cssi/SciSciGPT-SciSciNet huggingface dataset:
Elevated Brain Monoamine Oxidase Activity in SIV- and HIV-associated Neurological Disease

We recently demonstrated direct evidence of increased monoamine oxidase (MAO) activity in the brain of a simian immunodeficiency virus (SIV) model of human immunodeficiency virus (HIV)-associated central nervous system (CNS) disease, consistent with previously reported dopamine deficits in both SIV and HIV infection. In this study, we explored potential mechanisms behind this elevated activity. MAO B messenger RNA was highest in macaques with the most severe SIV-associated CNS lesions and was positively correlated with levels of CD68 and GFAP transcripts in the striatum. MAO B messenger RNA also correlated with viral loads in the CNS of SIV-infected macaques and with oxidative stress. Furthermore, in humans, striatal MAO activity was elevated in individuals with HIV encephalitis, compared with activity in HIV-seronegative controls. These data suggest that the neuroinflammation and oxidative stress caused by SIV infection in the CNS may provide the impetus for increased transcription of MAO B and that MAO, and more broadly, oxidative stress, have significant potential as therapeutic targets in CNS disease due to HIV.
Optimal assignments in broadcast networks

A program whose execution is distributed among several processors in a broadcast system has a total execution cost equal to the sum of processor costs and communication costs, which are functions of the amount of data transmitted and the average transmission delays. A critical delay x is a value of average transmission delay such that no assignment is minimum-cost for average delays both smaller and larger than x. An algorithm is presented for finding the set of all q critical delays of a program that requires computing O(q) optimal assignments at fixed values of average delay. For p=2 processors, H.S. Stone's (1977) assignment graph approach can be used to find an optimal assignment, while for p>2, S.H. Bokhari's (1981) dynamic programming approach for programs with tree-structured calls graphs, or an A* algorithm for the more general case, can be used. When more than one optimal assignment exists, an efficient algorithm is described for finding optimal assignments with minimum channel utilization for p=2 that involves the creation of a compact graphical representation of all optimal assignments of the program. Bokhari's algorithm and the A* algorithm can be easily extended to find optimal assignments with minimum transmission costs when p>2. >
Characterization of human striatal A2-adenosine receptors using radioligand binding and photoaffinity labeling.

AbstractThe adenosine agonist [3H]CGS21680 (2-[4-[[2-carboxyethyl]phenyl]ethyl-amino]-5′-N-ethylcarboxamidoadenosine) bound to A2 receptors in human striatal membranes with a Kd of 17.8±1.1 nM and a Bmax of 313± 10 fmol/mg protein. The addition of 100 μM GTP diminished both the affinity of agonist radioligand for A2 adenosine binding sites and the total binding, resulting in Kd and Bmax values of 28.6±1.0 nM and 185±22 fmol/mg of protein. Adenosine ligands competed for [3H]CGS21680 with the expected potency order. The adenosine antagonist [3H]XAC (8-[4-[[[[(2-aminoethyl)-amino]carbonyl]methyl]oxy]phenyl]-1,3-dipropylxanthine), although A1-selective in the rat, binds to human striatal A2 receptors with high affinity. 25 nM CPX (8-cyclopentyl-1,3-dipropylxanthine), an A1-selective antagonist, was added to the incubation medium and effectively eliminated 91% of [3H]XAC (1 nM) binding to human A1 receptors, yet preserved 90% of binding to A2 receptors. [3H]XAC exhibited saturable, specific binding (50% of tot...
Detection in impulsive noise based on robust whitening

Despite the widespread use of the additive Gaussian noise model, it has long been recognized that many important environments are distinctly nonGaussian. The authors present a detector which is designed to operate in a correlated plus impulsive noise environment. The detector robustly whitens the data and then uses a two-sided threshold test to determine the presence of impulsive samples. The impulsive samples are discarded and the remaining samples are used to detect the presence or absence of a signal using a matched filter. An approximate analysis is presented and simulations are used to demonstrate the effectiveness of this approach. >
Enhance learning through developing network security hands-on lab for online students

Our teaching experience tells us that hands-on exercises play a key role in terms of enhancing student learning capabilities, especially when connecting to theories covered in class. In this paper, we describe the challenges faced on graduate level designing hands-on labs of computer network security for online students, and briefly present the contents needed to cover in computer network security course. To meet these challenges, we designed eight hands-on labs to connect our online students from class theory to real-world exercise.
Extragenital Malignant Mixed Mullerian Tumor. Case Report and Review of the Literature

The second case of extragenital malignant mixed Mullerian tumor, heterologous type, occurring in the posterior peritoneum, and confirmed at autopsy, is presented. The histogenesis of this tumor is discussed.
WE-B-201-01: Introduction: Not Everything You Read Is True

Evidence is growing to suggest that many published clinical results cannot be replicated. At the same time, the number of published clinical papers is steadily increasing and most if not all base their conclusions on evidence provided by formal statistical tests. Medical physicists have a critical need to understand and be able to interpret the methods and results of these studies in order to judge their scientific quality and relevance. However many medical physicists have minimal or no training in the sort of practical statistical methods commonly found in the literature. They may therefore have an inadequate ability to detect statistical errors and limitations that are an unfortunately too frequent occurrence in clinical papers. In this session we will use published examples to demonstrate common statistical errors frequently encountered in peer-reviewed literature, distinctive symptoms that can help detect these errors, and explanations for how they might have been corrected. In the process, we will explain some of the basic concepts of inferential statistics. Some specific case studies we will cover will include misunderstanding the meaning of p-values and clinical significance, misinterpreting statistical power, not accounting for multiple-hypothesis testing, ignoring missing data, and faulty survival analysis. Learning Objectives: 1.Learn about the presence of statistical problems in published studies 2.Identify common signs and symptoms of potential problems in various types of statistical tests 3.Learn methods for correctly implementing statistical analyses of the type commonly found in clinical publications
The Anterior Hypothalamus and Salt-Sensitive Hypertension

Early studies in our laboratory suggested that in young (3–12 weeks of age) male spontaneously hypertensive rats (SHR), ingestion of a high NaCl diet exacerbates hypertension (Fig. 1), increases peripheral sympathetic nervous system activity and alters the norepinephrine (NE) content of a hypothalamic nucleus known to be involved blood pressure (BP) regulation (Winternitz et al, 1982a, b; Wyss et al., 1987). Exposure to a high (8% compared to 0.6%) NaCl diet for 2 weeks causes increases in both arterial pressure and peripheral sympathetic nervous system activity and a decrease in NE stores in anterior hypothalamic area but not in other brain regions tested in these animals. None of these NaCl-induced alterations occur in NaCl resistant normotensive WistarKyoto (WKY) rats or NaCl resistant SHR (Wyss et al, 1997). Subsequent studies demonstrated that exposure to a high NaCl diet selectively reduces the turnover of NE in the anterior hypothalamic nucleus (AHN), but not in other hypothalamic nuclei of young, NaCl sensitive male SHR (Chen et al., 1988). These findings are consistent with the hypothesis that dietary NaC1 supplementation exacerbates hypertension in SHR by decreasing the release of NE from nerve terminals in the AHN, thus reducing the activity of the AHN neurons and decreasing the inhibition of peripheral sympathetic nervous system activity (166-1). NaCl-resistant SHR (SHR-R) and WKY have a genetically based resistance to these effects of dietary NaCl and as a result do not display these responses to a high NaCl diet (Wyss et al., 1997). The pushpull microperfusion technique was then used to provide direct evidence of selective reduction in NE release from nerve terminals in the AHN of NaCl supplemented SHR (Chen et al., 1991) (Fig. 3). Dietary NaCl had no effect on NE release in other brain regions tested in SHR and no effect on NE release in the AHN of NaCl-resistant WKY. Subsequent studies focused on defining the functional significance of the selective NaCl-induced reduction in NE release in the AHN of SHR and identifying the local and systemic mechanisms responsible.
Control-display ratio enhancements for mobile interaction

Abstract Mobile devices pose new design challenges, prompting the development of indirect interaction techniques that improve performance by reducing the occlusion caused by touch input. Direct touch interaction (e.g., tap to select) is imprecise, due to occlusion and the finger's surface area. Many cursor-based interaction techniques have been proposed to address this issue; however, these techniques do not dynamically adjust the control-to-display movement ratio (CDratio) to improve accuracy and interaction times. This paper analyzes the performance benefits of applying adaptive CDratio enhancements to mobile device interaction for selecting targets placed among distractors. Existing desktop computer enhancement methods were compared to a new enhancement method, Magnetic Targets and a method that combines CDratio enhancements based on a greater context of the interactions. Magnetic Targets and the combined method both resulted in significantly better objective performance compared to the existing enhancements. The combined method performed similarly to Magnetic Targets or significantly better across the objective metrics. It is noted that an optimization process was not used to set the CDratio enhancement parameters; however, optimization of the parameters is expected to improve the interaction performance.
Vertical scaling of ultra-high-speed AlInAs-GaInAs HEMTs

The scaling of the vertical dimensions of 0.15- mu m-gate-length Al/sub 0.48/In/sub 0.52/As-Ga/sub 0.47/In/sub 0.53/As high-electron-mobility transistors (HEMTs) to reduce their well-known excessive gate leakage current, premature breakdown voltage, and poor output conductance is discussed. It is found that, with a proper choice of doping densities and layer thicknesses, it is possible to realize very-high-performance AlInAs-GaInAs HEMTs (f/sub T/=160 GHz, f/sub max/=300 GHz for 0.15- mu m*50- mu m devices) with low gate leakage current, high breakdown voltage (7.0 V), and very low DC output conductance (45-mS/mm). The DC output conductance exhibits a very strong dependence on the AlInAs doping-thickness product and appears to be a limiting factor in the device power gain. By reducing the doping-thickness product, it was possible to reduce the output conductance by a factor of 3 and thus increase the power gain cutoff frequency by a factor of 1.7. >
Ultrasound-guided intrasphincteric botulinum toxin injection relieves obstructive defecation due to Hirschsprung's disease and internal anal sphincter achalasia.

Abstract Purpose Chronic obstructive defecation can occur in patients with Hirschsprung Disease (HD) and internal anal sphincter (IAS) achalasia. Injection of Botulinum Toxin (BoTox) into the IAS can temporarily relieve obstructive defecation, but can be challenging when performed by tactile sense alone. We compared results of BoTox injections with and without ultrasound (US) guidance. Methods We retrospectively reviewed BoTox injections into the IAS for obstructive defecation over 5years. Analyzed outcomes included short-term improvement, defined as resolution of enterocolitis, new ability to spontaneously defecate, and/or normalization of bowel movement frequency 2weeks post-operatively, as well as requirement of more definitive surgical therapy (myotomy/myomectomy, colectomy, colostomy, cecostomy/appendicostomy, and/or sacral nerve stimulator implantation). Outcomes were compared using t-test and Fisher's Exact test, with significance defined as p Results Twelve patients who underwent BoTox injection were included, including 5 patients who underwent injections both with and without ultrasound. Ten underwent an ultrasound-guided injection (13 injection procedures), 5 of whom had HD. Seven underwent an injection without ultrasound guidance (17 injection procedures), 5 of whom had HD. Procedures performed with US resulted in greater short-term improvement (76% versus 65% without ultrasound) and less requirement of a definitive procedure for obstructive defecation (p Conclusions US-guided BoTox injection is safe and effective for obstructive defecation, and may decrease the need for a definitive operation. Level of Evidence III.
Shoulder Injuries in the Overhead Throwing Athlete

The overhead pitching motion is a coordinated sequence of movements that subjects the shoulder to extreme forces. The ultimate goal of this complex, dynamic activity is to generate high ball velocity and accuracy. In doing so, repetitive throwing can cause adaptive and pathologic changes in the thrower's shoulder. This article reviews the relevant shoulder anatomy, the kinetic chain, and throwing mechanics, as well as common shoulder injuries and surgical options for the treating orthopedic surgeon.
The Visible Heart® project and free-access website 'Atlas of Human Cardiac Anatomy'.

Aims Pre- and post-evaluations of implantable cardiac devices require innovative and critical testing in all phases of the design process. The Visible Heart ® Project was successfully launched in 1997 and 3 years later the Atlas of Human Cardiac Anatomy website was online. The Visible Heart ® methodologies and Atlas website can be used to better understand human cardiac anatomy, disease states and/or to improve cardiac device design throughout the development process. Methods and results To date, Visible® Heart methodologies have been used to reanimate 75 human hearts, all considered non-viable for transplantation. The Atlas is a unique free-access website featuring novel images of functional and fixed human cardiac anatomies from >400 human heart specimens. Furthermore, this website includes education tutorials on anatomy, physiology, congenital heart disease and various imaging modalities. For instance, the Device Tutorial provides examples of commonly deployed devices that were present at the time of in vitro reanimation or were subsequently delivered, including: leads, catheters, valves, annuloplasty rings, leadless pacemakers and stents. Another section of the website displays 3D models of vasculature, blood volumes, and/or tissue volumes reconstructed from computed tomography (CT) and magnetic resonance images (MRI) of various heart specimens. A new section allows the user to interact with various heart models. Conclusion Visible Heart® methodologies have enabled our laboratory to reanimate 75 human hearts and visualize functional cardiac anatomies and device/tissue interfaces. The website freely shares all images, video clips and CT/MRI DICOM files in honour of the generous gifts received from donors and their families.
Phase structure with nonzero Θ QCD and twisted mass fermions

We determine the phase diagram and chiral condensate for lattice QCD with two flavors of twisted-mass fermions in the presence of nondegenerate up and down quarks, discretization errors and a nonzero value of ${\mathrm{\ensuremath{\Theta}}}_{\mathrm{QCD}}$. Although such a theory has a complex action and cannot, at present, be simulated, the results are needed to understand how to tune to maximal twist in the presence of electromagnetism, a topic discussed in a companion paper. We find that, in general, the only phase structure is a first-order transition of finite length. Pion masses are nonvanishing throughout the phase plane except at the end points of the first-order line. Only for extremal values of the twist angle and ${\mathrm{\ensuremath{\Theta}}}_{\mathrm{QCD}}$ ($\ensuremath{\omega}=0$ or $\ensuremath{\pi}/2$ and ${\mathrm{\ensuremath{\Theta}}}_{\mathrm{QCD}}=0$ or $\ensuremath{\pi}$) are there second-order transitions.
Core versus specialty rotations do not affect students' surgical development.

Abstract Background Research is scarce on how the diversity of surgical rotations affects students. We sought to assess the effect of core rotations compared to specialty rotations on students’ development. Methods Students were given a suturing workshop at the beginning of their surgical clerkship along with a questionnaire. They performed both a simple and a complex suturing task at the beginning and end of the 2-month clerkship. The students were divided into 2 groups based on their surgical rotations. Technical skill and exam scores were compared. Results Thirty-eight students were included in the study. Objective scores increased for the simple task (14.2, standard deviation 4.5 vs 16.4, standard deviation 4.2, P = .04) and the complex task (12.9, standard deviation 5.3 vs 16.5, standard deviation 4.1, P Conclusion In this small study, it was found that the type of students’ rotations does not affect surgical skill or knowledge acquisition.
Considering the Scope of Advisal Duties Under Padilla

In Padilla v. Kentucky, the Supreme Court recognized the complexity and severity of immigration penalties triggered by criminal convictions and held that defense attorneys are obligated to advise clients of such consequences. In so doing, the Court explained that specific advice is required when a consequence is clear; at the same time, it acknowledged it is not alwys possible to ascertain the consequences of a criminal disposition and, when that is the case, counsel’s duty is more limited. The Court did not, however, elaborate on the circumstances in which the duty might be limited or explain what advice defense counsel owes a non-citizen defendant even under that limited duty. As post-Padilla practice has demonstrated, a more developed understanding of the extent of the duty to advise non-citizen defendants is now essential. This Article explains how the Padilla opinion provides direction on the scope of a defense attorney’s duty vis-a-vis non-citizen clients and argues that reading the “clear consequence” comment in light of the decision’s roots and rationale offers the necessary guidance. After parsing the Court’s statements, this Article looks at the concrete questions about attorneys' duties that have arisen in lower courts in Padilla’s wake. This inquiry shows that, where Padilla is interpreted narrowly, it seriously undermines non-citizen defendants’ Sixth Amendment rights. This Article then places the “clear consequence” discussion in context by considering the Padilla opinion as a whole and concludes by proposing an analytical approach that accounts for the directives that run throughout the opinion. Ultimately, understanding the basis of the decision and the practical problems that result from a narrow interpretation make clear that defense attorneys must advise non-citizen clients as specifically as research allows in order to adequately inform them about the immigration consequences of contemplated criminal dispositions.
Endoscopic Features of Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of children and adults. The disease is defined by clinicopathologic criteria, including symptoms of dysphagia and food impaction, esophageal biopsies with ≥15 eosinophils per high powered field and lack of response to antisecretory therapy. Patients with eosinophilic esophagitis have a wide variety of endoscopic findings and the disease does not have a uniform endoscopic appearance. In fact, one study suggested that only 38% of individuals thought to have eosinophilic esophagitis at the time of endoscopy had histologic confirmation of the disease and a subset of patients may also have an entirely normal appearing esophagus! Furthermore, endoscopic findings may vary by age. Endoscopy plays a key role in the diagnosis of EoE patients and the varied endoscopic features of this disease are the focus of this chapter.
Development and validation of the cigarette smoking consequences looming scale.

Abstract Introduction Experimental manipulations intended to alter cognitive appraisals of smoking-related threats may affect cigarette smoking and motivation to quit. However, no previous measure has directly assessed perceptions of smoking-related threats as increasing and coming closer in space and/or time (i.e., “looming”). The current research develops such a measure of dynamic smoking-related threat appraisal: the Cigarette Smoking Consequences Looming Scale (CSCLS). Methods In Study 1 (N = 124 daily smokers), the researchers created an initial, scenario-based version of the CSCLS and refined the measure based on factor analysis. In Study 2, 143 daily smokers completed a condensed CSCLS organized around two factors (Physical and Social consequence of smoking). In each study, participants also completed measures of dispositional looming perception, motivation to quit smoking, and smoking outcome expectancies. Results The CSCLS showed strong internal consistency and concurrent validity in that scores on the measure correlated as expected in both studies with a general tendency to perceive threats as looming, outcome expectancies for smoking, and motivation to quit smoking. Conclusions Measuring perceptions of smoking-related consequences as looming may provide greater insight into the cognitive factors associated with motivation to quit smoking, which in turn may inform communications about the risks of smoking.
Abstract 2833: Single-cell imaging reveals MAPK pathway reactivation in drug-tolerant melanoma cells

Spontaneous genetic mutations allow an initially drug-sensitive population of cancer cells to acquire a drug-resistant phenotype. However, little is known about how drug-sensitive cells first evade drug action and survive in the presence of drug, referred to as "drug tolerance," a crucial step on the road to resistance. In this study, we combined single-cell time-lapse microscopy and MATLAB-based automated cell tracking to identify the molecular basis of drug tolerance. By simultaneously monitoring CDK2 and ERK activity in single cells, we found that melanoma cells harboring a BRAF-V600E mutation have high ERK activity and consecutively cycled with an inter-mitotic time of around 14 hr in full growth media. Upon treatment with dabrafenib, an ATP competitive B-Raf inhibitor, all cells entered a CDK2-low quiescence with reduced ERK activity. Strikingly, after 72 hr of dabrafenib treatment, a fraction of cells escaped drug action, re-entered the cell cycle, and divided once in presence of drug before re-entering a transient quiescence. Additional cells continued to escape and divide in the presence of drug, with a steady-state level of about 10% of the population engaged in the cell cycle at any point during the week-long observation period. We refer to cells that re-entered the cell cycle as "escapees" and cells that stayed in quiescence during the observation period as "non-escapees." Remarkably, we found that escapees showed significantly higher ERK activity than non-escapees after a few days of treatment, even though their initial ERK activities were indistinguishable. To test whether reactivation of the MAPK pathway is the cause of cell cycle re-entry, we co-treated cells with dabrafenib and the MEK inhibitor trametinib. This co-treatment resulted in even lower ERK activity and elimination of the escapee population. This result implies that dabrafenib, even at high doses, does not fully turn off the MAPK pathway, thereby enabling eventual escape from drug. By monitoring escaping cells at the molecular level in real time, our work thus suggests a possible mechanism for cells to develop drug tolerance in less than three days, long before acquiring genetic mutations. Citation Format: Chen Yang, Chengzhe Tian, Sabrina L. Spencer. Single-cell imaging reveals MAPK pathway reactivation in drug-tolerant melanoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2833.
14.11 – Vasoactive Substances as Mediators of Renal Injury

Kidney function is regulated by a complex interplay between circulating and locally produced chemicals known as vasoactive substances. These substances affect the tone of the renal vasculature, leading to either vasodilation or vasoconstriction; and consequently affect renal blood flow and/or glomerular filtration rate. They belong to a chemically heterogeneous group and include proteins, peptides, lipids, and nucleosides. This chapter summarizes the role of these vasoactive substances in the maintenance of normal renal function and also highlights their role in disease states including acute kidney injury, chronic kidney disease, and hypertension.
Real-Time Data Transport Scheduling for Edge/Cloud-Based Internet of Things

The rapid development of numerous smart-world applications powered by the Internet of Things (IoT) calls for innovation in network architecture to meet the increasing demands and service. In this paper, we first discuss the challenges of integrating edge/cloud computing infrastructures to support human network-of-things applications and propose a new three-tiered architecture that consists of IoT Things, Edge, and Cloud. We then design a Real-time Data Transport Scheduling (RDTS) scheme for efficiently transporting the data from IoT devices to cloud systems. The RDTS proactively allocates link band-width resources at the IoT Things and Edge tiers by assigning proper weights such that the network capacity can be effectively distributed to all devices. To demonstrate the effectiveness of the scheduling scheme, we conduct a performance evaluation. Our results show the RDTS scheme can significantly improve network performance with respect to throughput, delay, and energy consumption. Additionally, we discuss some remaining issues concerning the architecture.
Input/Output and Communication with the Environment

In this chapter, we cover various SETL capabilities that have been ignored in the preceding chapters. These include additional facilities for input/output, for sensing aspects of the environment in which a SETL program is running, and for passing strings or integers as parameters to SETL runs in a particularly convenient way. A full account of all the memory options and listing control commands which can be used to modify various aspects of SETL compilation and execution is given.
Not So Predictable Mining Pools: Attacking Solo Mining Pools by Bagging Blocks and Conning Competitors.

In this paper we present three attacks against the predictable solo mining (PSM) scheme. In PSM, miners receive shares for submitting partially valid solutions to the current Proof of Work, adding those shares to their account. When the pool successfully mines a block, the block is awarded to the miner with the most shares, and the rewarded miner “pays” an amount of shares equal to the next highest miner’s to claim the block. Our attacks take advantage of the fact that the amount of shares expended winning two different blocks, which have the same monetary value, can vary by up to a factor of four. We show that by strategically spreading its shares across multiple accounts, a malicious miner can generate more revenue than a naive miner of the same computational power by only claiming blocks with a low share cost. By doing so, a miner can reduce computational power it must expend to win a block by more than 30%. Our other two attacks reduce the profitability of victim miners in the pool by minimizing the gap between first and second place when the victim wins a block. This drives up the average amount of computational power the victim must contribute to receive a reward. An adversary not concerned with cost can reduce the number of shares a victim retains after winning a block by up to 26%. We also find that an adversary with more computational power than their victim can reduce the number of shares the victim retains after winning a block by more than 8% with only limited impact on the adversary’s profitability.
Construction of an Infectious Poa semilatent virus cDNA Clone and Comparisons of Hordeivirus Cytopathology and Pathogenicity.

Poa semilatent virus (PSLV), Lychnis ringspot virus (LRSV), and Barley stripe mosaic virus (BSMV) are members of the genus Hordeivirus in the family Virgaviridae. However, the biological properties...
Sagnac Loop Phase-Modulated RF Photonic Link for Wideband High Dynamic Range Operation

We present a novel Sagnac loop phase modulated (PM) RF photonic link for wideband high dynamic range operation. With the help of a coherent homodyne optical detector, the Sagnac Loop PM RF photonic link structure not only allows the balanced photodetection, which is needed for mitigating the laser relative intensity noise (RIN), but also achieve a large spurious free dynamic range (SFDR) without high power photodetection. A proof-of-concept link demonstrated a large SFDR of $113.3 \mathrm{dB} \cdot \mathrm{Hz}^{2 / 3}$ with only 1.7mA detector photocurrent.
Microfabricated Nano-Gap Tunneling Current Zika Virus Sensors With Single Virus Detection Capabilities

Electron tunneling through thin ( ~ 1-50 nm), insulating materials can provide information regarding their band structure, density of states, surface and bulk defect densities and their energy levels and distributions. While electron tunneling has been used in thin inorganic insulating materials for nearly 7 decades, its applications in organic and biological materials, with exceptions of deoxyribonucleic acid and a few other materials, are not extensively explored. Here we report room temperature electron tunneling studies to differentiate between aptamers designed to attach to the capsid proteins on Zika viruses and the aptamer-Zika complexes. We show that the electron tunneling induced by the current versus voltage (I-V) measurements through these materials contain information that enable identification of the Zika virus without any need for DNA sequencing or additional molecular labels. The electron tunneling measurements were carried out using a conducting atomic force microscope, a home-made vertical tunneling junction and an electromigration-induced nanogap in a microfabricated 1 μm -wide gold line on silicon nitride bridges. The current through aptamers and aptamer-Zika complexes all have a threshold voltage just before the exponential increase in the junction current. Below this voltage, the leakage currents are different for the aptamer and aptamer-Zika samples. The tunnel nanogap device is suitable for detecting viruses that are nanometer-scale biomaterials.
Diacylglycerol kinases regulate TRPV1 channel activity.

The transient receptor potential vanilloid 1 (TRPV1) channel is activated by heat and by capsaicin, the pungent compound in chili peppers. Calcium influx through TRPV1 has been shown to activate a calcium-sensitive phospholipase C (PLC) enzyme and to lead to a robust decrease in phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] levels, which is a major contributor to channel desensitization. Diacylglycerol (DAG), the product of the PLC-catalyzed PI(4,5)P2 hydrolysis, activates protein kinase C (PKC). PKC is known to potentiate TRPV1 activity during activation of G protein–coupled receptors, but it is not known whether DAG modulates TRPV1 during desensitization. We found here that inhibition of diacylglycerol kinase (DAGK) enzymes reduces desensitization of native TRPV1 in dorsal root ganglion neurons as well as of recombinant TRPV1 expressed in HEK293 cells. The effect of DAGK inhibition was eliminated by mutating two PKC-targeted phosphorylation sites, Ser-502 and Ser-800, indicating involvement of PKC. TRPV1 activation induced only a small and transient increase in DAG levels, unlike the robust and more sustained increase induced by muscarinic receptor activation. DAGK inhibition substantially increased the DAG signal evoked by TRPV1 activation but not that evoked by M1 muscarinic receptor activation. Our results show that Ca2+ influx through TRPV1 activates PLC and DAGK enzymes and that the latter limits formation of DAG and negatively regulates TRPV1 channel activity. Our findings uncover a role of DAGK in ion channel regulation.
The Start Predicts the Finish: Factors Associated With Antidepressant Nonadherence Among Older Veterans During the Acute and Maintenance Treatment Phases.

OBJECTIVE To best prevent depression relapse and reduce recurrence, an understanding of the factors associated with continued maintenance treatment is needed. This study compared factors associated with antidepressant nonadherence during the acute (ie, during the first 4 months) and maintenance (ie, during 12 months) treatment phase among older veterans with depression. METHODS In this prospective, observational study of 278 older veterans with depression (Patient Health Questionnaire-9 score ≥ 5), patients had been given a new antidepressant prescription between 2008 and 2011. Participants completed initial and follow-up interviews at 4 and 12 months. Medication adherence was assessed by the Brief Medication Questionnaire. A generalized estimating equation was used to determine patient factors associated with nonadherence at each time point. RESULTS Nearly a third of veterans were nonadherent at 4- and 12-month follow-up. In adjusted analyses, nonadherence was significantly associated with African American race (adjusted odds ratio [AOR] = 2.69, 95% CI, 1.30-5.57; P = .01), being unmarried (AOR = 1.84; 95% CI, 1.16-2.92; P = .049), greater medical comorbidity (AOR = 1.30; 95% CI, 1.13-1.49; P < .001), functional impairment (AOR = 1.34; 95% CI, 1.10-1.63; P = .01), and self-reported side effects (AOR = 2.48; 95% CI, 1.57-3.94; P < .001) at both 4 and 12 months. Depression or anxiety severity did not predict antidepressant adherence at either time point. CONCLUSIONS Rates of and factors associated with antidepressant nonadherence were similar at 4 and 12 months. Further work is needed to develop tailored treatment programs to engage older veterans at higher risk of nonadherence in the early treatment period, which may ultimately help to both achieve remission and reduce relapse and recurrence.
Chapter 16 – Elastography

Elastography, a branch of tissue characterization, is the measurement and/or depiction of the elastic or viscoelastic properties of tissues. It provides the image contrast, needed to distinguish among the soft and stiff tissues, that is missing from conventional B-mode imaging. The underlying physics most often includes the propagation of longitudinal and shear waves, the conversion of longitudinal waves with a sound speed of 1500 m/s under nonlinear conditions into an acoustic radiation force field, which, in turn, generates low-frequency shear waves traveling at a few m/s. The excitation is usually a static force, a transient or continuous ultrasound wave. The displaced tissue can be sensed by various methods, such as ultrasound, acoustic surface sensors, optical devices, magnetic resonance imaging (MRI), and X ray. The elastography methods reviewed include one dimensional (1D), quasi-static, sonoelastography, shear wave elasticity imaging, acoustic radiation force impulse imaging, supersonic shear imaging, harmonic motion imaging, and natural imaging.
Effect and correction of optode coupling errors in breast imaging using diffuse optical tomography

In diffuse optical tomography (DOT) and spectroscopy (DOS) using handheld probes, tissue curvature can cause bad fiber-to-tissue contact. Understanding and minimizing image artifacts caused by these coupling errors would significantly improve DOT and DOS image quality. In this work, we utilized Monte Carlo simulations and experiments with gelatin-Intralipid phantoms to systematically study the influence of source or detector (optode) coupling errors. Optode coupling errors can increase the amplitude and decrease the phase of the measured diffuse reflectance, creating artifacts in the reconstructed absorption maps, such as hot spots on the edges. We propose an outlier removal algorithm that can correct these image artifacts, and we demonstrate its performance using simulations, phantom experiments, and breast patient data acquired with bad probe contact due to a dense or small breast. Further, we designed and implemented a new resistance-type thin-film force sensor array that provides real-time optode coupling feedback and guides the outlier removal to minimize optode coupling errors. Our approaches and study results have significant implications for reducing image artifacts arising from handheld probes, which are commonly used with mobile and wearable DOT and DOS devices.
LSTM Model for Single to Dual Track Piano MIDI File

Piano music scores saved by MIDI are easy for the machine to play, but when ordinary people want to play music with this score, they will find it difficult to distinguish the left and right-hand scores. In this article, we give the algorithm based on the neural network that combines long and short-term memory (LSTM) and “Map”. By using this algorithm, a single track piano score in a MIDI file can be divided into two-hand piano scores.
Extracellular Vesicles Derived from a Human Brain Endothelial Cell Line Increase Cellular ATP Levels

Engineered cell-derived extracellular vesicles (EVs) such as exosomes and microvesicles hold immense potential as safe and efficient drug carriers due to their lower immunogenicity and inherent homing capabilities to target cells. In addition to innate vesicular cargo such as lipids, proteins, and nucleic acids, EVs are also known to contain functional mitochondria/mitochondrial DNA that can be transferred to recipient cells to increase cellular bioenergetics. In this proof-of-concept study, we isolated naive EVs and engineered EVs loaded with an exogenous plasmid DNA encoding for brain-derived neurotrophic factor (BDNF-EVs) from hCMEC/D3, a human brain endothelial cell line, and RAW 264.7 macrophages. We tested whether mitochondrial components in naive or engineered EVs can increase ATP levels in the recipient brain endothelial cells. EVs (e.g., exosomes and microvesicles; EXOs and MVs) were isolated from the conditioned medium of either untreated (naive) or pDNA-transfected (Luc-DNA or BDNF-DNA) cells using a differential centrifugation method. RAW 264.7 cell line–derived EVs showed a significantly higher DNA loading and increased luciferase expression in the recipient hCMEC/D3 cells at 72 h compared with hCMEC/D3 cell line–derived EVs. Naive EVs from hCMEC/D3 cells and BDNF-EVs from RAW 264.7 cells showed a small, but a significantly greater increase in the ATP levels of recipient hCMEC/D3 cells at 24 and 48 h post-exposure. In summary, we have demonstrated (1) differences in exogenous pDNA loading into EVs as a function of cell type using brain endothelial and macrophage cell lines and (2) EV-mediated increases in the intracellular ATP levels in the recipient hCMEC/D3 monolayers.
Screening and managing obesity: understanding paediatric residents’ knowledge, attitudes and practice

STUDY PURPOSE Prior studies have identified paediatric attending physicians' screening and management patterns related to overweight/obesity, but less is known about resident physicians' behaviour. The objective was to understand paediatric resident physicians' knowledge, attitude and practice patterns of overweight/obesity screening and management. STUDY DESIGN We performed a retrospective chart review of preventive visits conducted by residents between August and October 2019. Charts of patients 2-18 years with body mass index ≥85th percentile at the visit were reviewed (85th-<95th for age and sex defined as overweight, ≥95th defined as obese). A survey was distributed to residents assessing knowledge, attitudes and barriers towards obesity management. RESULTS Of 1250 visits reviewed, 405 (32%) patients met the criteria for overweight or obesity. 39% were identified correctly by the provider, 53% were not identified and 8% were identified incorrectly. 89% of patients had diet history, 31% had physical activity and 43% had family history documented. Patients with obesity received physical activity documentation/counselling, portion size counselling, at least one referral, laboratory tests and a diagnosis more often than overweight patients. 84% of residents completed the survey. Although the majority of residents felt 'somewhat' or 'very' well prepared to counsel families about overweight/obesity, the majority thought their counselling on overweight/obesity was 'not at all' or 'slightly' effective. CONCLUSION Despite residents feeling prepared and comfortable discussing overweight/obesity with patients, these diagnoses were often under-recognised or incorrectly made and appropriate counselling was lacking. Future work will focus on specific strategies to improve diagnosis, screening and management of overweight/obesity and include educational interventions and electronic medical record adaptations.
The Known Unknowns of the Immune Response to Coccidioides

Coccidioidomycosis, otherwise known as Valley Fever, is caused by the dimorphic fungi Coccidioides immitis and C. posadasii. While most clinical cases present with self-limiting pulmonary infection, dissemination of Coccidioides spp. results in prolonged treatment and portends higher mortality rates. While the structure, genome, and niches for Coccidioides have provided some insight into the pathogenesis of disease, the underlying immunological mechanisms of clearance or inability to contain the infection in the lung are poorly understood. This review focuses on the known innate and adaptive immune responses to Coccidioides and highlights three important areas of uncertainty and potential approaches to address them. Closing these gaps in knowledge may enable new preventative and therapeutic strategies to be pursued.
Measurement and Analysis of Physical and Climatic Distribution Environment for Air Package Shipment

There has been a significant growth in the air package shipment business, which involves the multi-modal movement of a package in transportation and material handling systems that encompass conveyors, carts, trucks, delivery vans and aircrafts of various sizes and shapes. This study was aimed at establishing the ‘air package shipment’ conditions experienced by packages transported by air under ‘normal conditions of transport’. Air package shipment data (temperature, humidity, pressure, shock and vibration) were collected for several domestic and international routes through instrumented packages. The collected data were supplemented by previous research to measure and quantify this multi-modal shipping environment. This study also compared industry-accepted American Society for Testing and Materials (ASTM) pre-shipment test methods with the general requirements of package design qualification testing as outlined in 49 Code of Federal Regulations (CFR) Part 178, Subpart M. This review revealed that the design qualification testing for certain distribution-related hazard elements is not currently representative of the normal conditions of air transport. The data gathered in this study were analysed to represent the current ‘normal conditions of transport’, i.e. beginning-to-end delivery of air packages. The study used the time spent by the package in each of the segments of transportation to determine a ‘single profile’ or ‘test’ that would represent the average and normal expected levels for each hazard element and would serve as the basis of a minimum level for performance testing to establish normal conditions of transport by air. The recommended test methods and levels can be easily adopted by existing distribution packaging testing labs globally. Copyright © 2015 John Wiley & Sons, Ltd.
“Everywhere Felt and Nowhere Seen”: Chinua Achebe’s Things Fall Apart and the “Sovereign Paradox”

This paper argues that Chinua Achebe’s Things Fall Apart reflects what Giorgio Agamben refers to as the “sovereign paradox” on two levels: first—as reflected by the subject of the novel—on the juridico-political level, and second, on the level of the language and structure of the novel itself. The relationship between these two levels is made clear by Agamben, who uses language as the prime example of the “sovereign paradox” implicit to the juridical order. “Language,” he writes, “is the sovereign who, in a permanent state of exception, declares that there is nothing outside language and that language is always beyond itself” (21). Obeirika’s words in Things Fall Apart: “There is no story that is not true” (Achebe 14), illustrates this “sovereign paradox” by pointing on the one hand to the omniscient authority of the narrative text, while on the other directly undermining that authority. I argue that it is by doing away with the binary system of what can and should be considered true and untrue that the reflexive narrative – of which Achebe’s novel is a prime example – positions itself in a “permanent state of exception” (Agamben 21). Things Fall Apart establishes for itself “a zone of indistinction” (Agamben 47) characterized by the very impossibility of arriving at the “truth” as such, or “of distinguishing between outside and inside, nature and exception” (37). A “zone of indistinction” is constructed on a textual as well as a political-historical level by the novel’s transgression of its own narrative borders.
Inferring learning and attitudes from a Bayesian Network of log file data

A student's goals and attitudes while interacting with a tutor are typically unseen and unknowable. However their outward behavior (e.g. problem-solving time, mistakes and help requests) is easily recorded and can reflect hidden affect status. This research evaluates the accuracy of a Bayesian Network to infer a student's hidden attitude toward learning, amount learned and perception of the system from log-data. The long term goal is to develop tutors that self-improve their student models and their teaching, dynamically can adapt pedagogical decisions about hints and help improve student's affective, intellectual and learning situation based on inferences about their goals and attitude.