cssi/SciSciGPT-SciSciNet huggingface dataset:
Natural Disease History, Outcomes, and Co-mutations in a Series of Patients With BRAF-Mutated Non—small-cell Lung Cancer

Abstract Background BRAF mutations occur in 1% to 4% of non–small-cell lung cancer (NSCLC) cases. Previous retrospective studies have reported similar outcomes for BRAF-mutated NSCLC as compared with wild-type tumors without a known driver mutation or tumors harboring other mutations. However, select cases of prolonged survival have also been described, and thus, the natural history of BRAF-mutated NSCLC remains an area of ongoing study. The aim of this series was to describe the natural history, clinical outcomes, and occurrence of co-mutations in patients with BRAF-mutated NSCLC. Patients and Methods Patients with BRAF-mutated NSCLC seen at Stanford University Medical Center from January 1, 2006 through July 31, 2015 were reviewed. The Kaplan-Meier method was used to calculate median overall survival, and the generalized Wilcoxon test was used to compare median survivals across subgroups of patients. Results Within a cohort of 18 patients with BRAF-mutated NSCLC, V600E mutations were most common (72%; 13/18). Clinicopathologic features were similar between patients with V600E versus non-V600E mutations, although there was a trend toward more patients with non-V600E mutations being heavy smokers (80% vs. 31%; P = .12). Co-occurring mutations in TP53 were identified most commonly (28%; 5/18). The median overall survival for the entire cohort was 40.1 months, and the median survival from the onset of metastases (n = 16) was 28.1 months. Survival rates at 2 and 5 years from the onset of metastases were 56% and 13%, respectively. Conclusion The clinical behavior of BRAF-mutated NSCLC is variable, but favorable outcomes can be seen in a subset of patients.
Obesity in pediatric patients with acute lymphoblastic leukemia increases the risk of adverse events during pre-maintenance chemotherapy.

Purpose Obesity correlates with adverse events (AEs) in children with acute myelogenous leukemia and during maintenance therapy for acute lymphoblastic leukemia (ALL). Less is known about AEs in obese ALL patients during pre-maintenance chemotherapy. We evaluated the relationship between obesity (body mass index (BMI) ≥ 95th percentile) and AEs during pre-maintenance chemotherapy in pediatric patients with ALL. Methods One hundred fifty-five pediatric ALL patients diagnosed at a single institution between 2006 and 2012 were retrospectively evaluated for infections, treatment-requiring hypertension, insulin-requiring hyperglycemia, pancreatitis, pediatric intensive care unit admissions, sepsis, febrile neutropenia (FN) admissions, thrombosis, hepatotoxicity, and nephrotoxicity. Univariate and multivariable analyses compared proportions of obese versus nonobese patients experiencing AEs. Results AEs occurring significantly more frequently in obese patients by univariate analysis included treatment-requiring hypertension (17.5% vs 6.1%; OR, 3.27; 95% CI, 1.1-10.0, P = 0.0497) and insulin-requiring hyperglycemia (25.0% vs 11.3%; OR, 2.62; 95% CI, 1.04-6.56, P = 0.04). Obese patients had greater incidence rates for recurrent admission-requiring infections (incidence rate ratio (IRR) 1.64; 95% CI, 1.08-2.48, P = 0.02) and recurrent FN admissions (IRR, 1.53; 95% CI, 1.10-2.12, P = 0.01). Accounting for combined age and NCI risk status, obesity was a risk factor for treatment-requiring hypertension (OR, 3.90; 95% CI, 1.19-12.76, P = 0.02), insulin-requiring hyperglycemia (OR, 3.92; 95% CI, 1.39-11.05, P = 0.01), and FN admission (OR, 2.92; 95% CI, 1.27-6.73, P = 0.01). Conclusions During pre-maintenance chemotherapy for ALL, obesity is a risk factor for the development of hypertension, hyperglycemia, and FN admissions. This research provides implications for augmented preventive and supportive care guidelines in obese ALL patients.
Emerging Therapeutic Targets and Therapies in Idiopathic Pulmonary Fibrosis

The human respiratory system is primarily comprised of airways and lungs which work efficiently in sync to promote efficient gaseous exchange. While the tissues of the respiratory system, especially lungs, provide a vast surface area which is instrumental in efficient gaseous exchange and drug absorption, this attribute also inadvertently exposes the respiratory system to the outside environment and hence imposes higher potential for injury and infections. Any injury (including infections) to any of the components of the respiratory system will affect the primary function of the respiratory system, leading to respiratory disorders. One of the major classes of restrictive lung diseases is known as “interstitial lung disease (ILD),” which is comprised of more than 200 lung diseases, characterized by involvement of the lung interstitium. One of the primary disorders classified as ILD is idiopathic pulmonary fibrosis (IPF), a fatal disorder characterized by the continued decline in lung function. While the underlying disease mechanisms in IPF are mostly unknown, however, it is characterized by the progressive scarring of both lungs. This scarring results in alveolar epithelial cell injury, the formation of myofibroblast foci, and buildup of extracellular matrix in the lung parenchyma leading to scarring (thickening) of the lungs. Numerous clinical trials are still in progress to develop a medication to treat this disease. In this chapter, we summarize the state of the art of IPF therapies from preclinical animals through human clinical trials. We present evidence for the role of co-occurring disorders (i.e., gastroesophageal reflux disease, pulmonary hypertension, cardiovascular disease, osteoporosis, infectious agents, and other genetic factors) on the severity of the progression of human IPF disease. We then discuss the evolving therapeutic targets, including alveolar epithelial cell injury, WNT/beta-catenin signaling, MMPs, and how these related to the traditional therapies like corticosteroids and immunomodulators with new treatments including anticoagulants, antifibrotic agents, antioxidants, and beyond which hold promise for future therapies and understanding of the pathogenesis of IPF.
In vivo cell type-specific CRISPR gene editing for sleep research

Sleep is an innate behavior conserved in all animals and, in vertebrates, is regulated by neuronal circuits in the brain. The conventional techniques of forward and reverse genetics have enabled researchers to investigate the molecular mechanisms that regulate sleep and arousal. However, functional interrogation of genes in specific cell subtypes in the brain remains a challenge. Here, we review the background of newly developed gene-editing technologies using engineered CRISPR/Cas9 system and describe the application to interrogate gene functions within genetically-defined brain cell populations in sleep research.
Development and Modification of an Outcome Measure to Follow Symptoms of Children with Sinusitis.

Objective To develop a parent-reported Pediatric Rhinosinusitis Symptom Scale (PRSS) that could be used to monitor symptoms of young children with acute sinusitis in response to therapy. Study design We developed an 8-item symptom severity scale and evaluated its internal reliability, construct validity, and responsiveness in children 2-12 years of age with acute sinusitis. Parents of 258 children with acute sinusitis completed the PRSS at the time of diagnosis, as a diary at home, and at the follow-up visit at days 10-12. Based on psychometric results and additional parent feedback, we revised the scale. We evaluated the revised version in 185 children with acute sinusitis. Results Correlations between the scale and reference measures on the day of enrollment were in the expected direction and of the expected magnitude. PRSS scores at the time of presentation correlated with radiographic findings (P Conclusions We have developed an outcome measure to track the symptoms of acute sinusitis. Data presented here support the use of the PRSS as a measure of change in symptom burden in clinical trials of children with acute sinusitis.
“It Was the Best of Times, It was The Worst of Times”: Cardiovascular Disease and Troponins

There have been significant changes in the diagnosis and definition of acute myocardial infarction over the years. From its first description and definition over 150 years ago to the high sensitivity cardiac troponin assays of today, we have come a long way in the diagnosis, management, and treatment of those with cardiovascular disease. With the recent Food and Drug Administration’s (FDA) clearance of a fifth generation high-sensitivity cardiac troponin assay, a new history in diagnosing, treatment and managing those with heart disease is just beginning. The three articles associated with this focus series describe advances in diagnosis and definition of acute myocardial infarction (AMI) with a specific focus on troponins. The first article presents an in-depth description into the structure and function of troponin in health and disease. The second article presents a description of myocardial infarction (MI), how the diagnosis and definition of MI has changed over the years and ends with a description of the high sensitive troponin assays. The third article presents clinical implications of the new high sensitivity troponin assays.
Defining the impact of mutation accumulation on replicative lifespan in yeast using cancer-associated mutator phenotypes

Mutations accumulate within somatic cells and have been proposed to contribute to aging. It is unclear what level of mutation burden may be required to consistently reduce cellular lifespan. Human cancers driven by a mutator phenotype represent an intriguing model to test this hypothesis, since they carry the highest mutation burdens of any human cell. However, it remains technically challenging to measure the replicative lifespan of individual mammalian cells. Here, we modeled the consequences of cancer-related mutator phenotypes on lifespan using yeast defective for mismatch repair (MMR) and/or leading strand (Pole) or lagging strand (Polδ) DNA polymerase proofreading. Only haploid mutator cells with significant lifetime mutation accumulation (MA) exhibited shorter lifespans. Diploid strains, derived by mating haploids of various genotypes, carried variable numbers of fixed mutations and a range of mutator phenotypes. Some diploid strains with fewer than two mutations per megabase displayed a 25% decrease in lifespan, suggesting that moderate numbers of random heterozygous mutations can increase mortality rate. As mutation rates and burdens climbed, lifespan steadily eroded. Strong diploid mutator phenotypes produced a form of genetic anticipation with regard to aging, where the longer a lineage persisted, the shorter lived cells became. Using MA lines, we established a relationship between mutation burden and lifespan, as well as population doubling time. Our observations define a threshold of random mutation burden that consistently decreases cellular longevity in diploid yeast cells. Many human cancers carry comparable mutation burdens, suggesting that while cancers appear immortal, individual cancer cells may suffer diminished lifespan due to accrued mutation burden.
Success is not final: onward to the future of evidence-based practice.

The Oncology Nursing Society (ONS) is celebrating its 40th anniversary, so it seems only fitting that this column focuses on how evidence-based practice (EBP) has evolved for oncology nurses and ONS during the past 40 years. EBP has been around for a very long time. In the famous Notes on Nursing published in 1860, Florence Nightingale noted that, "The most important practical lesson that can be given to nurses is to teach them what to observe-how to observe-what symptoms can indicate improvement-what the reverse-which are important-which are of none" (p. 5). This quote seems pertinent given that a large part of what oncology nurses do is related to the management of symptoms, either from cancer or its treatment (e.g., chemotherapy, radiation). In addition, during the past 10-15 years, nurses have been immersed in providing symptom management interventions that are based on evidence, not just in hearsay or ritual. .
"Puffy shirt appearance": Cell crowding at low magnification may represent nevoid melanoma.

Background Melanoma, particularly nevoid melanoma, can masquerade as benign. Helpful differentiating features include nuclear pleomorphism, atypia, prominent nucleoli, absent maturation, and increased mitotic figures. These can be subtle and easily missed unless carefully sought. Thus, the "puffy shirt appearance" concept was born from a Seinfeld episode in which the namesake character unintentionally agreed to wear a pirate-like puffy shirt. Consequently, he found himself out of place, sporting an outfit with "too much shirt in too little space". Similarly, at low-power, nevoid melanoma appears to have "too many cells in too little space". This is more pronounced and easier to appreciate when there is an associated nevus, where crowded, subtly malignant melanocytes stand out from the evenly distributed, more spaced out benign melanocytes. Methods Twelve practicing dermatopathologists familiar with the puffy shirt concept in the context of melanoma were surveyed. Results Hundred percent of participants found it most helpful as a triaging tool, prompting additional work up including higher magnification evaluation, additional levels, consultation, and/or immunohistochemistry. Conclusions The crowded cells in the "puffy shirt appearance" catch the eye and should provoke a more thorough inspection of the lesion. This sign is not pathognomonic for melanoma, but prompts more careful evaluation and helps prevent misdiagnosis.
THE ASSOCIATION OF CARDIOVASCULAR RISK FACTORS AND CALCIUM VOLUME, DENSITY, NUMBER, AND TYPE OF CORONARY VESSEL WITH CALCIFIED PLAQUE IN SOUTH ASIANS LIVING IN THE US AND OTHER RACIAL/ETHNIC GROUPS: COMPARING MASALA AND MESA STUDIES

South Asians (SA) experience disproportionately higher rates of atherosclerotic cardiovascular disease (ASCVD). We evaluated prevalence, patterns, and determinants of advanced coronary artery calcium (CAC) measures (specific coronary vessel involvement, plaque volume and density) in SA versus other
Blue Ocean Shift to Adjust the Pendulum in IB Publications: Why Our Field Needs to Nurture a New Breed of Journals

In its early years after splitting off from the business policy discipline and becoming its own discipline about 50 years ago, international business started to take off by conducting phenomenon-based research in an interdisciplinary and engaging way. Yet, some scholars have recently noted that IB research, while grown in quantity ever since, has become characterized by debatable quality and fading impact and relevance. With the launch of AIB Insights around the turn of the century, the Academy of International Business has developed a new breed of IB journals that may contribute to making our field of IB more relevant again.
Commercial ground corn grain samples vary in particle size metrics and in situ rumen starch digestibility

ABSTRACT Objective Commercial dry and ground shelled corn is not a uniform feed. Geometric mean particle size (GMPS; μm) has been related to rumen digestibility, but researchers have specifically sourced or created varied particle size to assess relationships. Researchers have not sourced corn from differing commercial feed manufacturers. The objectives of our work were to assess variation in commercially ground corn sample particle size, prolamin protein content, and in situ rumen starch digestibility. Further, our objective was to relate prolamin protein and particle size measures to in situ rumen starch digestibility for survey samples. Materials and Methods Commercial dry and ground shelled corn samples (n = 38) were collected from the eastern and midwestern United States and analyzed for starch (% of DM), prolamin (% of DM), GMPS, surface area (cm2∙g−1; SA), and in situ rumen starch digestibility (% of starch) following 0, 7, and 16 h of incubation in 3 cannulated, lactating dairy cattle. Survey data were analyzed using multivariate methods to report correlations, and ANOVA was carried out between starch, prolamin protein, and particle size relative to in situ rumen starch digestibility measures using JMP v14.3 (SAS Institute Inc., Cary, NC). Results and Discussion Substantial variability was observed for particle size measures; GMPS (μm) = 715 ± 233 and surface area (cm2∙g−1) = 92.7 ± 20.8. Further, GMPS and surface area were related to in situ rumen starch digestibility at 16 h (P Implications and Applications This observation suggests that both the mean and SD around the mean should be accounted for when evaluating commercial dry and ground shelled corn.
Giant cell arteritis associated with inflammatory bowel disease: a case-series and review of the literature.

To describe the clinical characteristics, management, and outcome of a series of patients with giant cell arteritis (GCA) and inflammatory bowel disease (IBD). Patients with both GCA and IBD evaluated between 1/1/1996 and 12/30/2018 were retrospectively identified. Clinical characteristics, laboratory parameters, radiologic features, histopathology, management and outcomes were abstracted. A systematic literature review identifying patients with IBD and GCA was performed via a Medline and EMBASE search from inception through December 31 2019. Six patients were identified with GCA and IBD (66% male). Five (83%) had ulcerative colitis (UC) and one had Crohn’s disease (CD). Diagnosis of IBD preceded GCA in four patients with an average interval of 30 years (range 14–42). Average time to IBD diagnosis in those with prior GCA diagnosis was 1.5 years. During mean follow-up of 4.3 years, GCA relapse was infrequent with only one patient with relapse observed. Systematic literature review identified six additional patients with confirmed coexistence of GCA and IBD. Similar to the current series, male sex was more common and ulcerative colitis was the predominant IBD phenotype. The current study reports findings from the largest single-institution case-series of co-existent GCA and IBD. In contrast to Takayasu arteritis with co-existent IBD, which displays a predilection for female sex and Crohn’s disease phenotype, both the current study and review of literature demonstrate a stronger association of GCA with male sex and ulcerative colitis. Further studies addressing a potential pathophysiologic connection between GCA and IBD are suggested.
Cervical spinal injury compromises caudal spinal tissue oxygenation and undermines acute intermittent hypoxia-induced phrenic long-term facilitation.

Abstract An important model of respiratory motor plasticity is phrenic long-term facilitation (pLTF), a persistent increase in phrenic burst amplitude following acute intermittent hypoxia (AIH). Moderate AIH elicits pLTF by a serotonin-dependent mechanism known as the Q pathway to phrenic motor facilitation. In contrast, severe AIH (greater hypoxemia) increases spinal adenosine accumulation and activates phrenic motor neuron adenosine 2A receptors, thereby initiating a distinct mechanism of plasticity known as the S pathway. Since the Q and S pathways interact via mutual cross-talk inhibition, the balance between spinal serotonin release and adenosine accumulation is an important pLTF regulator. Spinal injury decreases spinal tissue oxygen pressure (PtO2) caudal to injury. Since AIH is being explored as a neurotherapeutic to restore breathing ability after cervical spinal injury, we tested the hypothesis that decreased PtO2 in the phrenic motor nucleus after C2 spinal hemisection (C2Hx) undermines moderate AIH-induced pLTF, likely due to shifts in the adenosine/serotonin balance. We recorded C3/4 ventral cervical PtO2 with an optode, and bilateral phrenic nerve activity in anesthetized, paralyzed and ventilated rats, with and without C2Hx. In intact rats, PtO2 was lower during severe versus moderate AIH as expected. In chronic C2Hx rats (> 8 weeks post-injury), PtO2 was lower during baseline and moderate hypoxic episodes, approaching severe AIH levels in intact rats. After C2Hx, pLTF was blunted ipsilateral, but observed contralateral to injury. We conclude that C2Hx compromises PtO2 near the phrenic motor nucleus and undermines pLTF, presumably due to a shift in the serotonin versus adenosine balance during hypoxic episodes. These findings have important implications for optimizing AIH protocols in our efforts to restore breathing ability with therapeutic AIH in people with chronic cervical spinal injury.
Alphabetical ordering of author surnames in academic publishing: A detriment to teamwork.

Introduction In academia, many institutions use journal article publication productivity for making decisions on tenure and promotion, funding grants, and rewarding stellar scholars. Although non-alphabetical sequencing of article coauthoring by the spelling of surnames signals the extent to which a scholar has contributed to a project, many disciplines in academia follow the norm of alphabetical ordering of coauthors in journal publications. By assessing business academic publications, this study investigates the hypothesis that author alphabetical ordering disincentivizes teamwork and reduces the overall quality of scholarship. Methods To address our objectives, we accessed data from 21,353 articles published over a 20-year period across the four main business subdisciplines. The articles selected are all those published by the four highest-ranked journals (in each year) and four lower-ranked journals (in each year) for accounting, business technology, marketing, and organizational behavior. Poisson regression and binary logistic regression were utilized for hypothesis testing. Results This study finds that, although team size among business scholars is increasing over time, alphabetical ordering as a convention in journal article publishing disincentivizes author teamwork. This disincentive results in fewer authors per publication than for publications using contribution-based ordering of authors. Importantly, article authoring teamwork is related to article quality. Specifically, articles written by a single author typically are of lesser quality than articles published by coauthors, but the number of coauthors exhibits decreasing returns to scale-coauthoring teams of one to three are positively related to high-quality articles, but larger teams are not. Alphabetical ordering itself, however, is positively associated with quality even though it inhibits teamwork, but journal article coauthoring has a greater impact on article quality than does alphabetical ordering. Conclusions These findings have important implications for academia. Scholars respond to incentives, yet alphabetical ordering of journal article authors conflicts with what is beneficial for the progress of academic disciplines. Based on these findings, we recommend that, to drive the highest-quality research, teamwork should be incentivized-all fields should adopt a contribution-based journal article author-ordering convention and avoid author ordering based upon the spelling of surnames. Although this study was undertaken using articles from business journals, its findings should generalize across all academia.
New Nickel-Based Catalytic System with Pincer Pyrrole-Functionalized N-Heterocyclic Carbene as Ligand for Suzuki-Miyaura Cross-Coupling Reactions

Abstract A new catalytic system with Ni(NO3)2·6H2O as the catalyst and a pincer pyrrole-functionalized N-heterocyclic carbene as the ligand was employed in the Suzuki-Miyaura cross-coupling reactions of aryl iodides with arylboronic acids. With 5 mol% catalyst, the catalytic reactions proceeded at 160 °C, giving coupling products in isolated yields of up to 94% in short reaction times (1-4 h). The system worked efficiently with aryl iodides bearing electron-donating or electron-withdrawing groups and arylboronic acids with electron-donating groups. Steric effects were observed for both aryl iodides and arylboronic acids. It is proposed that the reactions underwent a Ni(I)/Ni(III) catalytic cycle.
ψ Spectroscopy of a Charm String

We report the results of the application of the quark-confining string to the $\ensuremath{\psi}$ spectrum. The model is defined by a relativisticallly invariant action of quarks and color gauge fields. In the Schr\"odinger limit, where light quarks are neglected, this model (with two parameters) reduced to the charmonium model (with a linearly rising potential) plus additional vibrational levels. In the ${e}^{+}{e}^{\ensuremath{-}}$ channel, the first vibrational levels come at about 4.0 and 4.4 GeV.
Experimental Studies of the Dynamics of Herring Bodies. Ultrastructure of Axon Dilatations Developing at the Site of Compression or Transection of Neurosecretory Axons in the Grass Frog Rana pipiens

Herring bodies are dilatations of neurosecretory axons that have been well characterized ultrastructurally (for review see DELLMANN, 1973). Their formation and possible involution has been studied (PICKERING et al., 1975) and is more subject to hypothetical speculations. This study of the sequence of ultrastructural changes occurring during experimentally induced formation of axon dilatations, is the first step in elucidating dynamic changes in Herring bodies.
A Time-Delay Analog for Thermal-Acoustic Oscillations

Thermal-acoustic oscillations are thermally driven oscillations in low rate and fluid pressure and temperature which sometimes occur in forced convection. The oscillations are sustained and occur at frequencies which can be related to acoustic frequencies. A possible cause of these oscillations are perturbations during heat transfer. Following the perturbation, the flow relaxes toward steady conditions as the disturbance is propagated throughout the system by a pressure wave, traveling at the velocity of sound, and by a slower density wave, traveling at the velocity of the fluid. If there is a controlling downstream restriction, such as an orifice or a valve, the arrival of the slower density perturbation there will again perturb the flow rate, and hence heat transfer. The net effect is a delayed feedback of the perturbation to its source, which can sustain oscillations if the feedback is sufficiently strong. The mechanical analog for this system, which can generate oscillations having the characteristics of Helmholtz resonance, is a damped spring-mass system with the addition of a term that is proportional to displacement at an earlier time. The time delay corresponds to the time required to feed the perturbation back to its source. It will be shown that this analog can account for the qualitative differences in stability limits reported by Hendricks et al. [1] and by Thurston et al. [2]. It also quantitatively accounts for the departure from acoustic Helmholtz frequencies which the latter authors experimentally observed.
The Intrinsic Apoptotic Pathway

The intrinsic apoptotic pathway, also known as the mitochondria-mediated apoptotic pathway, plays important roles in a variety of biological processes and is involved in the pathogenesis of human diseases ranging from immune disorders and neurodegeneration to cancer. Over the last two decades, much has been learned about the molecular basis of this pathway as well as its delicate regulatory mechanisms. The central role of the cellular organelle, the mitochondrion, in this pathway is well appreciated. Importantly, several potential therapeutic agents have been developed to target specific components of this pathway. Further, growing evidence indicates that cytochrome c release from mitochondria, a hallmark of the pathway, does not always lead to irreversible cell death; and the downstream caspase activation can also perform certain non-death biological functions. This chapter reviews our understanding of the intrinsic apoptotic pathway with a focus on the mechanisms and regulation downstream of cytochrome c release. We also discuss unsolved questions and new challenges in this exciting research area. Other important topics, such as the role of the Bcl-2 family in this pathway and the relationship of this pathway with cancer, will be discussed in other chapters of this book and thus will not be elaborated in detail in this chapter.
A half-century of studies of growth hormone insensitivity/Laron syndrome: A historical perspective.

Abstract A growth hormone (GH) dependent substance responsible for sulfate uptake by costal cartilage of hypophysectomized rats, labeled sulfation factor, was reported in 1957. In 1962 the radioimmunoassay for GH was described. The clinical picture of severe GH deficiency but with high serum concentrations of GH was reported in 3 siblings in 1966 and followed by a 1968 report of 22 patients belonging to 14 consanguineous oriental Jewish families in Israel. Defective sulfation factor generation was demonstrated in 15 of these individuals and in a 1971 report; FFA response to IV GH and growth response to GH injections suggested competitive saturation of peripheral tissue receptors by an abnormal GH. However, studies published in 1973 demonstrated normal fractionation of their circulating GH, and normal binding of GH from 22 patients to various antisera used for radioimmunoassay. In 1976, the Israeli investigators reported that circulating GH from 7 patients reacted normally in the recently developed radioreceptor assay for GH. In 1984, using hepatic microsome pellets, they demonstrated that the defect was a failure of GH binding to receptors. Characterization of the human GH receptor (GHR) gene, reported in 1989, included the initial description of a genetic defect of the GHR in 2 of 9 Israeli patients. At about the same time began the identification in Ecuador of what was to become the largest population of GH insensitivity in the world, ~ 100 individuals, and the only substantial population with a common mutation of the GH receptor. Treatment studies with recombinant IGF-I began in 1990. Growth response was modest compared to that of GH treated GH deficient subjects. The spectrum of GH insensitivity has expanded beyond GH receptor deficiency to include postreceptor abnormalities: IGF-I gene mutation (1996); IGF-I receptor mutation (2003); signal transducer and activator of transcription 5b mutation (2003); and mutation of the GH-dependent acid labile subunit (2004). Conclusion Rare conditions of GH insensitivity caused by GH receptor and postreceptor abnormalities have provided insights into the processes of growth, body composition, and metabolism.
Tarski’s 1944 Polemical Remarks and Naess’ “Experimental Philosophy”

Many of Tarski’s better known papers are either about or include lengthy discussions of how to properly define various concepts: truth, logical consequence, semantic concepts, or definability. In general, these papers identify two primary conditions for successful definitions: formal correctness and material (or intuitive) adequacy. Material adequacy requires that the concept expressed by the formal definition capture the intuitive content of truth. Our primary interest in this paper is to better understand Tarski’s thinking about material adequacy, and whether components of his view developed over time. More precisely, we are concerned with how Tarski’s understanding of the content of the common-sense, every-day usage of truth may have developed over time. We distinguish this concern from the character of the extensional criterion of adequacy Tarski proposes: that a materially adequate definition must entail all instances of Convention T. We will develop our reading of Tarski as follows: first, we will review the “Polemical Remarks,” focusing primarily on §§14 and 17, and Tarski’s references to Naess’ empirical research. Next, we will provide a summary and discussion of Naess’ work, especially his findings with respect to Tarski’s definition of truth and his research that suggests there is no single common or everyday concept of truth. Third, we will consider several possible objections to our interpretation of the Tarski–Naess dialectic. We will conclude that Tarski’s conception of material adequacy developed over time, potentially because of what he had learned through his interactions with Naess.
Voices and Time

My critique of the casuist proposal serves to highlight several points of interest. With its insistence on practical reason as at once more grounded in our moral history and more capable of appreciating the exigencies of moral discourse, Jonsen and Toulmin’s approach strikes me as very productive. It nevertheless has certain unanswered problems, as was suggested, and in the end remains too centered on the ethics consultant’s relation to the physician—both of which are simply taken for granted as having priority as regards the identification and resolution of moral difficulties in clinical situations. (It bears notice at the outset that many of the more than 2,500 consultations I conducted between 1981 and my retirement in 2002, involved serious cross-professional and cross-specialty issues: for instance, how quarrels with obstetrics affected which babies were after birth given over to neonatology for care; or, how care for critically ill patients was differently perceived by nurses and by doctors.) Hardly any attention is paid to those persons whose circumstances are most often at issue—patients and their significant others—and almost none to other clinical participants whose words and actions help to constitute the clinical encounter and clearly help to shape the moral issues embedded in any clinical encounter—nurses, physician consultants, therapists, and many others.
Burmese Arched Harp

Our knowledge of the history, construction, and tunings of the Burmese arched harp (saung gauk) comes from a variety of sources. Conversations with master harpists, together with recordings made of their performances between 1960 and 1980, provide richly detailed examples of the effect of Western music on a non-Western musical tradition. Scholars’ essays and conference proceedings complement these first-hand accounts, expanding our understanding of Burmese music and musical instruments.
Abstract 14664: SIRT3 Protects Cardiomyocytes From Doxorubicin-induced Mitochondrial Damage and Cell-death by Activating Opa1

Introduction: The anti-cancer drug therapy with doxorubicin (Dox) is known to produce cardiomyopathy associated with fragmentation of mitochondria and excess production of reactive oxygen species (ROS). Sirtuin3 (SIRT3), a mitochondrial deacetylase regulates many mitochondrial functions including energy production, ROS synthesis and cell-death. A role of SIRT3 in regulating the aging process and aging-associated diseases like heart failure, cancer and diabetes has been also documented. This study was undertaken to investigate whether SIRT3 can protect cardiomyocytes from Dox-induced mitochondrial damage and cell-death. Methods and Results: Neonatal rat cardiomyocytes were over expressed with a vector synthesizing SIRT3 or a mock vector. Cells were treated with Dox (100nM) for 72 hours and cell-death was analyzed by measuring TUNEL-positive nuclei, ROS synthesis and expression of apoptotic markers by the western blotting. There was marked reduction of TUNEL-positive nuclei, ROS levels and expression of apo...
Sediment Transport on Gentle Slope due to Waves

A criterion for initiation of sediment movement on a gentle slope is established by balancing the forces acting on a sediment particle lying on the slope. A relationship for the instantaneous rate of bedload transport on a gentle slope is then derived from a simple and quasi-steady analysis of the motion of sediment particles. A gentle slope produces net movement of sediment even in pure oscillatory flow. The theory is in reasonable agreement with experiments conducted on a horizontal bed, corresponding to zero slope. The relationship derived for the net rate of bedload transport is applied to the problem of infilling of relatively small and symmetric trenches caused by wave action. The analysis includes the influence of the disposal distance of dredge spoil on the infilling. The model qualitatively explains observed infilling of test pits for San Francisco’s ocean outfall and smoothing of ice gouges due to summer storms in the Southern Beaufort Sea north of Alaska, for which limited data is available.
Computing the topology of configuration space

The problem of planning collision-free paths for manipulators is considered. An algorithm is presented for generating the connectivity graph for a class of articulated manipulators. The algorithm is based upon the ability to determine whether two distinct obstacles in configuration space intersect. The efficiency of the test which is developed lies in the ability to determine the intersection relation by evaluating the curves which describe the configuration space obstacles at only a small number of points. >
Exploration of self-healing circuits for timing resilient design using emerging memristor devices

Advanced nanoscale Very Large Scale Integrated (VLSI) circuits are facing significant timing closure challenges especially due to random on-chip threshold voltage variation. When dealing with the exaggerated timing issues in nanoscale technologies, conventional use of design guard-band significantly trade off the performance while more sophisticated statistical based timing analysis often requires expensive verification effort. The recent development of emerging non-volatile resistive device provides a potential new paradigm for solving the current design dilemma, i.e. balance between performance and design margin. This paper explores a new application of the emerging memristor. By deploying a self-tuning memristor into the sequential circuits, we show that the circuits could heal itself under excessive process variation and thus reduce the required design margin. A new design methodology is proposed to incorporate the use of self-tuning. A pipelined FFT processor in 45nm technology was implemented as a demonstration of the proposed circuits and design methodology.
Abstract W MP72: Sleep and Timing of Recurrent Events in a Mild Stroke Population: Results of the SWIFT Study

Sleep is an important contributor to cardiovascular disease; we have previously reported it is a risk factor for incident vascular events. It is thought that sleep apena may be the primary mechanism through which sleep disturbance is associated with vascular events. Little is known, however, about the association between sleep and recurrent events. The aim of this analysis was to determine the association between sleep problems and the risk of recurrent vascular events in an elderly, multiethnic population. This analysis uses data from SWIFT, a randomized clinical trial conducted in northern Manhattan designed to test a stroke preparedness intervention. Sleep was measured with the MOS sleep scale. MOS is a 12 item questionnaire that produces 8 validated scales. We report results using the snoring (1 question), shortness of breath during sleep (1 question), and sleep problem index 2 (9 questions) scales. Outcomes were collected prospectively through active surveillance. We used Cox Models to test whether o...
Addressing the Selective Superiority Problem: Automatic Algorithm/Model Class Selection

The results of empirical comparisons of existing learning algorithms illustrate that each algorithm has a selective superiority ; it is best for some but not all tasks. Given a data set, it is often not clear beforehand which algorithm will yield the best performance. In such cases one must search the space of available algorithms to find the one that produces the best classifier. In this paper we present an approach that applies knowledge about the representational biases of a set of learning algorithms to conduct this search automatically. In addition, the approach permits the available algorithms' model classes to be mixed in a recursive tree-structured hybrid. We describe an implementation of the approach, MCS, that performs a heuristic bestfirst search for the best hybrid classifier for a set of data. An empirical comparison of MCS to each of its primitive learning algorithms, and to the computationally intensive method of cross-validation, illustrates that automatic selection of learning algorithms using knowledge can be used to solve the selective superiority problem.
Computation of Twinning

In studying twinning in crystals one is lead to studying combinations of gradients which come from the potential wells of the material energy. Our approach to determining these possible microstructures is to form a particular energy and to numerically construct approximate minimizers. In this paper, we give a brief introduction to the two-well problem and our computational approach to solving it. Then we present and discuss our results for two and more variant microstructures.
Enhanced urinary excretion of Co60 vitamin B12 produced by delayed release capsules.

1. Patients without known hematologic disease were given 8 µg. (0.2 µc. Co 60 vitamin B 12 as a water solution or in various types of delayed release capsules. 2. All groups showed approximately equal fecal excretion. However, the cobalt 60 -labeled vitamin B 12 delayed release capsules showed a greater urinary excretion after a loading dose of stable B 12 than did the water solution of labeled vitamin B 12 .
PURIFICATION AND CHARACTERIZATION OF A FERULIC ACID DECARBOXYLASE FROM PSEUDOMONAS FLUORESCENS

A ferulic acid decarboxylase enzyme which catalyzes the decarboxylation of ferulic acid to 4-hydroxy-3-methoxystyrene was purified from Pseudomonas fluorescens UI 670. The enzyme requires no cofactors and contains no prosthetic groups. Gel filtration estimated an apparent molecular mass of 40.4 (+/- 6%) kDa, whereas sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed a molecular mass of 20.4 kDa, indicating that ferulic acid decarboxylase is a homodimer in solution. The purified enzyme displayed an optimum temperature range of 27 to 30 degrees C, exhibited an optimum pH of 7.3 in potassium phosphate buffer, and had a Km of 7.9 mM for ferulic acid. This enzyme also decarboxylated 4-hydroxycinnamic acid but not 2- or 3-hydroxycinnamic acid, indicating that a hydroxy group para to the carboxylic acid-containing side chain is required for the enzymatic reaction. The enzyme was inactivated by Hg2+, Cu2+, p-chloromercuribenzoic acid, and N-ethylmaleimide, suggesting that sulfhydryl groups are necessary for enzyme activity. Diethyl pyrocarbonate, a histidine-specific inhibitor, did not affect enzyme activity.
Determination of Ractopamine Hydrochloride in Swine and Turkey Tissues by Liquid Chromatography with Coulometric Detection

A liquid chromatographic (LC) method is described for determination of ractopamine hydrochloride (LY031537) in swine and turkey tissues. Liver, kidney, muscle, and fat samples were homogenized in methanol. An aliquot of the extract was evaporated, diluted with water, and buffered to pH 10.5 +/- 0.5 with sodium carbonate to convert ractopamine hydrochloride to a free base. The free base was extracted from the buffered sample with ethyl acetate. The extract was further purified on a Bond Elut acid-washed silica solid-phase extraction cartridge. After converting the free base back to the salt form with pH 4.5 buffer, analytical separation and quantitation of ractopamine hydrochloride was performed on an IBM C18 column with coulometric detection at +600 mV. The limit of detection of the method was approximately 0.5 ppb as determined in swine liver. Overall recovery levels ranged between 75 and 100% for samples of liver, kidney, muscle, and fat fortified at 1 to 100 ppb. The coefficients of variation ranged from 2 to 18% for samples fortified at 1 to 100 ppb.
Chemical relaxation molecular beam studies of reactive gas-solid scattering: II. Reaction of ozone with heated germanium surfaces

The reaction probability of room temperature ozone with (111) germanium was found to be 0.2–0.5 at ozone pressures of about 5 × 10−6 torr above surface temperatures of 800°K. Modulated molecular beam and mass spectrometric techniques were employed to measure the desorption rate constant of the GeO formed. Between 800 and 900°K the rate constant was found to be (kd)1 = 7 × 1015e−55000RTs The high value of the pre-exponential factor suggests a transition state with a high degree of freedom. The results are consistent with the reaction sequence Ge(s) + O3(g)) → O(a) +O2(g) → GeO(a) → GeO(g).
Intrinsic Cramer-Rao bounds and subspace estimation accuracy

Signal processing estimation problems are traditionally posed for a set of given, if unknown, parameters, such as angle and/or Doppler. Nevertheless, there are estimation problems on manifolds where no set of intrinsic coordinates exist. One example encountered frequently is the problem of estimating a particular subspace. The set of subspaces, called the Grassmann manifold, has no fixed coordinate system associated with it. This paper addresses the problem of applying classical Cramer-Rao analysis to determine tire fundamental bounds of estimation accuracy on arbitrary manifolds. Coordinate-free versions of the Cramer-Rao bound are derived to accomplish this. These bounds are then applied to the specific problem of estimating the subspace given an independent collection of data snapshots. The root-mean-square-error of the standard method of estimating subspaces using singular valve decomposition is compared to the intrinsic Cramer-Rao bound by varying both the SNR of the unknown subspace and the sample support. It will be seen that this SVD-based method yields accuracies very close to Cramer-Rao bound, establishing that the principal invariant subspace provides an excellent estimator of an unknown subspace, a conclusion that would not in general be possible without coordinate-free Cramer-Rao bounds.
Helium generation rates in isotopically tailored FeCrNi alloys irradiated in FFTF/MOTA

Abstract Three FeCrNi alloys have been doped with 0.4% 59 Ni for side-by-side irradiations of doped and undoped materials in order to determine the effects of fusion-relevant levels of helium production on microstructural development and mechanical properties. The alloys were irradiated in three successive cycles of the Materials Open Test Assembly (MOTA) located in the Fast Flux Test Facility (FFTF). Following irradiation, helium levels were measured by isotope dilution mass spectrometry. The highest level of helium achieved in doped alloys was 172 appm at 9.1 dpa for a helium(appm)-to-dpa ratio of 18.9. The overall pattern of predicted helium generation rates in doped and undoped alloys is in good agreement with the helium measurements.