cssi/SciSciGPT-SciSciNet huggingface dataset:
Ehrlichia canis and tropical canine pancytopaenia.

Summary Ehrlichia canis was isolated from a military Jog with tropical canine pancytopaenia and experimental infections were studied in 34 dogs. All dogs developed a high fever. Overt clinical signs were more severe in Beagles than in mongreb, but the haemorrhages seen in naturally and experimentally infected Alsatians did not occur. The main haematological changes were: thrombocytopaenia with altered platelet morphology, increased erythrocyte sedimentation rate and a little later, anaemia. Leucopaenia was less marked. The dogs recovered condition but the infection and thrombocytopaenia persisted for many months. It may be possible to control the infection chemotherapeutically. Administration of a thiosemi-carbazone derivative during the incubation period markedly delayed the onset of infection. Dogs fed a diet containing Oxytetracycline failed to develop infection after experimental challenges, but they were found to be susceptible to E. canis when the antibiotic was withdrawn.
Divorce and the child with cystic fibrosis: the therapeutic and legal implications

Divorce in families of patients with cystic fibrosis (CF) may lead to increased health risk for the child. Five case studies illustrating the adverse impact on the disease status of patients where chronic disagreement and strife occurred between the divorced or separating parents are reviewed. Problems such as denial, poor understanding of the disease, treatment noncompliance, desertion of the child, and remarriage with new spouses can lead to decreased commitment to the intense CF treatment regimen. Health care professionals can be effective advocates on behalf of the child caught in the problem of divorce. They can help the legal system become more sensitive to the needs of the child in the decisions for custody and parental rights as they might impact on the maintenance of treatment and the understanding of a child's vulnerability. Guidelines are discussed for parents, lawyers and judges.
Data Reliability Challenge of Cyber-Physical Systems

Abstract A growing number of cyber-physical systems (CPSs) application domains, such as transportation, energy, sustainability, health, and disaster response, involve humans in nontrivial ways. An emerging application paradigm along with this trend is the use of humans as sensors , which is also commonly known as social sensing . A critical challenge in social sensing is that data sources may be unreliable: a common thread in CPS research focusing on the reliability of CPSs. Current research has mostly focused on the correctness of temporal behavior and correctness of software function . In order for social sensing to become a viable component in CPS feedback loops, it is crucial to understand the correctness of collected observations from unreliable individuals as well. We call this latter challenge the data reliability challenge . This chapter will review recent progress and the state-of-the-art techniques developed in various communities to address the emerging data reliability challenge in CPS.
Abstract 3300: Concerted epigenetic and signaling mechanisms regulate normal stem cell radiosensitivity

Side effects resulting from ionizing radiation (IR) during cancer radiotherapy often involve normal tissue injury including depletion of tissue regenerative capacity. Utilizing multiple in vivo tissue niches and cell culture models, we demonstrate that normal stem cells are highly radiosensitive while differentiated progeny are radioresistant, and IR-induced apoptosis of stem cells is observed broadly throughout the cell cycle independent of proliferation status. Our study demonstrates that normal stem cells fail to activate the DDR, do not display IR-induced foci in vivo as well as in culture, and exhibit severely attenuated DNA repair. Despite normal sensing of DNA breaks, recruitment/ retention of repair factors at DNA break sites is repressed in stem cells. Stem cells are unable to eliminate constitutive phosphorylation of H2AX-Y142 around break sites, abetting stem cells toward an apoptotic instead of repair pathway. The abrogated DDR in normal stem cells is associated with a constitutively enhanced histone-3 lysine-56 acetylation, which epigenetically contributes to muted retention of repair factors. Reinforced PP2A phosphatase expression was also identified as substantial regulators of stem cell radiosensitivity and transient inhibition of phosphatase activity restores stem cell survival. We thus identify pluralistic interacting molecular and epigenetic mechanisms that collectively control and impart IR hypersensitive phenotype to the normal stem cells. These insights will be crucial in development of prevention and intervention therapeutic strategies to minimize IR-induced stem cell dropout and increase the efficacy of radiotherapy. Citation Format: Keith M. Jacobs, Sandeep Misri, Barbara Meyer, Suyash Raj, Cheri L. Zobel, Barry P. Sleckman, Dennis E. Hallahan, Girdhar G. Sharma. Concerted epigenetic and signaling mechanisms regulate normal stem cell radiosensitivity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3300. doi:10.1158/1538-7445.AM2015-3300
Evidence accumulation detected in BOLD signal using slow perceptual decision making

Abstract Background We assessed whether evidence accumulation could be observed in the BOLD signal during perceptual decision making. This presents a challenge since the hemodynamic response is slow, while perceptual decisions are typically fast. New method Guided by theoretical predictions of the drift diffusion model, we slowed down decisions by penalizing participants for incorrect responses. Second, we distinguished BOLD activity related to stimulus detection (modeled using a boxcar) from activity related to integration (modeled using a ramp) by minimizing the collinearity of GLM regressors. This was achieved by dissecting a boxcar into its two most orthogonal components: an “up-ramp” and a “down-ramp.” Third, we used a control condition in which stimuli and responses were similar to the experimental condition, but that did not engage evidence accumulation of the stimuli. Results The results revealed an absence of areas in parietal cortex that have been proposed to drive perceptual decision making but have recently come into question; and newly identified regions that are candidates for involvement in evidence accumulation. Comparison with existing methods Previous fMRI studies have either used fast perceptual decision making, which precludes the measurement of evidence accumulation, or slowed down responses by gradually revealing stimuli. The latter approach confounds perceptual detection with evidence accumulation because accumulation is constrained by perceptual input. Conclusions We slowed down the decision making process itself while leaving perceptual information intact. This provided a more sensitive and selective observation of brain regions associated with the evidence accumulation processes underlying perceptual decision making than previous methods.
An experimental comparison of various methods of nearfield acoustic holography

Abstract An experimental comparison of four different methods of nearfield acoustic holography (NAH) for planar acoustic sources is presented in this study. The four NAH methods considered in this study are based on: (1) spatial Fourier transform, (2) equivalent sources model, (3) boundary element methods and (4) statistically optimized NAH. Two dimensional measurements were obtained at distances ranging from one-half to sixteen microphone spacings away from a sound source and the NAH methods were used to reconstruct the sound field at the source surface. Reconstructed particle velocity and acoustic pressure fields presented in this study showed that the equivalent sources model based algorithm along with Tikhonov regularization provided the best localization of the sources. Reconstruction errors were found to be smaller for the equivalent sources model based algorithm and the statistically optimized NAH algorithm. The effects of hologram distance on the performance of various algorithms are discussed in detail. The study also compares the computational time required by each algorithm to calculate the reconstruction. Four different regularization parameter choice methods were compared. The L-curve method provided more accurate reconstructions than the generalized cross validation and the Morozov discrepancy principle at larger measurement distances. The performance of fixed parameter regularization was comparable to that of the L-curve method.
An Iterative Scheme for Computing Combination Weights in Diffusion Wireless Networks

In this letter, we propose an iterative scheme for computing combination matrices of adaptive networks used in diffusion of data among nodes. In particular, we study the performance of diffusion least-mean-squares algorithms over wireless networks for different choices of left-stochastic combination matrices. We formulate a convex optimization problem using an upper bound of the mean-squares deviation of the network and obtain a closed-form expression to find these matrices. We also propose an adaptive scheme to obtain the optimal weights that runs in real-time along with the estimation process over the network. Numerical experiments support the theoretical findings of this letter.
The Black-Litterman Model in Detail

In this paper we survey the literature on the Black-Litterman model. This survey is provided both as a chronology and a taxonomy as there are many claims on the model in the literature. We provide a complete description of the canonical model including full derivations from the underlying principles using both Theil's Mixed Estimation model and Bayes Theory. The various parameters of the model are considered, along with information on their computation or calibration. Further consideration is given to several of the key papers, with worked examples illustrating the concepts.
Lecture 2: The Componential Subtheory

The first part of the triarchic theory specifies the internal mental mechanisms that are responsible for intelligent behaviour. These mental mechanisms are referred to as information-processing components~ A component is a mental process that may translate a sensory input into a mental representation, transform one mental representation into another, or translate a mental representation into a motor output. Components perform three kinds of functions. Metacomponents are higher order processes used in planning, monitoring, and evaluating one’s task performance. Performance components are processes used in the execution of a task. Knowledge-acquisition components are processes used in learning new things. It is essential to understand the nature of these components, because they form the mental bases for other parts of the theory, that is, for dealing with novel kinds of tasks and situations, for automatising information processing, and for adapting to, shaping, and selecting environments.
Cerebrospinal Fluid Alterations Associated with Central Nervous System Infections

This Chapter represents an extensive literature review of the cellular and chemical alterations in cerebrospinal fluid (CSF) associated with bacterial, fungal, mycobacterial, viral, and parasitic infections of the central nervous system. In addition, CSF reactions secondary to noninfectious meningoencephalitic disorders are discussed. The data herein have been summarized in tabular form to facilitate clinical differential diagnosis.
Fully polarimetrie FMCW instrumentation radar at 228 GHz

The paper reports on a new fully-polarimetric instrumentation radar operating at 228 GHz. The radar is designed to operate in FMCW mode and enjoys high angular and range resolutions and fast data acquisition.
Economic viability of deficit irrigation in the Western US

Abstract In many arid regions of the world, population growth, groundwater depletion, and uncertain supplies have caused water for agricultural production to become increasingly scarce. Deficit irrigation (DI) provides a potential response to water scarcity, but no consensus exists on its economic viability. In this paper, we develop an agro-economic model that connects plant growth-stage-specific evapotranspiration (ET) targets with farm profitability. We use the model to determine the economic conditions under which ET targets of less than 100% are optimal for profit-maximizing maize farmers in Colorado. With 2015 input costs, as maize grain prices increase beyond $0.19 kg−1, DI can become optimal during the late vegetative growth stage but requires a water cost greater than U.S. $0.21 m−3. Under some output price and water cost combinations, DI in the maturation stage also becomes optimal. These results suggest that producers could respond to increasing water scarcity with deficit irrigation, but only in a range of water costs that depends on output price and production costs.
Spectroscopic fast neutron transmission imaging in a treaty verification setting

Measurements of the geometric configuration of objects and their material composition are needed for nuclear treaty verification purposes. We experimentally demonstrate a simple method based on monoenergetic fast neutron transmission to realize crude imaging of the geometric configuration of special nuclear material, confirm its fissionable content, and obtain information on its approximate fissile mass. In the experiment, we used monoenergetic neutrons from D(d, n)3He and T(d, n)4He reactions and a linear array of liquid scintillation detectors to perform spectroscopic neutron imaging of up to 13.7 kg of highly enriched uranium in a spherical geometry. We also show an example of detection of material diversion and confirm the presence of fissionable material based on the measurement of high-energy prompt fission neutrons, including estimating the quantity of material from the comparison of measured and predicted fission neutron emission rate. The combination of crude imaging and fissionable material detection and quantification in a simple approach may be attractive in certain treaty verification scenarios.
Use of Intranasal Dexmedetomidine as a Solo Sedative for MRI of Infants

BACKGROUND: Dexmedetomidine, a selective α-2 receptor agonist, can be delivered via the intranasal (IN) route and be used for procedural sedation. The drug’s favorable hemodynamic profile and relative ease of application make it a promising agent for sedation during radiologic procedures, although there are few studies on its efficacy for MRI studies. METHODS: A retrospective chart review was performed between June 2014 and December 2016. Outpatients between 1 and 12 months of age who received 4 μg/kg of IN dexmedetomidine for MRI were included in the analysis. Our aim with this study was to determine the rate of successful completion of the sedation procedure without the need for a rescue drug (other than repeat IN dexmedetomidine). RESULTS: A total of 52 subjects were included in our study. Median (interquartile range) patient age was 7 (5–8) months. Median (interquartile range) procedure length was 40 (35–50) minutes. Overall success rate (including first dose and any rescue dose IN) of dexmedetomidine was 96.2%. None of the patients had significant adverse effects related to dexmedetomidine. CONCLUSIONS: IN dexmedetomidine is an effective solo sedative agent for MRI in infants.
Treatment of acute exacerbations of interstitial lung disease

Introduction: Interstitial lung diseases (ILD) include a broad range of diffuse parenchymal lung disorders of known and unknown etiologies. Patients with ILD can experience acute exacerbations (AE) which are associated with extremely high morbidity and mortality. Little is known about the etiology of AEs, and whether inciting triggers (such as infection) result in an aberrant inflammatory response in a predisposed host.Areas covered: The majority of data regarding AE-ILD comes from the idiopathic pulmonary fibrosis (IPF) population and is extrapolated to other forms of ILD. For the purposes of this review we have summarized the current literature regarding AE of IPF, and when available have included data from AE of other ILDs.Expert commentary: Therapeutic options for AE are limited without definitive treatments available, and the prognosis is often poor. Treatment is mainly based on correcting hypoxemia, looking for reversible etiologies of respiratory decline, and palliation of symptoms. Overall...
Yield degradation in inertial-confinement-fusion implosions due to shock-driven kinetic fuel-species stratification and viscous heating

Anomalous thermonuclear yield degradation (i.e., that not describable by single-fluid radiation hydrodynamics) in Inertial Confinement Fusion (ICF) implosions is ubiquitously observed in both Omega and National Ignition experiments. Multiple experimental and theoretical studies have been carried out to investigate the origin of such a degradation. Relative concentration changes of fuel-ion species, as well as kinetically enhanced viscous heating, have been among possible explanations proposed for certain classes of ICF experiments. In this study, we investigate the role of such kinetic plasma effects in detail. To this end, we use the iFP code to perform multi-species ion Vlasov-Fokker-Planck simulations of ICF capsule implosions with the fuel comprising various hydrodynamically equivalent mixtures of deuterium (D) and helium-3 (3He), as in the original Rygg experiments [J. R. Rygg et al., Phys. Plasmas 13, 052702 (2006)]. We employ the same computational setup as in O. Larroche [Phys. Plasmas 19, 122706 ...
Infinite Continued Fractions

We dabbled a little into the theory of continued fractions (that is, fractions that continue on and on and on ...) way back on the exercises of Section 3.4. In this chapter we concentrate on this fascinating subject.
Charles Morris and Christian Norberg-Schulz: The Social Basis of Meaning in Architecture

The title of these sessions on architectural meaning could have been given by George Herbert Mead. The intellectual life of Mead was devoted to describing the social foundations of the many dimensions of human life, especially such notions as mind and self. Had he turned his attention to architectural meaning, social foundations would have been his point of departure.
Do Retroviruses Contribute to the Genesis of Intron-Less Pseudogenes?

Vertebrates carry intron-less pseudogenes in their genome. The structure of these pseudogenes suggests that they arose by the retrotransposition of mature (spliced) mRNAs. We have developed a retroviral vector system to investigate whether retrovirus proteins participated in this process. We find that mRNAs which lack all cis-acting sequences required for normal retroviral replication are encapsidated into retroviral particles at an efficiency of 10-4. They are reverse transcribed and integrated into the genome of infected target cells at efficiencies of 10-2 and 10-1, respectively. However, such cDNA genes are truncated at both the 5’ and the 3’ ends; they do not contain poly(A) sequences, and - in three cases investigated so far - are not flanked by direct repeats. Therefore, cDNA genes formed by retroviral proteins lack the typical hallmarks of naturally occurring intron-less pseudogenes.
A Conceptual Framework for Disruptive Innovation in Advising

Institutions of higher education seek innovative opportunities to keep up with changing student needs. Accordingly, frameworks such as Christensen’s Disruptive Innovation theory may appear attractive on the surface to improve advising practices, but a deeper under-standing of context and objectives is imperative to recognizing the applicability of such frame-works to practice. By clarifying what Disruptive Innovation is, and is not (i.e., sustaining innovation), it has been argued that the theory has been misunderstood and misapplied (Christensen et al., “What is Disruptive Innovation?”). A closer look reveals that in addition to benefits, the Disruptive Innovation framework also poses a number of challenges to advising. This study sets out to (1) clarify the theoretical framework of Disruptive Innovation and explore the relationship between Disruptive Innovation and advising; (2) examine the extent to which Disruptive Innovation theory can be applied in advising, via a case study; and (3) discuss the implications for Disruptive Innovation in advising.
3D printed microfluidic devices with immunoaffinity monoliths for extraction of preterm birth biomarkers

Preterm birth (PTB) is defined as birth before the 37th week of pregnancy and results in 15 million early deliveries worldwide every year. Presently, there is no clinical test to determine PTB risk; however, a panel of nine biomarkers found in maternal blood serum has predictive power for a subsequent PTB. A significant step in creating a clinical diagnostic for PTB is designing an automated method to extract and purify these biomarkers from blood serum. Here, microfluidic devices with 45 μm × 50 μm cross-section channels were 3D printed with a built-in polymerization window to allow a glycidyl methacrylate monolith to be site-specifically polymerized within the channel. This monolith was then used as a solid support to attach antibodies for PTB biomarker extraction. Using these functionalized monoliths, it was possible to selectively extract a PTB biomarker, ferritin, from buffer and a human blood serum matrix. This is the first demonstration of monolith formation in a 3D printed microfluidic device for immunoaffinity extraction. Notably, this work is a crucial first step toward developing a 3D printed microfluidic clinical diagnostic for PTB risk.
Trends in stage at diagnosis for young breast cancer patients in the United States.

Purpose Previous studies reported increasing rates of metastatic breast cancer among young US women. However, these studies were based on limited geographic areas and did not account for the sharp decline in unknown-stage disease. In this study, we examined trends in early-onset breast cancer incidence rates by stage at diagnosis in a national dataset, after correcting for temporal changes in unstaged disease. Methods Using data from 42 states, covering 82% of the US population, we examined trends in incidence rates by stage at diagnosis and race/ethnicity in women ages 20-39 years. Stage was imputed for non-Hispanic (NH) white and NH black cases with missing information by distributing cases proportionally according to survival statistics. Results During 2001-2015, incidence rates of early-onset metastatic breast cancer increased sharply among NH white, NH black, Hispanic, and Asian/Pacific Islander (API) women. Increasing trends were also observed for local-stage disease (all racial/ethnic groups) and regional-stage disease (NH white and API). In contrast, rates decreased sharply for unstaged disease among all groups. After imputing stage for cases with missing information, the increasing trends for regional- and distant-stage disease in NH whites and local-stage disease in NH blacks were no longer statistically significant, but the increase in distant-stage disease in NH blacks was unchanged. Conclusions After accounting for the sharp decline in unstaged cases, the increase in incidence rates for distant-stage disease became non-significant in NH whites but not in NH blacks. Future studies should consider accounting for temporal changes in unstaged disease when examining stage-specific incidence trends.
Antimicrobial Activity of a Bioemulsifiеr Рroduced by Saccharomyces cerevisiae

This study was designed to evaluate the ability of bioemulsifier to inhibit the growth of some рathogenic microorganisms. Different Iraqi source of Saccharomyces cerevisiae were tested for their ability to рroduce bioemulsifier. The рroduction of bioemulsifier was detected by determination of emulsificаtion index (E24%), extracted and purified, the antimicrobial activity of рurifiеd bioemulsifier was tested against some рathogenic microorganisms. Results revealed that bioemulsifier reduced the growth of bacteria (Escherichia coli, Staрhylococcus aureus, Рsеudomonas aeruginosa, Bacillus cereus, Bacillus subtilis.
Perceptions of Low-Income Students Completing a Nutrition Education Program.

Abstract Objective To capture students’ perceptions of participating in a nutrition education program. Design Focus groups (n = 16). Setting Low-income schools in Rhode Island. Participants A total of 64 low-income, ethnically and racially diverse third-grade students, 93.5% of whom were eligible for free or reduced-price meals, 62% of whom were Hispanic, and 16% of whom were black. Main Outcome Measure(s) Perceptions about the program's impact on food and beverage consumption, the value of the program, potential changes for improvement, and barriers to change. Analysis Focus groups were recorded, transcribed, and coded using a hybrid approach of inductive and deductive thematic analysis. Interrater agreement was calculated. Results Students perceived that the program positively influenced their attitudes toward making healthy choices and what they and their families were eating. Students reported increased empowerment, bravery to try new foods, and knowledge. Students enjoyed the program but suggested increasing the duration and frequency of lessons and including peer-to-peer education. Students felt that the tastiness of unhealthy food was a barrier to choosing healthier food. Conclusions and Implications Findings suggest that the program may have improved students’ knowledge, empowerment, and bravery, and that this had a positive influence on healthy food consumption for students and their families. Input from students will help inform future modifications to the curriculum.
Chapter 1 Diterpene Alkaloids From Aconitum, Delphinium, and Garry A Species: The C19-Diterpene Alkaloids

Publisher Summary This chapter discusses C19-diterpene alkaloids. The structures of the more complicated diterpene alkaloids may be subdivided into two general types that are closely related. The first is the lycoctonine-type that is based on the parent alkaloid lycoctonine, and the second is the aconitine-type based on the parent alkaloid of the same name. Derivatives of both lycoctonine and aconitine have been subjected to X-ray crystallographic analysis and their absolute configurations have been established from these studies. A small group of diterpene alkaloids occurring in the liquors of Aconitum heterophyllum Wall is modeled on a modified lycoctonine-type skeleton and contains a lactone ring. The most prevalent of these compounds, heteratisine, is related in a simple fashion to the other members of the series, therefore, its chemistry is discussed in the chapter. The chapter also discusses uncharacterized alkaloids, such as lappaconitine, talatisine, and talatisamine.
Implementation of a medical coding curriculum for surgery residents.

Abstract Background Medical coding knowledge is important for practice. We hypothesized that general surgery residents lack confidence in medical coding (MC) and that implementation of focused didactics would increase resident confidence and knowledge. Methods A MC curriculum was delivered to general surgery residents covering domains of the global procedural period (GPP), evaluation and management (E/M) coding, and hospital payment and quality metrics (HPQM). A 21-question survey was developed to assess resident comfort coding knowledge. Efficacy of the MC curriculum was measured by anonymous paper pre-test and post-test surveys. Results Pre-test (n = 50) findings revealed that residents were uncomfortable with MC. Following three MC lectures, the post-test (n = 24) demonstrated significant increases in resident comfort with MC (p Conclusions Residents feel uncomfortable with MC without formal education. This study supports a focused curriculum to prepare residents for practice.
Transethnic meta-analysis of metabolic syndrome in a multiethnic study.

Genome-wide association studies (GWAS) have been used to establish thousands of genetic associations across numerous phenotypes. To improve the power of GWAS and generalize associations across ethnic groups, transethnic meta-analysis methods are used to combine the results of several GWAS from diverse ancestries. The goal of this study is to identify genetic associations for eight quantitative metabolic syndrome (MetS) traits through a meta-analysis across four ethnic groups. Traits were measured in the GENetics of Noninsulin dependent Diabetes Mellitus (GENNID) Study which consists of African-American (families = 73, individuals = 288), European-American (families = 79, individuals = 519), Japanese-American (families = 17, individuals = 132), and Mexican-American (families = 113, individuals = 610) samples. Genome-wide association results from these four ethnic groups were combined using four meta-analysis methods: fixed effects, random effects, TransMeta, and MR-MEGA. We provide an empirical comparison of the four meta-analysis methods from the GENNID results, discuss which types of loci (characterized by allelic heterogeneity) appear to be better detected by each of the four meta-analysis methods in the GENNID Study, and validate our results using previous genetic discoveries. We specifically compare the two transethnic methods, TransMeta and MR-MEGA, and discuss how each transethnic method's framework relates to the types of loci best detected by each method.
Effect of genetic liability to migraine on cognition and brain volume: A Mendelian randomization study.

ObjectiveTo investigate potential causality between genetic liability to migraine and Alzheimer’s disease, intelligence, and brain volume using two-sample Mendelian randomization.MethodsThe exposur...
Changes in knee kinematics from applied external Tibial torque: Implications for stabilizing an anterior cruciate ligament deficient knee.

Abstract Background Changes in knee kinematics from internal tibial torque under tibiofemoral compression force have been studied, but the potentially stabilizing effects of external tibial torque have not been reported. We hypothesized that for a given knee flexion angle, 1) external torque would significantly reduce anterior tibial translation, internal tibial rotation, and valgus tibial rotation before and after sectioning the anterior cruciate ligament and 2) changes in kinematics from applied external torque would be significantly greater with the cruciate cut. Methods A robotic test system was used to flex intact human knees continuously from 0° to 50° under 200 N compression, without and with 5 Nm external torque. Tests were repeated after cruciate section. Findings With the cruciate intact, external torque had no significant effect on anterior translation, and significantly reduced internal and valgus rotations at all flexion angles. With the cruciate cut, external torque significantly reduced anterior translation beyond 25° flexion, significantly reduced internal rotation at all flexion angles, and significantly reduced valgus rotation beyond 15° flexion. Although external torque had no significant effect on anterior translation with the ACL intact, external torque produced relatively large decreases in anterior translation with the cruciate sectioned (−11.6 mm at 50° flexion). Reductions in valgus rotation from applied external torque were significantly greater for cruciate deficient knees beyond 25° flexion. Interpretation We conclude that external tibial torque may be important for controlling the abnormal kinematics associated with an anterior cruciate ligament deficient knee, and possibly help stabilize the knee during in vivo activities.
Nature versus Nurture: Assessing the Impact of Strain Diversity and Pregrowth Conditions on Salmonella enterica, Escherichia coli, and Listeria Species Growth and Survival on Selected Produce Items.

ABSTRACT Inoculation studies are important when assessing microbial survival and growth in food products. These studies typically involve the pregrowth of multiple strains of a target pathogen under a single condition; this emphasizes strain diversity. To gain a better understanding of the impacts of strain diversity (“nature”) and pregrowth conditions (“nurture”) on subsequent bacterial growth in foods, we assessed the growth and survival of Salmonella enterica (n = 5), Escherichia coli (n = 6), and Listeria (n = 5) inoculated onto tomatoes, precut lettuce, and cantaloupe rind, respectively. Pregrowth conditions included (i) 37°C to stationary phase (baseline), (ii) low pH, (iii) high salt, (iv) reduced water activity, (v) log phase, (vi) minimal medium, and (vii) 21°C. Inoculated tomatoes were incubated at 21°C; lettuce and cantaloupe were incubated at 7°C. Bacterial counts were assessed over three phases, including initial reduction (phase 1), change in bacterial numbers over the first 24 h of incubation (phase 2), and change over the 7-day incubation (phase 3). E. coli showed overall decline in counts ( IMPORTANCE Our findings suggest that inclusion of multiple pregrowth conditions in inoculation studies can best capture the range of growth and survival patterns expected for Salmonella enterica and Escherichia coli present on produce. This is particularly important for fresh and fresh-cut produce, where stress conditions encountered by pathogens prior to contamination can vary widely, making selection of a typical pregrowth condition virtually impossible. Pathogen growth and survival data generated using multiple pregrowth conditions will allow for more robust microbial risk assessments that account more accurately for uncertainty.
Identification of LRRK2 missense variants in the accelerating medicines partnership Parkinson's disease cohort.

Pathogenic missense variants in the leucine-rich repeat kinase 2 (LRRK2) gene have been identified through linkage analysis in familial Parkinson disease (PD). Subsequently, other missense variants with lower effect sizes on PD risk have emerged, as well as non-coding polymorphisms (e.g. rs76904798) enriched in PD cases in genome-wide association studies. Here we leverage recent whole-genome sequences from the Accelerating Medicines Partnership-Parkinson's Disease (AMP-PD) and the Genome Aggregation (gnomAD) databases to characterize novel missense variants in LRRK2 and explore their relationships with known pathogenic and PD-linked missense variants. Using a computational prediction tool that successfully classifies known pathogenic LRRK2 missense variants, we describe an online web-based resource that catalogs characteristics of over twelve-hundred LRRK2 missense variants of unknown significance. Novel high-pathogenicity scoring variants, some identified exclusively in PD cases, tightly cluster within the ROC-COR-Kinase domains. Structure-function predictions support that some of these variants exert gain-of-function effects with respect to LRRK2 kinase activity. In AMP-PD participants, all p.R1441G carriers (N = 89) are also carriers of the more common PD-linked variant p.M1646T. In addition, nearly all carriers of the PD-linked p.N2081D missense variant are also carriers of the LRRK2 PD-risk variant rs76904798. These results provide a compendium of LRRK2 missense variants and how they associate with one another. While the pathogenic p.G2019S variant is by far the most frequent high-pathogenicity scoring variant, our results suggest that ultra-rare missense variants may have an important cumulative impact in increasing the number of individuals with LRRK2-linked PD.
Restorative Justice From Prosecutors' Perspective

Restorative justice processes have been promoted as an alternative to criminal adjudication for many years outside the United States and, in recent years, in the United States as well. In the United States, restorative justice processes are used in some jurisdictions in cases involving juvenile offenders or low-level, nonviolent offenses by adults, but they have rarely been used in cases of adult felony offenders charged with serious violent crimes. Whether restorative justice processes will be used more broadly depends largely on whether prosecutors become receptive to their use. A handful of newly elected “progressive prosecutors” have expressed interest in applying restorative justice processes in these and other kinds of felony cases involving adult defendants. But conventional prosecutors generally remain uninterested in or hostile to restorative justice, even though most accept problem-solving courts and other alternatives to prosecution and incarceration. This Article explores why mainstream U.S. prosecutors are disposed against restorative justice and suggest how their concerns might best be addressed by restorative justice proponents.
Human Papillomavirus and Survival of Sinonasal Squamous Cell Carcinoma Patients: A Systematic Review and Meta-Analysis.

Human papillomavirus (HPV) is detectable in a subset of sinonasal squamous cell carcinoma (SNSCC), but the impact on patient outcomes is presently unclear due to a modest number of studies with limited statistical power. Therefore, we conducted a systematic review and meta-analysis to better clarify this relationship. A PubMed search was conducted to identify all studies reporting on overall (OS) or disease-free survival (DFS) for SNSCC by HPV status. Hazard ratios (HR) and corresponding 95% confidence intervals (CI) were extracted or, when not provided, indirectly estimated from each manuscript. Summary survival curves for 5-year OS and estimating survival probability by HPV status at pre-specified time intervals from study-specific Kaplan-Meier curves generated 2-year DFS. Log HRs and log CIs were combined across studies to generate summary estimates and a corresponding 95% CIs for OS and DFS. We identified ten unique studies reporting on OS and four for DFS. We observed a significant association between HPV and OS (summary HR = 0.51, 95% CI: 0.38–0.70) with relatively low heterogeneity between studies. These results indicate that HPV is a significant predictor of more favorable survival for SNSCC, and thus may be a useful biomarker for prognostication and, potentially, treatment modulation.
Novel allosteric ligands of the angiotensin receptor AT1R as autoantibody blockers

While orthosteric ligands of the angiotensin II (AngII) type 1 receptor (AT1R) are available for clinical and research applications, allosteric ligands are not known for this important G protein-coupled receptor (GPCR). Allosteric ligands are useful tools to modulate receptor pharmacology and subtype selectivity. Here, we report AT1R allosteric ligands for a potential application to block autoimmune antibodies. The epitope of autoantibodies for AT1R is outside the orthosteric pocket in the extracellular loop 2. A molecular dynamics simulation study of AT1R structure reveals the presence of a druggable allosteric pocket encompassing the autoantibody epitope. Small molecule binders were then identified for this pocket using structure-based high-throughput virtual screening. The top 18 hits obtained inhibited the binding of antibody to AT1R and modulated agonist-induced calcium response of AT1R. Two compounds out of 18 studied in detail exerted a negative allosteric modulator effect on the functions of the natural agonist AngII. They blocked antibody-enhanced calcium response and reactive oxygen species production in vascular smooth muscle cells as well as AngII-induced constriction of blood vessels, demonstrating their efficacy in vivo. Our study thus demonstrates the feasibility of discovering inhibitors of the disease-causing autoantibodies for GPCRs. Specifically, for AT1R, we anticipate development of more potent allosteric drug candidates for intervention in autoimmune maladies such as preeclampsia, bilateral adrenal hyperplasia, and the rejection of organ transplants.
Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection.

Lyme Disease caused by infection with Borrelia burgdorferi is an emerging infectious disease and already by far the most common vector-borne disease in the U.S. Similar to many other infections, infection with B. burgdorferi results in strong antibody response induction, which can be used clinically as a diagnostic measure of prior exposure. However, clinical studies have shown a sometimes-precipitous decline of such antibodies shortly following antibiotic treatment, revealing a potential deficit in the host’s ability to induce and/or maintain long-term protective antibodies. This is further supported by reports of frequent repeat infections with B. burgdorferi in endemic areas. The mechanisms underlying such a lack of long-term humoral immunity, however, remain unknown. We show here that B. burgdorferi infected mice show a similar rapid disappearance of Borrelia-specific antibodies after infection and subsequent antibiotic treatment. This failure was associated with development of only short-lived germinal centers, micro-anatomical locations from which long-lived immunity originates. These showed structural abnormalities and failed to induce memory B cells and long-lived plasma cells for months after the infection, rendering the mice susceptible to reinfection with the same strain of B. burgdorferi. The inability to induce long-lived immune responses was not due to the particular nature of the immunogenic antigens of B. burgdorferi, as antibodies to both T-dependent and T-independent Borrelia antigens lacked longevity and B cell memory induction. Furthermore, influenza immunization administered at the time of Borrelia infection also failed to induce robust antibody responses, dramatically reducing the protective antiviral capacity of the humoral response. Collectively, these studies show that B. burgdorferi-infection results in targeted and temporary immunosuppression of the host and bring new insight into the mechanisms underlying the failure to develop long-term immunity to this emerging disease threat.
Balancing computational science and computer science research on a terascale computing facility

The design and deployment of Virginia Tech's terascale computing cluster is described. The goal of this project is to demonstrate that world-class on-campus supercomputing is possible and affordable, and to explore the resulting benefits for an academic community consisting of both computational scientists and computer science researchers and students. Computer science research in high performance computing systems benefits significantly from hands-on access to this system and from close collaborations with the local computational science user community. We describe an example of this computer science research, in the area of dynamically resizable parallel applications.
Immunostimulatory early phenotype of tumor-associated macrophages does not predict tumor growth outcome in the HLA-DR mouse model of prostate cancer (TUM4P.923)

Tumor-associated macrophages (TAM) were shown to support progression of many solid tumors. However, anti-tumor properties of TAM were also reported in several types of cancer. Here, we investigated the phenotype and functions of TAM in two transgenic mouse models of prostate cancer displaying striking differences in the tumor growth outcome. Mice expressing Prostate-Specific Antigen as a self-antigen in the prostate ( PSA tg mice) rejected PSA-expressing TRAMP tumors with high frequency. However, introduction of HLA-DRB1*1501(DR2b) transgene aggravated the growth of TRAMP-PSA tumors in DR2bxPSA F1 mice. Despite the difference in the tumor growth outcome, tumors in both strains were equally and intensively infiltrated by TAM at the first week after tumor challenge. TAM exhibited mixed M1/M2 polarization characterized by the production of pro-inflammatory (TNFα, IL1β) and anti-inflammatory (IL10) cytokines. They also secreted T cell/NK cell-recruiting chemokines (CXCL10, CCL2, CCL3, CCL4, CCL5) and expressed high levels of MHC class II and co-stimulatory molecules. Functionally, TAM demonstrated pronounced immunostimulatory activity in a mixed leukocyte reaction and induced apoptosis of tumor cells. We conclude that during early stages of tumor progression, the phenotype and functional properties of TAM did not predict tumor growth outcome in our model. Furthermore, we demonstrate that at this stage TAM have a potential to activate T cell immunity and mediate anti-tumor effects.
Analytic RISM theory of polymer alloys: molecular closure predictions for structurally symmetric blends

Polymer reference interaction site model (PRISM) theory with new molecular closure approximations is applied to analytically calculate the phase behavior and effective SANS χ parameter of binary blends composed of long threadlike chains. A general analysis of the validity of incompressible approaches to computing thermodynamics and scattering patterns is presented. The special case of structurally symmetric mixtures is then considered in depth, and the influence of density and coupled density/concentration fluctuations, or «compressibility effects», is investigated. Significant corrections to mean field Flory-Huggins theory are found for short and intermediate length polymers
On the formation of meteoritic chondrules by aerodynamic drag heating in the solar nebula

During the formation of the solar nebula, interstellar grains were falling into the nebula with velocities of the order of 10 km/s at the radial distance where the meteorites were to form. This kinetic energy is 20 times the amount of thermal energy needed to melt the grains. The grains were decelerated by aerodynamic drag in the nebula. Where grain-rich parcels of interstellar material fell into the nebula, heat generated by drag could not be radiated away because of the opacity imparted to the system by the grains, and high temperatures were reached. In this situation presolar aggregations of grains would melt to form chondrules. Many of the properties of chondrules (and also Ca/Al-rich inclusions) are consistent with their formation by this means. The infall-heating concept provides a new framework in which the formation and significance of chondritic meteorites can be understood.
New Insights into Prostate Cancer Biology

Prostate cancer is common, biologically heterogeneous, and protean in its clinical manifestations. Through the use and analysis of isogenic cell lines, xeno-grafts, transgenic mice, and human tumors, one begins to deconvolute the precise biologic mechanisms that combine to create the native complexity and heterogeneity of this disease. In this article, the authors have underscored compelling recent discoveries in prostate cancer so as to provide the reader with molecular paradigms with which to interpret future insights into its biology. Although it was inevitably necessary to omit a significant amount of important research in prostate cancer, the work discussed here is exemplary of current prostate cancer research. Looking forward, it is hoped that the collective work of mapping genetic and biologic interactions among key regulators of prostate epithelial cells, epithelial-stromal interactions, host immune system, and host genetics will eventually result in a comprehensive understanding of prostate cancer. Although it is likely that the molecular characteristics of an individual's prostate cancer will be analyzed using limited molecular tools in the near future, eventual application of genomic technologies and nanotechnology offers the promise of robust future characterization. Such a characterization is likely to be required to maximize our ability to optimize and individualize preventive and treatment strategies.
Molecular mechanisms in atrial fibrillation

Atrial fibrillation is the most common, significant clinical arrhythmia, yet relatively little is known about the primary etiology of this condition and it remains difficult to treat or prevent. Atrial fibrillation induces remodeling of atrial myocytes that in turn helps to sustain the arrhythmia and increases susceptibility to recurrence. Recent work suggests that atrial fibrillation is a heterogeneous syndrome but subsets with specific etiologies are beginning to be uncovered. Identification of the discrete causes of atrial fibrillation will enable the development of targeted strategies for the prevention and treatment of this morbid disorder.