cssi/SciSciGPT-SciSciNet huggingface dataset:
Treatment of Relapsed/Refractory Acute Myeloid Leukemia

Approximately 40–45% of younger and 10–20% of older adults with acute myeloid leukemia (AML) will be cured with current standard chemotherapy. The outlook is particularly gloomy for patients with relapsed and/or refractory disease (cure rates no higher than 10%). Allogeneic hematopoietic stem cell transplantation (HSCT), the only realistic hope of cure for these patients, is an option for only a minority. In recent years, much has been learned about the genomic and epigenomic landscapes of AML, and the clonal architecture of both de novo and secondary AML has begun to be unraveled. These advances have paved the way for rational drug development as new “drugable” targets have emerged. Although no new drug has been approved for AML in over four decades, with the exception of gemtuzumab ozogamycin, which was subsequently withdrawn, there is progress on the horizon with the possible regulatory approval soon of agents such as CPX-351 and midostaurin, the Food and Drug Administration “breakthrough” designation granted to venetoclax, and promising agents such as the IDH inhibitors AG-221 and AG-120, the smoothened inhibitor glasdegib and the histone deacetylase inhibitor pracinostat. In our practice, we treat most patients with relapsed/refractory AML on clinical trials, taking into consideration their prior treatment history and response to the same. We utilize targeted sequencing of genes frequently mutated in AML to identify “actionable” mutations, e.g., in FLT3 or IDH1/2, and incorporate small-molecule inhibitors of these oncogenic kinases into our therapeutic regimens whenever possible. In the absence of actionable mutations, we rationally combine conventional agents with other novel therapies such as monoclonal antibodies and other targeted drugs. For fit patients up to the age of 65, we often use high-dose cytarabine-containing backbone regimens. For older or unfit patients, we prefer hypomethylating agent-based therapy. Finally, all patients with relapsed/refractory AML are evaluated for allogeneic HSCT.
Demonstration of Prognostics-Enabled Decision Making Algorithms on a Hardware Mobile Robot Test Platform

Prognostics-enabled Decision Making (PDM) is an emerging research area that aims to integrate prognostic health information and knowledge about the future operating conditions into the process of selecting subsequent actions for the system. Previous work developing and testing PDM algorithms has been done in simulation; this paper describes the effort leading to a successful demonstration of PDM algorithms on a hardware mobile robot platform. The hardware platform, based on the K11 planetary rover prototype, was modified to allow injection of selected fault modes related to the rover’s electrical power subsystem. The PDM algorithms were adapted to the hardware platform, including development of a software module framework, a new route planner, and modifications to increase the algorithms’ robustness to sensor noise and system timing issues. A set of test scenarios was chosen to demonstrate the algorithms’ capabilities. The modifications to run with a hardware platform, the test scenarios, and the test results are described in detail. The results show a successful use of PDM algorithms on a hardware test platform to optimize mission planning in the presence of electrical system faults.
Analysis framework for systematically studying ionospheric response to impulsive events from below

Impulsive phenomena in the Earth's atmosphere produce acoustic and gravity waves which perturb the ionosphere. Such perturbations are often measured using total electron content fluctuations (TEC), derived from ground-based Global Positioning System data. Using TEC data from the Japanese GEONET ground network after the Tōhoku earthquake on 11 March 2011, we demonstrate capabilities of a new framework of methodologies for analyzing ionospheric perturbations. The framework consists of several new techniques: calculating velocity along a single direction to reduce error due to anisotropic propagation, producing normalized bidirectional band-pass spectra that preserve relative timing between various frequencies and allowing a more systematic determination of broadband pulses, and utilizing a wavelet-based technique that considers instantaneous wave phase changes, rather than best fit time differences, to evaluate wave characteristics (speed, direction, and wavelength) within spectral ranges of interest. Using these techniques together decreases subjectivity and reduces errors in attributing fluctuations to given sources. In validating this framework using the Tōhoku case, we consistently identify three kinds of waves: a broad-band pulse (speed: >2000 m/s, max range: >1400 km) arriving in the ionosphere 10–15 min after the quake, acoustic waves following the pulse (period: 3–5 min, speed: 700–1000 m/s, max range: 1400 km) propagating away from the epicenter, consistent with theory and demonstrated in previous studies. This framework also can be applied to other impulsive events in the atmosphere that are more difficult to detect and attribute to sources.
The BMP2/4 ortholog Dpp functions as an inter-organ signal that regulates developmental timing in Drosophila

For many organisms, developmental transitions are triggered by a neuroendocrine axis and are contingent upon multiple organs achieving sufficient growth and maturation. How the status of peripheral organs is communicated to the neuroendocrine axis is not known. In Drosophila larvae, metamorphosis is triggered by the steroid hormone ecdysone, secreted by the prothoracic gland (PG). Here we show that the BMP2/4 ortholog Dpp, which regulates growth and patterning of larval imaginal discs, also functions as a systemic signal to regulate developmental timing. Dpp from peripheral tissues, mostly imaginal discs, can reach the PG and inhibit ecdysone biosynthesis. As the discs grow, Dpp signaling decreases in the PG, thus alleviating the inhibition of ecdysone biosynthesis, and permitting entry into metamorphosis. We suggest that if a tissue can trap more morphogen locally as it grows and matures, then circulating levels of morphogen can provide a systemic readout of organ size and maturation.
Associations and determinants of tobacco consumption in Thailand

Abstract This paper presents a study of household tobacco consumption in Thailand from 2006 to 2011. We investigated the nonlinear relationships between this behavior and household alcohol expenditure, household gambling expenditure, and demographic factors and used TreeNet to analyze datasets drawn from socio-economic surveys. Across all the years included in the survey period, we found consistent results whereby the likelihood of tobacco consumption was higher for households with higher expenditure on alcohol both consumed at home and away from home, located in the South or the Northeast, with lower income, a head of household with a lower educational level, a male head of household, and a head of household employed by a private company. We also found that over the focal period of the study, households headed by an older person were more likely to consume tobacco in the first half of the study period but this relationship changed such that households headed by a younger person (aged 18–25 years), showed the highest likelihood of consuming tobacco by the end of the study period. The discussion behind this shift, and how it is related to strategies from the tobacco industry are also provided.
Alkylation and Oxidative Damages to DNA: Constitutive and Inducible Repair Systems

Simple chemical agents that damage DNA are of both environmental and intracellular origin. Among these are carcinogen-related compounds, including simple alkylating agents (e.g., S-adenosyl methionine) and simple oxidizing agents (e.g., oxygen radicals). Living cells have therefore to counter the potentially mutagenic and carcinogenic effects of physiological compounds on a daily basis, and not just when they encounter an occasional environmental challenge.
A Pharmacy-Based Electronic Handoff Tool to Reduce Discharge Prescribing of Atypical Antipsychotics Initiated in the Intensive Care Unit: A Quality Improvement Initiative.

Purpose:To evaluate whether a pharmacist-initiated electronic handoff tool can reduce the overall, and potentially inappropriate, hospital discharge prescribing rate of atypical antipsychotics (AAP...
Spatial Dispersion Induced Birefringence in Cubic Semiconductors

A procedure to calculate the lowest order spatial dispersion effects in the dielectric constant of a germanium-type semiconductor is presented. The contribution of the lowest direct edge (E0 E0 +A0), the E1 – E1 + Δ1 edge, and the Penn gap is given. These results are used to estimate the birefringence for light propagation along [110]. Good agreement with recent experimental results for Ge, GaAs, and Si is found.
Mental Health: Affective Disorders

People have long noticed similarity and overlap among people suffering from mental disorders and those recognized as creative. Biographies and empirical research have examined this connection, first emphasizing personality disorders, then schizophrenia, and most recently mood disorders, particularly bipolar affective disorder. Types of psychopathology may be associated with forms of perception, cognition, feeling, and behavior beneficial to particular types (and epochs) of creative endeavor. This entry examines conceptual connections between genius and madness, reviews literature on relationships among traits, symptoms, diagnostic categories, and creativity, and discusses implications for mental health treatment and our views of positive human functioning.
Living on the Edge

Why do we need vaccines? This question seems to be missing from the current immunization debate. Simply put, they are necessities. They have been developed for humane reasons, to relieve the suffering, disability, and death of individual children, and to protect the commonweal. A mere hundred years ago, the USA posted the worst infant and childhood health record among industrialized nations. This chapter, tapping morbidity and mortality rates, provides a brief yet comprehensive overview of diseases, their symptoms, and consequences that plagued children during the early twentieth century. Infantile paralysis receives special attention. Each summer reintroduced this onslaught, sowing dread and despair. While children either recovered or died from other infections, whether bacterial or viral, poliomyelitis often left a permanent legacy: disability, a personal and social burden. The medical community, for decades, knew little about its symptoms, how it spread, and which treatments worked, all of which compounded fears.
Management of acute myocardial infarction. Synopsis of ACC and AHA practice guidelines. American College of Cardiology and American Heart Association.

PREVIEWThe average time that elapses from a patient's first awareness of heart attack symptoms to start-up of specific reperfusion therapy is currently 4 hours. The National Heart Attack Alert Program wants to see this time reduced to 2 hours. Such dispatch would surely benefit patients, because when it comes to thrombolytic therapy, the sooner the better. Dr Ryan summarizes the new recommendations for handling patients with acute myocardial infarction rapidly and efficiently, from the 911 call and transport to the emergency department, through the important first 24 hours of hospitalization, to hospital discharge and long-term management.
AutoEncoded Domains with Mean Activation for DGA Botnet Detection

Botnets are the powerful and effective way of performing malicious activities over the internet. Over the years, it has evolved into many forms. Earlier bots used static IP to communicate with their command and control server. This method stopped working as soon as that specific IP was identified and blocked. These days, domain fluxing botnets are mostly in practice. The idea is, using Dynamically Generation Algorithm (DGA) to generate domains and use it to connect with C&C server. Numerous researches have been done to detect DGA botnets. These includes deriving features based on alphanumeric distribution of DGA domains and performing classification on it. Other studies include network logs analysis, time series analysis etc. Most of these domain classification works rely upon the features developed and may not work well if the botmaster decides to generate domain with completely new features. We are concerned with developing algorithm that is resilient to feature change that also work well for domain generated by completely new algorithm that was not seen before. We generated 16 bit representation of domains using autoencoder and classified it as benign or DGA generated using supervised learning(with neural net and SVM). To make it work with previously unseen algorithm, we tweaked our method with mean activation of 16-bit domain representation. This helped improve classification accuracy for completely new set of domain generation algorithm by up to 16%.
A Retrospective Study of Early vs Delayed Home Dose Basal Insulin in the Acute Management of Diabetic Ketoacidosis.

Background Insulin via continuous intravenous infusion (ICII) is a standard of care for treating patients with diabetic ketoacidosis (DKA). Once DKA is resolved, ICII is transitioned to subcutaneous therapy. However, recent guidelines recommend continuation of home dose subcutaneous basal insulin (HDBI) in patients with DKA. The objective of this study was to evaluate outcomes in patients who received early vs delayed HDBI. Methods This is a retrospective cohort study of patients ≥16 years old admitted to the medical intensive care unit between 1 July 2012 and 30 June 2015 with a primary diagnosis of DKA who received ICII and HDBI. Patients were stratified into early or delayed groups if they received HDBI before or after resolution of DKA, respectively. The primary outcome was incidence of transitional failure, defined as resumption of ICII or recurrence of DKA after initial ICII discontinuation. Results A total of 106 admissions were included for analysis; 33 (31.1%) received early HDBI. The incidence of transitional failure was similar between the early and delayed groups (OR, 0.60; 95% CI, 0.26 to 1.44; P = 0.72). In the early group, ICII duration was shorter at 13.8 hours [interquartile range (IQR), 10.1 to 16.5] vs 17.1 hours (IQR, 12.6 to 21.1; P = 0.04), with a trend toward lower rates of hypoglycemia (OR, 0.41; 95% CI, 0.16 to 1.05; P = 0.058). Conclusion There was no significant difference in incidence of transitional failure between early and delayed HDBI. Early HDBI was associated with a shorter duration of ICII and a trend toward less hypoglycemia. A prospective analysis is needed to confirm these findings.
Chiral Synthesis via Organoboranes. 43. Selective Reductions. 58. Reagent-Controlled Diastereoselective Reduction of (+)- and (−)-α-Chiral Ketones with (+)- and (−)-B-Chlorodiisopinocampheylborane

Asymmetric reduction of (+)- and (−)-α-chiral ketones with (+)- and (−)-B-chlorodiisopinocampheylborane provides the product alcohols in very high diastereomeric excess, with the matched pairs providing >100:1 selectivity and the mismatched pairs showing 4:1−15:1 selectivity. The high selectivity achieved even in the mismatched pairs reveals the power of the reagent to control the stereochemical outcome. The rates of the reaction of the matched pairs are faster than those of the mismatched pairs. In all the cases studied thus far, the (−)-reagent (dIpc2BCl) and (S)-ketone or the (+)-reagent (lIpc2BCl) and (R)-ketone constitute matched pairs and the (−)-reagent and (R)-ketone or the (+)-reagent and (S)-ketone constitute mismatched pairs. A possible mechanism for the reductions is discussed.
A New Family of Constrained Codes with Applications in Data Storage

Line codes make it possible to mitigate interference, to prevent short pulses, and to generate streams of bipolar signals with no direct-current (DC) power content through balancing. They find application in magnetic recording (MR) devices, in Flash devices, and in optical recording devices. This paper introduces a new family of fixed-length, binary constrained codes, named lexicographically-ordered constrained codes (LOCO codes), for bipolar non-return-to-zero signaling. LOCO codes are capacity achieving, the lexicographic indexing enables simple, practical encoding and decoding, and this simplicity is demonstrated through analysis of circuit complexity. Experimental results demonstrate a gain of up to 10% in rate achieved by LOCO codes with respect to practical run-length-limited codes designed for the same purpose. Simulation results suggest that it is possible to achieve channel density gains of about 20% in MR systems by using a LOCO code to encode only the parity bits of a low-density parity-check code before writing.
Evidence-Based Hospital Procedural Volumes as Predictors of Outcomes After Revision Hip Arthroplasty.

Abstract Introduction Our goal was to define the evidence-based institutional volume-outcome relationship in revision hip arthroplasty. We hypothesized that high-volume centers would be associated with superior outcomes, and that stratum-specific likelihood ratio (SSLR) analysis would delineate concrete volume thresholds for optimizing outcomes. Methods The Nationwide Readmission Database was queried from 2011-2016 for patients undergoing revision hip arthroplasty. Stratum-specific likelihood ratio (SSLR) analysis was used to determine hospital volume cutoffs specific for outcomes of interest. Volume categories were confirmed with multivariate regression. Results SSLR analysis produced distinct hospital volume cut-offs for all outcomes. Each subsequent volume threshold diminished patients' risk for adverse outcomes. Tertiles were identified for 90-day infection (≤6, 7-51, ≥52 cases/year). Quartiles were found for 90-day readmission (≤5, 6-15, 16-79, ≥80), 90-day prosthesis-related complication (≤5, 6-16, 17-65, ≥66), 90-day dislocation (≤5, 6-19, 20-79, ≥80), and non-home discharge (≤5, 6-15, 16-40, and ≥41). Quintiles were generated for extended length of stay >2 days (≤2, 3-10, 11-20, 21-30, ≥31). Heptiles were produced for medical complication within 90 days (≤2, 3-8, 9-16, 17-51, 52-89, ≥90). Conclusion This is the first known study to define evidence-based thresholds for the impact of hospital volume on revision joint arthroplasty. This supports the notion that institutional volume functions as a surrogate for protocolized interdisciplinary coordination of care and surgical experience, and that high-volume centers offer enhanced outcomes for complex cases. Additional studies should investigate the potential role for incentivization of such institutions, as they offer optimal outcomes for revision hip arthroplasty.
Reducing fat, oil, and grease (FOG) deposits formation and adhesion on sewer collection system structures through the use of fly ash replaced cement-based materials.

Abstract The accumulation of fat, oil, and grease (FOG) deposits in sewer pipes reduces their conveyance and results in Sanitary Sewer Overflows (SSOs). Previous research has shown that concrete used in sewer lines is a significant source for calcium ion, which participates in the FOG deposit formation mechanism. However, no research has been conducted to understand the effect of calcium leaching from cement on FOG deposits formation and adhesion. This study quantifies the reduction in FOG deposit formation when Fly Ash (FA), a Supplementary Cementitious Material (SCM), is used to replace cement in the production of High Volume Fly Ash (HVFA) concrete materials. Results show that after 90 days of leaching test under controlled pH conditions, 75% and 86% reduction in calcium release were achieved from 50% and 75% FA replacement, respectively. After 30 days of FOG deposits formation tests on HVFA samples, 58% and 81% reduction in FOG deposit formation was found for 50% and 75% FA replacement, respectively. FTIR analyses of FOG deposits formed on concrete samples without FA replacement exhibited high calcium soap content (48%), while, FOG deposit formed on HVFA concrete materials showed low calcium soap percentage (22~29%). Furthermore, FTIR analyses report the first spatial variation found in FOG deposits that includes a surface layer of hard FOG deposits with high calcium soap absorbance and an outer layer of soft FOG deposits consisting of a low calcium absorbance. FTIR analyses revealed that the FOG deposit formation mechanism is affected by the availability of calcium and pH near the concrete surface. Finally, HVFA concrete materials were tested for compressive strength and durability against microbially induced concrete corrosion (MICC). After 180 days of sealed curing, HVFA concrete exhibited adequate compressive strength necessary for the sewer line construction and 50% FA replacement revealed satisfactory durability against MICC.
Instructor's Reference for Integrating Mass Spectrometry into the General Chemistry Classroom.

Mass spectrometry is one of the few instrumental analysis techniques that can be relatively well-understood with physics/chemistry knowledge typical of an advanced high school or a beginning underg...
Leukocyte mitochondrial DNA copy number and built environment in Mexican Americans: a cross-sectional study.

Mitochondrial DNA (mtDNA) copy number in leukocytes has been regarded as a biomarker for various environmental exposures and chronic diseases. Our previous study showed that certain demographic factors (e.g. age, gender, BMI, etc.) significantly affect levels of leukocyte mtDNA copy number in Mexican Americans. However, the effect of the built environment on leukocyte mtDNA copy number has not been studied previously. In this cross-sectional study, we examined the association between multiple components of the built environment with leukocyte mtDNA copy number among 5,502 Mexican American adults enrolled in Mano-A-Mano, the Mexican American Cohort Study (MACS). Based on the median levels of mtDNA copy number, the study population was stratified into low mtDNA copy number group (< median) and high mtDNA copy number group (≥ median). Among all built environment exposure variables, household density and road/intersection ratio were found to be statistically significant between groups with low and high mtDNA copy number (P < 0.001 and 0.002, respectively). In the multivariate logistic regression analysis, individuals living in areas with elevated levels of household density had 1.24-fold increased odds of having high levels of mtDNA copy number [Odds ratio (OR) = 1.24, 95% confidence interval (CIs) 1.08, 1.36]. Similarly, those living in areas with elevated levels of road/intersection ratio had 1.12-fold increased odds of having high levels of mtDNA copy number (OR = 1.12, 95% CI 1.01, 1.27). In further analysis, when both variables were analyzed together in a multivariate logistic regression model, the significant associations remained. In summary, our results suggest that selected built environment variables (e.g. population density and road/intersection ratio) may influence levels of mtDNA copy number in leukocytes in Mexican Americans.
Frequency-dependent sonochemical degradation of perfluoroalkyl substances and numerical analysis of cavity dynamics

Abstract Ultrasonic breakdown of perfluorooctanoic acid and perfluorooctane sulfonic acid were evaluated at various ultrasonic frequency (575 kHz, 860 kHz, and 1140 kHz), pH (3–12), bulk water temperature (14.5–30 °C), and gases (Helium, Nitrogen, Oxygen, Ozone, Argon). Contrary to the result reported in the literature, we observed an increase in the rate kinetics of PFOA and PFOS decomposition in an air environment (i.e., without sparging any gases), at higher pH, and higher bulk water temperature. The rate kinetics of PFOA degradation in gases follows the order as Helium > Nitrogen > Argon > Oxygen > Ozone. The present work concludes that the presence of known/unknown chemical compounds formed during sonolysis, influence the interaction of PFOA and PFOS with the cavity-water interface. The cavity collapse simulation using Gilmore equation showed that an increase in acoustic pressure increases the compression ratio and bubble radial velocity of the collapsible cavity. This study suggests that the lower degradation rate of PFOS as compared to PFOA, over a range of ultrasound frequencies, is due to the lower number of active cavities collapsing at higher temperatures. The radius of active collapsible cavities, with maximum compression ratio and bubble radial velocity, was 3.2 µm, 2 µm, and 1.7 µm at an ultrasonic frequency of 575 kHz, 860 kHz, and 1140 kHz, respectively.
The sounds of prehistoric speech

Evidence is reviewed for widespread phonological and phonetic tendencies in contemporary languages. The evidence is based largely on the frequency of sound types in word lists and in phoneme inventories across the world's languages. The data reviewed point to likely tendencies in the languages of the Upper Palaeolithic. These tendencies include the reliance on specific nasal and voiceless stop consonants, the relative dispreference for posterior voiced consonants and the use of peripheral vowels. More tenuous hypotheses related to prehistoric languages are also reviewed. These include the propositions that such languages lacked labiodental consonants and relied more heavily on vowels, when contrasted to many contemporary languages. Such hypotheses suggest speech has adapted to subtle pressures that may in some cases vary across populations. This article is part of the theme issue 'Reconstructing prehistoric languages'.
Combination targeted treatment may enhance antitumor activity in ERBB3 amplified high-grade serous endometrial cancer cells resistant to single agent targeted therapy

Objectives: Up-regulation of ERBB pathways represent targetable alterations in many high grade endometrial cancers (EC); ERBB3 amplifications in particular may contribute to ineffective pathway targeting due to persistent co-activation of other ERBB binding partners, leading to tumor growth and survival. The efficacy of downstream dual-inhibition of MEK+AKT or MEK+PI3K in an ERBB3 amplified EC primary tumor was studied using a microcancer 3D ex-vivo tumor cell viability assay. Methods: Tumor was prospectively collected from a patient with stage II, FIGO grade 3, serous EC and genomic characterization was performed using multiple sequencing methods: whole exome, RNA, and MatePair analysis. Somatic mutations, structural variance, with transcriptomic profiling was used to identify potential driver pathways for subsequent pharmacologic inhibition. Primary tumor cells were grown in a three-dimensional environment and the formed microcancers were subjected to drug treatment. Cell viability was determined by the CellTiter-Glow Luminescent Assay. Data transformation and dose-response curves were generated using GraphPad PRISM using four parameter logistic regression. CompuSyn software with the Chou-Talalay method was used to analyze drug interactions and synergy. The Fractional response-Combination index (Fa-CI) plot was generated with Microsoft Excel. Capivasertib, GDC-0084, and cobimetinib were used to inhibit AKT, PI3K/mTOR, and MEK, respectively. Inhibitory effect was defined as percent reduction in ATP at clinically-defined predicted plasma maximum concentration (Cmax) values. Results: Genomic sequencing revealed overexpression of a mutated ERBB3 (c.889G>T; p.Asp297Tyr) transcript within a 6N focal amplification. Additional pertinent alterations included a MYC mid-level gain, and TP53 double hit (loss and exonic splicing silencer (ESS)). Inhibition of cell viability was moderate by single agents: capivasertib, cobimetanib, or GDC-0084, as shown by inhibitory effect values of 33.9%, 35.9% and 49.9%, respectively. Two combinations with cobimetinib demonstrated increasing inhibitory effect values of 76.2% for cobimetanib/capivasertib at the Cmax of capivasertib and 79.7% for cobimetanib/GDC-0084 at the Cmax of cobimetanib. Synergy was evidenced by a combination index 0.8 (Figure 1). Download : Download high-res image (185KB) Download : Download full-size image Conclusions: Combined inhibition of MEK and PI3K-AKT-mTOR pathways synergistically suppress viability in a patient-derived high-grade serous EC harboring a ERBB3 amplification. Further ex-vivo testing should be performed in endometrial tumors with other ERBB3 aberrations to allow generalization of results.
Mining the Microenvironment for Therapeutic Targets in Chronic Lymphocytic Leukemia.

ABSTRACT The leukemia cells of patients with chronic lymphocytic leukemia (CLL) are highly fastidious, requiring stimulation by soluble factors and interactions with accessory cells within the supportive niches of lymphoid tissue that comprise the leukemia microenvironment. The advent of therapies that can disrupt some of the stimulatory signaling afforded by the microenvironment has ushered in a new era of targeted therapy, which has dramatically improved clinical outcome and patient survival. Future advances are required for patients who develop intolerance or resistance to current targeted therapies. These may be found by investigating novel drugs that can inhibit identified targets, such as the pathways involved in B-cell receptor signaling, or by developing agents that inhibit additional targets of the leukemia microenvironment. This review describes some of the molecules involved in promoting the growth and/or survival of CLL cells and discusses targeting strategies that may become tomorrow's therapy for patients with CLL.
Making Training Relevant

Abstract Principles of adult learning indicate that field instructor training will be more relevant to the participants when they have an active role in determining both the content and structure of the training. While existing literature suggests content areas for training curricula, field instructors' perceptions of their training needs have not been studied. In this study, focus groups were held to explore field instructors' perceptions of their training needs and identify relevant content and methods for field instructor training programs. Separate focus groups were held with both new and experienced field instructors. Analysis of the focus group interviews identifies several areas of training needs not regularly addressed in the literature, including advanced content concerning their mission and purpose, concrete educational tools to assist in their supervision, and mentoring by experienced field instructors.
Cognitively Impaired Sexually Abused Women: The Most Vulnerable of All?

Edited byJacquelyn H. Flaskerud, RN, PhD, FAANUniversity of California-Los Angeles, School of Nursing, Los Angeles, California, USAThe room was silent and dimly lit. Mary, her eyes closed, lay quie...
Enhanced in Vitro Proliferation and in Vivo Tumorigenic Potential of Mammary Epithelium from BALB/c Mice Exposed in Vivo to γ-Radiation and/or 7,12-Dimethylbenz[a]anthracene

Virgin female BALB/c mice were exposed in vivo to whole body gamma-radiation and/or to 7,12-dimethylbenz[a]anthracene (DMBA) p.o. Mammary epithelial cells were isolated and assayed for carcinogen altered cell populations both in vitro by an epithelial focus assay and in vivo by injection into cleared fat pads of syngeneic host mice. Five groups of mice were exposed as follows: (a) sham controls; (b) 50-rad gamma-radiation; (c) 100-rad gamma-radiation; (d) 75 micrograms DMBA; or (e) 50-rad gamma-radiation followed in 1 week by 75 micrograms DMBA. Mammary epithelial cells were isolated and assayed at 24 h and at 1, 4, 16, and 52 weeks after in vivo exposure. Four to 12 mice per treatment per time point were individually assayed. Altered in vitro growth potential was characterized by the proliferation of carcinogen exposed (but not control) cells as epithelial foci which persisted at least 12 weeks in primary culture. Epithelial foci which could then be subcultured at least four times were termed subculturable epithelial foci. Altered in vivo morphogenic potential was characterized by dysplastic or neoplastic growth in host fat pads. With increased time in situ between exposure and assay, cell populations emerged which exhibited both increased in vitro subculturability and enhanced tumorigenic potential including a host response upon injection in vivo. Further, combined radiation and DMBA resulted in higher frequencies of subculturable epithelial foci than either treatment alone. The relevance of these progressive cellular changes to the process of mammary tumor development is discussed.
Possible 0 -+ glueball candidate X(1835)

The possibility of X(1835) discovered by BESII as a 0{sup -+} glueball is studied in this paper. The decay rates of X(1835){yields}pp, VV are associated with the gluon spin contents of proton and vector mesons, respectively. Estimations of the decay rates of X(1835){yields}VV, {gamma}V, {gamma}{gamma} and the cross sections of {gamma}{gamma}{yields}X(1835){yields}f and h{sub 1}+h{sub 2}{yields}X(1835)+... are presented. It predicts that as a glueball X(1835) is unlikely to be produced in J/{psi} hadronic decays but as a pp it is likely.
Noise in RF Amplifiers

This chapter contains sections titled: Sources of Noise Thermal Noise Shot Noise Noise Circuit Analysis Amplifier Noise Characterization Noise Measurement Noisy Two-Port Circuits Two-Port Noise Factor Derivation Fukui Noise Model for Transistors Problems References
The continuing relevance of F.A. Hayek's political economy

This chapter explores the political economy of F.A. Hayek with emphasis on the continued relevance of his work for contemporary scholars. We focus on the theme of coordination throughout Hayek's research program. This general theme can be traced from Hayek's technical economics up through his later writings in political philosophy. After considering Hayek's major works in political and legal theory, we conclude by discussing the contemporary implications of Hayek's political economy. Specifically, we discuss eight areas where modern economists should pay close attention to the main lessons and themes in Hayek's writings.
Effect of thermal aging on board level drop reliability for Pb-free BGA packages

The drive for Pb-free solders in the microelectronics industry presents several new reliability challenges. Examples include package compatibility with higher process temperatures, new solder compound failure mechanisms, and the selection of the proper Pb-free alloy to maximize product lifetime. In addition to the challenges posed by the Pb-free material conversion, the migration of market focus from desktop computing to portable applications is changing the critical system failure mode of interest from conventional temperature cycling (T/C) induced solder fatigue opens to drop impact induced solder joint fracture. In this paper a study was conducted to investigate the influence of intermetallic compound (IMC) growth on the solder joint reliability of Pb-free ball grid array (BGA) packages under drop loading conditions. Thermal aging at homologous temperatures between 0.76 and 0.91 with microstructural analysis was conducted to analyze the solid phase IMC growth at the solder to BGA pad interface. Component level,ball shear and pull tests were also conducted to investigate the aging effect on solder joint strength. A key finding from this work is that Kirkendall voids formed at the bulk solder to package bare Cu pad interface under relative low 100/spl deg/C aging. Void formation and coalesce is shown to be the dominant mechanism for solder joint strength and board level drop reliability degradation.
Modeling Computer Users' Interest in the World Wide Web across the Adult Life Span: The Role of Age, Education, Ability, and Discontentment

The current study examined the factors related to the interest in Web related activities across the adult life span. Using the mediation model put forth by Ellis and Allaire (in press), the extent to which age, education, Web ability, and Web discontentment are related to computer users' interest in the World Wide Web was examined. It was hypothesized that Web ability and discontentment would fully mediate the effects of age and education on Web interest. Six hundred surveys, sampled from the Project 2000 data (Novak & Hoffman, 1997), were used to examine this model. Using structural equation modeling techniques, the mediation model was largely supported. The Web discontentment was found to fully mediate the effect of Web ability, age and education on Web interest.
Microsomal 17beta-hydroxysteroid dehydrogenase of guinea pig liver: detergent solubilization and a comparison of kinetic and stability properties of bound and solubilized forms.

Abstract Microsomal 17β-hydroxy steroid dehydrogenase of guinea pig liver, solubilized in Triton X-100, was obtained in phospholipid-free form and physical parameters were estimated by agarose gel chromtography and density gradient centrifugation. The values for the sedimentation constant, s20,w = 5.2 s, partial specific volume, v = 0.78 ml/g , and Stokes radius, a = 66 A, indicated a molecular weight of 176,000 for the solubilized enzyme and were consistent with the presence of a significant amount of bound detergent. Triton X-100 was an inhibitor competitive with testosterone with a K1 of 0.11%. With solubilization the apparent km for testosterone was increased from 2.2 μM to 7.3 μM and the apparent KM for NAD+ reduced from 164 to 100 μM. The susceptibility to urea or trypsin inactivation was increased after solubilization. Enzymatic activity was stable for at least 48 h in 1% (v/v) Triton X-100 but was lost within 24 h in deoxycholate. The results show that phospholipids are not absolutely required for activity but the changes in kinetic and stability properties with solubilization are consistent with a role for membrane components or bound detergent in affecting the structure and catalytic properties of the enzyme.
Surface site dependence to negative ion formation

Abstract The processes of electron transfer and dissociative scattering are explored for collisions of hyperthermal NO + on GaAs(110). The experiments reveal a marked angular dependence to O − emergence. A strong correlation between the O − scattering angle and the final atom-surface interaction site provides a map of the lateral dependence to reactivity. The results are modeled by sequential neutralization, dissociation, and electron attachment steps. Classical trajectory calculations, in conjunction with an empirical opacity function, accurately reproduce the experimental results. The opacity function is interpreted as the probability that an electron will attach to a departing O fragment as a function of the last surface site the atom impacts. The experiments indicate that O − emergence occurs predominantly for oxygen atoms which come in close contact with the localized dangling bond states of GaAs(110).
An Inexpensive Optical Scanner for the Laboratory Computer

An electrooptical attachment for an incremental plotter was developed for use with a laboratory computer to provide of digitizing drawings, waveforms, and other graphic Excellent sensitivity was achieved with components than $100. Fiber optics, solid-state devices, and a simple incandescent light source were employed.
HYDROXYSTEROL AND BILE ACID METABOLISM: TRANSITION FROM FETAL TO NEONATAL LIFE

We have developed a noninvasive approach using stable isotopes that describes quantitatively the transition in hydroxysterol and bile acid metabolism. Deuterated (D4)-26-hydroxycholesterol disulfate (50 μg) dissolved in MCT oil is given to normal neonates before initial feeding and diapers collected at approximately 2 hr intervals for 72 hours. Prior to analysis, a radioactive standard is added which permits calculation of total recovery of endogenous and isotopic 26-hydroxycholesterol after quantitation by isotope ratio mass spectrometry. The data from 3 normal neonates indicates rapid excretion of a preformed pool. In one instance, 82% recovery of D4 implied enterohepatic circulation, confirmed by identification of isotope in urine. Our approach (1) defines the normal transition from fetal to neonatal life, (2) gives insight into the role of altered bile acid metabolism in the pathogenesis of neonatal cholestasis (3) is generally applicable to a variety of metabolic pathways.
Factor V Leiden, prothrombin 20210A and the risk of venous thrombosis among cancer patients

Cancer patients have an increased risk of venous thrombosis (VT). The association of factor V Leiden (FVL) and the prothrombin 20210A variant with VT in cancer patients is not established. We genotyped 101 cancer patients with VT and 101 cancer patients without VT for these polymorphisms. Five cases and three controls were heterozygous for FVL, yielding an odds ratio of 1.7 (95% confidence interval (CI) 0.3-10.7). Five cases and no controls were heterozygous for prothrombin 20210A, for an odds ratio of 6.7 (95% CI 0.9-infinity). Prothrombin 20210A may be associated with VT risk among cancer patients.
ISLET CELL DESTRUCTION AND GROWTH STUDIED IN TRANSGENIC ANIMAL MODELS

We have produced and studied several transgenic models of insulin dependent diabetes mellitus (IDDM). For understanding the etiology of IDDM, we have investigated the consequences of expression of host defense molecules in the pancreatic islets. IFN-γ is produced in response to infection and has immune-stimulatory and proliferative activities. To investigate the potential role of IFN-γ in inflammatory autoimmune diseases, transgenic mice expressing IFN-γ in pancreatic beta cells were created. These mice suffer from islet cell loss following the appearance of increasing numbers of lymphocytes within and surrounding the islets. We have studied the islet destruction in these mice and have demonstrated that it is mediated by inflammatory cells. Interestingly a proliferative/regenerative response opposes the lymphocyte destruction. We have recently been characterizing this proliferative axis in the transgenic pancreas. We have acquired evidence that it is initiated by duct cell proliferation and with the appearance of more primitive neuroendocrine progenitor cells along the apical regions of the ducts. The regenerative process in the ins-IFN-γ transgenic mice appears similar to the events that occur during embryonic islet cell development. These studies underscore the lymphokine's ability to initiate a complex “transdifferentiation” pathway within a terminally differentiated structure. Another fascinating molecule with potential relevance for treatment of IDDM is the cytokine IL-10. This molecule appears to have immuno-inhibitory effects that include the suppression of antigen presentation by macrophages. We have recently investigated the effects of the cytokine IL-10 on the pancreatic islets. These efforts were designed to test whether the expression of IL-10 could allow the creation of neutral islet tissue for allografting. Our work demonstrates that this molecule has both the ability to attract lymphocytes in vivo as well as to suppress the anti-islet immune response. We have utilized several experimental protocols to study the in vivo effects of this molecule. The results of these studies argue that this cytokine could be relevant for therapeutic intervention in IDDM. Our methodologies should clarify the potentially pathogenic capabilities of host defense molecules when expressed in vivo. Additional IDDM models, produced by ourselves as well as our colleagues will be discussed.
Feasibility of simultaneous dual-isotope myocardial perfusion acquisition using a lower dose of sestamibi.

The feasibility of simultaneous dual-isotope myocardial perfusion imaging was assessed using a ca. 12 mCi dose of technetium-99m sestamibi (MIBI) and ca. 3 mCi thallium-201. Planar and single-photon emission tomographic (SPET) data from 40 patients (41 studies) imaged with both a single- and a dual-isotope protocol were analyzed. Rest injected201Tl (pure-Tl) images were acquired using 20% windows at 70 and 166 keV about 15 min after the201Tl injection. Patients were then stressed, and at peak stress99mTc-sestamibi was injected. About 30 min later99mTc data were recorded with a 20% window center at 140 keV, and simultaneous201Tl (dual-Tl) data were recorded with a single 20% window centered at 80 keV. Total myocardial counts based on SPET data in the dual-Tl images were increased by 18.61%±2.91% (SEM) (range: −12.8% to 84.1%) compared to pure-Tl images. Region of interest analysis revealed the greater increase in counts in the apical region and the least in the lateral wall. Pure Tl and dual-Tl images were visually evaluated for image quality (IQ) on a five-point scale (0=unacceptable to 4=excellent). Dual-Tl IQ was lower than that of pure-Tl in 61% of cases, and similar in 37% (12% of the pure-Tl and 41% of the dual-Tl images fell into the 0 and 1 categories). Thallium perfusion abnormalities were of similar extent in 70% of segments, less severe in 18%, and more severe in 12%. There was an inverse correlation with patient weight, such that patients weighing more than 180 lbs had substantially worse images than those below this cutoff value. While dual-tracer images are of lower quality, they are interpretable if the patient is not severely overweight.
Overview of future NASA tether applications

The groundwork has been laid for tether applications in space. NASA has developed tether technology for space applications since the 1960's. Important recent milestones include retrieval of a tether in space (TSS-1, 1992), successful deployment of a 20-km-long tether in space (SEDS-1, 1993), and operation of an electrodynamic tether with tether current driven in both directions-power and thrust modes (PMG, 1993). Various types of tethers and systems can be used for space transportation. Short electrodynamic tethers can use solar power to 'push' against a planetary magnetic field to achieve propulsion without the expenditure of propellant. The planned Propulsive Small Expendable Deployer System (ProSEDS) experiment will demonstrate electrodynamic tether thrust during its flight in early 2000. Utilizing completely different physical principles, long non-conducting tethers can exchange momentum between two masses in orbit to place one body into a higher orbit or a transfer orbit for lunar and planetary missions. Recently completed system studies of this concept indicate that it would be a relatively low-cost in-space asset with long-term multi-mission capability. Tethers can also be used to support space science by providing a mechanism for precision formation flying and for reaching regions of the upper atmosphere that were previously inaccessible.
Calf vein thrombi are not a benign finding

Abstract Background: Currently, there is no consensus in the literature regarding which patients with calf vein thrombi are at high risk for proximal propagation. This study examined patients with isolated calf vein thrombi with serial duplex scans in order to identify risk factors that would predict outcome. Patients and methods: Between May 1989 and November 1994, 288 patients were identified with isolated calf vein thrombi. One hundred ninety-two of them had sequential scans performed. Results: Fifty-three (28%) of the 192 patients had propagation of their initial thrombi. The most proximal level of propagation was the popliteal vein in 11 patients, the superficial femoral vein in 5, the common femoral vein in 5, adjacent tibial or soleal veins in 24, adjacent soleal veins alone in 7, and the lesser saphenous vein in 1. Three patients whose thrombi propagated had free-floating thrombus tips in the large veins of their thighs. Symptoms, prophylaxis, and risk factor analysis comparing those patients whose thrombi propagated to those whose thrombi did not found no statistically significant prognostic value. Single or multiple calf vein thrombi did not predict propagation. Of the 23 patients treated with heparin, only 3 had thrombus propagation. None of these reached the level of the knee (including popilteal vein). Conclusions: The natural history of distal lower extremity thrombosis does not appear to be as benign as previously believed.