cssi/SciSciGPT-SciSciNet huggingface dataset:
Discovery of Potent and Selective Histone Deacetylase Inhibitors via Focused Combinatorial Libraries of Cyclic α3β-Tetrapeptides

Histone deacetylase (HDAC) inhibitors are powerful tools in understanding epigenetic regulation and have proven especially promising for the treatment of various cancers, but the discovery of potent, isoform-selective HDAC inhibitors has been a major challenge. We recently developed a cyclic alpha(3)beta-tetrapeptide scaffold for the preparation of HDAC inhibitors with novel selectivity profiles ( J. Am. Chem. Soc. 2009 , 131 , 3033 ). In this study, we elaborate this scaffold with respect to side chain diversity by synthesizing one-bead-one-compound combinatorial libraries of cyclic tetrapeptide analogues and applying two generations of these focused libraries to the discovery of potent HDAC ligands using a convenient screening platform. Our studies led to the first HDAC6-selective cyclic tetrapeptide analogue, which extends the use of cyclic tetrapeptides to the class II HDAC isoforms. These findings highlight the persistent potential of cyclic tetrapeptides as epigenetic modulators and possible anticancer drug lead compounds.
Trigeminal collaterals in the nasal epithelium and olfactory bulb: a potential route for direct modulation of olfactory information by trigeminal stimuli.

The nasal epithelium is richly invested with peptidergic (substance P and calcitonin gene-related peptide [CGRP]) trigeminal polymodal nociceptors, which respond to numerous odorants as well as irritants. Peptidergic trigeminal sensory fibers also enter the glomerular layer of the olfactory bulb. To test whether the trigeminal fibers in the olfactory bulb are collaterals of the epithelial trigeminal fibers, we utilized dual retrograde labeling techniques in rats to identify the trigeminal ganglion cells innervating each of these territories. Nuclear Yellow was injected into the dorsal nasal epithelium, and True Blue was injected into the olfactory bulb of the same side. Following a survival period of 3-7 days, the trigeminal ganglion contained double-labeled, small (11.8 x 8.0 microm), ellipsoid ganglion cells within the ethmoid nerve region of the ganglion. Tracer injections into the spinal trigeminal complex established that these branched trigeminal ganglion cells also extended an axon into the brainstem. These results indicate that some trigeminal ganglion cells with sensory endings in the nasal epithelium also have branches reaching directly into both the olfactory bulb and the spinal trigeminal complex. These trigeminal ganglion cells are unique among primary sensory neurons in having two branches entering the central nervous system at widely distant points. Furthermore, the collateral innervation of the epithelium and bulb may provide an avenue whereby nasal irritants could affect processing of coincident olfactory stimuli.
Cooperative Coding for OFDM Systems

In this paper, we study Orthogonal Frequency Division Multiplexing (OFDM) systems with cooperative coding over frequency selective Rayleigh fading channels. We derive the pairwise error probability (PEP) for the block-fading OFDM channel model. We use the derived PEP to get an upper bound on the frame error probability for the coded cooperative OFDM system. This bound is then utilized in the study of the diversity and coding gains achievable through cooperative coding in OFDM systems for various inter-user channel qualities. We consider the design of cooperative convolutional codes based on the principle of overlays and provide simulation results for different cooperation scenarios. We observe significant gains over conventional non-cooperative OFDM systems. Finally, based on some simple approximations, we provide guidelines for the choice of partners in coded cooperative OFDM systems.
Conjugated Polyelectrolyte‐Antibody Hybrid Materials for Highly Fluorescent Live Cell‐Imaging

Conjugated polyelectrolyte-antibody hybrid materials promise to enhance the utility of conjugated polymers in bioimaging field. Polymer-antibody conjugates that are biologically safe and highly sensitive and selective to cells are designed to image human T or B lymphocytes. In the clear state, the observed efficiency of luminescence is superior to that of commercially available FITC-antibody probe.
Concept mediation in trilingual translation: Evidence from response time and repetition priming patterns

Translation responses to individual words were elicited from 48 English-Spanish-French trilinguals, who translated in six directions at study and two directions at test. Patterns of translation response times and error rates at study reflected the relative proficiency of the trilinguals in comprehension and production of their three languages. At test, repeated items were translated more quickly than new items, with the strongest priming effects occurring for identical repetitions. Repetition priming was also substantial when only the stimulus language or only the response language matched from study to test, implying that repeated comprehension and production processes contribute to priming in translation. Patterns of response times and repetition priming indicate that translation in all directions involved conceptual access. Additive patterns in response time asymmetries and repetition priming were consistent with the treatment of word comprehension and production processes of translation as independent.
Okazaki fragment maturation: nucleases take centre stage

Completion of lagging strand DNA synthesis requires processing of up to 50 million Okazaki fragments per cell cycle in mammalian cells. Even in yeast, the Okazaki fragment maturation happens approximately a million times during a single round of DNA replication. Therefore, efficient processing of Okazaki fragments is vital for DNA replication and cell proliferation. During this process, primase-synthesized RNA/DNA primers are removed, and Okazaki fragments are joined into an intact lagging strand DNA. The processing of RNA/DNA primers requires a group of structure-specific nucleases typified by flap endonuclease 1 (FEN1). Here, we summarize the distinct roles of these nucleases in different pathways for removal of RNA/DNA primers. Recent findings reveal that Okazaki fragment maturation is highly coordinated. The dynamic interactions of polymerase δ, FEN1 and DNA ligase I with proliferating cell nuclear antigen allow these enzymes to act sequentially during Okazaki fragment maturation. Such protein–protein interactions may be regulated by post-translational modifications. We also discuss studies using mutant mouse models that suggest two distinct cancer etiological mechanisms arising from defects in different steps of Okazaki fragment maturation. Mutations that affect the efficiency of RNA primer removal may result in accumulation of unligated nicks and DNA double-strand breaks. These DNA strand breaks can cause varying forms of chromosome aberrations, contributing to development of cancer that associates with aneuploidy and gross chromosomal rearrangement. On the other hand, mutations that impair editing out of polymerase α incorporation errors result in cancer displaying a strong mutator phenotype.
Multi-parameter study of external sulfate attack in blended cement materials

A conventional solution in reducing the potential damage in concrete structures from external sulfate attack is to partially replace the Portland cement with appropriate fly ash. Presently, the compatibility of fly ash as a remedial cement substitution is based on empirically developed ASTM classifications. With proper testing techniques and multi-parameter approaches, one can better correlate the properties of blended cements with the expected level of damage. In this paper, parameters affecting the sulfate resistance of concrete are reviewed and the modifications to conventional expansion tests are discussed. The role of fly ash chemical composition on the level of damage was studied experimentally at macro and micro-scales. The linear expansions were determined both in paste and mortar systems using standard size and modified size specimens. Microstructural studies using ESEM and quantitative EDS were used to characterize the nature of reaction products and fronts. Statistical analysis of data indicated that the sulfate resistance of cementitious materials is significantly influenced by the chemical composition and the transport properties of the system which can be improved by appropriate fly ash substitution. It is also demonstrated that the study of these mechanisms can be expedited using modified size specimens.
Estrogen protects against global ischemia-induced neuronal death and prevents activation of apoptotic signaling cascades in the hippocampal CA1

The importance of postmenopausal estrogen replacement therapy in affording protection against the selective and delayed neuronal death associated with cardiac arrest or cardiac surgery in women remains controversial. Here we report that exogenous estrogen at levels that are physiological for hormone replacement in postmenopausal women affords protection against global ischemia-induced neuronal death and prevents activation of apoptotic signaling cascades in the hippocampal CA1 of male gerbils. Global ischemia induced a marked increase in activated caspase-3 in CA1, evident at 6 hr after ischemia. Global ischemia induced a marked upregulation of the proapoptotic neurotrophin receptor p75(NTR) in CA1, evident at 48 hr. p75(NTR) expression was induced primarily in terminal deoxynucleotidyl transferase-mediated UTP nick-end labeling-positive cells, indicating expression in neurons undergoing apoptosis. Global ischemia also induced a marked downregulation of mRNA encoding the AMPA receptor GluR2 subunit in CA1. Caspase-3, p75(NTR), and GluR2 were not significantly changed in CA3 and dentate gyrus, indicating that the ischemia-induced changes in gene expression were cell specific. Exogenous estrogen attenuated the ischemia-induced increases in activated caspase-3 and blocked the increase in p75(NTR) in post-ischemic CA1 neurons but did not prevent ischemia-induced downregulation of GluR2. These findings demonstrate that long-term estrogen at physiological levels ameliorates ischemia-induced hippocampal injury and indicate that estrogen intervenes at the level of apoptotic signaling cascades to prevent onset of death in neurons otherwise "destined to die."
Preliminary validation of the sanctification of social justice scale

This study presents psychometric results for the initial validation of the Sanctification of Social Justice Scale (SSJS). We conceptualized the sanctification of social justice as how strongly individuals connect working for social justice to an expression of God’s will and what it means to be Christian. Across 4 studies including over 1,200 Christian college students, an exploratory factor analysis, confirmatory factor analysis, internal consistency, and convergent validity results all provide psychometric support for the 1-factor 5-item SSJS. This study extends sanctification theory to the previously unexamined domain of working for social justice and provides preliminary validation of a scale for use in research, intervention, and collaboration with Christian individuals and organizations. Limitations and implications for future research and use of the SSJS also are discussed.
Giant Blood Cyst of the Aortic Valve

Beyond infancy, blood cyst of the aortic valve is not known to occur. We describe a16-year-old girl who had aortic valve stenosis and regurgitation and giant blood cyst of the aortic valve. Serial echocardiograms over a 12-year period demonstrated gradual enlargement of the cyst.
Report of the National Institutes of Health Task Force on Research Standards for Chronic Low Back Pain

Abstract Objectives Despite rapidly increasing intervention, functional disability due to chronic low back pain (cLBP) has increased in recent decades. We often cannot identify mechanisms to explain the major negative impact cLBP has on patients' lives. Such cLBP is often termed nonspecific and may be due to multiple biologic and behavioral etiologies. Researchers use varied inclusion criteria, definitions, baseline assessments, and outcome measures, which impede comparisons and consensus. The purpose of this article is to disseminate the report of the National Institutes of Health (NIH) task force on research standards for cLBP. Methods The NIH Pain Consortium charged a research task force (RTF) to draft standards for research on cLBP. The resulting multidisciplinary panel developed a 3-stage process, each with a 2-day meeting. Results The panel recommended using 2 questions to define cLBP; classifying cLBP by its impact (defined by pain intensity, pain interference, and physical function); use of a minimal data set to describe research subjects (drawing heavily on the Patient Reported Outcomes Measurement Information System methodology); reporting "responder analyses" in addition to mean outcome scores; and suggestions for future research and dissemination. The Pain Consortium has approved these recommendations, which investigators should incorporate into NIH grant proposals. Conclusions The RTF believes that these recommendations will advance the field, help to resolve controversies, and facilitate future research addressing the genomic, neurologic, and other mechanistic substrates of cLBP. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes. We expect the RTF recommendations will become a dynamic document and undergo continual improvement.
State Budget Politics and Judicial Independence: An Emerging Crisis for the Courts as a Political Branch

Courts face a "catch-22" as a independent branch. On one hand court officials feel the need to remain "above politics" in order to secure the legitimacy of the branch and to remain independent. On other hand, courts must negotiate the very political budget process, interact effectively with the other branches, and must behave politically in order to be successful. This paper discusses the implication of this "catch-22" on budget politics, notes problems with how courts approach budget politics and ends with implications and reforms that may lead to budget success and success with intergovernmental relations.
Preparation and Properties of Co/SiO2 and Co3O4/SiO2 Composites

Films of Co/SiO2 composites were prepared by sequential sputtering from Co and SiO2 targets in Ar. As-grown films as well as films annealed in H2/N2 atmospheres consist of hcp Co particles of uniform size embedded in the SiO2 matrix. The measured optical absorption spectra of these composites are consistent with the Maxwell-Garnett theory except for the absence of the predicted structure that arises from the interband transitions of cobalt. Composites consisting of semiconducting Co3 O4 particles embedded in SiO2 were prepared by post-growth annealing of Co/SiO2 films in air. The optical properties of these composites were found to be comparable to those of CO3O4.
The Relationship of Heparin Activity to Platelet Concentration

ConclusionsCholine caused reabsorption of aortic atherosclerosis in the majority of rabbits whose lesion had been produced by cholesterol feeding.
Gender differences in pain and cardiovascular responses to forearm ischemia

Objective To examine gender-related differences in pain and cardiovascular responses to forearm ischemia. Design Forearm ischemia was produced by the submaximal effort tourniquet procedure. Participants performed 2 min of dynamic hand exercise at 30% maximum grip strength. Forearm ischemia was maintained until the report of ischemic pain tolerance or until 20 min elapsed. Arterial blood pressure, heart rate, and verbal reports of ischemic pain were assessed at 2 min intervals. Subjects Thirty four male and 33 female participants of similar age. Results The times to ischemic pain onset and ischemic pain tolerance were similar for both male and female participants. However, during the ischemic period, females reported ischemic pain to be more intense and of greater unpleasantness than male participants. The relative changes in arterial blood pressure and heart rate during the exercise and occlusion period were equivalent for both male and female participants. In contrast, arterial blood pressure responses during the postexercise ischemic period were gender-dependent. Arm ischemia evoked pressor responses in male participants and either a decrease or no change in arterial pressure in female participants. Changes in arterial pressure during the postexercise ischemic period were significantly and positively correlated with verbal measures of ischemic pain for male subjects but not for female subjects. Conclusions The data demonstrated that gender influences both the sensory and the cardiovascular responses to a tonic noxious stressor.
[Analysis of malaria situation in Quanzhou City, 1963-2012].

Objective To understand the situation of malaria in Quanzhou City for 50 years, so as to provide the evidence for eliminating malaria. Methods The data of epidemic situation of malaria and intermediary surveillance were collected and analyzed statistically from 1963 to 2012. Results The incidence of malaria has been periodically increased, but seasonal distribution was not obvious. The incidence in economically developed areas was significantly lower than that in the slow economic development areas. The patients were mainly young adults, and the careers were mainly the farmer, worker and migrant worker. The vivax malaria was the main type and the main vector was Anopheles minimus. The incidence of malaria has been less than 1/100,000 since 1997. From 2004, all of the patients were imported, mainly came from Africa and Southeast Asia. Conclusions After more than 50 years' comprehensive prevention and treatment, the incidence of malaria has been maintained at a low level. We should strengthen the control and management of imported malaria, and consolidate the achievements in malaria prevention, so as to achieve the aim of malaria elimination.
Determination of cyp6d1 gene mutation in Musca domestica by high-resolution melting analysis

Objective To investigate the mechanism of deltamethrin resistance in Musca domestica.Methods The mutation and amplification of cyp6d1,a deltamethrin resistance gene in M.domestica,were determined by high-resolution melting(HRM) analysis and semiquantitative PCR.The accuracy of HRM analysis was validated by sequencing of PCR products.Results The mRNA expression of cyp6d1 in deltamethrin-resistant strain was 50.7-fold that in deltamethrin-sensitive strain,showing significant difference between the two strains(P=0.0002).The PCR products were classified into three genotypes,type A(Tm=85.5 ℃),type B(Tm=87.3 ℃),and type C(Tm=88.5 ℃),according to the mutation analysis of cyp6d1 by HRM.The results from HRM corresponded to the sequences of the three genotypes.As for the genotypes,type A was homozygous 1087G,1101T,and 1155A(GenBank No.U22367.1),type C was homozygous 1087A,1101G,and 1155G,and type B was heterozygous for type A and type C.Bioinformatic analysis revealed that this mutation was non-sense mutation.Conclusion The mRNA expression of cyp6d1 is significantly increased in the deltamethrin-resistant strain of M.domestica in Hangzhou,China,which may be one of the mechanisms of deltamethrin resistance increase in M.domestica.
Effect observation of Xiyanping Injection on autumnal diarrhea in 63 children

Objective:To investigate the effect of Xiyanping Injection in treatment of children's autumnal diarrhea and its safety.Methods:One hundred and twenty-six children with autumnal diarrhea were randomly divided into treatment group and control group. Two groups received routine treatment including intravenously liquid supplement therapy. In addition, the control group was given intravenously virazol and the treatment group was given intravenously Xiyanping Injection. Results:The duration of fever and diarrhea in treatment group were significantly shorter than those in control group(P0.05 or P0.01). The improving rate of treatment group was significantly higher than that of control group (36.5% vs 19.1%, P0.05). The total effectiveness rate of treatment group was significantly higher than that of control group(90.9% vs 66.7%, P0.01), and had few side effects occurred.Conclusion:Xiyanping Injection is effective and safe in treating children's autumnal diarrhea, and it can be widely used in clinic.
Child abuse: why should I report it?

In Indiana, dental professionals are mandated by law to report suspected child abuse and neglect to Child Protective Services (CPS) or the law enforcement agency in their county. The penalty for non-reporting is fine and/or jail. This article will give dental professionals information on child abuse injuries that can be identified in the dental office, how to talk to the child and family members regarding suspicions, and how to report those suspicions to your local CPS or law enforcement agency. Dental professionals will receive reassurance and encouragement from this article to report suspected cases of child abuse to CPS or law enforcement. The report is not meant to be punitive, but is intended to get the family connected to services to assist them, the child, and any other children they have or may have in the future, to avoid further abuse, and to attempt to break the cycle of abuse. To report suspicions of child abuse in Indiana, dial: 1-800-800-5556. Language: en
An Empirical Evaluation of the Host Selling Commercial and the Announcer Commercial When Used on Children

This research paper evaluates the host selling commercial and the announcer commercial in light of the recent court decision eliminating the NAB Code. This paper questions the use of host selling commercials since no significant differences were found between the host selling commercial and the announcer commercial on either recall or product selections.
Pseudospectra Analysis, Nonlinear Eigenvalue Problems, and Studying Linear Systems with Delays

Time delays occur naturally in many physical and social systems. Computer simulations of such systems require that models of these systems be stable, and perhaps even passive, if several such systems are to be joined together in the simulation. We present a visual procedure for studying the stability and passivity of such systems. This procedure uses ideas from pseudospectra analysis. It is applicable to systems of linear, delay-differential-algebraic equations. There are no a priori restrictions on the types or sizes of the delays. No approximations to the original system are made. All approximations are confined to the grid used in the visualization procedure, and the procedure parallelizes readily. We apply this procedure to the study of the stability and passivity of proposed models for simulations of the behavior of currents and voltages in packaged VLSI interconnects (wires and planes) in computers. Simulations are required to verify that internal electromagnetic fields do not significantly delay or distort circuit signals.
Physics-based and human-derived information fusion for analysts

Recent trends in physics-based and human-derived information fusion (PHIF) have amplified the capabilities of analysts; however with the big data opportunities there is a need for open architecture designs, methods of distributed team collaboration, and visualizations. In this paper, we explore recent trends in the information fusion to support user interaction and machine analytics. Challenging scenarios requiring PHIF include combing physics-based video data with human-derived text data for enhanced simultaneous tracking and identification. A driving effort would be to provide analysts with applications, tools, and interfaces that afford effective and affordable solutions for timely decision making. Fusion at scale should be developed to allow analysts to access data, call analytics routines, enter solutions, update models, and store results for distributed decision making.
Are Antiplatelet Agents Beneficial in Essential Thrombocythemia? Maybe Yes, Probably No

Chu and colleagues' systematic review examined the benefits and risks of treating patients with essential thrombocythemia with antiplatelet agents. The editorialist discusses the uncertainty the re...
Rocking-Chair Ammonium-Ion Battery: A Highly Reversible Aqueous Energy Storage System.

Aqueous rechargeable batteries are promising solutions for large-scale energy storage. Such batteries have the merit of low cost, innate safety, and environmental friendliness. To date, most known aqueous ion batteries employ metal cation charge carriers. Here, we report the first "rocking-chair" NH4-ion battery at the full-cell scale by employing an ammonium Prussian white analogue, (NH4)2Ni[Fe(CN)6], as the cathode, an organic solid, 3,4,9,10-Perylenetetracarboxylic diimide (PTCDI) as the anode, and 1 M (NH4)2SO4 aqueous electrolyte. This novel aqueous NH4-ion battery demonstrates amenable electrochemical performance: an average operation voltage of ~1.0 V, an attractive energy density of ~43 Wh kg-1 based on electrodes' active mass, and excellent cycle life over 1000 cycles with 67% capacity retention. The topochemistry results of NH4+ in these electrodes point to a new paradigm of NH4+-ion based energy storage.
Improving mechanical properties of injectable polymers and composites

Abstract: Injectable polymers and composites have been widely explored for biomedical applications due to their potential use in minimally invasive surgeries and advantages in filling irregular-shaped tissue defects. To improve overall performance and tissue integration of injectable materials, specific mechanical properties are often required. This chapter focuses on the relationship between material structure and mechanical properties, with particular emphasis on reviewing means to improve the mechanical properties of injectable polymers and composites. Potential applications of each type of injectable polymer/composite (including both hydrophilic and hydrophobic polymers) are discussed, and current challenges relating to enhancing mechanical properties of injectable biomaterials are highlighted.
An Empirical Investigation Into The Administrative Procedures Taken In Response To The Detection Of Medical Errors Within Acute Care Hospitals In Pennsylvania

This researcher investigates the procedures taken by healthcare administrators within Pennsylvania acute care hospitals with respect to the detection of medical errors in order to provide corrective measures. In response to structured interview questions, the overwhelming majority of research participants stated that the procedures for corrective actions focused upon various training interventions as deemed appropriate by management. However, scholarly literature states that the majority of medical errors do not occur due to the lack of competence, skills, or knowledge of healthcare professionals. Thus, using training interventions to solve non-training problems may not prove effective. The outcome of the study has lead to several important implications for the healthcare industry. Lastly, further research was suggested as it relates to patient safety and the reduction of medical errors.
Disorders of metal metabolism

Trace elements are chemical elements needed in minute amounts for normal physiology. Some of the physiologically relevant trace elements include iodine, copper, iron, manganese, zinc, selenium, cobalt and molybdenum. Of these, some are metals, and in particular, transition metals. The different electron shells of an atom carry different energy levels, with those closest to the nucleus being lowest in energy. The number of electrons in the outermost shell determines the reactivity of such an atom. The electron shells are divided in sub-shells, and in particular the third shell has s, p and d sub-shells. Transition metals are strictly defined as elements whose atom has an incomplete d sub-shell. This incomplete d sub-shell makes them prone to chemical reactions, particularly redox reactions. Transition metals of biologic importance include copper, iron, manganese, cobalt and molybdenum. Zinc is not a transition metal, since it has a complete d sub-shell. Selenium, on the other hand, is strictly speaking a nonmetal, although given its chemical properties between those of metals and nonmetals, it is sometimes considered a metalloid. In this review, we summarize the current knowledge on the inborn errors of metal and metalloid metabolism.
Tumori nell’anziano

La maggior parte dei tumori testa e collo si sviluppa durante il quinto e sesto decennio di vita [1], ma il 24% colpisce le persone di 70 e piu anni [1]. Alcune caratteristiche cliniche differenziano il tumore testa collo delle persone di 70 e piu anni da quello dei piu giovani. La percentuale di donne affette da cancro testa e collo aumenta con l’eta, un fatto che si puo spiegare in parte con la maggiore aspettativa di vita media nelle donne. Anche la percentuale di pazienti con i piu comuni fattori di rischio — fumo e alcol — diminuisce con l’eta, al punto che ci si e chiesto se l’eta non sia un fattore di rischio per queste neoplasie.
Data-Driven Correlation Analysis Between Observed 3D Fatigue-Crack Path and Computed Fields from High-Fidelity, Crystal-Plasticity, Finite-Element Simulations

Systematic correlation analysis was performed between simulated micromechanical fields in an uncracked polycrystal and the known path of an eventual fatigue-crack surface based on experimental observation. Concurrent multiscale finite-element simulation of cyclic loading was performed using a high-fidelity representation of grain structure obtained from near-field high-energy x-ray diffraction microscopy measurements. An algorithm was developed to parameterize and systematically correlate the three-dimensional (3D) micromechanical fields from simulation with the 3D fatigue-failure surface from experiment. For comparison, correlation coefficients were also computed between the micromechanical fields and hypothetical, alternative surfaces. The correlation of the fields with hypothetical surfaces was found to be consistently weaker than that with the known crack surface, suggesting that the micromechanical fields of the cyclically loaded, uncracked microstructure might provide some degree of predictiveness for microstructurally small fatigue-crack paths, although the extent of such predictiveness remains to be tested. In general, gradients of the field variables exhibit stronger correlations with crack path than the field variables themselves. Results from the data-driven approach implemented here can be leveraged in future model development for prediction of fatigue-failure surfaces (for example, to facilitate univariate feature selection required by convolution-based models).
Constitutive Activation of the JAK2/STAT5 Signal Transduction Pathway Correlates With Growth Factor Independence of Megakaryocytic Leukemic Cell Lines

The factor-independent Dami/HEL and Meg-01 and factor-dependent Mo7e leukemic cell lines were used as models to investigate JAK/STAT signal transduction pathways in leukemic cell proliferation. Although Dami/HEL and Meg-01 cell proliferation in vitro was independent of and unresponsive to exogenous cytokines including granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), IL-6, thrombopoietin (TPO), and tumor necrosis factor-alpha (TNF-alpha), the growth of Mo7e cells was dependent on hematopoietic growth factors. When these cell lines were cultured in medium without cytokines, a constitutively activated STAT-like DNA-binding factor was detected in nuclear extracts from both Dami/HEL and Meg-01 cells. However, the STAT-like factor was not detectable in untreated Mo7e cells, but was activated transiently in Mo7e cells in response to cytokine treatments. The constitutively activated and cytokine-induced STAT-like DNA-binding factor in these three cell lines was identified as STAT5 by oligonucleotide competition gel mobility assays and by specific anti-STAT antibody gel supershift assays. Constitutive activation of JAK2 also was detected in the factor-independent cell lines, but not in Mo7e cells without cytokine exposure. Meg-01 cells express a p185 BCR/ABL oncogene, which may be responsible for the constitutive activation of STAT5. Dami/HEL cells do not express the BCR/ABL oncogene, but increased constitutive phosphorylation of Raf-1 oncoprotein was detected. In cytokine bioassays using growth factor-dependent Mo7e and TF-1 cells as targets, conditioned media from Dami/HEL and Meg-01 cells did not show stimulatory effects on cell proliferation. Our results indicate that the constitutive activation of JAK2/STAT5 correlates with the factor-independent growth of Dami/HEL and Meg-01 cells. The constitutive activation of JAK2/STAT5 in Dami/HEL cells is triggered by a mechanism other than autocrine cytokines or the BCR/ABL oncoprotein.
Diversity of visuomotor reflexes in two Drosophila species

For adaptive behavior, an organism must identify and assign subjective value to salient sensory information, but what stimuli are salient could change depending upon the local features of the environment. Insects such as fruit flies (Drosophila), for example, rely on olfactory cues to locate food and oviposition sites. But not all Drosophila species find the same stimuli to be salient: for example, four geographically isolated populations of Drosophila mojavensis, which feed and oviposit on necrotic cacti, show olfactory-driven behavioral preferences for host cacti specific to the local environment of each population [1,2]. We wondered whether visual features specific to certain environments could drive divergent visuomotor responses. We compared the visuomotor reflexes of D. melanogaster, a cosmopolitan generalist found in moderately dense visual environments, with D. mojavensis, a cactophilic specialist found in comparatively sparse visual landscapes. We found that, like D. melanogaster, D. mojavensis steer towards long vertical stripes, such as landscape features [3], but in contrast to D. melanogaster's aversion to small objects [3], D. mojavensis find small objects attractive or of neutral value.
High Fidelity Cryopreservation and Recovery of Primary Rodent Cortical Neurons

Cell cryopreservation improves reproducibility and enables flexibility in experimental design. Although conventional freezing methodologies have been used to preserve primary neurons, poor cell viability and reduced survival severely limited their utility. We screened several high-performance freezing media and found that CryoStor10 (CS10) provided superior cryoprotection to primary mouse embryonic cortical neurons compared to other commercially-available or traditional reagents, permitting the recovery of 68.8% of cells relative to a fresh dissection. We characterized developmental, morphometric, and functional indicators of neuron maturation and found that, without exception, neurons recovered from cryostorage in CS10 media faithfully recapitulate in vitro neurodevelopment in-step with neurons obtained by fresh dissection. Our method establishes cryopreserved neurons as a reliable, efficient, and equivalent model to fresh neuron cultures.
Fisetin is a senotherapeutic that extends health and lifespan

Abstract Background Senescence is a tumor suppressor mechanism activated in stressed cells to prevent replication of damaged DNA. Senescent cells have been demonstrated to play a causal role in driving aging and age-related diseases using genetic and pharmacologic approaches. We previously demonstrated that the combination of dasatinib and the flavonoid quercetin is a potent senolytic improving numerous age-related conditions including frailty, osteoporosis and cardiovascular disease. The goal of this study was to identify flavonoids with more potent senolytic activity. Methods A panel of flavonoid polyphenols was screened for senolytic activity using senescent murine and human fibroblasts, driven by oxidative and genotoxic stress, respectively. The top senotherapeutic flavonoid was tested in mice modeling a progeroid syndrome carrying a p16INK4a-luciferase reporter and aged wild-type mice to determine the effects of fisetin on senescence markers, age-related histopathology, disease markers, health span and lifespan. Human adipose tissue explants were used to determine if results translated. Findings Of the 10 flavonoids tested, fisetin was the most potent senolytic. Acute or intermittent treatment of progeroid and old mice with fisetin reduced senescence markers in multiple tissues, consistent with a hit-and-run senolytic mechanism. Fisetin reduced senescence in a subset of cells in murine and human adipose tissue, demonstrating cell-type specificity. Administration of fisetin to wild-type mice late in life restored tissue homeostasis, reduced age-related pathology, and extended median and maximum lifespan. Interpretation The natural product fisetin has senotherapeutic activity in mice and in human tissues. Late life intervention was sufficient to yield a potent health benefit. These characteristics suggest the feasibility to translation to human clinical studies. Fund NIH grants P01 AG043376 (PDR, LJN), U19 AG056278 (PDR, LJN, WLL), R24 AG047115 (WLL), R37 AG013925 (JLK), R21 AG047984 (JLK), P30 DK050456 (Adipocyte Subcore, JLK), a Glenn Foundation/American Federation for Aging Research (AFAR) BIG Award (JLK), Glenn/AFAR (LJN, CEB), the Ted Nash Long Life and Noaber Foundations (JLK), the Connor Group (JLK), Robert J. and Theresa W. Ryan (JLK), and a Minnesota Partnership Grant (AMAY-UMN#99)-P004610401–1 (JLK, EAA).
Hypogyrification and its association with cognitive impairment in children with 22q11.2 deletion Syndrome: A preliminary report

22q11.2 Deletion Syndrome (22qDS) is a neurogenetic disorder resulting in cognitive deficits and hypogyrification, but relationships between these processes have not been established. 22qDS youth and healthy controls (HC) were administered a battery of cognitive tasks. Gyrification measurements were extracted from structural T1 scans using Freesurfer, contrasted between groups, and correlated to cognition. Data was adjusted for age, sex, socio-economic status and intracranial volume. 22qDS displayed significant hypogyrification which was associated with poorer executive functioning and verbal learning in orbitofrontal and anterior cingulate cortex. Our preliminary findings identified neurodevelopmental deficits in 22qDS shown by hypogyria, which relate to cognitive impairments.
A simulation model for estimating root zone saturation indices of agricultural crops in a shallow aquifer and canal system

Abstract Shallow aquifers significantly impact crop growth as saturated soil conditions may occur. Canals are widely constructed in such areas to mitigate groundwater saturation or flooding. We applied a simulation model to estimate the occurrence of root zone saturation [root zone saturation index (RZSI)] for agricultural crops and to identify factors that influence root zone saturation in a shallow coastal aquifer and canal system. Results indicated that groundwater modeling combined with multiple linear regression can relate the influencing factors and root zone saturation durations in low lying farmland adjacent to canal systems. In our study, most areas had a low RZSI, but areas towards the northwest and southeast where the land surface elevation is generally low were predicted to have a greater RZSI. In general, positive correlations were found between the root zone saturation durations and rainfall amount, antecedent groundwater table elevation and average canal stages in areas where the higher RZSIs were predicted. Rainfall amount played a more important role than antecedent groundwater table elevation and canal stage in determining the root zone saturation during the wet season, while antecedent groundwater table elevation and canal stage played a more important role than rainfall amount during dry season. Correlations between the predicted root zone saturation duration and land surface elevation were negative and stronger during the wet season than the dry season, and the correlations were stronger in the deep (0–61 cm) root zone than with the shallow (0–18 cm) root zone. In area where the land surface elevation is relatively high, the root zone saturation duration was not influenced by rainfall amount, antecedent groundwater table elevation or canal stage, at least under the current management practices and climate conditions.
Therapeutic advances in spinal muscular atrophy

Abstract Spinal muscular atrophy (SMA) is a rare neuromuscular condition, characterized by loss of motor neurons as a result of a mutation in the survival motor neuron gene. This results in muscle wasting and in the most common and severe type, death before 24 months. Over the recent years there has been a dynamic shift in the therapeutic options for these patients involving both clinical trials in genetic modifying therapies to indirectly improve the survival motor neuron protein level and hence strength, muscle promotor therapies, up/down regulation of modifier genes and more recently gene therapy to replace the mutated survival motor neuron gene. This review addresses the pathogenesis of SMA and the resultant therapeutic approaches as well as the current state in clinical trials and future development.
Evaluating approaches to marketing cognitive behavioral therapy: does evidence matter to consumers?

Direct-to-consumer marketing initiatives may improve utilization of evidence-based therapy. An important decision in such marketing efforts is how to effectively present scientific evidence suppor...
Oysters' Gape Measurement System

The Mississippi Based RESTORE Act Center of Excellence (MBRACE) is a consortium of four research universities: Jackson State University (JSU), Mississippi State University (MSU), the University of Mississippi (UM), and the University of Southern Mississippi (USM), where USM takes the lead in the research. MBRACE sponsored four projects in studying the importance of the environmental condition of oysters in the Mississippi Gulf Oyster Reefs with each university being assigned a specific project. JSU's team was tasked with the responsibility of developing biosensors for the measurement of Bivalve Valve Movement [15]. In this work, the hardware and software used in developing a bivalve gape measurement system have been explored. This system employs the Hall-effect phenomenon to accurately measure and report the gape of a bivalve. This system has been designed to operate in the field as well as in a laboratory environment.
Path-Dependent Deadlock: Institutional Causes of the Euro Crisis

We argue that the characterization of the financial turmoil in the European Monetary Union as merely a sovereign debt crisis is inaccurate insofar as the deterioration of public finances represents the culmination of a process: legal and institutional flaws laid the ground for a public debt crisis. The institutional failure was the embedding of a unified monetary policy accompanied by a failure to introduce a coordinated fiscal and labor policy. The latent consequences of these flaws were brought into full view with the onset of the Global Financial Crisis. There was a lack of real convergence between the countries of the core (Germany) and the periphery (especially Greece, Ireland, Italy, Portugal and Spain, the so-called GIIPS.) This was exacerbated by the “one-size-fits-all” monetary policy, distorted fiscal policy, and the lack of a common approach to wage determination. In sum, instead of fostering learning and convergence, the asymmetric EMU design catapulted the GIIPS and Germany onto divergent growth paths, which ultimately translated into “destabilizing macroeconomic imbalances.” This analysis will draw upon knowledge-production systems and learning theories in order to contribute to a deeper understanding of the EMU crisis. In particular, we take a contextualized approach by examining the path-dependent evolution of the EMU and how institutional failures have turned the GFC into a sovereign debt crisis.
Legacies of the Twin Towers of the World Trade Center

....Forever enshrined, not only in a city which holds strong symbols of enduring bonds of friendship amongst peoples of different cultures, but also in the lives and hearts of those cultures and nations touched by these legacies - as well​ as those to whom it continues to serve as a wonderful melting pot. It had been a huge year - not only from​ the perspective of having secured my desired ACCA professional qualifications, but also in terms of having just received my LLM certificate. Having just spent the summer with my uncle and cousins in Mannheim and Heidelberg, I was working as an intern in the legal offices of Menold & Aulinger - well in advance as preparations for the commencement of work at Ernst & Young - its sister office and affiliate. I was scheduled to commence work in the Hamburg branch (Ernst & Young) in the Autumn. On that 9/11 day - a day which I (and millions of people) will never forget, I was working at the Dortmund office (Menold & Aulinger) of my supervisor, Dr Wolfgang Nockelmann - Attorney-at-Law, New York As well as analyzing the impacts and legacies of the Twin Towers of the World Trade Center, this chapter also highlights​ why globalisation is impacting many nations - particularly from the perspective of inflation targeting, as well as how monetary policy responses are being implemented in many economies - notably Asian economies, in the aftermath of 9/11 and the recent Financial Crisis. "Because of globalisation, monetary policy in one country has an impact on others. We face considerable challenges in areas such as inflation targeting, the use of unconventional measures and the formulation of macro prudential counter cyclical policies........"
A Social Process

(1987). A Social Process. Journal of Physical Education, Recreation & Dance: Vol. 58, No. 4, pp. 50-53.
Respiratory Syncytial Virus

Development of a safe, effective, and inexpensive prophylactic for respiratory syncytial virus has been a long-sought goal that may finally be within reach. Decades of research into the molecular biology of virus-host interactions and the consequent cellular immune responses has provided several potential targets for antiviral intervention. Knowledge of RSV biology and the complex cascade of events the innate and adaptive immune systems perform in the body’s attempt to clear the viral invaders have shown us its weak points where we may be able to block infection. Like a true predator, however, RSV targets the very young and the very old and this fact makes the job of prevention more difficult and challenging. The immature infant immune system and the aged immune system are very different and require unique approaches for prophylaxis and therapy for respiratory infections. The interdisciplinary attack by bioengineers, molecular biologists, clinical researchers, drug discovery experts, and others has produced many possible weapons and it is hoped that globally applicable controls of RSV may soon be added to the clinician’s arsenal.