cssi/SciSciGPT-SciSciNet huggingface dataset:
Effects of Four Preparations of 0.05% Chlorhexidine Diacetate on Wound Healing in Dogs

Four chlorhexidine diacetate (CHD) antiseptic wound lavage preparations were evaluated in vivo to determine their effects on second intention wound healing in the dog in vitro to determine their relative antibacterial activity against Staphylococcus intermedius. Chlorhexidine was diluted to 0.05% in sterile water, 0.9% sodium chloride, lactated Ringers solution (LRS), and LRS that was allowed to form a precipitate with CHD. Control solutions included sterile water and LRS. There were no significant differences in wound contraction or epithelialization. All 0.05% CHD preparations provided 100% bacterial kill.
Genomics in Coccidioides: Insights into evolution, ecology, and pathogenesis

Coccidioides immitis and C. posadasii, the causative agents of the mammalian disease coccidioidomycosis, are dimorphic fungal pathogens distributed throughout desert-like environments in North and South America. Coccidioides spp. are members of the Onygenales, a diverse group of pathogenic and nonpathogenic fungi. Recently, full genomes have been published for Coccidioides and a number of other Onygenales species. Phylogenomic comparisons and additional studies in Coccidioides population genomics and gene expression have shed light on the ecology and pathogenesis of Coccidioides and the other medically important species in this clade. Observed patterns of gene family expansion/contraction and evidence of gene flow have provided insight to the evolution of Coccidioides and greatly broadened our understanding of the diversity and sources of genetic variation found in fungi. In the future, expansion of the number of sequenced isolates from all populations will allow deeper insight into the evolutionary processes that have shaped this unique human pathogen. In addition, deep sequencing of isolates from a single Coccidioides population and pairing of those data with phenotype information on growth and pathogenicity for genome-wide association analysis will allow researchers to find genes responsible for any phenotype, virulence included, that shows variation in the population.
Considering the kinetics of mRNA synthesis in the analysis of the genome and epigenome reveals determinants of co-transcriptional splicing

When messenger RNA splicing occurs co-transcriptionally, the potential for kinetic control based on transcription dynamics is widely recognized. Indeed, perturbation studies have reported that when transcription kinetics are perturbed genetically or pharmacologically splice patterns may change. However, whether kinetic control is contributing to the control of splicing within the normal range of physiological conditions remains unknown. We examined if the kinetic determinants for co-transcriptional splicing (CTS) might be reflected in the structure and expression patterns of the genome and epigenome. To identify and then quantitatively relate multiple, simultaneous CTS determinants, we constructed a scalable mathematical model of the kinetic interplay of RNA synthesis and CTS and parameterized it with diverse next generation sequencing (NGS) data. We thus found a variety of CTS determinants encoded in vertebrate genomes and epigenomes, and that these combine variously for different groups of genes such as housekeeping versus regulated genes. Together, our findings indicate that the kinetic basis of splicing is functionally and physiologically relevant, and may meaningfully inform the analysis of genomic and epigenomic data to provide insights that are missed when relying on statistical approaches alone.
Time Series Models

A time series is a sequence of observations taken over time, for example, a sequence of daily log returns on a stock. In this chapter, we study statistical models for times series. These models are widely used in econometrics as well as in other areas of business and operations research. For example, time series models are routinely used in operations research to model the output of simulations and are used in supply chain management for forecasting demand.
Nitrogen transformations in a through‐flow wetland revealed using whole‐ecosystem pulsed 15N additions

We used pulsed and continuous additions of 15N together with whole-ecosystem metabolism measurements to elucidate the mechanisms of nitrogen (N) transformations in a small (1170 m2) through-flow wetland situated along a stream. From measurements of the wetland inflow and outflow, we observed a consistent decrease in nitrate (by 10% of inflow concentrations), while ammonium increased by an order of magnitude. Outflow ammonium concentrations oscillated in a diel cycle, inverse to the concentration of dissolved oxygen (i.e., greater ammonium export at night). The pulsed 15N additions showed little uptake of nitrate over time in the wetland and rapid daytime uptake of ammonium from the water column (rate constant, kt 5 0.11 h21). A steady-state 15Nammonium addition demonstrated a similar rate of ammonium uptake (kt 5 0.067 h21), no detectable nitrification, and highlighted the spatial pattern of ammonium and nitrate uptake within the wetland. Porewater concentration profiles suggest high rates of net ammonium diffusion from the sediments. Ecosystem metabolism measurements indicate that release was attenuated during the day by autotrophic uptake, resulting in lower ammonium export during the day. Denitrification rates were modeled from dissolved N2 : Ar ratios, but they were not sufficient to account for the observed loss in nitrate. Nitrate was removed near the pond inflow but not actively cycled throughout the pond, while the balance between sediment release and subsequent uptake of ammonium from the water-column dominated N cycling in this wetland.
Smart Phone, Dumb Security

Over one-third of Americans use a smartphone daily and recently there has been a substantial increase in the incidents of malicious software on these devices. Smartphones, being just miniature computers, suffer from the kinds of hacker exploits that were prevalent in the early days of the proliferation of the PC. However, the differences in the ecosystem of these phones with Android being open, Apple which is closed but can be opened and BlackBerry which is completely closed and encrypted, has a profound effect on the security of these devices.
Leishmania donovani ornithine decarboxylase is indispensable for parasite survival in the mammalian host

Mutations within the polyamine biosynthetic pathway of Leishmania donovani, the etiological agent of visceral leishmaniasis, confer polyamine auxotrophy to the insect vector or promastigote form of the parasite. However, whether the infectious or amastigote form of the parasite requires an intact polyamine pathway has remained an open question. To address this issue, conditionally lethal Δodc mutants lacking ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, were created by double targeted gene replacement within a virulent strain of L. donovani. ODC-deficient promastigotes and axenic amastigotes were auxotrophic for polyamines and capable of robust growth only when exogenous putrescine was supplied in the culture medium, confirming that polyamine biosynthesis is an essential nutritional pathway for L. donovani promastigotes. To assess whether the Δodc lesion also affected the ability of amastigotes to sustain a robust infection, macrophage and mouse infectivity experiments were performed. Parasite loads in murine macrophages infected with each of two independent Δodc knockout lines were decreased ∼80% compared to their wild-type counterpart. Furthermore, α-difluoromethylornithine, a suicide inhibitor of ODC, inhibited growth of wild-type L. donovani amastigotes and effectively cured macrophages of parasites, thereby preventing host cell destruction. Strikingly, however, parasitemias of both Δodc null mutants were reduced by 6 and 3 orders of magnitude, respectively, in livers and spleens of BALB/c mice. The compromised infectivity phenotypes of the Δodc knockouts in both macrophages and mice were rescued by episomal complementation of the genetic lesion. These genetic and pharmacological studies strongly implicate ODC as an essential cellular determinant that is necessary for the viability and growth of both L. donovani promastigotes and amastigotes and intimate that pharmacological inhibition of ODC is a promising therapeutic paradigm for the treatment of visceral and perhaps other forms of leishmaniasis.
Contribution of Selection for Protein Folding Stability in Shaping the Patterns of Polymorphisms in Coding Regions

The patterns of polymorphisms in genomes are imprints of the evolutionary forces at play in nature. In particular, polymorphisms have been extensively used to infer the fitness effects of mutations and their dynamics of fixation. However, the role and contribution of molecular biophysics to these observations remain unclear. Here, we couple robust findings from protein biophysics, enzymatic flux theory, the selection against the cytotoxic effects of protein misfolding, and explicit population dynamics simulations in the polyclonal regime. First, we recapitulate results on the dynamics of clonal interference and on the shape of the DFE, thus providing them with a molecular and mechanistic foundation. Second, we predict that if evolution is indeed under the dynamic equilibrium of mutation-selection balance, the fraction of stabilizing and destabilizing mutations is almost equal among single-nucleotide polymorphisms segregating at high allele frequencies. This prediction is proven true for polymorphisms in the human coding region. Overall, our results show how selection for protein folding stability predominantly shapes the patterns of polymorphisms in coding regions.
Signal transduction and the Ets family of transcription factors

Cellular responses to environmental stimuli are controlled by a series of signaling cascades that transduce extracellular signals from ligand-activated cell surface receptors to the nucleus. Although most pathways were initially thought to be linear, it has become apparent that there is a dynamic interplay between signaling pathways that result in the complex pattern of cell-type specific responses required for proliferation, differentiation and survival. One group of nuclear effectors of these signaling pathways are the Ets family of transcription factors, directing cytoplasmic signals to the control of gene expression. This family is defined by a highly conserved DNA binding domain that binds the core consensus sequence GGAA/T. Signaling pathways such as the MAP kinases, Erk1 and 2, p38 and JNK, the PI3 kinases and Ca2+-specific signals activated by growth factors or cellular stresses, converge on the Ets family of factors, controlling their activity, protein partnerships and specification of downstream target genes. Interestingly, Ets family members can act as both upstream and downstream effectors of signaling pathways. As downstream effectors their activities are directly controlled by specific phosphorylations, resulting in their ability to activate or repress specific target genes. As upstream effectors they are responsible for the spacial and temporal expression or numerous growth factor receptors. This review provides a brief survey of what is known to date about how this family of transcription factors is regulated by cellular signaling with a special focus on Ras responsive elements (RREs), the MAP kinases (Erks, p38 and JNK) and Ca2+-specific pathways and includes a description of the multiple roles of Ets family members in the lymphoid system. Finally, we will discuss other potential mechanisms and pathways involved in the regulation of this important family of transcription factors.
Experimental results of covert channel limitation in one-way communication systems

With the increasing growth of electronic communications, it is becoming important to provide a mechanism for enforcing various security policies on network communications. This paper discusses our implementation of several previously proposed protocols that enforce the Bell-LaPadula (1973) security model. We also introduce a new protocol called "Quantized Pump" that offers several advantages, and present experimental results to support our claims.
Integrated Trim and Structural Design Process for Active Aeroelastic Wing Technology

Presented at the 42nd AIAA/ASME/ASCE/AHS/ASC Structures, Structural Dynamics, and Materials Conference, Seattle, WA, April 2001.
Ethical Challenges for the Medical Expert Witness.

Medical expert witnesses are ethically and legally obligated to provide honest testimony that meets the standards of the Daubert test.
Covalent bonding modulated graphene–metal interfacial thermal transport

We report the covalent bonding enabled modulation of the interfacial thermal conductance between graphene and metals Cu, Al, and Pt by controlling the oxidation of graphene. By combining comprehensive X-ray photoelectron spectroscopy (XPS) analysis and time-domain thermoreflectance measurements, we quantify the effect of graphene oxidation on interfacial thermal conductance. It was found that thermal conductance increases with the degree of graphene oxidation until a peak value is obtained at an oxygen/carbon atom percentage of ∼7.7%. The maximum enhancement in thermal conductance was measured to be 55%, 38%, and 49% for interfaces between oxidized graphene and Cu, Al, and Pt, respectively. In situ XPS measurements show that oxygen covalently binds to Cu and graphene simultaneously, forming a highly efficient bridge to enhance the thermal transport. Our molecular dynamics simulations verify that strong interfacial covalent bonds are the key to the thermal conductance enhancement. This work provides valuable insights into the mechanism of functionalization-induced thermal conductance enhancement and design guidelines for graphene-based devices.
Configuration Spaces of Sn+1, n > 1

The configuration spares of spheres, as to be expected, are intimately related to those of the Euclidean spaces of the same dimension. Nevertheless, they present important novel features. The primary difference is due to the fact that the tangent bundle of the sphere is nontrivial except for the cases when the sphere S m is S 1, S 3, or S 7. In this chapter we consider the case m > 2 only, so the relevant configuration spaces are simply connected. The case S 2 presents a new kind of difficulty, as the corresponding configuration spaces are no longer simply connected. It will be taken up in Chapter IV.
Capitalism and Democracy

The Renaissance was an era of fundamental change; it paved the way for the transition from the preindustrial, predominantly agricultural age to the industrial age. Expansion of trade, economic diversity, great geographical discoveries, religious reform, political restructuring, and important scientific developments and technological innovations were largely responsible for civilizational change. Kings and princes during that era were interested in consolidating their political power, while traders and city dwellers were interested in protecting their social and economic freedoms. As a consequence, representatives of the forces of the political and economic processes joined hands to fight and defeat the Church and its political authority and economic doctrine. Since the new state could no longer claim or wish to claim a religious mandate, it had to have the implicit, if not the explicit, consent of its citizens to gain legitimacy and rule.
Availability Optimization in Cloud-Based In-Memory Data Grids

This paper presents a Constraint Programming (CP)-based application for dynamic cache distribution in Oracle Coherence In-Memory Data Grid (IMDG). A re-sizable decomposition method using CP is developed to ensure high availability through incremental optimization of load distribution and data replication. The application highlights the flexibility and efficiency that the CP technology offers for (1) concisely capturing the multiple dynamic aspects and complex constraints of the Oracle Coherence IMDG cache distribution problem; and (2) solving large-scale problem instances in a dynamic cloud environment. Extensive computational results are presented to assess the scalability and efficiency of the proposed solution.
Sex chromosome loss after allogeneic hematopoietic stem cell transplant in patients with hematologic neoplasms: a diagnostic dilemma for clinical cytogeneticists

Background Sex chromosome loss (SCL), including loss of an X chromosome (-X) in females and loss of the Y chromosome (-Y) in males, resulting in a karyotype of 45,X, rarely occurs in patients post an allogeneic hematopoietic stem cell transplant (alloHSCT). However, origin of this abnormal clone and its clinical significance remains unknown.
Determination of the system matrix used in list-mode EM reconstruction of PET

The system matrix bridges measured lines-of- response (LORs) in PET to the object being imaged. Accurate determination of the system matrix remains challenging since every object is different and pre-computing and storing the entire matrix is not feasible due to the large number of scintillation crystals present in current PET scanners. A ray tracing algorithm in list-mode expectation-maximization (EM) reconstruction is commonly used to simplify and calculate the system matrix on-the-fly. The EM algorithm requires an estimate of the sensitivity image which is the summation of the system matrix over all possible LORs and is sometimes computed through a limited sampling of possible LORs. A problem with this approach is that the variation within the sensitivity image can contribute a large amount to the variance of reconstruction through error propagation. Furthermore, it is not feasible to accurately model the detector response for each reconstruction. In this study, we approximated the sensitivity image to be object- independent, thus making it possible to use an accurate Monte Carlo simulator such as GATE to model all interactions within the detector and to pre-compute the sensitivity image only once. Traditionally, the measured LORs contain paired detector IDs but no 3D position information due to limited spatial resolution. We propose a method to model the 3D positions of LORs including the depth of interaction (DOI) in the determination of the system matrix. We investigated the impact of using different techniques for assigning the end-point positions of the LOR in the projection and backprojection operations. Results showed that assigning the end-points to be located in the center of the crystal surface provided the worst performance. Better performance could be achieved by either randomly perturbing the end-points in 2D (across the crystal face), or 3D (including depth) in a 2D PET. The best performance was achieved by using a Monte Carlo derived position distribution. In conclusion, combining a Monte Carlo simulated sensitivity image for a given PET system with a correct LOR 3D position sampling according to a realistic photon distribution in the corresponding detector crystals can significantly improve list-mode EM reconstruction.
Preliminary Thoughts on the Application of Real-Time AI Game-Tree Search to Control

Abstract We introduce a formal definition of a general hybrid system control game, and a decision procedure for an agent which uses simulation to inform game-playing decisions in real-time. We discuss heuristics informing the estimation of expected utilities of actions, describe metalevel reasoning criteria which direct game-tree expansion according to decision relevance, and point out challenges in applying ideas from AI real-time game-tree search to control.
The effect of animation controller and avatar on player perceptions

Real-time animation controllers are fundamental for animating characters in response to player input in digital games. However, the design of such controllers requires making trade-offs between the naturalness of the character's motions and the promptness of the character's response. In this paper, we investigate the effects of such trade-offs on the players' enjoyment, control, satisfaction, and opinion of the character in a simple platform game. In our first experiment, we compare three controllers having the same responsiveness, but varying levels of naturalness. In the second experiment, we compare three controllers having increasing realism at the expense of responsiveness. In our third experiment, we keep motion naturalness and responsiveness constant but vary the avatar. Not surprisingly, our least responsive controller negatively affects players' performance and perceived ability to control the character. However, we also find that players are most satisfied with their own performance using our least natural controller, that differences in animation can significantly alter players' enjoyment with responsiveness being equal, that players do not report increased motion quality with our most natural controller, although viewers outside of the game context do, and that the avatar model affected the perception of the character but not players' enjoyment or perceived realism.
Campus Speech and Harassment

A theoretical question that runs through the debate on the constitutionality of campus speech codes asks whether free speech values are best preserved by categorical rules or balancing factors. Whether campus codes are constitutional should be analyzed through a doctrinal and statutory framework developed outside university settings, in cases involving incitement and harassment. Passionate debates over these matters have in recent years drawn journalistic and legal attention with the burgeoning of clamorous national and local movements calling for university administrators to suppress microagressions, issue trigger warnings, and designate safe spaces.The context of the debate is informed by widely publicized verbal confrontations on U.S. campuses. Much disagreement exists about the legitimacy of universities hosting safe spaces and giving trigger warnings while prohibiting hate speech and microagressions. Various Supreme Court and lower court opinions inform the proper administration of university campuses in a manner conducive to the educational needs of student bodies.Doctrinal avenues exist for creating effective campus codes. Assessment of their constitutionality should be informed by the U.S. Supreme Court’s true threats, fighting words, and defamation doctrines. In addition to the constitutional issues involved, college administrators should obtain guidance from federal statutory anti-harassment policy. Arguably, federal civil rights law requires colleges to take affirmative steps to prevent harassment on campuses. This framework provides the legal foundation for examining and analyzing the constitutionality of campus speech codes that have been promulgated by universities around the country, including the University of Chicago and the University of California.
Skeletal muscle autophagy and its role in sarcopenia and organismal aging

Sarcopenia, the loss of skeletal muscle mass and strength in the aged, is an important medical condition but its etiology is incompletely understood. Because autophagy promotes myofiber atrophy in the young, it was believed that autophagy inhibition would prevent sarcopenia. However, recent studies have revealed that autophagy actually maintains muscle mass and that its function declines during muscle aging. Consistently, boosting basal autophagy protects from age-related muscle dysfunction by promoting the selective degradation of misfolded proteins and dysfunctional organelles. Conversely, autophagy inhibition leads to loss of muscle strength and induces a maladaptive stress response responsible for myofiber atrophy in the aged. In addition to cell-autonomous effects, muscle autophagy and associated signaling pathways induce systemic responses in other aging tissues by modulating the expression and secretion of myokines. We propose that myokines and pharmacologic interventions that boost selective autophagy may prevent sarcopenia, delay systemic aging, and extend health span.
The Clinical Manifestations, Natural History and Results of Treatment of Superior Oblique Myokymia

Superior oblique myokymia is a disorder of unknown etiology, that is characterized symptomatically by oscillopsia, vertical or torsional diplopia, or both. Affected patients show uniocular bursts o...
Two-Dimensional NMR Spectrum Editing of Carbohydrates

Expansion of the application of multiple-pulse NMR methods to chemical analysis has been accompanied by the development of many different NMR spectrum editing techniques that are directed towards selective display of the spectra of various molecular features. One of the most popular one-dimensional (1D) methods of this type has been the Distortionless Enhancement by Polarization Transfer (DEPT) technique (Doddrell et. al., 1982), which is often used to generate carbon-hydrogen multiplicity information for use in automated 13C database and spectral search programs. In its most common form, (Doddrell et al., 1982; Bendall et al., 1982) the 1D DEPT method involves the acquisition of three spectra at three polarization transfer pulse flip angles (θ) of 45°, 90°, and 135°, followed by the construction of three linear combinations of the spectra which form the XH, XH2, and XH3 heteronuclear subspectra (X = 13C or 15N, or other nuclei).
Issues in Seismic Risk Assessment of Transportation Networks

Seismic risk assessment of transportation networks has been the subject of several studies over the past two decades. Many advances have been made during this time, however, numerous issues remain. Recent research addressing some of these issues has demonstrated their importance for rational decision making. In this paper an overview is presented of the most commonly used transportation network risk assessment methodology. Important issues that have received limited attention over the years are identified and recent developments to address these issues are presented. The paper draws on research conducted under the Pacific Earthquake Engineering Center with many contributors (Moore et al., 2005; Fan and Nie, 2006; Kiremidjian et al., 2003; Lee and Kiremidjian 2006; Stergiou and Kiremidjian, 2006).
Phage-encoded cationic antimicrobial peptide used for outer membrane disruption in lysis

Spanins are required for the last step in bacteriophage lysis: the disruption of the outer membrane. Bioinformatic analysis has shown that ~15% of phages lack a spanin gene, which suggests an alternate mechanism of outer membrane disruption. To address this, we selected virulent podophage ϕKT as a spaninless exemplar and tested ϕKT genes for outer membrane disruption during lysis. Hypothetical novel gene 28 causes outer membrane disruption when coexpressed with ϕKT lysis genes and complements the lysis defect of a λ spanin mutant. Gp28 is a 56 aa cationic peptide with predicted amphipathic helical structure and is associated with the particulate fraction after lysis. Urea and KCl washes did not release gp28 from the particulate, suggesting a strong hydrophobic interaction with the membrane. Super high-resolution microscopy supports a primarily outer membrane localization for the peptide. Additionally, holin function is not required for gp28-mediated lysis. Gp28 is similar in size, charge, predicted fold, and membrane association to the human cathelicidin antimicrobial peptide LL-37. In standard assays to measure bactericidal and inhibitory effects of antimicrobial peptides on bacterial cells, synthesized gp28 performed equivalently to LL-37. The studies presented here suggest that ϕKT gp28 disrupts bacterial outer membranes during lysis in a manner akin to antimicrobial peptides. Significance: Here we provide evidence that ϕKT produces an antimicrobial peptide for outer membrane disruption during lysis. The disruptin is a new paradigm for phage lysis, and has no similarities to other known lysis genes. Many mechanisms have been proposed for the function of antimicrobial peptides, however there is not a consensus on the molecular basis of membrane disruption. Additionally, there is no established genetic selection system to support such studies. Therefore, the ϕKT disruptin may represent the first genetically tractable antimicrobial peptide.
Longitudinal association between internalized HIV stigma and antiretroviral therapy adherence for women living with HIV: the mediating role of depression.

Objective We investigated whether internalized HIV-related stigma predicts adherence to antiretroviral therapy (ART) longitudinally in women living with HIV in the United States, and whether depression symptoms mediate the relationship between internalized stigma and suboptimal ART adherence. Design Observational longitudinal study utilizing data from the Women's Interagency HIV Study cohort. Methods A measure of internalized HIV-related stigma was added to the battery of Women's Interagency HIV Study measures in 2013. For current analyses, participants' first assessment of internalized HIV-related stigma and assessments of other variables at that time were used as baseline measures (Time one or T1, visit occurring in 2013/14), with outcomes measured approximately 2 years later (T3, 2015/16; n = 914). A measure of depression symptoms, assessed approximately 18 months after the baseline (T2, 2014/15), was used in mediation analyses (n = 862). Results Higher internalized HIV-related stigma at T1 predicted lower odds of optimal ART adherence at T3 (adjusted odds ratio = 0.61, P = 0.001, 95% confidence interval [0.45, 0.82]). Results were similar when ART adherence at T1 was added as a control variable. Mediation analysis revealed a significant indirect effect of internalized HIV stigma at T1 on ART adherence at T3 through depression symptoms at T2 (while controlling for depression symptoms and ART adherence at T1; B = -0.05, SE = 0.03, 95% confidence interval [-0.11, -0.006]). Conclusion These results provide strong longitudinal support for the hypothesis that internalized HIV-related stigma results in suboptimal ART adherence in a large sample of women living with HIV in the United States, working through the pathway of increased depression symptoms.
Adaptive industrial IOT/CPS messaging strategies for improved edge compute utility

Messaging strategies for data transport play a central role in large scale IIoT/CPS systems. Research to date in these domains has focused on comparative studies of different messaging protocols and various congestion control techniques. This paper presents an experimental evaluation of the latency and throughput for different message payload strategies using the same protocol combined with a novel congestion control algorithm. The results provide key insights based on experiments carried out in a real-world IOT wireless sensor network deployment. The approach presented dynamically varies the message schema and sizes in response to the utilization of edge nodes. The goal is to achieve the highest possible data throughput that fits within the available edge based compute capacity without requiring auto-scaling of back end cloud resources.
Treatment of Dystonia: Deep Brain Stimulation

Deep brain stimulation (DBS) currently has FDA humanitarian device exemption status for the management of hereditary dystonia but is frequently used for a variety of nongenetic forms of dystonia including isolated, adult-onset dystonia and tardive dystonia. The degree and latency of improvement following DBS can be highly variable, particularly for secondary forms of dystonia, with some patients responding almost immediately and others requiring several months before any benefit is achieved. Despite these challenges, the management principles of DBS for primary and secondary dystonia are similar in terms of programming parameters and approach to adjustments.
Abstract 3218: Anti-PD1 and -CTLA-4 combination in vivo enhances DC-based tumor-associated mitochondria antigen immunotherapy efficacy

Somatic mitochondria DNA (mtDNA) abnormalities have been identified in various types of human cancers. Previously, we generated tumor protective immunity under prophylactic and therapeutic approaches employing a murine kidney tumor model system and dendritic cell (DC)-based vaccination containing RENCA-derived mitochondria enriched lysates. Our results shown that tumor-associated mitochondria antigens (TAMAs) are targetable antigens for cancer immunotherapy (PMID: 26378078). Preliminary data also revealed increased endogenous PD-L1 mRNA expression levels in RENCA tumors of treated mice versus healthy kidney tissue. To investigate the impact of PD1/PD-L1 axis antagonism, Balb/C mice were challenged with RENCA cells at day 0 followed by TAMA-vaccination at day 3 and concurrent administration of anti-PD1 (aPD1) 5 times every 3 days. Interestingly, the aPD1-TAMA treatment resulted in reduced tumor growth, greater T CD4+ and T CD8+ cell infiltration, and lower intratumoral-MDSC as compared to the TAMA vaccine alone. In addition, we observed higher T cell activation from the aPD1-TAMA group upon co-culture with bone marrow-derived dendritic cells exposed to RENCA mitochondria lysate, suggesting that the inhibition of PD1 also enhanced the immunogenicity of the TAMA vaccine. Further analysis of the tumor environment revealed that the PD1-PD-L1 axis antagonism correlated with an increment of intratumoral CTLA4 expression and recruitment of T regulatory (Treg) cells. We introduced a third arm of treatment including a CTLA4 antagonist antibody in combination with aPD1 and TAMA vaccine in vivo. Strikingly, the tumor progression was greatly impacted causing tumor rejection in the majority of tumor-bearing animals, sustained tumor volume reduction in the others, a decrease in Treg cell recruitment, and concomitant increment of T CD8+ cell infiltration and activation. Altogether, the combination of check point inhibitors in vivo significantly improved the efficacy of the TAMA immunotherapy by remodeling the tumor microenvironment, reducing the immunosuppressive potential, and facilitating the infiltration of effector T cells into the tumor. Citation Format: Renzo F. Perales-Linares, Stefano Pierini, Mireia Uribe, Sergei Pustylnikov, Francesca Costabile, Silvia Beghi, Andrea Facciabene. Anti-PD1 and -CTLA-4 combination in vivo enhances DC-based tumor-associated mitochondria antigen immunotherapy efficacy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3218.
Does an Observership Count

“Does an observership count?” This question is asked by many IMGs who have graduated from the medical school and wonder whether doing an observership adds value for application. This chapter deals with this conundrum and answers most frequently asked questions about observership that will help IMGs to determine the importance, timing and type of specialty where they should decide to do. This chapter also deals with the cost incurred, visa requirements, and what documents can be expected from the programs that offer observership.
What Defines Different Modes of Snake Locomotion

Animals move in diverse ways, as indicated in part by the wide variety of gaits and modes that have been described for vertebrate locomotion. Much variation in the gaits of limbed animals is associated with changing speed, whereas different modes of snake locomotion are often associated with moving on different surfaces. For several decades different types of snake locomotion have been categorized as one of four major modes: rectilinear, lateral undulation, sidewinding, and concertina. Recent empirical work shows that the scheme of four modes of snake locomotion is overly conservative. For example, during aquatic lateral undulation, the timing between muscle activity and lateral bending changes along the length of the snake, which is unlike terrestrial lateral undulation. The motor pattern used to prevent sagging while bridging gaps also suggests that arboreal lateral undulation on narrow surfaces or with a few discrete points of support has a different motor pattern than terrestrial lateral undulation when the entire length of the snake is supported. In all types of concertina locomotion, the distance from the head to the tail changes substantially as snakes alternately flex and then extend different portions of their body. However, snakes climbing cylinders with concertina exert forces medially to attain a purchase on the branch, whereas tunnels require pushing laterally to form an anchoring region. Furthermore, different motor patterns are used for these two types of concertina movement. Some snakes climb vertical cylinders with helical wrapping completely around the cylinder, whereas all other forms of concertina bend regions of the body alternately to the left and right. Current data support rectilinear locomotion and sidewinding as being distinct modes, whereas lateral undulation and concertina are best used for defining categories of gaits with some unifying similarities. Partly as a result of different motor patterns, I propose recognizing five and four distinct types of lateral undulation and concertina, respectively, resulting in a total of 11 distinct gaits previously recognized as only four.
History Taking for Chronic Pain

The goal of a thorough history is to gather information in order to arrive at a diagnoses causing the chronic pain. A thorough description and documentation of the patient’s pain decreases litigation risk. Helpful questions enable you to decide origin of pain: neuropathic or nociceptive. Keep a wide systems based differential on pain. If patient is on opioid medications, documentation needs to support your treatment decisions as to continuation or adjustment of opioid dosage. This may include benefits, side effects, psychiatric symptoms, substance abuse, and absence of diversion.
Patients’ Views About the Disclosure of Collateral Findings in Pragmatic Clinical Trials: a Focus Group Study

Background Pragmatic clinical trials (PCTs) are increasingly being conducted to efficiently generate evidence to inform healthcare decision-making. Despite their growing acceptance, PCTs may involve a variety of ethical issues, including the management of pragmatic clinical trial-collateral findings (PCT-CFs), that is, information that emerges in PCTs that is unrelated to the primary research questions but may have implications for patients, clinicians, and health systems. Objective We sought to understand patients' views about PCT-CF disclosure, including how, by whom, and the nature and extent of information provided. Design Prospective, qualitative focus group study. Participants Focus groups were conducted in Baltimore, MD; Houston, TX; and Seattle, WA (overall N = 66), during July and August 2019. Approach All groups discussed a hypothetical scenario involving the detection of a PCT-CF of contraindicated medications. Participants were asked about their reactions to the PCT-CF and issues related to its disclosure. Key results Reactions to learning about the PCT-CF were mixed, ranging from fear of a significant health problem, anger that the contraindicated medications had gone unnoticed and/or for being included in research without their permission, to gratitude for the information. Preferences for how such disclosures are made varied but were driven by several consistent desires, namely minimizing patient harm and anxiety and demonstrating trust and respect. Many wanted their treating clinician to be informed of the PCT-CF so that they would be prepared to answer patients' questions and to discuss treatment options. Conclusions The detection of PCT-CFs is likely to increase with further expansion of PCTs. As such, clinicians will undoubtedly become involved in the management of PCT-CFs. Our data illustrate some of the challenges clinicians may face when their patients are informed of a PCT-CF and the need to develop guidance for disclosing PCT-CFs in ways that align with patients' preferences and values.
Temporal and spatial variation among single dopaminergic neuron transcriptomes informs cellular phenotype diversity and Parkinson's Disease gene prioritization

Parkinson's Disease (PD) causes collapse of substantia nigra (SN) dopaminergic (DA) neurons of the midbrain (MB), while other DA populations are relatively spared. Here, we used single-cell RNA-seq (scRNA-seq) to characterize DA neuron populations in the mouse brain at embryonic and postnatal timepoints. These data allow for the discrimination between olfactory bulb (OB), forebrain (FB), and MB DA populations as well identification of subpopulations of DA neurons in each region. We observe a longitudinal axis of MB DA development, during which specialization and heterogeneity increases. We identify three distinct subpopulations of known MB DA neurons and provide evidence of a postnatal MB DA precursor, identifying novel markers for each subpopulation. Further, we discover gene regulatory networks (GRNs) that are significantly associated with neurodegenerative diseases and highly correlated with specific DA neuron subpopulations. By integrating these data with published genome-wide association studies (GWAS), we prioritize candidate genes in all 32 PD associated loci. Collectively, our data reveal genes and pathways that may begin to explain the selective vulnerability of SN DA neurons and allow for the systematic prioritization of genes in PD GWAS loci for functional evaluation.
Clinical Benefit Index

Abstract There are limited methods to analyze both efficacy of a drug and toxicity to a patient in response to treatment. We have developed a metric, the clinical benefit index (CBI) which is quantitative, and a scalable way to integrate patient-reported side effects and efficacy for adaptive randomization. Instead of using efficacy as a singular attribute in decision making for agent selection, we will consider the impact on QoL since many of the newer agents will be less toxic. This will be developed in effort to standardize PRO analysis methods. The clinical benefit index provides an alternative framework for evaluation and would help us to develop a regulatory model for approval of those drugs that have less toxicity by providing a replicable model for measuring toxicity and integrating it with efficacy. Reporting of clinical data can inform the management of toxicity and the integration into a clinical benefit index will help promote regulatory evaluation and preference for less toxic drug/combinations.
Preliminary rib support requirements for solid coal ribs using a coal pillar rib rating (CPRR)

Abstract Researchers from the National Institute for Occupational Safety and Health (NIOSH) are developing a coal pillar rib rating (CPRR) technique to measure the integrity of coal ribs. The CPRR characterizes the rib composition and evaluates its impact on the inherent stability of the coal ribs. The CPRR utilizes four parameters: rib homogeneity, bedding condition, face cleat orientation with respect to entry direction, and rib height. All these parameters are measurable in the field. A rib data collecting procedure and a simple sheet to calculate the CPRR were developed. The developed CPRR can be used as a rib quality mapping tool in underground coal mines and to determine the potential of local rib instabilities and support requirements associated with overburden depth. CPRR calculations were conducted for 22 surveyed solid coal ribs, mainly composed of coal units. Based on this study, the rib performance was classified into four categories. A preliminary minimum primary rib support density (PRSD) line was obtained from these surveyed cases. Two sample cases are presented that illustrate the data collection form and CPRR calculations.
Sex robots for older adults with disabilities: reply to critics.

In ‘Nothing to Be Ashamed of: Sex Robots for Older Adults with Disabilities,’1 I make the case that the unwanted absence of sex from a person’s life represents not just a loss of physical pleasure, but a loss of dignity. Since people aged 65 and over suffer disproportionately from disabilities that impair sexual functioning, I focus on this population. Drawing on an analysis of dignity developed at greater length elsewhere,2 I argue that sex robots can help older adults with disabilities and that societies ought to take reasonable steps to make them available to this population. Unlike other assistive technologies, robots invite human-robot relationships and can form close connections with older adults.3 In response to the proposal, four commentators have introduced objections that I address below. Sorell4 argues that people who are young and able-bodied may wish for sex in their lives too and its absence may be a bigger concern for them than for older people. In reply, while my focus is older adults with disabilities that impair sexual function, I also acknowledge that loss of sexual function can occur at any age as …
Should I Stay or Should I Go?: The Joint Effects of Valuation Specialists’ Knowledge Domain and Employer Type on Perceptions of Organizational-Professional Conflict

Despite specialists’ role in producing fair value measurements, they often encounter tensions that give rise to conflict between the specialists and both their organizational and professional demands. This study surveyed 222 highly qualified specialists to examine how differences in specialists’ domain knowledge and their employer type influence perceptions of a particular type of conflict—organizational-professional conflict (OPC). First, we find that specialists who primarily value financial instruments and are employed by non-professional services firms (e.g., banks) report significantly higher OPC levels, lower job satisfaction, and higher turnover intentions. Next, we find that prior experience in an organization like one’s current employer mitigates your perceived OPC level. Lastly, we find that specialists who have a dual role in working with auditors and management report higher OPC levels when they spend more of their time assisting auditors in evaluating fair value measurements’ reasonableness.
Balancing String Instruction in an Instrumental Lab Setting: An Intrinsic Evaluative Case Study:

There is an expected increase in the need to provide adequate string-specific training for non-string specialists in the future and for preservice music teachers to develop the requisite pedagogica...
Thermodynamics of hydrogen in graphite at high temperature and the effects of oxidation, irradiation and isotopics

Abstract The interaction between hydrogen isotopes and graphite at temperatures of 500–800 °C and a few Pa partial pressure is of importance to the management of tritium produced in fission and fusion reactors. Data are compiled on uptake and desorption from nuclear graphite above 500 °C and up to tens of kPa partial pressures. The enthalpies of reaction at the different types of reactive carbon sites (RCS) are reviewed and then used to discuss how temperature and pressure extrapolations could be performed in order to fill the gaps in available hydrogen uptake data. Chemisorption is the dominant pathway of hydrogen uptake at the conditions of interest. The importance of Trap 2 for reversible hydrogen uptake is emphasized. Neutron irradiation and pre-oxidation of graphite impact the abundance of available RCS and the relative distribution between Trap 1 and Trap 2. Isotopic effects will impact differently the occupancy fraction of Trap 1 and Trap 2.
Similar Solutions of Compressible Boundary-Layer Equations

d F where the suffix w refers to the surface conditions. The condition of heat insulation at the surface is simply 5 = Sw = 0; in that case, Eq. (10) is an identity, while the problem reduces to the solution of the incompressible boundary-layer equation with a main-stream velocity Vi. For the general cases with heat flow across the surface, we must, however, consider Eqs. (9) and (10), together with the boundary conditions, Eqs. (15). If, in Eq. (15), Sw = constant, we can construct similar solutions for the system, Eqs. (9), (10), and (15). To find such similar solutions of the compressible boundary-layer equations, we introduce/, g, v\ as follows: * -rVtfW (16) 5 = Swg(v) (17) Y = ZVi7i (18) where a, b, p, and q are constant parameters satisfying the following conditions simultaneously: dVi dZ K,z-vr (19)