cssi/SciSciGPT-SciSciNet huggingface dataset:
Dietary soy protein induces hepatic lipogenic enzyme gene expression while suppressing hepatosteatosis in obese female Zucker rats bearing DMBA-initiated mammary tumors.

Fatty liver is associated with obesity and breast cancer. We used an obese rat model of mammary cancer to examine whether hepatosteatosis is modifiable by diet and associated with altered expression of hepatic lipogenic enzyme genes, thyroid hormone system genes and cholesterol metabolism-related genes. Beginning at the age of 5 weeks, lean and obese female Zucker rats were fed high-isoflavone soy protein- or casein (control protein)-containing diets. Rats were euthanized at 200 days of age [corresponding to 147 days after administration of carcinogen to induce mammary tumors; (Hakkak et al. in, Oncol Lett 2:29–36, 2011)]. Obese rats had a greater degree of liver steatosis than lean rats. Obese casein-fed rats had marked steatosis with small foci of mononuclear infiltration, whereas obese soy protein-fed rats had a significantly lower steatosis index. Comparisons between lean and obese casein-fed rats showed that obesity was associated with significant reductions in hepatic mRNA abundance for Glucose 6-Phosphate Dehydrogenase (G6PD), 6-Phosphogluconate Dehydrogenase (6PGD), Thyroid Receptor Alpha 1 (TRα1), Thyroid Receptor Beta 1 (TRβ1) and Iodothyronine Deiodinase 1 (DIO1). The soy protein diet was associated with increased expression of Fatty Acid Synthase (FASN), Malic Enzyme 1 (ME1), 6PGD, Sterol Regulatory Element Binding Protein-1c (SREBP-1c) and SREBP-2 genes in the livers of obese but not lean rats. Western blot analysis showed a significant induction of ME1 protein expression in the livers of obese, soy protein-fed rats, which paralleled the increased serum insulin level in this group. Long-term soy protein consumption can counter hepatic steatosis while coincidently promoting hepatic lipogenic gene expression, the latter likely a consequence of elevated serum insulin. We suggest that elevations in serum insulin, hepatic lipogenesis and cholesterol synthesis all contributed to the increased tumorigenesis previously observed for the obese, soy protein-fed rats.
Pharmacokinetics of the aldose reductase inhibitor tolrestat: Studies in healthy young and elderly male and female subjects and in subjects with diabetes

Tolrestat is an aldose reductase inhibitor undergoing clinical trials in diabetic subjects that may reduce the severity of chronic tissue damage associated with hyperglycemia. These studies were conducted to evaluate the pharmacokinetics of tolrestat in healthy young and elderly male and female subjects and in young and elderly subjects with diabetes. The drug was administered in a multiple-dose regimen, and steady-state parameters were obtained. There were no important gender-related differences, but mean values for apparent oral clearance, renal clearance, and corresponding unbound parameters were significantly lower for the elderly healthy subjects than for the young healthy subjects. The drug is highly bound to plasma proteins, and the unbound fraction (0.75%) did not differ among the subjects. The results from young and elderly diabetic subjects suggest that diabetes per se has no influence on tolrestat disposition but that there is an age-related reduction in apparent oral clearance (30 versus 18 ml/hr/kg) and a corresponding increase in the minimum steady-state plasma concentration (1.2 versus 1.9 μg/ml). These data indicate a possible need to reduce the dose of tolrestat in elderly subjects, assuming the same concentration-response relationship. Clinical Pharmacology & Therapeutics (1996) 59, 603–612; doi:
Study of self-interference incoherent digital holography for the application of retinal imaging

Adaptive optics (AO) using digital holography (DH) is more effective in terms of complexity and cost than other AO techniques. However, use of coherent illumination is problematic in applying DHAO for retinal imaging because of speckle noise. Self-interference incoherent digital holography (SIDH) is a technique to record holographic information from the object illuminated by incoherent light. By adopting SIDH for the full-field imaging, the speckle noise problem can be avoided with incoherent illumination. However, the guide-star hologram for AO requires the guide-star to be smaller than retinal cell size to achieve sufficient resolution. Hence, the proposed SIDH AO system is configured with a hybrid illumination system which uses incoherent illumination for recording of full-field hologram while laser is used for guide-star hologram. Preliminary experiment using an array of micro-spheres for the object shows that the full-field hologram and guide-star hologram can be recorded by proposed optical configuration.
Formation and dissociation of intra-intermolecular hydrogen-bonded solute-solvent complexes : Chemical exchange two-dimensional infrared vibrational echo spectroscopy

2-Methoxyphenol (2MP) solutes form weak complexes with toluene solvent molecules. The complexes are unusual in that the 2MP hydroxyl has an intramolecular hydrogen bond and simultaneously forms an intermolecular hydrogen bond with toluene and other aromatic solvents. In the equilibrated solute-solvent solution, there exists approximately the same concentration of 2MP-toluene complex and free 2MP. The very fast formation and dissociation (chemical exchange) of this type of three-centered hydrogen bond complex were observed in real time under thermal equilibrium conditions with two-dimensional (2D) infrared vibrational echo spectroscopy. Chemical exchange is manifested in the 2D spectrum by the growth of off-diagonal peaks. Both the formation and dissociation can be characterized in terms of the dissociation time constant, which was determined to be 3 ps for the 2MP-toluene complex. The intra-intermolecular hydrogen bond formation is influenced by subtle details of the molecular structure. Although 2MP forms a complex with toluene, it is demonstrated that 2-ethoxyphenol (2EP) does not form complexes to any significant extent. Density functional calculations at the B3LYP/6-31+G(d,p) level suggest that steric effects caused by the extra methyl group in 2EP are responsible for the difference.
Analytical, numerical and experimental analysis of continuous indentation of a flat hyperelastic circular membrane by a rigid cylindrical indenter

Abstract Several researchers have studied the process of the indentation of a membrane by rigid objects, but there is currently a lack of continuous indentation studies and experimental data to validate the theoretical formulations that model membrane behaviour. This research presents a numerical and analytical formulation as well as a finite element model and experimental validation for the behaviour of a circular flat membrane subjected to continuous indentation by a rigid circular cylindrical indenter. The material of the membrane is modelled as a homogenous, isotropic, hyperelastic material. The model considered Neo-Hookean and Mooney Rivlin material behaviours. The contact between the membrane and the rigid cylindrical indenter is assumed to be frictionless. The numerical model divides the continuum into three stages, and the equilibrium equations and boundary conditions for each stage are obtained by the principle of stationary potential energy. The nonlinear equilibrium equations are solved using the symbolic software package Maple©. The model was validated with results from finite elements analysis as well as experimental results. The comparison of the numerical and analytical solutions gives interesting insights for researchers who are only interested in calculating maximum tension stresses.
An Etiologic Dilemma of Wandering Spleen in Childhood: Is it Congenital or Acquired?

To the Editor: Wanderingspleen(WS) isdefined ashypermo-bility of spleen due to lack of fixation and abnormally longsplenicpedicle.WeherepresentapatientwithWSanddiscussthe etiology of this rare entity.A 15-y-old girl presented to the emergency departmentwith an acute left quadrant abdominal pain, lasting for sixhours, with associated nausea and vomiting. She had amonozygotic twin sibling. Physical examination revealeddiffuse abdominal tenderness with rebound tenderness andguarding. Plain radiograph of the abdomen showed bowelloops occupying the left upper quadrant (Fig.1). Abdom-inal ultrasonography demonstrated a inferomedial dis-placement of the spleen. An abdominal contrast enhancedcomputed tomography revealed that the spleen was locat-ed inferomedial of its normal anatomical position andshowed normal enhancement pattern with a long splenicpedicle (Fig. 2). An urgent explorative laparotomyshowed the laxity of splenic ligamentous attachments with360° clockwise torsion of a macroscopically normalspleen around its exceptionally long pedicle. Followingthe derotation, the spleen was sutured to the diaphragmand abdominal wall directly. Her monozygotic twin sib-ling’s ultrasonography was normal.CongenitalandacquiredetiologicalfactorsareproposedtoexplaintheetiologyofWS,becauseofthehighincidencebothin childhood and in women during the active reproductiveyears [1–3]. According to congenital theory, absence ofligaments or abnormal development of the splenic peritonealattachments results in an abnormally long splenic pedicle andhypermobilityofspleen.Thistheoryissupportedbydetectingthe pancreatic tail in the splenic pedicle during the surgicalmanagement and the presence of recurrent pancreatitis asso-ciated with WS [4]. According to acquired theory, the in-creased association of WS with pregnancy and multiparityreveals that the alteration of hormone levels and the laxity ofabdominalwallresultsinlengtheningofthesplenicligaments[5]. In our case, monozygotic twin sibling had a normallocated spleen. We suggest that congenital maldevelopmentof primary splenic ligaments is not the only predisposingfactor. The increased female:male ratio after ten years of age can
‘Psyche, ideology and the creation of the political subject’: a summary

This paper shows how in an interdisciplinary context psychoanalysis can illuminate the interface between ideology and mental states that produces citizens' identification with repressive political trends. It argues for a socially conscious clinical psychoanalysis that includes an awareness of and respectful exploration of the social as well as the psychic origins of patients' deep anxieties and conflicts. Copyright © 2008 John Wiley & Sons, Ltd
Normative messages promoting energy conservation will be underestimated by experts … unless you show them the data

Social influence researchers have identified normative social influence as an effective behavioral strategy for addressing global climate change. However, strategies alone are useless if they are not adopted by energy outreach and education experts. In the present study we were interested in understanding and changing energy experts’ perceptions of normative messages compared to other motivational messages. In Study 1 a sample of energy experts was asked to evaluate the motivating potential of five conservation messages used in previous research. Results showed that energy experts perceived the financial appeal to conservation to be the most motivating, while the normative message was judged to be less motivating. In addition, energy experts said they would be least likely to use the normative message in their future outreach and education programs. In Study 2 participants were exposed to empirical research highlighting the effectiveness of normative appeals. Results showed that this exposure did increase...
"It's like a circus in here!": affect and information sharing in an emergency department

The following research begins to address the relationship between affect and information sharing in order to inform the design of collaborative systems. Through ethnographic observations of affect and face-to-face information sharing in an emergency department we begin to see trends on the occurrence of affect due to context as well as the relationship between affect and information sharing outcomes.
Abstract 3748: Perfusion MRI estimation of glioma microvascular density to predict tumor recurrence and treatment response: Validation study through stereotactic tissue analysis

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Purpose: This study uses spatially accurate image-guided tissue analysis to evaluate the correlation between Perfusion MRI (pMRI) and tissue microvascular density parameters as markers for tumor recurrence and treatment response in high-grade glioma (HGG). Methods: Following Institutional Review Board approval, we recruited previously treated (including chemo-radiation therapy) HGG patients undergoing surgical re-resection of new enhancing lesions on surveillance MRI. Preoperatively, we acquired pMRI and contrast-enhanced stereotactic T1-Weighted (T1W) MRI data sets. Intraoperatively, we recorded stereotactic locations of multiple biopsies based on T1W data sets that guided surgery. Following surgery, we coregistered pMRI and T1W data sets to calculate localized relative cerebral blood volume (rCBV) for each stereotactic specimen location. For each specimen, we performed 1) standard HE and 2) immunohistochemical analysis with CD34 to highlight tissue vessels. We analyzed CD-34 stained slides with Axiovision Automeasure 3.4 (Zeiss, Germany) to calculate both total microvessel number (MVN) and total microvessel area (MVA), each normalized to total slide specimen area (μm2). We calculated Pearson correlations to establish relationships between a) rCBV and MVN; and b) rCBV and MVA. We also performed t-test to compare MVN, MVA, and rCBV values between tumor and PTRE samples. A neuroradiologist performed all coregistration and pMRI calculations, and a neuropathologist analyzed all tissue specimens, without knowledge of corresponding data. A biostatistician performed all statistical comparisons. Results: In this preliminary study, we included 16 tissue specimens (from 8 subjects), each diagnosed as either tumor (n=7) or PTRE (n=9). We successfully calculated localized rCBV and determined both MVA and MVN for each specimen. The rCBV values showed highest correlation with total vessel area (MVA) (r=0.65, p=0.007) and slightly less correlation with vessel number (MVN) (r=0.52, p=0.04). Tumor showed significantly higher values than PTRE for all parameters: rCBV (1.87 + 0.82 versus 0.78 + 0.2, p=.002); MVA (0.22 + 0.03 versus 0.04 + 0.007, p=0.0001); and MVN (0.0068 + 0.001 versus. 0.0016 + 0.0006, p=0.0004). Conclusion: These preliminary results show the promise of Perfusion MRI to non-invasively estimate tissue microvessel density and distinguish tumor recurrence from treatment effects. The current study is ongoing to confirm results in a larger patient population. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3748.
Papillary glioneuronal tumor: a case report and review of the literature

Papillary glioneuronal tumor is a recently described central nervous system neoplasm that almost always occurs adjacent to the lateral ventricle. We present a case of this rare entity, representing the 21st case of this lesion, which exhibits a mixed astrocytic and neuronal differentiation. This case was an incidental finding in a young woman who presented secondary to a traumatic injury to the left eye. Histologic evaluation after surgical removal showed a cystic tumor consisting of 2 distinct components: a unique pseudopapillary architecture admixed with foci of solid areas. The pseudopapillae were composed of thick hyalinized vessels enclosed by a single layer of glial fibrillary acid protein-positive astrocytes and variously sized synaptophysin-positive and chromogranin-negative neuronal cells in the interpapillary regions. Abundant Rosenthal fibers, foci of calcification, areas of hemosiderin deposition, gliosis, areas of vascular proliferation associated with piloid gliosis, and chronic inflammatory infiltrate were identified. The combination of cytologic benignity, lack of necrosis, and low proliferative index as evidenced by immunohistochemistry using antibody to Ki-67 confirmed the low malignant potential of this tumor. Knowledge and precise classification of this entity are important to avoid unnecessary use of chemo- and/or radiotherapy for treatment.
Sequential track-to-track fusion algorithm: exact solution and approximate implementation

Track-to-track fusion (T2TF) is very important in distributed tracking systems. When tracks of a target at different sensors are fused for increased accuracy, an important issue is to account for the crosscorrelations among the tracks. In this paper, an exact solution for the general problem of T2TF is proposed. It can be used with various information structures, e.g., memoryless T2TF or sequential T2TF with information feedback at arbitrary times. Simulation results for a 1-D tracking scenario evaluate the benefit of the various configurations for T2TF. It is also observed that T2TF, although done optimally, can be suboptimal w.r.t. centralized measurement fusion. This is because the locally optimal filter gains are, in general, globally suboptimal. Furthermore, it is shown that feedback can lead to degradation of the accuracy of the (optimally) fused tracks. Based on the exact T2TF algorithms, an approximate implementation which requires less communications between the fusion center and the local trackers is also proposed. This allows the algorithms to be implemented in distributed tracking systems with low communication capacity. Examples of tracking in two dimensions with two radars, show that the proposed T2TF algorithms are consistent and can provide significant improvement in accuracy over unfused tracks. For the sensors-target geometry considered, the T2TF algorithm can even meet the performance bound of the centralized measurement fusion at the fusion times.
Collusion Detection in Reputation Systems for Peer-to-Peer Networks

In peer-to-peer networks (P2Ps), many autonomous nodes without preexisting trust relationships share resources (e.g., files) between each other. Due to their open environment, P2Ps usually employ reputation systems to provide guidance in selecting trustworthy resource providers for high system reliability and security. A reputation system computes and publishes reputation score for each node based on a collection of opinions from others about the node. However, collusion behaviors impair the effectiveness of reputation systems in trustworthy node selection. Though many reputation calculation methods have been proposed to mitigate collusion's influence, little effort has been devoted to specifically tackling collusion. In this paper, we analyze transaction ratings in the Amazon and Overstock online transaction platforms during one year. The analysis of real trace confirms the existence of collusion as well as its important behavior characteristics and influence on reputation values in real reputation systems. Accordingly, we propose a collusion detection method to specifically thwart collusion behaviors. We further optimize the method by reducing the computing cost. Experimental results show that the proposed method can significantly enhance the capability of existing reputation systems to deter collusion with low cost.
Ultrasound guidance versus the landmark technique for the placement of central venous catheters in the emergency department

Objective: To compare ultrasound (US)-guided vs. landmark-guided techniques for central venous access (CVA) in the emergency department. Methods: This was a prospective study of consecutive patients enrolled at a university teaching hospital with an annual census of approximately 100,000. On even days patients had CVA with ultrasonic assistance; patients presenting on odd days had CVA via traditional landmark techniques. Ultrasound users were emergency medicine faculty or residents who completed a one-hour training session. A data collection tool with 17 variables was completed for each central line placed. Variables were compared using the independent t-test, Fisher's exact test, and the non-parametric Mann-Whitney U test. Results: Between August 1, 2000, and February 1, 2001, data for 122 subjects (n = 51 for US, and n = 71 for landmark) were collected. Variables with statistically significant differences are as follows. Mean (±SD) time from skin puncture to blood flash was 115 (±184) seconds for the US group vs. 512 (±698) seconds for the landmark group (p < 0.0001). The mean number of CVA attempts in the US group was 1.6 (±1.0) vs. 3.5 (±2.7) in the landmark group (p < 0.0001). Acute complications were comparable between groups. Comparisons for time, number of CVA attempts, and complications were done specifically for a subset of patients considered to be “difficult stick” due to predefined criteria regarding body habitus or vascular disease. Patients considered to be “difficult sticks” required a significantly longer amount of time (p < 0.001) for CVA via the landmark technique than patients considered to be “difficult sticks” who had CVA with ultrasonic guidance. Time to line placement for the landmark group was 462.7 (±627) seconds vs. 93.3 (±176) seconds in the US group. Comparing the same subset also revealed an increase in number of required CVA attempts for the landmark technique group. The number of acute complications in the “difficult stick” patients did not show statistical significance (p = 1.00). The landmark group had 60%“difficult sticks,” while the ultrasound group had 80%, although the difference was not statistically significant (p = 0.08). Conclusions: Emergency physicians with limited training and experience are able to use ultrasound as an adjunct for central venous access. Ultrasound technology may decrease the number of CVA attempts required to cannulate a central vein and will decrease the amount of time required to cannulate the vein starting from the time when the needle is on the skin, after the ultrasound machine has been set up and turned on. These results are especially true for those patients considered to be “difficult sticks.”
Lubrication Behavior of Slug Mucus

Crawling worms such as slugs are natural tribological species able to deal with varied surface textures as they crawl. Slug mucus has the ability to act as both an adhesive and a lubricant. In order to understand the principles behind slugs’ crawling motion, the frictional behavior of slug mucus was studied, as well as its rheological and morphological properties. The solid constituents of the mucus were confirmed by means of nuclear magnetic resonance. A shear thinning behavior was observed using a rheometer. Slug mucus has a low friction coefficient, and the presence of water enhanced its capacity as a lubricant. The nano-scale physical structure of the solid constituents of the slug mucus was determined by means of atomic force microscopy. It was found that the macro-scale shear thinning behavior works in conjunction with the slug’s method of locomotion to provide lubrication for sliding and gel-like adhesion. This overlooked animal might offer a world of intelligent design in engineering biomimetic systems that can both adhere and slide simultaneously. Furthermore, biodegradable and water-compatible features of slug mucus shed light on the formulation of a new generation of lubricants.
Discontinuously reinforced aluminum: Current status and future direction

There are now a number of important production applications for DRA, which span the transportation, aerospace, recreation, and electronics industries and that demonstrate the material’s attractive combination of structural, thermal management, an d wear properties. While large materials suppliers have mostly exited the area, many smaller suppliers are forging ahead to make DRA a success.
Recent State Minimum Temperature Records in the Midwest

State minimum temperature records were set or tied in Indiana (−37.8°C) and Kentucky (−38.3°C) in January 1994, and in Illinois (−37.2°C), Iowa (−43.9°C), Minnesota (−51.1°C), and Wisconsin (−48.3°C) in February 1996. The veracity of these temperatures was examined in the context of the large-scale synoptic situation, station location and history, observer, local terrain, instrumentation, and other factors related to extreme temperatures. New state minimum temperature records for states listed above were found to be acceptable; however, a state minimum initially reported for Michigan (−46.7°C) in January 1994 was found to be unreliable and not accepted as a state record.
Fatty infiltration does not progress after rotator cuff repair in a rabbit model.

Purpose: The purpose of this study is to evaluate the changes in fatty infiltration of the rotator cuff after it is repaired. Methods: The supraspinatus muscle was unilaterally detached from the greater tuberosity in 15 New Zealand white rabbits. Six weeks after muscle detachment, 5 rabbits were killed to halt the process of fatty infiltration and 10 rabbits underwent primary repair of the rotator cuff. Six months after repair, the remaining 10 rabbits were killed, and the muscle specimens were examined microscopically to evaluate the muscle with respect to fatty infiltration. Results: Fatty infiltration was evident 6 weeks after detachment of the supraspinatus tendon ( P = .0012, analysis of variance). This infiltration was greatest at the musculotendinous junction ( P = .0005) and decreased toward the muscle origin ( P = .29). Six months after repair of the supraspinatus, there was no progression of fatty infiltration in the repaired muscle as compared with the controls ( P = .3). Conclusions: Fatty infiltration of the rotator cuff in this animal model occurs as early as 6 weeks after a rotator cuff tear. After repair of the rotator cuff, the process of fatty infiltration does not progress any further. The changes that take place in this rabbit model in the first 6 weeks after a rotator cuff tear appear to be irreversible even with successful rotator cuff repair. Clinical Relevance: The presence of fatty infiltration of a torn rotator cuff does not preclude a successful repair. The repair can prevent further progression and atrophy of the rotator cuff, but the changes that appear in the muscle as early as 6 weeks after a rotator cuff tear appear to be irreversible.
VOCATIONAL INTEREST AND PERSONALITY CORRELATES OF DIFFERENTIAL ABILITIES

Based upon the proposal of Yonge and Regan (1975) that the six Holland vocational groups show different patterns of abilities, the vocational interest correlates of differential combinations of abilities were investigated. From the Scholastic Aptitude Test scores of a sample of 412 college freshmen, three ability groups were created: (1) verbal greater than mathematical, (2) verbal equal to mathematical, and (3) mathematical greater than verbal. Based on responses to the Vocational Preference Inventory and 16 PF, significant differences in group means were found on scales related to artistic interests. For both sexes the highest scores on these scales were made by the high verbal-low mathematical group.
Influence of neurons on lipopolysaccharide-stimulated production of nitric oxide and tumor necrosis factor-α by cultured glia

Cerebral inflammation often originates in a region where neuronal death occurs and thereafter slowly spreads outward. This study aimed to elucidate the roles of neurons in modulating the production of inflammatory factors stimulated by the bacterial endotoxin lipopolysaccharide (LPS). Culturing neurons with mixed glia reduced nitrite and tumor necrosis factor-alpha (TNF-alpha) production compared to cultures with only mixed glia, and shifted the dose-response curve to the right. The decreased nitrite and TNF-alpha production were not due to the cytotoxicity of LPS. Immunocytochemical analysis of glia-neuron co-cultures revealed the morphological changes in the activated microglia. Culturing PC12 cells with rat mixed-glia also reduced nitrite production. The influence of neurons on glial inflammation was partly due to the cell-cell contacts between neurons and glia via neural cell adhesion molecules (NCAM) because NCAM significantly reduced LPS-stimulated nitrite production. These results demonstrate that neurons reduce the production of inflammatory factors by glia. Since cerebral inflammation is important in many neurological disorders, this study might provide insight about the role of glia-neuron interactions in inflammatory responses in the brain.
Hedgehog signaling pathway and cancer therapeutics: Progress to date

The Hedgehog (Hh) pathway is a developmental signaling pathway involved in numerous developmental processes, including determination of cell fate, patterning, proliferation, survival, and differentiation. While this pathway is silenced in most adult tissues, aberrant activation of it has been documented in a variety of malignancies. In cancers such as basal cell carcinoma (BCC), ligand-independent mechanisms lead to constitutive Hh pathway activation through mutations in components of the pathway, including patched-1 (PTCH1) or smoothened (SMO). On the contrary, numerous other solid and hematologic tumors have been shown to harbor ligand-dependent activation of the Hh pathway by autocrine or paracrine mechanisms. Given that aberrant Hh pathway signaling has been seen in a number of malignancies, this pathway has been an attractive target for drug development. While the best-characterized approach is to target the SMO receptor, other rational approaches for inhibiting the Hh pathway include inhibiting downstream components or directly binding Hh ligands. In January of 2012, vismodegib, a SMO antagonist, became the first agent to target the Hh pathway to receive approval by the United States Food and Drug Administration (FDA) after this agent showed remarkable activity in phase I and II trials for the treatment of BCC. Despite promising preclinical studies with Hh pathway inhibitors in other malignancies that have suggested a potential role for these agents, attempts to translate this potential to clinical benefit has been disappointing. Future efforts will require further careful interpretation and analysis to determine the potential determinants and predictors of efficacy. Currently, several phase I and II trials evaluating Hh inhibitors in a variety of tumor settings are underway.
Epitaxial ice crystal growth on covellite (CuS) II. Growth characteristics of basal plane steps

Abstract Ice crystals were grown epitaxially from the vapor on the mineral covellite (CuS). The growth velocity of non-thickening basal steps was measured as a function of temperature (-3 to -30°C), supersaturation (up to 20% over ice) and air pressure (25 to 750 Torr) using time lapse photography and an optical interference technique. The velocity increased with decreasing air pressure, consistent with a water vapor diffusivity pressure dependence. The observed temperature variation of step velocity was similar in shape at different pressures and showed a local maximum and minimum at -14 and -9.5°C, respectively. The basal plane of epitaxial crystals was found to thicken continously from -3 to -7°C even at a very small (
Modeling epidemics of multidrug-resistant M. tuberculosis of heterogeneous fitness

Mathematical models have recently been used to predict the future burden of multidrug-resistant tuberculosis (MDRTB). These models suggest the threat of multidrug resistance to TB control will depend on the relative 'fitness' of MDR strains and imply that if the average fitness of MDR strains is considerably less than that of drug-sensitive strains, the emergence of resistance will not jeopardize the success of tuberculosis control efforts. Multidrug resistance in M. tuberculosis is conferred by the sequential acquisition of a number of different single-locus mutations that have been shown to have heterogeneous phenotypic effects. Here we model the impact of initial fitness estimates on the emergence of MDRTB assuming that the relative fitness of MDR strains is heterogeneous. We find that even when the average relative fitness of MDR strains is low and a well-functioning control program is in place, a small subpopulation of a relatively fit MDR strain may eventually outcompete both the drug-sensitive strains and the less fit MDR strains. These results imply that current epidemiological measures and short-term trends in the burden of MDRTB do not provide evidence that MDRTB strains can be contained in the absence of specific efforts to limit transmission from those with MDR disease.
Sulfonylurea receptor expression in rat brain: Effect of chronic hypoxia during development

Sulfonylurea receptors are believed to be related to ATP-sensitive potassium channels and play a key role during hypoxia/ischemia in the CNS. Our previous work has shown that these receptors in rat brainstem neurons are more important in the adult rat than in the newborn during hypoxia. In the present study, we studied the time course of postnatal development of sulfonylurea receptors in detail and the effect of chronic hypoxia on receptor density in newborn pups and adult rats exposed to hypoxia either as fetuses or as 90-d-old rats using receptor binding and autoradiography. Our current results show that sulfonylurea receptor density 1) was very low at birth and developed fast within the first 2 postnatal wk and then gradually reached adult levels and 2) continued to increase in the cortex and cerebellum but decreased in the brainstem with little or no change in other areas after postnatal wk 5. Chronic hypoxia 1) decreased body weight, brain size, and brain protein concentration and 2) increased sulfonylurea receptor density in utero but had much less of an effect in the adult. From these data, we conclude that sulfonylurea receptors develop mostly in the first 2 wk postnatally and chronic hypoxia increases sulfonylurea receptor expression in utero in spite of the fact that overall protein decreases.
Skin friction and pressure: the “footprints” of turbulence

Abstract The problems of exact state reconstruction and approximate state estimation based on wall information in a wall-bounded incompressible unsteady flow are addressed. It is shown that, if in an arbitrarily small neighborhood of time t precise measurements are made of the two components of wall skin friction and the wall pressure, all terms in the Taylor-series expansions of the unsteady flow state near the wall at time t may be determined (in the linear setting, this determination may be made based on skin-friction measurements alone). Combining this fact with the analyticity of solutions of the nonlinear Navier–Stokes equation and the unique continuation theorem for analytic functions, in theory complete reconstruction of a fully-developed turbulent flow in a channel at any Reynolds number at time t is possible given only information about the unsteady flow available at the wall in a neighborhood of time t , without knowledge of the initial conditions of the flow. Thus, skin-friction and pressure measurements on the wall in a neighborhood of time t provide a unique “footprint” of the entire unsteady turbulent flow state; no other flow can have the same footprint. Indeed, higher-order terms are shown to uniformly improve the correlation of truncated Taylor-series expansions with the DNS of a turbulent flow near the wall. However, such series extrapolations amplify measurement noise, as they require differentiation in both space and time of the measurements, and the radius of convergence of the Taylor series expansions is less than 10 wall units. The so-called linear stochastic estimation technique, in which the polynomials forming the basis of the series expansion are replaced by well-behaved functions (such as POD modes) on the entire flow domain also demonstrates very poor convergence. In light of these limitations on direct extrapolations from measurements in the practical setting, an adjoint-based algorithm is presented and numerically tested for estimating the state of an entire turbulent channel-flow system based on a time history of noisy measurements at the wall. This algorithm effectively uses the unsteady nonlinear Navier–Stokes equation itself as a filter to find the flow solution that is most consistent with the available measurements.
Deuteron optical model calculations including a Tp tensor interaction

Deuteron-nucleus optical model calculations which include two types of tensor spin-orbit interactions are compared. The interactions considered are of the forms VTR(r)Tr and 12[VTP(r)Tp + TpVTP(r)] where the operators Tr and Tp are defined as Tr  (s · r)2 − 23 and Tp  (s · p)2 − 23p2. Here, s, r and p are the deuteron spin, position, and momentum operators, respectively. If a physically reasonable radial dependence VTP(r) is used, the S-matrix elements (and hence all observables) calculated using a Tp tensor potential are found to be similar to those calculated using a suitably chosen Tr potential, provided that the incident deuteron energy is small compared to the real central potential. At higher deuteron energies, the differences between the effects of Tr and Tp potentials are more pronounced.
Mitogenic effects of hepatic stimulator substance on cultured nonparenchymal liver epithelial cells.

We determined whether hepatic stimulator substance shares its mitogenic specificity for hepatocytes with nonparenchymal epithelial cells in the hepatocyte lineage. Cell lines designated HTC (derived from a rat hepatoma known to respond to hepatic stimulator substance) and FNRL, K-16 and K-22 (derived from rat liver nonparenchymal epithelial cells) were used. After exposure to hepatic stimulator substance, [3H]-thymidine incorporation into DNA was significantly increased (p < 0.001) in HTC, FNRL and K-16 cells, but not in K-22 cells. Fluorescence-activated cell sorting demonstrated that the mitogenic response to hepatic stimulator substance was associated with a greater proportion of cells entering the S phase. Epidermal growth factor, alone or in combination with hepatic stimulator substance, had no significant mitogenic effect on FNRL cells, but exposure of these cells to transforming growth factor-β1 inhibited [3H]-thymidine incorporation into DNA and reduced the proportion of cells in the S and G2/M phases. Simultaneous exposure of FNRL cells to hepatic stimulator substance and transforming growth factor-β1 abrogated the inhibitory effect of transforming growth factor-β1. Comparison of butyrate-synchronized HTC cells with hepatic stimulator substance–treated HTC cells showed that S-phase progression in these conditions was different, with no intervening cell cycle arrest after treatment with hepatic stimulator substance. Mitogenic stimulation of FNRL and K-16 cells with the liver-specific growth factor hepatic stimulator substance suggests that these cells are of hepatocyte lineage. These results strengthen the evidence for a possible link between hepatocytes and nonparenchymal liver epithelial cells during liver biogenesis and differentiation. (Hepatology 1992;15:485–491).
Was the Russo‐Japanese War World War Zero?

As with any war in history, the Russo-Japanese War enjoys its share of myths and legends that range from Admiral Alekseev's barber being a Japanese spy to the saga of the Baltic Fleet becoming the "fleet that had to die." Perhaps because of such legends, or perhaps because World War I broke out less than a decade after the Russo-Japanese War formally ended with the Treaty of Portsmouth in 1905, the centennial anniversary of Japan's stunning victory witnessed a resurgence in Russo-Japanese War studies. Scholars from around the world responded to this date by convening various seminars, workshops, and conferences to reopen the study of a conflict that, while never completely forgotten, was largely overlooked after World War I. Always considered a bilateral engagement between two military powers, which it was in its most basic sense, the aim of all of these scholarly endeavors was to broaden our understanding of not only the war but also its global impact. The three following articles represent the work of one of the first such intellectual endeavors, a conference on "Re-imagining Culture in the Russo-Japanese War" that was held at Birkbeck College in London in March 2004.1 By addressing the impact of the conflict on society from its art and literature to the public reaction to the war as it progressed, Naoko Shimazu, Rosamund Bartlett, and David Crowley exhibit the depth of engagement that existed at every level of the civil-military nexus. Cultural history, therefore, provides a deeper understanding of the impact of conflict on the societies that military establishments absolutely depended on especially at the time of the Russo-Japanese War. The beginning of the twentieth century became synonymous with the dawn of a new age based on a belief in hope and human progress because of the accomplishments of industrialization and the accompanying maturing of some form of participatory government that could be held responsible to the body politic. Citizens/subjects of nations/empires
Intragraft drug infusion as an adjunct to balloon catheter thrombectomy for salvage of thrombosed infragenicular vein grafts: a preliminary report.

Abstract Early infragenicular vein graft thrombosis is associated with poor secondary patency, particularly when no correctable defect is identified. We have attempted to improve patency of thrombosed vein grafts by direct infusion of vasodilator and anticoagulant drugs after surgical thrombectomy. Among 212 infragenicular vein grafts, 16 (7.5%) required thrombectomy within 30 days of surgery (14 in situ saphenous vein, 1 composite vein, and 1 cephalic vein graft). Causes for failure were corrected in four (graft twist, intimal tear, suture failure, and external compression), resulting in prolonged patency. No cause for failure was apparent in the 12 remaining grafts after balloon catheter thrombectomy and arteriography. Two of these grafts occluded within 10 days despite multiple attempts at vein patch angioplasty, distal graft extension, and repeat thrombectomy with systemic anticoagulation. In the remaining 10 grafts, a small polyethylene catheter was placed in a proximal vein branch for direct intragraft drug infusion. Heparin (10 units/min) and nitroglycerin (50 μg/min) were the agents infused most frequently, for a mean duration of 52 hours after thrombectomy. Of these 10 infused grafts, 8 remained patent during a mean 17-month follow-up (range, 6 to 38 months). This was accomplished despite previous and repeated failures of thrombectomy and systemic anticoagulation in seven of these eight grafts. Two infused grafts rethrombosed within 30 days of infusion, resulting in amputation. No catheter-related complications occurred. Increased thrombogenicity, intimal injury, and spasm after balloon catheter thrombectomy may contribute to vein graft rethrombosis in the absence of technical defects. Direct intragraft infusion of nitroglycerin and heparin contributed to prolonged salvage of 80% of thrombosed vein grafts in this preliminary experience. (J VASC SURG 1990;11:753-60.)
Phase-space holes due to electron and ion beams accelerated by a current-driven potential ramp

Abstract. One-dimensional open-boundary simulations have been carried out in a current-carrying plasma seeded with a neutral density depression and with no initial electric field. These simulations show the development of a variety of nonlinear localized electric field structures: double layers (unipolar localized fields), fast electron phase-space holes (bipolar fields) moving in the direction of electrons accelerated by the double layer and trains of slow alternating electron and ion phase-space holes (wave-like fields) moving in the direction of ions accelerated by the double layer. The principal new result in this paper is to show by means of a linear stability analysis that the slow-moving trains of electron and ion holes are likely to be the result of saturation via trapping of a kinetic-Buneman instability driven by the interaction of accelerated ions with unaccelerated electrons.
Preparing LGBTQ-allies and combating homophobia in a U.S. teacher education program

Abstract Interns in a US teacher education program were surveyed regarding their attitudes towards diversity, particularly issues of sexuality, their feelings of “cultural competence” around diversity, and the repertoires of practices and resources they feel prepared to draw on in their work with middle and high schools students (11–18 year olds). Analysis of course materials provided insight into distinctions between anti-homophobia and LGBTQ-ally stances among students. Extensive semi-structured interviews with 7 students explored these issues in more depth, documenting their sense of preparedness and cultural competence, where locate and how they identify “useful experiences in learning how to teach LGBTQ youth, and the concerns they face in their work against heterosexism and homophobia in schools.
Defense against spoofed IP traffic using hop-count filtering

IP spoofing has often been exploited by Distributed Denial of Service (DDoS) attacks to: 1) conceal flooding sources and dilute localities in flooding traffic, and 2) coax legitimate hosts into becoming reflectors, redirecting and amplifying flooding traffic. Thus, the ability to filter spoofed IP packets near victim servers is essential to their own protection and prevention of becoming involuntary DoS reflectors. Although an attacker can forge any field in the IP header, he cannot falsify the number of hops an IP packet takes to reach its destination. More importantly, since the hop-count values are diverse, an attacker cannot randomly spoof IP addresses while maintaining consistent hop-counts. On the other hand, an Internet server can easily infer the hop-count information from the Time-to-Live (TTL) field of the IP header. Using a mapping between IP addresses and their hop-counts, the server can distinguish spoofed IP packets from legitimate ones. Based on this observation, we present a novel filtering technique, called Hop-Count Filtering (HCF)--which builds an accurate IP-to-hop-count (IP2HC) mapping table--to detect and discard spoofed IP packets. HCF is easy to deploy, as it does not require any support from the underlying network. Through analysis using network measurement data, we show that HCF can identify close to 90% of spoofed IP packets, and then discard them with little collateral damage. We implement and evaluate HCF in the Linux kernel, demonstrating its effectiveness with experimental measurements.
Effect of chronic infusion of placental lactogen on ovine fetal growth in late gestation

Abstract To test the hypothesis that placental lactogen (PL) is a Immoral regulator of fetal growth, six singleton sheep fetuses received a continuous intravenous fusion of 1.2 mg/d of purified ovine PL (oPL) for 14 d, beginning on Day 122 of gestation. The plasma concentration of oPL was approximately four-fold higher in infused fetuses than in six control fetuses that received a continuous infusion of saline. The circulating insulin-like growth factor 1 (IGF-1) concentration was also significantly elevated in PL-infused fetuses (43.1 ± 1.7 vs. 31.9 ± 4.l ng/ml; P
Cardiac teratogenesis of halogenated hydrocarbon-contaminated drinking water.

AbstractObjectives. The purpose of this study was to test the hypothesis that administration of trichloroethylene and dichloroethylene to pregnant rats during organogenesis would produce a signific...