cssi/SciSciGPT-SciSciNet huggingface dataset:
A Stepwise Approach for Postlobectomy Bronchopleural Fistula

Although rare, bronchopleural fistula (BPF) following anatomic lung resection is a serious complication associated with high rates of mortality (25%-71%). Risk factors for BPF include surgical approach, neoadjuvant therapy, diabetes mellitus, and chronic obstructive pulmonary disease. As neoadjuvant treatment is increasingly being administered to patients with locally advanced lung cancer, and as more patients are being diagnosed with lung cancer at an older age—elderly patients present with a higher index of multiple comorbidities—the incidence of BPF among patients undergoing anatomic resection for lung cancer is expected to increase. In this manuscript, we detail risk factors and considerations for BPF and describe a stepwise approach to treat BPF following lobectomy for lung cancer.
Regional and practitioner variations in reporting infant mortality

Objective: Assess regional differences in categorization of preterm delivery outcomes and impact on variation in reported infant mortality rates.Study design: A 27-item questionnaire was distribute...
Washing packed red blood cells decreases red blood cell storage lesion formation.

Abstract Background Transfusion of blood products is the ideal resuscitative strategy after hemorrhage. Unfortunately, older packed red blood cells have been associated with increased morbidity and mortality after massive transfusion. These packed red blood cells accumulate biochemical and structural changes known as the red blood cell storage lesions. The effect of washing on the formation of red blood cell storage lesions is unknown. We hypothesized that washing packed red blood cells during storage would decrease the development of the red blood cell storage lesions. Methods Blood from 8- to 10-week-old male mice donors was stored as packed red blood cells for 14 days. A subset of packed red blood cells were washed with phosphate-buffered saline on storage day 7 and resuspended in AS-1 solution for an additional 7 days as washed packed red blood cells. Subsequently, the packed red blood cells were analyzed for microvesicle release, band-3 erythrocyte membrane integrity protein (Band-3), expression of phosphatidylserine, cell viability (calcein), accumulation of cell-free hemoglobin, and osmotic fragility. Results In the washed packed red blood cells group, there was less microvesicle accumulation, greater Band-3 expression, less phosphatidylserine expression, a decrease in cell-free hemoglobin accumulation, and a decrease in osmotic fragility, but no differences in red blood cells viability. Conclusion Washing packed red blood cells during storage decreases the accumulation of red blood cell storage lesions. This strategy may lessen the sequelae associated with transfusion of older packed red blood cells.
Association of Patient Health Outcomes with Caregiver Burden after LVAD in Destination Therapy and as a Bridge to Transplant

Purpose While left ventricular assist devices (LVADs) are known to improve heart failure (HF) patient survival and health status (i.e., symptoms, function, and quality of life), they also require substantial support from caregivers (CG). In fact, excessive CG burden is a relative contraindication to LVAD implantation. Importantly, CG burden can be a transient state and whether or not this improves in patients’ whose health status improves from before to after LVAD implantation has not been described. Methods Between 10/1/15 and 12/31/18, 96 patients and their CGs were recruited from 13 U.S. sites; data through 1 year after LVAD implantation were used. Patient health status was defined by Kansas City Cardiomyopathy Questionnaire-12 (KCCQ) Overall Summary score, where higher scores indicate better health status. CG burden was measured using the Oberst Caregiver Burden Scale (OCBS): 15 items (range=1-5), measuring perceived amount of time spent and difficulty of tasks (higher score=more time on task and more difficulty), respectively. Linear regression was used to identify patient and CG factors independently associated with change in CG burden. Results LVAD recipients were 67.5±5.4 years old, 86% male, and with an implant strategy of destination therapy (65%) and bridge to transplant (35%). Their baseline KCCQ score was 45.5±23.9. Their CGs were 60.7±10.3 years old, 91% female and had baseline OCBS time and burden scores of 2.4±0.7 and 1.4±0.5, respectively. Better baseline and greater improvements in patients’ health status was strongly associated with improvements in CG burden, both time and difficulty (Table). Conclusion This study highlights the complex dyadic relationship between HF patients and their CGs. After LVAD implantation, the greater the improvement in HF patient health status, the greater the reduction in CG burden. The likelihood of patient improvement with LVAD implantation should be considered when there is concern about CG burden prior to implantation.
Corporate Governance and Tax Avoidance: Evidence from Governance Reform

Prior literature struggles to find evidence in U.S. settings to support the Desai and Dharmapala (2006) theory on how corporate governance affects tax avoidance. Most studies rely on equity incentive compensation as their governance proxy. We use a Mexican setting to examine this association and find firms with stronger governance engage in less tax avoidance. We rely on both a hand-collected governance index and governance reform to show improved corporate governance pushes tax avoidance toward a new equilibrium. Supplementary analyses show associations between governance and tax avoidance are greatest for tax-cost-sensitive family-owned firms and non-cross-listed firms with naturally weaker governance. A one standard deviation increase in governance corresponds to an increase of between one and three percentage points in a firm’s effective tax rate. Our findings suggest these governance reforms effectively reduce rent extraction by majority shareholders and identify Board independence and audit committees as channels responsible for decreased tax avoidance.
Disease site matters: Ovarian carcinosarcoma has far more genomic similarity to high-grade serous ovarian carcinoma than to uterine carcinosarcoma

Objectives: To determine if the genomic behavior of ovarian carcinosarcoma (OCS), based on mutations identified in next-generation sequencing (NGS) tumor profiling, is more similar to its histologic counterpart, uterine carcinosarcoma (UCS) or high-grade serous ovarian carcinoma (HGSOC). Methods: Preliminary data was collected from AACR's Project GENIE v8.0, a collection of multi-institutional Next Genome Sequencing (NGS) genomic profiling data, via cBioPortal ( http://genie.cbioportal.org ). Ovarian Carcinosarcoma (OCS), High Grade Serous Ovarian Cancer (HGSOC) and Uterine Carcinosarcoma (UCS) were selected and analyzed for mutation frequencies. The initial analysis determined which genes had a difference in mutation frequency between the HGSOC and UCS groups using a Fisher's Exact Test. We then selected the genes with p-value less than 0.0005 to create a signature to distinguish between HGSOC and UCS. This gene signature was then used to determine whether each OCS sample was more genetically similar to HGSOC or UCS. Results: In the analysis, there were 454 patients with HGSOC, 40 patients with OCS, and 72 patients with UCS. Five genes (FBXW7, KRAS, PIK3CA, PIK3R1, and PTEN) were the only genes idenitifed that predicted the difference between HGSOC and UCS with a p-value Download : Download high-res image (60KB) Download : Download full-size image Conclusions: OCS appears to be more similar genomically to HGSOC than UCS. These findings support current NCCN guidelines that recommend adjuvant treatment of OCS follow the same paradigm as HGSOC. Furthermore, these findings add to the growing consensus that patients with OCS should be considered for inclusion in clinical trials for epithelial ovarian cancer.
Complex vulnerabilities of the water and aquatic carbon cycles to permafrost thaw

The spatial distribution and depth of permafrost are changing in response to warming and landscape disturbance across northern Arctic and boreal regions. This alters the infiltration, flow, surface and subsurface distribution, and hydrologic connectivity of inland waters. Such changes in the water cycle consequently alter the source, transport, and biogeochemical cycling of aquatic carbon (C), its role in the production and emission of greenhouse gases, and C delivery to inland waters and the Arctic Ocean. Responses to permafrost thaw across heterogeneous boreal landscapes will be neither spatially uniform nor synchronous, thus giving rise to expressions of low to medium confidence in predicting hydrologic and aquatic C response despite very high confidence in projections of widespread near-surface permafrost disappearance as described in the 2019 Intergovernmental Panel on Climate Change Special Report on the Ocean and Cryosphere in a Changing Climate: Polar Regions. Here, we describe the state of the science regarding mechanisms and factors that influence aquatic C and hydrologic responses to permafrost thaw. Through synthesis of recent topical field and modeling studies and evaluation of influential landscape characteristics, we present a framework for assessing vulnerabilities of northern permafrost landscapes to specific modes of thaw affecting local to regional hydrology and aquatic C biogeochemistry and transport. Lastly, we discuss scaling challenges relevant to model prediction of these impacts in heterogeneous permafrost landscapes.
T Cell Development and T Cell Receptor Structure

B and T lymphocytes differentiate from the common lymphoid progenitor in the bone marrow. While B cells develop in the bone marrow, thymocytes differentiated from the common lymphoid progenitor migrate from the bone marrow into the thymus, and enter the cortex of the thymus from blood vessels located in the corticomedullary junction. The thymocytes lack T cell markers and are therefore CD4−CD8− or double negative (DN) for both coreceptor molecules. Recombination activating genes (RAG) 1 and 2 expression begins in the early lymphoid progenitor stage. Products of the RAG1/2 genes are essential for T cell receptor gene rearrangement. Four stages of DN development occur. DN1 cells express CD44+CD25−, DN2 cells express CD44+CD25+, DN3 express CD44−CD25+PreTCR and DN4 express CD44−CD25−preTCR+. Within the subcapsular cortex of the thymus, the TCR gene rearrangement is initiated at DN2 and is followed by expression of the coreceptor molecules, resulting in the development of double positive (DP) cells expressing both CD4+ and CD8+ molecules. γδ and β genes rearrange and at the DN3 stage, β chain selection occurs along with preTCR expression. Rearrangement is completed at the DN4 stage with the rearrangement of the α gene resulting in DP cell development. γδ TCR expressing T cells migrate out of the thymus very early as DN T cells. With T cell commitment the double positive T cells expressing CD4+CD8+TCR+ further develop into single positive T cells with the expression of either CD4 or CD8 with the TCR. Double positive thymocytes can develop into NKT cells, intraepithelial lymphocytes (IELs) or regulatory T cells (TREGs).
Multi-fidelity prediction of molecular optical peaks with deep learning

Optical properties are central to molecular design for many applications, including solar cells and biomedical imaging. A variety of ab initio and statistical methods have been developed for their prediction, each with a trade-off between accuracy, generality, and cost. Existing theoretical methods such as time-dependent density functional theory (TD-DFT) are generalizable across chemical space because of their robust physics-based foundations but still exhibit random and systematic errors with respect to experiment despite their high computational cost. Statistical methods can achieve high accuracy at a lower cost, but data sparsity and unoptimized molecule and solvent representations often limit their ability to generalize. Here, we utilize directed message passing neural networks (D-MPNNs) to represent both dye molecules and solvents for predictions of molecular absorption peaks in solution. Additionally, we demonstrate a multi-fidelity approach based on an auxiliary model trained on over 28,000 TD-DFT calculations that further improves accuracy and generalizability, as shown through rigorous splitting strategies. Combining several openly-available experimental datasets, we benchmark these methods against a state-of-the-art regression tree algorithm and compare the D-MPNN solvent representation to several alternatives. Finally, we explore the interpretability of the learned representations using dimensionality reduction and evaluate the use of ensemble variance as an estimator of the epistemic uncertainty in our predictions of molecular peak absorption in solution. The prediction methods proposed herein can be integrated with active learning, generative modeling, and experimental workflows to enable the more rapid design of molecules with targeted optical properties.
Tracking accelerated aging of composites with ultrasonic attenuation measurements

Composite materials are steadily replacing traditional materials in many industries. For many carbon composite materials, particularly in aerospace applications, durability is a critical design parameter which must be accurately characterized. Lawrence Livermore National Laboratory (LLNL) and Boeing Commercial Airplane Group have established a cooperative research and development agreement (CRADA) to assist in the high speed research program at Boeing. LLNL`s expertise in fiber composites, computer modeling, mechanical testing, chemical analysis and nondestructive evaluation (ND) will contribute to the study of advanced composite materials in commercial aerospace applications. Through thermo-mechanical experiments with periodic chemical analysis and nondestructive evaluation, the aging mechanisms in several continuous fiber polymer composites will be studied. Several measurement techniques are being studied for their correlation with aging. This paper describes through-transmission ultrasonic attenuation measurements of isothermally aged composite materials and their use as a tracking parameter for accelerated aging.
Light‐activated sealing of skin wounds

Background and Objectives We have developed a light-activated technology for rapidly sealing skin surgical wounds called photochemical tissue bonding (PTB). The goals of this study were to evaluate parameters influencing PTB in order to optimize its clinical efficacy and to determine whether PTB can be used to seal wounds in moderately to highly pigmented skin. Study Design/Materials and Methods Application of Rose Bengal (RB) followed by exposure to 532 nm was used to seal linear incisions (1.5 mm deep, 2 cm long) in lightly pigmented (Yorkshire) and darkly pigmented (Yucatan) swine skin. The force required to open the seal (the bonding strength) was measured by in situ tensiometry. Reflectance spectra, epidermal transmission spectra, and histology were used to characterize the skin. The relationships of RB concentration and fluence to bonding strength were established in Yorkshire skin. Surface temperature was measured during irradiations and cooling was used while sealing incisions in Yucatan skin. Monte Carlo simulations were carried out to estimate the effect of epidermal melanin on the power absorbed in the dermis at the incision interface. Results The lowest fluence, 25 J/cm2, delivered at an irradiance of 0.5 W/cm2 substantially increased the bonding strength (∼10-fold) compared to controls in Yorkshire swine skin. Increasing the fluence to 100 J/cm2 enhanced bonding strength by a further 1.5-fold. Application of 0.1% RB for 2 minutes produced the greatest bonding strength using 100 J/cm2 and limited the penetration of RB to an ∼50 μm band on the dermal incision wall. Reflectance spectra indicated that Yorkshire skin had minimal melanin and that Yucatan skin was a good model for highly pigmented human skin. In Yucatan skin, the bonding strength increased 1.7-fold using 0.1% RB and 200 J/cm2 at 1.5 W/cm2 with cooling and epinephrine. Monte Carlo simulation indicated that absorption of 532 nm light by epidermal melanin in dark skin decreased the power absorbed along the incision in the dermis by a factor of 2.7. Conclusions These results suggest that in lightly pigmented skin the PTB treatment time can be shortened without compromising the bonding strength. Sealing incisions using PTB in moderately and highly pigmented skin will require a careful balance of irradiance and cooling. Lasers Surg. Med. 47:17–29, 2015. © 2014 Wiley Periodicals, Inc.
Young Children's Responding to Interparental Conflict: Associations with Marital Aggression and Child Adjustment

We designed this study to examine children's self-reported and observed emotional and behavioral responding to marital conflict as a potential mechanism linking marital physical aggression (as reported by the parents) and children's behavioral adjustment (as reported by their preschool teachers). In a sample of 48 preschoolers, parental marital physical aggression was positively associated with children's observed dysregulated responding to interparental conflict and negatively associated with children's self-reported behavioral disruption. Marital aggression and children's self-reported responding to marital conflict predicted teacher-reported behavior problems, with both variables adding unique variance. Our findings suggested a potential pathway linking exposure to marital conflict, children's regulatory strategies, and children's behavioral adjustment outside the home.
Dietary β-Carotene Absorption and Metabolism in Ferrets and Rats

The ability of the ferret (Mustela putorius furo) to absorb dietary beta-carotene was studied to determine its appropriateness as a laboratory animal model for studies on beta-carotene metabolism. At baseline, the mean serum beta-carotene level in ferrets was 0.6 micrograms/dl and no beta-carotene was present in liver or adipose tissue. After the ferrets were fed 4 or 20 mg of beta-carotene/kg body wt daily for 2 wk, serum levels were 15.3 and 41.5 micrograms/dl, liver values were 0.9 and 4.1 micrograms/g and adipose tissue values were 0.1 and 0.2 microgram/g of beta-carotene, respectively. Thus, like humans, ferrets are able to absorb dietary beta-carotene intact. Further, these animals can store quantifiable amounts of dietary beta-carotene in their liver and, to a lesser extent, in adipose tissue. In contrast, serum beta-carotene levels in rats fed the two levels of beta-carotene were very low (0.5 to 0.6 microgram/dl) and no beta-carotene was found in liver or adipose tissue. Thus, the ferret is a more appropriate animal model for studying the intestinal absorption of beta-carotene and its storage and metabolism in body tissues.
A quantum mechanical quantitative structure-property relationship study of the melting point of a variety of organosilicons.

Abstract We have developed quantitative structure–property relationship (QSPR) models that correlate the melting points of chain and cyclic silanes and siloxanes with their molecular structures. A comprehensive correlation was derived for a variety of molecules, but the quality of the comprehensive model was modest at best. This provided the impetus for the development of two additional models focused on silanes and siloxanes, respectively. Statistical analyses confirm the robustness of the refined models, and the chemical interpretation of the descriptors was consistent with effects expected for melting.
Mantle dynamics and the heat flow into the Earth's continents

REDUCEDcontinental heat flow, defined as the measured heat flow minus that due to radiogenic sources in the upper crust, initially decreases with time after the last thermotectonic event in a region1, but then tends to stabilize at a roughly constant value, which is higher than would be predicted by a conductive cooling model (Fig. 1). Here we argue that this behaviour results from the influence that continents have on mantle heat loss. The finite thermal conductivity of continental crust and the fact that it is not recycled into the mantle on a large scale, as is oceanic crust, allows stable continental blocks to limit the local heat flux out of the mantle. Numerical models that allow blocks of crust to form over a mantle layer demonstrate how thermal perturbations associated with mantle convection penetrate into continents, causing lateral temperature variations at their base that parallel those in the mantle just below. This tends to establish a constant flux of heat from the mantle into the continents, which accounts for the trend in reduced heat flow.
An empirical study of the ISO 9000 certification in global supply chain of maquiladoras

This research examined two sets of constructs in maquiladoras with respect to ISO 9000 certification. The managerial support and employee involvement as well as quality systems were internal constructs and the global supplier selection criteria were external constructs. The maquiladora industry is a manufacturing model that uses the Mexican workforce and foreign investment and technology on the border area between the United States and Mexico. The standards of ISO certification were studied and analysed through a survey instrument and extensive field interviews with experts of maquiladora plants in El Paso, TX and Juarez, Mexico. There was a 78% response rate with 171 usable questionnaires. There were also 11 in-depth interviews conducted with quality and supply chain experts from eight industries in maquiladoras. Extensive statistical analyses including reliability and validity analyses and factor analyses were performed. Based on the results of factor analyses, ISO-certified companies exemplified better...
A quinidine-responsive plastic membrane electrode.

Abstract A membrane electrode based on quinidine tetraphenylborate in a PVC matrix is described. The electrode exhibits a rapid and near-Nernstian response in the range 3.5 × 10 −5 −1 × 10 −2 M quinidine sulphate at pH 6–8. In an acidic medium the electrode responds to diprotonated quinidine. In sodium tetraphenylboron (Na TPB) solutions the response is linear in respect of log (TPB − ) over the range 10 −4 −10 −2 M . Direct potentiometry and potentiometric titrations are used to determine quinidine in pharmaceutical preparations.
Experiments to find or exclude a long-lived, light gluino.

Gluinos in the mass range \ensuremath{\sim}11/2--31/2 GeV are absolutely excluded. Lighter gluinos are allowed, except for certain ranges of lifetime. Only small parts of the mass-lifetime parameter space are excluded for larger masses unless the lifetime is shorter than \ensuremath{\sim}2\ifmmode\times\else\texttimes\fi{}${10}^{\mathrm{\ensuremath{-}}11}$(${\mathit{m}}_{\mathit{g}\mathrm{\ifmmode \tilde{}\else \~{}\fi{}}}$/1 GeV) sec. Refined mass and lifetime estimates for R hadrons are given, present direct and indirect experimental constraints are reviewed, and experiments to find or definitively exclude these possibilities are suggested.
Mineralogical and hydrogeologic properties of a partially unconsolidated Pleistocene limestone in the east central Yucatán: implications for the development of subsurface flow constructed wetlands (SFCWs) in the region

A partially unconsolidated Pleistocene limestone from a roadside quarry near kilometer 175 on route 307 in the eastern Yucatan was investigated to assess suitability for use in subsurface flow constructed wetlands (SFCWs) in the region. Powder X-ray diffraction investigation of bulk samples indicates that the mineralogy consists of calcite with minor amounts of quartz. Clay-sized insoluble materials in the limestone constitute approximately 2-8 wt% of samples. Powder X-ray diffraction combined with transmission electron microscopy indicates that insoluble materials are dominantly Ca-montmorillonite with trace amounts of kaolinite and minor amounts of amorphous aluminum-silicon oxides. Bulk properties are generally appropriate for use as media with hydraulic conductivity values (K) varying from approximately 0.0001-0.0393 cm/s. Uniformity coefficients (Cu) vary from 3 to 5.35. Owing to the partially unconsolidated nature of the limestone, it is possible to modify the materials to desired parameters for needs of a given SFCW. The occurrence of Ca-montmorillonite and Al-Si oxides in the material has some environmental advantages in being able to absorb a wider range of pollutants over current aragonite and calcite-based aggregate. The aggregate source is in a geographically strategic location to serve the expanding development of tourism infrastructure. The limestone material is an environmentally sound and economically advantageous target material for use in SFCWs because transportation costs and crushing costs are minimized and mining would be from an already disturbed portion of the landscape.
Autonomous Soaring for Improved Endurance of a Small Uninhabited Air Vehicle

A relatively unexplored method to improve the endurance of an autonomous aircraft is to use buoyant plumes of air found in the lower atmosphere called thermals or updrafts. Glider pilots and birds commonly use updrafts to improve range, endurance, or cross-country speed. This report presents a quantitative analysis of a small electric-powered uninhabited air vehicle using updrafts to extend its endurance over a target location. A three-degree-of-freedom simulation of the uninhabited air vehicle was used to determine the yearly effect of updrafts on performance. Surface radiation and rawinsonde balloon measurements taken at Desert Rock, Nevada, were used to determine updraft size, strength, spacing, shape, and maximum height for the simulation. A fixed-width spiral path was used to search for updrafts at the same time as maintaining line-of-sight to the surface target position. Power was used only when the aircraft was flying at the lower-altitude limit in search of updrafts. Results show that an uninhabited air vehicle with a nominal endurance of 2 hours can fly a maximum of 14 hours using updrafts during the summer and a maximum of 8 hours during the winter. The performance benefit and the chance of finding updrafts both depend on what time of day the uninhabited air vehicle is launched. Good endurance and probability of finding updrafts during the year was obtained when the uninhabited air vehicle was launched 30 percent into the daylight hours after sunrise each day. Yearly average endurance was found to be 8.6 hours with these launch times.
LSB-first SAR ADC with bit-repeating for reduced energy consumption

Least-significant bit first quantization (LSBFQ) is presented as an energy-efficient method for analog-to-digital conversion (ADC) when input signal activity is low. LSBFQ has been shown to conserve switching energy and comparator bitcycles, but certain code transitions will force unnecessarily large steps in the DAC output code and degrade the performance. A novel bit-repeating LSBFQ algorithm is proposed which prevents these undesirable code steps. It is shown that the proposed algorithm saves switching energy over previously published LSBFQ in all cases. For low signal activity (the intended target application for LSBFQ) the proposed LSBFQ method even outperforms merged capacitor switching (MCS), which is the most energy-efficient of the traditional MSB-first SAR methods.
Recent results in the theory and applications of CARMA processes

Just as ARMA processes play a central role in the representation of stationary time series with discrete time parameter, \((Y_n)_{n\in \mathbb {Z}}\), CARMA processes play an analogous role in the representation of stationary time series with continuous time parameter, \((Y(t))_{t\in \mathbb {R}}\). Levy-driven CARMA processes permit the modelling of heavy-tailed and asymmetric time series and incorporate both distributional and sample-path information. In this article we provide a review of the basic theory and applications, emphasizing developments which have occurred since the earlier review in Brockwell (2001a, In D. N. Shanbhag and C. R. Rao (Eds.), Handbook of Statistics 19; Stochastic Processes: Theory and Methods (pp. 249–276), Amsterdam: Elsevier).
The correlation radiometer- A new application in MM-wave total power radiometry

We describe the design and performance of a 180 GHz correlation radiometer suitable for remote sensing. The radiometer provides continuous comparisons between a the observed signal and a reference load to provide stable radiometric baselines. The radiometer was assembled and tested using parts from the GeoSTAR-II instrument and is fully compatible with operation in a synthetic aperture radiometer or as a standalone technology for use in microwave sounding and imaging . This new radiometer was tested over several days easily demonstrating the required 6 hour stability requirement for observations of mean brightness temperature for a geostationary instrument.
Simulating the inventory cycle

Abstract Simulations of the inventory cycle utilizing a model based on 84 interacting firms in 21 industries reveals that the ratio of the variance of sales to the variance of output is an unreliable indicator of how seriously firms attempt to smooth production or whether such efforts, in the aggregate, even out economic fluctuations. It is also shown that the ‘two slow’ estimates of the speed of adjustment reported in many econometric studies of United States data may result in part from aggregation bias rather than from limitations of the flexible accelerator model itself.
The TRIMming on an erythroid repressor complex.

In this issue of Blood, Hosoya et al identify a requirement for the corepressor Tripartite Motif Protein 28 (TRIM28) in erythroblast maturation.[1][1] ![Figure][2] Cartoon showing possible repressor complexes formed through mutually exclusive recruitment of TRIM28, HDAC3, or the NuRD or
The E3-11.6-kDa Adenovirus Death Protein (ADP) Is Required for Efficient Cell Death: Characterization of Cells Infected withadpMutants

We have reported that an 11,600-Da nuclear membrane glycoprotein named adenovirus death protein (ADP), encoded by the E3 region, is required for the efficient death (lysis) of adenovirus (Ad)-infected cells. We postulated that ADP mediates the release of virions from cells at the conclusion of replication. Here we provide further characterization of cells infected by adp+ and adp- Ads. Using virus mutants with deletions in the individual E3 genes, we show that only mutants that lack ADP have small plaques that are slow to develop. Mutants in the adp gene replicated as well as wild-type Ad, but the cells lysed much more slowly. Cell lysis and viability were determined by plaque size, cell morphology, trypan blue exclusion, the release of lactate dehydrogenase, and the MTT assay for mitochondrial activity. ADP is required for efficient lysis of human A549, KB, 293, and MCF-7 cells. A549 cells infected with adp+ Ads began to die at 2-3 days postinfection and were dead by 6 days. With adp mutants, > 80% of cells remained viable for 5-6 days; when the medium was changed, > 80% of cells were viable after 7 days and 10-20% after 14 days. When the MTT assay was used, there was an increase in mitochondrial activity, suggesting that Ad infection stimulates respiratory metabolism. Nearly all nuclei from wild-type Adinfected cells lacked DAPI-stained DNA by 7 days, whereas with an adp mutant nearly all nuclei stained brightly after 15 days. Nuclei from adp mutant-infected cells were extremely swollen and full of virus, and appeared to have an intact nuclear membrane. Cells infected with wild-type Ad had many vacuoles and perhaps a disrupted nuclear membrane; they did not display features typical of apoptosis.
Next-generation sequencing in precision oncology: challenges and opportunities.

High throughput gene sequencing is transforming the utilization of genomics in patient care by providing physicians with a powerful tool to aid the diagnosis and management of disease, particularly in precision oncology. As next-generation sequencing (NGS)-based diagnostic assays are developed, significant hurdles such as assessing tumor heterogeneity, characterizing ‘driver’ and ‘passenger’ mutations, typing molecular signatures of individual cancers and determining limits of detection pose significant challenges for clinical laboratories and downstream bioinformatics analyses. Despite these challenges, NGS has the potential to affect all facets of cancer treatment, including early detection and diagnosis through cancer screening in at-risk populations and assessing therapeutic efficacy by detection of circulating tumor DNA via noninvasive blood draws. As the utilization of NGS in precision oncology matures, NGS-based laboratory tests could be used throughout the evolution of cancer in patients and allow...
Modeling the Phase I Thorney Island experiments

Abstract Laboratory experimental instantaneous releases of right circular cylindrical volumes of heavy gas mixtures (Freon-12/air) with initial volumes ranging from 0.034 m 3 to 0.135 m 3 and specific gravities ranging from 2.2 to 4.2 are described. Ground level peak gas concentrations are reported, and comparisons are made with corresponding 0.4 m elevation peak gas concentrations measured in Thorney Island Phase I Trials 7 through 16. An initial dilution phase in the Thorney trials immediately following release is observed which appears relatively unaffected by the ambient wind and which results in an order of magnitude dilution of the gas cloud. This initial phase of the Thorney Island trials, which prevails for lower wind speeds, is modeled accurately by the calm-air laboratory experiments at ∼ 1 : 50 scale. A mathematical model developed for incorporation in the U.S. Coast Guard Hazard Assessment Computer System (HACS) is described, and simulations of selected Thorney Island Phase I trials are compared with field measurements.
Using system dynamics for conservation policy analysis in the Pacific Northwest

The Bonneville Power Administration uses system dynamics to assist in its analysis of conservation policies for the Pacific Northwest electric system. This article describes the system dynamics models—the Conservation Policy Analysis Models—and explains why they are useful. After briefly describing model design and assumptions, the article gives examples of model application. One example involves simulation studies of a hypothetical policy by contractors. The second example involves Bonneville's own study of policies under consideration in the 1986 resource strategy. Key features that have made the models useful at Bonneville are noted.
Real-Time Template-Assisted Manipulation of Nanoparticles in a Multilayer Nanofluidic Chip

The ability to control dynamically the flow and placement of nanoscale particles and biomolecules in a biocompatible, aqueous environment will have profound impact in advancing the fields of nanoplasmonics, nanophotonics, and medicine. Here, an approach based on electrokinetic forces is demonstrated that enables dynamically controlled placement of nanoparticles into a predefined pattern. The technique uses an applied voltage to manipulate nanoparticles in a multilayer nanofluidic chip architecture. Simulations of the nanoparticles' motion in the nanofluidic chip validate the approach and are confirmed by experimental demonstration to produce uniform 200-nm-diameter spherical nanoparticle arrays. The results are important as they provide a new method that is capable of dynamically capturing and releasing nanoscale particles and biomolecules in an aqueous environment, which could lead to the creation of reconfigurable nanostructure patterns for nanoplasmonic, nanophotonic, biological sensing, and drug-delivery applications.
Asbestos and the lung.

The asbestos-related pulmonary disorders to be discussed here include asbestosis, bronchogenic carcinoma, benign pleural diseases including effusions and plaque, and mesothelioma. I will briefly describe clinical features associated with these disorders, as well as selected features of their proposed pathogenesis
Coulomb corrections for extracting spectroscopic factors using analyticity

The Coulomb scattering and Coulomb distortions are included in the optimal expansion technique in the $cos\ensuremath{\theta}$ plane. From $p$-$^{3}\mathrm{He}$ elastic scattering from 4-20 MeV, an energy independent spectroscopic factor for $^{3}\mathrm{H}_{e}\ensuremath{\rightarrow}p+d$ is found, with an accuracy of a few percent. The method seems most promising for transfer reactions.NUCLEAR REACTIONS Dispersion relations, Coulomb corrections for $cos\ensuremath{\theta}$ analyticity.
Co-operation in the use of computers in Bavarian schools

Abstract The distribution of computers in German schools has reached a point where coordination of the activities and support of the teachers is indispensable. A method of solution in Bavaria is described.
Microfluidic encapsulated nanoelectromechanical resonators

Resonant nanoelectromechanical systems have been demonstrated as sensitive mass detectors with subattogram and even single molecule sensitivity [Ilic et al., Nano Lett. 5, 925 (2005); Ilic et al., J. Appl. Phys. 95, 3694 (2004)]. Measurements of sub-ng/ml protein concentrations and DNA hybridization using deflection based microelectromechanical system (MEMS) devices have also been shown [Wu et al., Nat. Biotechnol. 19, 856 (2001); Fritz et al., Science 288, 316 (2000)]. Sample delivery is generally difficult in such cases requiring the entire device chip to be submersed into an analyte containing mixture. Additionally, in the case of MEMS resonators, high vacuum is required to remove viscous damping to improve sensitivity. In this work, the authors present a method where arrays of nanoelectromechanical devices are encapsulated in individually accessible, parallel microfluidic channels. The microchannels were used for delivery of liquids and nitrogen (for drying). The channels were pumped down to pressures...
Screening for Malignancy After Augmentation Cystoplasty in Children With Spina Bifida: A Decision Analysis

Purpose: Augmentation cystoplasty is the mainstay of surgical treatment for medically refractory neurogenic bladder in patients with spina bifida. Concerns regarding an increased risk of malignancy have prompted many centers to consider routine postoperative screening. We examine the potential cost-effectiveness of such screening.Materials and Methods: A Markov model was used to compare 2 screening strategies among patients with spina bifida after cystoplasty, namely annual screening cystoscopy and cytology and usual care. Model parameters were informed via a systematic review of post-augmentation malignancy and cost estimates from published reports or government sources.Results: In a hypothetical cohort the individual increase in life expectancy for the entire cohort was 2.3 months with an average lifetime cost of $55,200 per capita, for an incremental cost-effectiveness ratio of $273,718 per life-year gained. One-way and two-way sensitivity analyses suggest the screening strategy could be cost effective...
A Failure to Normalize Biochemical and Metabolic Insults During Morphine Withdrawal Disrupts Synaptic Repair in Mice Transgenic for HIV-gp120

Drug abuse in HIV-infected individuals accelerates the onset and progression of HIV-associated neurocognitive disorders (HAND). Opiates are a class of commonly abused drugs that have interactive effects with neurotoxic HIV proteins that facilitate glial dysfunction, neuronal damage and death. While the combined effects of neurotoxic HIV proteins and morphine have been extensively studied in the setting of chronic and acute morphine use, very little in known about the effects of HIV proteins during drug withdrawal. Since opiate withdrawal can induce considerable neuronal stress, we determined the effects of opiates (morphine) on brain redox balance, sphingolipid metabolism and synaptic integrity during both chronic and withdrawal conditions in non-transgenic mice (nTg), and in mice transgenic for the HIV-coat protein gp120 (gp120tg). In nTg mice, we found that chronic morphine increased brain oxidative capacity and induced synaptic damage that was largely reversed during drug withdrawal. Gp120tg mice showed a similar response to chronic morphine, but the diminished oxidative capacity and synaptic damage failed to normalize during drug withdrawal. In nTg mice, brain sphingolipid content was not affected by morphine during chronic or withdrawal conditions. In gp120tg mice there was a baseline perturbation in sphingolipid metabolism that manifest as decreased sphingomyelin with accumulations of the bioactive lipid ceramide. Sphingolipid metabolism was highly reactive to morphine in gp120tg mice. Chronic morphine increased sphingomyelin content with a consequent reduction in ceramide. During drug withdrawal, these effects reversed, and sphingomyelin levels were reduced with consequent increases of ceramide. We interpret these findings to suggest that neuronal repair during morphine withdrawal is inhibited in the setting of gp120 by mechanisms that involve sustained oxidative insult and accumulations of the highly reactive intermediate ceramide.
Derivation of a monoclonal anti-murine IL-4 antibody specific for an epitope expressed on denatured molecules.

Abstract Monoclonal antibodies to interleukin 4 (IL-4) were generated by immunization with recombinant IL-4 and screening by binding to IL-4 adsorbed to plastic surfaces. Three antibodies were obtained that scored well in this assay and one, 13E1, was studied in detail. It was very effective in detecting IL-4 by Western blotting whereas a neutralizing anti-IL-4 antibody, 11B11, was 50–100-fold less sensitive as a detecting agent. Sequential immunoprecipitation and biosynthetic labelling studies indicated that the 11B11 and 13E1 epitopes are largely expressed on different forms of IL-4. 13E1 was able to detect cytosolic IL-4 both by immunohistochemical and flow cytometric analysis of fixed cells. This was routinely successful in an insect cell line (Sf9) expressing large amounts of IL-4 as a result of infection with a recombinant ‘IL-4 baculovirus’. Although stimulated D10 cells could also be shown to express IL-4 in their cytosol, positive results were not obtained in all such studies and we have failed to detect IL-4 production by normal T cells using this method. This antibody may have substantial value in detecting IL-4 by Western blots and as a tool to analyze the biosynthesis of IL-4. With suitable improvement in sensitivity, it also may prove valuable in the detection of IL-4 in the cytosol of individual cells.
The duty to disclose (even more) adverse clinical trial results.

In their target article, Liao and colleagues (2009) argue that there is a duty to disclose adverse clinical trial results to potential participants. They believe that disclosure is necessary to pro...
EGFR signaling is required for regenerative proliferation in the cochlea: conservation in birds and mammals.

Abstract Proliferation and transdifferentiaton of supporting cells in the damaged auditory organ of birds lead to robust regeneration of sensory hair cells. In contrast, regeneration of lost auditory hair cells does not occur in deafened mammals, resulting in permanent hearing loss. In spite of this failure of regeneration in mammals, we have previously shown that the perinatal mouse supporting cells harbor a latent potential for cell division. Here we show that in a subset of supporting cells marked by p75, EGFR signaling is required for proliferation, and this requirement is conserved between birds and mammals. Purified p75 + mouse supporting cells express receptors and ligands for the EGF signaling pathway, and their proliferation in culture can be blocked with the EGFR inhibitor AG1478. Similarly, in cultured chicken basilar papillae, supporting cell proliferation in response to hair cell ablation requires EGFR signaling. In addition, we show that EGFR signaling in p75 + mouse supporting cells is required for the down-regulation of the cell cycle inhibitor p27 Kip1 (CDKN1b) to enable cell cycle re-entry. Taken together, our data suggest that a conserved mechanism involving EGFR signaling governs proliferation of auditory supporting cells in birds and mammals and may represent a target for future hair cell regeneration strategies.
Interactions of insulin with bovine endothelium

Bovine endothelial cells have been isolated from pulmonary and systemic vessels and grown in culture as primary, passaged and passaged cloned-strains. The cultures were shown to be endothelial in nature on the basis of several endothelial-specific and endothelial-associated traits. Endothelial cells from all sources had specific receptors for insulin in primary culture and after serial passage. Endothelial cells derived from pulmonary arteries and aortas bound 2.5 times more insulin than cells derived from the pulmonary vein. Each endothelial cell type maintained a specific complement of receptors through at least 25 passages in vitro. Coupled with previous findings of insulin receptors on endothelial cells from human umbilical vessels, these data suggest that insulin receptors may be an intrinsic component of all vascular endothelium.
Frequency of the Male Infertility Evaluation: Data from the National Survey of Family Growth

Purpose: An estimated 7 million American couples per year seek infertility care in the United States. A male factor contributes to 50% of cases but it is unclear what proportion of infertile couples undergoes male evaluation.Materials and Methods: We analyzed data from cycles 5 to 7 of the National Survey of Family Growth performed by the Centers for Disease Control to determine the frequency of a male infertility evaluation, and associated reproductive and demographic factors.Results: A total of 25,846 women and 11,067 men were surveyed. Male evaluation was not completed in 18% of couples when the male partner was asked vs 27% when female partners were asked. This corresponds to approximately 370,000 to 860,000 men in the population who were not evaluated at the time of infertility evaluation. Longer infertility duration and white race were associated with increased odds of male infertility evaluation. The male and female samples showed no change in the receipt of male examination with time.Conclusions: ...
Awareness: The Heart of Cultural Competence

Cultural competency in critical care is providing care to patients and their families that is compatible with their values and the traditions of their faiths. This requires awareness of one's own values and those of the healthcare system. The nurse must also become aware of the cultural and spiritual values of patients and families. Although knowledge of many cultures is impossible, willingness to learn about, respect, and work with persons from different backgrounds is critical to providing culturally competent care. This article discusses elements essential for increasing cultural competency.
TGF-ß Signaling in Fibroblasts Modulates the Oncogenic Potential of Adjacent Epithelia

Stromal cells can have a significant impact on the carcinogenic process in adjacent epithelia. The role of transforming growth factor-beta (TGF-beta) signaling in such epithelial-mesenchymal interactions was determined by conditional inactivation of the TGF-beta type II receptor gene in mouse fibroblasts (Tgfbr2fspKO). The loss of TGF-beta responsiveness in fibroblasts resulted in intraepithelial neoplasia in prostate and invasive squamous cell carcinoma of the forestomach, both associated with an increased abundance of stromal cells. Activation of paracrine hepatocyte growth factor (HGF) signaling was identified as one possible mechanism for stimulation of epithelial proliferation. Thus, TGF-beta signaling in fibroblasts modulates the growth and oncogenic potential of adjacent epithelia in selected tissues.