cssi/SciSciGPT-SciSciNet huggingface dataset:
Fibroblast growth factor 22 contributes to the development of retinal nerve terminals in the dorsal lateral geniculate nucleus.

At least three forms of signaling between pre and postsynaptic partners are necessary during synapse formation. First, ‘targeting’ signals instruct presynaptic axons to recognize and adhere to the correct portion of a postsynaptic target cell. Second, trans-synaptic ‘organizing’ signals induce differentiation in their synaptic partner so that each side of the synapse is specialized for synaptic transmission. Finally, in many regions of the nervous system an excess of synapses are initially formed, therefore ‘refinement’ signals must either stabilize or destabilize the synapse to reinforce or eliminate connections, respectively. Because of both their importance in processing visual information and their accessibility, retinogeniculate synapses have served as a model for studying synaptic development. Molecular signals that drive retinogeniculate ‘targeting’ and ‘refinement’ have been identified, however, little is known about what ‘organizing’ cues are necessary for the differentiation of retinal axons into presynaptic terminals. Here we show that fibroblast growth factor 22 (FGF22) is required for the timely organization of retinogeniculate synapses. To identify ‘organizing’ cues, we used microarray analysis to assess whether any target-derived ‘synaptic organizers’ were enriched in the mouse dorsal lateral geniculate nucleus (dLGN) during retinogeniculate synapse formation. One candidate ‘organizing’ molecule enriched in perinatal dLGN was FGF22, a secreted cue that induces the formation of excitatory nerve terminals in muscle, hippocampus and cerebellum. In FGF22 knockout mice, the development of retinal terminals in dLGN was impaired. Thus, FGF22 is an important ‘organizing’ cue for retinogeniculate synapses.
Disruption Risk and Optimal Sourcing in Multitier Supply Networks

We study sourcing in a supply chain with three levels: a manufacturer, tier 1 suppliers, and tier 2 suppliers prone to disruption from, e.g., natural disasters such as earthquakes or floods. The manufacturer may not directly dictate which tier 2 suppliers are used but may influence the sourcing decisions of tier 1 suppliers via contract parameters. The manufacturer’s optimal strategy depends critically on the degree of overlap in the supply chain: if tier 1 suppliers share tier 2 suppliers, resulting in a “diamond-shaped” supply chain, the manufacturer relies less on direct mitigation (procuring excess inventory and multisourcing in tier 1) and more on indirect mitigation (inducing tier 1 suppliers to mitigate disruption risk). We also show that while the manufacturer always prefers less overlap, tier 1 suppliers may prefer a more overlapped supply chain and hence may strategically choose to form a diamond-shaped supply chain. This preference conflict worsens as the manufacturer’s profit margin increases,...
Association of Cigarette Smoking with Extraprostatic Prostate Cancer in Young Men

ABSTRACTPurpose: A few recent studies have revealed that cumulative or recent smoking is associated with death from prostate cancer suggesting that smoking may influence progression to more advanced disease. We evaluate the association of cigarette smoking with extraprostatic and/or Gleason sum 7 or greater prostate cancer in young men.Materials and Methods: The study included men who underwent radical prostatectomy before age 55 years for prostate cancer between 1992 and 1999. A survey soliciting cigarette smoking history and other exposures was mailed to 498 eligible men. The response rate was 73%. Cases were defined as men with Gleason sum 7 or greater, extraprostatic or Gleason sum 7 or greater/extraprostatic disease based on pathologic analysis. All remaining participants were considered noncases for each case definition. We used logistic regression modeling to estimate the odds ratio (OR) for Gleason sum 7 or greater, extraprostatic and Gleason sum 7 or greater/extraprostatic disease with cigarette ...
Salton Trough Regional Deformation Estimated from Combined Trilateration and Survey-Mode GPS Data

The Salton Trough in southeastern California, United States, has one of the highest seismicity and deformation rates in southern California, including 20 earthquakes M 6 or larger since 1892. From 1972 through 1987, the U.S. Geological Survey (USGS) measured a 41-station trilateration network in this region. We re-measured 37 of the USGS baselines using survey-mode Global Positioning System methods from 1995 through 1999. We estimate the Salton Trough deformation field over a nearly 30-year period through combined analysis of baseline length time series from these two datasets. Our primary result is that strain accumulation has been steady over our observation span, at a resolution of about 0.05 μstrain/yr at 95% confidence, with no evidence for significant long-term strain transients despite the occurrence of seven large regional earthquakes during our observation period. Similar to earlier studies, we find that the regional strain field is consistent with 0.5 ± 0.03 μstrain/yr total engineering shear strain along an axis oriented 311.6° ± 23° east of north, approximately parallel to the strike of the major regional faults, the San Andreas and San Jacinto (all uncertainties in the text and tables are standard deviations unless otherwise noted). We also find that (1) the shear strain rate near the San Jacinto fault is at least as high as it is near the San Andreas fault, (2) the areal dilatation near the southeastern Salton Sea is significant, and (3) one station near the southeastern Salton Sea moved anomalously during the period 1987.95-1995.11. Online material: Tables of stations used in this study and of estimated strain fields. Manuscript received 8 January 2003.
Protein Kinase A Catalytic Subunit Primed for Action: Time-Lapse Crystallography of Michaelis Complex Formation.

Summary The catalytic subunit of the cyclic AMP-dependent protein kinase A (PKAc) catalyzes the transfer of the γ-phosphate of bound Mg 2 ATP to a serine or threonine residue of a protein substrate. Here, time-lapse X-ray crystallography was used to capture a series of complexes of PKAc with an oligopeptide substrate and unreacted Mg 2 ATP, including the Michaelis complex, that reveal important geometric rearrangements in and near the active site preceding the phosphoryl transfer reaction. Contrary to the prevailing view, Mg 2+ binds first to the M1 site as a complex with ATP and is followed by Mg 2+ binding to the M2 site. Concurrently, the target serine hydroxyl of the peptide substrate rotates away from the active site toward the bulk solvent, which breaks the hydrogen bond with D166. Lastly, the serine hydroxyl of the substrate rotates back toward D166 to form the Michaelis complex with the active site primed for phosphoryl transfer.
Process and practice: groupness, ethnicity, and habitus in Carpathian Rus’

This article synthesizes Wimmer's and Brubaker's processual approach to analyzing ethnic groups with Jenkins and Bentley's practice-based theories of ethnicity to explain the role played by socio-emotional experiences and practical concerns in Carpatho-Rusyns, both mobilizing as an ethnic group as well as resisting such mobilization. Data were gathered from interviews and participant observation during the eight months of fieldwork in 10 different villages, towns, and cities in the Presov region of Slovakia and the Zakarpattia oblast of Ukraine. Carpatho-Rusyns live in an area where borders have changed frequently and where religions, states, and political movements have encouraged the inhabitants’ assimilation to a new or larger group. Rusyns tend to describe ethnicity as instrumentalist theorists do, that is, something largely produced as a result of struggles over territory, resources, and political power. Nevertheless, they evince a profound emotional connection to their language, land, and spirituali...
The Group of Rational Points on the Unit Circle

There have been several attempts to present the basic idea of this marvelous proof to a wider mathematical audience ([2, 7, 81). Another recent paper [31 provides more details. Wiles' proof is based on the theory of elliptic curves, i.e., curves defined by cubic equations. A big part of this theory is devoted to understanding the "rational points" (points whose coordinates are rational numbers) on these curves. The set of rational points on an elliptic curve has a natural group structure, which will be described very briefly later. It is often very difficult, however, to find all the rational points on an elliptic curve. In this paper we take a much easier and more familiar example-the unit circle-and show how to compute the group structure of its rational points. Next, some applications are given. Finally, for comparison, we give a brief summary of known results on the 'group structure for rational points on elliptic curves.
Remarks on special emphasis programs of the national institute of allergy and infectious diseases.

In addition to support through grants to the broad field of medical microbiology and immunology, the NIAID has a responsibility to foster original investigations on disease problems of greatest national importance. Financial constraints now placed upon the budget of this Institute and the entire NIH have made it even more imperative to assure support for research relevant to health needs. The Institute, with the advice of its advisory committees, particularly the National Advisory Allergy and Infectious Diseases Council, has given thoughtful consideration to ways in which this can be achieved in the extramural
Studies of leukemia L2C in guinea pigs.

1. Leukemia L2C is transmissible, in routine passages, with high-speed centrifuged leukemic spleen extracts. The extracts were prepared from leukemic spleen cells which had been disrupted by several methods. 2. Leukemia L2C is transmissible, in routine passages, with highspeed centrifuged leukemic plasma which had been harvested at early or late stages of the disease. 3. Leukemia L2C has been transmitted, in repeated experiments, with leukemic spleen extract, leukemic brain extract, or leukemic serum after these materials had been passed through bacteria-tight filters of various types. 4. Susceptibility to leukemia L2C appears to be essentially limited to inbred strain No. 2 guinea pigs or to F1 hybrids born from crossmating susceptible with resistant guinea pigs. These is some evidence to suggest that susceptibility of strain No. 2 guinea pigs to leukemia L2C is inherited as a dominant characteristic. 5. The leukemogenic agent is capable of passing the placenta in the leukemic animal. Embryos of leukemic mothers may appear normal, but their tissues could be shown to harbor the disease-transmitting agent. 6. When injected intraperitoneally into susceptible guinea pigs, the leukemogenic agent appeared in the plasma of the animal for the first time on the 4th day and was thereafter regularly present in all subsequent plasma samples. Whole blood transmitted leukemia at the 24 h and 48 h intervals, but not at the 72 h interval. Beginning with the 4th day again, all subsequent whole blood samples transmitted the disease. In the resistant animal, the leukemogenic agent was sporadically present during the first five days in plasma or in whole blood. Samples taken after that time no longer transmitted leukemia.
[Formula: see text]Expert beliefs and practices regarding neuropsychological validity testing.

AbstractObjective: The current study investigated expert beliefs and practices as they relate to neuropsychological validity testing. Methods: North American neuropsychologists with expertise in neuropsychological validity testing (n = 24) were surveyed on numerous items related to validity testing. Results were analyzed and compared to findings from a prior expert survey and a recent survey of a general sample of neuropsychological practitioners. Results: Responses varied among experts on some items, indicating that experts have differences of opinion and practice regarding certain validity testing topics. However, expert opinion converged on a number of topics central to validity testing, particularly those highlighting the need for and importance of validity testing in neuropsychological assessment. Notably, expert responses on these topics often agreed with responses obtained from a prior expert sample and a general sample of neuropsychological practitioners. Conclusions: The results allow practitione...
Structures of divalent transition metal salts of 4-aminonaphthalene-1-sulfonate: unexpected variations in layering pattern

Salts of 4-aminonaphthalene-1-sulfonate with divalent Mg, Mn, Co, and Ni cations have been crystallized and their structures determined by single crystal X-ray methods. The Mg and Mn salts are isostructural. Crystal data for hexa-aquamagnesium(II) 4-aminonaphthalene-1-sulfonate dihydrate, [Mg(H2O)6](H2NC10H6SO3)2 ⋅ 2H 2O: monoclinic, P21/c, Z = 2, a = 8.622(3), b = 7.043(3), c = 23.178(3) A, β=93.78(2)°, V = 1404.3(7) A3; hexa-aquamanganese(II) 4-aminonaphthalene-1-sulfonate dihydrate, [Mn(H2O)6](H2NC10H6SO3)2 ⋅ 2H 2O: monoclinic, P21/c, Z = 2, a = 8.652(3), b = 7.031(4), c = 23.402(2) A, β=93.09(2)°, V = 1421.5(9) A3. The structures are composed of alternating layers of octahedral metal–aqua complexes and sulfonate anions linked by an extensive network of hydrogen bonds. The extra water molecules of crystallization are located in the hexa-aquametal cation layers. The repeat unit along the c axis is a double layer. The Co and Ni compounds are isostructural with each other, but compared to the Mg and Mn compounds, have a strikingly different structure. Crystal data for hexa-aquacobalt(II) 4-aminonaphthalene-1-sulfonate trihydrate, [Co(H2O)6](H2NC10H6SO3)2 ⋅ 3H 2O: orthorhombic, Pbca, Z = 8, a = 8.518(1), b = 14.327(2), c = 45.367(6) A, V = 5536(1) A3; hexa-aquanickel(II) 4-aminonaphthalene-1-sulfonate trihydrate, [Ni(H2O)6](H2NC10H6SO3)2 ⋅ 3H 2O: orthorhombic, Pbca, Z = 8, a = 8.4976(6), b = 14.288(1), c = 45.076(3) A, V = 5472.9(7) A3. These structures also contain layers of octahedral hexa-aquametal complexes and additional water molecules of crystallization sandwiched by layers of sulfonate anions, however the stacking pattern is more complex with a quadruple layer repeat unit and two different types of anion layers.
Necessary and Sufficient Conditions for Cerenkov Radiation

Abstract It is shown that in the case of charged beams of finite dimensions and/or finite electromagnetic wave-guiding structures, the condition v&c/n is a necessary but not a sufficient condition for generation of Cerenkov radiation. Depending upon the modulation, size and geometry of the beams, and dimensions of the wave-guiding structures, selected lines can be eliminated from the radiation spectrum. Since the lines in the spectrum are size and geometry dependent it is suggested that the analysis of the Cerenkov radiation spectrum may be utilized in the determination of sizes and shapes of charged particles.
Benchmarking Clinical Engineering Program

Professional labor shortage in healthcare delivery system and specifically the management of staffing effectiveness in clinical engineering field are recent developments where shortage of comparative information exist and almost no information on its impact on performance outcomes. We attempted over the past few years to define and measure optimal application of manpower to medical technology management in the hospital setting. Others who studied in this issue suggested several indicators that can predict manpower loading and efficiency; however, the assessment model is yet to be tested. So far, studies showed that the best predictor of staffing needs is the medical technology level of comprehensiveness, the volume of the managed inventory, the conditions of the inventory and the competency of the labor force and management model deployed. This presentation will attempt to review the suggested indicators and a proposal for data collection that can be used as benchmark for comparing clinical engineering programs.
Use of Multi-Dimensional Life Tables for Studying Insect Population Dynamics

In classical life table analyses, density and mortality are measured for many generations as average values across an area. We present here as an alternative the measurement of density and mortality from a multi-dimensional spatial matrix of sample points. This method is applied to studies of gypsy moth, Lymantria dispar, population dynamics. Analysis for key factors and density-dependence may yield substantially different results between the two methods. Identification of a key mortality factor from classical life table data indicates that the mortality is correlated with between generation changes in density. In contrast, identification of a key factor from spatial data indicated that the mortality explains changes in the spatial heterogeneity of density. Conclusions about key factors and density-dependence derived from spatial data often vary among generations. Multidimensional life tables may be used to detect density-dependence that occurs on a finer spatial scale than the classic approach would detect. The multi-dimensional approach is viewed as a technique that complements, rather than replaces, traditional life table data.
Real-time segmentation of strawberry flesh and calyx from images of singulated strawberries during postharvest processing

An image processing to extract the flesh and the calyx from an image is proposed.It relies on image color segmentation in a two dimensional color space.Results are improved thanks to a blob detection and selection stage.The algorithm is to tune and allows accurate extraction of the areas of interest.It deals with natural variation in strawberry shape and visual appearance. This paper presents an image processing algorithm that automatically extracts the flesh and calyx areas from strawberry images. Images are captured by a camera included in a strawberry de-capping machine. Lighting is controlled and the background is known, conditions that are typical of postharvest processing. The goal is to extract as many flesh and calyx pixels as possible while rejecting any pixels belonging to the background. The proposed approach relies on image color segmentation in a two-dimensional color space, followed by a blob detection and selection stage. A set of 250 images is used to analyze the sensitivity of the algorithm with respect to user-defined parameters, and evaluate the performance of the approach. The algorithm appears to be easy to tune and allows accurate extraction of the areas of interest despite natural variation in strawberry shape and visual appearance. More than 98% of the flesh area was successfully extracted by the algorithm with less than 1% of the background pixels falsely included. Moreover, up to 79% of the calyx area could be extracted with less than 0.25% erroneous background pixels. Finally, the algorithm has been implemented using the C++ and Cuda languages and can be executed in real-time.
Optimizing treatment in recurrent epithelial ovarian cancer.

Introduction: Optimal management of recurrent ovarian cancer (ROC) remains an area of uncertainty. An estimated 85% of patients with epithelial ovarian cancer who achieve a full remission following...
Aging, hematopoiesis, and the myelodysplastic syndromes

The aging hematopoietic system undergoes numerous changes, including reduced production of red blood cells and lymphocytes as well as a relative increase in the production of myeloid cells. Emerging evidence indicates that many of these changes are due to selection pressures from cell-intrinsic and cell-extrinsic factors that result in clonal shifts in the hematopoietic stem cell (HSC) pool, resulting in predominant HSC clones that exhibit the functional characteristics associated with HSC aging. Given the recent descriptions of clonal hematopoiesis in aged populations, the increased risk of developing hematologic malignancies in individuals with clonal hematopoiesis, and the many similarities in hematopoietic aging and acquired bone marrow failure (BMF) syndromes, such as myelodysplastic syndromes (MDS), this raises significant questions regarding the relationship between aging hematopoiesis and MDS, including the factors that regulate HSC aging, whether clonal hematopoiesis is required for the development of MDS, and even whether BMF is an inevitable consequence of aging. In this article, we will review our current understanding of these processes and the potential intersections among them.
Properties of Block Bootstrap Methods for the Sample Mean

In this chapter, we study the first-order properties of the MBB, the NBB, the CBB, and the SB for the sample mean. Note that for the first three block bootstrap methods, the block length is nonrandom. In Section 3.2, we establish consistency of these block bootstrap methods for variance and distribution function estimations for the sample mean. The SB method uses a random block length and hence, requires a somewhat different treatment. We study consistency properties of the SB method for the sample mean in Section 3.3.
Transport of Copper

Broadly interpreted, copper transport encompasses events and intermediates that move copper progressively from gut to cells and to copper requiring enzymes within. Ceruloplasmin, the major copper-binding protein in plasma, may be an important, but not exclusive source of copper for extrahepatic cells. We have attempted to learn the mechanism by which the six to seven tightly bound and catalytically functional copper atoms in ceruloplasmin are transferred to tissue enzymes. The data suggest that carriers for ionic copper may work in conjunction with a ceruloplasmin-mediated mechanism.
Rethinking Interaction Techniques for Personal Fabrication

In this article, we are re-thinking the current interaction paradigm with personal fabrication tools: Rather than first creating a digital model, and then producing physical output at the end, we propose a new tightly coupled workflow in which physical output is created continuously while the user is interacting.
Human Papillomavirus (HPV) Testing on Cervical Cytology Specimens

Human papillomavirus (HPV) testing has been recommended for cervical cancer screening in the USA for more than a decade, either in conjunction/co-testing with Pap cytology test or as a primary screening tool. The cervical cancer screening strategy in the USA is still evolving, either to improve HPV testing efficacy to predict cervical precancers or to reduce the cost and the complexity of HPV/Pap cytology screening for cervical cancer prevention. Multiple HPV testing assays that have been approved by the US Food and Drug Administration (FDA) added more complexity to the issue. For cytopathologists and health-care administrators, it is critical to choose an appropriate cervical cancer screening strategy and HPV testing assay to fit patient care in a given clinical setting in order to achieve an optimal clinical efficacy.
Effect of treatment with human chorionic gonadotropin 7 days after artificial insemination or at the time of embryo transfer on reproductive outcomes in nulliparous Holstein heifers

Our objective was to assess the effect of treatment with human chorionic gonadotropin (hCG) 7 d after artificial insemination (AI) or at the time of in vitro-fertilized (IVF) embryo transfer on reproductive outcomes, including progesterone (P4), interferon-tau stimulated gene 15 (ISG15), pregnancy-specific protein B (PSPB), and pregnancies per AI (P/AI) or pregnancies per embryo transfer (P/ET), in nulliparous Holstein heifers. Heifers in experiment 1 were randomly assigned to receive no treatment (control; n = 129) or 2,000 IU of hCG 7 d after AI to a detected estrus (estrus = experimental d 0; hCG; n = 132). Heifers in experiment 2 were randomly assigned to receive no treatment (control; n = 143) or 2,000 IU of hCG (hCG; n = 148) at transfer of an IVF embryo 7 d after the last GnRH treatment of a 5-d controlled internal drug release-synch protocol (last GnRH = experimental d 0). Blood samples were collected from a subgroup of heifers (experiment 1, n = 82; experiment 2, n = 104) at d 7, 11, 18, 20, 25, 28, and 32, and blood samples from heifers diagnosed pregnant were collected on d 35, 39, 46, 53, 60, and 67. Blood samples were assayed for P4 by RIA and for PSPB by ELISA, and expression of ISG15 was assessed in mRNA isolated from blood leukocytes on d 18 and 20. Data were analyzed by ANOVA and logistic regression using the MIXED and GLIMMIX procedures. In both experiments, treatment with hCG increased P4 concentrations from d 11 to 32; however, treatment did not affect P/AI or P/ET at d 32 or 67, PSPB concentrations from d 11 to 67 of pregnancy, or relative ISG15 mRNA concentrations on d 18 or 20. Heifers diagnosed not pregnant at d 32 in experiment 2 with an extended luteal phase (>20 d) and treated with hCG had greater relative ISG15 mRNA concentrations on d 20 than control heifers. Treatment with hCG did not affect pregnancy loss in experiment 1, whereas heifers treated with hCG at the time of IVF embryo transfer had fewer pregnancy losses from d 32 to 67 than control heifers. We concluded that treatment with 2,000 IU of hCG 7 d after AI or at the time of embryo transfer increased P4 concentrations without affecting P/AI or P/ET in nulliparous Holstein heifers.
“Not an Ounce of Hollywood Bullshit”: A Narrative Analysis of News Media Coverage of Spotlight’s Oscar Win:

A narrative analysis was conducted of news media coverage of the Academy Award-winning movie Spotlight from January 1, 2015, until June 1, 2016, with a focus on how journalists, film critics, and c...
Echo planar time-resolved imaging with subspace reconstruction and optimized spatiotemporal encoding.

Purpose To develop new encoding and reconstruction techniques for fast multi-contrast/quantitative imaging. Methods The recently proposed Echo Planar Time-resolved Imaging (EPTI) technique can achieve fast distortion- and blurring-free multi-contrast/quantitative imaging. In this work, a subspace reconstruction framework is developed to improve the reconstruction accuracy of EPTI at high encoding accelerations. The number of unknowns in the reconstruction is significantly reduced by modeling the temporal signal evolutions using low-rank subspace. As part of the proposed reconstruction approach, a B0 -update algorithm and a shot-to-shot B0 variation correction method are developed to enable the reconstruction of high-resolution tissue phase images and to mitigate artifacts from shot-to-shot phase variations. Moreover, the EPTI concept is extended to 3D k-space for 3D GE-EPTI, where a new "temporal-variant" of CAIPI encoding is proposed to further improve performance. Results The effectiveness of the proposed subspace reconstruction was demonstrated first in 2D GESE EPTI, where the reconstruction achieved higher accuracy when compared to conventional B0 -informed GRAPPA. For 3D GE-EPTI, a retrospective undersampling experiment demonstrates that the new temporal-variant CAIPI encoding can achieve up to 72× acceleration with close to 2× reduction in reconstruction error when compared to conventional spatiotemporal-CAIPI encoding. In a prospective undersampling experiment, high-quality whole-brain T 2 ∗ and tissue phase maps at 1 mm isotropic resolution were acquired in 52 seconds at 3T using 3D GE-EPTI with temporal-variant CAIPI encoding. Conclusion The proposed subspace reconstruction and optimized temporal-variant CAIPI encoding can further improve the performance of EPTI for fast quantitative mapping.
Comparison of Cardiac Events Associated With Azithromycin vs Amoxicillin.

Importance Conflicting evidence exists on the association between azithromycin use and cardiac events. Objective To compare the odds of cardiac events among new users of azithromycin relative to new users of amoxicillin using real-world data. Design, Setting, and Participants This retrospective cohort study used data from Truven Health Analytics MarketScan database from January 1, 2009, to June 30, 2015. Patients receiving either amoxicillin or azithromycin and enrolled in a health care plan 365 days before (baseline period) the dispensing date (index date) were included in the study. Patients were matched 1:1 on high-dimensional propensity scores. Data were analyzed from October 1, 2018, to December 31, 2019. Exposures New use of azithromycin compared with new use of amoxicillin. Main Outcomes and Measures The primary outcome consisted of cardiac events, including syncope, palpitations, ventricular arrhythmias, cardiac arrest, or death as a primary diagnosis for hospitalization at 5, 10, and 30 days from the index date. Logistic regression models were used to estimate odds ratios (ORs) with 95% CIs. Results After matching, the final cohort included 2 141 285 episodes of each index therapy (N = 4 282 570) (mean [SD] age of patients, 35.7 [22.3] years; 52.6% female). Within 5 days after therapy initiation, 1474 cardiac events (0.03%) occurred (708 in the amoxicillin cohort and 766 in the azithromycin cohort). The 2 most frequent events were syncope (1032 [70.0%]) and palpitations (331 [22.5%]). The odds of cardiac events with azithromycin compared with amoxicillin were not significantly higher at 5 days (OR, 1.08; 95% CI, 0.98-1.20), 10 days (OR, 1.05; 95% CI, 0.97-1.15), and 30 days (OR, 0.98; 95% CI, 0.92-1.04). Among patients receiving any concurrent QT-prolonging drug, the odds of cardiac events with azithromycin were 1.40 (95% CI, 1.04-1.87) greater compared with amoxicillin. Among patients 65 years or older and those with a history of cardiovascular disease and other risk factors, no increased risk of cardiac events with azithromycin was noted. Conclusions and Relevance This study found no association of cardiac events with azithromycin compared with amoxicillin except among patients using other QT-prolonging drugs concurrently. Although azithromycin is a safe therapy, clinicians should carefully consider its use among patients concurrently using other QT-prolonging drugs.
Abstract 1307: Assessment of long IVT mRNA fragments with the Fragment Analyzer system

Quality control analysis of long in vitro transcribed (IVT) RNAs is challenging due to the lack of commercially available kits for sizing RNA over 6,000 nt, thus, to analyze long IVT RNAs, an extended separation method was developed for the Agilent 5200 Fragment Analyzer using a commercially available RNA ladder. IVT mRNA was produced using the RiboMAX Large Scale RNA Production System (Promega). RNA transcripts 9,000 and 10,000 nt in length were diluted in nuclease-free water and separated on the Agilent 5200 Fragment Analyzer system with the Agilent RNA kit (15 nt) (p/n DNF-471) with the following modifications. The Lonza RNA marker (Lonza) (long RNA Ladder) replaced the Agilent RNA Ladder and was diluted in nuclease-free water to 96 ng/μL. The long RNA Ladder was added to the Agilent RNA Diluent Marker (15 nt) (p/n DNF-369-0004) according to the RNA kit protocol. The standard separation method (8 kV for 45 minutes) for the RNA kit (15 nt) was manually altered to the extended RNA method (4 kV for 90 minutes) in the Agilent 5200 Fragment Analyzer software for fragments greater than 6,000 nt. The extended RNA method with the long RNA Ladder was employed for all subsequent runs. The long RNA Ladder separated with the extended method displayed enhanced resolution compared to separation with the standard method as seen by the increased spacing between the ladder peaks and the increased sharpness of the 9,000 nt peak. The extended RNA method reported a lower average sizing percent error (-0.7 %) over the entire concentration range of the kit compared to the standard RNA method (8.4 %) for the 9,000 nt sample. The 10,000 nt IVT mRNA average percent sizing error was similar between the two separation methods throughout the dilution series. Using the extended method, the 9,000 and 10,000 nt IVT mRNA samples were successfully analyzed with good sizing precision and accuracy, demonstrating that a commercially available RNA ladder can be used with the Fragment Analyzer system to provide accurate sizing of large IVT mRNA samples. The extended RNA method is recommended when extremely accurate sizing or high resolution is needed for determining the presence of degradation or sizing differences from incomplete transcription in IVT mRNA samples longer than 6,000 nt. For Research Use Only. Not for use in diagnostic procedures. Citation Format: Kyle D. Luttgeharm, Solange Borg, Chava Pocernich. Assessment of long IVT mRNA fragments with the Fragment Analyzer system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1307.
Online resources for brain injury

This article provides an overview of available brain injury information online for health care professionals and consumers. An increasing amount of high quality medical information is available online, primarily via the World Wide Web. Recommendations in regard to type of Internet access and software are provided to assist the new and intermediate users. Electronic mail, proprietary online services, and Internet applications are briefly reviewed. In addition well established online resources, such as the Medline database are highlighted. The World Wide Web sites catalogued in this article have been linked to a single site, allowing ready access to these sites while reviewing the article; Internet address: http://griffin.vcu.edu/htmIjpmr/trowland/brainref.html. The intended audience of the article is health care professionals, including those limited experience with computers and the Internet.
Migration Policies, Selection Pressure, and Parallel Evolutionary Algorithms

This paper investigates how the policy used to select migrants and the individuals they replace affects the selection pressure in parallel evolutionary algorithms (EAs) with multiple populations. The four possible combinations of random and fitness-based emigration and replacement of existing individuals are considered. The investigation follows two approaches. The first is to calculate the takeover time under the four migration policies. This approach makes several simplifying assumptions, but the qualitative conclusions that are derived from the calculations are confirmed by the second approach. The second approach consists on quantifying the increase in the selection intensity. The selection intensity is a domain-independent adimensional quantity that can be used to compare the selection pressure of common selection methods with the pressure caused by migration. The results may help to avoid excessively high (or low) selection pressures that may cause the search to fail, and offer a plausible explanation to the frequent claims of superlinear speedups in parallel EAs.
Non-monotonic Reasoning on Beowulf Platforms

Non-monotonic logic programming systems, such as the various implementations of Answer Set Programming (ASP), are frequently used to solve problems with large search spaces. In spite of the impressive improvements in implementation technology, the sheer size of realistic computations required to solve problems of interest often makes such problems inaccessible to existing sequential technology. This paper presents some preliminary results obtained in the development of solutions for execution of Answer Set Programs on parallel architectures. We identify different forms of parallelism that can be automatically exploited in a typical ASP execution, and we describe the execution models we have experimented with to take advantage of some of these. Performance results obtained on a Beowulf system are presented.
Object-Oriented Programming with Visual Basic.NET: Object Persistence: Serialization

Serialization is the process of capturing the current state of a class object and writing the state to disk. Serialization allows you to make a class object persistent, which means that you can save the current state of an object while a program is running and at a later time retrieve that state and continue using the object. In this chapter, we'll show you how to perform both serialization and deserialization, which is retrieving an object's state from disk. SERIALIZATION DEFINED Serialization in VB.NET involves writing out the state of a class object as a series of bytes to a byte stream. The CLR writes out a class object as an object-graph, which consists of the class object and all the member data associated with the object. To let the CLR know that a class can be serialized, it must be marked with the Serializable attribute. Although classes must be marked to be serialized, primitive types do not have to be marked as such. Therefore, all the primitive types within your class definition will be serialized automatically when the class is marked Serializable. Other objects (such as nested classes) within a class definition must be tagged with the Serializable attribute if they are to be serialized with the rest of the class types. A class is physically serialized using a formatter. A formatter, as its name suggests, defines the format of the data stream that is written to disk.
A capacitively phase-coupled low noise, low power 0.8-to-28.2GHz quadrature ring VCO in 40nm CMOS

This paper presents a novel tunable wide-operating range capacitively phase-coupled low noise, low power ring-based voltage controlled oscillator (VCO) for use in multi-GHz phase-locked loops (PLLs). The basic building blocks of the ring oscillator (RO) design are discussed along with a technique to expand the VCO to a variety of phases and frequencies without the use of physical inductors. Improved performance with minimal phase noise are achieved in this ring VCO design through distributed passive-element injection locking (IL) of the staged phases via a network of symmetrically placed metal interconnect capacitors. Using this method, a 0.8-to-28.2 GHz quadrature ring VCO was designed, fabricated, and physically tested with a PLL in an all-digital 40nm TSMC CMOS process. Most notably the proposed quadrature VCO occupies an area of 0.0024mm2, consumes a power of 0.88mW at a 1.0V supply voltage, and possesses a phase noise of −124.5dBc/Hz at the 10MHz offset for a carrier frequency of 28.0GHz.
Health risk behaviors of black male college students: seat belt use, smoking, and obesity status

This paper examined health behaviors (seatbelt use, tobacco use, and obesity status) of 127 black male college students using data obtained from the National College Health Risk Behavior Survey. The majority of the participants were freshmen and sophomores (70%), full time students (95%), and lived on campus (85%). The results indicated that black males often failed to use seatbelts while riding as a passenger (69%) or driving (48%). Although 15% of the students smoked, 1/3 of the smokers began smoking during college. Approximately 50% of the students were overweight or obese; among students attempting to lose weight, exercise versus nutrient intake was used as a means to lose weight. The study recommendations included the need to increase educational efforts to alert black males to their risks for a premature death, and to provide programming/mentoring initiatives to assist males in dealing with stress and discrimination that may impact their health-related decision making. The implications of this study suggest that even educated black males are at risk for premature disease and disability as a result of their health behaviors. Language: en
Analysis of Intracellular Organelles by Flow Cytometry or Microscopy

Functional analysis of cellular organelles can be accomplished by staining cells with suitable organelle-specific dyes and analyzing the fluorescence of the stained cells with a flow cytometer. With this methodology it is possible to resolve suspected heterogeneity in organelle function or content within a population of cells. Morphological information can be provided by quantitative microscopy (confocal microscope or video microscope with digital image-analysis system). The thirteen protocols cover flow cytometry and microscopy for both live and fixed cells.
Solving the straggler problem with bounded staleness

Many important applications fall into the broad class of iterative convergent algorithms. Parallel implementations of these algorithms are naturally expressed using the Bulk Synchronous Parallel (BSP) model of computation. However, implementations using BSP are plagued by the straggler problem, where every transient slowdown of any given thread can delay all other threads. This paper presents the Stale Synchronous Parallel (SSP) model as a generalization of BSP that preserves many of its advantages, while avoiding the straggler problem. Algorithms using SSP can execute efficiently, even with significant delays in some threads, addressing the oft-faced straggler problem.
Drak2 Regulates the Survival of Activated T Cells and Is Required for Organ-Specific Autoimmune Disease

Drak2 is a serine/threonine kinase expressed in T and B cells. The absence of Drak2 renders T cells hypersensitive to suboptimal stimulation, yet Drak2(-/-) mice are enigmatically resistant to experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. We show in this study that Drak2(-/-) mice were also completely resistant to type 1 diabetes when bred to the NOD strain of mice that spontaneously develop autoimmune diabetes. However, there was not a generalized suppression of the immune system, because Drak2(-/-) mice remained susceptible to other models of autoimmunity. Adoptive transfer experiments revealed that resistance to disease was intrinsic to the T cells and was due to a loss of T cell survival under conditions of chronic autoimmune stimulation. Importantly, the absence of Drak2 did not alter the survival of naive T cells, memory T cells, or T cells responding to an acute viral infection. These experiments reveal a distinction between the immune response to persistent self-encoded molecules and transiently present infectious agents. We present a model whereby T cell survival depends on a balance of TCR and costimulatory signals to explain how the absence of Drak2 affects autoimmune disease without generalized suppression of the immune system.
Intranasal deferoxamine improves performance in radial arm water maze, stabilizes HIF-1α, and phosphorylates GSK3β in P301L tau transgenic mice.

Deferoxamine (DFO), a metal chelator, has been previously reported to slow the loss of spatial memory in a mouse model of amyloid accumulation when delivered intranasally (IN). In this study, we determined whether IN DFO also has beneficial effects in the P301L mouse, which accumulates hyperphosphorylated tau. Mice were intranasally treated three times per week with either 10 % DFO (2.4 mg) or saline for 5 months, and a battery of behavioral tests were conducted before tissue collection and biochemical analyses of brain tissue with Western blot and ELISA. Wild-type (WT) mice statistically outperformed transgenic (TG) saline mice in the radial arm water maze, while performance of TG-DFO mice was not different than WT mice, suggesting improved performance in the radial arm water maze. Other behavioral changes were not evident. Beneficial changes in brain biochemistry were evident in DFO-treated mice for several proteins. The TG mice had significantly less pGSK3β and HIF-1α, with more interleukin-1β and total protein oxidation than wild-type controls, and for each protein, DFO treatment significantly reduced these differences. There was not a significant decrease in phosphorylated tau in brain tissue of DFO-treated mice at the sites we measured. These data suggest that IN DFO is a potential treatment not only for Alzheimer’s disease, but also for other neurodegenerative diseases and psychiatric disorders in which GSK3β and HIF-1α play a prominent role.
Diagnosis of multiple myeloma

Multiple myeloma (MM) is a neoplastic disorder characterized by the proliferation of a single clone of plasma cells derived from B cells in the bone marrow. Frequently, the myeloma invades adjacent bone, destroying skeletal structures and resulting in bone pain and fractures. Occasionally, plasma cells infiltrate multiple organs and produce other symptoms. The excessive production of a monoclonal (M) protein can lead to renal failure caused by Bence Jones proteinuria or hyperviscosity caused by excessive amounts of M protein in the blood. The diagnosis depends on the identification of abnormal monoclonal plasma cells in the bone marrow, M protein in the serum or urine, osteolytic lesions, and a clinical picture consistent with the diagnosis.
Leptin-resistant obese mice do not form biliary crystals on a high cholesterol diet.

Introduction: Human obesity is associated with leptin resistance, elevated serum lipids, hepatic steatosis, and cholesterol gallstone formation. We have previously demonstrated that leptin-resistant (Lepdb) obese mice fed a low cholesterol diet have enlarged gallbladders, but a decreased cholesterol saturation index, despite marked hepatic steatosis and elevated serum cholesterol. However, obese humans typically consume a high cholesterol diet and are prone to form gallstones. Therefore, we tested the hypothesis that on a high cholesterol diet, leptin-resistant obese mice would have large gallbladders, cholesterol saturated bile, and would readily form biliary crystals. Methods: Eight week old female lean control (C57BL/6J, n = 70) and leptin-resistant (Lepdb, n = 72) mice were fed a 1% cholesterol diet for four weeks. At 12 weeks, all animals were fasted overnight and underwent cholecystectomies. Gallbladder volume (μl) was measured and grouped into 7 lean control and 12 Lepdb pools for determination of cholesterol saturation index (CSI). Bile was examined for cholesterol crystals under polarized light microscopy (#/hpf). Serum cholesterol (mg/dl) and leptin levels (ng/ml) also were measured. Results were analyzed using the Student’s t-test. TABLE—ABSTRACT P57. GB vol CSI Crystals Serum XOL Leptin Lean 19.1 ± 0.9 1.15 ± .10 2.2 ± 0.5 131 ± 7 6 ± 0 Lepdb 35.8 ± 2.2∗ 0.91 ± .10† 0.0 ± 0.0∗ 278 ± 10∗ 229 ± 8∗ ∗ P < 0.001. † P < 0.03 vs C57b lean controls. Conclusions: These data suggest that leptin-resistant obese mice fed a high cholesterol diet have 1) increased gallbladder volume, 2) decreased biliary cholesterol saturation and crystal formation despite 3) elevated serum cholesterol compared to lean control mice. Therefore, we conclude that the link among obesity, diet, and gallstone formation does not require hypersecretion of biliary cholesterol and may be related to gallbladder stasis.
Developmental Aspects of Peritoneal Dialysis Kinetics in Dogs

To determine whether solute transfer during peritoneal dialysis is age related and to identify those factors which might explain age-related differences in dialysis kinetics, the peritoneal dialysance of [14C]urea (DU), [3H]inulin (DI), and the permeability index (DR = DI/DU) were examined in six puppies and five adult dogs. Exchange volume of lactated Ringer's (40 ml/kg) and exchange times (30 min) were identical in all studies. Theoretical calculations for urea dialysance for animals of differing body size were made. Assuming the existence of a similar functional peritoneal surface area per kg and the use of similar exchange volumes per kg and dwell times, theoretical values for the urea dialysance per kg for different sized animals were identical. The experimental studies demonstrated that DI per kg and DU per kg were higher in the puppies (0.146 +/- 0.023 and 0.765 +/- 0.054 ml/min kg; X +/- S.E.) than in the adult (0.052 +/- 0.01 and 0.462 +/- 0.05 ml/min/kg) (P less than 0.01). Also, DR was higher in the puppies (0.187 +/- 0.026), than in the adults (0.11 +/- 0.015) (P less than 0.05). The greater values for DI and DU per kg and DR in the young are best explained by the young having an increased peritoneal membrane permeability as well as an increase in functional peritoneal surface area relative to body weight. This increase in solute movement is independent of the dialysis mechanics used in an exchange and reflects age-related differences in the intrinsic characteristics of the peritoneal membrane.