cssi/SciSciGPT-SciSciNet huggingface dataset:
Expression of slow skeletal troponin I in adult transgenic mouse heart muscle reduces the force decline observed during acidic conditions

1Acidosis in cardiac muscle is associated with a decrease in developed force. We hypothesized that slow skeletal troponin I (ssTnI), which is expressed in neonatal hearts, is responsible for the observed decreased response to acidic conditions. To test this hypothesis directly, we used adult transgenic (TG) mice that express ssTnI in the heart. Cardiac TnI (cTnI) was completely replaced by ssTnI either with a FLAG epitope introduced into the N-terminus (TG-ssTnI*) or without the epitope (TG-ssTnI) in these mice. TG mice that express cTnI were also generated as a control TG line (TG-cTnI). Non-transgenic (NTG) littermates were used as controls. 2We measured the force-calcium relationship in all four groups at pH 7.0 and pH 6.5 in detergent-extracted fibre bundles prepared from left ventricular papillary muscles. The force-calcium relationship was identical in fibre bundles from NTG and TG-cTnI mouse hearts, therefore NTG mice served as controls for TG-ssTnI* and TG-ssTnI mice. Compared to NTG controls, the force generated by fibre bundles from TG mice expressing ssTnI was more sensitive to Ca2+. The shift in EC50 (the concentration of Ca2+ at which half-maximal force is generated) caused by acidic pH was significantly smaller in fibre bundles isolated from TG hearts compared to those from NTG hearts. However, there was no difference in the force-calcium relationship between hearts from the TG-ssTnI* and TG-ssTnI groups. 3We also isolated papillary muscles from the right ventricle of NTG and TG mouse hearts expressing ssTnI and measured isometric force at extracellular pH 7.33 and pH 6.75. At acidic pH, after an initial decline, twitch force recovered to 60 ± 3 % (n= 7) in NTG papillary muscles, 98 ± 2 % (n= 5) in muscles from TG-ssTnI* and 96 ± 3 % (n= 7) in muscles from TG-ssTnI hearts. Our results indicate that TnI isoform composition plays a crucial role in the determination of myocardial force sensitivity to acidosis.
Hypertension in children and adolescents: definition, pathophysiology, risk factors, and long-term sequelae

Abstract Background: Awareness of hypertension as an adult public health issue has increased dramatically during the past 3 decades, leading to substantial decreases in morbidity and mortality related to stroke and coronary artery disease. Awareness of blood pressure issues in the pediatric population also has increased, leading to conceptual changes in the diagnosis and treatment of childhood hypertension. The current focus has shifted to early identification of mild to moderate hypertension in asymptomatic, otherwise healthy children and adolescents. Objective: The purpose of this article was to define hypertension in the pediatric population and describe the secondary causes of childhood hypertension, risk factors and potential pathophysiology of essential hypertension in childhood, and the long-term sequelae for individuals with hypertension identified during childhood. Methods: Information regarding pediatric hypertension was identified through a MEDLINE ® search of the literature from 1985 to 2000. Results: Definitions of pediatric hypertension have been carefully refined over the past 30 years, and normative data are available for children and adolescents, based on age, sex, and height. Childhood hypertension may be identified during evaluation of an acutely ill child, but is increasingly identified during routine blood pressure screening, particularly in adolescents. Although, historically, most pediatric hypertension was believed to be secondary in origin (related to an identifiable underlying disorder), recent data suggest that almost 90% of hypertensive adolescents have essential hypertension. The proposed factors that may be involved in the pathophysiology of essential hypertension include familial and genetic influences, race, and salt sensitivity. Although an essential hypertension gene has not yet been identified, several monogenic forms of hypertension have been described, which may account for a minority of individuals with presumed essential hypertension. In addition, a number of candidate genes that may be involved in the complex genetic susceptibility to hypertension have been described. There is growing evidence concerning adverse long-term consequences of hypertension identified in childhood and adolescence, including increased incidence of cardiovascular and coronary heart disease. Conclusions: Based on the generally accepted concept that essential hypertension begins in childhood, early optimization of blood pressure control in childhood may reduce an individual's lifetime risk of cardiovascular morbidity and mortality. In addition, aggressive treatment of cardiovascular risk factors during childhood and adolescence may have a major impact on the prevalence of adult cardiovascular disease.
Functional Behavior Assessment in Schools: Current Status and Future Directions.

Functional behavior assessment is becoming a commonly used practice in school settings. Accompanying this growth has been an increase in research on functional behavior assessment. We reviewed the extant literature on documenting indirect and direct methods of functional behavior assessment in school settings. To discern best practice guidelines and directions for future research, we evaluated studies to identify the (a) type of FBA used, (b) participant characteristics, (c) settings in which functional behavior assessments commonly were conducted, and (d) trends in the use of various methods of functional behavior assessment over time.
Platune: a tuning framework for system-on-a-chip platforms

System-on-a-chip (SOC) platform manufacturers are increasingly adding configurable features that provide power and performance flexibility in order to increase a platform's applicability. This paper presents a framework, called Platune, for performance and power tuning of one such SOC platform. Platune is used to simulate an embedded application that is mapped onto the SOC platform and output performance and power metrics for any configuration of the SOC platform. Furthermore, Platune is used to automatically explore the large configuration space of such an SOC platform. The versatility, in terms of accuracy and speed of exploration, of Platune is demonstrated experimentally using three large benchmark examples. The power estimation techniques for processors, caches, memories, buses, and peripherals combined with the design space exploration algorithm deployed by Platune form a methodology for design-of tuning frameworks for parameterized SOC platforms in general.
Anomalous prefrontal-subcortical activation in familial pediatric bipolar disorder: a functional magnetic resonance imaging investigation.

Background The neurobiological features of pediatric bipolar disorder (BD) are largely unknown. Children and adolescents with BD may be important to study with functional neuroimaging techniques because of their unique status of early-onset BD and high familial loading for the disorder. Neuroimaging studies of adults with BD have implicated the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in the development of this disorder. Objectives To study children and adolescents with BD via functional magnetic resonance imaging using cognitive and affective tasks and to examine possible abnormalities in the DLPFC and ACC, as well as selected subcortical areas, in pediatric familial BD. Design We evaluated 12 male subjects aged 9 to 18 years with BD who had at least 1 parent with BD as well as 10 age- and IQ-matched healthy male controls. Stimulants were discontinued for at least 24 hours; other medications were continued. Subjects underwent functional magnetic resonance imaging at 3 T while performing a 2-back visuospatial working memory task and an affective task involving the visualization of positively, neutrally, or negatively valenced pictures. Setting An academic referral setting, drawing from the Bay Area of San Francisco, Calif. Results Compared with controls, for the visuospatial working memory task, subjects with BD had greater activation in several areas including the bilateral ACC, left putamen, left thalamus, left DLPFC, and right inferior frontal gyrus. Controls had greater activation in the cerebellar vermis. In viewing negatively valenced pictures, subjects with BD had greater activation in the bilateral DLPFC, inferior frontal gyrus, and right insula. Controls had greater activation in the right posterior cingulate gyrus. For positively valenced pictures, subjects with BD had greater activation in the bilateral caudate and thalamus, left middle/superior frontal gyrus, and left ACC, whereas controls had no areas of greater activation. Conclusions Children and adolescents with BD may have underlying abnormalities in the regulation of prefrontal-subcortical circuits. Further functional magnetic resonance imaging studies of attention and mood with greater sample sizes are needed.
Insurance regulation in America – playing out of its league

Purpose – The purpose of this editorial is to consider the effectiveness of the state‐based insurance regulatory system operating in the USA.Design/methodology/approach – The editorial begins by identifying two major challenges recently faced by America's state‐based regulatory system, and argues that state regulators handled these problems inadequately. It then discusses the fundamental weaknesses of the system.Findings – The shortcomings of the state‐based regulatory regime are responsible for its failure to prevent the mortgage‐industry crisis from threatening the solvency of at least one major insurance group.Originality/value – The editorial argues in favor of federal oversight of insurance in the USA.
Compressed pattern matching in DNA sequences

We propose derivative Boyer-Moore (d-BM), a new compressed pattern matching algorithm in DNA sequences. This algorithm is based on the Boyer-Moore method, which is one of the most popular string matching algorithms. In this approach, we compress both DNA sequences and patterns by using two bits to represent each A, T, C, G character. Experiments indicate that this compressed pattern matching algorithm searches long DNA patterns (length > 50) more than 10 times faster than the exact match routine of the software package Agrep, which is known as the fastest pattern matching tool. Moreover, compression of DNA sequences by this method gives a guaranteed space saving of 75%. In part the enhanced speed of the algorithm is due to the increased efficiency of the Boyer-Moore method resulting from an increase in alphabet size from 4 to 256.
Thermal characterization of Li-ion cells using calorimetric techniques

The thermal stability of Li-ion cells with intercalating carbon anodes and metal oxide cathodes was measured as a function of state of charge and temperature for two advanced cell chemistries. Cells of the 18650 design with Li/sub x/CoO/sub 2/ cathodes (commercial Sony cells) and Li/sub x/Ni/sub 0.8/Co/sub 0.2/O/sub 2/ cathodes were measured for thermal reactivity. Accelerating rate calorimetry (ARC) was used to measure cell thermal runaway as a function of state of charge (SOC), microcalorimetry was used to measure the time dependence of thermal output, and differential scanning calorimetry (DSC) was used to study the thermal reactivity of the individual components. Thermal decomposition of the anode solid electrolyte interphase (SEI) layer occurred at low temperatures and contributes to the initiation of thermal runaway. Low temperature reactions from 40/spl deg/C-70/spl deg/C were observed during the ARC runs that were SOC dependent. These reactions measured in the microcalorimeter decayed over time with power-law dependence and were highly sensitive to SOC and temperature. ARC runs of aged and cycled cells showed complete absence of these low-temperature reactions but showed abrupt exothermic spikes between 105-135/spl deg/C. These results suggest that during aging the anode SEI layer is decomposing from a metastable state to a stable composition that is breaking down at elevated temperatures.
Support for a Comprehensive Background Check Requirement and Expanded Denial Criteria for Firearm Transfers: Findings from the Firearms Licensee Survey

Federal and state policies on eligibility to purchase and possess firearms and background check requirements for firearm transfers are undergoing intensive review and, in some cases, modification. Our objective in this third report from the Firearms Licensee Survey (FLS) is to assess support among federally licensed firearms retailers (gun dealers and pawnbrokers) for a background check requirement on all firearm transfers and selected criteria for denying the purchase of handguns based on criminal convictions, alcohol abuse, and serious mental illness. The FLS was conducted by mail during June–August, 2011 on a random sample of 1,601 licensed dealers and pawnbrokers in 43 states who were believed to sell at least 50 firearms annually. The response rate was 36.9 %, typical of establishment surveys using such methods. Most respondents (55.4 %) endorsed a comprehensive background check requirement; 37.5 % strongly favored it. Support was more common and stronger among pawnbrokers than dealers and among respondents who believed that “it is too easy for criminals to get guns.” Support was positively associated with many establishment characteristics, including sales of inexpensive handguns, sales that were denied when the purchasers failed background checks, and sales of firearms that were later subjected to ownership tracing, and were negatively associated with sales at gun shows. Support for three existing and nine potential criteria for denial of handgun purchase involving criminal activity, alcohol abuse, and mental illness exceeded 90 % in six cases and fell below 2/3 in one. Support again increased with sales of inexpensive handguns and denied sales and decreased with sales of tactical (assault-type) rifles. In this survey, which was conducted prior to mass shootings in Aurora, Colorado; Oak Creek, Wisconsin; Newtown, Connecticut; and elsewhere, licensed firearm sellers exhibited moderate support for a comprehensive background check requirement and very strong support for additional criteria for denial of handgun purchases. In both cases, support was associated with the intensity of respondents’ exposure to illegal activities.
Resolution of diurnal incontinence and nocturnal enuresis after adenotonsillectomy in children.

Purpose: Adenotonsillar hyperplasia causes upper airway obstruction, leading to obstructive sleep apnea. We reviewed the incidence of nocturnal enuresis in a population of children with adenotonsillar hyperplasia. In addition, we investigated the rate of resolution or improvement in enuresis following surgery for relief of adenotonsillar hyperplasia.Materials and Methods: We studied 86 consecutive prepubertal children, 46 boys and 40 girls, who underwent adenotonsillectomy. Severity of adenotonsillar obstruction was graded on a scale of 1 to 4. A questionnaire regarding voiding problems, including nocturnal enuresis, voids per day and daytime enuresis episodes, was filled out preoperatively and postoperatively by the patients and their parents.Results: Among the 86 patients who underwent adenotonsillectomy 36 (42%) had nocturnal enuresis. In patients with nocturnal enuresis the number of episodes was significantly less after adenotonsillectomy. Overall, 12 patients (33%) had complete resolution, 11 (31%) ...
AREX: An Adaptive System for Secure Resource Access in Mobile P2P Systems

In open environments, such as mobile peer-to-peer systems, participants may need to access resources from unknown users. A critical security concern in such systems is the access of faulty resources, thereby wasting the requester's time and energy and possibly causing damage to her system. A common approach to mitigating the problem involves reputation mechanisms; however, since reputation relies on cooperation, a reputation mechanism's effectiveness can be significantly diminished in hostile environments. Reputation systems also require substantial communication among peers leading to: i) vulnerability to errors caused by intermittent connectivity; ii) message delivery disruptions caused by malicious peers; and iii) energy sapping message overheads. In this paper, we present AREX, a low-cost, adaptive mechanism designed to provide security for peers in hostile and uncertain environments, which are common in mobile P2P systems. AREX features an adaptive exploration strategy that increases the system's utility for benign peers and decreases the systempsilas utility for malicious peers. AREX reduces vulnerabilities and energy costs by operating without communication between peers. Through simulation, we demonstrate AREX's ability to reduce energy costs, protect benign peers, and diminish malicious peers' motivation to attack in a variety of hostile environments.
"But we can always get more!" Deportability, the State and Gendered Migration in the United Arab Emirates*

This paper focuses on the politics of states and inter-state relations, and their role in creating environments of deportability and expendability that structure trafficking-like situations for fem...
Replacing Dietary Palmitic Acid with Elaidic Acid (t-C18:1Δ9) Depresses HDL and Increases CETP Activity in Cebus Monkeys

The question whether dietary trans fatty acids affect lipoprotein metabolism similarly to specific saturated fatty acids was investigated in 11 normolipemic cebus monkeys by exchanging 5% dietary energy (%en) between elaidic (t-C18:1 delta9) and palmitic acid (16:0) in two test diets (30%en fat + 100 mg cholesterol/1000 kcal diet) conforming to the American Heart Association (AHA) Step 1 guidelines. These were compared with a normal control diet rich in saturated fat and cholesterol (38%en fat + 180 mg cholesterol/1000 kcal diet). The control diet was fed initially for 14 wk, followed by each of the the two test diets in a crossover design. Plasma lipid concentrations were determined four times between the 6th and 14th wk. Turnover studies (using 125I-HDL and 131I-LDL) were conducted after 9 wk in each dietary period. Relative to the control diet, both test diets significantly reduced plasma total cholesterol (TC), HDL cholesterol (HDL-C) and VLDL plus LDL cholesterol (LDL-C) concentrations; triglyceride (TG) concentrations tended to be lower. However, the trans diet resulted in a significantly greater reduction in HDL-C than the palmitate diet (124 +/- 17, 117 +/- 18 and 106 +/- 13 mg/dL for the control, palmitate and trans diets, respectively). The palmitate diet significantly decreased the TC/HDL-C ratio by 11% when compared with the control diet (1.68 +/- 0.17 vs. 1.89 +/- 0.30), whereas the trans diet had no effect (1.81 +/- 0.20 vs. 1.89 +/- 0.30). Kinetic studies revealed that, relative to the control diet, both test diets significantly lowered the LDL apolipoprotein B (apoB) pool size, principally reflecting an increase in the LDL apoB fractional catabolic rate (FCR) related to the reduced cholesterol intake. Between the two test diets, no significant differences in LDL kinetic parameters were observed. Both test diets significantly decreased HDL apoA1 concentrations in comparison with the control diet, which was partly explained by an increase in the fractional catabolic rate of HDL. Of the two test diets, the trans diet was associated with a 9.5% greater HDL FCR than the palmitate diet (P < 0.08) and a significant increase in plasma cholesteryl ester transfer protein (CETP) activity (% transfer 114 +/- 7 vs. 91 +/- 7; P < 0.03). Thus, palmitic acid- and elaidic acid-rich diets produced identical effects on LDL metabolism in normocholesterolemic cebus monkeys fed diets with low levels of cholesterol, whereas elaidic acid depressed HDL-C, attributable to both increased CETP activity and HDL clearance.
Complete design of fuzzy logic systems using genetic algorithms

The paper presents a general method for constructing accurate high-dimensional fuzzy logic systems (FLSs). Generally, the design of FLSs involves determination of the number of fuzzy rules, the structure of the rules, and membership function parameters. Most techniques treat these parts separately, which may result in a suboptimal solution. We propose to optimize all three parts simultaneously using genetic algorithm (GA) techniques. While GAs are very robust with respect to avoiding local minima, they can be slow in refining the solution once near the optimum. Thus, the FLS obtained from GA search is further fine-tuned using a conjugate gradient method. The advantages of the proposed method are demonstrated through a comparison with other fuzzy modeling techniques and feedforward neural networks on modeling a nonlinear dynamic system, and industrial process. >
Demonstration of a III-nitride vertical-cavity surface-emitting laser with a III-nitride tunnel junction intracavity contact

We report on a III-nitride vertical-cavity surface-emitting laser (VCSEL) with a III-nitride tunnel junction (TJ) intracavity contact. The violet nonpolar VCSEL employing the TJ is compared to an equivalent VCSEL with a tin-doped indium oxide (ITO) intracavity contact. The TJ VCSEL shows a threshold current density (Jth) of ∼3.5 kA/cm2, compared to the ITO VCSEL Jth of 8 kA/cm2. The differential efficiency of the TJ VCSEL is also observed to be significantly higher than that of the ITO VCSEL, reaching a peak power of ∼550 μW, compared to ∼80 μW for the ITO VCSEL. Both VCSELs display filamentary lasing in the current aperture, which we believe to be predominantly a result of local variations in contact resistance, which may induce local variations in refractive index and free carrier absorption. Beyond the analyses of the lasing characteristics, we discuss the molecular-beam epitaxy (MBE) regrowth of the TJ, as well as its unexpected performance based on band-diagram simulations. Furthermore, we investigat...
Developing a dual-frequency FM-CW radar to study precipitation

Using support from the Cooperative Institute for Research in Environmental Sciences (CIRES) Innovative Research Program, an inexpensive dual-frequency vertically pointing precipitation radar was developed utilizing technologies initially developed for the mobile phone, the police radar, and the video game industries. One radar operated in the frequency band used for point-to-point Internet service (5.8 GHz). And the other radar operated in the police radar frequency band (10.5 GHz). The radar hardware for both radar systems cost less than US$ 12 000. Both radars used the Frequency Modulated Continuous Wave (FM-CW) technique to observe at a 5-m range resolution from near the surface to over 300 m. A two Fourier transform (FFT) technique was used to estimate Doppler velocity power spectra at each range at a rate of 12 spectra per second. Another innovation of this project was using the parallel processing of the Cell Broadband Engine installed in a Sony Playstaion 3 to perform all post-data collection signal processing.
Managing cybersickness in virtual reality

If the physical side effects associated with virtual reality are not managed, the widespread adoption of VR may come to a halt.
Visualizing the quality of partially accruing data for use in decision making

Secondary use of clinical health data for near real-time public health surveillance presents challenges surrounding its utility due to data quality issues. Data used for real-time surveillance must be timely, accurate and complete if it is to be useful; if incomplete data are used for surveillance, understanding the structure of the incompleteness is necessary. Such data are commonly aggregated due to privacy concerns. The Distribute project was a near real-time influenza-like-illness (ILI) surveillance system that relied on aggregated secondary clinical health data. The goal of this work is to disseminate the data quality tools developed to gain insight into the data quality problems associated with these data. These tools apply in general to any system where aggregate data are accrued over time and were created through the end-user-as-developer paradigm. Each tool was developed during the exploratory analysis to gain insight into structural aspects of data quality. Our key finding is that data quality of partially accruing data must be studied in the context of accrual lag-the difference between the time an event occurs and the time data for that event are received, i.e. the time at which data become available to the surveillance system. Our visualization methods therefore revolve around visualizing dimensions of data quality affected by accrual lag, in particular the tradeoff between timeliness and completion, and the effects of accrual lag on accuracy. Accounting for accrual lag in partially accruing data is necessary to avoid misleading or biased conclusions about trends in indicator values and data quality.
2-Photon Characterization of Optical Proteolytic Beacons for Imaging Changes in Matrix-Metalloprotease Activity in a Mouse Model of Aneurysm

Abdominal aortic aneurysm is a multifactorial disease that is a leading cause of death in developed countries. Matrix-metalloproteases (MMPs) are part of the disease process, however, assessing their role in disease initiation and progression has been difficult and animal models have become essential. Combining Forster resonance energy transfer (FRET) proteolytic beacons activated in the presence of MMPs with 2-photon microscopy allows for a novel method of evaluating MMP activity within the extracellular matrix (ECM). Single and 2-photon spectra for proteolytic beacons were determined in vitro. Ex vivo experiments using the apolipoprotein E knockout angiotensin II-infused mouse model of aneurysm imaged ECM architecture simultaneously with the MMP-activated FRET beacons. 2-photon spectra of the two-color proteolytic beacons showed peaks for the individual fluorophores that enable imaging of MMP activity through proteolytic cleavage. Ex vivo imaging of the beacons within the ECM revealed both microstructure and MMP activity. 2-photon imaging of the beacons in aneurysmal tissue showed an increase in proteolytic cleavage within the ECM (p<0.001), thus indicating an increase in MMP activity. Our data suggest that FRET-based proteolytic beacons show promise in assessing MMP activity within the ECM and will therefore allow future studies to identify the heterogeneous distribution of simultaneous ECM remodeling and protease activity in aneurysmal disease.
Investigating Electron Transfer in Macromolecular Ruthenium Tris(bipyridyl) Complexes Using Collection Experiments at a Rotating Ring–Disk Electrode

Three transition metal complexes, based on the ruthenium tris-bipyridyl unit and containing two, three, and four metal centers, were synthesized and investigated with electrochemical techniques. While the bimetallic complex exhibited very similar properties to the parent ruthenium tris-bipyridine, the two larger complexes behaved differently. During cyclic voltammetry, upon the second ligand-based reduction, both the tri- and the tetra-metallic complex precipitated and adsorbed to the electrode surface, as evidenced by the characteristic voltammetric stripping wave observed both upon further reduction and upon reoxidation. Further, when these complexes were investigated with collection experiments at a rotating ring–disk electrode, anomalously low values of the collection efficiency were measured. This effect is attributed to the size of the molecules, which prevents all of the redox centers from being able to simultaneously access the electrode surface, leading to only a portion of the redox active sites...
Bcr phosphorylated on tyrosine 177 binds Grb2

We and others have shown that the Bcr-Abl oncoprotein binds activators of the Ras pathway such as Grb2 and Shc. Grb2 binding is mediated through a phosphorylated tyrosine residue (Y177) located within a consensus Grb2 binding site encoded by the first exon of the BCR gene. Our results indicate that P160 BCR is tyrosine phosphorylated at the same site by Bcr-Abl in kinase assays (Puil et al., 1994). We performed experiments to determine whether Bcr, which was tyrosine phosphorylated within cells by activated c-Abl, could also bind Grb2, and whether phosphotyrosine 177 was the major binding site. Complexes between Bcr and Abl were detected in a hemopoietic cell line lacking Bcr-Abl and in COS1 cells coexpressing both Bcr and Abl proteins. P160 BCR was tyrosine phosphorylated in COS1 cells coexpressing Abl and Bcr proteins. Similarly, various deletion mutants of Bcr including BCRN553, BCRN413 and BCRN221 were tyrosine phosphorylated by activated c-Abl whereas BCRN159 was not. Wild-type Bcr and Bcr Y177F were examined under these conditions for their ability to co-precipitate with Grb2. The results showed that while wild-type tyrosine phosphorylated Bcr efficiently bound Grb2, tyrosine phosphorylated Bcr Y177F had greatly reduced Grb2-binding ability. Studies with GST-SH2 (Grb2) revealed that tyrosine phosphorylated Bcr was able to bind to GST SH2 (Grb2) but tyrosine phosphorylated Bcr Y177F was deficient in binding. These results indicate that the Bcr protein when phosphorylated at tyrosine 177 binds Grb2, thereby implicating Bcr as a potantial activator of the Ras pathway.
Graphene Oxide Enhances Cellular Delivery of Hydrophilic Small Molecules by Co-incubation

The delivery of bioactive molecules into cells has broad applications in biology and medicine. Polymer-modified graphene oxide (GO) has recently emerged as a de facto noncovalent vehicle for hydrophobic drugs. Here, we investigate a different approach using native GO to deliver hydrophilic molecules by co-incubation in culture. GO adsorption and delivery were systematically studied with a library of 15 molecules synthesized with Gd(III) labels to enable quantitation. Amines were revealed to be a key chemical group for adsorption, while delivery was shown to be quantitatively predictable by molecular adsorption, GO sedimentation, and GO size. GO co-incubation was shown to enhance delivery by up to 13-fold and allowed for a 100-fold increase in molecular incubation concentration compared to the alternative of nanoconjugation. When tested in the application of Gd(III) cellular MRI, these advantages led to a nearly 10-fold improvement in sensitivity over the state-of-the-art. GO co-incubation is an effective ...
First-line Chemotherapy in Epithelial Ovarian Cancer

Advanced-stage epithelial ovarian cancer remains a highly lethal malignancy, despite effective cytoreductive surgery and primary chemotherapy. Phase III studies have evaluated multidrug combinations, dose-dense weekly scheduling, intraperitoneal delivery, neoadjuvant chemotherapy, maintenance therapy, and targeting of angiogenesis. Incremental gains in median progression-free or overall survival have been achieved, but without an impact on overall mortality. Data support intraperitoneal cisplatin, dose-dense weekly paclitaxel, or neoadjuvant chemotherapy with interval cytoreduction in appropriate patients. Encouraging data have emerged using antiangiogenic agents, but with questions regarding optimal timing and patient selection. The use of 3-drug combinations or maintenance chemotherapy is not supported.
Modeling the photophysics of Zn and Cd monomers, metallophilic dimers, and covalent excimers.

Density functional (Xα, BLYP, BPW91, B3LYP, and B3PW91), MP2, and coupled cluster with singles, doubles, and quasiperturbative triple excitations (CCSD(T)) methods in combination with LANL2DZ, cc-p...
25 years of HNPCC

Research on the genetic, molecular genetic, clinical features, and natural history of HNPCC has shown tremendous progress and evolution during the past 25 years. Specifically, HNPCC's autosomal dominant mode of genetic transmission has now been documented through linkage studies of the gene at 2p (MSH2) and at 3p (MLH1) with the cloning of these genes. Also, the tumor spectrum has increased, which now, in addition to carcinoma of the colon, endometrium, stomach, and ovary, includes transitional cell carcinoma of the ureter and renal pelvis, and adenocarcinomas of the small bowel and pancreas. Surveillance and management protocols for patients at high risk should include full colonoscopy since 70% of the colon cancers occur in the proximal colon. Because of the marked excess of synchronous and metachronous colorectal cancers (CRC), no less than a subtotal colectomy should be performed at the time of initial CRC. Women, in addition to colonoscopy, require endometrial aspiration biopsy. Should they develop CRC and if their procreation is completed, we recommend that they consider prophylactic hysterectomy and bilateral salpingo oophorectomy at the time of their subtotal colectomy. Now that the deleterious genes at 2p and 3p have been identified, we are offering candidates, in whom the MSH2 or MLH1 mutation has been verified, an option of prophylactic subtotal colectomy as opposed to annual life time colonoscopy. With the development of the International Hereditary Nonpolyposis Colorectal Cancer Collaborative Group, knowledge can be disseminated worldwide about the public health importance of HNPCC and the need to implement highly targeted surveillance and management strategies in all clinical practice settings.
Abstract CN11-03: SIRT3 is a mitochrondial tumor suppressor in breast cancer

It is a well-established scientific observation that mammalian cells contain fidelity or watchdog proteins that maintain the correct function of cellular organelles. Over the past several years, the Sirtuin deacetylase family protein Sirt3 has emerged as a mitochondrial fidelity protein that directs energy generation and regulates reactive oxygen species (ROS) scavenging proteins. Genetic deletion of these fidelity proteins has been shown to create a cellular environment that is permissive for the development of cellular damage associated with processes such as aging and breast ductal cell carcinogenesis. In this regard, we have previously shown that mice lacking the mitochondrial Sirtuin-3 (Sirt3) gene develop estrogen receptor (ER+) positive, p53 wild-type, poorly differentiated invasive ductal carcinomas (IDC) (Kim et al., 2010, Cancer Cell), a subtype of malignancy similar to luminal B breast cancer that is predominantly observed in older women. Mice lacking Sirt3 also exhibit increased ROS, including superoxide due to the aberrant acetylation of manganese superoxide dismutase (MnSOD) resulting in decreased enzymatic ROS scavenging activity. In addition, over expressing a mutant deacetylated-mimic MnSOD isoform, which exhibits increased SOD enzymatic activity, reversed the tumor permissive phenotype (Tao et al, 2010, Molecular Cell) observed in breast tumor cells lacking Sirt3. Finally, in collaboration with Dr. Joe Bass (Corresponding Author, Northwestern University) a link between SIRT3 and the clock proteins, in the form of mitochondrial NAD+ concentrations has been discovered. Specifically, a clock protein loop directs SIRT3, via NAD+ bioavailability, to regulate mitochondrial glycolytic and oxidative metabolism, as well as MnSOD lysine acetylation and detoxification activity. Furthermore, NAD+ supplementation decreased MnSOD acetylation and significantly restored mitochondrial function in circadian mutant mice by a mechanism involving SIRT3 activity (Peek et al., 2013, Science). These results suggest that circadian clock proteins coordinate mitochondrial metabolism, in part via the modulation of protein acetylation, to synchronize metabolic and oxidative pathways with circadian rhythms. Citation Format: David Gius. SIRT3 is a mitochrondial tumor suppressor in breast cancer. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr CN11-03.
A tokamak tritium production reactor

A concept is presented for a fusion neutron source based tritium production reactor called the Tokamak Tritium Production Reactor (TTPR), which could meet the U.S. needs for replenishment of weapons tritium during the first half of the next century. The TTPR concept is based on physics and technology that either exists or is being developed and will be tested under integrated, prototypical conditions in the International Thermonuclear Experimental Reactor (ITER). The TTPR can provide 2 kg/yr tritium for weapons replenishment operating at a fusion power level of 500 to 1000 MW and at a plant factor of 10 to 25%. No structural component should need to be replaced because of radiation damage during the 40-yr lifetime of the TTPR, and it should be possible to dispose of the TTPR on decommissioning as low-level waste that qualifies for shallow land burial.
The Biological Basis for Cardiac Repair After Myocardial Infarction: From Inflammation to Fibrosis

In adult mammals, massive sudden loss of cardiomyocytes after infarction overwhelms the limited regenerative capacity of the myocardium, resulting in the formation of a collagen-based scar. Necrotic cells release danger signals, activating innate immune pathways and triggering an intense inflammatory response. Stimulation of toll-like receptor signaling and complement activation induces expression of proinflammatory cytokines (such as interleukin-1 and tumor necrosis factor-α) and chemokines (such as monocyte chemoattractant protein-1/ chemokine (C-C motif) ligand 2 [CCL2]). Inflammatory signals promote adhesive interactions between leukocytes and endothelial cells, leading to extravasation of neutrophils and monocytes. As infiltrating leukocytes clear the infarct from dead cells, mediators repressing inflammation are released, and anti-inflammatory mononuclear cell subsets predominate. Suppression of the inflammatory response is associated with activation of reparative cells. Fibroblasts proliferate, undergo myofibroblast transdifferentiation, and deposit large amounts of extracellular matrix proteins maintaining the structural integrity of the infarcted ventricle. The renin–angiotensin–aldosterone system and members of the transforming growth factor-β family play an important role in activation of infarct myofibroblasts. Maturation of the scar follows, as a network of cross-linked collagenous matrix is formed and granulation tissue cells become apoptotic. This review discusses the cellular effectors and molecular signals regulating the inflammatory and reparative response after myocardial infarction. Dysregulation of immune pathways, impaired suppression of postinfarction inflammation, perturbed spatial containment of the inflammatory response, and overactive fibrosis may cause adverse remodeling in patients with infarction contributing to the pathogenesis of heart failure. Therapeutic modulation of the inflammatory and reparative response may hold promise for the prevention of postinfarction heart failure.
Should we be concerned about global warming

Accurate scientific predictions of the true human health outcomes of global climate change are significantly confounded by several effect modifiers that cannot be adjusted for analytically. Nevertheless, with the documented increase in average global surface temperature of 0.6 C. since 1975, there is uniform consensus in the international scientific community that the earth is warming from a variety of climatic effects, including cyclical re-warming and the cascading effects of greenhouse gas emissions to support human activities.
Gramene Database: A Hub for Comparative Plant Genomics

The rich collection of known genetic information and the recent completion of rice genome sequencing project provided the cereal plant researchers a useful tool to investigate the roles of genes and genomic organization that contribute to numerous agronomic traits. Gramene ( http://www.gramene.org ) is a unique database where users are allowed to query and explore the power of genomic colinearity and comparative genomics for genetic and genomic studies on plant genomes. Gramene presents a wholesome perspective by assimilating data from a broad range of publicly available data sources for cereals like rice, sorghum, maize, wild rice, wheat, oats, barley, and other agronomically important crop plants such as poplar and grape, and the model plant Arabidopsis. As part of the process, it preserves the original data, but also reanalyzes for integration into several knowledge domains of maps, markers, genes, proteins, pathways, phenotypes, including Quantitative Trait Loci (QTL) and genetic diversity/natural variation. This allows researchers to use this information resource to decipher the known and predicted interactions between the components of biological systems, and how these interactions regulate plant development. Using examples from rice, this article describes how the database can be helpful to researchers representing an array of knowledge domains ranging from plant biology, plant breeding, molecular biology, genomics, biochemistry, genetics, bioinformatics, and phylogenomics.
Geometric model of single scatter in PET

We present a mathematical model of single scatter in PET for a detector system possessing excellent energy resolution. Derivation of the model exploits assumptions widely used in PET and SPECT modalities for unscattered photons forward modeling. Integral equations describing a flux of photons emanating from the same annihilation event and undergoing a single scattering with a certain angle are derived in both 2D and 3D cases. Preliminary results of numerical experiments are presented.
A low-power impulse radio ultra-wideband (IRUWB) transmitter for biomedical sensor applications

In this paper an UWB impulse radio transmitter for a low-power wearable respiration monitoring sensor is proposed. The transmitter operates in the 3.1 to 5 GHz oscillation frequency range with a tunable channel bandwidth of 0.8 – 1.3 GHz. Implemented in a standard 130-nm CMOS process the proposed transmitter follows on-off keying (OOK) modulation scheme and consumes an average power of 8.2 µW with 1.2 V supply voltage. With a data rate of 1 Mbps, the entire system consumes only 82pJ/bit, which makes it suitable for short distance biomedical sensor applications. Simulation results show that the pulse duration and the amplitude of the impulse signal are 1ns and 0.9 V pp , respectively, with a peak emission power spectrum density of −41 dBm/MHz, which fully complies with the FCC spectral mask.
Price migration of oncology drugs launched in the United States between 2010 and 2015.

6606 Background: As discussions of value increasingly enter the oncology arena, the price, or cost, of drugs is becoming increasingly relevant. Here, we have reviewed new cancer drugs launches in t...
Shoulder Injury: MRI Pitfalls

Magnetic resonance imaging (MRI) is an established modality for the assessment of internal derangements of the shoulder. Accurate interpretation of MR images and understanding of differential diagnosis require familiarity with normal developmental variants and common diagnostic pitfalls. In this chapter, we present an overview of pitfalls that can confound the interpretations of conventional and arthrographic shoulder MRI. These pitfalls include anatomical variations and MRI artifacts that may mimic pathological abnormalities. We present strategies for addressing these challenges.
Kinetics of Ion Drift

In previous chapters, we have shown that various metal species, including barrier metals and self-forming barrier metals, can penetrate into dielectrics under BTS. Generally, the existence of metal contamination inside dielectrics will significantly degrade dielectric reliability, causing early breakdown and large leakage current [1]. Therefore, a main interest is to understand the impact of this metal contamination on dielectric reliability. Before we can proceed further on this topic, however, there is one question that needs to be clarified: the kinetics issue. How fast can these metallic species migrate inside the dielectrics? A key parameter needed to describe the kinetics is diffusivity (D). With a known stressing condition, diffusivity can be used to calculate the distribution of metal contamination inside the dielectric, from which the total number of metal species within the dielectric can be estimated. Also, the effective electric field distribution inside the dielectric, after including the ionic field effect, can be evaluated [2, 3]. These factors are crucial in order to predict the dielectric lifetime, which we will discuss further in Chap. 9. In addition, the operation of memory devices that uses the drift of ions to perform functions, such as resistive switches and solid electrolyte devices, relies on the buildup of a conductive metallic filament between the electrodes. To decide the working temperature and the threshold electric field needed for switching, it is necessary to know the metal migration speed inside the dielectric [4].
Procedural Justice and the Discursive Construction of Narratives at Trial

The structure and practices of justice systems in many parts of the world are undergoing what can be seen as a kind of revolution – and one not merely of professional interest to lawyers and judges. What we are seeing in nation after nation is a move from inquisitorial models of legal adjudication toward adversarial models. The discourses of adjudication in these contrasting types of trials are changing the ways in which lawyers, judges, and witnesses come to see their role in the process. The change has implications that extend far beyond the courtrooms in which trials play out, however. Because the shift from inquisitorial to adversarial justice models determines how legal narratives are created and deployed in trials, this change has the potential to impact popular perceptions of legal legitimacy, which in turn has implications for the relationship of citizens to their government and justice systems. This article will detail the global character of this change in the nature of the discourse used in legal adjudication and will explore its potential ramifications for legal professionals and for society more generally.
Is Perceived Growth Associated with Momentary Indicators of Health and Well-Being in People with Asthma or Rheumatoid Arthritis?

Background Perceived growth (PG) refers to perceptions of positive changes that unfold over time after experiencing trauma. Higher PG is often associated with positive long-term health, but the processes through which PG may influence health are unclear. The present study examines two potential pathways among individuals living with asthma or RA: (1) by promoting momentary indicators of health and well-being in everyday life, and (2) by buffering against stress. Method In a micro-longitudinal design, 128 participants with asthma (n = 97) or rheumatoid arthritis (n = 31) reported perceived growth using the Post-Traumatic Growth (PTG) Inventory and subsequently completed ecological momentary assessments (EMAs) for one week. Participants were signaled five times a day to report on health-related indicators, including affect, disease interference, social interactions, and stress. Results Multilevel modeling revealed that higher PTG was associated with significantly less negative affect and greater positive affect in everyday life. There were no significant associations between PTG and momentary disease interference, pleasantness of social interactions, or stress, nor evidence that PTG buffered against effects of stress on health-related outcomes. Conclusions This research highlights the utility of examining PG in everyday life. Results suggest that closer examination of momentary affect as a process by which PG may facilitate positive health outcomes is warranted.
Theory of Oxygen-Vacancy Defects in Silicon Dioxide

Large, asymmetric atomic relaxations are important features of oxygen-vacancy-related defects in silicon dioxide. To investigate these defects we have adapted the MIND0/3 and MOPN semiempirical molecular structure methods. In several cases (the E 1 ′ , E 2 ′ , and E 4 ′ centers) the defect is paramagnetic and its primary characteristic is a single sp3 electron localized on one Si and oriented towards or away from the O vacancy. Different atomic relaxations and charge states, along with the presence or absence of atomic H, distinguish these defects from one another. One important type of relaxation appears to be the displacement of a Si into a “back-bonds” interstitial position.