cssi/SciSciGPT-SciSciNet huggingface dataset:
Relationship between proverb familiarity and proverb interpretation: implications for clinical practice.

This study examined whether performance on measures of proverb interpretation is influenced by examinees' familiarity with the proverbs to be interpreted. Subjects used a seven-point Likert scale to indicate the extent to which they were familiar with the 12 proverbs included in a standardized proverbs test. The resulting scores were correlated with the scores the subjects obtained when they interpreted the proverbs. The sample included 103 college students. The results indicated that a proverb familiarity-interpretation relationship did emerge for five (or 40%) of the proverbs. Also, subjects' average familiarity score for those five proverbs was higher than their average familiarity score for the other (seven) proverbs. The findings are discussed in terms of their implications for clinical practice and suggestions are made regarding ways to offset the influence of proverb familiarity on proverb interpretation.
Review of Infant Mental Health papers

Cet article sur l'Etude du Processus de Changement effectuee par le Groupe de Boston etudie un probleme conceptuel non resolu: Comment peut-on codifier les etats intersubjectifs? Le transfert de concepts de la recherche infantile a la dyade therapeutique adulte represente plus qu'une analogie dans la mesure ou certains aspects primitifs de l'esprit apparaissent dans la petite enfance mais persistent toute la vie durant. Le reglement de la conscience est un exemple saillant. La dyade therapeutique adulte et la dyade mere/bebe peuvent toutes deux etre percues comme des systemes dynamiques se reglant eux-memes et se reparant eux-memes. Le concept de connaissance relationnelle implicite est presente comme une facon de penser alternative sur les relations d'objet internes.
Metabolism of Inhaled Brominated Hydrocarbons: Validation of Gas Uptake Results by Determination of a Stable Metabolite

Gas uptake studies infer metabolism from the disappearance of chemical from a recirculated atmosphere. To insure the validity of this technique, we studied the metabolism of several brominated hydrocarbons in rats both by gas uptake and by direct measurement of liberated inorganic bromide. Chemicals used were: vinyl bromide (VB), halothane (HAL), bromochloromethane (BCM), and methyl bromide (MB). Gas uptake was determined by previously published methods, and plasma bromide levels were measured by an ion-specific electrode. Based on bromide release, VB metabolism had two distinct saturable components, HAL metabolism had one saturable process, BCM metabolism was of mixed form having both first-order and saturable components, and MB metabolism was first order. Gas uptake results were similar, except only one saturable process was observed for VB, and HAL had contributions from both saturable and first-order component. First-order rate constants for MB and BCM from bromide release studies were, respectively, 0.32 and 0.085/kg/hr; from gas uptake they were 0.55 and 0.106/kg/hr. The first-order rate constant for HAL by gas uptake was 0.058/kg/hr. For VB, HAL, and BCM, bromide release studies gave estimates for Km of 33, 73, and 79 ppm, respectively. Estimates of Vmax were 2.3, 9.7, and 10.0 mg of parent compound metabolized/kg/hr. From gas uptake, Km were 18, 81, and 91 ppm, while the estimates of Vmax were 2.4, 10.0, and 10.5 mg/kg/hr. With these four chemicals, gas uptake studies provided reliable estimates of the kinetic constants of metabolism.
HEALTH STATUS OF EASTERN EUROPEAN (EE) ORPHANS REFERRED FOR ADOPTION.|[dagger]| 791

The orphanages of EE recently surpassed Korea (FY94 n=2,196 v 1,757) as the principal international source of children adopted in the US. Counseling prospective adoptive parents about medical needs of these children is challenging since little is known about their health status. Over a 24-month period, referral documents were evaluated for 252 orphans from EE(f/m-60/40-76%-Russia, 17%-other former USSR, 4%-Romania, 2%-Bulgaria, 1%-Poland. Low birth weight <2500g was common (48%) and could be accounted for by prematurity (27%) and nutritional insufficiency (mean birth weight-by-length z-score = -1.04±1.0, n=68). The child represented the fourth pregnancy or greater in 46% of cases (range 1-14). There was a significant relationship between increasing maternal parity and lower birth weight-by-length z-scores (p<0.01 by ANOVA). Reasons for children being available for adoption included death of both parents (4%), termination of parental rights (16%), foundling (5%) and voluntary relinquishment of parental rights (75%). Maternal alcoholism was noted in 17% and fetal alcohol syndrome in 2.4% of referrals. Children were referred at a mean age of 28.9±25.7m (range=0.75-125m) and had been living in orphanages for an average of 21.9±20.6m (range=0.75-100m). Stature was profoundly affected, with children falling behind one month of linear growth for each 3.4 months in the orphanage (r=0.68, p <.001). Head growth was also impaired in this population (mean OFC z-score = -1.1±1.9; 20% ≤-2.5). Because of the prevalence of low birth weight, alcohol exposure, high-risk social circumstances, long-term institutionalization, and linear and head growth failure, classifying children from EE orphanages as an “at-risk” group, with possible special needs (e.g., delays in motor, speech and social skills, behavioral and attachment issues) may assist prospective adoptive parents in their decision-making process.
Temporal evolution of spin accumulation in nonlocal spin valves

A temporal evolution of spin signals has been observed in nanoscale Co/Cu nonlocal spin valves. The spin diffusion length of Cu increases from ∼300 to ∼350 nm measured at 295 K over a 50-day period in the ambient environment after the fabrication of the devices. This is attributed to a gradual oxidation in the regions near the side surfaces of the Cu channel, where Co impurities are implanted during the fabrication. An increase of spin injection polarization is also found and attributed to the change of oxidation states at the interfaces.
Fragmentation of protonated ions of peptides containing cysteine, cysteine sulfinic acid, and cysteine sulfonic acid

The oxidation of the sulfhydryl group in cysteine to sulfenic acid, sulfinic acid, and sulfonic acid in proteins is important in a number of enzymatic processes. In this study we examined the fragmentation of four peptides containing cysteine, cysteine sulfinic acid (Cys-SO2H), and cysteine sulfonic acid (Cys-SO3H) in an ion-trap mass spectrometer. Our results show that the presence of a Cys-SO2H in a peptide leads to preferential cleavage of the amide bond at the C-terminal side of the oxidized cysteine residue. The results are important for the determination of the site of the cysteine oxidation and might be useful for the sequencing of cysteine-containing peptides.
RT distributional analysis of cognitive-control-related brain activity in first-episode schizophrenia

Impairments in cognitive control are a defining feature of schizophrenia. Aspects of cognitive control include proactive control-the maintenance of task rules or goals to bias attention and maintain preparedness-and reactive control-the engagement of attention in reaction to changing cognitive demands. Proactive control is thought to be particularly impaired in schizophrenia. We sought to examine proactive and reactive control in schizophrenia, as measured by reaction time (RT) variability, and especially long RTs, which are thought to represent lapses in proactive control, during the Stroop paradigm. Furthermore, we sought to examine the neural underpinnings of lapses in proactive control and the subsequent engagement of reactive control in those with schizophrenia, as compared to healthy controls, using fMRI. We found that patients with schizophrenia displayed greater RT variability and more extremely long RTs than controls suggesting that proactive control was weaker in the schizophrenia than in the control group. All of the subjects engaged regions of the cognitive control network during long RTs, consistent with an engagement of reactive control following a failure in proactive control on these trials. The schizophrenia group, however, displayed significantly diminished activity in these regions relative to controls. Our results suggest increased failures in proactive control, but also impaired reactive control, in schizophrenia as compared to healthy subjects.
Electrical resistivity study of CeZn11: Magnetic field and pressure phase diagram up to 5 GPa

Thorough resistivity measurements on single crystals of CeZn${}_{11}$ under pressure $p$ and magnetic field $H$ are presented. At ambient pressure, CeZn${}_{11}$ orders antiferromagnetically at ${T}_{N}=2$ K. The pressure dependence of the resistivity reveals an increase of the Kondo effect. We determine the pressure evolution of the magnetic exchange interaction between conduction and localized $4f$ electrons. It qualitatively reproduces the pressure evolution of the magnetic ordering temperature ${T}_{{O}_{1}}$ (with ${T}_{{O}_{1}}={T}_{N}$ at ambient pressure). In addition to ${T}_{{O}_{1}}$, a new anomaly ${T}_{{O}_{2}}$ appears under pressure. Both anomalies are found to increase with applied pressure up to $4.9$ GPa, indicating that CeZn${}_{11}$ is far from a pressure induced quantum critical point. Complex $T$-$H$ phase diagrams are obtained under pressure which reveal the instability of the ground state in this compound.
Immune mediators of chronic pelvic pain syndrome

The cause of chronic pelvic pain syndrome (CPPS) has yet to be established. Since the late 1980s, cytokine, chemokine, and immunological classification studies using human samples have focused on identifying biomarkers for CPPS, but no diagnostically beneficial biomarkers have been identified, and these studies have done little to deepen our understanding of the mechanisms underlying chronic prostatic pain. Given the large number of men thought to be affected by this condition and the ineffective nature of current treatments, there is a pressing need to elucidate these mechanisms. Prostatitis types IIIa and IIIb are classified according to the presence of pain without concurrent presence of bacteria; however, it is becoming more evident that, although levels of bacteria are not directly associated with levels of pain, the presence of bacteria might act as the initiating factor that drives primary activation of mast-cell-mediated inflammation in the prostate. Mast cell activation is also known to suppress regulatory T cell (Treg) control of self-tolerance and also activate neural sensitization. This combination of established autoimmunity coupled with peripheral and central neural sensitization can result in the development of multiple symptoms, including pelvic pain and bladder irritation. Identifying these mechanisms as central mediators in CPPS offers new insight into the prospective treatment of the disease.
Atmospheric black carbon can exhibit enhanced light absorption at high relative humidity

Abstract. Some estimates suggest atmospheric soot (a.k.a. black carbon, BC) warms Earth's climate by roughly 50% the magnitude of increased carbon dioxide. However, one uncertainty in the climate-forcing estimate for BC is the degree to which sunlight absorption is influenced by particle mixing state. Here we show that hygroscopic growth of atmospheric aerosol particles sampled at Houston, TX leads to an enhancement in both light scattering and absorption. Measurements suggest light absorption increases roughly three-four fold at high ambient humidity for coated soot particles. However, when the fraction of coated BC particles was reduced, the absorption enhancement was also reduced, suggesting coatings are crucial for the effect to occur. In addition, the extent to which MAC was increased at high humidity varied considerably over time, even for BC that consistently presented as being coated. This suggests the chemical composition of the coating and/or source of BC may also be an important parameter to constrain MAC enhancement at high humidity. Nonetheless, the results are largely consistent with previous laboratory and model results predicting absorption enhancement. We conclude that the enhanced absorption increases the warming effect of soot aerosol aloft, and global climate models should include parameterizations for RH effects to accurately describe absorptive heating by BC.
Integrated health systems: success or failure?

There continues to be an increasing number of healthcare delivery systems as a result of marketplace changes that include declining reimbursement and increasing costs for healthcare. However, the majority of these systems fail. Failures are a consequence of poor management, lack of a common mission
Neutral etching and shadowing in trench etching of semiconductors

Summary form only given, as follows. Etching profiles by neutral atoms in a plasma are analyzed for a semiconductor trench with neutral shadowing due to the trench acceptance angle. The etch rate is assumed proportional to the neutral flux incident on the semiconductor surface. Etch rates have been found to obey this relation for some substrates where the neutral species are depleted in the plasmas such that the ion energy flux is relatively large. The one-particle distribution function of the neutral species is modeled by a Maxwellian. The neutral flux to the semiconductor surface is found to be an exact analytical expression for the trench geometry. The vertical neutral flux reduces to the value for the midtrench already reported. The etching profiles are determined from points on the initial surface by numerical integration of trajectory equations with the exact analytical etch rates. The profiles are compared with etching profiles determined previously for neutral etching where the etch rate was a constant over the trench surface and for ion assisted etching where the etch rate was proportional to the ion energy flux.
Bertrand Russell on vagueness

(1969). Bertrand Russell on vagueness. Australasian Journal of Philosophy: Vol. 47, No. 1, pp. 31-41.
Influence of a cardiac rehabilitation program on the cardiovascular, psychological, and social functioning of cardiac patients.

Twenty-eight male cardiac patients who had either experienced myocardial infarction or undergone coronary bypass surgery were assigned to a treatment condition and participated in a 3-month, exercise-based Cardiac Rehabilitation Program, whereas 20 other cardiac patients were assigned to a routine-care condition and did not participate in the rehabilitation program. Cardiovascular, psychological, and psychosocial functioning were assessed before treatment or routine care was begun, after 3 months of treatment or routine care, and 4 months later. Results indicated that patients in the treatment condition evidenced reliably more efficient cardiovascular functioning (resting heart rate, resting diastolic blood pressure, treadmill exercise performance, exercise heart rate, exercise systolic blood pressure), better understanding of heart disease, better understanding of and reported compliance with treatment recommendations, more positive self-perceptions (health, body concept, self-concept, progress toward goals), and better psychosocial functioning (e.g., decreased employment-related stress, more active use and enjoyment of leisure time, more physical and sexual activity). Chronic patients benefited as much from the treatment as did acute patients, and the beneficial effects for all treated patients were evident not only just after rehabilitation, but also 4 months later. This investigation appears to be the first such test of effects of this type of treatment, and the results have wide generalizability and applicability.
Component bounds on Markov set-chain limiting sets

In this paper, exact component bounds are found for the limiting set of a Markov set-chain. The method employed is computationally efficient.
P3.064 Patterns of Sexual Partner Accrual Among Adolescent Women

Background Younger age and number of sexual partners are consistently identified STI risk factors, but the relative contributions of chronological age and total interval since first coital partner to accrual of partners has not been established in prospective studies. Methods Participants (N = 341; 14–17 years of age at enrollment; 90% African American) were English-speaking adolescent women from lower- and middle-income families residing in areas with high rates of pregnancy and STI. We collected quarterly sexual behaviour data for an average of 3.56 years (range 0.23–8.92 years). Median number of lifetime partners increased from 2 at enrollment to 6 at the last visit. Generalized Additive Mixed Models were used to estimate the cumulative number of partners as a function of time covariates. The cohort effect (enrollment age), the longitudinal effect (follow-up period) and their interaction were considered as predictors. Annual rate of the partner acquisition was estimated by the first derivative of the cumulative number of partners with respect to the “follow-up period”. Results Partner accrual was 2 or more partners per annum within the first 2 years of follow-up, but slowed down to about 1 partner per annum during the years 2 to 5 since enrollment. Rates of partner accrual were similar for all age groups at enrollment and declined at similar rates. Correlation between “enrollment age” and “age at first sex” was 0.26, possibly an indicator of STI and contraceptive care-seeking associated with sexual activity. Conclusions Cross-sectional studies of STI risk among adolescents may confound age-related cohort effects with variation in interval since first sexual intercourse. Our analysis shows that higher rates of partner accrual decrease within two years regardless of the age of first coitus. This suggests that STI prevention based on delay of coitus among adolescent women should be supplemented with efforts to reduce rates of partner accrual.
Well-posedness for a class of fourth order diffusions for image processing

A number of image denoising models based on higher order parabolic partial differential equations (PDEs) have been proposed in an effort to overcome some of the problems attendant to second order methods such as the famous Perona–Malik model. However, there is little analysis of these equations to be found in the literature. In this paper, methods of maximal regularity are used to prove the existence of unique local solutions to a class of fourth order PDEs for noise removal. The proof is laid out explicitly for two newly proposed fourth order models, and an outline is given for how to apply the techniques to other proposed models.
Phosphodiesterase-5 inhibitor tadalafil attenuates oxidative stress and protects against myocardial ischemia/reperfusion injury in type 2 diabetic mice

Diabetic patients exhibit increased risk for the development of cardiovascular diseases primarily because of impaired nitric oxide (NO) bioavailability. The phosphodiesterase-5 (PDE-5) inhibitor sildenafil restores NO signaling and protects against ischemia/reperfusion (I/R) injury. In this study, we determined the effect of the long-acting PDE-5 inhibitor tadalafil on diabetes-associated complications and its role in attenuating oxidative stress after I/R injury in type 2 diabetic db/db mice. Adult male db/db mice (n=40/group) were randomized to receive dimethyl sulfoxide (10% DMSO, 0.2ml, ip) or tadalafil (1mg/kg in 10% DMSO, ip) for 28 days. After 28 days treatment, the hearts were isolated and subjected to 30min global ischemia followed by 60min reperfusion in the Langendorff mode. Infarct size was measured using computer morphometry of tetrazolium-stained sections. Cardiomyocytes were isolated from a subset of hearts and subjected to 40min simulated ischemia followed by 1h of reoxygenation (SI/RO). Dichlorodihydrofluorescein diacetate and JC-1 staining was used to measure reactive oxygen species (ROS) generation and mitochondrial membrane potential (Δψm), respectively. Another subset of hearts was used for the estimation of lipid peroxidation, glutathione, and the expression of myocardial pRac1, Rac1, gp91(phox), p47(phox), and p67(phox) by Western blot. Tadalafil treatment improved the metabolic status and reduced infarct size compared to the untreated db/db mice (21.2±1.8% vs 45.8±2.8%; p<0.01). The db/db mice showed enhanced oxidative stress in cardiomyocytes as indicated by a significant increase in ROS production. Cardiac NAD(P)H oxidase activity, lipid peroxidation, and oxidized glutathione were also increased in db/db mice compared to nondiabetic control animals. Tadalafil treatment in db/db mice suppressed oxidative stress, attenuated myocardial expression of pRac1 and gp91(phox), and also preserved the loss of Δψm in cardiomyocytes after SI/RO. In conclusion, these results demonstrate that chronic treatment with tadalafil attenuates oxidative stress and improves mitochondrial integrity while providing powerful cardioprotective effects in type 2 diabetes.
SP8 regulates signaling centers during craniofacial development

Much of the bone, cartilage and smooth muscle of the vertebrate face is derived from neural crest (NC) cells. During craniofacial development, the anterior neural ridge (ANR) and olfactory pit (OP) signaling centers are responsible for driving the outgrowth, survival, and differentiation of NC populated facial prominences, primarily via FGF. While much is known about the functional importance of signaling centers, relatively little is understood of how these signaling centers are made and maintained. In this report we describe a dramatic craniofacial malformation in mice mutant for the zinc finger transcription factor gene Sp8. At E14.5 they show facial prominences that are reduced in size and underdeveloped, giving an almost faceless phenotype. At later times they show severe midline defects, excencephaly, hyperterlorism, cleft palate, and a striking loss of many NC and paraxial mesoderm derived cranial bones. Sp8 expression was primarily restricted to the ANR and OP regions during craniofacial development. Analysis of an extensive series of conditional Sp8 mutants confirmed the critical role of Sp8 in signaling centers, and not directly in the NC and paraxial mesoderm cells. The NC cells of the Sp8 mutants showed increased levels of apoptosis and decreased cell proliferation, thereby explaining the reduced sizes of the facial prominences. Perturbed gene expression in the Sp8 mutants was examined by laser capture microdissection coupled with microarrays, as well as in situ hybridization and immunostaining. The most dramatic differences included striking reductions in Fgf8 and Fgf17 expression in the ANR and OP signaling centers. We were also able to achieve genetic and pharmaceutical partial rescue of the Sp8 mutant phenotype by reducing Sonic Hedgehog (SHH) signaling. These results show that Sp8 primarily functions to promote Fgf expression in the ANR and OP signaling centers that drive the survival, proliferation, and differentiation of the NC and paraxial mesoderm that make the face.
Miocene Geologic History of Southern Salinian Block, California--Perspectives from a Stratigraphic Study of Monterey Formation: ABSTRACT

A better understanding of the Miocene geologic history of the southern Salinian block is aided by a stratigraphic and paleoenvironmental study of the Monterey Formation. Extensive subsurface and surface data enable construction of isopach, paleobathymetric, age-relationship, and paleogeographic maps that document the depositional history of the Monterey Formation. Isopach maps show that the formation ranges up to 1,400 m (4,500 ft) thick beneath Cuyama valley. Other areas of maximum accumulation occur in the northwest Caliente Range and the Indian Creek area. Offset of isopachs north of Barrett Ridge suggests approximately 15 km (9 mi) of post-middle Miocene right slip on the San Juan fault. Age-relationship maps of the upper and lower contacts of the Monterey Formation for the area from Cuyama Valley to the northern La Panza Range indicate that both the top and base of the formation become younger toward the northwest--the base ranging from Saucesian to Relizian and the top from Relizian to Mohnian. Paleobathymetric maps, based on the distribution of benthic Foraminifera, are plotted on four time slices: late Saucesian, Relizian, Luisian, and early Mohnian. These maps also indicate that the Cuyama basin filled from the southeast to the northwest, and they reflect the migration of maximum subsidence in that direction during the Miocene. The relationship of general stratigraphy to structural features in the Cuyama basin shows that certain faults and anticlines were active during the deposition of the Monterey Formation. Specifically, the Cox fault zone and South Cuyama End_Page 1693------------------------------ anticline show evidence of such movement, beginning in the early Miocene, which affected the distribution of the formation. These relationships reflect an episode of structural deformation preceding the late Neogene episode associated with movement on the San Andreas fault system, and they may be related to the earliest activity on this system. End_of_Article - Last_Page 1694------------
Antibiofilm Activity of Manuka Honey in Combination with Antibiotics

We assessed the in vitro activity of Manuka honey against biofilm bacteria in combination with antibiotics and visualized the effect of Manuka honey on bacterial biofilms using scanning electron microscopy. The fractional biofilm eradication concentration (∑FBEC) index for vancomycin plus Manuka honey against S. aureus IDRL-4284 biofilms was 0.34, indicating a synergistic interaction. The ∑FBEC index for gentamicin plus Manuka honey against P. aeruginosa PAO1 biofilms was 0.78-0.82, indicating an additive interaction. Scanning electron microscopy of S. aureus IDRL-4284 and P. aeruginosa PAO1 biofilms exposed to Manuka honey and artificial honey containing the same sugar composition as Manuka honey showed that the former had more pronounced effects than the latter on both S. aureus and P. aeruginosa biofilms. Visualized effects included distorted cell morphologies for both bacteria and a decrease in P. aeruginosa extracellular matrix. In conclusion, Manuka honey has a synergistic interaction with vancomycin against S. aureus biofilms and an additive interaction with gentamicin against P. aeruginosa biofilms.
Herpes Simplex Virus 1 US3 Phosphorylates Cellular KIF3A To Downregulate CD1d Expression.

UNLABELLED Herpes simplex virus 1 (HSV-1) causes one of the most prevalent herpesviral infections in humans and is the leading etiological agent of viral encephalitis and eye infections. Our understanding of how HSV-1 interacts with the host at the cellular and organismal levels is still limited. We and others previously reported that, upon infection, HSV-1 rapidly and efficiently downregulates CD1d cell surface expression and suppresses the function of NKT cells, a group of innate T cells with critical immunoregulatory function. The viral protein kinase US3 plays a major role in this immune evasion mechanism, and its kinase activity is required for this function. In this study, we investigated the cellular substrate(s) phosphorylated by US3 and how it mediates US3 suppression of CD1d recycling. We identified the type II kinesin motor protein KIF3A as a critical kinesin factor in the cell surface expression of CD1d. Interestingly, KIF3A is phosphorylated by US3 both in vitro and in infected cells. Mass spectrometry analysis of purified KIF3A showed that it is phosphorylated predominantly at serine 687 by US3. Ablation of this phosphorylation abolished US3-mediated downregulation of CD1d expression, suggesting that phosphorylation of KIF3A is the primary mechanism of HSV-1 suppression of CD1d expression by US3 protein. Understanding of the precise mechanism of viral modulation of CD1d expression will help to develop more efficient vaccines in the future to boost host NKT cell-mediated immune responses against herpesviruses. IMPORTANCE Herpes simplex virus 1 (HSV-1) is among the most common human pathogens. Little is known regarding the exact mechanism by which this virus evades the human immune system, particularly the innate immune system. We previously reported that HSV-1 employs its protein kinase US3 to modulate the expression of the key antigen-presenting molecule CD1d to evade the antiviral function of NKT cells. Here we identified the key cellular motor protein KIF3A as a cellular substrate phosphorylated by US3, and this phosphorylation event mediates US3-induced immune evasion.
Induction of cutaneous squamous cell carcinomas by RAF inhibitors: cause for concern?

Approximately 50% of melanomas harbor a mutation in the BRAF gene. Vemurafenib (formerly PLX4032) is an adenosine triphosphate– competitive inhibitor of RAF kinases that has shown profound activity in patients with advanced melanoma. A notable property of vemurafenib and other selective RAF inhibitors is that they inhibit RAF activation of extracellular signal–regulated kinase (ERK) only in tumors expressing mutant BRAF (Fig 1A). In BRAF wild-type tumors as well as normal cells, they activate this pathway (Fig 1B). This paradoxical activation of RAF signaling by the RAF inhibitor likely accounts for its unique toxicity profile. Approximately one third of patients treated with vemurafenib develop a keratosis pilaris–like rash. This rash is histologically characterized by perifollicular hyperplasia and is often accompanied by hyperkeratosis of the palms and soles (palma-plantar dysesthesia) and/or the development of papillomas (benign wart-like epidermal proliferations). This constellation of dermatologic toxicities is distinct from that associatedwiththeuseofepidermalgrowthfactorreceptorandMEKinhibitors, both of which inhibit RAF/ERK signaling in normal skin. Furthermore, up to one third of patients treated with vemurafenib develop keratoacanthomas (KAs) and/or cutaneous squamous cell carcinomas (cSCCs). With the goal of understanding the molecular basis for the induction of cSCC in patients treated with RAF inhibitors, Oberholzer et al report in Journal of Clinical Oncology a genomic analysis of 237 cSCCs and KAs, 19 of which were derived from patients treated with RAF inhibitors (either vermurafenib or sorafenib). The authors report that SCCs and KAs from RAF inhibitor–treated patients have a distinct mutational profile as compared with cSCCs arising sporadically or in patients treated with immunosuppressive agents. Specifically, they find that 21.1% of KAs and cSCCs resected from patients treated with RAF inhibitors harbor activating HRAS mutations, whereas RAS mutations are rare (3.2%) in tumors that developed in patients who had not been treated with these drugs. These findings are consistent with the known effect of mutant HRAS in promoting tumorigenesis in animal models of KA and with a second recently reported series of vemurafenib-treated patients. Furthermore, together with the rapid appearance of cSCC and KA after initiation of vemurafenib, the results of Oberholzer et al suggest that induction of RAF signaling by the drug promotes the hyperproliferation of preexistant dormant RAS mutant cancer cells. Vemurafenib was recently shown in a randomized phase III study to significantly prolong survival in patients with BRAF mutant melanomas. On the basis of these results, RAF inhibitors should become a standard treatment approach for advanced metastatic A
Semi-preparative high-performance liquid chromatographic separation of ceralure and related isomers

A semi-preparative high-performance liquid chromatographic procedure on 5-μm silica was developed for the isolation of gram quantities of ethyltrans-5-iodo-trans-2-methylcyclohexane-1-carboxylate (B1) and ethyltrans-4-iodo-trans-2-methylcyclohexane-1-carboxylate (B2) for comparative evaluation as male Mediterranean fruit fly,Ceratitis capitata, attractants and for NMR studies. This procedure can also be used analytically to determine the content of B1 (the attractive isomer) in ceralure, the ethyl 4- and 5-iodo-trans-2-methylcyclohexane-1-carboxylate mixture. 1,1-Dimethylethylcis-5-iodo-trans-2-methylcyclohexane-1-carboxylate (A) and 1,1-dimethylethylcis-4-iodo-trans-2-methylcyclohexane-1-carboxylate (C) were isolated and converted to their ethyl esters, thus supplying the fourtrans-isomers of ceralure.
Capability of Urine Analysis for the Disease Blastomycosis Using Infrared Spectroscopy with Eigenvector Signal to Noise Assessment

ABSTRACT Blastomyces dermatitidis is the etiological agent of the relatively common disease blastomycosis found in certain regions of the United States. In order to discern the presence of blastomycosis, microorganisms present in biofluids of infected individuals must be incubated and cultured and then identified by microscopic observation. This procedure is time consuming due to difficult incubation conditions and necessitates special safeguards. An enzyme-linked immunosorbent assay (ELISA) was developed in an attempt to quicken diagnosis. The immunological assay, however, also requires incubations as well as special reagents. This paper explores the potential of using infrared spectroscopy for determination of blastomycosis in urine samples from infected dogs. The regression methods of principal component regression (PCR) and partial least squares (PLS) are used to develop models. Recently introduced regression diagnostics in conjunction with new diagnostic tools described in this paper are used to dete...
Full house: 12 receptors for 27 cytokines.

With the sequencing of the human genome nearing completion, it appears that all members of the class II cytokine receptor family (CRF2) have been identified and partially characterized. The entire family is composed of exactly one dozen members. Eleven of them combine as various heterodimers to transduce signals across the cellular membrane for 27 cytokines divided into four structurally related groups: 6 cytokines of the IL-10 family, 17 type I IFNs, 1 type II IFN and 3 IFN-λs. The last CRF2 member is the soluble receptor which can neutralize the action of one of the cytokines of the IL-10 family, IL-22. Although the extracellular domains of all CRF2 proteins reveal primary and structural homology, their intracellular domains are very dissimilar. Nevertheless, signaling events induced through various combinations of CRF2 subunits partially overlap, leading to the induction of overlapping but cytokine-specific biological activities.
An Integrated Health Care System’s Approach to Development of a Process to Collect Patient Functional Outcomes on Total Joint Replacement Procedures

Health care organizations are challenged to find ways to measure not only process of care but also outcomes of care. Gundersen Health System’s Orthopaedic Surgery Department in the La Crosse, Wisconsin area developed a process to collect outcomes of care for patients having hip or knee arthroplasty procedures and planned to use these data to determine impact on patients’ lives. The Hip Osteoarthritis Outcomes Score and Knee Osteoarthritis Outcomes Score, adapted from the widely used Western Ontario and McMaster Universities Osteoarthritis Index, were collected preoperatively and at 1 year postoperatively. From these data, the health system determined that patients were experiencing significant improvement in 4 of 5 scales. Further recommendations include evaluating the impact of patients’ age, sex, and preoperative body mass index on outcomes, as well as evaluating the impact of more patient involvement in goal setting on recovery time and functional outcomes.
Discussions about cognitive impairment in first medical visits: Older patients' perceptions and preferences

Primary care physicians are the first medical contact for most patients with early-stage dementia. However, little is known about older patients' desire for discussions about cognitive problems or the frequency of discussions about cognitive status during primary care visits. To investigate this question, older patients and accompanying individuals were interviewed separately following the first visit with a primary care physician in an outpatient geriatric medical practice. Patients indicated that memory was discussed in 62 percent of visits. When memory was not discussed, almost one-third of patients stated that they would have wanted to discuss it. Physicians were more likely than patients to initiate discussions about memory. Patient factors, including age, gender, the presence of an accompanying individual, number of diagnoses, and the patient's statement that cognitive function was a main goal of the visit, were examined as predictors of the likelihood of discussion of memory during the first visit. Patients who identified discussing cognitive function as a goal of the visit were more likely to have a discussion about memory than those who did not.
Femoro-acetabular impingement: the diagnosis—a review

Background The recognition of the importance of femoral acetabular impingement (FAI) as a potential cause of hip pain has been stimulated by major efforts to salvage hip joints by reconstruction in order to prevent or delay the need for replacement. The purpose of this review is to define the nature of FAI, the various types, and how to make the diagnosis.
Understanding the Role of Immunoaffinity-Based Mass Spectrometry Methods for Clinical Applications

Both ligand binding assays (LBA)2 and mass spectrometry (MS) methods are widely used in routine clinical analysis. In recent years, an interesting trend has emerged which blends these 2 techniques to combine the selectivity of immunoaffinity (IA) extraction with the specificity of MS detection (IA-MS). The brief communication by Laha and coworkers in the current issue of Clinical Chemistry , entitled “Characterizing Antibody Cross-reactivity for Immunoaffinity Purification of Analytes prior to Multiplexed Liquid Chromatography–Tandem Mass Spectrometry,” is an excellent example of the power of this combined approach (1). These authors, who have had previous experience with multiplexed liquid chromatography–tandem MS (LC-MS/MS) vitamin D analysis (2), showed that the limited specificity of an anti–1α,25-dihydroxyvitamin D capture antibody could be used with LC-MS/MS to deliver a sensitive, highly specific assay for 5 vitamin D–related metabolites. Because of differing affinities of the capture antibody for the various metabolites and their wide range in concentrations (1000-fold), Laha et al. performed a detailed binding assessment by LC-MS/MS using synthetic standards to verify the suitability of their approach. Moreover, because 2 known interfering metabolites were shown not to bind to the antibody, the authors were able to use a shorter chromatographic run time. The report by Laha et al. highlights the growing awareness about the need for highly specific assays in clinical biomarker analysis. Historically, lipids have been measured by competitive LBA formats. However, accumulating evidence has raised concerns about the specificity of these approaches, and several assays have been replaced by more specific LC-MS/MS methods. Testosterone analysis is probably the most widely recognized example of this trend (3). Still, although LC/MS/MS is a well-established tool for clinical biomarker analysis, comparatively few IA-MS applications have appeared for small molecules (4), and the uptake of IA-MS utilization is uncertain. Interestingly, the situation is entirely different for …
Patterns of conflict among software components

Integrating a system of disparate components to form a single application is still a daunting, high risk task, especially for components with heterogeneous communication expectations. It benefits integration to know explicitly the interoperability conflicts that can arise based on the current application design and the components being considered. However, there is no consistent representation of identified conflicts that also defines strategies to resolve them. Instead, developers use prior experience which may have consequential gaps. In this paper, we formulate a common representation for six major interoperability conflicts that arise through discrepancies or direct mismatches among architectural properties of interacting components. We use an Extender-Translator-Controller (ETC) classification scheme to describe the conflict resolution strategies. Detailing these associations as patterns provides insight into formulating an overall integration architecture design reflecting the solution strategy for developers to codify with respect to all components in the application. This approach moves conflict detection and resolution toward automation, immediately reducing the risk associated with the development of component based integrated systems.
Preconditioning in immature rabbit hearts: role of KATP channels.

Background —The protective effects of ischemic preconditioning have been shown to occur in adult hearts of all species studied. We determined whether immature hearts normoxic or chronically hypoxic from birth could be preconditioned, the time window or memory of the cardioprotective effect, and the involvement of the KATP channel. Methods and Results —Isolated immature rabbit hearts (7 to 10 days old) were subjected to 0, 1, or 3 cycles of preconditioning consisting of 5 minutes of global ischemia plus 10 minutes of reperfusion. This was followed by 30 minutes of global ischemia and 35 minutes of reperfusion. Normoxic hearts (Fio2=0.21) subjected to 1 cycle of preconditioning recovered 70±7% of left ventricular developed pressure compared with 43±8% recovery in nonpreconditioned controls. Three cycles of preconditioning did not result in additional recovery (63±8%). Hearts from rabbits raised from birth in hypoxic conditions (Fio2=0.12) and subjected to 1 and 3 preconditioning cycles did not show increased recovery (68±8% and 65±5%) compared with nonpreconditioned hypoxic controls (63±9%), although the recovery was greater in chronically hypoxic hearts than in age-matched normoxic controls. Increasing the recovery period after the preconditioning stimulus from 10 to 30 minutes resulted in a loss of cardioprotection. Pretreatment of normoxic hearts for 30 minutes with the KATP channel blocker 5-hydroxydecanoate (300 μmol/L) completely abolished preconditioning (70±7% to 35±9%) but had no effect on nonpreconditioned hearts (40±8%). Conclusions —Immature hearts normoxic from birth can be preconditioned, whereas immature hearts hypoxic from birth cannot. Preconditioning in normoxic immature hearts is associated with activation of the KATP channel.
Visual stimuli recruit intrinsically generated cortical ensembles

The cortical microcircuit is built with recurrent excitatory connections, and it has long been suggested that the purpose of this design is to enable intrinsically driven reverberating activity. To understand the dynamics of neocortical intrinsic activity better, we performed two-photon calcium imaging of populations of neurons from the primary visual cortex of awake mice during visual stimulation and spontaneous activity. In both conditions, cortical activity is dominated by coactive groups of neurons, forming ensembles whose activation cannot be explained by the independent firing properties of their contributing neurons, considered in isolation. Moreover, individual neurons flexibly join multiple ensembles, vastly expanding the encoding potential of the circuit. Intriguingly, the same coactive ensembles can repeat spontaneously and in response to visual stimuli, indicating that stimulus-evoked responses arise from activating these intrinsic building blocks. Although the spatial properties of stimulus-driven and spontaneous ensembles are similar, spontaneous ensembles are active at random intervals, whereas visually evoked ensembles are time-locked to stimuli. We conclude that neuronal ensembles, built by the coactivation of flexible groups of neurons, are emergent functional units of cortical activity and propose that visual stimuli recruit intrinsically generated ensembles to represent visual attributes.
Human Milk Feedings and Infection Among Very Low Birth Weight Infants

Background. Preterm infants are immu- nologically immature at birth. Previous studies have demonstrated that human milk protects against infection in full-term infants, but there are few studies of its effect for preterm infants. Objective. To examine the effect of human milk feed- ings on infection incidence among very low birth weight (VLBW) infants during their initial hospitalization. Study Design. The sample consisted of 212 consecu- tive VLBW infants admitted to the Georgetown Univer- sity Medical Center neonatal intensive care unit (NICU) during 1992-1993 and surviving to receive enteral feed- ing. Type of feeding (human milk vs formula), presence of infection and sepsis/meningitis (clinical signs and positive cultures for pathogenic organisms), and poten- tial confounding variables were abstracted from medical records. Multiple logistic regression was used to control for confounders. Results. The incidence of infection (human milk (29.3%) vs formula (47.2%)) and sepsis/meningitis (hu- man milk (19.5%) vs formula (32.6%)) differed signifi- cantly by type of feeding. Major risk factors for infection were similar in both groups. Human milk feeding was independently correlated with a reduced odds of infec- tion (odds ratio (OR) 5 0.43; 95% confidence interval (CI): 0.23- 0.81), controlling for gestational age, 5-minute Ap- gar score, mechanical ventilation days, and days without enteral feedings; and was independently correlated with a reduced odds of sepsis/meningitis (OR 5 0.47, 95% CI:0.23- 0.95), controlling for gestational age, mechanical ventilation days, and days without enteral feedings. Conclusions. The incidence of any infection and sepsis/ meningitis are significantly reduced in human milk-fed VLBW infants compared with exclusively formula-fed VLBW infants. Pediatrics 1998;102(3). URL: http://www. pediatrics.org/cgi/content/full/102/3/e38; infection, sepsis, in- fant, low birth weight, human milk, breastfeeding.
From Seattle (and Ubon) to Bangkok: The Scales of Resistance to Corporate Globalization

Recent work by geographers has highlighted attempts by local groups to ‘jump scales’ in their efforts to contest the power of global capital. Sometimes such ‘scale jumping’ is also seen as part of an effort to bypass the nation-state. This paper explores a particular case of scale jumping, which illustrates some of the complexities of the process. Building on the anticorporate globalization momentum generated during the ‘battle in Seattle’ and the demonstrations during the February 2000 United Nations Commission on Trade and Development meetings in Bangkok, local antidam activists from Ubon Ratchathani province in Thailand scaled up their activities during 2000, utilizing various international connections to improve their visibility and strengthen their prospects for success. Rather than simply bypassing the nation-state, however, they have had to use both local and international resources to try to combat the policies of the nation-state, a project in which they have had real but still contested success....
Achievable rates in cognitive radio networks

In this paper, communication through an overlay cognitive radio network, wherein the cognitive ability of a secondary source needs to be acquired, i.e. the primary message may only be obtained by the cognitive source in a causal manner, is considered. A new achievable rate region for the discrete memoryless version of this network is derived using block Markov superposition coding (SPC), conditional rate-splitting, conditional Gel'fand-Pinkser (GP) binning, and cooperative relaying. This rate region is evaluated for Gaussian channels, and numerical results are presented to demonstrate the contributions of the various coding strategies, used in the proposed coding scheme, towards enlarging the achievable rate region.