cssi/SciSciGPT-SciSciNet huggingface dataset:
The Road to Whren and Beyond: Does the 'Would Have' Test Work?

In Whren v. United States, the United States Supreme Court held that when a police officer performs a traffic stop based on objective probable cause, a reviewing court need not concern itself with whether the officer was making the stop for the "right reason" or for some other, unconstitutional, ulterior motive. The Whren test has come to be known as the "could have" test: as long as a police officer could have stopped a car (there was objective probable cause), the police officer's motivations are irrelevant for Fourth Amendment purposes. Although the opinion has been widely criticized for allowing unfettered police discretion and the resulting narrowing of drivers' Fourth Amendment protections, Washington is the only state that has rejected the Whren decision, finding more protection for drivers under its state constitution than the Supreme Court found under the federal Constitution. In 1999, the Washington State Supreme Court, in State v. Ladson, held that its citizens had a constitutionally protected interest against warrantless traffic stops made on a pretextual basis. The court's inquiry in Washington is whether a reasonable police officer "would have" made the stop absent the invalid motive. In this article, the author examines in detail Washington case law since the Ladson decision and identifies several limitations with the application of the "would have" test. Courts primarily find pretextual police behavior either when an officer admits to using a pretext or the court finds the officer's testimony to be inherently incredible, both of which are relatively rare circumstances. Although recognizing the very real problems of racial profiling and other abuses of police discretion, the author argues that the Washington experience with the "would have" test suggests that states would be better served by adhering to the Whren "could have" test while exploring other avenues of relief to address police abuses of discretion.
Kidney intercalated cells are phagocytic and acidify internalized uropathogenic Escherichia coli

Kidney intercalated cells are involved in acid-base homeostasis via vacuolar ATPase expression. Here we report six human intercalated cell subtypes, including hybrid principal-intercalated cells identified from single cell transcriptomics. Phagosome maturation is a biological process that increases in biological pathway analysis rank following exposure to uropathogenic Escherichia coli in two of the intercalated cell subtypes. Real time confocal microscopy visualization of murine renal tubules perfused with green fluorescent protein expressing Escherichia coli or pHrodo Green E. coli BioParticles demonstrates that intercalated cells actively phagocytose bacteria then acidify phagolysosomes. Additionally, intercalated cells have increased vacuolar ATPase expression following in vivo experimental UTI. Taken together, intercalated cells exhibit a transcriptional response conducive to the kidney's defense, engulf bacteria and acidify the internalized bacteria. Intercalated cells represent an epithelial cell with characteristics of professional phagocytes like macrophages.
Cardiovascular toxicities associated with abiraterone compared to enzalutamide-A pharmacovigilance study

Abstract Background Androgen deprivation therapy (ADT) is standard-of-care for advanced prostate cancer. Studies have generally found increased cardiovascular risks associated with ADT, but the comparative risk of newer agents is under-characterized. We defined the cardiac risks of abiraterone and enzalutamide, using gonadotropic releasing hormone (GnRH) agonists to establish baseline ADT risk. Methods We used VigiBase, the World Health Organization pharmacovigilance database, to identify cardiac adverse drug reactions (ADRs) in a cohort taking GnRH agonists, abiraterone, or enzalutamide therapy for prostate cancer, comparing them to all other patients. To examine the relationship, we used an empirical Bayes estimator to screen for significance, then calculated the reporting odds ratio (ROR), a surrogate measure of association. A lower bound of a 95% confidence interval (CI) of ROR > 1 reflects a disproportionality signal that more ADRs are observed than expected due to chance. Findings We identified 2,433 cardiac ADRs, with higher odds for abiraterone compared to all other VigiBase drugs for overall cardiac events (ROR 1•59, 95% CI 1•48—1•71), myocardial infarction (1•35, 1•16—1•58), arrythmia (2•04, 1•82—2•30), and heart failure (3•02, 2•60—3•51), but found no signal for enzalutamide. Patients on GnRH agonists also had increased risk of cardiac events (ROR 1•21, 95% CI 1•12—1•30), myocardial infarction (1•80, 1•61—2•03) and heart failure (2•06, 1•76—2•41). Interpretation We found higher reported odds of cardiac events for abiraterone but not enzalutamide. Our data may suggest that patients with significant cardiac comorbidities may be better-suited for therapy with enzalutamide over abiraterone. Funding None
Machine learning algorithms for predicting undernutrition among under-five children in Ethiopia.

OBJECTIVE Child undernutrition is a global public health problem with serious implications. In this study, we estimate predictive algorithms for the determinants of childhood stunting by using various machine learning (ML) algorithms. DESIGN This study draws on data from the Ethiopian Demographic and Health Survey of 2016. Five ML algorithms including eXtreme gradient boosting, k-nearest neighbours (k-NN), random forest, neural network and the generalised linear models were considered to predict the socio-demographic risk factors for undernutrition in Ethiopia. SETTING Households in Ethiopia. PARTICIPANTS A total of 9471 children below 5 years of age participated in this study. RESULTS The descriptive results show substantial regional variations in child stunting, wasting and underweight in Ethiopia. Also, among the five ML algorithms, xgbTree algorithm shows a better prediction ability than the generalised linear mixed algorithm. The best predicting algorithm (xgbTree) shows diverse important predictors of undernutrition across the three outcomes which include time to water source, anaemia history, child age greater than 30 months, small birth size and maternal underweight, among others. CONCLUSIONS The xgbTree algorithm was a reasonably superior ML algorithm for predicting childhood undernutrition in Ethiopia compared to other ML algorithms considered in this study. The findings support improvement in access to water supply, food security and fertility regulation, among others, in the quest to considerably improve childhood nutrition in Ethiopia.
Effects of hyperglycemia on lonidamine‐induced acidification and de‐energization of human melanoma xenografts and sensitization to melphalan

We seek to exploit the natural tendency of melanomas and other tumors to convert glucose to lactate as a method for the selective intracellular acidification of cancer cells and for the potentiation of the activity of nitrogen-mustard antineoplastic agents. We performed this study to evaluate whether the induction of hyperglycemia (26 mM) could enhance the effects of lonidamine (LND, 100 mg/kg; intraperitoneally) on the induction of intracellular acidification, bioenergetic decline and potentiation of the activity of melphalan (LPAM) against DB-1 melanoma xenografts in mice. Intracellular pH (pHi ), extracellular pH (pHe ) and bioenergetics (β-nucleoside triphosphate to inorganic phosphate ratio, β-NTP/Pi) were reduced by 0.7 units (p 0.05) and 51.4% (p < 0.05), respectively. The therapeutic response to LPAM (7.5 mg/kg; intravenously) + LND (100 mg/kg; intraperitoneally) was reduced by about a factor of three under hyperglycemic conditions relative to normoglycemia, producing a growth delay of 7.76 days (tumor doubling time, 5.31 days; cell kill, 64%) compared with LND alone of 1.70 days and LPAM alone of 0.29 days. Under normoglycemic conditions, LND plus LPAM produced a growth delay of 17.75 days, corresponding to a cell kill of 90% at the same dose for each of these agents. The decrease in tumor cell kill under hyperglycemic conditions correlates with an increase in tumor ATP levels resulting from increased glycolytic activity. However, hyperglycemia substantially increases lactic acid production in tumors by a factor of approximately six (p < 0.05), but hyperglycemia did not increase the effects of LND on acidification of the tumor, most probably because of the strong buffering action of carbon dioxide (the pKa of carbonic acid is 6.4). Therefore, this study demonstrates that the addition of glucose during treatment with LND diminishes the activity of this agent.
Improve Tennis Service through Mathematics

(1981). Improve Tennis Service through Mathematics. Journal of Physical Education and Recreation: Vol. 52, No. 7, pp. 55-55.
Salsalate treatment improves glycemia without altering adipose tissue in nondiabetic obese hispanics.

Author(s): Alderete, Tanya L; Sattler, Fred R; Richey, Joyce M; Allayee, Hooman; Mittelman, Steven D; Sheng, Xia; Tucci, Jonathan; Gyllenhammer, Lauren E; Grant, Edward G; Goran, Michael I | Abstract: ObjectiveSalsalate treatment has well-known effects on improving glycemia, and the objective of this study was to examine whether the mechanism of this effect was related to changes in adipose tissue.MethodsA randomized double-blind and placebo-controlled trial in obese Hispanics (18-35 years) was conducted. The intervention consisted of 4 g day(-1) of salsalate (n = 11) versus placebo (n = 13) for 4 weeks. Outcome measures included glycemia, adiposity, ectopic fat, and adipose tissue gene expression and inflammation.ResultsIn those receiving salsalate, plasma fasting glucose decreased by 3.4% (P l 0.01), free fatty acids decreased by 42.5% (P = 0.06), and adiponectin increased by 27.7% (P l 0.01). Salsalate increased insulin AUC by 38% (P = 0.01) and HOMA-B by 47.2% (P l 0.01) while estimates of insulin sensitivity/resistance were unaffected. These metabolic improvements occurred without changes in total, abdominal, visceral, or liver fat. Plasma markers of inflammation/immune activation were unchanged following salsalate. Salsalate had no effects on adipose tissue including adipocyte size, presence of crown-like structures, or gene expression of adipokines, immune cell markers, or cytokines downstream of NF-κB with the exception of downregulation of IL-1β (P l 0.01).ConclusionsFindings suggest that metabolic improvements in response to salsalate occurred without alterations in adiposity, ectopic fat, or adipose tissue gene expression and inflammation.
Membrane Currents and Mechanisms of Olfactory Transduction

The term olfactory transduction refers to the mechanisms that transform chemical information into electrical signals. With the patch-clamp technique it is possible to record those signals and to infer something about the mechanism that produced them. The direct activation of a cation-permeable channel by cAMP is the final step in producing the odour-induced ionic current. Because it occupies a critical position in the transduction process, measurements of the ion channel's activity provide useful insights into the molecular processes underlying olfactory transduction. In addition to its activation by cAMP and cGMP, the channel is modulated by both extracellular and intracellular Ca2+ ions and by extracellular Mg2+ ions, all at physiological concentrations. These effects are probably important in promoting signal reliability. An unusual feature of this channel is its termination kinetics--it can remain active for hundreds of milliseconds after the agonist has been removed. This is likely to add to the integrating properties of the olfactory sensory neuron.
An advantage of the multiproduct firm: The transferability of firm-specific capital

Abstract In a world of uncertainty, particular benefits of multiproduct organization arise out of a need to revise production plans. When transactions for inputs are costly, production involves inputs which are firm-specific. The ability to transfer firm-specific inputs withi n the multiproduct firm yields benefits not available to the single product firm. These benefits to firm diversification are not dependent on the assumption of managerial risk aversion and cannot be replicated by investors diversifying their portfolios.
CTMCs with Costs and Rewards

We consider continuous-time Markov chains (CTMCs) where there are costs and rewards associated with each state. For such a CTMC, the objective usually is to calculate either the long-run average costs incurred per unit time or the total discounted cost incurred over an infinite horizon. We illustrate the calculations using several examples and conclude with applications to system performance analysis. Keywords: CTMC; average costs; discounted costs; steady-state probability
Sufficient Conditions for a Minimum

As we have noted repeatedly, the equations of Euler-Lagrange are necessary but not sufficient to characterize a minimum value for the integral function $$ F(Y) = \int_a^b {f(x,Y(x),Y'(x))dx = } \int_a^b {f[Y(x)]dx} $$ on set such as D = {Y ∈ C1([a,b])d: Y(a) = A, Y(b) = B}, since they are only conditions for the stationary of F. However, in the presence of [strong] convexity of f(x,f) these conditions do characterize [unique] minimization. [Cf.§3.2, Problem 3.33 et seq.] Not all such functions are convex, but we have also seen in §7.6 that a minimizing function Y0 must necessarily satisfy the Weierstrass condition ℰ(x, Y0(x),\( {{Y'}_0} \)(x),W) ≥ 0, ∀ W ∈ ℝd, x ∈ [a,b], where ℰ(x, Y, Z, W) $$ \mathop = \limits^{def} $$ f(x, Y, W) - f(x, Y, Z)- fz(x, Y, Z)⋅(W - Z), (1) and this is recognized as a convexity statement for f(x, Y, Z) along a trajectory in ℝ2d+1 defined by Y0.
Development and analytic validation of an enzyme-linked immunosorbent assay for the measurement of canine pancreatic lipase immunoreactivity in serum.

Recently, a radioimmunoassay (RIA) for measurement of canine pancreatic lipase immunoreactivity (cPLI) in serum was developed and validated. However, RIAs require frequent use of radioactive materials. Therefore, the goal of this project was to develop and validate an enzyme-linked immunosorbent assay (ELISA) for cPLI. After purifying cPL, we developed and purified antiserum against cPL in rabbits. The purified antibody was bound to microtitre plates and used to capture antigen. A portion of the purified antibody was biotinylated and used to identify the captured antigen. Streptavidin labelled with horseradish peroxidase and a horseradish peroxidase substrate were used for detection. The assay was validated by determination of sensitivity, working range, linearity, accuracy, precision, and reproducibility. The reference interval for serum cPLI was determined by the central 95th percentile in 74 clinically healthy dogs: 2.2 to 102.1 μg/L. The sensitivity and the upper limit of the working range were 0.1 and 999.2 μg/L, respectively. The ratios of observed to expected values for dilutional parallelism for 6 serum samples ranged from 0.0 to 148.8%; the ratios for spiking recovery for 4 serum samples ranged from 90.4 to 112.6%, assuming 55% recovery of the cPL. Coefficients of variation for intra- and interassay variability for 6 different serum samples were 2.4, 3.4, 4.1, 5.8, 7.4, and 10.0% and 5.9, 7.7, 11.6, 13.9, 23.5, and 46.2%, respectively. We conclude that the ELISA described here is sufficiently sensitive, linear, accurate, precise, and reproducible for clinical application. Evaluation of its clinical usefulness for the diagnosis of exocrine pancreatic disorders in dogs is under way.
Characteristics of Contemporary Patients Discharged From the Hospital After an Acute Coronary Syndrome

Abstract Background Limited contemporary data compare the clinical and psychosocial characteristics and acute management of patients hospitalized with an initial vs a recurrent episode of acute coronary disease. We describe these factors in a cohort of patients recruited from 6 hospitals in Massachusetts and Georgia after an acute coronary syndrome. Materials and Methods We performed structured baseline in-person interviews and medical record abstractions for 2174 eligible and consenting patients surviving hospitalization for an acute coronary syndrome between April 2011 and May 2013. Results The average patient age was 61 years, 64% were men, and 47% had a high school education or less; 29% had a low general quality of life, and 1 in 5 were cognitively impaired. Patients with a recurrent coronary episode had a greater burden of previously diagnosed comorbidities. Overall, psychosocial burden was high, and more so in those with a recurrent vs those with an initial episode. Patients with an initial coronary episode were as likely to have been treated with all 4 effective cardiac medications (51.6%) as patients with a recurrent episode (52.3%), but were significantly more likely to have undergone cardiac catheterization (97.9% vs 92.9%) and a percutaneous coronary intervention (73.7% vs 60.9%) ( P Conclusions Patients with a first episode of acute coronary artery disease have a more favorable psychosocial profile, less comorbidity, and receive more invasive procedures but similar medical management, than patients with previously diagnosed coronary disease. Implications of the high psychosocial burden on various patient-related outcomes require investigation.
Modified Model for End-Stage Liver Disease eXcluding INR (MELD-XI) Score Predicts Early Death After Pediatric Heart Transplantation

Background We sought to determine the ability of the Model for End-Stage Liver Disease eXcluding INR (MELD-XI) to predict short-term and long-term outcomes in pediatric patients undergoing orthotopic heart transplant. Methods The United Network for Organ Sharing Database was queried for all pediatric patients (aged 1 to 18 years) undergoing orthotopic heart transplant from 2000 to 2012. The logarithmic relationship between the serum creatinine and bilirubin was used to calculate the MELD-XI score. Lowess smoothing plots were referenced, and a score threshold of 12.2 was used to stratify patients into low (75%) and high (25%) MELD-XI cohorts. Patient-specific characteristics, intraoperative variables, and postoperative outcomes were compared between the two cohorts. Differences in survival at 30 days, 1 year, and 5 years between the MELD-XI cohorts were estimated by the Kaplan-Meier method. Cox proportional hazards modeling was used to determine the risk-adjusted effect of a high MELD-XI score on death. Results After patients with missing MELD-XI scores were excluded, 2,939 patients met the inclusion criteria. Unconditional 30-day (93.1% vs 98.0%, p p p p = 0.29) and 5-year survival excluding 1-year deaths (82.8% vs 85.6%, p = 0.09) were statistically equivalent. When modeled as a categoric variable, a high MELD-XI score was an independent predictor of death at 30 days (hazard ratio, 2.86; 95% confidence interval, 1.84 to 4.45; p p p p Conclusions The MELD-XI scoring system can be used in pediatric orthotopic heart transplant to identify patients at risk for poor outcomes. Because long-term survival is largely driven by early death, renal insufficiency and congestive hepatopathy should be optimized before transplant.
Triangulating the genetic basis of adaptation to multifarious selection.

Understanding how natural populations adapt to their local environments is a major research theme for ecological genomics. This endeavour begins by sleuthing for shared genetic similarities among unrelated natural populations sharing adaptive traits to documented selective pressures. When the selective pressures have low dimensionality, and the genetic response is localized to a few genes of major effect, this detective work is relatively straightforward. However, in the real world, populations face a complex mixture of selective pressures and many adaptive responses are the result of changes in quantitative traits that have a polygenic genetic basis. This complex relationship between environment and adaptation presents a significant challenge. How can we begin to identify drivers of adaptation in natural settings? In this issue of Molecular Ecology, Orsini et al. (2012) take advantage of the biological attributes of the freshwater microcrustacean Daphnia (Fig. 1) to disentangle multidimensional selection’s signature on the genome of populations that have repeatedly evolved adaptive responses to isolated selective pressures including predation, parasitism and anthropogenic changes in land use. Orsini et al. (2012) leverage a powerful combination of spatially structured populations in a geographic mosaic of environmental stressors, the historical archive of past genotypes preserved in lake-bottom sediments and selection experiments to identify sets of candidate genomic regions associated with adaptation in response to these three environmental stressors. This study provides a template for future investigation in ecological genomics, combining multiple experimental approaches with the genomic investigation of a well-studied ecological model species. Figure 1. Adult Daphnia magna carrying a resting egg in the brood pouch. The water flea Daphnia is a renowned ecological model system and rapidly developing as an ecological and environmental genomics model species. Photo credit Joachim Mergeay.
Coarse-grained modeling of vesicle responses to active rotational nanoparticles

In recent years, magnetically-driven-rotating superparamagnetic nanoparticles have been emerging as a valuable component in designing targeted drug delivery carriers and cellular killers via membranes’ physical rupture. The lack of an in-depth understanding of how to control the interaction of rotational nanoparticles (RNPs) with vesicles has hindered progress in the development of their relevant biomedical applications. Here we perform dissipative particle dynamics simulations to analyze the rotation frequencies, size, and coating patterns of the RNPs as they interact with the vesicle so as to provide novel designs of drug delivery applications. Results have revealed that the RNPs are capable of triggering local disturbance around the vesicle and therefore promoting the vesicle translocation toward the RNPs. By investigating the translocation time and driving forces required for RNPs to enter inside the vesicle at various rotation frequencies as well as the interaction energy between coated RNPs and the vesicle, we have tuned the coating pattern of the ligands on the surface of RNPs to open a specified channel in the vesicle for promoting drug delivery. Our findings can provide useful guidelines for the molecular design of patterned RNPs for controllable bio/inorganic interfaces and help establish qualitative rules for the organization and optimization of ligands on the surface of the desired drug delivery carriers.
Outcome-based Education: A Smarter Way to Assess Student Learning

(1989). Outcome-based Education: A Smarter Way to Assess Student Learning. The Clearing House: A Journal of Educational Strategies, Issues and Ideas: Vol. 63, No. 4, pp. 172-174.
Numerical modelling approaches for assessing improvements to the flow circulation in a small lake

Kamaniskeg Lake is a long, narrow, and deep small lake located in the northern part of Ontario, Canada. The goals of this paper were to examine various options to improve the water quality in the northern part of the lake by altering the local hydraulic flow conditions. Towards this end, a preliminary screening suggested that the flow circulation could be increased around a central island (Mask Island) in the northern part of the lake by opening up an existing causeway connecting the mainland and central island. Three-dimensional (3D) hydraulic and transport models were adopted in this paper to investigate the hydraulic conditions under various wind forces and causeway structures. The modelling results show that opening the causeway in a few places is unlikely to generate a large flow circulation around the central island. Full circulation only appears to be possible if the causeway is fully removed and a strong wind blows in a favourable direction. The possible reasons for existing water quality variations at the intake of a localWTP (water treatment plant) are also explored in the paper.
Characteristics Supporting Change in a Professional Development School.

We examine the work of one professional development school by studying the question, "What characteristics support change in a professional development school?" We suggest six guiding principles: (a) Role shifts of members of the school's steering group need careful nurturing; (b) the nature, direction, and pace of change need to evolve from the school community participants; (c) school community strengths need to serve as the foundation for change; (d) the expectation of continual growth needs to be established in the school community; (e) a balance needs to be struck between supporting and challenging professional development efforts; (f) the school community needs to acknowledge and embrace the complexities of curriculum and instruction.
The Emotional Context Facing Nursing Home Residents’ Families: A Call for Role Reinforcement Strategies from Nursing Homes and the Community

Objectives Identify useful concepts related to the emotional context facing family members of nursing home residents. These concepts can be used in future studies to design and test interventions that benefit family caregivers. Design Secondary data analyses of qualitative ethnographic data. Setting Two nursing homes in a large Midwestern city; 8 months of data collection in each. Participants 44 family members of nursing home residents whose health was considered, “declining.” Measurements Role theory was used to design and help interpret the findings. Data included transcripts of conversations between family members and researchers and were analyzed using a coding scheme developed for the secondary analysis. Results Comments about emotions related to the social role of family member were grouped into three categories: relief related to admission, stress, and decision making support/stress. Subcategories of stress include the role strain associated with “competing concerns” and the psychological pressures of 1) witnessing the decline of a loved one in a nursing home, and 2) guilt about placement. Decision-making was discussed as a challenge which family members did not want to face alone; support from the resident, health care professionals, and other family members was appreciated. Conclusions Family members may benefit from role reinforcement activities provided by nursing home staff and community members. All nursing home staff members (in particular social workers) and physicians are called upon to provide educationa and support regarding nursing home admissions, during the decline of the resident, and especially regarding medical decision-making. Community groups are asked to support the family member by offering assistance with concrete tasks (driving, visiting, etc.) and social support.
Less minimal supersymmetric standard model

Most of the phenomenological studies of supersymmetry have been carried out using the so-called minimal supergravity scenario, where one assumes a universal scalar mass, gaugino mass, and trilinear coupling at M{sub GUT}. Even though this is a useful simplifying assumption for phenomenological analyses, it is rather too restrictive to accommodate a large variety of phenomenological possibilities. It predicts, among other things, that the lightest supersymmetric particle (LSP) is an almost pure B-ino, and that the {mu}-parameter is larger than the masses of the SU(2){sub L} and U(1){sub Y} gauginos. We extend the minimal supergravity framework by introducing one extra parameter: the Fayet'Iliopoulos D-term for the hypercharge U(1), D{sub Y}. Allowing for this extra parameter, we find a much more diverse phenomenology, where the LSP is {tilde {nu}}{sub {tau}}, {tilde {tau}} or a neutralino with a large higgsino content. We discuss the relevance of the different possibilities to collider signatures. The same type of extension can be done to models with the gauge mediation of supersymmetry breaking. We argue that it is not wise to impose cosmological constraints on the parameter space.
Association of ClC-3 channel with Cl- transport by human nonpigmented ciliary epithelial cells.

Electrophysiologic and volumetric evidence link the swelling-activated Cl− channels [gCl(Vol)] of nonpigmented ciliary epithelial (NPE) cells with the Cl−- channel/Cl−-channel regulator protein pICln. However, inhibitors (verapamil and dideoxyforskolin) of another Cl− channel/regulator (MDR1) have been found to inhibit the volume-activated transport response [the regulatory volume decrease (RVD)] of bovine NPE cells. We have addressed the possible molecular basis for the NPE Cl− channels by volumetric measurements of ODM human NPE cells in hypotonic and isotonic test solutions, and by polymerase chain reaction (PCR) cloning and Northern analyses of the same cells. Verapamil and dideoxyforskolin did inhibit the RVD. However, at a concentration (100 μm) which blocks >90% of the MDR1-associated Cl− currents, forskolin had no effect on the volume-activated Cl− channels or on the inhibition of those channels by protein kinase C. High concentrations of ATP (3.5 and 10 mm) and niflumic acid (IC50∼ 200 μm) also block [gCl(Vol)]. The RVD is inhibited by 9-phenylanthranilic acid (DPC) and 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB), unaffected by anthracene-9-carboxylic acid (9-AC), and stimulated by ionomycin. The Cl−-channel blockers NPPB, niflumic acid, DPC and 9-AC, and the Ca2+-ionophore ionomycin had qualitatively similar effects on the rate of staurosporine-activated isotonic cell shrinkage. These results support the concept that the volume-sensitive protein pICln regulates the Cl− channels, and that the same conduits subserve volume- and staurosporine-activated Cl− release. Of the cloned and sequenced Cl− channels, ClC-3 uniquely conforms to the stationary currents and PKC sensitivity of the NPE Cl− channels. PCR amplifications of human cDNA libraries from ciliary body, NPE cells and retina with primers based on human ClC-3 and ClC-4 cDNA, and Northern analyses using the products generated indicated that ciliary epithelial cells express transcripts for ClC-3 (but not ClC-4). We suggest that ClC-3 provides the same conduit for both volume-activated and isotonically staurosporine-activated Cl− channels of human nonpigmented ciliary epithelial cells.
Purchasing and Supply M anagement's Participation in the Target Costing Process

SUMMARY This article explores the participation of the purchasing and supply management function in the process of target costing. Target costing is an emerging process whereby organizations calculate the allowable cost (i.e., target cost) for buying/producing the product or service they offer for sale by first determining the acceptable selling price in the marketplace and the organization's required internal margin on the product. Based on case studies of organizations that use target costing, this research is both descriptive and prescriptive in nature. The four primary issues addressed in this article are: 1Why do organizations undertake target costing? 2Is there a common pattern of participation for the purchasing and supply management function in target costing? 3What should the role of purchasing and supply management be in the target costing process? 4How can purchasing and supply management be most effectively involved in the target costing process?
Open trial of methotrexate as treatment for autoimmune hearing loss

Objective To assess the efficacy of low-dose methotrexate (MTX) administered for the treatment of autoimmune hearing loss. Methods This was a prospective, 12-month, open-label study of 17 patients with refractory autoimmune hearing loss. All patients had ongoing episodic worsening of hearing in one or both ears prior to enrollment despite traditional medical therapy. The MTX dose was 7.5–25 mg/week. Hearing loss and vertigo were evaluated at baseline and at completion of the study. Hearing improvement was defined as an improvement in pure tone threshold (PT) average of >10 dB or an increase in speech discrimination (SD) of >15%; worsening was defined as a decrease of >10 dB in PT or a decrease of >15% in SD in at least one ear. Results MTX was well tolerated. Among patients with Meniere's disease, 5 of 9 had improvement or resolution of vertigo. Equilibrium improved in all 3 patients with Cogan's syndrome and improved in 2 out of 3 patients with idiopathic hearing loss and this symptom. According to the parameters defined above, hearing improved in 11 patients (65%), was unchanged in 4 patients (23%), and worsened in 2 patients (12%). Conclusion Long-term low-dose MTX therapy may be a useful therapy for at least some patients who have hearing loss with a presumptively autoimmune-mediated component that is refractory to traditional therapies.
The proctological aspects of diarrhea

This communication attempts to present the proctological significance of diarrhea, or alteration in stool habitus, from the standpoint of diagnosis by direct visual inspection of the bowel mucosa. It is hoped that the general practitioner, the internist, the gastro-enterologist, and others will recognize that the judicious use of the proctosigmoidoscope should be part of their diagnostic procedures. Endoscopic examination of the anus, rectum and pelvic colon permits direct visualization of the terminal gut; there is no substitute for it. As with other investigative procedures, it is not always possible to arrive at a final diagnosis during the first examination: particularly if attempt is made to recognize pathology when the bowel has not been thoroughly emptied of all forms of residue. One cannot too severely condemn efforts at diagnosis made when the patient has not been properly prepared, or when the examiner does not completely and thoroughly inspect all of the mucosa within reach of the instrument. Stool examination should be augmented by direct smear and culture from the mucosal surface. Scraping should be examined grossly and microscopically more frequently than is the custom. Biopsy is indicated more commonly than is practiced. The presence of more than one disease, i.e. amebiasis complicating malignancy, should be kept in mind in the obscure and unusual case. The term “colitis” will mean something if we can demonstrate the cause which is truly producing inflammation of the bowel. Only in such events is it possible to have exhibited specific therapy for specific disease processes. Roentgenological investigation should be the harmonious accompaniment to the special diagnostic procedures common to the trained proctologist.
Spatial heterogeneity of endocardial voltage amplitude in viable, chronically dysfunctional myocardium

BACKGROUND Although electromechanical mapping has been used to assess cardiac physiology, interpretation is dependent upon the spatial variability of endocardial voltage and local shortening in normal and viable dysfunctional myocardium, which is currently unknown. METHODS NOGA mapping was performed in 13 pigs with an established model of viable dysfunctional myocardium produced by a chronic LAD stenosis, and five uninstrumented controls. Voltage maps (122 +/- 7 points each) were obtained in the closed-chest anesthetized state, and (18)F-2-deoxyglucose uptake and TTC staining confirmed viability. RESULTS There were systematic regional variations in voltage amplitude in both chronically-instrumented and control animals. Unipolar voltage was ~15% higher in LAD-supplied versus remote myocardium (10.8 +/- 0.3 vs. 8.9 +/- 0.4 mV, p < 0.001), with a similar relative difference in controls (14.0 +/- 0.5 vs. 12.0 +/- 0.4 mV, p < 0.02). In contrast, bipolar voltage was ~35% lower in the LAD territory of both groups (2.2 +/- 0.2 vs. 3.5 +/- 0.2 mV, p < 0.01 and 3.1 +/- 0.3 vs. 5.1 +/- 0.3 mV in controls, p < 0.01). The relative dispersion (SD/mean) of voltage was large, but significantly lower for unipolar versus bipolar measurements (39 +/- 1% vs. 70 +/- 2%, p < 0.001). Variability between hearts was partially related to end-systolic volume (r = 0.58, p < 0.05). Linear local shortening measurements were insensitive to detect anterior hypokinesis. CONCLUSIONS Our data demonstrates significant regional and spatial heterogeneity of endocardial voltage and NOGA-derived linear shortening in normal and viable dysfunctional myocardium, with large confidence intervals for individual measurements. Even though the absence of necrosis in this model precludes assessment of the sensitivity and specificity of NOGA mapping to identify infarction, our findings highlight important methodological limitations in using electromechanical mapping to determine viability.
Sphingosine kinase 1–mediated inhibition of Fas death signaling in rheumatoid arthritis B lymphoblastoid cells

Objective It is becoming increasingly apparent that B cells play an important role in the pathogenesis of rheumatoid arthritis (RA). Due to the scarcity of B cells in RA, it has been technically difficult to functionally characterize B cell apoptosis in this disease. As a necessary first step to identify candidate aberrations, we investigated Fas-mediated signaling events in immortalized peripheral blood B lymphoblastoid cell lines (LCLs) from patients with RA and controls. Methods Cell death was determined by the MTS assay, and apoptosis was detected by the TUNEL assay and DNA laddering. Proteolytic activation of caspase 3 was determined by immunoblotting, and its enzymatic activity was determined by a fluorometric technique. Messenger RNA (mRNA) expression was quantified by real-time polymerase chain reaction (PCR) analysis. The functional role of sphingosine kinase (SPHK) was determined by measuring its enzymatic activity, by quantifying the levels of its product, sphingosine 1-phosphate (S1P), and by investigating the ability of the SPHK inhibitor N,N-dimethylsphingosine and isozyme-specific small interfering RNA (siRNA) oligonucleotides to reverse signaling aberrations. Results LCLs from patients with RA displayed disease-specific Fas-mediated signal transduction impairment with consequent resistance to cell death. RA LCLs displayed high constitutive SPHK activity and increased levels of S1P. Real-time PCR analysis showed higher SPHK-1 mRNA expression levels in RA patients compared with paired controls. Increased SPHK-1 (but not SPHK-2) mRNA levels were observed in synovial tissue from RA patients. Competitive inhibitors of SPHK reversed the resistance of RA LCLs to Fas-induced apoptosis. Additionally, resistance to Fas-mediated signaling was reversed by siRNA oligonucleotides specific for SPHK-1 but not by oligonucleotides specific for SPHK-2. Conclusion These findings demonstrate disease-specific resistance to Fas-mediated death signaling in patients with RA and implicate increased SPHK-1 activity as the cause of this aberration.
Stability of the density-wave state of a dipolar condensate in a pancake-shaped trap

We study a dipolar boson-fermion mixture in a pancake geometry at absolute zero temperature, generalizing our previous work on the stability of polar condensates and the formation of a density-wave state in cylindrical traps. After examining the dependence of the polar condensate stability on the strength of the fermion-induced interaction, we determine the transition point from a ground-state Gaussian to a hexagonal density-wave state. We use a variational principle to analyze the stability properties of those density-wave state.
Realizing the allosteric potential of the tetrameric protein kinase A RIα holoenzyme.

Summary PKA holoenzymes containing two catalytic (C) subunits and a regulatory (R) subunit dimer are activated cooperatively by cAMP. While cooperativity involves the two tandem cAMP binding domains in each R-subunit, additional cooperativity is associated with the tetramer. Of critical importance is the flexible linker in R that contains an inhibitor site (IS). While the IS becomes ordered in the R:C heterodimer, the overall conformation of the tetramer is mediated largely by the N-Linker that connects the D/D domain to the IS. To understand how the N-Linker contributes to assembly of tetrameric holoenzymes, we engineered a monomeric RIα that contains most of the N-Linker, RIα(73-244), and crystallized a holoenzyme complex. Part of the N-linker is now ordered by interactions with a symmetry-related dimer. This complex of two symmetry-related dimers forms a tetramer that reveals novel mechanisms for allosteric regulation and has many features associated with full-length holoenzyme. A model of the tetrameric holoenzyme, based on this structure, is consistent with previous small angle X-ray and neutron scattering data, and is validated with new SAXS data and with an RIα mutation localized to a novel interface unique to the tetramer.
Inhibition of constitutively active Stat3 suppresses growth of human ovarian and breast cancer cells

Signal transducers and activators of transcription (STATs) are transcription factors activated in response to cytokines and growth factors. Constitutively active Stat3 has been shown to mediate oncogenic transformation in cultured cells and induce tumor formation in mice. An increasing number of tumor-derived cell lines as well as samples from human cancer have been reported to express constitutively active Stat3 protein. We previously demonstrated that ovarian cancer cell lines express high levels of constitutively active Stat3. In this study, we show that inhibition of the Stat3 signaling pathway using the Janus Kinase-selective inhibitor, AG490, and a dominant negative Stat3 (Stat3beta) significantly suppresses the growth of ovarian and breast cancer cell lines harboring constitutively active Stat3. In the ovarian cancer cell lines, AG490 also diminished the phosphorylation of Stat3, Stat3 DNA binding activity, and the expression of Bcl-x(L). Further, AG490 induced significant apoptosis in ovarian and breast cancer cell lines expressing high levels of constitutively active Stat3 but had a less profound effect on normal cells lacking constitutively active Stat3. AG490 also enhanced apoptosis induced by cisplatin in ovarian cancer cells. These results suggest that inhibition of Stat3 signaling may provide a potential therapeutic approach for treating ovarian and breast cancers.
Chemosensory integration in the spiny lobster: Ascending activity in the olfactory-globular tract

Chemical stimulation of the antennules (1st antennae) of the spiny lobster,Panulirus argus, activates olfactory-globular tract neurons that ascend the eyestalk of this organism. Extracellular records show that: 1. Receptor fields of these neurons are always unilateral. Fields of some units include medial as well as lateral filament chemoreceptors. Ipsilateral input predominates but some crossing over of contralateral input is evident (Table 1). 2. These neurons respond to antennular chemostimulation with a transient, concentration-dependent increase in firing frequency (Fig. 3). No inhibitory responses were noted. Thresholds to taurine stimulation average 2.4×10−5M (Table 3). 3. Responses decrement rapidly to repetitive stimulation (Fig. 4). Responses are not decremented or incremented by simultaneous bilateral chemostimulation (Table 4).
Emerging in a Digital World A Decade Review of Media Use, Effects, and Gratifications in Emerging Adulthood

This article reviews the recent literature on uses, effects, and gratifications of media during emerging adulthood. We examine traditional media forms, including television, films, video games, music, and books, and also newer media, such as cell phones, social networking sites, and other Internet use. We find that emerging adults spend more time using the media than they spend doing any other activity, with the most time being spent on the Internet and listening to music. We also find that exposure to certain types of media content can influence both positive and negative outcomes in emerging adulthood, including, aggressive and prosocial behavior, body image, sexual behavior, friendship quality, and academic achievement. We also show that emerging adults use the media to gratify certain needs; key among these are for autonomy, identity, and intimacy needs. Finally, we discuss areas for future research involving media and emerging adulthood.
Eperythrozoon coccoides: Influence on Course of Infection of Plasmodium chabaudi in Mouse

Mice infected with Plasmodium chabaudi obtained from two sources were found to be contaminated with Eperythrozoon coccoides. At each transfer of blood parasitized with plasmodia, eperythrozoa were also passed. In the presence of these organisms, the malarial infection assumed a low-level, chronic course infrequently resulting in death of the mice. When the eperythrozoa were eliminated through treatment with oxophenarsine hydrochloride, the malarial infection took an acute course always ending in death.
Benchmarking EV and HEV power electronics and electric machines

This paper presents information from an ongoing benchmarking project being conducted at Oak Ridge National Laboratory (ORNL) and funded by the Department of Energy (DOE). Beginning with the 2004 Toyota Prius, ORNL has benchmarked components from many on-the-road EVs, HEVs, and PHEVs. Detailed design, packaging, and operational assessments are presented on power electronic converters (such as inverters, buck converters, and bi-directional boost converters), electric motors (such as the primary drive motor and generator), and other associated components. Packaging assessments reveal mass, volume, and material compositions, and empirical evaluations provide efficiency, performance, and operational data throughout the entire operation range of each component.
The “Kluge‐Lüttge Kammer”: A Preliminary Evaluation of an Enclosed, Crassulacean Acid Metabolism (CAM) Mesocosm that Allows Separation of Synchronized and Desynchronized Contributions of Plants to Whole System Gas Exchange

Crassulacean acid metabolism (CAM) is recognized as a photosynthetic adaptation of plants to arid habitats. This paper presents a proof-of-concept evaluation of partitioning net CO2 exchanges for soil and plants in an arid, exclusively CAM mesocosm, with soil depth and succulent plant biomass approximating that of natural Sonoran Desert ecosystems. We present the first evidence that an enclosed CAM-dominated soil and plant community exposed to a substantial day/night temperature difference (30/20 degrees C), exhibits a diel gas exchange pattern consisting of four consecutive phases with a distinct nocturnal CO2 uptake. These phases were modulated by plant assimilation and soil respiration processes. Day-time stomatal closure of the CAM cycle during phase III was used to eliminate aboveground photosynthetic assimilation and respiration and thereby to estimate belowground plant plus soil respiration. Rapid changes in temperature appeared to synchronize single plant gas exchange but individual plant gas exchange patterns were desynchronized at constant day/night temperatures (25 degrees C), masking the distinct mesocosm pattern. Overall, the mean carbon budget of this CAM model Sonoran Desert system was negative, releasing an average of 22.5 mmol CO2 m-2 d-1. The capacity for nocturnal CO2 assimilation in this exclusively CAM mesocosm was inadequate to recycle CO2 released by plant and soil respiration.
Modeling the within-host dynamics of HIV infection

The new field of viral dynamics, based on within-host modeling of viral infections, began with models of human immunodeficiency virus (HIV), but now includes many viral infections. Here we review developments in HIV modeling, emphasizing quantitative findings about HIV biology uncovered by studying acute infection, the response to drug therapy and the rate of generation of HIV variants that escape immune responses. We show how modeling has revealed many dynamical features of HIV infection and how it may provide insight into the ultimate cure for this infection.