and compared with ab initio calculations of the vibrational wavenumbers at the B3-LYP level using the LanL2DZ basis set. An excellent fit is found between the experimental and calculated data, enabling precise vibrational assignments to be made. Surface-enhanced resonance Raman spectra were obtained following adsorption on Ag electrodes, with potentials in the range -0.1 to -1.1 V vs Ag/AgCl. There is evidence for contributions from both the electromagnetic and charge transfer (CT) surface enhancement mechanisms. The data indicate that variations in band intensities with electrode potential can be interpreted in terms of the CT mechanism.

The structures and conformational behaviour of the sulfenyl carbonyl compounds ClC(O)SCl and ClC(O)SCH3 have been investigated in the gas and crystalline states by a combination of quantum chemical (HF, MP2 and DFT approximations with the 6-31+G* basis set) calculations, IR studies of the matrix-isolated molecules, and X-ray crystallographic analysis of single crystals at low temperatures. Hence the predominance of the syn rotamer in the vapour of each compound has been confirmed; the anti rotamer must account for less than 1% of the vapour molecules. The crystals of the compounds are each composed exclusively of the planar syn rotamer with overall Cs symmetry.

Over the last decade, there has been a rapid expansion in the field of tumour immunology. There is now convincing evidence that both the cellular and humoral arms of the immune system are capable of interacting with tumour cells. The most significant advances have been in our understanding of cellular responses and the complex events that lead to T-lymphocyte activation, as well as in the identification of tumour antigens recognised by T-lymphocytes. This knowledge has led to the development of anticancer immunotherapies designed to produce tumour antigen-specific T-cell responses, adding to the earlier antibody or whole-cell vaccine approaches. In addition, new methods have been developed to quantify antigen-specific T-cell responses, and the emergent field of recombinant gene technology has led to an increasing number of novel methods for vaccine delivery. This review will explore these advances, as well as possible future directions, with an emphasis on colorectal cancer.

This paper describes a battery of physical exposure assessment methods used in a large prospective upper extremity musculoskeletal disorders study. Different from some previous prospective studies, this study collects health and physical exposure data for each study subject rather than at a group level. Subjects are recruited from different job categories based on their hand activity exposure categories. Multiple exposure assessment methods are used to measure job physical exposures such as force, repetition, and work posture. This will allow us to compare the sensitivity of different exposure assessment methods in predicting the risk for upper extremity musculoskeletal disorders. Procedures have also been taken to monitor inter-observer reliability for some observational analyses. During the first year of the study, baseline exposure measurements have been collected from 607 volunteers at 11 different worksites. Follow-up measurements have also been collected in these worksites. Whenever a participant has a significant job change, a new exposure assessment is conducted at the new job. This paper will primarily discuss the various exposure assessment methods used in this study, and use some preliminary results to demonstrate some of the data reduction methods.

Intake and sources of phylloquinone (vitamin K1) were examined according to socio-demographic and lifestyle factors in free-living British people aged 65 years and over, from the 1994-5 National Diet and Nutrition Survey. Complete 4-d weighed dietary records were obtained from 1152 participants living in private households. Using newly-available, mainly UK-specific food content data, the weighted geometric mean intake of phylloquinone was estimated at 65 (95 % CI 62, 67) microg/d for all participants, with higher intakes in men than in women (70 v. 61 microg/d respectively, P

Prosodic boundaries are marked in speech by modifications to dimensions such as F0, duration, and segmental quality. The experiment reported here tests the hypothesis that modifications at the end of a prosodic domain may be amplified or attenuated depending on the type of sentence (statement or question). The prosodic modifications investigated here for French are sentence-final lengthening and vowel devoicing, which is related to changes in voice quality. Six native speakers of French read 10 matched sets of sentences, which included both statements and questions. Measurements were made of the last vowel in each test sentence and of sentence-medial vowels in control sentences. Statement-final vowels were less periodic and more often devoiced than vowels at the end of questions or sentencemedial vowels, but question-final vowels were lengthened more than statement-final vowels. These results occurred in questions both with and without a final pitch rise, suggesting that sentence type is more important than final intonation contour in determining how prosodic finality is marked. The difference between statements and questions thus appears to be in the relative importance of lengthening and voice quality modification in marking finality, not in the overall extent to which it is marked.

Approximately 140 students take Introduction to Phonetics each year at the University of New Mexico. They are diverse in several ways: in age (many are returning to school after years away), in ethnicity (UNM is majority-minority), in major (the course serves Linguistics and Speech & Hearing), and in preparation (there are no prerequisites, but many students have some related coursework). This paper reports on design considerations and experience with the first online offering of this course. Studying online requires self-motivation and the ability to work independently, which are difficult for the large number of students with poor study skills and time management. This course attempts to counter these challenges with a high degree of structure, and activities in a variety of formats for learning and assessment. Although some in distance education view structure as a “constraint” for learner and teacher (Farquhar 2013 Eur. J. e-learning), this instructor believes that the flexibility and isolation of onl...

Background The use of fibrin sealant in the management of pilonidal sinus disease has not previously been described in children. We present our experience of primary pit excision and use of fibrin sealant (PEF) and compare outcomes with lateralising flap procedures (LFP). Methods A single centre retrospective case note review of all children who had undergone a definitive procedure for pilonidal sinus from August 2006 to Dec 2013 was performed using data expressed as median (range) and compared using Fisher’s exact test. P Results Forty-one children were identified having undergone 49 procedures, with median age 15 (12–16 years) and follow up 32 (8–92) months. Groups were comparable for disease severity. Ten children underwent primary PEF and twenty-six LFP. Two children had recurrence following primary PEF and had repeat PEF which was curative. Overall recurrence rates following PEF procedure were comparable to LFP (17% vs 21%; P = 1.0). There were no wound dehiscences in the PEF group and one wound infection. There was one wound dehiscence and one wound infection in the LFP group. Median operative time for PEF was lower than LFP (20 vs 60 min, P = 0.001). 83% of PEF procedures were performed as day cases. One child was lost to follow up, and two children progressed to adult services. Conclusions We recommend PEF in children with pilonidal sinus disease as primary treatment and for recurrence. PEF has comparable recurrence and wound infection rates to LFPs, is performed as day case, has shorter anaesthetic times, and the risk of wound dehiscence is avoided.

Introduction Cell surface thiol isomerase enzymes, principally protein disulphide isomerase (PDI), have emerged as important regulators of platelet function and tissue factor activation via their action on allosteric disulphide bonds. Allosteric disulphides are present in other haemostasis-related proteins, and we have therefore investigated whether thiol isomerase inhibition has any influence on two endothelial activities relevant to haemostatic regulation, namely activation of protein C and activation of plasminogen, with subsequent fibrinolysis. Materials and Methods The study was performed using the human microvascular endothelial cell line HMEC-1. Thiol isomerase gene expression was measured by RT-PCR and activation of protein C and plasminogen by cell-based assays using chromogenic substrates S2366 and S2251, respectively. Cell mediated fibrinolysis was measured by monitoring absorbance at 405 nm following fibrin clot formation on the surface of HMEC-1 monolayers. Results and Conclusions A variety of thiol isomerase enzymes, including PDI, were expressed by HMEC-1 cells and thiol reductase activity detectable on the cell surface was inhibited by both RL90 anti-PDI antibody and by the PDI inhibitor quercetin-3-rutinoside (rutin). In cell-based assays, activation of plasminogen, but not of protein C, was inhibited by RL90 antibody and, to a lesser extent, by rutin. Fibrin clot lysis occurring on a HMEC-1 monolayer was also significantly slowed by RL90 antibody and by rutin, but RL90-mediated inhibition was abolished in the presence of exogenous tissue plasminogen activator (tPA). We conclude that thiol isomerases, including PDI, are involved in fibrinolytic regulation at the endothelial surface, although not via a direct action on tPA. These findings broaden understanding of haemostatic regulation by PDI, and may aid in development of novel anti-thrombotic therapeutic strategies targeted via the fibrinolysis system.

We recently demonstrated that vasopressin (AVP) in the lateral septum modulates social play behavior differently in male and female juvenile rats. However, the extent to which different social contexts (i.e., exposure to an unfamiliar play partner in different environments) affect the regulation of social play remains largely unknown. Given that AVP and the closely related neuropeptide oxytocin (OXT) modulate social behavior as well as anxiety-like behavior, we hypothesized that these neuropeptides may regulate social play behavior differently in novel (novel cage) as opposed to familiar (home cage) social environments. Administration of the specific AVP V1a receptor (V1aR) antagonist (CH2)5Tyr(Me(2))AVP into the lateral septum enhanced home cage social play behavior in males but reduced it in females, confirming our previous findings. These effects were context-specific because V1aR blockade did not alter novel cage social play behavior in either sex. Furthermore, social play in females was reduced by AVP in the novel cage and by OXT in the home cage. Additionally, females administered the specific OXT receptor antagonist desGly-NH2,d(CH2)5-[Tyr(Me)(2),Thr(4)]OVT showed less social play in the novel as compared to the home cage. AVP enhanced anxiety-related behavior in males (tested on the elevated plus-maze), but failed to do so in females, suggesting that exogenous AVP alters social play and anxiety-related behavior via distinct and sex-specific mechanisms. Moreover, none of the other drug treatments that altered social play had an effect on anxiety, suggesting that these drug-induced behavioral alterations are relatively specific to social behavior. Overall, we showed that AVP and OXT systems in the lateral septum modulate social play in juvenile rats in neuropeptide-, sex- and social context-specific ways. These findings underscore the importance of considering not only sex, but also social context, in how AVP and OXT modulate social behavior.

Venous leg ulcers (VLUs) are one of the most prevalent types of chronic wounds. The aim of this study was to determine the safety and dose-response efficacy of the human synthetic peptide LL-37 in the treatment of hard-to-heal VLUs. This first-in-man trial included 34 participants with VLUs and comprised a 3-week, open-label, run-in period on placebo, followed by a 4-week randomized double-blind treatment phase with twice weekly applications of LL-37 (0.5, 1.6, or 3.2 mg/mL) or placebo, and a 4-week follow-up. The healing rate constants for 0.5 and 1.6 mg/mL of LL-37 were approximately six- and threefold higher than for placebo (p = 0.003 for 0.5 mg/mL and p = 0.088 for 1.6 mg/mL). Square-root transformed wound area data showed improved healing for the 0.5 and 1.6 mg/mL dose groups compared with pretreatment values (p 0.001 and p = 0.011, respectively). Consistently, treatment with the two lower doses markedly decreased the mean ulcer area (68% for 0.5 mg/mL and 50% for 1.6 mg/mL groups). No difference in healing was observed between the groups receiving 3.2 mg/mL of LL-37 and placebo. There were no safety concerns regarding local or systemic adverse events. In conclusion, topical treatment with LL-37 for chronic leg ulcers was safe and well tolerated with the marked effect on healing predictors at the two lower doses warranting further investigations.

Changes observed in the reflection anisotropy spectroscopy (RAS) profiles of monolayers of cytochrome P450 reductase adsorbed at Au(110)--electrolyte interfaces at 0.056 V following the addition of nicotinamide adenine dinucleotide phosphate $({\mathrm{NADP}}^{+})$ are explained in terms of a simple model as arising from changes in the orientation of an isoalloxazine ring located in the flavin mononucleotide binding domain of the protein. The model also accounts for the changes observed in the RAS as the potential applied to the Au(110) surface is varied and suggests that differences in the dependence of the RAS profile of the adsorbed protein on the potential applied to the electrode in the absence and presence of ${\mathrm{NADP}}^{+}$ are explicable as arising from a competition between the applied potential acting to reduce the protein and the ${\mathrm{NADP}}^{+}$ to oxidize it.

Objective: The objective of this prospective study is to investigate the exposure–response relationships between various workplace physical exposures of force, repetition, and their combination assessed at an individual level with lateral epicondylitis (LE). Background: Workplace upper extremity musculoskeletal disorders (UEMSDs) are prevalent, disabling, and expensive. LE is one of the major UEMSDs in active workers. Method: We used detailed health history, symptoms, and physical examination for identifying incidence and detailed exposure assessment to capture work tasks of each worker and to measure quantitative mechanical workload. We used counting process style input of proportional hazards regression for modeling cumulative incidence that accounts for changed exposure estimates during the follow-up period when respondents change jobs. Results: The incidence rate of LE on the dominant side was 4.91 per 100 person-years. Adjusted for age and gender, the combined effect of forearm pronation ≥45° for ≥40% of time and time spent with forceful exertion, including any power grip (hazard ratio [HR] = 2.8, 95% confidence interval [CI] = [1.35–5.77]), lifting for ≥3% of time (HR = 2.50, 95% CI = [1.19–5.24]), and duty cycle for forceful exertion for ≥10% (HR = 2.25, 95% CI = [1.09–4.66]), were significant predictors of dominant side LE, whereas neither the awkward posture nor the forceful exertion alone was significant. Older workers with jobs requiring a high percentage of time working with force in combination with awkward postures of forearm were more likely to predict LE. Conclusion: This study shows the evidence of the etiologic role of strenuous manual tasks in the occurrence of LE.

Background Acupuncture and other modalities of Chinese/East Asian medicine have been used to treat women’s health for many centuries. Gynecology specialties focus particularly on menstrual and reproductive disorders. Both the adoption of the use of acupuncture outside Asia, and the incorporation of scientific analysis in Asia have challenged biomedical conceptions of what can be achieved with this treatment method. The scale of research activity in relation to acupuncture and women’s health has increased over the last 20 years. Objective This review aims to explore the research evidence in relation to acupuncture use for women’s reproductive disorders, focusing on both clinical findings and experimental research on acupuncture’s mechanisms of action in relation to women’s health. Methods A narrative literature search was undertaken using searches of electronic databases and manual searches of journals and textbooks. The search included all literature published prior to June 2013. The literature was assessed as to the nature of the study it was reporting and findings synthesized into a commentary. Results For acupuncture’s mechanism of action the search resulted in 114 relevant documents; in relation to clinical reports on the use of acupuncture for women’s health 204 documents were found and assessed. Conclusion There is preliminary data indicating acupuncture may improve menstrual health and coping for women experiencing delays falling pregnant. There is experimental data showing that acupuncture can influence female reproductive functioning, although the actual mechanisms involved are not yet clarified. Further well-conducted clinical research would benefit our understanding of the usefulness of acupuncture to women’s health.

Melanocortin receptors (MCS, MC1–MC5) are GPCRs, activated with different affinities by the melanocortin peptides (?-, ?-, ?-MSH and ACTH). They are widely distributed throughout the body displaying a multitude of actions however their role in reproductive physiology is unclear. Previously, we have shown a reduction of pituitary hormone content and abnormalities in testes morphology in male MC3 null mice. The aim of this study was to characterise MCS expression in the male mouse reproductive axis and to investigate the effects of MCS agonists/antagonists on in vitro testicular testosterone production (TP). MCS expression patterns were determined in mRNAs from hypothalami, pituitaries and testes of Balb/c and C57BL/6 male mice by two-step reverse transcriptase (RT) - quantitative (q) PCR and analysed using qBaseplus. To examine the functions of MCS in gonads, testes of Balb/c and C57BL/6 mice were hemi-sected and incubated with the potent MC3 and, to a lesser extent, MC4 agonist ([D-TRP8]-?2-MSH; 0.3–10 ?g/ml) in the presence or absence of hCG (50 mIU/ml) and/or a MC3/MC4 antagonist and MC1/MC5 agonist (SHU9119; 10 ?g/ml) for 5 h at 35 °C in air. There were no significant differences in the pattern of MCS expression between C57BL/6 and Balb/c. The most abundant MC in the hypothalamus and pituitary appears to be MC3 whilst in the testis it was MC2. TP in C57BL/6 mice is 50% less than in Balb/c: confirming published data that the former mice are hypoandrogenic. Activation of MC3 and MC4 using [D-TRP8]-?2-MSH had no or inhibitory effects on basal TP in Balb/c and C57BL/6, respectively. The same ligand decreased TP in both strains in the presence of hCG. In contrast, SHU9119±hCG increased TP threefold compared to basal levels independently of ligand dose in Balb/c. This study suggests that activation of specific MCS can alter TP however further work is required.

One challenge in studying the second messenger inositol(1,4,5)-trisphosphate (InsP3) is that it is present in very low amounts and increases only transiently in response to stimuli. To identify events downstream of InsP3, we generated transgenic plants constitutively expressing the high specific activity, human phosphatidylinositol 4-phosphate 5-kinase Iα (HsPIPKIα). PIP5K is the enzyme that synthesizes phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2), this reaction is flux limiting in InsP3 biosynthesis in plants. Plasma membranes from transgenic Arabidopsis expressing HsPIPKIα had 2–3 fold higher PIP5K specific activity, and basal InsP3 levels in seedlings and leaves were &gt, 2-fold higher than wild type. Although there was no significant difference in photosynthetic electron transport, HsPIPKIα plants had significantly higher starch (2–4 fold) and 20% higher anthocyanin compared to controls. Starch content was higher both during the day and at the end of dark period. In addition, transcripts of genes involved in starch metabolism such as SEX1 (glucan water dikinase) and SEX4 (phosphoglucan phosphatase), DBE (debranching enzyme), MEX1 (maltose transporter), APL3 (ADP-glucose pyrophosphorylase) and glucose-6-phosphate transporter (Glc6PT) were up-regulated in the HsPIPKIα plants. Our results reveal that increasing the phosphoinositide (PI) pathway affects chloroplast carbon metabolism and suggest that InsP3 is one component of an inter-organelle signaling network regulating chloroplast metabolism.

A 16 channel reflectance anisotropy (RA) spectrometer capable of simultaneously acquiring reflectance spectra and real and imaginary RA spectra on the 0.1 s time-scale is reported. Its performance was evaluated by monitoring the electrolytic deposition/growth and removal of copper on a gold(110) surface. The slow deposition enabled very low noise spectra to be obtained, which served as the yardstick with which the spectra obtained during the rapid removal could be compared. The spectra obtained over the 15 s removal mirrored those obtained during the 500 s deposition period. The spectra are discussed in terms of the copper growth being in the form of aligned islands.

Euconodonts were the first vertebrates to produce a mineralized skeleton. It is concluded that the minor increments in the crown enamels of Protopanderodus varicostatus and Drepanodus robustus are probable homologues of the cross striations in hominoid enamel, although they are much more variable in thickness and represent daily to weekly growth. Major increments are superficially similar to lines of Retzuis, but represent a check in growth that is likely to have occurred at monthly intervals. Periods of above- and below-average growth are likely to have been seasonally moderated. The growth of P. varicostatus' elements are characterized by two distinct phases: the production of a triangular, asymmetrical juvenile 'proto-element' followed, in a second phase, by the development of the curved and twisted geometry of the adult element. These fundamentally different morphologies imply that juvenile and adult animals had different modes of life and/or feeding strategies. In these animals the growth of the elements was indeterminate. The growth model for euconodonts is clearly different from that of hominoid teeth as the enamel organ must have reformed repeatedly throughout life.

Objectives To identify the treatment patterns and early complication rates in women identified with a genital infection prior to a termination of pregnancy (TOP) and to re-assess our earlier work on contact attendance and treatment. The aim was to refine current prophylactic measures to provide the most efficient and effective way of reducing post-termination complications. Method Six-month retrospective analysis of all women with genital Chlamydia trachomatis or Neisseria gonorrhoeae identified prior to TOP. Data on the timing of positive results and treatment in relation to the TOP were recorded. Clinical signs of pelvic infection and the success of contact tracing and treatment were noted. Results Forty women were identified with infection, 31 (78%) proceeded to TOP; only five were treated adequately in the peri-TOP period. Twenty-six (84%) of the women undergoing TOP attended the genitourinary medicine (GUM) department after the TOP and received antimicrobial therapy where necessary. In total, four women (10%) were untreated. Approximately two thirds of results were reported prior to, or on the day of, the TOP. The majority of TOPs (71%) were carried out at 5 days or less from the initial assessment. Clinical signs of post-TOP pelvic inflammation developed in seven (28%) women with chlamydial infection. Contact tracing was successful in 24 (69%) of the 35 women who attended the GUM department. Conclusion The debate about the best option for the most effective management of women undergoing TOP continues. The options with respect to C. trachomatis include universal prophylaxis, screening and treating as necessary, or a 9belt and braces9 approach of screening all and treating all. Fundamental is the continuation of active contact tracing and GUM remains integral to this.

Introducing reflection anisotropy spectroscopy (RAS) as a new probe for solid-liquid interfaces, we present results for the Au(110)/electrolyte interface which serves as a model system. We demonstrate that RAS is sensitive to surface phase transitions, step morphology, and electronic surface states. Using an empirical approach, the RA spectra are reproduced and features are identified which reflect the known character of the bias voltage driven (2x1) to (1x1) phase transition. RAS is established as an experimental technique to probe the electronic structure of solid-liquid interfaces in real time to study a wide range of interface properties.

As stated in its Foreword, the Handbook is a ‘user’s manual’ for the International Phonetic Alphabet (IPA). It provides a variety of information about the philosophy and practice of IPA usage and in so doing, confronts a number of current issues in phonetics. But the goal of the Handbook remains resolutely practical, the intention being to give just ‘the information needed for getting to grips with the IPA’ (p. viii). Nonetheless, it provides much more information and discussion about transcription than the previous official source of information about the IPA, the 1949 Principles of the International Phonetic Association. The decision to produce a new Handbook was made at the 1989 Kiel Convention of the International Phonetic Association.

Background: The role of nutritional influences on bone health remains largely undefined because most studies have focused attention on calcium intake. Objective: We reported previously that intakes of nutrients found in abundance in fruit and vegetables are positively associated with bone health. We examined this finding further by considering axial and peripheral bone mass and markers of bone metabolism. Design: This was a cross-sectional study of 62 healthy women aged 45-55 y. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck and by peripheral quantitative computed tomography at the ultradistal radial total, trabecular, and cortical sites. Bone resorption was calculated by measuring urinary excretion of pyridinoline and deoxypyridinoline and bone formation by measuring serum osteocalcin. Nutrient intakes were assessed by using a validated food-frequency questionnaire; other lifestyle factors were assessed by additional questions. Results: After present energy intake was controlled for, higher intakes of magnesium, potassium, and alcohol were associated with higher total bone mass by Pearson correlation (P < 0.05 to P < 0.005). Femoral neck BMD was higher in women who had consumed high amounts of fruit in their childhood than in women who had consumed medium or low amounts (P < 0.01). In a regression analysis with age, weight, height, menstrual status, and dietary intake entered into the model, magnesium intake accounted for 12.3% of the variation in pyridinoline excretion and 12% of the variation in deoxypyridinoline excretion. Alcohol and potassium intakes accounted for 18.1% of the variation in total forearm bone mass. Conclusion: The BMD results confirm our previous work (but at peripheral bone mass sites), and our findings associating bone resorption with dietary factors provide further evidence of a positive link between fruit and vegetable consumption and bone health.

Voiced fricatives are often taken as an example of sound that is ‘difficult’ to produce. It might therefore be expected that speakers would choose to simplify them. In English, the most common simplification is devoicing, especially for voiced sibilants. The nature of this process was examined in productions of /z/ and /s/ by four speakers of American English. These were recorded in matched word and phrase positions using acoustic, airflow, and electroglottographic (EGG) data. Although many tokens of /z/ showed little or no vocal fold vibration in the EGG signal, durational and aerodynamic differences maintained the distinction between /z/ and /s/. The speakers varied in overall frequency of devoicing, but showed similar rank orderings for frequency of devoicing in different contexts. Devoicing was most frequent in two kinds of environments: those where it could be viewed as assimilation to an adjacent voiceless context, and those where articulatory and aerodynamic effort tends to be reduced. These contexts (unstressed syllables, and ends of words or phrases) have been shown to favor other kinds of prosodically-structured lenition.

Religiously involved lay women (N = 266), 31% of whom had been sexually abused in childhood, filled out the revised Spiritual Experience Index (SEI-R). Results showed higher SEI-R scores for the sexually abused group, with a more accepting attitude compared with those with a striving attitude. A subscale of the SEI-R revealed that the sexually abused may turn to their faith and spirituality for support. Those with the highest educational achievements, Catholics, and those who experienced emotional abuse scored high on the Spiritual Openness subscale. Implications for spiritual development and counseling are discussed.

The mini-clinical evaluation exercise (mini-CEX) is a widely used tool with a strong theoretical basis. It was introduced to UK foundation training in 2005.To assess current experiences, opinions and attitudes towards mini-CEX amongst foundation doctors, and explore what factors underpin these.Data were collected from foundation trainees via an on-line questionnaire.Ninety-eight per cent of respondents had used mini-CEX during FY1, however, only 32% had ever received formal teaching regarding its use. In terms of understanding of the purpose of mini-CEX, only 30% of trainees commented on there being a formative aspect or requirement for feedback. The majority of trainees did not feel that mini-CEX was a useful part of their training. The main themes were the poor attitude and understanding of assessors and difficulties finding sufficient time. However, those who had received formal teaching as students regarding the use of mini-CEX were significantly more likely as postgraduates to find it beneficial (p = 0.031).A more concerted effort to educate trainees and assessors regarding the correct use of mini-CEX will enhance its educational value. Increased education during undergraduate training regarding use of formative assessment may lead to more effective utilisation in the postgraduate setting.

The reflection anisotropy spectroscopy profiles of a variant of cytochrome P450 reductase adsorbed at the Au(110)--phosphate buffer interface depend on the sequence of potentials applied to the Au(110) electrode. It is suggested that this dependence arises from changes in the orientation of the isoalloxazine ring structures in the protein with respect to the Au(110) surface. This offers a method of monitoring conformational change in this protein by measuring variations in the reflection anisotropy spectrum arising from changes in the redox potential.

Background: The alpha+-thalassaemias are the most common monogenic disorders of humans, characterised by microcytic and hypochromic anaemia. Their high frequency reflects selective advantage against death from Plasmodium falciparum malaria. The most common type of alpha+- thalassaemia amongst people of African descent is the -?3.7 deletional type and affects 26-33% of Ghanaians. Plasmodium falciparum malaria is a major cause of mortality amongst children in sub-Saharan Africa. Unlike HbAS, HbAC and G6PD deficiency there remains debate about whether alpha+- thalassaemia protects against malaria and the mechanism for the protection. Methods: 1672 children of ?10 years were recruited and individuals with G6PD deficiency, HbAC and Hb AS reported to protect against malaria were excluded. 732 children with Plasmodium falciparum were tested for Hb, RBC, MCV, MCH and parasite density. The subjects were then categorised into normocytic and microcytic using a cut off MCV value of 76fL and normochromic and hypochromic using a cut off MCH value of 25 pg. Microcytic hypochromic individuals were genotyped by Polymerase Chain Reaction for the -?3.7 deletional thalassaemia mutation. Results: The frequency of Plasmodium falciparum malaria in the studied population was 54.1%. There was a frequency of 21.0% for the heterozygous (-?/??) and 8.3% for the homozygous (-?/-?) alpha+-thalassaemia, resulting in a carriage rate (?/?? & -?/-?) of 29.3%. Among the microcytic patients, geometric mean parasite density (GMPD) values were lower in the presence of an alpha+- thalassaemia genotype (-?/?? GMPD 9015, n=126 and -?/-? GMPD 6852, n=49) compared to normal genotype (??/?? GMPD 51794, n=358) (p 60 months for both the homozygous and heterozygous alpha+-thalassaemia were not significant at p=0.399 and p=0.207 respectively. Conclusion: The severity of Plasmodium falciparum parasitaemia measured, as either GMPD or prevalence of severe parasitaemia was significantly lower in both the -?/?? and -?/-?- groups compared to microcytic individuals with normal genotype. Even though GMPD differed significantly amongst all alpha+-thalassemia genotypes, it was not driven by hypochromasia. Among the homozygous and heterozygous alpha+-thalassaemias, children with severe anaemia had a significantly high GMPD than their counterparts who were not severely anaemic making them more susceptible to severe malaria anaemia. No loss of protection was seen in children younger or older than 60 months and therefore the protective effect from severe malaria might not wane with age. The mechanism of protection from severe Plasmodium falciparum malaria is not clear, however the influence of microcytosis and hypochromasia on parasite density requires more research.

Essential hypertension (HT) is associated with endothelial dysfunction augmented vasoconstriction (VC) which may be secondary to increased Rho/Rho-Kinase (ROCK)-dependent mechanisms. Our aim was to assess the in vivo magnitude of cutaneous VC to local cooling as a ROCK specific stimulus, and in vitro evaluate ROCK activity in skin from HT humans. Four microdialysis fibers were placed in the forearm of 9 pre- to stage I hypertensive (MAP: 106 ± 3 mmHg) and 11 normotensive (NT; 86 ± 1 mmHg) men and women: Ringers (control), 3 mM fasudil (ROCK inhibited), 5 mM yohimbine + 1 mM proprananol (α- and β-adrenoceptor inhibited; Y + P), Y + P + 3 mM fasudil (ROCK and adrenocepor inhibited). Skin blood flow was measured during local cooling (Tskl 24°C) and ROCK activity in skin biopsy samples was determined with western blot. In vitro phosphorylated myosin phosphatase target subunit 1 (pMYPT-1)/ROCK was increased in HT skin samples (p=0.0018). Functionally, no difference in basal vasomotor tone (Tskl 34°C) was observed between groups (HT: 0.36 ± 0.07 vs. NT: 0.31 ± 0.07 CVC), nor at the control site during local cooling. Pre- to stage 1 hypertensives show greater ROCK-mediated vasoconstriction at early (1–5 min; HT: −0.8±0.2 versus NT: −0.3±0.2 ΔCVC baseline 1; P

Background Neglected tropical diseases are co-endemic in many areas of the world, including sub Saharan Africa. Currently lymphatic filariasis (albendazole/ivermectin) and trachoma (azithromycin) are treated separately. Consequently, financial and logistical benefit can be gained from integration of preventive chemotherapy programs in such areas. Methodology/Findings 4 villages in two co-endemic districts (Kolondièba and Bougouni) of Sikasso, Mali, were randomly assigned to coadministered treatment (ivermectin/albendazole/azithromycin) or standard therapy (ivermectin/albendazole with azithromycin 1 week later). These villages had previously undergone 4 annual MDA campaigns with ivermectin/albendazole and 2 with azithromycin. One village was randomly assigned to each treatment arm in each district. There were 7515 eligible individuals in the 4 villages, 3011(40.1%) of whom participated in the study. No serious adverse events occurred, and the majority of adverse events were mild in intensity (mainly headache, abdominal pain, diarrhoea and “other signs/symptoms”). The median time to the onset of the first event, of any type, was later (8 days) in the two standard treatment villages than in the co-administration villages. Overall the number of subjects reporting any event was similar in the co-administration group compared to the standard treatment group [18.7% (281/1501) vs. 15.8% (239/1510)]. However, the event frequency was higher in the coadministration group (30.4%) than in the standard treatment group (11.0%) in Kolondièba, while the opposite was observed in Bougouni (7.1% and 20.9% respectively). Additionally, the overall frequency of adverse events in the co-administration group (18.7%) was comparable to or lower than published frequencies for ivermectin+albendazole alone. Conclusions These data suggest that co-administration of ivermectin+albendazole and azithromycin is safe; however the small number of villages studied and the large differences between them resulted in an inability to calculate a meaningful overall estimate of the difference in adverse event rates between the regimens. Further work is therefore needed before co-administration can be definitively recommended. Trial Registration ClinicalTrials.gov; NCT01586169, Author Summary Neglected tropical diseases are co-endemic in many areas of the world. Currently lymphatic filariasis (albendazole+ivermectin) and trachoma (azithromycin) are treated separately. Benefits can be gained from integration of preventive chemotherapy programs in such areas. To assess the safety of this approach, 4 villages in two co-endemic districts in Mali were randomly assigned to coadministered treatment (ivermectin/albendazole/azithromycin) or standard therapy (ivermectin/albendazole with azithromycin 1 week later). One village was randomly assigned to each treatment in each district. 3011(40.1%) of 7515 eligible individuals in the 4 villages participated in the study. No serious adverse events occurred, and most events were mild in intensity (mainly headache, abdominal pain, and diarrhoea). Overall the number of subjects reporting any event was similar with co-administration compared to standard treatment [18.7% (281/1501) vs. 15.8% (239/1510)]. The overall frequency of adverse events with co-administration was comparable to or lower than published frequencies for ivermectin/albendazole alone. These data suggest that co-administration is safe; however the small number of villages studied and the large differences between them meant that a meaningful estimate of the differences could not be calculated, and further work will be needed before a recommendation can be made.

Gravitropism is a universal plant response. It is initiated by the sensing of the primary signal (mass or pressure), which is then converted into chemical signals that are transduced and propagated in a precise spatial and temporal fashion, resulting in a differential growth response. Our thesis is that membrane lipids and lipid-mediated signaling pathways play critical roles in the initial signaling and in the establishment of polarity. In this review, we highlight results from recent literature and discuss the major questions that remain unanswered.

Childhood abuse is known to have a negative influence on human development. This study expected to find a spiritual attitude of acceptance, as measured by the Ego Grasping Orientation scale, would help mitigate effects of childhood abuse in the realm of spiritual development. Spiritual Experience Index (SEI) scores for 350 religious women were treated as a measure of spiritual maturity. Contrary to expectation, however, the sexually and the physically abused groups with a more accepting attitude scored lower on the SEI than the abused with a more controlling attitude and the nonabused. Implications for spiritual development and well-being are discussed.

The cyclic tetradentate ligand 1,4,7,11-tetra-azacyclotetradecane (isocyclam, = L) has been prepared by the Richman-Atkins procedure. The nickel(II) complexes of the ligand have been studied in detail. The complex [NiL](ClO4)2 undergoes a square planar ⇋ octahedral equilibrium in aqueous solution: [NiL]2+ + 2H2O ⇋K [NiL(OH2)2]2+; the equilibrium constant K has been determined as a function of temperature and ΔH° = −22.6 ± 1 kJ mol−1 and ΔS° = −74.9 ± 2 J K−1 mol−1. Reaction of ethylenediamine with [NiL](ClO4)2 leads to folding of the macrocyle and formation of the blue octahedral cis-[NiL(en)](ClO4)2. The complex [NiL]2+ displays a reversible one-electron reduction at −1.45 V versus SCE in aqueous solution and a reversible oxidation to the nickel(III) complex at +0.85 V versus SCE. [Ni(isocyclam)]2+ was found to be a good electrocatalyst for the two-electron reduction of CO2 to CO but is not as efficient as [Ni(cyclam)]2+.