cssi/SciSciGPT-SciSciNet huggingface dataset:
A Cas9 with Complete PAM Recognition for Adenine Dinucleotides

CRISPR-associated (Cas) DNA-endonucleases are remarkably effective tools for genome engineering, but have limited target ranges due to their protospacer adjacent motif (PAM) requirements. We demonstrate a critical expansion of the targetable sequence space for a Type-IIA CRISPR-associated enzyme through identification of the natural 5’-NAA-3’ PAM specificity of a Streptococcus macacae Cas9 (Smac Cas9). We further recombine protein domains between Smac Cas9 and its well-established ortholog from Streptococcus pyogenes (Spy Cas9), as well as an “increased” nucleolytic variant (iSpy Cas9), to achieve consistent mediation of gene modification and base editing. In a comparison to previously reported Cas9 and Cas12a enzymes, we show that our hybrids recognize all adenine dinucleotide PAM sequences and possess robust editing efficiency in human cells.
Detecting Reach to Grasp Activities using Motion and Muscle Activation Data

The performance of activities of daily living (ADLs) is directly related to recovery of motor function after an incident such as stroke. Because the recovery process occurs primarily in the home, many efforts have sought to capture gross body motion and limb motion using wearable sensors. One component of function not easily quantified but nonetheless important is the ability to interact with the environment using the upper extremities. In particular, environmental interaction requires the performance of reach-to-grasp (RTG) tasks. The goal of the proposed approach is to determine the extent to which the commercial Myo armband sensor provides a noninvasive mechanism for monitoring and recording RTG task performance. Our results indicated that accelerometer and rate gyroscope data varied significantly between task types, and that a classifier using motion and muscle activation data was capable of distinguishing between gestures with 93% accuracy.
Can we condition native plants to increase drought tolerance and improve restoration success

A common method in ecological restoration is the transplanting of nursery-grown seedlings to the field and, with proper resources, this technique can be highly successful. However, stressors such as drought may negatively impact plant performance and restoration success, especially in dryland ecosystems. Furthermore, increasing environmental change may hamper the ability of practitioners to restore native vegetation. A growing body of research suggests that exposing plants to a stressor may improve tolerance to subsequent stress events later in life. We sought to understand if such a phenomenon could be exploited in order to improve plant drought-tolerance and aid native plant restoration in southern California. In a multi-phase experiment, we first exposed seedlings of native perennials to episodic drought and then later compared the response of these plants to a second drought event to that of well-watered controls. We also transplanted replicates of both treatments to a restoration site in the field to test whether exposure to drought as a seedling could improve plant performance. Plant species responded to drought differently, with species exhibiting the full range of positive, neutral, and negative responses to temporal variability in water stress. However, some species appeared to benefit from drought preconditioning, exhibiting greater growth and increased water-use efficiency compared to well-watered plants. This suggests that simple applications of stress treatments could improve plant growth and stress tolerance, but the success of this method is likely very species specific. Restoration practitioners should consider conducting pilot studies with target plant species to better understand if this technique could assist in achieving restoration goals.
Mutation in Rpa1 results in defective DNA double-strand break repair, chromosomal instability, and cancer in mice

BA-1 Genomes of solid tumors can be highly rearranged. Recurrent genome rearrangements are known to involve genes that mediate a wide range of tumor functions including angiogenesis, immortality, survival, metastasis, and resistance to therapy. Genes linked to these rearrangements are increasingly targets of anti-tumor therapeutics. Tumor genomes are not collinear with their normal host genome and current technologies for studying tumor genome structure are not capable of elucidating the structural organization of tumor genomes at high resolution, or of relating it to he underlying sequence. Because of these inherent limitations, the role of translocations and inversions in solid tumors is not well understood. Indeed, even the structural organization of amplicons remains largely enigmatic due to indirect methods of analysis. ESP is a sequence-based method for directly determining the structural organization of tumor genomes, and for cloning structural rearrangements such as translocations, inversions, and complex rearrangements en masse. ESP begins with construction of a BAC library from a tumor. BAC end sequences are then generated for individual BAC clones and mapped onto the normal “reference” genome sequence. This process reveals all classes of structural aberrations including copy number changes, translocations, and inversions, and, importantly, identifies BAC clones spanning associated genome breakpoints. We first demonstrated the power of ESP in an analysis of the breast cancer cell line MCF7 and have now extended it to primary tumors of the brain and breast. For copy number analysis ESP and array CGH are highly concordant although ESP is capable of much higher resolution. In contrast to array CGH, ESP provides direct evidence for the packaging of amplified DNA from multiple loci, and that the packaged DNA may be highly rearranged. ESP provides evidence for independent mechanisms of amplification operating within a single tumor genome. Approximately 80% of identified translocations and inversions tested were confirmed, and evidence for chimeric transcripts is emerging. Whole genome ESP is being combined with robust mathematical methods for tumor genome assembly enabling the formal testing of hypotheses of tumor evolution. ESP is inherently integrative and thus brings the power of genetic analysis to interpretation of complex expression microarray and proteomic data. Further, it enables construction of mice transgenic for BAC clones carrying human tumor DNA, thus preserving the nuances of transcriptional regulation and alternative splicing and allowing for the functional dissection of inversions, translocations, and amplicons in model systems. Finally, ∼ 200 tumor genomes can be effectively immortalized and exhaustively analyzed by ESP for less than the cost of sequencing a single mammalian sized genome.
Development and Evaluation of a Model of Human Comfort and Cognitive Ability for Moderate Differences in Thermal Environment

Past research has established systematic effects of thermal stress on human comfort and cognitive performance. However, this research has primarily focused on extremes of temperature, ignoring moderate temperature ranges typically found in work environments and vehicles. Furthermore, models predicting the psychological impact of thermal environment have typically focused solely on perceived comfort, or when accounting for cognitive performance (e.g., Anno et al. 1996; Mueller et al. 2011) focused on in relatively extreme thermal conditions. As a consequence, there is limited empirical data, and no viable predictive models, for understanding the impact of moderate thermal stress on human comfort and performance. We report on an experimental study with 24 college-age participants that assessed cognitive performance (across a number of cognitive dimensions including manual dexterity, speed, dual-task performance, task switching, executive function, and attention), subjective measures of comfort and workload (including the CALM comfort scale, the affect grid, NASA-TLX, perceived effort, and other measures related to the thermal environment), and physiology (including heart rate, skin temperature, and breathing rate). Participants were tested during three 90-min sessions in a controlled thermal chamber in which the temperature was either cool (15 oC/59 °F), room temperature (22.5 oC/72.5 °F), or warm (30 oC/86 oF), during which they completed repeated rounds of comfort ratings, cognitive task performance, and rest. Results showed strong responses in physiological and comfort measures over time to differences in thermal environment. However, the thermal environment had differential effects on cognitive measures, with some producing little impairment, and others showing increases or decreases over time that were moderated by thermal environment. The results were examined within a latent variable model that suggests that comfort alone is not an adequate proxy for performance, even for moderate thermal stressors, and more complex predictive models are needed.
Redox-Based Electrochemical Affinity Sensor for Detection of Aqueous Pertechnetate Anion

Rapid, selective, and in situ detection of pertechnetate (TcO4–) in multicomponent matrices consisting of interfering anions such as the ubiquitous NO3– and Cl– or the isostructural CrO42– is chall...
Elementary time-delay dynamics of COVID-19 disease

An elementary model of COVID-19 dynamics, based on time-delay differential equations with a step-like survival function, is shown to be in good agreement with data from China and South Korea. The time-delal approach overcomes the major limitation of standard Susceptible-Exposed-Infected-Recovered (SEIR) models based on ordinary differential equations, namely their inability to predict the observed curve of infected individuals as a function of time. The model is also applied to countries where the epidemic is in earlier stages, such as Italy and Spain, to obtain estimates of the total number of cases and peak number of infected people that might be observed.
Sleep problems in active duty military personnel seeking treatment for posttraumatic stress disorder: presence, change, and impact on outcomes.

Study objectives To examine sleep disorder symptom reports at baseline and posttreatment in a sample of active duty U.S. Army Soldiers receiving treatment for posttraumatic stress disorder (PTSD). Explore sleep-related predictors of outcomes. Methods Sleep was evaluated in 128 participants in a parent randomized clinical trial comparing Spaced formats of Prolonged Exposure (PE) or Present Centered Therapy and a Massed format of PE. In the current study, Spaced formats were combined and evaluated separately from Massed. Results At baseline, the average sleep duration was 70%) and nightmares (>38%) posttreatment. Excessive daytime sleepiness significantly improved only in the Massed group, but 40% continued to report clinically significant levels at posttreatment. Short sleep (Spaced only), clinically significant insomnia and nightmares, excessive daytime sleepiness, and probable sleep apnea (Massed only) at baseline predicted higher PTSD symptoms across treatment course. Short weekends/off days sleep predicted lower PTSD symptom improvement in the Spaced treatments. Conclusions Various sleep disorder symptoms were high at baseline, were largely unchanged with PTSD treatment, and were related to worse PTSD treatment outcomes. Studies are needed with objective sleep assessments and targeted sleep disorders treatments in PTSD patients. Clinical trial registration NCT01049516.
A Case for Feedback Control to Prevent Delay

AbstractThis study was motivated by the work of researchers who conducted field experiments on roadways with no bottlenecks. The ring roads are circular roadways where passing was restricted. All d...
Comparison to Lesser Alternatives

This chapter considers smaller-bore, more familiar alternatives to the more fundamental reforms designed in Chap. 3. Among these are infrastructure banks, social impact bonds, tax reforms, and state public banks. The chapter argues that these proposals would all be steps in the right direction, but are properly viewed as truncated renditions or steps toward the more comprehensive reforms laid out in the prior chapter. As such they would be fitting of less ambitious, more ‘incrementalist’ greenification efforts, but not nearly sufficient for purposes of planning, executing, and overseeing the Green New Deal. It would be as if one were to attempt building a house with a toy hammer, thumbtacks, and a Swiss Army Knife saw. Comprehensive projects that cross industries, sectors, and levels of government require commensurately comprehensive financial modernization, not piggybanks.
Low-Dose Bisphenol A in a Rat Model of Endometrial Cancer: A CLARITY-BPA Study.

Background: Bisphenol A (BPA) is known to be biologically active in experimental models even at low levels of exposure. However, its impact on endometrial cancer remains unclear. Objectives: This s...
Applications of the Linear Mass-Sectional Breakage Population Balance to Various Milling Process Configurations

After an initial grounding discussion, in which the linear mass-sectional population balance is described, and models for reducing the number of its parameters are discussed, this modeling approach is applied to a wide range of processes including batch mills, single-pass continuous mills, mills in series, mills with recycle, milling circuits including classification, and recycled-batch milling. The linearity of the model allows its straightforward inclusion in calculations for all of these processes. The sensitivity of the model to its inputs (order of rate kernel in size, fragment distribution) is explored for batch operations. Then, the effects of key continuous process design variables are explored including the (a) number of mill passes in pendulum milling (mills in series), (b) classifier properties in circuits with classification, and (c) ratio of feed tank-to-mill residence time in recycled-batch operations.
Effect of the Weekend on Bowel Preparation Quality in Outpatient Colonoscopies.

Inadequate bowel preparation has been associated with a higher likelihood of missing adenomatous polyps. Colonoscopies immediately following a weekend may be prone to inadequate bowel preparation. This study aims to evaluate if day of the week is a predictor of bowel preparation adequacy, while assessing other patient and procedural variables and their effect on the Boston Bowel Preparation Scale (BBPS). A retrospective review was conducted of all adult patients undergoing outpatient colonoscopy between January 2015 and April 2020. Adequacy of bowel preparation was compared among all days of the week and days following federal holidays. Secondary outcomes included patient demographics, indication and timing of the procedure. Of 4,279 colonoscopies, Monday had the highest rate of inadequate preparation (BBPS < 6) (16.5%) compared to other days of the week (p < .001). Post-holiday procedures were not associated with poor bowel preparation (p = .901). Similarly, on multivariate analysis, we found that procedures on Monday (OR 1.67 95%CI 1.33–2.10, p < .001) and African-American race (OR 1.34 95%CI 1.11–1.62, p = .003) were associated with inadequate bowel preparation. Females were more likely to have adequate bowel preparation (OR 0.71 95%CI 0.59–0.86, p < .001). Bowel preparation on Mondays is more likely to be inadequate than other days of the week. Additionally, gender and ethnicity appear to be associated with quality of bowel preparation. A better characterization of procedural and patient variables can lead to a more personalized approach to bowel preparation.
Earth Mothers, Soy Boys, and Cool Dudes: Practicing Law While Protecting the Environment Protecting the Environment

The essay looks briefly at the gendered dimension of the environment and environmental law. Part of the WASHINGTON UNIVERSITY JOURNAL of LAW and POLICY's celebration of the sesquicentennial of the school's first women law students.
Security for a Smarter Planet

Bit by bit, our planet is getting smarter. By this, we mean the systems that run, the way we live and work as a society. Three things have brought this about - the world is becoming instrumented, interconnected and intelligent. Given the planet is becoming instrumented and interconnected, this opens up more risks that need to be managed. Escalating security and privacy concerns along with a renewed focus on organizational oversight are driving governance, risk management and compliance (GRC) to the forefront of the business. Compliance regulations have increasingly played a larger role by attempting to establish processes and controls that mitigate the internal and external risks organizations have today. To effectively meet the requirements of GRC, companies must prove that they have strong and consistent controls over who has access to critical applications and data. Security has to be applied within a business context and fused into the fabric of business and not as a widget to solve the next security threat. This presentation will discuss challenges planet face, what companies, societies, governments need to be doing to address these challenges, and technical approach around a solution.
Comparison of Tension, Compression, and Flexure Creep for Alumina and Silicon Nitride Ceramics

The stress sensitivity of the creep rate of commercially available Al{sub 2}O{sub 3} and Si{sub 3}N{sub 4} ceramics was measured at elevated temperatures using tension, compression, and flexure specimens. Pronounced differences in creep deformation behavior measured in compression and tension were observed for both ceramics. Fractographic studies suggested that these differences were attributed to the effects of creep cavitation which occurred under tensile loading. Data generated from the flexure creep testing were found to be in fair agreement with results predicted from existing creep deformation models. 16 refs., 8 figs.
Differential regulation of accumbal dopamine transmission in rats following cocaine, heroin and speedball self-administration.

Cocaine/heroin combinations (speedball) exert synergistic neurochemical and behavioral effects that are thought to contribute to the increased abuse potential and subjective effects reported by polydrug users. In vivo fast-scan cyclic voltammetry was used to examine the effects of chronic intravenous self-administration (25 consecutive sessions) of cocaine (250 μg/inf), heroin (4.95 μg/inf) and speedball (250/4.95 μg/inf cocaine/heroin) on changes in electrically evoked dopamine (DA) efflux, maximal rate of DA uptake (V(max)) and the apparent affinity (K(m)) of the DA transporter in the nucleus accumbens. The increase in electrically evoked DA was comparable following cocaine and speedball injection; however, heroin did not increase evoked DA. DA transporter K(m) values were similarly elevated following cocaine and speedball, but unaffected by heroin. However, speedball self-administration significantly increased baseline V(max), while heroin and cocaine did not change baseline V(max), compared with the baseline V(max) values of drug-naive animals. Overall, elevated DA clearance is a likely consequence of synergistic elevations of nucleus accumbens extracellular DA concentrations by chronic speedball self-administration, as reported previously in microdialysis studies. The present results indicate neuroadaptive processes that are unique to cocaine/heroin combinations and cannot be readily explained by simple additivity of changes observed with cocaine and heroin alone.
Herpes Simplex Virus Type 1 Serum Neutralizing Antibody Titers Increase during Latency in Rabbits Latently Infected with Latency-Associated Transcript (LAT)-Positive but Not LAT-Negative Viruses

The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) gene is essential for efficient spontaneous reactivation in the rabbit ocular model of HSV-1 latency and reactivation. LAT is also the only viral gene abundantly expressed during latency. Rabbits were ocularly infected with the wild-type HSV-1 strain McKrae or the McKrae-derived LAT null mutant dLAT2903. Serum neutralizing antibody titers were determined at various times during acute and latent infection. The neutralizing antibody titers induced by both viruses increased and were similar throughout the first 45 days after infection (P > 0.05). However, by day 59 postinfection (approximately 31 to 45 days after latency had been established), the neutralizing antibody titers induced by wild-type virus and dLAT2903 diverged significantly (P = 0.0005). The dLAT2903-induced neutralizing antibody titers decreased, while the wild-type virus-induced neutralizing antibody titers continued to increase. A rescuant of dLAT2903, in which spontaneous reactivation was fully restored, induced wild-type neutralizing antibody levels on day 59 postinfection. A second LAT mutant with impaired spontaneous reactivation had neutralizing antibody levels comparable to those of dLAT2903. In contrast to the results obtained in rabbits, in mice, neutralizing antibody titers did not increase over time during latency with any of the viruses. Since LAT is expressed in both rabbits and mice during latency, the difference in neutralizing antibody titers between these animals is unlikely to be due to expression of a LAT protein during latency. In contrast, LAT-positive (LAT(+)), but not LAT-negative (LAT(-)), viruses undergo efficient spontaneous reactivation in rabbits, while neither LAT(+) nor LAT(-) viruses undergo efficient spontaneous reactivation in mice. Thus, the increase in neutralizing antibody titers in rabbits latently infected with LAT(+) viruses may have been due to continued restimulation of the immune system by spontaneously reactivating virus.
Structure-Property Relationships of Bismaleimides

The purpose of this research was to control and systematically vary the network topology of bismaleimides through cure temperature and chemistry (addition of various coreactants) and subsequently attempt to determine structure-mechanical property relationships. Characterization of the bismaleimide structures by dielectric, rheological, and thermal analyses, and density measurements was subsequently correlated with mechanical properties such as modulus, yield strength, fracture energy, and stress relaxation. The model material used in this investigation was 4,4'-BismaleiMidodIphenyl methane (BMI). BMI was coreacted with either 4,4'-Methylene Dianiline (MDA), o,o'-diallyl bisphenol A (DABA) from Ciba Geigy, or Diamino Diphenyl Sulfone (DDS). Three cure paths were employed: a low- temperature cure of 140 C where chain extension should predominate, a high-temperature cure of 220 C where both chain extension and crosslinking should occur simultaneously, and a low-temperature (140 C) cure followed immediately by a high-temperature (220 C) cure where the chain extension reaction or amine addition precedes BMI homopolymerization or crosslinking. Samples of cured and postcured PMR-15 were also tested to determine the effects of postcuring on the mechanical properties. The low-temperature cure condition of BMI/MDA exhibited the highest modulus values for a given mole fraction of BMI with the modulus decreasing with decreasing concentration of BMI. The higher elastic modulus is the result of steric hindrance by unreacted BMI molecules in the glassy state. The moduli values for the high- and low/high-temperature cure conditions of BMI/MDA decreased as the amount of diamine increased. All the moduli values mimic the yield strength and density trends. For the high-temperature cure condition, the room- temperature modulus remained constant with decreasing mole fraction of BMT for the BMI/DABA and BMI/DDS systems. Postcuring PMR-15 increases the modulus over that of the cured material even though density values of cured and postcured PMR were essentially the same. Preliminary results of a continuous and intermittent stress relaxation experiment for BMI:MDA in a 2:1 molar ratio indicate that crosslinking is occurring when the sample is in the undeformed state. Computer simulation of properties such as density, glass transition temperature, and modulus for the low- temperature cure conditions of BMI/MDA and BMI/DABA were completed. The computer modeling was used to help further understand and confirm the structure characterization results. The simulations correctly predicted the trends of these properties versus mole fraction BMI and were extended to other BMI/diamine systems.
Roles of BCL6 in normal and transformed germinal center B cells

BCL6 is a transcriptional repressor required in mature B cells during the germinal center (GC) reaction. Multiple mechanisms act coordinately to timely modulate BCL6 expression at transcriptional and post-transcriptional levels. BCL6 prevents premature activation and differentiation of GC B cells and provides an environment tolerant of the DNA breaks associated with immunoglobulin gene remodeling mechanisms involved in the production of high-affinity antibodies of different isotypes. The critical functions exerted by BCL6 during normal B-cell development can be hijacked by the malignant transformation process. Indeed, BCL6 is targeted by genetic aberrations and acts as an oncogene in GC-derived lymphomas. The aberrations affecting BCL6 interfere with the multiple levels of regulation that grant a fine tuning of BCL6 expression and activity in physiologic conditions. This review summarizes the current knowledge on BCL6 function and its role in lymphomagenesis.
Current Status of Adjuvant Endocrine Therapy for Breast Cancer

Adjuvant endocrine therapy is a vitally important modality for treatment of women with resected hormone-sensitive breast cancer as indicated by the presence of estrogen and/or progesterone receptors in the tumor. It is not recommended in those patients whose tumors lack these hormone receptors. Tamoxifen for 5 years has been shown to reduce the risk of recurrence and death irrespective of menopausal status or use of adjuvant chemotherapy. In postmenopausal women, the major research emphasis relates to the use of third-generation aromatase inhibitors in sequence with, instead of, and in combination with tamoxifen. In premenopausal women, ovarian ablation/suppression has demonstrated efficacy comparable with some chemotherapy regimens, but its role in women receiving chemotherapy remains to be determined.
Compartmentalized microchannel array for high-throughput analysis of single cell polarized growth and dynamics

Interrogating polarized growth is technologically challenging due to extensive cellular branching and uncontrollable environmental conditions in conventional assays. Here we present a robust and high-performance microfluidic system that enables observations of polarized growth with enhanced temporal and spatial control over prolonged periods. The system has built-in tunability and versatility to accommodate a variety of scientific applications requiring precisely controlled environments. Using the model filamentous fungus, Neurospora crassa, our microfluidic system enabled direct visualization and analysis of cellular heterogeneity in a clonal fungal cell population, nuclear distribution and dynamics at the subhyphal level, and quantitative dynamics of gene expression with single hyphal compartment resolution in response to carbon source starvation and exchange. Although the microfluidic device is demonstrated on filamentous fungi, the technology is immediately extensible to a wide array of other biosystems that exhibit similar polarized cell growth, with applications ranging from bioenergy production to human health.
Beyond paired quantum Hall states: Parafermions and incompressible states in the first excited Landau level

The Pfaffian quantum Hall states, which can be viewed as involving pairing either of spin-polarized electrons or of composite fermions, are generalized by finding the exact ground states of certain Hamiltonians with $k+1$-body interactions, for all integers $kg~1.$ The remarkably simple wave functions of these states involve clusters of k particles, and are related to correlators of parafermion currents in two-dimensional conformal field theory. The $k=2$ case is the Pfaffian. For $kg~2,$ the quasiparticle excitations of these systems are expected to possess non-Abelian statistics, like those of the Pfaffian. For $k=3,$ these ground states have large overlaps with the ground states of the (two-body) Coulomb-interaction Hamiltonian for electrons in the first excited Landau level at total filling factors $\ensuremath{\nu}=2+3/5,2+2/5.$
Numerical bridge deck studies using finite elements. Part I: flutter

Abstract Wind-induced bridge motions are numerically investigated using structural and fluid finite elements (FEs). The fluid–structure interaction solutions are based on the incompressible Navier–Stokes equations fully coupled to an elastically suspended rigid body. The unsteady fluid field equations with advection-dominated flow are approximated using the weighted residuals method of Galerkin/least squares. The bridge deck is idealized as a lumped mass, spring–dashpot system. The flow simulation around a stationary bridge deck adopts the Eulerian scheme in the entire fluid domain, whereas the simulations of flow past a moving bridge deck apply the arbitrary Lagrangian–Eulerian formulation. Predicting the flutter limit, aiming at reducing the number of physical model tests currently required, is the first step and main objective in the validation of a numerical method applied to long-span bridge decks. It is shown that the low-frequency flexural–torsional flutter motion is the result of a different aerodynamic effect than vortex-induced bridge vibrations. Despite a laminar flow assumption, the two-dimensional self-excited flow solutions, on an irregular unstructured grid of 1884 nodes, predict a flutter limit in good agreement with wind tunnel experiments. The FE model appears to be a suitable method and could be applied as a supplementary tool to wind tunnel testing for the simulation of flutter instability. It was concluded that the prediction of flutter instability for sharp edge bridge decks does not appear sensitive to turbulence and three-dimensional flow structure modelling.
Translating science into public health practice: lessons from physical activity interventions.

It has been 10 years since the Surgeon General’s office ssued its landmark report on physical activity (PA), spellng out the scientific evidence for the health benefits of hysical fitness and urging Americans to exercise more. oday, despite an ever-growing evidence base and conerted efforts to get out the “get fit” message, Americans’ xercise patterns have changed little [1]. Why is this, and hat can be done? In light of the rapidly growing populaion of older adults, who stand to gain the most benefit from ncreasing PA, finding answers to these central questions as never been more urgent. There is clear consensus that PA is one of the best things eople can do for their bodies and minds, in terms of both imiting disease and improving quality of life [2]. Numerous ational and regional health surveys and prospective interentional studies variously conclude that regular PA inreases physical functioning and the ability to engage in ctivities of daily living [3]; reduces the risk and burden of oronary heart disease, hypertension, type 2 diabetes, colon ancer, and osteoporosis [4]; and extends years of life [1,5]. eviews in this supplement detail the growing evidence that A protects against cognitive decline, on the basis of epiemiologic studies, animal research, and prospective human rials [6–8]. Strong evidence also supports the relationship etween PA and emotional well-being. Moreover, by reducng cardiovascular risk, PA also lowers risk for cognitive ecline and dementia [9–11]. Thus, increasing one’s level of PA is not only directly ssociated with maintenance of cognitive health but might lso prevent cognitive decline indirectly by reducing cariovascular risk factors, although further research is war-
In vitro reciprocal exchange of apoproteins and nonpolar lipids between human high density lipoproteins and an artificial triglyceride-phospholipid emulsion (Intralipid)

To determine the nature of lipid and apoprotein exchange between human high density lipoproteins (HDL) and Intralipid particles of Sf greater than 400 (ILIP) we have studied their in vitro interaction during incubation in aqueous buffer and in lipoprotein-deficient serum (LPDS). We found that ILIP acquires apo A-I, apo A-IV and apo E from LPDS, and that this uptake is inhibited by the presence of HDL, which readily donate C-apoproteins to the ILIP surface. In the absence of LPDS exchange of only polar lipids occurred between ILIP and HDL, with HDL gaining phospholipid from, and donating free cholesterol to this fat emulsion. In the presence of LPDS the exchange of nonpolar lipids occurred between the two particles: in the case of HDL, cholesteryl ester content decreased, accompanied by an increase in triglyceride, causing a decrease in the hydrated density of the lipoprotein and an increase in its molecular weight; in the case of ILIP, reciprocal changes in lipid content were seen as a loss of triglyceride and the appearance of cholesteryl esters. When compared to literature data, our findings indicate that Intralipid Sf greater than 400 particles exhibit an in vitro behavior which is remarkably similar to that of nascent chylomicrons with respect to the exchange of A- and C-apoproteins and surface polar lipids with HDL. We postulate that since ILIP and HDL can participate in a LPDS-dependent exchange of non-polar core lipids, that this process may occur when this fat emulsion is administered in vivo.
Notes on the Glen Coe Cauldron Subsidence, Argyllshire, Scotland

General inward dip of the main boundary fault surrounding the Glen Coe cauldron subsidence indicates that the ring fault has the over-all form of an upward-opening cone. The cone shape is substantiated by peripheral upturning of down-dropped volcanic rocks against the encircling ring fault. Some rocks are even overturned. A peculiar zone of rhyolite and associated breccia that puzzled the pioneer geologists (Clough and others, 1909) contains rhyolitic dikes and intrusive breccias. Two rhyolitic dikes, composed of welded pyroclastic rocks, qualify as possible feeders for welded tuffs. Ignimbrites in the volcanic pile confirm repeated explosive activity during the evolution of the cauldron. Marked subsidence occurred after major episodes of explosive activity, as indicated by lake deposits and coarse sediments that overlie the ignimbrites. Flinty crush rock (Clough and others, 1909) is a fine-grained product of fluidization, as suggested by Reynolds (1956). Transported inclusions of volcanic rocks prove that the flinty crush rock is a fine-grained intrusive breccia. Most breccias near the main boundary fault are intrusive or explosion breccias, but the breccia (Hardie, 1963)south of Stob Mhic Mhartuin is probably of sedimentary origin. Fault intrusion (Clough and others, 1909) is a catchall name for a wide variety of plutonic and hypabyssal bodies. The common irregularity of many intrusions is a typical of ring dikes. The classification of igneous ring complexes is discussed. In Britain, there is no unequivocal example of an outward-dipping ring fracture at Ardnamurchan, Mull, or Slieve Gullion, but outward-dipping ring faults are present in the Mourne Mountains. The ring fracture that encircles the downdropped volcanic rocks on Ben Nevis is essentially vertical, as seen in exposures along the north and east sides of the annular fault. At Glen Coe, the writer did not recognize any evidence for resurgent doming.
Treatment of Diabetic and Nondiabetic Lumbosacral Radiculoplexus Neuropathy

Lumbosacral radiculoplexus neuropathy (LRPN) is a multifocal, asymmetric, painful neuropathic disorder affecting multiple levels of lumbosacral plexus, nerve roots, and distal nerves that emerge from the plexus. The disorder was first described in diabetic patients (DLRPN) and was later found to occur in nondiabetic patients as well. There have been debates as to the pathogenesis of DLRPN and LRPN. Recent detailed and extensive pathologic studies, however, have shown that the main pathogenesis is inflammation and microvasculitis affecting various components in the peripheral nerves, resulting in ischemic injury to the nerves. Even though studies on the natural history of this disorder have shown that the majority of patients recover within a few years after the attack without any treatment (although recovery is incomplete in many cases), it is a common practice, based on the pathophysiology and case series, to administer immunotherapy. Preliminary data from a controlled clinical trial failed to show significant improvement in outcomes measured by neurologic deficits (as judged by the Neuropathy Impairment Score) but did show improvement in symptoms (pain and positive sensory symptoms). Choices of immunotherapy include corticosteroids, intravenous immunoglobulin, plasma exchange, or a combination. Pain management, physical therapy, and treatment of depression remain mainstays for managing this disorder.
TH-A-214-02: Organ Dose, Effective Dose, and Dose Conversion Coefficients in Adult CT: Comparison of Mathematical, XCAT, and ICRP Reference Phantoms

Purpose: To compare organ dose, effective dose, and dose conversion coefficients in adult CT estimated using three types of reference phantoms: (1) hermaphrodite mathematical phantom employed by the imPACTCT dose calculator, (2) reference male and female extended cardiac‐torso (XCAT) phantoms, and (3) ICRP 110 reference male and female phantoms. Methods: Representative CT examinations were selected from the database of clinical adult CT protocols in use at our institution. Organ dose, effective dose, and dose conversion coefficients (the k factor) were estimated for these examinations for a clinical CT system (LightSpeed VCT, GE Healthcare) using three methods, each employing a different type of reference phantoms. The first method employed commercial dosimetrysoftwareimPACT using Monte Carlo methods for a reference mathematical hermaphrodite phantom. The second and third methods employed a Monte Carlo program previously developed and validated in our laboratory. In the second method, the male and female extended cardiac‐torso (XCAT) phantoms created from the Visible Human data were used. In the third method, the ICRP 110 male and female phantoms based on ICRP 89 tomographic anatomic data were used. Results: The k factor varied very little between phantoms, with average 0.019 mSv/mGy‐cm (ranging from 0.009 to 0.025) for imPACT phantom and 0.018 mSv/mGy‐cm (ranging from 0.013 to 0.022) for XCAT male phantom. Distributed organs tended to have similar dose values among different phantoms for the same protocol. The calculated percent difference between imPACT and XCAT male phantom was 1.4% for bone marrow and 9.3% for bone surface. Percent differences between phantoms were generally inversely proportional with scan length ranging from 21.1% for chest‐abdomen‐pelvis protocol to −94% for liver to kidneys protocol. Conclusions: This work suggests that gender averaged dose from anthropomorphic phantoms should be used as reference to adult patient CT dose.
Identification of Channels Promoting Calcium Spikes and Waves in HT1080 Tumor Cells: Their Apparent Roles in Cell Motility and Invasion

Intracellular Ca(2+) signals have been associated with cell polarization and locomotion. As cell motility underlies metastasis, we have sought to better characterize the Ca(2+) signaling events in HT1080 fibrosarcoma cells. We have tested the hypothesis that low voltage-activated (LVA) and nonvoltage-gated (NVG) channels of HT1080 cells participate in dynamic Ca(2+)-signaling events leading to cell migration and invasion. Immunofluorescence microscopy has shown that HT1080 cells express LVA T-type Ca(2+) channels uniformly about the cell periphery, whereas the transient receptor potential-1 (a NVG cation channel) protein appears as punctate spots about a cell's periphery. HT1080 cells exhibit periodic intracellular Ca(2+) spikes. High-speed imaging revealed that the Ca(2+) spikes were composed of a single Ca(2+) wave traveling unidirectionally about the periphery of the cytoplasm in a clockwise fashion (as viewed from basal to apical surfaces). The T-type Ca(2+) channel blocker mibefradil inhibited Ca(2+) spikes and waves on cells and, in parallel, inhibited cell motility and invasion in a dose-dependent manner. Similar changes were noted with the NVG cation channel blockers Gd(3+) and carboxyamido-triazole. The combination of LVA and NVG blockers further reduced Matrigel invasiveness. However, the Ca(2+) channel blockers nicardipine, SKF96365, diltiazem, and verapamil had no effect at appropriate doses. These results indicate that certain LVA and NVG channels regulate HT1080 cell motility. In addition to providing novel information regarding cancer cell motility, we suggest that it may be possible to design drugs that inhibit a key Ca(2+) wave, thereby enhancing the efficacy of emerging therapeutic protocols.
Progesterone is not essential to the differentiative potential of mammary epithelium in the male mouse.

In pursuit of a model system in which to determine whether or not exposure to progesterone is necessary for mammary epithelial cells to develop their differentiative potential, we explored hormone-dependent growth of the mammary epithelial rudiment in adult male mice. Initiation of the formation of ductal cells can be effected by administration of estradiol in the absence of endogenous progesterone and glucocorticoid, using adrenalectomized-castrated animals. The resulting epithelium contains three times more lactose synthetase activity per epithelial cell than that in midpregnant mice. The blood spermidine level in these doubly operated animals was similar to the concentration of spermidine required to substitute effectively for glucocorticoid during mammary differentiation in vitro. It is suggested hat spermidine can partially supplant glucocorticoid in vivo in milk protein synthesis. We also concluded that, unlike other secondary sex tissues, mammary cells do not require exposure to progeserone during ...
Thermal Deicing of Polymer Composite Helicopter Blades

This paper presents the results of an investigation to determine if thermal deicing methods (hot air, hot water, hot glycol, or radiative heat) would damage the composite materials in helicopter blades. Samples made from Blackhawk helicopter blades were thermally cycled in the regime of the temperatures of thermal deicing methods and then mechanically load tested. The strength reduction was compared with the number of thermal cycling and the temperatures of thermal cycling. The strength results and the modes of failure indicate that damages indeed do develop in the composites, especially along the bond line of the composite skin and the nomex core of the blade structure, and mechanical strength is reduced.
Effect of Caloric Restriction on the Metabolism of Benzo[a]pyrene (BaP) and the Formation of BaP-DNA Adducts in Male Fischer 344 Rats

Abstract The effect of caloric restriction (CR) on activities of xenobiotic metabolizing enzymes results in alterations in the metabolic activation of chemical carcinogens, with a resultant impact on DNA-carcinogen adduct formation. Using benzo[a]pyrene (BaP) as a model carcinogen, we have studied the effect of CR on the metabolic activation of BaP, in terms of both BaP metabolism and BaP-DNA adduct formation. Male Fischer 344 rats fed CR diets (60% of the food consumption of ad libitum−fed rats) showed higher activities of BaP metabolizing enzymes resulting in increases of BaP metabolism in vitro and BaP-DNA adduct formation in vivo. The results of the study of the effect of CR on the in vitro metabolism of BaP showed that CR increased the total BaP metabolism, as well as BaP-t-9, 10-diol and BaP-t-4, 5-diol formation. However, BaP-t-7, 8-diol, a proximate carcinogenic metabolite of BaP, was decreased by liver microsomes from CR-rats. Our results indicate that the effect of CR on metabolic activation of ...
Accumulation modes of alkylating agents on normal peripheral blood lymphocytes

The in vitro uptake by normal peripheral blood lymphocytes of 14C-labeled cyclophosphamide and nitrogen mustard has been measured in a manner which parallels cell exposure to drugs used in the nitrogen mustard-oncovin-procabazine-prednisone (MOPP) and cyclophosphamide-oncovin-procarbazine-prednisone (COPP) clinical protocols. Accumulation of these alkylating agents occurs in two recognizable patterns. The first exhibits a saturation phenomenon, since radioactivity can be partially blocked by an equal concentration of unlabelled drug, reflects stereospecificity, and represents a minor fraction of total deposition. The second form, proportionately larger than the first, is dependent on drug concentration in the suspending medium, with radioactivity increasing in an apparently limitless linear fashion, uninfluenced by competitive inhibition. This part also is less tenaciously held by the lymphocyte. While the mere presence of drug on the lymphocytes does not necessarily imply injury or lethality, the fact that these peripheral lymphocytes are able to accumulate cytotoxic agents and are partially interchangeable with an analogous fixed lymphoid cell mass suggests that clinical immunosuppression and lymphocytopenia may be related, in part, to cell drug deposition.
Solutions of the kinetic theory for bounded collisional granular flows

We consider collisional granular flows of nearly elastic spheres featuring a single constituent or binary mixtures in various bounded geometries. We review the equations of the kinetic theory for the conservation of mass, momentum, fluctuation energy and species concentration. We illustrate their solutions for shear flows in rectilinear or axisymmetric rectangular channels with or without a body force. We show that proper boundary conditions yield numerical solutions in good agreement with molecular dynamical simulations and with data from physical experiments carried out in microgravity.
ENHANCED DEPRESSANT EFFECT OF TETRABENAZINE AFTER REPEATED ADMINISTRATION.

Although the behavioral effects of a single administration of tetrabenazine last for only a few hours, the present experiment has demonstrated that a second dose of the drug, administered one or two weeks after a first dose, has a greater locomotor depressant action than the first dose. If a four week interval is allowed between two doses, the enhanced effect is no longer seen.
Estimation of Achilles Tendon Moment Arms In Vivo: A Novel Hybrid Method Using Ultrasound and Motion Analysis

The musculotendon moment arm (MA) is the perpendicular distance from a muscle’s line of action to the rotational center of a joint. Moment arms are important in muscle modeling [1], and thus their accuracy is of great importance. Current in vivo techniques for computing MAs include the center of rotation and tendon excursion methods [1, 2]. The tendon excursion (TE) method relates the change in musculotendon length to an angular change in joint position [3]. This requires two measurements of musculotendon length for each MA computed. Similarly, the center of rotation method requires multiple image-based geometry measurements to compute the MA for a specific joint angle. The TE and center of rotation methods are both prone to measurement error, and thus it is difficult to ascertain the accuracy of the resulting MA. In this paper we present a novel hybrid methodology combining ultrasound (US) and video-based motion capture to compute the Achilles tendon moment arm. An advantage of this approach is that data used to derive the MA are acquired using highly accurate and reliable measurement instruments (i.e, US & motion capture), which may improve the accuracy of the MA estimate. The purpose of this paper is to present the hybrid methodology and validation results based on testing the method using an animal model.Copyright © 2008 by ASME