cssi/SciSciGPT-SciSciNet huggingface dataset:
Developmental regulation of genes mediating murine brain glucose uptake

We examined the molecular mechanisms that mediate the developmental increase in murine whole brain 2-deoxyglucose uptake. Northern and Western blot analyses revealed an age-dependent increase in brain GLUT-1 (endothelial cell and glial) and GLUT-3 (neuronal) membrane-spanning facilitative glucose transporter mRNA and protein concentrations. Nuclear run-on experiments revealed that these developmental changes in GLUT-1 and -3 were regulated posttranscriptionally. In contrast, the mRNA and protein levels of the mitochondrially bound glucose phosphorylating hexokinase I enzyme were unaltered. However, hexokinase I enzyme activity increased in an age-dependent manner suggestive of a posttranslational modification that is necessary for enzymatic activation. Together, the postnatal increase in GLUT-1 and -3 concentrations and hexokinase I enzymatic activity led to a parallel increase in murine brain 2-deoxyglucose uptake. Whereas the molecular mechanisms regulating the increase in the three different gene products may vary, the age-dependent increase of all three constituents appears essential for meeting the increasing demand of the maturing brain to fuel the processes of cellular growth, differentiation, and neurotransmission.
Cultural Lag in Science

The phenomena to be discussed below are two. First, the existence and extent of cultural lag within the scientific community. Second, the denial of this fact by the scientific establishment. The theoretical proposal that will be made below is to replace Kuhn’s idea of distinguishing the scientific from the non-scientific fields of inquiry. He uses the qualitative distinctions between those which have a paradigm and those that do not. It is preferable to use a more, quantitative idea: of two fields of inquiry, that one is more progressive which has a smaller mean time lag between the appearance of an innovation and its public recognition. The proposal that will be made is of some institutional reforms within the commonwealth of learning, particularly such as to reduce the incentives for the Salieri effect and increase the incentive for talent scouting.
An evidence-based medicine approach for case presentations by trainees.

Background Evidence-based medicine (EBM) is a key aspect of medical training that can be challenging for trainees to learn. Tumour boards (TBs) are multidisciplinary meetings that are often opportunities for trainees to deliver patient case presentations, which is another integral part of medical education; however, TBs are time intensive, typically lack academic structure and may fail to emphasise EBM. Objective To design a systematic approach to improve both trainee satisfaction and the level of evidence cited at typical academic TBs. Methods From 2017 to 2018, Plan-Do-Study-Act (PDSA) methodology was used to develop a systematic approach for medical oncology trainees towards TBs. Statistical testing was used to assess which characteristics of a patient case made it more difficult to apply EBM. Anonymous surveys were distributed to trainees before and after the intervention to assess the educational utility. Results We developed a shared voluntary case database, so that references with higher levels of evidence could be rapidly recalled and applied to similar cases. We then developed EBM-focused review sessions to highlight database trends. Both the database and the review sessions had high participation rates (>90% cases had voluntary data entry), and each were reported to have educational value by trainees. Conclusions A two-step implementation of an easy-to-use case database followed by review sessions focused on high-yield sources of evidence improved trainee satisfaction for TBs, but did not significantly improve the strength of the evidence cited.
Optimization of Fuel in Saturated Steam Boiler through Preheating of Controlled Air-Fuel Mixture

Energy saving is an important concern in every industrial process that could be achieved by fuel optimization. Significant part of operating cost of any industrial process is associated with the fuel consumption. Therefore, a little optimization in fuel consumption can lead to a significant energy saving and lower operational costs along with reduced greenhouse gas emissions. In this study the goal of fuel optimization has been achieved by improving the efficiency of the boiler. The air to fuel ratio has been optimized along with premixing of air and fuel before it is introduced to the furnace. The boiler assembly has been modified by adding an air preheater that preheats the air- fuel mixture to 93°C. The use of preheated air-fuel mixture at this temperature improves the boiler efficiency by 4%. Simulation on ASPEN HYSYS® was performed to validate all the results and it also showed 4.92% reduction in fuel demand, thus making the process more economical.
Dimensions of semi-simple matrix algebras

For $n \geq 225$ we show that every integer of the form $n + 2m$ such that $0 \leq 2m \leq n^{2} - \frac{9}{2} n \sqrt{n}$ is the dimension of a connected semi-simple subalgebra of $\mathrm{M}_{n}(k)$, that is, a subalgebra isomorphic to a direct sum of $t$ disjoint subalgebras $\mathrm{M}_{n_{i}}(k)$, where $\sum_{i=1}^{t} n_{i} = n$. From this, we conclude that the density of integers in $[0,\ldots, n^{2}]$ which are the dimension of a semi-simple subalgebra of $\mathrm{M}_{n}(k)$ tends to $1$ as $n \rightarrow \infty$.
Channeling macrophage polarization by using a selective translation inhibitor

Abstract The increasing problem of infectious diseases caused by antibiotic-resistant bacteria has intensified a search for novel host-directed therapies aimed at either boosting immune-mediated bacterial control or reducing immunopathology. Macrophages play central roles in eliminating pathogens as well as in tissue homeostasis and repair via alternative activation programs, M1-like and M2-like, respectively. Macrophages of both phenotypes are often present at the sites of chronic unresolved inflammation, such infectious granulomas and solid tumors, where the M2-like macrophages generate microenvironment conducive for pathogen survival or tumor progression. Interferon-gamma is a major cytokine that drives M1-like macrophage activation, which is essential for control of intracellular bacterial pathogens. To evaluate M1-like macrophage polarization as a broad therapeutic strategy, we searched for small molecules capable of enhancing effects of low concentrations of IFNγ on M1 macrophage polarization. We identified synthetic rocaglates that potentiated macrophages responses to low concentrations of IFNγ. Although known as potent translation inhibitors in tumor cell lines, in primary macrophages select rocaglates induced the upregulation of IRF1, a master regulator of IFNγ-activated pathways, stimulated autophagy and increased macrophage resilience to oxidative stress. In contrast, rocaglates inhibited macrophage responsiveness to IL-4, a prototypical activator of the M2-like phenotype. The M1-like macrophage programing by rocaglates was mechanistically linked to selective translation inhibition and modulation of MAP kinase network. Thus, rocaglates represent a novel class of immunomodulators that can enforce macrophage polarization towards the M1-like phenotype in complex microenvironments associated with hypofunction of type 1 and/or hyperactivation of type 2 immunity, e.g., chronic bacterial infections, allergies and, possibly, certain tumors.
Evolution of Porous Polyethylene Ear Reconstruction

The technique of porous polyethylene ear reconstruction has evolved over the past three decades to optimize outcomes. Over time, all aspects of the reconstruction including the implant, soft tissue coverage, instrumentation, postoperative care, anesthesia, and hearing loss have been modified and improved. In this chapter, we will shed some light on all these changes and the rationale behind those changes. Hopefully, this chapter will help shorten a surgeon’s learning curve.
Propaganda and the Moving Image

Since the advent of film in the 1890s, it has been used for political or propaganda purposes. However, propaganda is a larger phenomenon than film propaganda; it also encompasses the written and spoken word, music, pictures, and as technology advances, propaganda’s reach likewise advances to include YouTube videos and Gifs. Propaganda can involve the moving image in all its complexity. Hence, as a broad social phenomenon, propaganda and the moving image reward philosophical contemplation, and it is important to have a rather broad conception of philosophy when subjecting the moving image to philosophical analysis because much of the scholarship about propaganda and the moving image occurs across several academic disciplines. The task here is to integrate a large body of scholarship in order to give an overview of how thinking about propaganda can enrich our understanding of film and how thinking about film (and the moving image more generally) can deepen our insights into propaganda’s machinations.
Failing at Remediation? College Remedial Coursetaking, Failure and Long-term Student Outcomes.

Colleges offer remedial coursework to help students enrolling in post-secondary education who are not adequately prepared to succeed in college-level courses. Despite the prevalence of remediation, previous research presents contradictory findings regarding its short- and long-term effects. This paper uses a doubly robust inverse probability weighting strategy to examine whether the degree completion and wage outcomes associated with remedial education vary by passing or failing remedial coursework. Using the NLSY Postsecondary Transcript-1997 data, we find that almost 30% of remedial course takers fail a remedial course. Students who took and passed their remedial coursework at both 2-year and 4-year colleges were more likely to graduate from college than similar students who did not take remediation. For both 2-year and 4-year college entrants, students who failed remedial coursework were less likely to obtain a bachelor’s degree and, among degree receivers, took longer to graduate. Students who entered 2-year or 4-year colleges and who failed remedial coursework earned lower wages over time compared to similar students who never took remediation. Among 4-year college entrants, these wage differences seem to be explained completely by degree completion. However, wage differences for 2-year college entrants still remain after accounting for degree receipt. Our findings thus suggest that while many students may benefit from remedial education, a substantial number of students struggle with remedial coursework and fail to realize the intended benefits.
Laparoscopic management of a degenerating cystic leiomyoma imitating an ovarian cyst: A case report.

Abstract Background Leiomyomas are usually easily identifiable on routine imaging. However, there is increasing difficulty with diagnosing leiomyomas following degeneration. Subserosal leiomyomas that undergo cystic degeneration can imitate ovarian pathology. Case We present the case of a 39-year-old nulligravid woman who underwent surgery for a large pelvic mass originally suspected to be of ovarian origin. Intraoperatively, the mass was found to originate from the uterus and determined to be a large pedunculated, fluid-filled cyst arising from a fibroid which had undergone cystic degeneration. The mass was successfully removed laparoscopically through a single, two-centimeter port. Conclusion Gynecologists and radiologists should take into account this presentation when encountering suspected enlarged ovarian cysts without clearly identifying an origin. Laparoscopic intervention should be considered as the first line of management.
Cervical, thoracolumbar, and sacral spine trauma classifications: past, present, and future.

Objective Traumatic spine injuries are a relatively common occurrence and are associated with functional impairment, loss of neurologic function, and spinal deformity. A number of spinal trauma classification systems have been developed with varying degrees of acceptance. This review provides a chronological overview of spinal trauma classification systems, with special consideration towards the benefits and pitfalls related to each. Cervical, thoracolumbar, and sacral trauma classification systems are discussed. Methods A review of the literature was performed. Published articles that reported on bony spinal trauma classification systems were examined. No year exemptions were identified. The reference lists of all selected articles were screened for additional studies. Article inclusion and exclusion criteria were defined a priori. Results A total of 20 classification systems were identified from years 1938-2017. Of these 20 classification systems, 6 were cervical, 11 were thoracolumbar and 3 were sacral. The modernization of bony spinal trauma classification has been characterized by the development of weighted scales that include injury morphology, integrity of associated ligamentous structures and neurologic status. Conclusion For widespread acceptance and adoption in the clinical setting, future spinal trauma scoring classification will need to remain simple, highly reproducible, and impart information with regard to clinical decision-making and prognosis that may be effectively communicated across each medical specialty involved in the care of these patients.
Medication adherence and rate of nicotine metabolism are associated with response to treatment with varenicline among smokers with HIV.

Abstract Introduction PLWHA who smoke have shown lower cessation rates within placebo-controlled randomized trials of varenicline. Adherence and rate of nicotine metabolism may be associated with quit rates in such clinical trials. Methods This secondary analysis of a randomized placebo-controlled trial of varenicline for smoking among PLWHA (N = 179) examined the relationship between varenicline adherence (pill count, ≥80% of pills), nicotine metabolism (based on the nicotine metabolite ratio; NMR) and end-of-treatment smoking cessation (self-reported 7-day point prevalence abstinence, confirmed with carbon monoxide of ≤ 8 ppm, at the end of treatment; EOT). Results Combining varenicline and placebo arms, greater adherence (OR = 1.011, 95% CI:1.00–1.02, p = 0.051) and faster nicotine metabolism (OR = 3.08, 95% CI:1.01–9.37, p = 0.047) were related to higher quit rates. In separate models, adherence (OR = 1.009, 95% CI:1.004–1.01, p Conclusions Increasing varenicline adherence and ensuring that fast nicotine metabolizers receive varenicline may increase quit rates for PLWHA.
A physics-based approach for predicting time-dependent progression length of backward erosion piping

The progression length at various stages of backward erosion piping (BEP) in levee systems can serve as a key engineering demand parameter for reliability and risk assessments. The main goal of thi...
A comparison of self-reported teaching practices focused on student skills in introductory geoscience courses at two-year and four-year institutions: Results from the National Geoscience Faculty Survey

Community colleges are a major entry point for many students to post-secondary education, particularly for minority, first-generation, low-income, and older students. A range of factors including t...
Adapting to the COVID-19 Pandemic

From early in the COVID-19 pandemic, economists have stressed the importance of individuals endogenously changing their behavior to reduce their risk of infection. This paper quantifies time variation in the endogenous behavioral response of economic activity to the prevalence of the virus using an estimated behavioral SIR model with time-varying parameters. We find significant variation in both the relationship between economic activity and viral prevalence and the relationship between transmissibility and economic activity. This variation reflects adaptation to the pandemic and has implications both for specification of behavioral SIR models and for the next stage of the pandemic.
Abstract PO030: Understanding the influence of adiposity on the endometrium using human primary endometrial organoids

Endometrial cancer is the most commonly diagnosed type of gynecological cancer, and obesity is a major risk factor for this disease. Despite rising rates of obesity and endometrial cancer, it is still unclear how obesity alters the benign endometrium and the endometrial hormonal response to promote carcinogenesis. We used an endometrial organoid model to investigate how adiposity predisposes women to develop endometrial cancer. We hypothesized that increased adiposity would directly alter endometrial gene expression and diminish the protective progesterone response of the benign endometrium. Scaffold-free, three-dimensional endometrial organoids consisting of both epithelial and stromal cells from benign endometrial tissue were generated. Organoids were cocultured with different numbers of adipocyte spheroids to represent different levels of adiposity and were treated with a menstrual cycle level of hormones (E2 + P4 +T) over 14 days. Endometrial organoid gene expression was investigated using RNA-seq. Coculturing endometrial organoids with 30 adipocyte spheroids in the presence of E2, P4, and T caused significant differential expression of pathways involved in metabolism, angiogenesis, chromatin modification, and metal ion response, compared to endometrial organoids cultured without adipocyte spheroids. We investigated the metal ion response pathways that were altered and found that many of the most significantly differentially regulated genes in the metal ion response pathways belonged to the metallothionein (MT) family of genes. The expression of MT1A, MT1M, MT1X, and MT2A decreased approximately 50% in endometrial organoids cocultured with 30 adipocyte spheroids. Furthermore, although the results were not statistically significant, we observed a downregulation of the progesterone-responsive genes HSD17B2, IGFBP1, PAEP, PRL, FOXO1, and SPP1 in the endometrial organoids cultured with 30 adipocyte spheroids. Our results show that culturing endometrial organoids in conditions of increased adiposity alters endometrial gene expression and may change the way the endometrium responds to progesterone. Metallothioneins, which are downregulated in the presence of adipocyte spheroids, are important modulators of zinc and copper ions and reactive oxygen species in the cell. Progesterone plays an important protective role against endometrial cancer. In summary, our data show that adipocytes may influence the progesterone response of the benign endometrium. Further investigation into the role of progesterone-driven metallothioneins in the endometrium is currently underway. Citation Format: Alina R. Murphy, J. Julie Kim. Understanding the influence of adiposity on the endometrium using human primary endometrial organoids [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr PO030.
Use of Passive Sensing in Psychotherapy Studies in Late Life: A Pilot Example, Opportunities and Challenges.

Late-life depression is heterogenous and patients vary in disease course over time. Most psychotherapy studies measure activity levels and symptoms solely using self-report scales, administered periodically. These scales may not capture granular changes during treatment. We introduce the potential utility of passive sensing data collected with smartphone to assess fluctuations in daily functioning in real time during psychotherapy for late life depression in elder abuse victims. To our knowledge, this is the first investigation of passive sensing among depressed elder abuse victims. We present data from three victims who received a 9-week intervention as part of a pilot randomized controlled trial and showed a significant decrease in depressive symptoms (50% reduction). Using a smartphone, we tracked participants’ daily number of smartphone unlocks, time spent at home, time spent in conversation, and step count over treatment. Independent assessment of depressive symptoms and behavioral activation were collected at intake, Week 6 and Week 9. Data revealed patient-level fluctuations in activity level over treatment, corresponding with self-reported behavioral activation. We demonstrate how passive sensing data could expand our understanding of heterogenous presentations of late-life depression among elder abuse. We illustrate how trajectories of change in activity levels as measured with passive sensing and subjective measures can be tracked concurrently over time. We outline challenges and potential solutions for application of passive sensing data collection in future studies with larger samples using novel advanced statistical modeling, such as artificial intelligence algorithms.
Sutureless Lamellar Keratoplasty

Purpose To determine whether a fibrin adhesive can facilitate the performance of sutureless lamellar keratoplasty and attachment of amnion to bare sclera.
Factor Models and Principal Components

High-dimensional data can be challenging to analyze. They are difficult to visualize, need extensive computer resources, and often require special statistical methodology. Fortunately, in many practical applications, high-dimensional data have most of their variation in a lower-dimensional space that can be found using dimension reduction techniques. There are many methods designed for dimension reduction, and in this chapter we will study two closely related techniques, factor analysis and principal components analysis, often called PCA.
Nonlinear adaptive tracking and stabilization of a robot manipulator

Control of a robot manipulator requires solution of ordinary, coupled nonlinear differential equations. In Sinha, Kayalar, and Yurtseven (1990), a model reference system was introduced by ignoring the Coriolis terms where the system of nonlinear equations were almost decoupled by careful selection of nonlinear input torque expression. Varying a single parameter provided a stable solution about a known equilibrium point. In this work, the authors propose to extend the model reference system of Seraji (1988) to the case where there is parameter uncertainty and noise due to model imperfections. It is shown that a linear state feedback type of input torque provides a stable solution under uncertainty. A new theoretical method of stabilization of robot manipulator dynamics by nonlinear feedback is given. A partial linearization of robot arm control may yield a simpler nonlinear feedback control which has not yet been considered. The results obtained apply to a large class of nonlinear control systems. >
Romanticism and Childhood: The Infantilization Of British Literary Culture

Introduction: the infantilization of British literary culture Part I. History of an Analogy: 'For the Savage is to Ages What the Child is to Years': 1. The child is father of the man 2. Infancy, poetry and the origins of language 3. Becoming human: animal, infant and developmental literary culture in the Romantic period Part II. Prattle and Trifles: 4. Retentive ears and prattling mouths: popular antiquarianism and childhood memory 5. One child's trifle is another man's relic: popular antiquarianism and childhood 6. The layers and forms of the child's mind: Scott, Wordsworth and antiquarianism.
Productivity Measurement with Nonstatic Expectations and Varying Capacity Utilization: An Integrated Approach

Abstract Typically measures of multi-factor productivity growth have been based on a non-parametric framework that assumes all inputs are instantaneously adjustable, thus ignoring the important impacts of short-run fixity of certain inputs. This paper focuses on the representation within a parametric production model of economic capacity utilization indexes and on the adjustment of observed productivity measures by these indexes for the effects of short-run fixity. A dynamic optimization model based on adjustment costs for quasi-fixed inputs is developed to calculate these capacity utilization adjustments. The resulting framework is then used to identify empirically the effects of capacity utilization, non-static expectation, non-constant returns to scale and adjustment costs for both capital and labor on productivity growth in the U.S. manufacturing sector, 1947–1979.
Synthesis of proteins in cells infected with herpesvirus. 3. Relative amino acid content of various proteins formed after infection.

Abstract The proteins synthesized by pseudorabies virus-infected rabbit kidney cells contain more arginine but less methionine, phenylalanine, tyrosine, isoleucine, and lysine relative to leucine than the proteins synthesized by uninfected cells. This change in amino acid composition would be expected on the basis of the difference between the base composition of cellular DNA and of viral DNA. The changes in the patterns of electrophoretic migration of the proteins synthesized at various stages of the infective process were determined. The proteins synthesized by infected and uninfected cells, which migrate to the same positions in polyacrylamide gels, have different average amino acid compositions. Proteins synthesized by infected cells which migrate to different positions in the gels differ from one another in their amino acid composition. Viral proteins synthesized between 4 hours post infection and the end of the infective process which migrate to a given position in the gels have approximately the same amino acid composition. These results indicate that during this period of time, at least, the main viral proteins synthesized by the cells are the same.
How Revised Article 9 Will Turn the Trustee's Strong Arm into a Weak Finger: A Potpouri of Cases

The ability of creditors to become secured was enhanced with the revisions to Article 9 of the Uniform Commercial Code that became effective in 2001. The broader scope of Revised Article 9, its increased ease of attachment, and the simplified rules for perfection simultaneously reduced the scope of the avoiding powers of the bankruptcy trustee.Although more than a decade has passed, the effects anticipated by reflecting on a set of well-known cases remains worthwhile.
Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial.

Background Suicide is a devastating public health problem and very few biological treatments have been found to be effective for quickly reducing the intensity of suicidal ideation (SI). We have previously shown that a single dose of ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, is associated with a rapid reduction in depressive symptom severity and SI in patients with treatment-resistant depression. Method We conducted a randomized, controlled trial of ketamine in patients with mood and anxiety spectrum disorders who presented with clinically significant SI (n = 24). Patients received a single infusion of ketamine or midazolam (as an active placebo) in addition to standard of care. SI measured using the Beck Scale for Suicidal Ideation (BSI) 24 h post-treatment represented the primary outcome. Secondary outcomes included the Montgomery-Asberg Depression Rating Scale--Suicidal Ideation (MADRS-SI) score at 24 h and additional measures beyond the 24-h time-point. Results The intervention was well tolerated and no dropouts occurred during the primary 7-day assessment period. BSI score was not different between the treatment groups at 24 h (p = 0.32); however, a significant difference emerged at 48 h (p = 0.047). MADRS-SI score was lower in the ketamine group compared to midazolam group at 24 h (p = 0.05). The treatment effect was no longer significant at the end of the 7-day assessment period. Conclusions The current findings provide initial support for the safety and tolerability of ketamine as an intervention for SI in patients who are at elevated risk for suicidal behavior. Larger, well-powered studies are warranted.
Black feminist theory: Charting a course for black women's studies in political science

Black feminist consciousness arises from an understanding of intersecting patterns of discrimination. If race and gender are studied as separate categories, one cannot explain how attitudes might c...
The effects of beta-adrenergic stimulation on the frequency-dependent electrophysiologic actions of amiodarone and sematilide in humans.

BACKGROUNDThe autonomic nervous system appears to play an important role in the development of clinical ventricular arrhythmias, and beta-adrenergic sympathetic stimulation may be important in modulating the electrophysiologic effects of class III antiarrhythmic agents. This study prospectively determined the effects of isoproterenol on the frequency-dependent actions of sematilide (a pure class III agent that selectively blocks the delayed rectifier potassium current) and amiodarone (a class III agent with a complex pharmacologic profile) on ventricular repolarization, refractoriness, and conduction.METHODS AND RESULTSThe frequency-dependent electrophysiologic effects of sematilide (n = 11) and amiodarone (n = 22) were determined at (1) drug-free baseline, (2) during steady-state (> 48 hours) dosing with sematilide (455 +/- 5 mg/d [mean +/- SEM]) or after 10.5 days of amiodarone loading (1618 +/- 32 mg/d), and (3) during isoproterenol administration (35 ng/kg per minute) to patients receiving sematilide ...
Securing a femtocell-based location service

Mobile device users are increasingly incented to falsify their locations to retain location privacy while capturing economic benefits such as location-based retail discounts. Location spoofing is easily achieved with several widely-used location services that rely on smartphone applications to convey GPS coordinates, IP addresses, or WiFi Positioning System radio environment data. In earlier work we introduced a network infrastructure-based system that provides spontaneous, rapid, and robust mobile device location authentication by supplementing existing 802.11x APs with off-the-shelf femtocells. The proposed system has the property of leveraging mobile operator infrastructure, without requiring operator participation in either providing or authenticating location. In this paper we present a security analysis of the location authentication system. We assess its resistance to DoS attacks, identify various approaches for a mobile user to deceive a location verifier with and without the assistance of a colluder, and explore the tradeoffs between cost and complexity in mounting such attacks. Finally, we identify a collection of system modifications and countermeasures to anticipated attacks designed to decrease location authentication system vulnerabilities and increase privacy protection.
Modified acetylenic steroids as potent mechanism-based inhibitors of cytochrome P-450SCC

Abstract Synthesized 20-(4-tetrahydropyranyl-1-butynyloxy)-5-pregnen-3α,20β-diol [steroid I] and 20-(3-tetrahydropyranyl-1-propargyloxy)-5-pregnen-3α,20β-diol [steroid III] have been found to inactivate purified adrenocortical cytochrome P-450SCC. When incubated with the enzyme under turnover conditions, steroid I inactivated cytochrome P-450SCC by about 85% in 40 min. This is in contrast to the free triol analog, steroid II which inactivated the enzyme by only 45% within the same incubation period. A comparison of steroid III with its free triol analog, steroid IV, also showed that the diol is a more effective inactivator of the enzyme than the triol. The partition ratio was calculated by two different methods. Each of the steroids I–IV bound to the enzyme with spectrophotometric dissociation constant (Ks) in the micromolar range, producing Type II low spin spectra changes during titration of the enzyme. In addition, it was found that the binding of each of the compounds to the enzyme occurred without inactivation of the enzyme and that the inactivation under turnover condition, is not as a result of conversion to the denatured P-420 species. This demonstrated that steroids I and III could correctly be designated as mechanism-based (suicide) inhibitors. The kinetic studies demonstrated that steroids with the tetrahydropyranyl substituent are more potent inhibitors of cytochrome P-450SCC as shown by an initial turnover rate of 0.06 min−1, an inactivation rate constant of 0.05 min−1, and a partition ratio of about 1.0 for steroid I. Based on our finding, possible mechanisms of inactivation of cytochrome P-450SCC by these acetylenic steroids are propsoed.
Toward Evaluating Computer Aided Instruction: Attitudes, Demographics, Context

Abstract With the growing adaptation of computers in teaching, it is becoming increasingly important to be able to assess the perceived effectiveness of computer aided instruction (CAI). In this paper we argue that there are three critical aspects to this evaluation—determining the predisposition of the users towards CAI, the technographics/demographics of the students, and the situatedness of the CAI application. Using the data from three different studies we demonstrate that it is important to assess all these aspects. Several sub-components of predisposition are identified including the perceptions of access to computers, help on computers, and the perceptions of the overall benefits of CAI. Additionally, technographic attributes such as gender, and level and categories of use also impact the perception of effectiveness. Moreover, contexts of use, such as team-teaching strategies are also shown to implicate the perceptions of effectiveness. Finally, we argue that all these elements need to be considered together to assess the impact of these factors on perceived effectiveness.
Cannabinoid-1 receptor antagonist, rimonabant, for management of obesity and related risks.

The prevalence of obesity has risen substantially during the past 25 years in the United States and most developed countries, with a related increase in type 2 diabetes mellitus.1,2 Almost one third of the adult US population is considered to be obese (body mass index [BMI] ≥30), and 1 in 20 is extremely obese (BMI ≥40).3 Nearly 17% of children and adolescents are overweight in the United States.3 Obesity is associated with increased risk for type 2 diabetes mellitus, coronary heart disease (CHD), hypertension, obstructive sleep apnea, and cancer, higher overall mortality rate,4–6 and decreased longevity.7,8 Extreme obesity can truncate life expectancy in young adults by 5 to 20 years.8 Accordingly, the expected benefits of weight reduction for obese individuals are profound. Weight loss of 5% to 10% generally lessens many health risks, including cardiovascular risks, although such improvements are most notably demonstrable in studies specifically conducted in high-risk populations, and the benefits are presumed to be greater when healthier weight is maintained for long periods.9,10 In overweight and obese individuals, weight loss achieved with most interventions over 1 to 2 years generally leads to improvements in blood pressure (BP), glycemic measures, and triglycerides (TGs). Improvements in total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) have been reported in studies using dietary interventions combined with exercise. When weight loss is achieved primarily via pharmacological interventions, these benefits have not occurred quite so consistently.11 Reduced caloric intake and increased physical activity are generally accepted as the foundations of any approach directed at weight reduction, but these lifestyle interventions do not appear to provide long-lasting success for obese individuals wishing to lose weight. About half of the weight lost with the help of lifestyle interventions is regained at 1 year; after …
Atlanta Life Insurance Company: Guardian of Black Economic Dignity

Story of the Atlanta Life Insurance Company, and how it became an economic base within the black community shortly after the turn of the century.
The timing of morphogenetic events in the regenerating forelimb of the axolotl, Ambystoma mexicanum

Abstract The timing of morphogenetic events in the regenerating forelimb of the axolotl was investigated by rotation of limb coverings at well-defined stages in the regenerative process. Both the skin covering the stump and the epidermis covering the regenerate were manipulated independently and together as a unit. The results show that the transmission of morphogenetic information covers a broad range of regenerative stages. This morphogenetic information seems first to become irreversibly fixed in the regenerate by the stage of late bud. The regenerate is sensitive to stump influences at early stages of regeneration, but it becomes insensitive to stump influences by the stage of palette. Evidence is presented which implies that epidermis that covers the regenerate is capable of influencing morphogenesis.
Crystallization, dehydration and preliminary X-ray analysis of excisionase (Xis) proteins cooperatively bound to DNA.

This paper describes the crystallization, dehydration and preliminary X-ray data analysis of a complex containing several bacteriophage lambda excisionase (Xis) [Bushman et al. (1984). Cell, 39, 699–706] proteins cooperatively bound to a 33-­mer DNA duplex (Xis–DNAX1-X2). Xis is expected to recognize this regulatory element in a novel manner by cooperatively binding and distorting multiple head-to-tail orientated DNA-binding sites. Crystals of this complex belonged to space group P3121 or P3221, with unit-cell parameters a = b = 107.7, c = 73.5 A, α = β = 90, γ = 120°. Based on the unit-cell parameters for the asymmetric unit, VM is 3.0 A3 Da−1, which corresponds to a solvent content of ∼59%. The approaches used to crystallize the unusually long DNA fragment in the complex and the dehydration technique applied that dramatically improved the diffraction of the crystals from 10 to 2.6 A are discussed.
Is there a need for clinical guidelines in the United States for the diagnosis of hereditary angioedema and the screening of family members of affected patients

Background Hereditary angioedema (HAE) is an autosomal dominant disorder characterized by a deficiency of C1 esterase inhibitor (C1 INH) protein or function. Guidelines do not exist regarding diagnostic criteria or routine testing of family members of patients with HAE. Laboratory data for diagnosis include complement factor 4 level; C1 INH antigenic protein level, which is reduced in approximately 85% of patients with HAE; and C1 INH functional assay, which is considered an unreliable test in the United States secondary to inconsistent standardization of assays. Objectives To assess the shortcomings of diagnosing HAE and to determine whether family members of patients with HAE are being adequately screened. Methods The top physician prescribers of danazol in the United States were screened via an Internet questionnaire focusing on the diagnosis and current management of HAE. To assess the patient perspective on HAE, affected individuals in the United States, the United Kingdom, France, Germany, and the Netherlands participated in the Web-based International Survey of Patient Experience of Hereditary Angioedema. Results All 80 physicians who completed the survey were allergist or immunologists with a mean of 7 patients with C1 INH deficiency in their practices. Almost 84% of physician respondents used C1 INH level and function for diagnosis, and 63.8% used complement factor 4 levels. A total of 313 patients with HAE completed the survey. Respondents noted that only 48% of immediate family members and 26% of extended family members had been tested. Conclusion Guidelines could potentially alleviate delays in diagnosis and incorrect diagnoses and could lead to adequate screening of family members.
Warm molecular hydrogen in outflows from ultraluminous infrared Galaxies

Ultraluminous infrared galaxies (ULIRGs) show on average three times more emission in the rotational transitions of molecular hydrogen than expected based on their star formation rates. Using Spitzer archival data we investigate the origin of excess warm H_2 emission in 115 ULIRGs of the IRAS 1 Jy sample. We find a strong correlation between H_2 and [FeII] line luminosities, suggesting that excess H_2 is produced in shocks propagating within neutral or partially ionized medium. This view is supported by the correlations between H_2 and optical line ratios diagnostic of such shocks. The galaxies powered by star formation and those powered by active nuclei follow the same relationship between H_2 and [FeII], with emission line width being the major difference between these classes (about 500 and 1000 km/sec, respectively). We conclude that excess H_2 emission is produced as the supernovae and active nuclei drive outflows into the neutral interstellar medium of the ULIRGs. A weak positive correlation between H_2 and the length of the tidal tails indicates that these outflows are more likely to be encountered in more advanced mergers, but there is no evidence for excess H_2 produced as a result of the collision shocks during the final coalescence.
Image-guided thoracic pedicle screw placement: a technical study in cadavers and preliminary clinical experience.

Object Thoracic pedicle screw fixation is effective and reliable in providing short-segment stabilization. Although the procedure is becoming more widely used, accurate insertion of the screws is difficult due to the small dimensions of thoracic pedicles, and the associated risk is high due to the proximity of the spinal cord. In previous studies authors have shown the accuracy of image-guided lumbar pedicle screw placement, but there have been no reported investigations into the accuracy of image-guided thoracic pedicle screw placement. The authors report their experience with such an investigation. Methods To evaluate the accuracy of image-guided thoracic pedicle screw placement in vitro and in vivo, thoracic pedicle screws were placed with an image-guidance system in five human cadavers and 10 patients. In cadavers, the accuracy of screw placement was assessed by postoperative computerized tomography and visual inspection and in patients by postoperative imaging studies. Of the 120 pedicle screws place...
Anthrax Lethal Toxin-Mediated Disruption of Endothelial VE-Cadherin Is Attenuated by Inhibition of the Rho-Associated Kinase Pathway

Systemic anthrax disease is characterized by vascular leakage pathologies. We previously reported that anthrax lethal toxin (LT) induces human endothelial barrier dysfunction in a cell death-independent manner with actin stress fiber formation and disruption of adherens junctions (AJs). In the present study, we further characterize the molecular changes in the AJ complex and investigate whether AJ structure and barrier function can be preserved by modulating key cytoskeletal signaling pathways. Here, we show that LT reduces total VE-cadherin protein and gene expression but the expression of the key linker protein beta-catenin remained unchanged. The changes in VE-cadherin expression correlated temporally with the appearance of actin stress fibers and a two-fold increase in phosphorylation of the stress fiber-associated protein myosin light chain (p-MLC) and cleavage of Rho-associated kinase-1 (ROCK-1). Co-treatment with ROCK inhibitors (H-1152 and Y27632), but not an inhibitor of MLC kinase (ML-7), blocked LT-induced p-MLC enhancement and stress fiber formation. This was accompanied by the restoration of VE-cadherin expression and membrane localization, and attenuation of the LT-induced increase in monolayer permeability to albumin. Together, these findings suggest the ROCK pathway may be a relevant target for countering LT-mediated endothelial barrier dysfunction.
Scanning force microscopy reveals ellipsoid shape of chicken erythrocyte nucleosomes

Scanning force microscopy was used to investigate the conformation of hypotonic spread chicken erythrocyte nucleosomes. Nucleosomal chains were prepared in low-salt conditions and fixed before centrifugation onto glass coverslips and air drying. The images of single nucleosomes were isolated by image processing, and the height and geometry of the resulting three-dimensional structures were investigated. An average nucleosome height of 4.2 +/- 1.1 nm was determined. A virtual cross section at half-maximum height of the nucleosome structure was used for a characterization of the nucleosome geometry. The shape of this cross section was best described by an ellipse with an aspect ratio (major/minor axis) of approximately 1.30.
Getting more information from relay-feedback tests

The relay-feedback test is a simple and widely used identification tool for obtaining dynamic information that is useful for tuning feedback controllers. The height of the change in the manipulated variable h is specified, the test is run, and two parameters are normally obtained: the amplitude of the periodic output curve a (from which the ultimate gain Ku can be calculated) and the ultimate period Pu. These two parameters provide important information, but they are not sufficient for determining controller tuning for some processes, the most important being processes with large deadtimes. Many authors have suggested methods for extending this type of test in order to obtain additional information: run an additional step test, run a second relay-feedback test with a known dynamic element inserted in the loop, etc. This paper discusses the idea of avoiding these additional tests by simply looking at the shape of the output curve. First-order processes with small deadtime-to-time constant ratios (D/τ) gi...
Postoperative Pain Medication Requirements in Patients Undergoing Computer-Assisted (“Robotic”) and Standard Laparoscopic Procedures for Newly Diagnosed Endometrial Cancer

Laparoscopy (LSC) offers superior patient outcomes compared to laparotomy. Small retrospective/prospective series have suggested robotics offers further reduction in postoperative pain and pain medication use compared to standard LSC. Our objective was to compare postoperative pain in patients undergoing robotically assisted (RBT) versus standard LSC for newly diagnosed endometrial cancer. All preoperative endometrial cancer cases scheduled for RBT and LSC from May 1, 2007 to June 9, 2010 were identified. For this analysis, we only included cases not requiring conversion to laparotomy. All patients were offered intravenous (IV) patient-controlled analgesia (PCA) postoperatively. Intraoperative equivalent fentanyl doses (IEFDs) and pain scores in the postanesthesia care unit (PACU) were assessed. IV PCA was used in 206 RBTs (86 %) and 208 LSCs (88 %). Median IEFD was 425 μg for LSCs and 500 μg for RBTs (P = 0.03). Median pain scores on PACU arrival were similar in both groups. Median highest pain score was 5 for LSCs and 4 for RBTs (P = 0.007). Linear regression demonstrated that the IEFD was not correlated with the highest pain score (R = 0.09; P = 0.07). Fentanyl was used postoperatively in 196 of 206 RBTs (95 %) and 187 of 208 LSCs (90 %). The total fentanyl doses were 242.5 (range 0–2705) μg and 380 (range 0–2625) μg, respectively (P < 0.001). The median hourly fentanyl doses were 16.7 (range 0–122.5) μg and 23.5 (range 0–132.4) μg, respectively (P = 0.005). Simultaneous multiple regression analysis further demonstrated RBT was independently associated with a lower total fentanyl dose compared to LSC (P = 0.02). RBT is independently associated with significantly lower postoperative pain and pain medication requirements compared to LSC. The amount of intraoperative fentanyl analgesia does not appear to correlate with postoperative pain.