cssi/SciSciGPT-SciSciNet huggingface dataset:
Molecular determinants of local anesthetic action of beta-blocking drugs: Implications for therapeutic management of long QT syndrome variant 3

The congenital long QT syndrome (LQTS) is a heritable arrhythmia in which mutations in genes coding for ion channels or ion channel associated proteins delay ventricular repolarization and place mutation carriers at risk for serious or fatal arrhythmias. Triggers and therapeutic management of LQTS arrhythmias have been shown to differ in a manner that depends strikingly on the gene that is mutated. Additionally, beta-blockers, effective in the management of LQT-1, have been thought to be potentially proarrhythmic in the treatment of LQT-3 because of concomitant slowing of heart rate that accompanies decreased adrenergic activity. Here we report that the beta-blocker propranolol interacts with wild type (WT) and LQT-3 mutant Na+ channels in a manner that resembles the actions of local anesthetic drugs. We demonstrate that propranolol blocks Na+ channels in a use-dependent manner; that propranolol efficacy is dependent on the inactivated state of the channel; that propranolol blocks late non-inactivating current more effectively than peak sodium current; and that mutation of the local anesthetic binding site greatly reduces the efficacy of propranolol block of peak and late Na+ channel current. Furthermore our results indicate that this activity, like that of local anesthetic drugs, differs both with drug structure and the biophysical changes in Na+ channel function caused by specific LQT-3 mutations.
Interactions of cultured endothelial cells with TGF-β, bFGF, PDGF and IGF-I

Endothelial cells in culture synthesize the growth factors transforming growth factor beta (TGF-beta), basic fibroblast growth factor (bFGF), platelet derived growth factor (PDGF) and, perhaps, insulin like growth factor I (IGF-I). We have previously demonstrated that IGF-I and PDGF have both high affinity receptors and stimulate glucose and AIB uptake in the microvessel cells under study and that IGF-I, but not PDGF, has similar high affinity receptors in cultured large vessel endothelial cells. In the present study, cultured bovine endothelial cells were exposed to these four growth factors to determine a) their effects on the acute metabolic processes of neutral amino acid (AIB) and glucose uptake and b) their interactions at the endothelial cell surface. In microvessel endothelial cells, each growth factor stimulated AIB and glucose uptake 2-4 fold whereas in large vessel endothelial cells only bFGF stimulated glucose uptake. Each growth factor had specific high affinity binding to the microvessel cells that was not influenced by the presence of the other growth factors. In large vessel endothelial cells, similar high affinity binding was present only for IGF-I and to a lesser degree TGF-beta. When cells were exposed to a given growth factor for 18 hours, homologous receptor downregulation was observed, with a maximal 60-95% decrease in surface binding. These findings suggest several potential levels of interaction of the growth factors TGF-beta, bFGF, PDGF and IGF-I in cultured vascular endothelial cells.
Immunological properties of canine prothrombin, its activation products, plasma and serum

Abstract Immunological properties of canine prothrombin(PO), prethrombin 1 (P1), fragment 1(F1), fragment 2(F2), thrombin(T1), plasma and serum were studied by the use of immunoelectrophoresis(IEP), crossed immunoelectrophoresis (CIEP) and Ouchterlony analysis. Antibodies against P0 and T1 were used. The results showed that P0, P1, F1, F2 and T1 all had a variable affinity with anti-PO antibody but that only P0, P1 and T1 had a demonstrable affinity with anti-T1 antibody. F1 and F2 did not show any detectable affinity. Quantitative affinity study by the use of I-125-labeled proteins gave the following average values for % bound I-125-proteins in 3 hr incubation with the antibody against P0 or T1: with anti-P0 antibody, 81 ± 2 (SD) % for I-125-P0, 79.1 ± 2(SD) % for I-125-P1, 23.5 ± 3(SD) % for I-125-F1, 25.5 ± 2(SD) % for I-125-F2 and 25.2 ± 3(SD) % for I-125-T1, and with anti-T1 antibody, 28 ± 2(SD) % for I-125-P0, 80.5 ± 2(SD) % for I-125-P1, 1.0 ± 0.03(SD) % for I-125-F1, 1.3 ± 0.03(SD) % for I-125-F2, and 81 ± 3(SD) % for I-125-T1. With the use of CIEP and anti-P0 antibody, serum was found to contain F1, F2 and a trace amount of P1, and plasma contained only P0, but upon activation with tissue thromboplastin, plasma was found to generate P1, F1, F2 and T1 with time. These results indicate that a simple, specific and quantitative immunoassay of T1 by the use of anti-T1 antibody or anti-P0 antibody may not be possible at least in dogs, but that CIEP by the use of anti-P0 antibody might be used as a diagnostic means of in vivo P0 activation.
Experiences with psychiatric services in a program for pregnant school-age girls

This paper describes the characteristics of girls referred to a consulting psychiatrist by the Young Mothers Clinic, part of a comprehensive service program for school-age mothers in New Haven, Conn. This program provided obstetrical, educational, and social services to the study group, which consisted of 180 patients who entered the clinic over a two year period. All of the study group were under 18 years of age and unwed when they registered for the clinic, and most were nonwhite. — Twenty-five of the 180 girls were referred to the psychiatrist. Common reasons for referral included lack of attention, delinquency, learning difficulties at school, withdrawn behavior, depression, suicidal threats, and chaotic home situations. Those referred were found frequently to have 1. a history of contact with juvenile court and/or 2. low scores on the Wechsler intelligence scales and poor scores on the Bender Gestalt test. — White girls were more likely to be referred than were nonwhite girls. Girls 15 years of age or under were more likely to be referred than older girls. These two groups (i.e. the younger group and the white group) tended to come from extremely disorganized homes. — Clinically, the psychiatrist was impressed by the repeated history of maternal deprivation among the referred patients. She hypothesized that the girls' unfulfilled yearning for closeness with their mothers may have driven them toward early physical relationships with boys, resulting in the pregnancies. Therapeutic recommendations were difficult to implement primarily because the girls, for various reasons, did not follow through with referrals to other sources of care.
Internal versus external determinants of Schistosoma japonicum transmission in irrigated agricultural villages

Currently schistosomiasis transmission has been suppressed to low levels in many historically endemic areas of China by widespread use of praziquantel in human and bovine populations and application of niclosamide for snail control. However, re-emergent transmission has signalled the need for sustainable interventions beyond these repeated chemical interventions. To take advantage of ongoing investment in rural infrastructure, an index of schistosomiasis transmission potential is needed to identify villages where environmental modifications would be particularly effective. Based on a retrospective analysis of data from 10 villages in Sichuan Province, an index linked to the basic reproductive number is shown to have promise in meeting this need. However, a lack of methods for estimating the spatial components of the proposed metric and for estimating the import of cercariae and miracidia from neighbouring villages leads to significant uncertainty in its estimation. These findings suggest a priority effort to develop methods for measuring the free-swimming forms of the parasite in surface waters. This need is underscored by the high cost and limited sensitivity of current methods for diagnosing human infection and mounting evidence of the inadequacy of snail surveys to identify environments supporting low levels of transmission.
Configuration management for designs of software systems

Configuration management systems are traditionally concerned only with source code. However in large-scale projects, capturing the evolution of design artifacts is crucial to the success of the software products. This paper presents a novel tool to provide version control and configuration management supports for design artifacts as well as specifications and documentations produced during a software life cycle. The tool is distinguished itself from existing ones by its ability to manage the evolution of the semantic relationships between design objects and implementation source code. This paper also describes the use of that tool in the software concordance integrated development environment to manage the evolution of software projects.
Molecular links between x-inactivation and autosomal imprinting: X-inactivation as a driving force for the evolution of imprinting?

In classical Mendelian inheritance, each parent donates a set of chromosomes to its offspring so that maternally and paternally encoded information is expressed equally. The phenomena of X-chromosome inactivation (XCI) and autosomal imprinting in mammals violate this dogma of genetic equality. In XCI, one of the two female X chromosomes is silenced to equalize X-linked gene dosage between XX and XY individuals. In genomic imprinting, parental marks determine which of the embryo's two autosomal alleles will be expressed. Although XCI and imprinting appear distinct, molecular evidence now shows that they share a surprising number of features. Among them are cis-acting control centers, long-distance regulation and differential DNA methylation. Perhaps one of the most intriguing similarities between XCI and imprinting has been their association with noncoding and antisense RNAs. Very recent data also suggest the common involvement of histone modifications and chromatin-associated factors such as CTCF. Collectively, the evidence suggests that XCI and genomic imprinting may have a common origin. Here, I hypothesize that the need for X-linked dosage compensation was a major driving force in the evolution of genomic imprinting in mammals. I propose that imprinting was first fixed on the X chromosome for XCI and subsequently acquired by autosomes.
Cytosolic Phosphoenolpyruvate Carboxykinase Does Not Solely Control the Rate of Hepatic Gluconeogenesis in the Intact Mouse Liver

When dietary carbohydrate is unavailable, glucose required to support metabolism in vital tissues is generated via gluconeogenesis in the liver. Expression of phosphoenolpyruvate carboxykinase (PEPCK), commonly considered the control point for liver gluconeogenesis, is normally regulated by circulating hormones to match systemic glucose demand. However, this regulation fails in diabetes. Because other molecular and metabolic factors can also influence gluconeogenesis, the explicit role of PEPCK protein content in the control of gluconeogenesis was unclear. In this study, metabolic control of liver gluconeogenesis was quantified in groups of mice with varying PEPCK protein content. Surprisingly, livers with a 90% reduction in PEPCK content showed only a approximately 40% reduction in gluconeogenic flux, indicating a lower than expected capacity for PEPCK protein content to control gluconeogenesis. However, PEPCK flux correlated tightly with TCA cycle activity, suggesting that under some conditions in mice, PEPCK expression must coordinate with hepatic energy metabolism to control gluconeogenesis.
Response of safflower (Carthamus tinctorius L.) to residual soil N following cotton (Gossypium spp.) in rotation in the San Joaquin Valley of California.

Deep-rooted crops used in rotation can improve the overall water and N use efficiencies of cropping systems and help minimize nitrate leaching to groundwater. Safflower (Carthamus tinctorius L.) is a deep-rooted annual crop grown in Mediterranean regions that might be useful for this purpose. Safflower's response to residual soil N measured to 2.7 m in the soil profile was evaluated in 1998 in field plots in the San Joaquin Valley, California, USA that were used previously for cotton over a 9-year period and had been fertilized with nine N rates from 0 to 230 kg N/ha. Residual soil NO 3 -N measured prior to safflower planting increased with prior cotton fertilization rates. Amounts present to a soil profile depth of 2.7 m varied from 760 to 2600 kg/ha. Safflower seed yield increased with increasing pre-plant residual NO 3 -N levels, from 1700 kg/ha in the control to 2200 kg/ha, and then declined to 1800 kg/ha at the largest residual N level. Oil per cent, and oil yield were affected by soil N only at the largest residual N level, while oil composition was not affected. Root growth and N uptake at depth increased in plots with larger amounts of residual N compared to those with less. Results suggest that N fertilization applied to safflower could be reduced or even eliminated following crops previously fertilized at economic levels. Residual N should be accounted in growers' management programmes.
Approximation of biholomorphic mappings by automorphisms of C n

In this paper we prove several results on approximation of biholomorphic mappings between domains in C" (n _>-2) by holomorphic automorphisms of C". Recall that the group of holomorphic automorphisms of C", denoted Aut C", consists of those holomorphic mappings ~ : C "--, C" that have a holomorphic inverse 4 1 : C" --* C". With the topology of uniform convergence on compact sets, Aut C" is a topological group. While the group Aut C 1 of automorphisms of the complex plane consists only of the linear mappings az + b (a, b e C, a 4= 0), the group Aut C" is very large and complicated when n > 2. Let us choose a linear coordinate system on C" and write the coordinates as z = (z ' ,w), where Z'~-(Z1, . . . ,Zn_I)C--C n 1 and w = z ,~ C. Then AutC n contains mappings of the form
Mammary tumours and prolactin

The reproductive cycle of the bitch is divided into four stages: pro-oestrus, oestrus, dioestrus and anoestrus. The main hormone responsible for prooestrus and oestrus is oestrogen, whereas the dominant hormone during dioestrus is progesterone (Fig. 1). The LH surge separates the endocrine prooestrus from the endocrine oestrus and is responsible for ovulation and development of the corpus luteum.
Quilt Snaps: a fabric based computational construction kit

In this paper we present Quilt Snaps, a fabric based construction kit consisting of a set of computationally enhanced quilting pieces. Our discussion focuses on three ways that children can engage with Quilt Snaps. First, Quilt Snaps allows children to act as the engineers, designers, and decorators of their own digital manipulatives. Second, by playing with the manipulatives that they've helped to construct, children can learn about concepts relevant to programming, graph theory, and dynamical systems. Finally, since Quilt Snaps is fabric based, children can use the pieces they construct as personal mobile display media.
Note-Revising Forecasts of Accounting Earnings: A Comparison with the Box-Jenkins Method

The purpose of this study was to contribute to the literature concerning forecasting the time series of accounting earnings. To accomplish this objective an experiment was conducted to compare the performance of Theil's Optimal Linear Correction technique for revising quarterly Box-Jenkins and other naive model forecasts of accounting earnings against the unrevised forecasts. Several results of this study are of particular interest. First, the study indicated that the Watts-Griffin parsimonious model outperformed other firm specific Box-Jenkins models. Second, the Optimal Linear Correction produced revised forecasts that were uniformly more accurate than the original unadjusted forecasts. Finally, the naive extrapolative time series models outperformed Box-Jenkins forecasts of accounting earnings.
Conservation of biodiversity in coffee agroecosystems: a tri-taxa comparison in southern Mexico

We compare species richness of birds, fruit-feeding butterflies and ground-foraging ants along a coffee intensification gradient represented by a reduction in the number of species of shade trees and percentage of shade cover in coffee plantations. We sampled the three taxa in the same plots within the same period of time. Two sites were selected in the Soconusco region of the state of Chiapas, Mexico. Within each site four habitat types were selected and within each habitat type four points were randomly selected. The habitat types were forest, rustic coffee, diverse shade coffee, and intensive coffee (low density of shade). We found different responses of the three taxa along the intensification gradient. While ants and butterflies generally decrease in species richness with the decrease of shade cover, birds declined in one site but increased in the other. Ant species richness appears to be more resistant to habitat modification, while butterfly species richness appears to be more sensitive. Bird species richness was correlated with distance from forest fragments but not with habitat type, suggesting that scale and landscape structure may be important for more mobile taxa. For each of these taxa, the rustic plantation was the one that maintained species richness most similar to the forest. We found no correlation between the three taxa, suggesting that none of these taxa are good candidates as surrogates for each other. We discuss the implications of these results for the conservation of biodiversity in coffee plantations, in particular, the importance of distinguishing between different levels of shade, and the possibility that different taxa might be responding to habitat changes at different spatial scales.
Complete mitochondrial genomes of three lizard species and the systematic position of the Lacertidae (Squamata)

Complete mitochondrial (mt) genomes were sequenced from representatives of three lacertid lizards: Podarcis siculus, Podarcis muralis and Phoenicolacerta kulzeri. In all three genomes the arrangement of the 22 tRNAs, the two rRNAs and the 13 protein-coding genes conforms to the common vertebrate arrangement. The phylogenetic position of Lacertidae within the order Squamata was determined through sequence analyses based on large sections of complete mt genomes. The number of nucleotide sites used for tree construction was 9234 when outgroup taxa were included, and 10 499 when only Squamata were compared. The phylogenetic analyses confirmed the sister group relationship between Lacertidae and Amphisbaenia as previously proposed on the basis of molecular data. Additionally, Bayesian analysis revealed a well supported clade comprising (Gekkonidae (Lacertidae + Amphisbaenia)), which is not in accordance with the traditional morphological view and most of the previous molecular studies. It confirms, however, the close relationship between Gekkonidae and Amphisbaenia as revealed in a recent study based on complete mt genomes from a smaller number of taxa. Intra- and intergeneric sequence comparisons of six commonly used marker genes showed rather high levels of divergence within the Lacertidae. In the intrageneric comparison the control region proved to be considerably more conserved than the protein coding genes.
IgG4-related paratesticular pseudotumor in a patient with autoimmune pancreatitis and retroperitoneal fibrosis: An extrapancreatic manifestation of IgG4-related disease

Summary In this report, we describe the first case of a patient with an IgG4–related paratesticular pseudotumor. He had histologically proven autoimmune pancreatitis, then later developed a scrotal mass. The orchiectomy specimen revealed that this was a paratesticular pseudotumor with histopathologic and immunohistochemistry findings characteristic of IgG4–related disease. Paratesticular pseudotumors are uncommon causes of intrascrotal masses and have an unexplained pathogenesis. A variety of genitourinary manifestations of IgG4–related disease including IgG4–related tubulointerstitial nephritis, IgG4–related ureteral pseudotumors, and IgG4–related prostatitis has been previously reported. The current case highlights the need to have a high index of suspicion for IgG4 –tissue infiltration in patients with known autoimmune pancreatitis, particularly those with a pseudotumor.
Noise temperature measurement uncertainty analysis using Monte Carlo simulations

Noise temperature measurement uncertainty is analyzed for a commercial noise measurement system. The system noise equation is used with measured data sets to develop a program to determine the receiver parameter uncertainties through the use of a Monte Carlo (MC) simulation, a non-linear fitting routine, and an uncertainty extraction routine. Noise temperature uncertainty results are presented for both correlated and uncorrelated underlying uncertainties. In addition, the dependence of the noise temperature uncertainty on receiver parameter uncertainties is also explored and the most significant results are presented.
Practical range camera calibration

This paper presents a calibration procedure adapted to a range camera intended for space applications. The range camera, which is based upon an auto-synchronized triangulation scheme, can measure objects from about 0.5 m to 100 m. The field of view is 30 degree(s) X 30 degree(s). Objects situated at distances beyond 10 m can be measured with the help of cooperative targets. Such a large volume of measurement presents significant challenges to a precise calibration. A two-step methodology is proposed. In the first step, the close-range volume (from 0.5 m to 1.5 m) is calibrated using an array of targets positioned at known locations in the field of view of the range camera. A large number of targets are evenly spaced in that field of view because this is the region of highest precision. In the second step, several targets are positioned at distances greater than 1.5 m with the help of an accurate theodolite and electronic distance measuring device. This second step will not be discussed fully here. The internal and external parameters of a model of the range camera are extracted with an iterative nonlinear simultaneous least-squares adjustment method. Experimental results obtained for a close-range calibration suggest a precision along the x, y and z axes of 200 micrometers , 200 micrometers , and 250 micrometers , respectively, and a bias of less than 100 micrometers in all directions.
Association between substandard classroom ventilation rates and students' academic achievement

Abstract This study focuses on the relationship between classroom ventilation rates and academic achievement. One hundred elementary schools of two school districts in the southwest United States were included in the study. Ventilation rates were estimated from fifth-grade classrooms (one per school) using CO2 concentrations measured during occupied school days. In addition, standardized test scores and background data related to students in the classrooms studied were obtained from the districts. Of 100 classrooms, 87 had ventilation rates below recommended guidelines based on ASHRAE Standard 62 as of 2004. There is a linear association between classroom ventilation rates and students’ academic achievement within the range of 0.9–7.1 l/s per person. For every unit (1 l/s per person) increase in the ventilation rate within that range, the proportion of students passing standardized test (i.e., scoring satisfactory or above) is expected to increase by 2.9% (95%CI 0.9–4.8%) for math and 2.7% (0.5–4.9%) for reading. The linear relationship observed may level off or change direction with higher ventilation rates, but given the limited number of observations, we were unable to test this hypothesis. A larger sample size is needed for estimating the effect of classroom ventilation rates higher than 7.1 l/s per person on academic achievement. Practical Implications The results of this study suggest that increasing the ventilation rates toward recommended guideline ventilation rates in classrooms should translate into improved academic achievement of students. More studies are needed to fully understand the relationships between ventilation rate, other indoor environmental quality parameters, and their effects on students’ health and achievement. Achieving the recommended guidelines and pursuing better understanding of the underlying relationships would ultimately support both sustainable and productive school environments for students and personnel.
Strong bandwidth and efficiency improvement by passive pulse shaping in cavity-enhanced OPCPA

An enhancement cavity can optimally reshape the small-signal gain across the interacting pulses of a chirped-pulse parametric amplifier, increasing the gain bandwidth dramatically while simultaneously boosting the conversion efficiency.
Dynamics of biosonar systems in Horseshoe bats

Horseshoe bats have an active ultrasonic sonar system that allows the animals to navigate and hunt prey in structure-rich natural environments. The physical components of this biosonar system contain an unusual dynamics that could play a key role in achieving the animals’ superior sensory performance. Horseshoe bat biosonar employs elaborate baffle shapes to diffract the outgoing and incoming ultrasonic wave packets; ultrasound is radiated from nostrils that are surrounded by noseleaves and received by large outer ears. Noseleaves and pinnae can be actuated while ultrasonic diffraction takes place. On the emission side, two noseleaf parts, the anterior leaf and the sella, have been shown to be in motion in synchrony with sound emission. On the reception side, the pinnae have been shown to change their shapes by up to 20% of their total length within ∼100 milliseconds. Due to these shape changes, diffraction of the incoming and outgoing waves is turned into a dynamic physical process. The dynamics of the diffraction process results in likewise dynamic device characteristics. If this additional dynamic dimension was found to enhance the encoding of sensory information substantially, horseshoe bat biosonar could be a model for the use of dynamic physical processes in sensing technology.
Four Blunders in the Electroweak Unification

We derive the Higgs mass to be 123 GeV; we also show that the standard electroweak theory is false by highlighting the fact that the photon nevertheless receives a rest mass along with the Z boson despite the linear transformation known as the Weinberg angle.
ESA 2010 Chapter 9 Supply and Use Tables and the Input-Output Framework

This chapter of the new European guidelines on national accounting (ESA 2010) provides an introduction and overview of supply and use tables and the input-output framework in the national accounts. It discusses its role as a statistical tool, e.g. in compiling estimates of value added by industry, estimates of GDP according to the various approaches or calculating price and volume measures. It also discusses its role as a tool for analysis.
An x-ray backlit Talbot-Lau deflectometer for high-energy-density electron density diagnostics

X-ray phase-contrast techniques can measure electron density gradients in high-energy-density plasmas through refraction induced phase shifts. An 8 keV Talbot-Lau interferometer consisting of free standing ultrathin gratings was deployed at an ultra-short, high-intensity laser system using K-shell emission from a 1-30 J, 8 ps laser pulse focused on thin Cu foil targets. Grating survival was demonstrated for 30 J, 8 ps laser pulses. The first x-ray deflectometry images obtained under laser backlighting showed up to 25% image contrast and thus enabled detection of electron areal density gradients with a maximum value of 8.1 ± 0.5 × 1023 cm−3 in a low-Z millimeter sized sample. An electron density profile was obtained from refraction measurements with an error of <8%. The 50 ± 15 μm spatial resolution achieved across the full field of view was found to be limited by the x-ray source-size, similar to conventional radiography.
Kinetics of Magnetite (Fe3O4) Oxidation to Hematite (Fe2O3) in Air for Chemical Looping Combustion

Thermogravimetric analysis (TGA) of magnetite (Fe3O4) oxidation was conducted at temperatures ranging from 750 to 900 °C over 10 oxidation cycles. Oxidation experiments were carried out in a continuous stream of air for period of 30 min. The oxidized magnetite (Fe3O4), which resulted in formation of hematite (Fe2O3), was then reduced by using continuous stream of CO (5% and 10%) with N2 balance. The rate of oxidation was determined by the oxygen weight gain. Analysis of the data indicated that the oxidation behavior followed a two-stage process. The initial oxidation, which was very fast, took place in 2 min and was described using nucleation and growth processes with a low activation energy of about 4.21 ± 0.45 kJ/mol. As the reaction developed within the surface, oxygen transport through the product layer become the rate-controlling step with activation energy of 53.58 ± 3.56 kJ/mol.
Tangible Prayer in Early Judaism and Early Christianity

Both the Jewish and Christian faiths view prayer as dialogue with the God of Israel. Prayer assumes that God is near to those in need and is attentive to the cries of the saints. Those who pray to God can hope and believe that God will hear or acknowledge their prayers. Yet there exists a tradition in both early Judaism and early Christianity, especially in apocalyptic thought but not exclusive to it, that views prayers as something tangible and, therefore, requiring an intermediary to transport and present before God. This notion of prayer complicates the assumption that God hears all prayers, for according to this tradition the angel bearing the prayers of the saints and/or God's response to the prayers may face obstacles while transporting the prayers to God or God's response to humans.
The Lab-on-a-Chip Approach for Molecular Diagnostics

Publisher Summary This chapter provides a brief introduction of the impact of the lab-on-a-chip approach upon future practices in clinical molecular diagnostics. Special emphasis is placed on biological sample preparation, as well as on-chip genetic analysis based on polymerase chain reaction (PCR) and detection of single molecules. Molecular diagnostics uses powerful tools such as DNA sequence analysis, gene expression profiling, and detection of biomarkers to determine the susceptibility of individuals to certain disease and existing disease states. In a typical laboratory setup, molecular diagnosis often involves multiple preparation steps (such as sample collection, extraction, purification, and transportation) prior to detection and data collection. Many of these steps are often time-consuming and expensive because they require manual operation by laboratory personnel. Current molecular diagnostic procedures need to be integrated, automated, and streamlined in order to increase the speed and throughput of the laboratory tests. In addition, there is an increasing need to decentralize the molecular diagnostics practices. The major benefits of such lab-on-a-chip approaches include speed, cost, and system integration and automation. In a microfluidic device, various diagnostic steps can be seamlessly integrated in a single microchip. As a result, diagnostic procedures can be dramatically simplified and accelerated. The development of microfluidics technologies combined with various molecular manipulations and sensing mechanisms is giving rise to a new platform for molecular diagnostics.
Analyzing cross-layer interaction in overlay networks

Overlay networks have recently gained popularity as a viable alternative to overcome functionality limitations of the Internet (e.g., lack of QoS, multicast routing). They offer enhanced functionality to end-users by forming an independent and customizable virtual network over the native network. Furthermore, they are being widely promoted as a potential architecture of the future Internet in the form of network virtualization, where multiple heterogeneous virtual networks may co-exist on top of a shared native network. The prominent characteristic in either context is that routing at the overlay layer operates independent of that at the underlying native layer. There are several potential problems with this approach because overlay networks are selfish entities that are chiefly concerned with achieving the routing objective of their own users. This leads to complex cross-layer interactions between the native and overlay layers, and often tends to degrade the achieved performance for both layers. As overlay applications proliferate and the amount of selfish overlay traffic surges, there is a clear need for understanding the complex interactions and for strategies to manage them appropriately. Our work addresses these issues in the context of service overlay networks, which represent virtual networks formed of persistent nodes that collaborate to offer improved services to actual end-systems. Typically, service overlays alter the route between the overlay nodes in a dynamic manner in order to satisfy a selfish objective. The objective of this thesis is to improve the stability and performance of overlay routing in this multi-layer environment. We investigate the common problems of functionality overlap, lack of cross-layer awareness, mismatch or misalignment in routing objectives and the contention for native resources between the two layers. These problems often lead to deterioration in performance for the end-users. This thesis presents an analysis of the cross-layer interaction during fault recovery, inter-domain policy enforcement and traffic engineering in the multi-layer context. Based on our characterization of the interaction, we propose effective strategies that improve overall routing performance, with minimal side-effects on other traffic. These strategies typically (1) increase the layer-awareness (awareness of information about the other layer) at each layer, (2) introduce better control over routing dynamics and (3) offer improved overlay node placement options. Our results demonstrate how applying these strategies lead to better management of the cross-layer interaction, which in turn leads to improved routing performance for end-users.
Fast indirect fluorine-18 labeling of protein/peptide using the useful 6-fluoronicotinic acid-2,3,5,6-tetrafluorophenyl prosthetic group: A method comparable to direct fluorination.

Fluorine-18 labeling of biomolecules is mostly performed by an indirect labeling method using a prosthetic group. Fluorine-18 labeled 6-fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester is a useful prosthetic group to radiolabel a protein. Recently, we reported an improved preparation of this prosthetic group. To test the conjugation efficiency of the labeled ester prepared by this method, we have performed conjugation reactions with a peptide, a protein, and a small molecule. Prostate-specific membrane antigen targeting small molecule [18 F]DCFPyL, αvβ3 integrin receptors targeting peptide [18 F]c(RGDfK) and [18 F]albumin were prepared in good radiochemical yields. The conjugation reactions were completed at 40°C to 50°C in 10 minutes. The overall radiochemical yield was 25% to 43% in 30 to 45 minutes.
In Vivo RNAi Screen Unveils PPARγ as a Regulator of Hematopoietic Stem Cell Homeostasis.

Summary Hematopoietic stem cell (HSC) defects can cause repopulating impairment leading to hematologic diseases. To target HSC deficiency in a disease setting, we exploited the repopulating defect of Fanconi anemia (FA) HSCs to conduct an in vivo short hairpin RNA (shRNA) screen. We exposed Fancd2 −/− HSCs to a lentiviral shRNA library targeting 947 genes. We found enrichment of shRNAs targeting genes involved in the PPARγ pathway that has not been linked to HSC homeostasis. PPARγ inhibition by shRNA or chemical compounds significantly improves the repopulating ability of Fancd2 −/− HSCs. Conversely, activation of PPARγ in wild-type HSCs impaired hematopoietic repopulation. In mouse HSCs and patient-derived lymphoblasts, PPARγ activation is manifested in upregulating the p53 target p21. PPARγ and co-activators are upregulated in total bone marrow and stem/progenitor cells from FA patients. Collectively, this work illustrates the utility of RNAi technology coupled with HSC transplantation for the discovery of novel genes and pathways involved in stress hematopoiesis.
A decentralized energy-optimal control framework for connected automated vehicles at signal-free intersections

Abstract We address the problem of optimally controlling connected and automated vehicles (CAVs) crossing an urban intersection without any explicit traffic signaling, so as to minimize energy consumption subject to a throughput maximization requirement. We show that the solution of the throughput maximization problem depends only on the hard safety constraints imposed on CAVs and its structure enables a decentralized optimal control problem formulation for energy minimization. We present a complete analytical solution of these decentralized problems and derive conditions under which feasible solutions satisfying all safety constraints always exist. The effectiveness of the proposed solution is illustrated through simulation which shows substantial dual benefits of the proposed decentralized framework by allowing CAVs to conserve momentum and fuel while also improving travel time.
Clinical overview of the current state and future applications of positron emission tomography in bone and soft tissue sarcoma

Positron emission tomography (PET) provides a noninvasive, functional assessment providing incremental diagnostic value over magnetic resonance imaging (MRI) and computed tomography (CT) for the initial staging, restaging, response assessment, and prognosis of bone and soft tissue sarcomas. The purpose of this article is to review the current state and future applications of PET in sarcoma imaging, including the clinical roles of 18F-fluorodeoxyglucose (FDG) and other PET radiotracers as well as the use of PET with concurrent MRI. A PubMed search using the query “(‘positron emission tomography’ OR PET) AND (‘CT’ OR ‘computed tomograph*’ OR ‘MR*’ OR ‘magnetic resonance’) AND (FDG OR hypox* OR prolif*) AND sarcoma*” for PET examinations involving bone and soft tissue sarcoma studies up to February 1, 2017 were performed. Additionally, analogous Google Scholar, Scopus, and Web of Science search queries were also performed. Subsequently, references for the retrieved articles were reviewed, and the relevant publications on the subject were also included. A total of 30 studies were included in the review. FDG-PET with concurrent computed tomography (CT) can provide incremental diagnostic value relative to MRI to provide additional insight into the grading, staging, restaging, and response assessment in sarcomas, particularly when neoadjuvant therapy is an option. FDG-PET/CT can be used for noninvasive prediction of tumor grade and assess regional heterogeneity, providing guidance for tissue sampling and reducing the risk of undergrading and understaging. In addition, early clinical studies of sarcoma PET imaging using hypoxia and cellular proliferation agents suggest incremental diagnostic benefit over FDG-PET. The use of PET/MRI is under active investigation and may yield additional clinically impactful findings over PET/CT. PET imaging used with concurrent CT or MRI provides a unique noninvasive way to assess regional biological and biochemical features for bone and soft tissue sarcomas.
Fungi and seed quality

Fungal organisms developing in grain in store lead to hot spots and increased moisture content. Uncontrolled, deterioration is rapid, resulting in loss of viability in grain for seed, and off-flavo...
Sturge–Weber Syndrome

A 6-year-old girl was brought to the emergency department with sudden onset of weakness in the left arm and leg. Physical examination and MRI suggested a diagnosis of the Sturge–Weber syndrome.
Central corneal thickness assessment after phacoemulsification: Subluxation versus Divide-and-Conquer.

Summary Purpose To compare the impact of two phacoemulsification techniques (subluxation versus divide-and-conquer) on postoperative corneal edema at postoperative hour 1 and day 4. Design Comparative study. Method Ninety-six consecutive patients (110 eyes; 43 men and 53 women, mean age 70.9 ± 9.8 years) with equivalent cataract grades underwent cataract surgery and were followed up for 6 months. The presence of corneal edema was determined using central corneal thickness (CCT). CCT was measured preoperatively, and at postoperative hour 1 and day 4. Main outcome measures Ultrasound power (US %), duration of ultrasound (TPA), effective ultrasound time (TPE), surgical duration and final suture (%). Results Eyes of participants were divided into two phacoemulsification technique groups: subluxation ( n = 50 eyes) and divide-and-conquer (n = 60 eyes). Non-inferiority analysis revealed similar CCT increases at postoperative hour 1 in both groups, with 69.9 ± 44.9 μm and 64.4 ± 42.9 μm, observed in the subluxation and divide-and-conquer groups, respectively (P = 0.033). TPE was similar in both groups, taking 6.2 ± 3.4 and 7.3 ± 4.5 seconds in the subluxation and divide-and-conquer groups, respectively (P = 0.150). No correlation was seen between TPE and edema at postoperative hour 1, or between TPE and day 4 edema. Rate of final suture use was similar between the subluxation and divide and conquer groups, at 36% and 30%, respectively. Conclusion The study findings suggest that cataract surgery performed using the subluxation technique does not result in greater CCT than the divide-and-conquer technique. CCT appears to normalize by postoperative day 4, regardless of the technique used.
Denouement: Notes on the End(s) of Activism

On June 26, 2015, the Supreme Court ruled that same-sex marriages were legal in the United States. Among those shedding tears of joy was Evan Wolfson, founder of the advocacy group Freedom to Marry.
The role of hepatic cytochrome P450s in the cytotoxicity of dronedarone

Dronedarone is used to treat patients with cardiac arrhythmias and has been reported to be associated with liver injury. Our previous mechanistic work demonstrated that DNA damage-induced apoptosis contributes to the cytotoxicity of dronedarone. In this study, we examined further the underlying mechanisms and found that after a 24-h treatment of HepG2 cells, dronedarone caused cytotoxicity, G1-phase cell cycle arrest, suppression of topoisomerase II, and DNA damage in a concentration-dependent manner. We also investigated the role of cytochrome P450s (CYPs)-mediated metabolism in the dronedarone-induced toxicity using our previously established HepG2 cell lines expressing individually 14 human CYPs (1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5, and 3A7). We demonstrated that CYP3A4, 3A5, and 2D6 were the major enzymes that metabolize dronedarone, and that CYP3A7, 2E1, 2C19, 2C18, 1A1, and 2B6 also metabolize dronedarone, but to a lesser extent. Our data showed that the cytotoxicity of dronedarone was decreased in CYP3A4-, 3A5-, or 2D6-overexpressing cells compared to the control HepG2 cells, indicating that the parent dronedarone has higher potency than the metabolites to induce cytotoxicity in these cells. In contrast, cytotoxicity was increased in CYP1A1-overexpressing cells, demonstrating that CYP1A1 exerts an opposite effect in dronedarone's toxicity, comparing to CYP3A4, 3A5, or 2D6. We also studied the involvement of topoisomerase II in dronedarone-induced toxicity, and demonstrated that the overexpression of topoisomerase II caused an increase in cell viability and a decrease in γ-H2A.X induction, suggesting that suppression of topoisomerase II may be one of the mechanisms involved in dronedarone-induced liver toxicity.
Are Karrikin Signaling Mechanisms Relevant to Strigolactone Perception

Karrikins found in smoke and the synthetic strigolactone GR24 induce similar developmental effects during early stages of Arabidopsis thaliana growth, including promotion of seed germination. Responses to karrikins and strigolactones are distinct at other growth stages, such as during the repression of axillary shoot growth. The F-box protein MAX2 is required for both signalling pathways. Two α-/β-hydrolase superfamily proteins, KAI2 and D14, control subsets of MAX2-regulated development. KAI2 is required for seed germination responses to karrikin and strigolactone treatments, while D14 mediates strigolactone-specific control of shoot branching. It is hypothesized that an orthologous pathway controls host-specific germination of the obligate parasitic Orobanchaceae.
Effects of exercise mode on hematologic adaptations to endurance training in adult females

Background: The subjects were 26 healthy, sedentary adult females with the following characteristics: maximal oxygen consumption (Vo 2 -max) 32.0 ± 7.2 ml . kg -1 . min -1 ; age = 32 ± 5 yr; body mass index (BMI) = 23.2 ± 3.4 kg. m -2 who were randomly assigned to control (CON; N = 8); treadmill training (TM; N = 8); or cycle ergometer training (CY; N = 10) to test the hypothesis that hematologic adaptations to endurance exercise training are specific to mode of exercise. Methods: Training, conducted 3-5 (3.4 ± 0.06) d. week -1 at 80% of mode specific Vo 2 max for 12 weeks, was supervised and progressive, with estimated exercise energy expenditure equated across training groups. Plasma volume (PV, T-1824 dilution); calculated total blood (THb) and red cell volumes (RCV); calculated total hemoglobin (THb) and other hematologic variables were measured at baseline and weeks 2, 4, 8 and 12 of training. Results: Across 12 weeks of training, PV was decreased (95% of baseline) in the TM group but increased (106% of baseline) in the CY group (p = 0.06). Similar trends were observed for RCV (p = 0.15) and TBV (p = 0.08). These results are in contrast to reported changes in PV, TBV and RCV in males following training. Hemodilution was observed in both training groups, reflected by decreases (p < 0.05) in hematocrit (Hct), hemoglobin (Hb) and RC count. Mean corpuscular Hb (MCH) and Hb content (MCHC) increased (p < 0.05) with training. These changes, as well a trend toward increased (p = 0.08) mean corpuscular volume (MCV), suggested the probable presence of a RC population with a lower mean age and decreased oxyhemoglobin affinity. The possibility of Type II error cannot be discounted in these trends, which suggest that PV, TBV and RCV may be affected by mode of endurance exercise in females.
Potential genetic resources in tomato species: clues from observations in native habitats.

Interspecific hybridization is playing an increasingly important role in the breeding of improved cultivars of higher plants. Lycopersicon is a good example of a genus in which the cultivated species (L. esculentum Mill.) is being improved in this fashion. The advantages offered by the tomato species for this purpose are: a. All species can be readily grown for experimental purposes, and L. esculentum is widely cultivated under a wide range of environmental conditions. b. Excellent sources of germ plasm now exist in the wild species as well as in modern and primitive cultivars of L. esculentum. c. All of the wild species can be hybridized with L. esculentumn, albeit requiring special aids in certain combinations; fertility and viability of the hybrid generations permit the intended gene transfers. All species have 12 pairs of chromosomes, which are essentially homologous. d. The cultivated species is well known genetically; its chromosomes have been mapped cytologically and genetically; it behaves as a basic diploid (27, 28).
Identification of the XRCC4 Gene: Complementation of the DSBR and V(D)J Recombination Defects of XR-1 Cells

Antigen receptor variable region genes are assembled from component gene segments during the differentiation of B and T lymphocytes (Lansford et al. 1995). This process, termed V(D)J recombination, is initiated by RAG-1 and RAG-2, the only lymphoid-specific proteins required for this reaction (Schatz et al. 1989; Oettinger et al. 1990; Mombaerts et al. 1992; Shinkai et al. 1992). Expression of RAG-1 and RAG-2 promotes cleavage at the junction of the V D, or J coding segments and their flanking recognition sequences (RS), generating hairpin-like coding ends and blunt RS ends (van Gent et al. 1995). Subsequent joining of the liberated DNA ends appears to involve more generally expressed proteins including several proteins that also participate in DNA double-strand break repair (DSBR) (reviewed by Taccioli and Alt 1995).