cssi/SciSciGPT-SciSciNet huggingface dataset:
Why Chemotherapy Should be Given Early for Men with Metastatic Prostate Cancer

Metastatic hormone-sensitive prostate cancer (mHSPC) is an incurable disease, and despite a high response rate to androgen-deprivation therapy (ADT), outcomes have not significantly changed for many decades. Earlier attempts at multitargeted strategies with the addition of cytotoxic chemotherapy to ADT did not affect survival. As more effective therapies are emerging, including cytotoxic therapy for patients with metastatic castrate-resistant prostate cancer (mCRPC), there is increasing interest for testing these drugs earlier in the disease course. The premise is that agents with clinical benefit in advanced mCRPC may have a better effect if used preemptively before the development of significant resistance and to attack earlier de novo androgen resistant/independent clones. The recent results of the phase III clinical trial E3805 investigating ADT with or without docetaxel in mHSPC provide compelling support for this strategy. Docetaxel combined with ADT significantly improved overall survival from 44 to 57.6 months (p=0.0003), particularly in patients with high-volume disease (from 32.2 to 49.2 months; p=0.0006). Longer follow-up is needed to assess the effect on patients with low disease burden. Further studies are needed to further maximize the antitumor effect in patients with mHSPC and to investigate the effects of advancing therapy to this disease setting on the efficacy of respective agents in the castration-resistant setting.
RADIOGRAPHY OF THE CANINE HEAD

Through the use of a purebred dog skull collection, specific positioning recommendations were established for radiography for the three skull types. It is suggested that the central ray of the beam be maintained at the following mean angles relative to the hard palate for the rostrodorsal-to-caudoventral oblique projection of the foramen magnum: dolicocephalic, 30° mesaticephalic, 20° and brachycephalic, 10°. It is recommended that the head be axially rotated as follows to radiographically separate the roots of the superior canine teeth: dolicocephalic, 48° mesaticephalic, 43° and brachycephalic, 35°. If only the cheek teeth require evaluation, the head should be rotated as follows: dolicocephalic, 37° mesaticephalic, 34° and brachycephalic, 25°. For evaluation of the inferior cheek teeth, it is recommended that the head be rotated as follows: dolicocephalic, 46° mesaticephalic, 44° and brachycephalic, 28°. It is recommended that radiographs of the temporo-mandibular joint be made with the skull axially rotated 10° and longitudinally obliqued as follows: dolicocephalic, 10° mesaticephalic, 14° and brachycephalic, 27°. Suggestions for open-mouth projections for evaluation of the tympanic bullae are that the central ray maintain the following angles relative to the hard palate: dolicocephalic, 4° mesaticephalic, 9° and brachycephalic, 21°. It is recommended that a caudoventral-rostrodorsal oblique projection of the nasal cavity made at 30° to the hard palate replace the open-mouth ventrodorsal in brachycephalic breeds.
Evaluation of a local grid refinement method for steady-state block-centered finite-difference groundwater models

A new method of local grid refinement for two-dimensional block-centered finite-difference meshes that uses an iteration-based feedback to couple two separate grids has been developed. Its convergence properties have been evaluated and comparisons with alternative methods have been completed (Mehl and Hill, in review a). This work further investigates a difficulty encountered with the traditional telescopic mesh refinement (TMR) methods that lack a feedback. Results indicate: (1) Coupling the coarse grid with the refined grid in a numerically rigorous way that allows for a feedback can improve the coarse grid results; this improvement is not possible using the TMR methods because there is no feedback. (2) The TMR methods work well in situations where the better resolution of the locally refined grid has little influence on the overall flow-system dynamics, but if this is not true, lack of a feedback mechanism produced errors in head up to 6.8% and errors in cell-to-cell fluxes up to 7.1% for the case presented. (3) For the TMR methods, coupling using flux boundary conditions produces significant inconsistencies in the head distribution at the boundary interface. TMR inaccuracies can substantially effect parameter estimation (Mehl and Hill, in review b).
Chapter 5 Tumor angiogenesis and its control by tumor suppressor genes

Publisher Summary Angiogenesis-dependent disease processes are a consequence of the overproduction of normal or aberrant forms of proangiogenic mediators and the result of a relative deficiency in angiogenesis inhibitors. This chapter describes these multifunctional mediator systems, discusses how they function in normal and pathological angiogenesis, and how loss or inactivation of tumor suppressor genes can lead to dysregulated angiogenesis. The implications of these findings in the development of novel strategies for the treatment of solid tumors and other angiogenesis-dependent disorders are also discussed. Angiogenic mediators can be broadly divided into two groups: Stimulators and inhibitors. The majority of the stimulatory molecules are proteins and many of them are growth factors that induce endothelial cells to divide, migrate directionally toward the inducing stimulus, and differentiate into tubular structures. Most are secreted by a variety of cells including endothelial cells themselves, in response to exogenous or endogenous stimuli, and are produced locally and function in a paracrine manner. These mediators can stimulate angiogenesis directly by interacting with receptors on the endothelial cell surface, or indirectly by attracting and activating accessory cells, i.e., inflammatory macrophages, and inducing them to produce angiogenic mediators. Others, such as copper may function as cofactors in key interstitial enzyme systems, or in the case of plasminogen activators can activate latent enzymes, such as transforming growth factor beta to reveal its angiogenic activity.
Postthymic development of CD28-CD8+ T cell subset: age-associated expansion and shift from memory to naive phenotype.

During human aging, one of the major changes in the T cell repertoire is a dramatic expansion of T cells with the atypical CD28−CD8+ phenotype. In this study, we show that this increase is a consequence not only of an expansion in the CD28−CD8+ population but also of a decrease in the number of CD28+CD8+ T cells. The decrease in circulating CD28+CD8+ T cells is dramatically accelerated after the age of 50 and is not accompanied by an equivalent reduction in the CD28+CD4+ subset. Our findings confirm that aging leads to an accumulation of CD45RO+ T cells within the CD28+CD8+ subset as previously observed. Surprisingly, we found an increase in CD45RA+ expression with age in the CD28−CD8+ subset. Immune-phenotyping for activation markers, measurement of telomere DNA content, and cytokine production analysis indicate that the large majority of CD28−CD8+ T cells are Ag-experienced, despite their CD45RA+ phenotype. Our study further demonstrates that the poor proliferative response displayed by CD28−CD8+ T cells is not a consequence of telomere shortening. Also, analysis of cytokine production at the single cell level revealed that the proportions of IFN-γ+, IL-4+, and IL-10+ T cells are considerably higher among the CD28−CD8+ than the CD28+CD8+ subset. In summary, these data explain the presence of CD45RA+ T cells in the elderly, shed light on the phylogenetic origin of CD28−CD8+ T cells, and suggest a role for these cells in the immune senescence process.
Epilepsy Postings on YouTube: Exercising Individuals' and Organizations' Right to Appear

Philosopher Hannah Arendt maintains that everyone has the right to appear in public as an embodied, singular individual. Because of the stigma attached to epilepsy, many with this condition are denied this right. Using grounded theory techniques, the author analyzes uploads of epilepsy on YouTube. The author argues that personal uploads on YouTube are the only mass media examples in which those with epilepsy can exercise their right to appear without the interpretation of intermediaries. Emerging themes relating to "the right to appear" allow social workers to deepen understanding of this and other devastating, often invisible and sometimes life-threatening illnesses.
Primary Cerebral Blood Flow Deficiency and Alzheimer's Disease: Shadows and Lights

Alzheimer's disease (AD) is a degenerative disorder characterized by a decreased regional cerebral blood flow (CBF). It is most likely that a reduction in CBF could displace a pathway leading to AD genesis, in so far neuron death explains a sustained reduction in the supply of oxygen, glucose, and nutrients. Nevertheless, the concept of secondary CBF deficiency cannot explain the critical stages of early memory loss while, on the other hand, the picture of progressive ischemia due to primary CBF decline sheds light on the course of AD in a most persuasive manner. The concept of primary CBF deficiency is even more strengthened by the lack of correlation between degree of dementia and amount of CBF. Vascular abnormalities, frequently observed to co-occur with AD, might play a critical role in the initiation and aggravation of AD pathology given that the elimination of amyloid-β (Aβ) through a vascular route is an important brain Aβ clearance mechanism and its failure leads to formation of vascular amyloidosis and dense-core plaques. The goal of this review is to provide scientists comprehensive knowledge of the state-of the art influence vascular damage and reduced perfusion have on the final development of AD and to hopefully stimulate more research in this area of neuroscience.
Oxidation of uroporphyrinogen by methylcholanthrene-induced cytochrome P-450: essential role of cytochrome P-450d

Abstract We have previously shown that uroporphyrinogen is oxidized to uroporphyrin by microsomes (microsomal fractions) from 3-methylcholanthrene-pretreated chick embryo liver [Sinclair, Lambrecht & Sinclair (1987) Biochem. Biophys. Res. Commun. 146, 1324-1329]. We report here that a specific antibody to chick liver methylcholanthrene-induced cytochrome P-450 (P-450) inhibited both uroporphyrinogen oxidation and ethoxyresorufin O-de-ethylation in chick-embryo liver microsomes. 3-Methylcholanthrene-pretreatment of rats and mice markedly increased uroporphyrinogen oxidation in hepatic microsomes as well as P-450-mediated ethoxyresorufin de-ethylation. In rodent microsomes, uroporphyrinogen oxidation required the addition of NADPH, whereas chick liver microsomes required both NADPH and 3,3',4,4'-tetrachlorobiphenyl. Treatment of rats with methylcholanthrene, hexachlorobenzene and o-aminoazotoluene increased uroporphyrinogen oxidation and P-450d, whereas phenobarbital did not increase either. The contribution of hepatic P-450c and P-450d to uroporphyrinogen oxidation and ethoxyresorufin O-de-ethylation in methylcholanthrene-induced microsomes was assessed by using specific antibodies to P-450c and P-450d. Uroporphyrinogen oxidation by methylcholanthrene-induced rat liver microsomes was inhibited up to 75% by specific antibodies to P-450d, but not by specific antibodies to P-450c. In contrast, ethoxyresorufin de-ethylation was inhibited only 20% by anti-P450d but 70% by anti-P450c. Methylcholanthrene-induced kidney microsomes which contain P-450c but non P-450d did not oxidize uroporphyrinogen. These data indicate that hepatic P-450d catalyses uroporphyrinogen oxidation. We suggest that the P-450d-catalysed oxidation of uroporphyrinogen has a role in the uroporphyria caused by hexachlorobenzene and other compounds.
Reduction of cardiovascular risk in chronic kidney disease by mineralocorticoid receptor antagonism

Cardiovascular disease is the leading cause of death and morbidity in people with chronic kidney disease, but there are few evidence-based treatments for reducing cardiovascular events in these patients. The failure of novel drug candidates to delay progression to end-stage renal disease and limit or abrogate cardiovascular morbidity and mortality has led to increased interest in a mineralocorticoid receptor (MR) antagonist-based treatment model to reduce cardiovascular risk in patients with chronic kidney disease and end-stage renal disease. Aldosterone concentrations and MR signalling are associated with an enhanced risk of cardiovascular injury and the incidence of sudden death, and MR blockade decreases the risk of cardiovascular events and sudden death in patients with reduced glomerular filtration rate. Since evidence from clinical trials shows that treatment with MR antagonists confers a morbidity and mortality advantage for patients with cardiovascular disorders, similar benefits might also accrue in patients with chronic kidney disease. Large prospective trials are urgently needed to answer this question. In this Review, I argue that despite differences in the pathophysiology and clinical features of cardiovascular disease in patients with and without chronic kidney disease, MR antagonists could provide cardiovascular benefit in patients with chronic kidney disease.
DIETARY FACTORS AND THEIR RELATION TO RESPIRATORY SYMPTOMS THE SECOND NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY

Dietary factors may influence inflammatory and antioxidant activity, and hence the development of chronic respiratory symptoms. To examine this hypothesis, the authors analyzed data from the Second National Health and Nutrition Examination Survey (NHANES II). NHANES II was conducted on a sample representative of the civilian, noninstitutionalized US population, which included 9,074 white and black adults aged 30 years or older. Dietary factors were derived from serum levels and from a 24-hour dietary recall questionnaire. The authors examined the relations of these dietary factors to the presence of currently active respiratory symptoms. The relation of serum vitamin C, dietary vitamin C intake, dietary fish intake, the ratio of dietary sodium to dietary potassium, and the ratio of serum zinc to serum copper to the respiratory symptoms of bronchitis and wheezing was assessed. Initially, nutrient-specific logistic regression analysis was performed, controlling for age, race, sex, calories, and pack-years of cigarette smoking. When multiple nutrients and total caloric intake were considered for each respiratory symptom outcome, bronchitis was negatively associated with serum vitamin C and with the serum zinc:copper ratio and was positively associated with the sodium:potassium ratio. Wheezing was negatively associated with serum vitamin C, niacin, and the serum zinc:copper ratio. Interactions between nutrients and smoking status were not significant. These data suggest that several dietary constituents may influence the occurrence of respiratory symptoms in adults, independently of cigarette smoking.
c-Jun N-terminal kinase mediates apoptotic signaling induced by N-(4-hydroxyphenyl)retinamide.

N-(4-Hydroxyphenyl)retinamide (4-HPR), a retinoic acid analog, induces apoptosis in several cell types. The mechanism by which 4-HPR initiates apoptosis remains poorly understood. We examined the effects of 4-HPR on two prostate carcinoma cell lines, LNCaP (an androgen-sensitive, p53+/+ cell line) and PC-3 (an androgen-insensitive, p53−/− cell line). 4-HPR caused sustained c-Jun N-terminal kinase (JNK) activation and apoptosis in LNCaP cells but not in PC-3 cells at the dosages tested. Activation of JNK by 4-HPR was independent of caspases because a pan-caspase inhibitor failed to suppress JNK activation. Ultraviolet-C and γ-radiation induced JNK activation in both LNCaP and PC-3 cells, suggesting that the failure of PC-3 cells to respond to 4-HPR was due to defects upstream of the JNK pathway. Furthermore, γ-radiation-induced JNK activation was suppressed by an antioxidant, but 4-HPR-induced JNK activation was not, indicating that these two stimuli induced JNK activation through different mechanisms. Forced expression of JNK1, but not a JNK1 mutant, caused apoptosis in both LNCaP and PC-3 cells, suggesting that p53 is not required for JNK-mediated apoptosis. 4-HPR-induced apoptosis in LNCaP cells was suppressed by curcumin, which inhibits JNK activation. Expression of dominant-negative mutants in the JNK pathway also inhibited 4-HPR-induced apoptosis in human embryonic kidney 293 cells. Collectively, these results suggest that the JNK pathway mediates 4-HPR-induced apoptotic signaling.
Allozyme diversity and introgression in the Galapagos Islands. Endemic Gossypium darwinii and its relationship to continental G. barbadense.

Abstract Gossypium darwinii Watt is a tetraploid cotton endemic to the Galapagos Islands. Opinion has been divided as to whether or not it deserves recognition at the specific rank, with some considering it a variety of its presumed progenitor, the widely distributed South American species G. barbadense L. A previous hypothesis states that much of the perceived intergradation between the two taxa arose as a consequence of introgression from G. barbadense following its introduction to the archipelago during the past several hundred years. We performed allozyme analysis on 58 accessions of G. darwinii from six islands, using 17 enzymes collectively encoded by 59 loci. Levels of variation were high for an island endemic, with a mean number of alleles per locus of 1.34 and an average panmictic heterozygosity of 0.062. Principal component analysis revealed clustering of accessions according to their island of origin, and a spatial pattern of island-clusters that approximates geographical relationships among islands. Genetic relationships of G. darwinii with G. barbadense and G. hirsutum L. were studied using previously generated allozyme data. Significant introgression of G. hirsutum alleles was detected; however morphological considerations support the hypothesis that much of G. darwinii's diversity stems from interspecific gene flow from G. barbadense , Evidence is presented suggesting that the occurrence of G. hirsutum alleles in G. darwinii derives not from direct hybridization, but from a mediated transfer through introduced, G. hirsutum -introgressed; G. barbadense . Gossypium darwinii and G. barbadense are nearly fixed for different alleles at four loci and each contains a large number of unique alleles. Notwithstanding the high interspecific Nei's genetic identity (0.949), the allozyme data support geographical and morphological evidence in suggesting that a specific rank for G. darwinii is warranted.
Performance of ceramic materials in high temperature steam and hydrogen

Abstract Materials considered for use in fusion blankets for synthetic fuel production were exposed to flowing steam and a combination of steam and hydrogen at temperatures up to 1668 K and flow velocities of 10 meters per second, which are characteristic of blanket design conditions. The penetration rate of 2mm per year on silicon carbide in steam at 1400 K increased to 6mm per year at 1600 K, while alumina, zirconia, and magnesia were below 0.1mm per year. Steam containing 32 to 44 volume percent hydrogen caused a large increase in the erosion rate of alumina, zirconia, and magnesia at elevated temperatures. The temperature above which the erosion rate greatly increased was 1400 K for magnesia, 1550 K for alumina, and 1600 K for zirconia. The penetration rates below these temperatures were less than 0.1 mm per year; however, 100 K above these temperatures, the penetration rate increased four to six times and continued to increase with temperature. The erosion rate on silicon carbide was unaffected by the presence of hydrogen in the steam. Carbon dioxide was substituted for steam and hydrogen in several runs up to 1670 K, and no significant weight losses occurred. The silicon carbide acquired a porous-glassy coating at the highest temperature.
An Adrenergic Mechanism for Hyperglycemia Induced by Diazoxide

Abstract An intravenous injection of diazoxide in dogs leads to profound hypotension followed by an increase of the catecholamine blood level and hyperglycemia. A similar correlation was shown between the hypotensive action of nitroprusside and the resulting hyperglycemia. Diazoxide hyperglycemia can be inhibited by an adrenergic blocking agent and adrenalectomy. In adrenalectomized rats, noradrenaline has been shown to restore the hyperglycemic effect of diazoxide supported to a lesser extent by corticosteroids. Four months administration of diazoxide to normal rats leads to no histologic changes in the islets of Langerhans and no permanent hyperglycemia, but marked adrenal hypertrophy. The foregoing experiments support an adrenal etiology as one of the mechanisms responsible for the diazoxide hyperglycemia.
Emotional facial paresis with striatocapsular infarction

Emotional facial paresis (EFP) refers to hemifacial paresis of emotionally evoked or spontaneous smiling or weeping with preserved volitional movements of the face. The anatomical location for this phenomenon has been controversial. We report a 15-year-old boy with EFP. Follow-up MRI demonstrated infarction limited to the head of the caudate, putamen and anterior limb of the internal capsule on the contralateral side. This case lends support for selective damage at a striatal or capsular site in the production of EFP.
The Role of Glycine in the Chemical Mechanical Planarization of Copper

Chemical mechanical polishing (CMPI is an essential process in the production of integrated circuits containing copper interconnects. The role of glycine in reactive slurries representative of those that might be used in copper CMP was studied with the aim of improving our understanding of the mechanisms at play. The electrochemical processes involved in the oxidative dissolution of copper were investigated by potentiodynamic polarization studies. To delineate the specific effect of glycine on the dissolution and polishing of copper, electrochemical tests were conducted in aqueous media with and without glycine. Experimentally measured polarization curves agreed well with potential-pH diagrams for the copper-water and copper-water-glycine systems. In situ electrochemical polarization experiments and open-circuit potential measurements were then conducted during polishing using slurries containing either no glycine or 10 -2 M glycine. These tests indicated that glycine curtails the formation of copper oxide films during polishing and hence may improve the CMP process by controlling the oxide thickness.
Wetting in a three-dimensional system: An exact solution.

On decrit un modele exactement, de trois dimensions, possedant une singularite de chaleur specifique divergente en logarythme
Synthesis of MgHf(WO4)3 and MgZr(WO4)3 using a non-hydrolytic sol-gel method

Magnesium zirconium tungstate and magnesium hafnium tungstate were successfully synthesized using a non-hydrolytic sol–gel method. Crystalline materials could be obtained at temperatures as low as 540 °C after as little as 3 h. The samples were composed of micron-size particles with defined morphology. Highly crystalline material was formed after a 0.5 h heat treatment of 1050 °C.
Mother-to-child speech at 2 years--effects of early postnatal contact.

Ten primiparous mothers were randomly selected from two groups of women who had spent different amounts of time with their newborn infants. The speech behavior of the mothers in the two groups was compared while they were addressing their 2-year-old children in an informal play situation. Speech patterns of the mothers revealed that those who had been given extra contact with their infants during the neonatal period used significantly more questions, adjectives, words per proposition, and fewer commands and content words than did the control mothers. These observations suggest that the linguistic behavior of the young child may be shaped by hospitalcare practices for mother and her infant.
Pulsed laser deposition of single phase LiNbO3 thin film waveguides

We performed a parametric study to suppress secondary phases in lithium niobate thin films by using pulsed laser deposition (PLD). By reducing the growth rate and changing the ambient gas pressure respectively, we found that the main parameter suppressing secondary phases is controlling the plume strength. For investigating the relation between film phases and the plume strength, extensive parametric studies were performed by changing the oxygen ambient pressure, the target to substrate distance, and also the Li content in the target. The surface morphologies of single phase films obtained with different deposition parameters are compared and deposition parameters to achieve lower loss single-phase films are discussed.
Tracking and disrupting dark networks: Challenges of data collection and analysis

The attack on September 11, 2001 set off numerous efforts to counter terrorism and insurgencies. Central to these efforts has been the drive to improve data collection and analysis. Section 1 summarizes some of the more notable improvements among U.S. government agencies as they strive to develop their capabilities. Although progress has been made, daunting challenges remain. Section 2 reviews the basic challenges to data collection and analysis focusing in some depth on the difficulties of data integration. Three general approaches to data integration are identified--discipline-centric, placed-centric and virtual. A summary of the major challenges in data integration confronting field operators in Iraq and Afghanistan illustrates the work that lies ahead. Section 3 shifts gears to focus on the future and introduces the discipline of Visual Analytics--an emerging field dedicated to improving data collection and analysis through the use of computer-mediated visualization techniques and tools. The purpose of Visual Analytics is to maximize human capability to perceive, understand, reason, make judgments and work collaboratively with multidimensional, conflicting, and dynamic data. The paper concludes with two excellent examples of analytic software platforms that have been developed for the intelligence community--Palantir and ORA. They signal the progress made in the field of Visual Analytics to date and illustrate the opportunities that await other IS researchers interested in applying their knowledge and skills to the tracking and disrupting of dark networks.
Introduction: The future of psychotherapy training: psychodynamic, experiential, and eclectic perspectives.

What does the future hold with regard to psychotherapy training? We posed that question to experts representing three important therapeutic approaches: Psychodynamic, Experiential, and Eclectic. In what follows we introduce this special section, provide our rationale for putting it together, and briefly highlight some interesting, substantive points made in the subsequent papers. © 1999 John Wiley & Sons, Inc. J Clin Psychol 55: 381–383, 1999.
The effects of foreign accents on employment‐related decisions

Purpose – Although statistical evidence clearly demonstrates discrimination against foreign‐accented individuals in the workplace, surprisingly little research attention has been paid to how such individuals are evaluated when they apply for jobs. Thus, the aim of this paper is to examine the effects of applicant accent on access‐related employment decisions across four jobs that differed on job status and communication demands.Design/methodology/approach – The study used a 3 (applicant accent: Standard American English, French, and Japanese) × 2 (job status: low vs high)×2 (communication demands: low vs high) mixed‐factorial design, and data from 286 college students at two different locations.Findings – Results show that in comparison with French‐accented applicants, Japanese‐accented applicants fared worse on employment‐related decisions, especially for jobs that had high communication demands, even after controlling for applicant understandability and location. French‐accented applicants were viewed a...
A Conference of the Baltic Heritage Network in Tartu, Estonia

The article summarizes the third conference of the Baltic Heritage Network, held in Tartu, Estonia on June 26–28, 2012.
Smoke development at different energy flux levels in an NBS smoke density chamber

An automatically controlled high-energy flux heater has been developed and utilized in an NBS Smoke Density Chamber.
Uniqueness via the adjoint problems for systems of conservation laws

We prove a result of uniqueness of the entropy weak solution to the Cauchy problem for a class of nonlinear hyperbolic systems of conservation laws that includes in particular the p-system of isentropic gas dynamics. Our result concerns weak solutions satisfying the, as we call it, Wave Entropy Condition, or WEC for short, introduced in this paper. The main feature of this condition is that it concerns both shock waves and rarefaction waves present in a solution. For the proof of uniqueness, we derive an existence result (respectively a uniqueness result) for the backward (respectively forward) adjoint problem associated with the nonlinear system. Our method also applies to obtain results of existence or uniqueness for some linear hyperbolic systems with discontinuous coefficients. © 1993 John Wiley & Sons, Inc.
The Gustatory and Olfactory Systems During Infancy: Implications for Development of Feeding Behaviors in the High-Risk Neonate

This article reviews the development of the senses of taste and smell, which provide information on the flavor of foods, and discusses how innate predispositions interact with early-life feeding experiences to form children's dietary preferences and habits. A basic understanding of the development and functioning of the chemical senses during early childhood may assist in forming evidence-based strategies to improve children's diets, especially for those who experience a discontinuity or disruption in early flavor experiences.
Transport of protons and hydrochloric acid through lipid bilayer membranes.

Transport of protons and hydrochloric acid through lipid bilayer membranes was studied by a combination of electrical conductance and pH electrode techniques. In the presence of large pH gradients, proton transport occurs primarily by diffusion of molecular HCl. The permeability of egg phosphatidylcholine/decane bilayers to HCl is about 3 cm . s-1, seven to nine order of magnitude higher than the permeability to H+, OH- or Cl-. The HCl permeability of phosphatidylserine or egg phosphatidylcholine/cholesterol (1 : 1) bilayers is about 50% lower than the permeability of egg phosphatidylcholine bilayers. Diffusion of molecular HCl may be an important process in tissues exposed to high HCl concentrations, e.g., gastric mucosa. However, at neutral pH the diffusion of molecular HCl is too slow to contribute significantly to net movements of H+ or Cl-.
Hypercalcemia complicating small-cell carcinoma.

Hypercalcemia is a common paraneoplastic syndrome complicating some varieties of lung cancer. It has rarely been reported with small-cell carcinoma of the lung. Seven cases of hypercalcemia complicating small-cell carcinoma of the lung are described; clinical features indicate that significant bone or bone marrow involvement is present in all cases. Parathor-mone assays were found to be generally in the normal range, though inappropriate for the level of hypercalcemia.
Composing high-performance memory allocators

Current general-purpose memory allocators do not provide sufficient speed or flexibility for modern high-performance applications. Highly-tuned general purpose allocators have per-operation costs around one hundred cycles, while the cost of an operation in a custom memory allocator can be just a handful of cycles. To achieve high performance, programmers often write custom memory allocators from scratch - a difficult and error-prone process. In this paper, we present a flexible and efficient infrastructure for building memory allocators that is based on C++ templates and inheritance. This novel approach allows programmers to build custom and general-purpose allocators as heap layers that can be composed without incurring any additional runtime overhead or additional programming cost. We show that this infrastructure simplifies allocator construction and results in allocators that either match or improve the performance of heavily-tuned allocators written in C, including the Kingsley allocator and the GNU obstack library. We further show this infrastructure can be used to rapidly build a general-purpose allocator that has performance comparable to the Lea allocator, one of the best uniprocessor allocators available. We thus demonstrate a clean, easy-to-use allocator interface that seamlessly combines the power and efficiency of any number of general and custom allocators within a single application.
Detection of occult bone marrow micrometastases in patients with operable lung carcinoma.

Objectives A large proportion of patients with operable lung carcinoma (no evidence of systemic spread of tumor) develop metastatic disease after primary therapy. More sensitive and specific methods are needed to identify patients at highest risk for recurrence who may benefit most from adjuvant therapy, while sparing those patients who do not require such treatment. Summary Background Data Using epithelial-specific monoclonal antibodies, the authors have developed an immunocytochemical assay capable of detecting as few as 2 lung cancer cells in 1 million bone marrow cells. Methods The assay was used to test the bone marrow (from resected ribs) of 43 patients with primary non-small cell lung carcinoma who showed no clinical or pathologic evidence of systemic disease. Results Occult bone marrow micrometastases (BMMs) were detected in 40% of patients (17/43) with non-small cell lung cancer, including 29% (5/17) of patients with stage I or II disease and 46% of whom (12/26) had stage III disease. The median follow-up was 13.6 months. Patients with occult BMMs had significantly shorter times to disease recurrence compared with patients without BMMs (7.3 vs. >35.1 months, p = 0.0009). Furthermore, for patients with stage I or II disease, the presence of occult BMMs was significantly associated with a higher rate of recurrence (p = 0.0004). Conclusions The detection of occult BMMs identifies patients with operable non-small cell lung carcinoma who are at significantly increased risk for recurrence, independent of tumor stage, and may be useful in evaluating patients for adjuvant treatment protocols.
Endogenous Preferences and the Study of Institutions.

The assumption that individual preferences, or attitudes, are fixed and exogenously determined is central to many studies of political and economic institutions, such as markets and elections. We present a Bayesian model of adaptive preferences and empirical evidence consistent with that model to argue that preferences are not always exogenous and fixed. The changing relationships between partisanship and preferences on civil rights issues between 1956 and 1964 and on the Vietnam War issue between 1968 and 1972 coincide with significant changes in the major parties' positions on these issues, suggesting that preferences are endogenous to the electoral process. We conclude with a discussion of the positive and normative implications of endogenous preferences.
Tests of linearity in the responses of eye-movement-sensitive vestibular neurons to sinusoidal yaw rotation

The rotational vestibulo-ocular reflex in primates is linear and stabilizes gaze in space over a large range of head movements. Best evidence suggests that position-vestibular-pause (PVP) and eye-head velocity (EHV) neurons in the vestibular nuclei are the primary mediators of vestibulo-ocular reflexes for rotational head movements, yet the linearity of these neurons has not been extensively tested. The current study was undertaken to understand how varying magnitudes of yaw rotation are coded in these neurons. Sixty-six PVP and 41 EHV neurons in the rostral vestibular nuclei of 7 awake rhesus macaques were recorded over a range of frequencies (0.1 to 2 Hz) and peak velocities (7.5 to 210°/s at 0.5 Hz). The sensitivity (gain) of the neurons decreased with increasing peak velocity of rotation for all PVP neurons and EHV neurons sensitive to ipsilateral rotation (type I). The sensitivity of contralateral rotation-sensitive (type II) EHV neurons did not significantly decrease with increasing peak velocity. These data show that, like non-eye-movement-related vestibular nuclear neurons that are believed to mediate nonlinear vestibular functions, PVP neurons involved in the linear vestibulo-ocular reflex also behave in a nonlinear fashion. Similar to other sensory nuclei, the magnitude of the vestibular stimulus is not linearly coded by the responses of vestibular neurons; rather, amplitude compression extends the dynamic range of PVP and type I EHV vestibular neurons.
InGaN Quantum Dots for High Efficiency Blue and Green Light Emitters

InGaN quantum dots at high densities (~10^11 dots/cm^2) are demonstrated using metalorganic chemical vapor deposition combined with post growth processing of InGaN materials. Optical and structural studies are performed to characterize InGaN quantum dots.
Agonist-stimulated β-Adrenergic Receptor Internalization Requires Dynamic Cytoskeletal Actin Turnover

Stimulation of β-adrenergic receptors (βARs) leads to sequential recruitment of β-arrestin, AP-2 adaptor protein, clathrin, and dynamin to the receptor complex, resulting in endocytosis. Whether a dynamic actin cytoskeleton is required for βAR endocytosis is not known. In this study, we have used β1- and β2 ARs, two ubiquitously expressed members of the βAR family, to comprehensively evaluate the requirement of the actin cytoskeleton in receptor internalization. The integrity of the actin cytoskeleton was manipulated with the agent latrunculin B (LB) and mutants of cofilin to depolymerize actin filaments. Treatment of cells with LB resulted in dose-dependent depolymerization of the cortical actin cytoskeleton that was associated with significant attenuation in internalization of β2ARs, β1ARs, and mutants of β1ARs that internalize via either clathrin- or caveolin-dependent pathways. Importantly, LB treatment did not inhibit β-arrestin translocation or dynamin recruitment to the agonist-stimulated receptor. To unequivocally demonstrate the requirement of the actin cytoskeleton for β2AR endocytosis, we used an actin-binding protein cofilin that biochemically depolymerizes and severs actin filaments. Isoproterenol-mediated internalization of β2AR was completely blocked in the presence of wild type cofilin, which could be rescued by a mutant of cofilin that mimics a constitutive phosphorylated state and leads to normal agonist-stimulated β2AR endocytosis. Finally, treatment with jasplakinolide, an inhibitor of actin turnover, resulted in dose-dependent inhibition of β2AR internalization, suggesting that turnover of actin filaments at the receptor complex is required for endocytosis. Taken together, these data demonstrate that intact and functional dynamic actin cytoskeleton is required for normal βAR internalization.
Psychopharmacologic and behavioral treatments for functional gastrointestinal disorders.

Functional gastrointestinal disorders (FGIDs) are commonly seen gastrointestinal (GI) conditions that are diagnosed using established symptom-based criteria. These disorders that typically defy traditional diagnostic methods based on structural abnormalities have intrigued researchers for several decades. This has led to the emergence of the current discipline of neurogastroenterology or the study of the "brain-gut axis," which is based on dysregulation of neuroenteric pathways as a key pathophysiologic feature of the FGIDs. Psychopharmacologic and behavioral treatments can influence the dysregulation of these pathways, especially at the severe end of the spectrum, and improve the clinical manifestations of these conditions, visceral discomfort or pain and bowel dysfunction. Their actions are mostly at spinal and supraspinal levels with some direct benefits at the level of the gut. Improvements in coping, global distress, and overall quality of life (QOL) have been shown more consistently with these treatments compared with improvement in GI symptoms. A successful approach to patients with these treatments requires a good physician–patient relationship. Strategizing treatments with these modalities is based on recognition of their dual effects on brain and gut, understanding the nature and severity of the GI symptoms and their psychosocial concomitants, and applying them within the context of the patient's understanding of their value.
Weaning of extracorporeal membrane oxygenation using continuous hemodynamic transesophageal echocardiography

Background Venoarterial extracorporeal membrane oxygenation (VA ECMO) has been used for profound cardiogenic shock to bridge to decision, ventricular assist device(s) (VADs), or transplant. To assess ventricular function and volume status along with hemodynamics during ECMO weaning, we developed a standardized weaning protocol, guided by a miniaturized transesophageal echocardiography probe designed for continuous hemodynamic monitoring (hemodynamic transesophageal echocardiography [hTEE]). We reviewed our experience with this weaning protocol with hTEE guidance to assess if we could predict patient outcomes. Methods During the academic year of 2011, hTEE-guided ECMO weaning was performed in 21 patients on VA ECMO. Left and right ventricular function and volume status were assessed by continuous hTEE, while attempting to wean ECMO after a standardized protocol. The clinical outcomes, management, and positive predictive value of the device were investigated and analyzed for this cohort of patients. Results Of the 21 patients, 6 (29%) had left and right ventricular recovery and underwent optimal medical therapy or revascularization for underlying coronary artery disease; 7 (33%) had nonrecoverable left and right ventricular function; and 8 (38%) had right ventricular recovery without improvement of the left ventricular function. These 8 patients underwent left VAD placement; none subsequently developed profound right ventricular failure. The positive predictive value for ventricular recovery by hTEE was 100% using our standardized ECMO weaning protocol (95% confidence interval, 73%-100%). Conclusions The hTEE-guided ECMO weaning protocol accurately predicted the ability to wean ECMO to decision. This protocol can be applied by cardiac intensivists as a part of standard bedside intensive care unit assessment.
Functional inactivation of neutrophils with a Mac-1 (CD11b/CD18) monoclonal antibody protects against ischemia-reperfusion injury in rat liver.

The role of neutrophil CD11b/CD18 (Mac-1) adhesion proteins in the pathogenesis of hepatic reperfusion injury was investigated in an experimental model. Male Fischer rats were treated with a CD11b monoclonal antibody or an isotype-matched IgM control antibody and subjected to 45 min of hepatic ischemic followed by 24 hr of reperfusion. Large numbers of neutrophils were present in postischemic liver lobes (1,241 +/- 64 polymorphonuclear cells/50 high-power fields) compared with numbers in baseline measurements (14 +/- 3 polymorphonuclear cells/50 high-power fields), and severe liver injury was observed after 24 hr of reperfusion (hepatic necrosis: 88% +/- 2%). Pretreatment with the CD11b antibody (two doses of 2 mg/kg each significantly attenuated liver injury and reduced the number of polymorphonuclear cells in the post-ischemic liver by 59%. Selective treatment with the antibody only during reperfusion was similarly effective. The increased spontaneous superoxide formation of neutrophils isolated from postischemic liver (1.05 +/- 0.11 nmol O2-/hr/10(6) cells) was reduced by 56% in neutrophils from CD11b antibody-treated animals. Flow cytometric analysis of CD11b/CD18 expression on circulating neutrophils demonstrated significant upregulation at all time points during reperfusion. Clone 17 also effectively inhibited neutrophil extravasation in a glycogen peritonitis model. Our data are consistent with a dual protective effect of the CD11b antibody in hepatic reperfusion injury in vivo (i.e., reduced accumulation of neutrophils and their functional inactivation).
Accelerating sparse matrix-matrix multiplication with 3D-stacked logic-in-memory hardware

This paper introduces a 3D-stacked logic-in-memory (LiM) system to accelerate the processing of sparse matrix data that is held in a 3D DRAM system. We build a customized content addressable memory (CAM) hardware structure to exploit the inherent sparse data patterns and model the LiM based hardware accelerator layers that are stacked in between DRAM dies for the efficient sparse matrix operations. Through silicon vias (TSVs) are used to provide the required high inter-layer bandwidth. Furthermore, we adapt the algorithm and data structure to fully leverage the underlying hardware capabilities, and develop the necessary design framework to facilitate the design space evaluation and LiM hardware synthesis. Our simulation demonstrates more than two orders of magnitude of performance and energy efficiency improvements compared with the traditional multithreaded software implementation on modern processors.
The Thiamine Biosynthetic Enzyme ThiC Catalyzes Multiple Turnovers and Is Inhibited by S-Adenosylmethionine (AdoMet) Metabolites

ThiC (4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase; EC 4.1.99.17) is a radical S-adenosylmethionine (AdoMet) enzyme that uses a [4Fe-4S]+ cluster to reductively cleave AdoMet to methionine and a 5′-deoxyadenosyl radical that initiates catalysis. In plants and bacteria, ThiC converts the purine intermediate 5-aminoimidazole ribotide to 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate, an intermediate of thiamine pyrophosphate (coenzyme B1) biosynthesis. In this study, assay conditions were implemented that consistently generated 5-fold molar excess of HMP, demonstrating that ThiC undergoes multiple turnovers. ThiC activity was improved by in situ removal of product 5′-deoxyadenosine. The activity was inhibited by AdoMet metabolites S-adenosylhomocysteine, adenosine, 5′-deoxyadenosine, S-methyl-5′-thioadenosine, methionine, and homocysteine. Neither adenosine nor S-methyl-5′-thioadenosine had been shown to inhibit radical AdoMet enzymes, suggesting that ThiC is distinct from other family members. The parameters for improved ThiC activity and turnover described here will facilitate kinetic and mechanistic analyses of ThiC. Background: ThiC is a radical S-adenosylmethionine (AdoMet) enzyme that synthesizes the thiamine pyrimidine 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate (HMP-P). Results: An increase in the ThiC catalytic rate was detected when product 5′-deoxyadenosine was hydrolyzed. ThiC was inhibited by AdoMet metabolites. Conclusion: ThiC is a multiple-turnover enzyme and is product-inhibited. Significance: This is the first report of ThiC catalytic turnover and the identification of two AdoMet metabolites that inhibit ThiC activity.
Particle deposition in the guinea pig respiratory tract

Abstract Equations relating particle size of aerosols to deposition by impaction, diffusion and sedimentation are applied to a previously established model of the guinea pig lung using a tidal volume of 4.44 cm 3 and a respiratory rate of 60 breath min −1 . These calculated deposition values are combined with measured values of nasal deposition to give an estimate of the particle deposition characteristics of the guinea pig respiratory tract. The nasopharyngeal-tracheobronchial (NP-TB) region removes 99% of unit density spherical particle 10 μm or more in diameter. Deposition in this region reaches a minimum of 10% at a particle diameter of 0.8 μm. For particles less than 0.8 μm, deposition increases because of diffusion. Deposition in the pulmonary region is about 17% for particle diameters from 0.08 to 4 μm. For typical polydisperse aerosols with mass median diameters above 1 μm, a greater fraction of the mass than of the count is deposited in the NP-TB region, while a smaller fraction of the mass than of the count is deposited in the pulmonary region. Aerosol clouds with mass median diameters less than 0.1 μm deposit a greater fraction of the count than of the mass in the NP-TB region and a smaller fraction of the count than of the mass in the pulmonary region.