cssi/SciSciGPT-SciSciNet huggingface dataset:
Scedosporium apiospermum fungemia successfully treated with voriconazole and terbinafine

Scedosporium apiospermum is ubiquitous in the environment and is considered an emerging infection. Immunocompromised hosts can have a wide spectrum of diseases ranging from cutaneous to disseminated disease that may involve pulmonary, central nervous system, or bone. Disseminated disease in immunocompetent hosts is uncommon. Treatment of deep-seated infections is challenging because of the limited susceptibility of the Scedosporium species to all current antifungal drugs. We report a case of Scedosporidium apiospermum fungemia with a presumed pulmonary involvement in an immunocompetent patient. The fungemia was successfully treated with oral voriconazole and terbinafine.
Protein kinase A mediates activation of ATP-sensitive K+ currents by CGRP in gallbladder smooth muscle

The signal transduction mechanisms underlying the activation of ATP-sensitive potassium (KATP) current by calcitonin gene-related peptide (CGRP) in gallbladder smooth muscle were examined with intracellular microelectrode recording and whole cell patch-clamp techniques. In the intact gallbladder preparation, the adenylyl cyclase activator forskolin hyperpolarized the membrane potential and abolished spontaneous action potentials. This response was inhibited by the KATP channel blocker glibenclamide. CGRP (10 nM), forskolin (10 microM), the membrane-permeable adenosine 3',5'-cyclic monophosphate (cAMP) analogue adenosine 3',5'-cyclic monophosphothioate (Sp-cAMP[S]; 500 microM), and the catalytic subunit of protein kinase A (100 U/ml) activated glibenclamide-sensitive currents in enzymatically dissociated gallbladder smooth muscle cells. CGRP activation of potassium currents was prevented by dialysis of the cell cytoplasm with guanosine 5'-O-(2-thiodiphosphate) (5 mM) or a specific peptide inhibitor of protein kinase A (2.3 microM). Okadaic acid (5 microM), a phosphatase inhibitor, slowed the deactivation of the KATP current, following removal of CGRP. The results of this study indicate that CGRP hyperpolarizes gallbladder smooth muscle by elevation of cAMP and subsequent stimulation of protein kinase A.
Nucleic acid oxidation is associated with biomarkers of neurodegeneration in CSF in people with HIV.

Objective To determine whether oxidative stress in virologically suppressed people with HIV (PWH) may contribute to or result from neurodegeneration, we measured 7,8-dihydro-8-oxoguanine (8-oxo-dG), a marker of DNA damage due to oxidative stress, and markers of age-related neurodegeneration, specifically, reduced levels of CSF Aβ-42, and elevated CSF total tau and neurofilament light (NFL). Methods This cross-sectional study prospectively enrolled participants at 6 US centers in the CNS HIV Antiretroviral Effects Research study. Inclusion criteria included HIV+ with a plasma level of HIV RNA ≤50 copies/mL. Exclusions included significant CNS confounding conditions. Measurements of total tau and Aβ-42 were performed by bead suspension array. NFL and 8-oxo-dG were measured using ELISA. Results Participants were 53 PWH, mean age 55 (±9.3) years, 19% women, and 48% non-Hispanic White. Higher 8-oxo-dG correlated with markers of AD-related neurodegeneration including lower CSF Aβ-42 (r = −0.34; p = 0.012) and higher CSF NFL (r = 0.39; p = 0.0091) and total tau (r = 0.6696; p Conclusions Among virologically suppressed PWH, nucleic acid oxidation was associated with standard CSF biomarkers of neurodegeneration. Potential sources of oxidative stress in PWH include low-level HIV replication, inflammation, mitochondrial dysfunction, and specific antiretroviral drugs. Results suggest that the higher levels of oxidative stress among PWH may play a role in neurodegeneration. Classification of evidence This study provides Class II evidence that among virologically suppressed PWH, nucleic acid oxidation is associated with standard CSF biomarkers of neurodegeneration.
African Migrants and Refugees in Latin America and the Caribbean

On Thursday, June 20, 2019, the world celebrated World Refugee Day to honor the strength, courage, and perseverance of millions of refugees. The United Nations suggests that persons become refugees due to persecution, conflict, violence, or human rights violations. The importance of such an observation is emphasized by the United Nations High Commissioner for Refugees (UNHCR) report that alerts readers to the unparalleled level of displacement of persons globally. The UNHCR affirms that over 10 years, the number of displaced persons (viz., people who are forced from their homes due to some adversity) worldwide grew from 43.3 million in 2009 to 70.8 million in 2018 – an increase of 27.5 million displaced persons worldwide. Of the 70.8 million displaced in 2018, 25.9 million of these persons were refugees. Of these 2018 refugee populations, about 50% was comprised of children younger than 18 years – a 9% increase over 10 years. Of interest to this discussion is that of these 25.9 million refugees in 2018, the UNHCR data suggest that 3.2 million of these refugees come from two African countries: Sudan and Somalia.
Gender Representation in Speaking Roles at the American Association of Hip and Knee Surgeons Annual Meeting: 2012-2019.

Abstract Background The American Association of Hip and Knee Surgeons (AAHKS) has one of the lowest percentages of women members among orthopedic surgery subspecialty societies, having increased from 1.3% to 3.1% since 2012. Our purpose was to report the representation of women in various speaking roles at the AAHKS annual meeting over this time period. Methods We accessed the 2012-2019 AAHKS annual meeting programs online and reviewed all paper presenters, symposium faculty, and session moderators. We recorded instances of women speakers and their degree and specialty. We calculated the percentage of women speakers, women orthopedic surgeon speakers, women session moderators, and women symposium faculty for the overall period of 2012-2019, and for each annual meeting. Results Between 2012 and 2019, 33/877 (3.8%) of all speakers at AAHKS were women. Of these, 21 were women orthopedic surgeons, or 2.4% of all speakers. The proportion of total women speakers per year ranged from 1.7% (2017) to 6.4% (2013). Twenty-four of 492 (4.9%) paper presenters were women, and 12/492(2.4%) were women orthopedic surgeons. Four of 143 (2.8%) session moderators were women, and all were orthopedic surgeons. Five of 245 (2.0%) symposium faculty were women, and 0/245 (0%) were women orthopedic surgeons. Conclusion Although the percentage of women AAHKS members has grown since 2012, the small percentage of women orthopedic surgeons speaking at AAHKS has not. There were no women orthopedic surgeons included on symposium faculty over this entire period. We appreciate and encourage efforts to improve gender diversity among speakers at AAHKS annual meetings.
The Liquidity Risk of REITs

This study examines the liquidity risk of real estate investment trusts (REITs) as measured by their return sensitivity to marketwide liquidity shocks. Due to their unique dividend payout rules and...
Opioid Management in Older Adults: Lessons Learned From a Geriatric Patient-Centered Medical Home.

Background The United States continues to confront an opioid crisis that also affects older adults. Best practices for prescription opioid management in older adults are challenging to implement in this population. We present our experience with a 1-year management of 48 high-risk older patients who received guideline-based best practices for chronic prescription opioid therapy at a US Department of Veterans Affairs (VA) patient aligned care team (PACT) patient-centered medical home. Methods The GeriPACT population at the Nashville Campus of the VA Tennessee Valley Healthcare System has an enrollment of 745 patients of whom 48 (6.5%) receive chronic prescription opioid therapy. The practice is supported by the VA Computerized Patients Record System, including the electronic patient portal, My healtheVet, and telemedicine capabilities. Data were collected by chart review and operations data. Results The mean (range) age of patients was 70.4 (66-93) years. Many patients had comorbid conditions, such as diabetes mellitus (35%), congestive heart failure (18.6%), and dementia (8.3%). More than half had an estimated glomerular filtration rates (eGFR) < 60 mL/min, indicating at least stage 3 chronic kidney disease, 41.7% used mental health services (41.7%), and 20.8% had a history of opioid use disorder. Most indications for chronic pain were for musculoskeletal pain (95.8%). The mean (range) morphine equivalent daily dose was 37 mg (10-109). More than half had been seen in the emergency department, and 20.8% had been hospitalized in the previous year for an opioid-related hospitalization, and 3% had expired. Over the year, dose reductions of benzodiazepines or narcotics was performed for 12.5% of patients, accidental overdoses occurred in 4.2%, and positive urine drug screens (UDSs) for cocaine and cannabinoid/tetrahydrocannabinol occurred in 10.4%. One patient was terminated from the program for multiple positive UDSs. Conclusions Guideline-based patient-centered medical home management of patients with chronic pain who were treated with opioids can be an effective model contributing to the health and well-being of older patients. Complex older patients on chronic opioid treatment are best managed by an interdisciplinary team.
SOMA: Security Evaluation of Obfuscation Methods via Attack Sequencing

Hardware intellectual properties (IPs) used in diverse electronic systems face several critical security issues during their life cycle, including piracy, reverse engineering, and extraction of design secrets. To combat these issues, pre-silicon hardware obfuscation or logic locking has emerged as a promising solution and has been an active research topic over the past decade. However, in parallel, a number of functional and structural attacks on obfuscation have been discovered by the research community to break the protection provided by the existing obfuscation schemes. These attacks have played a major role in enhancing the security of hardware obfuscation schemes. In this paper, we introduce a novel combined attack modality, referred to as SOMA, which relies on judiciously combining the existing attacks to produce a significantly more powerful one. We demonstrate that such an attack can expose hidden exploits and measure the level of security offered by a given obfuscation technique. SOMA creates a sequence of attacks, where the outcome of each attack is used to guide the next and concludes with a key-refinement measure to restore the functionality of a locked IP. We demonstrate that SOMA can easily break major existing locking schemes that are believed to be secure with an attack accuracy average of 94.88%.
Ultra-Deep Sequencing Reveals the Mutational Landscape of Classical Hodgkin Lymphoma

The malignant Hodgkin and Reed Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) are scarce in affected lymph nodes, creating a challenge to detect driver somatic mutations. As an alternative to cell purification techniques, we hypothesized that ultra-deep exome sequencing would allow genomic study of HRS cells, thereby streamlining analysis and avoiding technical pitfalls. To test this, 31 cHL tumor/normal pairs were exome sequenced to [~]1000x median depth of coverage. An orthogonal error-corrected sequencing approach verified >95% of the discovered mutations. We identified mutations in genes novel to cHL including: CDH5 and PCDH7; novel mutations in IL4R, and a novel pattern of recurrent mutations in pathways regulating Hippo signaling. This study provides proof-of-principle that ultra-deep exome sequencing can be utilized to identify recurrent mutations in HRS cells, allowing for the analysis for clinically relevant genomic variants in large cohorts of cHL patients.
Relevance of microRNAs to the regulation of the brain-placental axis in mice.

Abstract Introduction The development of fetal brain is intricately dependent upon placental functions. Recently, we showed that the placenta and fetal brain express genes in a coordinated manner in mice. But, how the brain-placental axis is regulated at the molecular level remains poorly understood. The microRNAs (miRNAs) play diverse roles in pregnancy including regulation of placenta function as well as brain development. Thus, we hypothesized that specific miRNAs are expressed in the placenta and fetal brain to coordinate gene regulation in the brain-placental axis. Methods To test this hypothesis, we performed deep sequencing of small RNAs in mouse placenta and fetal brain of both sexes. Results The findings study show that miRNAs are potent regulators of gene expression in the placenta and fetal brain. Our data provides evidence that fetal sex influences the regulation of miRNAs between the placenta and fetal brain. Functional annotation of known target genes of the differentially expressed miRNAs show that they are significantly enriched with specific signaling and transporter pathways. Discussion Together, the results of this study suggest that placental miRNAs are potent regulators of fetal brain development in mice.
Assessing Cannabis Use Disorder in Medical Cannabis Patients: Interim Analyses from an Observational, Longitudinal Study

Background: To date, no studies have directly assessed potential cannabis use disorder (CUD) in medical cannabis (MC) patients pre- vs post-MC treatment. Given that MC patients use cannabis for symptom alleviation rather than intoxication, we hypothesized that MC patients would exhibit few symptoms of CUD after initiating MC treatment. Methods: As part of an ongoing observational, longitudinal study, 54 MC patients completed baseline assessments prior to initiating MC use and returned for at least one follow-up assessment after three, six, and/or twelve months of a self-selected MC treatment regimen; detailed MC treatment information was collected and quantified. All patients completed the Cannabis Use Disorder Identification Test - Revised (CUDIT-R) at each visit. Changes in individual items scores and total scores were assessed over time, and we examined whether total CUDIT-R scores correlated with frequency of MC use, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) exposure. Further, Cronbach’s alpha analyses were conducted to provide preliminary data regarding the psychometric properties of the CUDIT-R when used among MC patients. Results: Although total CUDIT-R scores increased relative to baseline, on average, ratings fell below the ‘hazardous use’ threshold at each visit. Analyses of individual items revealed that increases in total scores were primarily attributable to increases in frequency of use and not necessarily other aspects of problematic use. Total CUDIT-R scores were not associated with number of MC uses or CBD exposure, but a significant relationship was detected between increased THC exposure and higher CUDIT-R scores. Importantly however, analyses revealed that the CUDIT-R does not appear to be an appropriate tool for identifying CUD in MC patients. Conclusions: Screening tools specifically designed to assess CUD in MC patients are needed and should distinguish between frequent use and problematic use; exposure to individual cannabinoids must also be considered.
Indigenous cultural landscapes and the politics of heritage

(Received 21 September 2011; final version received 31 January 2012) This paper examines the socio-political implications and consequences of heritage practices related to indigenous cultural landscapes in post-settler nations. Although cultural landscapes are natural and material, they are also, more importantly, inscribed with meaning by those for whom they are heritage. Using a critical heritage studies framework, this paper examines the historical, cultural and legal contexts of Tongariro National Park and its nomination to the World Heritage list. I argue that narratives surrounding the Gift of Tongariro silence the colonial histories of the Park. I show how the ecological integrity and scientific, aesthetic, and conservation values of the Park are promoted, and in the process, Maori people’s complex and multifaceted relationships to the land are reframed as a relationship to the ‘natural’ world. I argue that to truly decolonise heritage, we must locate and acknowledge how our models, theories and practices of heritage work through systems of power and exclusion.
Diflunisal 500–750 mg versus Aspirin 2600–3900 mg in the Treatment of Rheumatoid Arthritis

Diflunisal was compared to aspirin in a 12-week, double-blind, parallel, multicenter rheumatoid arthritis study. One hundred twenty-six (126) patients received diflunisal and 123 patients received aspirin. Both treatment groups demonstrated significant improvement from baseline in joint pain, morning stiffness, grip strength, walking time and painful and swollen joint scores. For these parameters, the only statistically significant difference between the groups was that diflunisal was more effective than aspirin for overall joint pain at week 2. The overall evaluation by patients and by investigators showed significantly better responses in those treated with diflunisal at weeks 1 and 12. Diflunisal produced significantly less gastrointestinal pain and tinnitus than aspirin. Neither drug showed unusual frequency of adverse effects as determined in the laboratory. Long-term studies using a higher-dose regimen are suggested to further define the efficacy and tolerability of diflunisal in the treatment of patients with rheumatoid arthritis.
The Failure of the Balance of Power in Medieval Japan, 1568-1600

Contrary to the predictions of balance of power theory that the balancing mechanism prevents the emergence of hegemonies in anarchic systems, and in contrast to the absence of hegemony in the European system for the last five centuries, hegemonies have occasionally been established at different points in history. Despite the odds against hegemonic order creation that stem from potential balancers and the dangers of overexpansion, why are domination seeking actors sometimes able to succeed in creating hegemonic orders in regional or global anarchic systems? This research project follows a recently renewed engagement with balance of power theory. According to balance of power theory, when one state begins to seek domination, other states balance against the domination seeker to preserve their autonomy. Structural realists argue that balancing is generally the modal behavior of states in response to domination seeking threats, but there is ample evidence of a variety of state responses to threats of domination. This project will consider causes of balancing and three alternatives, appeasement, bandwagoning, and buckpassing, to address why actors sometimes fail to prevent the creation of a hegemonic order. Many scholars have noted how balance of power theory has very rarely been tested outside of the premodern or non-European contexts. The project's argument is qualitatively tested with the unification of 16th century feudal Japan by the trio of warlords, Oda Nobunaga, Toyotomi Hideyoshi, and Tokugawa Ieyasu. The research for this project is currently being performed in Japan through archival and secondary source research and consultations with Japanese historians. Feudal Japan is well suited as a case to test international relations theory. From 1467 to 1600, a period known as the Warring States (Sengoku) period, Japan was an autonomous, isolated regional system broken up into independent domains, each ruled over by warlords who frequently fought each other over territory. The prevailing military shogunate of the time as well as the emperor had no capability of central governance. Thus, the structure of anarchy existed, and the governing void was filled by the warlords at the local level, who ruled their feudal domains as if they were their own states. Additionally, Japan was isolated from the rest of the world during this period, so there was no external pressure on the warlords' decision making. With many independent and heavily armed domains, no central rule, and isolation from the outside world and any external balancers or hegemons, Sengoku period Japan is a near perfect analogy for the international system to test balance of power theory.
Sex Discrimination Law vs. Civil Liberties

Sexual harassment law has become a serious threat to freedom of speech in the context of "hostile environment" claims. Freedom of association is under attack by state and local laws that ban discrimination on the basis of sex in public accommodations, with the phrase "public accommodations" defined to include private clubs and organizations. Religious employers, such as church schools, have seen their free exercise rights challenged by a series of lawsuits alleging sex discrimination for actions taken in accordance with the employers' religious beliefs.Courts generally have been unsympathetic to constitutional defenses to anti-discrimination lawsuits. The Supreme Court has led the way by consistently ruling that the government has a compelling interest in eliminating discrimination that trumps civil liberties. The compelling interest test is applied without regard to the specific facts of the case at bar. The author concludes that the Court's application of the compelling interest test permits courts to render decisions based on vague ideological commitments that have no basis in the Constitution. There are also many non-constitutional reasons that civil liberties should be protected from encroachment by anti-discrimination laws. Among other things, concern for civil liberties reflects appropriate skepticism of concentrating power in the hands of the government; offers protection of individual and group autonomy, including the autonomy of those protected by anti-discrimination laws; shields unpopular minority groups from discriminatory enforcement of anti-discrimination laws; limits church-state conflict; and protects against overly-zealous enforcement of anti-discrimination laws in contexts where such enforcement creates a clear net social loss.
Endogenous Opioid Activity in the Anterior Cingulate Cortex Is Required for Relief of Pain

Pain is aversive, and its relief elicits reward mediated by dopaminergic signaling in the nucleus accumbens (NAc), a part of the mesolimbic reward motivation pathway. How the reward pathway is engaged by pain-relieving treatments is not known. Endogenous opioid signaling in the anterior cingulate cortex (ACC), an area encoding pain aversiveness, contributes to pain modulation. We examined whether endogenous ACC opioid neurotransmission is required for relief of pain and subsequent downstream activation of NAc dopamine signaling. Conditioned place preference (CPP) and in vivo microdialysis were used to assess negative reinforcement and NAc dopaminergic transmission. In rats with postsurgical or neuropathic pain, blockade of opioid signaling in the rostral ACC (rACC) inhibited CPP and NAc dopamine release resulting from non-opioid pain-relieving treatments, including peripheral nerve block or spinal clonidine, an α2-adrenergic agonist. Conversely, pharmacological activation of rACC opioid receptors of injured, but not pain-free, animals was sufficient to stimulate dopamine release in the NAc and produce CPP. In neuropathic, but not sham-operated, rats, systemic doses of morphine that did not affect withdrawal thresholds elicited CPP and NAc dopamine release, effects that were prevented by blockade of ACC opioid receptors. The data provide a neural explanation for the preferential effects of opioids on pain affect and demonstrate that engagement of NAc dopaminergic transmission by non-opioid pain-relieving treatments depends on upstream ACC opioid circuits. Endogenous opioid signaling in the ACC appears to be both necessary and sufficient for relief of pain aversiveness.
Biochemical site of regulation of bile acid biosynthesis in the rat.

The production of bile salts by rat liver is regulated by a feedback mechanism, but it is not known which enzyme controls endogenous bile acid synthesis. In order to demonstrate the biochemical site of this control mechanism, bile fistula rats were infused intravenously with 14C-labeled bile acid precursors, and bile acid biosynthesis was inhibited as required by intraduodenal infusion of sodium taurocholate. The infusion of taurocholate (11–14 mg/100 g of rat per hr) inhibited the incorporation of acetate-1-14C, mevalonolactone-2-14C, and cholesterol-4-14C into bile acids by approximately 90%. In contrast, the incorporation of 7α-hydroxycholesterol-4-14C into bile acids was reduced by less than 10% during taurocholate infusion. These results indicate that the regulation of bile acid biosynthesis is exerted via cholesterol 7α-hydroxylase provided that hepatic cholesterol synthesis is adequate.
Method for Quantitating Formaldehyde Gas in Air

A quick, simple method for collecting and assaying the disinfecting concentrations of formaldehyde vapor is described.
Pediatricians' appraisals of patients' intelligence.

Four hundred seventy-seven estimates by pediatricians of developmental level and intelligence of 242 patients from 1 through 9 years of age were compared with results of standard psychologic tests. Approximately a half of the pediatricians' appraisals were accurate within 10 points of the psychologic test results, and about a third deviated more than 15 points. None of the attributes of the pediatricians or the conditions under which they made their appraisals were related to accuracy. However, not all estimates were made equally well. The greatest accuracy was shown in the estimates for children within the normal range of intelligence. The two groups most consistently misjudged by the pediatricians were the physically ill and the mentally retarded. Levels of development were most frequently underestimated in physically ill children and grossly overestimated in mentally retarded children. Implications of the findings for pediatric practice and education are presented.
Laser processing - the future of HDI manufacturing

Conventional electronics manufacturing technologies have become unsuitable for high density interconnect structures (HDIS) due to processing limitations, lower manufacturing yields, higher production costs and limited flexibility. Laser processing is one suitable solution for manufacturing HDIS. This is supported by published reports that over 90% of all microvias in HDI PWBs and chip package substrates are formed using laser technology (D.F. Downey et al, 1993). Lasers are ideal primarily due to their high-resolution processing capabilities, fast processing speeds, reliability, versatility and lower cost-of-ownership. Focusing on these factors, this paper highlights key developments in laser processing which are relevant for advancing HDI technology. Particular emphasis is placed on new developments in CO/sub 2/, UV and diode-pumped solid-state laser processing for improved HDI fabrication. Laser performance characteristics, including optimal selection of key process parameters for improved HDI fabrication, and cost-of-ownership models are presented for each laser technology. After discussing the benefits of using existing laser technologies for HDI manufacturing, this paper provides an insight into emerging laser technologies, which are currently under development and driven by the electronics industry. A preview of these technologies and the potential capabilities for the electronics manufacturing industry are presented.
The Leray-Schauder condition for continuous pseudo-contractive mappings

Over thirty years ago, Kirk raised the question of whether a nonexpansive mapping, defined on a convex domain with nonempty interior, has a fixed point under the Leray-Schauder condition, provided that its domain enjoys the Fixed Point Property with respect to nonexpansive self-mappings. In the present work we have found the answer to this question to be positive, even for a larger class of mappings. The result, indeed, represents a quite significant extension of a large number of theorems obtained in the last forty years. This also includes new theorems for nonexpansive mappings.
Direct determination of radial distribution function

Abstract A method of directly obtaining radial distribution functions (RDF) from XAFS measurements is discussed. This method uses the cumulant expansion to reconstruct low k XAFS data and a Fourier transform to obtain the RDF. Applications of the method to Al-Mn-Si alloys are discussed in detail. We especially note that errors in the low k extrapolation have little effect on the shape of the RDF and can be minimized by imposing the positive-definite nature of the RDF.
Teacher education: Research as reflective practice

Abstract Teacher educators are often torn between their practice of teaching and clinical work, and expectations for conducting research. This article argues that research and practice need not be thought of as separate; rather, teacher educators are asked to consider defining a broader conception of research, one which may be described as disciplined, reflective inquiry into practice. Drawing upon current conceptions and practices in teacher education, the author defines an approach toward research on practice. In her argument, she presents a rationale for reflective inquiry into teacher education, a description of the characteristics of such research and several exemplars.
Cell cycle regulation by the intrinsically disordered proteins p21 and p27

Today, it is widely accepted that proteins that lack highly defined globular three-dimensional structures, termed IDPs (intrinsically disordered proteins), play key roles in myriad biological processes. Our understanding of how intrinsic disorder mediates biological function is, however, incomplete. In the present paper, we review disorder-mediated cell cycle regulation by two intrinsically disordered proteins, p21 and p27. A structural adaptation mechanism involving a stretchable dynamic linker helix allows p21 to promiscuously recognize the various Cdk (cyclin-dependent kinase)–cyclin complexes that regulate cell division. Disorder within p27 mediates transmission of an N-terminal tyrosine phosphorylation signal to a C-terminal threonine phosphorylation, constituting a signalling conduit. These mechanisms are mediated by folding upon binding p21/p27′s regulatory targets. However, residual disorder within the bound state contributes critically to these functional mechanisms. Our studies provide insights into how intrinsic protein disorder mediates regulatory processes and opportunities for designing drugs that target cancer-associated IDPs.
Two-stage contamination during crustal assimilation: isotopic evidence from volcanic rocks in eastern Nevada

Thousands of cubic kilometers of dominantly intermediate composition, metaluminous magma erupted at approximately 35 Ma in eastern Nevada. Two stages of crustal contamination are inferred from detailed study of the earliest vocanic rocks. Fine-grained mafic rocks and rocks with mixed textures, ranging from basalt to rhyolite, were contaminated with a crustal component rich in Nd but poor in Sr. Overlying plagioclaserich andesites and dacites have greater Sr and 87Sr/86Sr, but less Nd and lower ɛNd and are interpreted to have been contaminated by a crustal component with the opposite elemental signature (i.e., poor in Nd but rich in Sr). The first contaminant represents a partial melt of the crust with plagioclase as a residual phase and the second contaminant is the residue of the partial melting event, or bulk crust. The net effect is bulk crustal assimilation, but in two “bites”. The separation of the crustal souree into two elementally distinct contaminants causes divergent trends with respect to the variation of 87Sr/ 86Sr versus eNd that could be misinterpreted to indicate the existence of isotopically distinct crustal reservoirs. Comparison of the calculated contaminants to melting relationships in pelites is consistent with the two contammants representing melt and residue at about 30% melting. The model age of the bulk crust is approximately 2.2 Ga, consistent with an early Proterozoic crustal province inferred by other workers.
Protein flexibility using constraints from molecular dynamics simulations

Proteins are held together in the native state by hydrophobic interactions, hydrogen bonds and interactions with the surrounding water, whose strength as well as spatial and temporal distribution affects protein flexibility and hence function. We study these effects using 10 ns molecular dynamics simulations of pure water and of two proteins, the glutamate receptor ligand binding domain and barnase. We find that most of the noncovalent interactions flicker on and off over typically nanoseconds, and so we can obtain good statistics from the molecular dynamics simulations. Based on this information, a topological network of rigid bonds corresponding to a protein structure with covalent and noncovalent bonds is constructed, with account being taken of the influence of the flickering hydrogen bonds. We define the duty cycle for the noncovalent interactions as the percentage of time a given interaction is present, which we use as an input to investigate flexibility/rigidity patterns, in the algorithm FIRST which constructs and analyses topological networks.
A combined-method psychometric analysis recommended modification of the multidimensional health locus of control scales

Abstract Objective The Multidimensional Health Locus of Control (MHLC) scales are widely used to measure beliefs about determinants of persons' health. We evaluated the scales over the largest-ever disease-specific sample of subjects using a combined-method psychometric approach. Study Design and Setting We performed a secondary analysis of data from 1,206 subjects from three osteoarthritis studies, using Rasch analysis and confirmatory factor analysis simultaneously. Differential item functioning (DIF) by gender and data source, scale dimensionality, and item fit were examined. The Rasch model fit the data if Rasch residual principal components analysis (PCA) corroborated three distinct dimensions and item fit statistics fell between 0.80 and 1.20. The confirmatory factor (CFA) model fit the data if factor loadings exceeded 0.50 for all items. Results DIF by gender or data source was not materially evident for any items. PCA supported existence of three dimensions in the data. Both Rasch and CFA models fit the data for 16 items; two items were detected as misperforming. When these items were removed, fit of both models improved. Conclusion Results of this large-sample evaluation of the MHLC scales corroborated earlier findings that removal of certain items improves the scales. The combined Rasch–CFA approach provided better insight to scale performance problems than either method alone provided.
The reactions of the phosphorylated pathway of l-serine biosynthesis: Thermodynamic relationships in rabbit liver in vivo

The thermodynamic relationships among the reactions of the phosphorylated pathway of L-serine biosynthesis have been determined in rabbit liver in vivo in different dietary states. The mass action ratios of the reactions involved were calculated from the concentrations of appropriate metabolites in freeze-clamped liver and compared with the equilibrium constants of the same reactions previously determined under physiological conditions. Toward this goal, a new, highly specific enzymatic assay for L-phosphoserine was developed to allow the accurate measurement of this intermediate in biological material. The level of L-phosphoserine, the immediate precursor of L-serine, varied significantly with diet, being 0.81, 0.38, and 0.21 mumol/g wet wt in the fed, and 24 h and 48 h fasted states, respectively. The tissue content of L-phosphoserine was also sensitive to anoxia, falling almost fivefold within 5 min after the liver was removed. Values of for the combined reactions of the first two steps of the pathway of L-serine biosynthesis [D-3-phosphoglycerate dehydrogenase (EC 1.1.1.95) and L-phosphoserine aminotransferase (EC 2.6.1.52)] in livers from animals in different dietary states were calculated to be 1.2 X 10(-4) (fed), 1.4 X 10(-4) (24 h starved), and 0.70 X 10(-4) (48 h starved), all being very close to the value of the combined equilibrium constant of the same reactions (2.44 X 10(-4). Even when there were major changes in the individual components of, such as a fivefold drop in L-phosphoserine and a sevenfold fall in alpha-ketoglutarate following 5 min of anoxia, remained relatively unchanged (2.7 X 10(-4). Thus, it has been concluded that, in rabbit liver under most normal conditions, the combined reactions of D-3-phosphoglycerate dehydrogenase and L-phosphoserine aminotransferase remain very near equilibrium, and that almost all of the disequilibrium of the pathway, amounting to a delta G of -5.5 kcal/mol in the fed state, is at the last step, the L-phosphoserine phosphatase reaction (EC 3.1.3.3).
Manganese oxide minerals: Crystal structures and economic and environmental significance

Manganese oxide minerals have been used for thousands of years—by the ancients for pigments and to clarify glass, and today as ores of Mn metal, catalysts, and battery material. More than 30 Mn oxide minerals occur in a wide variety of geological settings. They are major components of Mn nodules that pave huge areas of the ocean floor and bottoms of many fresh-water lakes. Mn oxide minerals are ubiquitous in soils and sediments and participate in a variety of chemical reactions that affect groundwater and bulk soil composition. Their typical occurrence as fine-grained mixtures makes it difficult to study their atomic structures and crystal chemistries. In recent years, however, investigations using transmission electron microscopy and powder x-ray and neutron diffraction methods have provided important new insights into the structures and properties of these materials. The crystal structures for todorokite and birnessite, two of the more common Mn oxide minerals in terrestrial deposits and ocean nodules, were determined by using powder x-ray diffraction data and the Rietveld refinement method. Because of the large tunnels in todorokite and related structures there is considerable interest in the use of these materials and synthetic analogues as catalysts and cation exchange agents. Birnessite-group minerals have layer structures and readily undergo oxidation reduction and cation-exchange reactions and play a major role in controlling groundwater chemistry.
Inference of haplotypes from samples of diploid populations: complexity and algorithms.

The next phase of human genomics will involve large-scale screens of populations for significant DNA polymorphisms, notably single nucleotide polymorphisms (SNPs). Dense human SNP maps are currentl...
Reliability and validity study of a Sufi personality typology: The enneagram

Initiated research on a Sufi personality typology that describes nine life stretegies as depicted by a nine-sided figure called the enneagram. Through workshops and classes, a S pool was formed that consisted of 390 adult and college-age Ss (311 females and 79 males) who knew the enneagram system well enough to type themselves. The stability of the typing was found to be satisfactory. The Myers-Briggs and Millon personality inventories were administered to the Ss, and on both instruments significantly different yet congruent profiles emerged among the enneagram types thereby providing some concurrent validity for the system. An objective 135-item test instrument was devised to differentiate the nine styles, and positive results were obtained. The enneagram typology appears to have diagnostic, prognostic, and heuristic value for the study of personality structure and dynamics.
Evidence that ADP hydrolysis by human cells is related to thrombogenic potential

Abstract Washed monolayer cultures of human cells provoke the platelet release reaction to an extent comparable to irreversible aggregation with the following frequencies: endothelial, 0.0; smooth muscle; 0.67; fibroblast, 0.31. The ability of each cell type to hydrolyze exogenous adenine nucleotides was also compared. Endothelial cells and fibroblasts readily hydrolyze ATP and ADP, but smooth muscle cells have very little ectonucleotidase activity. The kinetic data suggest that the ability of endothelial cells to degrade ADP may contribute to their non-thrombogenic nature. These observations suggest that vascular-type cells may retain some of their non-thrombogenic characteristics in culture and that this in vitro system may serve as a model for studying contributions of each portion of the vessel wall to hemostasis and thrombosis.
SIMMEL'S FORMS OF EXPERIENCING: THE ADVENTURE AS SYMBOLIC WORK

Simmel says the content of experience does not make the adventure, the form does! To help clarify this remark, the Simmelian adventurer here is recast, following leads from Mead, Burke, and the pragmatists, as an ephemeral role incumbent engaged in symbolic work. The adventure is presented in terms of symbolic conversions of the content of life’s experiences-physical things, social things, events, and persons-into objects of adventure. The form of experiencing engages the adventurer in symbolic work in which she or he symbolically synthesizes, antagonizes, and compromises Simmel’s fundamental categories of life: certainty-uncertainty, chance-necessity, and passivity-activity.
Hot Section Turbine Disk Lifing Philosophies

The life prediction of critical gas turbine engine components is carried out using a bank of laboratory test data which is also verified by a comprehensive program on full scale fatigue tests. These tests include carcass for containment, canopy for foreign body ingestion, disks for bolt hole and dovetail/firtree root cracks and blades for thermal shock and fatigue.The life of the majority of these components is limited by low cycle fatigue which eventually is based on ‘initiation’ concepts and first detection of a crack 0.8 mm deep. Safe life design requires a high confidence of 99.9% probability of crack free components. Using safe life design concepts there is a large number of prematurely retired disks from service which have a high potential of useful life left in them.Damage tolerance or fracture mechanics based lifing concepts attempt to utilize this ‘useful’ life by analyzing the cracks. However, these concepts depend on the accuracy of detecting cracks by Non-Destructive Inspection (NDI) techniques. The probability of detection curves do not follow a fixed statistical distribution to give sufficient confidence level to fix the next inspection interval. Probabilistic and deterministic fracture mechanics based lifing philosophies are overviewed.Copyright © 1993 by ASME
Bilateral mixed tumors of the palate.

T he English-language literature of t.he past 10 years regarding mixed tumors of the hard and soft palate was reviewed for the purpose of noting the incidence of multiple mixed tumors emanating from separate nodi in these sites,l-I1 and no report of such a case was found. It was therefore considered that a report of the case described here would have significance in the field of oncology. Elder, Kline, and Fader,6 reporting a series of cases of mixed tumors in this JOURNAL, made a comprehensive summary of the theories underlying the etiology and pathology of these lesions. Their excellent presentation of the material is SO complete that further discussion in the present article would be redundant and would serve no useful purpose.
A Parametric Study on the Infiltration of Fibrous Preform by Pure Al and Solidification Process in the Presence of Cooled Fibers

Numerical simulation of the injection process of pure liquid aluminum into a fibrous preform has been carried out. During the injection process the end of the fibrous preform is allowed to be cooled by a heat sink. The purpose of cooling by a heat sink is to achieve a higher cooling rate, which is essential in obtaining finer microstructures and enhancing the growth of aluminum dendrites. The injection of liquid aluminum is modeled as flow in a porous medium and the heat equation coupled with the Darcy’s equation are simultaneously solved to obtain the temperature and velocity field. There are many different processing parameters influencing the solidification of aluminum. Among these parameters are, but are not limited to, the heat sink temperature, the thermal conductivity and initial temperature of the mold, and the length of fiber that is extending out of the mold. This article presents the simulation results of the effects of these processing parameters on the solidification of pure aluminum during the infiltration process.Copyright © 2003 by ASME
Antipsychotics and mortality: adjusting for mortality risk scores to address confounding by terminal illness.

Objectives To determine whether adjustment for prognostic indices specifically developed for nursing home (NH) populations affect the magnitude of previously observed associations between mortality and conventional and atypical antipsychotics. Design Cohort study. Setting A merged data set of Medicaid, Medicare, Minimum Data Set (MDS), Online Survey Certification and Reporting system, and National Death Index for 2001 to 2005. Participants Dual-eligible individuals aged 65 and older who initiated antipsychotic treatment in a NH (N = 75,445). Measurements Three mortality risk scores (Mortality Risk Index Score, Revised MDS Mortality Risk Index, Advanced Dementia Prognostic Tool) were derived for each participant using baseline MDS data, and their performance was assessed using c-statistics and goodness-of-fit tests. The effect of adjusting for these indices in addition to propensity scores (PSs) on the association between antipsychotic medication and mortality was evaluated using Cox models with and without adjustment for risk scores. Results Each risk score showed moderate discrimination for 6-month mortality, with c-statistics ranging from 0.61 to 0.63. There was no evidence of lack of fit. Imbalances in risk scores between conventional and atypical antipsychotic users, suggesting potential confounding, were much lower within PS deciles than the imbalances in the full cohort. Accounting for each score in the Cox model did not change the relative risk estimates: 2.24 with PS-only adjustment versus 2.20, 2.20, and 2.22 after further adjustment for the three risk scores. Conclusion Although causality cannot be proven based on nonrandomized studies, this study adds to the body of evidence rejecting explanations other than causality for the greater mortality risk associated with conventional antipsychotics than with atypical antipsychotics.