Histidine Hydrogen-Deuterium Exchange Mass Spectrometry for Probing the Microenvironment of Histidine Residues in Dihydrofolate Reductase

Histidine Hydrogen-Deuterium Exchange Mass Spectrometry (His-HDX-MS) determines the HDX rates at the imidazole C(2)-hydrogen of histidine residues. This method provides not only the HDX rates but also the pK(a) values of histidine imidazole rings. His-HDX-MS was used to probe the microenvironment of histidine residues of E. coli dihydrofolate reductase (DHFR), an enzyme proposed to undergo multiple conformational changes during catalysis.Using His-HDX-MS, the pK(a) values and the half-lives (t(1/2)) of HDX reactions of five histidine residues of apo-DHFR, DHFR in complex with methotrexate (DHFR-MTX), DHFR in complex with MTX and NADPH (DHFR-MTX-NADPH), and DHFR in complex with folate and NADP+ (DHFR-folate-NADP+) were determined. The results showed that the two parameters (pK(a) and t(1/2)) are sensitive to the changes of the microenvironment around the histidine residues. Although four of the five histidine residues are located far from the active site, ligand binding affected their pK(a), t(1/2) or both. This is consistent with previous observations of ligand binding-induced distal conformational changes on DHFR. Most of the observed pK(a) and t(1/2) changes could be rationalized using the X-ray structures of apo-DHFR, DHFR-MTX-NADPH, and DHFR-folate-NADP+. The availability of the neutron diffraction structure of DHFR-MTX enabled us to compare the protonation states of histidine imidazole rings.Our results demonstrate the usefulness of His-HDX-MS in probing the microenvironments of histidine residues within proteins

Yukawa unification in SO(10) with light sparticle spectrum

We investigate supersymmetric SO(10) GUT model with \mu<0. The requirements of top-bottom-tau Yukawa unification, correct radiative electroweak symmetry breaking and agreement with the present experimental data may be met when the soft masses of scalars and gauginos are non-universal. We show how appropriate non-universalities can easily be obtained in the SO(10) GUT broken to the Standard Model. We discuss how values of BR(b-->s \gamma) and (g-2)_\mu simultaneously in a good agreement with the experimental data can be achieved in SO(10) model with \mu<0. In the region of the parameter space preferred by our analysis there are two main mechanisms leading to the LSP relic abundance consistent with the WMAP results. One is the co-annihilation with the stau and the second is the resonant annihilation via exchange of the Z boson or the light Higgs scalar. A very interesting feature of SO(10) models with negative \mu is that they predict relatively light sparticle spectra. Even the heaviest superpartners may easily have masses below 1.5 TeV in contrast to multi-TeV particles typical for models with positive \mu.Comment: 23 pages, 5 figure

Hadronic production of squark-squark pairs: The electroweak contributions

We compute the electroweak (EW) contributions to squark--squark pair production processes at the LHC within the framework of the Minimal Supersymmetric Standard Model (MSSM). Both tree-level EW contributions, of O(alpha_s alpha + alpha^2), and next-to-leading order (NLO) EW corrections, of O(alpha_s^2 alpha), are calculated. Depending on the flavor and chirality of the produced quarks, many interferences between EW-mediated and QCD-mediated diagrams give non-zero contributions at tree-level and NLO. We discuss the computational techniques and present an extensive numerical analysis for inclusive squark--squark production as well as for subsets and single processes. While the tree-level EW contributions to the integrated cross sections can reach the 20% level, the NLO EW corrections typically lower the LO prediction by a few percent.Comment: 36 pages, 18 figure

Hepatitis C Virus Screening Strategies to Improve Early Identification and Treatment: ​ A Scoping Review​

Purpose/Background Hepatitis C virus (HCV) is the most common bloodborne infection in the United States (Ludden et al., 2022). Sadly, over half of the individuals living with chronic HCV are unaware of their condition (Halket et al., 2022). Due to rising numbers, HCV screening guidelines have been updated to recommend that every adult be screened at least once (Patel et al, 2021). Despite these guidelines, screening rates remain low. This scoping review aims to examine current research on HCV screening and strategies to improve early diagnosis and treatment. Methods This review began with a literature search using CINAHL and PubMed and the key phrases hepatitis C, screening, birth cohort, CDC, electronic medical record (EMR), and lifestyle risk. Inclusion criteria were publication within the last five years, English language, and full-text availability. Seven of the 28 articles meeting this criteria were selected based on their applicability, high-quality, and rigor. Specific data points were abstracted from these articles and compiled in an Excel spreadsheet. Results Three studies that evaluated the effectiveness of universal screening versus risk and/or birth cohort screening found that universal screening resulted in higher screening rates. EMR interventions based on risk and/or birth cohort were evaluated in six of the studies, with all six reporting increased screening rates. Additionally, one study found that screening rates increased when EMR-based interventions were paired with provider education. Implications for Nursing Practice The results of this review suggest that application of universal screening and the incorporation of EMR-based interventions lead to an appreciable increase in HCV screening and diagnosis, but studies that implement these interventions based on universal screening guidelines are needed. Most importantly, this review revealed that healthcare providers and patients need education on current screening guidelines, testing, and treatment so HCV can be diagnosed and treated early

Long distance quantum teleportation of qubits from photons at 1300 nm to photons at 1550 nm wavelength

Elementary 2-dimensional quantum states (qubits) encoded in 1300 nm wavelength photons are teleported onto 1550 nm photons. The use of telecommunication wavelengths enables to take advantage of standard optical fibre and permits to teleport from one lab to a distant one, 55 m away, connected by 2 km of fibre. A teleportation fidelity of 81.2 % is reported. This is large enough to demonstrate the principles of quantum teleportation, in particular that entanglement is exploited. This experiment constitutes a first step towards a quantum repeater.Comment: 7 pages, 5 figures, Extended version of Nature lette

Experimental Quantum Teleportation of a Two-Qubit Composite System

Quantum teleportation, a way to transfer the state of a quantum system from one location to another, is central to quantum communication and plays an important role in a number of quantum computation protocols. Previous experimental demonstrations have been implemented with photonic or ionic qubits. Very recently long-distance teleportation and open-destination teleportation have also been realized. Until now, previous experiments have only been able to teleport single qubits. However, since teleportation of single qubits is insufficient for a large-scale realization of quantum communication and computation2-5, teleportation of a composite system containing two or more qubits has been seen as a long-standing goal in quantum information science. Here, we present the experimental realization of quantum teleportation of a two-qubit composite system. In the experiment, we develop and exploit a six-photon interferometer to teleport an arbitrary polarization state of two photons. The observed teleportation fidelities for different initial states are all well beyond the state estimation limit of 0.40 for a two-qubit system. Not only does our six-photon interferometer provide an important step towards teleportation of a complex system, it will also enable future experimental investigations on a number of fundamental quantum communication and computation protocols such as multi-stage realization of quantum-relay, fault-tolerant quantum computation, universal quantum error-correction and one-way quantum computation.Comment: 16pages, 4 figure

Comparison of breast and bowel cancer screening uptake patterns in a common cohort of South Asian women in England

Background: Inequalities in uptake of cancer screening by ethnic minority populations are well documented in a number of international studies. However, most studies to date have explored screening uptake for a single cancer only. This paper compares breast and bowel cancer screening uptake for a cohort of South Asian women invited to undertake both, and similarly investigates these women's breast cancer screening behaviour over a period of fifteen years. Methods: Screening data for rounds 1, 2 and 5 (1989-2004) of the NHS breast cancer screening programme and for round 1 of the NHS bowel screening pilot (2000-2002) were obtained for women aged 50-69 resident in the English bowel screening pilot site, Coventry and Warwickshire, who had been invited to undertake breast and bowel cancer screening in the period 2000-2002. Breast and bowel cancer screening uptake levels were calculated and compared using the chi-squared test. Results: 72,566 women were invited to breast and bowel cancer screening after exclusions. Of these, 3,539 were South Asian and 69,027 non-Asian; 18,730 had been invited to mammography over the previous fifteen years (rounds 1 to 5). South Asian women were significantly less likely to undertake both breast and bowel cancer screening; 29.9% (n = 1,057) compared to 59.4% (n = 40,969) for non-Asians (p < 0.001). Women in both groups who consistently chose to undertake breast cancer screening in rounds 1, 2 and 5 were more likely to complete round 1 bowel cancer screening. However, the likelihood of completion of bowel cancer screening was still significantly lower for South Asians; 49.5% vs. 82.3% for non-Asians, p < 0.001. South Asian women who undertook breast cancer screening in only one round were no more likely to complete bowel cancer screening than those who decided against breast cancer screening in all three rounds. In contrast, similar women in the non-Asian population had an increased likelihood of completing the new bowel cancer screening test. The likelihood of continued uptake of mammography after undertaking screening in round 1 differed between South Asian religio-linguistic groups. Noticeably, women in the Muslim population were less likely to continue to participate in mammography than those in other South Asian groups. Conclusions: Culturally appropriate targeted interventions are required to reduce observed disparities in cancer screening uptakes

Quantum Communication

Quantum communication, and indeed quantum information in general, has changed the way we think about quantum physics. In 1984 and 1991, the first protocol for quantum cryptography and the first application of quantum non-locality, respectively, attracted a diverse field of researchers in theoretical and experimental physics, mathematics and computer science. Since then we have seen a fundamental shift in how we understand information when it is encoded in quantum systems. We review the current state of research and future directions in this new field of science with special emphasis on quantum key distribution and quantum networks.Comment: Submitted version, 8 pg (2 cols) 5 fig

Foot pain and foot health in an educated population of adults: results from the Glasgow Caledonian University Alumni Foot Health Survey

Abstract Background Foot pain is common amongst the general population and impacts negatively on physical function and quality of life. Associations between personal health characteristics, lifestyle/behaviour factors and foot pain have been studied; however, the role of wider determinants of health on foot pain have received relatively little attention. Objectives of this study are i) to describe foot pain and foot health characteristics in an educated population of adults; ii) to explore associations between moderate-to-severe foot pain and a variety of factors including gender, age, medical conditions/co-morbidity/multi-morbidity, key indicators of general health, foot pathologies, and social determinants of health; and iii) to evaluate associations between moderate-to-severe foot pain and foot function, foot health and health-related quality-of-life. Methods Between February and March 2018, Glasgow Caledonian University Alumni with a working email address were invited to participate in the cross-sectional electronic survey (anonymously) by email via the Glasgow Caledonian University Alumni Office. The survey was constructed using the REDCap secure web online survey application and sought information on presence/absence of moderate-to-severe foot pain, patient characteristics (age, body mass index, socioeconomic status, occupation class, comorbidities, and foot pathologies). Prevalence data were expressed as absolute frequencies and percentages. Multivariate logistic and linear regressions were undertaken to identify associations 1) between independent variables and moderate-to-severe foot pain, and 2) between moderate-to-severe foot pain and foot function, foot health and health-related quality of life. Results Of 50,228 invitations distributed, there were 7707 unique views and 593 valid completions (median age [inter-quartile range] 42 [31–52], 67.3% female) of the survey (7.7% response rate). The sample was comprised predominantly of white Scottish/British (89.4%) working age adults (95%), the majority of whom were overweight or obese (57.9%), and in either full-time or part-time employment (82.5%) as professionals (72.5%). Over two-thirds (68.5%) of the sample were classified in the highest 6 deciles (most affluent) of social deprivation. Moderate-to-severe foot pain affected 236/593 respondents (39.8%). High body mass index, presence of bunions, back pain, rheumatoid arthritis, hip pain and lower occupation class were included in the final multivariate model and all were significantly and independently associated with moderate-to-severe foot pain (p < 0.05), except for rheumatoid arthritis (p = 0.057). Moderate-to-severe foot pain was significantly and independently associated lower foot function, foot health and health-related quality of life scores following adjustment for age, gender and body mass index (p < 0.05). Conclusions Moderate-to-severe foot pain was highly prevalent in a university-educated population and was independently associated with female gender, high body mass index, bunions, back pain, hip pain and lower occupational class. Presence of moderate-to-severe foot pain was associated with worse scores for foot function, foot health and health-related quality-of-life. Education attainment does not appear to be protective against moderate-to-severe foot pain

Variation of health-related quality of life assessed by caregivers and patients affected by severe childhood infections.

BACKGROUND: The agreement between self-reported and proxy measures of health status in ill children is not well established. This study aimed to quantify the variation in health-related quality of life (HRQOL) derived from young patients and their carers using different instruments. METHODS: A hospital-based cross-sectional survey was conducted between August 2010 and March 2011. Children with meningitis, bacteremia, pneumonia, acute otitis media, hearing loss, chronic lung disease, epilepsy, mild mental retardation, severe mental retardation, and mental retardation combined with epilepsy, aged between five to 14 years in seven tertiary hospitals were selected for participation in this study. The Health Utilities Index Mark 2 (HUI2), and Mark 3 (HUI3), and the EuroQoL Descriptive System (EQ-5D) and Visual Analogue Scale (EQ-VAS) were applied to both paediatric patients (self-assessment) and caregivers (proxy-assessment). RESULTS: The EQ-5D scores were lowest for acute conditions such as meningitis, bacteremia, and pneumonia, whereas the HUI3 scores were lowest for most chronic conditions such as hearing loss and severe mental retardation. Comparing patient and proxy scores (n = 74), the EQ-5D exhibited high correlation (r = 0.77) while in the HUI2 and HUI3 patient and caregiver scores were moderately correlated (r = 0.58 and 0.67 respectively). The mean difference between self and proxy-assessment using the HUI2, HUI3, EQ-5D and EQ-VAS scores were 0.03, 0.05, -0.03 and -0.02, respectively. In hearing-impaired and chronic lung patients the self-rated HRQOL differed significantly from their caregivers. CONCLUSIONS: The use of caregivers as proxies for measuring HRQOL in young patients affected by pneumococcal infection and its sequelae should be employed with caution. Given the high correlation between instruments, each of the HRQOL instruments appears acceptable apart from the EQ-VAS which exhibited low correlation with the others