cssi/SciSciGPT-SciSciNet huggingface dataset:
Plerixafor for Stem Cell Mobilization Prior to Autologous Stem Cell Transplant in Non-Hodgkin's Lymphoma and Multiple Myeloma

Objective:To review the pharmacology, pharmacokinetics, dosage, administration, clinical efficacy, safety, and place in therapy of plerixafor, a CXCR4 receptor antagonist used to mobilize stem cells prior to hematopoietic stem cell transplantation.Data Sources:Articles were identified by searching MEDLINE (1950-August 2009) and the American Society of Hematology abstract database using the key terms plerixafor, AMD3100, hematopoietic stem cell transplant, mobilization, multiple myeloma, and non-Hodgkin's lymphoma. Additional articles were obtained by using the reference sections of articles found during the literature search.Study Selection and Data Extraction:All articles identified from the literature search were reviewed for relevant information. Appropriate information was included in this review. The search was restricted to available English-language articles, including those on both preclinical and clinical trials.Data Synthesis:Plerixafor is a CXCR4 receptor antagonist approved by the FDA to assis...
Effects of bromocriptine in developing rat pups after 6-hydroxydopamine☆

Abstract The effects of low (0.5 mg/kg) and high (2.0 mg/kg) doses of bromocriptine (BCR) on activity and escape performance were examined during the first month of postnatal life in normal developing rat pups and littermates treated at 5 days of age with a combination of desmethylimipramine and 6-hydroxydopamine (6-OHDA). Such a procedure resulted in significant reductions in brain dopamine to concentrations 10–20% of vehicle controls while norepinephrine was unaffected. BCR increased general motor activity in vehicle pups at 13 and 19 days but had little effect on more mature animals. Pups who had not received BCR exhibited a decline in activity over the hour long observation period (habituation of activity) but this decline was abolished by both low (0.5 mg/kg) and high (2.0 mg/kg) doses of the agent. Stereotyped activity, particularly at 19 days was increased by BCR in 6-OHDA pups but not in vehicle animals, an effect suggesting denervation supersensitivity. Head dips in a hole box at 30 days of age were not influenced by BCR in vehicle pups but significantly reduced by BCR in 6-OHDA pups, suggesting that BCR might be acting to stimulate inhibitory dopaminergic mechanisms. Escape learning in a T-maze at 20 days and shuttle box at 28 days was disrupted by high doses of BCR in vehicle pups and both doses of BCR in 6-OHDA animals. The similarity with the behaviors observed in the clinical syndrome of attention deficit disorder with hyperactivity prompted a number of investigative groups including our own to suggest that the 6-OHDA model might serve as a useful and convenient paradigm to evaluate pharmacological agents that offer potential in the treatment of this most common disorder. From this perspective we would predict that BCR would have little clinical utility since it both failed to attenuate 6-OHDA induced hyperactivity and tended to disrupt performance in an avoidance learning task.
A Neural Representation of Depth from Motion Parallax in Macaque Visual Cortex

Depth perception in humans and other animals can be based on binocular vision, in which the brain compares images from each eye. We can also judge depth with one eye, but how the brain processes the many different cues available for monocular perception of depth is not known. A possible explanation for one cue has now been found. The neurons in the middle temporal area of the brain, as well as representing retinal motion, can combine visual information and physical movement to extract depth information from motion parallax, a powerful depth cue that we experience when viewing the scenery from the window of a moving train — objects on the horizon move slowly while the scene close to the train flashes by. It is shown that in addition to the well-documented representation of retinal motion, primate area middle temporal area neurons are sensitive to the relative depth of stimuli defined by motion parallax. Motion parallax is a powerful depth cue that arises when the observer is moving due to near and far objects moving across the retina at different speeds. Perception of depth is a fundamental challenge for the visual system, particularly for observers moving through their environment. The brain makes use of multiple visual cues to reconstruct the three-dimensional structure of a scene. One potent cue, motion parallax, frequently arises during translation of the observer because the images of objects at different distances move across the retina with different velocities. Human psychophysical studies have demonstrated that motion parallax can be a powerful depth cue1,2,3,4,5, and motion parallax seems to be heavily exploited by animal species that lack highly developed binocular vision6,7,8. However, little is known about the neural mechanisms that underlie this capacity. Here we show, by using a virtual-reality system to translate macaque monkeys (Macaca mulatta) while they viewed motion parallax displays that simulated objects at different depths, that many neurons in the middle temporal area (area MT) signal the sign of depth (near versus far) from motion parallax in the absence of other depth cues. To achieve this, neurons must combine visual motion with extra-retinal (non-visual) signals related to the animal’s movement. Our findings suggest a new neural substrate for depth perception and demonstrate a robust interaction of visual and non-visual cues in area MT. Combined with previous studies that implicate area MT in depth perception based on binocular disparities9,10,11,12, our results suggest that area MT contains a more general representation of three-dimensional space that makes use of multiple cues.
Application of duality to the multiperipheral model

Abstract By applying average (or semi-local) duality to the amplitude generated by a multiperipheral model, it is possible to get information on its output Regge trajectories. This, in turn, can be used to obtain simple bootstrap conditions on resonance widths.
Larval Trematodes: Double Infections in Common Mud-Flat Snail

Larvae of the trematode Zoogonus lasius are involved in most double infections of Nassarius obsoleta. The two most common trematode parasites of this snail do not occur together in double infections. Double infections were found in 14 of 340 infected snails in a total sample of 5025 snails.
A Comparative Report on the Profiles of Retailing in the Emerging Markets of Europe: Turkey, Poland, Hungary, Portugal, and Greece

ABSTRACT Nowadays, both in the transforming economies (such as Poland and Hungary) and in the developing economies (such as Turkey) of Europe, the most popular policy concepts seem to be deregulation, liberalization, privatization, and internationalization. In this study, we look into these seemingly comparable government policies and ask whether similar attempts, on the part of the governments, to move towards more market-oriented distribution systems, will produce further and sustainable similarities in their now diverse retail structures. Some resemblance, such as the recent appearance of the same new international actors in these markets, is obvious and, in fact, points to a larger convergence including countries such as Portugal and Greece as well. However, there are also more subtle similarities and differences. Here we provide some critical observations and thoughts concerning the convergence discussion, and partially answer the question as to whether we have already started to observe a real and s...
Use of a real-time viewer for endoscopic deployment of capsule endoscope in the pediatric population.

OBJECTIVES Wireless capsule endoscopy (WCE) is an increasingly used procedure for visualization of the small intestine. One challenge in pediatric WCE is the placement of the capsule in a population unable to swallow it for a variety of reasons. Here we present a novel use of the real-time (RT) viewer in the endoscopic deployment of the capsule endoscope. METHODS We performed a retrospective chart review on all WCE completed at the Children's Memorial Hospital from February 2010 to May 2011. Following a diagnostic upper endoscopy, the RT viewer was attached to the capsule recorder and image was noted before insertion. The endoscope and AdvanCE capsule delivery device were slowly advanced into duodenum while maintaining visualization on the RT viewer. RESULTS A total of 17 patients who underwent a WCE with endoscopic placement were identified. They ranged in ages from 2 to 19 years. Thirteen patients required endoscopic placement because of the inability to swallow the capsule, whereas 4 were placed during a scheduled procedure to take advantage of sedation and airway protection. All of the 17 patients had successful deployment of the capsule into the duodenal lumen. In each case, the endoscopist was able to confirm capsule location in duodenum during scope withdrawal. There was no evidence of iatrogenic trauma or bleeding in any patient. There were 5 incomplete studies, a completion rate consistent with that described in the literature. CONCLUSIONS The use of the RT viewer for endoscopic deployment of WCE is an effective technique to improve visualization of capsule placement in the pediatric population.
Land Reform in the Middle East

The success or failure of land reform programs in the past has been, in general, evaluated on the basis of whether agricultural output increases or decreases following their adoption and the implementation of their principal provisions. Yet this approach ignores other factors, such as the effect of prices on output, making it likely that the influence of land reform is under- or over-estimated. In this paper, we suggest that it is possible to isolate the effect of price on output from those of reform programs by using the Nerlove supply model. By applying this method to periods before and after the initiation of such programs, we can identify any change in the market responsiveness of the affected cultivators. In testing this approach, the output of major crops in Egypt, Syria and Iraq—countries which have seen major land reform efforts in the post-war era—was analyzed. Post-reform responsiveness was compared with that of earlier periods and with that of cultivators in two neighboring countries—Jordan and Lebanon—which underwent little reform.
Brillouin precursor waveforms pertaining to UWB noise radar signals propagating through dispersive media

The electromagnetic (EM) waves propagating through causal, linear, and lossy dispersive media (soil, foliage, plasma, water, biological tissue, etc.), experience frequency-dependent attenuation and phase distortion. This has assumed significant importance for systems operating with ultrawideband (UWB) spectrum. This paper analyzes the dynamical evolution of UWB noise radar signals through dispersive media. The effects on the signal propagation due to the evolution of the Brillouin precursor through dispersive media are discussed. The evolving waveforms are then compared with the Brillouin precursor due to rectangular sine-modulated deterministic signals. The advantages of random noise waveforms through dispersive media are also discussed.
Self-diffusivity of nitrogen in γ'-iron nitride (“Fe4N”)

The growth of γ'-iron nitride (“Fe4N”) on pure iron plate samples was followed by a thermogravimetric technique in the temperature range of 450–550 ° C at various nitrogen activities (fixed by H2/NH3 gas mixtures). The growth kinetics were characterized by an initial stage of nucleation and growth control followed by nitrogen diffusion controlled growth. At 450 ° C, the self-diffusivity of nitrogen D* is independent of nitrogen activities. At 500 ° C, D* decreases with increasing nitrogen activities. At 550°C, D* decreases to a minimum and then increases again with increasing nitrogen activities. It is suggested that the nitrogen diffusion mechanism in γ'-iron nitride is strongly related to the non-stoichiometry of this phase. At 450 and 500 ° C, the growth kinetics can be explained by a mechanism that involves the mixed control of two processes: (i) nitrogen diffusion via a small number of vacant regular sites (12, 12, 12) and (ii) nitrogen diffusion via a large number of disordered sites (12, 0, 0), (1, 12, 0), (0, 0, 12) as interstitials. At 550°C, the diffusion mechanism is controlled by nitrogen diffusion via the vacant regular sublattice sites at low nitrogen activities. At high nitrogen activities, the diffusion mechanism again becomes mixed control of the two diffusion processes. At the nitrogen activities of 100 and 174, D* can be represented, respectively, by: D* = (5.81 × 10−7cm2/s) · exp((−19.05 kcalmole)/RT) and D* = (2.45 × 10−9cm2/s) · exp((−11.16 kcalmole)/RT) It appears that the activation energy of diffusion for nitrogen diffusion via the disordered sites is higher than that via the regular sites.
Optimization of Escherichia coli growth by controlled addition of glucose

During aerobic growth of Escherichia coli (recombinant K-12 and strain B) on protein hydrolysate (L-broth) and a carbon source (glucose), acetic acid is produced via glucose metabolism until the late log phase. At this point, the culture pH starts to increase and the growth rate decreases. In cultures without further glucose supplementation, these changes are associated with the accumulation of ammonia, the utilization of acetic acid, the depletion of amino acids, and the complete depletion of glucose. We hypothesize that, after depletion of the glucose, the bacteria catabolize amino acids for energy and carbon and give off the nitrogen as ammonia. Also contributing to the overall increase in pH is the depletion of the acetic acid produced earlier as it is metabolized upon exhaustion of glucose. However, there is a lag time of about 1 hour after the initial pH increase before the sustained accumulation of ammonia begins. This lag indicates that an unidentified factor, in addition to the increase in ammonia, contributes to the increase in pH. Advantage was taken of the turnaround from acid production to base production as reflected in the culture pH to implement the addition of glucose. In growth experiments during which the pH was controlled in the basic direction by glucose addition, the observed decrease in growth rate was significantly postponed and the pH change in the basic direction was reversed as a result of acid production by the cells from the newly added glucose. Furthermore, coll densities of twice that obtained without glucose feeding were demonstrated. Based on the media cost per unit cell density, the data indicate a 31% cost savings.
A metaanalysis of studies of the effects of cancer chemotherapy on various domains of cognitive function

BACKGROUND Little is known about the effects of chemotherapy on cognitive function. The purposes of this metaanalysis were to estimate the effect sizes for the effect of chemotherapy on each domain of cognitive function and to differentiate effect sizes by each method of comparison of effects (i.e., normative data, control group, or baseline data). METHODS Sixteen studies that evaluated cognitive function in chemotherapy patients were included in the study. DSTAT metaanalysis software was used to calculate an effect size and confidence intervals for each neuropsychologic test. Tests were assigned to a specific cognitive domain, and an average effect size was determined for each domain. RESULTS Only one domain of cognitive function (i.e., visual memory) had significant chemotherapy-induced impairment across all comparison types. However, when the neuropsychologic test scores of chemotherapy patients were compared with normative data, significant effect sizes were found for four domains of cognitive function (i.e., executive function, information processing speed, verbal memory, visual memory). In addition, significant, albeit small, effect sizes were found for language and verbal memory when chemotherapy patients' test scores were compared with test scores of healthy matched controls. All significant averaged effect sizes were in the negative direction, indicating that mean scores on neuropsychologic tests for patients who had received chemotherapy were on average lower than comparison scores. CONCLUSION Data from this metaanalysis supported the hypothesis that chemotherapy can have a negative impact on cognitive function. However, most deficits in this study ranged from small to moderate and were nonsignificant. Cancer 2005. © 2005 American Cancer Society.
Lymphatic ascites following pelvic and paraaortic lymphadenectomy procedures for gynecologic malignancies.

Abstract Objective Lymphatic ascites is an unusual complication in patients with cancer. In the gynecologic oncology patient population, the most common etiology is operative lymph node dissection. The purpose of this study was to explore the incidence, presenting symptoms, methods of diagnosis and treatment modalities utilized for lymphatic ascites in patients undergoing lymph node dissection for gynecologic cancers. Methods This observational study retrospectively reviewed the charts of patients who underwent lymphadenectomy as part of the surgical management for a gynecologic cancer. Patients that developed postoperative lymphatic ascites between January 2000 and December 2010 were included for analysis. Data extracted from the medical records included tumor pathology, number of harvested lymph nodes, postoperative course, method of diagnosis and treatment. Results From a total of 300 surgical staging procedures, 12 patients with lymphatic ascites were identified (4%). The most common reported symptom was leakage of clear fluid per vagina (7, 58%), followed by abdominal distension (4, 33%). The median interval from surgery to development of symptoms was 12.5days (range 0–22days). 5 patients had complete resolution of symptoms with dietary modifications alone while 7 patients required paracentesis. The median time from surgery to resolution of symptoms was 44days (range 9–99). Conclusion Lymphatic ascites is an under recognized and infrequently reported postoperative complication. Although it usually resolves spontaneously or with conservative management without sequelae, this condition can significantly prolong postoperative recovery and cause patient discomfort. To our knowledge this is the largest group of patients undergoing gynecologic surgical staging procedures to be reviewed for the occurrence of lymphatic ascites.
Biosynthesis of hyaluronic acid in the vitreous. VI. Isolation of a complex containing hyaluronic acid and glycosyl transferase activity and studies on the activity of a soluble glycosyl transferase.

Addition of protamine sulfate to calf vitreous, after removal of hyalocytes, results in the formation of an insoluble complex of hyaluronic acid and protamine. The hyaluronic acid-protamine (HA-P) complex was found to possess glycosyl transferase activity, as shown by the incorporation of radioactivity from UDP-[14C]glucuronic acid and UDP-[14C]N-acetyl-glucosamine into the hyaluronic acid present in the complex. The incorporation of radio-activity was stimulated by the addition of Mg2+, and for optimal incorporation both nucleotide sugar precursors of hyaluronic acid were required. When the HA-P complex is dissolved in 0·5-1 m-NaCl solutions, the glycosyl transferase can be separated from protamine, thereby regenerating a soluble system for the study of hyaluronic acid biosynthesis. The present report also describes the results of experiments designed to determine which agents affect the activity and heat stability of a soluble glycosyl transferase, extracted from hyalocytes, which similarly catalyzes hyaluronic acid synthesis. Treatment of the enzyme with N-acetylimidazole results in an inhibition of enzyme activity. When the treatment was carried out in the presence of substrates, no protection against the inhibition was observed. The enzyme was also inhibited by UTP and UDP, suggesting the role of this portion of the nucleotide sugar substrates in binding to the enzyme. Treatment with urea caused the enzyme to be inactivated by heat either in the presence or absence of endogeneous hyaluronic acid.
Family demographics of clinically referred children: what we know and what we need to know.

Published empirical studies were reviewed to establish family demographics of clinically referred children and adolescents. Data on parental marital status were collected from studies of referred and nonreferred children and adolescents in six empirical journals. Data on family socioeconomic status (SES) and child race or ethnicity were also collected. Based on 86 studies that presented parental marital status, 56.4% of clinically referred children and adolescents live with both their biological mother and biological father. Family SES data were difficult to summarize because of the different methods of presenting this information. When considering race and ethnicity, 86% of the children and adolescents in the clinical samples were Caucasian American. Of the studies that were originally reviewed, 80.4% did not include parental marital status and 36. 7% did not include SES, race, or ethnicity of the participants. There were no significant differences between journals in the rates of inclusion of family demographic data. In addition to revealing family demographic information about children and adolescents who participate in clinical research, these data highlight the lack of consistency in the presentation of family demographic data in published research. Suggestions are provided to help researchers colled and present meaningful family demographic data in clinical and nonclinical research with children and adolescents.
Successful Treatment of Binge Eating Disorder With Combination Phentermine/Topiramate Extended Release.

To the Editor: Phentermine/topiramate extended release is a novel medication approved as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in obese adults. To our knowledge, phentermine/topiramate extended release has not yet been evaluated in binge eating disorder, which often co-occurs with obesity. We therefore present 2 patients with binge eating disorder and obesity who experienced cessation of binge-eating behaviors and clinically significant weight loss with phentermine/topiramate extended release.
A stimulus-control account of regulated drug intake in rats.

Rationale Patterns of drug self-administration are often highly regular, with a consistent pause after each self-injection. This pausing might occur because the animal has learned that additional injections are not reinforcing once the drug effect has reached a certain level, possibly due to the reinforcement system reaching full capacity. Thus, interoceptive effects of the drug might function as a discriminative stimulus, signaling when additional drug will be reinforcing and when it will not.
Prediction of death or myocardial infarction by exercise single photon emission computed tomography perfusion scintigraphy in patients who have had recent coronary artery stenting

Background Although practice guidelines do not recommend routine exercise testing of patients after coronary stenting, several small studies have suggested that stress myocardial perfusion imaging can provide prognostic information about future adverse cardiac events. We sought to determine if exercise nuclear testing provides independent prognostic information in patients after coronary stenting. Methods We analyzed the outcomes of 370 patients who underwent dual isotope exercise nuclear scintigraphy at least 1 month after coronary stenting and had testing between April 1996 and May 2002. Patients were classified according to presence or absence of any ischemia. The primary endpoint was all-cause mortality or myocardial infarction (MI) during a median of 30 months (range 6-59) of follow-up. Results There were 86 patients (23%) who had ischemia. Major events—death or MI—occurred in 62 patients including 22 deaths. Among patients with no ischemia, the 30-month event rate was 9.1%, whereas among patients with ischemia, the event rate was 17.0% ( P = .001). After adjusting for age, sex, standard cardiac risk factors, cardiac history, left ventricular ejection fraction, angiographic findings, procedural variables, exercise capacity, and heart-rate dynamics, the presence of scintigraphic evidence of ischemia predicted death or MI (adjusted hazard ratio 2.08, 95% CI 1.21-3.56, P = .008). The presence of ischemia similarly predicted events in asymptomatic patients (adjusted hazard ratio 2.19, 95% CI 1.17-4.11, P = .015). Conclusions In patients with recent coronary stent placement, reversible nuclear perfusion defects independently predicted risk of death or MI.
Migration of a water pulse through fractured porous media

Contaminant transport from waste-disposal sites is strongly affected by the presence of fractures and the degree of fracture matrix interaction. Characterization of potential contaminant plumes at such sites is difficult, both experimentally and numerically. Simulations of water flow through fractured rock were performed to examine the penetration depth of a large pulse of water entering such a system. Construction water traced with lithium bromide was released during the excavation of a tunnel at Yucca Mountain, Nevada, which is located in an unsaturated fractured tuff formation. Modeling of construction-water migration is qualitatively compared with bromide-to-chloride ratio (Br/Cl) data for pore-water salts extracted from drillcores. The influences of local heterogeneities in the fracture network and variations in hydrogeologic parameters were examined by sensitivity analyses and Monte Carlo simulations. The simulation results are qualitatively consistent with the observed Br/Cl signals, although these data may only indicate a minimum penetration depth, and water may have migrated farther through the fracture network.
Study of Periodic Surface Nanostructures Using Coherent Grating X-Ray Diffraction (CGXD)

It is shown that an x-ray interference phenomenon, Coherent Grating X-ray Diffraction (CGXD), can be used to study lateral nanostructure arrays on crystal surfaces and interfaces. Compared to Fraunhofer grating diffraction of visible light, x-ray grating diffraction contains information not only about geometric profiles of a surface, but also about the internal crystalline structures and lattice strain distributions in grating features. Grating diffraction patterns can also be measured in a white-beam Laue method using highly collimated polychromatic synchrotron radiation. This provides a way for parallel data collection and is useful in in-situ studies of structural evolution of nanostructure arrays.
Hume's Difficulty with the Virtue of Honesty

Etude de la conception de la vertu de l'honnetete developee par Hume dans le «Traite de la nature humaine» en rapport avec le respect de la propriete et la vertu de la fidelite a une promesse. Soulevant le paradoxe de la l'honnetete comme invention sociale et comme produit de la convention humaine, l'A. etudie les raisons qui font de l'honnetete une vertu d'abord artificielle, fondee sur la conformite des interets personnels et des regles de la propriete, puis une vertu naturelle au sens du travail actuel du sentiment moral
Tracing transgene expression in living zebrafish embryos.

Ectopic expression by injection of plasmid DNA is rarely used in zebrafish embryos due to a low frequency of cells expressing a transgene of interest at detectable levels. Furthermore, the mosaic nature of ectopic expression by plasmid injection requires the direct detection of transgene-expressing cells. We have used the transcriptional activator Gal4-VP16 to amplify transgene expression in living zebrafish embryos. In comparison to conventional expression vectors, Gal4-VP16-amplified expression results in a significant higher number of cells which express a transgene at detectable levels. The Gal4-VP16-activator and the Gal4-VP16-dependent transgene can be placed on a single expression vector. Using tissue-specific regulatory elements, we show that expression of a Gal4-VP16-dependent transgene can be reliably restricted to muscle, notochordal, or neuronal tissues. Furthermore, Gal4-VP16 can drive the expression of two or more transgenes from the same construct resulting in simultaneous coexpression of both genes in virtually all expressing cells. The reported expression system works effectively not only in zebrafish embryos but also in Xenopus embryos, chicken, mouse, and human cultured cells and is thus applicable to a broad variety of vertebrates. The high frequency of transgene expression together with the linked coexpression of more than one transgene opens the possibility of easily monitoring the behavior of individual transgene-expressing cells in real time by labeling them with the fluorescent reporter GFP. The combinatorial nature of the expression system greatly facilitates changing the tissue-specificity, the transgene expressed, or the cell compartment-specific GFP reporter, making it simpler to address a gene's function in different tissues as well as its cell biological consequences.
Abstract 4610: Small molecule inhibitors of membrane-bound MCL-1 and BCL-2.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Small molecule inhibitors of membrane-bound MCL-1 and BCL-2 Mcl-1 and Bcl-2 are anti-apoptotic members of the Bcl-2 family of proteins. These proteins sequester activators of Bax-Bak oligomerization and inhibit the subsequent mitochondrial depolarization. Knockdown of anti-apoptotic Bcl-2 family proteins has induced apoptosis in a variety of cancers, signifying that these malignancies are dependent on these proteins for survival. Thus, their inhibition by small molecules is an emerging strategy in cancer therapy. While Bcl-2 specific and pan-inhibitors have emerged, there remains a dearth of molecules that effectively inhibit Mcl-1. In fact, increased Mcl-1 expression is a common mechanism of resistance to these therapies. Previous efforts to identify small molecules that inhibit MCL-1 or BCL-2 function have exploited assays using soluble, truncated, bacterially-expressed recombinant proteins. Since in vivo MCL-1 and BCL-2 exist at full length and are membrane bound, we thought we could improve the identification of biologically active small molecules by screening in a more physiologically relevant environment. It is likely that membrane association affects the structure and access of binding sites. We have therefore developed a screening assay to assess inhibition of full-length Mcl-1 and Bcl-2 in a membrane-bound state. The screen identified compounds that selectively permeabilize membranes whose integrity depends on either MCL-1 or BCL-2. The screen was optimized for high-throughput 384-well format. Positive controls for screening were peptides representing the BH3 domains of Bad and Noxa, known to be selective inhibitors of Bcl-2 and Mcl-1, respectively. We screened >70,000 compound wells. These compounds include an assortment of known bioactives, natural product extract mixtures, and commercial library compounds. We have identified several lead compounds from the primary screen and have validated their performance in biochemical and biological assays. Citation Format: Luv G. Patel, Ronald M. Paranal, Jeremy Ryan, Kristopher Sarosiek, James E. Bradner, Anthony Letai. Small molecule inhibitors of membrane-bound MCL-1 and BCL-2. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4610. doi:10.1158/1538-7445.AM2013-4610
Learned Helplessness A Function of Attribution Style and Comparative Performance Information

This study examined the mediating influence of internal-external attribution style and comparative performance information on responses to task success and failure. Subjects classified as exhibiting either an internal or external attribution style were induced to either succeed or fail on an initial task and then attempted a second, solvable task. In addition, the initial task was performed either alone or in the presence of a confederate who succeeded on the task. Results indicated that subjects with an external attribution style were little influenced by the task success manipulation or by the presence of a successful co-participant. By contrast, internal subjects who failed on the first task in the presence of a successful confederate performed better on the second task than did subjects who performed the first task alone. These results complement previous research, which indicates that internally oriented individuals are more responsive to control contingencies, and under certain conditions, respond t...
Tropospheric sources of NOx: lightning and biology

Laboratory experiments to quantify the global production of NOx (NO + NO2) in the troposphere due to atmospheric lightning and biogenic activity in soil are presented. These laboratory experiments, as well as other studies, suggest that the global production of NOx by lightning probably ranges between 2 and 20 MT(N)y-1 of NO and is strongly dependent on the total energy deposited by lightning, a quantity not well-known. In our laboratory experiments, nitrifying micro-organisms is soil were found to be a significant source of both NO and nitrous oxide (N2O). The measured production ratio of NO to N2O averaged 2-3 for oxygen partial pressures of 0.5-10%. Extrapolating these laboratory measurements to the global scale, which is somewhat risky, suggests that nitrifying micro-organisms in soil may account for as much as 10 MT(N) y-1 of NO. Additional experiments with denitrifying micro-organisms gave an NO to N2O production ratio ranging from 2 to 4 for an oxygen partial pressure of 0.5% and a ratio of less than unity for oxygen partial pressures ranging from 1 to 20%. The production of NO and N2O, normalized with respect to micro-organism number indicates that the production of both NO and N2O by denitrifying micro-organisms is at least an order of magnitude less than production by nitrifying micro-organisms for the micro-organisms studied.
Connotative meanings assigned to contraceptive options.

Abstract Healthy People 2000: National Health Promotion and Disease Prevention Objectives states that the reduction of unintended pregnancies is one of the primary health objectives for college-aged people. In addition, the reduction in rates of sexually transmitted diseases, with special emphasis on reducing the incidence of HIV infection, is an important objective for this population. One way of addressing these objectives is through promoting use of effective contraception methods. Attitudes toward a particular contraceptive option may play an important role in acceptance of, and predisposition toward, using a given method. The authors used semantic differential scaling to study the connotative meanings college students assigned to 13 contraceptive methods. They asked 751 students (mean age ? 19.6 years) to rate each method of contraception, using 7-point scales composed of 15 bipolar adjective pairs. Scale internal consistency was estimated using Cronbach's alpha, and ranges were from .68 for douching...
Pilot Feasibility Study of a Brief, Tailored Mobile Health Intervention for Depression among Patients with Chronic Pain

This pilot feasibility study investigated a brief, tailored mobile health intervention to provide brief treatment and motivate further depression treatment seeking among patients with comorbid chronic pain. The computer tablet intervention was delivered in a hospital clinic using a blended motivational interviewing and cognitive behavioral therapy approach. Individuals were at least age 18, and screened positive for depression during a visit for chronic pain. Participants completed assessments before the intervention and at two-week follow-up. The 64 participants were most often over 50 years old, female, and Caucasian. Participant ratings demonstrated an increase in interest to seek depression treatment and willingness to make life changes to mitigate symptoms. A significant reduction in mean depression score and non-significant reductions on both measures of disability were observed. This intervention was feasible and acceptable, demonstrated promise in reducing depression and increasing treatment inter...
A typological approach to investigate the teaching career decision: Motivations and beliefs about teaching of prospective teacher candidates

This study utilized cluster analysis to identify typologies of prospective teachers enrolled in a teacher education program in the U.S. based upon their self-report motivations for teaching. A three-cluster solution generated three distinctive typologies of prospective teachers (N’s of 93, 70 and 52), and further differences among typologies were investigated with respect to participants’ beliefs about teaching. Follow-up semi-structured interviews confirmed meaningful differences found between the clusters with regard to unique combination of motivations and beliefs about teaching relevant to each typology. Implications for teacher education and teacher development are further discussed in relationship with study findings. Published by Elsevier Ltd.
Coping with Variations through System-Level Design

Manufacturing and operation-induced variations have emerged as a critical challenge in designing integrated circuits (ICs) under the nanometer technology regime. Most work on addressing variations has focused on device, circuit, and logic-level solutions. As the magnitude of parameter variations increases with technology scaling, these techniques are not sufficient to address the negative impact that variations have on IC performance, power, yield, and design time. Therefore, in recent years, the research community has shown great interest in techniques to address variations starting from the other end of the design process, i.e., at the system level. In this paper, we provide an overview of various techniques that we have developed for coping with variations through system-level design. The presented techniques include a paradigm for designing variation-tolerant systems through critical path isolation for timing adaptiveness, application-specific techniques to achieve variation-tolerance by trading off quality of the result, variation-aware system-level power analysis, and system-level power management under variations. These techniques demonstrate that addressing variations during system-level design can greatly mitigate the effects of variations, enabling the design of integrated circuits in scaled technologies.
Auditory skills, language development, and adaptive behavior of children with cochlear implants and additional disabilities

The objective of this study was to evaluate the development of functional auditory skills, language, and adaptive behavior in deaf children with cochlear implants (CI) who also have additional disabilities (AD). Design: A two-group, pre-test versus post-test design was used. Study sample: Comparisons were made between 23 children with CIs and ADs, and an age-matched comparison group of 23 children with CIs without ADs (No-AD). Assessments were obtained pre-CI and within 12 months post-CI. Results: All but two deaf children with ADs improved in auditory skills using the IT-MAIS. Most deaf children in the AD group made progress in receptive but not expressive language using the Preschool Language Scale, but their language quotients were lower than the No-AD group. Five of eight children with ADs made progress in daily living skills and socialization skills; two made progress in motor skills. Children with ADs who did not make progress in language, did show progress in adaptive behavior. Conclusions: Children with deafness and ADs made progress in functional auditory skills, receptive language, and adaptive behavior. Expanded assessment that includes adaptive functioning and multi-center collaboration is recom- mended to best determine benefi ts of implantation in areas of expected growth in this clinical population.
The cybersecurity risk

I l l u s t r a t I o n b y y a r e k W a s z u l T he r IsK of being “hacked”— whatever that expression actually means—is at the heart of our civilization’s chronic cybersecurity problem. Despite decades of computer security research, billions spent on secure operations, and growing training requirements, we seem incapable of operating computers securely. There are weekly reports of penetrations and data thefts at some of the world’s most sensitive, important, and heavily guarded computer systems. There is good evidence that global interconnectedness combined with the proliferation of hacker tools means that today’s computer systems are actually less secure than equivalent systems a decade ago. Numerous breakthroughs in cryptography, secure coding, and formal methods notwithstanding, cybersecurity is getting worse as we watch. So why the downward spiral? One reason is that cybersecurity’s goal of reducing successful hacks creates a large target to defend. Attackers have the luxury of choice. They can focus their efforts on the way our computers represent data, the applications that process the data, the operating systems on which those applications run, the networks by which those applications communicate, or any other area that is possibly subverted. And faced with a system that is beyond one’s technical hacking skills, an attacker can go around the security perimeter and use a range of other techniques, including social engineering, supply-chain insertion, or even kidnapping and extortion. It may be that cybersecurity appears to be getting worse simply because society as a whole is becoming much more dependent upon computers. Even if the vulnerability were not increasing, the successful hacks can have significantly more reach today than a decade ago. Views of Cybersecurity The breadth of the domain means many different approaches are being proposed for solving the cybersecurity problem: ˲ Cybersecurity can be viewed solely as an insider problem. What is needed, say advocates, are systems that prevent DOI:10.1145/2184319.2184330 Simson L. Garfinkel
Vitamin A and Carotene Requirements for the Maintenance of Adequate Blood Plasma Vitamin A in the Dairy Calf

Summary Studies have been made to determine the blood plasma concentrations and the intakes of carotene and vitamin A necessary for the growing calf. The data obtained showed that the blood plasma vitamin A was a more delicate measure of the state of vitamin A nutrition in the calf than either growth or blood carotene. A blood plasma vitamin A level of 10γ or more per 100 cc. was found to be necessary for adequate vitamin A nutrition of the growing calf. Blood plasma vitamin A levels of 7–8γ per 100 cc. were borderline levels while values below this were definitely inadequate. Daily intakes of vitamin A which would maintain deficient, borderline, and adequate concentrations of blood plasma vitamin A were found to be approximately 6,12 and 18γ per kg. of body weight respectively. The daily carotene requirements necessary to maintain an adequate plasma vitamin A and prevent deficiency symptoms were 75γ per kg. for Holstein yearlings and 125γ per kg. for Guernsey yearlings. The blood plasma carotene levels which would maintain an adequate blood vitamin A were 50–70γ of carotene per 100 cc. for Holsteins and 110–140γ of carotene per 100 cc. for Guernseys.
Steam reformer/burner integration and analysis for an indirect methanol fuel cell vehicle

Fuel cell vehicles powered using hydrogen/air fuel cells have received a lot of attention recently as possible alternatives to internal combustion engines. However, the combined problems of on-board hydrogen storage and the lack of hydrogen infrastructure represent major impediments to their wide-scale adoption as replacements for IC engine vehicles. On-board fuel processors that generate hydrogen from on-board liquid methanol (and other hydrocarbons) has been proposed as possible alternative sources of hydrogen needed by the fuel cell. This paper discusses the impact of proper thermal integration between two major components of the fuel processor (reformer and burner) on the dynamic operation of an on-board fuel processor for a fuel cell vehicle. The fuel processor uses the steam reformation of methanol to produce the requisite hydrogen. Since the steam reformation is an endothermic process, the thermal energy required is supplied by a catalytic burner. During dynamic operation of the fuel cell vehicle, the dynamics of the fuel processor become very critical and these dynamics are very strongly influenced by the extent of thermal integration between the reformer and the burner. In order to study these dynamics, the authors developed a fuel processor model in Matlab/Simulink modeling environment.
A high efficiency commercial GaAs MESFET power amplifier for PCM/CIA applications at 2.45 GHz

A low cost commercial, high performance two stage GaAs MESFET power amplifier has been developed for the 2.4 GHz Industrial, Scientific, and Medical (ISM) frequency band targeting portable wireless LAN applications. The amplifier is housed in a low cost plastic surface mount package, making it well suited for insertion into low profile PCM/CIA formats. Measured performance has demonstrated 24 dBm output power with greater than 65% power added efficiency when operated in gain compression with a 5 volt supply. Harmonic rejection greater than 18 dBc and 30 dBc is achieved on 2nd and 3rd order harmonics, respectively. On chip bias and power level control circuitry allows adjusting the output power level over a 20 dBc range with a single analog control voltage. Stringent cost goals are achieved by limiting chip size, choosing inexpensive plastic packaging, and by selecting an appropriate amplifier topology which places some components off chip.
Regulation of Sterol Biosynthesis in Solanum Species

Regulation of sterol synthesis was studied in Solanum species. A significant negative correlation was found between sterol content and rate of sterol synthesis from ( 114C) acetate in plant organs of Solanum nigrum and cell cultures of S. dulcamara. Exogenous cholesterol significantly inhibited the rate of sterol synthesis from (14C) acetate in cell cultures of S. dulcamara without affecting synthesis from (3H) mevalonate. Exogenous cholesterol stimulated the rate of total lipid synthesis from both (14C) acetate and (3H) mevalonate. Thus, cholesterol inhibited conversion of acetate to mevalonate; this is taken as evidence of a negative feedback control on sterol synthesis.
Echocardiographic assessment of left ventricular hypertrophy.

Although methodological problems still exist echocardiography provides the best available non-invasive method for assessing left ventricular hypertrophy (LVH). Indeed, with recent technical advances two-dimensional echocardiography may provide a method that is at hast as accurate as the older angiographic techniques which are the best available invasive techniques. Further, computerised analysis of M-mode echocardiograms provides data about left ventricular function which are not readily available from any other technique. Because echocardiography is non-invasive it is particularly suitable for long-term studies of LVH, serial assessment of the ventricular consequences of valve disease and valve replacement and the effects of therapy. In addition, echocardiographic assessment of the left ventricle may allow the most appropriate form of therapy to be chosen in patients with congestive heart failure. The concepts built up during the extensive study of left ventricular disorders by echocardiography will be relevant to newer techniques such as computerised roentgenographic and positron emission tomography and nuclear magnetic resonance when they are applied in the same situations.