cssi/SciSciGPT-SciSciNet huggingface dataset:
A 110 nW Resistive Frequency Locked On-Chip Oscillator with 34.3 ppm/°C Temperature Stability for System-on-Chip Designs

This work presents a sub- $\mu \text {W}$ on-chip oscillator for fully integrated system-on-chip designs. The proposed oscillator introduces a resistive frequency locked loop topology for accurate clock generation. In this topology, a switched-capacitor circuit is controlled by an internal voltage-controlled oscillator (VCO), and the equivalent resistance of this switched-capacitor is matched to a temperature-compensated on-chip resistor using an ultra-low power amplifier. This design yields a temperature-compensated frequency from the internal VCO. The approach eliminates the traditional comparator from the oscillation loop; this comparator typically consumes a significant portion of the total oscillator power and limits temperature stability in conventional RC relaxation oscillators due to its temperature-dependent delay. A test chip is fabricated in $0.18~\mu \text {m}$ CMOS that exhibits a temperature coefficient of 34.3 ppm/°C with long-term stability of less than 7 ppm (12 second integration time) while consuming 110 nW at 70.4 kHz. A radio transmitter circuit that uses the proposed oscillator as a baseband timing source is also presented to demonstrate a system-on-chip design using this oscillator.
Coping with Environmental Change: A Social Systems Model

Change in the physical environment affords an especially interesting context within which to examine the process of environmental coping. Recent work conducted by the Environmental Psychology Program at the City University of New York* in the psychiatric pavilion of a large municipal hospital, which we will call Bridgehaven, provided a unique opportunity for investigating how people cope with environmental change. In order to test the behavioral effects of variation in ward physical environment, we received permission to plan, finance, and direct the extensive remodeling of an admission ward in the hospital. This chapter discusses the fascinating manner in which ward staff members dealt with the challenge presented by this large-scale change in the ward setting.
Pathogenesis of Börjeson-Forssman-Lehmann syndrome: Insights from PHF6 function.

Intellectual disability encompasses a large set of neurodevelopmental disorders of cognition that are more common in males than females. Although mutations in over 100 X-linked genes associated to intellectual disability have been identified, only a few X-linked intellectual disability proteins have been intensively studied. Hence, the molecular mechanisms underlying the majority of X-linked intellectual disability disorders remain poorly understood. A substantial fraction of X-linked intellectual disability genes encode nuclear proteins, suggesting that elucidating their functions in the regulation of transcription may provide novel insights into the pathogenesis of intellectual disability. Recent studies have uncovered mechanisms by which mutations of the gene encoding plant homeodomain (PHD)-like finger protein 6 (PHF6) contribute to the pathogenesis of the X-linked intellectual disability disorder Borjeson-Forssman-Lehmann syndrome (BFLS). PHF6 plays a critical role in the migration of neurons in the mouse cerebral cortex in vivo, and patient-specific mutations disrupt the ability of PHF6 to promote neuronal migration. Interestingly, PHF6 physically associates with the PAF1 transcriptional elongation complex and thereby drives neuronal migration in the cerebral cortex. PHF6 also interacts with the NuRD chromatin remodeling complex and with the nucleolar transcriptional regulator UBF, though the biological role of these interactions remains to be characterized. In other studies, PHF6 mRNA has been identified as the target of the microRNA miR-128 in the cerebral cortex, providing new insights into regulation of PHF6 function in neuronal migration. Importantly, deregulation of PHF6 function in neuronal migration triggers the formation of white matter heterotopias that harbor neuronal hyperexcitability, which may be relevant to the pathogenesis of intellectual disability and seizures in BFLS. Collectively, these studies are beginning to provide key insights into the molecular pathogenesis of BFLS.
Overcoming the Computing Barriers in Statistical Causal Inference

The massive development in statistical causal inference to the era of big data commonly seen in public health applications can be always hindered due to the computational barriers. In this chapter we discuss a practical concern on computing barriers in statistical causal inference with example in optimal pair matching and consequently offer a novel solution by constructing a stratification tree based on exact matching and propensity scores. We demonstrate the implementation of this novel method with a large observational study from Philadelphia obstetric unit closure from 1995 to 2003 with 59 observed covariates in each of the 132,786 birth deliveries and 5,998,111 potential controls. Algorithms and R program code are also provided for interested readers.
Repurposing Approach Identifies Auranofin with Broad Spectrum Antifungal Activity That Targets Mia40-Erv1 Pathway

Current antifungal therapies have limited effectiveness in treating invasive fungal infections. Furthermore, the development of new antifungal is currently unable to keep pace with the urgent demand for safe and effective new drugs. Auranofin, an FDA-approved drug for the treatment of rheumatoid arthritis, inhibits growth of a diverse array of clinical isolates of fungi and represents a new antifungal agent with a previously unexploited mechanism of action. In addition to auranofin's potent antifungal activity against planktonic fungi, this drug significantly reduces the metabolic activity of Candida cells encased in a biofilm. Unbiased chemogenomic profiling, using heterozygous S. cerevisiae deletion strains, combined with growth assays revealed three probable targets for auranofin's antifungal activity-mia40, acn9, and coa4. Mia40 is of particular interest given its essential role in oxidation of cysteine rich proteins imported into the mitochondria. Biochemical analysis confirmed auranofin targets the Mia40-Erv1 pathway as the drug inhibited Mia40 from interacting with its substrate, Cmc1, in a dose-dependent manner similar to the control, MB-7. Furthermore, yeast mitochondria overexpressing Erv1 were shown to exhibit resistance to auranofin as an increase in Cmc1 import was observed compared to wild-type yeast. Further in vivo antifungal activity of auranofin was examined in a Caenorhabditis elegans animal model of Cryptococcus neoformans infection. Auranofin significantly reduced the fungal load in infected C. elegans. Collectively, the present study provides valuable evidence that auranofin has significant promise to be repurposed as a novel antifungal agent and may offer a safe, effective, and quick supplement to current approaches for treating fungal infections.
Effects of tramp grinding steel and iron fines on comminution, flotation and cyanidation

Comminution circuits are widely used in nonferrous and precious metals milling. Steel crushers, grinding mills and grinding media are typically used in comminution circuits. Comminution circuit wear products, in the form of metallic iron (steel) fines, are unavoidably produced and report to undersize products in the classification circuit, i.e., flotation or leach feed, while tramp grinding steel (TGS) reports to classification oversize products and returns to the grinding mill, building up in the circulating load. In laboratory studies, TGS reduced grinding efficiency significantly, the impact being dependent upon the size of the TGS present in the mill. Because iron fines adsorb flotation reagents effectively, iron fines increase reagent consumption and reduce flotation recovery. Iron fines are also capable of reducing gold recovery in cyanidation circuits via a cementation reaction. When using filtered gold solution from the cyanidation circuit of an Alaskan gold mine, the gold concentration in solution was reduced by 0.2 to 2.6% over various reaction periods when iron fines were present in the solution.
Abstract 2483: No Increased Risk of sICH in tPA Treated Stroke Patients With ECASS Exclusion Criteria

Introduction: Only about 2% of ischemic stroke patients are currently treated with IV tPA, with the most common reason for exclusion from treatment being time. The positive results of ECASS III exp...
African Americans, African Immigrants, and Afro-Caribbeans Differ in Social Determinants of Hypertension and Diabetes: Evidence from the National Health Interview Survey

In the United States (U.S.), Blacks have higher morbidity and mortality from cardiovascular disease (CVD) than other racial groups. The Black racial group includes African Americans (AAs), African immigrants (AIs), and Afro-Caribbeans (ACs); however, little research examines how social determinants differentially influence CVD risk factors in each ethnic subgroup. We analyzed the 2010-2014 National Health Interview Survey, a cross-sectional, nationally representative survey of non-institutionalized civilians. We included 40,838 Blacks: 36,881 AAs, 1660 AIs, and 2297 ACs. Age- and sex-adjusted hypertension prevalence was 37, 22, and 21% in AAs, ACs, and AIs, respectively. Age- and sex-adjusted diabetes prevalence was 12, 10, and 7% in AAs, ACs, and AIs, respectively. In the multivariable logistic regression analyses, social determinants of hypertension and diabetes differed by ethnicity. Higher income was associated with lower odds of hypertension in AAs (aOR 0.86, 95% CI 0.77-0.96) and ACs (aOR 0.55, 95% CI 0.37-0.83). In AAs, those with some college education (aOR 0.79, 95% CI 0.68-0.92) and college graduates (aOR 0.62, 95% CI 0.53-0.73) had lower odds of hypertension than those with < high school education. In AIs, having health insurance was associated with higher odds of hypertension (aOR 1.59, 95% CI 1.04-2.42) and diabetes (aOR 3.22, 95% CI 1.29-8.04) diagnoses. We observed that the social determinants associated with hypertension and diabetes differed by ethnicity. Socioeconomic factors of health insurance and income were associated with a disparate prevalence of hypertension by ethnic group. Future research among Blacks should stratify by ethnicity to adequately address the contributors to health disparities.
Perturbed Coulomb Problems via SO(2,1) Algebra

So far, we have not solved many perturbed Coulomb problems by conventional perturbation theory, that is, by the conventional radial and angular functions. The difficulty here is that perturbation terms which are functions of the radial coordinate, r, lead to an infinite number of nonzero matrix elements, connecting a bound state of definite, n, to all other bound states, as well as to the full spectrum of continuum states. The complete set of states includes both the bound states and the continuum states.
Stability of medial entorhinal cortex representations over time

Distinct functional cell types in the medial entorhinal cortex (mEC) have been shown to represent different aspects of experiences. To further characterize mEC cell populations, we examined whether spatial representations of neurons in mEC superficial layers depended on the scale of the environment and changed over extended time periods. Accordingly, mEC cells were recorded while rats repeatedly foraged in a small or a large environment in sessions that were separated by time intervals from minutes to hours. Comparing between large and small environments, we found that the overall precision of grid and non-grid cell spatial maps was higher in smaller environments. When examining the stability of spatial firing patterns over time, differences and similarities were observed across cell types. Within-session stability was higher for grid cells than for non-grid cell populations. Despite differences in baseline stability between cell types, stability levels remained consistent over time between sessions, up to 1 hr. Even for sessions separated by 6 hrs, activity patterns of grid cells and of most non-grid cells lacked any systematic decrease in spatial similarity over time. However, a subset of ~15% of mEC non-grid cells recorded preferentially from layer III exhibited dramatic, time dependent changes in firing patterns across 6 hrs, reminiscent of previous characterizations of the hippocampal CA2 subregion. Collectively, our data suggest that mEC grid cell input to hippocampus in conjunction with many time invariant non-grid cells may aid in stabilizing hippocampal spatial maps, while a subset of time varying non-grid cells could provide complementary temporal information.
Cultural diversity among grandparent caregivers: Implications for interventions and policy

Culture and ethnic diversity are critical factors in understanding the roles and well-being of grandparent caregivers. Values, beliefs, traditions continue to influence child rearing practices and may also be influential in persons’ responses to policies and services. Although culture can be a source of support, it can also create stress as persons feel they are not fulfilling expected roles or feel frustrated by demands of more assimilated grandchildren. Strengthening these families requires sensitivity to the cultures and concerns of diverse groups of grandparents at all levels of interventions.
Natural History and Treatment Trends in Pancreatic Cancer Subtypes

While pancreatic ductal adenocarcinoma is the most common form of pancreatic cancer, many other histologic forms of pancreatic cancer are also recognized. These histologic variants portray unique characteristics in terms of patient demographics, tumor behavior, survival, and responsiveness to treatments. Patients who underwent surgical resection of the pancreas for non-metastatic, invasive pancreatic cancer between 2004 and 2014 were selected from the National Cancer Data Base and categorized by histologic variant according to WHO classification guidelines. Patient demographics, tumor variables, treatment characteristics, and survival were compared between histologic groups and subgroups. A total of 57,804 patients met inclusion and exclusion criteria and were grouped into eight major histologic categories. Survival analysis by the histologic group showed median overall survival of 20.2 months for ductal adenocarcinoma, 20.5 months for squamous cell carcinoma, 26.8 months for mixed acinar-neuroendocrine carcinomas, 52.6 months for cystic mucinous neoplasms with an associated invasive carcinoma, 67.5 months for acinar cell carcinoma, and 69.3 months for mesenchymal tumors. Median survival was not reached for neuroendocrine tumors and solid-pseudopapillary neoplasms, with 5-year overall survival rates of 84% and 97% respectively. Rare subtypes of pancreatic cancer present unique clinicopathologic characteristics and display distinct tumor biologies. This study presents data on demographic, prognostic, treatment, and survival outcomes between rare forms of pancreatic neoplasms in order to aid understanding of the natural history and behavior of these neoplasms, with the hope of serving as a reference in clinical decision-making and ability to provide accurate prognostic information to patients.
Application of an external fixator vascular compressor (EFVC) in the critically injured trauma patient: a novel damage control technique

Methods of controlling hemorrhage in penetrating abdominal injuries are varied, ranging from electrocautery, ligation, laparotomy sponge packing, angiography, hemostatic agents, and direct manual pressure. Unfortunately, traditional methods are sometimes unsuccessful due to the location or nature of the hemorrhage, and manual pressure cannot be held indefinitely. We describe a novel damage control technique for hemorrhage control in these situations, followed by three cases where an external fixator vascular compressor (EFVC) was used to hold continual pressure. Three patients are presented to a Level 1 trauma center following multiple ballistic injuries, all requiring emergent exploratory laparotomy. The first had a two-pin iliac crest EFVC placed during repeat exploratory laparotomy to control bleeding. The second patient had a supra-acetabular EFVC placed during initial exploratory laparotomy after emergent embolization failed to control bleeding from the L3 vertebral body. The third patient had a two-pin iliac crest EFVC placed at initial exploratory laparotomy due to uncontrollable bleeding from the sacral venous plexus and internal iliac veins. Of the three patients, two stabilized and survived, while one passed away due to multi-organ failure. We describe a novel damage control technique that may be a useful means of temporarily stemming intraabdominal bleeding that is otherwise recalcitrant to traditional hemostatic methods. Additionally, we provided a limited case series of patients who have undergone this technique to illustrate its utility and versatility. This technique is simple, fast, effective, and adaptable to a variety of circumstances that may be encountered in patients with intraabdominal bleeding recalcitrant to conventional hemorrhage control.
Enhancing elementary science learning through organic chemistry modeling and visualization

The scientists of the future will need to begin studying science in great depth, much earlier in life, in order to keep up with the accelerating pace of discovery and technological innovation. For this to be possible, engaging and child-friendly pedagogical approaches need to be developed that leverage the natural enthusiasm of young science learners, as many students lose interest in science well before they encounter the rich subject matter of high school and college. This study provides evidence that a specially-designed chemistry curriculum can allow students 8-11 years old to rapidly learn advanced material while motivating them. The curriculum adhered to a backward design strategy and utilized a visual approach to chemistry learning. It also featured extensive use of hand-held organic chemistry model building and computerized molecular modeling activities. The 5-session study involved 63 students from grades 3-5 from an economically disadvantaged urban school in New Jersey. Despite the technical nature of the program, student motivation for chemistry learning was high, and assessment results showed students’ high-level understanding of the material.
Normal Form Design Theory

This chapter discusses the conceptual design of a data base. A file is a collection of record instances of a given type. As a file of records is also sometimes called a relation, the subject of normal forms is often included under relational data base theory. The theory of normal forms and the algorithms developed enable one to have confidence in a data base design. Redundancies, inconsistencies, and anomalies can be avoided. However, not all problems with data bases are solved by using normal forms. One of the first tasks of a data base designer is to determine the attributes of the data to be stored in the data base, and the functional dependencies. Functional dependencies have to do with the real world.
The lattice parameter – composition relationship of the body centered cubic uranium-niobium alloys

Abstract In-situ time-of-flight neutron diffraction experiments were performed on uranium-niobium alloy with 6 wt% Nb to study the lattice parameter-composition relationship for the body centered cubic (bcc) alloys. Based on lattice-parameter measurements of Nb-supersaturated γs phase over the range of 450 – 790 °C, an improved Vegard's-type relationship was established for determination of Nb concentrations at elevated temperatures. Neutron diffraction data were also collected as a function of aging time over the 450 - 600 °C range when γs phase decomposed isothermally into the mixture of orthorhombic α-U and Nb-rich bcc phase, as well as at room-temperature on the alloys aged ex-situ at 500 °C up to five years. From these measurements, the average Nb concentrations in the bcc phase were determined based on the Rietveld refinements of weight fraction and mass conservation relations (lever rule). Over the 15at% – 78at% range of Nb concentrations that correspond to different experimental aging times, the lattice parameters at constant temperatures exhibit a nonlinear S-shaped variation with Nb concentration, and the associated excess volumes of mixing can be described by a subregular solution model of the Redlich–Kister type of polynomial. Over the full range of composition the S-shaped deviation from Vegard's law can be modeled using a combination of an elastic continuum model and a perturbation to the radii of the solute atoms in the solvent, suggesting that electronic interactions between solute and solvent atoms could play an important role in the compositional dependence of lattice parameter for the γ-phase U-Nb alloys. While Vegard's law is a straightforward and reasonably good approximation for the bcc solid solutions in the U-Nb system, the Nb concentrations determined from the weight fraction refinements of diffraction data provide internally consistent, mass-conserving estimates of solute redistribution for the monotectoid reaction.
Identifying the antecedents of internal integration in improving green product innovation

Business managers have been investing more and more on green product innovation to deal with the increasing concerns regarding the potential negative environmental impacts of various business activities. Green product innovation has been extensively studied in the literature theoretically and empirically. Given limited empirical research exists in exploring underlying mechanisms and related drivers that contribute green product innovation. This study investigates the critical role of internal integration in improving green product innovation and identifies the antecedents of internal integration. Based on an organisational learning perspective, this study proposes a conceptual framework that specifies the relationship regarding the antecedents of internal integration and its impact on green product innovation. Using survey data from 231 companies in China, this study empirically tests the relationships specified in the conceptual framework. Managerial implications can be drawn from this study on the ways to increase green production innovation indirectly through learning orientation, open-mindedness and vision sharing.
The Economic Value of Equity Implied Volatility Forecasting with Machine Learning

We evaluate the importance of nonlinear interactions in volatility forecasting by comparing the predictive power of decision tree ensemble models relative to classical ones for normalized at-the-money implied volatility innovations. We measure the economic significance of these predictions in cross-sectional and time series pricing tests of delta-hedged option returns. Classification tree ensembles outperform a multinomial logit classifier by 0.35% to 0.46% monthly abnormal returns in delta-hedged option portfolio sorts on volatility innovation forecast data, while regression tree ensembles outperform OLS and LASSO models by 0.03% to 0.14%. Since the predictive variables are the same across all models, these performance differences likely capture the value of nonlinear interactions in implied volatility forecasts. Our results are robust to look-ahead bias and model over-fitting.
Relative Impact of Anticancer Therapy on Unplanned Hospital Care in Patients With Non–Small-Cell Lung Cancer

PURPOSE:In lung cancer, unplanned hospital care is a significant driver of costs. While toxicities of cancer therapies are well-known, there are little data on their relative contribution to unplan...
Racial differences in symptomatic postoperative venous thromboembolism rates after major oncologic resection.

Abstract Background Recent evidence suggests an increased incidence of venous thromboembolism among cancer patients of Black race. This study aimed to determine whether Black patients undergoing major oncologic resection experience increased rates of postoperative venous thromboembolism. Methods A cohort study of patients who underwent major oncologic resection was performed using American College of Surgeons National Surgical Quality Improvement Program (2016−2018). Primary outcome was venous thromboembolism within 30 days of surgery. Multivariable logistic regression was performed to evaluate the independent association of race and venous thromboembolism. Results Of 91,707 patients, 67.7% were White, 9.5% Black, and 22.9% other race. Venous thromboembolism rates differed slightly by race: 2.2% among Whites, 2.4% Blacks, and 1.8% other (P = .002). Black patients were older, with higher rates of obesity, diabetes, and smoking. By multivariable logistic regression, risk of venous thromboembolism was lower among patients of other compared with White race (odds ratio 0.83; 95% confidence interval, 0.74–0.94). There was no difference in odds of venous thromboembolism among Black relative to White patients (odds ratio 1.08; 95% confidence interval, 0.93–1.26). When stratified by age, rates of venous thromboembolism were >50% higher among Black patients older than 75 years compared with White patients (odds ratio 1.54; 95% confidence interval, 1.17–2.03). Conclusion Despite evidence that Black patients with cancer experience higher rates of venous thromboembolism, they do not appear to have an increased risk in the postoperative period.
Identification and Estimation of Causal Peer Effects Using Double Negative Controls for Unmeasured Network Confounding

Scientists have been interested in estimating causal peer effects to understand how people's behaviors are affected by their network peers. However, it is well known that identification and estimation of causal peer effects are challenging in observational studies for two reasons. The first is the identification challenge due to unmeasured network confounding, for example, homophily bias and contextual confounding. The second issue is network dependence of observations, which one must take into account for valid statistical inference. Negative control variables, also known as placebo variables, have been widely used in observational studies including peer effect analysis over networks, although they have been used primarily for bias detection. In this article, we establish a formal framework which leverages a pair of negative control outcome and exposure variables (double negative controls) to nonparametrically identify causal peer effects in the presence of unmeasured network confounding. We then propose a generalized method of moments estimator for causal peer effects, and establish its consistency and asymptotic normality under an assumption about $\psi$-network dependence. Finally, we provide a network heteroskedasticity and autocorrelation consistent variance estimator. Our methods are illustrated with an application to peer effects in education.
Thoracic meningioma with ossification: Case report.

Background The incidence of spinal meningiomas is 0.33/100000 population, and ossified spinal meningiomas are even less commonly encountered. Case description A 64-year-old male presented with a progressive T4-level thoracic myelopathy. MR imaging revealed an intradural extramedullary mass that significantly compressed the spinal cord. The accompanying CT demonstrated hyperdensities within the lesion consistent with punctate calcification vs. ossification (i.e. consistent with histological bone formations within tumor). The patient underwent complete resection of the tumor resulting in a full recovery of neurological function within 6 postoperative weeks. The pathological specimen showed findings consistent with an ossified spinal meningioma. Conclusion Here, we identified a rare case of an ossified thoracic T4 meningioma occurring in a 64-year-old male.
The Pedagogy of User Experience: Designing UX Assignments within a Community of Practice

Voices in technical communication have frequently called for programs to increase their focus on User Experience (UX). However, TPC instructors in those programs sometimes have little preparation in how to teach UX or incorporate it into TPC classes. This workshop brings together academics and practitioners to form a community of practice in UX Pedagogy. By providing evidence-based teaching practices in assignment design, participants will leave with revised assignments or new assignment designs.
The Construct of Content Validity

Many behavioral scientists argue that assessments used in social indicators research must be content-valid. However, the concept of content validity has been controversial since its inception. The current unitary conceptualization of validity argues against use of the term content validity, but stresses the importance of content representation in the instrument construction and evaluation processes. However, by arguing against use of this term, the importance of demonstrating content representativeness has been severely undermined. This paper reviews the history of content validity theory to underscore its importance in evaluating construct validity. It is concluded that although measures cannot be “validated” based on content validity evidence alone, demonstration of content validity is a fundamental requirement of all assessment instruments.
Text Categorization Models for Identifying Unproven Cancer Treatments on the Web

The nature of the internet as a non-peer-reviewed (and largely unregulated) publication medium has allowed wide-spread promotion of inaccurate and unproven medical claims in unprecedented scale. Patients with conditions that are not currently fully treatable are particularly susceptible to unproven and dangerous promises about miracle treatments. In extreme cases, fatal adverse outcomes have been documented. Most commonly, the cost is financial, psychological, and delayed application of imperfect but proven scientific modalities. To help protect patients, who may be desperately ill and thus prone to exploitation, we explored the use of machine learning techniques to identify web pages that make unproven claims. This feasibility study shows that the resulting models can identify web pages that make unproven claims in a fully automatic manner, and substantially better than previous web tools and state-of-the-art search engine technology.
Regulation of RhoBTB2 by the Cul3 Ubiquitin Ligase Complex

The recently identified RhoBTB family is a member of the Rho GTPase family. One family member, RhoBTB2, has been implicated as a tumor suppressor in lung and breast cancer. Studies have shown that RhoBTB2 binds to the ubiquitin ligase scaffold Cul3 and that Cul3 regulates RhoBTB2 protein levels by ubiquitinating RhoBTB2 directly, leading to its degradation by the proteasome. This chapter details the cell biological and biochemical methods for analyzing the regulation of RhoBTB2 by Cul3.
Paracrine pathways of cartilage destruction in osteoarthritis

Osteoarthritis (OA) has been considered a biomechanically driven, degenerative disease of cartilage. However, the OA disease process affects not only the cartilage, but also the entire joint structure; and within the bone, cartilage and synovium of affected joints, profound metabolic changes transpire, which include the production of growth factors, nitric oxide (NO), prostaglandins (PGs), leukotrienes (LTs), IL-1β, tumor necrosis factor alpha, IL-6, and IL-8. The autocrine production of IL-1β by OA cartilage has been of particular interest, since both ex vivo human and in vivo animal studies indicate that IL-1 antagonists effectively attenuate cartilage degradation. Microarray technology has demonstrated differential expression in OA cartilage of a variety of IL-1-induced, NFβB-dependent genes. Among IL-β-induced products of OA cartilage are various eicosanoids, which include E2, PGD2, LTB4, PGF1α, PGF2α and thromboxane. Treatment of OA cartilage with cyclooxygenase (COX) inhibitors increases LTB4 production threefold to fivefold, indicating shunting of arachidonate from the COX to the 5-LO pathway. Functional analyses of individual eicosanoids reveals that PGD2, in contrast to its derivative PGJ2, stimulates catabolic processes, including NO and PG production. Lipoxin and 15-epi-lipoxin are also spontaneously released by OA cartilage, where they act to inhibit the spontaneous production of NO, PGE2, IL-8 and IL-6. Consistent with the notion that OA is not simply a degenerative disease of cartilage, gene expression analysis of circulating peripheral blood mononuclear cells (PBMCs) shows upregulation of mRNA for IL-1β, COX-2, IL-6, and IL-8 in OA (but not normal) PBMCs. OA PBMCs produce threefold to fivefold more PGE2 in response to stimulation with IL-1β than do normal cells. Thus, PBMCs, like chondrocytes and synovial cells, are activated in OA, and merit evaluation as sensors of inflammatory processes in the OA joint.
Trade Secrets and Traditional Knowledge: Strengthening International Protection of Indigenous Innovation

A rational trade secret regime could serve as a valuable first step in protecting indigenous innovation. However, to assure that such a regime does not simply lock away such innovation from the public but assures that it is used and valued on terms that respect the rights of indigenous holders, the full flexibilities mandated by present international standards for trade secret protection must be applied. These flexibilities include recognition of the unfair competition basis of trade secret protection internationally which in turn allows for ethically applied considerations of secrecy, commercial value, and diasporic ownership. Ultimately, trade secret protection, applied with the full flexibility required under its unfair competition basis under TRIPS, could provide the critical legal foundation for the use of indigenous innovation as a critical source for sustainable development. But to reach these goals, present models for Material Transfer Agreements need to be more fully developed to accord full protection to indigenous innovation and TK databases and registers need to be crafted to avoid improvident loss of critical trade secrets.
Isolation rate, T-serotyping and susceptibility to antibiotics of Group A Streptococcus from pediatric infections in Athens*

Objective The epidemiology of Group A Streptococcus (GAS) in Greece is not known. We have therefore conducted this prospective study to investigate the isolation rate of GAS from pediatric specimens, determine T-serotype frequency and examine the susceptibility of GAS to penicillin, erythromycin and clindamycin. Methods Over a 3-year study-period (1993–95) 11 597 clinical specimens obtained from sick children were inoculated on appropriate culture media. The isolation and identification of GAS strains were assessed by conventional methods. T-typing was performed by slide agglutination. Serum opacity factor (OF) was detected by microwell method. The susceptibility of the strains was tested by the Kirby Bauer method. Results GAS were isolated from 1125 out of 11 597 (9.7%) clinical specimens, mostly from throat samples (15.6%). T-serotyping was performed in 652 GAS strains. A significant difference of the incidence of T-serotypes was observed within the 3 years studied (χ 2 = 70.3, DF=18, P Conclusions There was a wide distribution of GAS T-serotypes in Athens and a significant change in their annual predominance. All strains were susceptible to penicillin and clindamycin, but a low level of erythromycin resistance was observed.
Quantification of serotonin transporters with [11C]AFM: Evaluation of reference region methods

Mika Naganawa, B. Planeta-Wilson, N. Nabulsi, J. Ropchan, D. Labaree, A. Neumeister, Y. Huang, and R.E. Carson PET Center, Department of Diagnostic Radiology, Yale University, New Haven, CT, USA Department of Psychiatry, Yale University, New Haven, CT, USA Introduction: [C]AFM is a new, highly selective PET radioligand for the serotonin transporter [1]. Metabolism of [C]AFM is rapid with parent fraction of 30% and 8% at 30 and 90 min, respectively, and the accurate measurement of the metabolite or input function is difficult. The aim of this study is to investigate the suitability of reference region approaches for human [C]AFM studies with ROI analysis.
Intrapatient consistency of imaging biodistributions and their application to predicting therapeutic doses in a phase I clinical study of 90Y-based radioimmunotherapy.

Intrapatient variation in the biodistribution of the chimeric monoclonal antibody cT84.66 was assessed in 19 patients having a variety of carcinoembryonic antigen (CEA) positive tumors. The two studies, including whole-body imaging and blood and urine specimen collections, were conducted within 14 days of each other using 111 In-cT 84.66 at a fixed total proteindose of 5 mg per patient per study. An initial pretherapy infusion of 111 In-cT 84.66 was administered followed by a therapy coinfusion of 111 In-ct 84.66 and 90 Y-cT 84.66 A closed five-compartment model was used to integrate sourceorgan activity curves as residence time inputs into the MIRDOSE3 program. Normal organ absorbed doses were estimated for 90 Y-cT 84.66, the corresponding radiotherapeutic agent. For the two 111 In-cT 84.66 biodistributions, all data were modeled with a R 2 value of between 0.72 and 1.00 with the exception of the urine data taken during therapy. This was due to the need of diethylenetriaminepentaacetic acid during the therapy phase because of the possibility that yttrium might escape from the chelator attached to the antibody. With the assurance that the biodistributions were reproducible, we were able to estimate the 90 Y-cT 84.66 absorbed doses on a per-patient basis. Concordance coefficients showing the agreement between the imaging and therapy phase dose estimates were between the 0.60 and 0.99 levels for liver, spleen, red marrow, total body, and other organ systems. Median results were: 27, 17, and 2.7 rad/mCi of 90 Y-cT 84.66 for liver, spleen, and red marrow, respectively. Because of decreases in platelets and white cells as the amount of 90 Y was increased, dose-limiting toxicity was found at 22 mCi/m2. We conclude that patient biodistributions were consistent over time to 14 days so as to allow absorbed dose estimation in a radioimmunotherapy trial involving the cT84.66 anti-CEA antibody.
A simple model for predicting lung cancer occurrence in a lung cancer screening program: The Pittsburgh Predictor.

Background A user-friendly method for assessing lung cancer risk may help standardize selection of current and former smokers for screening. We evaluated a simple 4-factor model, the Pittsburgh Predictor, against two well-known, but more complicated models for predicting lung cancer risk.
Atmospheric Lens Effect; Another Loss for the Radar Range Equation

A small additional loss for radar range calculations at low grazing angles is described. This loss results because the variation in atmospheric refraction versus altitude makes the atmosphere act like a lens, causing thinning of radar signal energy to and from the target, independent of frequency. The magnitude of loss is derived and is plotted versus grazing angle and range. The maximum two-way loss, occurring at zero degrees grazing angle and a range well beyond the atmosphere, is 2.9 dB.
Rapid actions of progesterone on granulosa cells.

Abstract Ovarian granulosa cells are responsive to progesterone but do not express the nuclear progesterone receptor. In an attempt to identify a receptor for progesterone (P4) in granulosa cells (GCs), an antibody built against the ligand binding site of the P4 receptor (i.e. C-262) was used. This antibody detected a 60 kDa protein in GCs as well as spontaneously immortalized granulosa cells (SIGCs). This C-262 detectable protein localizes to the plasma membrane and binds P4. Importantly, this C-262 detectable protein appears to be involved in mediating P4’s biological actions. This is based on the findings that C-262 1) blocks P4’s ability to inhibit mitogen-induced mitosis and apoptosis and 2) FITC-BSA-conjugated P4 binding to granulosa cells. A C-262 detectable protein was isolated using a C-262 affinity column and sequenced. This analysis identified an unnamed protein referred to as RDA288 that was found in the rat genome (Accession number: XM 216160 ). A nearly identical unnamed protein was found in a cDNA library of mouse lung (Accession number: AK004678 ). Whether RDA288 functions as a membrane receptor for P4 remains to be determined.
Intra- and inter-specific comparisons of leaf UV-B absorbing-compound concentration of southern broadleaf trees in the United States

Increased concentration of leaf UV-B absorbing-compounds due to exposure to UV-B radiation is widely accepted as one of the plant adaptations to resist enhanced UV-B radiation. This paper reports a field comparative study of dynamics and temporal changes of UV-B absorbing-compound concentration in 35 southern broadleaf trees over a growing season. Leaf UV-B absorbing-compound, chlorophyll concentration, and leaf thickness were measured from the sun-exposed leaves of 35 tree species collected monthly from individual trees growing within the city of Baton Rouge, Louisiana from April to October in 2000. The USDA UV-B Monitoring Network Baton Rouge Station provided the ambient UV-B radiation data. Leaf UV-B absorbing-compound concentration varied significantly with leaf age and species. Intra-specifically, leaf UV-B absorbing-compound concentration exhibited a generally increasing trend during leaf growth and development in response to the increased exposure to natural UV-B/solar radiation during the growing season. Inter-specifically, significant differences existed in leaf UV-B absorbing-compound concentration. The species were compared and ranked based on the growing season averages of the leaf total UV-B absorbing-compound concentration. The species were further classified into three levels (high, medium, and low) based on the magnitude of UV-B absorbing-compound concentration.
Water in the oceanic upper mantle: implications for rheology, melt extraction and the evolution of the lithosphere

Abstract The influence of water on the dynamics of the oceanic upper mantle is re-evaluated based on recent experimental constraints on the solubility of water in mantle minerals and earlier experimental studies of olivine rheology. Experimental results indicate that the viscosity of olivine aggregates is reduced by a factor of ∼ 140 in the presence of water at a confining pressure of 300 MPa and that the influence of water on viscosity depends on the concentration of water in olivine. The water content of olivine in the MORB source is estimated to be810±490H10/6 Si, a value greater than the solubility of water in olivine at a confining pressure of 300 MPa (∼ 250H10/6 Si). We therefore conclude that the viscosity of the mantle in the MORB source region is 500±300 times less than that of dry olivine aggregates. The dependence of the solubility of water in olivine on pressure and water fugacity is used in conjunction with other petrological constraints to estimate the depth at which melting initiates beneath mid-ocean ridges. These calculations indicate that melting begins at a depth of ∼ 115 km, consistent with other geochemical observations. Owing to the relatively small amount of water present in the MORB source, only ∼ 1–2% melt is produced in the depth interval between the water-influenced solidus and the dry solidus. A discontinuity in mantle viscosity can develop at a depth of ∼ 60–70 km as a result of the extraction of water from olivine during the MORB melting process. In the mid-ocean ridge environment, the mantle viscosity at depths above this discontinuity may be large enough to produce lateral pressure gradients capable of focusing melt migration to the ridge axis. These observations indicate that the base of an oceanic plate is defined by a compositional rather than thermal boundary layer, or at least that the location of the thermal boundary layer is strongly influenced by a compositional boundary, and that the evolution of the oceanic upper mantle is strongly influenced by a viscosity structure that is controlled by the extraction of water from olivine at mid-ocean ridges.
GABA-immunoreactivity in ganglion cells of the rat retina

Ganglion cells in the rat retina were labeled with the fluorescent dye, Diamidino-yellow, by retrograde transport from the superior colliculus and subsequently reacted for GABA-like immunoreactivity with a rhodamine-conjugated antiserum. Examination of sectioned retinas by fluorescence microscopy showed double labeling in approximately 6% of the ganglion cells. The presence of GABA in these neurons suggests that they may be involved in providing direct inhibitory input to the rat tectum.
Phase I Hepatic Immunotherapy for Metastases study of intra-arterial chimeric antigen receptor modified T cell therapy for CEA+ liver metastases

Purpose: Chimeric antigen receptor–modified T cells (CAR-T) have demonstrated encouraging results in early-phase clinical trials. Successful adaptation of CAR-T technology for CEA-expressing adenocarcinoma liver metastases, a major cause of death in patients with gastrointestinal cancers, has yet to be achieved. We sought to test intrahepatic delivery of anti-CEA CAR-T through percutaneous hepatic artery infusions (HAIs). Experimental Design: We conducted a phase I trial to test HAI of CAR-T in patients with CEA + liver metastases. Six patients completed the protocol, and 3 received anti-CEA CAR-T HAIs alone in dose-escalation fashion (10 8 , 10 9 , and 10 10 cells). We treated an additional 3 patients with the maximum planned CAR-T HAI dose (10 10 cells × 3) along with systemic IL2 support. Results: Four patients had more than 10 liver metastases, and patients received a mean of 2.5 lines of conventional systemic therapy before enrollment. No patient suffered a grade 3 or 4 adverse event related to the CAR-T HAIs. One patient remains alive with stable disease at 23 months following CAR-T HAI, and 5 patients died of progressive disease. Among the patients in the cohort that received systemic IL2 support, CEA levels decreased 37% (range, 19%–48%) from baseline. Biopsies demonstrated an increase in liver metastasis necrosis or fibrosis in 4 of 6 patients. Elevated serum IFNγ levels correlated with IL2 administration and CEA decreases. Conclusions: We have demonstrated the safety of anti-CEA CAR-T HAIs with encouraging signals of clinical activity in a heavily pretreated population with large tumor burdens. Further clinical testing of CAR-T HAIs for liver metastases is warranted. Clin Cancer Res; 21(14); 3149–59. ©2015 AACR .
Feasibility of real-time 3-dimensional treadmill stress echocardiography.

Abstract Rapid acquisition of echocardiographic images is critical for the predictive accuracy of stress echocardiography. Real-time 3-dimensional echocardiography (RT3D) allows review of several standard 2-dimensional images from a single volumetric data set. To assess the feasibility of RT3D for treadmill stress echocardiography, we performed treadmill stress RT3D on 20 volunteers (10 men and 10 women; mean age 32 ± 6 years) with a device that uses a matrix phased-array transducer in a 60-degree pyramidal volume. Images are displayed as 2 steerable, intersecting B-scan sectors with adjustable C-scan planes parallel to the transducer face. At pre-exercise and immediate postexercise assessment, the volumetric data were obtained from apical and parasternal windows, respectively. Left ventricular segments were divided into 16 standard segments according to criteria defined by the American Society of Echocardiography. The use of both volume sets resulted in visualization of 98% of the segments at peak exercise. Even with only an apical volume set, 89% of the segments were adequately visualized. Image optimization and acquisition time at peak exercise was 35 ± 18 seconds from the apical window and 50 ± 28 seconds from the parasternal window. This preliminary study indicates that RT3D treadmill stress echocardiography is feasible and may be an important application of this new 3-dimensional device. (J Am Soc Echocardiogr 1999;12:285-9.)