cssi/SciSciGPT-SciSciNet huggingface dataset:
Preschoolers' Normative and Prescriptive Judgments about Relational and Overt Aggression

The present study examines preschoolers' judgments about responses to hypothetical aggressive provocation. Ninety-nine preschool children were read two stories, one depicting an overt provocation and the other depicting a relational provocation. Following each story, children were interviewed to assess their normative (what a peer would do) and prescriptive (what a peer should do) judgments about the victim's behavior. Additionally, perceptions about the relative degree of badness of different types of aggressive responses (physical, verbal, and relational) to the provocation were assessed. The results showed several significant effects with respect to aggression type, age, participant gender, and story-character gender. For example, in both of the provocation situations, participants reported that overtly aggressive responses (physical and verbal) would happen more often than they should happen. Moreover, in both the provocation situations, participants felt that relationally aggressive responses were mo...
Mixing device for generating simple chromatographic gradients

Abstract A linear gradient device consisting of two concentric reservoirs of equal cross-sectional area, in which the initial and limiting eluent solutions are maintained in hydrostatic equilibrium, may be constructed from several combinations of commercial acrylic resin cylinders. By the use of nesting cylinders, the areas of the reservoirs may be reduced independently, allowing an assortment of nonlinear gradients to be produced by simple adjustment of the area ratio of the two reservoirs.
On the critical coupling strength for Kuramoto oscillators

The celebrated Kuramoto model captures various synchronization phenomena in biological and man-made dynamical systems of coupled oscillators. It is well-known that there exists a critical coupling strength among the oscillators at which a phase transition from incoherency to synchronization occurs. This paper features three contributions. First, we characterize and distinguish the different notions of synchronization used throughout the literature and formally introduce the concept of phase cohesiveness as an analysis tool and performance index for synchronization. Second, we review the vast literature providing necessary, sufficient, implicit, and explicit estimates of the critical coupling strength in the finite and infinite-dimensional case. Finally, we present the first explicit necessary and sufficient condition on the critical coupling strength to achieve synchronization in the finite-dimensional Kuramoto model for an arbitrary distribution of the natural frequencies. The multiplicative gap in the synchronization condition yields a practical stability result determining the admissible initial and the guaranteed ultimate phase cohesiveness as well as the guaranteed asymptotic magnitude of the order parameter.
The Elephant and the Blind Men: Making Sense of PARP Inhibitors in Homologous Recombination Deficient Tumor Cells.

Poly(ADP-ribose) polymerase 1 (PARP1) is an important component of the base excision repair (BER) pathway as well as a regulator of homologous recombination (HR) and nonhomologous end-joining (NHEJ). Previous studies have demonstrated that treatment of HR-deficient cells with PARP inhibitors results in stalled and collapsed replication forks. Consequently, HR-deficient cells are extremely sensitive to PARP inhibitors. Several explanations have been advanced to explain this so-called synthetic lethality between HR deficiency and PARP inhibition: i) inhibition of base excision repair leading to enhanced DNA double-strand breaks, which cannot be repaired in the absence of HR; ii) trapping of inhibited PARP1 at sites of DNA damage, which inhibits access of other repair proteins; iii) failure to synthesize poly(ADP-ribose) polymer, which is required to recruit mutant BRCA1 to sites of DNA damage; and iv) activation of the NHEJ pathway, which selectively induces error-prone repair in HR-deficient cells. Here we review evidence regarding these various explanations for the ability of PARP inhibitors to selectively kill HR-deficient cancer cells.
Erratum to “Passive Decomposition and Control of Nonholomic Mechanical Systems”

In the previous paper, a production error occurred which resulted in the omission of the author's last set of changes to the final published paper. We sincerely regret this unfortunate mishap.
Are we studying the correct state of the stellate cell to elucidate mechanisms of chronic pancreatitis

Important insights into the states of pancreatic stellate cells and their relation to the disease conditions of the pancreas The processes of chronic pancreatitis include chronic inflammation and fibrosis with loss of parenchymal cells of the exocrine and endocrine pancreas. These processes lead to irreversible and debilitating exocrine and endocrine insufficiency and a severe chronic pain syndrome. Although elucidation of the mechanisms underlying chronic pancreatitis are incomplete, considerable progress has been made in our understanding of the fibrosis process as a result of identification and characterisation of pancreatic stellate cells (PSCs) starting in 1997.1–3 Studies with these cells suggest that they play a key role in chronic pancreatitis in a manner analogous to hepatic stellate cells and hepatic fibrosis4,5 In common with liver fibrosis and hepatic stellate cells there is increasing evidence demonstrating a central role for PSCs in pancreatic fibrosis and chronic pancreatitis. In the normal pancreas, quiescent PSCs are identified using antibodies to desmin, a cytoskeletal protein and specific PSC marker.1 They are present in the periacinar space with long cytoplasmic processes encircling the base of the acinus. Similar to hepatic stellate cells in their quiescent state, PSCs store significant amounts of vitamin A as lipid droplets in their cytoplasm. There is general acceptance that during …
Rotational motion of a single water molecule in a buckyball

Encapsulation of a single water molecule in a buckyball (C60) can provide fundamental insights into the properties of water. Investigation of a single water molecule is feasible through its solitary confinement in C60. In this paper, we performed a detailed study of the properties and dynamics of a single water molecule in a buckyball using DFT and MD simulations. We report on the enhancement of rotational diffusion and entropy of a water molecule in C60, compared to a bulk water molecule. H2O@C60 has zero translational diffusion and terahertz revolution frequency. The harmonic, high amplitude rotation of a single water molecule in C60 is compared to stochastic behavior of bulk water molecules. The combination of large rotational and negligible translational motion of water in C60 creates new opportunities in nanotechnology applications.
Polyp retrieval after colonoscopic polypectomy: Use of the Roth Retrieval Net

Abstract Background: All colon polyps removed during colonoscopy should be recovered and submitted for histopathologic analysis. Published information is scant regarding techniques and devices for retrieval of polyps after polypectomy. The Roth Retrieval Net is a novel device that has been used to retrieve foreign bodies from the GI tract, but its use as a polyp retrieval device has not previously been described. Methods: A chart review was conducted over a 7-month period by one gastroenterologist in an office setting of all patients who had polyps retrieved after piecemeal polypectomy by using the Roth Retrieval Net. Results: All resected polyps were completely retrieved in a time-efficient manner. Histopathologic evaluation was not compromised by the use of this device. Conclusions: The Roth Retrieval Net is well suited for retrieval of multiple polyp fragments after colonoscopic polypectomy.
Spatio-temporal analysis tool for modeling pulmonary nodules in MR images

To detect lung cancer at an earlier stage, a promising method is to apply perfusion magnetic resonance imaging (pMRI) modified to assess tumor angiogenesis. One key issue is to effectively characterize angiogenic patterns of pulmonary nodules. Based on our previous study addressing this issue, in this work, we develop STAT, a Spatio-Temporal Analysis Tool that implements not only our previously proposed pulmonary nodule modeling framework but also a user friendly interface and many extended functions. Our goal is to make STAT an easy-to-use tool that can be applied to more general cases. STAT employs the following overall strategy for modeling pulmonary nodules: (1) nodule identification using a correlation maximization method, (2) nodule segmentation using edge detection, morphological operations and model-based strategy, and (3) nodule registration using landmark approach and thin-plate spline interpolation. In nodule identification, STAT provides new schemes for selecting the template and refining results in difficult cases. In nodule segmentation, STAT provides additional flexibilities for creating the weighting mask, selecting morphological structure elements and individually fixing segmentation result. In nodule registration, our previous study uses principal component analysis for landmark extraction, which may not work in general. To overcome this limitation, STAT provides an enhanced approach that minimizes the bending energy of the thin plate spline interpolation or mean square distance between each landmark set and the template set. Our main application of STAT is to define blood arrival patterns in the lung to identify tumor angiogenesis as a means of early accurate diagnosis of cancer.
Institutional Legitimacy Building in a Context of Transition: The South African Land Claims Court

The success of societal transformation often depends on the legitimacy of the government institutions developed to mediate the transition. This article examines one case of institutional development and legitimacy building, the South African Land Claims Court. Formed in 1996 to help South Africa resolve land-claim concerns that surfaced as the nation transitioned to a postapartheid society, the court demonstrates the challenges of developing an institution in the context of large-scale societal transformation, reconciliation, and governmental legitimacy building. By tracing the evolution of the court and analyzing its first five years of activities, the article presents the challenges and opportunities of legitimacy building for entities working in transitional political and administrative settings.
Body Objectification, MTV, and Psychological Outcomes Among Female Adolescents

In response to the American Psychological Association's Task Force on the Sexualization of Girls, the present study explored the role of sexually objectifying media—in this case, music television—in a host of psychological consequences among a community sample of adolescents girls (M age = 13 years). Objectification theory posits that the consequences of sexual objectification involve the process of self-objectification. As such, we hypothesized that music television consumption would first and foremost be associated with self-objectification, which would, in turn, predict a number of body-related consequences. The findings support a model in which self-objectification mediates a direct relation between music television viewing and body esteem, dieting, depressive symptoms, anxiety, and confidence in math ability.
Landweber flat real pairs and ER(n)-cohomology

Abstract We take advantage of the internal algebraic structure of the Bockstein spectral sequence converging to E R ( n ) ⁎ ( p t ) to prove that for spaces Z that are part of Landweber flat real pairs with respect to E ( n ) (see Definition 2.9), the cohomology ring E R ( n ) ⁎ ( Z ) can be obtained from E ( n ) ⁎ ( Z ) by base change. In particular, our results allow us to compute the Real Johnson–Wilson cohomology of the Eilenberg–MacLane spaces Z = K ( Z , 2 m + 1 ) , K ( Z / 2 q , 2 m ) , K ( Z / 2 , m ) for any natural numbers m and q, as well as connective covers of BO: BO , BSO , BSpin and BO 〈 8 〉 .
Brain and serum glutamine in nephrectomized, uremic rats.

SummaryThe concentrations of brain and serum glutamine were found to be significantly lower than normal in bilaterally nephrectomized, uremic rats.The technical assistance of Mr. Barry Sonkin is gratefully acknowledged.
LIFO Adoption by Industry

We use proxies representing different aspects of industries' production and investment opportunity set to gain insight regarding the variation in the use of LIFO among industries. We find that industry-average effective tax rate significantly affects the tendency toward the use of LIFO. We further find that firms in industry with lower inventory turnover rate and increasing price level are more likely to apply LIFO. Consistent with positive theory, we find that firms in industry with higher leverage ratio are less likely to adopt LIFO while firms in industry that rely heavily on CEO compensation are more likely to adopt LIFO.
Plasmon optical trapping using silicon nitride trench waveguides

We theoretically demonstrate optical trapping using a silicon nitride (Si3N4) trench waveguide on which bow-tie plasmonic nanoantennas are employed for enhancing optical forces. The electric field tailing away from the waveguide is transformed and then enhanced by the plasmonic nanoantennas deposited on the waveguide surface. We show that, with gold bow-tie nanoantennas, the waveguide system exhibits outstanding trapping capability on a 10 nm radius polystyrene nanoparticle, due to a 60-fold electric field enhancement in the proximity of the nanoantenna gap. This enhancement causes a boost of the optical trapping force by 3 orders of magnitude. The gradient force in the vertical direction is also calculated semi-analytically by using a dipole approximation of a scattering polystyrene nanosphere, and the analytical solution well matches the full-wave simulations. Mode polarization effects are discussed in this paper as a way to switch trapping. These investigations indicate that the patterned Si3N4 trench waveguide is suitable for optical trapping and nanoparticle sensing applications.
A Brief Further Remark on "Pynchon's Anti-Quests"

Conspicuous by its absence, Tennyson's Idylls of the King has seemingly been ignored by critics concerned with the theme of quest and anti-quest in Pynchon's writing. And yet, the section of the Idylls devoted to the Holy Grail offers a supreme example of the anti-quest. Only Galahad achieves the quest, but his solipsistic vision destroys the remainder of the Round Table. The failed quest in Tennyson is intricately tied to what we would call today "the themes of entropy" which permeate the Idylls.
Leuprolide acetate: serum and follicular fluid concentrations and effects on human fertilization, embryo growth, and granulosa-lutein cell progesterone accumulation in vitro.

Data from various animal models have demonstrated significant extrapituitary effects of gonadotropin-releasing hormone agonists. The purpose of this study was to determine the effects of therapeutic concentrations of leuprolide acetate on human granulosa-lutein cell steroidogenesis, fertilization, and embryo growth rates in vitro. During leuprolide administration, mean serum concentrations of leuprolide were
Osteonecrosis of the Jaw in Cancer Patients Receiving IV Bisphosphonates

Cases of osteonecrosis of the jaw (ONJ) have been reported with an increasing frequency over the past few years. ONJ is most often identified in patients with cancer who are receiving intravenous bisphosphonate therapy but it has also been diagnosed in patients receiving oral bisphosphonates for nonmalignant conditions. The condition involves exposed bone of the maxilla or mandible. Although it is often associated with a recent dental surgical procedure, spontaneous ONJ can also occur. Patients commonly present with symptoms. Through case reporting and clinical experience, there is a suggestion that the incidence of ONJ in patients with cancer receiving intravenous bisphosphonates ranges between 1% and 10%. Management of ONJ focuses on maximizing oral health, conservative actions with mouth rinses, antibiotics, and avoidance of unnecessary invasive dental procedures. The currently available data on ONJ are reviewed here.
Ten Propositions for Communication Scholars Studying Space and Place

Here. You are here ↙, where you find yourselves in a word, line, paragraph, page. Here in this place on printed paper or glowing screen or narrated audio, in this instant, you insert yourself into ...
Diagnosing Oppositional Defiant Disorder Using the Anxiety Disorders Interview Schedule for DSM-IV: Parent Version and the Diagnostic Interview Schedule for Children

The purpose of this study was to determine whether the Anxiety Disorders Interview Schedule for DSM–IV: Parent Version (ADIS–P) is a valid diagnostic tool for the assessment of Oppositional Defiant Disorder (ODD) in youth. Although there is considerable evidence that the ADIS–P is effective in diagnosing anxiety disorders in youth, no studies have yet examined its validity in assessing ODD. In contrast, a number of studies support the Diagnostic Interview Schedule for Children–Version IV (DISC–IV) as a reliable and valid tool in the assessment of ODD. In the present study, the ADIS–P and DISC–IV ODD modules were administered in a counterbalanced order to the parents of a clinical sample of 106 children between 7 and 14 years of age referred for the treatment of ODD. It was hypothesized that the ODD module of the ADIS–P would be valid as determined by its concurrent and convergent validity with the DISC–IV, the Behavior Assessment System for Children (BASC) Aggression and Conduct Problems scales, and the Disruptive Behavior Disorders rating scale (DBD). Results demonstrated that ADIS–P ODD diagnoses had moderate agreement with DISC–IV ODD diagnoses (κ = .46, p < .001) and that Pearson correlations of ADIS symptom counts with questionnaire scales were similar in magnitude with correlations of DISC–IV symptom counts with the same questionnaires. Overall, findings suggest that clinicians and researchers can use the ADIS–P as an empirically-supported diagnostic interview for assessing children’s oppositional problems.
A streamlined method for the design and cloning of shRNAs into an optimized Dox-inducible lentiviral vector.

Short hairpin RNA (shRNA) is an established and effective tool for stable knock down of gene expression. Lentiviral vectors can be used to deliver shRNAs, thereby providing the ability to infect most mammalian cell types with high efficiency, regardless of proliferation state. Furthermore, the use of inducible promoters to drive shRNA expression allows for more thorough investigations into the specific timing of gene function in a variety of cellular processes. Moreover, inducible knockdown allows the investigation of genes that would be lethal or otherwise poorly tolerated if constitutively knocked down. Lentiviral inducible shRNA vectors are readily available, but unfortunately the process of cloning, screening, and testing shRNAs can be time-consuming and expensive. Therefore, we sought to refine a popular vector (Tet-pLKO-Puro) and streamline the cloning process with efficient protocols so that researchers can more efficiently utilize this powerful tool. First, we modified the Tet-pLKO-Puro vector to make it easy (“EZ”) for molecular cloning (EZ-Tet-pLKO-Puro). Our primary modification was to shrink the stuffer region, which allows vector purification via polyethylene glycol precipitation thereby avoiding the need to purify DNA through agarose. In addition, we generated EZ-Tet-pLKO vectors with hygromycin or blasticidin resistance to provide greater flexibility in cell line engineering. Furthermore, we provide a detailed guide for utilizing these vectors, including shRNA design strategy and simplified screening methods. Notably, we emphasize the importance of loop sequence design and demonstrate that the addition of a single mismatch in the loop stem can greatly improve shRNA efficiency. Lastly, we display the robustness of the system with a doxycycline titration and recovery time course and provide a cost/benefit analysis comparing our system with purchasing pre-designed shRNA vectors. Our aim was twofold: first, to take a very useful shRNA vector and make it more amenable for molecular cloning and, secondly, to provide a streamlined protocol and rationale for cost-effective design, cloning, and screening of shRNAs. With this knowledge, anyone can take advantage of this powerful tool to inducibly knockdown any gene of their choosing.
Identification and Quantitation of Malonic Acid Biomarkers of In-Born Error Metabolism by Targeted Metabolomics

Malonic acid (MA), methylmalonic acid (MMA), and ethylmalonic acid (EMA) metabolites are implicated in various non-cancer disorders that are associated with inborn-error metabolism. In this study, we have slightly modified the published 3-nitrophenylhydrazine (3NPH) derivatization method and applied it to derivatize MA, MMA, and EMA to their hydrazone derivatives, which were amenable for liquid chromatography- mass spectrometry (LC-MS) quantitation. 3NPH was used to derivatize MA, MMA, and EMA, and multiple reaction monitoring (MRM) transitions of the corresponding derivatives were determined by product-ion experiments. Data normalization and absolute quantitation were achieved by using 3NPH derivatized isotopic labeled compounds 13C2-MA, MMA-D3, and EMA-D3. The detection limits were found to be at nanomolar concentrations and a good linearity was achieved from nanomolar to millimolar concentrations. As a proof of concept study, we have investigated the levels of malonic acids in mouse plasma with malonyl-CoA decarboxylase deficiency (MCD-D), and we have successfully applied 3NPH method to identify and quantitate all three malonic acids in wild type (WT) and MCD-D plasma with high accuracy. The results of this method were compared with that of underivatized malonic acid standards experiments that were performed using hydrophilic interaction liquid chromatography (HILIC)-MRM. Compared with HILIC method, 3NPH derivatization strategy was found to be very efficient to identify these molecules as it greatly improved the sensitivity, quantitation accuracy, as well as peak shape and resolution. Furthermore, there was no matrix effect in LC-MS analysis and the derivatized metabolites were found to be very stable for longer time.
Intracranial Bypass of Posterior Inferior Cerebellar Artery Aneurysms: Indications, Technical Aspects, and Clinical Outcomes

Background For some posterior inferior cerebellar artery (PICA) aneurysms, there is no constructive endovascular or direct surgical clipping option. Intracranial bypass is an alternative to a deconstructive technique. Objective To evaluate the clinical features, surgical techniques, and outcome of PICA aneurysms treated with bypass and obliteration of the diseased segment. Methods Retrospective review of PICA aneurysms treated via intracranial bypass was performed. Outcome measurements included postoperative stroke, cranial nerve deficits, gastrostomy/tracheostomy requirement, bypass patency, modified Rankin scale (mRS) at discharge, and mRS at 6 mo. Results Seven patients with PICA aneurysms treated with intracranial bypass were identified. Five had fusiform aneurysms (4 ruptured, 1 unruptured), 1 had a giant partially thrombosed saccular aneurysm (unruptured), and 1 had a dissecting traumatic aneurysm (ruptured). Two aneurysms were at the anteromedullary segment, 4 at the lateral medullary segment, and 1 at the tonsillomedullary segment. Three patients underwent PICA-to-PICA side to side anastomoses, 2 PICA-to-PICA reanastomosis, 1 vertebral artery-to-PICA bypass, and 1 occipital artery-PICA bypass. Six out of 7 aneurysms were obliterated surgically and 1 with additional endovascular occlusion after the bypass. All bypasses were patent intraoperatively; 2 were later demonstrated occluded without radiological signs or symptoms of stroke. No patients had new cranial nerve deficit postoperatively. With the exception of 1 death due to pulmonary emboli 3 mo postoperatively, all others remain at a mRS ≤ 2. Conclusion Constructive bypass and aneurysm obliteration remains a viable alternative for treatment of PICA aneurysms not amenable to direct surgical clipping or to a vessel-preserving endovascular option.
Periodic Traveling Waves for a Nonlocal Integro-differential Model

We establish the existence, uniqueness and stability of periodic traveling wave solutions to an intrego-differential model for phase transitions.
Compact modeling and circuit-level simulation of silicon nanophotonic interconnects

Nanophotonic interconnects have been playing an increasingly important role in the datacom regime. Greater integration of silicon photonics demands modeling and simulation support for design validation, optimization and design space exploration. In this work, we develop compact models for a number of key photonic devices, which are extensively validated by the measurement data of a fabricated optical network-on-chip (ONoC). Implemented in SPICE-compatible Verilog-A, the models are used in circuit-level simulations of full optical links. The simulation results match well with the measurement data. Our model library and simulation approach enable the electro-optical (EO) co-simulation, allowing designers to include photonic devices in the whole system design space, and to co-optimize the transmitter, interconnect, and receiver jointly.
Psychology's Replication Crisis and the Grant Culture: Righting the Ship

The past several years have been a time for soul searching in psychology, as we have gradually come to grips with the reality that some of our cherished findings are less robust than we had assumed. Nevertheless, the replication crisis highlights the operation of psychological science at its best, as it reflects our growing humility. At the same time, institutional variables, especially the growing emphasis on external funding as an expectation or de facto requirement for faculty tenure and promotion, pose largely unappreciated hazards for psychological science, including (a) incentives for engaging in questionable research practices, (b) a single-minded focus on programmatic research, (c) intellectual hyperspecialization, (d) disincentives for conducting direct replications, (e) stifling of creativity and intellectual risk taking, (f) researchers promising more than they can deliver, and (g) diminished time for thinking deeply. Preregistration should assist with (a), but will do little about (b) through (g). Psychology is beginning to right the ship, but it will need to confront the increasingly deleterious impact of the grant culture on scientific inquiry.
The virulence-associated protein HsvA from the fire blight pathogen Erwinia amylovora is a polyamine amidinotransferase.

Studies of virulence determinants in the bacterial phytopathogen Erwinia amylovora, the cause of devastating fire blight disease in apple and pear, have shown that HsvA, a putative amidinotransferase enzyme located in the Hrp pathogenicity island, is required for systemic infection in apple. However, the mechanism by which HsvA contributes to virulence is unclear. To investigate the role of HsvA in virulence, we carried out a series of biochemical and structural studies to characterize the amidinotransferase activity of HsvA. We found that HsvA displays a preference for linear aliphatic polyamines as the amidino acceptor substrate, especially for spermidine and putrescine (Km values of 33 μm and 3.9 mm, respectively). The three-dimensional structure, determined at 2.30 Å resolution using X-ray crystallography, revealed that the overall architecture of HsvA is similar to that of the human arginine–glycine amidinotransferase in the creatine biosynthesis pathway. The active site is located in the core of the protein at the base of a long, narrow substrate access channel. Specific amino acids near the entrance of the channel may serve as major determinants of the substrate specificity, including a glutamate residue at the rim of the channel entrance that appears to be positioned to interact with the distal primary amine in the putrescine substrate as well as the internal and distal amines in the spermidine substrate. These results suggest potential in vivo functions for HsvA as a virulence factor in fire blight and may also provide a basis for strategies to control fire blight by inhibiting HsvA activity.
The Tiny Skull of the Peruvian Gecko Pseudogonatodes barbouri (Gekkota: Sphaerodactylidae) Obtained via a Divide-And-Conquer Approach to Morphological Data Acquisition

The Peruvian sphaerodactyl gecko, Pseudogonatodes barbouri, is among the smallest reptile species in South America. Morphological information about this species, or even the genus, is limited. In this study, we produced a bone-by-bone description from the skull and atlantoaxial complex to contribute new phenotypic information about this poorly known lizard. To achieve this objective, we employed a divide-and-conquer approach in which each author digitally isolated one or two bones from the skull and produced a written description of these elements, thereby reducing 3D imaging processing and description to a fraction of time. In addition to a reduced phalanx in the fourth toe of both the hand and foot, the genus is characterized by having nasal bones with a broad lateral wing, an ectopterygoid that clasps the pterygoid, and an anterior shifting of the paroccipital process and as consequence the position of the quadrate, and squamosal not participating in the quadrate suspension. There are also modifications in fenestration and foramina and a trend towards synostosis of the jaw bones (e.g., coronoid splenial, compound bone surangular). Pseudogonatodes bears four long processes on the intercentrum of the axis; which is a character of New World sphaerodactyls.
Evasion of the STING DNA-Sensing Pathway by VP11/12 of Herpes Simplex Virus 1

The stimulator of interferon (IFN) genes (STING) is a broad antimicrobial factor that restricts herpes simplex virus (HSV) by activating type I interferon and proinflammatory responses upon sensing of foreign DNA. UL46 is one of the most abundant tegument proteins of HSV-1, but a well-established function has yet to be found. We found that the HSV-1 UL46 protein interacts with and colocalizes with STING. A ΔUL46 virus displayed growth defects and activated innate immunity, but both effects were alleviated in STING knockdown cells. UL46 was also required for the inhibition of the 2′,3′-cyclic GMP-AMP (cGAMP)-dependent immune responses during infection. In cells expressing UL46, out of the context of the infection, innate immunity to a ΔICP0 virus was largely compromised, and that permitted ICP0-deficient mutants to replicate. The UL46-expressing cell lines also rescued the defects of the ΔUL46 virus and enhanced wild-type virus infection. The UL46-expressing cell lines did not activate interferon-stimulated gene (ISG) transcription following treatment with the noncanonical cyclic dinucleotide 2′,3′-cGAMP, suggesting that the STING pathway may be compromised. Indeed, we found that both proteins STING and IFI16 were eliminated in cells constitutively expressing UL46 and that the accumulation of their transcripts was blocked. Finally, we demonstrated that UL46 via its N terminus binds to STING and, via its C terminus, to TBK1. These interactions appear to modulate the functions of STING during HSV-1 infection. Taken together, our studies describe a novel function for one of the least-studied proteins of HSV, the tegument protein UL46, and that function involves the evasion of foreign DNA-sensing pathways. IMPORTANCE Herpes simplex virus 1 (HSV-1) afflicts 80% of the population worldwide, causing various diseases. After initial infection, the virus establishes latent reservoirs in sensory neurons and persists for life. Here we describe novel interactions between HSV-1 and the DNA sensor STING. We found that (i) HSV-1 tegument protein UL46 interacts with and colocalizes with STING; (ii) UL46 expressed out of the context of the infection blocks type I interferon triggered by STING stimuli, through the elimination of STING and of interferon-inducible protein 16 (IFI16); (iii) a ΔUL46 virus displayed growth defects, which were rescued in STING knockdown cells; (iv) the ΔUL46 virus failed to block innate immunity triggered by ligands of STING such as 2′,3′-cGAMP and also activated IFN-β and ISG expression; and (v) UL46 binds to both STING and TBK1 through different domains. We conclude that UL46 counteracts the actions of STING during HSV-1 infection.
Effects of Parity on Blood Pressure among African-American Women

It is a well established fact that age, ethnicity, weight, and lifestyle behaviors can affect blood pressure (BP). Co-morbid conditions such as HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), pre-eclampsia, and previous hypertension diagnosis might also be risks for chronic hypertension among women who have had children. Although parity has been linked to changes in blood pressure in White women, these findings have not been replicated among African-American women. The purpose of this study was to determine if the number of pregnancies urban African-American women have effects BMI and blood pressure readings later in life. Results indicated that women with a previous diagnosis of hypertension had higher SBP and DBP, and a slightly higher BMI than women who had never been diagnosed. Additionally, women with a prior history of hypertension had more children than those without a diagnosis of hypertension. As parity increased, SBP increased. However, DBP decreased after 3 to 4 children, even with increases in BMI. This study shows that parity may increase African-American women's risk for hypertension in terms of increased SBP and BMI with increased parity. However, increased parity and BMI may also serve as protective factors in lowering DBP. Further studies, with larger samples followed throughout their pregnancies, is needed before more definitive statements may be drawn about the effects of parity on BMI and blood pressure readings among African-American women can be made.
Providing health information to the general public: a survey of current practices in academic health sciences libraries.

A questionnaire was mailed to 148 publicly and privately supported academic health sciences libraries affiliated with Association of American Medical Colleges (AAMC)–accredited medical schools in the United States and Canada to determine level of access and services provided to the general public. For purposes of this study, “general public” was defined as nonaffiliated students or health care professionals, attorneys and other nonhealth-related professionals, patients from affiliated or other hospitals or clinics, and general consumers. One hundred five (71%) libraries responded. Results showed 98% of publicly supported libraries and 88% of privately supported libraries provided access to some or all of the general public. Publicly supported libraries saw greater numbers of public patrons, often provided more services, and were more likely to circulate materials from their collections than were privately supported libraries. A significant number of academic health sciences libraries housed a collection of consumer-oriented materials and many provided some level of document delivery service, usually for a fee. Most allowed the public to use some or all library computers. Results of this study indicated that academic health sciences libraries played a significant role in serving the information-seeking public and suggested a need to develop written policies or guidelines covering the services that will be provided to minimize the impact of this service on primary clientele.
Extended Analytic Device Optimization Employing Asymptotic Expansion

Analytic optimization of a thermoelectric junction often introduces several simplifying assumptionsincluding constant material properties, fixed known hot and cold shoe temperatures, and thermallyinsulated leg sides. In fact all of these simplifications will have an effect on device performance,ranging from negligible to significant depending on conditions. Numerical methods, such as FiniteElement Analysis or iterative techniques, are often used to perform more detailed analysis andaccount for these simplifications. While numerical methods may stand as a suitable solution scheme,they are weak in gaining physical understanding and only serve to optimize through iterativesearching techniques. Analytic and asymptotic expansion techniques can be used to solve thegoverning system of thermoelectric differential equations with fewer or less severe assumptionsthan the classic case. Analytic methods can provide meaningful closed form solutions and generatebetter physical understanding of the conditions for when simplifying assumptions may be valid.In obtaining the analytic solutions a set of dimensionless parameters, which characterize allthermoelectric couples, is formulated and provide the limiting cases for validating assumptions.Presentation includes optimization of both classic rectangular couples as well as practically andtheoretically interesting cylindrical couples using optimization parameters physically meaningful toa cylindrical couple. Solutions incorporate the physical behavior for i) thermal resistance of hot andcold shoes, ii) variable material properties with temperature, and iii) lateral heat transfer through legsides.
An open-label, single-dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cinacalcet in pediatric subjects aged 28 days to < 6 years with chronic kidney disease receiving dialysis.

Calcimimetics, shown to control biochemical parameters of secondary hyperparathyroidism (SHPT), have well-established safety and pharmacokinetic profiles in adult end-stage renal disease subjects treated with dialysis; however, such studies are limited in pediatric subjects. In this study, the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of cinacalcet were evaluated in children with chronic kidney disease (CKD) and SHPT receiving dialysis. Twelve subjects received a single dose of cinacalcet (0.25 mg/kg) orally or by nasogastric or gastric tube. Subjects were randomized to one of two parathyroid hormone (PTH) and serum calcium sampling sequences: [(1) 2, 8, 48 h; or (2) 2, 12, 48 h] and assessed for 72 h after dosing. Median plasma cinacalcet tmax was 1 h (range 0.5–4.0 h); mean (SD) Cmax and AUClast were 2.83 (1.98) ng/mL and 11.8 (8.74) h*ng/mL, respectively; mean (SD) half-life (t1/2) was 3.70 (2.57) h. Dose adjustments, based upon body weight (mg/kg), minimized the effects of age, body weight, body surface area, and body mass index on cinacalcet PK. Reductions in serum PTH levels from baseline were observed at 2 to 8 h post-dose (median 10.8 and 29.6%, respectively), returned towards baseline by 12–72 h and were inversely related to changes in the plasma cinacalcet PK profile. Single-dose cinacalcet was well-tolerated with no unexpected safety findings and a PK/PD, safety profile similar to adults. In conclusion, a single 0.25 mg/kg dose of cinacalcet was evaluated to be a safe starting dose in these children aged < 6 years.
Prediction-Based Eco-Approach and Departure at Signalized Intersections With Speed Forecasting on Preceding Vehicles

Using connected vehicle technology, a number of eco-approach and departure (EAD) strategies have been designed to guide vehicles through signalized intersections in an eco-friendly way. Most of the existing EAD applications have been developed and tested in traffic-free scenarios or in a fully connected environment, where the presence and behavior of all surrounding vehicles are detectable. In this paper, we describe a prediction-based EAD strategy that can be applied toward more realistic scenarios, where the surrounding vehicles can be either a connected or non-connected. Unlike highway scenarios, predicting speed trajectories along signalized corridors is much more challenging due to disturbances from signals, traffic queues, and pedestrians. Based on vehicle activity data available via inter-vehicle communication or onboard sensing (e.g., by radar), we evaluate three state-of-the-art nonlinear regression models to perform short-term speed forecasting of the preceding vehicle. It turns out radial basis function neural network outperformed both Gaussian process and multi-layer perceptron network in terms of prediction accuracy and computational efficiency. Using signal phase and timing information and the predicted state of the preceding vehicle, our prediction-based EAD algorithm achieved better fuel economy and emissions reduction in urban traffic and queues at intersections. Results from the numerical simulation using the next generation simulation data set show that the proposed prediction-based EAD system achieve 4.0% energy savings and 4.0% – 41.7% pollutant emission reduction compared with a conventional car following strategy. Prediction-based EAD saves 1.9% energy and reduces criteria pollutant emissions by 1.9% – 33.4% compared with an existing EAD algorithm without prediction in urban traffic.
Likelihood of Sustaining an Injury in the Setting of Multiple Falls.

Objectives To evaluate the relationship between number of falls and risk of injury after a specific fall. Design Prospective cohort study. Setting Greater New Haven, Connecticut. Participants Probability sample of 1,103 community‐living persons aged 72 and older. Measurements Falls and fall‐related injuries were ascertained monthly for 3 years using a fall calendar and follow‐up telephone interviews. Results Of 606 participants with a fall, 164 (27.0%) had at least 1 fall with a serious injury, and 455 (75.1%) had at least 1 fall with any injury; mean number of falls was 2.6±2.3 (range 1–18), of falls with serious injury was 0.3±0.6 (range 0–4), and of falls with any injury was 1.4±1.4 (range 0–9). On a per‐participant basis, risk of serious injury and any injury increased progressively as the number of falls increased (P < .001). On a per‐fall basis, risk of serious injury and any injury increased from 1 to 2 falls but then decreased from 2 to 3 or 4 falls and from 3 or 4 to 5 or more falls, although these differences were not statistically significant. The results were consistent for women and men and for analyses that evaluated the proportion of falls with injuries. Conclusion In community‐living older persons, risk of injury from a specific fall did not differ as the number of falls increased. Falls appear to operate independently in terms of conferring risk of injury in the setting of multiple falls. J Am Geriatr Soc 67:119–123, 2019.
Low blood selenium levels in alcoholics with and without advanced liver disease. Correlations with clinical and nutritional status.

Selenium deficiency has been implicated as a cause of hepatic injury, possibly from accentuated lipoperoxidation due to decreased activity of the selenoenzyme, glutathione peroxidase. Because of possible clinical and biochemical links between selenium and alcohol, we performed nutritional assessment and assayed red blood cell, plasma, and whole blood selenium by spectrofluorometry in 27 normals (group I), 30 asymptomatic alcoholics on admission to a detox unit (group II), and 16 alcoholics with severe liver disease (group III). We found a mean (±sd) whole blood selenium of 0.109 μg/ml±0.014 for group I vs 0.076±0.010 for group II (P<0.001), and 0.047±0.006 for group III (P<0.001 vs group I and II). For plasma, the mean (±sd) selenium was 0.095 μg/ml±0.016 for group I versus 0.065 μg/ml±0.012 in group II and 0.038 μg/ml± 0.007 in group III (AllP<0.001). Calculated red blood selenium levels were also significantly reduced in alcoholics versus controls. Whole blood and plasma selenium correlated directly with serum albumin. For whole blood selenium versus albumin,r=0.73 (P<0.01), and for plasma selenium versus albumin,r=0.71 (P<0.01). A significant inverse correlation was noted between whole blood selenium and the height of the total serum bilirubin (r=−0.46), alkaline phosphatase (r=−0.50), and AST (r=−0.51) (P<0.01 for all). Among alcoholics admitted for detoxification, selenium was diminished despite the absence of severe malnutrition, as determined by standard nutrition assessment parameters. We conclude that blood selenium levels are diminished in alcoholics, even in the absence of severe liver disease or malnutrition. This abnormality is markedly accentuated in the presence of severe liver disease and correlates directly with albumin and inversely with bilirubin. Associations between this finding and its role in liver disease, as well as other pathologic states attributed to alcoholism, deserves further consideration.
Intense threat switches dorsal raphe serotonin neurons to a paradoxical operational mode

Survival depends on the selection of behaviors adaptive for the current environment. For example, a mouse should run from a rapidly looming hawk but should freeze if the hawk is coasting across the sky. Although serotonin has been implicated in adaptive behavior, environmental regulation of its functional role remains poorly understood. In mice, we found that stimulation of dorsal raphe serotonin neurons suppressed movement in low- and moderate-threat environments but induced escape behavior in high-threat environments, and that movement-related dorsal raphe serotonin neural dynamics inverted in high-threat environments. Stimulation of dorsal raphe γ-aminobutyric acid (GABA) neurons promoted movement in negative but not positive environments, and movement-related GABA neural dynamics inverted between positive and negative environments. Thus, dorsal raphe circuits switch between distinct operational modes to promote environment-specific adaptive behaviors.
Abstract 1758: Splicing component ISY1 interacts with APE1 and regulates base excision repair

Cellular genome is continuously challenged by endogenous and exogenous DNA damaging agents. In the genome, base modifications are the most common form of DNA damage. Base excision DNA repair (BER) is the most important pathway for the removal of oxidized or alkylated DNA. If these base modifications continue to persist, the replisome may stall at DNA lesions, causing the replication fork to collapse, leading to genetic instability. While the main components of the BER pathway are well defined, its regulatory mechanism remains poorly understood. We report here that apurinic/apyrimidinic endonuclease 1 (APE1), a multifunctional protein interacts with the pre-mRNA splicing factor ISY1. However, this interaction is independent of DNA or RNA based upon our pull-down experimental results. ISY1 expression is induced by oxidative or DNA alkylation damage, which would then provide an immediate up-regulation of APE1 activity in vivo and enhanced BER of oxidized bases. This was supported from our results of in vitro reconstituted experiment suggesting that ISY1 can stimulate 5’-3’ endonuclease 1 activity of APE1 in both the short- and long-patch BER pathways and increase its binding to AP site DNA. The interaction between ISY1 and APE1 also establishes a connection between DNA damage repair and pre-mRNA splicing. Based upon these results, we propose that ISY1 is an important regulator of BER and enhances the ability of APE1 to efficiently recognize abasic sites in DNA. Role of ISY1 becomes important in aging tissues where decreased APE1 activity results in the accumulation of oxidative genomic damages. Therefore, ISY1 may work as an anti-aging factor. Induction of ISY1 in malignancies could constitute a mechanism to avoid apoptotic death after treatment with alkylating agents. Citation Format: Aruna Jaiswal, Elizabeth Williamson, Bhavita Patel, Gayathri Srinivasan, Kimi Kong, Carrie Lomelino, Satya Narayan, Robert Hromas. Splicing component ISY1 interacts with APE1 and regulates base excision repair [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1758.
Reflections on Sustainability and Resilience in the NGO Sector

This reflection outlines the origins of the terms “sustainability” and “resilience” and the meanings they have when applied to the nongovernmental sector. The use of specific jargon and language fo...