Preparation and Crystal Structure of a Platinum(II) Complex of [CH2N(CH2COOH)CH2CONH2]2, the Hydrolysis Product of an Anti-Tumour Bis(3,5-Dioxopiperazin-1-YL)Alkane

The synthesis and crystal and molecular structures of the platinum(II) complex Pt(HL)Cl where H2L is the diacid diamide –[CH2N(CH2COOH)CH2CONH2]2, a hydrolytic metabolite of an antitumour active bis(3,5-dioxopiperazin-1-yl)alkane are reported. The complex is square planar and contains HL– as a tridentate 2N (amino), O (carboxylate) donor. The metal to ligand bond distances are Pt-Cl 2.287(1) Å, Pt-O 2.002 (1) Å, Pt-Ntrans Cl 2.014(1) Å and Pt-Ntrans O 2.073 Å. There is extensive hydrogen bonding, each molecule of Pt(HL)Cl being intermolecularly hydrogen bonded to ten others giving a 3-dimensional network. There is also one intramolecular H-bond

Individually Optimal Choices Can Be Collectively Disastrous in COVID-19 Disease Control

Background: The word \u27pandemic\u27 conjures dystopian images of bodies stacked in the streets and societies on the brink of collapse. Despite this frightening picture, denialism and noncompliance with public health measures are common in the historical record, for example during the 1918 Influenza pandemic or the 2015 Ebola epidemic. The unique characteristics of SARS-CoV-2-its high basic reproduction number (R0), time-limited natural immunity and considerable potential for asymptomatic spread-exacerbate the public health repercussions of noncompliance with interventions (such as vaccines and masks) to limit disease transmission. Our work explores the rationality and impact of noncompliance with measures aimed at limiting the spread of SARS-CoV-2. Methods: In this work, we used game theory to explore when noncompliance confers a perceived benefit to individuals. We then used epidemiological modeling to predict the impact of noncompliance on control of SARS-CoV-2, demonstrating that the presence of a noncompliant subpopulation prevents suppression of disease spread. Results: Our modeling demonstrates that noncompliance is a Nash equilibrium under a broad set of conditions and that the existence of a noncompliant population can result in extensive endemic disease in the long-term after a return to pre-pandemic social and economic activity. Endemic disease poses a threat for both compliant and noncompliant individuals; all community members are protected if complete suppression is achieved, which is only possible with a high degree of compliance. For interventions that are highly effective at preventing disease spread, however, the consequences of noncompliance are borne disproportionately by noncompliant individuals. Conclusions: In sum, our work demonstrates the limits of free-market approaches to compliance with disease control measures during a pandemic. The act of noncompliance with disease intervention measures creates a negative externality, rendering suppression of SARS-CoV-2 spread ineffective. Our work underscores the importance of developing effective strategies for prophylaxis through public health measures aimed at complete suppression and the need to focus on compliance at a population level

Using Rheo-Small-Angle Neutron Scattering to Understand How Functionalised Dipeptides Form Gels

We explore the use of rheo-small-angle neutron scattering as a method to collect structural information from neutron scattering simultaneously with rheology to understand how low-molecular-weight hydrogels form and behave under shear. We examine three different gelling hydrogel systems to assess what structures are formed and how these influence the rheology. Furthermore, we probe what is happening to the network during syneresis and why the gels do not recover after an applied strain. All this information is vital when considering gels for applications such as 3D-printing and injection

Spectrum and Morphology of the Two Brightest Milagro Sources in the Cygnus Region: MGRO J2019+37 and MGRO J2031+41

The Cygnus region is a very bright and complex portion of the TeV sky, host to unidentified sources and a diffuse excess with respect to conventional cosmic-ray propagation models. Two of the brightest TeV sources, MGRO J2019+37 and MGRO J2031+41, are analyzed using Milagro data with a new technique, and their emission is tested under two different spectral assumptions: a power law and a power law with an exponential cutoff. The new analysis technique is based on an energy estimator that uses the fraction of photomultiplier tubes in the observatory that detect the extensive air shower. The photon spectrum is measured in the range 1 to 200 TeV using the last 3 years of Milagro data (2005-2008), with the detector in its final configuration. MGRO J2019+37 is detected with a significance of 12.3 standard deviations ($\sigma$), and is better fit by a power law with an exponential cutoff than by a simple power law, with a probability $>98$% (F-test). The best-fitting parameters for the power law with exponential cutoff model are a normalization at 10 TeV of $7^{+5}_{-2}\times10^{-10}$ $\mathrm{s^{-1}\: m^{-2}\: TeV^{-1}}$, a spectral index of $2.0^{+0.5}_{-1.0}$ and a cutoff energy of $29^{+50}_{-16}$ TeV. MGRO J2031+41 is detected with a significance of 7.3$\sigma$, with no evidence of a cutoff. The best-fitting parameters for a power law are a normalization of $2.4^{+0.6}_{-0.5}\times10^{-10}$ $\mathrm{s^{-1}\: m^{-2}\: TeV^{-1}}$ and a spectral index of $3.08^{+0.19}_{-0.17}$. The overall flux is subject to an $\sim$30% systematic uncertainty. The systematic uncertainty on the power law indices is $\sim$0.1. A comparison with previous results from TeV J2032+4130, MGRO J2031+41 and MGRO J2019+37 is also presented.Comment: 11 pages, 10 figure

The translation, validity and reliability of the German version of the Fremantle Back Awareness Questionnaire

Background: The Fremantle Back Awareness Questionnaire (FreBAQ) claims to assess disrupted self-perception of the back. The aim of this study was to develop a German version of the Fre-BAQ (FreBAQ-G) and assess its test-retest reliability, its known-groups validity and its convergent validity with another purported measure of back perception. Methods: The FreBaQ-G was translated following international guidelines for the transcultural adaptation of questionnaires. Thirty-five patients with non-specific CLBP and 48 healthy participants were recruited. Assessor one administered the FreBAQ-G to each patient with CLBP on two separate days to quantify intra-observer reliability. Assessor two administered the FreBaQ-G to each patient on day 1. The scores were compared to those obtained by assessor one on day 1 to assess inter-observer reliability. Known-groups validity was quantified by comparing the FreBAQ-G score between patients and healthy controls. To assess convergent validity, patient\u27s FreBAQ-G scores were correlated to their two-point discrimination (TPD) scores. Results: Intra- and Inter-observer reliability were both moderate with ICC3.1 = 0.88 (95%CI: 0.77 to 0.94) and 0.89 (95%CI: 0.79 to 0.94), respectively. Intra- and inter-observer limits of agreement (LoA) were 6.2 (95%CI: 5.0±8.1) and 6.0 (4.8±7.8), respectively. The adjusted mean difference between patients and controls was 5.4 (95%CI: 3.0 to 7.8, p\u3c0.01). Patient\u27s FreBAQ-G scores were not associated with TPD thresholds (Pearson\u27s r = -0.05, p = 0.79). Conclusions: The FreBAQ-G demonstrated a degree of reliability and known-groups validity. Interpretation of patient level data should be performed with caution because the LoA were substantial. It did not demonstrate convergent validity against TPD. Floor effects of some items of the FreBAQ-G may have influenced the validity and reliability results. The clinimetric properties of the FreBAQ-G require further investigation as a simple measure of disrupted self-perception of the back before firm recommendations on its use can be made

Thymidine Kinase 2 Deficiency-Induced Mitochondrial DNA Depletion Causes Abnormal Development of Adipose Tissues and Adipokine Levels in Mice

Mammal adipose tissues require mitochondrial activity for proper development and differentiation. The components of the mitochondrial respiratory chain/oxidative phosphorylation system (OXPHOS) are encoded by both mitochondrial and nuclear genomes. The maintenance of mitochondrial DNA (mtDNA) is a key element for a functional mitochondrial oxidative activity in mammalian cells. To ascertain the role of mtDNA levels in adipose tissue, we have analyzed the alterations in white (WAT) and brown (BAT) adipose tissues in thymidine kinase 2 (Tk2) H126N knockin mice, a model of TK2 deficiency-induced mtDNA depletion. We observed respectively severe and moderate mtDNA depletion in TK2-deficient BAT and WAT, showing both tissues moderate hypotrophy and reduced fat accumulation. Electron microscopy revealed altered mitochondrial morphology in brown but not in white adipocytes from TK2-deficient mice. Although significant reduction in mtDNA-encoded transcripts was observed both in WAT and BAT, protein levels from distinct OXPHOS complexes were significantly reduced only in TK2-deficient BAT. Accordingly, the activity of cytochrome c oxidase was significantly lowered only in BAT from TK2-deficient mice. The analysis of transcripts encoding up to fourteen components of specific adipose tissue functions revealed that, in both TK2-deficient WAT and BAT, there was a consistent reduction of thermogenesis related gene expression and a severe reduction in leptin mRNA. Reduced levels of resistin mRNA were found in BAT from TK2-deficient mice. Analysis of serum indicated a dramatic reduction in circulating levels of leptin and resistin. In summary, our present study establishes that mtDNA depletion leads to a moderate impairment in mitochondrial respiratory function, especially in BAT, causes substantial alterations in WAT and BAT development, and has a profound impact in the endocrine properties of adipose tissues