Higher Dimensional Cylindrical or Kasner Type Electrovacuum Solutions

We consider a D dimensional Kasner type diagonal spacetime where metric functions depend only on a single coordinate and electromagnetic field shares the symmetries of spacetime. These solutions can describe static cylindrical or cosmological Einstein-Maxwell vacuum spacetimes. We mainly focus on electrovacuum solutions and four different types of solutions are obtained in which one of them has no four dimensional counterpart. We also consider the properties of the general solution corresponding to the exterior field of a charged line mass and discuss its several properties. Although it resembles the same form with four dimensional one, there is a difference on the range of the solutions for fixed signs of the parameters. General magnetic field vacuum solution are also briefly discussed, which reduces to Bonnor-Melvin magnetic universe for a special choice of the parameters. The Kasner forms of the general solution are also presented for the cylindrical or cosmological cases.Comment: 16 pages, Revtex. Text and references are extended, Published versio

Temporal estimation with two moving objects: overt and covert pursuit

The current study examined temporal estimation in a prediction motion task where participants were cued to overtly pursue one of two moving objects, which could either arrive first, i.e., shortest [time to contact (TTC)] or second (i.e., longest TTC) after a period of occlusion. Participants were instructed to estimate TTC of the first-arriving object only, thus making it necessary to overtly pursue the cued object while at the same time covertly pursuing the other (non-cued) object. A control (baseline) condition was also included in which participants had to estimate TTC of a single, overtly pursued object. Results showed that participants were able to estimate the arrival order of the two objects with very high accuracy irrespective of whether they had overtly or covertly pursued the first-arriving object. However, compared to the single-object baseline, participants’ temporal estimation of the covert object was impaired when it arrived 500 ms before the overtly pursued object. In terms of eye movements, participants exhibited significantly more switches in gaze location during occlusion from the cued to the non-cued object but only when the latter arrived first. Still, comparison of trials with and without a switch in gaze location when the non-cued object arrived first indicated no advantage for temporal estimation. Taken together, our results indicate that overt pursuit is sufficient but not necessary for accurate temporal estimation. Covert pursuit can enable representation of a moving object’s trajectory and thereby accurate temporal estimation providing the object moves close to the overt attentional focus

Pharmacotherapy and the risk for community-acquired pneumonia

<p>Abstract</p> <p>Background</p> <p>Some forms of pharmacotherapy are shown to increase the risk of community-acquired pneumonia (CAP). The purpose of this study is to investigate whether pharmacotherapy with proton pump inhibitors (PPI), inhaled corticosteroids, and atypical antipsychotics was associated with the increased risk for CAP in hospitalized older adults with the adjustment of known risk factors (such as smoking status and serum albumin levels).</p> <p>Methods</p> <p>A retrospective case-control study of adults aged 65 years or older at a rural community hospital during 2004 and 2006 was conducted. Cases (N = 194) were those with radiographic evidence of pneumonia on admission. The controls were patients without the discharge diagnosis of pneumonia or acute exacerbation of chronic obstructive pulmonary disease (COPD) (N = 952). Patients with gastric tube feeding, ventilator support, requiring hemodialysis, metastatic diseases or active lung cancers were excluded.</p> <p>Results</p> <p>Multiple logistic regression analysis revealed that the current use of inhaled corticosteroids (adjusted odds ratio [AOR] = 2.89, 95% confidence interval [CI] = 1.56-5.35) and atypical antipsychotics (AOR = 2.26, 95% CI = 1.23-4.15) was an independent risk factor for CAP after adjusting for confounders, including age, serum albumin levels, sex, smoking status, a history of congestive heart failure, coronary artery disease, and COPD, the current use of PPI, β2 agonist and anticholinergic bronchodilators, antibiotic(s), iron supplement, narcotics, and non-steroidal anti-inflammatory drugs. The crude OR and the AOR of PPI use for CAP was 1.41 [95% CI = 1.03 - 1.93] and 1.18 [95% CI = 0.80 - 1.74] after adjusting for the above confounders, respectively. Lower serum albumin levels independently increased the risk of CAP 1.89- fold by decreasing a gram per deciliter (AOR = 2.89, 95% CI = 2.01 - 4.16).</p> <p>Conclusion</p> <p>Our study reaffirmed that the use of inhaled corticosteroids and atypical antipsychotics was both associated with an increased risk for CAP in hospitalized older adults of a rural community. No association was found between current PPI use and the risk for CAP in this patient population of our study.</p

Engineering yield and rate of reductive biotransformation in Escherichia coli by partial cyclization of the pentose phosphate pathway and PTS-independent glucose transport

Optimization of yields and productivities in reductive whole-cell biotransformations is an important issue for the industrial application of such processes. In a recent study with Escherichia coli, we analyzed the reduction of the prochiral β-ketoester methyl acetoacetate by an R-specific alcohol dehydrogenase (ADH) to the chiral hydroxy ester (R)-methyl 3-hydroxybutyrate (MHB) using glucose as substrate for the generation of NADPH. Deletion of the phosphofructokinase gene pfkA almost doubled the yield to 4.8 mol MHB per mole of glucose, and it was assumed that this effect was due to a partial cyclization of the pentose phosphate pathway (PPP). Here, this partial cyclization was confirmed by 13C metabolic flux analysis, which revealed a negative net flux from glucose 6-phosphate to fructose 6-phosphate catalyzed by phosphoglucose isomerase. For further process optimization, the genes encoding the glucose facilitator (glf) and glucokinase (glk) of Zymomonas mobilis were overexpressed in recombinant E. coli strains carrying ADH and deletions of either pgi (phosphoglucose isomerase), or pfkA, or pfkA plus pfkB. In all cases, the glucose uptake rate was increased (30–47%), and for strains Δpgi and ΔpfkA also, the specific MHB production rate was increased by 15% and 20%, respectively. The yield of the latter two strains slightly dropped by 11% and 6%, but was still 73% and 132% higher compared to the reference strain with intact pgi and pfkA genes and expressing glf and glk. Thus, metabolic engineering strategies are presented for improving yield and rate of reductive redox biocatalysis by partial cyclization of the PPP and by increasing glucose uptake, respectively

Dissecting the Transcriptional Regulatory Properties of Human Chromosome 16 Highly Conserved Non-Coding Regions

Non-coding DNA conservation across species has been often used as a predictor for transcriptional enhancer activity. However, only a few systematic analyses of the function of these highly conserved non-coding regions (HCNRs) have been performed. Here we use zebrafish transgenic assays to perform a systematic study of 113 HCNRs from human chromosome 16. By comparing transient and stable transgenesis, we show that the first method is highly inefficient, leading to 40% of false positives and 20% of false negatives. When analyzed in stable transgenic lines, a great majority of HCNRs were active in the central nervous system, although some of them drove expression in other organs such as the eye and the excretory system. Finally, by testing a fraction of the HCNRs lacking enhancer activity for in vivo insulator activity, we find that 20% of them may contain enhancer-blocking function. Altogether our data indicate that HCNRs may contain different types of cis-regulatory activity, including enhancer, insulators as well as other not yet discovered functions

A Cross-Species Analysis of a Mouse Model of Breast Cancer-Specific Osteolysis and Human Bone Metastases Using Gene Expression Profiling

<p>Abstract</p> <p>Background</p> <p>Breast cancer is the second leading cause of cancer-related death in women in the United States. During the advanced stages of disease, many breast cancer patients suffer from bone metastasis. These metastases are predominantly osteolytic and develop when tumor cells interact with bone. <it>In vivo </it>models that mimic the breast cancer-specific osteolytic bone microenvironment are limited. Previously, we developed a mouse model of tumor-bone interaction in which three mouse breast cancer cell lines were implanted onto the calvaria. Analysis of tumors from this model revealed that they exhibited strong bone resorption, induction of osteoclasts and intracranial penetration at the tumor bone (TB)-interface.</p> <p>Methods</p> <p>In this study, we identified and used a TB microenvironment-specific gene expression signature from this model to extend our understanding of the metastatic bone microenvironment in human disease and to predict potential therapeutic targets.</p> <p>Results</p> <p>We identified a TB signature consisting of 934 genes that were commonly (among our 3 cell lines) and specifically (as compared to tumor-alone area within the bone microenvironment) up- and down-regulated >2-fold at the TB interface in our mouse osteolytic model. By comparing the TB signature with gene expression profiles from human breast metastases and an <it>in vitro </it>osteoclast model, we demonstrate that our model mimics both the human breast cancer bone microenvironment and osteoclastogenesis. Furthermore, we observed enrichment in various signaling pathways specific to the TB interface; that is, TGF-β and myeloid self-renewal pathways were activated and the Wnt pathway was inactivated. Lastly, we used the TB-signature to predict cyclopenthiazide as a potential inhibitor of the TB interface.</p> <p>Conclusion</p> <p>Our mouse breast cancer model morphologically and genetically resembles the osteoclastic bone microenvironment observed in human disease. Characterization of the gene expression signature specific to the TB interface in our model revealed signaling mechanisms operative in human breast cancer metastases and predicted a therapeutic inhibitor of cancer-mediated osteolysis.</p

Current trends in cannulation and neuroprotection during surgery of the aortic arch in Europe†‡

OBJECTIVES To conduct a survey across European cardiac centres to evaluate the methods used for cerebral protection during aortic surgery involving the aortic arch. METHODS All European centres were contacted and surgeons were requested to fill out a short, comprehensive questionnaire on an internet-based platform. One-third of more than 400 contacted centres completed the survey correctly. RESULTS The most preferred site for arterial cannulation is the subclavian-axillary, both in acute and chronic presentation. The femoral artery is still frequently used in the acute condition, while the ascending aorta is a frequent second choice in the case of chronic presentation. Bilateral antegrade brain perfusion is chosen by the majority of centres (2/3 of cases), while retrograde perfusion or circulatory arrest is very seldom used and almost exclusively in acute clinical presentation. The same pumping system of the cardio pulmonary bypass is most of the time used for selective cerebral perfusion, and the perfusate temperature is usually maintained between 22 and 26°C. One-third of the centres use lower temperatures. Perfusate flow and pressure are fairly consistent among centres in the range of 10-15 ml/kg and 60 mmHg, respectively. In 60% of cases, barbiturates are added for cerebral protection, while visceral perfusion still receives little attention. Regarding cerebral monitoring, there is a general tendency to use near-infrared spectroscopy associated with bilateral radial pressure measurement. CONCLUSIONS These data represent a snapshot of the strategies used for cerebral protection during major aortic surgery in current practice, and may serve as a reference for standardization and refinement of different approache

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Mapping of intracellular pH in the in vivo rodent heart using hyperpolarized [1-13C]pyruvate

Purpose: To demonstrate the feasibility of mapping intracellular pH within the in vivo rodent heart. Introduction: Alterations in cardiac acid-base balance can lead to acute contractile depression and alterations in Ca2+ signalling. The transient reduction in ATP consumption and cardiac contractility may be initially beneficial; however, sustained pH changes can be maladaptive, leading to myocardial damage and electrical arrhythmias. Methods: Spectrally-selective RF pulses were used to excite the HCO3- and CO2 resonances individually while preserving signal from the injected hyperpolarized [1-13C]pyruvate. The large flip angle pulses were placed within a 3D imaging acquisition which exploited CA-mediated label exchange between HCO3- and CO2. Images at 4.5x4.5x5 mm3 resolution were obtained in the in vivo rodent heart. The technique was evaluated in healthy rodents scanned at baseline and during high cardiac workload induced by dobutamine infusion. Results: The intracellular pH was measured to be 7.15±0.04 at baseline, and decreased to 6.90±0.06 following 15 minutes of continuous β-adrenergic stimulation. Conclusion: Volumetric maps of intracellular pH can be obtained following an injection of hyperpolarized [1-13C]pyruvate. The new method is anticipated to enable assessment of stress-inducible ischaemia and potential ventricular arrythmogenic substrates within the ischaemic heart