cssi/SciSciGPT-SciSciNet huggingface dataset:
Bortezomib, Dexamethasone, Thalidomide and Melphalan (VDT-Mel) Preparative Regimen in Autologous Stem Cell Transplant (ASCT) Results in a Very High Stringent CR (sCR) Rate in Multiple Myeloma (MM)

Abstract Background: Melphalan 200mg/m2 is the standard preparative regimen in MM and addition of other cytotoxic drugs has not been found to result in superior activity. The novel agents have improved outcome in MM significantly, but data on their role in preparative regimens are scarce. The purpose of this study was to understand the toxicity and efficacy of triple therapy with VDT in combination with high-dose melphalan. Methods: An IRB approved retrospective analysis was performed on all patients who received an ASCT with the VDT-Mel during 2012-2014. Mel: 100 mg/m2 was given on days -4 and -1; V: 1 mg/m2 on days -4, -1, +2 and +5; T: 100 mg daily from -5 to +5; and D: 20 mg/day from -4 to -1 and +2 to +5. End points were treatment-related toxicity during the first 100 days and quality of response at 6 months post-transplant; 98 patients had follow-up ≥ 6 months. Patients in sCR were also minimal residual disease negative (MRD-) by 10-color flow cytometry with a sensitivity of 10-4. Results: 100 patients received 153 transplants; 47 patients underwent single and 53 had tandem transplants (TT); 64 patients received early (≤ 12 months of induction therapy) and 36 salvage transplantation. Median age was 61 y; median followup was 16.2 months. Only 1patient had achieved a sCR and 11 a CR prior to transplantation. Best responses at 6 months were 53% sCR (and MRD-), 24% CR, and 9% VGPR. The sCR rate after single transplant was 47% (overall) and 54% (early transplant) vs 59% and 60% after TT. Grade 3-5 non-hematologic toxicities were almost entirely related to infections (38% and 53% in single and TT, respectively); the 100-day mortality rate was 2.6% (4/153), 1.8% for early transplants and 4.5% for salvage transplants. Median time to ANC recovery > 500/µL was 12 days in both early and salvage transplantation. Conclusion: VDT-Mel is well-tolerated and resulted in minimal additional toxicity and a similar mortality rate when compared to historic data of MEL alone. Importantly, the sCR rate with MRD- by flow cytometry at 6 months in our study was very high compared to published reports. The ultimate sCR rate will be higher as at this time an additional 13 patients attained a sCR during further follow up past 6 months for a total of 66% sCR. Since both sCR and MRD- are proven early surrogate markers for progression-free and overall survival, it appears highly likely that this regimen will be superior to Mel alone and should become the new standard for ASCT in myeloma. Download : Download high-res image (66KB) Download : Download full-size image Figure 1 . Disclosures No relevant conflicts of interest to declare.
Functional activity of anti-LINGO-1 antibody opicinumab requires target engagement at a secondary binding site

LINGO-1 is a membrane protein of the central nervous system (CNS) that suppresses myelination of axons. Preclinical studies have revealed that blockade of LINGO-1 function leads to CNS repair in de...
Multi-scale approach for chain-mooring OPB-induced failure considering time-varying interlink bending stiffness and fairlead condition

Abstracts In this study, a multi-scale approach concept is introduced to estimate OPB (out of plane bending)-induced failure considering time-varying interlink bending stiffness by using both high-fidelity nonlinear-FEM (finite element method)-based local structural analysis and low-fidelity global-system-simulation program so that they can mutually be interfaced during the time-stepping procedure. In addition, time-varying interlink-angle measurement and its use with respect to the global-system simulation are devised. For the fully-coupled hull-mooring-riser global dynamics simulation, in-house program CHARM3D is extended to accommodate the time-varying OPB interlink stiffness. The hot spots for OPB fatigue are selected from the high-fidelity local FE analysis including residual stress after proof-loading test. It is clearly shown that interlink angles are under-estimated if chain-hawse is not modeled in the global simulation. The OPB interlink angles, bending moments, and accumulated fatigue damages greatly increase when the fairlead connection is changed from hinged to fixed condition. Moreover, fatigue damage is underestimated if the residual stress effect is not considered.
A Reflective Study of Online Faculty Teaching Experiences in Higher Education.

Despite the popularity of online course and degree offerings in higher education, a lack of data persists on the unique challenges and opportunities online faculty face. Gaining insights about these experiences is important to ensure the quality of online teaching as colleges and universities continue expanding e-learning programs. Therefore, the purpose of this study is to examine the online teaching experiences of two faculty members through the implementation of reflective study methods. Major findings show that faculty access to professional development and mentoring, isolation and connectedness to the campus community, and academic freedom and curriculum control have significant implications for online teaching and student learning. In the wake of COVID-19 as colleges across the nation suddenly are faced with moving to exclusively online learning, this study is needed more than ever.
Micro- and nanoplastic induced cellular toxicity in mammals: A review

Plastic based products are ubiquitous due to their tremendous utility in our daily lives. However, the limited biodegradable nature of plastics has recently raised pollution concerns globally, especially micro- and nanoplastics. These anthropogenic pollutants are either manufactured specifically in the small size range for various commercial applications or formed due to fragmentation of macro plastics in the environment. Micro- and nanoplastics are currently widespread in the oceans, freshwater bodies, land and even present in our food. The biological effects of micro- and nanoplastics on aquatic organisms are well documented but their impacts on mammalian system have not been rigorously investigated. This review discusses the potential routes of exposure to micro- and nanoplastics, biological effects of these particles in mammalian cells, factors influencing toxicity, and the probable mechanisms of cytotoxicity. In general, small size, positive charge, high dose, and presence of toxic additives or pollutants in the micro/nanoplastics appear to induce cellular toxicity through oxidative stress, membrane damage, immune response and genotoxicity. Understanding the cellular fate and toxicity of these materials may help extrapolate risks to mammals.
When Others’ Reactions to News Media Messages are Visible: The Influence of News User Comments on Presumed Media Influence

The presumed media influence framework (IPI) theorizes how mass media influence perceptions and behaviors. The present study uses an online experiment to test the hypotheses deriving from the IPI i...
Nanoparticle Delivered Anti-miR-141-3p for Stroke Therapy

Ischemic stroke and factors modifying ischemic stroke responses, such as social isolation, contribute to long-term disability worldwide. Several studies demonstrated that the aberrant levels of microRNAs contribute to ischemic stroke injury. In prior studies, we established that miR-141-3p increases after ischemic stroke and post-stroke isolation. Herein, we explored two different anti-miR oligonucleotides; peptide nucleic acid (PNAs) and phosphorothioates (PS) for ischemic stroke therapy. We used US FDA approved biocompatible poly (lactic-co-glycolic acid) (PLGA)-based nanoparticle formulations for delivery. The PNA and PS anti-miRs were encapsulated in PLGA nanoparticles by double emulsion solvent evaporation technique. All the formulated nanoparticles showed uniform morphology, size, distribution, and surface charge density. Nanoparticles also exhibited a controlled nucleic acid release profile for 48 h. Further, we performed in vivo studies in the mouse model of ischemic stroke. Ischemic stroke was induced by transient (60 min) occlusion of middle cerebral artery occlusion followed by a reperfusion for 48 or 72 h. We assessed the blood-brain barrier permeability of PLGA NPs containing fluorophore (TAMRA) anti-miR probe after systemic delivery. Confocal imaging shows uptake of fluorophore tagged anti-miR in the brain parenchyma. Next, we evaluated the therapeutic efficacy after systemic delivery of nanoparticles containing PNA and PS anti-miR-141-3p in mice after stroke. Post-treatment differentially reduced both miR-141-3p levels in brain tissue and infarct injury. We noted PNA-based anti-miR showed superior efficacy compared to PS-based anti-miR. Herein, we successfully established that nanoparticles encapsulating PNA or PS-based anti-miRs-141-3p probes could be used as a potential treatment for ischemic stroke.
Orthopaedic surgical dressings

Abstract The choice of which surgical dressing to use is an important step in the postoperative care of orthopaedic patients. This decision is influenced in part by the patient's level of activity prior to surgery, medical history, wound classification, and cost. As orthopaedic wounds are inherently complex, often overlying bony prominences, it is imperative that orthopaedic providers are aware of the dressings available and how best to deploy them. Classified into three categories (passive, active, and interactive), orthopaedic surgical dressings can vary based upon their mechanism of action, absorptive capacity, and ability to provide wound protection. Through the activation or promotion of one of the four stages of wound healing, orthopaedic surgical dressings act to optimize postoperative wound care, leading to improved patient outcomes and a decrease in associated complications. The combined use of multiple dressings, with varying attributes, provides the ultimate method for obtaining the ideal orthopaedic surgical dressing. Choosing the appropriate dressing and subsequent care regimen can prevent unnecessary hospitalizations and additional costs associated with complex wound care. Future prospective trials aimed at evaluating specific dressings and their utility in orthopaedics is warranted.
Visuomotor Synchronization: Military Normative Performance

Introduction Cognitive processes such as perception and reasoning are preceded and dependent on attention. Because of the close overlap between neural circuits of attention and eye movement, attention may be objectively quantified with recording of eye movements during an attention-dependent task. Our previous work demonstrated that performance scores on a circular visual tracking task that requires dynamic synchronization of the gaze with the target motion can be impacted by concussion, sleep deprivation, and attention deficit/hyperactivity disorder. The current study examined the characteristics of performance on a standardized predictive visual tracking task in a large sample from a U.S. Military population to provide military normative data. Materials and methods The sample consisted of 1,594 active duty military service members of either sex aged 18-29 years old who were stationed at Fort Hood Army Base. The protocol was reviewed and approved by the U.S. Army Medical Research and Materiel Command Institutional Review Board. Demographic, medical, and military history data were collected using questionnaires, and performance-based data were collected using a circular visual tracking test and Trail Making Test. Differences in visual tracking performance by demographic characteristics were examined with a multivariate analysis of variance, as well as a Kolmogorov-Smirnov test and a rank-sum test. Associations with other measures were examined with a rank-sum test or Spearman correlations. Results Robust sex differences in visual tracking performance were found across the various statistical models, as well as age differences in several isolated comparisons. Accordingly, norms of performance scores, described in terms of percentile standings, were developed adjusting for age and sex. The effects of other measures on visual tracking performance were small or statistically non-significant. An examination of the score distributions of various metrics suggested that strategies preferred by men and women may optimize different aspects of visual tracking performance. Conclusion This large-scale quantification of attention, using dynamic visuomotor synchronization performance, provides rigorously characterized age- and sex-based military population norms. This study establishes analytics for assessing normal and impaired attention and detecting changes within individuals over time. Practical applications for combat readiness and surveillance of attention impairment from sleep insufficiency, concussion, medication, or attention disorders will be enhanced with portable, easily accessible, fast, and reliable dynamic eye-tracking technologies.
The Peculiar Obstacles to Justice Facing Federal Employees Who Survive Sexual Violence

The survivor of sexual violence in the federal workplace faces peculiar obstacles to remedial justice in court. When any plaintiff brings a tort claim against the United States for intentional harm by a federal employee, the Federal Tort Claims Act expressly excludes liability for “[a]ny claim arising out of assault [or] battery.” However, that exception is itself subject to exception and is of doubtful continuing legitimacy. For example, the United States remains liable under some circumstances for negligent failure to prevent an assault or battery. As another example, the FTCA expressly permits claims for assault or battery committed by a federal law enforcement officer. Moreover, the assault-and-battery exception has been partially and now should be wholly repealed. But even if the exception can be avoided for others, the federal employee still is left without tort relief. First, most federal courts have held that employment discrimination statutes provide the exclusive remedy for sexual misconduct occurring in the workplace, despite the absence of any support for that result in the text of the statutes. Second, the United States insists that the federal workers’ compensation statute is the exclusive remedy, even for workplace injuries imposed by intentional co-worker misconduct. Third, the young women and men of the armed services who survive sexual assault are locked out of the courthouse by the judicially-implied Feres doctrine, which holds that a servicemember injured incident to service is barred from bring an action against the United States under the FTCA.
Adroid: Augmenting Hands-on Making with a Collaborative Robot

Adroid1 enables users to borrow precision and accuracy from a robotic arm when using hand-held tools. When a tool is mounted to the robot, the user can hold and move the tool directly—Adroid measures the user’s applied forces and commands the robot to move in response. Depending on the tool and scenario, Adroid can selectively restrict certain motions. In the resulting interaction, the robot acts like a virtual “jig” which constrains the tool’s motion, augmenting the user’s accuracy, technique, and strength, while not diminishing their agency during open-ended fabrication tasks. We complement these hands-on interactions with projected augmented reality for visual feedback about the state of the system. We show how tools augmented by Adroid can support hands-on making and discuss how it can be configured to support other tasks within and beyond fabrication.
Environmental Degradation in Jacobean Drama

Introduction 1. Middleton and ecological change 2. Jonson and the universe of things 3. Shakespeare's dirt 4. John Fletcher and the ecology of manhood 5. Dekker's walks and orchards 6. Heywood and the spectacle of the hunt Conclusion.
Field performance of bermudagrass germplasm expressing somaclonal variation selected for divergent responses to fall armyworm

Fall armyworm, Spodoptera frugiperda (J.E. Smith), is the major insect pest of bermudagrass, Cynodon dactylon (L.) Pers., in the Southeastern USA. Somaclonal variation in bermudagrass has produced distinctly divergent susceptibilities to fall armyworm under controlled conditions. Plant persistence, productivity, forage quality characteristics, and response to fall armyworm were assessed in field plots at Rosepine, Louisiana from 1995 through 1999. Forage quality characteristics were assessed each year, and natural infestations of fall armyworms were monitored in 1998 and 1999. Most of the somaclonal lines were similar to their parent cultivar in forage yield and quality, and none was consistently superior. Differences in forage quality characteristics among the bermudagrass lines were detected in 1996 and 1997, with little difference among lines in 1998 and 1999. All lines assessed were infested and sustained damage from natural infestations of fall armyworm larvae. Thus despite acceptable forage productivity and quality of most lines, expression of fall armyworm resistance under these field conditions was not detected. This lack of difference under field conditions, despite distinct resistance of some lines under controlled conditions, may primarily be due to either insufficient production of compounds deterring the insects for detectable effects under field conditions or loss of expression of the somaclonally acquired traits even with vegetative reproduction.
A low-overhead virtual rail technique for SRAM leakage power reduction

We propose a virtual supply rail control technique that reduces SRAM leakage. This method encompasses a cell-based image, serial tiling, pitch matching, small drive device overhead, and controlled power-on currents while incurring small circuit overhead. A virtual rail cell contains both the sleep transistor fingers and input/output drive transistors. The usual overhead associated with the drive circuit that controls the sleep transistors is significantly reduced due to reduced wire load and improved drive efficiency. This technique provides gradual power-on characteristics and good signal slews while effectively mitigating leakage current, maintaining read/write speed and achieving power-on latency compatible with high-performance designs.
Performance Optimization in the Presence of Norm Bounded Structured Uncertainty

A performance criterion given as a bound on the H ? norm of some transfer function is known to be equivalent to the stability condition with respect to the auxiliary unstructured uncertainty. Therefore, robust stability and performance of the system in the presence of a block diagonal norm bounded uncertainty with (m) elements is easily transformed into a structured singular value problem with respect to the overall diagonal uncertainty with (m+1) blocks. When the norm bounds on the uncertainty and the performance condition are known and scaled to the value of one, the synthesis becomes a search for a compensator that will make the associated structured singular value smaller than one. This is usually done by the "D-K" iteration introduced by Doyle. In this paper we look at the case where the norm bound on one of the blocks in the structured uncertainty is not known a priori. The problem then becomes one of finding the extreme value of that bound such that there exist a stabilizing compensator that guarantees robust stability and performance. An recursive algorithm based on altering standard "D-K" iteration is proposed.
Moral Development, Norm Systems and Social Modernization: A Normative Democratic Peace Model

This article offers a framework for understanding the democratic peace phenomenon across three levels of analysis. Specifically, Kohlberg’s structural-development model of moral reasoning offers an understanding of how individuals (e.g., national leaders, public officials) may approach ethically difficult decisions, such as whether or not to engage in war. In turn, this supports the normative strain of the democratic peace argument. Further, by applying a social constructivist approach to our understanding of the interaction between individual actors and social mores, the normative power and social foundation of the democratic peace argument is clarified. Finally, I argue that modernization & cultural change data from the World Values Survey supports the normative democratic peace proposition. Thus, I examine three different bodies of literature - individual moral development, normative democratic peace, and neo-modernization – and argue that the three are interrelated and aspects of the same meta-process. Therefore, I suggest a more complex, social understanding of non-conflict, predicated on normative and cultural-value ‘proximity’, which has been neglected in the literature, since most democratic peace scholars focus on structural explanatory variables.
Mitochondrial Biogenesis as a Pharmacological Target: A New Approach to Acute and Chronic Diseases

Mitochondrial dysfunction is a key pathophysiological component of many acute and chronic diseases. Maintenance of mitochondrial homeostasis through the balance of mitochondrial turnover, fission and fusion, and generation of new mitochondria via mitochondrial biogenesis is critical for tissue health. Pharmacological activation of mitochondrial biogenesis can enhance oxidative metabolism and tissue bioenergetics, and improve organ function in conditions characterized by mitochondrial dysfunction. However, owing to the complexity of mitochondrial assembly and maintenance, identification of specific activators of mitochondrial biogenesis has been difficult. This review provides an overview of the role of mitochondrial dysfunction in acute and chronic diseases, details the current state of therapeutics for the stimulation of mitochondrial biogenesis and their effects on disease outcomes, describes new screening methodologies to identify novel stimulators and noncanonical pathways of mitochondrial biogenesis,...
SIMD: an additional pattern for PLPP (pattern language for parallel programming)

Recent trends in hardware, such as IBM's Cell Broadband Engine and GPUs that can be used for general-purpose computing, have made widely available systems for which a SIMD (Single Instruction, Multiple Data) style of data-parallel programming is appropriate. This paper presents a pattern to help software developers construct parallel programs for environments that support this style of data parallelism. In this approach, the program is viewed as a single thread of control, with implicitly parallel updates to data. This pattern is a new addition to the Pattern Language for Parallel Programming (PLPP) presented in our previous work [18, 19].
Dependence of enhancer-mediated transcription of the immunoglobulin mu gene on nuclear matrix attachment regions

Transcription of the immunoglobulin mu heavy chain locus is regulated by an intronic enhancer that is flanked on both sides by nuclear matrix attachment regions (MARs). These MARs have now been shown to be essential for transcription of a rearranged mu gene in transgenic B lymphocytes, but they were not required in stably transfected tissue culture cells. Normal rates of transcriptional initiation at a variable region promoter and the formation of an extended deoxyribonuclease I (DNase I)--sensitive chromatin domain were dependent on MARs, although DNase I hypersensitivity at the enhancer was detected in the absence of MARs. Thus, transcriptional activation of the mu gene during normal lymphoid development requires a synergistic collaboration between the enhancer and flanking MARs.
Range-wide population structure and history of the northern quahog (Merceneria merceneria) inferred from mitochondrial DNA sequence data

Baker, P., Austin, J. D., Bowen, B. W., and Baker, S. M. 2008. Range-wide population structure and history of the northern quahog (Merceneria merceneria) inferred from mitochondrial DNA sequence data. - ICES Journal of Marine Science, 65: 155-163.The northern quahog (Mercenaria mercenaria) is a commercially important bivalve distributed in the NW Atlantic from Florida to Nova Scotia. We report on population genetic analyses, based on 528 bp of mitochondrial COI gene, for 10 locations across the range of M. mercenaria (n = 297). Our analyses revealed no evidence of cryptic evolutionary lineages, but modest population structure (φ ST = 0.0213; p = 0.0019) with a significant partition at Cape Hatteras and a weakly supported partition at Cape Cod. Samples from the west coast of Florida (Gulf of Mexico) were not significantly different from most Atlantic populations, despite a 600 km gap in distribution along South Florida, and a well-documented biogeographic break at Cape Canaveral. These findings support the thesis that the Gulf of Mexico population is the product of a recent introduction. Samples north of Hatteras decrease in diversity with increasing latitude, probably indicating post-glacial range extension, a conclusion supported by a highly significant Fu's F-statistic (−99.14; p < 0.001) indicating population expansion. Mercenaria mercenaria stocks in the Atlantic include a single evolutionary unit divided into at least three closely related populations, though this does not preclude regional adaptive differences between northern, central, and southern populations.
Ephemeral penalty functions for contact-impact dynamics

The use of penalty functions to treat a class of structural contact-impact problems is investigated, with emphasis on ones in which the impact phenomena are primarily nondestructive in nature and in which only the gross characterization of the response is required. The dynamic equations of motion are integrated by the difference method. The penalty is represented as an ephemeral fictitious nonlinear spring that is inserted on anticipation of contact. The magnitude and variation of the penalty force is determined through energy balancing considerations. The 'bell shape' of the penalty force function for positive gap was found to be satisfactory, as it depends on only two parameters that can be directly assigned the physical meaning of force and distance. The determination of force law parameters by energy balance worked well. The incorporation of restitution coefficients by the area balancing method yielded excellent results, and no substantial modifications are anticipated. Extensional penalty springs are obviously sufficient for the simple examples treated.
An Analysis of Writing and Postwriting Group Collaboration In Middle School Pre-Algebra

The current reform effort in mathematics education emphasizes the importance of students' being active in their own development and understanding of mathematical ideas. The reform recommends that students read, write, and discuss mathematics as a way of developing mathematical thinking. This study emphasizes writing as a way to help students learn to think mathematically. Typically, writing has been used as a dialogue between the teacher and the student or as a product for the teacher to examine. However, this study is significant because students wrote as a preparation for discourse with the teacher and other students. Qualitative analysis was used to understand how middle school students think about and approach problems while they wrote descriptions of why and how they solve problems. For this study, students wrote detailed descriptions of their approaches to nonroutine problems and then met in groups to discuss and evaluate their approaches. In order to understand their mathematical thinking, the researcher examined students' writing, participated in and audiotaped group discussions, and interviewed students. The results of the analysis showed that rich learning experiences are possible when writing is used as a way to prepare for small group discussion in mathematics.
Review of the Evidence for the Clinical Utility of Lipoprotein-Associated Phospholipase A2 as a Cardiovascular Risk Marker

A substantial body of peer-reviewed studies has been published validating the role of inflammation in atherogenesis and supporting lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) as a cardiovascular risk marker independent of and additive to traditional risk factors. As with elevated high-sensitivity C-reactive protein, an elevated Lp-PLA 2 level approximately doubles the risk for primary and secondary cardiovascular events. Interestingly, when both inflammatory markers are increased together, they provide an even greater predictive capability to help identify very-high-risk individuals who would benefit most from aggressive lipid-lowering therapy. High levels of Lp-PLA 2 are present in inflamed, rupture-prone plaques, and it appears that Lp-PLA 2 is released from these plaques into the circulation. Over 25 prospective epidemiologic studies have demonstrated the association of elevated Lp-PLA 2 levels with future coronary events and stroke—11 of 12 prospective studies have shown a statistically significant association between elevated Lp-PLA 2 and primary coronary or cardiovascular events, 12 of 13 have shown a statistically significant association with recurrent coronary or cardiovascular events, and 6 studies have shown a positive association with stroke. Lp-PLA 2 should be viewed today as an important cardiovascular risk marker whose utility is as an adjunct to the major risk factors to adjust absolute risk status and thereby modify low-density lipoprotein cholesterol goals. The low biologic fluctuation and high vascular specificity of Lp-PLA 2 makes it possible to use a single measurement in clinical decision making, and it also permits clinicians to follow the Lp-PLA 2 marker serially. Ultimately, Lp-PLA 2 may also be classified as a risk factor, but this should not detract from its utility today as a risk marker.
Expansion velocity of cosmological QCD bubbles

Abstract The expansion velocity of hadronic bubbles nucleated in the cosmological quark-hadron phase transition is estimated. For reasonable parameter values the expansion velocity is close to the maximum deflagration velocity allowed by entropy increase. The stability of the wall is also discussed.
Compositional variations of leaf monoterpenes in Cupressus macrocarpa, C. pygmaea, C. goveniana, C. abramsiana and C. sargentii

Abstract Two hundred and fifty trees of Cupressus macrocarpa, C. goveniana, C. abramsiana, C. pygmaea and C. sargentii sampled in 20 localities were analyzed by GLC to determine the monoterpene constituents of their foliage volatile oils. The results separated the species investigated into three distinct groups: C. sargentii and C. abramsiana, C. goveniana and C. pygmaea , and C. macrocarpa . The southernmost populations of C. sargentii , from Zaca Peak (Santa Barbara County) and Chorro Creek (San Luis Obispo County), appeared to be considerably different from the rest. In nearly all oils percentages of α- and γ-terpinene and terpinolene varied in direct proportion to one another which was interpreted by a large similarlty in their mechanisms of formation involving the splitting of α-protons from the 1- p -menthene-4-carbonium ion common intermediate.
Selective Substrate Supply in the Regulation of Yeast de Novo Sphingolipid Synthesis

The heat stress response of Saccharomyces cerevisiae is characterized by transient cell cycle arrest, altered gene expression, degradation of nutrient permeases, trehalose accumulation, and translation initiation of heat shock proteins. Importantly heat stress also induces de novo sphingolipid synthesis upon which many of these subprograms of the heat stress response depend. Despite extensive data addressing the roles for sphingolipids in heat stress, the mechanism(s) by which heat induces sphingolipid synthesis remains unknown. This study was undertaken to determine the events and/or factors required for heat stress-induced sphingolipid synthesis. Data presented indicate that heat does not directly alter the in vitro activity of serine palmitoyltransferase (SPT), the enzyme responsible for initiating de novo sphingolipid synthesis. Moreover deletion of the small peptide Tsc3p, which is thought to maximize SPT activity, specifically reduced production of C(20) sphingolipid species by over 70% but did not significantly decrease overall sphingoid base production. In contrast, the fatty-acid synthase inhibitor cerulenin nearly completely blocked sphingoid base production after heat, indicating a requirement for endogenous fatty acids for heat-mediated sphingoid base synthesis. Consistent with this, genetic studies show that fatty acid import does not contribute to heat-induced de novo synthesis under normal conditions. Interestingly the absence of medium serine also ameliorated heat-induced sphingoid base production, indicating a requirement for exogenous serine for the response, and consistent with this finding, disruption of synthesis of endogenous serine did not affect heat-induced sphingolipid synthesis. Serine uptake assays indicated that heat increased serine uptake from medium by 100% during the first 10 min of heat stress. Moreover treatments that increase serine uptake in the absence of heat including acute medium acidification and glucose treatment also enhanced de novo sphingoid base synthesis equivalent to that induced by heat stress. These data agree with findings from mammalian systems that availability of substrates is a key determinant of flux through sphingolipid synthesis. Moreover data presented here indicate that SPT activity can be driven by several factors that increase serine uptake in the absence of heat. These findings may provide insights into the many systems in which de novo synthesis is increased in the absence of elevated in vitro SPT activity.
Estimating the environment and the response of sprinkler links in compartment fires with draft curtains and fusible link-actuated ceiling vents—Theory

Abstract The physical basis and associated mathematical model for estimating the fire-generated environment and the response of sprinkler links in well-ventilated compartment fires with draft curtains and fusible link-actuated ceiling vents is developed. Complete equations and assumptions are presented. Phenomena taken into account include: the flow dynamics of the upward-driven, buoyant fire plume; growth of the elevated-temperature smoke layer in the curtained compartment; the flow of smoke from the layer to the outside through open ceiling vents; the flow of smoke below curtain partitions to building spaces adjacent to the curtained space of fire origin; continuation of the fire plume in the upper layer; heat transfer to the ceiling surface and the thermal response of the ceiling as a function of radial distance from the point of plume-ceiling impingement; the velocity and temperature distribution of plume-driven near-ceiling flows and the response of near-ceiling-deployed fusible links as functions of distance below the ceiling and distance from plume-ceiling impingement. The theory presented here is the basis of a user-friendly computer program, LAVENT, which is supported by a user guide and which can be used to study parametrically a wide range of relevant fire scenarios.
Nutritional sensitivity of fifth instar prothoracic glands in the tobacco hornworm, Manduca sexta

Insulin-regulated growth of the prothoracic glands appears to play a critical role in timing the last larval molt, and hence metamorphosis. The present study examined insulin signaling in relation to the growth and secretory activity of prothoracic glands in the tobacco hornworm, Manduca sexta. As larvae feed during the first half of the final larval stage, the prothoracic glands grow and ecdysone secretory capacity increases. During this period of growth, we verified the presence of insulin receptor transcript in the prothoracic glands and demonstrated that the glands were responsive to insulin, as evidenced by the in vitro phosphorylation of signaling proteins in the insulin pathway such as Akt/protein kinase B and FOXO. It was predicted that starvation would reduce ecdysone secretion with concomitant changes in insulin signaling. To test this prediction, larvae were starved and changes were quantified in two nutritionally sensitive transcripts, insulin receptor and the translation inhibitor 4EBP. In glands from starved larvae, growth and ecdysone secretory capacity were reduced, and insulin receptor and 4EBP transcripts were increased. The latter changes would be expected to accompany starvation in conjunction with enhanced insulin sensitivity and reduced protein synthesis. Increased transcription of insulin receptor and 4EBP strongly suggest that nutritional deprivation reduces the secretion of endogenous insulin-like hormones. When injected with insulin, 4EBP levels in the prothoracic glands of starved larvae decreased. Thus, insulin appeared to correct starvation-induced deficits in glandular protein synthesis. However, insulin injection did not enhance ecdysone secretion. Thus, although the prothoracic glands are insulin-responsive and insulin-like hormones may promote glandular growth as larvae feed, the effects of nutritional depletion on steroidogenesis in Manduca cannot be explained solely by reduced insulin.
How to Make a Tornado

The 2011 tornado season was particularly bad for tornadoes and their impacts on society, with nearly 1700 confirmed tornadoes (second highest total since 1950) and an estimated 550 fatalities (dead...
Characterization of random heterogeneities in polycrystalline microstructures using wave propagation simulation

The quantification of variability in the mechanical behavior of metallic materials is important in the design and reliability assessment of mechanical components. A combination of experimental and computational approaches is often required to alleviate the experimental burden and lack of data in constructing a probabilistic formalism for material design. The present work aims at integrating material characterization and computational modeling for the evaluation of variability in the elastodynamic response of random polycrystals. First, a procedure is presented for simulation of random 2D polycrystalline microstructures from limited experimental data. Second, the capability of the numerical model in capturing the variation of the scattered waves due to the random heterogeneities is investigated by introducing a suitable quantity of interest characterizing the intensity of the fluctuations of the stochastic waveforms. Two important types of heterogeneities are considered. The first is the inherent heterogeneity due to the mismatch in the grain orientations. The second is the heterogeneity due to fine scale defects in the form of random intergranular micro-cavities. The numerical model presented in this paper can be useful for the interpretation of experimental ultrasonic measurements for random heterogeneous material. The result is also applicable to the validation of multiscale probabilistic models for material prognosis.
COMPUTATION OF SCHOTTKY BARRIERS IN SEMICONDUCTING FERROELECTRIC BARIUM TITANATE IN REDUCING ATMOSPHERES

The time and temperature dependencies of the double Schottky barriers in semiconducting ferroelectric barium titanate (${\mathrm{BaTiO}}_{3}$) in the presence of a reducing or an oxidizing atmosphere are considered. Numerical computations of the local variation of barrier heights as a function of time and temperature are presented for both bulk and thin films. Experimental observations and theoretical results are analyzed for donor-doped semiconducting polycrystalline ${\mathrm{BaTiO}}_{3}$.
Technological society and its counterculture: An Hegelian analysis 1

The paper analyzes the American counterculture of the 1960s and early ‘70s, from the New Left through the hippies, revolutionaries and Jesus people, to the counterculture's collapse in artistry and the cynicism of Watergate; this evolution is viewed as a re‐enactment of Hegel's dialectic of ‘active reason’ in the Phenomenology of Spirit, from the critique of ‘observation’ to ‘society as a community of animals’. Secondly, an attempt is made to account for this re‐enactment in the twentieth century. The tentative conclusion is that the counterculture was America's discovery of the Hegelian idea of the state, but that, in an age of world economic interdependence and universal (if sometimes unacknowledged) military insecurity, this discovery came too late. The economic and military basis of the only world‐history which Hegel knew, the history of nation‐states all the way from oriental despotisms to modern ‘Germanic’ states is, it seems, in the process of disappearance.
Machine Harvesting of Lima Beans for Processing

ABSTRACT Pod stripper combines are the predominant method of harvesting lima beans for processing in the Mid-Atlantic region. Losses during harvest represent a significant economic loss to growers and processors. Eighty-four field tests in 1994 and 1995 showed that total crop loss during harvest averaged more than 540 kg/ha (475 lbs/acre) or 23.6% of the commercial yield. Results for four baby lima bean varieties and combines from five different manufacturers indicate the major field loss occurs at the header of the combine where the pods are stripped from the plant. Threshing and cleaning losses on the combine averaged less than 25% of the total crop loss. The cultivar ‘Maffei 15’ exhibited significantly higher header loss than the variety ‘8–78.’ There were no significant differences in loss between any of the combines evaluated. The predominant losses occurring at the combine header were loose pods and pods left on the plant. Trash content in the harvested beans averaged 13% by weight. Field levelness ...
Primary Erythromelalgia in a Child Responding to Intravenous Lidocaine and Oral Mexiletine Treatment

Erythromelalgia is a rare, chronic, debilitating condition characterized by redness, warmth, and severe burning pain of the distal extremities. The feet are more commonly affected than the hands. Pain is precipitated by increases in temperature and by exercise. Patients often obtain relief by immersing the affected extremity in cold water. The pain is often refractory to treatment. For many patients, multiple pain medications have been useless in achieving complete relief of pain symptoms. Previous reports of erythromelalgia among adolescents indicated prolonged relief of pain with sodium nitroprusside infusions, epidural infusions of local anesthetics, or gabapentin treatment. We present a case of an 11-year-old, white, male child with primary erythromelalgia, whose initial symptoms started in his preschool years and whose childhood was marked by escalating episodes of pain with warmth and redness of his feet, precipitated especially by increases in temperature and by activity. All conventional pain management techniques had failed to relieve our patient of his symptoms, and he obtained some relief only by soaking his affected extremities in ice water. He had experienced minimal benefit from seeing a pain psychologist, who helped him develop techniques to cope with the pain. At the time of presentation, the patient's episodes of pain had increased to 15 to 20 per day, and there was evidence of chronic immersion injury to the skin of his feet. Before his most recent hospitalization, the pain had spread to involve his hands as well. The patient was overwhelmed with anxiety and could not participate in school or social activities at the time of admission. During his current hospitalization, he did show some therapeutic response to sodium nitroprusside infusion, which unfortunately had to be discontinued because of side effects and because his family desired to leave the ICU environment, which was stressful to the patient. He also had some response to lumbar epidural infusion of local anesthetics, which could not be continued because he found the motor blockade that accompanied his analgesia intolerable. However, intravenous lidocaine infusion, with subsequent transition to oral mexiletine therapy, proved very effective in reducing the frequency and severity of the pain episodes. The patient was discharged from the hospital with oral mexiletine therapy and has been monitored at the pain management clinic. He returned to and completed school, attended summer camp, and enjoys an active happy life. He walks without precipitating pain in his feet and sleeps 9 to 10 hours every night. He has needed to soak his feet on only 4 occasions in the 6 months since his discharge from the hospital. His quality of life has improved significantly. He has shown no evidence of liver toxicity, and his mexiletine levels have been stable.
Clients' Perspectives on the Effects of Laparoscopic Ovariectomy on Equine Behavior and Medical Problems

Abstract Because laparoscopic surgery eliminates the side effects of general anesthesia, the success and therefore the use of laparoscopic surgery continues to broaden. Laparoscopic ovariectomy, once only used to treat medical problems such as granulosa cell tumors, is now being expanded to treat behavioral problems in mares. Thirty-five mares with behavioral or medical problems were treated with ovariectomies, and their owners were later contacted and questioned concerning the effect of ovariectomy on their mares. Behavioral improvement was seen in 83% (19/23) of mares treated for behavior-related problems. Aggression problems improved in 86% (12/14) of cases, general disagreeable demeanor improved in 81% (17/21), and excitability improved in 75% (12/16) of cases in which these behaviors were previously observed. Kicking and biting improved in 73% (8/11), problems in training improved in 72% (13/18), and frequent urination and problems with other horses improved in 64% (7/11 and 9/14, respectively) of cases. Owners with nonovariectomized mares also were contacted to compare the normal progression of mare behavior over time with the behavioral change in ovariectomized mares. A statistically significant change in behavior of ovariectomized mares over nonovariectomized mares was seen in the categories of decreased aggression ( P P P P In cases in which medical problems such as granulosa cell tumors, ovarian cysts, and cycle-related colic were treated with ovariectomy, all of the clients were very satisfied with the treatment, whereas clients attempting to treat cycle-related laminitis were dissatisfied.
The Impact of Participation in Undergraduate Extracurricular Activities on the Transformation of Habitus among American Medical Students

Building on the work of Pierre Bourdieu, we look at the question of whether extracurricular activities at the undergraduate level have an impact on American medical students' habitus, which we operationalize as a sense of inclusion, belonging. Using a national sample of 375 medical students and controlling for relevant variables, we find that for students from high-prestige backgrounds, being white is the major influence on sense of belonging. For students from low-prestige backgrounds, being white, multiple school acceptances, and participation in cultural activities as undergraduates are directly related to sense of belonging. The effect of participation in undergraduate cultural activities on sense of belonging illustrates the hysteresis effect. We discuss the consequences of cultural omnivorousness with its implications for a broad symbolic touch including the ability to decode a wide range of cultural texts in physician–patient communication in the context of a diverse population.
Is Qualitative Hedonism Incoherent

Geoffrey Scarre has recently argued that the version of qualitative hedonism which I attribute to Mill is unsatisfactory for various reasons. In his view, even if it is formally compatible with value monism, ‘the Mill/Riley line’ involves non-hedonistic elements and offers an implausible account of the relationship between ‘higher’ and ‘lower’ pleasures. In this paper, I show that his objections, which are similar in spirit to those pressed earlier by Bradley, Moore and others against Mill, are unfounded where not confused. The Mill/Riley line does not rely on non-hedonistic standards and has sufficient flexibility to account for many different kinds of pleasures and pleasing activities. It remains a coherent version of qualitative hedonism, worthy of further consideration and study.