cssi/SciSciGPT-SciSciNet huggingface dataset:
Quantitative tracking of inflammatory activity at the peak and trough plasma levels of tofacitinib, a Janus kinase inhibitor, via in vivo 18 F-FDG PET.

PURPOSE To assess the capability of in vivo positron emission tomography (PET) using 18 F-fluorodeoxyglucose (18 F-FDG) to quantify changes in inflammatory activity in response to tofacitinib, a Janus kinase (JAK) inhibitor, over a timeframe of a few hours to few days in a preclinical model of rheumatoid arthritis (RA). METHODS Twenty-four mice with collagen-induced arthritis in the following groups were assessed: Group 1, where the changes in PET measures for the extremity joints were evaluated at the peak and trough plasma drug levels after administration of a single dose of tofacitinib (4 hours apart); Group 2, where joint PET measures were assessed before treatment and after 6 days of administration of a daily dose of tofacitinib; and group 3 (controls), where joint PET measures were derived from the same mice, 6 days apart. RESULTS At about peak plasma levels of the drug after a single tofacitinib administration, there was a reduction in PET measures compared to pretreatment values, suggesting decreased inflammatory activity. These measures were equivalent to those obtained after 6 days of daily dosing by tofacitinib. However, PET measures at trough plasma levels of the drug from tofacitinib administration were significantly higher than those at peak plasma drug levels and equivalent to pretreatment measures. There were insignificant changes in PET measures for the control animals. CONCLUSION 18 F-FDG PET can detect changes in inflammatory activity occurring in response to the JAK inhibitor tofacitinib: (a) during peak and trough plasma drug levels, that is within mere hours of treatment; and (b) over a span of days.
How to address second and therapy‐related acute myelogenous leukaemia

Secondary acute myelogenous leukaemia (AML), as compared to de novo AML, occurs in the more elderly population, is independently more resistant to cytotoxic chemotherapy, has a higher relapse rate, and a worse prognosis. Secondary AML (sAML) is a heterogeneous disease, both biologically and clinically, even within the World Health Organization subgroups of sAML. Outcomes are the poorest in subgroups with sAML arising from an antecedent haematologic disorder which has been previously treated (ts-AML), and sAML in patients <55 years of age. This review describes the suboptimal outcomes of contemporary therapy, to support the notion of an unmet need for innovative treatment strategies in sAML. Despite the recent approval of CPX-351, long-term outcomes for this high-risk disease remain dismal. Resistance mechanisms to intensive chemotherapy contribute to relapse. Targeted immune therapy may avoid multidrug resistance mechanisms, but are unlikely to provide long-term remission due to a complex and rapidly evolving clonal disease profile. Advances for sAML will likely be accomplished by CAR T cell therapy or bispecific antibodies providing a bridge to allogeneic stem cell transplantation. Therefore, focus should be placed on novel strategies that can augment the untargeted effector function of allogeneic grafts.
Structures and Models of Glasses

The main objective of this article is to provide an up-to-date presentation of the structural models of inorganic glasses. First of all, a glass will be defined from the glass transition temperature and the main elements of the glass classification will be shown. Then, characterization of a disordered structure as glass, will be divided, depending on the range order, in two parts: the short-range order, constituted of basic structural units and, the medium-range order, constituted of superstructural units in a scale ranging from the dimension of the basic structural unit to scales of at least 2-5 nm. Almost all types of used techniques will be mentioned to illustrate selective information which can be obtained on different composition of glasses. In addition recent advances in optical glasses will also be provided.
Failure Analysis of a Steel Elbow Pipe from a Gas Well

A steel-type ASTM A234 WPB elbow pipe from a gas well, through which water pressurized at 4 kg/cm2 and at 10–30 °C temperature was circulated, was perforated, originating a water leakage. Several tests were carried out in order to determine the cause of the perforation: Visual and radiographic inspection, chemical analysis, hardness test and microstructure, microscopy and fractographic studies. The presence of CO2 in the water might be very important for the corrosion phenomenon in the welding area as a result of the presence of a galvanic couple between the weld bead and the pipeline steel. However, the CO2 was not the only cause of the pipe damage. The fractographic study of the perforations and the flow analysis indicated that cavities have been originated as a consequence of a cavitation–corrosion phenomenon which is a particular erosion process caused by the implosion of gas bubbles on the metal surface.
Multiorgan procurement is associated with a survival benefit after heart transplantation

We assessed the impact of donor multiorgan procurement on survival following orthotopic heart transplantation (OHT). From the UNOS STAR database, we included all adult (≥18 Y) heart transplants (OHT) performed since 2000 and used donor IDs to determine how many other organs were procured from the same donor as the recipient's heart allograft (regardless of recipient). The Kaplan-Meier survival functions and risk-adjusted Cox proportional hazards regression models were computed to assess the association of multiorgan procurement with post-heart transplantation mortality. We included 40 336 OHT patients. Including the heart, the median number of donor organs procured was 3 (IQR, 3-4). Heart donors underwent liver procurement in 89.7%; kidney(s) in 98.1% (single 95%, bilateral 5%); lung(s) in 38.0% (single 28%, bilateral 72%); pancreas in 10.4%; and intestine in 1.6%. Following risk adjustment across 16 recipient- and donor-specific variables, an increasing number of organs procured were independently associated with reduced post-OHT mortality (HR 0.98, 95% CI 0.96-0.99, P = .025). Though no significant associations were found examining specific organ types, double lung procurement trended toward a protective effect (HR 0.96, 0.92-1.01, P = .086), with counts of non-lung organs procured still bordering on significance (HR 0.97, 95% CI 0.95-1.00, P = .067). These results likely reflect improved multiorgan donor quality.
MET-dependent solid tumours - molecular diagnosis and targeted therapy

Attempts to develop MET-targeted therapies have historically focused on MET-expressing cancers, with limited success. Thus, MET expression in the absence of a genomic marker of MET dependence is a poor predictor of benefit from MET-targeted therapy. However, owing to the development of more sensitive methods of detecting genomic alterations, high-level MET amplification and activating MET mutations or fusions are all now known to be drivers of oncogenesis. MET mutations include those affecting the kinase or extracellular domains and those that result in exon 14 skipping. The activity of MET tyrosine kinase inhibitors varies by MET alteration category. The likelihood of benefit from MET-targeted therapies increases with increasing levels of MET amplification, although no consensus exists on the optimal diagnostic cut-off point for MET copy number gains identified using fluorescence in situ hybridization and, in particular, next-generation sequencing. Several agents targeting exon 14 skipping alterations are currently in clinical development, with promising data available from early-phase trials. By contrast, the therapeutic implications of MET fusions remain underexplored. Here we summarize and evaluate the utility of various diagnostic techniques and the roles of different classes of MET-targeted therapies in cancers with MET amplification, mutation and fusion, and MET overexpression.
Visualizing antibody production in a human lymph node in a dish

Development of a human lymphoid organoid system enables in vitro modeling of immune responses and antibody formation.
Too Good to be Nice: A Model of Corporate Social Responsibility Investment with Asymmetric Quality Information.

High-quality firms sometimes under-invest in Corporate Social Responsibility (CSR) compared to lower quality firms. We show that information asymmetry in product quality could explain this behavior. Specifically, in a monopoly with information asymmetry, if only a small fraction of consumers is informed about the true quality of a product, a high-quality firm may distort its investment downwards and make a lower CSR investment than the one a low-quality firm would make. Ironically, this downward distortion works by burning quality, i.e., decreasing the value of the high-quality product, which makes imitation by the low-quality firm less appealing by reducing the demand for the high-quality firm, a mechanism that is novel and distinct from both money burning and counter-signaling. Having established that CSR can have an informational role, we allow firms to engage in informative advertising. We find that, surprisingly, advertising will neither crowd out CSR nor inform all consumers. Instead, if the number of informed consumers is moderate, the high-quality firm will balance advertisement and CSR like substitutes, while it might treat them like complements when the number of informed consumers is low. We explore the boundaries of our results and find that they are robust to the assumptions about heterogeneity in consumers’ preferences, firms’ cost, or charity quality.
Characterizing Underlying Cognitive Components of ADHD Presentations and Co-morbid Diagnoses: A Diffusion Decision Model Analysis.

Objective:To Explore whether subtypes and comorbidities of attention-deficit hyperactivity disorder (ADHD) induce distinct biases in cognitive components involved in information processing.Method:P...
Plant population and community responses to removal of dominant species in the shortgrass steppe.

Question: What are the plant population- and community-level effects of removal of dominant plant species in the shortgrass steppe? Location: The Shortgrass Steppe Long-Term Ecological Research site in northern Colorado, USA. Methods: We annually measured plant cover and density by species for 10 years after a one-time aboveground removal of the dominant perennial grass, Bouteloua gracilis. Removal and control plots (3 m × 3 m) were within grazed and ungrazed locations to assess the influence of grazing on recovery dynamics. Our analyses examined plant species, functional type, and community responses to removal, paying special attention to the dynamics of subdominant and rare species. Results: Basal cover of B. gracilis increased by an average of 1% per year, but there was significantly less plant cover in treatment compared to control plots for 5 years following removal. In contrast to the lower cover in treatment plots, the plant density (number of plants m−2) of certain subdominant perennial grasses, herbaceous perennial and annual forbs, a dwarf shrub, and cactus increased after removal of the dominant species, with no major change in species richness (number of species per 1 m × 1 m) or diversity. Subdominant species were more similar between years than rare species, but dominant removal resulted in significantly lower similarity of the subdominant species in the short term and increased the similarity of rare species in the long term. Conclusions: Removal of B. gracilis, the dominant perennial grass in the shortgrass steppe, increased the absolute density of subdominant plants, but caused little compensation of plant cover by other plants in the community and changes in species diversity.
Characteristics of a 17-ketosteroid reaction.

An improved method for the determination of 17-ketosteroids is described, which involves an increase in sensitivity by the simple expedient of upsetting the equilibrium of the reaction in removing the products of reaction by precipitating the chromophore formed. This precipitation system appears to achieve about 1.6 times the color sensitivity for the same reaction carried out as a solution process. An alternative extraction step for color purification is described. Spectrums, variabilities in reagent parameters, and statistical evaluations are discussed.
Transposon insertions causing constitutive Sex-lethal activity in Drosophila melanogaster affect Sxl sex-specific transcript splicing

Sex-lethal (Sxl) gene products induce female development in Drosophila melanogaster and suppress the transcriptional hyperactivation of X-linked genes responsible for male X-chromosome dosage compensation. Control of Sxl functioning by the dose of X-chromosomes normally ensures that the female-specific functions of this developmental switch gene are only expressed in diplo-X individuals. Although the immediate effect of X-chromosome dose is on Sxl transcription, during most of the life cycle "on" vs. "off" reflects alternative Sxl RNA splicing, with the female (productive) splicing mode maintained by a positive feedback activity of SXL protein on Sxl pre-mRNA splicing. "Male-lethal" (SxlM) gain-of-function alleles subvert Sxl control by X-chromosome dose, allowing female Sxl functions to be expressed independent of the positive regulators upstream of Sxl. As a consequence, SxlM haplo-X animals (chromosomal males) die because of improper dosage compensation, and SxlM chromosomal females survive the otherwise lethal effects of mutations in upstream positive regulators. Five independent spontaneous SxlM alleles were shown previously to be transposon insertions into what was subsequently found to be the region of regulated sex-specific Sxl RNA splicing. We show that these five alleles represent three different mutant types: SxlM1, SxlM3, and SxlM4. SxlM1 is an insertion of a roo element 674 bp downstream of the translation-terminating male-specific exon. SxlM3 is an insertion of a hobo transposon (not 297 as previously reported) into the 3' splice site of the male exon, and SxlM4 is an insertion of a novel transposon into the male-specific exon itself. We show that these three gain-of-function mutants differ considerably in their ability to bypass the sex determination signal, with SxlM4 being the strongest and SxlM1 the weakest. This difference is also reflected in effects of these mutations on sex-specific RNA splicing and on the rate of appearance of SXL protein in male embryos. Transcript analysis of double-mutant male-viable SxlM derivatives in which the SxlM insertion is cis to loss-of-function mutations, combined with other results reported here, indicates that the constitutive character of these SxlM alleles is a consequence of an alteration of the structure of the pre-mRNA that allows some level of female splicing to occur even in the absence of functional SXL protein. Surprisingly, however, most of the constitutive character of SxlM alleles appears to depend on the mutant alleles' responsiveness, perhaps greater than wild-type, to the autoregulatory splicing activity of the wild-type SXL proteins they produce.
Fatty acid-related functions

The first recommendations for specific nutrient quantities that must be obtained to support health were made by the US Department of Agriculture before 1939. Hazel Stiebeling was the leader of this effort and the scientific background was published in the Yearbook of Agriculture. The recommendations clearly stated that food must be available to provide the nutrients to support health. The science of nutrition in the United States is engaged in the most thorough review and reexamination of the recommended dietary allowances in at least a generation of nutrition scientists. There is a new awareness of nutrition complexity and the likelihood of identification of new essential nutrients. This meeting was devoted to the search for functional endpoints to reach quantitative estimates of dietary substances needed to support a function. Included in that concept is determining a range of individual needs and identifying factors that alter these needs. We give the rationale for endpoints of fatty acid metabolism related to platelets and the risk of thrombosis, give the rationale for the recommendation for a new nutrient, and show the necessity for including nutrient interaction in the determination of needs for two nutrients.
A unique technique for intentional occlusion of an abdominal aortic aneurysm

We report the case of a 78-year-old man with coronary artery disease, chronic obstructive pulmonary disease, and chronic renal insufficiency with an enlarging 6.7-cm infrarenal abdominal aortic aneurysm. He also had a 4-cm right common iliac artery aneurysm, and right external iliac artery occlusion. The patient had a history of an axillobifemoral bypass graft placed 10 years prior for aortoiliac occlusive disease. We describe the use of an infrarenal aorto-uni-iliac graft and subsequent intentional graft occlusion as an endovascular solution to treat aneurysmal disease in this sick patient. He remains asymptomatic after surgery, with demonstrated occlusion of his aneurysms.
Comparability of the standing and supine standard electrocardiograms and standing sitting and supine stress electrocardiograms

The aim of this study was to evaluate whether change in the patients' position during the electrocardiogram (ECG) recording alters the various components of the ECG curve. Concerns whether ECGs in medically compromised patients recorded in a sitting position should be considered "standard" tracings and whether ECGs recorded in the supine and standing positions and ECGs recorded in different positions in the Exercise Laboratory are interchangeable provided the impetus for this study. The ECG was recorded in the supine and standing positions in 10 patients using standard electrode placement and in the sitting, standing, and supine positions in 16 patients using the Mason-Likar electrode system. Comparisons of sums of P waves and QRS complexes of various combinations of ECG leads from recordings in different positions and amplitudes of Q, R, and S waves of all 12 ECG leads revealed stability in the standard and stress ECGs, although few statistically significant but minor changes were noted in some comparisons, which, however, could not be expected to have any diagnostic significance. Comparison of standard ECGs recorded in patients in the supine and standing positions and stress ECGs recorded in the sitting, standing, and supine positions are interchangeable; this should allay concerns about recording the standard ECG in unconventional positions and may facilitate and make more cost-effective ECG recording in busy outpatient clinic environments.
Concentration profiles of non-Fickian diffusants in glassy polymers by Rutherford backscattering spectrometry

Rutherford backscattering spectrometry (RBS) is used to determine the concentration profile of 1,1,1 -trichloroethane (TCE) as it diffuses into a crosslinked polymethylmethacrylate (PMMA) glass. The penetration characteristics are those of Case II diffusion, i.e. a diffusion front moves into the glass at a velocity that is roughly constant. Due to the excellent depth resolution (<30 nm) and sensitivity (<500 p.p.m. Cl) of RBS the details of the front can be observed. Behind the front where the concentrationϕ of TCE is high and the PMMA is plasticized to a rubbery state, the concentration gradient of TCE is negligible, indicating that the diffusion coefficient of TCE in this region is greater than 10−9 cm2 sec−1. At the front the concentration of TCE decreases abruptly in less than 100 nm to a lower concentrationϕ 0, and subsequently decays exponentially with the distance x from the front. These results are consistent with the Fickian solution to diffusion ahead of a moving boundary, i.e.ϕ(x)=ϕ 0exp [− (υx/D)], whereυ is the velocity of the front and D is the (Fickian) diffusivity of the TCE in the glass ahead of the front. These observations are in qualitative agreement with the predictions of a model of Case II diffusion by Thomas and Windle, and a simplified version of their model is proposed.
Effect of SBE4-β-CD, a sulfobutyl ether β-cyclodextrin, on the stability and solubility of O6-benzylguanine (NSC-637037) in aqueous solutions

Abstract The effect of SBE4-β-CD, a sulfobutyl ether derivative of β-cyclodextrin on the solubility and aqueous hydrolysis of the antitumor drug O6-benzylguanine (BG) was studied. SBE4-β-CD is an apparently parenterally safe anionic β-cyclodextrin derivative with superior solubilizing properties in water. BG has poor aqueous solubility and undergoes rapid hydrolysis to the poorly water soluble guanine. The stability of a parenteral BG formulation was studied after storage at 25, 37 and 50°C. Compared to the intrinsic solubility of BG (0.14 mg/ml, 25°C), 0.05 M SBE4-β-CD enhanced its solubility to 2.9 mg/ml at 25°C and 3.9 mg/ml at 50°C. Solubility data yielded binding constants (Kb) of 565 M−1 at 25°C and 342 M−1 at 50°C. The solubility of guanine was only slightly enhanced by SBE4-β-CD. Hydrolysis kinetics of BG were studied at 50°C over a pH range of 1–9 and the maximum stability was observed at pH 8-8.5. In the presence of 0.05 M SBE4-β-CD, hydrolysis was about 9.5-times slower at pH 1, 14.6-times slower at pH 6 and 10-times slower at pH 8. The effect of SBE4-β-CD concentration was studied at pH 2.2 and 4.8 at 50°C. Hydrolysis rate constants decreased with increasing SBE4-β-CD concentrations. A non-linear regression analysis of this data yielded Kb values of 311 and 270 M−1 at pH 2.2 and 4.8, respectively. A formulation containing 2.5 mg/ml of BG and 0.05 M SBE4-β-CD in a pH 8 phosphate buffer was stored in ampoules at 25, 37 and 50°C. Guanine production in the samples was measured since its low solubility (2.5 μg/ml) imposed a limitation on the shelf life. Guanine levels exceeded its apparent solubility after 1–2 months of storage at 50°C. At 37°C guanine levels were only 1.6 μg/ml after 343 days of storage whereas those at 25°C were negligible and below the limit of quantitation (approx. 0.1 μg/ml). The greater stability at room temperature may be attributed to the higher Kb value observed and greater intrinsic stability of BG in the complex.
When Harm is at Stake: Ethical Value Orientation, Managerial Decisions, and Relational Outcomes

Relational dimensions of ethical decision making are a potentially interesting focus to enrich our understanding of decision-making processes. This study examines decision preferences and reactions to decisions in a situation of possible harm. Two ethical value orientations, just value orientation (JVO) and relational value orientation (RVO), are introduced. Participants chose relational cooperation, instrumental cooperation, or independence in dealing with an uncertain situation of possible harm. JVO contributes to a decision of relational cooperation. Only RVO was related to expected mutual benefit and relational connection. Overall, this study supports our central thesis that a relational dimension of ethical decisions provides interesting insights into behavioral ethics in organizations and could expand the scope of ethical decision research.
Flow cytometric analysis of fluorescein-labeled nerve growth factor binding to A875 human melanoma cells.

Abstract The interaction of fluorescein-labeled nerve growth factor (NGF) with human melanoma cells (A875) has been studied in order to assess better methodology for rigorous NGF binding studies. The NGF was modified at a single carboxyl group with iodoacetamidofluorescein after reaction with carbodiimide and cystamine. The modified NGF showed full binding competence in competition with radiolabeled NGF and full biological activity in neurite outgrowth assays compared to native NGF. Binding to unfixed, viable cells was assayed using flow cytometry. This method offers the advantage that unbound ligand need not be separated from that which is cell-associated, thus avoiding pertubation of the binding equilibrium, and accurate, extensive statistical analysis is possible. Binding of fluorescein-NGF was mainly specific and saturable, with analysis by three methods of data treatment indicating a K d of 0.8 to 3 n M at 4°C. Time-based data acquisition allowed a continuous time course for binding to be generated. Binding reached a steady-state level within 5 min of exposure of the cells to the ligand. Kinetic and steady-state results obtained using fluorescein-NGF agree well with previous data produced by 125 I-NGF binding studies. The main limitation of the flow cytometric method in the NGF system is the relative lack of sensitivity compared to the binding of radiolabeled NGF, partially due to unusual quenching of the fluorophore bound to NGF.
MMP-9 and uPAR regulated glioma cell migration

Integrin-dependent and -independent MMP-9 and uPAR signaling plays a key role in glioma cell migration and invasion. In this article, we comment on all the possible pathways and molecules associated with MMP-9- and uPAR-mediated glioma cell migration with a special emphasis on integrins, a family of cell adhesion molecules. Our recent research investigations highlighted the substantial benefit of silencing both MMP-9 and uPAR together compared with their individual treatments in glioma. Simultaneous knockdown of both MMP-9 and uPAR regulated a majority of the molecules associated with glioma cell migration and significantly reduced the migration potential of glioma cells. Our results point out that the bicistronic construct, which can simultaneously silence both MMP-9 and uPAR offers a great therapeutic potential and is worth developing as a new drug for treating GBM patients.
From nursing home to acute care: Signs, symptoms, and strategies used to prevent transfer

Older adults are vulnerable to experiencing physiologic changes that may permanently decrease functional abilities when transferring from the nursing home (NH) to the acute care setting. Making the right decision about who and when to transfer from the nursing home (NH) to acute care is critical for optimizing quality care. The specific aims of this study were to identify the common signs and symptoms exhibited by NH residents at the time of transfer to acute care and to identify strategies used to prevent transfer of NH residents. Using survey methodology, this descriptive study found change in level of consciousness, chest pressure/tightness, shortness of breath, decreased oxygenation, and muscle or bone pain were the highest ranked signs/symptoms requiring action. Actions to prevent transfer focused on stabilizing resident conditions and included hydration, oxygen, antibiotics, medications, symptom management, and providing additional physical assistance. When transfer was warranted, actions concentrated on the practical tasks of getting the residents transferred.
Construction of Solutions for Two Dimensional Riemann Problems

Solutions to the scalar quasilinear equation σu(t, x)σt + ∑i=12 σf1(u(t, x))σxi = 0 for fi ϵ C2:R → R with initial data given by a two-dimensional Riemann problem, are piecewise smooth if f1  f2  f, and f has at most one inflection point. We show that the “pieces” of this solution can be classified and are expressible in terms of two-dimensional nonlinear waves in analogy with the nonlinear rarefaction and shock waves of the Riemann problem in one spatial dimension. The two-dimensional waves can be expressed in almost-closed form. Explicit solutions are constructable from these waves. An application is illustrated by calculation of the interaction of water/oil banks in two-phase incompressible flow in reservoirs.
The incremental information content of replacement cost earnings

Abstract The study explores the incremental explanatory power of replacement cost earnings variables (derived from ASR 190 data) with respect to explaining cross sectional differences in security returns. As such, the study is a natural extension of previous research, including analyses of the effect of security returns of ASR 190 data at the time of disclosure, investigations of cross sectional relationships between security returns and historical cost earnings, and studies of multiple signals. The basic finding is that pre-holding gain net income provides no incremental explanatory powerm given knowledge of historical cost earnings. However, the converse does not hold. Taken together, the findings are consistent with the contention that pre-holding gain net income is a garbled version of historical cost earnings. The basic finding is robust under several extensions of the initial research design. The research design incorporates a two-stage approach which permits a determination of the incremental explanatory power of collinear variables. The findings are in contrast to those of a previous study by Easman et al. (1979). The nature of the difference in research design inducing the difference is identified. Potential reasons for the difference in findings are provided.
XLIX. The surface-tension of certain dilute aqueous solutions, determined by the method of ripples

(1897). XLIX. The surface-tension of certain dilute aqueous solutions, determined by the method of ripples. The London, Edinburgh, and Dublin Philosophical Magazine and Journal of Science: Vol. 44, No. 270, pp. 369-396.
The mechanical behavior of poly(lactic acid) unreinforced and nanocomposite films subjected to monotonic and fatigue loading conditions

The mechanical and fatigue behavior of neat poly(lactic acid) (PLA) films and PLA films reinforced with 5 wt% nanoclay particles has been examined using various analytical procedures. The results s...
Rat diaphragm oxidative capacity, antioxidant enzymes, and fatigue: newborn versus adult.

Little is known about the antioxidant capacity and oxidant-generating potential of newborn muscle, or how these properties compare with the adult and relate to fatigue resistance. We determined the 1) antioxidant enzyme activities [superoxide dismutase (SOD), catalase, glutathione peroxidase], 2) glutathione content, 3) oxidative capacity [indexed by succinic dehydrogenase activity], 4) extracellular cytochrome c reduction, and 5) efficacy of exogenously administered SOD in ameliorating fatigue in vitro of newborn and adult diaphragm (DIA). Newborn and adult DIA SOD activities were not different, whereas newborn catalase activity was greater, and newborn glutathione peroxidase activity and glutathione content less than adult DIA. Succinic dehydrogenase activity was ≈ 2-fold greater in the adult compared with the neonate. Repetitive contractions led to a significant deline in newborn and adult DIA force; this decline was greater in the adult (78± 4% decrement in force at 2 min) compared with newborn DIA (28± 8% decrement in force at 2 min). Extracellular cytochrome c reduction was greater in adult as compared with newborn DIA during fatiguing contractions. Exogenous SOD attenuated fatigue in the adult, but had no effect on newborn DIA. We conclude that the oxidative capacity of the adult DIA is greater than that of the newborn and not matched by a concomitant increase in SOD activity. Our data suggest that the increased oxidative capacity releative to SOD activity in adult DIA may lead to oxidative stress and an enhanced susceptibility to fatigue.
Hydration of isobutene in a trickle-bed reactor: Wetting efficiency and mass transfer

Reaction rates for the hydration of isobutene were measured at 323 K and atmospheric pressure in a trickle-bed reactor over a sixfold range of liquid rates. Three widely different feed conditions were used to vary the effect of mass transfer and wetting efficiency. The effect of wetting efficiency on the rate was analyzed using the additive procedure of Tan and Smith. The results showed that mass transfer from liquid to particle, wetting efficiency, and intraparticle kinetics all influenced the total rate, but that the gas-to-liquid mass transfer resistance was unimportant. Most of the resultant values of wetting efficiency and liquid-to-mass transfer coefficients were a little lower than literature values. This may be due to the high surface tension of our aqueous system. The derived total rate equations agreed well with the experimental rates, suggesting that the additive procedure is a satisfactory method of accounting for wetting efficiency.
Kinetic Studies on Immune Hemolysis. I. A Method.

A quantitative method for the study of the kinetics of immune hemolysis is described. In the presence of excess C' and limited amounts of antibody the kinetics of hemolysis resemble those of enzymatic processes. Assays of hemolytic antibody should therefore be based on velocity measurements rather than end point titrations.
Hashish VI 1 : conversion of (-)- 1(6) -tetrahydrocannabinol to (-)- 1(7) -tetrahydrocannabinol. Stability of (-)- 1 - and (-)- 1(6) -tetrahydrocannabinols.

Die Synthese von (—)-Δ1(7)-Tetrahydrocannabinol (THC) auf (—)-Δ1(6) wird beschrieben. Das Hauptprodukt der oxidativen Zerstorung von (—)-Δ1-THC ist Cannabinol. Beschleunigte Versuche der Luftoxidation von (—)-Δ1-THC und (—)-Δ1(6)-THC haben gezeigt, dass das letztere bestandiger ist. Dieser Unterschied kann mit der Reaktivitat des C3-benzylisch-allylischen Wasserstoffes in (—)-Δ1-THC erklart werden.
Racial differences in T-lymphocyte response to glucocorticoids

Background Asthma morbidity and mortality is increased in blacks. Objective The primary objective of this cross-sectional study was to determine if blacks, asthmatic or nonasthmatic, displayed diminished T-lymphocyte response to glucocorticoids in vitro compared to their white counterparts. If differences were noted, this would suggest a racial predisposition to decreased glucocorticoid responsiveness among blacks. Methods Asthmatic (n = 395, 27% blacks) and control (n = 202, 52% blacks) subjects recruited from National Jewish Medical and Research Center and from the surrounding community participated in the study. In vitro glucocorticoid responsiveness was determined by assessing the log-transformed concentration of dexamethasone required to suppress phytohemagglutinin-induced T-lymphocyte proliferation by 50% (log 10 IC 50 ). Asthma medication history, atopic status, and spirometric lung function measures corrected for race were collected. Results Black and white asthmatic subjects had similar FEV 1 percentage of predicted values and inhaled and oral glucocorticoid requirements. Black asthmatic subjects displayed significantly diminished glucocorticoid responsiveness compared to white asthmatic subjects, as follows: median (first, third quartile) log 10 IC 50 values of 1.00 nmol (0.48, 1.83) vs 0.78 nmol (0.29, 1.45) [p = 0.028]. Similar results were found between black and white control subjects, as follows: median, 1.26 nmol (0.70, 2.14) vs 0.95 nmol (0.55, 1.48) [p = 0.01]. Age, race, and basal T-lymphocyte activity were significantly positively correlated to the log 10 IC 50 values. Conclusion Our observation that black asthmatic subjects and non-asthmatic control subjects require greater concentrations of glucocorticoid in vitro to suppress T-lymphocyte activation suggests that blacks have a racial predisposition to diminished glucocorticoid responsiveness, which may contribute to their heightened asthma morbidity.
Isolation and primary culture of rat renal cortical epithelial cells

Methods are described for the isolation of rat renal cortical epithelial cells by a collagenase and hyaluronidase perfusion, followed by pressing fragments of renal cortex through an 80-mesh screen and further enzymatic dissociation in vitro. Primary monolayer cultures are derived from the resulting suspension of tubular fragments and cells. Fibroblast and endothelial cell overgrowth is suppressed by the use of medium lacking arginine and containingd-valine in place ofl-valine. Further separation of fibroblasts from epithelial cells is achieved by a technique that takes advantage of the differential rate of attachment of the two cell types. The presence of glomerular cells in the cultures is diminished by a complete medium change 48 h after plating the cells.
Determination of residual Kryptofix 2.2.2 levels in [18F]-labeled radiopharmaceuticals for human use.

Abstract 4,7,13,16,21,24-Hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane (Kryptofix ® 2.2.2) is used in the routine preparation of [ 18 F]-labeled tracers employed in positron emission tomography (PET) imaging. Confirming the absence of Kryptofix ® in radiopharmaceuticals is a quality control criterion required before they can be released for human use. Analysis of Kryptofix ® levels using the iodoplatinate spot-test can be complicated by false-positive results due to nitrogen containing tracers and/or false-negative results caused by added stabilizers. To overcome this issue, we have developed a universal TLC method for the rapid and reliable determination of Kryptofix ® levels in the wide range of fluorine-18 radiopharmaceuticals we prepare, including complex multi-component formulations.
The linear pulse stretching circuit

Accurate determination of the width of short-duration pulses, using common low-bandwidth equipment, is accomplished by the linear pulse stretching circuit. An unknown input pulse may be elongated by a known factor, and the wider pulse is more easily measured. Also included is an analysis of the associated wave-shaper, two methods of readout using available equipment, and the results of measurements.
Social inclusion in Mumbai: economics matters too

This paper questions the accuracy and validity of the criticisms made by Ananya Roy regarding the approach to community development of a Mumbai-based NGO, SPARC, and its partner grassroots federations in Mumbai. This includes the suggestion that the focus on sanitation rather than on land tenure is an appeal to middle-class values about cleanliness and that their support for relocating those who lived right next to the railway tracks made them agents of the state. When viewed through a demand-responsive economic perspective, SPARC’s support for community toilets was in response to what grassroots organizations asked for, and these also have high returns. Similarly, SPARC’s support for resettlement for those living alongside the railway tracks was for those who were going to be moved, and this support allowed them to have far more influence on where, when and how the resettlement took place. Here too, the high returns from faster, safer trains meant cost savings that were higher than the costs of providing...
Intramolecular hydrogen bonding as a synthetic tool to induce chemical selectivity in acid catalyzed porphyrin synthesis

A straightforward procedure based on the formation of intramolecular hydrogen bonds to impart selectivity in the preparation of multi-functionalized porphyrins has been developed. To illustrate the concept, the synthesis of a biomimetic artificial photosynthetic model able to undergo electron and proton transfer reactions upon irradiation is reported.
Dimer Preparation That Mimics the Transition State for the Adsorption of H2 on the Si(100)-2 × 1 Surface

A chemically induced dimer configuration was prepared on the silicon (Si) (100) surface and was characterized by scanning tunneling microscopy (STM) and spectroscopy (STS). These prepared dimers, which are essentially untilted and differ both electronically and structurally from the dynamically tilting dimers normally found on this surface, are more reactive than normal dimers. For molecular hydrogen (H 2 ) adsorption, the enhancement is about 10 9 at room temperature. There is no appreciable barrier for the H 2 reaction at prepared sites, indicating the prepared configuration closely approximates the actual dimer structure in the transition state. This previously unknown ability to prepare specific surface configurations has important implications for understanding and controlling reaction dynamics on semiconductor surfaces.
Hydrostatic Pressurization and Depletion of Trapped Lubricant Pool During Creep Contact of a Rippled Indenter Against a Biphasic Articular Cartilage Layer

This study presents an analysis of the contact of a rippled rigid impermeable indenter against a cartilage layer, which represents a first simulation of the contact of rough cartilage surfaces with lubricant entrapment. Cartilage was modeled with the biphasic theory for hydrated soft tissues, to account for fluid flow into or out of the lubricant pool. The findings of this study demonstrate that under contact creep, the trapped lubricant pool gets depleted within a time period on the order of seconds or minutes as a result of lubricant flow into the articular cartilage. Prior to depletion, hydrostatic fluid load support across the contact interface may be enhanced by the presence of the trapped lubricant pool, depending on the initial geometry of the lubricant pool. According to friction models based on the biphasic nature of the tissue, this enhancement in fluid load support produces a smaller minimum friction coefficient than would otherwise be predicted without a lubricant pool. The results of this study support the hypothesis that trapped lubricant decreases the initial friction coefficient following load application, independently of squeeze-film lubrication effects.
Transfer of n-type GaSb onto GaAs substrate by hydrogen implantation and wafer bonding

Many GaSb devices would greatly benefit from the availability of a semi-insulating substrate. Since semi-insulating GaSb is not currently available, the formation of thin GaSb layers through wafer bonding and tranfer onto a semi-insulating GaAs substrate was investigated. GaSb-on-insulator structures, formed on GaAs substrates, were realized by the ion-cut process using H+ ions. Blistering, bonding and layer splitting phenomena were studied to optimize the ion dose and the process window. Bonded structures of thin layers of GaSb bonded to GaAs wafers were formed using a borosilicate glass (BSG) layer. The transferred GaSb layers were characterized by atomic force microscopy, MeV helium ion channeling and high-resolution x-ray diffractometry. The transferred film possessed a narrow x-ray linewidth of about 140 arcsec indicating improved crystalline quality over the direct growth of GaSb on GaAs.
A novel role for matrix metalloproteinase-8 in sepsis*

Objectives: Matrix metalloproteinase-8 messenger RNA expression was previously found to be increased in whole blood of children with septic shock. The impact of this finding on the severity and inflammatory response to sepsis is unknown. Here, we investigate the relationship between matrix metalloproteinase-8 and disease severity in children with septic shock. We further corroborate the role of matrix metalloproteinase-8 in sepsis in a murine model. Design: Retrospective observational clinical study and randomized controlled laboratory experiments. Setting: Pediatric intensive care units and an animal research facility at an academic children's hospital. Patients and Subjects: Patients age ≤10 yrs admitted to the intensive care unit with a diagnosis of septic shock. For laboratory studies, we utilized male mice deficient for matrix metalloproteinase-8 and male wild-type C57BL/6J mice. Interventions: Blood from children with septic shock was analyzed for matrix metalloproteinase-8 messenger RNA expression and matrix metalloproteinase-8 activity, and correlated with disease severity based on mortality and degree of organ failure. A murine model of sepsis was used to explore the effect of genetic and pharmacologic inhibition of matrix metalloproteinase-8 on the inflammatory response to sepsis. Finally, activation of nuclear factor-κB was assessed both in vitro and in vivo. Measurements and Main Results: Increased matrix metalloproteinase-8 mRNA expression and activity in septic shock correlates with decreased survival and increased organ failure in pediatric patients. Genetic and pharmacologic inhibition of matrix metalloproteinase-8 leads to improved survival and a blunted inflammatory profile in a murine model of sepsis. We also identify matrix metalloproteinase-8 as a direct in vitro activator of the proinflammatory transcription factor, nuclear factor-κB. Conclusions: Matrix metalloproteinase-8 is a novel modulator of inflammation during sepsis and a potential therapeutic target.
Preparation and Characterization of Lactitol-Based Poly(Ether Polyol)S for Rigid Polyurethane Foam

Propoxylation of lactitol [4-O-β-D-galactopyranosyl-D-glucitol] under alkaline conditions afforded poly(ether polyol)s (PEP) which have been characterized by their unsaturation content, alpha color, hydroxyl number, viscosity, hygroscopicity, and molecular weight distribution. The analogous sucrose-based PEP were prepared for comparison. Lactitol was found to require shorter reaction times and produced lighter-colored polyols than did sucrose. Polyols produced from lactitol displayed similar physical properties to sucrose-based PEP. Molecular weight analysis by GPC using the universal calibration method showed lactitol PEP to have polydispersities between 1.04 and 1.07. Negligible decomposition of lactitol during propoxylation was confirmed by 13 C-NMR and GPC. 1 H-NMR of trifluoroacetyl derivatives of lactitol PEP afforded secondary determination of M n . In addition, rigid polyurethane foams (PURF) formulated with lactitol-, sucrose-, or commercial sucrose-glycerin-based polyols and PAPI 27 were prepared and characterized. Lactitol-based PURF were found to compare favorably with sucrose-based foams, displaying a density and compressive strength of 28.9 kg/m 3 and 1.213 X 10 5 N/M 2 , respectively.
Catechol antagonism to the EEG effects of reserpine, chlorpromazine, pentobarbital, and atropine

Summary In rabbits, 3–12 mg/kg of catechol given intravenously reversed the EEG synchrony observed normally or induced by the cerveau isole or encephale isole lesion, by reserpine (2 mg/kg), by chlorpromazine (5–15 mg/kg), by pentobarbital (6–12 mg/kg), and by atropine (2–10 mg/kg). Catechol also antagonized or reduced the behavioural effects of the CNS depressants. In these doses, catechol alone had no significant effect on blood pressure despite producing transient “trembling”. Other overt effects such as paresis and ataxia were also induced by catechol. Higher dose of catechol (30 mg/kg) may induce an EEG seizure pattern and a much delayed drop in blood pressure. Resorcinol and pyrogallol also evoked EEG activation in similar experiments but 100–200 mg/kg of pyrogallol was necessary and failed to produce tremor. Catechol (3–12 mg/kg) produced similar behavioural effects in otherwise normal dogs and reduced the EEG and overt effect of anesthetic doses of pentobarbital.
Doppler signal processing: a new technique.

Reference EPFL-STUDENT-158608View record in Web of Science Record created on 2010-11-25, modified on 2017-05-10
Bacterial flavohemoglobin: a molecular tool to probe mammalian nitric oxide biology

A wide range of mammalian signaling and stress pathways are mediated by nitric oxide (NO), which is synthesized in vivo by the nitric oxide synthase (NOS) family of enzymes. Experimental manipulations of NO are frequently achieved by either inhibition or activation of endogenous NOS or via providing exogenous NO sources. On the contrary, many microbes consume NO via flavohemoglobin (FlavoHb), a highly efficient NO-dioxygenase that protects from nitrosative stress. Here we report a novel resource for studying NO in mammalian cells by heterologously expressing Escherichia coli FlavoHb within a lentiviral delivery system. This technique boosts endogenous cellular consumption of NO, thus providing a simple and efficacious approach to studying mammalian NO biology that can be employed as both a primary experimental and confirmatory tool.