cssi/SciSciGPT-SciSciNet huggingface dataset:
Extracellular Fibrils of Pathogenic Yeast Cryptococcus gattii Are Important for Ecological Niche, Murine Virulence and Human Neutrophil Interactions

Cryptococcus gattii, an emerging fungal pathogen of humans and animals, is found on a variety of trees in tropical and temperate regions. The ecological niche and virulence of this yeast remain poorly defined. We used Arabidopsis thaliana plants and plant-derived substrates to model C. gattii in its natural habitat. Yeast cells readily colonized scratch-wounded plant leaves and formed distinctive extracellular fibrils (40–100 nm diameter ×500–3000 nm length). Extracellular fibrils were observed on live plants and plant-derived substrates by scanning electron microscopy (SEM) and by high voltage- EM (HVEM). Only encapsulated yeast cells formed extracellular fibrils as a capsule-deficient C. gattii mutant completely lacked fibrils. Cells deficient in environmental sensing only formed disorganized extracellular fibrils as apparent from experiments with a C. gattii STE12α mutant. C. gattii cells with extracellular fibrils were more virulent in murine model of pulmonary and systemic cryptococcosis than cells lacking fibrils. C. gattii cells with extracellular fibrils were also significantly more resistant to killing by human polymorphonuclear neutrophils (PMN) in vitro even though these PMN produced elaborate neutrophil extracellular traps (NETs). These observations suggest that extracellular fibril formation could be a structural adaptation of C. gattii for cell-to-cell, cell-to-substrate and/or cell-to- phagocyte communications. Such ecological adaptation of C. gattii could play roles in enhanced virulence in mammalian hosts at least initially via inhibition of host PMN– mediated killing.
CbrA Is a Stationary-Phase Regulator of Cell Surface Physiology and Legume Symbiosis in Sinorhizobium meliloti

Sinorhizobium meliloti produces an exopolysaccharide called succinoglycan that plays a critical role in promoting symbiosis with its host legume, alfalfa (Medicago sativa). We performed a transposon mutagenesis and screened for mutants with altered succinoglycan production and a defect in symbiosis. In this way, we identified a putative two-component histidine kinase associated with a PAS sensory domain, now designated CbrA (calcofluor-bright regulator A). The cbrA::Tn5 mutation causes overproduction of succinoglycan and results in increased accumulation of low-molecular-weight forms of this exopolysaccharide. Our results suggest the cbrA::Tn5 allele leads to this succinoglycan phenotype through increased expression of exo genes required for succinoglycan biosynthesis and modification. Interestingly, CbrA-dependent regulation of exo and exs genes is observed almost exclusively during stationary-phase growth. The cbrA::Tn5 mutant also has an apparent cell envelope defect, based on increased sensitivity to a number of toxic compounds, including the bile salt deoxycholate and the hydrophobic dye crystal violet. Growth of the cbrA mutant is also slowed under oxidative-stress conditions. The CbrA-regulated genes exsA and exsE encode putative inner membrane ABC transporters with a high degree of similarity to lipid exporters. ExsA is homologous to the Escherichia coli MsbA protein, which is required for lipopolysaccharide transport, while ExsE is a member of the eukaryotic family of ABCD/hALD peroxisomal membrane proteins involved in transport of very long-chain fatty acids, which are a unique component of the lipopolysaccharides of alphaproteobacteria. Thus, CbrA could play a role in regulating the lipopolysaccharide or lipoprotein components of the cell envelope.
An improved transmission strategy for multiple antenna channels with partial feedback

We investigate transmission strategies for multiple antenna systems with partial spatial information of channel available at the transmitter. A new beamforming method is proposed in which the beamforming matrix is determined from the partial spatial information in a novel but predefined way; as a result, the receiver also knows the beamforming matrix. With this beamforming scheme, we develop a multiple antenna system concept that enables better use of the multiple-input-multiple-output (MIMO) channels from a channel capacity perspective. The results show that the proposed methods lead to systems wherein the amount of channel feedback information can be significantly reduced with a minor sacrifice of achievable transmission rate.
A comparative study on the consistency of features in on-line signature verification

A large number of features have been proposed by researchers for on-line signature verification. However, little work has been done in measuring the consistency and discriminative power of these features. This paper presents a comparative study of features commonly used in on-line signature verification. A consistency model is developed by generalizing the existing feature-based measure to distance-based measure. Experimental results show that the simple features like X-, Y-coordinates, the speed of writing and the angle with the X-axis are amongst the most consistent.
Zebrafish stromal cells have endothelial properties and support hematopoietic cells

The goal of this study was to determine if we could establish a mesenchymal stromal line from zebrafish that would support hematopoietic cells. Such a coculture system would be a great benefit to study of the hematopoietic cell−stromal cell interaction in both in vitro and in vivo environments. Zebrafish stromal cells (ZStrC) were isolated from the "mesenchymal" tissue of the caudal tail and expanded in a specialized growth media. ZStrC were evaluated for phenotype, gene expression, and ability to maintain zebrafish marrow cells in coculture experiments. ZStrC showed mesenchymal and endothelial gene expression. Although ZStrC lacked the ability to differentiate into classic mesenchymal stromal cell lineages (i.e., osteocytes, adipocytes, chondrocytes), they did have the capacity for endotube formation on Matrigel and low-density lipoprotein uptake. ZStrC supported marrow cells for >2 weeks in vitro. Importantly, marrow cells were shown to retain homing ability in adoptive transfer experiments. ZStrC were also shown to improve hematopoietic recovery after sublethal irradiation after adoptive transfer. As the zebrafish model grows in popularity and importance in the study of hematopoiesis, new tools to aid in our understanding of the hematopoietic cell−stromal cell interaction are required. ZStrC represent an additional tool in the study of hematopoiesis and will be useful in understanding the factors that mediate the stromal cell−hematopoietic cell interactions that are important in hematopoietic cell maintenance.
A voltage-dependent gating transition induces use-dependent block by tetrodotoxin o rat IIA sodium channels expressed in xenopus oocytes

We have utilized molecular biological techniques to demonstrate that rat IIA sodium channels expressed in Xenopus oocytes were blocked by tetrodotoxin (TTX) in a use-dependent manner. This use dependence was the result of an increased affinity of the channels for TTX upon depolarization, most likely due to a conformational change in the channel. Using a mutant with a slower macroscopic rate of inactivation, we have demonstrated that this conformational change is not the transition into the fast-inactivated state. The transition is probably one occurring during activation of the channel, as suggested by the fact that one sodium channel mutant demonstrated comparable depolarizing shifts in the voltage dependence of both activation and use-dependent block by TTX. The transition occurred at potentials more negative than those resulting in channel conductance, suggesting that the conformational change that causes use-dependent block by TTX is a closed-state voltage-dependent gating transition.
Access to Courts and Preemption of State Remedies in Collective Action Perspective

Preemption of common law remedies for individual injuries such as harm to health raises fundamental questions about the proper allocation of authority between the federal and state governments and about the role of courts in interpreting statutes and providing remedies for those who suffer injuries. Developing a workable framework for analyzing what we call “remedial preemption” issues can help to ensure an appropriate accommodation of the federal and state interests at stake and promote consistent application of preemption doctrine to state judicial remedies. This article applies a “collective action” framework for preemption analysis to the issue of remedial preemption. Our analysis suggests that while remedial preemption may be justified in some cases, courts should not lightly infer remedial preemption unless: (1) a primary purpose of the federal law is to ensure uniform standards to promote free movement of goods, prevent the export of regulatory burdens by “downstream” states, or solve a not-in-my-backyard problem; and (2) there is strong evidence that state judicial remedies (as opposed to direct state regulation through legislation or the actions of administrative agencies) would interfere with the achievement of those goals. In addition, we conclude that preemption of one common law cause of action does not necessarily warrant preemption of different causes of action for remediation of the same injury. Finally, we argue that courts should be especially reluctant to read the preemptive effect of federal law so as to leave injured persons without any remedy whatsoever. In doing so we pay particular attention to the ways in which state judicial remedies differ from state regulation by means of statutes or administrative rules, including the differences between legislatures and courts, between legislative rules and judicial decisions, and among possible preemptive effects on judicial remedies. We conclude by analyzing how the Supreme Court’s 2009 holding in Wyeth v. Levine that state tort remedies based on failure-to-warn claims were not preempted by federal regulation of the content of warning labels for drugs comports with our analysis.
In the enemy's camp: Homer's Helen and Ferdowsi's Hojir

This paper will attempt to compare a famous scene in Ferdowsi's Shahnameh with an equally well-known one in Homer's Iliad. There are broadly three ways in which such a comparison can be made. Similarities and differences can be ascribed to reasons of genre, or to the nature of the underlying mythical material and sources utilized by the poets in question, or to a consciousness of, and use by, the later poet of the earlier poet's work, at whatever stage of remoteness. Elsewhere I have touched on genre as a cause for apparent similarities between the two superficially quite different epic traditions of Greece and Iran, indicating that the king/champion conflict described by W. T. H. Jackson as typical of the European epic is also a characteristic of the Iranian Shchncmeh.1 The most usual and perhaps most suggestively fruitful kind of comparison is that implying a common source in Indo-European myth for episodes in Greek mythology and episodes in the earlier mythical and legendary stages of the Shahnameh; the Greek story of Prometheus, for example, seems to be a close parallel to the story of Jamshid and Zahhak-Jamshid's introduction of the arts of civilization and his sense of himself as rivaling in power the supreme God echoing similar topoi in the story of Prometheus, and the punishment meted out to his rival, Zahhak, with whom he is closely associated, being a parallel to that meted out to Prometheus himself, so that what appears as a story about one mythological figure in the Greek sources appears as a story about two associated figures in the Persian sources.
Another thin-film limit of micromagnetics

We consider the variational problem of micromagnetics for soft, relatively small thin films with no applied magnetic field. In terms of the film thickness t, the diameter l and the magnetic exchange length w, we study the asymptotic behavior in the small-aspect-ratio limit t/l→0, when either (a) w2/l2≫(t/l)| log (t/l)| or (b) w2/l2∼(t/l)| log (t/l)|. Our analysis builds on prior work by Gioia & James and Carbou. The limiting variational problem is much simpler than 3D micromagnetics; in particular it is two-dimensional and local, with no small parameters. The contribution of shape anisotropy reduces, in this limit, to a constant times the boundary integral of (m·n)2.
Duodenal Gangliocytic Paraganglioma With Lymph Node Metastasis: A Case Report and Review of the Literature

A case of duodenal gangliocytic paraganglioma (DGP) in a 67-year-old woman is presented. The DGP arose in the second part of the duodenum. Although most of the reported cases of DGP are considered benign, in the present case, we found regional lymph nodes containing metastatic tumor. Previous reports have documented metastases containing only epithelioid cells. The current case demonstrates metastatic tumor in regional lymph nodes containing all 3 of the DGP components (spindle cells, ganglion-like cells, and epithelioid cells).
Purification of rat liver microsomal cytochrome P-450b without the use of nonionic detergent.

Sodium cholate, Emulgen 911, and (3-[(-cholamidopropyl)-dimethyl- ammonio]-1-propanesulfonate) (CHAPS) were selected to examine the effects of ionic, nonionic, and zwitterionic detergents on testosterone hydroxylation catalyzed by four purified isozymes of rat liver microsomal cytochrome P-450, namely P-450a, P-450b, P-450c, and P-450h, in reconstituted systems containing optimal amounts of dilauroylphosphatidylcholine and saturating amounts of NADPH- cytochrome P-450 reductase (reductase). The major phenobarbital-inducible form of rat liver microsomal cytochrome P-450, designated P-450b, was extremely sensitive to the inhibitory effects of Emulgen 911, which is used in several procedures to purify this and other forms of cytochrome P-450. In contrast, sodium cholate and CHAPS had little effect on the catalytic activity of cytochrome P-450b, even at ten times the concentration of Emulgen 911 effecting 50% inhibition (IC-50). By substituting the zwitterionic detergent CHAPS for Emulgen 911, we purified cytochrome P-450b without the use of nonionic detergent. The protein is designated cytochrome P-450b* to distinguish it from cytochrome P-450b purified with the use of Emulgen 911. NADPH-cytochrome P-450 reductase was also purified both with and without the use of nonionic detergent. The absolute spectra of cytochrome P-450b and P-450b* were indistinguishable, as were the carbon monoxide (CO)- and metyrapone-difference spectra of the dithionite-reduced hemoproteins. When reconstituted with NADPH-cytochrome P-450 reductase and dilauroylphosphatidylcholine, cytochromes P-450b and P-450b* catalyzed the N-demethylation of benzphetamine and aminopyrine, the 4-hydroxylation of aniline, the O-dealkylation of 7-ethoxycoumarin, the 3-hydroxylation of hexobarbital, and the 6-hydroxylation of zoxazolamine. Both hemo-proteins catalyzed the 16α- and 16β-hydroxylation of testosterone, as well as the 17-oxidation of testosterone to androstenedione. Both hemoproteins were poor catalysts of erythromycin demethylation and benzo[a]pyrene 3-/9-hydroxylation. The rate of biotransformation catalyzed by cytochrome P-450b* was up to 50% greater than the rate catalyzed by cytochrome P-450b when reconstituted with either reductase or reductase*. The activity of cytochrome P-450b and P-450b* increased up to 50% when reconstituted with reductase* instead of reductase. In addition to establishing the feasibility of purifying an isozyme of rat liver microsomal cytochrome P-450 without the use of nonionic detergent, these results indicate that the catalytic activity of cytochrome P-450 is not unduly compromised by residual contamination with the nonionic detergent Emulgen 911.
INTRINSIC DRUG RESISTANCE IN PRIMARY AND METASTATIC RENAL CELL CARCINOMA

AbstractMuch remains to be learned about drug resistance in the biology of RCC and its metastases.We measured MDR-1/P-glycoprotein expression in 19 tumor samples from patients with metastatic RCC by RNase protection and quantitative PCR assays. The median level of the 16 tumor metastases was 4.9 (range: 0.10 to 156.2) relative to the level of 10 assigned to a reference cell line, SW620, which has been characterized as expressing a minimum level of MDR-1. Since these levels were lower than expected for RCC, we asked whether the metastases possessed a phenotype different from primary RCC and examined MDR-1 expression in 5 paired cell lines derived from primary and metastatic RCC. In 8/10 lines, MDR-1 expression was >10. Relative to the level in the primary line, MDR-1 expression was decreased (3 to 50-fold) in 3 metastatic lines, was increased in 1, and unchanged in 1. MRP mRNA expression was lower in the metastatic lines while EGFR expression was variable. IC50 values for 6 compounds (including 4 standard ...
Joint Modeling and Estimation for Recurrent Event Processes and Failure Time Data

Recurrent event data are commonly encountered in longitudinal follow-up studies related to biomedical science, econometrics, reliability, and demography. In many studies, recurrent events serve as important measurements for evaluating disease progression, health deterioration, or insurance risk. When analyzing recurrent event data, an independent censoring condition is typically required for the construction of statistical methods. In some situations, however, the terminating time for observing recurrent events could be correlated with the recurrent event process, thus violating the assumption of independent censoring. In this article, we consider joint modeling of a recurrent event process and a failure time in which a common subject-specific latent variable is used to model the association between the intensity of the recurrent event process and the hazard of the failure time. The proposed joint model is flexible in that no parametric assumptions on the distributions of censoring times and latent variab...
Warana Unwired: Replacing PCs with mobile phones in a rural sugarcane cooperative

In this paper, we present what we believe to be the first documented experiment to replace an existing PC-based system that had goals of "bridging the digital divide" for an agricultural district with a mobile-phone-based system in which a small, but relevant amount of data is transferred to farmers via SMS text messaging. Implemented in rural Maharashtra, Warana Unwired sought to replace an existing PC-based system for managing information in a sugarcane cooperative with an SMS-based mobile-phone system. In an eight-month trial involving seven villages, Warana Unwired successfully replicated all of the PC-based functionality, and was found to be less expensive, more convenient, and more popular with farmers than the previous PC-based system. This paper discusses the early investigations of the Warana Wired Village Project that led to the conception and implementation of the Warana Unwired project. The new system is described in detail, and results, both quantitative and qualitative are analyzed.
A non-iterative procedure for maximum likelihood estimation of the parameters of mallows' model based on partial rankings

The problem of maximum likelihood estimation of the parameters of Mallows’ ranking model based on partial rankings (with a fixed number of tie groups) has been approached by Beckett (1992), applying the EM algorithm to estimate both the center and the scale parameter. This paper offers an alternative procedure for maximum likelihood estimation without relying on the EM algorithm:the center is estimated by minimizing the sum of the distances between the center and the observed partial rankings, and the scale parameter is estimated by solving a relatively simple equation.
An Examination of the Factor Structure and Construct Validity of the Gregorc Style Delineator

Cognitive learning style instruments continue to enjoy widespread use in educational and occupational contexts by researchers and practitioners alike, despite widespread questions about the valid measurement of cognitive learning styles. This investigation examines the psychometric properties of one well-known measure of cognitive learning style—the Gregorc Style Delineator (GSD). The GSD was administered to 467 undergraduate and graduate students (49% female) from two major colleges in the mid-Atlantic region of the United States. Using confirmatory and exploratory factor-analytic techniques, Gregorc’s channel theory was investigated as deployed and represented by the instrument. The Cronbach’s alpha coefficients, ranging from .54 to .68, were appreciably lower than those reported by the instrument’s developer. The data disconfirmed both the two- and four-factor confirmatory models. In the post hoc exploratory factor analyses, many of the factor pattern/structure coefficients were ambiguously associated ...
A warped time-frequency expansion for speech signal representation

A novel representation for speech signals is proposed. The time-varying frequency content of a speech segment is represented as a weighted sum of two-dimensional basis vectors; these incorporate both frequency warping and frequency-dependent time warping. This is quite flexible; for example, any arbitrary time or frequency warping function can easily be implemented, and any time-frequency representation can be used as the starting point. Examples are presented which demonstrate desirable characteristics of the representation: (1) explicit quantification of parameter trajectories, (2) time resolution which varies with respect to time and frequency, and (3) the ability to reconstruct a time-frequency plot which reflects the resolution characteristics of the representation. >
The Testing Effect: Illustrating a Fundamental Concept and Changing Study Strategies

An important recent finding is that testing improves learning and memory. In this article, the authors describe a demonstration that illustrates this principle and helps students incorporate more testing into their learning. The authors asked students to read one text using a Study–Study strategy and one text using a Study–Test strategy. One week later, the authors tested students’ memory for both texts with short-answer quizzes. The results revealed the standard testing effect and served as the basis for a laboratory report that required students to analyze and interpret the results and to answer questions about the testing effect and the experimental design. At the end of the term, students indicated that they were engaging in more testing during their studying.
Megakaryocyte-bone cell interactions.

Emerging data show that megakaryocytes (MKs) play a role in the replication and development of bone cells. Both in vivo and in vitro evidence now show that MKs can have significant effects on cells of the osteoclast (OC) and osteoblast (OB) lineage, with obvious manifestations on bone phenotype, and probable significance for human pathology.
Absence of circulating HL-A lymphocytotoxic antibodies in men 21 to 44 months after vasectomy.

Nineteen vasectomized men were followed for 21 to 42 months after surgery, and their sera were tested for the presence of HL-A lymphocytotoxic antibodies. In a previous study, the sera of two of these men had shown a definite increase in serum reactivity 6 to 12 months after surgery. Only one of the nineteen tested in the study demonstrated a single, weakly positive, reaction 24 months after surgery. It was considered that the initial stimulus for lymphocytotoxic antibody production was related to surgery. There was no evidence of antibody stimulation 21 to 44 months postoperatively.
Evaluation and Control of the Fertilizing Power of Sperm

In the great majority of mammals fertilization takes place in the ampulla of the oviduct. Fertilization is promoted by many biological mechanisms within the female tract which facilitate the transport of male and female gametes and their union. While a great deal of scientific information is now available on the biology of sperm transport in the female [reviewed by Overstreet (1)] and on fertilization in vivo [reviewed by Yanagimachi (2)], many of the experiments which examine the fertilizing power of sperm must necessarily be carried out in vitro.
Evaluation of Integrated Sandwich TPS design with Metal Foam Core for Launch Vehicles

§Two kinds of thermal protection systems for launch vehicles are compared for the launch and reentry phases of the mission. One is the integrated sandwich structure with titanium foam core as insulation, and the other is a structural panel with Safill™ insulation (fibrous alumina insulation) design. The weights of b oth designs are minimized subject to temperature constraints, stress constraints or both. The sandwich structure is analyzed by the method of Fourier expansion combined with the Galerkin method. Global buckling, shear crimping and face wrinkling are invest igated for the integrated sandwich structure for the launch. It is found that for temperature constraint only, integrated sandwich design tend to require thick insulation , while Safill design requires thin structure . Shear crimping is most critical among a ll the three failure modes we studied in integrated sandwich design.
Freeze-drying of Spiders and Immature Insects Using Commercial Equipment

Spiders from 6 families and immature insects from 12 families (4 orders) are successfully freeze-dried with commercial equipment. Vacuum pressure, heat sink temperature and area, specimen temperature, and distance of specimen from the heat sink affects the efficiency of freeze-drying. The time necessary for drying of a specimen varies with each species and is not related to the size of the specimen. Color preservation in all cases is superior to preservation in fluids and body distortions are minimal.
Preventable Tragedies: Heat Disaster and the Elderly

This study examines the socioeconomic, cultural and atmospheric factors that contribute to deaths in the elderly population due to heat wave disasters. The framework for this study is the Vulnerability Perspective (Blaikie, Cannon, Davis & Wisner, 1994) and the Hazard Coping Theory (Burton, Kates & White, 1978). Even though it is possible to predict heat waves better than many other natural disasters the message does not always reach the elderly and their caregivers who themselves may be of advanced age and isolated. The model of the Philadelphia, Pa. Hot Weather-Health Watch/Warning System is also discussed.
Limitations of fitting angular scattering from single cells(Conference Presentation)

The literature contains several reports of Mie-like fits to angular-domain elastic scattering measurements from multiple cells or isolated mitochondria. In these studies, the sampling volume typically contains hundreds or thousands of mitochondria, allowing for the size distribution of mitochondria to be modeled as a smooth function, (e.g. Gaussian or log-normal) with a small number of free parameters. In the case of a single-cell volume containing significantly fewer mitochondria, the true size distribution will no longer be as smooth. Increasing the number of free parameters can lead to unstable fits, however, as the forward-directed angular scattering pattern from such a population illuminated with 785 nm light is a monotonically decaying radial function with few distinct features. Using simulations, we have investigated the limitations of modeling single-cell mitochondrial scattering using smooth population distributions of Mie scatterers. In different instances, the fidelity of the estimated size information can be limited by the number of organelles, the angular detection range, or the non-ideality of the data (both speckle and shot noise). We will describe the conditions under which each of these effects dominates. We will also discuss whether mean and standard deviation are the best sizes to report from such Mie modeling, or if there are other size parameters that have greater fidelity to the true, non-smooth size distributions.
Effect of Shedanzhuifeng Pills on Hemorheology of Rats Model of Liver-qi Stagnation and Cold Coagulation Blood Stasis

Objective To observe the effect of Shedanzhuifeng pills on the hemorrheology of rats model of liver-qi stagnation and cold coagulation blood stasis.Methods The rats model of liver-qi stagnation and cold coagulation blood stasis was constructed by subcutaneous injection of 0.1% epinephrine with ice water bath method,The influence of Shedanzhuifeng pills on blood viscosity,hematocrit,erythrocyte aggregation index,rigidity index,deformation index,index of electrophoresis were observe.Results Shedanzhuifeng pills can lower the whole blood viscosity,whole blood reduced viscosity,erythrocyte aggregation index,and stiffness index in the blood stasis rats model.Conclusion Shedanzhuifeng pills can significantly improve the blood hemorheology index in rats model of liver-qi stagnation,cold coagulation blood stasis.It mainly works through its influence on erythrocyte aggregation.
Investigation and Thinking of Food Poisoning Caused by Nitrite

[Objective] To investigate the reasons for food poisonings caused by nitrite in Yixing city in recent years,and provide evidence for prevention and supervision.[Methods] Epidemiological investigation and laboratory detection were applied to analyze the 3 incidents.[Results] The 3 incidents of food poisoning events are caused by edible nitrite overdosed in food,edible nitrite overdosed in brawn,and mis-eating unlabeled "salt".[Conclusion]Propaganda should be strengthened through multiple channels,the people's consciousness of nitrite poisoning should be enhanced,and the administration of the nitrite in production and marketing should be enhanced,health supervising departments should strengthen supervision and training to reduce the occurrence of poisonings caused by mis-eating and over-dose.
Diffusion Bonded GaAs for SHG

We have built and tested a monolithic diffusion bonded quasi phase matched (DB-QPM) GaAs nonlinear crystal for second harmonic generation of 10.6 μm. This work was motivated by the need for nonlinear infrared materials with increased power handling capabilities and damage thresholds. These thermal related factors have limited the performance of other nonlinear infrared materials. Quasi phasematching extends the selection of nonlinear materials to include those that can not be phase matched by ordinary birefringent techniques. In this initial demonstration, we selected GaAs, which has a large nonlinear coefficient but is not birefringent. Diffusion bonding allows the construction of a monolithic structure retaining the excellent thermal and mechanical properties of bulk GaAs single crystals and significantly reduces losses at the multiple interfaces unavoidable in a stack of plates quasi phase matched structure.
Development of Myotendinous-like Junctions that Anchor Cardiac Valves Requires Fibromodulin and Lumican

Background: There are many patients that exhibit connective tissue related cardiac malformations but do not have mutations in collagen genes. The Small Leucine Rich Proteoglycans (SLRP) fibromodulin (FMOD) and lumican (LUM) bind collagen and regulate fibril assembly in other biological contexts. Results: FMOD deficient mice and double deficient FMOD;LUM mice exhibited anomalies in regions where cardiac valve tissue interdigitates with adjacent muscle for support. Ectopic connective and/or myocardial tissue(s) was associated with the more severe cardiac valve anomalies in FMOD;LUM deficient mice. At postnatal day 0 (P0) there was an increase in the mesenchymal cell number in the regions where valve cusps anchor in FMOD;LUM deficient mice compared to WT. The cardiac valve anomalies correlated with the highest levels of FMOD expression in the heart and also where myotendinous junctions (MTJ) components biglycan, collagen type I alpha 1, and collagen type VI, are also localized. Conclusion: The postnatal assembly of the collagen-rich ECM in regions where cardiac valves anchor, that we have designated ‘myotendinous-like junctions' (MTLJ) requires the SLRPs FMOD and LUM. Moreover, FMOD and LUM may facilitate mesenchymal cell differentiation in late stages of cardiac valve development. This article is protected by copyright. All rights reserved.
Glucose clamp algorithms and insulin time-action profiles.

Motivation: Most current insulin pumps include an insulin-on-board (IOB) feature to help subjects avoid problems associated with “insulin stacking.” In addition, many control algorithms proposed for a closed-loop artificial pancreas make use of IOB to reduce the probability of hypoglycemic events that often occur due to the integral action of the controller. The IOB curves are generated from the pharmacodynamic (time-activity profiles) actions of subcutaneous insulin, which are obtained from glycemic clamp studies. Methods: Glycemic clamp algorithms are reviewed and in silico studies are performed to analyze the effect of glucose meter bias and noise on glycemic control and the manipulated glucose infusion rates. The glucose infusion rates are used to obtain insulin time-activity profiles, which are then used to generate IOB curves. Results: A model-based, three-step-ahead controller is shown to be equivalent to a proportional-integral control algorithm with time-delay compensation. A systematic glucose meter bias of +6 mg/dl results in a decrease in the glucose area under the curve of 3% but no change in the IOB profiles. Conclusions: Based on these preliminary simulation studies, a substantial amount of glucose meter bias and noise during a glycemic clamp can be tolerated with little net effect on the IOB curves. It is suggested that handheld glucose meters can therefore be used in clamp studies if the measurements are filtered (averaged) before processing by the control algorithm. Clinical studies are needed to confirm these preliminary results.
Ultrasound speckle reduction using coded excitation, frequency compounding, and postprocessing despeckling filters

A technique for improvement of ultrasonic B-mode imaging that uses coded excitation, pulse compression, and frequency compounding was developed. A coded excitation and pulse compression technique known as resolution enhancement compression (REC) was used to enhance the bandwidth of an imaging system by a factor of two. This bandwidth was subdivided into smaller subbands through the speckle-reducing technique known as frequency compounding (REC-FC). Frequency compounded images were generated using various subband widths and then averaged to reduce speckle and to improve contrast while preserving spatial resolution, known as enhanced REC-FC (eREC-FC). In this study, further improvements in contrast and reduction in speckle were obtained by applying post-processing despeckling filters. The following post-processing despeckling filters were explored and analyzed in regard to contrast improvement, speckle reduction, and image feature preservation: median, Lee, homogeneous mask area, geometric, and speckle reducing anisotropic diffusion (SRAD). To quantify the performance of each filter, contrast-to-noise ratio was used. Data from thirty simulated phantoms and experimental data from a tissue-mimicking phantom were generated and filtered. Results demonstrated that post-processing despeckling filters coupled with the eREC-FC technique could improve the image by up to 563%, in terms of the contrast-to-noise ratio, when compared to conventional ultrasonic imaging.
Multi-energy SXR cameras for magnetically confined fusion plasmas (invited)

A compact multi-energy soft x-ray camera has been developed for time, energy and space-resolved measurements of the soft-x-ray emissivity in magnetically confined fusion plasmas. Multi-energy soft x-ray imaging provides a unique opportunity for measuring, simultaneously, a variety of important plasma properties (Te, nZ, ΔZeff, and ne,fast). The electron temperature can be obtained by modeling the slope of the continuum radiation from ratios of the available brightness and inverted radial emissivity profiles over multiple energy ranges. Impurity density measurements are also possible using the line-emission from medium- to high-Z impurities to separate the background as well as transient levels of metal contributions. This technique should be explored also as a burning plasma diagnostic in-view of its simplicity and robustness.
Rights and Responsibilities in Medical Science

It seems to me that there might be something worthwhile to be gained if I, a medical scientist, clinician, and teacher, try to engage in dialogue with modern Luddites who, despite, or perhaps because of their ignorance of the practicum of clinical medicine, seem intent on destroying not only the evident advantages that modern medical technology has provided for the common weal, but also on inhibiting the potential for future advantages that will accrue to mankind if technological and scientific enquiry does not become totally enwrapped in a jungle of bureaucratic and moralistic red tape. The thicket of do’s and don’t’s elaborated by self-appointed bioethicists and politically-appointed legislators threatens to strangle us. Franz Ingelfinger sounded a note of concern in 1975, with his paper on “The Unethical in Medical Ethics”, [2], and, to quote Tom Beauchamp, “Philosophers interested in public policy would do well to start in the midst of policy problems” ([1], p. 60). I will paraphrase that, and say, “philosophers, lawyers and legislators interested in medical problems and the application of medical research, would do well to start in the midst of clinical problems by participating in the activities of emergency rooms and intensive care units.” Ever since Plato, philosophers have been reluctant to get their hands dirty for fear of polluting their minds. The ivory tower is a perfectly valid option, but it obliges one to refrain from advising on the conduct of practical affairs. This has been recognized throughout the centuries. But today, in the area of biomedical ethics and the morality of control and regulation of biomedical research, some speculators are assuming rights of control without the formal responsibility for the practical results of their speculations.
Blood flow in humans following low-load exercise with and without blood flow restriction

Blood flow restriction (BFR) in combination with exercise has been used to increase muscle size and strength using relatively low loads (20%-30% 1-repetition maximum (1RM)). In research, the range of applied pressures based on a percentage of arterial occlusion pressure (AOP), is wide. The purpose of the study is to measure the blood flow response before exercise, following each set of exercise, and postexercise to low-load elbow flexion combined with no restriction (NOBFR), 40% of AOP (40BFR), and 80% of AOP (80BFR). One hundred and fifty-two participants volunteered; 140 completed the protocol (women = 75, men = 65). Participants were counter-balanced into 1 of 3 conditions. Following AOP and 1RM measurement, ultrasound was used to measure standing blood flow at rest in the right brachial artery. Participants performed 4 sets of elbow flexion at 30% 1RM. Blood flow was measured between sets and at 1 and 5 min postexercise. Blood flow decreased following inflation, with no difference between conditions (p 40BFR > 80BFR, p < 0.001). Blood flow increased from rest to after set 1 regardless of condition. Following cuff deflation, blood flow increased in both the 80BFR and 40BFR conditions. The reduction in hyperemia during BFR is pressure-dependent. Contrary to previous investigations, blood flow was increased above baseline following exercise.
EGFR Exon 19 Deletion in Pancreatic Adenocarcinoma Responds to Erlotinib, Followed by T790M-Mediated Resistance

The prognosis of metastatic pancreatic cancer remains poor despite recent advances in treatment with multidrug chemotherapy regimens. Use of immune checkpoint inhibitors and molecular targeted therapies has so far been disappointing. This report describes a patient with chemotherapy-refractory metastatic pancreatic ductal adenocarcinoma (PDAC) whose tumor was characterized by an activating mutation in exon 19 of the epidermal growth factor receptor (EGFR). He experienced response to erlotinib for 10 months, and then developed disease progression in association with emergence of the T790M mutation. Activating EGFR mutations in cancers other than lung are uncommon, but when present may predict response to EGFR tyrosine kinase inhibitors (TKIs). Development of the T790M mutation in this case suggests that EGFR-targeted TKIs may follow similar patterns of resistance regardless of tumor type. Although actionable mutations are detected infrequently in PDAC, this case illustrates the potential benefit of offering genomic analysis to all patients with advanced disease.
Recruitment and Habitat Use of Early Life Stage Tarpon ( Megalops atlanticus ) in South Carolina Estuaries

Our study was designed to examine early life stage tarpon (Megalops atlanticus) recruitment, habitat use, and residency in coastal environments near the northern limit of their distribution in the western Atlantic Ocean. We employed a multi-faceted approach to (1) collect ingressing larval tarpon on nighttime flood tides at multiple sites, (2) document larval and juvenile tarpon use of natural high marsh pools, and (3) examine juvenile tarpon movement and behavior in managed marsh impoundments, all in the North Inlet-Winyah Bay estuarine system of South Carolina, USA. The timing of recruitment (June through November) and size of larvae (mean ± standard deviation = 23 ± 3 mm standard length [SL]) during estuarine ingress was similar to that reported from other subtropical locations in the region. Soon after recruiting into the system, larval and small juvenile tarpon (47 ± 25 mm SL) co-occurred in high marsh pools from July to November, and large juveniles (201 ± 34 mm SL) were also present in marsh impoundments during this same time period. An increase in tarpon length over time during their residency in high marsh pools and the relatively large size they attain in marsh impoundments indicate these environments may function as favorable nursery habitats. As water temperatures decreased during October and November, juvenile tarpon emigrated from these estuarine habitats. Tarpon appear to use a variety of estuarine habitats in coastal South Carolina from summer through late fall during their early life stage development. The fate of these individuals after they leave estuarine habitats at the onset of winter in this region is currently unknown.
The Next Round is on me! The Effects of Workplace Stress and Strain on Problem Drinking

Problem drinking is an important behavioral phenomenon with numerous implications for employees’ health and well-being within and outside of the workplace. Yet, little is understood about how workp...
Safety and preliminary efficacy of vorinostat with R-EPOCH in high-risk HIV-associated non-Hodgkin's lymphoma (AMC-075)

Abstract Introduction Vorinostat (VOR), a histone deacetylase inhibitor, enhances the anti-tumor effects of rituximab (R) and cytotoxic chemotherapy, induces viral lytic expression and cell killing in Epstein-Barr virus-positive (EBV + ) or human herpesvirus-8-positive (HHV-8 + ) tumors, and reactivates latent human immunodeficiency virus (HIV) for possible eradication by combination antiretroviral therapy (cART). Patients and Methods We performed a phase I trial of VOR given with R-based infusional EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride) (n = 12) and cART in aggressive HIV-associated B-cell non-Hodgkin lymphoma (NHL) in order to identify safe dosing and schedule. VOR (300 or 400 mg) was given orally on days 1 to 5 with each cycle of R-EPOCH for 10 high-risk patients with diffuse large B-cell lymphoma (1 EBV + ), 1 EBV + /HHV-8 + primary effusion lymphoma, and 1 unclassifiable NHL. VOR was escalated from 300 to 400 mg using a standard 3 + 3 design based on dose-limiting toxicity observed in cycle 1 of R-EPOCH. Results The recommended phase II dose of VOR was 300 mg, with dose-limiting toxicity in 2 of 6 patients at 400 mg (grade 4 thrombocytopenia, grade 4 neutropenia), and 1 of 6 treated at 300 mg (grade 4 sepsis from tooth abscess). Neither VOR, nor cART regimen, significantly altered chemotherapy steady-state concentrations. VOR chemotherapy did not negatively impact CD4+ cell counts or HIV viral loads, which decreased or remained undetectable in most patients during treatment. The response rate in high-risk patients with NHL treated with VOR(R)-EPOCH was 100% (complete 83% and partial 17%) with a 1-year event-free survival of 83% (95% confidence interval, 51.6%-97.9%). Conclusion VOR combined with R-EPOCH was tolerable and seemingly efficacious in patients with aggressive HIV-NHL.
Diplopia and Transdermal Scopolamine: A Case Report

A 24 year old woman with previously-treated essential infantile esotropia had the onset of diplopia following the use of transdermal scopolamine. We suspect that the blur following inadvertent ocul...
Interpolation of matrices and matrix-valued densities: The unbalanced case

We propose unbalanced versions of the quantum mechanical version of optimal mass transport that is based on the Lindblad equation describing open quantum systems. One of them is a natural interpolation framework between matrices and matrix-valued measures via a quantum mechanical formulation of Fisher-Rao information and the matricial Wasserstein distance, and the second is an interpolation between Wasserstein distance and Frobenius norm. We also give analogous results for the matrix-valued density measures, i.e., we add a spatial dependency on the density matrices. This might extend the applications of the framework to interpolating matrix-valued densities/images with unequal masses.
Probing Molecular Structures of Buried Interfaces in Thick Multilayered Microelectronic Packages

The fast development of flip-chip (FC) devices has helped to keep ICs on pace for Moore’s law. FC devices have many buried interfaces, the structures of which all need to be investigated in order to optimize them. It is extremely difficult to examine molecular structures of buried interfaces in samples with multiple layers due to the lack of appropriate analytical tools. In this paper, real FC-on-leadframe devices, manufactured by Texas Instruments Incorporated, were investigated using the intrinsically interface-sensitive technique and sum-frequency generation (SFG) vibrational spectroscopy. By milling down the Si wafer, we can probe the polyimide (PI)/mold compound (MC) interface. By milling down further, we can examine the air/MC and the MC/leadframe (LF) interfaces. Methylene and methyl groups were detected from each of the three interfaces, and the orientation of methyl groups was determined at each interface. It was calculated that at the PI/MC interface, the methyl group tilt angle was 20° (from the surface normal). For the air/MC interface, the tilt angle was 43.5°, and for the LF/MC interface, the tilt angle was measured to be 45°. The deduced different methyl orientations at the two buried solid/solid interfaces can be interpreted by the interfacial interactions. The PI surface is more hydrophobic than the LF surface; therefore, it has more favorable interactions with the hydrophobic methyl groups, leading to a more “standing up” (smaller tilt angle) position for the methyl groups at the PI/MC interface. In this paper, SFG was successfully applied to study the buried interfaces in real devices. The SFG method used in this paper is general and can be applied to other real-world, complicated thick systems.
Through the Physician's Eyes: Evaluating Patients for Gastric Bypass Surgery.

A physician describes how patients are selected for gastric bypass surgery in his practice and the lifelong relationship he commits to with his surgical patients. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.
Framed! Reproducing and Revisiting 150-Year-Old Charts

The Statistical Atlases published by the Census Bureau in the late 1800s utilized a number of novel methods for displaying data. In this paper, we examine the use of framed spine and mosaic plots u...