cssi/SciSciGPT-SciSciNet huggingface dataset:
Identification of early alterations during hepatic oncogenesis in c-Myc/Tgfα transgenic mice by transcriptome analysis

3848 Hepatocellular carcinoma (HCC) is one of the most common cancers in the world, accounting for an estimated 600,000 deaths annually. Although much is known about both the etiological agents and the cellular changes that lead to HCC, the molecular pathogenesis of HCC is not well understood, partly due to the difficulty of analyzing the early stages of the disease. In this context, genetically engineered mice that recapitulate human HCC are valuable experimental models for a sequential analysis of tumor development. We previously reported that the gene expression profiles of HCCs derived from c-Myc/Tgfα transgenic mice closely reproduce those observed in a subset of human HCC with a poor prognosis (Nat. Genet., 36:1306-11, 2004). Here, we report a detailed characterization of HCC development in c-Myc/Tgfα mice starting from the early to late stages based on gene expression profiles. The tumor development in c-Myc/Tgfα mice was associated with progressive and cumulative transcriptional alterations. Already in 3 week old mice, microarray analysis revealed an induction of genes involved in replication (e.g. Mcm6, Mcm7, Myc), DNA repair (e.g. Ddb2, Rad51l1) and translation (e.g. Eef1b2, Eef2, Rpl13) characteristic of an active hepatocyte proliferation. Livers of 3 month old mice showed more extensive dysplastic changes, frequent mitosis, as well as the first signs of genomic instability along with an elevated production of reactive oxygen species. These cellular alterations coincided with an oxidative stress gene expression signature with the up-regulation of genes involved in DNA repair (e.g. Ddb2, Mlh1, Msh3, Rad51ap1), fatty acid beta-oxidation (e.g. Acaa1b, Acadm), and detoxication (e.g. Gsta1, Ugt1a9). At eight months, 100% of mice developed HCC in a background of wide-spread hepatic dysplasia. The gene expression profiles in the livers of 3 month old mice were highly similar to those of surrounding non-tumorous livers of 8 month old mice. However, the most noticeable difference was the simultaneous induction of ligands for natural killer cells (e.g. Raet1a-e) and the repression of MHC-I, specifically at 3 months. Flow cytometry experiments on purified hepatocytes confirmed these results that could be interpreted as an early mechanism of immunosurveillance to prevent the emergence and clonal expansion of progenitors for liver tumors. We conclude that tumor development in c-Myc/Tgfα mice results from a progressive accumulation of genetic alterations due to both a general metabolic disorder generating a chronic oxidative stress environment and an active hepatocyte proliferation. Moreover, our study strongly suggests that a disruption of the innate immune surveillance may contribute to a rapid selection of tumor clones at the early stages of hepatocarcinogenesis.
Proxy or Imposter? A Method and Case Study to Determine the Answer

As the HPC community moves toward exascale, understanding application behavior is more important due to the increase in size and complexity of systems. While applications also grow larger in size and complexity, the need for proxy applications is crucial because of their ease of use and fast execution. They have become an essential aid for system vendors to evaluate new advanced architectures and for application developers to more quickly resolve algorithm and optimization issues. Therefore, proxies must be representative in behavior and function of the applications they mimic. In this work, we present a methodology to understand if a proxy represents a parent application based on a comparison of computational kernels, appropriate dynamic execution characteristics, and hardware bottlenecks. Based on this method, we conclude that miniQMC is a fairly good proxy for QMCPACK, but could be improved based on our analysis.
Pancreas transplant alone

Abstract Pancreas transplantation can restore insulin independence in diabetic patients resulting in improved quality of life, eliminating glycemic excursions and stabilizing diabetic complications. Pancreas transplant alone (PTA) only accounts for 8%–10% of pancreas transplants in the United States each year. Patients with life- threatening complications of diabetes, namely severe episodes of hypo- and hyperglycemia, in the absence of renal failure have been shown to benefit from solitary pancreas transplantation. Type 1 diabetes is the traditional indication for pancreas transplant; however, more specifically pancreas transplant alone should be considered in insulin-dependent patients with a normal renal function that suffer from frequent, debilitating complications of diabetes despite optimal, supervised insulin therapy and especially frequent severe episodes of hypoglycemia. Despite the decreasing rates of PTA being performed, outcomes have improved, especially in the context of early graft survival. The International Pancreas Transplant Registry shows that PTA graft survival continues to improve with a 1-year graft survival of 85% and a 5-year graft survival of greater than 60%. The estimated half-life of a PTA is 7–14 years. Most importantly, patients experience a profound improvement in the quality of life following pancreas transplantation. Through the combination of careful allograft and patient selection in the setting of improved operative techniques, PTA offers a curative treatment option for insulin-dependent diabetics with preserved renal function.
Some Problems of Radiative Transfer

This chapter is intended to describe certain current areas of research in the field of radiative transfer that seem significant and timely. Another view of the subject and appraisal of current research is provided in Chapter 7 by Pai.
Menthol, Nicotine, and Flavoring Content of Capsule Cigarettes in the US.

Objectives Characterize physical design features of cigarette brands sold in the US according to the delivery method of menthol that may affect sensory perception among users. Methods Twelve cigarette brands, mentholated and non-mentholated, were purchased for analyses of the physical design characteristics, quantification of nicotine and menthol, and identification of flavor additives. Results Physical design characteristics did not differ significantly between the various cigarette brands. However, significant differences were seen in levels of menthol. Menthol levels were greatest in products that had dual delivery methods of menthol (6.7mg/cigarette; SE=0.27) followed by products mentholated in a filter capsule only (5.7mg/cigarette; SE=0.25), and those mentholated in the tobacco only (3.8mg/cigarette; SE=0.12); products that were not mentholated had the least (0.38mg/cigarette; SE=0.31). Finally, flavor additives with a mint flavor profile other than menthol were identified, such as pulegone and limonene, and differed between cigarette brands, which are likely contributing to the menthol flavor experience associated with use of these products. Conclusions The regulation of menthol delivery method, flavorings added to the capsule, and/or menthol concentration may be beneficial for the public health as these factors are likely creating unique sensory experiences.
Kolob Runs on Domo: Mormon Secrets and Transhumanist Code*

Mormon religiosity is deeply marked both by a culture of secrecy and also by a culture that obliquely indexes secret religious material as a means of communication. This secrecy, though, can at tim...
Criteria for risk stratification of vulvar and vaginal smooth muscle tumors: a follow-up study with application to leiomyoma variants, smooth muscle tumors of uncertain malignant potential, and leiomyosarcomas.

Summary Data have shown that uterine diagnostic criteria are universal for smooth muscle tumors (SMTs) originating in the ovary, vulva, vagina, broad ligament, and other supportive connective tissue and that uterine criteria outperform site-specific criteria for vulvar and vaginal SMTs. Classic benign and malignant spindled SMTs were well represented in our recent study comparing uterine and site-specific criteria in vulvovaginal SMTs, but leiomyoma variants and smooth muscle tumors of uncertain malignant potential (STUMPs) were relatively few. Therefore, we evaluated additional leiomyoma variants, STUMPs, and leiomyosarcomas from 17 patients (10 vaginal and 7 vulvar). The 10 vaginal tumors (59%) comprised cellular leiomyoma (n = 2), leiomyoma with bizarre nuclei (n = 3), STUMP (n = 1), and leiomyosarcoma (n = 4). The 7 vulvar tumors (41%) comprised leiomyoma with bizarre nuclei (n = 3), STUMP (n = 1), and leiomyosarcoma (n = 3). Follow-up was available for 13 patients (76.5%) ranging from 1 to 97 months (mean: 17.3; median: 7). Follow-up for some patients with leiomyosarcoma was limited (≤4 months for 4 patients). One vaginal STUMP locally recurred after 19 months, and 2 patients diagnosed with leiomyosarcoma developed distant metastases. All remaining patients had either no evidence of disease at last follow-up (10 patients, 58.8%) or their status was unknown (4 patients, 23.5%). Uterine criteria are valid for vulvovaginal leiomyoma variants and STUMPs and more appropriately classified these tumors than site-specific criteria. Our combined findings from the current and previous studies support use of uterine diagnostic thresholds for the entire spectrum of vulvovaginal SMTs.
Botrytis cinerea management in ornamental production: a continuous battle

Ornamental production systems are complicated to manage due to the many species and genera that may be grown and handled together on a single production site. Ornamentals are threatened by various ...
Graphene oxide/mussel foot protein composites for high-strength and ultra-tough thin films.

Graphene oxide (GO)-based composite materials have become widely popular in many applications due to the attractive properties of GO, such as high strength and high electrical conductivity at the nanoscale. Most current GO composites use organic polymer as the matrix material and thus, their synthesis suffers from the use of organic solvents or surfactants, which raise environmental and energy-consumption concerns. Inspired by mussel foot proteins (Mfp) secreted by the saltwater mussel, Mytilus galloprovincialis and by recent advances in microbial protein production, we developed an aqueous-based green synthesis strategy for preparing GO/Mfp film composites. These GO/Mfp films display high tensile strength (134-158 MPa), stretchability (~ 26% elongation), and high toughness (20-24 MJ/m3), beyond the capabilities of many existing GO composites. Renewable production of Mfp proteins and the facile fabrication process described provides a new avenue for composite material synthesis, while the unique combination of mechanical properties of GO/Mfp films will be attractive for a range of applications.
A Unique Presentation of Bouveret's Syndrome: Two Large Gallstones Obstructing Both the Gastric Outlet and the Common Bile Duct Simultaneously.

Bouveret’s syndrome refers to a gastric outlet obstruction secondary to impaction of a gallstone in the pylorus or proximal duodenum. Thus, it can be considered a very proximal form of gallstone ileus and is infrequent. We describe such a unique case that a female patient presents with Bouveret’s syndrome and concomitant common bile duct obstruction by a second gallstone. The decision over its surgical management is complicated, based on risk factors, clinical presentations, radiographic evidence, surgical risk assessment, and specific considerations tailored to individual case. Because of her stable clinical picture and low surgical risk, we proceeded with stone extractions, fistula take-down, and common bile duct exploration in a one-stage procedure. Her postoperative course was complicated by bile stained drainage through closed suction drain that resolved with conservative management.
Sleep Duration, Sleep Timing, and Sleep Disordered Breathing-Associations With Obesity and Gestational Diabetes in Pregnancy

Pregnant individuals may come into pregnancy with underlying sleep abnormalities but are also predisposed to developing sleep issues such as obstructive sleep apnea, due to the physiologic changes associated with the gravid state. This article will review the epidemiology of sleep duration, sleep timing, and sleep disordered breathing in pregnancy with a focus on how the prevalence of these sleep conditions relate to body mass index. In addition, it will summarize the literature suggesting a link between these sleep disturbances and an increased risk for gestational diabetes.
ODR and Mediation

Online mediation had been spreading rapidly as a mode of practice, even before the entire profession shifted online during the COVID-19 era. In this chapter, Ebner and Rainey survey the development of online mediation within the wider context of the growth of Online Dispute Resolution (ODR). The chapter presents a snapshot of the field’s status quo with respect to stakeholders, modes of communication and the technology utilized, and addresses substantive and process issues in online mediation: mediation process models, stages and issues; practitioner skills; professional issues; ethics, and practitioner standards.
Effects on Smoking Behavior of Switching Menthol Smokers to Non-menthol Cigarettes.

INTRODUCTION Bans of menthol characterizing flavor in cigarettes have been implemented in some localities and have been proposed more broadly. One proposed benefit of such a ban is to increase cessation rates among current menthol smokers. There is currently relatively limited data regarding how smoking behavior changes if menthol smokers switch to non-menthol cigarettes. AIMS AND METHODS African American menthol smokers interested in quitting smoking were randomized to either continue smoking menthol (n = 60) or switch to non-menthol cigarettes (n = 62) for 1 month prior to a cessation attempt. Cessation results were reported previously; this analysis reports the results from the pre-cessation visits at which amount smoked, exhaled carbon monoxide (CO) concentration, urinary cotinine concentrations, and subjective measures were assessed. RESULTS Over the 4-week study period, those switching to non-menthol (vs. continuing to smoke menthol) cigarettes smoked fewer cigarettes per day (mean ratio: 0.86; 95% confidence interval [CI]: 0.76, 0.98; p = .02), reported lower withdrawal symptom severity (mean difference -1.29; 95% CI: -2.6 to -0.01; p = .05) and higher perceived effectiveness of their skills for quitting smoking (mean difference 0.56; 95% CI: 0.02-1.10; p = .05). No significant differences were found between groups in exhaled CO, urinary cotinine concentrations, or most other subjective effects including support for a ban on menthol characterizing flavor in cigarettes. CONCLUSIONS These results suggest that were menthol cigarettes no longer available, those that switch to non-menthol cigarettes would not change their smoking behavior in a way that is likely to be more hazardous, with some indicators suggesting that there may be some benefit.Clinicaltrials.gov # NCT02342327. IMPLICATIONS A ban on menthol characterizing flavor in cigarettes has been proposed as a potential means by which to increase smoking cessation rates among current menthol cigarette smokers. This study evaluated how African American menthol cigarette smokers adjusted their smoking behavior after switching to non-menthol cigarettes. Although the overall differences between groups were modest, they were in a direction consistent with decreased smoking suggesting that current smokers would not adjust their behavior in a way that is likely to be more hazardous, with some indicators suggesting that there may be some benefits.
Investigation of air-water two-phase flow characteristics in a 25.4 mm diameter circular pipe

Abstract High-quality two-phase flow data are essential for further developing various two-phase flow models and validating two-phase flow codes. The work presented in this paper aims to perform detailed measurements of air-water two-phase flow in a 25.4 mm inner diameter pipe using several techniques developed recently. The gas-phase information is obtained by an integrated method synergizing conductivity probe, high-speed imaging system, and X-ray densitometry system while the Particle Image Velocimetry and Planar Laser-Induced Fluorescence (PIV-PLIF) technique are utilized to measure liquid-phase velocity and turbulence characteristics. Selected conditions in the bubbly, slug, and churn-turbulent flow regimes with the gas and liquid superficial velocities ranging from 0.05 to 4.99 m/s and from 0.10 to 3.88 m/s, respectively, are investigated in this work. The two-phase flow interfacial structures are visualized by both high-speed optical and X-ray images. In fully developed bubbly flows, “wall-peak” void profiles are observed, which is due to the transverse lift force effect. The gas-phase velocities share similar profiles as the liquid-phase velocity but have slightly higher magnitudes due to the buoyancy force effect. In this work, flow development in different flow regimes is investigated as well. As bubbly flows develop along the axial direction, the void profiles may change, and the discrepancy between gas-phase and liquid phase velocities will diminish in the process.
Offline Meta-Reinforcement Learning with Online Self-Supervision

Meta-reinforcement learning (RL) can meta-train policies that adapt to new tasks with orders of magnitude less data than standard RL, but meta-training itself is costly and time-consuming. If we can meta-train on offline data, then we can reuse the same static dataset, labeled once with rewards for different tasks, to meta-train policies that adapt to a variety of new tasks at meta-test time. Although this capability would make meta-RL a practical tool for real-world use, offline meta-RL presents additional challenges beyond online meta-RL or standard offline RL settings. Meta-RL learns an exploration strategy that collects data for adapting, and also meta-trains a policy that quickly adapts to data from a new task. Since this policy was meta-trained on a fixed, offline dataset, it might behave unpredictably when adapting to data collected by the learned exploration strategy, which differs systematically from the offline data and thus induces distributional shift. We do not want to remove this distributional shift by simply adopting a conservative exploration strategy, because learning an exploration strategy enables an agent to collect better data for faster adaptation. Instead, we propose a hybrid offline meta-RL algorithm, which uses offline data with rewards to meta-train an adaptive policy, and then collects additional unsupervised online data, without any reward labels to bridge this distribution shift. By not requiring reward labels for online collection, this data can be much cheaper to collect. We compare our method to prior work on offline meta-RL on simulated robot locomotion and manipulation tasks and find that using additional unsupervised online data collection leads to a dramatic improvement in the adaptive capabilities of the meta-trained policies, matching the performance of fully online meta-RL on a range of challenging domains that require generalization to new tasks.
P-107: NCOR2 mediated MYC upregulation drives drug resistance in multiple myeloma independent of Cereblon

Background MYC upregulation is associated with multidrug refractory patients in multiple myeloma (MM). We isolated patient derived MM cells with high MYC expression and discovered that NCOR2 was down-regulated in these cells. NCOR2 is a transcriptional coregulatory protein and its role in MM remains unknown. Method To define the role of NCOR2 in MM, we created NCOR2 knockout human myeloma cell lines and demonstrated that NCOR2 knockout led to high MYC expression. Results Furthermore, NCOR2 knockout conferred resistance to pomalidomide, BET and HDAC inhibitors, independent of Cereblon (CRBN), indicating high MYC expression as a cause of multidrug resistance. Moreover, NCOR2 interacted with the nucleosome remodeling and deacetylase (NuRD) complex and repressed the expression of CD180 by directly binding to its promoter and inducing MYC expression. Next, we generated lenalidomide-resistant and pomalidomide-resistant human myeloma cell lines. Whole exome sequencing revealed that these cell lines acquired the same exonic mutations of NCOR2. These cell lines showed NCOR2 down-regulation and MYC up-regulation independent of CRBN and demonstrated resistance to BET and HDAC inhibitors. Conclusion Our findings reveal a novel CRBN independent molecular mechanism associated with drug resistance. Low NCOR2 expression can serve as a potential biomarker for drug resistance and needs further validation in larger prospective studies.
Reactive Species Transport To Water Micro-Droplets In Atmospheric Pressure Rf Glow Discharges

Chemical reactivity transfer from gas-phase plasmas to liquid can be significantly enhanced when a plasma interacts with small liquid micro-droplets as opposed to bulk liquid. In this contribution, the role of • OH as well as non- • OH driven chemistry on the degradation of an organic compound (formate) by activation of water micro-droplets by atmospheric pressure diffuse RF glow plasmas in He and different gas admixtures (Ar, H 2 , O 2 , H 2 O) is explored. Using detailed gas-phase plasma diagnostics, droplet characterization and ex situ chemical analysis of the plasma- treated droplets, the effect of short-lived species such as O • , H • and • OH, O 2 ( a ), electrons/ions, and metastable atoms of He and Ar is quantified. With increasing droplet residence time, the formate decomposition increases in electronegative plasmas (He/H 2 O He/Ar/H 2 O, He/O 2 ), with a maximum of ~70% within ~15 ms, while an inverse trend is observed in electropositive plasmas (He, He/H 2 , He/Ar), with >75% degradation within ~5 ms.
Delamination failure in a unidirectional curved composite laminate

Delamination failure in a unidirectional curved composite laminate was investigated. The curved laminate failed unstably by delaminations developing around the curved region of the laminate at different depths through the thickness until virtually all bending stiffness was lost. Delamination was assumed to initiate at the location of the highest radial stress in the curved region. A closed form curved beam elasticity solution and a 2-D finite element analysis (FEA) were conducted to determine this location. The variation in the strain energy release rate, G, with delamination growth was then determined using the FEA. A strength-based failure criteria adequately predicted the interlaminar tension failure which caused initial delamination onset. Using the G analysis the delamination was predicted to extend into the arm and leg of the laminate, predominantly in mode I. As the initial delamination grew arould the curved region, the maximum radial stress in the newly formed inner sublaminate increased to a level sufficient to cause a new delamination to initiate in the sublaminate with no increase in applied load. This failure progression was observed experimentally.
Deductive Verification of Parameterized Fault-Tolerant Systems: A Case Study

We present a methodology and a formal toolset for verifying fault tolerant systems, based upon the temporal verification system STeP. Our test case is the modeling and verification of a parameterized fault-tolerant leader-election algorithm recently proposed in (Garavel and Mounier, 1996).
Canine gastric emptying of polycarbophil: An indigestible, particulate substance

We tested whether indigestible solids could empty from the canine stomach independently of gastric burst motor activity. Test meals contained polycarbophil, an indigestible particulate (1-3 mm diameter) substance. Test meals were slurries of 30 or 90 g of radiolabeled polycarbophil particles in saline. Meals were administered via an oral gastric tube. After 4 h, the stomach was drained via a gastric cannula, and the percentage of meal that had emptied into the duodenum was calculated. Antroduodenal motor responses to the meals were monitored with strain-gage force transducers. The motor responses to polycarbophil meals were compared with those after canned food and saline meals. Fifty percent of the 90-g polycarbophil meal emptied by 4 h; this occurred independently of gastric burst motor activity. Both polycarbophil and canned food elicited similar indexed motor responses and both delayed the postprandial reappearance of gastric burst motor activity. We conclude that small indigestible particles can stimulate fed state-like motility and empty from the stomach independently of gastric burst activity.
Down from Olympus: Archaeology and Philhellenism in Germany, 1750‐1970

Down from Olympus: Archaeology and Philhellenism in Germany, 1750-1970. Suzanne L. Marchand. Princeton, NJ: Princeton University Press, 1996. 400 pp.
Information Externalities, Underinvestment, and Organizational Remedies:

We examine the interaction between inter- and intradivisional learning and organizational design. In both periods of the model, managers make investment decisions. Innovation is costly because the ...
Latrogenic coronary occlusive disease in patients with prosthetic heart valves

Abstract Coronary occlusive disease is often a serious event in the postoperative course of patients with prosthetic heart valves. The clinical course of 6 such patients is reviewed. The interval between mitral or aortic disc or ball valve replacement and the time of myocardial infarction ranged from immediately after operation to 4 years. In 1 case a myocardial infarction pattern on electrocardiogram was noted immediately after operation and believed to be possibly related to difficulty in coronary artery cannulation at the time of surgery. In 4 patients, despite anticoagulation, there was evidence of multiple systemic emboli in the late postoperative period, including autopsy demonstration of coronary embolus in 2 of 4 cases. All 4 patients having postoperative angiography were demonstrated to have coronary artery occlusion. One patient with aortic and mitral prostheses sustained a myocardial infarction 2 years after valve replacement, secondary to extensive nonatheromatous intimal proliferation of the proximal 2 cm of the right and left coronary arteries. Early in the clinical course of all 6 patients, the exact cause of the myocardial infarction was not clear. No patients had evidence of bacterial endocarditis or significant coronary atherosclerosis. Coronary arteriography is important in the evaluation of coronary occlusion and myocardial infarction in patients with prosthetic heart valves.
B-cell depletion in Wegener's granulomatosis.

Wegener’s granulomatosis (WG) is a chronic, relapsing, systemic necrotizing vasculitis with typical pathologic findings of granulomatous inflammation and pauci-immune vasculitis. Untreated, the condition has a very high mortality, and contemporary treatment strategies carry a high risk of treatment-related morbidity. Antineutrophil cytoplasmic antibodies (ANCA) play a central role in the pathogenesis of the disease. It is unclear how ANCA develop, but B cells are of major importance in the disease pathogenesis as precursors of ANCA-producing plasma cells and, possibly, also as antigen-presenting and cytokine-producing cells. Therefore, the use of B-cell depletion therapy, e.g., with rituximab appears to be an attractive treatment option in WG. Several small clinical trials and case reports show promising results with a high rate of clinical remissions achieved in patients that were refractory to or intolerant of conventional treatment regimens. However, granulomatous manifestations seemed to be less responsive to B-cell depletion therapy. B-cell depletion therapy was generally well tolerated. A large prospective, randomized, double-blind clinical trial evaluating the efficacy of B-cell depletion therapy in WG is pending.
Protein synthesis within dendrites: ionic and neurotransmitter modulation of synthesis of particular polypeptides characterized by gel electrophoresis.

This study evaluates whether physiological variables differentially affect the local synthesis of protein constituents of synapses in subcellular fractions containing pinched-off dendrites (synaptodendrosomes). Synaptodendrosomes were pulse-labeled in a medium containing35S-methionine with 3 or 25 mM KCl and in the presence or absence of 0.5 mM EGTA or 10 μM glutamate. Synaptodendrosomes were then subfractionated to prepare synaptic plasma membranes and synaptic junctional complexes. The protein constituents of the synaptic plasma membrane and synaptic junctional complex fractions that were locally synthesized were identified using SDS-PAGE and two-dimensional gel electrophoresis and the extent of labeling of individual bands was analyzed using a Phosphorimager. Analysis of incorporation into individual bands resolved by SDS-PAGE revealed that depolarizing conditions (25 mM KCl) increased the extent of labeling of different bands to a different extent (ranging from 10–70% increases in labeling). Addition of 0.5 mM EGTA decreased the extent of labeling of the same group of bands in both 3 mM KCl and 25 mM KCl conditions. Addition of 10 μM glutamate reduced incorporation especially in the synaptodendrosomes incubated in 25 mM KCl. Two-dimensional gel electrophoresis analyses revealed that the labeled spots that showed differential labeling under the different conditions did not correspond to the most prominent Coomassie-stained spots. These results indicate that the proteins that are synthesized in synaptodendrosomes and regulated by physiological variables are not amongst the more abundant protein constituents of the fractions. Taken together, these results are consistent with the idea that protein synthesis within dendrites may be regulated by synaptic activity.
PIN and AUX/LAX proteins: their role in auxin accumulation

There is mounting evidence that plant tissues specialized for auxin transport coincide with local maxima in the auxin concentration. This result is difficult to reconcile with the traditional model of auxin transport, which relies on high levels of auxin efflux carrier expression. Because transporting cells maintain high levels of auxin efflux, one naively expects a depletion of auxin relative to surrounding tissues. Here I use a computer model of auxin transport in a background of parenchyma cells to evaluate the possible roles of the PIN and AUX/LAX families of putative auxin carriers in auxin accumulation. I describe two effective accumulation strategies and review the evidence that these strategies are used by plants.
The general complex bounded case of the strict weighted approximation problem

1. Preliminaries Throughout the remainder of this paper, X will denote a completely regular Tl-space, while all functions will be complex valued unless it is explicitly stated otherwise. We shall let C(X) denote the space of all continuous functions on X, B(X) denote the space of all bounded functions on X, and Bo(X) denote the subalgebra of B(X) consisting of those elements in B(X) which vanish at infinity. Further, let Cb(X)= C(X)nB(X) and Co(X)= C(X)nBo(X). ¥
T-plate fixation of distal radial closing wedge osteotomies for treatment of angular limb deformities in 18 dogs.

Objective— To describe the surgical technique and clinical results of treatment for forelimb angular limb deformities, secondary to premature distal radial or ulnar physeal closure, by using T-plate fixation of a distal radial closing wedge osteotomy in 18 dogs. Study Design— Retrospective clinical study. Sample Population— 18 client-owned dogs. Methods— The medical records of 18 dogs that underwent a distal radial closing wedge osteotomy with T-plate fixation for correction of a forelimb angular limb deformity were reviewed. Small pins (Kirschner wires) were used to obtain the appropriate alignment of the antebrachiocarpal and elbow joints and proper limb orientation. In-hospital follow-up evaluation was obtained at the time fracture healing was observed radiographically. Further long-term follow-up was obtained by owner interview. Results— Osteotomy sites were radiographically healed within 4 to 12 weeks (mean, 8 weeks) after surgery in the 14 dogs that returned for in-hospital follow-up. Limb function was graded as good or excellent in all dogs. Long-term follow-up by owner interview rated limb function and cosmetic appearance as good to excellent in all dogs. Plate removal was necessary in one dog 7 months after surgery because of osteopenia in the radius. Conclusion— This surgical technique was considered successful in the treatment of angular limb deformities in all dogs. A good to excellent prognosis is to be expected with this technique, with minimal complications. Clinical Relevance— The use of a T-plate for the correction of angular limb deformities has not been previously described in the literature. This technique permits accurate correction of the angular limb deformity and minimizes postoperative complications.
Methods for rotor aerodynamic and dynamic analysis

Abstract The complex problems associated with the aerodynamics of blade/vortex interactions, the dynamics of a blade displaced out of its plane of rotation, and the position control of a hovering helicopter are discussed. Simplified models help to describe, and appear to be adequate for analysing, many aspects of these problems. Free wake analyses are shown to be of importance in determining blade loads and performance for hovering flight or for wind turbines. Unsteady aerodynamics and careful definition of the wake formation are required when computing vibratory airloads in forward flight.
Nitric oxide-independent regulation of the vascular injury response

A plethora of cellular and molecular signaling pathways are elicited in response to vascular trauma that eventuates in formation of an invasive neointima and adaptive remodeling of the vessel wall. The pivotal role of nitric oxide (NO) and downstream soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) in mediating vasoprotection under both homeostatic and inimical conditions has been extensively studied in clinical medicine and basic science research. Recently, the parallel system of sGC-activating heme oxygenase (HO) and the diatomic gas carbon monoxide (CO) has emerged as a viable alternate pathway in mediating vascular protection following injury. Potential candidate factors involved in this regulation include inducible HO (HO-1) and CO and the novel exogenous sGC/cGMP-sensitizing agents YC-1 and BAY 41-2272. The overall goal of these studies is to elucidate potential protective influence of these NOindependent systems in regulating the neointimal and vascular remodeling responses to experimental carotid artery balloon injury in laboratory rats. Results show that HO-1 and CO independently attenuate neointima development 2 weeks following injury through inhibition of acute vascular smooth muscle cell (SMC) DNA synthesis and proliferation, decreased acute expression of growthpromoting TGF-β1 and the G1 cyclins E and A, and enhanced SMC apoptosis. Similar experiments utilizing the sGC-sensitizing benzyl indazole compound YC-1 found vessel wall cGMP to correlate with reduced vascular SMC growth and platelet function and diminished neointima formation. Promising early results suggest the NO-independent sGC activator BAY 41-2272 reduces the neointimal response to injury through anti-proliferative and anti-migratory actions on vascular SMCs. In addition, the anti-proliferative effects of BAY 41-2272 were significantly potentiated in the presence of the HO-1 inducer and substrate hemin. These cumulative results strongly suggest that the HO-1/CO system and novel NO-independent routes of sGC/cGMP activation exert salutary influence upon compromised blood vessels via regulation of various cellular growth-promoting functions and may represent attractive therapeutic strategies aimed at reducing vascular lesion formation. from 2nd International Conference of cGMP Generators, Effectors and Therapeutic Implications Potsdam, Germany, 10–12 June, 2005
Applying marketing strategy to private source grantsmanship

As funding opportunities for research and program development continue to decrease, faculty and administrators must understand, to be competitive, that a large part of grantsmanship is marketing. This paper discusses the rationale for seeking grant support, how faculty can identify potential funding sources, and how to target the final submission of the proposal. Understanding these topics will assist faculty in developing those skills required for competing successfully in an increasingly competitive environment.
Endoscopic simulator curriculum improves colonoscopy performance in novice surgical interns as demonstrated in a swine model.

The purpose of this study was to determine whether independent virtual endoscopic training accelerates the acquisition of endoscopic skill by novice surgical interns. Nine novice surgical interns participated in a prospective study comparing colonoscopy performance in a swine model before and after an independent simulator curriculum. An independent observer evaluated each intern for the ability to reach the cecum within 20 min and technical ability as determined by Global Assessment of Gastrointestinal Endoscopic Skills—Colonoscopy (GAGES-C) score and performance compared. In addition, at the conclusion of training, a post test of two basic simulated colonoscopy modules was completed and metrics evaluated. As a control, three attending physicians who routinely perform colonoscopy also completed colonoscopy in the swine model. Prior to endoscopic training, one (11 %) intern successfully intubated the cecum in 19.56 min. Following training, six (67 %) interns reached the cecum with mean time of 9.2 min (p < 0.05). Statistically significant improvement was demonstrated in four out of five GAGES-C criteria. All three experts reached the cecum, with a mean time of 4.40 min. Comparison of expert and post-curriculum intern times demonstrated the experts to be significantly faster (p < 0.05). Comparison of interns who were and were not able to reach the cecum following the simulator curriculum demonstrated significantly improved GI Mentor™ performance in the efficiency (79 vs. 67.1 %, p = 0.05) and time to cecum (3.37 vs. 5.59 min, p = 0.01) metrics. No other significant difference was demonstrated in GAGES-C categories or other simulator parameter. Simulator training on the GI Mentor™ alone significantly improved endoscopic skills in novice surgical interns as demonstrated in a swine model. This study also identified parameters on the GI Mentor™ that could indicate ‘clinical readiness’. This study supports the role for endoscopic simulator training in surgical resident education as an adjunct to clinical experience.
Toward a Positive Psychology of Academic Motivation

Abstract The purpose of this study was to integrate constructs from positive psychology with constructs from motivation theories that have received most of the attention in studies of academic motivation. Achievement goals, expectancy beliefs, and value were predictive of the positive psychology variables. Task goals were associated positively with optimism and with invitations, whereas performance-avoid goals were associated negatively with optimism and perceived authenticity. Expectancy and value constructs were associated positively with optimism, perceived authenticity, and invitations. Positive psychology variables were stronger in high-achieving students than in low-achieving students; boys had stronger perceived authenticity than girls did. Findings indicate that constructs drawn from positive psychology can help explain academic motivation and achievement.
Phospholipid biosynthesis in lung lamellar bodies.

Summary Lung Type II epithelial cells contain lamellar bodies, the storage form of surfactant, which is predominately dipalmitoyl-phosphatidylcholine. Isolated lamellar bodies, free of microsomal and mitochondrial contamination have significant phosphatidic acid phosphohydrolase activity. Calculations based on enzyme distribution indicate that as much as 40% of the phosphatidic acid phosphohydrolase activity within the Type II cell is associated with the lamellar bodies. This high concentration of phosphatidic acid phosphohydrolase, a key enzyme in phospholipid biosynthesis, suggests that the phosphatidylcholine stored within the lamellar bodies may be synthesized at the perilamellar surface.
Avoiding the Horrid and Beastly Sin of Drunkenness: Does Dissuasion Make a Difference?.

Nearly 3 centuries ago, an anonymous English author prepared an educational brochure to dissuade problem drinkers from the "horrid and beastly sin of drunkenness" (Anonymous, 1705). During the past 2 decades, more than 25 randomized trials have been conducted in 12 countries to evaluate 2 basic questions: (a) Does dissuasion make a difference, and (b) What kinds of dissuasion work best? In response to the first question, studies indicate that dissuasion does make a difference with heavy drinkers who have not developed severe alcohol dependence. In response to the second question, the evidence is more equivocal because of the practical and methodological problems encountered in the comparison of different interventions. It is concluded that changes sometimes attributed to specific behavioral and psychological interventions may be due to a combination of advice, individual motivation, and nonspecific social influence. Language: en
College as an Investment: The Role of Graduation Rates in Changing Occupational Inequality by Race, Ethnicity, and Gender

In this paper, we examine whether investments in higher education have contributed to changes in occupational inequality by focusing on the impact of college completion rates on movement into desirable occupations between 1983 and 2002. Since forces generating inequality vary by gender, race, and ethnicity, we examine trends for white, black, and Hispanic men and women in our study. Utilizing Ordinary Least Squares Regression on data from 20 Current Population Surveys, we find a modest decrease in both gender and racial inequality in access to desirable occupations and an increase in inequality between Hispanics and members of the other groups. College completion accounts for the progress made by white women and for the declines among Hispanic men. It does not explain changes for African Americans, either between men and women or when compared to whites.
Rapid MR imaging of a vascular challenge to focal ischemia in cat brain

Deoxygenated blood was effectively used as a magnetic resonance (MR) susceptibility contrast agent to distinguish perfused and nonperfused (ischemic) regions in a focal ischemia model in cat brain at 2 T. Modulation of cerebral blood oxygenation levels in response to apnea was followed in real time with T2*-weighted (gradient-recalled) echo-planar MR imaging. Signal loss in the T2*-weighted images occurred only in perfused tissues as blood became globally deoxygenated. These data complemented information from diffusion-weighted and contrast agent bolus–-tracking images. In addition, observation of the signal recovery behavior on reventilation in both normal and ischemic brain offered potentially useful information about the state of the cerebral autoregulatory mechanism.
Vitamin D, immune regulation, the microbiota, and inflammatory bowel disease.

The inflammatory bowel diseases are complex diseases caused by environmental, immunological, and genetic factors. Vitamin D status is low in patients with inflammatory bowel diseases, and experimental inflammatory bowel diseases are more severe in vitamin D-deficient or vitamin D receptor knockout animals. Vitamin D is beneficial in inflammatory bowel diseases because it regulates multiple checkpoints and processes essential for homeostasis in the gut. Vitamin D inhibits IFN-γ and IL-17 production while inducing regulatory T cells. In addition, vitamin D regulates epithelial cell integrity, innate immune responses, and the composition of the gut microbiota. Overall, vitamin D regulates multiple pathways that maintain gastrointestinal homeostasis. The data support improving vitamin D status in patients with inflammatory bowel diseases.
Rapid Evolution of a Homeodomain: Evidence for Positive Selection

One often-noted feature of homeobox genes is the conservation of the homeodomain among orthologous genes from distantly related species. This sequence conservation is presumed to reflect functional conservation, which indeed has been demonstrated in several cases. We analyzed the evolution of an orphan homeobox gene, Pem, which is expressed preferentially in male and female reproductive tissue. Sequence analysis of 12 species of mice and rats indicated that the Pem gene has evolved at a remarkably high rate. The most rapidly evolving region of the Pem protein is the amino portion of the homeodomain, including the flexible N-terminal arm, helices I and II, and the linker regions between the helices. In contrast, the third helix, which is known to mediate base-specific DNA contacts in other homeodomains, is conserved in the Pem protein. Analysis of the ratio of nonsynonymous and synonymous codon substitution rates within the Pem homeodomain suggested that its divergence was driven by adaptive selection. The rate of nonsynonymous substitutions in Pem was higher than that of the sex-determination gene Sry, which also appears to have undergone directional selection over a short evolutionary period. Despite the rapid evolution of the Pem gene, we detected no Pem polymorphisms and observed no variation in the homeobox sequence among closely related Mus species. This suggests that purifying episodes followed phases in which selection pressure drove the rapid divergence of this locus. We propose that transcription factors that function in reproductive events can be subject to rapid adaptive selection.
Multi-dimensional flow effects in pulse tube refrigerators

Pulse tube cryocoolers are often modeled as one-dimensional flow fields. We examine the adequacy of this assumption in this study. Two entire inertance tube pulse tube refrigerator (ITPTR) systems operating under a variety of thermal boundary conditions are modeled using a computational fluid dynamics (CFD) code. Each simulated ITPTRs includes a compressor, an after cooler, a regenerator, a pulse tube, cold and hot heat exchangers, an inertance tube, and a reservoir, and the simulations represent fully coupled systems operating in steady-periodic mode. The objectives are to ascertain the suitability of CFD methods for ITPTRs, and examine the extent of multi-dimensional flow effects in various ITPTR components. The results confirm that CFD simulations are capable of elucidating complex periodic processes in ITPTRs. The results also show that one-dimensional modeling is appropriate only when all the components in the system have large length-to-diameter (L/D) ratios. Significant multi-dimensional flow effects occur at the vicinity of component-to-component junctions, and secondary-flow recirculation patterns develop when one or more components have relatively small L/D ratios. Parameters in need of experimental measurement are discussed.
The Importance of Debriefing in Clinical Simulations

Abstract Background This education-focused research project evaluated the benefit of a structured debriefing session on students' learning after the students completed three pediatric-based clinical simulations. Method Eleven students participated in this study, in which their performance was videotaped during each simulation. They received a verbal debriefing at the conclusion of each clinical simulation and then received a structured debriefing session involving a review of the videotape during a qualitative focus group interview. Results and Conclusions Descriptive findings from the discussion of the debriefing session suggest that students have a strong need for debriefing immediately following the conclusion of each simulation to help them decompress and integrate the experience into their knowledge base.
Non-linear vibrations of beams and membranes

Non-linear vibrations of beams and membranes are considered using a modified perturbation method based on the Linstedt-Poincare technique, which avoids the secular terms.