cssi/SciSciGPT-SciSciNet huggingface dataset:
The Doubly Labeled Water Method Produces Highly Reproducible Longitudinal Results in Nutrition Studies

The doubly labeled water (DLW) method is considered the reference method for the measurement of energy expenditure under free-living conditions. However, the reproducibility of the DLW method in longitudinal studies is not well documented. This study was designed to evaluate the longitudinal reproducibility of the DLW method using 2 protocols developed and implemented in a multicenter clinical trial—the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE). To document the longitudinal reproducibility of the DLW method, 2 protocols, 1 based on repeated analysis of dose dilutions over the course of the clinical trial (dose-dilution protocol) and 1 based on repeated but blinded analysis of randomly selected DLW studies (test-retest protocol), were carried out. The dose-dilution protocol showed that the theoretical fractional turnover rates for 2 H and 18 O and the difference between the 2 fractional turnover rates were reproducible to within 1% and 5%, respectively, over 4.5 y. The Bland-Altman pair-wise comparisons of the results generated from 50 test-retest DLW studies showed that the fractional turnover rates and isotope dilution spaces for 2 H and 18 O, and total energy expenditure, were highly reproducible over 2.4 y. Our results show that the DLW method is reproducible in longitudinal studies and confirm the validity of this method to measure energy expenditure, define energy intake prescriptions, and monitor adherence and body composition changes over the period of 2.5–4.4 y. The 2 protocols can be adopted by other laboratories to document the longitudinal reproducibility of their measurements to ensure the long-term outcomes of interest are meaningful biologically. This trial was registered at clinicaltrials.gov as NCT00427193. J. Nutr. 144: 777–783, 2014.
Calmodulin antagonist effects on GnRH and secretogogue-induced release of bovine LH

A study was performed to determine the possible role of calmodulin (CaM) in regulating gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) release from the bovine pituitary using three structurally unrelated calmodulin antagonists. Primary calf anterior pituitary cell cultures (3 X 10(5)/well) were treated with either LH secretogogue (GnRH, 100 ng/ml; A23187, 2.5 microM; theophylline, 1 mM; prostaglandin E2, 1 microM; estradiol, 25 ng/ml; or KCl, 25 mM; final concentrations) or secretogogue plus CaM inhibitor in 1 ml Hanks' balanced salt solution plus 10 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid for 6 h. Significant (P less than 0.01) inhibition of GnRH- and A23187-stimulated LH release was obtained with calmidazolium (CMZ; 1-10 nM) and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7; 1-10 microM). Both CMZ (10 nM) and W-7 (10 microM) significantly reduced (P less than 0.05) LH release by all of the other agents tested as well. In contrast, trifluoperazine (TFP; 0.1-100 microM) had no effect against most of the secretogogues tested. These results suggest that GnRH-stimulated LH release is in part a Ca2+-CaM-dependent process and may implicate a common CaM-dependent mechanism for LH release in general. The data also demonstrate a marked dichotomy in response between the phenothiazine, TFP, and other CaM antagonists in the calf pituitary.
Modified polypeptides containing γ-benzyl glutamic acid as drug delivery platforms

Abstract We previously reported the development of diffusion-controlled biodegradable polypeptides for drug delivery purposes. In this paper, we describe the synthesis of three modified polypeptides that contain γ-benzyl glutamic acid as the common structural backbone. The properties of these polymers were characterized with regard to their potential application as drug delivery platforms. Procainamide hydrochloride, a hydrophilic drug, and protamine sulfate, a low molecular weight protein, were used as model drugs for examining release rate profiles from these polymers. The homopolymer of poly(γ-benzyl- l -glutamic acid), PBLG, showed a highly helical configuration and a moderate release rate of procainamide. Modification of structural attributes by random copolymerization of the d - and l - isomers of γ-benzyl glutamic acid produced poly(γ-benzyl- d,l -glutamic acid), PBDLG, which displayed a significantly slower release of procainamide when compared to PBLG. The modification of polymer bulk hydrophobicity by copolymerization of PBLG (A) with poly(ethylene glycol) (B) yielded an ABA triblock copolymer exhibiting much faster release rates for both procainamide and protamine than those demonstrated by the other two polymers. Using this triblock copolymer, protamine release rates ranging from 2 weeks to approximately 2 months were obtained by simply varying the polymer processing conditions and protein particle size. A nearly complete release of protein was obtained from the triblock copolymer blends and this occurred without reliance upon degradation of the polymer backbone. Fickian diffusion-controlled release mechanisms were implied for release of procainamide and protamine from these polypeptide formulations based on the linear relationship displayed between cumulative drug release and the square root of time.
Skin Manifestations of Cushing Disease in Children and Adolescents Before and After the Resolution of Hypercortisolemia

Cushing disease (CD) is a common cause of endogenous hypercortisolism in childhood. Its skin manifestations include striae, facial acne, hirsutism, acanthosis nigricans, fungal infections, hyperpigmentation and easy bruisability. We followed 36 children and adolescents with CD (14 boys and 22 girls), to define the natural history of skin disease in endogenous hypercortisolism. Physical examination and 24 hour urinary free cortisol (UFC) and 17-hydroxycorticosteroid (17-OHS) excretion values were obtained preoperatively and quarterly for 18 months. Preoperatively our patients exhibited purple subcutaneous striae (77.7%), steroid-induced acne (58.3%), hirsutism (63.7% of the 22 girls), acanthosis nigricans (27.7%), ecchymoses (27.7%), hyperpigmentation (16.6%), and fungal infections (11.1%). The levels of UFC and 17-OHS preoperatively were 351.84+/-243.85 microg/m2/day (mean+/-SD) and 17.92+/-7.86 mg/g creatinine/day, respectively. No correlation was found between these levels and the severity of the lesions. All patients were cured. Symptoms decreased dramatically within the 3 postoperative months and progressively disappeared within the first year of the follow-up period with the exception of light-colored striae; they were present in 5.6% of the patients at 18 months postoperatively. No acanthosis nigricans or hyperpigmentation were observed at 3 months postoperatively. Hirsutism was not present at 9 months postoperatively. We conclude that in children with CD the skin is affected at multiple sites; however, the severity of the manifestations does not correlate with the biochemical indices of the disease. With the exception of striae, cutaneous effects of endogenous hypercortisolism completely heal within the first year after surgical cure of the disease.
Ultra-scale environmental monitoring - The Intelligent River

Sensor network deployments monitor a wide range of properties in real-time, providing data streams describing a host of environments. The volume of data in these real-time streams can quickly overwhelm monitoring systems, communication infrastructure, and downstream processing system. To address these issues, we designed the Intelligent River, a three layer architecture consisting of a sensor fabric, a data communication network, and a data analytics system. Our sensor fabric can be adapted for use in multiple applications and environments by changing communication and sensor configurations. Wireless mesh networks for dense deployments, and cellular networks for remote deployments handle the back-end communication. The analytics system involves multiple processing queues for collecting and processing raw data, and a web-based portal presentation. The web portal provides modules to register sensor information with the cloud infrastructure, view real-time and historical data, and monitor the status of the deployments. In this demo, we will be presenting the end-to-end system through a physical testbed. We will also showcase our real time data-streams originating from various sensor fabrics deployed across various environments.
Space-time maps and two-bar interactions of different classes of direction-selective cells in macaque V-1.

We used one-dimensional sparse noise stimuli to generate first-order spatiotemporal maps and second-order two-bar interaction maps for 65 simple and 124 complex direction-selective cells in alert m...
Reliability and clinical utility of DSM-IV substance-induced psychiatric disorders in acute psychiatric inpatients.

The goal of this study was to evaluate in 1,951 acute psychiatric inpatients the reliability, construct, convergent, and predictive validity of substance-induced psychiatric syndrome ratings made by clinical attending psychiatrists. The primary admitting condition for each subject was categorically rated by clinical attendings as not, mildly, moderately, or mostly substance-induced at both admission and discharge. Individual substance categories were associated with characteristic demographic, clinical treatment response, and length of stay, findings indicating good construct, predictive validity, and clinical utility. A linear dimensional approach to rating substance-induced syndromes in acute clinical populations may be preferable to the simple dichotomous approach used in DSM-IV. (Am J Addict 2001;10:308- 318)
Statistical Tools on the World Wide Web

Abstract The World Wide Web (WWW) represents a powerful tool for furthering the development and practice of statistics. The GASP (Globally Accessible Statistical Procedures) WWW site has been set up as a primary listing of statistical procedures which can be used over the WWW. This article highlights several possible approaches for making a procedure WWW accessible. These approaches effectively solve many of the problems typically encountered when using a new statistical procedure. Applying the methods discussed, any statistical technique can be made available to anyone with a forms- or Java-capable WWW browser. Procedures can be delivered in a virtually platform-independent manner with only minimal requirements on a user's hardware or software.
An energy-efficient heterogeneous CMP based on hybrid TFET-CMOS cores

The steep sub-threshold characteristics of inter-band tunneling FETs (TFETs) make an attractive choice for low voltage operations. In this work, we propose a hybrid TFET-CMOS chip multiprocessor (CMP) that uses CMOS cores for higher voltages and TFETs for lower voltages by exploiting differences in application characteristics. Building from the device characterization to design and simulation of TFET based circuits, our work culminates with a workload evaluation of various single/multi-threaded applications. Our evaluation shows the promise of a new dimension to heterogeneous CMPs to achieve significant energy efficiencies (upto 50% energy benefit and 25% ED benefit with single-threaded applications, and 55% ED benefit with multi-threaded applications).
Characterizing Ballast Degradation Through Los Angeles Abrasion Test and Image Analysis

Ballast fouling, often associated with deteriorating railroad track performance, refers to the condition in which the ballast layer changes its composition and develops a much finer grain size distribution. Fouling is commonly caused by degradation or breakage of ballast aggregates under traffic loading, although other fine materials including but not limited to coal dust, fine-grained subgrade soils, and sand can also contaminate a clean and uniformly graded ballast layer. An experimental approach is described to characterize stages of railroad ballast degradation studied through Los Angeles abrasion testing in the laboratory. An aggregate image analysis approach is used to investigate ballast particle abrasion and breakage trends at every stage through detailed quantifications of individual ballast particle size and shape properties. The experimental study indicated that the fouling index (FI) commonly used by practitioners was indeed a good indicator of fouling conditions, especially when all voids cre...
Radiative shock solutions with grey nonequilibrium diffusion

This study describes a semi-analytic solution of planar radiative shock waves with a grey nonequilibrium diffusion radiation model. The solution may be used to verify radiation-hydrodynamics codes. Comparisons are made with the equilibrium diffusion solutions of Lowrie and Rauenzahn (Shock Waves 16(6):445–453, 2007). The solution also gives additional insight into the structure of radiative shocks. Previous work has assumed that the material temperature reaches its maximum at the post-shock state of the embedded hydrodynamic shock (Zel’dovich spike). We show that in many cases, the temperature may continue to increase after the hydrodynamic shock and reaches its maximum at the isothermal sonic point. Also, a temperature spike may exist even in the absence of an embedded hydrodynamic shock. We also derive an improved estimate for the maximum temperature.
Characterization of the Input Impedance of the Inset-Fed Rectangular Microstrip Antenna

The input impedance and radiation pattern of the inset-fed rectangular microstrip patch antenna are investigated. It is concluded that a shifted cosine-squared function describes well the variation of the resonant input resistance with the feed location (point of contact between the microstrip feed line and the notch) for a given patch and substrate geometry. The parameters of the shifted cosine-squared function depend on the notch width for a given patch and substrate geometry. The cross-polarization level is seen to increase as either the notch width or depth increases. However, for a fixed input resistance level, the notch depth decreases as the width increases, so that the cross-polarization level is not very sensitive to the notch width for a fixed input resistance.
Mitral apparatus assessment by delayed enhancement CMR - relative impact of papillary muscle and left ventricular wall infarction on ischemic mitral regurgitation

Summary Lateral wall infarction on DE-CMR, independent of papillary muscle involvement, confers increased risk for ischemic mitral regurgitation. Background The mitral apparatus contains two myocardial components - papillary muscles and the adjacent left ventricular (LV) wall. Delayed enhancement CMR (DE-CMR) enables in-vivo study of potential contributions of LV wall and papillary muscle infarction (PMI) to MR. This study examined the relative impact of papillary muscle and LV wall infarction on mitral regurgitation (MR) following ST elevation MI (STEMI). Methods Multimodality imaging was prospectively performed among patients with first STEMI: DE-CMR (IR-GRE, acquired 10-30 minutes post gadolinium [0.2 mmol/kg]) was used to assess LV infarct pattern - including PMI (graded by location and extent - complete or partial, stratified using threshold of >50% papillary myocardium) and LV wall infarction (17 segment model, 5 point score/segment). Cine-CMR (SSFP) was analyzed for cardiac function and geometry - including LV chamber size, regional wall motion (5 point score/segment), and mitral annular diameter. Echocardiography (echo) was used to quantify MR (0-4+ grade) using established consensus criteria. Each imaging modality was read independently.
The Benefit Principle as a Preferred Approach to Taxing Business in the Midwest

State-local tax policies to encourage growth and development have been roundly criticized as detrimental to social welfare. In response, recent proposals have included delimiting the ability of sta...
Comparison of in vivo and in vitro effects of continuous exposure of L1210 cells to 6-thioguanine.

Abstract In this study the cytokinetic and antitumor effects of 12-h continuous treatment with 6-thioguanine (TG) were studied in L1210 cells in vivo and in vitro . Loss of clonogenicity in vitro was maximized at a drug concentration of 0.2 µm. Higher drug concentrations produced less cell kill, and the surviving fraction observed after exposure to 25 µm TG was 1 log higher than at 0.2 µm (2% versus 0.2% of control cloning efficiency, respectively). Delayed G 2 arrest in vitro was also found to be most pronounced at 0.2 µm, with G 1 arrest more predominant at higher concentrations. Studies in vivo were conducted using C57BL × DBA/2 F 1 mice, with or without advanced L1210 ascites tumor. In initial experiments performed on animals without tumor, the 50% lethal dose for 12-h s.c. infusions of TG was approximately 0.8 µmol/kg/min. Correlation of steady-state TG plasma levels with infusion rate revealed a linear relationship up to 0.62 µmol/kg/min, above which the TG plasma concentration increased disproportionately to input rate. Total body clearance of TG, calculated from the linear portion of this curve, was 123 ml/kg/min. The antitumor effects of TG infusions were correlated with steady state plasma concentrations achieved in each individual animal, and it was found that dose rates yielding levels from 1 to 10 µm increased survival time by about 40%, with no apparent optimum plasma level in this range. Examination of the cytokinetic effects caused by TG infusions at the low and high ends of this maximally therapeutic range showed that, as was the case in vitro , lower concentrations of TG caused delayed G 2 arrest, while higher concentrations induced more rapid G 1 arrest. On the basis of these, as well as previous findings, we propose that the operative mechanism of cell kill by TG in vivo may be dose dependent and may be reflected by the relative degree of G 2 versus G 1 arrest. We also suggest that the appropriate strategy for the clinical use of TG is to determine the drug concentration which produces maximum G 2 arrest of tumor cells, and to infuse continuously at a rate to achieve that level for the maximum time tolerated by the patient, rather than to select an arbitrary length of infusion followed by escalation to maximum tolerated drug concentration.
Yield-Based Economic Thresholds for Grape Berry Moth (Lepidoptera: Tortricidae) in Juice Grapes

A 3-yr field study was conducted at commercial juice grape (Vitis labrusca L.) vineyards to develop an economic injury level (EIL) for grape berry moth, Paralobesia viteana (Clemens) (Lepidoptera: Tortricidae) and to determine patterns of cluster injury. Infestation of grape clusters by P. viteana was measured biweekly from bloom until harvest, and fruit was sampled immediately before harvest to determine the yield and level of fruit injury by this pest. Comparison of fruit infestation at each sampling date to that found just before harvest revealed stronger relationships over time, and by early August at least 50% of the variation in preharvest infestation was accounted for by previous infestation. Grape yield declined with increasing infestation by P. viteana, allowing calculation of the EIL at which the value of yield lost to infestation equaled the cost of insecticide applications to prevent the infestation. Using two scenarios of pest control programs based on pyrethroid or diamide insecticides, the EILs were calculated to be 9.9 and 17.7% of clusters damaged, respectively. For use in juice grape vineyard integrated pest management programs, we propose using 5 and 10% damaged clusters at harvest as action thresholds for further testing in field trials to evaluate sampling plans and the use of thresholds to guide vineyard pest management decision-making under different insecticide scenarios.
Additive Bases Representations and the Erdős-Turán Conjecture

We give a lower bound to the maximal number of representations by an additive basis of the natural numbers, in conjunction with a celebrated conjecture of Erdős and Turan.
Low-Level Radioactivity and Infant Mortality

Beginning in 1963, Dr. Stemglass [1] began advancing the suggestion that low-level radiation from radioactive decay of strontium-90 appearing as fallout from atomospheric testing of nuclear weapons has an extremely high effect on human fetuses and on infants. He states [2]: I agree that the (dose) levels are extremely low and by all ordinary present fallout calculations should not have produced the effect we observed. But, the point I am trying to make is precisely that strontium-90 appears to have a totally unexpected effect much larger than you would get by comparing it with cosmic radiation or external gamma or X-rays.
Multi-echelon inventory management under short-term take-or-pay contracts

We extend the Clark-Scarf serial multi-echelon inventory model to include procuring production inputs under short-term take-or-pay contracts at one or more stages. In each period, each such stage has the option to order/process at two different cost rates; the cheaper rate applies to units up to the contract quantity selected in the previous period. We prove that in each period and at each such stage, there are three base-stock levels that characterize an optimal policy, two for the inventory policy and one for the contract quantity selection policy. The optimal cost function is additively separable in its state variables, leading to conquering the curse of dimensionality and the opportunity to manage the supply chain using independently acting managers. We develop conditions under which myopic policies are optimal and illustrate the results using numerical examples. We establish and use a generic one-period result, which generalizes an important such result in the literature. Extensions to cover variants of take-or-pay contracts are included. Limitations are discussed.
Mission Design and Systems Architectures for a Venus Orbiter and Entry Probe

Despite several previous missions, Venus remains a mysterious planetary destination, with key questions remaining on the evolution of its atmosphere and climate, volatile cycles, and evolution of its surface. A New Frontiers mission concept that employs a single launch vehicle to deliver an orbiter and an atmospheric entry flight element to Venus can answer many of these questions. After the in-situ phase of the mission is complete, the orbiter is placed into a near-circular ~400 km orbit at 60-70° inclination about Venus to perform high resolution imaging and topographic reconnaissance with a radar instrument. Initial examinations show that this type of mission profile results in a total mission V requirement of approximately 4.5 km/s. For a two-flight element mission in a current cost-constrained environment, a variety of systems trade studies must be conducted to maximize the science return per dollar. Furthermore, the mission design and subsystem inputs for both flight elements are closely coupled with the mission operations strategy. This paper presents several mission design architectures for an orbiter/probe Venus mission, the associated systems trade studies, and their impacts on the overall system concept, including traditional metrics such as V, mass, power and complexity. The impacts on the spacecraft design, operational approach, and cost for various mission design solutions are also described. The architectures investigated are delineated by the propulsion choice, and include an all-chemical solution (with and without a solid rocket motor), solar electric propulsion (SEP), and aerobraking in the Venusian atmosphere.
Isolation of cortisol from guinea pig bile.

SummaryFree cortisol has been isolated in the bile from guinea pigs with high plasma concentrations of this steroid. A limited hepatic ability to hydroxylate this hormone in position 3 of its nucleus has been suggested as a possible cause.
Effect of Acidic Tumor Microenvironment on Non-Small-Cell Lung Cancer Cells

In order to adapt to hypoxic stress, cancer cells switch from oxidative phosphorylation to aerobic glycolysis resulting in the metabolism of glucose to lactic acid. Increased lactic acid production and lack of removal of metabolic acids due to inefficient vasculature results in an acidic environment in the tumor parenchyma. Little is known about the effect of an acidic tumor environment on the motility of non- small cell lung cancer (NSCLC) cells. Our research focuses on the effect of acidic tumor microenvironment on motility and epithelial to mesenchymal transition (EMT) of NSCLC cell lines. NCI-H1650 cells propagated in acidic pH media (pH ~ 6.5 to 6.7) showed a significant alteration in phenotype compared to the cells propagated in neutral pH media (pH ~ 7.2 to 7.4). Preliminary data on cell proliferation indicates that the acidic environment significantly decreased cell viability. No difference in motility was observed between H1650 cells propagated in acidic or neutral pH media. Expression of E- cadh...
A wearable chemical-electrophysiological hybrid biosensing system for real-time health and fitness monitoring

Flexible, wearable sensing devices can yield important information about the underlying physiology of a human subject for applications in real-time health and fitness monitoring. Despite significant progress in the fabrication of flexible biosensors that naturally comply with the epidermis, most designs measure only a small number of physical or electrophysiological parameters, and neglect the rich chemical information available from biomarkers. Here, we introduce a skin-worn wearable hybrid sensing system that offers simultaneous real-time monitoring of a biochemical (lactate) and an electrophysiological signal (electrocardiogram), for more comprehensive fitness monitoring than from physical or electrophysiological sensors alone. The two sensing modalities, comprising a three-electrode amperometric lactate biosensor and a bipolar electrocardiogram sensor, are co-fabricated on a flexible substrate and mounted on the skin. Human experiments reveal that physiochemistry and electrophysiology can be measured simultaneously with negligible cross-talk, enabling a new class of hybrid sensing devices.
Are the Contraceptive Recommendations of Family Medicine Educators Evidence-Based? A CERA Survey.

BACKGROUND AND OBJECTIVES: Our study aims were to: (1) describe the scope of contraceptive methods provided by US family medicine educators and (2) assess the extent to which US family medicine educators recommendations regarding eligibility criteria for contraceptive methods are consistent with Centers for Disease Control and Prevention (CDC) guidelines. METHODS: We contributed survey items as part of the 2014 Council of Academic Family Medicine Educational Research Alliance (CERA) omnibus survey which is distributed annually to a national cohort of US family medicine educators. We created two summary scales comprised of clinical scenarios to assess the extent to which provider recommendations regarding eligibility criteria for oral contraceptive pills (OCPs six scenarios) and the intrauterine device (IUD eight scenarios) were consistent with CDC guidelines. RESULTS: Among the 1054 respondents (33% response rate) 98% prescribe OCPs and 66% insert IUDs. The OCP scale mean was 4.6 +/- SD 1.6 (range 0-6) and the IUD scale mean was 4.8 SD +/- 2.3 (range 0-8). These scores reflect that 23% of providers OCP recommendations and 40% of their IUD recommendations were inconsistent with CDC guidelines. CONCLUSIONS: The contraceptive recommendations of this cohort of family medicine educators only partially reflected evidence-based guidelines. More misconceptions were noted regarding eligibility criteria for the IUD than for OCPs. To avoid denying safe and effective contraception to otherwise appropriate candidates and putting women at risk of unintended pregnancy evidence-based contraceptive recommendations must be improved among family medicine educators.
Update on Alzheimer's Disease: One Hundred Years After Dr. Alois Alzheimer

Alzheimer's disease was first described by Alois Alzheimer in 1906, and first appeared in the medical literature in 1907. The medical community has been ruminating about Alzheimer's disease for over 100 years, and only recently have Alzheimer's disease therapies begun to emerge. However, many vital questions remain, pertinent not only to physicians but to the public at large. For example, how likely is it that a particular individual will develop Alzheimer's disease? What can one do to avoid getting Alzheimer's disease? What are the current and promising treatments for Alzheimer's disease? While there are grey areas, the Alzheimer's disease field is beginning to find solid answers to these questions. There are risk factors that individuals can control, and emerging treatments are cause for optimism.
Accelerating the Transition of Technologies Created through the U.S. Department of Defense Small Business Innovation Research Program

This dissertation gains to understand the contextual effects on the success of the transition of technologies generated through the U.S. Department of Defense Small Business Innovation Research program.
Design and performance analysis of six element MIMO antenna for wireless routers

Compact, low profile multiple input multiple output (MIMO) antenna system for wireless access points and router applications is proposed. The designed multiband MIMO antenna covers the multiple communication standards including GPS/GLONASS, LTE/WWAN, WLAN, and WiMAX operations. The MIMO antenna system comprises the compact six loop antennas of size 30×s10×3mm3. Within the covered operating bands, VSWR is better than −6dB and isolation of >10dB is achieved without using any decoupling structure. Various design figure of merits including the S-parameters, radiation patterns, Envelop correlation coefficient, total efficiency, and diversity gain are presented and discussed.
The metabolic regulator mTORC1 controls terminal myeloid differentiation

Monocytes are derived from hematopoietic stem cells through a series of intermediate progenitor stages, but the factors that regulate this process are incompletely defined. Using a Ccr2/Cx3cr1 dual-reporter system to model murine monocyte ontogeny, we conducted a small-molecule screen that identified an essential role of mechanistic target of rapamycin complex 1 (mTORC1) in the development of monocytes and other myeloid cells. Confirmatory studies using mice with inducible deletion of the mTORC1 component Raptor demonstrated absence of mature circulating monocytes, as well as disruption in neutrophil and dendritic cell development, reflecting arrest of terminal differentiation at the granulocyte-monocyte progenitor stage. Conversely, excess activation of mTORC1 through deletion of the mTORC1 inhibitor tuberous sclerosis complex 2 promoted spontaneous myeloid cell development and maturation. Inhibitor studies and stage-specific expression profiling identified failure to down-regulate the transcription factor Myc by the mTORC1 target ribosomal S6 kinase 1 (S6K1) as the mechanistic basis for disrupted myelopoiesis. Together, these findings define the mTORC1-S6K1-Myc pathway as a key checkpoint in terminal myeloid development.
Wicked Problems Framework: Architectural Lessons from Recent Urban Disasters

This chapter extends the design framework of Horst Rittel (1930–1990), who argued that complex societal problems that cannot be addressed using linear systematic processes, namely, ‘tame’ problems, may need alternative approaches, since they are ‘wicked’ in nature. Urban issues such as informal settlements, poverty, and overcrowding, are merely the physical symptoms of deep systemic issues beyond the control of planners and architects alone, and hence, are ‘wicked’. Rittel, a thought leader of design thinking, coined the expression “Wicked Problems” in 1973 to describe the complex issues of society situated in the real world that cannot be solved using rationality alone. In fact, such issues need transdisciplinary understanding and action to optimise decision-making based on multiple viewpoints and methods of inquiry.
Analytical Performance Evaluation of a Feedback Policy in a Stochastic Manufacturing System

Abstract The production control problem in unreliable manufacturing systems has generated agreat deal of interest recently. The goal is the real-time calculation of production rates to minimize the totalexpected surplus and backlog costs of a production system. The calculation of the optimal production rates for asystem with a single unreliable machine that produces two part types requires the solution of the Bellman equation, which, in this case, is a set of hyperbolic partial differential equations. The boundary conditions depend on theoptimal policy, which makes it difficult to obtain an analytical solution. Furthermore, the space over which the solution is sought is partitioned into a set of regions and their boundaries. In this paper, we describe a method for solving the Bellman equations analytically for a particular policy when it is optimal. First, we solve the equations on one of the boundaries. Then, we propagate the solution over the surplus space, treating the partitions and their boundaries in a specific sequence
Looking inward: The impact of operative time on graft survival after liver transplantation.

Background Operative time often has been cited as an important factor for postoperative outcomes. Despite this belief, most efforts to improve liver transplant outcomes have largely focused on only patient and donor factors, and little attention has been paid on operative time. The primary objective of this project was to determine the impact of operative time on graft survival after liver transplant. Methods A retrospective review of 2,877 consecutive liver transplants performed at a single institution was studied. Data regarding recipient, donor, and operative characteristics, including detailed granular operative times were collected prospectively and retrospectively reviewed. Using an instrument variable approach, Cox multivariate modeling was performed to assess the impact of operative time without the confounding of known and unknown variables. Results Of the 2,396 patients who met the criteria for review, the most important factors determining liver transplant graft survival included recipient history of Hepatitis C (hazard ratio 1.45, P = .02), donor age (hazard ratio 1.23, P = .03), use of liver graft from donation after cardiac death donor (hazard ratio 1.50, P P = .01). In detailed analysis of stages of the liver transplant operation, the time interval from incision to anhepatic phase was associated with graft survival (hazard ratio 1.33; P = .02). Conclusion Using a novel instrument variable approach, we demonstrate that operative time (in particular, the time interval from incision to anhepatic time) has a significant impact on graft survival. It also seems that some of this efficiency is under the influence of the transplant surgeon.
Does Leukoaraiosis Have Any Significance in TPA Treated Patients

P56 Background: Leukoaraiosis (LA) has been associated with increased risk of hemorrhage in patients treated with anticoagulants in the SPIRIT, and has been associated with a higher incidence of deep intracerebral hemorrhages (ICH). Individuals with LA have a higher risk of death, and dependency 3 months after cerebral ischemia, recurrent strokes, MI, vascular deaths, and post-stroke dementia. Given the frequency of LA on CT, and its association with increased risk for hemorrhage with anticoagulants, this could represent a predictable risk for stroke patients about to receive TPA. We examined the correlation of LA with stroke severity, risk of hemorrhage, short-term outcome after TPA and associated stroke risk factors. Methods: We evaluated pre-treatment, non-contrast CT scans in patients with Middle Cerebral Artery (MCA) strokes, for the presence and extent of LA using the van Swieten rating system. The NIHSS scores were obtained at baseline and 24 hours. Lesion volumes were determined on a follow-up scan using the (A*B*C)/2 method. Admission systolic BP and glucose were also obtained. Results: A total of 54 TPA-treated patients were studied, aged (mean ±SD) 68 years ±14.9, and baseline NIHSS 16.5 ±6.1 (n=45). Leukoaraiosis was found in 37%(20/54) of all patients on pre-treatment CT scans. No relationship was found between LA presence on pre-treatment CT scans and hemorrhagic transformation, NIHSS scores at baseline and 24 hrs, age, gender, serum glucose, and ASPECT scores. There was, however, a negative correlation between LA scores and ASPECT scores (r=-0.32 p=0.05). Systolic blood pressure correlated significantly (r=0.38, p=0.01) with LA score. There was a non-significant trend towards higher LA scores and increasing age.
Liquid Crystal Infrared Modulation

Experimental liquid crystal 8 to 12 Am infrared modulators have been fabricated and operated utilizing the cholesteric-nematic phase change effect occurring with cyanobiphenyl liquid crystals. A one-mil-thick film of 4-cyano-4'-pentyl-biphenyl has an average transmission over the whole 8 to 12 Am region of =87%. Experiments to determine modulator response times and contrast are discussed as well as some of the basic limitations of infrared modulation using liquid crystals.
Kinetic Study of Living Ring-Opening Metathesis Polymerization with Third-Generation Grubbs Catalysts.

The rate of living ring-opening metathesis polymerization (ROMP) of N-hexyl-exo-norbornene-5,6-dicarboximide initiated by Grubbs third-generation catalyst precursors [(H2IMes)(py)2(Cl)2Ru═CHPh] and [(H2IMes)(3-Br-py)2(Cl)2Ru═CHPh] is measured to be independent of catalyst concentration. This result led to the development of a rate law describing living ROMP initiated by a Grubbs third-generation catalyst that includes an inverse first-order dependency in pyridine. Additionally, it is demonstrated that one of the two pyridines coordinated to the solid catalyst is fully dissociated in solution. The monopyridine adduct formation is confirmed in solution by 1H DOSY (diffusion-ordered NMR spectroscopy), and a Van’t Hoff analysis of the equilibrium between mono- and dipyridine adducts (extrapolated Keq,0 ∼ 0.5 at 25 °C). Finally, the difference in polymerization rates between two catalyst precursors is demonstrated to correspond to the difference in coordination strength between the two pyridines, suggesting th...
Prolinal dithioacetals: Highly efficient organocatalysts for the direct nitro-Michael additions in both organic and aqueous media

Abstract Some novel prolinal dithioacetal derivatives have been synthesized and applied as the organocatalysts for the direct Michael addition of ketones and aldehydes to nitroalkenes. High enantioselectivities and diastereoselectivities have been obtained in both organic and aqueous media (dichloromethane, water, or brine).
Relationships of family conflict, cohesion, and chaos in the home environment on maternal and child food-related behaviours

This study examined how food-related behaviours differed in mothers and their preschool children by levels of family functioning (cohesion and conflict) and household disorganization (chaos). A nationally representative sample of mothers of preschoolers completed an online survey assessing food-related behaviours of themselves and their children. Maternal and child diet, eating behaviours, and health status; household availability of fruits/vegetables, salty/fatty snacks, and sugar-sweetened beverages; family mealtime atmosphere; and family conflict, cohesion, and household chaos were assessed with valid, reliable scales. Cluster analyses assigned families into low, middle, and high conflict, cohesion, and chaos groups. Participants (n = 550) were 72% White, and 82% had some post-secondary education. Regression analysis examining the association of cluster grouping levels on diet-related behaviour measures revealed that positive home environments (i.e., low family conflict, high family cohesion, and low household chaos) were associated with healthier food-related behaviours (e.g., increased fruits/vegetables intake), whereas negative home environments (i.e., high family conflict, low family cohesion, and high household chaos) were associated with unhealthy food-related behaviours (e.g., greater % total calories from fat) even after controlling for sociodemographic and related behavioural factors. Findings suggest family functioning and household chaos are associated with food-related behaviours. This frequently overlooked component of family interaction may affect intervention outcomes and objectives of educational and interventional initiatives.
PD-L1 expression in non-small cell lung carcinoma: Comparison among cytology, small biopsy, and surgical resection specimens.

Background One immunotherapeutic agent for patients with advanced non-small cell lung carcinoma, pembrolizumab, has a companion immunohistochemistry (IHC)-based assay that predicts response by quantifying programmed death-ligand 1 (PD-L1) expression. The current study assessed the feasibility of quantifying PD-L1 expression using cytologic non-small cell lung carcinoma specimens and compared the results with those from small biopsy and surgical resection specimens. Methods PD-L1 expression was quantified using the IHC-based 22C3 pharmDx assay, with "positivity" defined as staining in ≥50% viable tumor cells; ≥ 100 tumor cells were required for test adequacy. For cytology specimens, IHC was performed on cell block sections. Results A total of 214 specimens were collected from 188 patients, 206 of which (96%) were found to be adequately cellular, including 36 of 40 cytology (90%) and 69 of 72 small biopsy (96%) specimens. There was no significant difference noted with regard to the feasibility of PD-L1 IHC on small biopsy specimens compared with surgical resection specimens (P = .99), or between the percentage of PD-L1-positive cytology and histology (including surgical resection and histologic small biopsy) specimens (P = .083). PD-L1 expression was found to be concordant among samples from 21 of 23 patients from whom > 1 specimen was collected (91%). There also was no significant difference observed with regard to rates of PD-L1 positivity when comparing age, sex, diagnosis, and specimen site. Conclusions Quantification of PD-L1 expression is feasible on cytology specimens, and the results are comparable to those obtained from surgical resection and small biopsy specimens, including in matched specimens and using a single predictive IHC marker. Future studies will be necessary to determine the comparative value of other antibodies and their ability to predict response to immunotherapy. Cancer Cytopathol 2017;125:896-907. © 2017 American Cancer Society.
Unraveling pH dependent cycling stability of ferricyanide/ferrocyanide in redox flow batteries

Abstract K3[Fe(CN)6] and K4[Fe(CN)6] have been frequently applied in redox flow batteries to achieve sustainable and economical renewable energy storage. However, fundamental knowledge of the redox couple of K3[Fe(CN)6] and K4[Fe(CN)6] regarding their flow battery performance is largely underdeveloped. Herein, we present a comprehensive study on the fundamental properties and electrochemical kinetics of K3[Fe(CN)6] and K4[Fe(CN)6] in aqueous supporting electrolytes at different pH values. Particularly, the charge/discharge cycling stability of the redox couple was evaluated at different pH values using a half-cell flow battery configuration. The battery results unambiguously confirmed that the redox couple functions best at neutral or near neutral conditions. Dramatic capacity decay of the redox couple was observed in a strong alkaline KOH electrolyte (pH =14), which is due to the chemical decomposition associated with the CN- ligand dissociation. The presented study not only advances an in-depth understanding of K3[Fe(CN)6] and K4[Fe(CN)6] regarding their flow battery applications but also highlights the challenge of acid-base side reactions of redox active molecules applied in aqueous acidic/alkaline redox flow batteries.
Primary Cell Culture

To obtain cells for culture, they must be isolated from a donor animal tissue or organ. When first initiated in culture, the cell isolates are termed primary cells. After the first subculture, they are called cell strains. Thus, all cell lines are cell strains (the converse is not necessarily true; see Chapter 8). Usually the primary cells are obtained to establish a culture that is composed of a single cell type. In some cases, however, the goal is to establish a mixture of cell types in the culture system. Examples are organ culture and mixtures of cells to examine cell interaction (see Laerum and Bjerkiv, 1990, as an example of comparison of single-cell and mixed-cell cultures derived from the same tissue).
Advances in Pharmacotherapy Development: Human Clinical Studies.

For more than 25 years, researchers have made advances in developing medications to treat alcohol use disorder (AUD), highlighted by the US Food and Drug Administration’s (FDA’s) approval of disulfiram, naltrexone (oral and long-acting), and acamprosate. These medications are also approved in Europe, where the European Medicines Agency (EMA) recently added a fourth medication, nalmefene, for AUD. Despite these advances, today’s medications have a small effect size, showing efficacy for only a limited number of individuals with AUD. However, a host of new medications, which act on variety of pharmacologic targets, are in the pipeline and have been evaluated in numerous human studies. This article reviews the efficacy and safety of medications currently being tested in human trials and looks at ongoing efforts to identify candidate compounds in human studies. As mentioned in the National Institute on Alcohol Abuse and Alcoholism’s Strategic Plan 2017–2021 (https://www.niaaa.nih.gov/sites/default/files/StrategicPlan_NIAAA_optimized_2017-2020.pdf), medications development remains a high priority. By developing more effective and safe medications, and identifying those patients who will benefit the most from these treatments, we can provide clinicians with the tools they need to treat this devastating disorder, providing relief for patients and their families and markedly improving public health and safety.
Protocol Design for Content Transfer in Deep Space Network

Space communications feature large round-trip time (RTT) delays and highly variable data error rates. In this paper, we propose a new content transfer protocol based on RaptorQ codes and turbo codes, incorporated with a real-time channel prediction model, to maximize file transfer from space vehicles to Earth stations. While turbo codes are used to correct channel errors, RaptorQ codes are applied to eliminate the need for negative-acknowledgment (NAK) of the loss of any specific packet. To reduce the effect of channel variation, a practical signal-to-noise ratio (SNR) prediction model that is used to periodically adjust the turbo encoder in distant source spacecraft is developed. This new protocol, termed as the dynamic code selection method (DCSM), is compared with two other methods: a turbo codes based genie method (upper bound of DCSM performance) assuming that the channel condition is perfectly known in advance and a static method in which a fixed turbo encoder is used throughout each communication pass. Simulation results demonstrate that the genie and the new DCSM methods can increase telemetry channel throughput by about 47% and 46%, respectively, compared to the static method. In addition, throughput performance using the DCSM is about 99% of the upper bound achieved with the genie method.