cssi/SciSciGPT-SciSciNet huggingface dataset:
111. HSV Vectors Retargeted for Infection of TrkA Receptor-Bearing, Pain-Sensing C-Fibers

Chronic pain represents a major cause of morbidity and effective pain therapy remains a significant unmet medical need. The standard of care relies primarily on systemic drug therapies that do not target the site of pain sensation. These therapies often have limited effectiveness, deleterious side effects, and ,induce tolerance. Herpes simplex viruses (HSV)-based gene therapy vectors offer an attractive alternative to drug therapy since therapeutic genes can be delivered to sensory nerve afferents where pain is arising. Our goal is to develop a transductionally retargeted HSV vector to selectively deliver therapeutic genes to those neurons activated during chronic pain states. NGF/TRKA signaling mediates the pain response associated with inflammatory hyperalgesia and neuropathic pain conditions, making TrkA-expressing cells an important target for chronic pain gene therapy. To obtain a fully retargeted HSV, the virus attachment/entry component glycoprotein D (gD) can be modified to eliminate recognition of its cognate receptors (HVEM and nectin1) and introduce a new ligand into the N-terminus of gD to allow entry through its corresponding cellular receptor. Therefore, we replaced the signal peptide and HVEM binding domain of gD with pre-pro-(pp) NGF to create a TrkA targeting protein, gD:ppNGF(Y38), that can still bind nectin1. Virus expressing gD:ppNGF(Y38) was propagated on cells expressing nectin1 and purified virus was shown to enter J1.1-2, nectin1-deficient cells, only when transduced with TrkA receptor (J/TrkA cells). To enhance the propagation of these vectors on complementing cells, we developed genetic selection methods to isolate retargeted virus variants that display enhanced entry and spread on J/TrkA cells. We found that a selected variant (J4H) had acquired mutations in other HSV envelope glycoproteins, including one glycoprotein involved in envelope-cell fusion events (gH) and two that were previously shown to contribute to virus spread (gE and gI). Moreover, we show that the gH mutation alone, when introduced into the parental virus backbone, enhances entry and minimally improves virus spread. We are currently investigating the specific phenotypes of the individual gE and gI mutations. A fully TrkA-retargeted J4H-based virus (J4HΔ38), further modified to completely eliminate nectin1-binding, also displays enhanced entry and spread on J/TrkA cells. We are currently testing the J4HΔ38 virus in primary sensory neurons in culture and in infections of animals in vivo. We suggest that the TrkA-vector retargeting will provide a means for transduction of pain sensing C-fibers to more precisely introduce pain-relieving gene products.
Subthalamic Nucleus Afferents: Anatomical and Immunocytochemical Features

The subthalamic nucleus (STN) may be the only CNS site at which a discrete destructive or biochemical lesion consistently results in a characteristic contralateral dyskinesia in man and monkey (Whittier,1947; Carpenter et al.,1950; Hammond et al.,1979). The STN, a hypothalamic derivative, consists of a single population of cells, virtually all of which are projections neurons (Richter, 1965; Van der Kooy and Hattori,1980). The neurotransmitter of STN neurons is unknown, but GABA immunoreactive terminals surround STN neurons in the monkey (Smith et al., 1987).
Coral Reef Drag Coefficients – Water Depth Dependence

AbstractA major challenge in modeling the circulation over coral reefs is uncertainty in the drag coefficient because existing estimates span two orders of magnitude. Current and pressure measurements from five coral reefs are used to estimate drag coefficients based on depth-average flow, assuming a balance between the cross-reef pressure gradient and the bottom stress. At two sites wind stress is a significant term in the cross-reef momentum balance and is included in estimating the drag coefficient. For the five coral reef sites and a previous laboratory study, estimated drag coefficients increase as the water depth decreases consistent with open channel flow theory. For example, for a typical coral reef hydrodynamic roughness of 5 cm, observational estimates, and the theory indicate that the drag coefficient decreases from 0.4 in 20 cm of water to 0.005 in 10 m of water. Synthesis of results from the new field observations with estimates from previous field and laboratory studies indicate that coral r...
Tips and tricks to optimize MRI protocols for cutaneous vascular anomalies

Magnetic resonance imaging (MRI) serves as the principal imaging modality to diagnose and plan treatment for children with cutaneous vascular anomalies. While routine MRI protocols can lead to the correct diagnosis in the majority of cases, the imaging appearances can sometimes be nonspecific or confusing, yielding more than one possible diagnosis. This review highlights specific MRI sequence recommendations and scanning tips that can optimize the imaging protocol to increase diagnostic confidence.
Did Everybody Come

Clay Shirkys influential book Here Comes Everybody: The Power of Organizing Without Organizations explored the potential for Internet-based social networking to change society by making it easier for people to come together. This column evaluates that claim, concluding that Shirky might have overestimated how much people, campaigning aside, really do want to come together.
Relationships of Regional Cerebral Blood Flow, Evoked Potential Responses, and Systemic Hemodynamics During Intracranial Hypertension

Several studies have described changes in somatosensory evoked potentials occurring when cerebral blood flow is reduced below 15 to 20 ml·min-l·100g-1 (Branston et al. 1984; Gregory et al. 1979; Lesnick et al. 1984). These studies generally manipulated arterial perfusion pressure to change regional blood flow. Changes in evoked potentials have also been demonstrated in models of intracranial hypertension employing an expanding mass (Nagao et al. 1979) or fluid infusion into the cerebrospinal fluid (CSF) space (Sohmer et al. 1982). However, the relationship of evoked potential alterations to cerebral blood flow and to cerebral oxygen uptake has not been well-described in these latter models, although regional blood flow is undoubtedly decreased (Nagao et al. 1984). The objective of the present study was to determine the relationships of changes in somatosensory evoked potentials (SEP) and brainstem auditory evoked responses (BAER) to regional cerebral blood flow (CBF) in a model of spatially diffuse intracranial hypertension produced by infusion of artificial CSF. Because the decrease in regional CBF would be expected to be reasonably uniform, one advantage of this model is that changes in global O2 uptake can be calculated from mixed cerebral venous O2 content. Thus, functional changes in SEP can be related to cerebral O2 uptake.
The Mapping Dynamics of a Three-Piecewise Linear System under a Periodic Excitation

The mapping dynamics of non-smooth dynamical systems is presented through a three-piecewise linear system with a periodic excitation. The mapping structures for periodic motions are developed and a transition from a periodic motion to another one is qualitatively discussed through the mapping structures. From such mapping structures, the stable and unstable periodic motions can be uniquely determined, and generic mapping series in chaotic motion can be certainly found. This methodology is extendable to any non-smooth dynamical system.
Natural Orienting Behaviors For Measuring Lateral Line Function

The naturally-occurring orienting response found in some fish and aquatic amphibians has been the behavior of choice for investigating lateral line sensory capabilities. Although this unconditioned behavior is most useful in measuring the ability of animals to localize sources of water disturbance, it can also be used to measure threshold levels of detection. Furthermore, the orienting response can be operantly conditioned to shape discriminatory behavior. Potential problems associated with this natural behavior include (1) uncertainty as to the sensory components or range of stimuli that drive the behavior, (2) difficulty in maintaining high levels of motivation and response reliability, and (3) frequent spontaneous movements of animals. The major advantage of the orienting response and natural behaviors in general are that they give us insights on sensory performance and function in biologically relevant contexts.
Adsorption and biodegradation of azo dye in biofilm processes

The removal of a common azo dye, acid orange 7 (AO7), in biofilm systems was investigated in this study. The abiotic and biotic fate of AO7 was examined under a variety of operating conditions: aerobic nitrification, anoxic denitrification and anaerobic digestion. A comparison of the performance between biofilm and activated sludge treatment processes was made. The adsorption of AO7 onto biofilm matrix and activated sludge flocs was found to fit the Langmuir equation. However, there is a significant difference in the adsorption capacities between biofilm and activated sludge. AO7 was recalcitrant in both biofilm and activated sludge systems under aerobic conditions. Under anaerobic conditions, AO7 was readily decolorized. AO7 decolorization was also observed under anoxic conditions. However, the presence of nitrate inhibited AO7 decolorization.
SRCIROR: a toolset for mutation testing of C source code and LLVM intermediate representation

We present SRCIROR (pronounced “sorcerer”), a toolset for performing mutation testing at the levels of C/C++ source code (SRC) and the LLVM compiler intermediate representation (IR). At the SRC level, SRCIROR identifies program constructs for mutation by pattern-matching on the Clang AST. At the IR level, SRCIROR directly mutates the LLVM IR instructions through LLVM passes. Our implementation enables SRCIROR to (1) handle any program that Clang can handle, extending to large programs with a minimal overhead, and (2) have a small percentage of invalid mutants that do not compile. SRCIROR enables performing mutation testing using the same classes of mutation operators at both the SRC and IR levels, and it is easily extensible to support more operators. In addition, SRCIROR can collect coverage to generate mutants only for covered code elements. Our tool is publicly available on GitHub (https://github.com/TestingResearchIllinois/srciror). We evaluate SRCIROR on Coreutils subjects. Our evaluation shows interesting differences between SRC and IR, demonstrating the value of SR-CIROR in enabling mutation testing research across different levels of code representation.
Chapter 1 – Theory of polymer characterization

This chapter describes the approach that is necessary to go from spectroscopic measurements of the microstructure of the polymer chain to an evaluation of the nature of the copolymerization addition mechanism and finally the determination of the fundamental parameters of the polymerization process. Through spectroscopic technique, one can only measure the average structure of the polymer chains in the sample. Therefore, one can try to relate the structural parameters to the performance properties of the polymer in end use. If the polymer chains are completely characterized and the structural basis of its properties is known, then the polymerization reaction can be optimized and controlled to produce the optimum properties from the particular chemical system.
Symposium review: Immunological detection of the bovine conceptus during early pregnancy

Infertility and subfertility reduce the economic viability of dairy production. Inflammation reduces conception rates in dairy cattle, but surprisingly little information exists about the populations and the functions of immune cells at the conceptus-maternal interface during the periattachment period in dairy cattle. Early pregnancy is accompanied by immune stimulation at insemination and conceptus secretion of IFN-τ, pregnancy-associated glycoproteins, prostaglandins, and other molecules whose effects on immune function during early pregnancy have not been determined. Our working hypothesis is that pregnancy induces changes in immune cell populations and functions that are biased toward immunological tolerance, tissue remodeling, and angiogenesis. This review summarizes current knowledge, starting with insemination and proceeding through early pregnancy, as this is the period of maximal embryo loss. Results indicated that early pregnancy is accompanied by a marked increase in the proportion of endometrial immune cells expressing markers for natural killer (CD335) cells and cytotoxic T cells (CD8) along with an increase in cells expressing major histocompatibility class II antigens (macrophages and dendritic cells). This is accompanied by increased abundance of mRNA for IL-15, a natural killer growth factor, and IL-10 in the endometrium during early pregnancy. Furthermore, expression of indoleamine 2,3 dioxygenase was 15-fold greater in pregnant compared with cyclic heifers at d 17, but then declined by d 20. This enzyme converts tryptophan to kynurenine, which alters immune function by creating a localized tryptophan deficiency and by activation of the aryl hydrocarbon receptor and induction of downstream tolerogenic mediators. Expression of the aryl hydrocarbon receptor is abundant in the bovine uterus, but its temporal and spatial regulation during early pregnancy have not been characterized. Pregnancy is also associated with increased expression of proteins known to inhibit immune activation, including programed cell death ligand-1 (CD274), lymphocyte activation gene-3 (CD223), and cytotoxic T-lymphocyte associated protein-4 (CD152). These molecules interact with receptors on antigen-presenting cells and induce lymphocyte tolerance. Current results support the hypothesis that early pregnancy signaling in dairy heifers involves changes in the proportions of immune cells in the endometrium as well as induction of molecules known to mediate tolerance. These changes are likely essential for uterine wall remodeling, placentation, and successful pregnancy.
Correction to: Generalized rectifiability of measures and the identification problem

The article, “Generalized rectifiability of measures and the identification problem ”, written by Matthew Badger was originally published electronically on the publisher’s internet portal (currently SpringerLink) on March 6, 2019, as open access, with “© The Author(s)”; instead, it should be “© Springer Nature Switzerland AG” and the article is forthwith distributed under the terms of copyright.
The Line Becomes a River: Dispatches from the Border

The Line Becomes a River is a tribute to the phenomenon of illegal immigration. The timing of Francisco Cantu’s book cannot be more perfect and relevant to the current themes, particularly on the U...
The Racialization of Ethnicity: The New Face of White Ethnicity in Postmillennial America:

In his landmark work, Richard Alba predicted that white ethnicity would fade into its twilight in the twenty-first century. Where direct inquiries into American white ethnicity have been scant sinc...
A Reconsideration of the Theory of Monopoly: Inelastic Demand, Profit Maximization and Absolute Consumer Misery

This paper develops a model of monopoly in goods essential for existence. Such goods are characterized by inelastic demand and cannot be analyzed by the standard model of monopoly. Profit maximization reduces consumers to absolute misery and in one specification causes the death of extramarginal consumers. The model offers insights into market behavior ranging from AIDS drugs to the salt tax — a tax Adam Smith (1776, p. 855) considered so pernicious that “[t]hose who consider the blood of the people as nothing in comparison with the revenue of the prince, may perhaps approve of this method of levying taxes."
A Research Agenda for Climate Change Communication and Public Opinion: The Role of Scientific Consensus Messaging and Beyond

That climate change has been accelerated by human activity is supported by a near-universal consensus of climate scientists. In this paper, we review many of the studies that have been done on the ...
Loss of ASH1L in developing brains causes autistic-like behaviors in a mouse model

Autism spectrum disorder (ASD) is a neurodevelopmental disease associated with various gene mutations. Recent genetic and clinical studies report that mutations of the epigenetic gene ASH1L are highly associated with human ASD and intellectual disability (ID). However, the causal link between ASH1L mutations and ASD/ID remains undetermined. Here we show loss of ASH1L in developing mouse brains is sufficient to cause multiple developmental defects, core autistic-like behaviors, and impaired cognitive memory. Gene expression analyses uncover critical roles of ASH1L in regulating gene expression during neural cell development. Thus, our study establishes a new ASD/ID mouse model revealing the critical function of ASH1L in normal brain development, a causality between Ash1L mutations and ASD/ID-like behaviors in mice, and potential molecular mechanisms linking Ash1L mutations to brain functional abnormalities.
Mode-evolution-based ultra-broadband polarization beam splitter using adiabatically tapered extreme skin-depth waveguide.

We present an ultra-broadband silicon photonic polarization beam splitter (PBS) using adiabatically tapered extreme skin-depth (eskid) waveguides. Highly anisotropic metamaterial claddings of the eskid waveguides suppress the crosstalk of transverse-electric (TE) mode, while the large birefringence of the eskid waveguide efficiently cross-couples the transverse-magnetic (TM) mode. Two eskid waveguides are adiabatically tapered to smoothly translate TM mode to the coupled port via mode evolution while keeping the TE mode in the through port. The tapered cross-section of the eskid PBS was designed numerically, achieving a large bandwidth at 1400–1650 nm with extinction ratios >20dB. We experimentally demonstrated the tapered-eskid PBS and confirmed its broad bandwidth at 1490–1640 nm, limited by laser bandwidth. With its mode evolution, the tapered-eskid PBS is tolerant to fabrication imperfections and should be crucial for controlling polarizations in photonic circuits.
Radiomic Correlates of Mandibular Osteoradionecrosis After Radiation Treatment of Head and Neck Cancer Patients

Purpose/Objective(s) This study aims to identify radiomic features extracted from contrast-enhanced CT scans that differentiate osteoradionecrosis (ORN) from normal mandibular bone in head and neck cancer patients treated with radiotherapy. Materials/Methods Contrast-enhanced CT images were collected for patients with confirmed ORN diagnosis at MD Anderson Cancer Center between 2008 and 2018. The ORN region of interest (ROI) was segmented manually in each image. The control ROIs of the contralateral health mandible were generated by a Python script then adjusted manually in each image. An open-source software was then used to extract the radiomic features from both ORN and control ROIs after the application of intrinsic filters. The pairwise correlation filter was used to remove radiomic features whose pairwise correlation was ≥0.99. Filter algorithms were then used to further reduce the number of radiomic features. After that, wrapper and embedded methods were applied on the resulting radiomic features. Finally, Gini importance and Recursive Feature Elimination (RFE) were used to select the final radiomic features for the predictive model. The support vector machine (SVM) with linear kernel was used for the binary classification of ORN and normal mandibular bone. The performance of the model was evaluated using the Area Under Curve (AUC). Results 150 patients with radiologically established ORN were included. The mean age was 62.3 years (range 27-82). The mean time between the end of RT and ORN detection was 32.6 months. A total of Initial 1316 radiomic features were considered. The pairwise correlation omitted 432 features with a correlation ≥ 0.99. The RFE based on the Gini index selected 5 radiomics features in our HNC cohort. We validated this binary classification model using 5-fold cross-validation. During this validation, the range of AUC was (0.84–0.95) & the average AUC was 0.90. This AUC range reflect the high performance of the final classifier in the differentiation between ORN and normal mandible using CECT images. Conclusion Radiomic features were successfully used to build a model to discriminate ORN and normal mandibular bone in head and neck cancer patients. Our statistical model achieved satisfying prediction accuracy and can be potentially used for ORN prediction purpose upon external validation.
Cadmium-113 nuclear magnetic resonance applied to metalloproteins.

Publisher Summary Among the naturally occurring isotopes of cadmium there are two, 113 Cd and 111 Cd, that have a nuclear spin of ½ and are useful as nuclear magnetic resonance (NMR) probes for cadmium-containing molecules. Both isotopes are present at a significant percent natural abundance, namely, 12.75 and 12.26% for 111 Cd and 113 Cd, respectively. They are both obtainable in 96% purity. Although there is only one naturally occurring well-characterized protein, metallothionein, that accumulates cadmium, most metalloproteins containing the Zn 2+ ion—5 d 10 electron configuration—can be substituted with the heavier Cd 2+ ion (6 d 10 ). In the case of metalloenzymes, the Cd substitution has often led to a protein that maintains measurable catalytic activity. For a variety of Zn-containing DNA-binding proteins that require Zn to maintain the fold required for DNA recognition and binding, the Cd-substituted proteins have retained DNA binding. Thus, from both structural and functional standpoints 113 Cd ( 111 Cd) NMR can be used as a valuable probe of zinc metalloprotein structure and function. The cadmium(II) ion has an ionic radius of 0.97 A nearly the same as that of Ca 2+ , 0.99 A (Pauling radii). Thus, Cd 2+ can be substituted at most Ca 2+ binding sites found in proteins. The Cd 2+ ion can also fit the sites occupied by the Cu + ion (5 d 10 ) and thus can be used to probe the metal sites in copper electron transfer proteins in which copper alternates between the Cu + and Cu 2+ states. Metal ion replacement employs anaerobic techniques under which the Cu + ion is removed and replaced by 113 Cd 2+ . This chapter describes the application of 113 Cd NMR methods to the study of metalloproteins.
Purification and Properties of an Avian Carbonic Anhydrase from the Erythrocytes of Gallus domesticus

Abstract Homogeneous carbonic anhydrase has been prepared from the erythrocytes of single comb, white Leghorn hens (Gallus domesticus). The procedure involved chloroform-ethanol precipitation of the hemoglobin, gel filtration of the resulting extract on a Sephadex G-75 column, and ion exchange chromatography of the pooled active fractions from the Sephadex column by salt gradient elution on carboxymethylcellulose. The presence of reducing agents, dithiothreitol or 2-mercaptoethanol, was essential throughout the entire preparation to maintain the stability of the carbonic anhydrase. Only one form of carbonic anhydrase was found in chicken erythrocytes. The purified enzyme behaves as a single molecular entity in sedimentation and diffusion and in polyacrylamide gel electrophoresis. It is active as an esterase, with p-nitrophenyl acetate as substrate; its amino acid composition and its catalytic properties suggest that it belongs to the "high activity" class of carbonic anhydrases. Its general properties are similar to those of other vertebrate carbonic anhydrase: s20, w0 is 2.9 S, the frictional ratio is about 1.2, the molecular weight is 28,000 ± 1,200 from sedimentation equilibrium studies, and there is 1 atom of tightly bound zinc per molecule. Attempts to remove the zinc reversibly have not yet succeeded. Acetazolamide strongly inhibits both the CO2 hydration and the esterase activities (Ki ≅ 10-7 m). The esterase activity rises with increasing pH between 6.5 and 9.5. Measurements of ultraviolet absorption, optical rotatory dispersion, and circular dichroism reveal close similarities with other vertebrate carbonic anhydrases, including the presence of Cotton effects in the region between 285 and 295 nm. Chicken carbonic anhydrase differs most strikingly from the corresponding mammalian enzymes in its high half-cystine content: 7 moles of half-cystine per mole of enzyme. The avian enzyme is reversibly inhibited by p-chloromercuribenzoate, and requires the presence of a reducing agent in vitro for maximal enzymatic activity and structural integrity.
Intralesional Interferon-α-2B Injections for the Treatment of Peyronie's Disease

Background Intralesional therapies provide an alternative to surgical treatment of Peyronie's disease (PD). This study examines the efficacy of intraplaque injections of interferon-alpha-2B (IFN-alpha-2B) in the treatment of PD. Methods Twenty-five patients were enrolled in the study with 21 completing the study. The average age of the study participants was 55.8 years, with 10 of the 21 having diabetes, hypertension, or both. Seven patients received placebo injections using 10 ml saline biweekly for 6 weeks before interferon therapy, and all 21 patients received biweekly injections of 2 x 10(6) U IFN-alpha-2B for 6 weeks before reevaluation. Patients were evaluated with duplex Doppler ultrasonography to assess penile curvature and blood flow. Results The International Index of Erectile Function questionnaire was completed by 14 of 21 men to assess severity of erectile dysfunction (ED) before and after treatment. Improvements of 20% or more in penile curvature occurred in 14 (67%) of 21 men. Penile pain decreased in eight (80%) of 10, and plaque size decreased subjectively in 15 (71%) of 21 participants. The International Index of Erectile Function questionnaire showed significant improvement of ED in five (71%) of seven men with baseline moderate to severe ED. Peak systolic blood flow improved in three (43%) of seven men with baseline hemodynamic impairment, and veno-occlusive disease resolved in three (18%) of 17 individuals. IFN-alpha-2B injections led to significant improvements in penile pain and curvature caused by PD. Conclusion Results of intralesional IFN-alpha-2B injections in improving ED are encouraging. The study findings warrant further investigation of the effectiveness of IFN-alpha-2B injections for treatment of PD.
Recent Developments in BSIM for CMOS RF ac and Noise Modeling

A major barrier to the successful realization of commercial CMOS RF communication systems is the relatively slow progress in the development of CMOS RF compact models. This paper reviews the recent activities of the B SIM development team in addressing this need. Both RF ac and noise models based on BSIM3v3 were proposed and evaluated with 2-D simulations and experimental data. Good agreement has been achieved in the GHz range. These models will enable the accurate simulations of new emerging CMOS RF LSI communication systems using SPICE.
Effects of O-linked glycosylation on the cell surface expression and stability of decay-accelerating factor, a glycophospholipid-anchored membrane protein.

Abstract Decay accelerating factor (DAF) is a glycophospholipid-anchored membrane glycoprotein that protects mammalian host cells from inadvertant complement lysis. The effects of inhibiting mucin-type O-glycosylation on the cell surface expression of DAF were studied by introducing an expression vector for human DAF into wild-type Chinese hamster ovary and ldlD cells. The ldlD cells express reversible defects in the addition of galactose and N-acetylgalactosamine (GalNAc) to oligosaccharide chains on glycoproteins and glycolipids. Mucin-type O-glycosylation of proteins is inhibited in ldlD cells and can be selectively corrected by the addition of GalNAc to the culture medium. The attachment of a phosphatidylinositol phospholipase C-sensitive glycolipid anchor to DAF and its efficient sorting to the cell surface in ldlD cells were independent of galactose and GalNAc additions to glycolipids and proteins. Attachment of galactose and GalNAc to DAF's glycolipid anchor were apparently not required for its normal function. However, in the absence of O-glycosylation DAF was proteolytically cleaved soon after reaching the cell surface, and a large fragment of DAF was released into the culture medium. This rapid proteolysis/release resulted in the expression of very low steady state levels of O-glycosylation-deficient DAF as measured by immunoblotting. These results, in conjunction with those obtained from studies of three other membrane glycoproteins expressed in ldlD cells, suggest that O-linked sugars on membrane glycoproteins may frequently play a role in determining the level of cell surface expression of these proteins.
Tissue Identification Through Back End Sensing on da Vinci EndoWrist Surgical Tool

Surgical robots are becoming more common in the operating room. Although surgeons utilize these robots for improved dexterity, scalable movements, and enhanced vision, they lose their sense of tactile and haptic feedback [1]. Okamura demonstrated a negative consequence of this by showing that forces exerted during robotic sutures significantly exceed that of hand sutures [2]. This excess in force can lead to a variety of complications including tissue crushing, which has been shown to be a clinically relevant problem [3]. Sie et al. proposed tissue-aware grasping as a solution for tissue crush injury, which may obviate the need for tactile and haptic feedback altogether [4]. By coupling online tissue identification with tissue-specific thresholds for crush injury, the surgical robot can warn of imminent tissue crushing or potentially prevent it. Sie et al. provided relevant work in this area by validating an approach for online tissue identification within the first 0.3 s of a grasp. This work was done with a modified manual laparoscopic Babcock grasper; this is a specialized instrument not commonly used in surgery. We herein aim to extend the results of Sie et al. to a much more common surgical tool: the da Vinci EndoWrist surgical instrument (Intuitive Surgical, Sunnyvale, CA). We demonstrate that tissue identification is possible using existing robotic tools without additional sensors or modifications to the tool tip, by using only motor torque and position data at the proximal end of the tool.
Criteria and designs for surge couplers and back-filters

A review is presented of the principal areas in which surge coupling and filtering problems exist. It is proposed that each coupling mode be described in terms of the displacement of every line in the system with respect to ground. Rules are developed for specifying and designing surge coupling configurations, so that different surge test equipment can produce the same test results for a given piece of equipment under test (EUT). Three criteria are proposed, in the form of rules, as the basis for improved and better-standardized surge coupler/filters: surge the intended lines and no others; do not materially change the impedances driving EUT input lines; and allow at least some power follow. >
T-Cell Immunity to Oncogenic Proteins Including Mutated RAS and Chimeric BCR-ABL

The process of malignant transformation can be ascribed to a series of characteristics and definable mutations of genes which encode proteins that control cell growth and differentiation. During the course of malignant transformation the cancer-related genes are altered by a variety of mechanisms including translocations, deletions, and point mutations which commonly result in the expression of aberrant proteins. Our laboratory has focused on determining the extent to which cancer-specific proteins expressed by aberrant cancer-related genes can function as tumor-specific antigens. The current paper reviews our studies with two prototype cancer-specific proteins, mutated p21ras protein and chimeric p210bcr-abl protein. Ras protooncogenes are activated by point mutation in approximately 20% of human malignancies. The mutations occur primarily at codons 12 or 61 and result in the expression of p21ras proteins with single substituted amino acids. Only a limited number of amino acid substitutions occur. Murine studies demonstrate that immunization with synthetic peptides corresponding to the mutated segment can elicit both class II restricted CD4+ helper/inducer T-cell responses and class I restricted CD8+ cytotoxic T-cell responses specific for mutated p21ras protein. In addition, the existence in vivo of tumors expressing mutated ras proteins can be detected by assaying for T-cell immunity to the mutated segment of ras protein. Preliminary human studies show that some patients with colon cancer have existent antibody responses to p21ras protein, implying the possible existence of autochthonous T-cell immunity to mutated ras proteins in those patients. In chronic myelogenous leukemia the human c-abl protooncogene from chromosome 9 is translocated to the specific breakpoint cluster (bcr) region on chromosome 22. The translocation results in the formation of a bcr-abl fusion gene that encodes at 210-kD chimeric protein. The joining region segment of chimeric bcr-abl protein is composed of a unique combination of c-abl and bcr amino acids and is expressed only by malignant cells. Studies demonstrate that immunization of mice with synthetic peptides corresponding to the joining region segment can elicit class II restricted CD4+ T-cell responses to p210bcr-abl proteins. Preliminary studies show that bcr-abl peptides can bind in the groove of both murine and human class I MHC molecules and can elicit bcr-abl peptide-specific cytotoxic T lymphocytes (CTL). Whether bcr-abl peptide-specific CTL can lyse cells expressing bcr-abl protein is a yet unknown. In summary, the results of the studies reviewed confirm that cancer-specific oncogenic proteins can serve as tumor-specific antigens.
Chronic ventricular arrhythmias: comparative drug effectiveness and toxicity.

Abstract The management of chronic arrhythmias begins with the identification of the patients to receive antiarrhythmic therapy. Two broad subgroups of patients can be identified (Fig. 1).
The h‐index, h‐core citation rate and the bibliometric profile of the Web of Science database in three configurations

Purpose – The purpose of this paper is to discuss the new version of the Web of Science (WoS) software.Design/methodology/approach – This paper discusses the new version of the Web of Science (WoS) software.Findings – The new version of the Web of Science (WoS) software released in mid‐2011 eliminated the 100,000‐record limit in the search results. This, in turn, makes it possible to study the bibliometric profile of the entire WoS database (which consists of 50 million unique records), and/or any subset licensed by a library. In addition the maximum record set for the automatic production of the informative citation report was doubled from 5,000 to 10,000 records. These are important developments for getting a realistic picture of WoS, and gauging the most widely used gauge. It also helps in comparing WoS with the Scopus database using traceable and reproducible quantitative measures, including the h‐index and its variants, the citation rate of the documents making up the h‐core (the set of records that ...
The molecular basis of herpes simplex virus pathogenicity

Abstract The key features of herpes simplex viruses are cell destruction with considerable pathology, particularly in productive infections of the central nervous system, and ability to remain latent in sensory and autonomic neurons of the peripheral nervous system. In cells in culture, approximately half of the 74 known different genes of the virus are not essential for viral replication. For the most part, these genes are required for efficient viral replication in experimental animal models. Mutations in a small number of viral genes have been shown to decrease the ability of the virus to access the central nervous system or in ability to multiply efficiently. These genes play a key role in defining the pathogenic properties of the virus. Current evidence suggests that viral gene expression is not required for initiation and maintenance of the latent state. Latency reflects the capacity of the cell to specifically and transiently repress viral gene expression.
The interactive effect of neighborhood peer cigarette use and 5HTTLPR genotype on individual cigarette use.

Abstract Background Previous cross-sectional research has shown that adolescents' cigarette use is interactively associated with that of their school peers and their 5HTTLPR genotype, such that the cigarette use of persons with more copies of the 5HTTLPR*S′ allele is more dependent on school peers' cigarette use behaviors than their counterparts. This analysis seeks to extend this novel finding by examining whether the same conclusion can be reached when substituting neighborhood peers for school peers and examining the timing of the initiation of any and regular smoking in adolescence. Methods This analysis employs an independent sample with longitudinal measures of cigarette use among 6th through 8th graders clustered in 82 neighborhoods, of whom 1098 contributed genetic data. The proportion of respondents who had ever smoked cigarettes by the first wave was calculated for each census block group in the study. 5HTTLPR genotype was assayed using the method of Whisman et al. (2011). The timing of any or regular smoking initiation and over four years were modeled as dependent variables using Cox proportional hazard models. Results The interaction of neighborhood peer smoking behavior in the first wave and 5HTTLPR genotype statistically significantly predicted any smoking initiation (hazard ratio: 3.532; p-value = 0.002) and regular smoking initiation (hazard ratio: 5.686; p-value = 0.000), net of controls for sex, race/ethnicity, grade in the first wave of data, and parental educational attainment. These findings reach the same conclusions as previous cross-sectional research. Conclusions These results differ in the model of gene–environment interaction that they support. The findings for any smoking initiation are consistent with the diathesis–stress model of gene–environment interaction; the findings for regular smoking initiation are consistent with the differential susceptibility model.
Glucagon deficiency as a cause of hypoglycemia

Abstract The relative number of alpha to beta cells was determined as it appeared in the pancreas of 3 patients presenting the classic symptoms and laboratory findings of hyperinsulinism but in whom no adenoma was demonstrable. In all 3 patients there was a marked deficiency of alpha cells suggesting that their hypoglycemic reactions were a consequence of glucagon deficiency. Glucagon deficiency should be considered as a potential cause in the pathogenesis of some cases of hypoglycemia.
Angioarchitectural features of brain arteriovenous malformations associated with seizures: a single center retrospective series.

Background and purpose Epileptic seizures account for 24–40% of all clinical onsets in patients with brain arteriovenous malformations (AVMs). Methods We retrospectively reviewed the angioarchitectural features of AVMs associated with seizures in 168 patients admitted to our Department from 1997 to 2012. Patients were dichotomized according to demographic characteristics, type of treatment, bleeding occurrence, and morphological and topographic features. Clinical status at admission and discharge was also recorded. The association of each one of these variables with seizures occurrence was statistically tested. Continuous variables and outcome were compared with Student's t-test, whereas categorical ones were compared using Fisher's exact test. The independent contribution of some seizures predictors was assessed with a logistic regression model. Associations were considered significant for P < 0.05. Results About 29% patients showed seizures and 47% bleeding. No significant difference in age and sex was observed between patients with and without seizures. AVMs > 4 cm (P = 0.001) and those fed by dilated arterial feeders (P = 0.02) were associated with increased risk of seizures. A higher risk of seizures occurrence was also observed in cortical AVMs compared with deeper ones (75.5% vs. 55.4%; P = 0.01), and in AVMs fed by middle and posterior cerebral arteries branches compared with the other vessels (81.6% vs. 45.3%; P 4 cm also appeared as an independent risk factor of seizures occurrence (OR 2.82; 95% CI, 1.26–6.31; P = 0.009) at logistic regression analysis. Conclusions AVM morphology, especially nidus dimension, appeared to more significantly influence seizures occurrence than their topography.
Thickness-dependent evolution of magnetization reversal in micron-scale polycrystalline Fe rings

The evolution of magnetic switching mechanism is investigated for micron-scale polycrystalline Fe ring arrays with Fe layer thickness, tFe, varying between 10 nm and 50 nm. Single-step and double-step switching are observed for the 10 nm and 50 nm rings, with the 30 nm sample showing a transient behavior. As thickness increases, the first-step switching field, Hc1, increases, while the second-step switching field, Hc2, and remanent magnetization, Mr decreases. Magnetic force microscopy imaging and micromagnetic simulations reveal that in the reversal process, Hc1 and Hc2 correspond to the switching fields of two distinct halves of the ring. The relative separation between these two fields decides the switching behavior of the ring.
Quantitative prediction of radiation belt electrons at geostationary orbit based on solar wind measurements

Solar wind measurements are used to predict the MeV electron radiation belt flux at the position of geostationary orbit. Using a model based on the standard radial diffusion equation, a prediction efficiency of 0.81 and a linear correlation of 0.90 were achieved for the years 1995–1996 for the logarithm of average daily flux. Model parameters based on the years 1995-1996 gave a prediction efficiency and a linear correlation for the years 1995–1999 of 0.59 and 0.80, respectively. The radial diffusion equation is solved after making the diffusion coefficient a function of the solar wind velocity and interplanetary magnetic field. The solar wind velocity is the most important parameter governing relativistic electron fluxes at geostationary orbit. The model also provides a physical explanation to several long standing mysteries of the variation of the MeV electrons.
Leadership training for managers: An Adlerian approach

Adlerian theory—a social model of human behavior—provides an effective framework to improve managerial practices and enhance organizational leadership. Developed by Alfred Adler (1870–1937), founder of the influential school of individual psychology, Adlerian theory promotes principles of social interest, democracy, and encouragement. These principles may guide leaders in building collaborative, productive workforces through participative management, coaching, and employee engagement. Experiential training exercises that integrate Adlerian principles can help managers expand their interpersonal competencies and increase leadership effectiveness.
A Cationic Imido Complex of Permethyltantalocene: H2 and Carbon−Hydrogen Bond Activation, [2 + 2] Cycloaddition Reactions, and an Unusual Reaction with Carbon Dioxide That Affords Coordinated Isocyanate

Treatment of the imido hydride complex Cp*2Ta(NCMe3)H (Cp* = (η5-C5Me5)) with [Ph3C][B(C6F5)4] in tetrahydrofuran solution yields the cationic imido complex [Cp*2Ta(NCMe3)(THF)][B(C6F5)4] (1). Cation 1 reacts cleanly with H2 to yield [Cp*2Ta(NHCMe3)H][B(C6F5)4]. Carbon−hydrogen bond-activation reactions are observed with propyne or phenylacetylene to afford [Cp*2Ta(NHCMe3)(C≡CR)][B(C6F5)4] (R = CH3, C6H5). In the reaction with propyne, an initial mixture of the [2 + 2] cycloaddition product and C−H activation product is thermally driven to the C−H activation product. The heterolytic cleavage reactions for 1 may be rationalized in terms of the presence of both electrophilic and nucleophilic sites of reactivity in the same molecule. Intramolecular activation of a carbon−hydrogen bond of a Cp* methyl group to ultimately C−H activation of the carbon−hydrogen bonds of methane. An unusual reaction occurs with carbon dioxide: dealkylation of the imido group is observed, liberating isobutylene and yielding the i...
A survivor population of wild colonies of European honeybees in the northeastern United States: investigating its genetic structure

There is a widespread belief that wild colonies of European honeybees have been eradicated in Europe and North America, killed by viruses spread by the introduced ectoparasitic mite, Varroa destructor. In reality, however, several populations of wild colonies of honeybees in Europe and North America are persisting despite exposure to Varroa. To help understand how this is happening, we tested whether the bees in one of these populations of wild colonies—those living in and around the Arnot Forest (NY, USA)—are genetically distinct from the bees in the nearest managed colonies. We found that the Arnot Forest honeybees are genetically distinct from the honeybees in the two apiaries within 6 km of the forest. Evidently, the population of Arnot Forest honeybees is not supported by a heavy influx of swarms from the nearest managed colonies, which implies that it is self-sustaining. These results suggest that if a closed population of honeybee colonies is allowed to live naturally, it will develop a balanced relationship with its agents of disease. Indeed, it is likely to become well adapted to its local environment as a whole. We suggest four ways to modify beekeeping practices to help honeybees live in greater health.
Heavy Doping Effect In P-N Junction Photodetector Cell

ABSTRACT The effect of heavy doping (N D >10 20 cm -3 ) in n + p region of n+p junction devices were studied. The experimental investigation was done by fabricating different specially fabricated n + junctions with different carrier concentrations ranging 1 x 10 18 - 5 x 10 20 cm -3 on a p-type boron doped silicon substrate. The heavy doping was found to have introduced a narrowing of bandgap energy. The contradictory behavior of bandgap shrinkage above 2 x 10 20 cm -3 donor density was explained on the basis of FermiDirac Statistics. Lastly, the experimental data had been utilized to arrive at an empirical equation which through iteratively least squares reweighted techniques described the dependence of FDSE on doping concentration.
The haptic Müller-Lyer illusion in sighted and blind people.

We examined the effect of visual experience on the haptic Muller-Lyer illusion. Subjects made size estimates of raised lines by using a sliding haptic ruler. Independent groups of blindfolded-sighted, late-blind, congenitally blind, and low-vision subjects judged the sizes of wings-in and wings-out stimuli, plain lines, and lines with short vertical ends. An illusion was found, since the wings-in stimuli were judged as shorter than the wings-out patterns and all of the other stimuli. Subjects generally underestimated the lengths of lines. In a second experiment we found a nonsignificant difference between length judgments of raised lines as opposed to smooth wooden dowels. The strength of the haptic illusion depends upon the angles of the wings, with a much stronger illusion for more acute angles. The effect of visual status was nonsignificant, suggesting that spatial distortion in the haptic Muller-Lyer illusion does not depend upon visual imagery or visual experience.
Economic sensor/actuator selection and its application to flexible structure control

A systematic design method is proposed for the selecting of actuators and sensors in the structural control in order to minimize the instrumental cost. With actuators and sensors placed at all the admissible locations initially, an iterative minimization algorithm is carried out to identify the sensor/actuator that requires the least precision. By deleting the roughest sensor/actuator each time till loss of feasibility, one can conclude simultaneously the necessary number and type of sensor/actuator, and the location and precision for each sensor/actuator. A tensegrity structure example has been solved as an application of the proposed algorithm.