cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 487: Cardiac Sympathetic Afferent Denervation Improves Cardiac Inflammation and Ameliorates Cardiac Remodeling in Post-MI Rats

A recent study from our laboratory demonstrated that chronic and selective cardiac sympathetic afferent denervation at the time of myocardial infarction (MI) by epicardial application of resiniferatoxin (RTX), a neuronal toxin capable of inducing rapid degeneration of transient receptor potential vanilloid 1 (TRPV1)-expressing afferent neurons and fibers, largely prevented the deleterious cardiac remodeling process 9-11 weeks post-MI. This included reduced cardiac hypertrophy, fibrosis and apoptosis. Here, we further investigated the effect of epicardial application of RTX during MI on cardiac extracellular matrix (ECM) remodeling at 10 weeks post-MI. Echocardiographic and morphologic data demonstrated that, compared to MI+vehicle, MI+RTX exhibited a significantly slower LV chamber dilation (6-week echocardiographic data: left ventricular end-diastolic diameter, 10.7 ± 0.2 vs. 9.6 ± 0.3 mm; left ventricular end-systolic diameter: 8.8 ± 0.2 vs. 7.8 ± 0.3 mm; MI+vehicle vs. MI+RTX, n=18, P<0.05). To further explore its molecular mechanism, we used zymography to evaluate the effect of RTX application on the matrix metalloproteinase (MMP) activity, which is responsible for degrading ECM and cardiac dilation after MI. Our preliminary data show that MMP9 activity was increased by 3.9 times in the peri-infarct myocardium post-MI compared to sham. This was largely abolished by RTX application (peri-infarct area: 3.9 ± 0.5 vs. 1.7 ± 0.4, MI+vehicle vs. MI+RTX, n=3, p=0.03). We further investigated the effect of RTX application on MI-induced cardiac inflammation, which has been reported as an upstream mechanism triggering MMP activation post-MI. Our data show that cardiac TNF alpha levels are markedly increased in the peri-infarct or remote myocardium of post-MI rats, which was largely abolished by RTX application during MI (TNF alpha levels in peri-infarct area: 214.2 ± 13.1 vs. 647.5 ± 45.1 vs. 357.3 ± 25.4 pg/mg protein, sham+vehicle vs. MI+vehicle vs. MI+RTX, n=5/each, p<0.05). These data suggest that cardiac sympathetic afferent denervation during MI exerts a local anti-inflammatory effect and reduces the ECM remodeling by preventing excessive MMP activation in post-MI rats.
Use of bacteriophage to target bacterial surface structures required for virulence: a systematic search for antibiotic alternatives.

Bacteriophages (phage) that infect pathogenic bacteria often attach to surface receptors that are coincidentally required for virulence. Receptor loss or modification through mutation renders mutants both attenuated and phage resistant. Such attenuated mutants frequently have no apparent laboratory growth defects, but in the host, they fail to exhibit properties needed to produce disease such as mucosal colonization or survival within professional phagocytic cells. The connection between attenuation and phage resistance has been exploited in experimental demonstrations of phage therapy. In such experiments, phage resistant mutants that arise naturally during therapy are inconsequential because of their attenuated status. A more contemporary approach to exploiting this connection involves identifying small effector molecules, identified in high-throughput screens, that inhibit one or more of the steps needed to produce a functioning phage receptor. Since such biosynthetic steps are unique to bacteria, inhibitors can be utilized therapeutically, in lieu of antibiotics. Also, since the inhibitor is specific to a particular bacterium or group of bacteria, no off-target resistance is generated in the host’s commensal bacterial population. This brief review covers examples of how mutations that confer phage resistance produce attenuation, and how this coincidental relationship can be exploited in the search for the next generation of therapeutic agents for bacterial diseases.
Analysis of 49 cases of sepsis in children

Objective To analyse the clinical features and bacterial resistance in children with sepsis. Methods To review and analyse clinical features and bacterial resistance of children patients with sepsis. Results 42 0~3-year-old cases, 7 over-three-year-old cases; more infectious ways were respiratory tract, digestive tract and skin-mucosa. Bacterial culture were 35 cases of staphylococcus (13 cases of staphylococcus aureus). Conclusion Clinical features in children with sepsis had no specificity and staphylococcus was the major part. The drug resistance was high for penicillin, ampicillin and enythromycin,but amikacin, cephalosporin Ⅲ and vancomycin had higher sensitivity.
Composite control for electric load simulator based on iterative learning

A composite torque controller combining iterative learning control and the feedforward compensation of a rudder angle was built for an electric load simulator in order to increase loading accuracy. The spring beam was used to improve the system stability and the loading accuracy, and constraints to the stiffness coefficient of the spring beam were analyzed based on system response speed, frequency width and stability. The mathematical models of plants were established, and three close loops were used. The feedforward compensation of the rudder angular displacement was introduced into the torque controller. The iterative learning controller was designed by modifying the magnitude and the phase of the command torque to improve loading effects, and P-type iterative learning controller was used. Finally,experiments of loading torque and testing the extraneous torque were performed, and experiment results proved that this controller is effective in achieving a perfect torque tracking accuracy and restraining the extraneous torque for electric load simulators.
A Profile of Extension Courses Offered by Business Schools

A research study was undertaken to investigate the nature and direction of extension programs available in a selected group of state‐ supported schools in order to ascertain the national trends in business program offerings.
Abstract 1684: Mesothelin regulates epithelial-to-mesenchymal transition and tumorigenicity of human lung cancer and mesothelioma cells

Lung cancer and malignant mesothelioma are two of the most deadly forms of cancers. The prognosis of lung cancer and mesothelioma is poor due to limited treatment modalities and lack of understanding of the underlying disease mechanisms. Mesothelin (MLSN), a plasma membrane differentiation antigen, is expressed at a high level in several human cancers, including 70% of lung cancer and nearly all mesotheliomas. Recent studies have shown that plasma and/or pleural effusion MSLN may be used as a biomarker for certain cancers and malignant pleural mesothelioma. However, the role of MLSN in lung cancer and mesothelioma is relatively unknown. In this study, we found that MLSN plays an important role in controlling epithelial-to-mesenchymal transition (EMT) and stem properties of human lung epithelial and mesothelial cells, which control their tumorigenicity. Firstly, MLSN was found to be highly upregulated in human non-small cell lung cancer tissues and in lung cancer and mesothelioma cells, as compared to normal tissues and non-tumorigenic lung epithelial and mesothelial cells. Secondly, knockdown of MLSN by RNA interference significantly reduced anchorage-independent cell growth, tumor sphere formation, and cell migration and invasion in vitro, as well as tumor formation in vivo. Thirdly, knockdown of MLSN attenuated cancer stem cell marker (ALDH) activity and several EMT markers in lung cancer and mesothelioma cell lines. These findings indicate the essential role of MLSN in EMT and malignant properties of human lung cancer and mesothelioma cells. Since EMT is an important process in tumor progression and metastasis, our finding on the role of MLSN may provide new insights into the disease mechanisms and treatment strategies for aggressive lung cancer and mesothelioma. Citation Format: Xiaoqing He, Liying Wang, Emily Despeaux, Yon Rojanasakul. Mesothelin regulates epithelial-to-mesenchymal transition and tumorigenicity of human lung cancer and mesothelioma cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1684.
Extracellular-signal regulated kinase 8 of Trypanosoma brucei uniquely phosphorylates its proliferating cell nuclear antigen homolog and reveals exploitable properties

The Trypanosoma brucei subspecies T. brucei gambiense and T. brucei rhodesiense are vector-borne pathogens that cause sleeping sickness also known as Human African Trypanosomiasis (HAT), which is fatal if left untreated. The drugs that treat HAT are ineffective and cause toxic side effects. One strategy for identifying safer and more effective HAT drugs is to therapeutically exploit essential gene targets in T. brucei. Genes that make up a basic mitogen-activated protein kinase (MAPK) network are present in T. brucei. Tb927.10.5140 encodes an essential MAPK that is homologous to the human extracellular-signal regulated kinase 8 (HsERK8) which forms a tight complex with the replication factor proliferating cell nuclear antigen (PCNA) to stabilize intracellular PCNA levels. Here we demonstrate that (TbPCNA) is uniquely phos-phorylated on serine (S) and threonine (T) residues in T. brucei and that TbERK8 phosphorylates TbPCNA at each of these residues. The ability of an ERK8 homolog to phosphorylate a PCNA homolog is a novel biochemical property that is first demonstrated here in T. brucei and may be unique to this pathogen. We demonstrate that the potent HsERK8 inhibitor Ro318220, has an IC50 for TbERK8 that is several hundred times higher than its reported IC50 for HsERK8. This indicated that the active sites of TbERK8 and HsERK8 can be selectively inhibited, which provides a rational basis for discovering inhibitors that specifically target this essential parasite MAPK to kill the parasite.
Identification of the First Riboflavin Catabolic Gene Cluster Isolated from Microbacterium maritypicum G10

Riboflavin is a common cofactor, and its biosynthetic pathway is well characterized. However, its catabolic pathway, despite intriguing hints in a few distinct organisms, has never been established. This article describes the isolation of a Microbacterium maritypicum riboflavin catabolic strain, and the cloning of the riboflavin catabolic genes. RcaA, RcaB, RcaD, and RcaE were overexpressed and biochemically characterized as riboflavin kinase, riboflavin reductase, ribokinase, and riboflavin hydrolase, respectively. Based on these activities, a pathway for riboflavin catabolism is proposed.
Post-traumatic stress disorder and cardiometabolic disease: improving causal inference to inform practice

Post-traumatic stress disorder (PTSD) has been declared 'a life sentence' based on evidence that the disorder leads to a host of physical health problems. Some of the strongest empirical research - in terms of methodology and findings - has shown that PTSD predicts higher risk of cardiometabolic diseases, specifically cardiovascular disease (CVD) and type 2 diabetes (T2D). Despite mounting evidence, PTSD is not currently acknowledged as a risk factor by cardiovascular or endocrinological medicine. This view is unlikely to change absent compelling evidence that PTSD causally contributes to cardiometabolic disease. This review suggests that with developments in methods for epidemiological research and the rapidly expanding knowledge of the behavioral and biological effects of PTSD the field is poised to provide more definitive answers to questions of causality. First, we discuss methods to improve causal inference using the observational data most often used in studies of PTSD and health, with particular reference to issues of temporality and confounding. Second, we consider recent work linking PTSD with specific behaviors and biological processes, and evaluate whether these may plausibly serve as mechanisms by which PTSD leads to cardiometabolic disease. Third, we evaluate how looking more comprehensively into the PTSD phenotype provides insight into whether specific aspects of PTSD phenomenology are particularly relevant to cardiometabolic disease. Finally, we discuss new areas of research that are feasible and could enhance understanding of the PTSD-cardiometabolic relationship, such as testing whether treatment of PTSD can halt or even reverse the cardiometabolic risk factors causally related to CVD and T2D.
Strain Relaxation Due to Phosphorus Implantation into Strained Si/SiGe/Si Heterostructure

Ion implantation has been established as an important process tool to introduce precise amount of dopants into semiconductors. However, it is known to create several defects in the form of point defects and misfit dislocations. Annealing is generally performed to achieve dopant activation which also minimizes channeling tails and decrease residual extended defect densities. In this paper we have reported the annealing behavior of phosphorus implanted into strained SiGe layer at room temperature. The implantation was performed at 155 KeV with a dose of 1 × 1014/cm2. Post implantation annealing was performed at 600, 700, 800 and 900°C for 10 seconds in a Rapid Thermal Process furnace. I-V, C-V and DLTS measurements hint towards presence of permanent dislocation loops created as a consequence of implantation and annealing.
Health promotion in physician organizations ☆: Results from a national study

Abstract Background Health promotion programs can be effective in improving the delivery of clinical preventive services and in improving population health; however, the availability of health promotion programs offered through physician organizations, such as medical groups and independent practice associations, are largely unknown. Methods This research uses data from the National Study of Physician Organizations and the Management of Chronic Illness, conducted by the University of California, Berkeley, to document the extent to which physician organizations offer health promotion programs. Of 1587 physician organizations nationally with 20 or more physicians, 1104 participated, for a response rate of 70%. Results Overall, 60% of physician organizations offer at least one health promotion program targeting one or more of eight areas: prenatal education (42%), smoking cessation (39%), nutrition (39%), weight loss (34%), health risk assessments (25%), stress management (25%), substance abuse (20%), and sexually transmitted disease prevention (16%). Factors positively associated with offering health promotion programs include the following: outside reporting of quality measures, public recognition for quality measures, clinical information technology systems, being a medical group, and ownership by a hospital or health plan. Conclusions Physician organizations in the United States have a long way to go in offering these important programs to their patients. However, our findings also suggest that health plans, purchasers, and policymakers can play a positive role in increasing the use of these programs. By offering recognition and incentives for quality improvement, and by funding the expansion of information technology, the healthcare community can encourage and enable physician organizations to increase the availability of health promotion programs nationally.
Optimal trade-off between accuracy and network cost of distributed learning in Mobile Edge Computing: An analytical approach

The most widely adopted approach for knowledge extraction from raw data generated at the edges of the Internet (e.g., by IoT or personal mobile devices) is through global cloud platforms, where data is collected from devices, and analysed. However, with the increasing number of devices spread in the physical environment, this approach rises several concerns. The data gravity concept, one of the basis of Fog and Mobile Edge Computing, points towards a decentralisation of computation for data analysis, whereby the latter is performed closer to where data is generated, for both scalability and privacy reasons. Hence, data produced by devices might be processed according to one of the following approaches: (i) directly on devices that collected it (ii) in the cloud, or (iii) through fog/mobile edge computing techniques, i.e., at intermediate nodes in the network, running distributed analytics after collecting subsets of the data. Clearly, (i) and (ii) are the two extreme cases of (iii). It is worth noting that the same analytics task executed at different collection points in the network, comes at different costs in terms of traffic generated over the network. Precisely, these costs refer to the traffic generated to move data towards the collection point selected (e.g. the Edge or the Cloud) and the one induced by the distributed analytics process. Until now, deciding if to use intermediate collection points, and which one they should be in order to both obtain a target accuracy and minimise the network traffic, is an open question. In this paper, we propose an analytical framework able to cope with this problem. Precisely, we consider learning tasks, and define a model linking the accuracy of the learning task performed with a certain set of collection points, with the corresponding network traffic. The model can be used to identify, given the specification of the learning problem (e.g. binary classification, regression, etc.), and its target accuracy, what is the optimal level for collecting data in order to minimise the total network cost. We validate our model through simulations in order to show that setting, in simulation, the level of intermediate collection indicated by our model, leads to the minimum cost for the target accuracy.
Season matters when sampling streams for swine CAFO waste pollution impacts

Concentrated (or confined) animal feed operations (CAFOs) are the principal means of livestock production in the United States, and such facilities pollute nearby waterways because of their waste management practices; CAFO waste is pumped from the confinement structure into a cesspit and sprayed on a field. Stocking Head Creek is located in eastern North Carolina, a state with >9,000,000 head of swine confined in CAFOs. This watershed contains 40 swine CAFOs; stream water quality was investigated at seven sites during 2016, with five sampling dates in early spring and five in summer. Geometric mean fecal coliform counts were in the thousands/100 mL at five sites in spring and all seven sites in summer. Excessive nitrate pollution was widespread with concentrations up to >11.0 mg N/L. Seasonality played an important role in pollutant concentrations. In North Carolina, spraying animal waste on adjoining fields is permissible from March 1 through September 30. Seasonal data showed significantly higher (p < 0.01) concentrations of conductivity, nitrate, total nitrogen, total organic carbon, and fecal bacteria in summer as opposed to early spring. Thus, sampling performed only in winter-early spring would significantly underestimate impacts from swine CAFO spray fields on nearby waterways.
Study of Opto-Mechanical Properties of Tubular Water Quenched Polyethylene Films

Tubular Water Quench (TWQ) is commonly used process to make Polypropylene based films (TQPP). This process has been tried for the first time to make Polyethylene films (TQPE) from HDPE-LLDPE blend. Polyethylene inculcates the inherent materialistic property of softness and better feel to the film. The key requirement for TWQ films are Openability and transparency. This paper focuses on novel developmental work done, using Polyethylene blend for making TQPE film, comparing it’s optical and mechanical properties with TQPP films.
Nondestructive Methods for the Determination of Mechanical Properties of Materials

The nondestructive determination of mechanical properties of materials is desirable because of the rising cost of both materials and labor as well as safety concerns. In most alloys, changes in thermal and/or mechanical history results in microstructural changes and consequently different mechanical properties. Thermal or mechanical cycles may result from processing or occur in service. Therefore nondestructive detection of microstructure and mechanical properties would prove useful in all phases of metallurgical use. This paper reports on efforts to determine selected mechanical properties of structural materials by nondestructive means such as electrical, acoustic and magnetic techniques as well as hardness. Various thermal and mechanical conditions have been imposed on aluminum, titanium and ferrous alloys to arrive at a wide range of mechanical properties. It is concluded that the intimate knowledge of the microstructure and environmental effects are essential to select the nondestructive method that is most sensitive to property changes.
Special Considerations of Adherence in Older Adults

Optimizing medication adherence is a significant challenge for clinicians caring for older adults, particularly those with multiple chronic health conditions. Nearly half of all adults aged 65 or older take five or more medications regularly; however, adherence to chronic pharmacological therapies is often poor [1]. Overall, 40% of older Medicare beneficiaries reported one or more forms of medication non-adherence in the previous year [1]. Older patients are often more susceptible to the outcomes of poor adherence including worsening symptoms of disease and disease severity, increased hospital admissions, costs, and mortality [2, 3]. Older adults face many of the barriers to adherence discussed in previous chapters; however, age-related physical or cognitive impairments, multiple chronic health conditions, and/or complex treatment regimens frequently create distinct challenges related to adherence in this population. The aims of this chapter are to discuss special considerations related to medication adherence in older adults and to offer practical advice for improving medication adherence in this population.
A photomechanics material for elastoplastic stress analysis

The object of this investigation was to develop a technique or method for elastoplastic stress analysis using the optical effects of transparent materials. Of paramount importance was the selection and characterization of a suitable model material. In particular, it was desirable that the material be able to undergo large plastic strains while, at the same time, exhibiting a suitable level of optical response. A mixture of flexible and rigid polyester resins was found suitable, i.e., the mixture exhibited large strains and good optical response. It was found that unload birefringence (fringe order immediately upon removal of load) could be used to determine strain for a uniaxial-stress field. In particular, it provided a means for evaluating stress- and strain-concentration factors. Comparisons with other methods showed that the proposed method was reliable and gave results that are similar to those by other means. The usefulness of the material and method for two- and three-dimensional problems awaits further study.
Nymphs and Ritual Bathing

Illustrations of similar-appearing, curvaceous, petite women (or nymphs) with blonde hair in various styles, bathing or cavorting in green pools connected by tubes suggestive of plumbing or vascular systems, are among the most bizarre features of the Voynich Codex. The bathing images are reminiscent of both Western and Aztec art. The plumbing suggests gynecological allusions such a fallopian tubes or ovaries. The nymphs are often shown in an explicit frontal view. Rear views are not found. Often, they are depicted carrying various objects including a crucifix, a large metallic ring or collar with a knob or nub, a torpedo-like object, sticks, or balls. The large ring suggests the iron collar of subjugation used by the Spanish, and the oblong, torpedo-shaped object resembles the pear of anguish, a gruesome torture device. The bathing nymphs suggest a symbolic example of ritual bathing. There are many bathing images in Aztec illustrations and abundant archeological remains of baths and bathhouses in Aztec culture. The bathing scenes represent a fusion of European and Aztec customs, suggesting a Western-trained artist with Aztec sensibilities.
Approximating Probabilistic Automata by Regular Languages

A probabilistic finite automaton (PFA) A is said to be regular-approximable with respect to (x,y), if there is a regular language that contains all words accepted by A with probability at least x+y, but does not contain any word accepted with probability at most x. We show that the problem of determining if a PFA A is regular-approximable with respect to (x,y) is not recursively enumerable. We then show that many tractable sub-classes of PFAs identified in the literature - hierarchical PFAs, polynomially ambiguous PFAs, and eventually weakly ergodic PFAs - are regular-approximable with respect to all (x,y). Establishing the regular-approximability of a PFA has the nice consequence that its value can be effectively approximated, and the emptiness problem can be decided under the assumption of isolation.
Supporting Effective Strategies for Resolving Vulnerabilities Reported by Static Analysis Tools

Static analysis tools detect potentially costly security defects early in the software development process. However, these defects can be difficult for developers to accurately and efficiently resolve. The goal of this work is to understand the vulnerability resolution process so that we can build tools that support more effective strategies for resolving vulnerabilities. In this work, I study developers as they resolve security vulnerabilities to identify their information needs and current strategies. Next, I study existing tools to understand how they support developers' strategies. Finally, I plan to demonstrate how strategy-aware tools can help developers resolve security vulnerabilities more accurately and efficiently.
Incomplete Tests for Undetectable Faults to Improve Test Set Quality

The presence of undetectable faults in a set of target faults implies that tests, which may be important for detecting defects, are missing from the test set. This article suggests an approach for addressing missing tests that fits with the rationale for computing an n-detection test set. The artcile defines the concept of an incomplete test that is relevant when a target fault is undetectable. An incomplete test activates the fault but fails to detect it because of one or more assignments that are missing from the test. The procedure described in this article improves the quality of a test set by attempting to ensure that every undetectable fault has n incomplete tests with the smallest possible numbers of missing assignments, for a constant n ≥ 1. The incomplete tests are expected to contribute to the detection of detectable defects around the site of the undetectable fault. The computation of missing assignments for a test is performed in linear time by avoiding fault simulation and considering all the undetectable faults simultaneously. Experimental results demonstrate the extent to which a given test set can be improved without increasing the number of tests.
Assessment of Deep Natural Language Processing in Ascertaining Oncologic Outcomes From Radiology Reports.

Importance A rapid learning health care system for oncology will require scalable methods for extracting clinical end points from electronic health records (EHRs). Outside of clinical trials, end points such as cancer progression and response are not routinely encoded into structured data. Objective To determine whether deep natural language processing can extract relevant cancer outcomes from radiologic reports, a ubiquitous but unstructured EHR data source. Design, Setting, and Participants A retrospective cohort study evaluated 1112 patients who underwent tumor genotyping for a diagnosis of lung cancer and participated in the Dana-Farber Cancer Institute PROFILE study from June 26, 2013, to July 2, 2018. Exposures Patients were divided into curation and reserve sets. Human abstractors applied a structured framework to radiologic reports for the curation set to ascertain the presence of cancer and changes in cancer status over time (ie, worsening/progressing vs improving/responding). Deep learning models were then trained to capture these outcomes from report text and subsequently evaluated in a 10% held-out test subset of curation patients. Cox proportional hazards regression models compared human and machine curations of disease-free survival, progression-free survival, and time to improvement/response in the curation set, and measured associations between report classification and overall survival in the curation and reserve sets. Main Outcomes and Measures The primary outcome was area under the receiver operating characteristic curve (AUC) for deep learning models; secondary outcomes were time to improvement/response, disease-free survival, progression-free survival, and overall survival. Results A total of 2406 patients were included (mean [SD] age, 66.5 [10.8] years; 1428 female [59.7%]; 2170 [90.2%] white). Radiologic reports (n = 14 230) were manually reviewed for 1112 patients in the curation set. In the test subset (n = 109), deep learning models identified the presence of cancer, improvement/response, and worsening/progression with accurate discrimination (AUC >0.90). Machine and human curation yielded similar measurements of disease-free survival (hazard ratio [HR] for machine vs human curation, 1.18; 95% CI, 0.71-1.95); progression-free survival (HR, 1.11; 95% CI, 0.71-1.71); and time to improvement/response (HR, 1.03; 95% CI, 0.65-1.64). Among 15 000 additional reports for 1294 reserve set patients, algorithm-detected cancer worsening/progression was associated with decreased overall survival (HR for mortality, 4.04; 95% CI, 2.78-5.85), and improvement/response was associated with increased overall survival (HR, 0.41; 95% CI, 0.22-0.77). Conclusions and Relevance Deep natural language processing appears to speed curation of relevant cancer outcomes and facilitate rapid learning from EHR data.
Nanopore sequencing undergoes catastrophic sequence failure at inverted duplicated DNA sequences

Inverted duplicated sequences are a common feature of structural variants (SVs) and copy number variants (CNVs). Analysis of CNVs containing inverted duplicated sequences using nanopore sequencing identified recurrent aberrant behavior characterized by incorrect and low confidence base calls that result from a systematic elevation in the current recorded by the sequencing pore. The coincidence of inverted duplicated sequences with catastrophic sequence failure suggests that secondary DNA structures may impair transit through the nanopore.
Irinotecan treatment in cancer patients with UGT1A1 polymorphisms.

Abstract At the present time, pharmacogenetic investigation of irinotecan (CPT-11, Camptosar) therapy is mainly focused on the clinical relevance of genetic variation in the UDP-glucuronosyltransferase (UGT1A1) gene. The glucuronidation of the potent topoisomerase I inhibitor SN-38 is a major inactivation pathway of irinotecan metabolism. UGT1A1 genotypes associated with Gilbert's syndrome (a mild intermittent hyperbilirubinemia) are characterized by reduced glucuronidation of SN-38. Such UGT1A1 genetic variants have different distribution across individuals of different ethnicity. The (TA)n TAA polymorphism in the promoter is more frequent in Caucasians as compared to Asians, in whom missense polymorphisms in the exons are more common. Two recent pharmacogenetic trials (one performed in the United States and the other in Japan) investigated the clinical significance of UGT1A1 gene mutations for both the pharmacokinetics of irinotecan metabolites and the toxicity profile. The results of these association studies showed that preliminary genotyping of the (TA)n polymorphism might predict the occurrence of toxicity in genetically predisposed patients.
Cardy's Conjecture and the Spectrum of Infrared Strongly-Coupled Quantum Field Theories

Cardy's conjecture about the evolution of the trace anomaly under renormalization group (RG) flows is re-interpreted as an exact, non-perturbative statement about the scaling dimension of terms in the Lagrangian of the theory. When viewed in this way, the conjecture implies that field theories which are strongly coupled in the infrared (IR) may generically host states that are not manifest as solutions to the ultraviolet (UV) complete theory's equations of motion. In particular, the scaling dimension of operators in the Hamiltonian may deviate from their classical values by $\mathcal{O}(1)$ corrections in the IR, circumventing an old argument by Derrick about the non-existence of such states\cite{1}. We show that this framework provides a natural way to estimate the masses of these states using perturbation theory, and suggests a preferred reorganization of the degrees of freedom in the IR.
Characterization of Human Glioblastoma versus Normal Plasma-Derived Extracellular Vesicles Preisolated by Differential Centrifugation Using Cyclical Electrical Field-Flow Fractionation.

Although many properties for small extracellular vesicles (sEVs, formerly termed “exosomes”) isolated at ∼100 000g are known, a wide range of values are reported for their electrophoretic mobility ...
A 35-Year-Old Man with Persistent Pain After Hand Injury (Complex Regional Pain Syndrome)

Complex regional pain syndrome is a pain condition that most often affects limbs, but can involve the rest of the human body. This condition may develop after trauma, surgery, or even minor injury. Its progression is phenotypically variable ranging from self-limiting mild to chronic debilitating disease, affecting patient’s quality of life and creating a burden for both the patient and the society. Early recognition and aggressive treatment may limit the disease progression. However, its underlying pathophysiology is complicated and poorly understood, making its diagnosis and treatment challenging. The diagnosis of complex regional pain syndrome relies on clinical findings as there is currently no specific diagnostic test to confirm it. A variety of therapies have been used to treat complex regional pain syndrome; however, most of the evidence for these treatments is of low quality. Further large-scale, well-designed clinical trials are needed to investigate the pathophysiological mechanisms and treatment modalities of the disorder.
BAF Complexes and the Glucocorticoid Receptor in Breast Cancers

Abstract Breast cancers are a diverse group of diseases and are often characterized by their expression of receptors for hormones such as estrogen and progesterone. Recently, another steroid hormone receptor, the glucocorticoid receptor has been shown to be a key player in breast cancer progression, metastasis, and treatment. These receptors bind to chromatin to elicit transcriptional changes within cells, which are often inhibited by the structure of chromatin itself. Chromatin-remodeling proteins, such as Brahma-related gene 1, function to overcome this physical inhibition of transcription factor function and have been linked to many cancers including breast cancer. Recent efforts to understand the interactions of Brahma-related gene 1 and the glucocorticoid receptor, including genomic and single-cell analyses, within breast cancers may give insight into personalized medicine and other potential treatments.
Recent advances in clinical trial design considerations in Thera"nostics".

Abstract Theranostics in drug development is an evolving framework, known as combining ‘thera’ (a therapeutic drug) with ‘nostics’ (a diagnostic imaging drug) and with the latter being mostly used to select patient for evaluation of safety and efficacy of an investigational therapeutics. However, when a diagnostic imaging drug is still investigational, patient selection performance of a nostics imaging has not been demonstrated. Clinical trials conducted to assess the effect of an investigational therapeutics in a theranostics setting may focus only on the therapeutics development and not necessarily require definitive truth standard or reference standard to also assess patient selection performance of an investigational diagnostic imaging drug. We propose an In-Parallel with Leveraging development pathway in view of current practice of theranostics for a nostics imaging development. We rationalize minimum statistical metrics necessary for patient selection to allow for rigors of a nostics or diagnostics imaging drug development. We highlight tangible benefits with newer design considerations. We articulate potential indications of a nostics development including prognostic, predictive and treatment response monitoring in addition to patient selection. We further articulate potential additional clinical utilities of risk stratification and clinical management. To take full advantage and the likely payoff in the benefit of leveraging, a group sequential design or an adaptive design for the therapeutic trial is highly encouraged.
Disrupting the Flow of Perception-Action through Design:

It is usually a mark of good design when technologies and tools that mediate goal-directed action are such that the user’s attentional focus is maintained on the intended ends of action rather than...
Ultralow-switching current density multilevel phase-change memory on a flexible substrate.

Phase-change memory (PCM) is a promising candidate for data storage in flexible electronics, but its high switching current and power are often drawbacks. In this study, we demonstrate a switching ...
Assessment of upper airway patency in spontaneously breathing non-intubated neonates and infants undergoing conventional MRI of head and neck.

Neonates and infants frequently undergo MRI examinations of the brain or head and neck in spontaneous respiration. This study aims to evaluate the patency of the upper airway and associated risk factors in spontaneously breathing neonates and infants undergoing MRI of head and neck. Airway patency was assessed on sagittal and axial MRI images of the head and neck region for neonates and infants retrospectively. Anteroposterior diameters were measured at the soft palate and tongue levels as well as a lateral diameter at the tongue level for the patent airway. Chart review for risk factors was carried out. A total of 831 children between 0 and 12 months of age had an MRI. Eighty-two children with spontaneous ventilation were included. The airway was occluded in 29/82 (35 %) of children. Twenty-four out of 29 (83 %) children with airway occlusion had a depressed level of consciousness, 7/24 (29 %) of whom were sedated with a single dose of benzodiazepine and 17/24 (71 %) were on anti-epileptic therapy for an underlying seizure disorder and/or hypoxic ischemic encephalopathy. Forty-three out of 82 (65 %) of children had an open airway. The airway diameters (mean ± SD) were 5.9 ± 2 mm (anteroposterior (AP) at soft palate), 7.4 ± 2.9 mm (lateral at soft palate), and 6.3 mm ± 1.6 (AP at dorsum of tongue). A significant proportion of spontaneously breathing neonates and infants with hypoxic ischemic encephalopathy or sedation show evidence of airway obstruction during MRI. Careful pre-MRI screening for decision of spontaneous breathing versus artificial airway support during MRI and robust airway monitoring during MRI are required for these vulnerable children.
Wiring Diagram of the RAS

The wiring diagram of the main nuclei of the reticular activating system (RAS) is well known, as are the intrinsic membrane properties of cells in these nuclei. The major transmitter inputs to these cells have also been described, as have the main cell types and their transmitter outputs. In addition, the presence of electrical coupling in some cells in these nuclei has been determined. These properties allow us to gain a measure of the types of firing patterns that these neurons are capable of maintaining. The firing patterns and transmitter inputs of these cells across the wake–sleep cycle have also been determined. Current research is directed at how the cell clusters within the RAS nuclei function to modulate thalamic and cortical EEG rhythms in the presence of sporadic and continuous sensory inputs. This information is critical for determining how the states of waking and REM sleep are modulated by the RAS.
Adaptive Management and Law

Although adaptive management has been widely discussed in the fields of ecology and conservation biology for decades, its incorporation into natural resource management in the United States is relatively recent. It is increasingly recognized as a valuable approach to natural resource and environmental management challenges that involve high degrees of uncertainty. The legal rules and requirements that drive environmental protection efforts in the United States, however, are often considered barriers to successful implementation of adaptive management. This chapter explores the challenges and opportunities associated with the integration of adaptive management into current legal and regulatory frameworks in the United States. It summarizes current literature on adaptive management and law, with particular emphasis on scholarship that highlights the challenges associated with incorporating adaptive management into current institutional arrangements. It then provides some basic background regarding the overall structure of government in the United States and explains the critical role of the executive and judicial branches in implementation and enforcement of adaptive management plans. A summary of current federal court decisions regarding how agencies are using adaptive management is provided to highlight the challenges associated with balancing the need for administrative flexibility with the competing need for legal enforceability. Finally, we conclude with some suggestions for more successful incorporation of adaptive management by federal agencies in the United States.
Studies of monoamine oxidases. Inhibition of bovine brain MAO in intact mitochondria by tricyclic antidepressant drugs.

Abstract Tricyclic antidepressant drugs (TCA) were found to reversibly inhibit monoamine oxidase (MAO) in intact mitochondria of beef brain cortex, I50, values were in the range of 10−4 to 10−3 M, using chlorimipramine, amitriptyline, desimipramine, imipramine and doxepin. Unlike TCA inhibition reported for MAO in rabbit tissues, the inhibition observed with beef brain MAO was greater for the A-type enzyme, indicated by serotonin (5-HT) deamination, than for the B-type enzyme, indicated by phenylethylamine (PEA) deamination. Chlorimipramine was the most effective of the five tricyclic antidepressant drugs tested for the inhibition of 5-HT deamination, while amitriptyline was the most effective for inhibiting PEA deamination. Kinetic analyses also revealed marked differences in the interaction of the tricyclics with the A form and the B form of MAO. Inhibition was found to be of a mixed type by reciprocal plots, but Dixon plots indicated that the inhibition was parabolic with 5-HT and either linear or hyperbolic with PEA, depending on the TCA used. Mixed inhibitor studies were also carried out, combining a TCA with a selective (clorgyline or deprenyl) or a non-selective (tranylcypromine) MAO inhibitor. Such combinations did not result in a potentiation of inhibition of either the MAO-A or MAO-B type enzyme activity. The present results indicate that the inhibition of MAO may be of only minor significance in the therapeutic efficacy of TCA in the treatment of depression, especially in combined therapy. However, this conclusion must be tempered by the knowledge that there are marked variations in MAO properties from different enzyme sources, as evidenced by these results.
Cloning of an aroF allele encoding a tyrosine-insensitive 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase.

Abstract In Escherichia coli, genes aroF+, aroG+, and aroH+ encode isoenzymes of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthases that are feedback inhibited by tyrosine, phenylalanine, and tryptophan, respectively. A single base pair change in aroF causes a Pro-148-to-Leu-148 substitution and results in a tyrosine-insensitive enzyme.
Program Synthesis and Transformation Techniques for Simulation, Optimization, and Constraint Satisfaction

Scientists and engineers face recurring problems of constructing, testing and modifying numerical simulation programs. The process of coding and revising such simulators is extremely time-consuming, because they are almost always written in conventional programming languages. Scientists and engineers can therefore benefit from software that facilitates construction of programs for simulating physical systems. Our research adapts the methodology of deductive program synthesis to the problem of constructing numerical simulation codes. We have focused on simulators that can be represented as second order functional programs composed of numerical integration and root extraction routines. We have developed a system that uses first order Horn logic to synthesize numerical simulators built from these components. Our approach is based on two ideas: First, we axiomatize only the relationship between integration and differentiation. We neither attempt nor require a complete axiomatization of mathematical analysis. Second, our system uses a representation in which functions are reified as objects. Function objects are encoded as lambda expressions. Our knowledge base includes an axiomatization of term equality in the lambda calculus. It also includes axioms defining the semantics of numerical integration and root extraction routines. We use depth bounded SLD resolution to construct proofs and synthesize programs. Our system has successfully constructed numerical simulators for computational design of jet engine nozzles and sailing yachts, among others. Our results demonstrate that deductive synthesis techniques can be used to construct numerical simulation programs for realistic applications [EM98].
Seamlessly Selecting the Best Copy from Internet-Wide Replicated Web Servers

The explosion of the web has led to a situation where a majority of the traffic on the Internet is web related. Today, practically all of the popular web sites arc served from single locations. This necessitates frequent long distance network transfers of data (potentially repeatedly) which results in a high response time for users, and is wasteful of the available network bandwidth. Moreover, it commonly creates a single point of failure between the web site and its Internet provider. This paper presents a new approach to web replication, where each of the replicas resides in a different part of the network, and the browser is automatically and transparently directed to the “best” server. Implementing this architecture for popular web sites will result in a better response-time and a higher availability of these sites. Equally important, this architecture will potentially cut down a significant fraction of the traffic on the Internet, freeing bandwidth for other uses.
Observations on the Etiology of Gall Stones

Excerpt The most accepted general cause of the origin of gall stones is bile stasis. Beyond this, views vary widely. Naunyn1believes that a second cause is an ascending infection which causes "the ...
Restriction formula for stable basis of the Springer resolution

We give restriction formula for stable basis of the Springer resolution and generalize it to cotangent bundles of partial flag varieties. By a limiting process, we get the restriction formula of Schubert varieties.