cssi/SciSciGPT-SciSciNet huggingface dataset:
Sensitivity of estimated elastic moduli to completeness of wave type, measurement type, and illumination apertures at a receiver in multicomponent VSP data

Inversion of phase slowness and polarization vectors measured from multicomponent vertical seismic profile data can yield estimates of all 21 density-normalized elastic moduli for anisotropic elastic media in the neighborhood of each 3C geophone. Synthetic test data are produced by direct evaluation of the Christoffel equation, and by finite-difference solution of the elastodynamic equations. Incompleteness of the data, with respect to illumination (polar and azimuth angle) apertures (qP and/or qS) wave types, wave-propagation directions, and the amount of data (e.g., with or without horizontal slowness components), produces solutions with variations in quality, as revealed by the distribution of model parameter correlations. In a good solution, with all parameters well constrained by the data, the correlation matrix is diagonally dominant. qP-only and qS-only solutions typically produce complementary distributions in their correlation matrices, as they are orthogonal in their sampling of the medium with respect to polarization. The elastic moduli become less independent as the data apertures decrease. If the other input data are relatively complete, the horizontal components of the slowness vector are not needed as the information they contain is redundant. The main consequence of omitting horizontal slowness components is slower convergence. When modest amounts of random noise are added to the slowness and polarization data, in otherwise adequately sampled apertures, the solution is still very close to the correct model, but with larger residual variance.
Constitutive activation and transgenic evaluation of the function of an arabidopsis PKS protein kinase.

A novel family of SOS2 (salt overly sensitive 2)-like protein kinase genes (designated PKSes) have been recently identified in Arabidopsis. The biochemical characteristics as well as in vivo roles of most of the PKSes are unclear at present. In this work, we isolated and characterized one of the PKSes, PKS18. PKS18 was expressed in leaves of matureArabidopsis plants. The glutathioneS-transferase (GST)-PKS18 fusion protein was inactive by itself in substrate phosphorylation. An activation loop Thr169 to Asp mutation, however, highly activated this kinase in vitro (designated PKS18T/D). Kinase activity of the PKS18T/D preferred Mn2+ to Mg2+. The activated kinase showed a substrate specificity, and high catalytic efficiency for a peptide substrate p3 and for ATP. Interestingly,PKS18T/D transgenic plants were hypersensitive to the phytohormone abscisic acid (ABA) in seed germination and seedling growth, whereas silencing the kinase gene by RNA interference (RNAi) conferred ABA-insensitivity, indicating the involvement of PKS18 in plant ABA signaling.
Coupled Rectangular Bars Between Parallel Plates

Curves are presented giving the even-mode fringing capacitance, the odd-mode fringing capacitance, and the difference between odd- and even-mode fringing capacitances for wide ranges of thickness and spacing of rectangular bars centered between parallel plates. Simple formulas are given relating these capacitances to even- and odd-mode characteristic impedances of coupled rectangular bars. possible applications to strip-line and other circuits are described. The appendix gives the derivation of the fringing, capacitances by conformal mapping techniques. The results are exact for bars extending in width infinitely far from the coupling region, and have only small error (less than 1.24 per cent) for bars whose width is greater than about 35 per cent of the difference between plate spacing and bar thickness.
Conducting environmental assessments for physical activity: Determining traffic volume in walkability audits in two west virginia communities

Background: In this article, we examine the possibility of reducing time to conduct traffic volume audits through (1) reducing time for manual traffic counting and (2) using Department of Transportation (DOT) information. Methods: In audits of 824 road segments in 2 West Virginia (WV) communities, manual traffic counts were recorded for 1, 2, and 5 minutes in duration. Annual Average Daily Traffic (AADT) was calculated from counts. Available AADT from DOT was also collected. Percent agreement and a weighted kappa were calculated between 5-minute count and 1- and 2-minute count AADT categories and between 5-minute count and DOT AADT categories. Results: One- and 2-minute counts produced identical AADT categories as 5-minute counts in 93.4% and 95.0% of segments, respectively. Weighted kappa was 0.79 (95% CI = 0.74–0.85) and 0.85 (95% CI = 0.80–0.89), respectively. Forty-two segments (5.1%) had DOT data. Conclusions: DOT AADT was available for a small percentage of road segments assessed. The high agreement...
CASE STUDY: Naloxone Increases Serum Calcium Concentrations after Parturition in Multiparous Holstein Cows

This experiment was conducted to investigate the effect of naloxone, an opioid receptor antagonist, within the first 6 h postpartum in Holstein cows on serum Ca concentrations. Six hours after parturition and first milking, cows were assigned randomly to receive (i.v.) either saline (n = 6) or 0.01 mg/kg of BW of naloxone (n = 6). Blood samples were collected at 10 min intervals from 10 min before until 50 min after treatments. Mean serum Ca was not different (P > 0.05) between groups before treatments. Naloxone caused a transient increase (P < 0.05) in serum Ca concentrations within 20 min after bolus administration. Mean serum Ca was not altered (P = 0.30) in saline-treated cows. The results provide evidence that endogenous opioid peptides play a role in Ca homeostasis, and that their action is mediated through opioid receptors.
MB-24SILAC BASED QUANTITATIVE PROTEOMICS OF MYC-AMPLIFIED MEDULLOBLASTOMA

Despite landmark advances in the genomics of medulloblastoma, significant ambiguity exists in the translation these findings into therapeutic advances. We propose that quantitative proteomics can be used to better discern driver aberrations and more directly view the functional, and therefore targetable, biology of this disease. METHODS: We created a Stable isotope Labeling of Amino acids in cell Culture (SILAC) reference atlas of proteins from 4 medulloblastoma cell lines and spiked it into cell lysates of low passage medulloblastoma cultures. A Hybrid LTQ-Orbitrap mass spectrometer was used to quantitate proteins relative to the atlas. RESULTS AND DISCUSSION: We used the SILAC reference atlas to quantitate the proteome of myc-amplified and non-myc-amplified group 3 low passage medulloblastoma cells. Accurate quantitation was achieved for an average of 1215 proteins per primary cell line. Technical replicates resulted in r2 values between 0.91 and 0.98. The differentially abundant proteins myc-amplified tumors reveal protein-protein connectivity networks associated with alternative splicing, ribosome biogenesis and metabolism. At the junction of splicing and metabolism, we confirmed the upregulation of specific splicing factors (HNRNPs) in the myc-amplified group. We demonstrate the HNRNP control of PKM isoform generation and the subsequent effect upon tumor cell metabolism and resistance to hypoxia. Furthermore, we confirm these proteomic findings using independent medulloblastoma tissue samples and show they are conserved in low passage primary tumor cultures. CONCLUSIONS: Our results demonstrate the advantages of quantitative proteomic profiling to discover oncogenic driver molecules. This is particularly significant given the emerging evidence of the poor correlation between mRNA abundance and protein abundance. Ultimately, insight into the protein level biology provided by these types of studies will yield more readily accessible therapeutic targets and allow clearer inferences of disease biology.
Energy Portfolio Optimization of Data Centers

Data centers have diverse options to procure electricity. However, the current literature on exploiting these options is very fractured. Specifically, it is still not clear how utilizing one energy option may affect selecting other energy options. To address this open problem, we propose a unified energy portfolio optimization framework that takes into consideration a broad range of energy choices for data centers. Despite the complexity and nonlinearity of the original models, the proposed analysis boils down to solving tractable linear mixed-integer stochastic programs. Using experimental electricity market and Internet workload data, various insightful numerical observations are reported. It is shown that the key to link different energy options with different short- and long-term profit characteristics is to conduct risk management at different time horizons. Also, there is a direct relationship between data centers’ service-level agreement parameters and their ability to exploit certain energy options. The use of on-site storage and the deployment of geographical workload distribution can particularly help data centers in utilizing high-risk energy choices, such as offering ancillary services or participating in wholesale electricity markets.
Wound Irrigation Pressure Did Not Affect Reoperation Rate After Open Fracture Repair, but Normal Saline Solution Was Better Than Castile Soap.

FLOW Investigators, Bhandari M, Jeray KJ, Petrisor BA, Devereaux PJ, Heels-Ansdell D, Schemitsch EH, Anglen J, Della Rocca GJ, Jones C, Kreder H, Liew S, McKay P, Papp S, Sancheti P, Sprague S, Stone TB, Sun X, Tanner SL, Tornetta P 3rd, Tufescu T, Walter S, Guyatt GH. A trial of wound irrigation in the initial management of open fracture wounds. N Engl J Med. 2015 Dec 31;373(27):2629-41. ### Question: In patients undergoing irrigation and debridement of an open fracture, what is the optimum irrigation pressure, and is normal saline solution or castile soap the more effective irrigation solution? ### Design: Randomized (allocation concealed), blinded (patients, outcome assessors, and data analysts), controlled trial with 12 months of follow-up. ### Setting: 41 sites in the United States, Canada, Australia, Norway, and India. ### Patients: 2,551 patients ≥18 years of age with an open fracture of the arm, wrist, leg, ankle, foot, clavicle, or scapula were enrolled. Patients with fractures of …
Targeting the latent reservoir to achieve functional HIV cure

While highly active anti-retroviral therapy has greatly improved the lives of HIV-infected individuals, current treatments are unable to completely eradicate the virus. This is due to the presence of HIV latently infected cells which harbor transcriptionally silent HIV. Latent HIV does not replicate or produce viral proteins, thereby preventing efficient targeting by anti-retroviral drugs. Strategies to target the HIV latent reservoir include viral reactivation, enhancing host defense mechanisms, keeping latent HIV silent, and using gene therapy techniques to knock out or reactivate latent HIV. While research into each of these areas has yielded promising results, currently no one mechanism eradicates latent HIV. Instead, combinations of these approaches should be considered for a potential HIV functional cure.
Supporting Collaborative Writing with Microtasks

This paper presents the MicroWriter, a system that decomposes the task of writing into three types of microtasks to produce a single report: 1) generating ideas, 2) labeling ideas to organize them, and 3) writing paragraphs given a few related ideas. Because each microtask can be completed individually with limited awareness of what has been already done and what others are doing, this decomposition can change the experience of collaborative writing. Prior work has used microtasking to support collaborative writing with unaffiliated crowd workers. To instead study its impact on collaboration among writers with context and investment in the writing project, we asked six groups of co-workers (or 19 people in total) to use the MicroWriter in a synchronous, collocated setting to write a report about a shared work goal. Our observations suggest ways that recent advances in microtasking and crowd work can be used to support collaborative writing within preexisting groups.
Mental Retardation: Cognitive Aspects

Standard definitions of mental retardation include three criteria: significantly subaverage intelligence, significant limitations in adaptive skills, and onset during the developmental period. Given the first two criteria, it is clear that cognitive limitations must play a major role in mental retardation. Mental retardation is further divided into four levels, typically on the basis of IQ. Mental retardation may be due to genetic causes (e.g., Down syndrome) and/or environmental causes (e.g., lead poisoning). Three approaches to the study of cognitive aspects of mental retardation are considered. In the ‘difference approach,’ individuals with mental retardation are assumed to differ from individuals with normal development in specific and fundamental ways, beyond simply intellectual slowness. In contrast, in the ‘developmental approach,’ individuals with mental retardation are considered to follow the same sequences of development and have the same structures of intelligence as the general population (i.e., no particular domains of cognitive strength or weakness), although progress is slower and the end point differs. The ‘etiological approach’ is founded on the assumption that the various genetic and environmental causes of mental retardation are likely to have differing effects on brain structure and function, leading to differences across syndromes in characteristic cognitive profiles. The cognitive profiles for Williams syndrome and Down's syndrome are presented.
Lactate Metabolism in Human Lung Tumors

Summary Cancer cells consume glucose and secrete lactate in culture. It is unknown whether lactate contributes to energy metabolism in living tumors. We previously reported that human non-small-cell lung cancers (NSCLCs) oxidize glucose in the tricarboxylic acid (TCA) cycle. Here, we show that lactate is also a TCA cycle carbon source for NSCLC. In human NSCLC, evidence of lactate utilization was most apparent in tumors with high 18 fluorodeoxyglucose uptake and aggressive oncological behavior. Infusing human NSCLC patients with 13 C-lactate revealed extensive labeling of TCA cycle metabolites. In mice, deleting monocarboxylate transporter-1 (MCT1) from tumor cells eliminated lactate-dependent metabolite labeling, confirming tumor-cell-autonomous lactate uptake. Strikingly, directly comparing lactate and glucose metabolism in vivo indicated that lactate's contribution to the TCA cycle predominates. The data indicate that tumors, including bona fide human NSCLC, can use lactate as a fuel in vivo .
Monte Carlo and Discrete Ordinates Calculations of 14-MeV Neutrons Streaming Through a Stainless Steel Duct: Comparison with Experiment I

Measured and calculated neutron and gamma-ray energy spectra from approx. 14 MeV neutrons streaming through a stainless-steel duct having a length-to-diameter ratio of 4.6 are compared. The 1.45-m-long duct is imbedded in a concrete block. The spectra were measured with an NE-213 liquid scintillator as a function of detector location relative to the mouth of the duct. The calculated data were obtained using the Monte Carlo code MCNP and the discrete ordinates code DOT 4.3. The calculations were performed using a two-dimensional cylindrical model of the experiment with symmetry about the duct axis. The measured and calculated neutron and gamma-ray spectra are compared at two distances from the mouth of the duct and at detector locations on and off the duct axis. The neutron spectra calculated with MCNP agree with the measured data within approx. 5 to 50% at all detector locations. The data calculated using the discrete ordinates method are in good agreement with the experiment for the cases where the detector is on axis but are in poor agreement at the off axis detector locations. The gamma-ray spectra calculated with both radiation transport methods are in good agreement (approx. 5 to 25% depending on photon energy) with themore » measured spectra.« less
Integrating country and brand images: Using the product—Country image framework to understand travelers' loyalty towards responsible tourism operators

Abstract While much research into loyalty has been conducted at the destination level, tourists' loyalty towards their intermediary has not been considered. To address this gap, the present study develops a model of tourists' loyalty towards responsible tourism operators by integrating two streams of literature. The first stream pertains to branding, consumer behavior, and international business, specifically Product-Country Image (PCI), while the second stream pertains to the extensive work concerning the concepts of destination image and destination loyalty in tourism. Data were collected using an Internet survey of domestic and international travelers to five responsible tourism operators in India. Results indicate that tourists' motivations to participate in responsible tourism and their perceptions of the destination and the operator's brand constitute the determinants of their attitudinal and behavioral loyalty towards their operator. The study advances the PCI framework in the context of tourism, thus contributing to the literature on image measurement and also extending place image theory. The findings have important product development and positioning implications for operators and destination marketers in India.
A 3.5 GHz AlN S1 lamb mode resonator

This paper presents a 3.5 GHz aluminum nitride (AlN) microelectromechanical system (MEMS) resonator. The high frequency resonance is attained by exploiting the high phase velocity S1 Lamb mode in an AlN thin film. Finite element analyses (FEA) are employed to show a high phase velocity larger than 50000 m/s and a large electromechanical coupling of 3.6% for S1 when h AlN =0.1λ. As predicted by the simulation, the fabricated resonator demonstrates a high frequency resonance at 3.5 GHz and a large electromechanical coupling (k t 2) of 3.59%. Among the demonstrated S1 mode deviecs, this work has achieved the highest product of merit, f • k t 2 • Q, of 69.1.
Cognates interfere with language selection but enhance monitoring in connected speech.

The current study investigated the contribution of phonology to bilingual language control in connected speech. Speech production was elicited by asking Mandarin–English bilinguals to read aloud paragraphs either in Chinese or English, while six words were switched to the other language in each paragraph. The switch words were either cognates or noncognates, and switching difficulty was measured by production of cross-language intrusion errors on the switch words (e.g., mistakenly saying 巧克力 (qiao3-ke4-li4) instead of chocolate). All the bilinguals were Mandarin-dominant, but produced more intrusion errors when target words were written in Chinese than when written in English (i.e., they exhibited robust reversed dominance effects). Most critically, bilinguals produced significantly more intrusions on Chinese cognates, but also detected and self-corrected these same errors more quickly than with noncognates. Phonological overlap boosts dual-language activation thus leading to greater competition between languages, and increased response conflict, thereby increasing production of intrusions but also facilitating error detection during speech monitoring.
Universal Rim Thickness in Unsteady Sheet Fragmentation

Unsteady fragmentation of a fluid bulk into droplets is important for epidemiology as it governs the transport of pathogens from sneezes and coughs, or from contaminated crops in agriculture. It is also ubiquitous in industrial processes such as paint, coating, and combustion. Unsteady fragmentation is distinct from steady fragmentation on which most theoretical efforts have been focused thus far. We address this gap by studying a canonical unsteady fragmentation process: the breakup from a drop impact on a finite surface where the drop fluid is transferred to a free expanding sheet of time-varying properties and bounded by a rim of time-varying thickness. The continuous rim destabilization selects the final spray droplets, yet this process remains poorly understood. We combine theory with advanced image analysis to study the unsteady rim destabilization. We show that, at all times, the rim thickness is governed by a local instantaneous Bond number equal to unity, defined with the instantaneous, local, unsteady rim acceleration. This criterion is found to be robust and universal for a family of unsteady inviscid fluid sheet fragmentation phenomena, from impacts of drops on various surface geometries to impacts on films. We discuss under which viscous and viscoelastic conditions the criterion continues to govern the unsteady rim thickness.
Youth Work: Emerging Perspectives in Youth Development By Edginton, C., Kowalski, C., & Randall, S.

(2005). Youth Work: Emerging Perspectives in Youth Development By Edginton, C., Kowalski, C., & Randall, S. SCHOLE: A Journal of Leisure Studies and Recreation Education: Vol. 20, No. 1, pp. 105-108.
Catecholamines in Behavior and Sensorimotor Integration: The Neostriatal System

The basal ganglia and their significance for behavior and brain function continue to provide major challenges to neurobiology. Indeed, the enormous progress of the past 15 years in the neurochemistry and neuropharmacology of the corpus striatum has not simply solved old problems; it has recast many of them in a new light and added quite a few new ones of its own.
Exploring mobile proxies for better password authentication

Traditional textual password authentication techniques have numerous well documented security and usability flaws, yet have seen near universal deployment due to their desirable efficiency properties. As a result, many users who may prefer alternative authentication approaches are forced to use passwords or PINs on a daily basis due to a lack of control over third party servers. This work explores the use of a mobile device as a proxy for password management in an attempt to improve remote password authentication without making changes to remote servers. A universal proxy-based authentication framework is presented which allows users to employ a method of their own choice to authenticate locally to their mobile devices (e.g., biometrics or graphical passwords). The framework is also compatible with many communication channels between the mobile proxy and local terminal (e.g., Bluetooth or audio). To demonstrate the practicality of this general framework, a concrete implementation using an "out-of-band" audio channel, called PIN-Audio, is also provided. While existing password management solutions may provide a reasonable level of security for commonplace services, PIN-Audio is recommended for a user-friendly deployment for security critical applications, such as online banking.
Do Charters Pose a Threat to Private Schools? Evidence from Nationally Representative Surveys of U.S. Parents.

ABSTRACTCharter schools increasingly challenge both district and private schools for student enrollments in the United States. With more parents able to choose among the sectors, the success of eac...
Acute heart failure

Acute heart failure (AHF) is one of the most common causes for hospital admission and is associated with a high risk of mortality. Compared to chronic heart failure, there is less robust evidence to guide diagnosis, risk stratification and management of AHF. This state-of-the art review aims to summarize new developments in this field. We also highlight areas of ongoing work including novel vasoactive agents, alternative models to traditional hospital admission and strategies to improve patient engagement.
Evaluating Improvement in Situation Awareness and Decision-Making Through Automation : (Poster)

Automated systems such as information extraction (IE) pipelines are designed to facilitate situation awareness by providing human decision makers with relevant information, but beyond the validity of the pipeline itself, designing the output of the pipeline for optimal human understanding should be a goal. This paper presents results comparing comprehension of text documents with and without markup from a (simulated) IE pipeline in a simulated intelligence task. While previous work suggests that markup hurts both objective and subjective measures of performance and preference, this paper uses handgenerated markup designed to be maximally accurate and task relevant, finding more favorable results. These results, however, still point toward the limitations of markup and the importance of the task it is intended to facilitate.
ESRA19-0359 Ultrasound-guided percutaneous cryoneurolysis for analgesia following traumatic RIB fractures

Background and aims Rib fractures occur in 10% of trauma patients, predisposing patients to pulmonary complications with associated morbidity and mortality. Local anesthetic (LA)-based nerve blocks improve pain scores and pulmonary function, but their duration is shorter than the duration of pain. Ultrasound-guided percutaneous cryoneurolysis is an alternative analgesic modality with the potential to provide multiple weeks of analgesia. Methods Patients provided written informed consent for publication. Case 1: An 80-year-old woman presented with fractures of the left 4th through 8th ribs requiring intubation for hypercarbic/hypoxemic respiratory failure. The patient was unable to take adequate tidal volumes secondary to pain. Percutaneous intercostal cryoneurolysis was performed to the associated intercostal nerves, resulting in precipitous decrease in opioid consumption and successful extubation. Case 2: A 64-year-old woman presented with right 4th to 8th rib fractures. Pain at rest was rated 3/10, increasing to 10/10 with coughing or incentive spirometer (IS) use. After cryoneurolysis, her pain at rest decreased to 0/10 and IS values increased from 500 mL to 1500 mL. Case 3: A 73-year-old male presented with right 3rd to 6th rib fractures. Pain scores were 6/10 at rest and 8/10 with IS use. After cryoneurolysis, these decreased to 2/10 and 4/10, respectively. IS values increased from 1000 mL to 1750 mL. Results At 3-month follow up, no patient reported any adverse events or symptoms of neuropathic pain. Conclusions In these three cases, intercostal nerve cryoneurolysis provided sustained analgesia which lasted for several weeks, demonstrating the successful use of this modality for extended analgesia in patients with traumatic rib fractures.
ComplexIoT: Behavior-Based Trust For IoT Networks

This work takes a novel approach to classifying the behavior of devices by exploiting the single-purpose nature of IoT devices and analyzing the complexity and variance of their network traffic. We develop a formalized measurement of complexity for IoT devices, and use this measurement to precisely tune an anomaly detection algorithm for each device. We postulate that IoT devices with low complexity lead to a high confidence in their behavioral model and have a correspondingly more precise decision boundary on their predicted behavior. Conversely, complex general purpose devices have lower confidence and a more generalized decision boundary. We show that there is a positive correlation to our complexity measure and the number of outliers found by an anomaly detection algorithm. By tuning this decision boundary based on device complexity we are able to build a behavioral framework for each device that reduces false positive outliers. Finally, we propose an architecture that can use this tuned behavioral model to rank each flow on the network and calculate a trust score ranking of all traffic to and from a device which allows the network to autonomously make access control decisions on a per-flow basis.
Changes in Soil Properties Under No-Tillage

When farmers shift from a system of agricultural production that includes numerous tillage operations to a reduced or no-tillage system it is reasonable to show concern about how this change in soil management may affect soil properties. For any crop production system to be widely accepted and used it must maintain the physical properties of the soil, and allow for replacement of nutrient removal and other losses. It must also maintain a soil environment favorable for the numerous necessary biological reactions. The microbial activity of the soil is largely determined by the chemical and physical properties of the soil. For example, the placement and amount of organic material directly influences biological activity, as it also does the chemical and physical properties.
Investigating the Effects of Self-Avatars and Story-Relevant Avatars on Children's Creative Storytelling

Storytelling is a critical step in the cognitive development of children. Particularly, this requires children to mentally project into the story context and to identify with the thoughts of the characters in their stories. We propose to support free imagination in creative storytelling through an enactment-based approach that allows children to embody an avatar and perform as the story character. We designed our story creation interface with two modes of avatar: the story-relevant avatar and the self-avatar, to investigate the effects of avatar design on the quality of children's creative products. In our study with 20 child participants, the results indicate that self-avatars can create a stronger sense of identification and embodied presence, while story-relevant avatars can provide a scaffold for mental projection.
1073-P: Phase 2 Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Soluble Guanylate Cyclase Stimulator Praliciguat in Patients with Diabetic Kidney Disease

Background: Impaired nitric oxide (NO) signaling has been implicated in the progression of diabetic kidney disease (DKD). Praliciguat (PRL) is a soluble guanylate cyclase stimulator that augments NO signaling in vitro and reduces proteinuria and fasting plasma glucose in the ZSF1 rat model of DKD. Methods: We evaluated the safety and efficacy of PRL in adults (25-75 y) with type 2 diabetes, eGFR 30-75 mL/min/1.73 m2, urine albumin creatinine ratio (UACR) 200-5000 mg/g, hemoglobin A1c (HbA1c) Results: A total of 156 participants enrolled and 140 completed treatment. Model estimates of mean UACR CFB [90% CI] [intent-to-treat (ITT)] were -28% [-36, -18] for pooled PRL and -15% [-27, 0] for PBO; PBO-adjusted UACR CFB was -15% [-31, 4] (p=0.17). Quality checks identified a site with data inconsistent with that from the overall study population. In a post-hoc sensitivity analysis excluding this site, PBO-adjusted UACR CFB for PRL was -20% [-33, 5], nominal p=0.03. PBO-adjusted CFB for other variables at week 12 (ITT) were 24 h systolic BP -4.2 mmHg [-7.5, -0.8], 24 h heart rate 3.4 bpm [1.6, 5.2], HbA1c -0.27% [-0.50, 0.03], and cholesterol 10.1 mg/dL [-19.2, -1.0]. Both praliciguat doses were well tolerated. Conclusion: PRL did not significantly reduce UACR in the primary ITT analysis, but positive trends in UACR, BP, and metabolic variables warrant further clinical study of PRL in DKD. Disclosure J.P. Hanrahan: Employee; Self; Cyclerion Therapeutics. I. de Boer: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Consultant; Self; George Clinical, Goldfinch Bio, Ironwood Pharmaceuticals. G. Bakris: Consultant; Self; Alnylam, Merck & Co., Inc., Relypsa, Inc., Teijin Pharma Limited. Other Relationship; Self; Bayer AG, Novo Nordisk Inc., Vascular Dynamics. P. Wilson: Employee; Self; Cyclerion Therapeutics. J.D. Wakefield: Stock/Shareholder; Self; Cyclerion Therapeutics. J.P. Seferovic: Employee; Self; Cyclerion Therapeutics. J. Chickering: None. M. Cressman: Employee; Self; Covance, LabCorp. M. Currie: Employee; Self; Cyclerion Therapeutics. Stock/Shareholder; Self; Cyclerion Therapeutics. G.T. Milne: None. A.T. Profy: Employee; Self; Cyclerion Therapeutics, Ironwood Pharmaceuticals. Employee; Spouse/Partner; UpToDate. Stock/Shareholder; Self; Cyclerion Therapeutics, Ironwood Pharmaceuticals. Funding Cyclerion Therapeutics
The Power of Place: Travel to Explore Structural Racism and Health Disparities.

Problem Dismantling structural racism is essential to achieving health equity, but there is little guidance for medical educators who wish to teach learners to recognize and confront structural racism. Approach Critical consciousness provides a framework to identify and dismantle structural racism. Using a critical consciousness approach, the authors developed a novel five-day travel experience to the American South for medical residents and faculty to explore the history and legacy of structural racism and the Civil Rights Movement. The purpose of the travel was to examine the connection between structural racism, especially anti-Black racism, and health disparities in order to better address health inequities within the participants' own home environment. Throughout the trip, faculty leaders applied principles of cultural humility and techniques from critical pedagogy, including recognizing the value of everyone in the room, creating cognitive disequilibrium, and promoting authentic dialogue. Outcomes End-of-week surveys revealed that the trip was well received. Organizers learned important lessons related to faculty and resident dynamics, race-based affinity group meetings, and the respectful use of stories as a tool for learning. Post-trip surveys at 1, 6, and 12 months revealed three major themes: participants experienced (1) transformed understanding of structural racism, (2) increased motivation and bravery to act when witnessing interpersonal and structural racism, and (3) increased practice of cultural humility. Next steps Cultural humility and critical pedagogy can be used with travel to support learners in recognizing and confronting structural racism. The application of such techniques should be explored in local learning environments to foster commitment and action towards dismantling structural racism. In teaching structural racism, medical educators must be willing to consider new ways of teaching and learning.
An Explanation for Repetitive Motor Behaviors in Autism: Facilitating Inventions via Trial-and-Error Discovery.

Clare Harrop, a leading researcher of restricted and repetitive behaviors (RRBs), wrote with her colleagues, “.as a field we do not understand what causes RRBs, and this is particularly difficult to ascertain when children are minimally verbal.” (1). The current account is a response to this request for new ideas about the cause of repetitive behaviors. Motor repetitions in autism are an alternative phenotype which has adaptive and functional consequences: fueling trial-and-error tinkering which could lead to inventions, i.e., novel, useful configurations of objects. This hypothesis is consistent with the proposed mechanism of heterochrony (11), and is complementary to other theories which take a strength-based approach to autism (8, 19). This hypothesis helps explain similarities between motor repetitions and circumscribe interests, illuminates parents' observations of their child's motor repetitions [e.g., (30)], and has heuristic value in providing ideas for therapists to introduce flexibility into the motor routines of minimally verbal children.
Systematic Review of Serum Biomarkers in Traumatic Brain Injury.

Traumatic brain injury (TBI) is responsible for the majority of trauma-related deaths and is a leading cause of disability. It is characterized by an inflammatory process involved in the progression of secondary brain injury. TBI is measured by the Glasgow Coma Scale (GCS) with scores ranging from 15-3, demonstrating mild to severe brain injury. Apart from this clinical assessment of TBI, compendiums of literature have been published on TBI-related serum markers.Herein we create a comprehensive appraisal of the most prominent serum biomarkers used in the assessment and care of TBI.The PubMed, Scopus, Cochrane, and Web of Science databases were queried with the terms "biomarker" and "traumatic brain injury" as search terms with only full-text, English articles within the past 10 years selected. Non-human studies were excluded, and only adult patients fell within the purview of this analysis. A total of 528 articles were analyzed in the initial search with 289 selected for screening. A further 152 were excluded for primary screening. Of the remaining 137, 54 were included in the final analysis. Serum biomarkers were listed into the following broad categories for ease of discussion: immune markers and markers of inflammation, hormones as biomarkers, coagulation and vasculature, genetic polymorphisms, antioxidants and oxidative stress, apoptosis and degradation pathways, and protein markers. Glial fibrillary acidic protein(GFAP), S100, and neurons specific enolase (NSE) were the most prominent and frequently cited markers. Amongst these three, no single serum biomarker demonstrated neither superior sensitivity nor specificity compared to the other two, therefore noninvasive panels should incorporate these three serum biomarkers to retain sensitivity and maximize specificity for TBI.
Systems Approaches to Dissecting Immunity

Systems biology is the comprehensive and quantitative analysis of the interactions between all of the components of biological systems over time. Cells of the innate immune system are the first line of defense against invading pathogens and orchestrate the ensuing adaptive response, which is critical to the establishment of long-term protective immunity. Innate immunity is well suited for systems analysis, because the relevant cells can be isolated in various functional states and many of their interactions can be reconstituted in a biologically meaningful manner. Application of the tools of systems biology to the innate immune system will enable comprehensive analysis of the complex interactions that maintain the fine balance between host defense and inflammatory disease. In this review, we discuss innate immunity in the context of the systems biology concepts, emergence, robustness, and modularity. We also describe recent efforts to apply these approaches to enable rational vaccine design and accelerate the pace of clinical vaccine trials.
Arterial Hypertension in Children And Adolescents [Article in Serbian]

Arterial hypertension in children and adolescents is defined as systolic and/or diastolic blood pressure (BP) that is, on repeated measurements â‰¥95th percentile for gender, age, and height. BP between the 90th and 95th percentile is termed â€žprehypertensiveâ€œ and is an indication for lifestyle modifications. Children older than 3 years old should have their BP measured at least once during every health care episode, while younger ones needs BP measurements at least once a year. The use of casual BP measurements, when performed carefully by trained personnel using calibrated and well-maintained devices, remains the primary screening tool to assess hypertension. Mercury and aneroid devices agree quite closely regarding the pressure that they detect, while oscillometry certainly differs from auscultatory methods, but comes closest to intra-arterial determinations. Ambulatory BP monitoring is now commonly used in diagnosis of pediatric hypertension, especially white coat hypertension, masked hypertension, BP load, and altered circadian BP rhythm. Overall, most childhood hypertension is secondary to an underlying disorder, which, in most cases, is renal disease. Primary hypertension becomes more common with increasing age, obesity and a sedentary lifestyle. Antihypertensive treatment requires a comprehensive approach, incorporating patient and family education, non pharmacologic measures, and if necessary antihypertensive medications, as well as monitoring for medication side effects and treatment response.
Structural integrity of the ribonuclease H domain in HIV-1 reverse transcriptase

The mature form of reverse transcriptase (RT) is a heterodimer comprising the intact 66-kDa subunit (p66) and a smaller 51-kDa subunit (p51) that is generated by removal of most of the RNase H (RNH) domain from a p66 subunit by proteolytic cleavage between residues 440/441. Viral infectivity is eliminated by mutations such as F440A and E438N in the proteolytic cleavage sequence, while normal processing and virus infectivity are restored by a compensatory mutation, T477A, that is located more than 10 A away from the processing site. The molecular basis for this compensatory effect has remained unclear. We therefore investigated structural characteristics of RNH mutants using computational and experimental approaches. Our Nuclear Magnetic Resonance and Differential Scanning Fluorimetry results show that both F440A and E438N mutations disrupt RNH folding. Addition of the T477A mutation restores correct folding of the RNH domain despite the presence of the F440A or E438N mutations. Molecular dynamics simulations suggest that the T477A mutation affects the processing site by altering relative orientations of secondary structure elements. Predictions of sequence tolerance suggest that phenylalanine and tyrosine are structurally preferred at residues 440 and 441, respectively, which are the P1 and P1’ substrate residues known to require bulky side chains for substrate specificity. Interestingly, our study demonstrates that the processing site residues, which are critical for protease substrate specificity and must be exposed to the solvent for efficient processing, also function to maintain proper RNH folding in the p66/p51 heterodimer.
Prereperfusion flushing of ischemic territory: a therapeutic study in which histological and behavioral assessments were used to measure ischemia-reperfusion injury in rats with stroke.

Object. In ischemic stroke, the ischemic crisis activates a cascade of traumatic events that are potentiated by reperfusion and eventually lead to neuronal degeneration. The primary aim of this study was to investigate a procedure that could minimize this damage by interfering with the interactions between reestablished blood flow and ischemically damaged tissue, as well as by improving regional microcirculation. Methods. Using a novel hollow filament, the authors flushed the ischemic territory with heparinized saline before vascular reperfusion after occlusion of the middle cerebral artery (MCA). The results demonstrate a statistically significant (p < 0.001) reduction in infarct volume (75%; from 45.3 ± 3.6% to 11.4 ± 1.7%, determined with Nissl staining) in rats in which a 2-hour MCA occlusion was followed by a 48-hour reperfusion. Infarction and neuronal degeneration were confirmed using silver staining, which revealed a significantly larger infarct (36.3%, p < 0.05) than that detected with Nissl stai...
THE CULTIVATION AND IMMUNOLOGICAL REACTIONS OF THE GLOBOID BODIES IN POLIOMYELITIS

Two additional cultures of globoid bodies, obtained from the nervous tissues of monkeys in which experimental poliomyelitis was produced, and identical with the original cultures described by Flexner and Noguchi, are reported in this paper. The highly parasitic cultures, like Treponema pallidum, are refractory to artificial cultivation. After long cultivation outside the body, the globoid bodies acquire saprophytic properties and then grow more readily and in a considerable variety of media, provided, however, that they carry a certain quantity of protein matter not denatured. The rabbit responds slightly with the production of antibodies to the injection of cultures of the globoid bodies. The monkey responds only occasionally under the same conditions and apparently only when the cultures are injected into the central nervous system. This response is small and at most leads to slight reactions of agglutination and complement deviation with the cultures. The serum obtained from monkeys recovered from experimental poliomyelitis shows even less agglutination and no complement deviation. The maximal agglutinative and morphological changes produced in the globoid bodies cultivated in immune monkey serum are obtained in the first generation; after several subcultures in the immune serum, the reversion to normal takes place in one generation in a non-immune medium. The serum of human beings in the acute or early subacute stages of poliomyelitis gives no complement deviation with the antigen derived from the globoid bodies. The cultivation of the saprophytized globoid bodies through several generations in immune monkey or human serum did not confer upon them pathogenic properties for monkeys. The serum of human beings and monkeys which have survived attacks of poliomyelitis does not fix complement in the presence of antigens prepared from organs of the monkey succumbing to the experimental disease. The globoid bodies and Treponema pallidum present many analogies in cultural, immunological, and pathogenic properties.
Potential effects of glucocorticoids on serum iron concentration in dogs.

Prednisone was give norally(2mg/kg b.i.d.) to seven healthy mixed breed dogs for 3 consecutive days. Serum iron concentration increased significantly (p < 0.05) from 142 +/- 26 micro g/dl (mean +/- SE) before a drug adminis- tration on Day 0 to a maximum of 307 +/- 47 micro g/dl on Day 2, and returned to the Day 0 value by Day 5. Mean total iron binding capacity did not vary more than 25% from the Day 0 value during the 9 day long study. The percent saturation of transferrin with iron increased from 33 +/- 6% on Day 0 to a maximum of 71 +/- 9% on Day 3. This determination had decreased to 34 +/- 3% on Day 5. No statistically significant changes occurred in these parameters studied in six control dogs that were not given the drug. To determine whether serum iron concentration might be correlated with endogenous serum cortisol concentration, these tests were determined in serum collected from nine dogs at 7 a.m., 3 p.m., and 11 p.m. each day for 3 consecutive days. Serum iron concentration was lower at 7 a.m. (147 +/- 9 micro g/dl) than at 3 p.m. (164 +/- 9 micro g/dl) or 11 p.m. (159 +/- 10 micro g/dl). Likewise serum cortisol was lower at 7 a.m. (1.29 +/- 0.18 micro g/dl) than at 3 p.m. (1.49 +/- 0.19 micro g/dl) or 11 p.m. (1.51 +/- 0.22 micro g/dl). There was a significant positive linear correlation between serum iron and serum cortisol concentrations when they were compared using mean values for each dog. From these studies, it appears that exogenously administered glucocorticoids and endogenous increases in serum cortisol concentrations may result in increased serum iron concentrations in dogs.