The spatial biology of transcription and translation in rapidly growing Escherichia coli.

Single-molecule fluorescence provides high resolution spatial distributions of ribosomes and RNA polymerase (RNAP) in live, rapidly growing Escherichia coli. Ribosomes are more strongly segregated from the nucleoids (chromosomal DNA) than previous widefield fluorescence studies suggested. While most transcription may be co-translational, the evidence indicates that most translation occurs on free mRNA copies that have diffused from the nucleoids to a ribosome-rich region. Analysis of time-resolved images of the nucleoid spatial distribution after treatment with the transcription-halting drug rifampicin and the translation-halting drug chloramphenicol shows that both drugs cause nucleoid contraction on the 0-3 min timescale. This is consistent with the transertion hypothesis. We suggest that the longer-term (20-30 min) nucleoid expansion after Rif treatment arises from conversion of 70S-polysomes to 30S and 50S subunits, which readily penetrate the nucleoids. Monte Carlo simulations of a polymer bead model built to mimic the chromosomal DNA and ribosomes (either 70S-polysomes or 30S and 50S subunits) explain spatial segregation or mixing of ribosomes and nucleoids in terms of excluded volume and entropic effects alone. A comprehensive model of the transcription-translation-transertion system incorporates this new information about the spatial organization of the E. coli cytoplasm. We propose that transertion, which radially expands the nucleoids, is essential for recycling of 30S and 50S subunits from ribosome-rich regions back into the nucleoids. There they initiate co-transcriptional translation, which is an important mechanism for maintaining RNAP forward progress and protecting the nascent mRNA chain. Segregation of 70S-polysomes from the nucleoid may facilitate rapid growth by shortening the search time for ribosomes to find free mRNA concentrated outside the nucleoid and the search time for RNAP concentrated within the nucleoid to find transcription initiation sites

A new diagrammatic representation for correlation functions in the in-in formalism

In this paper we provide an alternative method to compute correlation functions in the in-in formalism, with a modified set of Feynman rules to compute loop corrections. The diagrammatic expansion is based on an iterative solution of the equation of motion for the quantum operators with only retarded propagators, which makes each diagram intrinsically local (whereas in the standard case locality is the result of several cancellations) and endowed with a straightforward physical interpretation. While the final result is strictly equivalent, as a bonus the formulation presented here also contains less graphs than other diagrammatic approaches to in-in correlation functions. Our method is particularly suitable for applications to cosmology.Comment: 14 pages, matches the published version. includes a modified version of axodraw.sty that works with the Revtex4 clas

Unmet Needs in the Pathogenesis and Treatment of Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease with a prevalence of approximately 1 in 1000. Over the last 30 years, advances in treatment such as use of corticosteroids and immunosuppressants have improved life expectancy and quality of life for patients with lupus and the key unmet needs have therefore changed. With the reduced mortality from disease activity, development of cardiovascular disease (CVD) has become an increasingly important cause of death in patients with SLE. The increased CVD risk in these patients is partly, but not fully explained by standard risk factors, and abnormalities in the immune response to lipids may play a role. Invariant natural killer T cells, which are triggered specifically by lipid antigens, may protect against progression of subclinical atherosclerosis. However, currently our recommendation is that clinicians should focus on optimal management of standard CVD risk factors such as smoking, blood pressure and lipid levels. Fatigue is one of the most common and most limiting symptoms suffered by patients with SLE. The cause of fatigue is multifactorial and disease activity does not explain this symptom. Consequently, therapies directed towards reducing inflammation and disease activity do not reliably reduce fatigue and new approaches are needed. Currently, we recommend asking about sleep pattern, optimising pain relief and excluding other causes of fatigue such as anaemia and metabolic disturbances. For the subgroup of patients whose disease activity is not fully controlled by standard treatment regimes, a range of different biologic agents have been proposed and subjected to clinical trials. Many of these trials have given disappointing results, though belimumab, which targets B lymphocytes, did meet its primary endpoint. New biologics targeting B cells, T cells or cytokines (especially interferon) are still going through trials raising the hope that novel therapies for patients with refractory SLE may be available soon

Predicting gas-flow distribution in pilot-scale fluidized beds using cfd simulations

Bubbling fluidized beds are used extensively in energy and chemical industries because of their excellent heat and mass transfer characteristics. Recently, CFD has been identified as a useful tool for predicting reactor performance, but application to large scales continues to be challenging because of limitations on computational resources. Given that the hydrodynamics can largely be characterized by bubbles rising through the bed, a more feasible approach for investigating large-scale reactors is to quantify bubble dynamics and specifically, gas distribution in different phases- visible bubble flow, bubble-through flow and dense-phase flow. In this study, 3D CFD simulations of bubbling fluidized beds are first conducted to establish the impact of scale (bed diameter) on the hydrodynamics. Using solids circulation and bubble statistics (1), it is established that wall effects cease to be significant in beds larger than 50 cm (bed aspect ratio less than 1). At this scale, simulations are then carried out for two distinct Geldart B particles and data is subsequently analyzed for gas-flow distribution in the bed. Bubble statistics are also compared with existing correlations and their relation to solids circulation and mixing is investigated. The physical model and numerical tool were developed and validated in previous studies (1,2), while 3D Bubble statistics are computed using MS3DATA (Multiphase Statistics using 3D Detection and Tracking Algorithm) (3). Accurate description of the gas-flow is crucial for large-scale combustor design since quantifying gas distribution will indicate both fuel rich zones as well as oxidant bypass through bubbles leading to inefficient performance. Please click Additional Files below to see the full abstract

Numerical Approximations Using Chebyshev Polynomial Expansions

We present numerical solutions for differential equations by expanding the unknown function in terms of Chebyshev polynomials and solving a system of linear equations directly for the values of the function at the extrema (or zeros) of the Chebyshev polynomial of order N (El-gendi's method). The solutions are exact at these points, apart from round-off computer errors and the convergence of other numerical methods used in connection to solving the linear system of equations. Applications to initial value problems in time-dependent quantum field theory, and second order boundary value problems in fluid dynamics are presented.Comment: minor wording changes, some typos have been eliminate

Measuring case severity: a novel tool for benchmarking and clinical documentation improvement

BACKGROUND: Severity of illness (SOI) is an All Patients Refined Diagnosis Related Groups (APR DRG) modifier based on comorbidity capture. Tracking SOI helps hospitals improve performance and resource distribution. Furthermore, benchmarking SOI plays a key role in Quality Improvement (QI) efforts such as Clinical Documentation Improvement (CDI) programs. The current SOI system highly relies on the 3 M APR DRG grouper that is updated annually, making it difficult to track severity longitudinally and benchmark against hospitals with different patient populations. Here, we describe an alternative SOI scoring system that is grouper-independent and that can be tracked longitudinally. METHODS: Admission data for 2019-2020 U.S. News and World Report Honor Roll facilities were downloaded from the Vizient Clinical Database and split into training and testing datasets. Elixhauser comorbidities, body systems developed from the Healthcare Cost and Utilization Project (HCUP), and ICD-10-CM complication and comorbidity (CC/MCC) indicators were selected as the predictors for orthogonal polynomial regression models to predict patients\u27 admission and discharge SOI. Receiver operating characteristic (ROC) and Precision-Recall (PR) analysis, and prediction accuracy were used to evaluate model performance. RESULTS: In the training dataset, the full model including both Elixhauser comorbidities and body system CC/MCC indicators had the highest ROC AUC, PR AUC and predication accuracy for both admission (ROC AUC: 92.9%; PR AUC: 91.0%; prediction accuracy: 85.4%) and discharge SOI (ROC AUC: 93.6%; PR AUC: 92.8%; prediction accuracy: 86.2%). The model including only body system CC/MCC indicators had similar performance for admission (ROC AUC: 92.4%; PR AUC: 90.4%; prediction accuracy: 84.8%) and discharge SOI (ROC AUC: 93.1%; PR AUC: 92.2%; prediction accuracy: 85.6%) as the full model. The model including only Elixhauser comorbidities exhibited the lowest performance. Similarly, in the validation dataset, the prediction accuracy was 86.2% for the full model, 85.6% for the body system model, and 79.3% for the comorbidity model. With fewer variables and less model complexity, the body system model was more efficient and was determined to be the optimal model. The probabilities generated from this model, named J_Score and J_Score_POA, successfully measured SOI and had practical applications in assessment of CDI performance. CONCLUSIONS: The J_Scores generated from the body system model have significant value in evaluating admission and discharge severity of illness. We believe that this new scoring system will provide a useful tool for healthcare institutions to benchmark patients\u27 illness severity and augment Quality Improvement (QI) efforts

Ethylene receptors signal via a noncanonical pathway to regulate abscisic acid Responses

Ethylene is a gaseous plant hormone perceived by a family of receptors in Arabidopsis (Arabidopsis thaliana) including ETHYLENE RESPONSE1 (ETR1) and ETR2. Previously we showed that etr1-6 loss-of-function plants germinate better and etr2-3 loss-of-function plants germinate worse than wild-type under NaCl stress and in response to abscisic acid (ABA). In this study, we expanded these results by showing that ETR1 and ETR2 have contrasting roles in the control of germination under a variety of inhibitory conditions for seed germination such as treatment with KCl, CuSO4, ZnSO4, and ethanol. Pharmacological and molecular biology results support a model where ETR1 and ETR2 are indirectly affecting the expression of genes encoding ABA signaling proteins to affect ABA sensitivity. The receiver domain of ETR1 is involved in this function in germination under these conditions and controlling the expression of genes encoding ABA signaling proteins. Epistasis analysis demonstrated that these contrasting roles of ETR1 and ETR2 do not require the canonical ethylene signaling pathway. To explore the importance of receptor-protein interactions, we conducted yeast two-hybrid screens using the cytosolic domains of ETR1 and ETR2 as bait. Unique interacting partners with either ETR1 or ETR2 were identified. We focused on three of these proteins and confirmed the interactions with receptors. Loss of these proteins led to faster germination in response to ABA, showing that they are involved in ABA responses. Thus, ETR1 and ETR2 have both ethylene-dependent and -independent roles in plant cells that affect responses to ABA

Shear viscosity of hot scalar field theory in the real-time formalism

Within the closed time path formalism a general nonperturbative expression is derived which resums through the Bethe-Salpter equation all leading order contributions to the shear viscosity in hot scalar field theory. Using a previously derived generalized fluctuation-dissipation theorem for nonlinear response functions in the real-time formalism, it is shown that the Bethe-Salpeter equation decouples in the so-called (r,a) basis. The general result is applied to scalar field theory with pure lambda*phi**4 and mixed g*phi**3+lambda*phi**4 interactions. In both cases our calculation confirms the leading order expression for the shear viscosity previously obtained in the imaginary time formalism.Comment: Expanded introduction and conclusions. Several references and a footnote added. Fig.5 and its discussion in the text modified to avoid double counting. Signs in Eqs. (45) and (53) correcte

Adult hypertrophic pyloric stenosis due to peptic ulcer disease: a rare presentation

Primary adult hypertrophic stenosis is uncommon with an uncertain etiopathogenesis and associated gastric outlet obstruction mimics gastric carcinoma. We present a case of AHPS as sequel of peptic ulcer disease in a 72 year old male. With the advent of proton pump inhibitors as a mainstay of medical therapy, complication into gastric outlet obstruction is a rare disease today. Upper GI endoscopy revealed a distended stomach, residual food and a hyperemic bulky pylorus not accommodating the endoscope. Barium meal follow-through revealed a dilated stomach and minimal barium passing through the pylorus. Histological analysis revealed mild dysplasia at the focus with dense inflammatory infiltrates composed of lymphocytes and eosinophils in the lamina propria. No evidence of malignancy was noted, favouring chronic gastritis. The condition mimics other forms of proliferative disorders like carcinoma, gastrointestinal stromal tumors. We present the clinical findings, imaging analysis and discuss etiopathogenesis and management