cssi/SciSciGPT-SciSciNet huggingface dataset:
Removal of a single minor-groove functional group eliminates A-tract curvature.

Much of the work in studying the phenomenon of A-tract curvature has involved the insertion of modified residues into the A-tract sequence and then cross-correlation of the structural differences with the resulting curvature effects. In the A-tract sequence d(A−T)5, removal of a single functional group (the O2-carbonyl of the central dT residue) by its replacement with hydrogen completely eliminates the curvature properties. This atom-specific change was accomplished by using the C-nucleoside dm32P in which the O2-carbonyl is replaced with −H but normal Watson−Crick hydrogen bonding is maintained. Similar derivatives with −F (dF62P) or −CH3 (dm62P) when present for the central dT residue also eliminate curvature. Finally, we have shown that the extent of curvature for sequences containing this carbonyl are sensitive to the [Mg2+], while those lacking the carbonyl show little to no Mg2+ dependence, strongly suggesting, we believe, a role for Na+/Mg2+ cooperative interactions in the minor groove to explain ...
Negative or positive cloud optical depth feedback

In conclusion, my RCM study indicates that the cloud optical depth feedback in the Roeckner et al. GCM simulations is positive. Of course the RCM is not the GCM, so the final, conclusive result will have to await a comparison to the appropriate GCM simulation. In any event, because of the complexity of cloud processes in nature, many additional modelling and observational studies will be required to determine the sign of the actual cloud optical depth feedback, let alone its magnitude.
Hybrid structures and improving forecasting and scheduling in project management

Abstract In many areas of managerial decision-making and analysis, there are classical dichotomies, such as subjective versus objective forecasting methods, short-range versus long-range forecasting, heuristic versus optimization algorithms, and logic programming versus functional programming. This article describes some hybrid concepts and techniques that attempt to synthesize the strengths and minimize the weaknesses of seemingly incompatible classical approaches to problems that are central to project management and scheduling and to operations management in general.
The Association Between Dialysis Facility Quality and Facility Characteristics, Neighborhood Demographics, and Region

The Centers for Medicare & Medicaid Services (CMS) initiated the End-Stage Renal Disease Quality Incentive Program in 2012. For each dialysis facility, an overall quality performance score is determined based on various quality measures. This article studies the association between the overall dialysis facility quality and facility characteristics, neighborhood demographics, and region. Data from the CMS Payment Year 2014 Dialysis Compare File were used, and were linked to 2010 US Census data (n = 4086). Multiple linear regression was used to examine the association between dialysis facility quality and facility characteristics, neighborhood demographics, and region. The analysis demonstrates that dialysis facility quality varies significantly by facility profit status, chain membership, and facility size. Dialysis facilities in neighborhoods with a higher proportion of African Americans have significantly lower quality. Regional differences in quality exist.
Organochlorines in stranded pilot whales (Globicephala melaena) from the coast of Massachusetts.

Pilot whales strand periodically along the U.S. coast, and these strandings offer an opportunity for the collection of tissues for biomonitoring of contaminant exposure in cetaceans, as well as for specimen archiving. Concentrations of organochlorine (OC) contaminants (e.g., PCB congeners, pesticides, DDTs) were measured in tissue samples from pilot whales that stranded in 1986 and 1990 along the Massachusetts coast. Adult and fetal samples of blubber, liver, brain, and kidney were collected, as well as ovaries from mature female whales. Many of the OCs found in maternal tissues were detected in corresponding fetal tissues indicating maternal transfer of OCs to the fetus. The concentrations of individual OCs in tissues varied considerably among the animals. Statistically significant differences were found between females and males for the concentrations of certain analytes (e.g., SigmaPCBs, p,p'-DDE) and these differences may be partially due to contaminants being transferred by the female whales during gestation and lactation. The concentrations of OCs in different tissues were similar when based on total lipid weight, except for the brain, which contained the lowest lipid-normalized OC concentrations. The low concentrations in brain may be related to the disparate lipid compositions in this tissue as well as the presence of the blood-brain barrier. The availability of data on these archived and biomonitoring samples provides a baseline for future retrospective studies.
Variability, vagueness and comparison methods for ecological models

A unified approach is presented for the construction and analysis of models for the dynamics of populations and communities in the presence of temporal variability, vague density dependence, chaos or analytical intractability. The approach is based on comparisons involving simpler models which provide ceilings and floors to the densities predicted by the full models. The method is applied to examples of several types of models, including difference equations, ordinary differential equations, non-linear Leslie matrices and reaction-diffusion equations. The models treated describe various ecological phenomena including self-regulation, competition, predator-prey interactions, age structure and spatial structure. Some results needed for the analysis of matrix models and patch models are given in the Appendix.
Occurrence of 5,9,19-octacosatrienoic, 5,9-hexacosadienoic and 17-hexacosenoic acids in the marine spongeXestospongia halichondroides

The marine spongeXestospongia halichondroides contains 13% 28∶3Δ5,9,19, 27% 26∶2Δ5,9, and 21% 26∶1Δ17 in its total fatty acids. Thecis-5,cis-9,cis-19-octacosatrienoic acid structure is unknown in other living organisms.
Isolation and preliminary characterization of temperature-sensitive mutants of visna virus.

Abstract Temperature-sensitive mutants of visna virus have been isolated from N-methyl-N′-nitro-N-nitroso-guanidine mutagenized virus. These mutants have been partially characterized and have been separated into three classes based on the time after infection when the temperature-sensitive function was expressed.
Acquisition of luteolytic capacity involves differential regulation by prostaglandin F2α of genes involved in progesterone biosynthesis in the porcine corpus luteum

Luteolytic capacity is defined as the ability of corpora lutea (CL) to undergo luteolysis after prostaglandin (PG) F2alpha treatment. The mechanisms causing acquisition of luteolytic capacity are not yet identified but CL without luteolytic capacity have PGF2alpha receptors and respond to PGF2alpha with some changes in gene expression. Inhibition of progesterone biosynthesis is a key feature of luteolysis and therefore we postulated that genes involved in progesterone biosynthesis would be regulated by PGF2alpha differently in CL with or without luteolytic capacity. Gilts on day 9 after estrus (lack luteolytic capacity) or day 17 of pseudopregnancy (with luteolytic capacity) were treated with saline or a PGF2alpha analog (cloprostenol) and CL were collected 0.5 (Experiment I) or 10 h (Experiment II) later. In Experiment III, large luteal cells from CL on day 9 or 17 were cultured for 1, 12 and 24h with or without PGF2alpha. PGF2alpha decreased LDL receptor mRNA (27%), steroidogenic acute regulatory protein (StAR) mRNA (41%), StAR protein (75%), LH receptor mRNA (55%), and LH receptor protein (45%) at 10 h after treatment in day 17 but not day 9 CL. PGF2alpha increased DAX-1 mRNA at 0.5 h (43%) and 10 h (46%) after PGF2alpha in day 17 but not day 9 CL but decreased 3betaHSD mRNA ( approximately 20% at 10 h) in both days 9 and 17 CL. In vitro, PGF2alpha decreased StAR mRNA at 12 h only in day 17 luteal cells; however, continuous treatment with PGF2alpha for 24 h decreased StAR mRNA in both days 9 and 17 luteal cells. Thus, luteolytic capacity involves a critical change in responsiveness of DAX-1, StAR, and LH receptor to PGF2alpha that results in inhibition of luteal progesterone biosynthesis.
The restricted nature of HIV-1 tropism for cultured neural cells

Infection of the central nervous system by HIV-1, the agent of AIDS, is characterized by the presence of infected and giant microglial cells as well as astrocytosis, demyelination, and neuronal loss. To determine whether cells of neuroectoderm origin can be infected by HIV-1, we have inoculated primary cultures derived from adult human brain with a lymphotropic virus (LAV) or a neurotropic virus (Jr-FL) isolated from a patient with AIDS dementia. While Jr-FL invariably causes productive infection of cultured brain microglia, neither astrocytes nor oligodendrocytes became productively infected by these viral strains. Moreover, the cultured oligodendrocytes develop a normal network of processes and express differentiation antigens in the presence of an ongoing lytic infection of microglial cells. No HIV-1 proviral DNA was detected in primary astrocyte cultures devoid of microglial after inoculation of either HIV-1 strain. Similarly, the neuronal cell line HCN-1 in its differentiated state did not allow the virus to go through cycles of reverse transcription and replication. LAV, however, was able to replicate in undifferentiated HCN-1 cells. Thus, tropism of HIV-1 appears tightly restricted to only one type of differentiated cell in the CNS, the microglia.
Tubificid behavior as a stress indicator

Abstract An inexpensive, rapid protocol is described to assess water-borne insults by integrating sewage worm (tubificid) regulatory behavior with increased oxygen consumption. Data are provided to demonstrate how oxygen uptake rates in tubificid worms can be correlated with behavior to identify chronic levels of toxicity. When flow rate to the treatment replicates' respiratory chambers was dropped from 1.71 to 0.65 ml min−1, the respiration rates decreased significantly from 0.31 to 0.17 mg O2g−1h−1 respectively. Concommitantly, the treatments initially mobilized compensatory ventilation measures but subsequently exhibited avoidance behavior. The controls continued to remain dispersed and unagitated.
On-chip mode-division multiplexer

We demonstrate micron-scale on-chip mode-division multiplexing device with low crosstalk using add-drop silicon ring resonators array. We taper the bus waveguide width to selectively phase-match the different bus waveguide modes to the ring mode.
The Achilles' heel of an enduring relationship: Appropriation of rents between a manufacturer and its foreign distributor

Abstract A blind spot in the resource based view (RBV) of the firm is the rent appropriation process. The RBV argues that rents accrue directly to holders of competitive resources. In reality, the potential rents in an international partnership are up for grabs as they arise on both sides of the border. Dysfunctional acts may strain even the longest and most successful relationships. With this predisposition the literature focuses on opportunistic behavior in partner switching. Our study considers a more complex mechanism where satisfaction in expropriating rent drives partner switching likelihood. The notion of a time-tested stable relationship is a misnomer; vulnerability grows over time, as one or both partners gain bargaining power in an enduring relationship. Establishing significant credible commitment, not the eradication of opportunism, builds satisfactory cross-border relationships. The higher the stakes and the longer the relationship, the stronger is the satisfaction between the committed partners.
Effects of theophylline, terbutaline, and prednisone on antigen-induced bronchospasm and mediator release

Abstract Eleven subjects demonstrating clinical, skin, and inhalation sensitivity to grass or ragweed pollen underwent serial inhalation challenges, with and without orally administered theophylline, terbutaline, and prednisone. Comparisons of antigen sensitivity and mediator release were made during these challenges. All three drugs significantly reduced antigen sensitivity (PD 20 inhalation units increasing from 670 to ≧ 3,280). Peak plasma histamine levels after antigen challenge decreased from 11.4 ng/ml to ≦ 3.4 ng/ml during all drug administrations. Similarly, the percent increase in serum neutrophil chemotactic activity (NCA) also decreased, from 96% to ≦ 36% during drug administrations. However, even at antigen doses resulting in bronchospasm during drug administration the systemic appearance of NCA and histamine were reduced. We conclude that prednisone, theophylline, and terbutaline significantly reduce antigen-induced bronchospasm and mediator release. The occurrence of bronchospasm despite the inhibition of histamine and NCA suggests either that the local concentration of these mediators are critical or that other mediators produce the bronchospasm observed.
What Is Discomfort in Persons With Dementia Who Are Agitated

To the Editor It is important to evaluate quality of life in persons with dementia, especially in those who cannot communicate possible sources of discomfort. Therefore, it is important to have tools to evaluate the presence of discomfort. A recent Research Letter proposed a Source of Discomfort Scale (SODS) and reported that when it was applied in 179 agitated nursing home residents, the mean number of 20 observed items was 3. 1 Possible pain, measured in only 89 residents, was responsible for only 8% of variance in the SODS. The main problem with this scale is that the most common source of discomfort was that “the resident was sleepy or tired.” Daytime sleepiness is very common in persons with dementia, especially in those who have advanced disease. 2 There is no reason to assume that the person who is sleepy is uncomfortable. Being tired may actually be a good state because it may mean that the person had recently participated in some meaningful activity. Similarly, the fact that the person “has been sitting in the same place without movement for over 2 hours” may not necessarily indicate presence of discomfort. If the sitting arrangement is comfortable (eg, in recliner instead to wheel chair) the person may enjoy it, especially since spontaneous movement is limited in advanced dementia. Some of the other items in the SODS may indicate the presence of discomfort but may not be applicable in noncommunicative residents, eg, signs of hunger or thirst. The authors do not discuss the relationship between discomfort and agitation because many symptoms of agitation in a widely used scale 3 may also be considered a sign of discomfort.
Palaeobiology and evolution of the late Cenozoic freshwater molluscs of the Turkana Basin: Unionidae Rafinesque, 1820, partim Coelatura (Bivalvia: Unionoidea)

The Plio-Pleistocene freshwater molluscs of the Omo-Turkana Basin were long considered to be a prima facie example of punctuated equilibrium evolution. However, the absence of a study on their taxonomy has significantly hampered the debate on assumed evolutionary patterns. This paper addresses the systematics and palaeobiology of the bivalve genus Coelatura Conrad, 1853 in the basin. It reveals that a Coelatura species was assigned to the extinct genus Pseudobovaria Adam, 1957 in earlier studies, while another species formerly assigned to Coelatura is not discussed here because it belongs to the extinct Pseudodiplon Adam, 1957. Six Coelatura species are recognized in the Plio-Pleistocene Omo-Turkana Basin, two of which are new to science: C. rhomboidalis sp. nov. and C. magna sp. nov. These two species are considered lacustrine adapted species, both with a strongly dorsally protruded umbo. This adaptation apparently evolved twice independently in the basin within a ∼1 Ma period, but it is not observed in ...
Characterization of a peptidase from Diplococcus pneumoniae.

Some properties of a purified peptidase fromDiplococcus pneumoniae have been studied. The enzyme has a broad pH optimum between 6 and 8 and a Km (onl-leucylglycylglycine) of 2.8mm. It is activated by low levels of Hg++ and is inhibited by Mn++, Co++, β-mercaptoethanol and EDTA. Substrate specificity studies show that the enzyme is an exopeptidase of the aminopeptidase type, most active on tripeptide substrates bearing bulky substituents at the NH2− terminal end.
Induced formation of phenylalanine ammonia lyase and pisatin by chlorpromazine and other phenothiazine derivatives.

Abstract Chlorpromazine and 16 other phenothiazine derivatives induced up to 11-fold increases in phenylalanine ammonia lyase activity and the de novo synthesis of up to 200 μg pisatin per g of pea pod tissue. The induction of phenylalanine ammonia lyase was dependent on new RNA and protein synthesis and was accompanied by increased synthesis of an array of cellular proteins.
StVEC: A Vector Instruction Extension for High Performance Stencil Computation

Stencil computations comprise the compute-intensive core of many scientific applications. The data access pattern of stencil computations often requires several adjacent data elements of arrays to be accessed in innermost parallel loops. Although such loops are vectorized by current compilers like GCC and ICC that target short-vector SIMD instruction sets, a number of redundant loads or additional intra-register data shuffle operations are required, reducing the achievable performance. Thus, even when all arrays are cache resident, the peak performance achieved with stencil computations is considerably lower than machine peak. In this paper, we present a hardware-based solution for this problem. We propose an extension to the standard addressing mode of vector floating-point instructions in ISAs such as SSE, AVX, VMX etc. We propose an extended mode of paired-register addressing and its hardware implementation, to overcome the performance limitation of current short-vector SIMD ISA's for stencil computations. Further, we present a code generation approach that can be used by a vectorizing compiler for processors with such an instructions set. Using an optimistic as well as a pessimistic emulation of the proposed instruction extension, we demonstrate the effectiveness of the proposed approach on top of SSE and AVX capable processors. We also synthesize parts of the proposed design using a 45nm CMOS library and show minimal impact on processor cycle time.
Combining beams from separated telescopes.

In the present paper, work is discussed which arose in the context of optical design studies for the proposed space-based COSMIC (Coherent Optical System of Modular Interferometric Collectors) telescope. The operation of COSMIC involves the combination of a number of parallel beams with a central beam-combining telescope which forms an image of the sky. The paper is mainly concerned with the aspects of beam combination. The paraxial constraint condition is considered along with tolerances regarding the individual optical elements, and imaging as a nonshearing recombination. A first-order requirement for achieving a finite field of view is discussed, taking into account specifically the case of a coherent imaging optical system.
The challenges of breeding from the mare

ABSTRACT:This article provides a brief overview of breeding from a mare. The first section details the oestrous cycle with some basic physiology. Considerations of the mare's health are discussed, with reference to general health (laminitis and other orthopaedic problems, teeth, vaccinations) and reproductive health (vulval conformation, conditions of the cervix, uterus and ovaries). Descriptions of different breeding strategies, in particular natural mating and artificial insemination, are discussed in the third section. Finally, there is a brief review of pregnancy diagnosis by ultrasonography.
The Trillium user interface design environment

Trillium is a computer-based environment for simulating and experimenting with interfaces for simple machines. For the past four years it has been use by Xerox designers for fast prototyping and testing of interfaces for copiers and printers. This paper defines the class of “functioning frame” interfaces which Trillium is used to design, discusses the major concerns that have driven the design of Trillium, and describes the Trillium mechanisms chosen to satisfy them.
Duplex Directed Caval Filter Insertion in Multi-Trauma and Critically Ill Patients

This study was undertaken to determine the safety and feasibility of inferior vena cava (IVC) filter insertion at the bedside using duplex imaging in multi-trauma and/or critically ill patients. From February 1996 to August 1997, 53 multi-trauma and/or critically ill patients, who were in the intensive care unit and referred for an IVC filter, were prospectively evaluated for possible duplex directed caval filter (DDCF) insertion. Screening IVC duplex scans were performed in all patients. Satisfactory ultrasound visualization in 46 patients (87%) allowed attempted DDCF insertion. All procedures were percutaneously performed at the bedside using Vena Tech IVC filters. The results from this series showed that DDCF insertion can be safely and rapidly performed at the bedside in multi-trauma or critically ill patients. The procedure is dependent on satisfactory visualization of the IVC by duplex ultrasonography, which was possible in 45 out of 53 (85%) patients. Insertion at the bedside substantially reduces the procedural cost and avoids the need for transport, radiation exposure, and intravenous contrast.
Use of synthetic drugs among people who inject drugs in San Diego, CA

s / Drug and Alcohol Dependence 140 (2014) e169–e251 e235 Methods: Data are from a large, well-retained urban, low socioeconomic status sample of 378 full-term African American infants (195 PCE, 183 non-PCE) who were enrolled prospectively at birth in the longitudinal Miami Prenatal Cocaine Study (MPCS) and were currently residing in Florida at the 18/19 year followup visit. PCE was assessed via maternal self-report and toxicology assays in maternal urine and infant urine and meconium. ACE was assessed by toxicology assays only. Arrests for violent offenses in early adulthood were based on search of official Florida arrest records. Estimates are presented, with and without consideration of other sources of variation such as prenatal exposure to alcohol, marijuana, and tobacco, and caregiver arrest record. Results: Estimates fromstratified analyses found arrests for violent offenses in early adulthood for an estimated 22% ofmales with neither PCE nor ACE versus 46% for males with both PCE and ACE (p 0.05). The male risk ratio for combined PCE and ACE associated occurrence of arrest for violent offenses of approximately 2.0 (p<0.05) did not change appreciably with covariate adjustments for other prenatal drug exposures and caregiver arrest record. Conclusions: PCE combined with ACE was robustly predictive of arrests for violent offenses, especially in young adult males. Limitations of adolescent self-report are constrained via focus on toxicological assays and official arrest statistics. Financial support: NIH National Institute on Drug Abuse and Office of Research on Women’s Health (ORWH): R01DA006556 (ESB); P50DA024584 (ESB); P50DA024584-S4 (ESB; DCV); K01DA016720 (VHA); K05DA15799 (JCA). http://dx.doi.org/10.1016/j.drugalcdep.2014.02.649 Use of synthetic drugs among people who inject drugs in San Diego, CA Karla D. Wagner, J. Cuevas-Mota, R.F. Armenta, Steffanie Strathdee, R.S. Garfein University of California San Diego, San Diego, CA,
Filial cannibalism and nocturnal illumination in paradise fish, Macropodus opercularis

Informal observations had suggested that low-level nocturnal illumination was necessary for egg survival following normal spawning of Macropodus opercularis. To confirm those observations, spawned pairs of M. opercularis were left overnight with their eggs, with either low-level illumination (n = 21) or in complete darkness (n = 23). In complete darkness 17 of 23 pairs showed complete egg loss the following morning, while none of the low-level illumination group showed evidence of egg loss. Possible explanations of this phenomenon are discussed.
Possible Approach to the Induction of Universal Human Histocompatibility Tolerance in the Heterologous Animal

Possible Approach to the Induction of Universal Human Histocompatibility Tolerance in the Heterologous Animal
Surgical complexity score and oncologic outcomes following optimal or complete cytoreductive surgery for ovarian, fallopian tube and primary peritoneal cancers

PDS as 42.7 months compared with NACT as 32.9 months (P b 0.001), but median survival was the same for stage IV disease (30.2 vs. 30.6 months). In multivariate analysis, patients who received NACT compared to PDS with stage IIIC disease had a slightly greater mortality risk (HR = 1.23), but the relative risk was less profound than age N71 years (1.64), comorbidities (1.62), grade 3 disease (1.70), CT alone (2.12), or surgery alone (1.64). Conclusions: Evidence suggests that patients with greater adverse risk factors are more likely to receive NACT than PDS. Although patients who receive NACT have a somewhat worse mortality compared to PDS, this may be a reflection of older, medically infirm patients with advanced disease rather than an inherently inferior treatment option.
Learning and retention of a shock avoidance task by rat using deafferented hind limb.

Abstract Learning and retention of a shock avoidance task were studied in the absence of proprioceptive or other topographic feedback. Rats with a deafferented hind limb were trained using the instrumental shock avoidance and retention paradigm of Horridge. Rats received shock whenever they lowered an electrode attached to a deafferented hind foot into an electrolyte bath; yoked-control rats received the shocks to a deafferented hind food along with the experimental animals. Experimental animals consistently held their feet above the electrolyte ( p p p
The Interactive Evolution of the Oceanic and Atmospheric Boundary Layers in the Source Regions of the Trades

Abstract Subtropical status tends to form over relatively cold water, its presence then keeps the water cold. We have investigated the resultant downstream development in the framework of an interactive, two-dimensional, steady-state model of the oceanic and atmospheric mixed layers. Upstream boundary and interior conditions in both media, and irradiance and advection velocities are specified; mixed-layer temperature salinity, heat and moisture content are evolving dependent variables. The integration is continued downstream until convective instability develops or, failing that, for a distance of 2000 km. Sensitivity tests show this development to be strongly affected by the upstream boundary conditions, implying an effect of coastal upwelling processes upon oceanic and atmospheric temperature profiles for a long distance downstream. The dependence on the advection velocity is very nonlinear. The amplitude of temperature changes is of the same order in both media, despite the greater oceanic heat capacit...
Electronic structure studies on silylalkanes, alkylsilanes and silysilanes

The authors report ab initio calculations on the H, C, Si cluster molecules Si2H6, C2H6, SiH3CH3, Si5H12, (SiH3)4C, (CH3)4Si and C5H12. The method involved the use of pseudopotentials to replace the Si core. Total energy differences show that, at least at the SCF level of theory, Coulombic stabilisation largely compensates for loss of maximal overlap, thus rendering the C-Si bond very slightly stable against disproportionation. The orbital energy changes and charge populations imply that bonding differences can be understood very largely in terms of local interactions, so that the delocalisation properties occurring in silanes must arise from second-order interactions involving relatively low-lying excited states. The tetrasilyl methane molecule is predicted to be rather stable.
Survey of monoclonal antibody disposition in man utilizing a minimal physiologically-based pharmacokinetic model

Minimal physiologically based pharmacokinetic (mPBPK) models provide a simple and sensible approach that incorporates physiological elements into pharmacokinetic (PK) analysis when only plasma data are available. With this modeling concept, a second-generation mPBPK model was further developed with specific accommodations for the unique PK properties of monoclonal antibodies (mAb). This study applied this model to extensively survey mAb PK in man in order to seek general perspectives on mAb distributional and elimination features. Profiles for 72 antibodies were successfully analyzed with this model. The model results provide assessment regarding: (1) predominant clearance site, in plasma or interstitial fluid (ISF); (2) mAb ISF concentrations in two groups of lumped tissues with continuous (Vtight) or fenestrated (Vleaky) vascular endothelium; (3) Transcapillary escape rate (TER), an indicator of systemic vascular permeability. For 93 % of surveyed mAbs, the model assuming clearance from plasma (CLp) produced better or at least equivalent model performance than the model with clearance from ISF and yielded most consistent values of vascular reflection coefficients (σ1 and σ2) among all antibodies. The average mAb ISF concentration in Vtight and Vleaky at equilibrium was predicted to be about 6.8 and 37.9 % of that in plasma. A positive correlation was detected between plasma clearance and TER among most mAbs, which could be interpreted as both parameters having common determinants related to ISF tissue distribution in this model context. The mAbs with relative higher plasma clearance (>0.035 L/h/70 kg) did not reveal such positive correlation between clearance and TER, implying that the factors contributing to high clearance may not necessarily increase tissue distribution and penetration. In conclusion, this mPBPK model offers a more mechanistic approach for analyzing plasma mAb PK than compartment models and generates parameters providing useful intrinsic distributional and elimination insights for a large number of mAbs that were examined in man.
Detecting the error threshold for rule-based programs: a logit model

Abstract Two measures of error-proneness for rule-based programs are proposed and empirically tested using a set of 80 commercially developed rule-based programs. The measures are derived by representing a rule-based (Prolog) program in its most abstract graphical form as calls between predicates, and then counting the number of unique predicate names (UPN), and the number of calls between UPNs (ARCS). Correlation and t -tests show the veracity of the measures in detecting errors. Finally, logistic regression is applied to determine the threshold point at which programs become error-prone. This threshold represents a quality mark that can be used to control the development of future rule-based programs. When a rule-based program exceeds this threshold, the program is significantly more likely to develop an error.
Coordinated feedback regulation of muscle glycogen metabolism: inhibition of purified phosphorylase phosphatase by glycogen

An assay method was devised for accurately measuring the activity of phosphorylase phosphatase in the presence of glycogen. Both oyster glycogen and rabbit liver glycogen inhibited the activity of purified phosphorylase phosphatase catalytic subunit in a concentration-dependent manner. In the presence of 120 mM KCl, micromolar AMP increased the sensitivity of the phosphatase to glycogen inhibition. The present studies suggest that glycogen feedback inhibition may be a coordinated mechanism producing a decrease in phosphorylase phosphatase activity as well as glycogen synthase phosphatase activity.
Foundations of Team Building: Introduction to the Team Building primer

Abstract This article provides an infroduction to the Team Building Special Edition. Following the presentation of the purpoec of the special edition. basic concepts including definitional, conceptual. and practical perspectives on team building are presented. The article concludes by summarizing each of the contributions included within the special edition.
Review of Regional and Ethnic Conflicts: Perspectives from the Front Lines

Nearly two decades have passed since ethnopolitical conflict was identified as a major source of violence, human suffering, and instability in the world. A steady stream of books and scholarly arti...
Calculation of individual isotope equilibrium constants for geochemical reactions

Abstract Theory is derived from the work of Urey (Urey H. C. [1947] The thermodynamic properties of isotopic substances. J. Chem. Soc. 562–581) to calculate equilibrium constants commonly used in geochemical equilibrium and reaction-transport models for reactions of individual isotopic species. Urey showed that equilibrium constants of isotope exchange reactions for molecules that contain two or more atoms of the same element in equivalent positions are related to isotope fractionation factors by α = (Kex)1/n, where n is the number of atoms exchanged. This relation is extended to include species containing multiple isotopes, for example 13C16O18O and 1H2H18O. The equilibrium constants of the isotope exchange reactions can be expressed as ratios of individual isotope equilibrium constants for geochemical reactions. Knowledge of the equilibrium constant for the dominant isotopic species can then be used to calculate the individual isotope equilibrium constants. Individual isotope equilibrium constants are calculated for the reaction CO2g = CO2aq for all species that can be formed from 12C, 13C, 16O, and 18O; for the reaction between 12C18O2aq and 1H218Ol; and among the various 1H, 2H, 16O, and 18O species of H2O. This is a subset of a larger number of equilibrium constants calculated elsewhere (Thorstenson D. C. and Parkhurst D. L. [2002] Calculation of individual isotope equilibrium constants for implementation in geochemical models. Water-Resources Investigation Report 02-4172. U.S. Geological Survey). Activity coefficients, activity-concentration conventions for the isotopic variants of H2O in the solvent 1H2 16Ol, and salt effects on isotope fractionation have been included in the derivations. The effects of nonideality are small because of the chemical similarity of different isotopic species of the same molecule or ion. The temperature dependence of the individual isotope equilibrium constants can be calculated from the temperature dependence of the fractionation factors. The derivations can be extended to calculation of individual isotope equilibrium constants for ion pairs and equilibrium constants for isotopic species of other chemical elements. The individual isotope approach calculates the same phase isotopic compositions as existing methods, but also provides concentrations of individual species, which are needed in calculations of mass-dependent effects in transport processes. The equilibrium constants derived in this paper are used to calculate the example of gas-water equilibrium for CO2 in an acidic aqueous solution.
Effects of blood glucose transcription mismatches on a computer-based intensive insulin therapy protocol

Purpose Computerized clinical decision support systems (CDSS) for intensive insulin therapy (IIT) generate recommendations using blood glucose (BG) values manually transcribed from testing devices to computers, a potential source of error. We quantified the frequency and effect of blood glucose transcription mismatches on IIT protocol performance.
The effects of immobilization on the primate temporomandibular joint: A histologic and histochemical study

The effects of prolonged immobilization on the primate temporomandibular joint (TMJ) condylar cartilage are reported. After eight weeks of immobilization, changes were assayed histochemically using the specific glycosaminoglycan (GAG) stain safranin O. Following the immobilization period, the articulating cartilage showed marked thinning, disorganization, and loss of the superficial GAG stain. After two weeks of remobilization, further thinning had occurred and GAG staining was nearly absent. Sections from condyles of animals sacrificed serially from two weeks to eight months after immobilization showed a gradual return to the thickness and GAG content of the control animals' condyles. But even at this stage, GAG staining was less marked than in the controls, and zonal reorganization was incomplete. These results suggest that TMJ immobilization is not a wholly benign procedure.
Potential of flow cytometry for “pump and probe” fluorescence measurements of phytoplankton photosynthetic characteristics.

“Pump and probe” fluorescence assays provide information about the photosynthetic characteristics of phytoplankton in situ, but at present they measure bulk water samples and thus provide only average values for the whole community (including detritus). We used dual beam flow cytometry to investigate the potential for measuring “pump and probe” fluorescence of single cells. For Lauderia borealis (a centric diatom ∼30 µm in diameter) in different stages of N-limited batch culture, the fluorescence yield enhancement due to the presence of a “pump” beam was correlated with DCMU-enhanced bulk fluorescence, as expected. However, at the appropriate excitation power, fluorescence signals from single cells are so small that for most types of phytoplankton in the oceans, population averaging of signals will be necessary.
Lipoprotein-Associated Phospholipase A2 Is an Independent Marker for Coronary Endothelial Dysfunction in Humans

Objective— The purpose of the current study was to determine whether lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with coronary endothelial dysfunction and is a predictor of endothelial dysfunction in humans. Methods and Results— Patients (172) with no significant coronary artery disease (<30% stenosis) undergoing assessment of coronary endothelial function were studied. Endothelial function was assessed by the change in coronary blood flow and coronary artery diameter in response to intracoronary acetylcholine. Plasma concentrations of Lp-PLA2 were measured, and patients were divided into tertiles. Patients in tertiles 2 and 3 had a significantly lower change in coronary blood flow (63.8±73.2 and 32.0±71.7 versus 78.4±73.2%; P <0.001) and greater epicardial coronary artery vasoconstriction (−14.1±14.7 and −23.3±25.1 versus −9.5±15.2% mean diameter change; P <0.001) in response to acetylcholine. Patients with coronary endothelial dysfunction had significantly higher serum concentrations of Lp-PLA2 than those with normal endothelial function (246.2±71.6 versus 209±56.7 ng/mL; P =0.001). The odds ratio for coronary endothelial dysfunction in patients with Lp-PLA2 in the highest tertile was 3.3 (95% CI, 1.6 to 6.6). Conclusions— Lp-PLA2 is independently associated with coronary artery endothelial dysfunction and is a strong predictor of endothelial dysfunction in humans.
Probing limits of acoustic nanometrology using coherent extreme ultraviolet light

Photoacoustic nanometrology using coherent extreme ultraviolet (EUV) light detection is a unique and powerful tool for probing ultrathin films with a wide range of mechanical properties and thicknesses well under 100 nm. In this technique, short wavelength acoustic waves are generated through laser excitation of a nano-patterned metallic grating, and then probed by diffracting coherent EUV beams from the dynamic surface deformation. Both longitudinal and surface acoustic waves within thin films and metallic nanostructures can be observed using EUV light as a phase-sensitive probe. The use of nanostructured metal transducers enables the generation of particularly short wavelength surface acoustic waves, which truly confine the measurement within the ultrathin film layer of interest, to thicknesses < 50 nm for the first time. Simultaneous measurement of longitudinal and transverse surface wave velocities yields both the Young’s modulus and Poisson’s ratio of the film. In the future, this approach will make possible precise mechanical characterization of nanostructured systems at sub-10 nm length scales.
State of the art; microbiology in health and disease. Intestinal bacterial flora in autism

Autism of the regressive variety is selected as an example of the importance of intestinal bacterial microflora in disease other than classical infection. Our studies have indicated that intestinal bacteria play a role in this disease since it responds to oral vancomycin, a drug that is not absorbed from the GI tract. Pyrosequencing studies document an abnormal gut microflora in regressive autism subjects as compared to controls. Finally, we present preliminary evidence suggesting that Desulfovibrio may play a key role in this disease.
Interactions among osteoblastic cells, Staphylococcus aureus, and chitosan-immobilized titanium implants in a postoperative coculture system: An in vitro study

Biomaterial-related infections (BRIs) have become a major challenge in the field of orthopedic implants. In this study, we delved into the problem of BRI and attempted to reduce the possibility of BRI incidence via surface modification of titanium (Ti) with chitosan (SA-CS-Ti). To comprehensively evaluate the anti-infection potential of SA-CS-Ti, we first constructed a postoperative infection (POI) model with varying concentrations of bacteria (102 CFU/sample and 104 CFU/sample) and a constant number of SaOS-2 cells (105 /sample). Then, we biologically characterized the interactions between the SaOS-2 cells, bacteria, and different Ti implants using the POI model. The results from the osteoblastic cell and bacterial attachment tests demonstrated that the SA-CS-Ti surfaces exhibit superior osteogenic behavior relative to other Ti surfaces studied while showing significant anti-infective activities in the POI model with a low infection ratio (bacteria: cell ratio of 0.001:1) 30 min after infection. Additionally, the SA-CS-Ti surfaces showed significantly reduced (p < 0.05) bacteria proliferation compared to the control Ti surfaces (UN-Ti), demonstrating their antifouling property. The significantly increased (p < 0.05) sensitivity of Staphylococcus. aureus adhered to the SA-CS-Ti surfaces against cefazolin (1 mg/L treatment) and gentamicin (10 mg/L and 100 mg/L treatment) in the coculture system augmented potential of SA-CS-Ti to be used as orthopedic implants. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 586-594, 2016.
Design of a heterotetrameric coiled coil

We have successfully designed a simple peptide sequence that forms highly stable coiled-coil heterotetramers. Our model system is based on the GCN4-pLI parallel coiled-coil tetramer, first described by Kim and coworkers (Harbury et al., Science 1993;262:1401-1407). We introduced glutamates at all of the e and c heptad positions of one sequence (ecE) and lysines at the same positions in a second sequence (ecK). Based on a modeling study, these sidechains are close enough in space to form structure-stabilizing salt bridges. We show that ecE and ecK are highly unstable by themselves but form very stable parallel helical tetramers when mixed, as judged by circular dichroism, analytical ultracentrifugation, and disulfide crosslinking studies. The origin of the difference in stabilities between the homomeric structures and the heteromeric structures comes from a combination of the relief of electrostatic repulsions with concomitant formation of electrostatic attractive interactions based on pH and NaCl screening experiments. We quantify the stability of the heterotetrameric coiled coil from a thermodynamic analysis and compare the finding to other similar coiled-coil systems.
The Impact of World Views on Professional Life-Styling.

A world view expresses the presuppositions a person makes about his or her world. These basic presuppositions center on the nature of ultimate reality, of the universe, of mankind, the meaning of death, the basis of ethics, and the meaning of human history. The four perspectives of theism, deism, agnosticism, and atheism summarize views regarding these six issues. Then the influence of each of the four perspectives on certain counseling issues that are seen as the warp and woof of a counselor's value system are analyzed. These special counseling issues are the counselor-client relationship, motives for counseling, counseling goals, the method of dealing with special problems, and the choice of counseling strategies. One implication of this analysis is that counselors-in-training should study all the perspectives and also formulate for themselves a personal counseling approach that reflects thinking on both the six world issues and the special counseling issues. The second implication of the analysis is that the authentic counselor can work with others in a climate of respect for world views that differ from his or hers. The counselor does not threaten their beliefs—even when helping them to explore, clarify, and develop personal values. Jeffry Tindall reviews the philosophical approach that Smith proposes and urges that the emphasis of counselors be focused in the philosophical area of axiology.
Glacier mass balances (1993–2001), Taylor Valley, McMurdo Dry Valleys, Antarctica

Mass balances were measured on four glaciers in Taylor Valley, Antarctica, from 1993 to 2001. We used a piecewise linear regression, which provided an objective assessment of error, to estimate the mass balance with elevation. Missing measurements were estimated from linear regressions between points and showed a significant improvement over other methods. Unlike temperate glaciers the accumulation zone of these polar glaciers accumulates mass in summer and winter and the ablation zone loses mass in both seasons. A strong spatial trend of smaller mass-balance values with distance inland (r 2 = 0.80) reflects a climatic gradient to warmer air temperatures, faster wind speeds and less precipitation. Annual and seasonal mass-balance values range only several tens of millimeters in magnitude and no temporal trend is evident. The glaciers of Taylor Valley, and probably the entire McMurdo Dry Valleys, are in equilibrium with the current climate, and contrast with glacier trends elsewhere on the Antarctic Peninsula and in temperate latitudes.
Many-to-Many Aggregation for Sensor Networks

Wireless sensor networks have enormous potential to aid data collection in a number of areas, such as environmental and wildlife research. In this paper, we address the challenges of supporting many-to-many aggregation in a sensor network. An application of many-to-many aggregation is in-network control of sensors. For expensive sensing tasks such as sap flux measurements and camera repositioning, we use low-cost information obtained at multiple other nodes in the network to control such tasks, e.g., decreasing sampling rates when readings are predictable or unimportant, while increasing sampling rates when there are interesting activities. In general, there is a many-to-many relationship between sources (nodes providing control inputs) and destinations (nodes requiring control outputs). We present a method for implementing many-to-many aggregation in a sensor network that minimizes the communication cost by optimally balancing a combination of multicast and in-network aggregation. Our optimization technique is efficient in finding the initial solution and handling dynamic updates.