Study of peptide on-line complexation with transition-metal ions generated from sacrificial electrodes in thin-chip polymer microsprays

A miniaturized polymer electrospray-type interface is used to study metal-ion chelation with model peptides. Taking advantage of the intrinsic electrochemical behavior of electrospray, a sacrificial electrode is used to generate at the same time electrospray and transition-metal ions coming from the anodic dissolution of the electrode. The microspray interface provides enhanced mass transport due to its small dimensions, increasing the yield of possible reactions, in particular complex formation. Transition-metal electrodes, e.g. copper, zinc, nickel, iron and silver, are used to obtain on-line complexation with model peptides. It is demonstrated that the use of in-reservoir sacrificial electrodes is an efficient way to generate metal ions in order to form and study complexes with peptides, avoiding the addition of metallic salts

Hypothyroidism in rats decreases peripheral glucose utilisation, a defect partially corrected by central leptin infusion

Aims/hypothesis: The aims of this work were to determine the effect of hypothyroidism on insulin-stimulated glucose turnover and to unravel the potential mechanisms involved in such an effect. Methods: Hypothyroidism was induced by administration of propylthiouracil, with partial T4 substitution. Euglycaemic-hyperinsulinaemic clamps, associated with the labelled 2-deoxy-d-glucose technique for measuring tissue-specific glucose utilisation, were used. To assess a possible involvement of leptin in the modulation of glucose metabolism by hypothyroidism, leptin was infused intracerebroventricularly for 6 days. A group of leptin-infused rats was treated with rT3 to determine a potential role of T3 in mediating the leptin effects. Results: Compared with euthyroid rats, hypothyroid animals exhibited decreased overall glucose turnover and decreased glucose utilisation indices in skeletal muscle and adipose tissue. Leptinaemia in hypothyroid rats was lower while resistin mRNA expression in adipose tissue was higher than in euthyroid animals. Intracerebroventricular leptin infusion in hypothyroid rats partially restored overall, muscle and adipose tissue insulin-stimulated glucose utilisation and improved the reduced glycaemic response observed during insulin tolerance tests. The leptin effects were due neither to the observed increase in plasma T3 levels nor to changes in the high adipose tissue resistin expression of hypothyroid rats. The administration of leptin to hypothyroid animals was accompanied by increased expression of muscle and adipose tissue carnitine palmitoyl transferases, decreased plasma NEFA levels and reduced muscle triglyceride content. Conclusions/interpretation: Hypothyroidism is characterised by decreased insulin responsiveness, partly mediated by an exaggerated glucose-fatty acid cycle that is partly alleviated by intracerebroventricular leptin administratio

SnBrP-A SnIP-type representative in the Sn-Br-P system

One-dimensional semiconductors are interesting materials due to their unique structural features and anisotropy, which grant them intriguing optical, dielectric and mechanical properties. In this work, we report on SnBrP, a lighter homologue of the first inorganic double helix compound SnIP. This class of compounds is characterized by intriguing mechanical and electronic properties, featuring a high flexibility without modulation of physical properties. Semiconducting SnBrP can be synthesized from red phosphorus, tin and tin(II)bromide at elevated temperatures and crystallizes as red-orange, cleavable needles. Raman measurements pointed towards a double helical building unit in SnBrP, showing similarities to the SnIP structure. After taking PL measurements, HR-TEM, and quantum chemical calculations into account, we were able to propose a sense full structure model for SnBrP

Oxidation Behavior of Glassy Carbon in Acidic Electrolyte

Glassy carbon is frequently used in electrochemical research due to its presumed robust electrochemical performance. Although it is widely utilized as a rotating disc electrode material, the modification of glassy carbon during electro-catalytic process is rarely emphasized or characterized. In this report, we investigated the structural modification of glassy carbon imparted by electrochemical oxidation in acidic media and compared the behavior with graphite. The functional groups generated from electrochemical oxidation in both electrodes possess similar electrochemical properties. However, above an oxidation potential of 1.8 V (vs. reversibly hydrogen electrode), glassy carbon exhibits a lower electrochemical capacitance compared to graphite. We propose that the existence of electrochemically inactive species, originating from the non-graphitic portion of glassy carbon is attributed to such deterioration. Additionally, high resolution scanning electron microscopy (HR-SEM) and high-resolution transmission electron microscopy (HR-TEM) images corroborate how electrochemical oxidation prevails for glassy carbon electrodes at oxidative potentials. The overall analysis leads us to propose a corrosion mechanism for glassy carbon in acidic solution

Cervical cancer screening cascade for women living with HIV: a cohort study from Zimbabwe

Countries with high HIV prevalence, predominantly in sub-Sahahran Africa, have the highest cervical cancer rates globally. HIV care cascades successfully facilitated the scale-up of antiretroviral therapy. A cascade approach could similarly succeed to scale-up cervical cancer screening, supporting WHO's goal to eliminate cervical cancer. We defined a Cervical Cancer Screening Cascade for women living with HIV (WLHIV), evaluating the continuum of cervical cancer screening integrated into an HIV clinic in Zimbabwe. We included WLHIV aged ≥18 years enrolled at Newlands Clinic in Harare from June 2012-2017 and followed them until June 2018. We used a cascade approach to evaluate the full continuum of secondary prevention from screening to treatment of pre-cancer and follow-up. We report percentages, median time to reach cascade stages, and cumulative incidence at two years with 95% confidence intervals (CI). We used univariable Cox proportional hazard regressions to calculate cause-specific hazard ratios with 95% CIs for factors associated with completing the cascade stages. We included 1624 WLHIV in the study. The cumulative incidence of cervical screening was 85.4% (95% CI 83.5-87.1) at two years. Among the 396 WLHIV who received screen-positive tests in the study, the cumulative incidence of treatment after a positive screening test was 79.5% (95% CI 75.1-83.2) at two years. The cumulative incidence of testing negative at re-screening after treatment was 36.1% (95% CI 31.2-40.7) at two years. Using a cascade approach to evaluate the full continuum of cervical cancer screening, we found less-than 80% of WLHIV received treatment after screen-positive tests and less-than 40% were screen-negative at follow-up. Interventions to improve linkage to treatment for screen-positive WLHIV and studies to understand the clinical significance of screen-positive tests at follow-up among WLHIV are needed. These gaps in the continuum of care must be addressed in order to prevent cervical cancer

Cohort profile: the South African HIV Cancer Match (SAM) study, a national population-based cohort

Purpose The South African HIV Cancer Match (SAM) Study is a national cohort of people living with HIV (PLWH). It was created using probabilistic record linkages of routine laboratory records of PLWH retrieved by National Health Laboratory Services (NHLS) and cancer data from the National Cancer Registry. The SAM Study aims to assess the spectrum and risk of cancer in PLWH in the context of the evolving South African HIV epidemic. The SAM Study's overarching goal is to inform cancer prevention and control programmes in PLWH in the era of antiretroviral treatment in South Africa. Participants PLWH (both adults and children) who accessed HIV care in public sector facilities and had HIV diagnostic or monitoring laboratory tests from NHLS. Findings to date The SAM cohort currently includes 5 248 648 PLWH for the period 2004 to 2014; 69% of these are women. The median age at cohort entry was 33.0 years (IQR: 26.2-40.9). The overall cancer incidence in males and females was 235.9 (95% CI: 231.5 to 240.5) and 183.7 (181.2-186.2) per 100 000 person-years, respectively. Using data from the SAM Study, we examined national cancer incidence in PLWH and the association of different cancers with immunodeficiency. Cancers with the highest incidence rates were Kaposi sarcoma, cervix, breast, non-Hodgkin's lymphoma and eye cancer. Future plans The SAM Study is a unique, evolving resource for research and surveillance of malignancies in PLWH. The SAM Study will be regularly updated. We plan to enrich the SAM Study through record linkages with other laboratory data within the NHLS (eg, tuberculosis, diabetes and lipid profile data), mortality data and socioeconomic data to facilitate comprehensive epidemiological research of comorbidities among PLWH

Overfeeding, Autonomic Regulation and Metabolic Consequences

The autonomic nervous system plays an important role in the regulation of body processes in health and disease. Overfeeding and obesity (a disproportional increase of the fat mass of the body) are often accompanied by alterations in both sympathetic and parasympathetic autonomic functions. The overfeeding-induced changes in autonomic outflow occur with typical symptoms such as adiposity and hyperinsulinemia. There might be a causal relationship between autonomic disturbances and the consequences of overfeeding and obesity. Therefore studies were designed to investigate autonomic functioning in experimentally and genetically hyperphagic rats. Special emphasis was given to the processes that are involved in the regulation of peripheral energy substrate homeostasis. The data revealed that overfeeding is accompanied by increased parasympathetic outflow. Typical indices of vagal activity (such as the cephalic insulin release during food ingestion) were increased in all our rat models for hyperphagia. Overfeeding was also accompanied by increased sympathetic tone, reflected by enhanced baseline plasma norepinephrine (NE) levels in both VMH-lesioned animals and rats rendered obese by hyperalimentation. Plasma levels of NE during exercise were, however, reduced in these two groups of animals. This diminished increase in the exercise-induced NE outflow could be normalized by prior food deprivation. It was concluded from these experiments that overfeeding is associated with increased parasympathetic and sympathetic tone. In models for hyperphagia that display a continuously elevated nutrient intake such as the VMH-lesioned and the overfed rat, this increased sympathetic tone was accompanied by a diminished NE response to exercise. This attenuated outflow of NE was directly related to the size of the fat reserves, indicating that the feedback mechanism from the periphery to the central nervous system is altered in the overfed state.

Characteristics of Terrorism

Individual terrorist are frequently behaving seemingly absurd, e.g. by carrying out suicide operations, while activities of the terrorist organisations as a whole often seem to be conducted in a very effective way. These facts caused many researchers to regard the leaders representing the organisations like rational entities, while the followers are supposed to be just obeying and, hence, to be irrational. In this paper we offer a different approach which postulates rationality of all involved agents. We demonstrate how these agents’ behaviour could be modelled, while taking into account options of the terrorist leaders to influence their followers. From our model approaches to counter terrorism on both the leadership as well as the follower level can be derived

How much should we sequence? An analysis of the Swiss SARS-CoV-2 surveillance effort.

During the SARS-CoV-2 pandemic, many countries directed substantial resources toward genomic surveillance to detect and track viral variants. There is a debate over how much sequencing effort is necessary in national surveillance programs for SARS-CoV-2 and future pandemic threats. We aimed to investigate the effect of reduced sequencing on surveillance outcomes in a large genomic data set from Switzerland, comprising more than 143k sequences. We employed a uniform downsampling strategy using 100 iterations each to investigate the effects of fewer available sequences on the surveillance outcomes: (i) first detection of variants of concern (VOCs), (ii) speed of introduction of VOCs, (iii) diversity of lineages, (iv) first cluster detection of VOCs, (v) density of active clusters, and (vi) geographic spread of clusters. The impact of downsampling on VOC detection is disparate for the three VOC lineages, but many outcomes including introduction and cluster detection could be recapitulated even with only 35% of the original sequencing effort. The effect on the observed speed of introduction and first detection of clusters was more sensitive to reduced sequencing effort for some VOCs, in particular Omicron and Delta, respectively. A genomic surveillance program needs a balance between societal benefits and costs. While the overall national dynamics of the pandemic could be recapitulated by a reduced sequencing effort, the effect is strongly lineage-dependent-something that is unknown at the time of sequencing-and comes at the cost of accuracy, in particular for tracking the emergence of potential VOCs.IMPORTANCESwitzerland had one of the most comprehensive genomic surveillance systems during the COVID-19 pandemic. Such programs need to strike a balance between societal benefits and program costs. Our study aims to answer the question: How would surveillance outcomes have changed had we sequenced less? We find that some outcomes but also certain viral lineages are more affected than others by sequencing less. However, sequencing to around a third of the original effort still captured many important outcomes for the variants of concern such as their first detection but affected more strongly other measures like the detection of first transmission clusters for some lineages. Our work highlights the importance of setting predefined targets for a national genomic surveillance program based on which sequencing effort should be determined. Additionally, the use of a centralized surveillance platform facilitates aggregating data on a national level for rapid public health responses as well as post-analyses