cssi/SciSciGPT-SciSciNet huggingface dataset:
Possible Nephrotoxicity of Gentamicin

Clinical experience with patients with acute renal failure suggested an association between administration of gentamicin and renal failure. Therefore, the effect of gentamicin on renal function of the dog was studied experimentally. Glomerular filtration rate, renal blood flow, and the urinary clearance of gentamicin were measured. Renal function after the administration of gentamicin was not significantly altered from control values. Thus, although clinical evidence suggests that gentamicin adversely effects the kidneys, the nephrotoxicity of gentamicin could not be reproduced in experiments. In our recent experience in treating patients with the syndrome of acute renal failure, it has become apparent that a significant number have received gentamicin before the onset of the syndrome. To evaluate the possible role of gentamicin as a cause of acute renal failure and in an effort to define a common physiologic setting or interaction of drugs that might contribute to the renal failure, we reviewed the records of all patients who developed
An Ethics of Nicotine: Writing a Subjectivity of Process in ITALO SVEVO'S LA COSCIENZA DI ZENO

In La coscienza di Zeno (1923), Italo Svevo's protagonist, Zeno, engage in a determined battle with nicotine, smoking a repeated “last cigrette” that tastes, time and time again, of victory. I cont...
Application of Scanning Electron Microscope in Failure Analysis

Failure analysis is important method for identification of engineering failure.And scanning electron microscope(SEM) is instrument of failure analysis.Both two are effecting widely across engineering field especially application of fracture analysis.Failure mode and root cause can be identified;meanwhile countermeasure can be made through SEM.This article will explain application of failure analysis by SEM through an actual engineering failure case.In this case,root cause is identified and countermeasure is made through aid of SEM.
Analyzing the effect of human body and metallic objects for indoor geolocation

Recently a special attention has been directed toward indoor localization and body area networks for medical purposes which, has its root in their broad applicability in that area. We understand that time-of-arrival (ToA) based techniques provide immense accuracy compare to received-signal-strength (RSS) and the angle-of-arrival (AoA) based techniques in situations that line-of-sight (LOS) exists. It is known that possible ranging errors introduce limitations on the accuracy of such systems for indoor environment as well as in and around human body which, are due to hindrance of the direct path and diffraction of the rays around the edges of metallic objects and around human bodies. Result of multiple scholarly literatures has proven modeling ranging estimates in the proximity of metallic objects and human bodies are rather complex leaving room for further investigations in those research areas. We leverage this paper to provide an overview on applicability of multiple computational and analytical electromagnetic (EM) methods to study modeling of ranging error and diffraction associated with TOA-based techniques around metallic object and human body.
Toughness: An Opponent Process

Although he did not name the outcome “toughness,” 125 years ago, in The principles of psychology, William James wrote a brief theory of toughness in the form of a lifestyle recommendation: Keep the faculty of effort alive in you by a little gratuitous exercise every day. That is, be systematically heroic in little unnecessary points, do every day or two something for no other reason than its difficulty, so that, when the hour of dire need draws nigh, it may find you not unnerved or untrained to stand the test … So with the man who had daily inured himself to habits of concentrated attention, energetic volition, and self-denial in unnecessary things. He will stand like a tower when everything rocks around him, and his softer fellow-mortals are winnowed like chaff in the blast. (James, 1890, pp. 126–7)
BORON CARBIDE IN THE GRAPHITIZATION OF THE LAMPBLACK CARBON BRUSH CONSTITUENT

In studying the influence of high percentages of boron carbide on the graphitization of conventional carbon brush mixes, the following points represent the findings: 1. Boron carbide in the graphitizing furnace at the 25% B4C level causes complete disappearance of the normally non-graphitizable lampblack constituent. The mixed product has a silvery appearance similar to natural graphite. It consists of large crystalline carbonaceous material associated with B4C. With the graphitizable coke constituent, normally forming either very small crystals or spots (crystallites) of graphite, there is a similar reaction. In each case there is formation of large, long, rough, crystals which are shown by the sensitive tint photomicrography method described below to be graphite. These are as much as a few tenths of a millimeter long. 2. At the 8% B4C level in the lampblack case, only islands of large crystals are present. They are surrounded by very small crystals or crystallites filling up the lampblack structure. 3. At the 5% level, the reacted areas are reduced to normally visible white spots. Large graphite crystals fail to appear in these spots but, in the lampblack type these are areas where the lampblack has begun to change to crystallites of graphite. This step, for each white spot, is identified by green and red micro-spots which reverse color on stage rotation with the sensitive tint photomicrography method of Pincus and Gendron. Preparation in this method is by epoxy resin impregnation and mounting, then polishing the surface, for the porous sample. These barely converted area crystallites also show up in polarized light photomicrographs as a speckled bright white, while large crystals would be white at most rotations. The boron carbide shows by neither method at this low concentration but is normally a non-responding lavender under sensitive tint and is dark in polarized light.
The Radiation Safety Information Computational Center (RSICC): A resource for nuclear science pplications

The Radiation Safety Information Computational Center (RSICC) has been in existence since 1963. RSICC collects, organizes, evaluates and disseminates technical information (software and nuclear data) involving the transport of neutral and charged particle radiation, and shielding and protection from the radiation associated with: nuclear weapons and materials, fission and fusion reactors, outer space, accelerators, medical facilities, and nuclear waste management. RSICC serves over 12,000 scientists and engineers from about 100 countries.
Lineage-Specific Activation of p53 in Response to Ribosomal Haploinsufficiency in Human Bone Marrow Cells.

Abstract Abstract 948 Haploinsufficiency for the ribosomal protein genes RPS14 and RPS19 have been implicated in the erythroid defect in the 5q- syndrome and Diamond Blackfan Anemia, respectively. However, the mechanism by which defective ribosome biogenesis causes erythroid failure is unknown. In this study, we found that shRNA mediated knockdown of RPS14 or RPS19 in primary human CD34+ cells stabilize TP53 by day 4 after infection with concomitant arrest of these cells at G1 stage of cell cycle. The levels of TP53 attained are comparable to the levels observed following gamma irradiation (5Gy) of the CD34+ cells. Using quantitative PCR, we confirmed that stabilized TP53 activates expression of downstream target genes MDM2, p21, Bax and Wig-1. Furthermore, treatment of the CD34+ cells with Nutlin-3 phenocopies RPS14 or RPS19 knockdown, suggesting that the mechanism of TP53 activation is mediated by MDM2 pathway. Conversely, treatment with pifithrin-alpha, which inhibits the transactivation activity of TP53, rescues the effects of RPS14 or RPS19 knockdown. The in vitro activation of TP53 in CD34+ cells was restricted to erythroid cell lineage, consistent with the clinical phenotype of RPS14 or RPS19 haploinsufficiency. Moreover, immunohistochemical analysis of bone marrow biopsies from patient with the 5q- syndrome demonstrated intense staining of TP53 that was restricted to erythroid progenitor cells. Taken together our study indicates that inhibition of ribosomal biogenesis causes TP53 activation selectively in erythroid progenitor cells. Clinically, TP53 staining of patient samples could be used as a diagnostic marker for some types of MDS. Disclosures: No relevant conflicts of interest to declare.
Third Party Invariant Natural Killer T Cells Protect from Graft-Versus-Host Disease Lethality through Expansion of Donor CD4 + FoxP3 + Regulatory T Cells

Graft-versus-host disease (GVHD) is driven by extensive activation and proliferation of alloreactive donor T cells causing significant morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Invariant natural killer T (iNKT) cells are potent regulators of immune responses in both humans (TCRα Vα24-Jα18) and mice (TCRα Vα14-Jα18). As the iNKT cell receptor and the glycolipid-presenting molecule CD1d interaction is highly conserved, we explored the role of adoptively transferred third party CD4 + iNKT cells in a murine model of allogeneic HCT. BALB/c (H-2K d ) recipient mice were irradiated with 8 Gy and transplanted with T cell-depleted bone marrow together with 1x10 6 CD4 + /CD8 + T cells (Tcon) from C57BL/6 (H-2K b ) donor mice. Adoptive transfer of purified (>95%) 5x10 4 CD4 + iNKT cells from FVB/N (H-2K q ) third party mice resulted in a significant survival benefit ( p p =0.002). Consistently, weight and GVHD scores improved in mice that received a single injection of third party CD4 + iNKT cells as compared to animals that received Tcon alone. Notably, CD4 + iNKT cells from third party mice were as protective as CD4 + iNKT cells from donor mice ( p =0.50). Signal intensity deriving from expanding luciferase expressing alloreactive Tcon was significantly lower in animals treated with third party CD4 + iNKT cells ( p =0.003). Interestingly, inhibition of Tcon proliferation was similar to animals that received CD4 + iNKT cells from donor mice ( p =0.90). In addition, adoptive transfer of third party CD4 + iNKT cells promoted a Th2-biased cytokine response of alloreactive donor T cells. Although we found that third party CD4 + iNKT cells were rejected by day +10 after allogeneic HCT, adoptive transfer of these cells resulted in a robust expansion of luciferase expressing donor CD4 + FoxP3 + regulatory T cells (Treg) as measured by bioluminescence imaging ( p =0.006). Using FoxP3 DTR C57BL/6 donor mice, depletion of Treg from the graft abrogated both donor Treg expansion and protection from GVHD lethality through third party CD4 + iNKT cells. We conclude that low numbers of highly purified and adoptively transferred third party CD4 + iNKT cells protect from lethal GVHD through activation and expansion of donor Treg with retained GVT effects. Despite the fact that iNKT cells are a rare cell population, the in vivo activity of small numbers of cells and feasibility of in vitro expansion provide the basis for clinical translation. Disclosures No relevant conflicts of interest to declare.
Abstract IA23: Immune landscape of human pancreatic cancer

Survival rates for pancreatic ductal adenocarcinoma (PDA) remain dismal. Immunotherapy has the potential to improve outcomes, but clinical trial results – particularly those employing single-agent CTLA4 or PD1/PD-L1 inhibition – have thus far been disappointing. We stratified human PDA based on a signature of cytolytic T-cell activity. Differences in cytolytic index correlated with defined PDA subtypes and distinct mutational events. Specifically, PDA tumors with low cytolytic activity exhibited increased genomic structural variation, including reproducible copy number alterations in MYC, FGFR1, NOTCH2, and CDKN2. In contrast to other tumors such as kidney cancer or melanoma, PDA tumors with a high cytolytic index lacked an increased mutation or neo-epitope load. Tumors with high cytolytic activity exhibited increased expression of several immune checkpoint genes, but PD-L1 expression was uniformly low. These data establish a link between genomic alterations and immune activation in PDA and suggest that immune checkpoints other than PD-L1/PD-1 may be attractive therapeutic targets in this lethal disease. Citation Format: David Balli, Andrew J. Rech, Ben Z. Stanger, Robert H. Vonderheide.{Authors}. Immune landscape of human pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr IA23.
Magnetic and electric properties of triangular lattice antiferromagnets Ba3ATa2O9 (A = Ni and Co)

Abstract We investigated magnetic and electric properties of two triangular lattice antiferromagnets (TLAFs), Ba 3 A Ta 2 O 9 ( A = Ni and Co). Ba 3 NiTa 2 O 9 shows (i) a single antiferromagnetic phase transition to 120 degree ordered state at T N ∼ 3.3 K, (ii) a weak spin-flop-like transition in isothermal magnetization curves around 4 T, and the saturation magnetization about 1.6 μ B per Ni 2+ above 9.2 T, and (iii) a weak magnetoelectric effect could be removed without ferroelectricity. Comparing to the isostructural TLAF, Ba 3 NiNb 2 O 9 [Phys. Rev. Lett. 109 , 257205 (2012)], which exhibits successive magnetic phase transitions and ferroelectricity, Ba 3 NiTa 2 O 9 shows lower T N , smaller saturation magnetization, no successive phase transition, and no ferroelectricity. These differences indicate that the higher order superexchange interaction involving Ta atomic orbitals in Ba 3 NiTa 2 O 9 disrupts not only the exotic magnetic phases, also ferroelectricity. We show that this scenario can be also applied to explain the differences between Ba 3 CoTa 2 O 9 and Ba 3 CoNb 2 O 9 [Phys. Rev. B 89 , 104420 (2014)].
The Delphic Spirit in Sports

(1966). The Delphic Spirit in Sports. Journal of Health, Physical Education, Recreation: Vol. 37, No. 2, pp. 43-45.
Tragedy’s Philosophy

Tragedy highlights what is perishable, what is fragile and what is slow moving about us. In a world defined by relentless speed and the unending acceleration of information flows that cultivate amnesia and an endless thirst for the short-term future allegedly guaranteed through worship of the new prosthetic Gods of technology, tragedy is a way of applying what Walter Benjamin saw as the emergency brake. Tragedy slows things down by confronting us with what we do not know about ourselves: an unknown force that nonetheless unleashes violent effects on us on a daily, indeed often minute-by-minute basis. Such is what psychoanalysis calls a symptom, whose source is unconscious. Such is the sometimes terrifying presence of the past that we might seek to disavow but which will have its victory in the end, if only in the form of our mortality. In the words of Paul Thomas Anderson’s movie, Magnolia, ‘We might be through with the past, but the past isn’t through with us’. Through its sudden reversals of fortune and rageful recognition of the truth of our origins, tragedy permits us to come face to face with what we do not know about ourselves but which makes those selves the things they are. Tragedy provokes what snags in our being, the snares and booby traps of the past that we blindly trip over in our relentless, stumbling, forward movement. This is what the ancients called ‘fate’ and it requires our complicity in order to come down on us.
Thermal Predictions of the AGR-3/4 Experiment Using PIE-Measured Time Varying Gas Gaps

A thermal analysis was performed for the Advanced Gas Reactor test experiment (AGR-3/4) with Post Irradiation Examination (PIE) measured time varying gas gaps. The experiment was irradiated at the Advanced Test Reactor (ATR) at the Idaho National Laboratory (INL). Several fuel irradiation experiments are planned for the AGR Fuel Development and Qualification Program which supports the development of the Very-High-Temperature gas-cooled Reactor (VHTR) under the Next-Generation Nuclear Plant (NGNP) project.AGR-3/4 combines two tests in a series of planned AGR experiments to test tri-structural-isotropic (TRISO)-coated, low-enriched uranium oxy-carbide fuel. The AGR-3/4 test was designed primarily to assess fission product transport through various graphite materials. The AGR-3/4 test irradiation in the ATR started in December 2011 and finished in April 2014. Forty-eight (48) TRISO fueled compacts were inserted into twelve separate capsules for the experiment (four compacts per capsule).The purpose of this analysis was to calculate the temperatures of each compact and graphite layer to obtain daily average temperatures using PIE-measured time (fast neutron fluence) varying gas gaps and to compare with experimentally measured thermocouple data. PIE-measured experimental data was used for the graphite shrinkage versus fast neutron fluence. Heat rates were input from a detailed physics analysis using the Monte Carlo N-Particle (MCNP) code for each day during the experiment. Individual heat rates for each non-fuel component were input as well. A steady-state thermal analysis was performed for each daily calculation. A finite element model was created for each capsule using the commercial finite element heat transfer and stress analysis package ABAQUS. The fission and neutron gamma heat rates were calculated with the nuclear physics code MCNP. ATR outer shim control cylinders and neck shim rods along with driver fuel power and fuel depletion were incorporated into the daily physics heat rate calculations. Compact and graphite thermal conductivity were input as a function of temperature and fast neutron fluence with the field variable option in ABAQUS. Surface-to-surface radiation heat transfer along with conduction heat transfer through the gas mixture of helium-neon (used for temperature control) was used in these models. Model results are compared to thermocouple data taken during the experiment.Copyright © 2016 by ASME
Hip and Knee Arthroplasty in Osteoarthritis

Osteoarthritis (OA) of the hip and knee continues to increase in prevalence with the increasing age of our population. This condition is characterized by joint pain, stiffness, and limitations in activities of daily living. Management options are initially aimed at preventing the progression of disease and delaying the need for total joint arthroplasty (TJA). This includes nonoperative measures, as well as surgical interventions, including arthroscopy, osteotomy, and arthrodesis. However, once patients fail alternative therapy, TJA is indicated. Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are highly effective procedures at reducing pain and improving functional status. Patients report high satisfaction rates after TJA and experience minimal complications. Moreover, these procedures are cost effective. Significant research into patient-specific implants (PSI) and computer-navigation-assisted surgery shows improved component positioning; however, further research is needed to determine the clinical effect of this innovation. Wear rates in both TKA and THA have improved significantly over the past decade, with highly cross-linked ultra-high molecular-weight polyethylene showing promising results. New minimally invasive surgical techniques are also showing excellent short-term results, but long-term data is still lacking. Overall, hip and knee OA is a debilitating condition that can be effectively managed with TKA or THA. Indications continue to expand for these procedures and innovation continues to aim for improved outcomes.
Proteolytic cleavages in the extracellular domain of receptor tyrosine kinases by membrane-associated serine proteases

// Li-Mei Chen 1 and Karl X. Chai 1 1 Burnett School of Biomedical Sciences, Division of Cancer Research, University of Central Florida College of Medicine, Orlando, FL 32816-2364, USA Correspondence to: Karl X. Chai, email: kxchai@mail.ucf.edu Keywords: receptor tyrosine kinase, matriptase, prostasin, Herceptin, breast cancer Received: August 05, 2016 Accepted: March 21, 2017 Published: April 10, 2017 ABSTRACT The epithelial extracellular membrane-associated serine proteases matriptase, hepsin, and prostasin are proteolytic modifying enzymes of the extracellular domain (ECD) of the epidermal growth factor receptor (EGFR). Matriptase also cleaves the ECD of the vascular endothelial growth factor receptor 2 (VEGFR2) and the angiopoietin receptor Tie2. In this study we tested the hypothesis that these serine proteases may cleave the ECD of additional receptor tyrosine kinases (RTKs). We co-expressed the proteases in an epithelial cell line with Her2, Her3, Her4, insulin receptor (INSR), insulin-like growth factor I receptor (IGF-1R), the platelet-derived growth factor receptors (PDGFRs) α and β, or nerve growth factor receptor A (TrkA). Western blot analysis was performed to detect the carboxyl-terminal fragments (CTFs) of the RTKs. Matriptase and hepsin were found to cleave the ECD of all RTKs tested, while TMPRSS6/matriptase-2 cleaves the ECD of Her4, INSR, and PDGFR α and β. Prostasin was able to cleave the ECD of Her3 and PDGFRα. Matriptase cleaves phosphorylated Her2 at Arg558 and Arg599 and the Arg599 cleavage produces a CTF not recognized by the monoclonal antibody trastuzumab/Herceptin. Her2 cleavages by matriptase can be inhibited by the hepatocyte growth factor activator inhibitor 1 (HAI-1) in the MDA-MB-231 human breast cancer cells. Matriptase silencing in the Her2, matriptase, and HAI-1 triple-positive SKBR3 human breast cancer cells enhanced Her2 protein down-regulation induced by a sustained exposure to phorbol 12-myristate 13-acetate (PMA), which down-regulated matriptase protein. The novel Her2 cleavage and expression regulation mechanisms mediated by matriptase may have potential impacts in Her2-targeting therapies.
The virtual cone: A novel technique to generate spherical dose distributions using a multileaf collimator and standardized control-point sequence for small target radiation surgery.

Abstract Purpose The study aimed to develop and demonstrate a standardized linear accelerator multileaf collimator-based method of delivering small, spherical dose distributions suitable for radiosurgical treatment of small targets such as the trigeminal nerve. Methods and materials The virtual cone is composed of a multileaf collimator–defined field with the central 2 leaves set to a small gap. For 5 table positions, clockwise and counter-clockwise arcs were used with collimator angles of 45 and 135 degrees, respectively. The dose per degree was proportional to the sine of the gantry angle. The dose distribution was calculated by the treatment planning system and measured using radiochromic film in a skull phantom for leaf gaps of 1.6, 2.1, and 2.6 mm. Cones with a diameter of 4 mm and 5 mm were measured for comparison. Output factor constancy was investigated using a parallel-plate chamber. Results The mean ratio of the measured-to-calculated dose was 0.99, 1.03, and 1.05 for 1.6, 2.1, and 2.6 mm leaf gaps, respectively. The diameter of the measured (calculated) 50% isodose line was 4.9 (4.6) mm, 5.2 (5.1) mm, and 5.5 (5.5) mm for the 1.6, 2.1, and 2.6 mm leaf gap, respectively. The measured diameter of the 50% isodose line was 4.5 and 5.7 mm for the 4 mm and 5 mm cones, respectively. The standard deviation of the parallel-plate chamber signal relative to a 10 cm × 10 cm field was less than 0.4%. The relative signal changed 32% per millimeter change in leaf gap, indicating that the parallel-plate chamber is sensitive to changes in gap width. Conclusions The virtual cone is an efficient technique for treatment of small spherical targets. Patient-specific quality assurance measurements will not be necessary in routine clinical use. Integration directly into the treatment planning system will make planning using this technique extremely efficient.
Local and distributed concept representation via colimits: An example

Abstract An issue in the representation by a neural network of objects detected by its sensors is whether such representations are based at a single neural cell or require a distributed subnetwork. We perform an analysis near the sensor level of a simple geometric shape and show that given the appropriate mathematical structure, representations can be both local and distributed. Moreover, as simulations demonstrate, using the proposed structures in neural network design leads to improved performance in object discrimination.
A verrucous presentation of mycosis fungoides

Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma and can have a variety of clinical and histological manifestations, including erythrodermic, pustular, bullous, hypo/hyperpigmented, and verrucous forms. We describe a case of a 59-year-old woman who presented with verrucous hyperkeratotic plaques on her distal fingertips, dorsal feet, and areolae that were subsequently biopsied and shown to be mycosis fungoides. This case highlights one of the many atypical manifestations of MF and underscores the need to have a high clinical suspicion for the disease.
THE DEVELOPMENT OF PLATELET FACTOR 3 ACTIVITY BY LATEX PARTICLES--AN INTERACTION WITH PLASMA.

Platelet factor 3 activity of polystyrene latex particles was found to be absent when the particles were tested without prior incubation with plasma. Following such incubation, the particles developed considerable but suboptimal activity. An interaction between the particles and some plasma component(s) during the incubation period which gives rise to a labile type of activity has been postulated.
InAs/InAsSb Type-II Superlattice Mid-Wavelength Infrared Focal Plane Array With Significantly Higher Operating Temperature Than InSb

We report focal plane array (FPA) results on a mid-wavelength InAs/InAsSb type-II strained layer superlattice (T2SLS) unipolar barrier infrared detector with a cutoff wavelength of 5.4 μm. For 300 K background in the 3–5-μm band, f/2 aperture, an FPA operating at 150 K exhibits a mean noise equivalent differential temperature (NEDT) of 18.5 mK, and an NEDT operability of 99.7%. The NEΔT distribution has a width of 8 mK, with no noticeable distribution tail, indicating excellent uniformity. The mean noise-equivalent irradiance is 9.1 × 1011 photons/sec-cm2. The mean quantum efficiency is 49.1% without antireflection coating, and the mean specific detectivity (D*) is 2.53 × 1011 cm-Hz½/W. Benefitting from an absorber material with a much longer Shockley–Read–Hall minority carrier lifetime, and a device architecture that suppresses generation-recombination and surface-leakage dark current, the InAs/InAsSb T2SLS barrier infrared detector FPA has demonstrated a significantly higher operating temperature than the mid-wavelength infrared market-leading InSb.
Effects of disorder in frozen-mode light

We employ renormalization ideas in order to describe the interplay between a frozen mode regime—a scattering feature associated with the presence of stationary inflection point (SIP) singularities—and disorder in photonic systems. Specifically, we demonstrate the existence of a β-function for a (rescaled) Wigner delay time PL at SIP frequencies which depends on PL itself and controls its variation with the system size L and disorder strength.
The role of task-based neural activation research in understanding cognitive deficits in pediatric epilepsy

Children with epilepsy can experience significant cognitive dysfunction that can lead to academic underachievement. Traditionally believed to be primarily due to the effects of factors such as the chronicity of epilepsy, medication effects, or the location of the primary epileptogenic lesion;, recent evidence has indicated that disruption of cognition-specific distributed neural networks may play a significant role as well. Specifically, over the last decade, researchers have begun to characterize the mechanisms underlying disrupted cognitive substrates by evaluating neural network abnormalities observed during specific cognitive tasks, using task-based functional magnetic resonance imaging (fMRI). This targeted review assesses the current literature investigating the relationship between neural network abnormalities and cognitive deficits in pediatric epilepsy. The findings indicate that there are indeed neural network abnormalities associated with deficits in executive function, language, processing speed, and memory. Overall, cognitive dysfunction in pediatric epilepsy is associated with a decrease in neural network activation/deactivation as well as increased recruitment of brain regions not typically related to the specific cognitive task under investigation. The research to date has focused primarily on children with focal epilepsy syndromes with small sample sizes and differing research protocols. More extensive research in children with a wider representation of epilepsy syndromes (including generalized epilepsy syndromes) is necessary to fully understand these relationships and begin to identify underlying cognitive phenotypes that may account for the variability observed across children with epilepsy. Furthermore, more uniformity in fMRI protocols and neuropsychological tasks would be ideal to advance this literature.
MICAL-L1 coordinates ciliogenesis by recruiting EHD1 to the primary cilium

The endocytic protein EHD1 plays an important role in ciliogenesis by facilitating fusion of the ciliary vesicle and removal of CP110 (also known as CCP110) from the mother centriole, as well as removal of Cep215 (also known as CDK5RAP2) from centrioles to permit disengagement and duplication. However, the mechanism of its centrosomal recruitment remains unknown. Here, we address the role of the EHD1 interaction partner MICAL-L1 in ciliogenesis. MICAL-L1 knockdown impairs ciliogenesis in a similar manner to EHD1 knockdown, and MICAL-L1 localizes to cilia and centrosomes in both ciliated and non-ciliated cells. Consistent with EHD1 function, MICAL-L1-depletion prevents CP110 removal from the mother centriole. Moreover, upon MICAL-L1-depletion, EHD1 fails to localize to basal bodies. Since MICAL-L1 localizes to the centrosome even in non-ciliated cells, we hypothesized that it might be anchored to the centrosome via an interaction with centrosomal proteins. By performing mass spectrometry, we identified several tubulins as potential MICAL-L1 interaction partners, and found a direct interaction between MICAL-L1 and both α-tubulin-β-tubulin heterodimers and γ-tubulin. Our data support the notion that a pool of centriolar γ-tubulin and/or α-tubulin-β-tubulin heterodimers anchor MICAL-L1 to the centriole, where it might recruit EHD1 to promote ciliogenesis.
Biomarkers and Precision Medicine: State of the Art

Critical illness syndromes, including sepsis and the acute respiratory distress syndrome (ARDS), are identified using consensus definitions that are based on broad, clinically available criteria and include patients with heterogeneous biology. This heterogeneity is a barrier to developing and testing effective therapies for these syndromes. Biomarkers identify clinically distinct molecular phenotypes of ARDS and sepsis. These molecular phenotypes are associated with differences in mortality and predict response to several treatments in retrospective analyses of clinical trials. Biomarkers can be used for prognostic and predictive enrichment of clinical trials in critical illness to incorporate precision medicine in critical care.
Revitalizing African Languages for Transformation

Local languages are the repositories of the indigenous knowledge base of societies. Marginalization of certain languages is a form of devaluing not only the languages but the knowledge and culture embodied in those languages. This paper explores the effects the devaluation of African languages have had on the indigenous knowledge base and culture of African countries and considers possibilities for the transformation of Africa through re-valuing African languages.
Associations between unmet palliative care needs and cognitive impairment in a sample of diverse, community-based older adults.

Objective Given a large number of community-based older adults with mild cognitive impairment, it is essential to better understand the relationship between unmet palliative care (PC) needs and mild cognitive impairment in community-based samples. Method Participants consisted of adults ages 60+ receiving services at senior centers located in New York City. The Montreal Cognitive Assessment (MoCA) and the Unmet Palliative Care Needs screening tool were used to assess participants’ cognitive status and PC needs. Results Our results revealed a quadratic relationship between unmet PC needs and mild cognitive impairment, controlling for gender, living status, and age. Participants with either low or high MoCA scores reported lower PC needs than participants with average MoCA scores, mean difference of the contrast (low and high vs. middle) = 2.15, P = 0.08. Significance of results This study is a first step toward elucidating the relationship between cognitive impairment and PC needs in a diverse community sample of older adults. More research is needed to better understand the unique PC needs of older adults with cognitive impairment living in the community.
Allopurinol use during pediatric acute lymphoblastic leukemia maintenance therapy safely corrects skewed 6-mercaptopurine metabolism, improving inadequate myelosuppression and reducing gastrointestinal toxicity

Background Inadequate myelosuppression during maintenance therapy for acute lymphoblastic leukemia (ALL) is associated with an increased risk of relapse. One mechanism is skewed metabolism of 6-mercaptopurine (6MP), a major component of maintenance therapy, which results in preferential formation of the hepatotoxic metabolite (6-methyl mercaptopurine [6MMP]) with low levels of the antileukemic metabolite, 6-thioguanine nucleotides (6TGN). Allopurinol can modify 6MP metabolism to favor 6TGN production and reduce 6MMP. Methods Patients in maintenance were considered for allopurinol treatment who had the following features: (a) Grade ≥3 hepatotoxicity; (b) Grade ≥2 nonhepatic gastrointestinal (GI) toxicity; or (c) persistently elevated absolute neutrophil count (ANC) despite >150% protocol dosing of oral chemotherapy. Results From 2013 to 2017, 13 ALL patients received allopurinol: nine for hepatotoxicity, five for inadequate myelosuppression, and three for nonhepatic GI toxicity (four met multiple criteria). Allopurinol was well tolerated, without significant adverse events. Allopurinol resulted in a significant decrease in the average 6MMP/6TGN ratio (mean reduction 89.1, P = .0001), with a significant increase in 6TGN (mean 550.4, P = .0008) and a significant decrease in 6MMP (mean 13 755, P = .0013). Patients with hepatotoxicity had a significant decrease in transaminase elevation after starting allopurinol (alanine transaminase [ALT] mean decrease 22.1%, P = .02), and all with nonhepatic GI toxicity had improved symptoms. Those with inadequate myelosuppression had a significant increase in the time with ANC in goal (mean increase 26.4%, P = .0004). Conclusions Allopurinol during ALL maintenance chemotherapy is a safe, feasible, and effective intervention for those who have altered metabolism of 6MP causing toxicity or inadequate myelosuppression.
Cluster Detection of Cancer Incidence: Analyzing Childhood Residential Location Linked to Later Life Cancer Records

BackgroundChildhood environmental exposures are now recognized contributors to cancer later in life. However, direct measurement of environmental contaminants is not feasible using most retrospecti...
Association of polycyclic aromatic hydrocarbons in moss with blood biomarker among nearby residents in Portland, Oregon

Polycyclic aromatic hydrocarbons (PAHs) are a component of air pollutants that are costly to measure using traditional air-quality monitoring methods. We used an epiphytic bio-indicator (moss genus: Orthotrichum) to cost-effectively evaluate atmospheric deposition of PAHs in Portland, Oregon in May 2013. However, it is unclear if measurements derived from these bioindicators are good proxies for human exposure. To address this question, we simultaneously, measured PAH-DNA adducts in blood samples of non-smokers residing close to the sites of moss measurements. We accounted for individual determinants of PAH uptake that are not related to environmental air quality through questionnaires, e.g., wood fires, consumption of barbecued and fried meats. Correlation and linear regression (to control for confounders from the lifestyle factors) evaluated the associations. We did not observe evidence of an association between PAH levels in moss and PAH-DNA adducts in blood of nearby residents, but higher level of adduct were evident in those who used wood fire in their houses in the last 48 hours. It remains to be determined whether bio-indicators in moss can be used for human health risk assessment. HighlightsO_LIConcentration of PAH in moss do not relate to DNA adducts of PAH in blood of nearby residents in our sample. C_LIO_LIContent of moss may not be suitable for assessing exposure to PAH among humans. C_LI
El cine de la crisis: respuestas cinematográficas a la crisis económica española en el siglo XXI: edited by María José Hellín García and Helena Talaya Manso, Barcelona, Editorial de la Universitat Oberta de Catalunya, 2018, 282 pp. 29€ (paperback), ISBN13 978-8491800538.

The onset of the global financial crisis in 2008 has had a lasting impact on social, political and cultural life in Spain. The collapse of the real estate bubble, unprecedented unemployment rates a...
Who let the DoGs out? – biogenesis of stress-induced readthrough transcripts

Readthrough transcription caused by inefficient 3′-end cleavage of nascent mRNAs has emerged as a hallmark of the mammalian cellular stress response and results in the production of long noncoding RNAs known as downstream-of-gene (DoG)-containing transcripts. DoGs arise from around 10% of human protein-coding genes and are retained in the nucleus. They are produced minutes after cell exposure to stress and can be detected hours after stress removal. However, their biogenesis and the role(s) that DoGs or their production play in the cellular stress response are incompletely understood. We discuss findings that implicate host and viral proteins in the mechanisms underlying DoG production, as well as the transcriptional landscapes that accompany DoG induction under different stress conditions.
Effects of Ag/adjuvant ratio on the systemic and mucosal antibody responses of BALB/c mice immunized intradermally with CfaEB, a minor-major subunit fusion of the enterotoxigenic E. coli CFA/I fimbriae, and LT(R192G/L211A) (VAC9P.1104)

The ratio of Ag/adjuvant in a vaccine can modulate the immune response as well as side effects. We studied the effects of different doses of CfaEB, a minor-major subunit fusion of the enterotoxigenic E. coli (ETEC) CFA/I fimbriae, given ID with the adjuvant LT(R192G/L211A), or dmLT, an attenuated form of the ETEC heat-labile enterotoxin. BALB/c mice were immunized with 0.1, 1, 10 or 100 mg of CfaEB alone or with 10 or 100 ng of dmLT on days 0 and 21. Sera from days 21 and 28 were tested by ELISA and hemagglutination inhibition assay. Mucosal responses were assessed in day 28 fecal pellets. Serum anti-CfaE IgG Ab titers directly correlated with the dose in groups receiving no adjuvant but the highest titers were seen in the two groups receiving 10 mg of CfaEB plus 10 or 100 ng dmLT. A similar pattern was observed with serum anti-CfaE IgA responses, although 100 mg of CfaEB plus 10 or 100 ng of adjuvant elicited the highest levels. Groups receiving 10 or 100 mg of CfaEB plus 100 ng dmLT manifested the highest functional Ab titers. The adjuvant at either dose was required to elicit a strong fecal anti-CfaE IgA response, and it directly correlated with CfaEB dose in the adjuvanted groups. Our results demonstrate the importance of dmLT in promoting mucosal Ab responses to our vaccine when given by the ID route. Since optimal mucosal vs. systemic functional Ab responses are elicited by different Ag/adjuvant ratios, the ratio should be selected to elicit the desired immune response.
Fully-isolated NLDMOS behavior investigation during reverse recovery of parasitic diodes

The behavior of the fully-isolated laterally diffused MOSFETs (LDMOS) during reverse recovery of parasitic diodes such as buck converter or white light emitting diode (WLED) driver application was presented. The fully-isolated MOSFETs with parasitic diodes have been realized for high power application, but the related reverse recovery charge (Qrr) model fitting accuracy is still an issue for these devices. Generally, only a single model is used to cover all of the applications. However, Qrr behaviors are different between WLED driver and buck converter. In WLED output stage, two parasitic diodes within high-side switch MOS will be turned on. In buck converter application, there is only one parasitic diode within low-side switch MOS during dead time. We performed the measurement with decoupling Qrr extraction method to fit model under high-side and low-side operations. This resulted in significant Qrr model fitting accuracy improvement by 4 times.
Effect of hard X-rays on the emission lines of Seyfert galaxies and QSOs.

Models of photoionized emission-line regions show that inclusion of a hard X-ray component in the ionizing continuum has relatively minor effects on most optical line intensities but helps to explain the strong O VI emission observed from QSOs. The optical-forbidden lines of NGC 4151 indicate roughly solar abundances ratios of N/O/Ne/Fe. The X-ray absorption arises largely in neutral portions of the emission-line clouds.
The role of user profiles in context-aware query processing for the semantic web

Many queries processed on the World Wide Web do not return the desired results because they fail to take into account the context of the query and information about user’s situation and preferences. In this research, we propose the use of user profiles as a way to increase the accuracy of web pages returned from the Web. A methodology for creating, representing, and using user profiles is proposed. A frame-based representation captures the initial user’s profile. The user’s query history and post query analysis is intended to further update and augment the user’s profile. The effectiveness of the approach for creating and using user profiles is demonstrated by testing various queries.
Expert Witness, Statistician as

The practice of inferential statistics in the courts, although quite modest before 1975, was given a burst of enthusiasm when the Supreme Court began to deal with the Civil Rights Act. The SC needed some kind of inference procedures to assess whether, say, the difference in hire rates between two groups was the usual play of chance, or did that fact evince enthusiasm for hiring one group of applicants in preference to another. They chose of course, the usual statistical inference procedures. Keywords: law; Supreme Court; inferential statistics; expert witnesses
Introduction to Non-Baryonic Dark Matter

These lectures on non-baryonic dark matter matter are divided into two parts. In the first part, I discuss the need for non-baryonic dark matter in light of recent results in cosmology, and I present some of the most popular candidates for non-baryonic dark matter. These include neutrinos, axions, neutralinos, WIMPZILLAs, etc. In the second part, I overview several observational techniques that can be employed to search for WIMPs (weakly interacting massive particles) as non-baryonic dark matter. Among these techniques, I discuss the direct detection of WIMP dark matter, and its indirect detection through high-energy neutrinos, gamma-rays, positrons, etc.
Effects of ɛ-Pyridoxyllysine Bound to Dietary Protein on the Vitamin B-6 Status of Rats

The nutritional properties of protein bound epsilon-pyridoxyllysine residues in a phosphopyridoxyl bovine serum albumin (PP-BSA) preparation were examined by rat bioassay employing various levels of PP-BSA and pyridoxine (PN) fortification in the diets. Previous studies have shown that vitamin B-6 aldehydes can reductively bind to food proteins as epsilon-pyridoxyllysine complexes during processing and storage. The bound pyridoxyllysine was found to possess 50% molar vitamin B-6 activity, as indicated by slope ratios for rat growth, feed efficiency and liver pyridoxal 5'-phosphate concentration. The response curves indicated that high dosages of epsilon-pyridoxyllysine would fully satisfy the vitamin B-6 requirement. Direct antivitamin B-6 activity of epsilon-pyridoxyllysine was observed in diets containing low levels of PP-BSA. Classical rat acrodynia symptoms, depression of erythrocyte aspartate aminotransferase (AspAT) activity and elevation of in vitro coenzyme stimulation of AspAT were observed to be inversely related to PP-BSA concentration in the diet. The antivitamin B-6 effects were readily prevented by the presence of added 0.5--1.0 micrograms pyridoxing/g diet. In contrast to the previous study, the presence of PP-BSA in the diet did not inhibit the utilization of added PN. This difference was postulated to be due to a difference in vitamin B-6 concentration of the basal diets. The results of this study indicate that protein bound epsilon-pyridoxyllysine is nutritionally significant, presumably by its participation in the normal metabolism of vitamin B-6. The metabolic implications are discussed.
Implementing Family-Centered Prevention in Rural African American Communities: a Randomized Effectiveness Trial of the Strong African American Families Program

Efforts to disseminate evidence-based prevention programs are hampered by a lack of real-world effectiveness trials undertaken with community providers. The Strong African American Families (SAAF) program is an empirically validated intervention designed to prevent problem behavior among rural African American youth. To evaluate the effectiveness of SAAF and its implementation protocols when delivered by a community provider, we conducted a randomized, wait-list-controlled trial with outcome measurements assessed longitudinally at baseline and 6 months after baseline. A total of 465 African American youth and their parents were recruited randomly from public school lists of fifth- and sixth-grade students in eight rural counties in south Georgia. Youth and parents assessed targeted outcomes in their homes. The main outcome, problem behavior vulnerability, was operationalized as a latent construct comprising three indicators: tolerance for deviance, intentions to engage in risky behavior, and affiliations with risk-taking peers. SAAF was implemented with uniformly high levels of adherence (85.5 %; SD = 10.8) and attendance (M = 4.1, SD = 2.9, range = 0–7). Intent-to-treat and complier average causal effect analyses revealed significant program effects on intervention-targeted parenting practices, youth self-regulatory processes, and problem behavior vulnerability. SAAF influenced problem behavior vulnerability indirectly via effects on targeted parenting and youth processes. This study supported the effectiveness of SAAF in a community setting when a systematic implementation model supports participant engagement and intervention adherence.
The Pace of Change in the Paleolithic

Before Lascaux: The Complex Record of the Early Upper Paleolithic. H. Knecht, A. Pike-Tay, and R. White, eds.