cssi/SciSciGPT-SciSciNet huggingface dataset:
Biometrical genetic analysis of ethanol's psychomotor stimulant effect.

Hereditary influences on psychomotor stimulant effects of ethanol (ETOH) were studied in a classical Mendelian cross of DBA/2Abg (D2) and C57BL/6Abg (B6) inbred mouse strains. A dose-response study with nine doses (0–3.5 g/kg ip) indicated that B6 mice lack the activational limb of the biphasic curve ( 1.5 g/kg), as assessed in a 15-min test. D2 mice ran greater distances and ran faster, at doses up to 2.5 g/kg. B6 mice showed no increments in speed or distance at these doses that activated D2 mice. Several other indices reinforced the conclusion of ETOH-induced behavioral activation in D2 mice and lack there of in B6 mice (traditional photobeam interruptions—horizontal counts; center distance; vertical movements; inactive time; as well as derived indices of running speed and average length of each movement). The F1, F2, and backcross generations produced dose-response curves that showed additive inheritance of the activational response to doses below 1.5 g/kg. A second study (n= 1446) examined response to 1.5 g/kg with a within-subjects design in the full Mendelian cross. This study verified the completely additive mode of inheritance for the total distance measure suggested in the dose-response study, and showed that sex linkage and sex differences were not present. Narrow sense heritability of the ETOH activation response (indexed by total distance) was calculated at 0.35 and ∼3 loci were estimated to be responsible for the B6/D2 difference. The other phenotypes (described above) also showed strongly additive genetic control. These studies indicate that the psychomotor stimulant effect of ETOH in mice is under genetic influence and that the control mechanism is a simple, small-sized polygenic system, with an uncomplicated mode of inheritance that should make it amenable to further characterization at a functional level.
Quantitative spectrophotometric determination of human and rat urinary dimethylamine

Abstract A simple, specific, quantitative, and reproducible method for the determination of urinary dimethylamine (DMA) was described. It is based on removal of interfering compounds from urine by cation-exchange chromatography and quantitation of eluted DMA by formation of its copper dimethyldithiocarbamate complex. In benzene, this complex had an absorption maximum at 434 nm, which was linearly related to the original DMA concentration in the range of 0–160 nmol/ml. The method was employed to determine human and rat urinary excretion levels and to determine the extent of DMA metabolism in rats. Values obtained were in close agreement with those previously reported in the literature.
Erythropoietin (Ep) production and Kupffer cell alterations following nephrectomy, hypoxia, or combined nephrectomy and hypoxia.

SummaryHepatic cells were evaluated using scintillation scanning and counting, autoradiography, and planimetry under conditions favoring extrarenal Ep production. In general, Kupffer cell activity paralleled Ep production whereas the liver parenchymal cells did not manifest significant changes. The studies suggest that the Kupffer cell may be an extrarenal cellular site of Ep production.
Regulation of cytochrome b5 gene transcription by Sp3, GATA-6, and steroidogenic factor 1 in human adrenal NCI-H295A cells

Sex steroid synthesis requires the 17,20 lyase activity of P450c17, which is enhanced by cytochrome b5, acting as an allosteric factor to promote association of P450c17 with its electron donor, P450 oxidoreductase. Cytochrome b5 is preferentially expressed in the fetal adrenal and postadrenarchal adrenal zona reticularis; the basis of this tissue-specific, developmentally regulated transcription of the b5 gene is unknown. We found b5 expression in all cell lines tested, including human adrenal NCI-H295A cells, where its mRNA is reduced by cAMP and phorbol ester. Multiple sites, between -83 and -122 bp upstream from the first ATG, initiate transcription. Deletional mutagenesis localized all detectable promoter activity within -327/+15, and deoxyribonuclease I footprinting identified protein binding at -72/-107 and -157/-197. DNA segments -65/-40, -114/-70 and -270/-245 fused to TK32/Luc yielded significant activity, and mutations in their Sp sites abolished that activity; electrophoretic mobility shift assay (EMSA) showed that Sp3, but not Sp1, binds to these Sp sites. Nuclear factor 1 (NF-1) and GATA-6, but not GATA-4 bind to the NF-1 and GATA sites in -157/-197. In Drosophila S2 cells, Sp3 increased -327/Luc activity 58-fold, but Sp1 and NF-1 isoforms were inactive. Mutating the three Sp sites ablated activity without or with cotransfection of Sp1/Sp3. In NCI-H295A cells, mutating the three Sp sites reduced activity to 39%; mutating the Sp, GATA, and NF-1 sites abolished activity. In JEG-3 cells, GATA-4 was inactive, GATA-6 augmented -327/Luc activity to 231% over the control, and steroidogenic factor 1 augmented activity to 655% over the control; these activities required the Sp and NF-1 sites. Transcription of cytochrome b5 shares many features with the regulation of P450c17, whose activity it enhances.
Dose–response model for Burkholderia pseudomallei (melioidosis)

Aims: The objective of this study was development of a dose–response model for exposure to Burkholderia pseudomallei in different animal hosts and analysis of the results. The data sets with which the model was developed were taken from the open literature. Methods and Results: All data sets were initially tested for a trend between dose and outcome using the Cochran–Armitage test. Only data showing a statistically significant trend were subjected to further analysis (fitting with parametric dose–response relationships). Dose–response relationships (exponential, beta-Poisson and log-probit) were fit to data using the method of maximum likelihood estimation. Conclusions: Dose–response analysis of BALB/c mice, C57BL/6 mice, guinea pigs and diabetic rats showed that BALB/c mice exposed intranasally (i.n.) and guinea pigs exposed intraperitoneally (i.p.) are significantly more sensitive to B. pseudomallei than C57BL/6 mice exposed i.n. and diabetic rats exposed i.p. Significance and Impact of the Study: The results confirmed the findings of a study of outbreak data that the diabetic population is more susceptible to infection with B. pseudomallei than the general population. The low dose prediction from best fit dose–response models can be used to draw guidelines for public health decision making processes, including consideration of sensitive subpopulations.
Biosynthesis of succinoglycan, a symbiotically important exopolysaccharide of Rhizobium meliloti

The exo genes of Rhizobium meliloti are needed for the synthesis of an acidic exopolysaccharide, succinoglycan. We have assigned biosynthetic roles to the products of the exo genes by characterizing succinoglycan biosynthetic intermediates from exo mutant strains. We propose a model of succinoglycan biosynthesis in which the products of the exoY and exoF genes function in the addition of the first sugar, galactose, to the lipid carrier; the products of the exoA, exoL, exoM, exoO, exoU, and exoW genes function in subsequent sugar additions; and the product of the exoV gene functions in the addition of pyruvate. The products of the exoP, exoQ, and exoT genes are required for polymerization of the octasaccharide subunits or transport of the completed polymer.
Barth on the divine 'conscription' of language

L'A. evalue la position traditionnelle mais difficile de Karl Barth selon laquelle Dieu affecte a travers sa revelation le langage humain en lui faisant faire reference aux realites divines et en lui donnant la possibilite de pretendre a la verite. Ce theme apparait frequemment dans les Church Dogmatics. L'A. propose six interpretations possibles de la position de Barth tout en affirmant que seule la derniere fait justice des mots de Barth. En plus de creer de graves problemes semantiques, la proposition de Barth est contradictoire. Ceci provient de sa conception de la revelation
X-ray Crystallographic Analyses of Pig Pancreatic α-Amylase with Limit Dextrin, Oligosaccharide and α-Cyclodextrin †,‡

Further refinement of the model using maximum likelihood procedures and re-evaluation of the native electron density map has shown that crystals of pig pancreatic α-amylase, whose structure we reported more than fifteen years ago, in fact contain a substantial amount of carbohydrate. The carbohydrate fragments are the products of glycogen digestion carried out as an essential step of the protein's purification procedure. In particular, the substrate-binding cleft contains a limit dextrin of six glucose residues, one of which contains both α-(1,4) and α-(1,6) linkages to contiguous residues. The disaccharide in the original model, shared between two amylase molecules in the crystal lattice, but also occupying a portion of the substrate binding cleft, is now seen to be a tetrasaccharide. There are, in addition, several other probable monosaccharide binding sites. To these results we have further reviewed our X-ray diffraction analysis of α-amylase complexed with α-cyclodextrin. α-Amylase binds three cyclodextrin molecules. Glucose residues of two of the rings superimpose upon the limit dextrin and the tetrasaccharide. The limit dextrin superimposes in large part upon linear oligosaccharide inhibitors visualized by other investigators. By comprehensive integration of these complexes we have constructed a model for the binding of polysaccharides having the helical character known to be present in natural substrates such as starch and glycogen.
The Search for Electromagnetic Induction 1820–1831

The discovery in 1820 by Hans Christian Oersted (1777–1851) of the magnetic field that surrounds a conductor during the passage of an electric current, aroused a wave of interest among men of science in England, France, Germany, Italy, and the United States. The apparatus required to verify his results was easily put together, and anyone who cared to do so could see for himself the nature of the indissoluble connection between electricity and magnetism, which, though long suspected and vaguely adumbrated, was now precisely defined and made a permanent portion of the corpus of science. As one subsequent discovery after another was announced from various places, the recognition became widespread that a large and unexploited field for investigations and applications had been opened up. Only one week after word of Oersted’s experiment reached Paris, Andre-Marie Ampere (1775–1836) discovered that two parallel wires carrying parallel currents attract each other. Less than two months after Oersted’s publication, J.S.C. Schweigger (1779–1857), at the University of Halle, reasoned that if the current in a single wire held above the compass needle would deflect the needle to the right, while the same wire placed beneath the needle would deflect it to the left, one turn of wire, placed around the needle in the plane of the magnetic meridian, would exert twice the deflecting force of a single wire; and a coil made of ten turns of insulated wire would exert twenty times the force. Thus were born Schweigger’s multiplier and Ampere’s solenoid. In rapid succession followed the electromagnet (Arago and Davy), the astatic galvanometer (Nobili), electromagnetic rotations (Wollaston and Faraday), and the science of electrodynamics (Ampere).
Numerical Experiments on Adiabatic Shear Band Formation in One Dimension

Abstract Adiabatic shear band formation in an elastic, thermoviscoplastic, simple material is studied in the context of unidirectional shearing of a slab. The effect of varying the thermal softening behavior of the material on localization strain and postlocalization morphology is studied for a rigid, perfectly plastic material; the material parameters are appropriate for a high-strength steel. In this case it is demonstrated that localization of the strain rate can be transient . A coupling between linear-elastic response and the basic thermoviscoplastic localization mechanism is explored in the absence of strain hardening. Last, the flow law is modified to include strain hardening in order to simulate a high-rate torsion test on OFHC copper. In this case localization is initiated by thermal boundary layer diffusion and the solution takes on a complex, apparently nonperiodic, postlocalization morphology quite different from that in the perfectly plastic cases.
An integrated transcriptional regulatory circuit that reinforces the breast cancer stem cell state

Cancer stem-like cells (CSCs) are a highly tumorigenic cell type present as a minority population in developmentally diverse tumors and cell lines. Using a genetic screen in an inducible model of CSC formation in a breast cell line, we identify microRNAs (miRNAs) that inhibit CSC growth and are down-regulated in CSCs. Aside from the previously identified miR-200 family, these include the miR-15/16 (miR-16, miR-15b) and miR-103/107 (miR-103, miR-107) families as well as miR-145, miR-335, and miR-128b. Interestingly, these miRNAs affect common target genes that encode the Bmi1 and Suz12 components of the polycomb repressor complexes as well as the DNA-binding transcription factors Zeb1, Zeb2, and Klf4. Conversely, expression of the CSC-modulating miRNAs is inhibited by Zeb1 and Zeb2. There is an inverse relationship between the levels of CSC-regulating miRNAs and their respective targets in samples from triple-negative breast cancer patients, providing evidence for the relevance of these interactions in human cancer. In addition, combinatorial overexpression of these miRNAs progressively attenuates the growth of CSCs derived from triple-negative breast cancers. These observations suggest that CSC formation and function are reinforced by an integrated regulatory circuit of miRNAs, transcription factors, and chromatin-modifying activities that can act as a bistable switch to drive cells into either the CSC or the nonstem state within the population of cancer cells.
Oxalate exposure promotes reinitiation of the DNA synthesis and apoptosis of HK-2 cells, a line of human renal epithelial cells.

: Oxalate, a metabolic end product, is a major constituent of kidney stones. Previously, we and others have demonstrated that oxalate is toxic to renal epithelial cells. In the present study, we characterized oxalate-induced cell death in HK2 cells, a line of renal epithelial cells from the human kidney. For these studies, HK2 cells were exposed to oxalate for various time points. Cells were examined for nuclear morphology, DNA fragmentation, and expression of various apoptosis-related proteins. Apoptotic mode of cell death was also confirmed by TUNEL assay. Results from these studies revealed that oxalate exposure resulted in time-dependent increase in DNA fragmentation. Maximum DNA fragmentation was observed at 2–24 hours following oxalate exposure. Results from Western blot analysis demonstrated an increased expression of the FAS ligand. Taken together, these data reveal that oxalate-associated nephrotoxicity results from oxalate-induced apoptosis of renal epithelial cells.
A Review of Mixture and Non-Local Continuum Mechanics with Example Applications to Cohesive Sediments

The purpose here is to assess the potential application of mixture and nonlocal continuum models to cohesive sediments. Mixture models are discussed first. A review of this theory shows that this approach requires continuity and equations of motion for each constituent. A general constitutive model based on concepts from viscoelasticity is developed. The problem of the propagation of acoustic waves is examined as a special case of the model. For a two-constituent medium two dispersive acoustical modes are found; however, one is strongly attenuated. A mixture model is also applied to the problem of plane shear. The analysis shows solid displacement and fluid velocity profiles which can differ remarkably from the classic linear solutions. Next non-local models are investigated. This approach results in stress strain relations which are integrodifferential equations. Acoustical propagation for three different integral kernels is studied. All three models exhibit dispersion at low frequencies; however, there seems to be little practical difference between the solutions associated with the different kernels. The plane shear problem is also investigated. The analysis reveals displacement profiles which differ from the classic solution. The paper is concluded with a brief summary of results and some suggestions for more realistic applications.
Stepwise Recruitment of Components of the Preinitiation Complex by Upstream Activators In Vivo

Recently, it was found that if either the TATA binding protein or RNA polymerase II holoenzyme is artificially tethered to a promoter, transcription is activated. This finding provided presumptive evidence that upstream activating proteins function by recruiting components of the preinitiation complex (PIC) to the promoter. To date, however, there have been no studies demonstrating that upstream factors actually recruit components of the PIC to the promoter in vivo. Therefore, we have studied the mechanism of action of two disparate transactivating domains. We present a series of in vivo functional assays that demonstrate that each of these proteins targets different components of the PIC for recruitment. We show that, by targeting different components of the PIC for recruitment, these activating domains can cooperate with each other to activate transcription synergistically and that, even within one protein, two different activating subdomains can activate transcription synergistically by cooperating to recruit different components of the PIC. Finally, considering our work together with previous studies, we propose that certain transcription factors both recruit components of the PIC and facilitate steps in transcriptional activation that occur subsequent to recruitment.
Congressional Legitimation of Municipal Reform in the Philippines, 1954–1960

Filipino political leaders have been addressing themselves to the issue of municipal reform since the dawn of the twentieth century, but discussion of the issue never reached a high intensity until the then Institute of Public Administration of the University of the Philippines (established in 1954 under the aegis of American technical assistance) defined the issues more clearly. The thrust of this renewed enthusiasm in local government reform included greater local powers, lesser national supervision over local administrative activities, and lesser legislative meddling in municipal affairs. Being a highly centralized political system under which local and national officials (both elected and appointed) have created a civic culture consisting of national review of some local administrative decisions and local dependence upon congressional pork barrels for the financing of municipal projects, any advocacy of local autonomy had to come from the top of the Philippine political totem pole and any legitimation of municipal reform policy must take place in Congress.
Closed-streamline flows past rotating single cylinders and spheres - Inertia effects

The flow around a cylinder and a sphere rotating freely in a simple shear was studied experimentally for moderate values of the shear Reynolds number Re. For a freely rotating cylinder, the data were found to be consistent with the results obtained numerically by Kossack & Acrivos (1974), at least for Reynolds numbers up to about 10. Rates of rotation of a freely suspended sphere were also obtained over the same range of Reynolds numbers and showed that, with increasing Re, the dimensionless angular velocity does not decrease as fast for a sphere as it does for a cylinder. In both cases, photographs of the streamline patterns around the objects were consistent with this behaviour. Furthermore, it was found in each case that the asymptotic solutions for Re [Lt ] 1 derived by Robertson & Acrivos (1970) for a cylinder and by Lin, Peery & Schowalter (1970) for a sphere are not valid for Reynolds numbers greater than about 0.1, and that the flow remains steady only up to values of Re of about 6.
ADVANCED FMEA USING META BEHAVIOR MODELING FOR CONCURRENT DESIGN OF PRODUCTS AND CONTROLS

This paper presents the use of Advanced Failure Modes and Effects Analysis (AFMEA) as a methodology for the concurrent design of electro-mecha nical products and their control systems. The past two years have seen the extension of AFMEA to simulate dynamic changes of device operations using meta-behavior modeling. This approach can help engineers identify failure modes associated with controls and their interaction with physical systems and drive system design toward more reliable solutions. The proposed method uses behavior modeling to map control functions to physical entities and identifies failure modes as the departure from intended control functions. AFMEA provides a framework for controls and hardware developers to discuss and understand the relationship between sub-systems, controls, and overall system performance. An example of a power generation system illustrates how AFMEA applies to the early stages of layout and controls design.
Comparison of GH, IGF-I, and testosterone with mRNA of receptors and myostatin in skeletal muscle in older men

Growth hormone (GH), insulin-like growth factor I (IGF-I), and testosterone (T) are important mediators of muscle protein synthesis, and thus muscle mass, all of which decline with age. We hypothesized that circulating hormones would be related to the transcriptional levels of their respective receptors and that this expression would be negatively related to expression of the myostatin gene. We therefore determined content of mRNA transcripts (by RT-PCR) for GH receptor (GHR), IGF-I, androgen receptor (AR), and myostatin in skeletal muscle biopsy samples from 27 healthy men >65 yr of age. There were no significant relationships between age, lean body mass, or percent body fat and transcript levels of GHR, IGF-I, AR, or myostatin. Moreover, there were no significant correlations of serum GH, IGF-I, or T with their corresponding target mRNA levels (GHR, intramuscular IGF-I, or AR) in skeletal muscle. However, GHR was negatively correlated (r = -0.60, P = 0.001) with myostatin mRNA levels. The lack of apparent relationships of muscle transcripts with their respective ligands in healthy older adults suggests that age-related deficits in both GH and T may lead to an increase in myostatin expression and a disassociation in autocrine IGF-I effects on muscle protein synthesis, both of which could contribute to age-related sarcopenia.
Density Shock Waves in Confined Microswimmers.

Motile and driven particles confined in microfluidic channels exhibit interesting emergent behavior, from propagating density bands to density shock waves. A deeper understanding of the physical mechanisms responsible for these emergent structures is relevant to a number of physical and biomedical applications. Here, we study the formation of density shock waves in the context of an idealized model of microswimmers confined in a narrow channel and subject to a uniform external flow. Interestingly, these density shock waves exhibit a transition from ``subsonic'' with compression at the back to ``supersonic'' with compression at the front of the population as the intensity of the external flow increases. This behavior is the result of a nontrivial interplay between hydrodynamic interactions and geometric confinement, and it is confirmed by a novel quasilinear wave model that properly captures the dependence of the shock formation on the external flow. These findings can be used to guide the development of novel mechanisms for controlling the emergent density distribution and the average population speed, with potentially profound implications on various processes in industry and biotechnology, such as the transport and sorting of cells in flow channels.
Phase Distribution of Bubbly Flows under Terrestrial and Microgravity Conditions

We use direct numerical simulations to study phase distribution of bubbles under terrestrial and microgravity conditions. The full Navier-Stokes and en- ergy equations, for the flows inside and outside the bub- bles, are solved using a front tracking/finite difference technique. Both nearly spherical and deformable bub- bles are considered. For buoyancy-driven flows, spheri- cal bubbles at Re = O(10) and deformable ones at Re = O(100) exhibit a uniform spatial distribution at quasi steady-stateconditions,whilenearly spherical bubblesat Re = O(100) form horizontal rafts. Bubbles, driven by thermocapillary effects in microgravity, also form hori- zontal rafts, but due to an entirely different mechanism. When thermocapillary and buoyancy forces act in oppo- site directions, the raft formation is prevented and the bubbles form a large cluster that moves in the direction of buoyancy.
Multi-Fidelity Design Optimization Studies for Supersonic Jets Using Surrogate Management Frame Method

Design of the realistic supersonic jets has been challenging problem. The design space for a ground boom is known to be non-smooth and discontinuous. Due to those particular characteristics as such, gradient-based optimizer can not be employed to locate the global minimum, and gradient-free search method is more suitable for an extensive exploration in design sites. In this study we employ one of the direct search method, pattern search method which has been used for a general constrained optimization on filter methods. A general pattern search (GPS) method is the search algorithm which composes of the search step and the local poll step. Random global search is performed in the search step. In the poll step, the search directions are selected in a way that they can accelerate the convergence of search. A filter algorithm is combined with the PS to handle the mission constraints in a aggregate way. Moreover, to overcome the restriction to a finite set of directions in the GPS for local exploration, mesh adaptive direct search (MADS) method is introduced providing more search directions. A virtual mesh on the design space is constructed and as the algorithm iterates, the mesh can be refined or coarsened corresponding to the success of the search. This method is applied to the shape optimization of the low boom supersonic jet and the pattern search proceeds through the several iterations, until all the mission constrains are satisfied and aerodynamic/boom performance is improved. The objective function is the minimization of MTOW and the low ground boom is treated as one of the constraints.
Pneumoconiosis incidence analysis in 1956-2011 in Zhabei District of Shanghai

[Objective] To analyze the incidence of pneumoconiosis from 1956 to 2011 in Zhabei district in Shanghaiand to provide a basis for exploring intervention methods of pneumoconiosis.[Methods] The pneumoconiosis cases diagnosed in 1956-2011 were analyzed in Zhabei District.[Results] Since 1956,418 cases of pneumoconiosis have been diagnosed that mainly were stage Ⅰ,and tuberculosis rate was 13.40%.Male was dominant(92.58%),whose average age was 52.26 years with professional seniority being 21.05 years.Silicosis was dominant(60.00%),followed by founder pneumoconiosis(25.84%).Starting as a different era of dust exposure,the pneumoconiosis type became different significantly.The main types were silicosis and founder pneumoconiosis before the 1980s while the main types became welders pneumoconiosis and silicosis after the 1980s.After 2000,more welders pneumoconiosis were diagnosed that were even more than silicosis standing first on the list.The age of onset and professional seniority of pneumoconiosis were different significantly in different times.Different types of pneumoconiosis occurred at different ages of onset with different professional seniority.[Conclusion] The protection for dust-exposed work should be strengthened and the protection awareness of the workers should be improved so as to reduce the incidence of pneumoconiosis.
Anomalies of form and number, fused primary teeth, a correlation of the dentitions.

Fusion is rare in the primary dentition (range .14 percent to 3 percent). Patients with fused primary lateral incisors and canines have about a 75 percent chance of lacking the succedaneous lateral incisor. Patients with fused incisors have less than a 20 percent chance of having a missing permanent tooth.
Chronic effects of non-weathered and weathered crude oil and dispersant associated with the Deepwater Horizon incident on development of larvae of the eastern oyster, Crassostrea virginica.

The present study examined the effects of chronic exposure of eastern oyster (Crassostrea virginica) larvae to the water-accommodated fractions of fresh and weathered oils collected from the Deepwater Horizon incident, with and without additions of the dispersant Corexit 9500A, as well as to solutions of Corexit alone. Both shell growth of larvae exposed to test materials for a period of 10 d and larval settlement after 28 d of exposure were the most sensitive endpoints, with the 10-d growth endpoint being less variable among replicates. Growth and settlement endpoints were more sensitive than larval survival and normal development after 10 d and 28 d. Acute-to-chronic ratios calculated in the present study suggest that acute toxicities of oils and dispersant for oysters are not predictive of chronic effect levels for growth and settlement; therefore, chronic bioassays are necessary to assess these sublethal effects, in addition to standard 48-h acute toxicity tests. Comparison of 10% effective concentration (EC10) values for chronic 10-d growth and 28-d settlement endpoints with concentrations of total polycyclic aromatic hydrocarbons and dipropylene glycol n-butyl ether (a marker for Corexit) in seawater samples, collected during and after the Deepwater Horizon incident, indicated it was unlikely that elevated concentrations of water-soluble fractions of oil and dispersant in the nearshore environment had significant adverse effects on the growth and settlement of eastern oyster larvae. Environ Toxicol Chem 2016;35:2029-2040. © 2016 SETAC.
The Future of Information Technology

Publisher Summary This chapter reviews some of the issues in this new communications era and, in particular, reviews the work at Dartmouth College to develop the “library of the future.” The chapter discusses new information technologies that have remarkable potential and suggests that their development and deployment must proceed hand in hand with new applications and services that will pay for the technology and drive the demand for it. Our present vantage point on future services is based on our current and past experiences, and is limited by the boundaries created by those past technologies. There are numerous past examples in which predictions of future directions based on past extrapolations have led to blind alleys and wasted resources. The development of appropriate novel services and applications will require creativity and capital commensurate with the resources devoted to building new physical infrastructure.
Sexual Behavior Latent Classes Among Men Who Have Sex With Men: Associations With Sexually Transmitted Infections

Men who have sex with men (MSM) are at disproportionate risk of acquisition of sexually transmitted infections (STIs). We used latent class analysis (LCA) to examine patterns of sexual behavior among MSM and how those patterns are related to STIs. We examined patterns of sexual behavior using behavioral and clinical data from a cross-sectional study of 235 MSM who presented to an urban sexual health clinic for STI testing. Analyzed data were collected using a combination of interviewer- and self-administered surveys and electronic health records. We used LCA to identify underlying subgroups of men based on their sexual behavior, described the demographics of the latent classes, and examined the association between the latent classes and STI status. We identified three latent classes of sexual behavior: Unprotected Anal Intercourse (UAI) Only (67%), Partner Seekers (14%), and Multiple Behaviors (19%). Men in the Multiple Behaviors class had a 67% probability of being STI positive, followed by men in the UA...
Electrolyzed Saline Irrigation for Elimination of Bacterial Colonization in the Empyema Space

Abstract Background: The empyema space is refractory to elimination of bacterial colonization. Electrolyzed saline (ES) was used as intra-pleural irrigation for rapid disinfection of the empyema space. Patients and Methods: Twenty consecutive patients with para-pneumonic empyema were reviewed in this study from 2007 to 2015. The empyema space was irrigated by miniaturized thoracoscopic surgery (mini VATS), and the efficacy and safety of the use of ES were evaluated. Results: Sixteen patients were male and four were female, with a mean age of 66.5 ± 9.5 y (27–90 y). Bacterial cultures of the purulent effusions from all 20 patients had positive results. Seventeen patients subsequently underwent continuous catheter irrigation and drainage. No patient had chest pain during ES irrigation. Fever duration after mini VATS was 2.8 ± 1.8 d (0–5 d). Catheter indwelling time was 10.3 ± 7.2 d (3–33 d). Inflammatory markers significantly improved (p < 0.05) within a week after mini VATS. Eighteen patients achieved pleu...
Who’s in, Who’s out?

This study utilizes interviews with 53 full-time digital journalists to understand how they construct their identity. With social identity theory as a framework, the study found that medium, organizational backing, and role conception represent characteristics essential to being a digital journalist (the in-group). While the journalists also identified blogging, social media, and citizen journalism as characteristics that, in some cases, exclude persons from calling themselves digital journalists (the out-group). These results are then interpreted through the lens of social identity theory.
Design considerations for switched-capacitor analog memories

The authors review the application of switched-capacitor analog memories in detector instrumentation for high-energy and nuclear physics experiments. They discuss the various factors which limit the performance of this type of memory, and they indicate design considerations which are important for the application of these memories in detector front-end systems at the new collider accelerators. It is shown that, in spite of its inherently simple structure, the switched-capacitor analog memory requires many design tradeoffs. The process of dimensioning the cell switch and capacitor (and choosing their relative placement) alone involves compromises between response time, accuracy, dynamic range, cell-to-cell uniformity, and silicon area. >
Analysis of a nonlocal-in-time parabolic equation

In this paper, we consider an initial boundary value problem for nonlocal-in-time parabolic equations involving a nonlocal in time derivative. We first show the uniqueness and existence of the weak solution of the nonlocal-in-time parabolic equation, and also the spatial smoothing properties. Moreover, we develop a new framework to study the local limit of the nonlocal model as the horizon parameter δ approaches 0. Exploiting the spatial smoothing properties, we develop a semi-discrete scheme using standard Galerkin finite element method for the spatial discretization, and derive error estimates dependent on data smoothness. Finally, extensive numerical results are presented to illustrate our theoretical findings.
Therapeutic inhibition of BCL-2 and related family members

ABSTRACTIntroduction: BCL-2 proteins are key players in the balance of cell life and death. Their roles in the development and biology of cancer have been well established and continue to be investigated. Understanding the mechanisms by which these proteins regulate apoptosis has led to the development of small molecule targeted therapies that act to overcome the cell’s ability to evade programmed cell death.Areas covered: The biology of the intrinsic apoptotic pathway is reviewed with attention to the varied roles of the anti-apoptotic members of the BCL-2 family. BH3 profiling is reviewed. Historical therapeutic agents are addressed, and currently investigated BH3 mimetics are described with attention to clinical significance. The limitations of BCL-2 family targeted drugs with regard to on-target and off-target toxicities are explored. Agents under development for targeting MCL-1 and other BCL-2 family members are discussed.Expert opinion: ABT-199 (venetoclax) and other BH3 mimetics have entered the cl...
The Protein Chaperone ClpX Targets Native and Non-native Aggregated Substrates for Remodeling, Disassembly, and Degradation with ClpP.

ClpX is a member of the Clp/Hsp100 family of ATP-dependent chaperones and partners with ClpP, a compartmentalized protease, to degrade protein substrates bearing specific recognition signals. ClpX targets specific proteins for degradation directly or with substrate-specific adaptor proteins. Native substrates of ClpXP include proteins that form large oligomeric assemblies, such as MuA, FtsZ and Dps in Escherichia coli. To remodel large oligomeric substrates, ClpX utilizes multivalent targeting strategies and discriminates between assembled and unassembled substrate conformations. Although ClpX and ClpP are known to associate with protein aggregates in E. coli, a potential role for ClpXP in disaggregation remains poorly characterized. Here, we discuss strategies utilized by ClpX to recognize native and non-native protein aggregates and the mechanisms by which ClpX alone, and with ClpP, remodels the conformations of various aggregates. We show that ClpX promotes the disassembly and reactivation of aggregated Gfp-ssrA through specific substrate remodeling. In the presence of ClpP, ClpX promotes disassembly and degradation of aggregated substrates bearing specific ClpX recognition signals, including heat-aggregated Gfp-ssrA, as well as polymeric and heat-aggregated FtsZ, which is a native ClpXP substrate in E. coli. Finally, we show that ClpX is present in insoluble aggregates and prevents the accumulation of thermal FtsZ aggregates in vivo, suggesting that ClpXP participates in the management of aggregates bearing ClpX recognition signals.
A Physical-Based Model Reduction Metric with an Application to Vehicle Dynamics

Abstract In recent years, modeling metrics and algorithms have been developed to help automate the production of dynamic system models. More specifically, an energy-based modeling metric called the activity index has been developed by the authors. Also, the Model Order Reduction Algorithm (MORA) has been developed based on the activity index. The purpose of this paper is to extend the application of the energy-based activity index to nonlinear systems under transient conditions. This metric and procedure are applied to a large nonlinear rigid body model of a heavy duty tractor-semitrailer. The extension of the activity as developed in this paper appears to hold much promise as a general purpose model reduction metric when physical based model states and parameters are required.
Measurement of Turbulence in Water

A study of hot-film anemometer measurements in water resulted in a hypothesis that: Dirt and air bubbles accumulating on the hot-film sensor change the mean voltage for a given velocity, but have only a minor, outside the frequency domain in water, effect on the frequency response of the sensor to velocity fluctuations. And for a given sensor there is a unique family of voltage/velocity relations that can be defined by calibration with different overheat ratios. The hypothesis was experimentally verified by comparing turbulence measurements made in the same flow field with well filtered and with very dirty water. The method was used to measure the characteristics of turbulence measurements made in ordinary laboratory water for flow over hydraulically-rough and hydraulically-smooth boundaries. Reynolds numbers ranged from 8,000 to 20,000 and mean velocities from 0.3 fps to 2.8 fps. Relative turbulent intensities for flow over the smooth boundary were in good agreement with Laufer's measurements in air. Power spectrum analysis of the turbulence showed very little energy in frequencies larger than 100 Hz.
Alternative microglial activation is associated with cessation of progressive dopamine neuron loss in mice systemically administered lipopolysaccharide.

Inflammation arising from central and/or peripheral sources contributes to the pathogenesis of multiple neurodegenerative diseases including Parkinson's disease (PD). Emerging data suggest that differential activation of glia could lead to the pathogenesis and progression of PD. Here, we sought to determine the relationship between lipopolysaccharide (LPS) treatment, loss of dopaminergic neurons and differential activation of glia. Using a model of repeated injections with LPS (1 mg/kg, i.p. for 4 days), we found that LPS induced a 34% loss of dopamine neurons in the substantia nigra 19 days after initiation of treatment, but no further cell loss was observed at 36 days. LPS induced a strong pro-inflammatory response with increased mRNA expression of pro-inflammatory markers, including tumor necrosis factor-α (4.8-fold), inducible nitric oxide synthase (2.0-fold), interleukin-1 beta (8.9-fold), interleukin-6 (10.7-fold), and robust glial activation were observed at 1 day after final dose of LPS. These pro-inflammatory genes were then reduced at 19 days after treatment, when there was a rise in the anti-inflammatory genes Ym1 (1.8-fold) and arginase-1 (2.6-fold). Additionally, 36 days after the last LPS injection there was a significant increase in interleukin-10 (2.1-fold) expression. The qPCR data results were supported by protein data, including cytokine measurements, western blotting, and immunofluorescence in brain microglia. Taken together, these data demonstrate that progressive neurodegeneration in the substantia nigra following LPS is likely arrested by microglia shifting to an anti-inflammatory phenotype. Thus, strategies to promote resolution of neuroinflammation may be a promising avenue to slow the progressive loss of dopamine neurons in PD.
Checkpoint Blockade Immunotherapy for Glioblastoma: Progress and Challenges

Abstract Conventional therapy for glioblastoma (GBM) fails to specifically target and eliminate tumor cells, resulting in nonspecific toxicity that limits therapeutic efficacy. In contrast, immunotherapy utilizes the immune system to eradicate tumor cells with exquisite specificity. Specifically, checkpoint blockade therapy has emerged as a promising strategy for reducing tumor-mediated immunosuppression and promoting endogenous antitumor T cell responses. Recent approvals by the Food and Drug and Administration for the novel immune therapeutics ipilimumab and nivolumab have served to validate this overall treatment modality. In this chapter, we summarize the clinical progress of antibody-based checkpoint blockade and its relevance to GBM immunotherapy. We provide an overview of immune checkpoint biology in cancer, the feasibility of antibody-based immunomodulation as a therapeutic strategy for central nervous system malignancies, preclinical and clinical experiences with checkpoint therapy, and the ongoing progress of checkpoint blockade for GBM treatment.
Identity Development Among Sexual-Minority Youth

Sexual identity is the name and meaning individuals assign to themselves based on the most salient sexual aspects of their life – such as sexual attractions, fantasies, desires, and behaviors. Sexual identities usually fall within existing social categories, such as straight, bisexual, or lesbian/gay, and are historically and culturally specific. Youth in today’s cohort have expanded the list of sexual identities, moving beyond traditional notions of a gay, bisexual, or heterosexual orientation to include gender identity and partner characteristics. Social scientists from a variety of disciplines have proposed models of sexual identity. In this chapter, the most frequently cited and tested sexual identity model, Cass’s homosexual identity formation model, is evaluated. An alternative perspective, differential developmental trajectories, has recently been proposed that focuses on developmental milestones that contribute to a sexual identity. Besides recognizing the inherent uniqueness of every life, this perspective proposes that in many developmental processes, sexual-minority youth are similar to all other adolescents of their sex, ethnicity, class, and cohort. Also discussed are the possibility of a “straight sexual identity” and two major problems with sexual identity models – the instability of sexual identity over time and its occasional inconsistency with sexual behavior and attraction. The distinctive aspects of growing up lesbian or gay have greatly diminished as the current cohort of youth has increasingly accepted sexual diversity as normative, acceptable, and even desirable. Thus, the demise of sexual identity is forecast as youth of all sexualities are refusing and resisting sexual identity labels.
C/EBPδ drives interactions between human MAIT cells and endothelial cells that are important for extravasation

Lymphocytes are a type of cell found in the blood that can detect and fight infections: in particular, some of them can leave the bloodstream to enter infected or inflamed tissues. To do so, these lymphocytes use proteins on their surface to roll along the inside wall of the blood vessel; then they stick to this wall and finally they pass through it. For some types of lymphocytes the details of this mechanism – such as precisely which surface proteins are necessary – remain unclear. Here, Lee et al. collect human lymphocytes from the blood of healthy donors, and they identify a subgroup of lymphocytes, called MAIT cells, that are particularly good at moving from blood to infected or inflamed tissues, and further experiments reveal the types of surface proteins that help them do so. Some of these proteins, for example selectin ligands, are important so the MAIT cell can roll on the wall of the blood vessel. Others, like CCR6, are essential for the cell to stop rolling and stick to the wall. Lee et al. also identify C/EBPδ, a regulatory protein inside the MAIT cell that controls how these other two types of proteins are produced. Finally, Lee et al. show that additional proteins, such as CCR2, are necessary for the lymphocyte to cross the vessel wall. The proteins that help lymphocytes move from blood to tissues represent important targets to fight diseases. For example, blocking these proteins could prevent lymphocytes from invading and damaging healthy tissues, which happens in autoimmune diseases like multiple sclerosis. Alternatively, manipulating these proteins could help to engineer lymphocytes that can invade and kill tumor tissues in cancers.
Undrained Monotonic Shear Response of MICP-Treated Silty Sands

AbstractThe effect of nonplastic fines on the undrained shear response of sand depends on many variables, including fines content, skeleton void ratio (es), interfine void ratio (ef), global void r...
School enrollment effects in a South-South migration context

Abstract In contrast to the heavily studied South-North migration of Latin Americans to the United States, this investigation assesses the lesser-studied influence of South-South labor migration on left-behind children’s educational attainment. Specifically, it asks the question, ‘Does the migration of Nicaraguan parents to Costa Rica contribute to better or worse education outcomes for their left-behind children?’ Based on migration and education data for 3951 children from 1858 distinct households collected within Nicaragua’s 1998 and 2001 Living Standards Measurement Studies, fixed effect model results indicate that paternal migration has a depressive effect on school enrollment but has no effect on school attendance or grade-for-age progression. Given the relatively low bar to migration establishment vis-a-vis the lack of barriers that necessitate significant monetary commitments and time delays, school enrollment results are unexpected.