cssi/SciSciGPT-SciSciNet huggingface dataset:
Resisting the Great Endarkenment: On the Future of Philosophy

Elijah Millgram’s book The Great Endarkenment takes philosophy to task for failing to note the kinds of creatures we are (serial hyperspecializers) and what that means for philosophy. In this commentary, I will complicate the picture he draws, while suggesting a more hopeful path forward. First, I argue that we are not actually serial hyperspecializers. Nevertheless, we are hyperspecializers, and this is the main source of the looming endarkenment. I will suggest that a proper understanding of expertise, particularly the requirement that experts (at least experts whose success is not readily assessable) be required to explicate their judgments helps to mitigate the threat of siloed expertise and endarkenment. Further, I argue that grappling directly with the institutional structures that encourage narrow and isolated hyperspecialists in academia can be a way to avoid endarkenment problems. The current landscape of academia, with its valorization of narrow disciplinary expertise, is neither necessary nor sustainable. In order to change this landscape, we need to understand how current incentives construct epistemic niches, and what we might change in order to reshape the ecology of academia.
Epigenetically Altered T Cells Contribute to Lupus Flares.

Lupus flares when genetically predisposed people encounter exogenous agents such as infections and sun exposure and drugs such as procainamide and hydralazine, but the mechanisms by which these agents trigger the flares has been unclear. Current evidence indicates that procainamide and hydralazine, as well as inflammation caused by the environmental agents, can cause overexpression of genes normally silenced by DNA methylation in CD4+ T cells, converting them into autoreactive, proinflammatory cytotoxic cells that are sufficient to cause lupus in mice, and similar cells are found in patients with active lupus. More recent studies demonstrate that these cells comprise a distinct CD4+ T cell subset, making it a therapeutic target for the treatment of lupus flares. Transcriptional analyses of this subset reveal proteins uniquely expressed by this subset, which may serve as therapeutic to deplete these cells, treating lupus flares.
Abstract OI: Breast Cancer in Young Women: Understanding Differences to Improve Outcomes

Breast cancer is the leading cause of cancer related deaths in women age 40 years and younger in the United States, and a major cause of morbidity and mortality worldwide. Young women are more likely to develop more aggressive subtypes of breast cancer. Emerging data suggest the effect of age on breast cancer recurrence and death varies by tumor subtype, with young age particularly prognostic in women with ER-positive disease. Greater understanding of the biologic and genetic underpinnings of cancers that arise in younger women, potential differences in tumor and host responses including disease presenting in very premenopausal women or recently pregnant women, is critical to develop novel treatments to improve outcomes. There is also mounting evidence that access to care and behavioral differences leading to suboptimal treatment contribute to disparities in young women, including relatively poor adherence to adjuvant hormonal therapy. Prevention, detection and management of non-adherence, with attention to unique issues facing young women including desire for future fertility and pregnancy, has been the subject of recent research for this vulnerable population who, unsurprisingly, are at increased risk of psychosocial distress compared with older breast cancer survivors. Decision-support tools, and innovative, acceptable, scalable interventions to address anxiety and distress are under investigation. Finally, given that most young women will live for many decades after a diagnosis of breast cancer, it is imperative that we follow this population, in particular, over time and study their long-term, late effects in survivorship. Citation Format: Partridge A. Breast Cancer in Young Women: Understanding Differences to Improve Outcomes [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OI.
Hollow fiber gas membrane-based removal and recovery of ammonia from water in three different scales and types of modules

Abstract Ammonia present in many industrial process streams and effluent streams is beginning to be recovered by means of microporous hydrophobic hollow fiber-based membrane contactor devices with gas-filled pores; the process is often characterized as supported gas membrane (SGM) process. Ammonium sulfate is usually obtained in a sulfuric acid stream on the other side of the membrane. It is useful to develop a quantitative basis for the extent of ammonia removal in such devices. Unlike deoxygenation of aqueous streams in such devices, membrane resistance is quite important for ammonia transport. Ammonia transport modeling in such devices is hampered by the complexity of feed liquid flow in the shell side of commercially used devices and lack of information on membrane resistance where membrane tortuosity introduces considerable uncertainty. The approach adopted here involves studying ammonia transport with the feed solution flowing through the hollow fiber bore where the fluid mechanics is simpler than shell-side flows. Comparison of model-based predictions of overall mass transfer coefficient (ko) with experimentally observed values allows estimation of the membrane mass transfer coefficient (km). One can use such estimates of km to model the observed ammonia transport in small crossflow devices and develop an empirical guidance of the dependences of the shell side mass transfer correlations. Guided by such information and deoxygenation SGM literature, a model was developed for large modules used for ammonia recovery via SGM. Model predictions of performances of the large modules are likely to be useful for various process considerations including the effect of temperature and feed flow rate variations on ammonia removal.
Infant Vagal Tone and Maternal Depressive Symptoms: A Bottom-Up Perspective.

Children vary in their susceptibility to environmental exposures such as maternal depression, but little is known about how children shape those same environments. When raising an infant with low a...
Dislocation dynamics in niobium-oxygen

The dislocation velocity-stress exponentm has been calculated from measurements of the strain rate sensitivity of the effective stress τ for single crystals of niobium-oxygen solid solutions which exhibit alloy softening. The values ofm evaluated at small plastic strains are found to be a sensitive function of temperature and oxygen concentration. Analysis of these results in terms of Peierls-Nabarro and dislocation-interstitial solute hardening mechanisms infers the latter is rate controlling. Furthermore, alloy softening is best interpreted in terms of the effects which solute interaction processes have on the thermally activated hardening caused by oxygen.
Many paths to the same goal: metaheuristic operation of brains during natural behavior

Abstract During self-guided behaviors animals rapidly identify the constraints of the problems they face and adaptively employ appropriate cognitive strategies and heuristics to solve these problems1,2. This ability is currently an area of active investigation in artificial intelligence3. Recent work in computer science has suggested that this type of flexible problem solving could be achievable with metaheuristic approaches in which specific algorithms are selected based upon the identified demands of the problem to be solved4,5,6,7. Investigating how animals employ such metaheuristics while solving self-guided natural problems is a fertile area for biologically inspired algorithm development. Here we show that animals adaptively shift cognitive resources between sensory and memory systems during natural behavior to optimize performance under uncertainty. We demonstrate this using a new, laboratory-based discovery method to define the strategies used to solve a difficult optimization scenario, the stochastic “traveling salesman” problem5,8,9. Using this system we precisely manipulated the strength of prior information available to animals as well as the complexity of the problem. We find that rats are capable of efficiently solving this problem, even under conditions in which prior information is unreliable and the space of possible solutions is large. We compared animal performance to a Bayesian search and found that performance is consistent with a metaheuristic approach that adaptively allocates cognitive resources between sensory processing and memory, enhancing sensory acuity and reducing memory load under conditions in which prior information is unreliable. Our findings set the foundation for new approaches to understand the neural substrates of natural behavior as well as the rational development of biologically inspired metaheuristic approaches for complex real-world optimization.
On-site Applied Learning with the Use of Mixed Methods as a Reflective Learning Model in International Business

This chapter discusses a transformational learning model for application within international business courses that is grounded in an on-site learning experience where student teams work on a live corporate challenge. The model offers a two-fold approach. First, for learners to develop skills by: applying the model to learn new skills to address a set problem; improving their ability to seek and receive feedback; reflecting on the feedback and learning; and offering a new proposal. Second, the intention is for faculty to adopt the learning model to design assignments that deliberately assess applied elements of learning, such as adaptive and critical thinking skills.
188 Point-of-care surrogate biomarkers for cervical cancer screening: feasibility of E7 oncoprotein and P16INK4A detection in cervical samples

Objectives As E7 oncoprotein is synthesized in the latter stages of cervical carcinogenesis, it may be a more specific biomarker for dysplasia than Pap and HPV. By sequestering cations, E7 monomers form oligomers detectable by Dynamic Light Scattering (DLS). p16INK4a staining has been used as an adjunct to cytology but not in a point-of-care setting. Our aim is to detect E7 oncoproteins using DLS and p16INK4a using immunodetection in cervical samples. Methods Protein lysates from HeLa cells, which express E7 and p16INK4a, and third trimester placenta (3TP), which do not express E7 or p16INK4a, were characterized by DLS as well as p16INK4a antibody by Western blot to establish positive and negative reference standards, respectively. Patient samples were profiled by DLS and Western blots and correlated with clinical findings. Results Addition of 10mM EDTA resulted in a monomorphic peak at ∼75nm in diameter for HeLa that is distinct from 3TP (∼160nm) by DLS, corresponding to a likely E7 oligomer of ∼1100kDa on native Western blot. 60 patient samples have been collected thus far with DLS patterns that roughly correlate to those seen using cell lines. Western blot probed with p16INK4a antibody was positive and negative for patients with dysplasia/cancer and without cervical abnormalities respectively. Conclusions Preliminary results suggest feasibility of detecting E7 oligomers by DLS and p16INK4a by immunodetection in patient samples and its potential as a point-of-care test. The presence of E7 in patient samples will be confirmed with mass spectrometry and sensitivity and specificity of p16INKa will be determined with additional patient samples.
Designing an Accelerated Graduate Evaluation Course Using the First Principles of Instruction and Interactive Media

Evaluation skills are complex and require careful design to teach effectively. In our master’s program in Instructional Design and Performance Technology, students experienced unnecessary difficult...
Effects of Tilmicosin Treatment on the Nasopharyngeal Microbiota of Feedlot Cattle With Respiratory Disease During the First Week of Clinical Recovery.

While the nasopharyngeal (NP) microbiota is believed to be a key player in bovine respiratory health, there is limited published information about the change of NP microbiota associated with clinical recovery from bovine respiratory disease (BRD). The objective of this study was to evaluate the effect of tilmicosin treatment on the NP microbiota composition and diversity of BRD-affected calves during the first week of clinical recovery. Deep NP swabs were collected from diseased calves at the initial diagnosis of BRD, and again 7 days after the administration of a single dose of tilmicosin. As an experimental control, samples were collected from clinically healthy, pen-matched calves at the time of initial BRD diagnosis. In general, the NP microbiota from the control calves were more diverse than the NP microbiota from tilmicosin treated and BRD-affected calves. Principle coordinate analysis (PCOA) of Bray-Curtis and Jaccard dissimilarity also revealed that the overall composition of NP microbial communities in tilmicosin-treated calves closely resembled that of BRD-affected calves but differed significantly from pen-matched healthy calves. Overall, it appeared that there were only minor changes in NP microbial communities following tilmicosin treatment and, during the early phase of clinical recovery the NP microbiota in treated animals was disparate from that observed in healthy control calves. Understanding the potential impact of this prolonged recovery in mucosal microbiota would be important in optimizing the use of antimicrobials in health management programs in the feedlot industry. Keywords: Respiratory disease, Feedlot, Microbiota, Tilimicosin, 16S rRNA gene.
Experience Design in Leisure and Recreation Curriculum

Experience design is a term that has risen to the forefront in a variety of professional fields and has relevance for the field of park and recreation. Park and recreation professionals are primari...
Police Productivity and Performance Over the Career Course: A Latent Class Growth Analysis of the First 10 Years of Law Enforcement:

The present research investigates the productivity and performance of a large sample of police officers, beginning in the police academy and through their first 10 years of policing. Using longitud...
Chapter 57 – Pulmonary Vasodilators

Publisher Summary Pulmonary hypertension is a serious complication of chronic obstructive pulmonary disease (COPD) and significantly affects its morbidity and mortality. In the context of COPD, acute exacerbations result in worsening gas exchange, which produces acute deteriorations in pulmonary hemodynamics that further compromise oxygen transport to peripheral tissues, thereby resulting in pulmonary hypertension. The rationale for the use of vasodilators treating pulmonary hypertension in COPD is based on the fact that active vasoconstriction is a key element in its pathogenesis, and some systemic vasodilators exert this effect on the pulmonary circulation, thereby resulting in reducing pulmonary artery pressure. However, remodeling also plays a vital role in the pulmonary hypertensive state. Therefore, antihypertensive drugs that also have vascular remodeling effects are preferred to treat hypertensive pulmonary vascular disease. With advances in the understanding of the molecular basis for the pulmonary vascular remodeling in COPD, it can be noted that targeted therapy can be feasible and combined with other modalities to prevent or treat the vascular complications of end-stage chronic obstructive pulmonary disease.
Fracture Mechanics and Composite Materials: A Critical Analysis

The emergence of advanced filamentary composite materials as a structural material comes at a time of increasing concern over reliability. This places increasing emphasis on the ability to characterize the fracture and fatigue behavior of these materials. The importance of understanding fracture behavior is intensified because of the characteristic statistical variability in material strength and the observation of fracture phenomena that are significantly different from those of metals. This paper discusses what appear to be the three main approaches being pursued. The first applies classical fracture mechanics (CFM) on a macroscopic level, treating composites as homogeneous, anisotropic materials. The second recognizes material heterogeneity and applies CFM to the problems of crack propagation in the matrix and fiber phases and interfaces separately. The third method, which might be called the material modeling approach, uses approximate models in order to represent the major effects of heterogeneity and simplify the analysis. The advantages and limitations of each of the three approaches are discussed and predictions compared with available experimental data. The emphasis is on material modeling, and it is shown that with the use of relatively simple models it is possible to predict many of the unusual fracture phenomena that are observed.
The role of health literacy, depression, disease knowledge, and self-efficacy in self-care among adults with heart failure: An updated model.

Abstract Background Patients with inadequate health literacy and heart failure face high healthcare costs, more hospitalizations, and greater mortality. To address these negative consequences, patients need to improve heart failure self-care. Multiple factors may influence self-care, but the exact model by which they do so is not fully understood. Objectives The objective of this study was to examine a model exploring the contribution of health literacy, depression, disease knowledge, and self-efficacy to the performance of heart failure self-care. Methods Using a cross-sectional design, patients were recruited from a heart failure clinic and completed validated assessments of their cognition, health literacy, depression, knowledge, self-efficacy and self-care. Patients were separated into two groups according to their health literacy level: inadequate/marginal and adequate. Differences between groups were assessed with an independent t-test. Hypothesized paths and mediated relationships were estimated and tested using observed variable path analysis. Results Participants (n = 100) were mainly male (67%), white (93%), and at least had a high school education (85%). Health literacy was associated with disease knowledge (path coefficient=0.346, p = 0.002), depression was negatively associated with self-efficacy (path coefficient=-0.211, p = 0.037), self-efficacy was positively associated with self-care (path coefficient=0.402, p Conclusions Self-efficacy and depression are associated with heart failure self-care. Data generated from the model suggest that healthcare professionals should actively engage all patients to gain self-efficacy and address depression to positively affect heart failure self-care.
Setting One’s Sights on Sight: Observations on Sense Perception in Sayf al-Dīn al-Āmidī

This chapter considers the possible philosophical motivation driving al-Āmidī’s theory of vision as it appears in his Kashf, which is a super-commentary on Fakhr al-Dīn al-Rāzī’s commentary on Avicenna’s Ishārāt. It suggests how certain advancements in medieval Islamic theories of vision (like the punctiform analysis of light) affected theories of cognition as well as how developments in one’s theory of cognition (such as the rejection of the assimilation theory of perception) affected one’s theory of vision. The chapter concludes with an alternative explanation to that of Laura Hassan for al-Āmidī’s apparent rejection of his earlier theory of vision.
Tumor immune microenvironment in brain metastases from gynecologic malignancies.

The density and distribution of the tumor immune microenvironment associated with brain metastases (BM) from gynecologic malignancies are unknown and have not been previously reported. We sought to describe the clinical features of a cohort of patients with BM from gynecologic malignancies and to characterize the tumor immune microenvironment from available archival surgical specimens. We performed a retrospective review of electronic medical records from 2002 to 2018 for patients with BM from gynecologic malignancies. Data on patient characteristics, treatment regimens, and clinical outcomes were procured. CD4, CD8, CD45RO, CD68, CD163, and FOXP3 immunohistochemistry were evaluated from available archival surgical specimens from primary disease site and neurosurgical resection. A cohort of 44 patients with BM from gynecologic malignancies was identified, 21 (47.7%) endometrial primaries and 23 (52.3%) ovarian primaries. Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) were evaluated in 13 primary cases and 15 BM cases. For the 13 primary cases, CD4+ TILs were evident in 76.9% of cases, CD8+ in 92.3%, CD45RO+ in 92.3%, and FOXP3+ in 46.2%, as well as CD68+ TAMs in 100% and CD163+ in 100%. For the 15 BM cases, CD4+ TILs were evident in 60.0% of cases, CD8+ in 93.3%, CD45RO+ in 73.3%, and FOXP3+ in 35.7%, as well as CD68+ TAMs in 86.7% and CD163+ in 100%. An active tumor immune microenvironment is present with similar distribution in the primary disease site and BM from patients with gynecologic malignancies.
Microbiological Water Quality for Optimal Livestock Production and Health

Relative to standards for humans, water in the cattle environment is often of poor or unknown microbiological quality, whether it is surface drinking water, recycled flush water, wash water, cooling water or drinking water in troughs. The microbial ecology is complex and not well understood. Microbial contamination originates from the environment, the feces of cattle or other animals, and, due to oral residues, even the normal act of drinking. In many circumstances, the quality is regarded as uncontrollable at best. Although pathogenic bacteria and zoonotic foodborne pathogens are found in cattle water with some frequency, the health, production and food safety risks associated with cattle drinking or contacting water contaminated with these microorganisms remains largely undefined. As production and health consequences from the presence of these agents are certainly biologically plausible and some evidence suggests that they do exist, additional research is needed to quantify these risks. If these risks prove to be unacceptable under current management conditions and consumer expectations, methods to ensure microbiologically cleaner water for livestock will need to be identified.
An Optimized Zebrafish Nursery Feeding Regimen Improves Growth Rates and Labor Costs.

Setting nutritional standards for larval zebrafish (Danio rerio) that maximize growth, survival, and reproductive success is challenging. We evaluated the effects of different feeding regimens on l...
Raising doubt about the anticipated consequences of suicidal behavior: Evidence for a new approach from laboratory and real-world experiments

Abstract Objective Converging evidence from basic science and experimental suicide research suggest that the anticipated consequences of suicide may have direct causal effects on suicidal behavior and accordingly represent a promising intervention target. Raising doubt about individuals’ desirable anticipated consequences of suicide may be one means of disrupting this target. We tested this possibility across two complementary experimental studies. Method Study 1 tested the effects of raising doubt about desirable anticipated consequences on virtual reality (VR) suicide in the lab, randomizing 413 participants across four conditions. In Study 2, 226 suicidal adults were randomized to an anticipated consequence manipulation or control condition then re-assessed at 2- and 8-weeks post-baseline. Results In Study 1, anticipating that engaging in VR suicide would guarantee a desirable outcome significantly increased the VR suicide rate; conversely, raising doubt about the desirable anticipated consequences significantly reduced the VR suicide rate. In Study 2, raising doubt about the anticipated consequences of attempting suicide by firearm significantly reduced the perceived lethality of firearms as well as self-predicted likelihood of future suicide attempts, with effects sustained at 2-week follow-up. Conclusions Findings suggest that raising doubt about desirable anticipated consequences of suicide merits further research as one potential approach to inhibit suicidal behavior.
Acute amiodarone pulmonary toxicity in the form of organizing pneumonia triggered by orthotopic heart transplantation

We report a case of a 60-year-old man who underwent orthotopic heart transplantation after short-term receipt of low-dose oral amiodarone for the management of ventricular tachycardia. Prior to transplant surgery, he had a normal chest radiograph and was free of supplemental oxygen. His initial postoperative chest radiograph showed subtle infiltrates, and thereafter his chest imaging continued to worsen. Although he was eventually able to wean off mechanical ventilation via a tracheostomy, he remained dyspneic and oxygen-dependent with persistently abnormal chest imaging as his post-transplant corticosteroid regimen was being tapered. In light of progressively worsening diffuse lung disease, he underwent bronchoscopy with transbronchial biopsies. Histology revealed foamy macrophages in association with foci of organizing pneumonia, a picture consistent with amiodarone pulmonary toxicity. Given these findings, corticosteroid dosing was increased for the clinical diagnosis of acute amiodarone pulmonary toxicity with subsequent normalization of oxygen saturation and chest radiography. Our case is the first to identify orthotopic heart transplantation as a potential trigger for acute amiodarone pulmonary toxicity. It is also only the second documented example of organizing pneumonia as the histological substrate of amiodarone pulmonary toxicity, which is an association that has therapeutic implications.
Project evaluation with crowding out effects

Consider the technically feasible project (AX; AX^^; AX^) * Project output AX is achieved using a technology requiring the use of AX^ of input 1 and the quantity AX2 of input 2, If the project is scale neutral then we may write the technology of the project as (1; AX^^/^; ^2/^) where th latter ratios are input-output coefficients.-^ Both the scale and the input-output ratios are chosen autonomously but not arbitrarily. Typically the project output-input vector will reflect specific technological innovations such that it is not a subset of the currently known industry production function or technology set. The choice of project scale and s. ' * * technology reflects the (economic) rationality of the agency that proposes the project.
The First Account of Transcendental Perfect Identity: The Foundation of Secret Causes

Proto-objects, I claim, are the necessary conceptual building blocks for an idea of an object that admits of perfect identity. Also, ideas of objects that admit of perfect identity, must, according to Hume, be imagined. In this chapter, we examine Hume’s somewhat implicit first account of perfect identity, given in 1.3.2. In the course of doing so, we begin to see how and why proto-objects enable us to imagine objects that admit of a perfect identity. However, the reader should note that this chapter merely serves as an introduction to Hume’s theory of imagined causes and perfect identity, while Chaps. 6, 7, and 8 provide us with a more fully-developed version.
Abstract 18257: Cardiovascular Response to Energy Drink Consumption in Healthy Adults

Introduction: An increasing number of healthy adults consume energy drinks to enhance their physical and mental performance. Energy drinks contain caffeine and multiple other “natural” stimulants and their combined effects on cardiac hemodynamics in healthy individuals are unclear. Hypothesis: We hypothesized that drinking a commercially available energy drink, Rockstar , compared to a placebo drink, increases resting blood pressure and heart rate in healthy adults, and these increases would be further accentuated by stress conditions. Methods: We enrolled 25 healthy, normotensive subjects (14 males), aged 29±1 years, with body mass index 24.5±1 kg/m 2 , in a randomized, double-blind, placebo-controlled, crossover study. Each subject consumed a placebo drink and a commercially available Rockstar energy drink (473 ml), in random order on two separate study days. Blood pressure and heart rate responses were recorded and compared before and 30 minutes after drink consumption, both at rest and then in response to physical, mental and cold stressors. Results: The Rockstar energy drink induced a 6±1% increase in resting systolic blood pressure, compared to 3±1% with the placebo drink (P=0.0078). Diastolic blood pressure increased by 7±1% vs 0±1% with the placebo drink (P=0.0007; Figure 1). Heart rate increased similarly in both groups, by 5±2% in the energy drink group vs. 7±2% in the placebo group. Blood pressure and heart rate increases during the stress stimuli (sustained handgrip, mental stress and cold stress) did not differ between energy drink and placebo. Conclusions: Drinking a commercially available Rockstar energy drink significantly increases resting blood pressure in young healthy adults. Blood pressure increases are not further accentuated by exercise, mental or cold pressor stress stimuli. These hemodynamic changes induced by energy drink consumption could predispose to cardiovascular events.
Mucosal Pathogenesis of HIV Infection

Like HIV-infected humans, simian immunodeficiency virus rapidly and selectively infects, replicates in, and destroys memory CD4+ T cells co-expressing CCR5 (viral "target"cells) resulting in loss of the majority of the bodies CD4+ T cell pool within 21 days of infection. The vast majority of these cells reside in the intestinal tract and other mucosal tissues but selective loss of these target cells is detectable throughout the lymphoid system. Restoration of memory CD4+CCR5+ T cells directly correlates with improved clinical course and lower viremia, but these cells are never restored in macaques that progress to AIDS. Continuous and effective antiviral treatment initiated within days of SIV infection can rescue mucosal CD4+ T cells, but delaying therapy for a couple of weeks does not restore these vital helper memory cells, despite effective control of viremia. Similarly, monkeys that "appear" protected in vaccine challenge studies may in fact harbor smouldering infection in the intestine with continuous CD4+ T cell loss, despite undetectable plasma viremia. The rapidity and severity of the loss of memory CD4+ T cell function is likely the major reason no cure or vaccine is in sight. In fact, converging evidence suggests that other primate species changed fundamental properties of their immune system, such as eliminating the need for CD4+CCR5+ T cells (yet maintaining CD8+CCR5+ T cells), rather than cope with this subversive infection. This and other data suggest that conventional immune responses simply may not be adequate to control or prevent HIV infection. from 2005 International Meeting of The Institute of Human Virology Baltimore, USA, 29 August – 2 September 2005
A novel two-step optimization method for tandem and ovoid high-dose-rate brachytherapy treatment for locally advanced cervical cancer

Abstract Purpose To present a novel method allowing fast volumetric optimization of tandem and ovoid high-dose-rate treatments and to quantify its benefits. Methods and Materials Twenty-seven CT-based treatment plans from 6 consecutive cervical cancer patients treated with four to five intracavitary tandem and ovoid insertions were used. Initial single-step optimized plans were manually optimized, approved, and delivered plans created with a goal to cover high-risk clinical target volume (HR-CTV) with D90 >90% and minimize rectum, bladder, and sigmoid D2cc. For the two-step optimized (TSO) plan, each single-step optimized plan was replanned adding a structure created from prescription isodose line to the existent physician delineated HR-CTV, rectum, bladder, and sigmoid. New, more rigorous dose–volume histogram constraints for the critical organs at risks (OARs) were used for the optimization. HR-CTV D90 and OAR D2ccs were evaluated in both plans. Results TSO plans had consistently smaller D2ccs for all three OARs while preserving HR-CTV D90. On plans with “excellent” CTV coverage, average D90 of 96% (91–102%), sigmoid, bladder, and rectum D2cc, respectively, reduced on average by 37% (16–73%), 28% (20–47%), and 27% (15–45%). Similar reductions were obtained on plans with “good” coverage, average D90 of 93% (90–99%). For plans with “inferior” coverage, average D90 of 81%, the coverage increased to 87% with concurrent D2cc reductions of 31%, 18%, and 11% for sigmoid, bladder, and rectum, respectively. Conclusions The TSO can be added with minimal planning time increase but with the potential of dramatic and systematic reductions in OAR D2ccs and in some cases with concurrent increase in target dose coverage. These single-fraction modifications would be magnified over the course of four to five intracavitary insertions and may have real clinical implications in terms of decreasing both acute and late toxicities.
Polysulfane Antitumor Agents from o-Benzyne. An Odd−Even Alternation Found in the Stability of Products o-C6H4Sx (x = 1−8)

Benzyne is shown to add elemental sulfur and give rise to a series of polysulfane compounds. A computational and experimental study is presented. Odd-membered o-C6H4Sx rings (x = 1-8), except x = 1, which suffers from ring strain, have enhanced stability compared to even-membered rings. The acquisition of "odd-even" data may shed new light, revealing patterns on polysulfane stability and structure.
Should Scientific Publication be Controlled

AFTER a delay of many years, the great work (576 pages, 67 plates) on the Caddis flies, by Cornelius Betten, has at last been published by the New York State Museum at Albany. It is reviewed by Dr. C. H. Kennedy in Annals of the Entomological Society of America, June 1935. The reviewer remarks: ” This much needed volume has finally appeared. The reviewer saw the revised manuscript at Cornell in 1915. It had been practically completed nine years before. Projects of more immediate use to the tax-payer used the Museum funds that had been planned for its publication. One new species after another was scooped by various casual students of the order. The last scoop was accomplished by one who had had the privilege of studying the manuscript and who rushed two papers through by publishing privately after the present volume was on the press.”
Use of and inhospital outcomes after early clopidogrel therapy in patients not undergoing an early invasive strategy for treatment of non-ST-segment elevation myocardial infarction: Results from Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association guidelines (CRUSADE)

Background Although current guidelines recommend early initiation of clopidogrel in patients with non–ST-segment elevation myocardial infarction (NSTEMI), the degree to which it has been adopted in clinical practice remains unclear. We sought to determine patterns of early ( Methods Using data from the CRUSADE initiative, after the exclusion of patients who underwent PCI within 24 hours of arrival, we studied trends in early clopidogrel use among 93,045 patients with NSTEMI. Multivariable logistic regression models were used to determine the association between early clopidogrel treatment and inhospital outcomes. Results A total of 38.6% of the NSTEMI patients not undergoing PCI within 24 hours of arrival received early clopidogrel. Adjusted inhospital mortality rate was lower in the early clopidogrel group compared to the group that did not receive it on admission (odds ratio 0.68, 95% CI 0.61-0.77). The rate of major bleeding in patients not undergoing coronary artery bypass surgery was similar among the groups treated with and without early clopidogrel (9.5% vs 9.5%, P = .90). Conclusions Until recently, up to 50% of NSTEMI patients in contemporary practice in the United States not undergoing PCI within 24 hours of arrival in the United States are not treated according to guideline recommendations. Among a high-risk NSTEMI population not undergoing PCI within 24 hours of arrival, the nonrandomized short-term use of clopidogrel is associated with a lower risk of inhospital mortality without an increased risk of major bleeding.
1453 COMPARISON OF INTRAVENOUS AND INTRAMUSCULAR ADMINISTRATION OF GENTAMICIN IN NEONATES

Intravenous (IV) genta is widely used in neonates, however a constant IV site may be difficult in prematures. We compared the pharmacokinetic profile of genta after IV and IM therapy in 16 neonates during the first wk of life. Genta was given (2.5 mg/kg/12 hr) IV as an infusion over 5 minutes on study days 1 & 2, then IM on days 3 & 4. In Group I, serum samples were obtained by heelstick 2,4,7, and 12 hours after genta was given IV on day 2 (4th dose) and after IM on day 4 (8th dose). In Group II, serum samples were obtained prior to and 20, 40, 60 and 120 minutes after IV and IM genta administration on day 2 and 4 respectively. Serum creatinine were also determined. All samples were frozen until analyzed by enzyme immunoassay (*EMIT system-Syva Corp.). Mean serum concentration obtained for both IV and IM routes in Groupl and II were similar (p>0.05). Peak serum concentrations were attained at approximately 20-40′ after IM administration for most patients and at or prior to 20′ for IV administration. t-test for mean serum concentrations at 120′ between Group I and II for bothlV and IM administration revealed no significant difference (p>0.05). This suggests that the combined serum concentration profiles generated in Group I and II could reflect actual serum concentrations of individual patients throughout the entire dosing period. IM administration of genta offers rapid drug absorption in neonates and provides serum drug concentration comparable to IV administration.Therefore, IM administration of genta can be a reasonable alternative to IV administration.
The dimensionality of movement trajectories and the degrees of freedom problem: A tutorial

Abstract A framework for investigating the degrees of freedom problem (how the large number of degrees of freedom ( df s) at micro-levels of analysis are compressed to the smaller number of df s at the macro-level of behavior) is discussed. The discussion centers around the use of dynamical systems as models of coordinative structures. Dimensionality analysis, a technique for assessing the df s of an observable behavior, is explained both intuitively and in detail. By measuring the df s being produced by actors, we can constrain our dynamical models of how actors produce coordinated behavior.
A 43-Nucleotide RNACis-Acting Element Governs the Site-Specific Formation of the 3′ End of a Poxvirus Late mRNA☆

The 3' ends of late mRNAs of the ati gene, encoding the major component of the A-type inclusions, are generated by endoribonucleolytic cleavage at a specific site in the primary transcript [Antczak et al., (1992), Proc. Natl. Acad. Sci. USA 89, 12033-12037]. In this study, sequence analysis of cDNAs of the 3' ends of ati mRNAs showed these mRNAs are 3' polyadenylated at the RNA cleavage site. This suggests that ati mRNA 3' end formation involves cleavage of a late transcript, with subsequent 3' polyadenylation of the 5' cleavage product. The RNA cis-acting element, the AX element, directing orientation-dependent formation of these mRNA 3' ends, was mapped to a 345-bp AluI-XbaI fragment. Deletion analyses of this fragment showed that the boundaries of the AX element are within -5 and +38 of the RNA cleavage site. Scanning mutagenesis showed that the AX element contains at least two subelements: subelement I, 5'-UUUAU downward arrowCCGAUAAUUC-3', containing the cleavage site ( downward arrow), separated from the downstream subelement II, 5'-AAUUUCGGAUUUGAAUGC-3', by a 10-nucleotide region, whose composition may be altered without effect on RNA 3' end formation. These features, which differ from those of other elements controlling RNA processing, suggest that the AX element is a component of a novel mechanism of RNA 3' end formation.
Matching pursuit for imaging high-contrast conductivity

We show that imaging an isotropic, high contrast, conductive medium is asymptotically equivalent to the identification of a unique resistor network, given measurements of currents and voltages at the boundary. We show that a matching pursuit approach can be used effectively towards the numerical solution of the high-contrast imaging problem, if the library of functions is constructed carefully and in accordance with the asymptotic theory. We also show how other libraries of functions that at first glance seem reasonable, in fact, do not work well. When the contrast in the conductivity is not so high, we show that wavelets can be used, especially non-orthogonal wavelet libraries. However, the library of functions that is based on the high-contrast asymptotic theory is more robust, even for intermediate contrasts, and especially so in the presence of noise.
Propagation and second-harmonic generation of electromagnetic waves in a coupled-resonator optical waveguide

Using both the tight-binding approximation and the finite-difference time domain method, we analyze two types of coupled-resonator optical waveguide (CROW), a coupled-microdisks waveguide and a waveguide composed of coupled defect cavities in a two-dimensional photonic crystal. We find that the dispersion relation of the CROW band can be simply described by a small coupling parameter , and the spatial characteristics of the CROW modes remain the same as those of the single-resonator high Q modes. As applications of these unique properties, we demonstrate that CROWs can be utilized in constructing waveguides without cross talk and enhance the efficiency of second-harmonic generation.
Death of follicular lymphoma cells—the long and the short of it

The low-grade lymphomas are characterized by low rates of cell proliferation with alterations in the regulation of apoptosis. In follicular lymphoma, there are near invariable high levels of expression of B-cell leukemia/lymphoma-2 (BCL-2), in most cases as a result of dysregulation of the bcl-2
The Superoxide Synthases of Rose Cells : Comparison of Assays

In an effort to identify the enzymatic mechanism responsible for the synthesis of reactive oxygen species produced during the hypersensitive response, preparations of rose (Rosa damascena) cell plasma membranes, partially solubilized plasma membrane protein, and cytosol were assayed for the NADH- and NADPH-dependent synthesis of superoxide using assays for the reduction of cytochrome c (Cyt c), assays for the reduction of nitroblue tetrazolium, and assays for the chemiluminescence of N,N'-dimethyl-9,9'-biacridium dinitrate (lucigenin). Each assay ascribed the highest activity to a different preparation: the Cyt c assay to cytosol, the nitroblue tetrazolium assay to plasma membrane, and the lucigenin assay to the partially solubilized plasma membrane protein (with NADH). This suggests that no two assays measure the same set of enzymes and that none of the assays is suitable for comparisons of superoxide synthesis among different cell fractions. With the plasma membrane preparation, the presence of large amounts of superoxide-dismutase-insensitive Cyt c reductase confounded attempts to use Cyt c to measure superoxide synthesis. With the partially solubilized membrane protein, direct reduction of lucigenin probably contributed to the chemiluminescence. Superoxide synthesis detected with lucigenin should be confirmed by superoxide-dismutase-sensitive Cyt c reduction.
The development and fine structure of the allantoic placental barrier in the bat Tadarida brasiliensis cynocephalal

A light- and electron microscopic study of the establishment and differentiation of the chorioallantoic placenta in Tadarida has been completed. A hemochorial placental relationship has been shown to exist throughout the entire functional state of this structure. Maternal endothelium is present in the larger vessels but not in the smaller channels of the labyrinth. The electron microscope has revealed that the trophoblast surrounding the maternal channels is cellular, not syncytial as previously thought, and that the apical plasma membrane of these trophoblastic cells is in direct contact with the maternal blood. The misconception of an “enucleate” maternal endothelium has been shown to be the result of activity by the trophoblast. The trophoblast displaces a homogeneous substance that is present in the center of the trophoblastic cord prior to maternal blood flow to an intermittent ring beneath the surface of the cells. A thin layer of trophoblastic cytoplasm remains above this ring in contact with the maternal blood. This layer was previously interpreted as an “enucleate” maternal endothelium. A sparse population of microvilli extends from the trophoblast into the maternal blood and, as the length of gestation increases, numerous coated vesicles are seen within the trophoblastic portion of the barrier. At term, the placental barrier may be reduced to less than 0.04 μ. This barrier comprises a thin layer of trophoblast—a basement membrane common to both the trophoblast and the fetal endothelium which is also part of the barrier.
Academic perspectives on dietary supplements use: the need for new guidelines.

The use of bdietary supplementsQ in the United States has escalated in the past decade, driven by the public’s desire to exert control over their health and by the mistaken belief that the safety of dietary supplements is assured by the FDA. In fact, the marketing of largely unregulated herbal supplements presents significant risks to public health (Fig. 1) [1]. A major driving force in creating this situation was the passage of the 1994 federal law governing dietary supplements, which effectively freed the dietary supplement industry from oversight by transferring the burden of proof for establishing safety from the manufacturer to the FDA. As a result, botanical products, in particular, lack the basic safeguards that accompany marketing of over-the-counter and prescription drugs. All persons taking non-standardized, untested supplements are thus at risk of encountering adverse effects, with certain populations being at significantly increased risk, such as those taking prescription drugs together with herbal remedies. Also of concern is the abundance of misleading information on herbal supplements that appears in popular magazines and on the Internet; likewise, in advertising promoting the $27 billion-a-year dietary supplement industry. Consumer misinformation is
Multiple modes of inhibition of spore germination and outgrowth by reduced pH and sorbate

Germination and outgrowth of three strains of Clostridium botulinum in PYEG medium were measured by phase contrast microscopy. Reduction in pH from 7 to 5.5 completely inhibited germination of strain 12885A, reduced the extent of germination of strain 62A and had no effect on the extent of germination of strain 53B. At pH 5.5, 225 mg/l of undissociated sorbic acid had no effect on the germination of strain 53B, while at pH 6.5, 225 mg/l of undissociated sorbic acid completely inhibited germination of strains 62A and 12885A. Outgrowth of germinated spores of strains 62A and 53B was not inhibited at pH 5.5, but the addition of sorbate (225 mg/l undissociated sorbic acid) completely inhibited outgrowth. Sorbate inhibited germination of Cl. botulinum and Bacillus cereus spores triggered to germinate by amino acids. Inhibition occurred after germinant binding, as measured by commitment to germinate.