cssi/SciSciGPT-SciSciNet huggingface dataset:
SOD1 Down-Regulates NF-κB and c-Myc Expression in Mice after Transient Focal Cerebral Ischemia:

Reactive oxygen species (ROS) are implicated in reperfusion injury after focal cerebral ischemia (FCI). Reactive oxygen species regulate activity of transcription factors like NF-kappaB. The authors investigated the role of ROS in NF-kappaB activity after FCI using transgenic mice that overexpressed human copper/zinc-superoxide dismutase (SOD1) and that had reduced infarction volume after FCI. Superoxide dismutase transgenic and wild-type mice were subjected to 1 hour of middle cerebral artery occlusion (MCAO) and subsequent reperfusion. Immunohistochemistry showed SOD1 overexpression attenuated ischemia-induced NF-kappaB p65 immunoreactivity. Colocalization of NF-kappaB and the neuronal marker, microtubule-associated proteins (MAPs), showed that NF-kappaB was up-regulated in neurons after FCI. Electrophoretic mobility shift assays showed that SODI overexpression reduced ischemia-induced NF-kappaB DNA binding activity. Supershift assays showed that DNA-protein complexes contained p65 and p50 subunits. Immunoreactivity of c-myc, an NF-kappaB downstream gene, was increased in the ischemic cortex and colocalized with NF-kappaB. Western blotting showed that SOD1 overexpression reduced NF-kappaB and c-Myc protein levels in the ischemic brain. Colocalization of c-Myc and TUNEL staining was observed 24 hours after FCI. The current findings provide the first evidence that SOD1 overexpression attenuates activation of NF-kappaB after transient FCI in mice and that preventing this early activation may block expression of downstream deleterious genes like c-myc, thereby reducing ischemic damage.
Crystalline forms and aqueous solubilities of an IBS drug, tegaserod

Tegaserod is shown to exist in the tautomeric form II in the free base and also in a monohydrate. The Tegaserod nicotinate salt has a 6-fold better aqueous solubility than the marketed Tegaserod maleate (form A, Zelnorm™).
X-ray reflectivity study of the water-hexane interface

Synchrotron X-ray reflectivity is used to study the electron density profile normal to the bulk water−hexane interface. This first measurement of the microscopic interfacial width of a neat water−oil interface relied upon the development of a novel technique to flatten the liquid−liquid interface. The measurement is interpreted in terms of an error function electron density profile to yield an interfacial width of 0.33 ± 0.025 nm. Within the context of capillary wave theory, it is shown that this microscopic parameter is in agreement with macroscopic measurements of the interfacial tension. These measurements are compared to computer simulations of water−alkane interfaces.
An Existential-Phenomenological Approach to the Psychology of Religion

A primary aspect of existential and phenomenological methodologies is an attempt to understand one’s experience. In particular, phenomenology attempts to understand one’s experience in as pure of a form as possible. From an existential perspective, additional emphasis is placed upon the lived aspects of one’s experience. This paper outlines an existential-phenomenological approach to the psychology of religion. First, a brief history and summary of major themes of existential psychology is introduced. Next, this is applied to the psychology of religion. Last, the existential-phenomenological approach is considered in the context of the existential givens.
The Other Side of the Broken Window: A Methodology that Translates Building Permits into an Ecometric of Investment by Community Members

Much research has focused on physical disorder in urban neighborhoods as evidence that the community does not maintain local norms and spaces. Little attention has been paid to the opposite: indicators of proactive investment in the neighborhood’s upkeep. This manuscript presents a methodology that translates a database of approved building permits into an ecometric of investment by community members, establishing basic content, criteria for reliability, and construct validity. A database from Boston, MA contained 150,493 permits spanning 2.5 years, each record including the property to be modified, permit type, and date issued. Investment was operationalized as the proportion of properties in a census block group that underwent an addition or renovation, excluding larger developments involving the demolition or construction of a building. The reliability analysis found that robust measures could be generated every 6 months, and that longitudinal analysis could differentiate between trajectories across neighborhoods. The validity analysis supported two hypotheses: investment was best predicted by homeownership and median income; and maintained an independent relationship with measures of physical disorder despite controlling for demographics, implying that it captures the other end of a spectrum of neighborhood maintenance. Possible uses for the measure in research and policy are discussed.
Infarction alters both the distribution and noradrenergic properties of cardiac sympathetic neurons

Regional changes occur in the sympathetic innervation of the heart after myocardial infarction (MI), including loss of norepinephrine (NE) uptake and depletion of neuronal NE. This apparent denervation is accompanied by increased cardiac NE spillover. One potential explanation for these apparently contradictory findings is that the sympathetic neurons innervating the heart are exposed to environmental stimuli that alter neuronal function. To understand the changes that occur in the innervation of the heart after MI, immunohistochemical, biochemical, and molecular analyses were carried out in the heart and stellate ganglia of control and MI rats. Immunohistochemistry with panneuronal markers revealed extensive denervation in the left ventricle (LV) below the infarct, but sympathetic nerve fibers were retained in the base of the heart. Western blot analysis revealed that tyrosine hydroxylase (TH) expression (normalized to a panneuronal marker) was increased significantly in the base of the heart and in the stellate ganglia but decreased in the LV below the MI. NE transporter (NET) binding sites, normalized to total protein, were unchanged, except in the LV, where [3H]nisoxetine binding was decreased. TH mRNA was increased significantly in the left and right stellate ganglia after MI, while NET mRNA was not. In the base of the heart, increased TH coupled with no change in NET may explain the increase in extracellular NE observed after MI. Coupled with substantial denervation in the LV, these changes likely contribute to the onset of cardiac arrhythmias.
Out of Equilibrium

Abstract This review article takes the volume by Mario Amendola and Jean-Luc Gaffard Out of Equilibrium as the starting point of a general assessment of the scope and perspectives of out-of-equilibrium economics. After describing the particular subject-matter covered by Amendola and Gaffard, the author calls attention upon he fundamental role in their treatment of time, coordination, and the magnitude of responses. The general foundations of the ‘out-of-equilibrium’ approach are then considered. In this connection, the author argues that making use of illustrations (rather than formal proofs) can still show in a conclusive way that widely held beliefs are not valid as general propositions. It is also maintained that, apart from these ‘anti-general’ results, the out-of-equilibrium approach can lead to positive generalizations of considerable power and significance. In conclusion, this essay maintains that coexistence of equilibrium and out-of-equilibrium analysis is possible, and mentions research and policy areas (such as coordination failures and rational regulatory policy) in which equilibrium theory can provide invaluable insights for an out-of-equilibrium investigation
Effects of tannins from different sources on airway epithelial and platelet function

The uniqueness of tannin isolated from aqueous extracts of cotton bracts (CBE) on the electrophysiological and ion transport properties of the canine tracheal epithelium and on 5-hydroxytryptamine (5-HT) release from platelets was investigated. The effect of CBE from Deltapine 41 cotton picked before (green, containing high-concentration, high-molecular-weight tannin) and after (brown, containing low-concentration, low-molecular-weight tannin) senescence and Darjeeling tea extracts and tannin isolated from Darjeeling tea were compared to the effects of Acala SJ-2 CBE and Acala SJ-2 tannin. Green Deltapine 41 CBE was similar to Acala SJ-2 CBE in decreasing short-circuit current (Isc) and net chloride secretion and in producing a dose-response release of 5-HT from platelets. Both Green and Brown Deltapine 41 CBE altered the paracellular pathway, but were less potent than Acala SJ-2 CBE. Brown Deltapine 41 CBE stimulated chloride transport in the airway epithelium and did not produce 5-HT release from human platelets. Darjeeling tea and tea tannin increased Isc and net chloride secretion and caused 5-HT release from platelets only at high concentrations. These studies demonstrate that all tannins are not alike; they suggest that molecular weight and concentration may be important for tannin activity and that the tannin in cotton bracts extract may be unique to cotton in its effect on the airway epithelium and on platelets.
Shape and Individual Variability of the Blur Adaptation Curve

We are interested in clinical implications of adaptation to blurred and sharpened images. Therefore, we investigated repeatability, individual variability and characteristics of the adaptation curves of 39 normally-sighted individuals. The point of subjective neutrality (PSN - the slope of the spatial spectrum of the image that appears normal) following adaptation was measured for each adaptation level and was used to derive individual adaptation curves for each subject. Adaptation curves were fitted with a modified Tukey biweight function as the curves were found to be tumbled-S shaped and asymmetrical for blur and sharp in some subjects. The adaptation curve was found to be an individual characteristic as inter-subject variability exceeds test/re-test variability. The existence of individual variability may have implications for the prescription and clinical success of optical devices as well as image enhancement rehabilitation options.
Hydrocarbons and real output in Algeria: is there an asymmetric relationship?

It is often suggested that variations in the international market for hydrocarbons contribute greatly to business‐cycle swings of oil‐importing economies. These variations would also impact oil‐exporting economies such as Algeria. This study utilises co‐integrated time series to assess the nature of the relationship between international hydrocarbon price changes and long‐run real output for Algeria. The study also examines whether an asymmetric relationship has characterised this association, specifically whether the impact of international hydrocarbon market conditions on real output are more pronounced during cyclical downturns in comparison to upturns. The study offers statistical evidence that variations in hydrocarbon market conditions are associated with variations in Algerian real output. Also found is evidence that these two variables exhibit a statistically significant asymmetric relationship (i.e. there is a greater negative impact on real output from sustained falling energy prices than there ...
Observation of Surface Rearrangement of Polymers Using ESCA

Abstract Electron spectroscopy for chemical analysis (ESCA) at cryogenic temperatures is investigated as a means of characterizing the "hydrated" surface composition of polymers. Artifacts and contamination rates are considered. The use of variable take-off-angle, high-resolution ESCA allows rearrangements to be observed, if they result in a change in average surface composition. Rearrangement of the hydrated surface structure back to a dehydrated surface structure occurs at widely varying rates in different polymer systems. Hydroxyethyl methacrylate (HEMA) grafted onto silicone elastomer exhibited, in the hydrated state, a HEMA-enriched surface which rapidly rearranged upon dehydration to a silicone-enriched surface so that it could only be detected with cryogenic sample handling and analysis. A pHEMA-polystyrene (PS) block copolymer also exhibited pHEMA surface enrichment as a result of hydration. This enrichment could be detected at room temperature, but not to the same degree as at low temperature. Biomer and Pellethane did not exhibit measurable rearrangement. A poly(ether urethane) (PEU) with a poly(ethylene glycol) soft segment showed evidence of a subtle rearrangement. A PEU containing a poly(dimethyl siloxane) (PDMS) soft segment and a commercial PEU, Biomer, contaminated with PDMS both exhibited a decrease in PDMS at the surface as a result of hydration. This decrease was more pronounced in samples analyzed at low temperature than in samples analyzed at room temperature.
Engaging the community in coalition efforts to address childhood asthma.

For health improvement efforts to effectively address community needs, community members must be engaged in planning and implementing public health initiatives. For Allies Against Asthma’s coalitions, the community included not only the subpopulation of individuals who suffer disproportionately from asthma but also the individuals and institutions that surround them. Through a quantitative self-assessment survey, informal discussion among coalition leadership, and interviews with key informants, data relevant to community engagement identified a number of important ways the Allies coalitions approached community involvement. Respondents’ comments made clear that the way the coalitions conduct their work is often as important as what they do. Across coalitions, factors that were identified as important for community involvement included (a) establishing a commitment to community involvement, (b) building trust, (c) making participation feasible and comfortable, (d) responding to community identified needs,...
CHARACTERISTICS OF SUPPLY CHAIN MANAGEMENT AND THE IMPLICATIONS FOR PURCHASING AND LOGISTICS STRATEGY.

The concepts of a supply chain and supply chain management are receiving increased attention as means of becoming or remaining competitive in a globally challenging environment. What distinguishes supply chain management from other channel relationships? This paper presents a framework for differentiating between traditional systems and supply chain management systems. These characteristics are then related to the process of establishing and managing a supply chain. A particular focus of this paper is on the implications of supply chain management for purchasing and logistics.
Inhaled corticosteroid adherence and emergency department utilization among Medicaid-enrolled children with asthma

AbstractObjectives: Asthma is the most prevalent chronic disease among children enrolled in Medicaid. This study measured real-world adherence and outcomes after an initial prescription for inhaled corticosteroid therapy in a multi-state Medicaid population. Methods: We conducted a retrospective study among Medicaid-enrolled children aged 5–12 years with asthma in 14 southern states using 2007 Medicaid Analytic eXtract file claims data to assess adherence and outcomes over the 3 months following an initial prescription drug claim for inhaled corticosteroids (ICS-Rx). Adherence was measured by the long-term controller-to-total asthma drug claims ratio. Results: Only one-third of children (33.4%) with an initial ICS-Rx achieved a controller-to-total drug ratio >0.5 over the next 90 days. Children for whom long-term control drugs represented less than half of their total asthma drug claims had a 21% higher risk of emergency department (ED) visit (adjusted odds ratio (AOR) 1.21 [95% CI 1.14, 1.27]), and a 70%...
Paradoxical hypersecretion of growth hormone in response to glucose.

Paradoxical hypersecretion of growth hormone during hyperglycemia has been observed in 2 adults with acromegaly and in a child with an optic glioma which encroached upon the hypothalamus. This abnormal secretion of growth hormone was not seen in 19 other patients with pituitary tumors. Short stature, despite high fasting plasma levels of growth hormone, was an additional unusual feature in the patient with the optic nerve tumor.
Antibodies against Adhesion Molecules Reduce Apoptosis after Transient Middle Cerebral Artery Occlusion in Rat Brain

We tested the hypothesis that treatment of transient focal cerebral ischemia in rat with antibodies directed against adhesion molecules reduces apoptosis. Rats (n = 31) were subjected to 2 h of middle cerebral artery (MCA) occlusion induced by intraluminal insertion of a nylon monofilament into the internal carotid artery. Upon reperfusion, animals were treated with monoclonal antibodies directed against intercellular adhesion molecule (ICAM)-1) (n = 8) or integrin CD11b/CD18 (n = 10), or administered IgG1 as a control (n = 13). At 48 h after ischemia, animals were killed and the brains analyzed for ischemic cell damage, using hematoxylin and eosin (H/E); apoptosis, using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) method; and inflammatory cells, using immunohistochemistry with an anti-myeloperoxidase (MPO) antibody. Data revealed a significant reduction in the volume of infarction (p < 0.01) and a decline in the absolute (p < 0.001), and normalized (to the ischemic areas, p < 0.05) numbers of apoptotic cells in both animals treated with anti-ICAM-1 and anti-CD11b antibodies compared to control animals. The numbers of immunoreactive MPO cells were also reduced in the treatment groups compared to those in the control group (p < 0.05). These data suggest that treatment with anti-adhesion molecule antibodies selectively reduce apoptosis, and that a contributing factor to the beneficial effect of antibody treatment for reducing ischemic cell damage may be a reduction in numbers of apoptotic cells.
A review of informal learning literature, theory and implications for practice in developing global professional competence

Informal learning's roots emerged from educational philosophers John Dewey, Kurt Lewin and Mary Parker Follett to theorists Malcolm Knowles and other successive researchers. This paper explores the background and definitions of informal learning and applications to the global workplace. Informal learning's challenges are applied to developing global professional competence, including theory, practice and policy implications. The paper argues that informal learning plays a considerable role in developing professional expertise in the workplace and private life, yet believes no current theoretical model exists to balance conflicts between the role of individual and organizational benefits in a global context.
Associative productivity as a function of creativity level and type of verbal stimulus

High creative (HC) and less creative (LC) Ss, selected on the basis of the Remote Associates Test (RAT), gave word associations to abstract and concrete word stimuli. HC individuals produced more associations over a longer period of time than did LC Ss, but creativity level did not interact significantly either with type of word stimulus or with associative output across time. Concrete words elicited more associations, but associations evoked by abstract words were more evenly distributed across time. Creativity groups did not differ in degree of stereotypy of the associations produced.
Dexamethasone Normalizes Brain Tumor Hemodynamics as Indicated by Dynamic Susceptibility Contrast MRI Perfusion Parameters

The purpose of this study is to demonstrate the utility of dynamic susceptibility contrast (DSC) MRI-derived perfusion parameters to characterize the hemodynamic effects of dexamethasone in a 9L gl...
Studies on the mechanism of 5-fluoroorotic acid inhibition of serine dehydratase induction☆

Abstract Administration of glucagon to rats fed a protein-free diet caused a significant induction of the liver enzyme, serine dehydratase. This effect of glucagon is inhibited by the concomitant administration of fluoroorotic acid. This inhibition was enhanced by pretreatment with glucosamine or galactosamine, probably through depletion of the intracellular uridine pools. Although less than a doubling of enzyme activity was observed after glucagon plus fluoroorotic acid administration, the amount of protein precipitable by antisera specifically reactive against serine dehydratase increased 4.5 times. Ouchterlony double-diffusion analysis showed a completely cross-reacting single precipitin band from liver extracts of untreated animals and rats treated with the analog. Analysis of the antigen-antibody complex by Na dodecyl sulfate-gel electrophoresis indicated that a single protein was being immunochemically precipitated from both the glucagon- and glucagon plus fluoroorotic acid-treated rats. In the latter, the precipitated protein had a molecular weight similar to purified serine dehydratase. These results are consistent with the concept that the incorporation of fluoroorotic acid into mRNA results in the synthesis of a protein with characteristics similar to authentic serine dehydratase but without normal enzymatic activity. Other possible mechanisms to explain the production of this abnormal protein are discussed.
Statin-induced rhabdomyolysis

Simvastatin and other HMG-CoA reductase inhibitors (statins) are one of the most frequently prescribed class of medications in the United States, with over 15 million Americans taking these drugs. Relatively rare adverse effects related to the known toxic effects of these drugs are more common than generally realized. Clinically significant statin-induced rhabdomyolysis is an uncommon but life-threatening adverse effect. We describe a case of simvastatin-induced rhabdomyolysis. Current knowledge of the pharmacology of the HMG-CoA reductase inhibitors and the drug interactions that potentiate these adverse effects are discussed. The clinical features of rhabdomyolysis and current treatment recommendations are presented.
Behavioral treatments of primary dysmenorrhea: a review.

Abstract Behavioral interventions for primary dysmenorrhea are reviewed under four categories: hypnotherapy; Lamaze exercises; biofeedback training; and desensi found in only the last category and even here, the extent to which positive results stem from desensitization-based treatments themselves as opposed to nonspecific factors associated with these treatments is unresolved. Additional issues that bear upon behavioral treatments for primary dysmenorrhea are: (a) the need for further taxonomic refinement; and (b) the need to incorporate pathophysiological findings within the treatment of this disorder.
Regulation of the mitochondrial adenine nucleotide pool size.

Abstract A mechanism by which normal adult rat liver mitochondria may regulate the matrix adenine nucleotide content was studied in vitro. If mitochondria were incubated with 1 m m ATP at 30 ° C in 225 m m sucrose, 2 m m K2HPO4, 5 m m MgCl2, and 10 m m Tris-Cl (pH 7.4), the adenine nucleotide pool size increased at a rate of 0.44 ± 0.02 nmol/mg mitochondrial protein/min. The rate of adenine nucleotide accumulation under these conditions was concentration dependent and specific for ATP or ADP; AMP was not taken up. The rate of net ADP uptake was 50–75% slower than that for ATP. The Km values for net uptake of ATP and ADP were 2.08 and 0.36 m m , respectively. Adenine nucleotide uptake was stoichiometrically dependent on Mg2+ and stimulated by inorganic phosphate. Net uptake was inhibited by n-ethylmaleimide, or mersalyl, but not by n-butylmalonate. Nigericin inhibited net uptake, but valinomycin did not. In the presence of uncouplers, net uptake was not only inhibited, but adenine nucleotide efflux was observed instead. Like uptake, uncoupler-induced efflux of adenine nucleotides was inhibited by mersalyl, indicating that a protein was required for net flux in either direction. Carboxyatractyloside, bongkrekic acid, or respiratory substrates reduced the rate of adenine nucleotide accumulation, however, this did not appear to be a direct inhibition of the transport process, but rather was probably related indirectly to an increase in the matrix ATP ADP ratio. The collective properties of the transport mechanism(s) for adenine uptake and efflux were different from those which characterize any of the known transport systems. It is proposed that uptake and efflux operate to regulate the total matrix adenine nucleotide pool size: a constant pool size is maintained if the rates of uptake and efflux are equal. Transient alterations in the relative rates of uptake and efflux may occur in response to hormones or other metabolic signals, to bring about net changes in the pool size.
Left ventricular systolic function in sickle cell anemia: a meta-analysis

Abstract Background We sought to evaluate whether patients with sickle cell anemia (SCA) have left ventricular (LV) systolic dysfunction. Methods and Results We conducted a Medline, Embase, Ebscohost, and Google scholar literature search articles published before April 2010. All studies that compared any measure of LV function (eg, ejection fraction [EF], fractional shortening [FS], or cardiac index [CI]) between normal control subjects and SCA (hemoglobin SS) patients were included. Among 57 studies that qualified for review, 19 studies including 841 SCA patients and 554 control subjects met the inclusion criteria. There were no significant differences in either LVEF (Hedge g = 0.15; 95% confidence interval −0.84 to 1.14; P = .76) or FS ( P = .28) between SCA patients and control subjects. CI was significantly higher ( P P P Conclusions SCA patients have similar load-dependent but lower load-independent measures of LV systolic function than control subjects. SCA is associated with LV dilation. LV structural and functional abnormalities appear to be age dependent with progressive LV dilation and impairment over time.
The child with a high tetraplegic spinal cord injury

Caring for children and adolescents with high tetraplegic spinal cord injury (SCI) is particularly challenging because of the significant impact that their severe neurologic impairment has on all spheres of their lives. Distinctive anatomic, physiologic, growth, and development characteristics of children and adolescents result in unique manifestations, complications, and consequences in this population. This article will highlight several of the unique and critical aspects of high tetraplegic SCI in children and adolescents.
Infrared absorption spectra of inorganic solids—III Selenates and selenites

Abstract The infrared absorption spectra of four selenates and five selenites are presented for the region 400–4000 cm −1 . Spectral information below 400 cm −1 was obtained, using CsBr optics, and is also tabulated. The infrared-active, characteristic vibrational modes for the SeO 4 = ion in solid inorganic selenates fall in the regions ∼420 cm −1 (bending) and ∼895 cm −1 (stretching) whereas for solid inorganic selenites they are at ∼460 cm −1 and ∼740 cm −1 , respectively. In crystalline environments the bands often show considerable splitting. Hydrated selenites and selenates have complicated spectra probably due to the formation of selenic or selenious acids, and hydrogen-bonded structures. The thermal decomposition of calcium and cadmium selenates to selenites has been qualitatively followed by spectral curves. Silver selenate gradually decomposes to a black selenide at ∼200°C.
Neural Correlates of Phonological and Semantic Based Anomia Treatment in Aphasia

Most naming treatments in aphasia either assume a phonological or semantic emphasis or a combination thereof. However, it is unclear whether semantic or phonological treatments recruit the same or different cortical areas in chronic aphasia. Employing three persons with aphasia, two of whom were non-fluent, the present study compared changes in neural recruitment associated with phonologic and semantic based naming treatments. The participants with non-fluent aphasia were able to name more items following both treatment approaches. Although this was not the case for the participant who had fluent aphasia, her naming errors decreased considerably following treatment. Post-treatment fMRI revealed similar changes in neural activity bilaterally in the precuneus among the two non-fluent participants – increased activity was noted in the right entorhinal cortex and posterior thalamus on post treatment scans for the third participant. These findings imply that cortical areas not traditionally related to language processing may support anomia recovery in some patients with chronic aphasia.
The primacy of β1 integrin activation in the metastatic cascade.

After neoplastic cells leave the primary tumor and circulate, they may extravasate from the vasculature and colonize tissues to form metastases. β1 integrins play diverse roles in tumorigenesis and tumor progression, including extravasation. In blood cells, activation of β1 integrins can be regulated by “inside-out” signals leading to extravasation from the circulation into tissues. However, a role for inside-out β1 activation in tumor cell metastasis is uncertain. Here we show that β1 integrin activation promotes tumor metastasis and that activated β1 integrin may serve as a biomarker of metastatic human melanoma. To determine whether β1 integrin activation can influence tumor cell metastasis, the β1 integrin subunit in melanoma and breast cancer cell lines was stably knocked down with shRNA and replaced with wild-type or constitutively-active β1. When tumor cells expressing constitutively-active β1 integrins were injected intravenously into chick embryos or mice, they demonstrated increased colonization of the liver when compared to cells expressing wild-type β1 integrins. Rescue expression with mutant β1 integrins revealed that tumor cell extravasation and hepatic colonization required extracellular ligand binding to β1 as well as β1 interaction with talin, an intracellular mediator of integrin activation by the Rap1 GTPase. Furthermore, shRNA-mediated knock down of talin reduced hepatic colonization by tumor cells expressing wild-type β1, but not constitutively-active β1. Overexpression in tumor cells of the tumor suppressor, Rap1GAP, inhibited Rap1 and β1 integrin activation as well as hepatic colonization. Using an antibody that detects activated β1 integrin, we found higher levels of activated β1 integrins in human metastatic melanomas compared to primary melanomas, suggesting that activated β1 integrin may serve as a biomarker of invasive tumor cells. Altogether, these studies establish that inside-out activation of β1 integrins promotes tumor cell extravasation and colonization, suggesting diagnostic and therapeutic approaches for targeting of β1 integrin signaling in neoplasia.
Proteolysis at a specific extracellular residue implicates integral membrane CLAG3 in malaria parasite nutrient channels.

The plasmodial surface anion channel mediates uptake of nutrients and other solutes into erythrocytes infected with malaria parasites. The clag3 genes of P. falciparum determine this channel’s activity in human malaria, but how the encoded proteins contribute to transport is unknown. Here, we used proteases to examine the channel’s composition and function. While proteases with distinct specificities all cleaved within an extracellular domain of CLAG3, they produced differing degrees of transport inhibition. Chymotrypsin-induced inhibition depended on parasite genotype, with channels induced by the HB3 parasite affected to a greater extent than those of the Dd2 clone. Inheritance of functional proteolysis in the HB3×Dd2 genetic cross, DNA transfection, and gene silencing experiments all pointed to the clag3 genes, providing independent evidence for a role of these genes. Protease protection assays with a Dd2-specific inhibitor and site-directed mutagenesis revealed that a variant L1115F residue on a CLAG3 extracellular loop contributes to inhibitor binding and accounts for differences in functional proteolysis. These findings indicate that surface-exposed CLAG3 is the relevant pool of this protein for channel function. They also suggest structural models for how exposed CLAG3 domains contribute to pore formation and parasite nutrient uptake.
Periodate oxidation products of hydroxylysine in the synthesis of 5-substituted prolines.

The amino acid hydroxylysine was subjected to oxidation by sodium metaperiodate under various conditions. It was found that in acid and high temperature, the initial oxidation product α-aminoglutaric γ-semialdehyde was converted to glutamic acid with a yield of 60%. The use of alkaline conditions of oxidation favored the cyclization of α-aminoglutaric γ-semialdehyde to form Δ1-pyrroline 5-carboxylic acid. Addition of NaCN to this intermediate generated new proline analogs, likely a mixture of cis- and trans-5-cyanoprolines, with a yield of 30%. Upon hydrolysis, the 5-cyanoprolines were converted to a probable mixture of cis- and trans-5-carboxyprolines. Infrared and high-resolution mass spectral data of the analogs and visual absorption spectra of the ninhydrin products were obtained to confirm the structures.
Psychological adjustment of Southeast Asian refugees: The contribution of sense of coherence.

This study examines the contribution of sense of coherence and resistance deficits and resources to the psychological adjustment of five Southeast Asian refugee groups (713 Vietnamese, 492 Cambodians, 551 Laotians, 231 Hmong, 245 Chinese-Vietnamese). It is hypothesized that sense of coherence (i.e., the experience of life as comprehensible, manageable, and meaningful) (Antonovsky, 1979, 1987) directly predicts psychological adjustment as measured by happiness and demoralization. Also, resistance deficits (being male, the experience of trauma, and cultural traditionalism) and resistance resources (a younger age at arrival and longer residence in the United States, higher education, employment, greater English competence, and living in an area with a greater co-ethnic density) are postulated to both directly and indirectly (through their effect on sense of coherence) predict happiness and demoralization. These hypotheses are generally supported by the results of this study, with sense of coherence emerging as a most powerful predictor of psychological adjustment for refugees. Implications of the findings are discussed. © 1997 John Wiley & Sons, Inc., Inc.
Nonlinear estimation for partial differential equations

Abstract The sequential estimation of the states of a process described by a set of nonlinear hyperbolic or parabolic partial differential equations subject to both stochastic input disturbances and measurement errors is considered. A functional partial differential equation of Hamilton—Jacobi type is derived for the minimum least square estimate error, which is solved approximately in the region of the optimal estimate by a second-order expansion. The optimal estimate is given as the solution of an initial value problem. In the linear case the estimator equations represent analogs of the well-known Kalman filter equations for lumped parameter systems. The determination of the state of a process governed by one-dimensional heat equation from noisy measurements is considered.
Bio) medical informatics in the next decade.

Even though medical informatics is most often viewed from the perspective of its host disciplines in clinical and biologic medicine, it has an identity and agenda of its own. This paper is an attempt to promote discussion about the long-term role and agenda for medical informatics as a discipline into the next decade. The discussion has two main lines of argument, one about the ''engineering'' goals of informatics and the other about the ''basic research'' goals. These are, of course, influenced by ongoing developments in computing, communications, and software infrastructures, but informatics is now mature enough that many of its goals transcend these changes. n JAMIA. 1998;5:416 - 420. In an earlier article we tried to project the priorities for medical informatics into the next decade from the perspective of the intersection and synthesis of infor- matics with clinical research and with research in the basic biomedical sciences. 1 The core argument in that paper is that clinical research and genomics research are on a ''collision course'' for merger and synthesis and that they must unavoidably share computer- based infrastructure, encoded and structured infor- mation methodologies, information-analysis and de- cision-support tools, and a communication-based collaborative framework. This paper is an attempt to view informatics a bit more expansively and to project future directions for medical informatics as a disci- pline unto itself. This sketch of the long-term role and agenda for informatics is not intended to be exhaus- tive in any sense. It is intended primarily to promote discussion. The presentation is broken into two main sections, one discussing the ''engineering'' goals of in- formatics for the next decade and one discussing the ''basic research'' goals of informatics. A concluding section attempts to project the future of informatics as a separate discipline, especially in relation to the ex-
Managing an E-Mentoring Community to Support Students with Disabilities: A Case Study

This article provides an introduction to mentor, near-peer,and peer support as they apply to promoting the academicand career success of young people with disabilities. Theauthors discuss specific benefits of mentoring and documentaccess challenges encountered by students with disabilities.They present a case study of a successful internet-basedmentoring community for college-bound youth withdisabilities. The experiences and recommendations sharedcan be used by others to design, implement, and sustainmentoring communities online.
Interactions between aggressive ions and the surface of a magnesium-yttrium alloy

Magnesium alloys possess many desirable properties for biodegradable orthopedic implants. Unfortunately, magnesium degrades too rapidly in vivo. This rapid degradation reduces the alloys' mechanical properties and increases the alkalinity of the local environment. Controlling the degradation rate and mode is an essential step in the development of magnesium based biomaterials. Accomplishing this essential step will require an improved understanding of magnesium alloy degradation. Herein, three interacting factors controlling magnesium degradation were investigated; (1) alloy composition, (2) alloy surface, (3) presence of aggressive ions in the immersion media. The magnesium-yttrium alloy was more susceptible to degradation in water than the high purity magnesium alloy. However, the polished surface magnesium-yttrium alloy had the least susceptibility to degradation in phosphate buffered saline (PBS) among all the sample compositions and surfaces.
Monolithic Main Memory--New Reliability and Serviceability Environment

A combination of error-correcting circuitry and one-bit/card organization gives increased reliability by masking intermittents and by offering a wide range of servicing strategies. The net result will be higher system availability and lower service costs.
Toward a Model Theory of Actions: How Agents do it in Branching Time

A clear understanding and formalization of actions is essential to computing, and especially so to reasoning about and constructing intelligent agents. Several approaches have been proposed over the years. However, most approaches concentrate on the causes and effects of actions, but do not give general characterizations of actions themselves. A useful formalization of actions would be based on a general, possibly nondiscrete, model of time that allows branching (to capture agents'' choices). A desirable formalization would also allow actions to be of arbitrary duration and would permit multiple agents to act concurrently. We develop a branching-time framework that allows great flexibility in how time and action are modeled. We motivate and formalize several coherence constraints on our models, which capture some nice intuitions and validate some useful inferences relating actions with time.
Tensor factorization by simultaneous estimation of mixing factors for robust face recognition and synthesis

Facial images change appearance due to multiple factors such as poses, lighting variations, facial expressions, etc. Tensor approach, an extension of conventional matrix, is appropriate to analyze facial factors since we can construct multilinear models consisting of multiple factors using tensor framework. However, given a test image, tensor factorization, i.e., decomposition of mixing factors, is a difficult problem especially when the factor parameters are unknown or are not in the training set. In this paper, we propose a novel tensor factorization method to decompose the mixing factors of a test image. We set up a tensor factorization problem as a least squares problem with a quadratic equality constraint, and solve it using numerical optimization techniques. The novelty in our approach compared to previous work is that our tensor factorization method does not require any knowledge or assumption of test images. We have conducted several experiments to show the versatility of the method for both face recognition and face synthesis.
Potassium-Argon Geochronometry of Mesozoic Igneous Rocks in Nevada, Utah, and Southern California

K-Ar dates for 123 mineral separates from 91 samples of granitic rocks, and 3 samples of Orocopia and Vitrefax Schist from Nevada, western Utah, the Mojave Desert, the Colorado Desert, and the northern and eastern Peninsular Ranges of southern California, range in age from 218 to 19 m.y.; however, most of the dates lie between 160 and 50 m.y. A majority of the hornblende and muscovite dates are nearly concordant with, but generally a few m.y. older than, coexisting biotite dates; some are highly discordant. The oldest plutons gave Late Triassic to Early Jurassic dates (El Paso and San Bernardino Mountains, 218 to 194 m.y.). Jurassic igneous activity reached a culmination slightly before 150 m.y. ago over a large area in northern Nevada and western Utah and supplied ash to the Morrison Formation of the Colorado Plateau. Several plutons of the northeastern Mojave Desert yielded similar dates. A similar major culmination of Mesozoic pluton emplacement in early and middle Late Cretaceous time is represented by scattered plutons in Nevada and probably by most of the plutons in the Peninsular Ranges and southern deserts of California. Earliest Tertiary dates were obtained from far-southeastern California (50 to 66 m.y.). Most dates in the Cordilleran batholith belt of the Southwest, which parallels the edge of the late Mesozoic continent, are between 160 and 75 m.y. and are essentially coeval with metamorphism in the parallel high-pressure, low-temperature Franciscan belt to the west (approximately 150 to 75 m.y.). About 75 m.y. ago, this pattern abruptly changed to a Laramide one with abundant 75 to 50 m.y. dates in a belt running through southern Arizona into southeastern California at a high angle to the edge of the continent. Only very sparse dates of this age are found in Nevada. Abundant Laramide dates are not encountered again until the Idaho, Boulder, and Coast Range batholiths. These important changes in Cordilleran tectonics may be effects of a change from dominantly dip-slip subduction during Franciscan time to dominantly north-northeast strike-slip subduction during Laramide time. Furthermore, the initiation of rifting of eastern North America in Triassic time, changes in spreading rate, and reorientation of spreading directions in the Atlantic Ocean appear to correlate with the beginning of widespread pluton emplacement in western North America, changes in the rate of magma generation in the Cordillera, and shifts of the Cordilleran tectonic pattern, respectively, during Mesozoic time.
The Relationships Among Shell Membrane, Selected Chemical Properties, and the Resistance to Shell Failure of Gallus domesticus Eggs

Abstract STUDIES of the chemical properties of egg shells and their relationship to shell strength have been very limited. Almquist and Burmester (1934) investigated an abnormal type of shell which they termed a “glassy shell.” It was found to have a reduced shell thickness and breaking strength when compared to normal shells. The “glassy shell” had an average content of 2.38 percent organic material expressed as protein and 95.42 percent calcium carbonate compared to 1.76 percent organic matter and 97.00 percent calcium carbonate in the normal shell. It was further observed that the percentage of protein decreased as the shell thickness increased in normal shells and that the concentration of protein did not influence the breaking strength. Tyler (1958) and Tyler and Geake (1953) reported that the percentages of calcium, magnesium, and carbonate in nitrogenfree shells were practically constant. Similarly, very little research has been attempted to elucidate the chemical composition…
Thrombotic Microangiopathy Associated with Sirolimus Level after Allogeneic Hematopoietic Cell Transplantation with Tacrolimus/Sirolimus-Based Graft-versus-Host Disease Prophylaxis

Abstract Posttransplantation thrombotic microangiopathy (TMA) is a multifactorial complication of allogeneic hematopoietic cell transplantation (allo-HCT) whose incidence is increased with the use of a sirolimus plus tacrolimus (SIR/TAC) regimen for acute graft-versus-host disease (aGVHD) prophylaxis. We evaluated the incidence and possible risk factors for TMA in a case series of 177 patients who received allo-HCT using SIR/TAC-based GVHD prophylaxis. The patients received either a sibling donor graft (n = 82) or a matched unrelated donor graft (n = 95). Within the first 100 days post-HCT, 30 patients (17%) were diagnosed with TMA, and an additional 9 patients (5%) were classified as probable TMA cases. The median time to onset of TMA was 4.6 weeks (range, 1.6-10.6 weeks). Thirty-four patients developed both TMA and aGVHD, with the majority (81%) developing aGVHD first. Multivariate analysis identified the following factors as associated with increased risk of TMA: day 14 serum sirolimus level ≥9.9 ng/mL (hazard ratio [HR], 2.19; 95% confidence interval [CI], 1.13-4.27; P = .02), presence of previous aGVHD grade II-IV (HR, 3.04; 95% CI, 1.38-6.71; P
The Thyrotropin Receptor Hinge Region Is Not Simply a Scaffold for the Leucine-Rich Domain but Contributes to Ligand Binding and Signal Transduction

The glycoprotein hormone receptor hinge region connects the leucine-rich and transmembrane domains. The prevalent concept is that the hinge does not play a significant role in ligand binding and signal transduction. Portions of the hinge are redundant and can be deleted by mutagenesis or are absent in certain species. A minimal hinge will be more amenable to future investigation of its structure and function. We, therefore, combined and progressively extended previous deletions (Delta) in the TSH receptor (TSHR) hinge region (residues 277-418). TSHRDelta287-366, Delta287-371, Delta287-376, and Delta287-384 progressively lost their response to TSH stimulation of cAMP generation in intact cells, consistent with a progressive loss of TSH binding. The longest deletion (TSHRDelta287-384), reducing the hinge region from 141 to 43 amino acids, totally lost both functions. Surprisingly, however, with deletions extending from residues 371-384, constitutive (ligand-independent) activity increased severalfold, reversing the suppressive (inverse agonist) effect of the TSHR extracellular domain. TSHR-activating point mutations I486F and I568T in the first and second extracellular loops (especially the former) had reduced activity on a background of TSHRDelta287-371. In summary, our data support the concept that the TSHR hinge contributes significantly to ligand binding affinity and signal transduction. Residues within the hinge, particularly between positions 371-384, appear involved in ectodomain inverse agonist activity. In addition, the hinge is necessary for functionality of activating mutations in the first and second extracellular loops. Rather than being an inert linker between the leucine-rich and transmembrane domains, the TSHR hinge is a signaling-specificity domain.