cssi/SciSciGPT-SciSciNet huggingface dataset:
Mechanisms of Glucose Lowering of Dipeptidyl Peptidase-4 Inhibitor Sitagliptin When Used Alone or With Metformin in Type 2 Diabetes:: A double-tracer study

OBJECTIVE To assess glucose-lowering mechanisms of sitagliptin (S), metformin (M), and the two combined (M+S). RESEARCH DESIGN AND METHODS We randomized 16 patients with type 2 diabetes mellitus (T2DM) to four 6-week treatments with placebo (P), M, S, and M+S. After each period, subjects received a 6-h meal tolerance test (MTT) with [ 14 C]glucose to calculate glucose kinetics. Fasting plasma glucose (FPG), fasting plasma insulin, C-peptide (insulin secretory rate [ISR]), fasting plasma glucagon, and bioactive glucagon-like peptide (GLP-1) and gastrointestinal insulinotropic peptide (GIP) were measured. RESULTS FPG decreased from P, 160 ± 4 to M, 150 ± 4; S, 154 ± 4; and M+S, 125 ± 3 mg/dL. Mean post-MTT plasma glucose decreased from P, 207 ± 5 to M, 191 ± 4; S, 195 ± 4; and M+S, 161 ± 3 mg/dL ( P P P P P P CONCLUSIONS M+S combined produce additive effects to 1 ) reduce FPG and postmeal plasma glucose, 2 ) augment GLP-1 secretion and β-cell function, 3 ) decrease plasma glucagon, and 4 ) inhibit fasting and postmeal EGP compared with M or S monotherapy.
Cell-Specific Regulation of Nucleic Acid Sensor Cascades: a Controlling Interest in the Antiviral Response

In this study, we examined the capacities of non-antigen-presenting cell types to propagate antiviral signals following infection with recombinant adenovirus or by direct nucleic acid transfection. Three murine cell lines (RAW264.7 macrophages as a positive control, FL83B hepatocytes, and MS1 endothelial cells) were assessed following exposure to adenovirus, DNA, or RNA ligands. Based on primary (interferon response factor 3 [IRF3] phosphorylation) and secondary (STAT1/2 phosphorylation) response markers, we found each cell line presented a unique response profile: RAW cells were highly responsive, MS1 cells were modified in their response, and FL83B cells were essentially nonresponsive. Comparative reverse transcription-quantitative PCR (RT-qPCR) of nucleic acid sensing components revealed major differences between the three cell types. A prominent difference was at the level of adaptor molecules; TRIF, MyD88, MAVS, and STING. TRIF was absent in MS1 and FL83B cells, whereas MyD88 levels were diminished in FL83B hepatocytes. These differences resulted in compromised TLR-mediated activation. While the cytosolic adaptor MAVS was well represented in all cell lines, the DNA adaptor STING was deficient in FL83B hepatocytes (down by nearly 3 log units). The absence of STING provides an explanation for the lack of DNA responsiveness in these cells. This hypothesis was confirmed by acquisition of IRF3 activation in Flag-STING FL83B cells following DNA transfection. To consolidate the central role of adaptors in MS1 endothelial cells, short hairpin RNA (shRNA) knockdown of STING and MAVS resulted in a ligand-specific loss of IRF3 responsiveness. In contrast to the requirement for specific adaptor proteins, a requirement for a specific DNA sensor (AIM2, DDx41, or p204) in the IRF3 activation response was not detected by shRNA knockdown in MS1 cells. The data reveal that cell-specific regulation of nucleic acid sensing cascade components influences antiviral recognition responses, that controlling levels of adaptor molecules is a recurring strategy in regulating antiviral recognition response functions, and that comparative RT-qPCR has predictive value for antiviral/innate response functions in these cells.
Gonadotropin-releasing hormone increases CD4 T-lymphocyte numbers in an animal model of immunodeficiency.

Background: Gonadotropin-releasing hormone (GnRH) possesses immunostimulatory properties. We have previously demonstrated that GnRH antagonists decrease lymphocyte numbers in an animal model of autoimmune disease. We speculated that the converse might be true, that GnRH administration would increase lymphocyte numbers or alter lymphocyte subsets in an immunodeficiency state. Objective: Our purpose was to test the hypothesis that GnRH agonist would increase IgG and CD4 counts in a rat model of immunodeficiency independently of gonadal steroids. Methods: We used diabetes-prone (DP) BB rats. This model has been characterized to have an AIDS-like lymphocyte profile, with lymphopenia and depressed CD4 counts. Ovariectomized female DP rats were randomized to receive subcutaneous injections with GnRH or vehicle 6 times weekly. DR rats were ovariectomized and treated with vehicle as controls. We performed flow cytometric analysis and complete blood cell counts at baseline, 3.5 weeks, and 7 weeks of treatment. We also measured total serum IgG and luteinizing hormone levels. Results: GnRH administration significantly increased total serum IgG levels in DP rats compared with vehicle. The percentages of CD4+ cells in blood were also significantly increased in the GnRH-treated group compared with the vehicle-treated group and compared with baseline. Similarly, the absolute numbers of CD4+ positive T cells were increased over controls at 7 weeks. The effects of GnRH were specific for the CD4 subset because there were no significant differences in numbers of CD8+ positive cells between the 2 treatment groups. Conclusion: GnRH shows potential utility as an immunostimulatory agent in immunodeficient states manifesting diminished numbers of immunocompetent CD4+ T lymphocytes. (J Allergy Clin Immunol 1999;104:653-8.)
Partial purification from hepatoma cells of an intracellular substance which mediates the effects of insulin on pyruvate dehydrogenase and low Km cyclic AMP phosphodiesterase

Abstract A substance capable of stimulating the activities of pyruvate dehydrogenase and low K m cyclic AMP phosphodiesterase was prepared from H4-II-EC3′ hepatoma cells by acid extraction and partially purified by molecular exclusion chromatography. The material thus prepared by gel chromatography was found to stimulate the activities of these enzymes in a concentration-dependent manner. The amount or activity of the pyruvate dehydrogenase stimulating factor was increased in cells which had been treated with physiological concentrations of insulin (0.2 mU/ml). Increasing the concentration of insulin increased the amount or activity of the factor generated. High concentrations of insulin did not cause a reversal of the effects of insulin. The stimulation of pyruvate dehydrogenase activity by the factor was eliminated when sodium fluoride (75 m m ) was present in the enzyme assay, implying that activation was mediated by the pyruvate dehydrogenase phosphatase. The enzyme-stimulating factor isolated from hepatoma cells shares a number of important characteristics with the putative second messenger of insulin prepared from other cell types: (1) it is heat and acid stable, (2) it has a similar apparent molecular weight, (3) it is generated in an insulin-dependent manner, (4) it stimulates the activity of pyruvate dehydrogenase by a fluoride-sensitive mechanism, and (5) it elutes from the anion-exchange resin AG 1-X8 at an ionic strength of 0.4 m . These findings suggest that the stimulator of pyruvate dehydrogenase and of low K m cyclic AMP phosphodiesterase isolated from hepatoma cells has chemical properties identical with those of the putative second messenger of insulin action isolated from a number of other insulin-sensitive tissues.
Improving California's Infrastructure Services: The California Infrastructure Initiative

This paper builds on the work of Dowall and Whittington, and recent discussions concerning Governor Schwarzenegger’s proposed PBI California initiative. It first defines an overarching policy framework on performance-based infrastructure; and second, outlines how California might launch a series of integrated policy and program initiatives to establish new and innovative approaches for providing California’s citizens and businesses with high-quality infrastructure services. The paper explains the potential benefits of doing so in California and offers recommendations on how the policy dialogue should proceed in Sacramento and around the State.
Complementary TEM and AFM Force Spectroscopy to Characterize the Nanomechanical Properties of Nanoparticle Chain Aggregates

Nanoparticle chain aggregates are used as reinforcing fillers in elastomers (rubber) and significantly enhance the mechanical properties (tensile strength, Young's modulus) of elastomers. Insight into mechanisms of the performance of nanoparticle chain aggregates can be obtained from force vs displacement (force spectroscopy) measurements made with an AFM tip and an aggregate-coated substrate. Distinctive sawtooth patterns were observed which were interpreted as aggregate stretching and breaking events. Based on the measurements, estimates of the aggregate nanomechanical properties were made.
Utilization of reducing power in growing cultures of Chromatium.

The overall composition of cell material in the stationary growth phase of cultures of Chromatium strain 6412 cultivated with sulfide as electron donor is approximately (C5H8O2N). At the moment that sulfide became depleted, 42% had been oxidized to sulfur and 58% to sulfate. Thus at this time 69% of the reducing power initially present had been utilized. However, the amount of structural cell material produced was only 56% of the amount present in the stationary phase of growth. This discrepancy appeared to be due to the accumulation of storage carbohydrate. Storage carbohydrate was synthesized as long as sulfide was available and consumed after sulfide depletion. Increase in structural cell material after sulfide depletion could not be accounted for by CO2 fixation only, which indicates that storage carbohydrate can be converted into structural cell material. When stationary-phase cultures were again supplied with sulfide, growth was not observable in the first few hours, even though sulfide was oxidized, mainly to sulfur. Under these conditions reducing power was utilized for the synthesis of storage carbohydrate from CO2.
Ergonomic intervention in the treatment of a patient with upper extremity and neck pain.

Background and Purpose: Work-related musculoskeletal disorders are widespread among computer users and costly to the health care system. Workstation setup and worker postures contribute to upper-extremity and neck symptoms among computer users. Ergonomic interventions such as work risk analysis and workstation modifications can improve workers' symptoms. However, ergonomic interventions do not appear to be a common component of traditional physical therapy treatment. Case Description: The patient was a 26-year-old woman with right upper-extremity and neck pain referred for physical therapy. A course of traditional physical therapy treatment was performed followed by an ergonomic intervention. Outcomes: Following 4 weeks of traditional physical therapy, the patient showed a 1.0-cm improvement in her resting pain level but no change in her pain level during exacerbations on the visual analog scale. An ergonomic intervention was performed following traditional physical therapy. At the conclusion of the full course of treatment (traditional physical therapy plus ergonomic intervention), resting pain level decreased by 4.6 cm and exacerbation pain level decreased by 3.2 cm. Improvements in Rapid Upper Limb Assessment and Workstyle scores also were realized. Discussion: This case report demonstrates the importance of examining the work habits and work-related postures of a patient who complains of upper-extremity and neck pain that is exacerbated by work. Providing an ergonomic intervention in concert with traditional physical therapy may be the most beneficial course of treatment.
An educational Program in Product Realization

As part of the Manufacturing Engineering Educational Partnership (MEEP) design and manufacturing courses have been restructured into a sequence leading to a Program in Products Realization (PPR) in our undergraduate engineering curriculum. The purpose is to provide a broad based, interdisciplinary program for undergraduate students interested in the design and manufacturing of industrial products. Although each school has taken a slightly different approach to the implementation, the students at the three schools experience design and manufacturing activities each semester (or quarter) in residence. The program bridges the gap between engineering science and practice, and allows students to work in teams on real industrial problems. The implementation of the program has required restructuring of existing courses, the addition of new resources, and the creation of Learning Factories at each of the institutions. The Learning Factories provide modern facilities for design, manufacturing, fabrication, and testing of products. In addition, the program has attracted the support of over 100 industrial sponsors, who have helped promote hands-on experience and provided projects and class room support. This paper describes the new program at each of the institutions, the resources required, and operational experiences to date. This project was supported by the ARPA Technology Reinvestment Program and the National Science Foundation.
Rotating Hydraulics and Upstream Basin Circulation

The flow in a source-fed f -plane basin drained through a strait is explored using a single-layer (reduced gravity) shallow-water numerical model that resolves the hydraulic flow within the strait. The steady upstream basin circulation is found to be sensitive to the nature of the mass source (uniform downwelling, localized downwelling, or boundary inflow). In contrast, the hydraulically controlled flow in the strait is nearly independent of the basin circulation and agrees very well with the Gill-theory solution obtained using the strait geometry and the numerically determined average potential vorticity in the strait entrance region. This Gill solution, however, gives a unique value of the upstream boundary layer flux splitting that does not agree with any of the full numerical solutions. The coupled basin‐strait system is shown to select an average overflow potential vorticity corresponding to the Gill solution with maximum fluid depth on the strait boundaries. This state also corresponds to one of maximal upstream basin potential energy. This result is robust to changes in the basin geometry, strait characteristics, the dissipation parameter (linear drag), and the net mass flux. The nonunique relation between basin conditions and overflow transport is significant with regard to deep overflow transport monitoring. It is shown that the potential vorticity selection leads to overflow, or ‘‘weir,’’ transport relations that are well approximated by the zero potential vorticity theory. However, accurate estimates of the transport can only be obtained if conditions within the strait entrance region, and not the basin, are used.
Motion and Loads of An Articulated Loading Platform In Waves

This paper presents a preliminary study of an analysis of motions and loads of an articulated loading platform (ALP) in regular waves, without a tanker moored to it. For the evaluation of the wave-exciting forces and moment, Newman's linear theory of a slender vertical body of revolution has been employed. The pitching motions of the ALP and the axial and lateral shear loads at the universal joint have been calculated within the framework of linearization. An attempt has been made to compare the analytical results with available experimental data which have been obtained from a model test in a different environmental condition, i.e., a combination of noncollinear wind, current, and random seas; thus, the experimental response amplitude operators (RAOs) will no longer satisfy the linearity law.
Patterns of co-occurrence and body size overlap among ants in Florida's upland ecosystems

Within ant communities, competitive asymmetry is hypothesized to dictate, in part, the co-occurrence patterns of species. I intensively sampled ant communities from 5 upland ecosystem types in Florida, USA. I used null model analyses to test two general assembly rules and one specific to ant communities: (1) reduced co-occurrence of species among communities, (2) regular spacing of body sizes within communities, and (3) competition hierarchies. Species were segregated by habitat (species co-occurrence was reduced among ecosystems) but there was no evidence for competition hierarchies at local scales (species co-occurrence patterns were random within ecosystems). There was limited evidence that body size distributions are regularly spaced at both the regional and local scale. Thus, while competition between species may result in character displacement between similar species, it does not appear to form competition hierarchies at the local scale at which ants actually interact.
‘A tract that is wholly sand:’ engineering military environments in Libya

In the late 1940s and early 1950s engineers from the U.S. Army Corps of Engineers constructed military facilities across newly independent Libya. This article examines how the local environment - namely the Sahara - shaped how these engineers planned for and carried out their assigned tasks. Though engineers initially hoped to apply experiences from the U.S. to things such as runway construction, they quickly learned that blowing sand, high temperatures and locust invasions could stymie their efforts. Engineers had to rethink what they thought they knew about things as mundane as concrete mixtures and wind-bearing loads. In doing so they created new networks of knowledge about building in hostile environments. Indeed, though long ignored in the scholarly literature on engineering, aviation and U.S. strategic deployments, the environment is everywhere in the documentary record about postwar military construction programs. This article, like the people it considers, takes the sand seriously. In doing so it also illuminates the surprisingly intimate ways that national security meets the everyday.
Sorafenib-mediated Mcl-1 and cFLIPL down-regulation synergistically increase TRAIL lethality in human leukemia cells

B42 In the present study, interactions between the Raf and multi-kinase inhibitor Sorafenib and TRAIL (TNF-related apoptosis-inducing ligand) were investigated in malignant hematopoietic cells. Pretreatment (24h) of U937 leukemia cells with 7.5 μM sorafenib, a concentration that was minimally toxic, dramatically and synergistically potentiated apoptosis induced by sub-lethal concentrations of TRAIL/Apo2L (e.g., 75ng/ml). Similar interactions were observed in other malignant hematopoietic cells including Raji, Jurkat, Karpas, K562, U266 cells and primary AML blasts. Notably, the combination was minimally toxic to normal CD34+ bone marrow cells. Exposure of sorafenib-pretreated cells to TRAIL potently and rapidly induced mitochondrial injury and release of cytochrome c, Smac and AIF into the cytosol, and caspase -9, -3, -7, and -8 activation. Sorafenib pretreatment also downregulated Bcl-xL and abrogated Mcl-1 expression, while co-administration of TRAIL strikingly increased Bid activation, conformational change of Bak (ccBak) and Bax (ccBax), and Bax translocation. Ectopic Mcl-1 expression significantly attenuated sorafenib/TRAIL-mediated lethality and dramatically reduced ccBak while minimally affecting levels of ccBax. Similarly, inhibition of the receptor-mediated apoptotic cascade (i.e., in U937 cells ectopically expressing a caspase-8 dominant-negative construct) significantly blocked Sorafenib/TRAIL-induced lethality but not Mcl-1 down-regulation or Bak/Bax conformational change, indicating that TRAIL-mediated receptor pathway activation is required for maximal lethality. No changes were observed in levels of DR4/DR5 or recruitment of procaspase-8 or FADD to the death-inducing signaling complex (DISC); however, sequential administration of sorafenib/TRAIL strikingly increased activation of DISC-associated procaspase-8. Attention then focused on cFLIP (FLICE-inhibitory protein), a potent procaspase-8 inhibitor. Pre-exposure of cells to sorafenib led to marked cFLIPL down-regulation, but no changes in expression of the short form of this protein (cFLIPS). Mooreover, sorafenib-mediated cFLIPL downregulation involved a translational mechanism associated with diminished eIF4E phosphorylation. Notably, ectopic expression of cFLIPL significantly reduced sorafenib/TRAIL lethality. Together, these results, taken in conjunction with earlier findings, suggest that in human leukemia cells, sorafenib potentiates TRAIL-induced lethality by down-regulating Mcl-1 and cFLIPL, most likely at the translational level, and these events cooperate to promote simultaneous engagement of the intrinsic and extrinsic apoptotic cascades, culminating in pronounced mitochondrial injury and apoptosis. They also suggest that a strategy combining sorafenib with TRAIL warrants attention in leukemia and possibly other hematologic malignancies.
Statistical monitoring of over-dispersed multivariate count data using approximate likelihood ratio tests

In this paper, we develop a statistical monitoring scheme for multivariate count data. In many applications involving multivariate count data, individual variables are not only correlated to each other, but also over-dispersed. Traditional statistical monitoring methods for multivariate count data that assume simple statistical models fail to fit the data collected when the underlying process is under normal working state, also referred to as the in-control state. Therefore, we propose a monitoring scheme which is based on the Poisson–multivariate Gaussian mixed model. Although such models are quite flexible, efficient statistical monitoring schemes for such models have not been developed. In this paper, we develop likelihood ratio test-based monitoring schemes that are shown to be superior to standard multivariate statistical monitoring schemes. The key challenge in developing likelihood ratio test for the Poisson–multivariate Gaussian mixed models is that the likelihood function can only be calculated b...
Reproductive Behavior by a Female Songbird: Differential Stimulation by Natal and Alien Song Dialects

Les femelles de Zonotrichia leucophrys nuttalli repondent plus au point de vue reproducteur (construction du nid) au chant des mâles qui possede leur dialecte natal (clair) qu'au chant qui comporte un dialecte etranger (avec vibrations)
A Child's Game with Permutations

forming a hexahedron. 6. Tuck D under AB (or A under DC) and press up on B and C until DC and BA coincide. The rigid, self-stabilized model with no open edges thus produced can be collapsed for storage or transportation and reconstituted when desired without staples or adhesives. The tetrahedron is a bisphenoid or double wedge, a special isosceles tetrahedron. The envelope must have r = BC/AB > 1. The larger r is, the more elongated the tetrahedron. The smaller r is, the flatter the tetrahedron. When r = 1, the cut envelope flattens into three superposed squares. For the average small business envelope, r is about 1.76 which deviates little from \/3, so the tetrahedron formed from it is almost regular. Raw material for the model making is plentiful in used envelopes slit open along the long flap edge, and in the return envelopes so often included in junk mail. The ratio r can always be modified by cutting the envelope. If an envelope of the desired size and r is not available, one can always be made by folding a rectangular sheet of the proper dimensions into two superposed rectangles and joining them along the shorter edges with sticky tape or, preferably, with flaps previously provided for gluing. The larger the envelope, the stiffer the paper should be. When told about this construction method, Mary Krimmel of La Jolla, California, was so enthusiastic that she used new envelopes to make tetrahedral place cards for her next dinner party. Messages were placed inside in Chinese fortune cookie fashion.
Mechanisms for the Generation of Oxygen Radicals by Drugs

In this report I will give a brief overview of drug-dependent metabolic reactions that can generate reactive oxygen species in tissues. The term drug is used here in its widest sense and includes any physiologically useless compound, either synthetic or naturally occurring, that can transfer one or two electrons to dioxygen via enzyme-catalyzed reactions. At the molecular level it is an enzyme that recognizes a specific structure and sustains the reaction. Therefore, a discussion of biochemical mechanisms is primarily concerned with the nature of the reaction and the identity of enzymes that catalyze reactions. The following review follows this general plan and focuses on enzymes that catalyze oxidation or reduction of functional groups in xenobiotics that often lead to the generation of oxygen radicals.
ACUTE COMPARTMENT SYNDROME OF THE ARM

Compartment syndrome of the arm, although uncommon, may result in significant disability if the diagnosis is missed. A high index of suspicion is needed, particularly in those patients at high risk, especially intoxicated or comatose patients. This article discusses the relevant anatomy, pathogenesis, diagnosis, prognosis, and complications of this syndrome.
Ribosomal Protein S24 Gene Is Mutated in Diamond-Blackfan Anemia.

Diamond-Blackfan anemia (DBA) is a congenital red cell aplasia with marked clinical heterogeneity, an increased risk of malignancy and mutations in ribosomal protein (RP) S19 in 25% of probands. To identify other gene(s) mutated in DBA and investigate their expression and function, we performed a genome-wide screen using a 10,000 single nucleotide polymorphism mapping set (Affymetrix) on a large family comprising 10 informative meioses. We found linkage of the DBA phenotype to regions on chromosome 8q, 10 and 6. The RP gene RPS24, is located in the linked region on chromosome 10; we sequenced exons, intron-exon boundaries and the promoter regions in this family, and found a nonsense mutation (316C>T) in exon 4 of RPS24 in five affected individuals, and a wild type sequence in five unaffected family members. This mutation causes the change of Gln106STOP and is predicted to result in formation of a truncated RPS24 protein. Subsequently, we sequenced DNA from 215 unrelated DBA probands, 30 with RPS19 mutations and 185 without. We found another nonsense mutation in exon 2 in a sporadic case, and a splice site deletion resulting in skipped exon 2 in another proband and in his father; over 200 control individuals did not have any of the above sequence changes, indicating that they are pathogenic mutations. To explore the normal role of RPS24 and consider how its dysfunction might result in DBA we performed real time RT-PCR (rt-PCR) and western blotting experiments on 20 normal human tissues and on lymphoblastoid cell lines from diseased and control individuals. Interestingly, rt-PCR of total human RPS24 and RPS19 mRNA revealed a tissue-specific variation in expression level. We found co-ordinate expression of both genes in the majority of studied tissues. Lymphoblastoid cell lines from both probands with nonsense mutations showed a reduced level of RPS24 mRNA, suggesting degradation of mutated transcripts due to nonsense mediated decay, while the RPS19 mRNA level in these patients was normal or elevated. Western blot experiments revealed a reduction of RPS24 protein in lymphoblastoid cell lines from all three mutated probands compared to control samples. Interestingly, co-ordinate expression of RPS24 and RPS19 protein was found in these patients as well as in other patients with RPS19 mutations or without any mutations, suggesting co-regulation of RP expression. To determine whether recruitment of mRNA to polysomes was impaired in DBA patients, we separated lymphoblast cell line lysates from nine diseased and four control individuals on sucrose gradients. We did not detect any significant difference in the RNA ratio of polysome-bound/free ribosomal subunits between diseased and control samples (p In summary, our results suggest that in addition to RPS24 and RPS19, which are mutated in ~ 27% of index cases, other DBA genes are also RP genes or genes involved in ribosome biogenesis or translation, and reinforce the notion that DBA is a ribosomal disease. This study opens new avenues for studying and understanding the pathogenesis of DBA.
Channelized front ends for broadband analog & RF signal processing with merged LO synthesis

Frequency domain processing of broadband signals that relies on decomposing the incident spectrum into multiple channels for digitization is an attractive alternative to timedomain processing. Channelized architectures can be utilized for several analog and RF signal processing tasks, such as data conversion, broadband radio receivers and spectrum analysis. A channelized front end based on cascaded image-reject stages which significantly simplifies the frequency synthesis requirement in such architectures is proposed in this paper. Analog non-idealities in such front ends are discussed.
Topics in Perturbative QCD Beyond the Leading Order

Quantum Chromodynamics (QCD) is the most promising candidate for a theory of strong interactions.
T-Lymphocytes: Mature Polyclonal and Antigen-Specific Cell Culture

Methods for T-cell culture, manipulation and functional evaluation continue to evolve at an astonishing rate. The discovery of IL-2 and other cytokines as well as the surface receptors and coreceptors important in T-cell activation has led to the design of reagents that have improved T-cell culture. Because lymphoid cells are composed of a heterogeneous mixture of cell lineages, it is most important to work with a well-defined and phenotyped population of T-cells. The development of techniques such as membrane cell tracking dyes and intracellular cytokine staining now allow the characterization of individual T-cells and T-cell subsets. Previously, cells had to be separated and cultured as individual subsets or clones to acquire the information now available through these techniques. Because of the interdependence of T-cell subsets such as helper and cytotoxic cells, separate culture does not permit physiologic interaction among cells. In vitro culture itself is only a rough approximation of the interactions in vivo. As more is learned about the cytokines and surface receptors important to T-cell interactions with other cells in the body, in vitro models will likely evolve to emulate the structure of a lymph node, an evolutionarily optimized T-cell culture vessel.
Spatial-temporal campus crime pattern mining from historical alert messages

A recent slew of violence-related events have incited a flood of discussions revolving around issues such as gun control and domestic safety abroad. An issue that hits close to home is the concern of safety at urban universities. Studying the geo-temporal distribution of crime within and around a university setting is important for understanding crime type occurrence patterns. These patterns can be mined from alert messages posted by universities on various media outlets, such as email, Twitter, and Facebook. We believe that the knowledge inferred from this data can be a crucial factor in creating a safe environment to protect students, faculty members, and administration. The observed patterns can help devise more effective crime prevention practices within and around a university campus, such as the optimization of the deployment of law enforcement resources according to recognized temporal and location patterns or the modification of patrol routes of police officers. Additionally, the observed geo-temporal patterns may help establish joint crime prevention programs between a university and the city. This research project aims to develop a system that automatically collects crime-logged data from publicly available sources, organizes it for mining, and creates visual mining tools to explore the data. We use Google Maps to render the data geographically.
Toddler hand preference trajectories predict 3-year language outcome.

A growing body of work suggests that early motor experience affects development in unexpected domains. In the current study, children's hand preference for role-differentiated bimanual manipulation (RDBM) was measured at monthly intervals from 18 to 24 months of age (N = 90). At 3 years of age, children's language ability was assessed using the Preschool Language Scales 5th edition (PLS™-5). Three distinct RDBM hand preference trajectories were identified using latent class growth analysis: (1) children with a left hand preference but a moderate amount of right hand use; (2) children with a right hand preference but a moderate amount of left hand use; and (3) children with a right hand preference and only a mild amount of left hand use. Stability over time within all three trajectories indicated that children did not change hand use patterns from 18 to 24 months. Children with the greatest amount of preferred (i.e., right) hand use demonstrated higher expressive language scores compared to children in both trajectories with moderate levels of non-preferred hand use. Children with the greatest amount of right hand use also had higher scores for receptive language compared to children with a right hand preference but moderate left hand use. Results support that consistency in handedness as measured by the amount of preferred hand use is related to distal language outcomes in development.
Nitrite/Nitrate and Estrogen Receptor-alpha Activation

3658 The incidence of breast cancer is 1 out of 7 women in the United States. Although the exact cause of breast cancer is not known, studies suggest that environmental and dietary exposures to chemicals that mimic estrogens may be risk factors for the disease. Nitrite and nitrate are anions that we are exposed to through the environment as well as the diet. To determine whether nitrite and/or nitrate have estrogen-like activity, the effects of these anions on estrogen receptor-alpha (ERα), estrogen-regulated genes and protein were measured in MCF-7 human breast cancer cells. Treatment of cells with 1uM nitrite or 1uM nitrate resulted in a 2.5-fold increase in progesterone receptor (PgR) mRNA and a 2.9-fold increase in PgR protein that were blocked by the antiestrogen ICI-182,780 suggesting that the effects of nitrite and nitrate are mediated by ERα. Treatment of cells with 1uM nitrite or 1uM nitrate also induced a 2.5-fold increase in pS2 mRNA and a 2-fold increase in cathepsin D mRNA that were blocked by the antiestrogen ICI-182,780 further suppporting a role of ERα. In transient cotransfection assays of wild type ERα and an estrogen response element-reporter construct, nitrite and nitrate stimulated chloramphenicol acetyltransferase (CAT) activity 2.5-3 fold. In growth assays, both anions significantly stimulated the proliferation of MCF-7 cells compared with cells grown in estrogen-depleted medium. By day four, there was a 4-fold increase in cell number. The addition of an antiestrogen blocked growth. In binding assays, nitrite blocked the binding of estradiol to ERα with an approximate Ki = 10-10 M, suggesting that the compound has a high affinity interaction with the ligand binding domain of the receptor. Cos-1 cells transfected with the chimeric receptor GAL-ER, containing the ligand binding domain of ERα, showed that the effects of nitrite and nitrate are mediated through the hormone binding domain of the receptor. Mutational analysis demonstrated that the amino acids C381, C417, C447, H516, K520, K529 and N532 in the ligand binding domain may be involved in interactions with nitrite and nitrate. In summary, this data show that nitrite and nitrate may be potential risk factors for breast cancer.
Angioplasty to promote arteriovenous fistula maturation and maintenance

The arteriovenous fistula is currently the best permanent access for the hemodialysis patient. Unfortunately, stenosis impairs maturation, long-term survival, and function of the arteriovenous fistula. Angioplasty currently is the best procedure for the treatment of immature and dysfunctional arteriovenous fistulas. In this review, the authors discuss the optimum time to evaluate arteriovenous fistulas for maturity, methods of evaluation for maturity, and the role of angioplasty in salvaging immature arteriovenous fistulas. The review also discusses the effect of stenosis on dysfunction in mature arteriovenous fistulas and the role of angioplasty to treat this complication. Finally, the impact of cutting balloons and drug-eluting balloons in the treatment of resistant and recurrent stenosis, respectively, is also discussed.
BODY IMPEDANCE OF NONHUMAN PRIMATES UNDER CONSTANT VOLTAGE SHOCK CONDITIONS

ABSTRACT Tests were conducted on two Rhesus monkeys to determine the range of variation in body impedance under constant-voltage, low-source-impedance shock conditions. Shock voltages ranged from 10 to 240 volts for various hand-electrode conditions including dry hands, hands wetted with saline water, and mixtures of saline water and detergents. The duration of exposure was limited by ground fault current interrupters to prevent fibrillation during the tests. Considerable data resulted and representative summaries of these data are presented in two groups: (1) dual trace oscillographs of applied voltage and current; and (2) plots of the instantaneous relationship between voltage and currents for several different body paths, such as hand-to-hand, foot-to-foot, and hand-to-foot. One important development during these tests was the identification of a precursor current spike. This spike was significantly larger than the follow current. The plots of the instantaneous relationship between applied voltage and body currents showed a high degree of nonlinearity and time dependence. For example, at low voltages, the body impedance was strongly capacitive, whereas at higher voltages it became largely resistive. In one animal test, the high-impedance skin broke down, resulting in much lower body impedance. Such phenomena as the precursor current spike or the breakdown of the high-impedance skin could be unnoticed factors which aggravate the electrical shock hazard.
Model Reduction with Mean-Axes in Deformable Multibody Dynamics

Dynamic analysis of multibody systems containing deformable bodies is computationally time consuming due to the large number of deformation degrees-of-freedom. Transforming the equations of motion to modal space and then truncating a significant number of higher frequency modes can greatly reduce the problem size and hence improve the computational time. There is a misconception that if mean-axes are adopted as the floating reference frame for a deformable body, modal truncation will yield inaccurate results. This may be due to the misunderstanding that only free-free modes are compatible with the mean-axes and, therefore, mean-axes cannot be used for constrained systems. This paper attempts to clarify this issue and shows that it is perfectly fine to use the standard static and normal modes, as they are obtained in structural analysis, in conjunction with the mean-axis conditions.
Comment on “Volumetric and compressibility behavior of l-valine in aqueous poly ethylene glycol solutions at T = (298.15, 308.15 and 318.15) K”

Abstract Search of the chemical literature reveals that the limiting apparent molal volumes for l -valine dissolved in water differ significantly from published literature values. The calculated limiting apparent molal volumes reported by Moradian and coworkers [J. Mol. Liq., in press, doi: https://doi.org/10.1016/j.molliq.2018.08.027 ] were φvo = −145.8768 cm3 mol−1 and φvo = −273.5163 cm3 mol–1 at 308.15 K and 318.15 K, respectively. Published literature values were in the range of about φvo = 90 cm3 mol−1 to φvo = 92 cm3 mol−1.
Variable subject pronominal expression in non-finite clauses: Implications for variant patterns and emergent contexts

Abstract This work presents the first large-scale analysis of the typologically and dialectally unusual appearance of variable pronominal subjects in non-finite clauses. A comparative variationist analysis of 703 Spanish adverbial purpose clauses (both finite and non-finite) reveals that, despite a significant difference in rates of pronoun expression across clause types (subjunctive and infinitival), the linguistic factors constraining null vs. expressed pronominal subjects are nearly identical. This result suggests a similar function for subject pronouns that operates independently of clause types (finite/non-finite). The usage-based analysis allows us to identify the locus of emergence for the unusual morphosyntactic construction [para + ( subject ) + infinitive ] as appearing in a non-canonical discourse context. This construction may be evidence in favor of a hypothesized general pattern of SVO word order solidification in Caribbean Spanish.
Don't Reinvent the Wheel: Capitalizing on What Others Already Know about Teaching Topics in Evolution

What knowledge do you need to be an effective instructor? One key type of knowledge is pedagogical content knowledge (PCK), which includes awareness of how students are likely to think about a topic and where they will struggle as they learn that topic. We propose PCK as a valuable framework for reflecting on your own knowledge for teaching topics in evolution. We have created a searchable file that uses PCK as a framework to organize over 400 peer-reviewed papers from 40+ journals to give you better access to relevant resources for teaching evolution to undergraduates and advanced high school students. None of us have time to read 400 papers to inform our teaching, so we provide tips to maximize your use of this collective knowledge in the time you have available. We have written these to be useful to instructors across career stages.
The Roles of Human DNA Methyltransferases and Their Isoforms in Shaping the Epigenome

A DNA sequence is the hard copy of the human genome and it is a driving force in determining the physiological processes in an organism. Concurrently, the chemical modification of the genome and its related histone proteins is dynamically involved in regulating physiological processes and diseases, which overall constitutes the epigenome network. Among the various forms of epigenetic modifications, DNA methylation at the C-5 position of cytosine in the cytosine–guanine (CpG) dinucleotide is one of the most well studied epigenetic modifications. DNA methyltransferases (DNMTs) are a family of enzymes involved in generating and maintaining CpG methylation across the genome. In mammalian systems, DNA methylation is performed by DNMT1 and DNMT3s (DNMT3A and 3B). DNMT1 is predominantly involved in the maintenance of DNA methylation during cell division, while DNMT3s are involved in establishing de novo cytosine methylation and maintenance in both embryonic and somatic cells. In general, all DNMTs require accessory proteins, such as ubiquitin-like containing plant homeodomain (PHD) and really interesting new gene (RING) finger domain 1 (UHRF1) or DNMT3-like (DNMT3L), for their biological function. This review mainly focuses on the role of DNMT3B and its isoforms in de novo methylation and maintenance of DNA methylation, especially with respect to their role as an accessory protein.
Next Generation of Adeno-Associated Virus Vectors for Gene Therapy for Human Liver Diseases

Recombinant vectors based on a nonpathogenic parvovirus, the adeno-associated virus (AAV), have taken center stage in the past decade. The safety of AAV vectors in clinical trials and clinical efficacy in several human diseases are now well documented. Despite these achievements, it is increasingly clear that the full potential of AAV vectors composed of the naturally occurring capsids is unlikely to be realized. This article describes advances that have been made and challenges that remain in the optimal use of AAV vectors in human gene therapy applications.
Predictive value of olfactory impairment for cognitive decline among cognitively normal adults.

Objective Dementia affects over 47 million people worldwide. Olfactory impairment (OI) is a well-established predictive marker of conversion to dementia among those with mild cognitive impairment. This systematic review aims to describe the predictive value of OI for future cognitive decline among cognitively normal adults. Methods A literature search encompassing PubMed, EMBASE, and Cochrane for longitudinal cohort studies following cognitively normal adults with baseline OI in comparison to those without OI reporting incident cognitive impairment or dementia was included. Study design, participant demographics, olfactory testing method, and incidence of cognitive decline or dementia were abstracted. Two investigators independently reviewed all articles. Results The search yielded 964 nonduplicate abstracts and titles, from which 19 full-text articles were reviewed and 10 were included. Studies included were all good quality (mean score 8.7 of 9), and all studies (100%) found a statistically significant association between baseline OI and incident cognitive decline compared with normosmic controls. Conclusion The existing literature suggests that OI predicts future cognitive decline among cognitively normal adults, supporting olfactory evaluation as a low-cost, minimally invasive, and widely available screening tool to be used in combination with other tests to identify adults at early risk of dementia. Level of evidence NA Laryngoscope, 130:840-847, 2020.
The influence of superabsorbent polymer on the properties of alkali-activated slag pastes

Abstract This paper discusses the interaction between superabsorbent polymer (SAP) and alkali-activated slag pastes and the influence of SAP on the properties of the pastes. SAP showed higher absorption in pore solutions extracted from alkali-activated slag pastes compared to that extracted from portland cement paste. Hydrogel desorption in alkali-activated slag matrix activated with Na2CO3 was noticeably delayed compared to alkali-activated slag matrix activated with NaOH matrix or portland cement matrix; this is attributed to a significant delay in the solid skeleton development in this matrix. Addition of SAP was shown to be effective in reducing autogenous shrinkage in alkali-activated slag pastes. A general reduction in compressive strength and electrical resistivity was observed in alkali-activated slag pastes when SAP was added; macrovoid formation and increased overall water/binder are possible reasons for this reduction, respectively.
A Fast High-Affinity Fluorescent Serotonin Biosensor Engineered from a Tick Lipocalin

Serotonin (5-HT) is an important signaling monoamine in and beyond the central nervous system (CNS). We report structure-guided engineering of a green fluorescent, genetically encoded serotonin sensor (G-GESS) from a 5-HT-binding lipocalin in the soft tick. G-GESS shows fast response kinetics and high affinity, specificity, brightness, and photostability. We used G-GESS to image 5-HT dynamics in vitro and in behaving mice, demonstrating the broad utility of this novel biosensor.
THE ROLE OF NUMERACY AND IMPULSIVITY IN INTERTEMPORAL CHOICE AND DECISION MAKING

A growing body of research has indicated a relationship between numeracy and decision making and that lower numerate people display more disadvantageous decisions. In the domain of intertemporal choice, researchers have long been using impulsivity to address choice preference. To further illuminate the psychological mechanisms of making intertemporal choices, the present study examined the role of impulsivity and numeracy in intertemporal choice, in the presence of each other. The study adopted both subjective and numeracy scales. These scales correlated with each other and with intertemporal choice preference. Moreover, it was found that after controlling for impulsivity, the object numeracy was significantly associated with choice preference, with higher numerate participants showing a stronger preference toward the later larger gains over the sooner smaller gains. Thus, the study indicated that intertemporal choice preference could be attributed to both impulsivity and numeracy.