cssi/SciSciGPT-SciSciNet huggingface dataset:
Molecular cloning and expression of two hexamerin cDNAs from the mosquito, Aedes aegypti.

Fourth-instar larvae of Aedes aegypti synthesize two types of hexamerins, Hexamerin-1 (AaHex-1) and Hexamerin-2 (AaHex-2), whose subunits are distinguished by different methionine and aromatic amino acid contents. In early female pupae only the methionine-rich AaHex-1γ subunit accumulates to two-fold higher levels than in males. To investigate the relationship between hexamerin structure and the roles of Hex-1 and Hex-2 during mosquito development and reproduction, we have cloned and sequenced cDNAs encoding the AaHex-2α, -2β and AaHex-1γ subunits. Comparison with other insect hexamerins revealed that the Aedes Hex-1 and Hex-2 proteins belong, respectively, to the two hexamerin subfamilies previously defined for brachyceran Diptera. Probes specific for the Hex-2α and Hex-1γ transcripts showed that expression of both genes follows the same developmental timetable. However, greater Hex-1γ mRNA accumulation may contribute to the higher levels of Hex-1γ protein in early female pupae.
The prevalence of transmitted HIV drug resistance among MSM in Anhui province, China

To optimize treatment regimens, we assessed human immunodeficiency virus (HIV) diversity and the prevalence of transmitted drug resistance (TDR) among men who have sex with men (MSM) in Anhui province, China. A total of 139 MSM who were newly diagnosed and antiretroviral treatment-naive were enrolled in Anhui in 2011. A partial pol fragment was amplified and sequenced, and HIV subtypes were determined by phylogenetic analyses. Surveillance/transmitted drug resistance mutations (SDRMs) were identified according to the 2009 World Health Organization (WHO) list. A total of 133 (95.7%) samples were successfully amplified and sequenced. Based on phylogenetic analyses of the pol fragment, CRF01_AE accounted for 55.6% (74/133) of the infections, followed by CRF07_BC with 32.3% (43/133), B with 5.3% (7/133), and unique recombinant forms with 6.8% (9/133). A total of 3.0% (4/133) of the subjects were found to harbor HIV variants with SDRMs, including 1.5% with NRTI-related mutations and 1.5% with NNRTI-related mutations. PI-related mutations were absent. The SDRMs included L210W (1.5%), Y181C (0.8%), and G190A (0.8%). In Anhui, CRF01_AE strains contributed to most of the HIV infections among MSM, and the prevalence of TDR was relatively low in this population. Further studies should be performed to evaluate the trend of TDR among MSM in Anhui and to inform first-line antiretroviral treatment.
Iron Deficiency and Marginal Vitamin A Deficiency Affect Growth, Hematological Indices and the Regulation of Iron Metabolism Genes in Rats

Iron deficiency and marginal vitamin A (VA) deficiency frequently coexist and affect billions of people, mostly children and women, worldwide. The effects of these micronutrient deficiencies alone and in combination on hematologic, biochemical and molecular indices of iron and VA status were investigated in a 2 x 2 randomized blocked study conducted in growing male Sprague-Dawley rats. From 3-8 wk of age, rats were fed one of four purified diets that were either adequate or restricted in iron (Fe) and adequate or marginal in VA: (+)Fe(+)VA, 20.3 and 0.367 micro g/g, respectively, denoted control diet; (-)Fe(+)VA, 3.34 and 0.405 micro g/g; (+)FeVA(m), 22.2 and 0.051 micro g/g; or (-)FeVA(m), 3.03 and 0.055 micro g/g. Weight-matched rats fed adequate micronutrients were included to control for possible confounding effects of Fe deficiency on growth and feed efficiency. Iron restriction reduced (P < 0.05) weight gain, feed efficiency, blood hemoglobin and hematocrit. Plasma and liver iron and plasma transferrin saturation were reduced by approximately 50%, whereas liver transferrin mRNA and protein and transferrin receptor mRNA were elevated, as was liver ferritin light-chain protein and light-chain mRNA. Liver heavy-chain ferritin mRNA, hemopexin, ceruloplasmin and cellular retinol-binding protein mRNA were not affected by iron or VA restriction. Although marginal VA deficiency did not exacerbate indices of poor iron status during iron deficiency, iron deficiency was associated with lower plasma retinol and elevated liver VA concentrations. These results are consistent with an impaired mobilization of liver retinol during iron deficiency as well as multiple alterations in iron metabolism.
Spectroscopic and potentiometric studies of the interaction of adenine with trivalent metal ions

Potentiometric titration was used to determine the potentiometric diagrams of complexes of adenine with Al3+, Cr3+, and Fe3+. IR and Raman spectra of solids show that the interaction of adenine with Cr3+ is not as strong as the other metals. Fe3+ binds to adenine at low and medium pH values at an Fe3+–adenine ratio of 6, while Al3+ binds to adenine at all pH values at an Al3+–adenine ratio of 8. The IR band associated with N-9–H is split into two components at high and low wavenumbers; IR band splitting has been observed for groups with a large dipole moment such as carbonyl and phosphate. To the best of our knowledge, this is the first time to see the splitting of IR bands involving a nitrogen. We also obtained potentiometric titration plots for adenine with Al3+, Cr3+, and Fe3+, independently, in various molar ratios which showed an interaction with adenine, consistent with the IR and Raman findings. Metal–adenine-hydroxo complexes were formed.
Diabatic Electron-Ion Recombination in a Polar Solvent

Electron transfer, such as occurs between ions in solution or between an ion and an electrode, is one of the most fundamental processes in Chemistry. Recent advances in theoryl,2 and simulation techniques3–12 now make it possible to study different aspects of the behavior of electrons in polar fluids. In the near future, it may even prove possible to study electron transfer processes via simulation techniques. However, for the present we focus on a slightly simpler problem which will serve as a prototypic example of electron transfer: the transfer of an electron from its solvated state to an ion, in solution. We have chosen to study first the recombination reaction between a solvated electron and a lithium ion solvated in liquid ammonia. It is now a relatively routine matter to use classical simulation techniques to examine ionic solvation in polar fluids. Thus, the study of a lithium ion in liquid ammonia presents few problems or challenges other than deciding on the potential models for use in the Monte Carlo or molecular dynamics calculation.® In the case of the electron, the Feynman path integral formulation of quantum statistical mechanics enables us to not only treat the electron quantum mechanically but also to treat the classical ion (Li+) and the solvent molecules (ammonia) on an equal footing.6
Abrasion Studies of Sized Cotton Yarns Before and After Weaving

Cotton warp yams treated with various sizing formulations were subjected to weaving trials. Warp yams extracted from the greige fabrics (woven yarns) and those from their antecedent loom beams (feed yarns) were subjected to abrasion resistance mea surements with the Zweigle yam abrader and TRI's multistation cyclic tensile abrader (CTA), as well as to tensile measurements of breaking force. CTA abrasion resistance values were much more sensitive to differences in size treatments than Zweigle values, and there were significant differences in the rankings by the two methods. In general, correlations were good between weaving performance and CTA values for both feed and woven yams and Zweigle values for feed yams only. A statistical analysis was developed for finding the fraction of "most vulnerable" yam specimens for each sample. Using CTA data, this fraction showed good correlation with weaving performance for both feed and woven yams. Using CTA measure ents of the abrasion resistance of warp yams from gre...
Conventional and glyphosate-resistant maize yields across plant densities in single- and twin-row configurations

Maize (Zea mays L.) produced in narrow rows can increase yields and accelerate canopy closure. Costly equipment modifications make narrow rows impractical, but a twin-row configuration may boost production with fewer equipment modifications. Four field experiments were conducted to measure weed biomass, leaf area index (LAI), and yield for a conventional (CN) and a glyphosate-resistant (GR) hybrid across three plant densities (low 4.0–4.4 plants m −2 ; medium 5.9–6.4 plants m −2 ; and high 7.9–8.4 plants m −2 ) and two row configurations (single vs. twin) in a conservation tillage system during the 2005 growing season. The experimental design was a split–split plot with a RCB arrangement of whole plots where hybrids were assigned to main plots, row configurations to subplots, and plant density to sub-subplots with four replications. Row configuration had little effect on weed biomass compared to plant density and hybrid. Leaf area index increased with higher plant density at all locations. In general, LAI increased with the twin-row configuration, but LAI also varied with hybrid based on interactions between hybrid and plant density or row configuration. Row configuration had little impact on maize yields, while plant density had the most effect on yields. Plant density also interacted with hybrid or row configuration at multiple locations, although maize yields did not always increase with higher plant density. Conventional hybrids may also provide an alternative to GR hybrids, particularly at lower plant densities. Maize yield increases with twin rows were minimal and may not justify twin row conversion under dryland conditions, but growers that already utilize twin-row equipment will not suffer yield decreases by planting twin rows. Published by Elsevier B.V.
Reaction to the Major Contribution: Training for Skills Competency in Counseling Psychology: Integrating Models

The authors of the Major Contribution have developed a complex and elegant three-level training model on which they suggest advanced microskills may be built. Prior to the description of their model, they have built a case that current microskills training has proved foundationally important but insufficient to training needs. They then invite colleagues to evaluate their model for viability and utility.This reaction suggests that the model could be enriched by incorporating survey data regarding how doctoral programs are currently teaching advanced psychotherapy/counseling skills, outcome data from common factors and master therapists’ research, and the APA Competency Benchmarks work. In addition, the contribution contains a detailed, very useful teaching application, and some similarly detailed research suggestions would be helpful to encourage research on the model.
Rapid adaptation of cardiac ryanodine receptors: modulation by Mg2+ and phosphorylation

Channel adaptation is a fundamental feature of sarcoplasmic reticulum calcium release channels (called ryanodine receptors, RyRs). It permits successive increases in the intracellular concentration of calcium (Ca2+) to repeatedly but transiently activate channels. Adaptation of RyRs in the absence of magnesium (Mg2+) and adenosine triphosphate is an extremely slow process (taking seconds). Photorelease of Ca2+ from nitrophenyl-EGTA, a photolabile Ca2+ chelator, demonstrated that RyR adaptation is rapid (milliseconds) in canine heart muscle when physiological Mg2+ concentrations are present. Phosphorylation of the RyR by protein kinase A increased the responsiveness of the channel to Ca2+ and accelerated the kinetics of adaptation. These properties of the RyR from heart may also be relevant to other cells in which multiple agonist-dependent triggering events regulate cellular functions.
Performance-driven constructive placement

A new approach to the performance-driven placement based on a window concept is presented. We first convert timing constraints to geometric shapes using the defined windows. A window represents a region in which all the modules along a given path can be placed without degrading the circuit performance. Then a constructive placement process uses the window information to select an unplaced module, and to find an appropriate position for the module. This approach represents a unified way to consider both timing and geometric constraints during the placement process. The experimental results show that the improvement of circuit performance can be achieved by the sufficient use of the window information.
IMPLICACIONES PARA EL ESTUDIO DE LA NEUROBIOLOGÍA DE LA EXPERIENCIA CONSCIENTE. EL ACTO IMPULSIVO

Conciencia e impulsividad son dos constructos multidimensionales relacionados con el control del pensamiento y comportamiento humano. Impulsividad es un rasgo de personalidad complejo caracterizado por una elevada tendencia a actuar sin pensar, incapacidad para planear actividades futuras y disminucion de la capacidad de concentracion. Conciencia por su parte, es un constructo que cobija una serie de procesos fisiologicos relacionados con la generacion de experiencia conciente y la adquisicion de conocimientos. Con respecto al control sobre la accion humana, conciencia e impulsividad parece estar relacionados con comportamientos opuestos. Historicamente, los esfuerzos realizados por diversas disciplinas con el fin de estudiar estos constructos han llevado al desarrollo de definiciones divergentes y a una serie de medidas, causando una mayor confusion. Los propositos de este articulo son: 1) describir ejemplos de posibles soluciones al estado de confusion en el campo de la investigacion sobre impulsividad y discutir como el estudio de la conciencia puede beneficiarse de la investigacion de la impulsividad; 2) discutir algunas de las maneras utilizadas para medir impulsividad en el laboratorio y como hacer de estos constructos variables experimentales; 3) resumir algunas de las lecciones derivadas de la comparacion de los actos impulsivos con los premeditados desde una perspectiva integral y multidimensional; 4) discutir las implicaciones derivadas del uso de un enfoque multidimensional para el estudio de la conciencia.
Molecular cloning and characterization of a Leishmania donovani alpha-tubulin gene.

We have isolated a cDNA for an α-tubulin mRNA from L. donovani promastigotes and determined its complete nucleotide sequence. Both nucleotide and deduced amino acid sequence analysis of this cDNA showed significant similarity with a previously reported, partial sequence of an L. enriettii α-tubulin and the complete sequence of human α-tubulin. Further, the in vitro translated L. donovani α-tubulin gene product was specifically immunoprecipitated with a monoclonal antibody against human α-tubulin. Northern blot analysis revealed that there was little change in the expression of the L. donovani α-tubulin RNA during parasite differentiation from promastigote to the in vitro grown amastigote form. Southern blot analysis revealed a simple genomic organization for the L. donovani α-tubulin gene with more than one copy of the α-tubulin gene in the parasite genome. To our knowledge, this is the first complete sequence of an α-tubulin for Leishmania to be reported in the literature.
Use of chatroom abbreviations and shorthand symbols in pen computing

This paper describes an efficient system for entering data into a pen-enabled computer, particularly handheld devices. While keyboard input typically is faster than handwriting input, this is not true for the small PDA interfaces. For this reason, we designed and developed a prototype that uses chatroom abbreviations and shorthand symbols to increase the speed of data entry for these devices. This system was also developed as a prototype system that would enable persons with speech impairments to rapidly convert hand-drawn symbols on a pen-enabled device into speech output. We created a library of chatroom abbreviations and shorthand symbols, and developed a k-nn classification system to recognize the symbols. Experimental results show the effectiveness of the system in terms of speed and accuracy.
Parallel Auditory Pathways: I — Structure and Connections

The remarkable hypertrophy of the central auditory pathways in microchiropteran bats was recognized long before the bionsonar system of these animals was discovered. Some of the first experimental studies of the auditory pathways were conducted using the echolocating bat Rhinolophus (Poljak, 1926). In this historical context, it seems a paradox that after the discovery of echolocation, studies of the connections of central auditory pathways lagged far behind physiological and behavioral studies. It was not until the last sonar conference that the first studies to use modern neuroanatomical techniques were reported (Schweizer,1980; Zook and Casseday,1980).
Taking stock of blocks: Promises and challenges of blocks programming languages

Blocks programming environments (e.g., Scratch, Blockly, App Inventor, Snap!, Pencil Code, Alice/Looking Glass, AgentSheets/AgentCubes) represent program syntax trees as compositions of visual blocks. Through activities like Code.org's Hour of Code, these languages have become extremely popular ways to introduce programming and computational thinking to tens of millions of people of all ages and backgrounds, from grade-schoolers to President Obama. Proponents of blocks languages claim that blocks languages lower barriers to programming and enhance learning, while detractors complain that they are not particularly visual and are just toy languages from which it is difficult to transition to “real” text-based programming.
Intravenous (i.v.) busulfan (Bu) plus melphalan (Mel) is a well-tolerated preparative regimen for stem cell transplantation (SCT) in patients (pts) with advanced lymphoid malignancies

6548 Background: High dose chemotherapy and SCT is an accepted treatment option for pts with relapsed lymphoid malignancies. However, relapse remains a significant problem. A double alkylating regi...
Introduction: Origin and Evolution of the Sierra Nevada and Walker Lane

This Geosphere themed issue is an outgrowth of our Penrose Conference: Origin and Uplift of the Sierra Nevada, California , which was held in Bridgeport, California, August 16–20, 2010. The theme is here expanded to include the Walker Lane ([Fig. 1][1]), since a large number of our Penrose
339 ACTIVATION OF SRC FAMILY TYROSINE KINASES AND PHOSPHORYLATION OF VAV1 DOWNSTREAM FROM MYD88 AND TRAF6 IN MURINE MACROPHAGES.

Background We and others have reported that exposure of macrophages to LPS, CpG DNA, and other Toll-like receptor (TLR) ligands triggers the activation of multiple src family tyrosine kinases (SFKs) and the subsequent phosphorylation of vav1. However, the mechanism(s) leading to the activation of SFKs downstream from TLRs are unknown. Purpose We sought to determine whether SFK activation and vav1 phosphorylation occur downstream from two key signaling intermediates in the TLR cascade, MyD88 and TRAF6. Methods We used two subclones of RAW 264.7 murine macrophages that have been engineered to express forms of MyD88 and TRAF6, respectively, that can be activated upon addition of the antibiotic coumermycin, leading to the production of inflammatory mediators, including tumor necrosis factor (TNF). Selective inhibitors of SFKs (PP1, PP2, SU6656) were used to test the involvement of these kinases in stimulation of TNF secretion downstream from MyD88 and TRAF6. Finally, we used immunoblotting to detect phosphorylation of vav1 on tyrosine 174 (an event known to be mediated by SFKs). Results TLR-ligand-independent activation of either MyD88 or TRAF6 led to robust TNF secretion in these RAW subclones. Preincubation with any of the three SFK inhibitors resulted in dramatic reductions in the magnitude of TNF secretion by these cells (75-85% less in response to MyD88 activation; 50-60% less in response to TRAF6 activation). Finally, the tyrosine phosphorylation of vav1 on tyrosine 174 was detected within 10 to 20 minutes of coumermycin-induced activation of either MyD88 or TRAF6. Conclusions Our data indicate that one or more SFKs are activated downstream from the TLR signaling cascade components MyD88 and TRAF6 in macrophages, leading to the phosphorylation of vav1 and playing an important role in the up-regulation of TNF production.
Improvement and analysis of routine detection method for hand,foot and mouth disease

Objective To designe and use new primers in the detection of pan-enterovirus(PE),coxsackievirus A16(CVA16) and enterovirus 71(EV71) for the diagnosis of hand,food and mouth disease(HFMD) using both reverse transcription-PCR(RT-PCR) and real-time RT-PCR.Methods Both RT-PCR and real-time RT-PCR were performed for the detection of PE,CVA16 and EV71 in 100 stool specimens from cases of HFMD and 50 normal control samples.The primers were refined to reexamine CVA16 in RT-PCR.The specificity of primers was checked with Basic Local Aligment Search Tool(BLAST) of National Center and analyzed with Primer Premier 6.0 and Oligo 6.62.Results The positive rates of the samples were 36%,33%,71% and 20%,27%,64% for CVA16,EV71 and PE with real-time RT-PCR and RT-PCR assays,respectively.Except CVA16,no significant difference was found in the detection rates of PE or EV71 between the two methods.The utilization of refined primers in RT-PCR could significantly increase the positive rate for CVA16 up to 35%(P0.05),and the coincidence rate with clinic diagnosis increased by 10%,which was close to that of real-time RT-PCR assay.There were no significant differences between the two methods in specificity,misdiagnosis rate and missed diagnosis rate.Conclusion Routine RT-PCR method has a low sensitivity in detectoin of CVA16 and the detection rate could be increased to the level of real-time RT-PCR with newly designed primers.
Attrition rates of pediatric emergency medicine fellowship graduates.

Objectives To identify the percentage of alumni of one Pediatric Emergency Medicine (PEM) fellowship program who consider themselves to still practice in the field. Methods A brief survey (5 questions) was sent to all physicians who began the PEM fellowship program at the University of Alabama at Birmingham between the years 1986 and 2006. Survey included demographics, length of time out of fellowship, present work location, and whether the respondent considered themselves to be in the field of pediatric emergency medicine. Results Forty-three physicians were identified as beginning fellowship between 1986 and 2006. One physician was excluded as she was deceased. Forty (95%) of the 42 individuals graduated from a PEM fellowship program. Analyzing the 39 responding PEM graduates, 29 (74%) consider themselves practicing pediatric emergency medicine. Six (60%) of those not considered practicing in PEM (n = 10) are women. Four of these 10 individuals are still in academic medicine. Overall attrition rate for this cohort of PEM fellowship-trained physicians is 25.6% (95% confidence interval, 13.0-42.1). Conclusion Overall attrition rates of fellowship-trained PEM physicians seems to mirror that of adult trained counterparts.
3.13 – Short-Term and Working Memory Systems

Working memory refers to the temporary retention of information that has just arrived to the senses or been retrieved from long-term memory. Although internal representations of external stimuli have a natural tendency to decay, they can be kept ‘in mind’ through the action of maintenance or rehearsal strategies and can be subjected to various operations that manipulate information in the service of ongoing behavior. Empirical studies of working memory using the tools of neuroscience, such as electrophysiological recordings in monkeys and functional neuroimaging in humans, have advanced our knowledge of the underlying neural mechanisms of working memory.
Plexin C1 deficiency permits synaptotagmin 7–mediated macrophage migration and enhances mammalian lung fibrosis

Pulmonary fibrosis is a progressive and often fatal condition that is believed to be partially orchestrated by macrophages. Mechanisms that control migration of these cells into and within the lung remain undefined. We evaluated the contributions of the semaphorin receptor, plexin C1 (PLXNC1), and the exocytic calcium sensor, synaptotagmin 7 (Syt7), in these processes. We evaluated the role of PLXNC1 in macrophage migration by using Boyden chambers and scratch tests, characterized its contribution to experimentally induced lung fibrosis in mice, and defined the mechanism for our observations. Our findings reveal that relative to control participants, patients with idiopathic pulmonary fibrosis demonstrate excessive monocyte migration and underexpression of PLXNC1 in the lungs and circulation, a finding that is recapitulated in the setting of scleroderma-related interstitial lung disease. Relative to wild type, PLXNC1-/- mouse macrophages are excessively migratory, and PLXNC1-/- mice show exacerbated collagen accumulation in response to either inhaled bleomycin or inducible lung targeted TGF-β1 overexpression. These findings are ameliorated by replacement of PLXNC1 on bone marrow-derived cells or by genetic deletion of Syt7. These data demonstrate the previously unrecognized observation that PLXNC1 deficiency permits Syt7-mediated macrophage migration and enhances mammalian lung fibrosis.-Peng, X., Moore, M., Mathur, A., Zhou, Y., Sun, H., Gan, Y., Herazo-Maya, J. D., Kaminski, N., Hu, X., Pan, H., Ryu, C., Osafo-Addo, A., Homer, R. J., Feghali-Bostwick, C., Fares, W. H., Gulati, M., Hu, B., Lee, C.-G., Elias, J. A., Herzog, E. L. Plexin C1 deficiency permits synaptotagmin 7-mediated macrophage migration and enhances mammalian lung fibrosis.
Blood CD34 Count in Myelofibrosis with Myeloid Metaplasia: A Prospective Evaluation of Prognostic Value in 94 Patients.

Abstract Background: Previously established adverse prognostic factors in myelofibrosis with myeloid metaplasia (MMM) include anemia (hemoglobin Methods: A concurrent evaluation of PB CD34 count, bone marrow histology, and other clinical and laboratory parameters was conducted in a consecutive cohort of both newly and previously diagnosed patients with MMM. The study patients were prospectively followed for a minimum of 3 years in order to determine the prognostic value of PB CD34 count on survival, leukemic transformation, and disease progression from the time of PB CD34 analysis. Results: i. Patient cohort: A total of 94 patients (median age 61 years, range 26–81; 61 males) were accrued between January 2000 and August 2001 and subsequently followed through July 2004. MMM subtypes included agnogenic myeloid metaplasia (AMM; 58 patients), post-polycythemic myeloid metaplasia (PPMM; 12 patients), post-thrombocythemic myeloid metaplasia (PTMM; 12 patients), cellular phase MMM (8 patients) and hypocellular variant MMM (4 patients). At the time of study entry, 19 patients (20%) were newly diagnosed and 75 were established cases (median of 36 months from initial diagnosis, range 4–221). The Dupriez prognostic scores were 0 in 37 (39%), 1 in 37 (39%), and 2 in 20 patients (21%). ii) Clinical correlates of PB CD34 count: The median PB CD34 count for the entire study cohort was 54.7 x 106/L (range 0–5345) with 85% patients having increased values (> 5 x 106/L). Cellular phase MMM and PPMM had significantly lower PB CD34 counts compared to the other MMM subtypes. On univariate analysis, PB CD34 count significantly correlated with Dupriez prognostic score, leukocyte count, circulating blast or immature myeloid cell percentage, and presence of hypercatabolic symptoms but not with age, gender, anemia (hemoglobin iii) Prognostic evaluation of PB CD34 count : As of July 16, 2004, 43 patients (46%) have died and median duration of follow up in the surviving patients was 41 months (range 36–54). The projected overall survival at 5 years was 50%. On Cox proportional regression analysis, individual variables that correlated with inferior survival included anemia (hemoglobin Conclusion: PB CD34 count is often but not always increased in MMM and correlates significantly with leukocytosis and degree of PB myeloid immaturity. The current prospective study does not support an independent prognostic value for PB CD34 count in MMM.
Detection, Comprehensive Analysis and Clinical Validation of Chromosomal Aberrations by Multiplex Ligation-Dependent Probe Amplification In Chronic Lymphocytic Leukemia

Abstract Abstract 2716 Background: Current strategies based on karyotyping or fluorescent in situ hybridization (FISH) for detection of chromosomal abnormalities in chronic lymphocytic leukemia (CLL) are laborious, time-consuming, and costly and have limitations in resolution. Multiplex ligation-dependent probe amplification (MLPA) can simultaneously detect copy number changes of multiple loci in a single PCR, making it an attractive alternative. We developed and validated an MLPA protocol for comprehensive, automated data analysis and interpretation of chromosome abnormalities associated with CLL. Patients and Methods: Reference ranges for individual MLPA probes were established from a group of 50 healthy control subjects. Using these ranges we built an automated spreadsheet-based analysis system that includes multiple quality checks; samples that fail these checks are flagged and not reported. Each target was given a call of “deletion,” “normal,” or “amplification,” depending on whether the normalized ratio fell within or outside of the established normal range (mean ± 2SD or mean ± 3SD). After establishing the normal references ranges for each probe, we used the MLPA assay to characterize chromosome abnormalities in blood samples from 100 patients with suspected CLL that had been previously tested with FISH. Results: The maximum normal ranges were distributed between 0.82 and 1.18 for the mean ± 2SD values (ie, 95% CI, P = 0.05), and between 0.73 and 1.27 for the mean ± 3SD values (ie, 99.7% CI, P = 0.01). MLPA showed good concordance with FISH results in the 100 clinically suspected CLL cases. In 6 of these cases, abnormalities detected by MLPA were in regions not covered by FISH, including additional copy number gains on chromosomes 18q21.1 and 19, and novel micro-deletions at 19q13.43 and 19p13.2 loci. Excluding these cases, MLPA showed 94% sensitivity, 94% concordance, and 93% specificity relative to FISH. MLPA detected abnormalities in 3 FISH-negative cases and failed to detect abnormalities in three 13q- cases with low percentages of leukemic cells (7%, 12% and 19%). The limit of detection of the CLL MLPA assay was about 20% leukemic clones. Conclusions: This MLPA-based assay for chromosome abnormalities in CLL showed excellent concordance with FISH. This multiplex assay represents a fast (roughly 2–3 days total process to report time vs 7–10 days for FISH), high-throughput, accurate, and user-friendly process for that has potential for use as a first-line screening test for detection of chromosome abnormalities associated with CLL in the clinical laboratory. Disclosures: No relevant conflicts of interest to declare.
Where Have All The Teachers Gone

During my three short years serving as principal of a small elementary school, I have often discovered new areas in which I need to improve my knowledege level, skills, and performance.
Thermal Imaging for the Analysis of Energy Balance During Crack Propagation

Earlier [1] we described an experimental procedure aimed at examining the spatial and temporal distribution of energy dissipation during crack initiation and propagation in a ductile polymer. The experiment combines a table-top tensile tester and an infrared imaging system. Because of the intense heating of the crack tip region, direct observation of the temperature rise not only provides an accurate measurement of the position of the crack tip, and thus the propagation velocity, but also much information for the analysis of plastic deformation, energy conversion, and evaluation of thermal properties of polymer materials. In the present paper, we will present an analysis of the energy balance in such measurements.
Symptom reduction and termination: client change and therapist identified reasons for saying goodbye

AbstractEmpirical efforts have focused on predicting whether or not clients prematurely terminate therapy, with nonattendance of last session equated to premature termination. However, this fails t...
Pregnant Women and Cervical Cancer: Balancing Best Interest of Mother and Fetus

An examination of how a doctor should counsel a pregnant woman through the ethical and medical challenges of being diagnosed with stage II cervical cancer. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.
Prions and endotoxins: reprocessing strategies for reusable medical devices

Abstract: The apparent high level of resistance of Creutzfeldt-Jakob disease (CJD) and variant Creutzfeldt-Jakob disease (vCJD) prions to inactivation by conventional means of device reprocessing poses an infection prevention challenge to a hospital’s central sterilization department. This chapter will focus on prion inactivation methods for instrument reprocessing that are currently recommended by public health agencies for the prevention of iatrogenic transmissible spongiform encephalopathy (TSE) transmission. Important factors such as cleaning/ decontamination efficacy and steel quality are discussed. Research continues to evaluate the potential use of alternative sterilizing agents and methods for prion inactivation. Additionally, the reprocessing strategies for the removal or inactivation of bacterial endotoxin are discussed briefly.
More Supply, More Demand: The Changing Nature of Campaign Financing for Presidential Primary Candidates

Financing a presidential party nomination campaign has been a complicated affair for some time: candidates face contribution limits, source limitations, extensive reporting requirements, and, for those candidates opting into the voluntary public financing program, a strict spending limit. Moreover, the campaign financing system is not only complex but dynamic. The system recently has undergone two fundamental changes: (1) the voluntary public financing system, with its accompanying strict spending limit, is no longer an option for serious presidential candidates, who would be grossly outspent by nonparticipating rivals; and (2), the campaigns have come to rely ever more upon campaign finance bundlers, who collect maximum contributions (currently set at $2,300) from friends and associates, and upon "micro-donors," who give less than $200 in the aggregate to a primary campaign. These changes arose because of the changing legal rules governing money in presidential elections and a dramatic lowering of the costs of campaigning facilitated by the Internet. They may alter both the nature of presidential campaigns as well as the types of candidates who are viable to become general election candidates. This paper has three parts. First, it describes the two recently-emerging fundamental changes in the campaign financing system for presidential primary candidates. Second, it explains why these changes have emerged now. Finally, it evaluates whether these changes are likely to be positive or negative from the standpoint of political equality and in terms of the quality and type of presidential candidates who win their parties' nominations.
Mineralogical Investigation of an Enterolith from a Grant's Zebra

An enterolith surgically removed from a Grant's zebra was investigated by standard mineralogical techniques including X-ray diffraction, scanning electron microscopy and electron microprobe analysis. It was predominantly composed of a suite of phosphate minerals which have precipitated on and between aggregates of undigested plant material. It was apparently cored by a small nidus of granitic rock which served as a site for heterogeneous nucleation for the larger phosphatic overgrowth. Phosphate was deposited by at least two distinct mechanisms. In the enterolith's core, phosphate minerals replaced or rimmed silicate grains (e.g. feldspars and quartz) which are relics of the disaggregated granitic nidus. As the enterolith subsequently accreted outwards from the nidus, struvite was precipitated directly onto fibres of plant material, or within the pore spaces between them. The generally fine grain size of struvite in enteroliths, relative to that in urinary calculi, may be due to the ubiquitous presence of the undigested plant fibres. Struvite, close to (NH3)0.9K0.1MgPO4 · 6H2O in composition, is the only phosphate mineral in the outer portions of the enterolith. Within the enterolith's interior, struvite occurs subequally with Mg-vivianite, close to Mg2.9Fe0.1(PO4)2 · 8H2O in composition. Textural relations suggest that the mineralogical transformation of struvite to Mg-vivianite is a consequence of diagenesis, presumably related to a decrease in pH and/or (NH4)+ activity, within the core of the enterolith. If enterolith growth is mediated by the accumulation of a particular form of undigested plant fibre (e.g. lucerne hay), the identification and dietary removal of this material may prevent or at least impede the development of enteroliths.
Novel stem cell and gene therapy in diabetic retinopathy, age related macular degeneration, and retinitis pigmentosa

Degenerative retinal disease leads to significant visual morbidity worldwide. Diabetic retinopathy and macular degeneration are leading causes of blindness in the developed world. While current therapies for these diseases slow disease progression, stem cell and gene therapy may also reverse the effects of these, and other, degenerative retinal conditions. Novel therapies being investigated include the use of various types of stem cells in the regeneration of atrophic or damaged retinal tissue, the prolonged administration of neurotrophic factors and/or drug delivery, immunomodulation, as well as the replacement of mutant genes, and immunomodulation through viral vector delivery. This review will update the reader on aspects of stem cell and gene therapy in diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa and other less common inherited retinal dystrophies. These therapies include the use of adeno-associated viral vector-based therapies for treatment of various types of retinitis pigmentosa and dry age-related macular degeneration. Other potential therapies reviewed include the use of mesenchymal stem cells in local immunomodulation, and the use of stem cells in generating structures like three-dimensional retinal sheets for transplantation into degenerative retinas. Finally, aspects of stem cell and gene therapy in diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, and other less common inherited retinal dystrophies will be reviewed.
Extensive Transcriptional and Translational Regulation Occur During the Maturation of Malaria Parasite Sporozoites

Abstract Plasmodium sporozoites are transmitted from an infected mosquito to mammals in which they infect the liver. The infectivity profile of sporozoites changes as they egress from oocysts on the mosquito midgut into the hemocoel, and then invade the salivary glands, where they maintain a poised and infectious state until transmission occurs. Upon transmission, the sporozoite must then navigate the host skin, vasculature, and liver. All of these feats require distinct repertoires of proteins and capabilities that are coordinated in an appropriate temporal manner. Here, we report the comprehensive and dynamic transcriptomes and proteomes of both oocyst sporozoite and salivary gland sporozoite stages in both rodent-infectious Plasmodium yoelii parasites and human-infectious Plasmodium falciparum parasites. These data robustly define mRNAs and proteins that are Upregulated in Oocyst Sporozoites (UOS) or Upregulated in Infectious Sporozoites (UIS), which include critical gene products for sporozoite functions, as well as many of unknown importance that are similarly regulated. Moreover, we found that Plasmodium uses two overlapping, extensive, and independent programs of translational repression across sporozoite maturation to temporally regulate specific genes necessary to successfully navigate the mosquito vector and mammalian host environments. Finally, gene-specific validation experiments of selected, translationally repressed transcripts in P. yoelii confirmed the interpretations of the global transcriptomic and proteomic datasets. Together, these data indicate that two waves of translational repression are implemented and relieved at different times in sporozoite maturation to promote its successful life cycle progression.
Progress of supercritical fluid technology in polymerization and its applications in biomedical engineering

Abstract Supercritical fluid technology has emerged as a cost-effective and low-hazard alternative to solvent-based methodologies in polymer synthesis, pharmaceutical science, and related biomedical applications. In this review, we first briefly describe the distinctive features of a supercritical fluid, biodegradable polyesters, and lipases. We will then cover the latest progress of supercritical fluid technology in polymerization. Lipase-catalyzed polymerization in supercritical carbon dioxide (SC−CO2) will be the focus of the synthesis section. The last section presents the biomedical applications employing SC−CO2 polymerization, including microcapsule formation for drug delivery, microcellular scaffold fabrication, and SC−CO2-assisted processes for polymer-based treatments, such as surface functionalization, aerogel formation, and fine particle formation. Each topic is illustrated with the most successful examples. Understanding the current progress in SC−CO2 polymerization is an essential step to facilitate the exploration with this green technology in new research frontiers.
An Analysis of SARS-CoV-2 Using ViReport

Author(s): Song, Miranda; Moshiri, Niema | Abstract: The ongoing outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in millions of cases and hundreds of thousands of deaths. Given the current lack of treatments or vaccines available, it may be useful to trace the evolu-tion and spread of the virus to better develop methods of preventative intervention. In this study, we analyzed over 4,000 full genome sequences of human SARS-CoV-2 using novel tool ViReport [13], an automated workflow for performing phylogenetic analyses on viral sequences and generating comprehensive molecular epidemiologi-cal reports. The complete ViReport output can be found at https://github.com/mirandajsong/ViReport-SARS-CoV-2 .
Protein Requirements during Hypocaloric Nutrition for the Older Patient With Critical Illness and Obesity: An Approach to Clinical Practice

Current guidelines recommend a hypocaloric, high protein nutrition regimen for patients with obesity and critical illness. The impact of advancing age presents with unique challenges in which a greater protein intake is required to overcome the anabolic resistance associated with aging in the face of presumed decreased renal function. The primary objective of this review is to provide an overview of the impact of obesity and advancing age on protein requirements for patients with critical illness and review the scientific evidence supporting the rationale for hypocaloric, high protein nutrition for this subpopulation, as well as provide some practical suggestions for their clinical management.
Differences in the sugar content of fast-food products across three countries

Objective: To compare the sugar content of items at four multinational fast-food chains, across three countries. Design: Total sugar (g)/per serving was extracted from online nutrition information, and sugar/100 g serving was calculated. Foods were categorised as: breakfast sandwiches, burgers, sandwiches, desserts and condiments. Beverages were categorised as fountain, frozen or pre-packaged. Sugar (g) was compared across countries using linear mixed-effects models. Pairwise comparisons were performed with Tukey–Kramer adjustments. Setting: USA, Germany and Australia. Participants: Burger King™ (Hungry Jack’s™), Kentucky Fried Chicken™, McDonald’s™ and Subway™. Results: Differences in total sugar/100 g or ml were observed across countries for burgers (n 104), desserts (n 110), sandwiches (n 178), pre-packaged beverages (n 36) and frozen beverages (n 72). Comparing identical items across countries (e.g. BigMacTM from McDonalds in USA, Germany and Australia), burgers (n 10 available in all three countries) had lower sugar content in Australia (3·4 g/100 g) compared with the USA (4·7 g/100 g, P = 0·02) or Germany (4·6 g/100 g, P = 0·04), yet no differences were observed in other food categories. Comparing the same beverages across countries (e.g. chocolate shake from Burger King), frozen beverages (n 4 available in all three countries) had lower sugar content in Australia (14·2 g/100 ml), compared with the USA (20·3 g/100 ml, P = 0·0005) or Germany (17·8 g/100 ml, P = 0·0148), yet no differences were observed in other beverage categories. Conclusions: Heterogeneity in fast-food sugar content across countries suggests that reductions are possible and should be implemented to reduce health risks associated with excess added sugar intake.
What Does Stock and Accounting Performance Tell Us About Outsourcing

We investigate a large sample of US domestic outsourcing transactions from 1990 to 2003. We construct a data set that identifies the outsourcing client and vendor firms and use this data set to examine announcement effects on firm values and the post-event changes in accounting performance measures. We find that around the contract announcement date, vendor firms experience significantly positive abnormal returns; while in the long-run client firms realize significantly positive buy-and-hold abnormal returns. We also find evidence that our client firms experience significant improvement in operating efficiency for each of the three years following the contract taking effect. This change in operating efficiency is significantly positively related to the client firm's long-run abnormal stock returns. Our findings suggest that outsourcing contracts are beneficial to contract signatories, and the stock market recognizes this benefit. To our knowledge, this is the first study to investigate US domestic outsourcing contracts from the financial market and accounting performance perspectives.
Fluorescence Resonant Energy Transfer-Based Quantum Dot Sensor for the Detection of Calcium Ions

A simple optical aptasensor has been synthesized for the detection of calcium ions. This sensing approach employs a semiconductor quantum dot (QD) – gold nanoparticle as the donor – quencher pair and operates on the principle of fluorescence resonant energy transfer (FRET). On binding with calcium ions, the DNA aptamer undergoes a conformational change, which changes the distance between the quantum dot and the gold nanoparticle, conjugated on the 5’ terminal and 3’ terminal of the aptamer respectively. This phenomenon results in the quenching of the quantum dot emission. In this sensor, a maximum quenching of 22.42 ± 0.71 % has been achieved at 35 nM calcium ion concentration while the limit of detection has been determined to be 3.77 pM. The sensor has been found to have high specificity for calcium ions in comparison to other metal ions like sodium, magnesium and potassium. The molecular aptabeacons also demonstrated successful endocytosis and FRET based calcium ion detection in osteocyte cells when conjugated with a cell penetrating peptide (DSS).