cssi/SciSciGPT-SciSciNet huggingface dataset:
Testing the hadronuclear origin of PeV neutrinos observed with IceCube

We consider implications of the IceCube signal for hadronuclear ($pp$) scenarios of neutrino sources such as galaxy clusters/groups and star-forming galaxies. Since the observed neutrino flux is comparable to the diffuse $\ensuremath{\gamma}$-ray background flux obtained by Fermi, we place new, strong upper limits on the source spectral index, $\ensuremath{\Gamma}\ensuremath{\lesssim}2.1--2.2$. In addition, the new IceCube data imply that these sources contribute at least 30%--40% of the diffuse $\ensuremath{\gamma}$-ray background in the 100 GeV range and even $\ensuremath{\sim}100%$ for softer spectra. Our results, which are insensitive to details of the $pp$ source models, are one of the first strong examples of the multimessenger approach combining the measured neutrino and $\ensuremath{\gamma}$-ray fluxes. The $pp$ origin of the IceCube signal can further be tested by constraining $\ensuremath{\Gamma}$ with sub-PeV neutrino observations, by unveiling the sub-TeV diffuse $\ensuremath{\gamma}$-ray background and by observing such $pp$ sources with TeV $\ensuremath{\gamma}$-ray detectors. We also discuss specific $pp$ source models with a multi-PeV neutrino break/cutoff, which are consistent with the current IceCube data.
Land assembly and urban renewal

Abstract When a developer who wants to assemble several parcels of land to undertake a project with positive externalities cannot make a credible all-or-nothing offer, the optimal acquisition is unlikely to take place. Urban renewal is the traditional way to deal with this inefficiency. Urban renewal tries to correct a real problem, but it does not do so perfectly, or possibly even very well.
Nitrogenase activity is required for the activation of iron-stress response in iron-inefficient T203 soybean

Abstract Iron (Fe)‐stress response and symbiotic nitrogen (N2) fixation are chemical reduction processes within the roots which interact to the extent that nodulated, Fe‐stressed, Fe‐inefficient soybean initiates Fe‐stress response, but similar nonnodulated soybean does not. The objective of this study was to examine the relationship between nitrogenase activity and Fe‐stress response in the Fe‐inefficient T203 soybean by inoculating plants with effective or ineffective strains of Bradyrhizobium japonicum on either side of split‐root systems. Half the roots of each plant were either inoculated with effective or ineffective strains or left uninoculated. Nodules formed on roots inoculated with the ineffective B. japonicum strain, SM5, were similar in number and shape to those on roots inoculated with the effective strain, 61A209, but roots inoculated with SM5 were free of nitrogenase activity. Hydrogen ion and reductant were not released from uninoculated roots or roots inoculated with SM5, but were release...
The politics of barstool biology: Environmental knowledge and power in greater Northern Yellowstone

Abstract Critical researchers of underdevelopment have established a well-known record celebrating the environmental knowledges of subsistence communities in contested wildlife conservation zones. Similar battles are being fought over science, uncertainty, and wild animals in the American west, however, with far less attention to local epistemologies. Often dismissed as “barstool biology”, the ecological knowledges of local hunters in the Northern Yellowstone ecosystem are rooted in environmental experience and situated politics. How does local hunter knowledge diverge or converge with that of state officials, environmentalists, ranchers, and other constituencies, and to what effect on wildlife management policy? This paper seeks to answer that question, reviewing recent research amongst local resource users, managers, and activists in Montana. By rendering empirical the question of local knowledge around America’s oldest national park, rather than trying to “read it off” political affiliation, education, or livelihood, a clearer picture of power, knowledge, and conservation emerges. The results suggest that emerging management policies have developed from the discursive alliance of landowners, outfitters, and environmentalists, shifting priorities towards enclosure and exclusion in wildlife at the expense of other silent constituencies.
Formal games in diagnosis and therapy.

Abstract Formal games with rules are a normal activity of children 6 to 12 years old. Suitable games for use in psychiatric diagnosis and treatment of children in this age group can be classified into games of physical skill, cognitive skill, and chance. Games also vary in levels of complexity, which can be compared with a child's known abilities. In therapy, the game board is a projection of the relationship between child and therapist, allowing the child to communicate in this mode, and also allowing the therapist to make interventions in the context of the game, as well as verbally.
Noninvasive Dynamic Magnetic Resonance Angiography With Time-Resolved Imaging of Contrast KineticS (TRICKS) in the Evaluation of Orbital Vascular Lesions

Objective To evaluate the clinical utility of time-resolved contrast-enhanced magnetic resonance angiography (MRA) in the evaluation of vascular orbital tumors. Methods Retrospective medical record review of patients with vascular orbital lesions imaged with Time-Resolved Imaging of Contrast KineticS (TRICKS; GE Healthcare [Chalfont St Giles, England]) MRA, a noninvasive dynamic imaging modality. Results Five patients with orbital vascular tumors were evaluated using TRICKS MRA. These included 1 patient with a cavernous hemangioma, 2 patients with orbital varices, 1 patient with an orbitocutaneous arteriovenous malformation, and 1 patient who had a solitary fibrous tumor with features of a hemangiopericytoma. In 2 patients, diagnoses were altered as a result of TRICKS MRA. In addition, a young patient with a large orbitocutaneous arteriovenous malformation involving the ophthalmic artery was followed perioperatively and noninvasively using TRICKS MRA, which produced exquisite images and added substantial value in the care of these patients. Conclusion Dynamic MRA in the form of TRICKS is a newly available imaging modality with great potential for improving the evaluation and management of patients with complex orbital tumors.
Rapid cost-effective analysis of microbial activity in soils using modified fluorescein diacetate method

Fluorescein diacetate (FDA) is commonly used to determine the hydrolyzing activity of microbial organisms in the soil. However, the costs of chemical reagents and time required to perform routine analysis of large number of samples by soil testing laboratories are limiting. Moreover, existing methods generate significant volumes of hazardous waste. In this context, this study was designed to determine the minimum amount of terminating chemical reagent needed to evaluate microbial hydrolyzing activity. The results showed that 0.2 mL of chloroform was enough to effectively stop the hydrolyzing activity in soil. This proposed terminating chemical reagent (0.2 mL chloroform) was also evaluated by comparing with the 10 mL of chloroform and 5 mL of methanol used in the Adam and Duncan method.
Tenure and Promotion Experiences of Academic Librarians of Color.

This study broadly examines factors impacting work-life experiences of library faculty of color within the framework of tenure policies and processes. An online survey was sent out to academic librarians of color to gauge perceptions of tenure and promotion policies and processes, professional activities and productivity, organizational climate and culture, and job satisfaction and retention. Results of the survey showed mixed findings regarding the impact of race on the tenure and promotion process. Findings can be used to inform future discussions of recruitment and retention for academic librarians of color and to improve the overall tenure experience.
Gastrointestinal Nuclear Medicine

Hepatobiliary scintigraphy is an NM test that uses bilirubin-like radiotracer that offers dynamic visualization of the hepatocyte function (clearance of radiotracer from the blood by the liver), bile flow (radiotracer passage from the liver), and patency of the biliary tree (radiotracer tracking through), as well as its intestinal passage. The common RF used is 99mTc-mebrofenin. The most common indications for this test include acute cholecystitis (AC), chronic abdominal pain due to functional gallbladder disorders (goes by many other terms, e.g., “gallbladder dyskinesia”, etc.), and biliary leak. The imaging is usually carried out in dynamic planar mode (Fig 37.1a), but static planar imaging and occasionally SPECT or SPECT/CT may be helpful to clarify or resolve uncertain findings.
Feline hip dysplasia A challenge to recognise and treat

Practical relevance:The reported incidence of hip dysplasia (HD) in cats varies dramatically between studies, but the condition is likely more common than we realise. There is little doubt that cats with HD and associated osteoarthritis (OA) suffer pain, and this warrants appropriate therapy.Diagnostic challenges:Clinical signs of HD in cats are often gradual in onset, making them difficult to appreciate, but may include inactivity, pelvic limb lameness, difficulty jumping and climbing stairs, and reluctance to squat to defecate. Often lameness is bilateral, and can be particularly difficult to recognise. The most common radiographic finding is an abnormally shallow acetabulum. Subluxation, however, is not consistently associated with OA in cats and therefore the role that joint laxity plays in disease progression remains uncertain. Degenerative changes of the femoral head and neck seem to develop later than in the dog, and are less marked.Therapeutic challenges:The majority of cats respond to non-surgica...
A Novel Method for CFD Analysis of a Two-Zone Mixing Model for HCCI Engines

Increasing need for clean and efficient energy conversion devices in the automotive sector has pushed technologies such as homogeneous charge compression ignition (HCCI) to the forefront of research. While it offers a number of major advantages in terms of efficiency and emissions, HCCI has significant challenges to overcome before it can be used in a production setting. Among those challenges is the need to control the start of combustion, and one method for doing that is to use variable valve timing to utilize hot, residual exhaust gas. Critical to these residual-affected methods is the role of mixing on the thermodynamic state. This work presents a method for validating a control-oriented two-zone mixing model for HCCI using CFD software. A method of discretizing, extracting, and analyzing the results of the CFD simulation is described, and it is compared with the two-zone model. There is strong correlation, but there is also evidence that the two-zone model needs to be further developed to fully capture the dynamics of mixing.Copyright © 2011 by ASME
Ghost Imaging: A Theme with Variations

Ghost imaging, originally correlation-based image formation using entangled light beams, has grown to encompass a wide range of related computational approaches. This paper surveys the physics and computational aspects of ghost imaging.
Little Business on the Prairie: Entrepreneurship, Prosperity, and Challenge in South Dakota . By Robert E. Wright.

Little Business on the Prairie: Entrepreneurship, Prosperity, and Challenge in South Dakota . Prairie Plains Series. By Robert E. Wright. (Sioux Falls, SD: Center for Western Studies, Augustana College, 2015. x + 340 pp. Illustrations, map, charts, table, notes, bibliography, index. $16.95, paper.) From the title, I expected this book to explore how a single business survived and even thrived in the wilds of South Dakota. Instead, I discovered it to be a sweeping economic history of the state in the context of Robert E. Wright presenting his “entrepreneurship growth model” (p. 8). Basically, this model states that with more freedom comes more innovation and growth, and Wright sees South Dakota as the exemplar of freedom: “it is a free port in a sea of high taxes, ubiquitous regulatory shoals, and …
On Reviser Tang Hezheng of The Pilgrimage to the West——Reading Chen Yuanzhi′s Preface(Part One)

The 1592 Shidetang edition of The Pilgrimage to the West had originally a preface that was attributed to a seemingly real person by the name of Chen Yuanzhi.Due to the lack of in-depth studies on this preface,however,scholars have remained up to now uncertain or in disagreement as to who was Chen Yuanzhi,who was Master of Huayang Cave,and who was the official Tang Guanglu mentioned in the preface.After a detailed analysis of Chen Yuanzhi′s preface to find out by textual research that Tang Guanglu was none other than Tang Hezheng(1538—1619),son of Tang Shunzhi(1507—1560),and he not only wrote the preface for The Pilgrimage to the West,but also revised and expanded it.So comes to the different conclusion that The Pilgrimage to the West was originally written by the father Tang Shunzhi and was revised by the son Tang Hezheng.
Automating inhabitant interactions in home and workplace environments through data-driven generation of hierarchical partially-observable markov decision processes

Markov models provide a useful representation of system behavioral actions and state observations, but they do not scale well. Utilizing a hierarchy and abstraction through hierarchical hidden Markov models (HHMMs) improves scalability, but these structures are usually constructed manually using knowledge engineering techniques. We introduce a new method of automatically constructing HHMMs using the output of a sequential data-mining algorithm, Episode Discovery, and apply it to solving automation problems in the intelligent environment domain. Repetitive behavioral actions in sensor rich environments such as smart homes can be observed and categorized into periodic and frequent episodes through data-mining techniques utilizing the minimum description length principle. Utilizing this approach, we provide an architecture and a set of algorithms for a pervasive computing system showing that inhabitant interactions in home and workplace environments can be accurately automated through sensor observation and intelligent control using a data-driven approach to automatically generate hierarchical inhabitant interaction models in the form of HPOMDPs and these models may be modified using temporal-difference reinforcement learning techniques to continually adapt to changes in the inhabitant's patterns until a new model should be generated. We present our life-long learning system and apply this work in our MavPad and MavLab environments where we have been successful at automating up to 40% of the life of a real inhabitant and 76% of a virtual inhabitant as well as dynamically adapting to concept changes over time. Findings from several case studies are provided to show the feasibility of this approach.
Control of Behavior by Stimuli Associated with Drug Injections

In the life of an addict the actual taking of drugs is highly intermittent. Each drug injection is preceded by a set sequence of behavior involving obtaining money, purchasing the drug, and preparing to inject the drug. The environmental stimuli associated with this set sequence of behavior, such as locations, injection rituals, and the presence of friends, come to play a very important role in the maintenance of drugseeking behavior. Although the importance of this set sequence of behavior has been extensively discussed, notably by Wikler (e.g., 1965) and Vaillant (e.g., 1969), and is generally accepted, there is little direct experimental evidence that is relevant. Studies of the performance of experimental animals under complex schedules of drug injection analogous to those operating with human addicts might provide such evidence. The present paper describes briefly a way of exploring long and orderly sequences of behavior controlled by scheduled presentations of stimuli which are intermittently associated with drug injections.
An Investigation of the Relationship between In-Class and Out-of-Class Efforts on Student Learning: Empirical Evidence and Strategy Suggestion

In this paper we explore and discuss an important research question in higher education – is there a trade-off relationship between in-class and out-of-class efforts for students? We used an empirical model to test the trade-off hypothesis between these two efforts. We identified a trade-off between in-class and out-of-class efforts, especially for those students who do not perform well on examinations. We clarified possible reasons for this relationship in a lower-performing student group and noted potentially harmful implications for higher education. We recommended that instructors work individually with students in setting appropriate goals for each exam and frequently offering feedback. Doing so can strengthen rapport between students and faculty, thereby enhancing students’ motivation to learn and confidence in utilizing faculty as a learning resource. We also recommended a classroom-based game play strategy to promote students’ motivation to learn and encourage their participation.
An experimental method for controlled generation and characterization of microchannel slug flow boiling

Abstract This study uses high-speed imaging to characterize microchannel slug flow boiling using a novel experimental test facility that generates an archetypal flow regime suitable for high-fidelity characterization of key hydrodynamic and heat transfer parameters. Vapor and liquid phases of the fluorinated dielectric fluid HFE-7100 are independently injected into a T-junction to create a saturated two-phase slug flow, thereby eliminating the flow instabilities and flow-regime transitions that would otherwise result from stochastic generation of vapor bubbles by nucleation from a superheated channel wall. Slug flow boiling is characterized in a heated, 500 μm-diameter borosilicate glass microchannel. A thin layer of optically transparent and electrically conductive indium tin oxide coated on the outside surface of the microchannel provides a uniform heat flux via Joule heating. High-speed flow visualization images are analyzed to quantify the uniformity of the vapor bubbles and liquid slugs generated, as well as the growth of vapor bubbles under heat fluxes ranging from 30 W/m2 to 5160 W/m2. A method is demonstrated for measuring liquid film thickness from the visualizations using a ray-tracing procedure to correct for optical distortions. Characterization of the slug flow boiling regime that is generated demonstrates the unique ability of the facility to precisely control and quantify hydrodynamic and heat transfer characteristics. The experimental approach demonstrated in this study provides a unique platform for the investigation of microchannel slug flow boiling transport under controlled, stable conditions suitable for model validation.
She’s supporting them; who’s supporting her?Preschool center-level social-emotional supports and teacher well-being

Preschool teachers across the country have been charged to prepare children socially and emotionally for kindergarten. Teachers working in preschool centers are supporting children's social and emotional learning (SEL) within a rich ecology of emotion and social relationships and the present study considers how the supports implemented for children's SEL at the center-level are associated with teachers' psychological health and workplace experiences. Hierarchical linear models were constructed using data from the Head Start Family and Child Experiences Survey 2009 cohort. Results indicate that although teachers work in individual classrooms, they share common perceptions at the center-level of their workplace climate, access to support, and, although to a lesser extent, experience commonalities in psychological health and job satisfaction. Furthermore, in centers that had implemented more supports for children's SEL (including access to mental health consultants, classroom curriculum, and training and resources for teachers) teachers were less depressed, more satisfied with their jobs, felt more supported in managing challenging behavior, and viewed the workplace climate of their center as more positive. Findings are discussed in light of the national efforts to increase and retain a high-quality early childhood workforce.
Effects of Preemergence Herbicides on Hosta and Daylily

Abstract Thirteen preemergence herbicides were evaluated for phytotoxicity to container grown hosta (Hosta spp. Tratt. ‘Hyacinthina’) and daylily (Hemerocallis spp. L. ‘Sammy Russell’). Severe injury (28 to 55%) was observed from Ronstar (oxadiazon) and Goal (oxyfluorfen) for both species. The other herbicides did not cause visual injury. Three herbicides, Surflan (oryzalin), Endurance (prodiamine) and Pennant (metolachlor), were selected to investigate plant tolerance in field plantings at 1.1, 2.2, and 4.5 kg/ha (1, 2, and 4 lb/A). None of these herbicides caused visual injury or reduced shoot or root weight for 60 or 90 days after treatment. Daylily flower number was not affected by any of the herbicide treatments.
Shock Wave Response of Iron-Based Metallic Glass Matrix Composites

The response of amorphous steels to shock wave compression has been explored for the first time. Further, the effect of the presence of partial crystallinity on the shock response of bulk metallic glasses is examined by conducting experiments on two iron-based in situ metallic glass matrix composites, containing varying amounts of crystalline precipitates, both with initial composition Fe49.7Cr17.7Mn1.9Mo7.4W1.6B15.2C3.8Si2.4. The samples, designated SAM2X5-630 and SAM2X5- 600, are partially crystalline and X-ray amorphous, respectively, due to differences in sintering parameters during sample preparation. Shock response is determined by making velocity measurements at the rear free surface of the samples, which have been subjected to impact from a high-velocity projectile. Experiments have yielded results indicating a Hugoniot Elastic Limit (HEL) to be about 12.5 GPa for SAM2X5-630 and 8 GPa for SAM2X5-600. The former HEL result is higher than elastic limits for any BMG reported in the literature thus far. Both SAM2X5-630 and SAM2X5-600 undergo strain-softening beyond the HEL but seem to recover post-yield strength at a certain higher threshold peak stress. The presence of crystallinity within the amorphous matrix is thus seen to significantly aid in strengthening the material as well as preserving material strength beyond yielding.
The epidemiology of primary hyperparathyroidism in North America.

The impact of primary hyperparathyroidism (HPT) on the population has not been well documented, particularly with respect to asymptomatic HPT. Only 83 deaths were attributed to hyperparathyroidism in the United States in 1999, for a reported death rate of just 0.3 per million per year. Many more patients are affected, of course, and the national hospitalization rate for HPT was 8.0 per 100,000 in 1999, counting 22,000 all-listed diagnoses, and 1.8 per 100,000 counting only the 5000 admissions where HPT was the first-listed discharge diagnosis. Surgery was performed on approximately 12,000 hospitalized patients in the United States in 1999, for a parathyroidectomy rate of about 4.4 per 100,000 per year. Overall, the annual incidence of HPT was 20.8 per 100,000 in Rochester, MN, during 1983-1992, although this represented a substantial decline from incidence rates reported a decade earlier. There are no estimates of HPT prevalence from this country, but the figure was 4.3 per 1000 in one Swedish survey. By any of these measures, HPT is more common in women than men and increases with aging in both sexes. Other risk factors are obscure. The cost of parathyroidectomies for HPT has been estimated at $282 million annually in the United States, but no reliable estimate of overall expenditures for HPT has been made, and no formal assessment of the cost-effectiveness of any treatment approach has been carried out. Better data on the disability and costs related to HPT and its treatment will be needed to devise the most efficient approaches to patient management.
Insane Arsonists: An Early 21st Century Sample

We studied all individuals (n = 41) who had been found not guilty by reason of insanity for arson and who were committed to a California state psychiatric hospital on October 1, 2016 in a cross-sectional analysis. This group of insane arsonists contained 33 (80.5%) males and eight (19.5%) females with a mean age at the time of the index arson of 35.9 years. At least 87.8% (n = 36) were considered to not have been participating in psychiatric treatment at the time of the index arson. Five (12.2%) of the insane arsonists had previously been found not guilty by reason of insanity for arson or had been convicted of having committed arson. Our findings suggest that lack of participation in psychiatric treatment was the most important factor in contributing to the index arson and the most important problem to be addressed in subsequent psychiatric treatment plans.
A Tunable Series Negative Capacitor Using Distributed Amplifier-Based Reconfigurable Negative Group Delay Circuit

A novel tunable non-Foster negative capacitor with unconditional stability using a two-stage microwave distributed amplifier (DA) based negative group delay (NGD) is presented. The tuning mechanism is realized by changing both the transistor's transconductance and input/output phase responses. To achieve this, the transistors placed at each stage of the DA are tuned separately, and two identical varactors placed at the input port and output port are tuned by one single voltage. As proof-of-concept, a prototype of the proposed DA-NGD circuit based tunable negative capacitor is built and tested. The measurement results show that, the negative capacitor can be successfully tuned between −0.5 pF to −1.0 pF.
Adaptive Design and Analysis of Starvation Free Controller Area Network for Multi-Robot System: Barrier Synchronization Technique Applied

The Controller Area Network (CAN) is a message based event-triggered communication service, and primarily applied in automotive and various industries such as vehicles, multi-robot, real-time communication systems and others. The CAN bus connects several independent CAN modules and allows them to communicate and work together asynchronously and/or synchronously. All nodes can simultaneously transmit data to the CAN bus, and the collision of multiple messages on the bus is resolved by a bitwise arbitration algorithm, which operates by assigning a node with low-priority message to switch to a "listening" mode while a node with high-priority message remains in a "transmitting" mode. This arbitration mechanism results in the starvation of lower priority messages. Previous studies resolving the CAN starvation problem have been mostly focused on the arbitration between two nodes, not considering simultaneous transmission of two or more nodes. In this paper, we present a starvation free CAN model that resolves the arbitration of multiple simultaneous transmission of two or more messages.
Constructing the rapist: patterns of reporting sexual violence to the police

ABSTRACTExisting research establishes the importance of social identities and public discourse in reifying existing power structures. By examining the poignant case of the crime of sexual violence,...
CONCOMITANT PROCEDURES: MAPPING, ABLATION, AND LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION

Optimizing ventricular tachycardia (VT) ablation at the time of left ventricular assist device (LVAD) implantation in high-risk patient using open chest electroanatomic mapping is not common. A 58-year-old male with non-ischemic cardiomyopathy (EF 5-10%) status post implantable cardioverter
Diffusiophoretic and diffusioosmotic velocities for mixtures of valence-asymmetric electrolytes

The diffusioosmotic slip velocity due to an applied concentration gradient of the ions in the bulk is predicted for a mixture of valence-asymmetric electrolytes at arbitrary zeta potentials in the limit of a thin double layer.
Spillover as a cause of bias in baseline evaluation methods for demand response programs

Abstract Prior research has shown load reduction estimates from residential event-driven demand response programs (e.g., Critical Peak Pricing) using X of the highest Y days with a weather adjustment method are the best performing within the class of currently used baseline methods. However, they are still biased relative to estimates produced from randomized control trials (RCTs), the unbiased “gold standard” evaluation method. In this paper we identify underlying factors that cause some of the bias found in one commonly used baseline method. Rather than simply quantifying bias, our research provides a deeper understanding of what causes the bias and thus can be used to develop more accurate methods that are not subject to these underlying factors. Previous studies have compared various baseline methods relative to each other; however, because all baseline methods are biased, it is impossible to determine the true bias that exists in them. We have access to a unique RCT dataset: the Sacramento Municipal Utility District’s study of critical peak pricing. Our analysis of 23 event days over two summers allows us to identify the true bias on load reduction estimates by using the RCT estimates as the unbiased gold standard against which we compare the estimates from the baseline methods. We found that spillover of energy reductions, from hours targeted by a program onto other hours, is one underlying factor that is a major cause of bias in baseline methods. We discuss alternative baseline methods that may not be subject to this same bias.
Biomechanical improvements following foot strike biofeedback training for a patient using a passive dynamic ankle-foot orthosis during running.

Background and Purpose:Passive dynamic ankle-foot orthoses have potential to facilitate return to running after a lower limb trauma. However, transitioning patients to new movement patterns that en...
Cathelicidin Peptides Restrict Bacterial Growth via Membrane Perturbation and Induction of Reactive Oxygen Species.

ABSTRACT All metazoans produce antimicrobial peptides (AMPs) that have both broad antimicrobial and immunomodulatory activity. Cathelicidins are AMPs that preferentially kill Gram-negative bacteria in vitro, purportedly by assembling into higher-order structures that perforate the membrane. We utilized high-resolution, single-cell fluorescence microscopy to examine their mechanism of action in real time. Engineered cathelicidins rapidly bound to Gram-negative and Gram-positive cells and penetrated the cytoplasmic membrane. Rapid failure of the peptidoglycan superstructure in regions of active turnover caused leakage of cytoplasmic contents and the formation of membrane-bound blebs. A mutation anticipated to destabilize interactions between cathelicidin subunits had no effect on bactericidal activity, suggesting that cathelicidins have activities beyond perforating the membrane. Nanomolar concentrations of cathelicidins, although not bactericidal, reduced the growth rate of Gram-negative and Gram-positive bacteria. The cells exhibited expression changes in multiple essential processes, including protein synthesis, peptidoglycan biosynthesis, respiration, and the detoxification of reactive oxygen species (ROS). Time-lapse imaging revealed that ROS accumulation preceded bleb formation, and treatments that reduced cellular ROS levels overcame these bactericidal effects. We propose that that the primary effect of cathelicidins is to induce the production of ROS that damage bacterial molecules, leading to slowed growth or cell death. Given their low circulating levels in vivo, AMPs may serve to slow bacterial population expansion so that cellular immunity systems can respond to and battle the infection. IMPORTANCE Antimicrobial peptides (AMPs) are an important part of the mammalian innate immune system in the battle against microbial infection. How AMPs function to control bacteria is not clear, as nearly all activity studies use nonphysiological levels of AMPs. We monitored peptide action in live bacterial cells over short time frames with single-cell resolution and found that the primary effect of cathelicidin peptides is to increase the production of oxidative molecules that cause cellular damage in Gram-positive and Gram-negative bacteria.
Findings of the advanced research workshop

As reported in previous chapters, the “Advanced Research Workshop on Explosives Detection” (the Workshop) represented an important gathering of scientists, engineers, policy-makers, and administrators working within the framework of the NATO Science for Peace and Security (SPS) Programme. The three pillars of SPS are Science, Partnership, and Security, and this workshop thoroughly embodied all three in ways that will be discussed in this chapter. However, participants also identified avenues to strengthen these pillars – especially in Partnership – and we reserve discussion of this pillar for last.
Acute Reversible Cerebral Vasoconstriction Syndrome With Low-Dose Dihydroergotamine Possibly Potentiated by Valproic Acid and Erenumab: A Case Report

Dihydroergotamine (DHE), in the setting of polypharmacy, may increase the possibility of reversible cerebral vasoconstriction syndrome (RCVS). A 64-year-old woman with chronic migraine and medication-overuse headache (on amitriptyline, duloxetine, erenumab) was electively admitted for 5 days of intravenous (IV) ketamine (up to 55 mg/h) to treat intractable migraine pain. On the seventh day, upon receiving her forth dose of IV DHE (0.25 mg) and the first of IV valproic acid (VPA) (500 mg) adjunctively, she developed acute bilateral decreased visual acuity, bitemporal visual field deficit, and unsteady gait. Brain magnetic resonance imaging/magnetic resonance angiography (MRI/MRA) showed confluent bilateral T2 hyperintensities with punctate restricted diffusion in the occipital lobes associated with multi-segmental narrowing involving anterior, middle, posterior cerebral, and basilar arteries consistent with RCVS. Verapamil was initiated, whereas DHE, neuroleptics, and serotonergic agents were discontinued. Though she continued to have constant, non-thunderclap migrainous headache, her other neurologic symptoms resolved in 24 h. Concomitant use of VPA and erenumab with DHE may result in RCVS. VPA likely displaces the protein-bound DHE causing a transient surge of free DHE level in the serum. Erenumab may have impaired the protective vasodilatory mechanism, augmenting DHE’s vasoconstrictive effect. This case report highlights the importance and awareness of such a drug-drug interaction with DHE. J Neurol Res. 2020;10(1):20-24 doi: https://doi.org/10.14740/jnr558
Starting dose selection and dose escalation for oncology small molecule first-in-patient trials: Learnings from a survey of approved drugs.

e15648Background: The ideal starting dose (SD) for an oncology first-in-patient (FIP) trial should be low enough to be safe but not too far removed from therapeutically relevant doses. A low SD com...
An Improved in Vitro Blood-Brain Barrier Model for Applications in Therapeutics’ Delivery to Brain

Blood-brain barrier (BBB) imposes a major obstacle for entry of therapeutics to brain. In vitro BBB models that can provide reliable prediction of therapeutics’ ability to cross BBB are thus, critical for the advancement of brain therapeutics. Towards the development of an improved BBB model, here we studied the individual and combinatorial effect of few different culture conditions on the quality of the commonly used trans-well BBB model. Specifically, we investigated how the addition of (i) astrocyte co-culture, (ii) astrocyte-conditioned media (ACM), and (iii) astrocyte co-culture along with ACM, affects the characteristics of BBB. The resultant BBB models were characterized for trans-endothelial electrical resistance (TEER), permeability, and expression of a tight-junction protein ZO-1. We found that addition of ACM and astrocytes, individually, had similar impact on BBB’s TEER, increasing it by ~2 fold. Interestingly, the presence of both astrocytes and ACM had a significantly greater impact on TEER and increased it by ~3 fold. Addition of ACM, with and without astrocyte co-culture, led to a reduction in permeability of this BBB model. Moreover, addition of ACM and astrocyte co-culture, both individually and in combination, led to a noticeable increase in ZO-1 expression in the BBB endothelial cells. These findings provide a new approach for further improvement of the commonly used trans-well BBB system.
Exploring support for LGBTQ youth transitioning from foster care to emerging adulthood

Abstract Former foster youth are often uniquely disenfranchised, as many suffer from a lack of support (e.g., financial, informational, emotional) resulting from their involvement in foster care. Although all youth who exit foster care as adults may have difficulty accessing the support they need to become healthy-functioning adults, these issues may be exacerbated for LGBTQ (lesbian, gay, bisexual, transgender, queer and questioning) youth who face added health and wellbeing challenges associated with their sexual and/or gender minority statuses. This study used face-to-face, qualitative interviewing and eco-mapping techniques to explore the experiences and perspectives of 21 LGBTQ foster youth, ages 17–21, to identify and describe who provides them with support, the kinds of support they have received, and whether there were any specific support-related needs and challenges they may be experiencing during this critical time. Results revealed that although many LGBTQ foster youth included a variety of child welfare professionals (e.g., caseworkers, foster parents) and other service providers (e.g., teachers, therapists) within their support networks, the majority experienced several unmet needs and challenges—most of which were associated with their sexual and/or gender minority statuses. Multiple themes were identified, including a lack of attention to safety and protection from risks of harm and access to essential care and services (e.g., LGBTQ affirming health care, safe and supportive housing, LGBTQ community-based resources, guidance related to LGBTQ identity development). Results provide initial understanding and awareness of some of the support-related issues and challenges faced by these youth, and help to build a framework of knowledge from which to develop further hypotheses regarding how LGBTQ youth are faring in our nation’s child welfare system. Implications for child welfare policy, practice, and research are discussed.
Intrafibrillar mineralization deficiency and osteogenesis imperfecta mouse bone fragility.

Abstract Osteogenesis imperfecta (OI), a brittle bone disease, is known to result in severe bone fragility. However, its ultrastructural origins are still poorly understood. In this study, we hypothesized that deficient intrafibrillar mineralization is a key contributor to the OI induced bone brittleness. To test this hypothesis, we explored the mechanical and ultrastructural changes in OI bone using the osteogenesis imperfecta murine (oim) model. Synchrotron X-ray scattering experiments indicated that oim bone had much less intrafibrillar mineralization than wild type bone, thus verifying that the loss of mineral crystals indeed primarily occurred in the intrafibrillar space of oim bone. It was also found that the mineral crystals were organized from preferentially in longitudinal axis in wild type bone to more randomly in oim bone. Moreover, it revealed that the deformation of mineral crystals was more coordinated with collagen fibrils in wild type than in oim bone, suggesting that the load transfer deteriorated between the two phases in oim bone. The micropillar test revealed that the compression work to fracture of oim bone (8.2 ± 0.9 MJ/m3) was significantly smaller (p 0.05) between the two genotype groups. In contrast, the uniaxial tensile test showed that the ultimate strength of wild type bone (50 ± 4.5 MPa) was significantly greater (p
Warfarin Induces Calcification of the Aortic Valve Through Extracellular Signal-regulated Kinase 1/2 and β-catenin Signaling.

Abstract Background Recent clinical evidence suggests an association between warfarin use and calcification of the aortic valve. We sought to determine the effect of warfarin on aortic valve interstitial cell (AVIC) osteogenic protein expression and the signaling pathways by which this effect is mediated. Methods Human AVICs were isolated from normal aortic valves of patients undergoing cardiac transplantation while diseased AVICs were isolated from patients undergoing aortic valve replacement for aortic stenosis. AVICs were treated with various anticoagulants and osteogenic protein expression was evaluated using immunoblotting. Phosphorylation of LRP6 and ERK1/2 was evaluated following treatment with warfarin. AVICs were pretreated with LRP6 inhibitor dkk1 and ERK1/2 inhibitor PD98059 followed by treatment with warfarin and osteogenic protein expression was evaluated. Results Warfarin, but not heparin or dabigatran, significantly increased Runx-2 and Osx expression in both normal and diseased human AVICs. Upregulation of β-catenin protein expression and nuclear translocation occurred in diseased AVICs, but not normal AVICs after warfarin treatment. Warfarin induced phosphorylation of LRP6 in diseased AVICs only, and phosphorylation of ERK1/2 in both normal and diseased AVICs. LRP6 inhibition attenuated warfarin-induced Runx-2 expression in diseased AVICs. ERK1/2 inhibition attenuated warfarin-induced Runx-2 expression in both normal and diseased AVICs. Conclusions Warfarin induces osteogenic activity in normal and diseased isolated human AVICs. This effect is mediated by ERK1/2 in both diseased and normal AVICs, but in diseased AVICs, β-catenin signaling also plays a role. These results implicate the role of warfarin in aortic valve calcification and highlight potential mechanisms for warfarin-induced aortic stenosis.
Maximizing and minimizing the boundary scattering mean free path in diameter-modulated coaxial cylindrical nanowires

The thermal conductivity ( k) of semiconducting nanomaterials is influenced by the geometry-dependent phonon boundary scattering mean free path ( Λ Bdy). Although prior work has calculated Λ Bdy of periodically corrugated rectangular nanowires and used these results to study phonon backscattering in nanomaterials, Λ Bdy remains unknown for recently fabricated periodic coaxial cylindrical nanowires. Here, we use phonon ray tracing simulations to comprehensively study the effect of geometric parameters on Λ Bdy in coaxial cylindrical nanowires. We find that for a fixed smaller cylinder diameter ( D 1) and cylinder length ratio, Λ Bdy of periodic nanowires can be maximized or minimized via geometric control of the pitch ( p) and larger cylinder diameter ( D 2). Our simulations show that saturated phonon backscattering for small pitch ratio ( p r) nanowires gives rise to a minimum in Λ Bdy / D 1 at p r near unity, while the maximum in Λ Bdy / D 1 for large p r nanowires can be understood using a simple thermal resistor model for two individual nanowires in series. Combining our Λ Bdy calculations with analytical phonon dispersion and bulk scattering models, we predict that k of periodic silicon nanowires with fixed D 1 can be tuned by up to 34% in the boundary scattering dominated regime by modifying D 2 and p and that variations as large as 135% can be observed in the normalized thermal conductance. Our results provide insight into geometry-dependent phonon backscattering and can be used to predict k of periodic cylindrical nanowires over a range of temperatures and geometric lengthscales.
Contaminants of emerging concern (CECs) in Zea mays: Uptake, translocation and distribution tissue patterns over the time and its relation with physicochemical properties and plant transpiration rate.

Abstract Passive uptake of contaminants of emerging concern (CECs) and its relationship with physicochemical properties, such as lipophilicity (LogKow), ionization behavior (pKa), distribution coefficient (LogDow) and transpiration rate are scarcely studied. In the current study, hydroponically grown corn (Zea mays) was exposed to carbamazepine (CBZ), fluoxetine (FLX), gemfibrozil (GBZ), triclosan (TRI) and atrazine (ATZ)) at environmentally relevant concentrations (20 μg/L each one). Plant tissue concentrations of CECs were determined several times over 21 days. Eighteen plants were used, nine exposed to the CECs and nine untreated. Whole plants were harvested at 7, 14 and 21 days and separated into roots, stem, leaf and male bud flower (only at 21 days). Hydroponic solution was maintained at pH 5.5 throughout the study. CECs concentrations in the exposure solution and tissues were determined by LC-MS/MS. ATZ metabolites desisopropylatrazine (DIA) and desethylatrazine (DEA) were determined by LC-DAD. In shoot tissues, CBZ, FLX and ATZ were detected, while TRI and GBZ were detected only in roots. Root concentrations were related with LogKow (R2ROOT = 0.415). Leaf and stem concentrations of CBZ, FLX and ATZ were linked with LogKow and strongly linked with pKa. Transpiration was related with CBZ and ATZ in shoot, but not related with FLX shoot levels. Neutral compounds such as CBZ (pKa = 13.94; 100% neutral) and ATZ (pKa = 1.6; 85% neutral) were taken up passively with transpiration. Root accumulation was related with CECs lipophilicity, while translocation and bioaccumulation in shoot were not only related with lipophilicity, but also with CECs ionization behavior and transpiration.
Analysis of multisource non-linguistic sound recognition among cochlear implant subjects

Naturalistic sounds carry rich information related to situational context or subject/system properties that contribute towards an acoustic awareness of the ambient environment. Sensorineural hearing loss reduces the functionality of the cochlea, auditory nerve, or central auditory pathways leading to degradation in auditory processing. Cochlear Implants (CIs) have been widely used to restore impaired auditory function and research advancements have focused on improving speech recognition and overall hearing-related quality of life. However, relatively few studies have investigated non-linguistic Sound Recognition (SR) among CI subjects. In this study, the recognition of sounds in CI users is assessed in a competing condition involving at least two non-linguistic sound sources. Furthermore, an end-to-end audio source separation neural network, SuDoRM-RF, with negative and permutation invariance training, is used for audio source recovery and comparatively assessed for potential identification improvement of non-linguistic sounds among CI users. Objective metrics such as classification accuracy, scale-invariant signal-to-distortion-ratio, and other audio quality related measures are used for assessment and subjective evaluation and compared against listener testing with CI subjects. The proposed study can model multi-source non-linguistic sound problems, the cocktail party effect and potentially provide an effective simulation for realistic listening test scenarios. [Study supported by NIH DC010494-01A.]
Ran hits the ground running.

The identification of proteins that are important for microtubule nucleation, regulation of microtubule dynamics and spindle assembly has been an exciting area of research. A series of recent papers have now provided key insights into these processes by identifying downstream targets of Ran that result in aster formation and spindle assembly.