cssi/SciSciGPT-SciSciNet huggingface dataset:
Analyzing Mitochondrial Function in Brown Adipocytes with a Bioenergetic Analyzer

Brown adipocytes are a cell type with high mitochondrial content and bioenergetic capacity. A critical means to measure mitochondrial function, macromolecule fuel usage, and other important phenotypes is with a bioenergetic analyzer. Here, we describe how to isolate, culture, and differentiate brown preadipocytes into mature adipocytes. We also explain how to perform a mitochondrial (mito) stress test, using the bioenergetic analyzer. The mito stress test is able to give researchers a plethora of insights into mitochondrial function, including basal respiration, proton leak, ATP production, maximal respiration, and reserve capacity, making it a powerful tool for analyzing brown adipocytes.
PHYSICIAN CHARACTERISTICS THAT INFLUENCE PATIENT PARTICIPATION IN THE TREATMENT OF PRIMARY IMMUNODEFICIENCY.

Abstract Objective Shared decision making (SDM) is recommended to improve healthcare quality. Physicians who use a rational decision-making style and patient-centric approach are more likely to incorporate SDM into clinical practice. This paper explores how certain physician characteristics such as gender, age, race, experience, and specialty explain patient participation. Methods A multi-group structural equation model tested the relationship between physician decision-making styles, patient-centered care, physician characteristics, and patient participation in clinical treatment decisions. A survey was completed by 330 physicians who treat primary immunodeficiency. Sample group responses were compared between groups across specialty, age, race, experience, or gender. Results A patient-centric approach was the main factor that encouraged SDM independent of physician decision-making style with both treatment protocols and product choices. The positive effect of patient-centrism is stronger for immunologists, more experienced physicians, or male physicians. A rational decision-making style increases participation for non-immunologists, older physicians, white physicians, less-experienced physicians and female physicians. Conclusion A patient-centric approach, rational decision-making and certain physician characteristics help explain patient participation in clinical decisions. Practice Implications Future SDM research and policy initiatives should focus on physician adoption of patient-centric approaches to chronic care diseases and the potential bias associated with physician characteristics and decision-making style.
Stage Presentation, Care Patterns, Treatment Outcomes, and Impact of Radiotherapy on Overall Survival for Adrenocortical Carcinoma.

Abstract Introduction Adrenocortical carcinoma (ACC) is a rare cancer with few well-powered studies regarding epidemiology or outcomes and even fewer studies to guide an evidence-based management approach. The effect of radiation therapy (RT) is particularly understudied and remains unclear, outside of general oncologic principles. We sought to describe current care patterns in the management of ACC and how these practices affect survival outcomes using the Surveillance, Epidemiology, and End Results (SEER) database. Methods Patients with ACC who could be staged by the American Joint Committee on Cancer (AJCC) system diagnosed between 1988 and 2015 were included. A classification and regression tree analysis identified subgroups of patients who may have benefitted from RT. Multivariable Cox regression analysis was used to compare overall survival (OS). Propensity score adjustment was used to compare OS for a subset of node-negative, nonmetastatic patients who received adjuvant RT following radical surgery. Results Among 865 eligible patients included in the analysis, only 10.5% received RT. In stage III node-negative patients, adjuvant RT following radical surgery was associated with a significantly improved OS compared with surgery alone. Conclusion Medically fit persons with stage III, node-negative ACC should receive adjuvant RT after surgical resection.
Concealment of a Sexual Minority Identity in the Workplace: The Role of Workplace Climate and Identity Centrality.

Concealing a sexual minority identity at work has been linked to adverse health and employment outcomes. The authors of this paper examine whether LGBQ employee levels of concealment from coworkers...
Virtual reality and celebrity humanitarianism: Rashida Jones in Lebanon:

The paper brings together two segments of contemporary humanitarian practice – celebrity advocacy and virtual reality (VR) – in order to more fully comprehend the relationship between emergent tech...
Spectrally filtered photodiode pairs for on-chip ratiometric aptasensing of cytokine dynamics

Abstract Miniaturized, cost-effective cytokine sensing devices are essential for health monitoring and critical care of patients with acute immune responses. Here we report an on-chip ratiometric aptasensing device to monitor the dynamics of an essential immune response biomarker, interferon-gamma. Our device is formed by pairs of spectrally filtered silicon photodiodes that are surface functionalized with aptamer probes. These photodiode pairs are able to rapidly detect two-color fluorescence changes transduced from aptamer-cytokine binding events within c.a. 6 min at picomolar levels, which are sufficient to capture the cytokine transients in point-of-care settings. Furthermore, our device can be reset to baseline by simple washing steps, yielding consistent readout in consecutive runs. Combined with their chip-scale construct and real-time operation, our cytokine sensors may have possible use in point-of-care and therapeutic screening applications.
Repeat angiography in patients undergoing conventional catheter-directed thrombolysis for submassive pulmonary embolism: a large single-center experience.

Purpose Few studies have examined conventional catheter directed thrombolysis (CDT) for the treatment of submassive pulmonary embolism (PE). Moreover, angiographic resolution of thrombus burden following CDT has infrequently been characterized. This study describes a single-center experience treating submassive PE with CDT while utilizing repeat angiography to determine treatment efficacy. Methods A retrospective analysis of 140 consecutive patients who underwent CDT for submassive PE from December 2012 to June 2019 was performed. Angiographic resolution of thrombus burden after CDT was reported as high (>75%), moderate (51-75%), low (26-50%), or insignificant (≤25%). All angiograms were reviewed by two interventional radiologists. Secondary endpoints included reduction in pulmonary artery pressure (PAP) and clinical outcomes. Bleeding events were classified according to the Society of Interventional Radiology (SIR) adverse event criteria. Results CDT was performed in 140 patients with a mean rtPA dose of 25.3 mg and a mean treatment time of 26.0 hours. Angiographic resolution of thrombus burden was high in 70.0%, moderate in 19.3%, low in 5.7%, and insignificant in 3.6%; in 2 patients (1.4%) repeat angiography was not performed. Systolic PAP was reduced (47 vs. 35 mmHg, p Conclusion In patients with submassive PE undergoing CDT, angiographic resolution of thrombus burden is a safe and directly observable metric that can be used to determine procedural success. In this study, CDT with repeat angiography was associated with a 5.7% bleeding event rate and thirty-day mortality of 1.4%.
Vagal neuron expression of the microbiota-derived metabolite receptor, free fatty acid receptor (FFAR3), is necessary for normal feeding behavior

Abstract Objective The vagus nerve provides a direct line of communication between the gut and the brain for proper regulation of energy balance and glucose homeostasis. Short-chain fatty acids (SCFAs) produced via gut microbiota fermentation of dietary fiber have been proposed to regulate host metabolism and feeding behavior via the vagus nerve, but the molecular mechanisms have not yet been elucidated. We sought to identify the G-protein-coupled receptors within vagal neurons that mediate the physiological and therapeutic benefits of SCFAs. Methods SCFA, particularly propionate, signaling occurs via free fatty acid receptor 3 (FFAR3), that we found expressed in vagal sensory neurons innervating throughout the gut. The lack of cell-specific animal models has impeded our understanding of gut/brain communication; therefore, we generated a mouse model for cre-recombinase-driven deletion of Ffar3. We comprehensively characterized the feeding behavior of control and vagal-FFAR3 knockout (KO) mice in response to various conditions including fasting/refeeding, western diet (WD) feeding, and propionate supplementation. We also utilized ex vivo organotypic vagal cultures to investigate the signaling pathways downstream of propionate FFAR3 activation. Results Vagal-FFAR3KO led to increased meal size in males and females, and increased food intake during fasting/refeeding and WD challenges. In addition, the anorectic effect of propionate supplementation was lost in vagal-FFAR3KO mice. Sequencing approaches combining ex vivo and in vivo experiments revealed that the cross-talk of FFAR3 signaling with cholecystokinin (CCK) and leptin receptor pathways leads to alterations in food intake. Conclusion Altogether, our data demonstrate that FFAR3 expressed in vagal neurons regulates feeding behavior and mediates propionate-induced decrease in food intake.
Technical Publications as Graduate Class Projects: Advantages and Potential Disadvantages

Graduate students are rewarded with better job opportunities if they can demonstrate a productive publishing record. In this article we report on a writing program that generated technical publications in a discipline-based graduate class. Seventeen student authors were interviewed about the influence of the experience on their professional development. For many students the most powerful experience was working as a member of a research team. Master’s students benefited from being able to transfer research experience into their thesis programs. Doctoral students stretched the definitions of their disciplines and learned new research methods. One cost of the research project was that less discipline-specific content was covered in the course. Overall, students improved soft skills through participation in the project.
Phase Theory: An Introduction

Introduction 1. The Minimalist Program 2. Introducing phases 3. Phasehood diagnostics 4. Classic phases 5. Other ph(r)ases 6. Variation in phasehood 7. Phases and the interfaces 8. Conclusion.
Chapter 36 Peripheral neuropathies associated with plasma cell dyscrasias

Publisher Summary This chapter describes the electrophysiologic and pathological findings encountered with the Plasma cell dyscrasias (PCD)-associated neuropathies. Information of the immunological aspects of the monoclonal gammopathies is vastly expanding and shedding light on the pathogenetic relationship of the monoclonal proteins and paraproteinemic neuropathies. Though they are diverse in presentation, these neuropathies are classifiable according to key clinical and electrodiagnostic features detectable by the clinician. Though diverse in presentation, there are certain clinical and electrodiagnostic features that may guide the clinician. The pathogenetic relationship of the M-protein, although well established in some syndromes, is more often ill defined. Familiarity with the characteristic and electrophysiologic features of each will enable the clinician to recognize these disorders. Appropriate management is usually aimed at suppressing the monoclonal protein if there is proven anti-nerve antibody activity. Careful study of these patients will lead to a better understanding of these neuropathies and may help in the search for more beneficial treatments in the management of these immune-mediated polyneuropathy.
Hofstede's Model of National Culture: A Social Science Contribution to International Business

ABSTRACT The extent to which Hofstede's model of national culture has been applied within a business context is reviewed. A search of a computerized index of scholarly business journals provided a total of 54 articles published within the business disciplines since 1980 which used Hofstede's model as a research technique. Those articles are classified by their level of analysis-country (22 articles), organization (12 articles), and individual (20 articles)-and then subclassified by their specific foci. This study indicates that Hofstede's model is indeed robust and has been successfully used to conduct both empirical and conceptual research across a great breadth of subjects.
Studies on human alpha-fetoprotein. Isolation and characterization of monomeric and polymeric forms and amino-terminal sequence analysis.

Human α-fetoprotein has been isolated from the serum and ascitic fluid of a patient with hepatoma by a combination of immunoadsorbent column chromatography and Sephadex G-150 gel filtration. Human α-fetoprotein is a sialylated glycoprotein with an estimated molecular weight of 67 500, composed of a single-chain polypeptide of approximately 580 amino acid residues and 3.6% carbohydrate. It is a negatively charged protein with an acid isoelectric point (pH 4.57). In addition to the monomeric form of α-fetoprotein, we have identified human α-fetoprotein polymers, including dimeric and trimeric forms, which dissociate to the monomer only upon exposure to disulfide-reducing reagents, implying that their formation is dependent upon intermolecular disulfide bonds. These polymers are found in human α-fetoprotein isolated by isoelectric focusing in both the major (pI 4.57) and minor (pI 5.2) α-fetoprotein fractions. The first 17 residues of the NH2-terminal amino acid sequence of the hepatoma-derived human α-fetoprotein have been identified. Fetal α-fetoprotein is indistinguishable from hepatoma α-fetoprotein by several criteria, including immunoelectrophoresis, acrylamide gel electrophoresis, and proclivity for dimerization.
Incorporating domain knowledge into evolutionary computing for discovering gene-gene interaction

Understanding the genetic underpinnings of common heritable human traits has enormous public health benefits with implications for risk prediction, development of novel drugs, and personalized medicine. Many complex human traits are highly heritable, yet little of the variability in such traits can be accounted for by examining single DNA variants at a time. Seldom explored non-additive gene-gene interactions are thought to be one source of this "missing" heritability. Approaches that can account for this complexity are more aptly suited to find combinations of genetic and environmental exposures that can lead to disease. Stochastic methods employing evolutionary algorithms have demonstrated promise in being able to detect and model gene-gene interactions that influence human traits, yet the search space is nearly infinite because of the vast number of variables collected in contemporary human genetics studies. In this work we assess the performance and feasibility of sensible initialization of an evolutionary algorithm using domain knowledge.
Vitamin C Deficiency

Vitamin C is an essential micronutrient involved in many biological and biochemical functions. Nutritional vitamin C deficiency is rare in developed countries but is seen in individuals on restricted diets. Keywords: antioxidant; deficiency; scurvy; recommended daily allowance; vitamin C
Diatoms in Biofilms

Some Diatom Microbiology Keywords: biofilms; algal biofilms; diatoms in biofilms
Biochemical properties of anti-inflammatory drugs. XII. Inhibition of urate binding to human albumin by salicylate and phenylbutazone analogues and some novel anti-antiflammatory drugs.

Abstract We have previously reported that 0.2 mM phenylbutazone and salicylate inhibit the binding of urate in vitro to human albumin by over 50 per cent. This communication describes similar studies with over 60 other compounds. Only gentisate, per-fluorosalicylate, diiodosalicylate, salicylimide, Trimethazone, Diflumidone, the fenamic acids, 3-hydroxycinchophen and several acidic sulfonamides were as potent as phenyl-butazone or salicylate. A structure-action relationship was delineated for salicylate analogues. There was a consistent relationship between the ability of an acidic compound to displace albumin-bound urate and its relative avidity for the primary dansylamide (DNSA)-binding site(s) of the albumin. Some advantages of using DNSA, vis a vis other dyestufis, for measuring drug binding to albumin are discussed. Since some of the uricosuric action of certain drugs may depend on the displacement of urate from albumin or other proteins by the drugs, the assays in vitro for urate displacement which are described may facilitate pharmacological screening for potential uricosuric activity.
Interleukin-4 inhibition of interleukin-1-induced expression of matrix metalloproteinase-3 (MMP-3) is independent of lipoxygenase and PPARγ activation in human gingival fibroblasts

Background Interleukin 4 (IL-4) has been shown to suppress interleukin-1 (IL-1) induced expression of matrix metalloproteinase-3 (MMP-3) in human synovial and gingival fibroblasts, but the mechanism of suppression has not been determined. Activators of peroxisome proliferator-activated receptor-γ (PPARγ) have been shown to inhibit cytokine induced expression of MMPs in other cell types, and IL-4 has been shown to activate PPARγ by stimulating production of ligands through the lipoxygenase pathway. It has been suggested that PPARγ may inhibit expression of MMPs by competing with transcription factor AP-1 for binding to a putative composite binding element in the promoters. The objective of this study was to determine whether the suppressive effects of IL-4 on the IL-1 induced expression of MMP-3 involve activation of lipoxygenase and/or PPARγ.
The Molecular Structure of Indium Oxine

The radiopharmaceutical use of [111In]oxine for radiolabeling of blood products has recently met with FDA approval. The molecular structure of tris(8-quinolinolato) indium(III), “indium oxine”, was determined by x-ray crystallography using a single yellow crystal grown from ethanol solution. The structural study reveals an asymmetric pseudo-octahedral N3O3 metal coordination sphere with meridional stereo chemistry. This asymmetry is not detected in solution by proton NMR spectroscopy at room temperature; however, at −90°C spectroscopic changes suggest slowing of a fluxional process. The molecule unexpectedly crystallized with a molecule of ethanol hydrogen-bonded to an oxygen atom of one of the oxine ligands, suggesting that hydrogen-bonding will play a role in the solvation of this complex in protic solvents.
Responding to the Idea of Transboundary Conservation

SUMMARY Over 300 organizations support the Yellowstone to Yukon Conservation Initiative (Y2Y), an effort to ensure long-term protection for biodiversity in the “Northern Rockies” of the United States and Canada. Y2Y has been described as an organization, a coalition, a network, and other institutional designations. Alternatively, many characterize Y2Y as a “vision” for broad-based and long-term conservation in the Northern Rockies. After introducing the multifarious character of Y2Y, this article presents a summary overview of the high volume of favorable responses to the idea of Y2Y. This is followed by a more extensive review of vocal opposition to Y2Y. Judging from both widespread support for and backlash against Y2Y, there seems little doubt that the Y2Y vision has effectively posed a provocative challenge to traditional conceptions of land use and conservation in the Northern Rockies.
Complex Systems Analysis of Cell Cycling Models in Carcinogenesis

A new approach to the modular, complex systems analysis of nonlinear dynamics in cell cycling network transformations involved in carcinogenesis is proposed. Carcinogenesis is a complex process that involves dynamically inter-connected biomolecules in the intercellular, membrane, cytosolic, nuclear and nucleolar compartments that form numerous inter-related pathways referred to as networks.The variable biotopology of such dynamic networks is highly complex, and has a number of interesting properties that can be formally characterized at one level of organization by mathematical structures called 'biogroupoids'.One such family of pathways contains the cell cyclins. Cyclins are proteins that link several critical pro-apoptotic and other cell cycling/ division components, including the tumor suppressor gene TP53 and its product, the Thomsen-Friedenreich antigen (T antigen), Rb, mdm2, c-Myc, p21, p27, Bax, Bad and Bcl-2, which all play major roles in carcinogenesis of many cancers. A novel theoretical analysis is thus possible based on recently published studies of cyclin signaling, with special emphasis placed on the roles of cyclins D1 and E, suggests novel clinical trials and rational therapies of cancer through reestablishment of cell cycling inhibition in metastatic cancer cells.
Expanding the Role of K‐5 Science Instruction in Educational Reform: Implications of an Interdisciplinary Model for Integrating Science and Reading

Addressed is the current practice in educational reform of reducing time for science instruction in favor of traditional reading/language arts instruction. In contrast, presented is an evidence-based rationale for increasing instructional time for K-5 science instruction as an educational reform initiative. Overviewed are consensus interdisciplinary research and complementary multi-year findings of the Science IDEAS model demonstrating the effectiveness of integrating conceptually-relevant reading within science instruction in improving student achievement in both science and reading comprehension. Based on research summarized, increasing time for integrated K-5 science is advocated as a meaningful reform-based approach to science learning and reading comprehension proficiency that, in turn, better prepares students for subsequent success in science and content-area reading comprehension across upper elementary and middle school grades (3–8).
Anti-Inflammatory Efficacy of Dexamethasone and Nrf2 Activators in the CNS Using Brain Slices as a Model of Acute Injury

Limiting excessive production of inflammatory mediators is an effective therapeutic strategy for many diseases. It’s also a promising remedy for neurodegenerative diseases and central nervous system (CNS) injuries. Glucocorticoids are valuable anti-inflammatory agents, but their use is constrained by adverse side-effects. Activators of NF-E2-related factor-2 (Nrf2) signaling represent an attractive anti-inflammatory alternative. In this study, dexamethasone, a synthetic glucocorticoid, and several molecular activators of Nrf2 were evaluated for efficacy in slices of cerebral cortex derived from adult SJL/J mice. Cortical explants increased expression of IL-1β and TNF-α mRNAs in culture within 5 h of sectioning. This expression was inhibited with dexamethasone in the explant medium or injected systemically in mice before sectioning. Semi-synthetic triterpenoid (SST) derivatives, potent activators of the Nrf2 pathway, demonstrated fast-acting anti-inflammatory activity in microglia cultures, but not in the cortical slice system. Quercetin, luteolin, and dimethyl fumarate were also evaluated as molecular activators of Nrf2. While expression of inflammatory mediators in microglia cultures was inhibited, these compounds did not demonstrate anti-inflammatory efficacy in cortical slices. In conclusion, brain slices were amenable to pharmacological modification as demonstrated by anti-inflammatory activity with dexamethasone. The utilization of Nrf2 activators to limit inflammatory mediators within the CNS requires further investigation. Inactivity in CNS tissue, however, suggests their safe use without neurological side-effects in treating non-CNS disorders. Short-term CNS explants may provide a more accurate model of in vivo conditions than microglia cultures since the complex tissue microenvironment is maintained.
Vicissitudes of non-visual objects: Comments on Macpherson, O’Callaghan, and Batty

The papers by Macpherson, O’Callaghan, and Batty reveal some startling differences in the objects and properties represented by different modalities. They also reveal some tensions between different ways of understanding what it is for any one modality to represent objects and properties.
Improving operating room safety

Despite the introduction of the Universal Protocol, patient safety in surgery remains a daily challenge in the operating room. This present study describes one community health system's efforts to improve operating room safety through human factors training and ultimately the development of a surgical checklist. Using a combination of formal training, local studies documenting operating room safety issues and peer to peer mentoring we were able to substantially change the culture of our operating room. Our efforts have prepared us for successfully implementing a standardized checklist to improve operating room safety throughout our entire system. Based on these findings we recommend a multimodal approach to improving operating room safety.
The attributional model of depression: a path analysis test in a naturalistic setting.

A path analysis test of the attributional model of depression was conducted in a naturalistic achievement setting (N = 77). Relatively depressed and nondepressed students reported their attributions on an academic test, and then their subsequent test performance were measured. In support of the attributional model of depression, the results indicated that for successful outcomes the attribution dimension of stability (i.e., stable vs. unstable across different situational contexts) served to buffer the influence of depression on later test performances. The results thus show that stability attributions for a successful behavior, defined in terms of consistency across different situational contexts, play a mediating role in the behavioral consequences of depression.
The Maturation of Airway Structure and Function

After completing this article, readers should be able to: 1. Explain the physiologic reasons that immature infants are at a greater risk of mechanical ventilation-induced airway damage than are more mature infants. 2. Describe the age-related differences in airway function during perinatal development. 3. Delineate how differential expression of smooth muscle myosin heavy-chain isoforms affects airway smooth muscle physiology and airway mechanics. 4. Explain how expression of smooth muscle proteins contributes to the functional maturation of airway smooth muscle. Airway formation is one of the earliest events in the development of the respiratory system. However, continued maturation of the airway continues well into postnatal life. With advances in the medical care of increasingly preterm infants, an understanding of developmental airway physiology becomes imperative. This article reviews maturation of the airway and its components as well as their contributions to airway function during development. Airway development in the human begins during the fourth week of gestation when the respiratory diverticulum, or lung bud, branches from the embryonic foregut. The esophagotracheal septum forms and separates the foregut into the esophagus dorsally and the trachea ventrally. Thus, the developing airway is of foregut endodermal origin. Elongation of the respiratory diverticulum forms the trachea; branching forms the main stem bronchi. Growth and elongation continues in the caudal direction under the influence of airway secretions and physical forces. By the end of the 16th week of gestation, branching of the conducting airways is complete. The airway matures initially in the trachea and proceeds distally. Tracheal cartilage begins to form during the seventh week of gestation. Maturation of the distal airway cartilage is not complete until after birth. Epithelial differentiation begins in the trachea during the 10th week of gestation. Together with phasic contractions of the fetal airway smooth muscle, which are present following the 23rd gestational week, lung fluid …
Materials Research in Nuclear Waste Management: Reflections on Twenty-Five MRS Symposia

The MRS symposium, “Scientific Basis for Nuclear Waste Management” was first held in Boston, November 28th to December 1st, 1978. This symposium marks the twenty-fifth in a series that now rotate to meeting sites around the world. During the past 24 years, there has been considerable progress in the development and understanding of the behavior of materials that are used in the processing, transport, containment and disposal of radioactive waste. The design and selection of materials for long-term performance has required a uniquely interdisciplinary effort. Over the same period, there have been important developments in the regulatory framework that guides the scientific and engineering needs of nuclear waste management. This paper provides a subjective commentary on the major developments and innovations during the past 25 symposia. The future challenge will be the proper and constructive integration of the science into the development of nuclear waste disposal strategies.
Polarization sensitive, three-dimensional, single-molecule imaging of cells with a double-helix system

Double-helix point spread function photoactivation-localization microscopy allows three-dimensional (3D) superresolution imaging of objects smaller than the optical diffraction-limit. We demonstrate polarization sensitive detection with 3D super-localization of single-molecules and unveil 3D polarization specific characteristics of single-molecules within the intracellular structure of PtK1 cells expressing photoactivatable green fluorescent protein. The system modulates orthogonal polarization components of single-molecule emissions with a single spatial light modulator and detects them separately with a single detector. Information obtained from the two polarization channels demonstrates polarization based contrast in 3D superresolution imaging. Further, we show that the 3D information from the two channels can be optimally combined to yield up to 30% improvement in localization precision relative to a single polarization channel system.
Phase II trial of temozolomide (TMZ) plus irinotecan (CPT-11) in adults with newly diagnosed glioblastoma multiforme before radiotherapy.

This phase II trial evaluated efficacy and safety of temozolomide (TMZ) in combination with irinotecan (CPT-11) before radiotherapy in patients with newly diagnosed glioblastoma multiforme (GBM). Prior to radiotherapy, patients were treated with a maximum of three 6-week cycles of TMZ and CPT-11. Patients received TMZ at a dose of 200 mg/m2/day on days 1–5 and CPT-11 on days 1, 8, 22, and 29, with a dose adjustment for enzyme-inducing antiepileptic drug use. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival (OS), safety, and tumor O6-methylguanine-DNA methyltransferase (MGMT) expression. Of the 42 patients treated, 8 (19%) patients achieved a partial response. Median PFS and median OS were 3.1 and 13.8 months, respectively. Grade 3 or 4 AEs were documented in 36% of patients, most of which were hematologic (29%). Twenty-four percent of patients had grade 3 or 4 non-hematologic AEs, with gastrointestinal AEs being the most common (12%) Two patients died, one of intracranial hemorrhage and one of treatment-related renal failure. Low MGMT expression, compared with high MGMT expression, showed no significant difference in ORR (25 vs. 8%), median PFS (14 vs. 5 months) or OS (21 vs. 15 months). Although TMZ plus CPT-11 is at least comparable in efficacy to TMZ alone, this combination appears more toxic and poorly tolerated. The lack of correlation of activity with MGMT expression is intriguing, but needs further evaluation in subsequent trials.
Death and the Meaning of Life

AbstractThoughts of mortality sometimes bring on a crisis in confidence in the meaning in one's life. One expression of this collapse is the midlife crisis. In a recent article, Kieran Setiya argues that if one can value activities as opposed to accomplishments as the primary goods in one's life then one might avoid the midlife crisis. I argue that Setiya's advice, rather than safeguarding the meaning in one's life, substitutes for it something else, a kind of happiness. I use Susan Wolf's concept of meaning in order to make this case. Wolf has not written much about the importance of death, but I argue that her account of meaning shares essential features with the theories developed by Jean-Paul Sartre and Martin Heidegger. Sartre argues that death is an unqualified harm, while Heidegger argues that there is meaning in life only because we are mortal. I conclude by showing how Heidegger's theory of mortality underwrites accounts of meaning like those found in Wolf.
Every Thursday: advertorials by Mobil Oil on the op-ed page of The New York Times

Abstract Advertorials are paid messages in the media sponsored by organized interests to create and sustain a favorable political environment to pursue their respective goals. Advertorials, a form of outside lobbying, take two broad forms: (a) image advertorials designed to create a positive impression of the sponsor and a favorable climate of opinion, and (b) advocacy advertorials intended to win support for an interest's viewpoints on controversial issues. We analyze the population of 819 op-ed page advertorials placed by Mobil from 1985 through 2000 to reach the elite audience of The New York Times. Typologies of advertorials and policy content are used to document over time the placement of advertorials, what types of advertorials were used, which issue areas received attention, and the links between Mobil's advertorials and events in the political environment.
The Effects of Combined Androgen Blockade on Cognitive Function During the First Cycle of Intermittent Androgen Suppression in Patients With Prostate Cancer

ABSTRACTPurpose: Men with prostate specific antigen (PSA) only relapse of prostate cancer after primary therapy are generally fully functional and asymptomatic with a life expectancy of up to 10 or more years. These patients are often treated with androgen suppression. We evaluate the effects of androgen suppression on cognitive function.Materials and Methods: Hormone naive patients without evidence of metastases with an increasing PSA were treated with intermittent androgen suppression consisting of 9 months of leuprolide and flutamide followed by an off treatment period determined by the increase in PSA. Cognitive function tests were administered at baseline, after 9 months of androgen suppression and after 3 months off treatment. Cognitive tests measured spatial abilities, spatial memory, verbal fluency, verbal memory and selective attention. A total of 19 patients 52 to 76 years old completed the intermittent androgen suppression study along with 15 healthy community dwelling control participants.Resu...
Analysis of stagnation point flow toward a stretching sheet

Abstract There has been much recent interest in the stagnation point flow of a fluid toward a stretching sheet. Investigations that may include oblique stagnation flow and heat transfer to a horizontal plate all involve the same boundary value problem (BVP): f ‴ + ff ″ - ( f ′ ) 2 + b 2 = 0 , f ( 0 ) = 0 , f ′ ( 0 ) = 1 , f ′ ( ∞ ) = b . Here b is the ratio of the stagnation flow strain rate to the stretch rate of the sheet. Through numerical analysis of the problem, several authors have conjectured the existence of a solution for all values of b > 0 . In this note we present numerical evidence that a second solution exists for 0 b b c ≈ 0.16906 . Further we present a mathematical proof that for all b > 0 there exists a monotonic solution to the BVP and if b > 1 , this solution is unique. If b 1 it can be shown that any further solutions cannot be monotonic and the second solution found here numerically is non-monotonic. The asymptotic behavior of solutions near b = 0 and 1 is also presented. Finally, a stability analysis is performed to show that solutions on the upper branch of the dual solutions are linearly stable, while those on the lower branch are linearly unstable.
Determination of metabolizable energy contents of feed ingredients for ducks

The objective of the present experiments was to determine the AMEn and TMEn of various feed ingredients used in duck diets. In each of two experiments, 48 mature, male, White Pekin ducks were assigned in pairs to 24 cages based on initial weight. In each experiment, 12 ducks were assigned to each of three test ingredients and 12 ducks received dextrose for determination of endogenous losses of nitrogen and energy. The test ingredients were tube-fed in wet form and consisted of corn, barley, and pearl millet in Experiment 1, and corn, sorghum, and triticale in Experiment 2. Feed was withdrawn 48 h prior to feeding the test ingredients and ducks were tube-fed 30 g of dextrose in 100 mL of water at 8 and 32 h after feed withdrawal. Ducks were tube-fed 30 g of their assigned test ingredient in 100 mL of water at 48 and 54 h after feed withdrawal. Ducks used in estimating endogenous nitrogen and energy losses were tube-fed 30 g of dextrose in 100 mL of water at 48 and 54 h after feed withdrawal. The method of excreta collection utilized was surgical fixation of a collection apparatus to the vent area of ducks to facilitate total collection of excreta. Collection of excreta was initiated at the first feeding of test ingredients and was continued for a total of 54 h. In Experiment 1, the AMEn and TMEn of corn, barley, and pearl millet on an as-fed basis were determined to be 3.208 and 3.339, 2.730 and 2.863, and 3.350 and 3.484 kcal/g, respectively. In Experiment 2, the AMEn and TMEn of corn, sorghum, and triticale on an as-fed basis were determined to be 3.151 and 3.459, 3.260 and 3.567, and 2.757 and 3.065 kcal/g, respectively. In conclusion, the use of the modified TME assay, in addition to total collection of excreta from individual ducks, provides a means of accurately estimating the ME content of feed ingredients used to formulate diets for ducks.
Nutrition, sensory evaluation, and performance analysis of trans fat‐free nonhydrogenated frying oils

The American Food and Drug Administration is enforcing the law requiring labeling of trans fats on nutrition labels since January 1, 2006. This law has created a push to reformulate deep-fat frying oils. Prior to this law, frying oils contained trans fats because they gave oils a longer frying life. In this study, oil performance, sensory evaluation and nutritional analysis were conducted on seven trans fat-free and two trans fat oils through a 10-day degradation process using French fries to degrade oil. Sensory ratings of appearance, color, texture and overall liking indicated that fries from blended trans fat-free oils were preferred. The most stable oils were blended oils based on peroxide value, lovibond color and free fatty acid percentage. Based on these findings, industries considering using the trans fat-free frying oils should consider blended oils because of excellent oil stability, lower oil usage and sensory panelists' preference.
A del T poly T (8) mutation in the 3' untranslated region (UTR) of the CDK2-AP1 gene is functionally significant causing decreased mRNA stability resulting in decreased CDK2-AP1 expression in human microsatellite unstable (MSI) colorectal cancer (CRC).

Background We have previously published results indicating that decreased expression of CDK2-AP1 in MSI human colorectal cancer is associated with deletion mutations in the poly (T) 8 repeat sequence within the 3′-UTR of the CDK2-AP1 gene. In this study, we test the hypothesis that the del T mutation results in decreased CDK2-AP1 expression by causing reduced mRNA stability. Methods We introduced wild-type and mutant 3′-UTR sequences fused to a green fluorescent protein (GFP) gene separately into human CRC cell lines and quantified the expression of the GFP gene. Native CDK2-AP1 mRNA stability was measured in human CRC cell lines, using an actinomycin D assay and the mRNA structure folding software mfold 3.2. Results Mutant GFP-3′-UTR samples demonstrated significantly reduced GFP expression compared with wild-type GFP-3′-UTR as measured by both FACS and real-time PCR. Both the actinomycin D assay and mfold software demonstrated significantly reduced mRNA stability for the del T poly (T) 8 transcript compared with the wild type. Conclusions In summary, these novel results support our hypotheses that the del T poly (T) 8 observed in the 3′-UTR of the CDK2-AP1 gene in human MSI CRC is functionally significant and results in decreased CDK2-AP1 expression. The results also indicate the mechanism of this decreased expression is caused at least in part by decreased mRNA stability.
The lanthanide-induced-shift-assisted determination of proton spin-lattice relaxation times

Abstract A new method is proposed for the determination of NMR relaxation times in second-order (strongly coupled) spectra. The method exploits the shifting abilities of the lanthanide shift reagent, Eu(fod)3. It is shown that, in favorable cases, the spectral dispersion afforded by a shift reagent can allow one to determine T2's and then extrapolate them back to zero LIS (absence of shift reagent) to get the relaxation times for the protons in the strongly coupled spectra. It is shown that complications due to cross-relaxation are absent. The technique is illustrated for the case of adamantanone interacting with Eu(fod)3 in CDCI3 as solvent. Data derived from 13C NMR spin-lattice relaxation on the same molecule can be used to determine what percentage of the proton relaxation is caused by the dipolar relaxation mechanism.
III. Comparison of the antinociceptive action of Mu and delta opioid receptor ligands in the periaqueductal gray matter, medial and paramedial ventral medulla in the rat as studied by the microinjection technique

In rats stereotaxically implanted with microinjection cannula in either the periaqueductal gray matter (PAG) or the medial/paramedial medullary reticular formation (MRF), microinjection of morphine, sufentanil,d-Ala2-d-Leu5-enkephalin (DADL) ord-Ser2- Thr6-leucine enkephalin (DSTLE) produced dose-dependent elevations in the response latency on tail-flick and hot plate tests. These effects were reversed by naloxone administered by microinjection into the same intracerebral site. Both mu (morphine and sufentanil) and delta (DADL and DSTLE) opioid receptor ligands produced a maximal elevation in the supraspinally mediated hot plate response when administered into either the PAG or the MRF. Similarly, mu and delta receptor ligands produced maximum elevations in the spinally mediated tail-flick response when microinjected into the PAG. In contrast, delta, but not mu, receptor agonists produced a total blockade of the tail-flick response following administraion into the MRF. Microinjection of mu (morphine) or delta (DADL) agonists into the PAG or the MRF also resulted in a naloxone-reversible inhibition of the visceral chemical evoked writhing response. These observations suggest that mu and delta opioid receptor linked systems within the MRF but not the PAG produce their antinociceptive effects by discriminable mechanisms with a differential action on spinopetal vs supraspinal modulatory systems.
Identification of barriers to appropriate dietary behavior in low-income patients with type 2 diabetes mellitus

Objective To identify barriers to appropriate dietary behavior in an urban, low-income population of patients with type 2 diabetes and to examine a new instrument in the identification of these barriers in this population.
Studies of the thyrotropin-releasing factor. II. Conformations of TRF and some analogs

The conformation of the thyrotropin-releasing factor (TRF) and four analogs have been studied by the CNDO/2 molecular orbital method. The Nδ-protonated tautomer of TRF is predicted to be the more stable of the two tautomeric forms; however, it is postulated that the Ne-tautomer possesses the most active minimum-energy conformation. The peptide backbone for the five compounds remains nearly constant. The conformations predicted from model fragments are very near to those found for the full compound.
A mortality study of workers at seven beryllium processing plants

The International Agency for Research on Cancer (IARC) has found that the evidence for the carcinogenicity of beryllium is sufficient based on animal data but "limited" based on human data. This analysis reports on a retrospective cohort mortality study among 9,225 male workers employed at seven beryllium processing facilities for at least 2 days between January 1, 1940, and December 31, 1969. Vital status was ascertained through December 31, 1988. The standardized mortality ratio (SMR) for lung cancer in the total cohort was 1.26 (95% confidence interval [CI] = 1.12-1.42); significant SMRs for lung cancer were observed for two of the oldest plants located in Lorain, Ohio (SMR = 1.69; 95% CI = 1.28-2.19) and Reading, Pennsylvania (SMR = 1.24; 95% CI = 1.03-1.48). For the overall cohort, significantly elevated SMRs were found for "all deaths" (SMR = 1.05; 95% CI = 1.01-1.08), "ischemic heart disease" (SMR = 1.08; 95% CI = 1.01-1.14), "pneumoconiosis and other respiratory diseases" (SMR = 1.48; 95% CI = 1.21-1.80), and "chronic and unspecified nephritis, renal failure, and other renal sclerosis" (SMR = 1.49; 95% CI = 1.00-2.12). Lung cancer SMRs did not increase with longer duration of employment, but did increase with longer latency (time since first exposure). Lung cancer was particularly elevated (SMR = 3.33; 95% CI = 1.66-5.95) among workers at the Lorain plant with a history of (primarily) acute beryllium disease, which is associated with very high beryllium exposure. The lung cancer excess was not restricted to plants operating in the 1940s, when beryllium exposures were known to be extraordinarily high. Elevated lung cancer SMRs were also observed for four of the five plants operating in the 1950s for workers hired during that decade. Neither smoking nor geographic location fully explains the increased lung cancer risk. Occupational exposure to beryllium compounds is the most plausible explanation for the increased risk of lung cancer observed in this study. Continued mortality follow-up of this cohort will provide a more definitive assessment of lung cancer risk at the newer plants and among cohort members hired in the 1950s or later at the older plants. Further clarification of the potential for specific beryllium compounds to induce lung cancer in humans, and the possible contribution of other exposures in specific processes at these plants, would require a nested case-control study. We are currently assessing whether available industrial hygiene data would support such an analysis.
Substrate-based atom waveguide using guided two-color evanescent light fields

We propose a dipole-force linear waveguide which confines neutral atoms up to $\ensuremath{\lambda}/2$ above a microfabricated single-mode dielectric optical guide. The optical guide carries far blue-detuned light in the horizontally-polarized TE mode and far red-detuned light in the vertically-polarized TM mode, with both modes close to optical cut-off. A trapping minimum in the transverse plane is formed above the optical guide due to the differing evanescent decay lengths of the two modes. This design allows manufacture of mechanically stable atom-optical elements on a substrate. We calculate the full vector bound modes for an arbitrary guide shape using two-dimensional non-uniform finite elements in the frequency-domain, allowing us to optimize atom waveguide properties. We find that a rectangular optical guide of $0.8\ensuremath{\mu}\mathrm{m}$ by $0.2\ensuremath{\mu}\mathrm{m}$ carrying 6 mW of total laser power (detuning $\ifmmode\pm\else\textpm\fi{}15\mathrm{nm}$ about the $D2$ line) gives a trap depth of $200\ensuremath{\mu}\mathrm{K}$ for cesium atoms ${(m}_{F}=0),$ transverse oscillation frequencies of ${f}_{x}=40\mathrm{kHz}$ and ${f}_{y}=160\mathrm{kHz},$ collection area $\ensuremath{\sim}1\ensuremath{\mu}{\mathrm{m}}^{2}$ and coherence time of 9 ms. We discuss the effects of non-zero ${m}_{F},$ the $D1$ line, surface interactions, heating rate, the substrate refractive index, and the limits on waveguide bending radius.