cssi/SciSciGPT-SciSciNet huggingface dataset:
Acute Barbital Poisoning in Dehydration and Diuresis

In several previous communications1, 2, 3 we brought forth some evidence showing that diuretic measures increased neither the rate nor the percentage of elimination of barbital, nor did they shorten the recovery period from barbital depression. Since Gower and Van de Erve4 recently again stated definitely that diuresis hastens recovery from barbital poisoning, and because of the practical therapeutic importance of the matter involved we decided to reinvestigate the problem.Dogs were used throughout the experiments. Sodium barbital was administered in doses ranging from 225 to 600 mg. per kg. intravenously. Diuresis was produced by intravenous injection of appropriate doses of 10% glucose, physiological salt solution, 3% calcium chloride, and from 0.5 to 1.0% ammonium chloride. In contrast to the diuretic measures, dogs were dehydrated by withholding of fluids for 48 hours and by bleeding (12 cc. of blood per kg. withdrawn from the saphenous vein) immediately before barbital administration.These intravenou...
Scaling Theory of Elasticity and Fracture in Disordered Networks

We discuss scaling theories for the elasticity and tensile fracture of random central force spring networks with bond dilution disorder. Effective medium theory works quite well for elasticity but needs very new ingredients to be even qualitatively correct for tensile fracture. A novel “extreme scaling theory” predicts a dilute limit singularity and a size effect in the tensile strength. These predictions are supported by numerical simulations. We extend the above arguments to networks with distributions of bond disorder, and compare the central force network theories to models currently used in the study of rigid cellular materials.
Modeling the evolution of equiaxed miorostructures in castings

With the goal of expanding the scope of solidification modeling, research initiatives have ranged from simply predicting the path of the isotherms to exploring the more complex problem of predicting microstructural evolution. This article presents the mathematical and physical principles involved in this type of modeling and provides examples for a number of Al-Si, Al-Cu, gray iron and ductile iron alloys. Clearly micro- and macrostructural modeling represents significant progress in the field of solidification and the subsequent cooling of castings.
Balancing Jury Critique in Design Reviews

Jury critique is a widely accepted practice in architectural design teaching. Whilst this norm has changed little in recent years, debates about studio culture have highlighted some of its inadequacies. This paper contends that jurors provide an undue emphasis upon what they perceive to be weaknesses and deficiencies in students’ work, rather than their accomplishments. It argues that many of these judgements are based upon an insufficient understanding and consideration of project objectives, constraints, and learning environments, despite attempts to instil this information into jurors at an early stage. This paper explores and evaluates mechanisms designed to encourage a fairer system of critical review that ensures that a full range of issues are considered during review, rather than concentrating upon a narrowly focussed personalised agenda. Recommendations are made based on lessons learned from the evaluations of the jury critique outcomes from the Advanced Comprehensive Design Studio projects completed by the students of the author in USA. The conclusion is that a jury critique that considers a wide range of issues, offers a greater value, and enriches students’ learning experience, rather than providing an over-emphasis on their inadequacies.
Recovery of an Uncontrolled, Asymmetric Spacecraft with Limited Controls

This paper investigates the problem of stabilization of a spinning mass using weak control inputs. It is inspired by a scene from a recent popular movie in which an already docked space ship attempts to utilize its controls to stabilize an asymmetric space station that is spinning uncontrolled. Based on visual data, limited information, and offline estimation of parameters, a model of a space station is created and used to design a Linear Quadratic Gaussian Controller to find the optimal control gains that stops the spin and stabilizes the space station. The primary weighted variable in the cost reduction function is the spin rate about the maximum principal axis of inertia. The unbalanced torques applied due to the variation in moment arms between the thrusters is also analyzed by monitoring the fluctuation in precession and nutation. Results presented in the paper show that the controller can successfully stabilize the space station but a lot more time is needed than shown in the scene. Based upon the simulation results, it is judged that the particular failure scenario is not feasible, due mainly to the amount of thrust required to stop spinning the spacecraft within the elapsed time of the scene.
The Occurrence of a Nemotode, Diploscapter lycostoma, in the Pharyngeal Glands of the Argentine Ant, Iridomyrmex humilis

Juvenile forms of the nematode Diploscapter lycostoma Volk were found inhabiting the pharyngeal glands of laboratory-reared Argentine ants, Iridomyrmex humilis (Mayr). Although the infested glands were destroyed, the nematode did not appear to injure the host or affect its behavior.
Molecular Signaling in Benign Odontogenic Neoplasia Pathogenesis

Several molecular pathways have been shown to play critical roles in the pathogenesis of odontogenic tumors. These neoplasms arise from the epithelial or mesenchymal cells of the dental apparatus in the jaw or oral mucosa. Next generation genomic sequencing has identified gene mutations or single nucleotide polymorphisms associated with many of these tumors. In this review, we focus on two of the most common odontogenic tumor subtypes: ameloblastoma and keratocystic odontogenic tumors. We highlight gene expression and protein immunohistological findings and known genetic alterations in the hedgehog, BRAF/Ras/MAPK, epidermal growth factor receptor, Wnt and Akt signaling pathways relevant to these tumors. These various pathways are explored to potentially target odontogenic tumors cells and prevent growth and recurrence of disease. Through an understanding of these signaling pathways and their crosstalk, molecular diagnostics may emerge as well as the ability to exploit identified molecular differences to develop novel molecular therapeutics for the treatment of odontogenic tumors.
Optimization Design of Multi-level Vibration Isolation System

This paper puts forward two-level vibration isolation system plan composed of double Ruzicka isolators,analyzes the influence of system parameters of a vibration isolator on the performance of two-level vibration isolation system composed of double Ruzicka isolators,and finally,by analyzing the optimization design for the vibration isolation system,obtains the optimal damp ratio of the system under given conditions.
NASBA for the rapid and sensitive detection of Salmonella

Objective:To establish NASBA method which amplified DNA and RNA by isothermal way.Methods: Salmonella RNA was extracted from the patient′s serum by conventional method.dnak gene.RNA was amplified by standard NASBA system with two primers deduced from dnak gene.The NASBA product was converted to DNA by PCR assay usinn two primers inside this amplification area.Results: The dnak gene.RNA was amplified after 50min NASBA reaction,and the product was positive in the Northern Plot assay,usinn and labeled olinonucleic acid as aerobe.After the dinestion of PCR product of NASBA with restriction enzyme Sma I two DNA bands were observed: 120 bp.Conclusion: The product of NASBA method was specific and it can be auseful tool in the investinati on of dnak gene.RNA and the diannosis of Salmonella infection.
The Downsides of Information Transmission for Voting: A Problem and Some Institutional Remedies

I analyze a model of information transmission in collective choice environments. An Expert possesses private information about the consequences of passing an exogenous proposal and may engage in cheap talk to persuade the voters to pass or reject the proposal. In some cases, the Expert may successfully persuade the voters to take her preferred action even though all or most voters would receive a better ex ante payoff with no information transmission. I consider several remedies that an institutional designer may consider in order to avoid this problem while allowing information transmission that benefits the voters. Specifically, I evaluate the effects of (i) limiting Expert communication to to binary endorsements, (ii) encouraging competition between Experts, and (iii) restricting the agenda in order to consider only one issue at a time. None of these proposals completely eliminate negative persuasion outcomes, but limiting the Expert to binary endorsements would avoid the worst forms of Expert manipulation while preserving equilibria in which information transmission is beneficial for the voters.
Establishing a regulatory value chain model: An innovative approach to strengthening medicines regulatory systems in resource-constrained settings

ABSTRACT Medicines Regulatory Authorities (MRAs) are an essential part of national health systems and are charged with protecting and promoting public health through regulation of medicines. However, MRAs in resource-constrained settings often struggle to provide effective oversight of market entry and use of health commodities. This paper proposes a regulatory value chain model (RVCM) that policymakers and regulators can use as a conceptual framework to guide investments aimed at strengthening regulatory systems. The RVCM incorporates nine core functions of MRAs into five modules: (i) clear guidelines and requirements; (ii) control of clinical trials; (iii) market authorization of medical products; (iv) pre-market quality control; and (v) post-market activities. Application of the RVCM allows national stakeholders to identify and prioritize investments according to where they can add the most value to the regulatory process. Depending on the economy, capacity, and needs of a country, some functions can be elevated to a regional or supranational level, while others can be maintained at the national level. In contrast to a “one size fits all” approach to regulation in which each country manages the full regulatory process at the national level, the RVCM encourages leveraging the expertise and capabilities of other MRAs where shared processes strengthen regulation. This value chain approach provides a framework for policymakers to maximize investment impact while striving to reach the goal of safe, affordable, and rapidly accessible medicines for all.
Cryptosporidium parvum Infection Following Contact with Livestock.

Context: Scours, or calf diarrhea, is an infectious gastrointestinal disease commonly found in the calves of dairy farms. It primarily presents with diarrhea that can be life threatening to the animal and is also contagious and threatening to the other livestock. Cryptosporidium is one of the major causes of scours and can be transmitted to humans via fecal-oral route, resulting in diarrheal illnesses. Cryptosporidiosis infection usually occurs as a waterborne outbreak with the potential to affect many people at once. Case Report: We report a case of a 24-year-old female farmer who presented to the emergency department with diarrhea after taking care of ill cattle with similar symptoms. Fecal cultures were positive for Cryptosporidium parvum. Given the patient was immunocompetent, no further treatment was warranted. Conclusion: Confirmed cases should be reported, however, treatment is only recommended in children and immunocompromised adults. Clinicians should educate patients on the importance of proper hygiene and handling techniques in order to decrease transmission and recurrence of the protozoan infection.
Chemical Mechanism of the Branched-Chain Aminotransferase IlvE from Mycobacterium tuberculosis

The biosynthetic pathway of the branched-chain amino acids is essential for Mycobacterium tuberculosis growth and survival. We report here the kinetic and chemical mechanism of the pyridoxal 5′-phosphate (PLP)-dependent branched-chain aminotransferase, IlvE, from M. tuberculosis (MtIlvE). This enzyme is responsible for the final step of the synthesis of the branched-chain amino acids isoleucine, leucine, and valine. As seen in other aminotransferases, MtIlvE displays a ping-pong kinetic mechanism. pK values were identified from the pH dependence on V as well as V/K, indicating that the phosphate ester of the PLP cofactor, and the α-amino group from l-glutamate and the active site Lys204, play roles in acid–base catalysis and binding, respectively. An intrinsic primary kinetic isotope effect was identified for the α-C–H bond cleavage of l-glutamate. Large solvent kinetic isotope effect values for the ping and pong half-reactions were also identified. The absence of a quininoid intermediate in combination w...
Combination of Akt/PKB Inhibition (Perifosine) and Farnesyl Transferase Inhibition (Tipifarnib) Results in Increased Cell Death in Myeloma Cells Lines.

Abstract Introduction Multiple myeloma is a clonal plasma cell malignancy characterized by proliferation and accumulation of plasma cells in the bone marrow. Most patients are incurable with the current treatment modalities. Clearly novel agents are needed to improve the outcome for patients with myeloma. We have previously shown that the combination of bortezomib and tipifarnib results in synergistic myeloma cell death. This increase in apoptosis is associated with down regulation of phosphorylated AKT, a potent anti-apoptotic signaling molecule. Therefore, agents that target AKT represent ideal compounds for further study in myeloma. Perifosine is a novel, oral bioavailable alkylphospholipid. Perifosine has displayed apoptotic and antipropliferative activity in vitro and in vivo in several human cancer models including leukemia. Perifosine exerts its actions by interfering with key intracellular pathways including AKT, MAPK, JNK, p21waf1. Our hypothesis is that targeting AKT via multiple upstream pathways will result in increased myeloma cell apoptosis. Therefore, we assessed the effects of single agent perifosine with and without tipifarnib on multiple myeloma cell lines. Method The myeloma cell line RPMI8226 was used. Cell viability and proliferation were assessed using MTT assays. Cells were incubated with increasing concentrations of both agents alone and in combination. Cell proliferation was assayed at 24, 48 and 72 hours. Western blots were then carried out to evaluate the effects of the intracellular protein PDK1, one of the critical signaling molecules that phosphorylates and activates AKT. Results As we and others have previously shown, tipifarnib at concentrations that can be achieved clinically is associated with minimal cytotoxicity. At 5 μM, tipifarnib decrease proliferation by only 20%. In contrast, there is a potent dose response effect of single agent perifosine (Fig. 1). These results were apparent as early as 24 hours. When tipifarnib at 5 μM is used in combination with a subtherapeutic dose of perifosine (2 μM), there is a marked decrease in cell proliferation (Fig. 2). In addition, combination therapy resulted in a reduction in the phosphorylated form of PDK1, a critical finding that was not seen with either drug alone. Conclusion Combination therapy with tipifarnib and perifosine results in less cell proliferation compared to either agent used alone in the RPMI8226 myeloma cell line. The dosages employed in these in-vitro studies are lower than those used in previously published data and are clinically achievable. Studies targeting other cell lines including MM.1R, MM.1S, and U266 are in progress. Analysis of AKT, Caspase 3, 8 and 9 are being explored to help delineate the mechanism of this novel combination. The goal is to develop further effective treatment options for patients with myeloma. Download : Download high-res image (66KB) Download : Download full-size image Download : Download high-res image (86KB) Download : Download full-size image
LilyPad Arduino: rethinking the materials and cultures of educational technology

The LilyPad Arduino is a construction kit that enables students to construct and program tangible interactive devices (Buechley, 2008). Similar to Lego Mindstorms, it consists of a set of controllable input and output pieces like temperature sensors, light sensors, motors, and LEDs, but users of the LilyPad build interactive textiles instead of robots. Soft, wearable artifacts are made by stitching sewable components together with silver-plated, electrically conductive thread. Figure 3 shows a picture of the kit and a sample design, a jacket with turn signals on its back that was designed for cycling.
Independent and Interactive Effects of OPRM1 and DAT1 Polymorphisms on Alcohol Consumption and Subjective Responses in Social Drinkers.

Background The current study examined independent and interactive effects of polymorphisms of the mu opioid receptor gene (OPRM1, A118G) and variable number tandem repeats of the dopamine transporter gene (DAT1, SLC6A3) on alcohol consumption and subjective responses to alcohol in 127 young, healthy, social drinkers. Methods Participants completed an in-person assessment, which included self-reported alcohol drinking patterns and blood sampling for DNA, and in a second visit, a cumulative alcohol dosing procedure with subjective ratings across multiple time points and breath alcohol contents (0.03 to 0.1%). DNA was analyzed for OPRM1 AA versus AG/GG (*G) genotypes, DAT1 10-repeat allele (A10) versus 9 or lesser alleles (A9), and ancestral informative markers. Results There were significant epistatic interactions between OPRM1 and DAT1 genotypes. Subjective High Assessment Scale scores after alcohol consumption were highest in *G and A9 carriers, and lowest in *G and A10 carriers. Negative subjective effects were also highest in *G and A9 carriers. Effects were similar in a sensitivity analysis limited to Caucasian subjects. There were independent and epistatic interactions on drinking. The OPRM1 *G allele was independently associated with fewer heavy drinking days. The A9 allele was associated with a greater number of drinking days, which was attenuated in carriers of the *G allele. Conclusions These findings highlight the biological importance of interactions between these 2 genes and interactions between brain opioid and dopamine systems.
Iron-Doped Apatite Nanoparticles Delivered via Electrospun Fiber Mesh for Maximized Bacterial Killing by Bacteriophage

According to the Centers for Disease Control (CDC) and prevention, at least 2 million people in the United States become infected with antibiotic-resistant bacteria, and at least 23, 000 people die each year as a direct result of those infections. One alternative to traditional antibiotics is bacteriophage (phage) therapy. Phage therapy utilizes bacteria-specific viruses to infect and kill bacteria cells. The specificity of these viruses is beneficial in that phage used for therapeutic purposes do not harm the human microbiota, nor do phage infect eukaryotic cells. It has been discovered that iron-doped apatite nanoparticles (IDANPs) significantly enhance phage killing of bacteria cells. The biocompatibility of apatite, coupled with its effectiveness as an adjuvant to enhance an alternative antibiotic therapy, makes it of interest for medical applications. Previously, researchers have encased phage in a microfluidic channel in coaxially electrospun fibers, allowing phage to remain viable after several weeks storage at 4 °C. Here, we have constructed a polymer fiber layer using electrospinning (ES) for delivery of IDANP adjuvants to compliment phage treatment delivery fibers. The IDANP delivery layer constructed is composed of polyethylene oxide (PEO) doped with the nanoparticles. When compared to media-only and IDANP-only controls, results show IDANPs delivered through a PEO fiber mesh remain effective at enhancement of phage infectivity.
Multiple-instrument evaluation of the consistency and long-term stability of tip width calibration for critical dimension atomic force microscopy

Since 2004, standards for calibration of critical dimension atomic force microscope (CD-AFM) tip width have been available both commercially and through the National Metrology Institutes, such as the National Institute of Standards and Technology in the United States. There have been interlaboratory and intermethod comparisons performed on such samples, but less attention has been paid to the long-term stability of standards and monitoring for damage, wear, or contamination. Using three different CD-AFM instruments, we have tested the consistency and long-term stability of two independent reference calibrations for CD-AFM tip width. Both of these tip width calibrations were based on independently implemented transmission electron microscope reference measurements. There were circumstances in which damage occurred or samples needed to be cleaned. Nevertheless, our results show agreement within the uncertainties and stability over a period exceeding 10 years.
Picosecond-Resonance Coherent Anti-Stokes Raman Scattering in Biophysics: Power Dependence in the Bacteriorhodopsin Photocycle

Picosecond resonance coherent anti-Stokes Raman (PR/CARS) spectra in the C=C stretching region (1400–1640 cm−1) of the BR photocycle are recorded with 8-ps pulses and measured as a function of w l laser power. These PR/CARS data are quantitatively fit to third-order susceptibility (χ(3)) relationships to obtain the band origins, bandwidths, relative amplitudes, and electronic resonant phase factors of the observed features. Variations in the w l power alters the relative populations of the primary BR photocycle intermediates from which PR/CARS is generated. For w l pulse energies of 0.7 nJ or lower, PR/CARS scattering occurs from BR-570 only. An analysis of the BR photocycle species which may contribute to the PR/CARS spectra recorded at higher w l energies is also presented. These results provide insight into how the w l power controls these relative populations, an understanding of importance in the design of picosecond time-resolved CARS spectroscopy from the BR photocycle.
Concentration of Distributions at Entropy Maxima (1979)

After sending off the ‘Where Do We Stand?’ manuscript for the MIT Proceedings Volume, my thoughts returned to Rudolph Wolf’s dice data. The hastily concocted argument for five degree of freedom instead of three bothered me a bit, and I decided to calculate how much Chi-squared could have been reduced if the parameters λ1, λ2 bad been chosen to minimize it, rather than from the Maxent rule. But first, as a check on the old computer program, I recalculated the entropies of those various distributions. Quite by accident, I noticed that the numerical values of NΔH were in every case just half the values of Chi-squared in the MIT article.
Children of Dialysis Patients

The poignancy of a child’s confrontation with stressful life experiences has engaged the interest and concern of many people. With respect to physical illness, previous study was focused almost exclusively on the sick child and his family, while little attention has been given to the well child of a physically ill parent. Our pilot study was motivated by an interest in the impact of chronic hemodialysis of a parent on the children living at home and on their relationship with the sick parent. We were interested in understanding how children perceived their parent’s illness and treatment by obtaining some knowledge of their fantasy life. We studied both center and home dialysis patients and their families in order to assess the impact of home therapy on the child.
Impacts of Modeling Errors and Randomness on Topology Identification of Electric Distribution Network

A few models have been established to study the relationship between SCADA voltages in the cyber layer and the topology of electric distribution networks in the physical layer. While these models could identify the topology of distribution networks under some assumptions, one of the issues that havent been deeply studied is whether the topology of distribution networks could be identified when violating these assumptions. We define the violation of these assumptions as the impact of modeling errors which may have different characteristics comparing to other errors. When the model of using SCADA voltage correlation to identify the topology of distribution networks is constructed, a few assumptions are made such as uniformed $L$ / $R$ ratio and the uncorrelated injective power which is a very strict restriction in practice. This paper focuses on understanding the impact of the identification result when violating some of these assumptions that used to established the model. Specifically, 4 cases are presented in this paper while each case contains whether violates the assumption of uniformed $L$ / $R$ ratio and uncorrelated injective power or not. The analysis results show that violating each individual assumptions could cause inaccurate identification result. Also, the results show that the errors could be decreased by increasing the sample size of the SCADA voltage. Understanding the impact of errors is useful to better understand weakness of the model and find the way of decreasing errors.
"Chromosomes and genes, spawned these fateful scenes": Rapid adaptation in an introduced fish.

Humans by their very nature alter the distribution of species. Be it introduction of exotic species, habitat alterations or construction of barriers, anthropogenic changes provide novel experimental systems for the molecular ecologist to study evolutionary change. These events often provide a contradiction. Effective population sizes are generally low, and introduced populations are typically characterized by reduced diversity consistent with theoretical predictions of population bottlenecks and founder effects. However, despite reduced diversity, rapid change sometimes occurs. Identification of genomic regions associated with these rapid adaptive responses to novel selection pressures provides a window into genomic regions important in adaptive diversity, both in the novel and native ranges. These studies also provide an important means to estimate the pace of evolutionary change. In this issue, Willoughby et al. () compared the heterozygosity of steelhead (the anadromous form of rainbow trout Oncorhynchus mykiss) introduced into Lake Michigan in the late 1880s to the putative source population from the ancestral California range. After 25 generations of isolation in Lake Michigan, Willoughby et al. () found consistent genomewide reductions in genetic diversity as estimated by a measure of pooled heterozygosity. Despite this overall reduction in heterozygosity, three chromosomal regions showed signals of rapid adaptation and contained genes associated with osmoregulatory and wound-healing functions.
Staging identifies non-CNS malignancies in a large cohort with newly diagnosed lymphomatous brain lesions.

Lymphomatous brain lesions can represent primary central nervous system (CNS) lymphoma or secondary involvement as part of systemic disease (SCNSL). In this study, we characterize staging evaluatio...
Extremely deep Bayesian learning with Gromov's method

We have invented two new Bayesian deep learning algorithms using stochastic particle flow to compute Bayesâ€™ rule. These learning algorithms have a continuum of layers, in contrast with 10 to 100 discrete layers in standard deep learning neural nets. We compute Bayesâ€™ rule for learning using a stochastic particle flow designed with Gromovâ€™s method. Both deep learning and standard particle filters suffer from the curse of dimensionality, and we mitigate this problem by using stochastic particle flow to compute Bayesâ€™ rule. The intuitive explanation for the dramatic reduction in computational complexity is that stochastic particle flow adaptively moves particles to the correct region of d dimensional space to represent the multivariate probability density of the state vector conditioned on the data. There is nothing analogous to this in standard neural nets (deep or shallow), where the geometry of the network is fixed.
A Case Study of Implementing Grant-Funded Integrated Care in a Community Mental Health Center

The US government funds integrated care demonstration projects to decrease health disparities for individuals with serious mental illness. Drawing on the Exploration Preparation Implementation Sustainability (EPIS) implementation framework, this case study of a community mental health clinic describes implementation barriers and sustainability challenges with grant-funded integrated care. Findings demonstrate that integrated care practices evolve during implementation and the following factors influenced sustainability: workforce rigidity, intervention clarity, policy and funding congruence between the agency and state/federal regulations, on-going support and training in practice application, and professional institutions. Implementation strategies for primary care integration within CMHCs include creating a flexible workforce, shared definition of integrated care, policy and funding congruence, and on-going support and training.
Continuous Time Bayesian Networks in Prognosis and Health Management of Centrifugal Pumps

This paper presents a novel method for performing risk-based prognosis and health management (rPHM) on centrifugal pumps. We present the rPHM framework and apply common modeling tools used in reliability and testability analysis---dependency (D) matrices and fault tree analysis---as a basis for constructing an underlying predictive model. We then introduce the mathematics of the Continuous Time Bayesian Network (CTBN), which is a probabilistic graphical model based on a factored Markov process that is designed to capture system evolution through time, and we explain how to apply a CTBN derived from D-matrices and fault trees to consider the impact of a set of faults common to centrifugal pumps on emerging hazards in the pump system. We demonstrate the utility of using CTBNs for rPHM analysis with two experiments showing the descriptive power of our modeling approach.
New insight into the mechanism of cellulose and callose biosynthesis: proteases may regulate callose biosynthesis upon wounding

Using a silver-enhanced, gold-secondary antibody immuno-location approach, we investigated the mechanisms for the switch from β-1,4- to β-1,3-glucan biosynthesis upon wounding. Antibodies against β-1,4- and β-1,3-glucan synthases were used to locate these synthases before and after wounding of Mung bean (Vigna radiata var Berken) hypocotyls. Within 5 min of wounding, β-1,4-glucan synthases which were densely localized on plasma membranes adjacent to the secondary walls at the wound site completely disappeared, and β-1,3-glucan synthases became labeled. The immuno-location of the β-1,3-glucan synthases in the secondary walls was in good accordance with the region where the β-1,4-glucan synthases were localized before wounding. Aniline blue was also utilized to visualize the deposition of callose upon wounding. Within 5 min of wounding, callose had accumulated in the corresponding region where the immuno-labeling of β-1,3-glucan synthase was detected after wounding. The β-1,3-glucan synthases were always detected from the sieve plate and plasmodesmata which are known to have constitutive synthesis of callose regardless of wounding. Secondary walls located distantly into the tissue away from the wound site were consistently labeled by the β-1,4-glucan synthase antibody even after wounding. Immuno-blot analysis clearly shows that the levels of β-1,4-glucan synthase subunit Ces A decreased dramatically within 30 min, whereas the β-1,3-glucan synthase subunit CFL1 levels increased significantly after wounding. The intensity of labeling reached a maximum at the wound site, and gradually decreased in correspondence with the distance from the wound site. When a protease inhibitor cocktail was applied upon wounding, neither the β-1,3-glucan synthase appeared nor callose was deposited during the first 5 min of wounding. On the other hand, β-1,4-glucan synthase was detected at the wound site, implying that activation of β-1,3-glucan synthase may rely on the degradation of the β-1,4-glucan synthase. Our study may provide new insight into β-glucan synthesis in higher plants.
PD-1 Expression Is Markedly Upregulated on Intratumoral CD4+ and CD8+ T Cells in Follicular Lymphoma and Is Associated with T-Cell Exhaustion.

Follicular lymphoma is one of the most immune-responsive of all human malignancies. However, immunoregulatory mechanisms in the tumor microenvironment may impair the efficacy of immunotherapies such as vaccines and adoptive T-cell therapy. The inhibitory receptor programmed death 1 (PD1), a negative regulator of activated T cells was recently shown to be upregulated on the surface of HIV-specific CD4+ and CD8+ T cells in humans and was associated with impaired T-cell function. Blockade of the immunoregulatory PD-1/PD-ligand 1 (PD-L1) pathway with antibodies against the PD-L1 augmented the function of HIV-specific CD4+ and CD8+ T cells (Day CL et al, Nature, 2006). To investigate the role of PD-1 in lymphoma, we examined PD-1 expression on peripheral blood mononuclear cells (PBMC) and intratumoral T cells in patients with follicular lymphoma prior to therapy. We observed that PD-1 expression is significantly upregulated on peripheral blood and intratumoral CD4+ and CD8+ T cells in patients with follicular lymphoma as compared with normal donor PBMC. Furthermore, PD-1 expression was significantly higher on intratumoral (mean 61%, range 34% to 86%) compared with peripheral blood CD4+ T cells (mean 25%, range 9 to 40%). Likewise, PD-1 expression was significantly higher on intratumoral (mean 44%, range 31% to 69%) compared with peripheral blood CD8+ T cells (mean 16%, range 9 to 31%). PD-1 expression on CD4+ and CD8+ T cells was associated with impaired type 1 cytokine production (IL-2, TNFa, and IFNg) and blockade of the PD-1/PD-ligand pathway with antibodies against PD-1 significantly enhanced T-cell function. These data indicate that the immunoregulatory PD-1/PD-ligand pathway is operative in patients with follicular lymphoma. Moreover, this pathway of reversible T-cell impairment provides a potential target for enhancing the function of exhausted T-cells in follicular lymphoma in combination with other immunomodulatory strategies such as vaccines and adoptive T-cell therapy.
Testing a model of body image in the bariatric surgery patient.

Abstract Purpose The purpose was to test a published model of body image in the bariatric surgery patient in the clinical office setting. Background A model was created based on clinical observations during field work and the literature. It focuses on five concepts of body image: body attitude, body checking, appearance orientation, perceived body size, and perceived body space. Testing this model 3 months after surgery is important because morphology changes rapidly influencing early changes in body image, yet there is a paucity of research at this time point. Methods For this study of 67 bariatric surgery patients, sequential sampling was used. Body image and anthropometric measures (body mass index and other weight loss indicators) were obtained at baseline and 3-months postoperatively. Established model testing criteria were used. Results Over 3 months, mean body mass index was significantly reduced. Mean body image was significantly improved regarding all concepts in the model, except body checking. Body image improvement varied widely when individual responses were examined. Conclusions The model was successfully tested. Data on the five concepts in the model provided a body image profile at 3 months indicating individuals' degree of improvement. Areas of non-improvement in the early postoperative phase may signal the need for interventions, like support or psychological counseling, for patients who might be struggling with views of themselves after surgery. Preliminary recommendations are made regarding several of the instruments and their use clinically. Researchers should take into consideration the study's short 3-month time frame when designing future studies.
Stem Cell-Derived Exosomes Ameliorate Doxorubicin-Induced Muscle Toxicity through Counteracting Pyroptosis.

Doxorubicin (Dox)-induced muscle toxicity (DIMT) is a common occurrence in cancer patients; however, the cause of its development and progression is not established. We tested whether inflammation-triggered cell death, “pyroptosis” plays a role in DIMT. We also examined the potential role of exosomes derived from embryonic stem cells (ES-Exos) in attenuating DIMT. C57BL/6J mice (10 ± 2 wks age) underwent the following treatments: Control (saline), Dox, Dox+ES-Exos, and Dox+MEF-Exos (mouse-embryonic fibroblast-derived exosomes, negative control). Our results demonstrated that Dox significantly reduced muscle function in mice, which was associated with a significant increase in NLRP3 inflammasome and initiation marker TLR4 as compared with controls. Pyroptosis activator, ASC, was significantly increased compared to controls with an upregulation of specific markers (caspase-1, IL-1β, and IL-18). Treatment with ES-Exos but not MEF-Exos showed a significant reduction in inflammasome and pyroptosis along with improved muscle function. Additionally, we detected a significant increase in pro-inflammatory cytokines (TNF-α and IL-6) and inflammatory M1 macrophages in Dox-treated animals. Treatment with ES-Exos decreased M1 macrophages and upregulated anti-inflammatory M2 macrophages. Furthermore, ES-Exos showed a significant reduction in muscular atrophy and fibrosis. In conclusion, these results suggest that DIMT is mediated through inflammation and pyroptosis, which is attenuated following treatment with ES-Exos.
Is a paired-stimuli configuration necessary to obtain typical evoked response differences in studies of psychosis? An MEG study

Abstract Paired-stimuli (S1-S2) procedures have long been used to assess auditory processing in psychosis. Such studies have shown aberrant evoked responses (ERPs) following long (S1 response) and/or short (S2 response) inter-stimulus intervals. The historical tendency from paired stimuli outcomes in the schizophrenia (SZ) literature is for (i) response to the first stimulus (S1) to be smaller among SZ, and (ii) response to the second stimulus (S2) to be larger among SZ in relation to the size of their S1. An interpretation of these two findings is that SZ have poor auditory response suppression to redundant stimuli (“poor gating”). The present study sought to determine if the reported S1 and S2 effects in SZ (smaller S1 and larger S2 in relation to S1 magnitude) require the paired-stimuli presentation format. Participants (18 schizophrenia and 17 healthy persons) were administered the equivalent of S1 (after a 4.5-sec ISI – “long ISI”) and S2 (after a 500-ms ISI – “short ISI”) stimuli under four conditions (traditional paired long and short, randomly interleaved long and short, block of long, block of short). Neural activity differences were consistent between-groups independent of condition: (i) schizophrenia cases had greater activity in the pre-stimulus to very early post-stimulus period, (ii) healthy persons had greater M100 activity to long ISI stimuli, and (iii) healthy persons had greater activity after the M50/M100 evoked fields (recovery phase) following short ISI stimuli. Simple early auditory processing in psychosis may be largely independent of stimulus presentation condition, an outcome that may help re-frame future translational studies. Traditional paired-stimuli auditory neural response effects may not require the paired-stimuli format.
Abstract 16979: Hemodynamic Comparison of Tricuspid Ring Annuloplasty vs. Hetzer Annuloplasty Technique to Repair Functional Tricuspid Regurgitation

Introduction: Surgical repair of functional tricuspid regurgitation (FTR) is increasingly performed, and the techniques are evolving. Annuloplasty is currently the technique of choice, with differe...
Maternal verbal scaffolding: association with higher language skills for 20-month-old children with prenatal polysubstance exposure.

Abstract Background The number of children with prenatal polysubstance exposure is increasing. Supportive mother-child interaction is a protective factor, which can ameliorate adverse effects of prenatal polysubstance exposure on developmental outcomes. Aim To examine the role of maternal verbal scaffolding on cognitive and language development in children with prenatal polysubstance exposure. Study design Pregnant women were recruited, and we prospectively followed mother-child dyads to 20 months of age. This analysis included 66 dyads (33 healthy controls and 33 with prenatal polysubstance exposure). Multivariable linear regression modelling was used to examine the cross-sectional association between maternal scaffolding and Bayley Scales of Infant and Toddler Development (BSID-III) score, as well as an interaction between the study group and scaffolding score. Outcome measures The BSID-III cognitive and language score was used. Videotaped mother-child play was coded to obtain a maternal verbal scaffolding score. Effect sizes were measured using average differences in scores between groups. Results There was no evidence of an association between study group and maternal scaffolding scores. Children in the polysubstance exposure group had lower cognitive and language scores compared to controls, but this association was not statistically significant after controlling for maternal education. Maternal scaffolding was predictive of language scores, with scores increasing by 1.24 points on average (95% CI: 0.42, 2.06) for every 1-point increase in scaffolding score after adjustment for covariates. There was no evidence of a study group-by-scaffolding interaction with respect to the language or cognitive scores. Conclusions Maternal scaffolding during play was associated with language development in children with and without prenatal polysubstance exposure.
Developing a distress-based traffic equivalency to efficiently evaluate the effect of traffic loads on pavement performance

Traffic loading is considered one of the main factors contributing to pavement deterioration. Large illegal loads in the form of vehicles traveling with axle loads above the permissible legal limit...
Recommending Clinical Interventions to Patients Via Iot-Enabled Health Information System Considering Trust-Dependent Patient Adherence

The internet of things (IoT) has ushered in a world of possibilities in chronic care management. Connected to the health information network, a consumer health device, such as wearables, can continuously monitor and provide intervention recommendations to patients in real-time. However, this new health information system (HIS) may face the risk of patients not following the system’s recommendations. In this paper, we develop an analytical framework to investigate various aspects of the patient–HIS interaction and show how those factors can be accommodated in designing the patient alerting strategy using an IoT-based asthma management system. We consider patients’ trust in the HIS a key factor driving their adherence to the system’s recommendation. Our method acknowledges that patient’s trust may change over time based on their experience of using the system, which may influence their future adherence behavior. We analytically derive the structural properties of our solution and show that our alerting policy can improve patients’ quality of life compared to the existing methods through computational studies. Furthermore, we show that our model can be modified to accommodate different practical scenarios. From our findings, valuable insights can be shared with patients, care providers, and companies in the technology-enabled healthcare business sector.
Factors in the Genetic Background Suppress the Engrailed-1 Cerebellar Phenotype

The mouse homeodomain protein, Engrailed-1, is generally viewed as an essential player in the early establishment and maintenance of the midbrain/hindbrain region that gives rise to the cerebellum and midbrain. In keeping with this, engineered null mutations at this locus have been reported to lead to perinatal lethality accompanied by near-total absence of cerebellar and caudal midbrain structures. We report here that these cerebellar phenotypes are nearly completely suppressed on a C57BL/6J genetic background. All cell types are present and arranged properly in both the cortex and the deep nuclei, and cell counts reveal no significant absence of cerebellar Purkinje cells. Folial patterns are nearly normal, although an apparent fusion of lobules IV and V is consistently noted. Significantly, no change in the Engrailed-2 mutant phenotype occurs after a similar background switch, and whole-mount in situ hybridization reveals identical En2 expression patterns in wild-type C57BL/6J and 129/Sv mice. One likely mechanism for the En1-/- phenotype suppression is a temporal and/or spatial change in the pattern of Engrailed-2 expression apparent only in the absence of Engrailed-1. In support of this, C57BL/6-En1-/- embryos that are also En2+/- lack a cerebellum and caudal midbrain: a phenotype identical to 129/Sv-En1-/- mice.
R Factor Proteins Synthesized in Escherichia coli Minicells: Incorporation Studies with Different R Factors and Detection of Deoxyribonucleic Acid-Binding Proteins

Abstract Analysis of the protein synthesized by Escherichia coli minicells containing R factors demonstrated a variety of low- and high-molecular-weight polypeptides in sodium dodecyl sulfate (SDS)-polyacrylamide gels. Only half of this protein was released into a soluble fraction on lysis of these minicells. The other half remained associated with the minicell envelope. The efficiency of precursor incorporation into protein and the kinds of proteins synthesized changed with the age of the minicells at the time of harvest. About 1 to 2% of the soluble R factor-coded protein bound to calf thymus, E. coli, or R factor DNA-cellulose. Although most of these proteins were excluded from Sephadex G-100 columns, they migrated chiefly as low-molecular-weight-polypeptides (13,000 to 15,000) in SDS-polyacrylamide gels. Additional DNA-binding proteins that appeared to be higher-molecular-weight peptides were noted in extracts from younger minicells. At least one protein, identified as an SDS band, appeared to bind selectively to R factor DNA-cellulose. Minicells with R factors also contained DNA-binding proteins of cell origin, including the core RNA polymerase. No such binding proteins were found in R− minicells. These studies suggest that: (i) R factors code for proteins that may be involved in their own DNA metabolism; (ii) R factor DNA-binding proteins may be associated with larger host cell DNA-binding proteins or subunits of larger R factor proteins; and (iii) the age of the minicell influences the extent of protein synthesis and the kinds of proteins synthesized by R factors in minicells.