cssi/SciSciGPT-SciSciNet huggingface dataset:
Evidence for glutamatergic projections from the cochlear nucleus to the superior olive and the ventral nucleus of the lateral lemniscus.

This study attempts to determine if projections ascending from the guinea pig cochlear nucleus (CN) could be glutamatergic and/or aspartatergic. Multiple radio frequency lesions were made to ablate the right CN. The ablation was verified histologically. To identify the principal targets of CN efferents, silver impregnation methods were used to localize the preterminal degeneration of fibers in transverse sections of the brainstem 5 and 7 days after CN ablation. CN efferents projected heavily to the lateral superior olive (LSO) ipsilaterally, the medial superior olive (MSO) bilaterally, and contralaterally to the medial (MNTB) and ventral (VNTB) nuclei of the trapezoid body, the ventral (VNLL) and intermediate nuclei of the lateral lemniscus and the central nucleus of the inferior colliculus (ICc). There were smaller projections to the lateral nucleus of the trapezoid body ipsilaterally, the dorsal and dorsomedial periolivary nuclei bilaterally, and the dorsal nucleus of the lateral lemniscus contralaterally. There were sparse projections to the VNLL and ICc ipsilaterally and the CN contralaterally, and a very sparse projection to the contralateral LSO. To determine if CN efferents were glutamatergic and/or aspartatergic, the fresh brainstem was sectioned transversely and samples of the LSO, MSO, MNTB, VNLL, and ICc were taken to measure the electrically evoked release and the uptake of D-[ 3 H]Asp and [ 14 C]Gly or [ 14 C]GABA 3-5 days after the CN ablation. The release studies suggest that only certain of the histologically identified projections ascending from the CN may be glutamatergic and/or aspartatergic. CN ablation depressed D-[ 3 H]Asp release in the MSO bilaterally and in the contralateral MNTB and VNLL, suggesting that the CN efferents to these nuclei may use glutamate or aspartate as a transmitter. It was unclear whether a marginal depression of D-[ 3 H]Asp release in the ipsilateral LSO reflected the presence of glutamatergic CN projections to this nucleus. D-[ 3 H]Asp release in the ICc was unaffected, suggesting that CN efferents to this nucleus may not be glutamatergic. There were no deficits in D-[ 3 H]Asp uptake. [ 14 C]Gly release from the LSO and MSO was unchanged. [ 14 C]Gly uptake was unchanged in the MSO and depressed only in the contralateral LSO, possibly reflecting subnormal uptake activity in endings contributed by contralateral MNTB cells that had lost their CN efferents. [ 14 C]GABA uptake in the MNTB, VNLL, and ICc was unchanged. [ 14 C]GABA release was unchanged in the VNLL and ICc. [ 14 C]GABA release was depressed only in the contralateral MNTB, possibly reflecting the loss of a small complement of GABAergic CN efferents and the reaction of GABAergic projections from the contralateral VNTB to their loss of CN efferents
Frequency of the first feature in action sequences influences feature binding

We investigated whether binding among perception and action feature codes is a preliminary step toward creating a more durable memory trace of an action event. If so, increasing the frequency of a particular event (e.g., a stimulus requiring a movement with the left or right hand in an up or down direction) should increase the strength and speed of feature binding for this event. The results from two experiments, using a partial-repetition paradigm, confirmed that feature binding increased in strength and/or occurred earlier for a high-frequency (e.g., left hand moving up) than for a low-frequency (e.g., right hand moving down) event. Moreover, increasing the frequency of the first-specified feature in the action sequence alone (e.g., “left” hand) increased the strength and/or speed of action feature binding (e.g., between the “left” hand and movement in an “up” or “down” direction). The latter finding suggests an update to the theory of event coding, as not all features in the action sequence equally determine binding strength. We conclude that action planning involves serial binding of features in the order of action feature execution (i.e., associations among features are not bidirectional but are directional), which can lead to a more durable memory trace. This is consistent with physiological evidence suggesting that serial order is preserved in an action plan executed from memory and that the first feature in the action sequence may be critical in preserving this serial order.
Administration of adalimumab in the treatment of Crohn's disease of the ileal pouch.

Summary Background Crohn’s disease (CD) of the pouch can develop in patients with ileal pouch-anal anastomosis (IPAA). Scant data are available on the treatment of this disease entity. Aim To evaluate efficacy and safety of adalimumab in treating CD of the ileal pouch. Methods From June 2007 to June 2008, 17 IPAA patients with inflammatory (n = 10), fibrostenotic (n = 2) or fistulizing (n = 5) CD of the pouch treated with adalimumab were evaluated. Inclusion criteria were CD of the pouch who failed medical therapy and were otherwise qualified for permanent pouch diversion or excision. All qualified patients received the standard dosing regimen of subcutaneous injection adalimumab (160 mg at week 0, 80 mg at week 1, and 40 mg every other week thereafter). Complete clinical response was defined as resolution of symptoms. Partial clinical response was defined as improvement in symptoms. Endoscopic inflammation before and after therapy was recorded, using the Pouchitis Disease Activity Index (PDAI) endoscopy subscores. Results The median age was 36 years with 12 patients (70.6%) being male. At 4 weeks, seven patients (41.2%) had a complete symptom response and 6 (35.3%) had a partial response. There was also a significant improvement in the PDAI endoscopy subscores at week 4 (P < 0.05). At the last follow-up (median of 8 weeks), eight patients (47.1%) had a complete symptom response and 4 (23.5%) had a partial response. Four patients (23.6%) developed adverse effects. Three patients (17.7%) eventually had pouch failure after failing to respond to adalimumab therapy. Conclusion Adalimumab appeared to be well-tolerated and efficacious in treating CD of the pouch in this open-labelled induction study.
Effect of L-glutamic acid on glucocorticoid-induced cleft palate in gestating albino mice.

Abstract l -Glutamic acid produced a significant degree of protection against cortisone-induced (320 mg/kg, im) cleft palate but had no effect against prednisone- and prednisolone-induced (330 mg/kg, im) cleft palate when it was administered as a dietary supplement in gestating Swiss ICR:Ha albino mice. A comparison of the soluble and depo forms of methylprednisolone demonstrated that both preparations exhibited similar levels of embryolethality but different spectrums of teratogenicity. The soluble form produced a significant increase in the incidence of exencephaly without any clejt palate, while the depo form produced significant increases in both cleft palate and fetuses that were born with their eyes open.
Assessment of Life-Cycle Benefit-Cost of Composites in Construction

So far, composite materials have found only moderate acceptance in the construction industry. This has been due primarily to technical and economic barriers such as limited information on life-cycle costs and anticipated performance and benefits. To enhance the application of composites in construction, it is important to develop a model that allows life-cycle benefit-cost assessment based on limited available information. This paper presents such a life-cycle benefit-cost model for composites in construction that does not require monetary quantification of benefits for comparison of alternative materials. The model has been explained through an example application for highway bridge column rehabilitation. The example considers composite column wraps versus conventional steel jackets to illustrate the application of the model.
Lean systems approaches to health technology assessment: a patient-focused alternative to cost-effectiveness analysis.

Many countries now use health technology assessment (HTA) to review new and emerging technologies, especially with regard to reimbursement, pricing and/or clinical guidelines. One of the common, but not universal, features of these systems is the use of economic evaluation, normally cost-effectiveness analysis (CEA), to confirm that new technologies offer value for money. Many have criticised these systems as primarily being concerned with cost containment, rather than advancing the interests of patients or innovators. This paper calls into question the underlying principles of CEA by arguing that value in the healthcare system may in fact be unconstrained. It is suggested that ‘lean management principles’ can be used not only to trim waste from the health system, but as a method of creating real incentives for innovation and value creation. Following the lean paradigm, this value must be defined purely from the patients’ perspective, and the entire health system needs to work towards the creation of such value. This paper offers as a practical example a lean approach to HTA, arguing that such an approach would lead to better incentives for innovation in health, as well as more patient-friendly outcomes in the long run.
The Rationale for Fundamental Pension Reform in the Germany and the United States: An Assessment

This paper considers the arguments for fundamental pension reform in Germany and the United States. The two countries have recently made or are considering reforms that would reduce the generosity of the traditional, pay-as-you-go pension system. Some or all of the lost benefits would be replaced by pensions from newly created individual, defined-benefit, retirement accounts. The paper addresses three questions that are relevant for assessing fundamental reform: (1) Should the pension system move toward advance funding of future benefit obligations? (2) What financial assets should be accumulated to back future pension promises? (3) Should the existing system be reformed to include individual retirement accounts?
Autism in children and adolescents with cancer.

Background The causes of autistic disorders (AD) are not known. Abnormalities of tumor suppressor genes have suggested that these genes may be important to the development of autism in some cases, and result in an increased risk of developing cancer or other neoplasms. We explore possible associations between AD and childhood cancer. Procedure We reviewed our institutional pediatric cancer database for all new cancer diagnoses 1997–2007. Medical records from patients older than 2 years at last visit were reviewed for a diagnosis of AD. The prevalence of AD was estimated for neoplasms overall and for specific tumor types, and compared with that in the general pediatric population. Results Of 702 eligible patients, 7 (1%; 95% CI: (0.4%, 2.04%)) were labeled as AD, not different than the prevalence of AD in North Carolina's general population (0.65%, P = 0.35). Cancer diagnoses for these 7 children were acute lymphoblastic leukemia (n = 1), acute nonlymphocytic leukemia (n = 2), non-Hodgkin lymphoma (n = 1), Hodgkin Disease (n = 1), brain tumor (n = 1), osteogenic sarcoma (n = 1). Conclusions These data do not suggest that there is a high concordance between AD and childhood cancer. However, studies of large rigorously characterized AD cohorts will be needed to definitively address this issue. Pediatr Blood Cancer 2010; 54:144–147. © 2009 Wiley-Liss, Inc.
Metabolic dissociation of short-lived barium-137m from its cesium-137 parent.

At 4 to 7 days after Cs137 administration, Ba137m was found to exceed Cs137-Ba137m equilibrium proportions in bone and plasma by factors of 3 and 14, respectively, in the living animal. This demonstrated the in vivo escape of Ba137m from sites of Cs137 accumulation. Liver tissue was slightly deficient in Ba137m, whereas tissues such as bone marrow and spleen showed little or no deviation from equilibrium.
Current Effectiveness and Risks of Isolated Septal Myectomy for Hypertrophic Obstructive Cardiomyopathy

Background Septal myectomy is the gold-standard therapy for hypertrophic obstructive cardiomyopathy (HOCM). However, it is being challenged by a less-invasive alternative: alcohol septal ablation. This study examined the clinical effectiveness and risks of isolated septal myectomy for HOCM. Methods From January 1994 to January 2005, 323 patients underwent isolated septal myectomy (mean age 50 ± 14 years, 53% male). Preoperative septal thickness was 2.3 ± 0.46 cm and peak left ventricular outflow tract (LVOT) gradient 68 ± 43 mm Hg. Effectiveness of myectomy was assessed by echocardiography, sudden death, and functional limitation, early risks by intraoperative and postoperative complications, and late risks by follow-up for HOMC-related reoperation, heart block, and all-cause mortality (mean 3.6 ± 2.8 years, 1,152 patient-years, 10% followed ≥8 years). Results Myectomy was effective, resulting in sustained decrease in septal thickness and LVOT gradient, absence of sudden death, and improved functional status. Early in-hospital morbidity was low, with no hospital deaths; two iatrogenic ventricular septal defects were repaired uneventfully, and 22 pacemakers were required for heart block. In the intermediate term, 10 patients required HOCM-related reoperations (4 redo myectomies, 6 mitral valve procedures), with 92% freedom from reoperation at eight years. Seventy-nine percent were free of pacemakers by 8 years, and survival was 90%, equivalent to that of the general population. Conclusions Isolated septal myectomy is effective in eliminating LVOT obstruction and sudden death and in improving functional status, with low operative morbidity and mortality. Few reoperations are required late and outcomes are excellent. It should be considered the treatment of choice for HOCM.
Community ecology of the Middle Miocene primates of La Venta, Colombia: the relationship between ecological diversity, divergence time, and phylogenetic richness

It has been suggested that the degree of ecological diversity that characterizes a primate community correlates positively with both its phylogenetic richness and the time since the members of that community diverged (Fleagle and Reed in Primate communities. Cambridge University Press, New York, pp 92–115, 1999). It is therefore questionable whether or not a community with a relatively recent divergence time but high phylogenetic richness would be as ecologically variable as a community with similar phylogenetic richness but a more distant divergence time. To address this question, the ecological diversity of a fossil primate community from La Venta, Colombia, a Middle Miocene platyrrhine community with phylogenetic diversity comparable with extant platyrrhine communities but a relatively short time since divergence, was compared with that of modern Neotropical primate communities. Shearing quotients and molar lengths, which together are reliable indicators of diet, for both fossil and extant species were plotted against each other to describe the dietary “ecospace” occupied by each community. Community diversity was calculated as the area of the minimum convex polygon encompassing all community members. The diversity of the fossil community was then compared with that of extant communities to test whether the fossil community was less diverse than extant communities while taking phylogenetic richness into account. Results indicate that the La Ventan community was not significantly less ecologically diverse than modern communities, supporting the idea that ecological diversification occurred along with phylogenetic diversification early in platyrrhine evolution.
Catfish hybrid Ictalurus punctatus × I. furcatus exhibits higher resistance to columnaris disease than the parental species.

We present experimental data on susceptibility to columnaris disease, caused by the bacterium Flavobacterium columnare, in hybrid catfish (female channel catfish Ictalurus puncta- tus × male blue catfish I. furcatus) (C×B). Under our experimental conditions, C×B hybrids were significantly more resistant to columnaris disease caused by the highly virulent strain of F. columnare BGFS-27 (genomovar II) than channel catfish and blue catfish. Channel and blue catfish cumulative mortalities after immersion challenge were 74 and 87%, respectively, whereas mortality in the C×B hybrid was 31%. Susceptibility to the strain ARS-1 (genomovar I) was lower among all catfishes, although channel catfish was the least resistant species at 32% cumulative mortality. By contrast, C×B hybrid and blue catfishes were strongly resistant to the ARS-1 strain, with <10% mortality. Our data suggest enhanced disease resistance of the C×B hybrid to colum- naris disease.
Divergence Between Flight Crew Mental Model and Aircraft System State in Auto-Throttle Mode Confusion Accident and Incident Cases

In many aircraft accidents relating to pilot error, flight crews held an inconsistent assumption of the actual state of the system when reacting to a failure or abnormal situation. This paper formally defines divergence between flight crew mental model and actual system state, describes a developed framework to understand the mechanisms behind divergence, and discusses results of analysis of divergence in eight auto-throttle mode confusion accidents and incidents. The framework revealed that divergence occurred in all auto-throttle cases. As divergence was analyzed, it became apparent that reconvergence was also prominent in the accidents and incidents, where seven of eight cases indicated that the crew’s mental model and actual system state regained consistency at some point during the accident timeline. Success of recovery actions was dependent on the timing of reconvergence in relation to the criticality of the situation. Consistent with existing literature, the framework also revealed that breakdowns in situation awareness were apparent during the onset of divergence and as an inhibition of reconvergence. The analysis using the framework of divergence showed that for auto-throttle mode confusion accidents, mitigation efforts would be most effective if targeted toward promoting situation awareness of system state prior to the situation degrading beyond recoverability.
Harmonic structure of field line eigenmodes generated by ionospheric feedback instability

[1] Ionospheric feedback instability generates field line eigenmodes under favorable conditions of low ionospheric conductivity and high electric convection. A numerical study has been performed using a two-dimensional model in dipole magnetic field geometry that includes active ionospheric feedback and shear Alfven wave dynamics of the magnetospheric response. Strong parallel inhomogeneities of the magnetospheric parameters included in the numerical model permit the simultaneous development of local ionospheric resonator modes (fast feedback) trapped between the ionosphere and Alfven speed maximum above it and field line eigenmodes (slow feedback) that stand along the entire magnetic field line between two conjugate ionospheres. Fourier analysis of the numerical solution has been used to investigate the relative contribution of fast and slow feedback in the global dynamics of magnetosphere–ionosphere coupling. While many harmonics of the global magnetospheric resonator can be simultaneously generated by the ionospheric feedback instability, all modes above the fundamental eigenmode are strongly suppressed by Alfven wave dispersion. The numerical results suggest that ionospheric feedback is a generating mechanism for the formation of narrow field line resonances.
Optimal Delay-Reconstruction Tradeoffs in Peer-to-Peer Networks

We study the tradeoff between delay and partial reconstruction in peer-to-peer networks, i.e., the number of messages a peer must obtain to reconstruct a given fraction of the file. We present a coding scheme based on erasure compression and Slepian-Wolf binning, in which peers generate coded messages based on their current knowledge of the file. Assuming symmetric peers, we show that the coding scheme provides a Pareto optimal tradeoff between delay and reconstruction, which we characterize. In the process of proving the result, we establish an improved outer bound on the rate region of the general multi-terminal source coding problem. We further show that in the case of asymmetric peers, the coding scheme is not optimal.
Design considerations for sub-0.35 mu m buried channel P-MOSFET devices

Based on simulation and experimental work it is shown that the most important parameters are the LDD dose and the p/sup +/ source/drain junction depth, not the buried junction channel. It is also shown that buried channels can readily be scaled down to 0.2 mu m geometries by adjusting the source/drain construction. The design considerations presented are confirmed by fabricated 0.25- mu m-gate (L/sub eff/ approximately=0.19 mu m) buried p MOSFETs with off-leakage current below 1 pA/ mu m at V/sub G/=0 V, V/sub DS/=-3.3 V. In addition, it is shown that buried channels can readily be scaled down to 0.2- mu m geometries by adjusting the source/drain parameters while maintaining a reasonably high back-end thermal budget. >
As percepções docentes sobre a dimensão metodológica no processo ensino-aprendizagem

This article analyses the reports of Science and Maths’ teachers, who were students on a Master’s degree course in Sciences and Mathematics Education. The research aims at identifying the principles which underpin the pedagogic work of the teachers involved in the research. In order to identify these principles, an analysis was made of the texts written by the teachers answering questions related to their pedagogic practices. Among the several conclusions, the paper emphasises that it is necessary to diversify methodological procedures in the classroom, contextualizing the content, and departing from the students’ previous knowledge, aiming to guarantee them the development of more complex knowledge which contributes to the formation of critical citizens.
Exploring Donors' and Recipients' Attitudes about Living Donor Kidney Transplantation

Context—There is a growing interest in living donor kidney transplantation because of its potential to reduce the current kidney shortage.Objective—To explore the experience of potential recipients, recipients, potential donors, and donors with regard to living donor kidney transplantation and laparoscopic living donor nephrectomy.Method—Twenty-five patients participated in a series of focus group interviews. The interviews were tape-recorded and a content analysis was performed.Results—All participants had a positive attitude toward living donor kidney transplantation and laparoscopic living donor nephrectomy, though this procedure was not a factor that influenced potential donors' decision to donate a kidney. None of the potential donors and donors felt coerced into giving a kidney; they were motivated by a desire to help a loved one who was suffering. The main perceived impediment to donate a kidney was the potential recipients' reluctance to accept the offer. Potential recipients and recipients found ...
Human placental cholinergic system. Occurrence, distribution and variation with gestational age of acetylcholine in human placenta.

Abstract Although acetylcholine (ACh)-like activity was demonstrated in human placental extracts by a number of investigators, substances responsible for this activity were not identified. We found by gas Chromatographic techniques that the major component of the ACh-like activity of the term placenta was ACh (112 ± 7 nmoles/g of wet tissue). These results were confirmed by the separation of ACh from other quaternary ammonium compounds by column chromalography using Amberlite CG-50 resin. The placenta could be stored at 4 for a number of days without significant loss of ACh. Freezing and thawing of the placenta destroyed ACh. This indicates that ACh is bound within membranes. There were high concentrations of ACh in all segments of the placenta. The ACh concentrations in the concentric segments next to the periphery and the umbilical cord were lower than ACh concentrations in other segments. The concentrations of ACh in floating villi and the basal plate, which included the anchoring villi, were about 322 and 210% respectively, of that of the chorionic plate. There was variation in ACh content with gestational age: the highest concentration was found at about 22 weeks (wk) of gestation (nmoles/g at 9–12 wk, 129; 13–16 wk, 342 ± 31; 17–20 wk, 317 ± 32; 21–24 wk, 723 ± 63; 25–28 wk, 231; 29–32 wk, 249; 33–36 wk, 153 ± 15; 37–40 wk, 105 ± 7; and 41–44 wk, 88 ± 5). These observations associate ACh with syncytiotrophoblast. Choline acetyltransferase (ChA) has a similar pattern of variation with gestational age. The placental cholinergic system (as indicated by ChA ACh) was fully formed at the early fetal period of histogenesis and functional maturation, during which the fetus exhibits the fastest rate of growth.
Mass balance for lead in the California South Coast Air Basin: An update

Abstract A mass balance for lead for the year 1989 in the South Coast Air Basin has inputs to the atmosphere of 600±190 kg/day and outputs of 580±160 kg/day, showing rough agreement. Stationary sources are responsible for only about 5% of the total lead emissions. The bulk of the lead is emitted from vehicles using leaded gasoline (37%) and unleaded gasoline (15%), as well as from resuspension of previously deposited lead on roads (43%). Over half of the total emitted lead deposits on roads and nearby soil, while about one-third is carried out of the basin by wind. A small amount, less than 10%, is deposited on surfaces throughout the basin. These percentages are approximately the same as those in a mass balance for the same region calculated for 1972, when lead emissions from leaded gasoline were about a factor of 70 greater than leaded gas emissions in 1989. When the lead emissions are used as inputs to a simple continuously stirred flow reactor model for the basin, reasonable agreement is obtained between calculated and measured concentrations.
How to climb a tree: lizards accelerate faster, but pause more, when escaping on vertical surfaces

Many species of lizards effectively traverse both two and three-dimensional habitats. However, few studies have examined maximum locomotor performance on different inclines. Do maximum acceleration and velocity differ on a level and inclined surface? Do lizards pause more on an inclined surface? To address these questions, Sceloporus woodi lizards (N = 12) were run in the laboratory on a level trackway and a vertical tree trunk. This species is known to frequently utilize both vertical and horizontal aspects of its habitat. Average maximum acceleration on the vertical surface exceeded that on the level surface, although average maximum velocity exhibited the opposite pattern. The average number of pauses during level locomotion was lower compared to vertical locomotion. In addition, the average location of the first pause on the level surface was 0.51 m, which is farther than the average for vertical locomotion where the first pause was at 0.35 m. The combination of performance and pause data suggests that the relative lack of pausing during level locomotion allows individuals to reach higher maximum velocities on level surfaces because they accelerate over greater distances. The increased pausing when moving vertically could be a result of high energetic demands of vertical locomotion, or greater microhabitat complexity as a result of branching and/or refuges. The faster acceleration exhibited during vertical locomotion by S. woodi likely offsets the frequent pauses. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 102, 83–90.
Collision detection for planning collision-free motion of two robot arms

The authors focus on collision detection for planning collision-free motion of two robot arms in a common workspace. A collision-free motion is obtained by detecting collisions along the straight-line trajectories of the robots using a sphere model for the wrists and then replanning the paths and/or trajectories of one or both of the robots to avoid collisions. A novel approach to collision detection is presented and a discussion on collision avoidance is given. >
The effectiveness of US mitigation and monitoring practices for the threatened Valley elderberry longhorn beetle

Habitat mitigation frequently leads to planting of new habitat, assuming that it can replace lost natural habitat. Yet this practice has rarely been examined in detail. In the USA habitat mitigation is frequently allowed under the US Endangered Species Act, providing monitoring reports which represent a potentially valuable data source for imperiled species. We used publicly available reports for the US threatened Valley elderberry longhorn beetle (Desmocerus californicus dimorphus) to assess record keeping practices used by US Fish and Wildlife Service (FWS), and the utility of such analyses for improving conservation. A large portion of mitigation reports known to exist were missing from FWS files, indicating problems with data management, and a loss of important information. Transplanted brought mature beetle host plants and beetles to sites, promoting beetle colonization. Conversely, few sites with seedlings were colonized. Results indicate a need for improved data management by FWS and longer term monitoring.
Abstract A58: High Throughput Search for a Combination Cancer Preventive Treatment

Identification of safer chemopreventive drugs is essential for the future of cancer preventive treatment. Although the feasibility for chemoprevention of estrogen receptor (ER) -positive breast cancers has been exemplified by the use of selective estrogen response modifiers (SERMs), we are still lacking preventive options for many other disease types, including breast cancers not dependent on ER status. Rexinoids are a class of agents that effectively reduce the incidence of both ER-positive and -negative tumors in animal models of breast cancer and thus may be better cancer preventive drugs than the current standard SERMs. However, significant side-effects at the effective clinical dose, including hypertriglyceridemia and weight gain, limit its generalized use. A phase II biomarker trial of the synthetic rexinoid, bexarotene (Targretin, LGD1069) demonstrated that bexarotene reduces expression of the proliferation markers Ki67 and Cyclin D1 in normal breast epithelium of postmenopausal women, suggesting that the cancer preventive effects of bexarotene are associated with its ability to elicit cell cycle blockade and inhibit proliferation of premalignant mammary epithelial cells. Here we hypothesize that the combination of repurposed drugs and some small molecule compounds with low dose rexinoid will minimize toxicity and result in effective anti-proliferative in premalignant cells. Therefore, we designed an image-based in vitro assay system to conduct high throughput screens to identify existing drugs and drug-like small molecules which enhance the growth suppressive effect of cancer preventive rexinoids. We used an automated 96 well platform to test the NIH clinical collection of drugs and a library of structurally diverse compounds (MayBridge Hitfinder) alone or in combination with 100nM bexarotene. Through multiparametric determination of cell counts, DNA content and cellular toxicity, we identified combination treatments of premalignant breast cells that fit the above criteria and report on dose-response studies and secondary screens for optimal dose and cell health. Validation of some of the candidate agents and plans for in vivo testing of their chemopreventive activity will be discussed. Citation Format: Ivan P. Uray, Powel H. Brown. High-throughput search for a combination cancer preventive treatment. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A58.
THE EFFECT ON THE EXTERNAL PARATHYROID GLANDS OF THE EXPOSURE OF RABBITS TO ULTRA-VIOLET LIGHT

Because many instances have been observed of the effects of light on metabolic processes, and because in the higher animals tbe glands of internal secretion act in part as chemical regulators of metabolism, we are undertaking certain studies on the effects on the endocrine tissues of exposure of the skin to ultra-violet light. In preparation for these studies it seemed desirable to make preliminary observations on the reactions of all the ductless glands available for examination, and to note such changes in weight and microscopic appearance as might indicate abnormal activity. Such a study is the more necessary because of various interrelationships among the endocrine glands that make isolated observations on a single tissue of doubtful value. Dr. Wade H. Brown and Dr. Louise Pearce have directed attention to this interdependence among certain of the glands of internal secretion in connection with their extensive studies on experimental syphilis and carcinoma in the rabbit. During the past 2 years they have collected data on individual and seasonal variations in the size, appearance, and functional activity of the endocrine tissues of a large number of normal animals. 1 These valuable records, mostly unpublished, they have kindly placed at our disposal. It would have been fruitless to make the observations on which this paper is based without the extensive control material thus afforded us. Even during the period covered by the experiments--November to February--there occurred in certain of the endocrine tissues a change, regarded as
New Policies for a New Rural America

The U.S. rural economy is undergoing huge changes as the twenty-first century begins. The most compelling feature of these several changes is unevenness: some rural areas are booming while many others struggle. Looking forward, rural America faces five major challenges. Closing the digital divide will help rural America top e-business opportunities. Urging on rural entrepreneurs will help fuel new economic activity on Main Street. Leveraging a new product-oriented agriculture will boost growth in some farming communities, but probably not all. Sustaining the rural environment will provide a strong economic foundation for many scenic rural areas. And boosting rural human capital will be essential for most rural growth strategies. Public policy will play an important supporting role as rural America meets these challenges. But rural policies in the twenty-first century will have to go far beyond a historical focus on agriculture. The period ahead will likely see a rich debate on the goals and mechanisms of ...
Coherent optical code-division multiple access with dynamic encoder and decoder

A new implementation of spectral coherent code-division multiple access is proposed, offering dynamic encoding/decoding capabilities through a wavelength-to-time mapping by dispersion of a short pulse. Experimental results are shown, including a two-channel eye-diagram measurement
Occupational Performance Differences Between Psychiatric Groups

This study compared the occupational performance of non-disabled people, people with depression and people with schizophrenia, in order to investigate the hypothesis that they fall along a continuum of decreasing ability. The study sample consisted of 43 people from each diagnostic category, matched for age and gender. The Assessment of Motor and Process Skills (AMPS) was used to measure the participants' motor and process abilities during the performance of instrumental or personal activities of daily living (ADL). The results reveal that all three groups differed significantly in both motor and process mean ADL ability measures, indicating a continuum of ADL ability among the three groups, with the participants with schizophrenia on the less able end, participants with depression in the middle and those without disability on the higher end. This study indicates that we must acknowledge both ADL motor and ADL process deficits as they affect occupational performance, recognizing individual differences wit...
Renegotiation and the Impossibility of Optimal Investment

In a model with asymmetric information and external equity financing, it is impossible to achieve socially optimal investment because of renegotiation possibilities. The contractual solution suggested by Dybvig and Zender (1991) is not dynamically consistent--the manager's contract would be renegotiated, resulting in inefficient investment. Moreover, no other compensation contract that would induce the manager to invest efficiently survives renegotiation. Contracts that pay the manager based on the stock price, while producing suboptimal investment as in Myers and Majluf (1984), are robust to renegotiation. Article published by Oxford University Press on behalf of the Society for Financial Studies in its journal, The Review of Financial Studies.
Propofol's effects on phagocytosis, proliferation, nitrate production, and cytokine secretion in pressure-stimulated microglial cells.

Background Intracranial hypertension complicates severe traumatic brain injury frequently and might be associated with poor outcomes. Traumatic brain injury induces a neuroinflammatory response by microglial activation and upregulation of proinflammatory cytokines, such as interleukin-1β, tumor necrosis factor alpha, and interleukin-6. To elucidate the effect of increased intracranial pressure on microglial function, we studied the effects of increased extracellular pressure on primary human microglial cell phagocytosis, proliferation, cytokine secretion, and total nitrate production. In addition, because many patients receive propofol during anesthesia or intensive care unit sedation, we evaluated whether propofol alters the effects of pressure. Methods Human microglial cells were pretreated with (2.5–20 μg/mL) propofol or Intralipid as a vehicle control were incubated at ambient atmospheric pressure or at 15 or 30 mm Hg increased pressure for 2 h for phagocytosis assays or 24 h for proliferation, cytokine secretion, and total nitrate production studies. Phagocytosis was determined by incorporation of intracellular fluorescent latex beads. Tumor necrosis factor alpha, interleukin-1β, and interleukin-6 were assayed by sandwich enzyme-linked immunosorbent assay and total nitrate by Greiss reagent. Results Increased extracellular pressure stimulated phagocytosis versus untreated microglial cells or cells treated with an Intralipid vehicle control. Propofol also stimulated microglial phagocytosis at ambient pressure. Increased pressure, however, decreased phagocytosis in the presence of propofol. Pressure also increased microglial tumor necrosis factor-α and interleukin-1β secretion and propofol pretreatment blocked the pressure-stimulated effect. Interleukin-6 production was not altered either by pressure or by propofol. Pressure also induced total nitrate secretion, and propofol pretreatment decreased basal as well as pressure-induced microglial nitrate production. Conclusion Extracellular pressures consistent with increased intracranial pressure after a head injury activate inflammatory signals in human primary microglial cells in vitro, stimulating phagocytosis, proliferation, tumor necrosis factor-α, interleukin-1β, and total nitrate secretion but not affecting interleukin-6. Such inflammatory events may contribute to the worsened prognosis of traumatic brain injury after increased intracranial pressure. Because propofol alleviated these potentially proinflammatory effects, these results suggest that the inflammatory cascade activated by intracranial pressure might be targeted by propofol in patients with increased intracranial pressure after traumatic brain injury.
Mechanism of expression of DNA repair gene vsr, an Escherichia coli gene that overlaps the DNA cytosine methylase gene, dcm.

Summary The DNA cytosine methylase gene of Escherichia coli, dem, overlaps an open reading frame (ORF) that continues in +1 register past the end of dcm. This ORF codes for a gene, vsr, that is required for a T:G to C:G base mismatch correction process. In this study, mutants that affect the level of expression of the two genes were constructed and characterized. Further, a previously isolated mutant, dcm-6, was cloned and mutations within it were identified. Northern blots were used to identify dcm-specific RNA species in wild type and dcm-6 cells. Based on these studies we conclude that there is a six-codon overlap between vsr and dcm. The two proteins appear to be made from a single RNA transcript and translation of dcm is required for the efficient synthesis of Vsr. Further, Vsr is active by itself and may not be produced as a fusion with Dem. This is the first example of chromosomal genes that overlap in their coding regions and produce proteins with distinct functions.
The distribution of power in Ugandan society

Understanding the dynamics of various forms of societal power is important when analysing change in a society. This article seeks to develop a model that aids in analysing the distribution of four types of societal power: political, economic, citizen, and cultural. Each of these types of power is acquired through different processes. These processes are described in this article. Following the description of the model, the model is used to analyse Ugandan society under Museveni. The analysis reveals that Museveni has acquired broad systemic power that portends negatively for any possible changes in power to occur. Given the level of centralization of power with Museveni, the likelihood of transferring power to citizens through peaceful means is unlikely.
Improvement of epoxy adhesion to polyimide passivation

Adhesion of epoxy to polyimide passivation is very important in electronic packaging. Pyromellitic dianhydride-4,4'-oxydianiline polyimide (PMDA-ODA PI) showed lower adhesion to most epoxy formulations. Different approaches were explored to improve the adhesion of epoxy formulations to PMDA-ODA PI. Silane coupling agents did not improve the adhesion of epoxy to PMDA-ODA PI, but they improved the adhesion hydrolytic stability. Amine and sodium hydroxide were used to treat the PMDA-ODA PI surface. Sodium hydroxide treatment was more effective in improving the adhesion between PMDA-ODA PI and epoxy than the amine treatment. The hydrolytic stability of adhesion between epoxy and sodium hydroxide treated PMDA-ODA PI depends on the curing condition of the epoxy formulation. When the formulation was cured at temperature of 200/spl deg/C or below, the hydrolytic stability of adhesion between epoxy and sodium hydroxide treated PI was worse than that of adhesion between epoxy and untreated PMDA-ODA PI. When epoxy formulation was cured at 250/spl deg/C, the hydrolytic stability of adhesion between epoxy and sodium hydroxide treated PI did not degrade. In addition, it was discovered that epoxy cured with imidazole or its derivatives showed excellent adhesion to PMDA-ODA PI. The surface treatment of PI could not further improve the adhesion of PMDA-ODA PI passivation to epoxy cured with imidazole or its derivatives.
A diagnostic framework for planning

The traditional framework for strategy formulation in the field of business policy is deliberately broad and generalized, so as to encompass an almost limitless number of potentially influential factors. There is also a need for a more focused view, a means for showing similarities and differences among firms and how these relate to strategy formulation—a framework, in other words, that allows companies to be diagnosed by key situational elements and uses these, in turn, to define the appropriate strategy alternatives. What is proposed is a framework based on three familiar key elements—organizational levels, management styles, and stages of growth—integrated with and related to four basic strategy alternatives.
Policing the homeless: An evaluation of efforts to reduce homeless-related crime

Research Summary Police officials across the United States are increasingly relying on place-based approaches for crime prevention. In this article, we examine the Safer Cities Initiative, a widely publicized place-based policing intervention implemented in Los Angeles's “Skid Row” that focused on crime and disorder associated with homeless encampments. Crime reduction was the goal. The police division in which the program was undertaken provides 8 years of time-series data serving as the observations for the treatment condition. Four adjacent police divisions in which the program was not undertaken provide 8 years of time-series data serving as the observations for the comparison condition. The data are analyzed using a generalized additive model. On balance, we find that this place-based intervention is associated with meaningful reductions in violent, property, and nuisance street crimes. There is no evidence of crime displacement. Policy Implications This study provides further evidence that geographically targeted police interventions can lead to significant crime prevention benefits, with no evidence that crime is simply displaced to other areas. Criminologists and the media have given the Los Angeles Police Department (LAPD) little credit for major reductions in crime that have occurred during the past 5 years following a number of major policy reforms. We suggest that researchers should look more closely at the targeted interventions the LAPD has undertaken for evidence-based examples of effective policing. Importantly, this work suggests that crime associated with homeless encampments can be meaningfully reduced with targeted police actions. However, law enforcement actions do not address the roots of homelessness nor most of its consequences. Getting tough on the homeless should not be confused with policies or programs that respond fundamentally to the social and personal problems that homelessness presents.
Understanding virulence mechanisms in M. tuberculosis infection via A circuit-based simulation framework

Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (Mtb), is a growing international health crisis. Mtb is able to persist in host tissues in a non-replicating persistent (NRP) or latent state. This presents a challenge in the treatment of TB. Latent TB can re-activate in 10% of individuals with normal immune systems, higher for those with compromised immune systems. A quantitative understanding of latency-associated virulence mechanisms may help researchers develop more effective methods to battle the spread and reduce TB associated fatalities. Leveraging BioXyce's ability to simulate whole-cell and multi-cellular systems we are developing a circuit-based framework to investigate the impact of pathogenicity-associated pathways on the latency/reactivation phase of tuberculosis infection. We discuss efforts to simulate metabolic pathways that potentially impact the ability of Mtb to persist within host immune cells. We demonstrate how simulation studies can provide insight regarding the efficacy of potential anti-TB agents on biological networks critical to Mtb pathogenicity using a systems chemical biology approach.
A new quantitative assay for glycosaminoglycans.

Abstract A direct dye-binding technique has been developed to measure total glycosaminoglycans in urine. Fifty or 100 μ1 of urine was mixed with a solution of Azure A (10 mg/l) and Azure B (10 mg/l) and the resulting decrease in absorbance at 610 nm was measured. The standard curve with chondroitin sulfate C was linear from 1 to 20 gmg/assay. The normal value for total urinary glycosaminoglycans in adults was 1.8 ± 0.6 g/mol creatinine. Other normal values were age-dependent. The assay is inexpensive, simple, precise, sensitive and suitable for screening for the mucopolysaccharidoses in pediatrie patients.