Staphylococcus aureus DivIB is a peptidoglycan-binding protein that is required for a morphological checkpoint in cell division

Bacterial cell division is a fundamental process that requires the coordinated actions of a number of proteins which form a complex macromolecular machine known as the divisome. The membrane-spanning proteins DivIB and its orthologue FtsQ are crucial divisome components in Gram-positive and Gram-negative bacteria respectively. However, the role of almost all of the integral division proteins, including DivIB, still remains largely unknown. Here we show that the extracellular domain of DivIB is able to bind peptidoglycan and have mapped the binding to its β subdomain. Conditional mutational studies show that divIB is essential for Staphylococcus aureus growth, while phenotypic analyses following depletion of DivIB results in a block in the completion, but not initiation, of septum formation. Localisation studies suggest that DivIB only transiently localises to the division site and may mark previous sites of septation. We propose that DivIB is required for a molecular checkpoint during division to ensure the correct assembly of the divisome at midcell and to prevent hydrolytic growth of the cell in the absence of a completed septum

Comparison between the Cramer-Rao and the mini-max approaches in quantum channel estimation

In a unified viewpoint in quantum channel estimation, we compare the Cramer-Rao and the mini-max approaches, which gives the Bayesian bound in the group covariant model. For this purpose, we introduce the local asymptotic mini-max bound, whose maximum is shown to be equal to the asymptotic limit of the mini-max bound. It is shown that the local asymptotic mini-max bound is strictly larger than the Cramer-Rao bound in the phase estimation case while the both bounds coincide when the minimum mean square error decreases with the order O(1/n). We also derive a sufficient condition for that the minimum mean square error decreases with the order O(1/n).Comment: In this revision, some unlcear parts are clarifie

Structure, Photophysics and the Order-Disorder Transition to the Beta Phase in Poly(9,9-(di -n,n-octyl)fluorene)

X-ray diffraction, UV-vis absorption and photoluminescence (PL) spectroscopy have been used to study the well-known order-disorder transition (ODT) to the beta phase in poly(9,9-(di n,n-octyl)fluorene)) (PF8) thin film samples through combination of time-dependent and temperature-dependent measurements. The ODT is well described by a simple Avrami picture of one-dimensional nucleation and growth but crystallization, on cooling, proceeds only after molecular-level conformational relaxation to the so called beta phase. Rapid thermal quenching is employed for PF8 studies of pure alpha phase samples while extended low-temperature annealing is used for improved beta phase formation. Low temperature PL studies reveal sharp Franck-Condon type emission bands and, in the beta phase, two distinguishable vibronic sub-bands with energies of approximately 199 and 158 meV at 25 K. This improved molecular level structural order leads to a more complete analysis of the higher-order vibronic bands. A net Huang-Rhys coupling parameter of just under 0.7 is typically observed but the relative contributions by the two distinguishable vibronic sub-bands exhibit an anomalous temperature dependence. The PL studies also identify strongly correlated behavior between the relative beta phase 0-0 PL peak position and peak width. This relationship is modeled under the assumption that emission represents excitons in thermodynamic equilibrium from states at the bottom of a quasi-one-dimensional exciton band. The crystalline phase, as observed in annealed thin-film samples, has scattering peaks which are incompatible with a simple hexagonal packing of the PF8 chains.Comment: Submitted to PRB, 12 files; 1 tex, 1 bbl, 10 eps figure

Malignant islet-cell tumors of the pancreas

Although malignant islet-cell tumors are uncommon, they are an important group of pancreatic neoplasms because appropriate treatment can often result in effective palliation even though cure is infrequent. In general, these tumors are relatively slow growing so that a combination of surgical and chemotherapeutic measures may prove very beneficial. In some patients with tumors hypersecreting insulin, gastrin, glucagon, or vasoactive intestinal polypeptide (VIP), the hormonal effects of the neoplasm can be life-threatening. Surgical treatment must, therefore, consider both the functional and malignant characteristics of the individual tumor. In many patients with functional tumors, surgical debulking of the primary tumor may be indicated even when a curative resection cannot be accomplished. Some malignancies may be cured by an appropriate pancreatic resection even when peripancreatic lymph nodes are already involved. Although a Whipple procedure is not indicated when hepatic metastases are present, this procedure may cure tumors localized to the pancreatic head and/or peripancreatic lymph nodes. Because hepatic metastases are usually multiple and involve both lobes, liver resections, other than wedge excisions of peripherally located functional metastases, are not indicated. Malignant nonfunctioning islet-cell tumors are probably best treated with systemic or regional chemotherapy when metastatic. Surgical resections or bypass procedures may be infrequently useful in those cases in which the primary tumor causes either duodenal or bile duct obstruction. The most effective methods used to control hepatic metastases are systemic and hepatic arterial chemotherapy. An alternative is selective hepatic artery embolization. Recently, an implantable hepatic arterial infusion pump has been used with encouraging results in this group of patients. The chemotherapeutic agents that have been most effective in the treatment of hepatic metastases include streptozotocin, DTIC, and fluorouracil . Les tumeurs insulaires malignes sont rares mais elles présentent un grand intérêt car si le traitement entraîne exceptionnellement leur guérison il assure une survie des malades qui en sont porteurs. Ce sont en effet des tumeurs malignes à développement lent, sensibles à l'action de l'association de la chimiothérapie et de la chirurgie. Chez certains sujets les tumeurs secrétant de l'insuline, de la gastrine, du glucagon, du V.I.P. peuvent mettre en jeu la vie du malade sous l'effet de l'hypersecrétion hormonale. Le traitement chirurgical dépend de ce fait, des caractères fonctionnels et du degré de malignité de chaque type de tumeur. En présence de lésions hypersecrétantes l'exérèse de la tumeur primitive doit être envisagée alors même que la possibilité d'obtenir une guérison définitive ne peut être escomptée. Il est aussi à noter que certaines lésions malignes ont été traitées avec succès alors que les ganglions lymphatiques correspondants étaient déjà envahis. Si l'opération est contre-indiquée en présence de métastases hépatiques la duodénopancréatectomie céphalique s'applique aux tumeurs insulaires céphaliques qu'elles s'accompagnent ou non d'un envahissement des ganglions juxta-pancréatiques. Du fait que les métastases hépatiques sont souvent multiples et qu'elles intéressent les deux lobes l'action sur le foie se limite à l'éxérèse des métastases accessibles à la résection hépatique segmentaire. Les tumeurs insulaires malignes qui ne sont pas hypersecrétantes relèvent de la chimiothérapie par voie générale ou de la chimiothérapie régionale dès lors qu'elles s'accompagnent de métastases. C'est seulement lorsque ces lésions entraînent une obstruction de la voie biliaire principale ou du duodénum que la résection ou les anastomoses de dérivation sont indiquées. La chimiothérapie par voie générale ou par la voie de l'artère hépatique ou encore l'embolisation de cette dernière représentent les meilleures méthodes de traitement des métastases hépatiques. L'emploi récent de pompes à infusion de l'artère hépatique a donné des résultats intéressants chez ces malades. Les agents chimiques les plus efficaces sont la streptozotocine, le DTIC et le Fluorouracil. Aunque los tumores malignos de células insulares del páncreas son raros, éstos constituyen un grupo importante entre las neoplasias pancreáticas por cuanto el tratamiento apropiado con frecuencia resulta en una paliación efectiva a pesar de que la curación sea poco frecuente. En general estos tumores son de crecimiento lento y la combinación de la cirugía con quimioterapia puede llegar a ser beneficiosa. En algunos pacientes con tumores que hipersecretan insulina, gastrina, glucagón o VIP (polipéptido vasoactivo intestinal), los efectos hormonales del neoplasma pueden poner en peligro la vida. Por ello el tratamiento quirúrgico debe considerar tanto las caracteristicas funcionales como las de malignidad de cada tumor en particular. En muchos pacientes con neoplasmas funcionantes, el debultamiento quirúrgico del tumor primario puede estar indicado cuando la resección curativa no es realizable. Algunas neoplasias malignas pueden ser curadas mediante una resección pancreática adecuada a pesar de que los ganglios linfáticos peripancreáticos ya se hallen afectados. Aún cuando el procedimiento de Whipple no esta indicado en presencia de metástasis hepáticas, esta operación puede curar tumores localizados en la cabeza del páncreas y/o en los ganglios linfáticos peripancreáticos. Debido a que las metástasis hepáticas generalmente son múlitples y afectan a ambos lóbulos, las resecciones hepáticas, diferentes de las resecciones en cuña para lesiones funcionantes localizadas en la periferie del higado no están indicadas. Los tumores malignos no funcionantes de células insulares probablemente deben ser tratadas con quimioterapia sistémica o regional cuando se encuentren en fase metastásica. Las resecciones quirúrgicas o los procedimientos derivativos infrecuentemente son de utilidad en aquellos casos en los cuales el tumor primario causa obstrucción duodenal o del conducto biliar. Los métodos de mayor efectividad en el control de las metéstasis hepáticas son los de quimioterapia sistémica y arterial hepática. Una alternativa es la embolización selectiva de la arteria hepática. Recientemente ha venido a ser utilizada una bomba implantable de infusión arterial heptica con resultados halagadores en este grupo de pacientes. Los agentes quimioterapéuticos que han probado ser de mayor efectividad en el tratamiento de las metástasis hepáticas incluyen la estreptozotocina, la dimetiltrizenoimidazol carboxamida (DTIC) y el Fluorouracilo.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41316/1/268_2005_Article_BF01656036.pd

Integrated assessment of social and environmental sustainability dynamics in the Ganges-Brahmaputra-Meghna delta, Bangladesh

Deltas provide diverse ecosystem services and benefits for their populations. At the same time, deltas are also recognised as one of the most vulnerable coastal environments, with a range of drivers operating at multiple scales, from global climate change and sea-level rise to deltaic-scale subsidence and land cover change. These drivers threaten these ecosystem services, which often provide livelihoods for the poorest communities in these regions. The imperative to maintain ecosystem services presents a development challenge: how to develop deltaic areas in ways that are sustainable and benefit all residents including the most vulnerable. Here we present an integrated framework to analyse changing ecosystem services in deltas and the implications for human well-being, focussing in particular on the provisioning ecosystem services of agriculture, inland and offshore capture fisheries, aquaculture and mangroves that directly support livelihoods. The framework is applied to the world’s most populated delta, the Ganges-Brahmaputra-Meghna Delta within Bangladesh. The framework adopts a systemic perspective to represent the principal biophysical and socio-ecological components and their interaction. A range of methods are integrated within a quantitative framework, including biophysical and socio-economic modelling and analyses of governance through scenario development. The approach is iterative, with learning both within the project team and with national policy-making stakeholders. The analysis is used to explore physical and social outcomes for the delta under different scenarios and policy choices. We consider how the approach is transferable to other deltas and potentially other coastal areas

Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19.

BACKGROUND: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support-free days, on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support-free days, or both. RESULTS: Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support-free days was 10 (interquartile range, -1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, -1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists. CONCLUSIONS: In critically ill patients with Covid-19 receiving organ support in ICUs, treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.)