cssi/SciSciGPT-SciSciNet huggingface dataset:
Lipase maturation factor 1 affects redox homeostasis in the endoplasmic reticulum

Lipoprotein lipase (LPL) is a secreted lipase that clears triglycerides from the blood. Proper LPL folding and exit from the endoplasmic reticulum (ER) require lipase maturation factor 1 (LMF1), an ER-resident transmembrane protein, but the mechanism involved is unknown. We used proteomics to identify LMF1-binding partners necessary for LPL secretion in HEK293 cells and found these to include oxidoreductases and lectin chaperones, suggesting that LMF1 facilitates the formation of LPL's five disulfide bonds. In accordance with this role, we found that LPL aggregates in LMF1-deficient cells due to the formation of incorrect intermolecular disulfide bonds. Cells lacking LMF1 were hypersensitive to depletion of glutathione, but not DTT treatment, suggesting that LMF1 helps reduce the ER Accordingly, we found that loss of LMF1 results in a more oxidized ER Our data show that LMF1 has a broader role than simply folding lipases, and we identified fibronectin and the low-density lipoprotein receptor (LDLR) as novel LMF1 clients that contain multiple, non-sequential disulfide bonds. We conclude that LMF1 is needed for secretion of some ER client proteins that require reduction of non-native disulfides during their folding.
A more efficient method for calibrating discrete element method parameters for simulations of metallic powder used in additive manufacturing

Laser powder bed fusion (LPBF) is an additive manufacturing (AM) process that uses a high-power laser to selectively melt metal powder that has been spread, layer-by-layer, to create parts with highly complex features. Because of the strong influence that the powder spreading process has on the final part quality, a better understanding of the powder behavior and its interactions with existing powder layers and the solidified surfaces during this process is needed. Discrete element method simulations (DEM) provide a particle-scale approach capable of examining these mechanisms. While proper calibration of these simulations provides confidence in the quantitative results, the usual calibration process (hopper method) is computationally time intensive. Because of the wide variety of powder material used in LPBF, which will affect the powder spreading process, and because of the large numbers of particles present in only a small volume of powder, a more efficient calibration process was necessary. Use of a new cloud method was shown to make calibrations more tractable and reduce simulation times by up to 89% when compared to a typical hopper method. Similar to previous studies shown in the literature, a reduction in the particle material’s Young’s modulus was also used to reduce simulation times by up to 62%. Both sliding and rolling friction were needed for the DEM angles of repose to match the empirical data because of the non-sphericity of some of the powder particles, which has been quantified. The calibrated parameters resulted in determination of a powder density within 10% and an angle of repose within 1% of the targeted experimental values. These parameters will be used in extensive future DEM simulations of the LPBF powder spreading process. While AM processes were the main motivation for this work, the calibration procedures summarized herein can be extended to other gas-atomized powders used in injection molding and other metallurgical fields, as well as many other granular materials.
Policing young minds: Education and security policy in British Southeast Asia:

What factors contributed to the centralization of colonial rule over time? I argue that internal and external threats to the control of territories and populations can lead to the adoption of centr...
Dose-Dependent Effects of Aloin on the Intestinal Bacterial Community Structure, Short Chain Fatty Acids Metabolism and Intestinal Epithelial Cell Permeability.

Aloe leaf or purified aloin products possess numerous therapeutic and pharmaceutical properties. It is widely used as ingredients in a variety of food, cosmetic and pharmaceutical products. Animal studies have shown that consumption of aloe or purified aloin cause intestinal goblet cell hyperplasia, and malignancy. Here, we tested antibacterial effects of aloin, against intestinal commensal microbiota. Minimum inhibitory concentration of aloin for several human commensal bacterial species (Gram+ve and Gram-ve) ranged from 1 to 4 mg/ml. Metabolism studies indicated that Enterococcus faecium was capable of degrading aloin into aloe-emodin at a slower-rate compared to Eubacterium spp. As a proof of concept, we incubated 3% rat fecal-slurry (an in vitro model to simulate human colon content) with 0.5, 1, and 2 mg/ml of aloin to test antimicrobial properties. Low aloin concentrations showed minor perturbations to intestinal bacteria, whereas high concentration increased Lactobacillus spp. counts. Aloin also decreased butyrate-production in fecal microbiota in a dose-dependent manner after 24hr exposure. The 16S rRNA sequence-data revealed that aloin decreases the abundance of butyrate-producing bacterial species. Transepithelial resistant result revealed that aloin alters the intestinal barrier-function at higher concentrations (500 µM). In conclusion, aloin exhibits antibacterial property for certain commensal bacteria and decreases butyrate-production.
Sharing personal information about anatomical body donors: What first-year medical students want to know and how it affects emotional responses to dissection.

Among educators who teach in the human anatomy laboratory, there has been lively debate about sharing information about anatomical donors. One consideration in this debate is concern about the emotional effect of personalizing donors on the students. The purpose of this study was to evaluate student responses to being exposed to donor information (DI). Three cohorts of first-year medical students (n = 284) were surveyed at four time points throughout the year. Surveys queried students about positive and negative responses to working in the laboratory, wanting to know specific DI, and if knowing this DI would/did affect their responses to working with donors. Analyses examined the relationships between desire to know DI and indices of the following: positive response index (PRI), negative response index (NRI), avoid-approach index (AAI), and compassion-respect index. Across all surveys, a majority of respondents wanted to know some form of DI. At all time points, a majority of respondents felt that knowing all types of DI would increase their positive responses to working with donors. A greater PRI and AAI tended to be associated with wanting to know more personal DI (e.g., names and personal histories). A greater NRI tended to be associated with anticipating that learning personal DI would increase their negative responses before entering the laboratory, which did not persist after dissection began. These data suggest that for a majority of students, knowing personal DI increases their positive response and does not elicit negative responses to dissection or working with anatomical donors. Clin. Anat. 32:1019-1032, 2019. © 2019 Wiley Periodicals, Inc.
Elastic Kelvin-Poisson-Poynting solids described through scalar conjugate stress/strain pairs derived from a QR factorization of F

Abstract The authors (Freed and Zamani, 2018) recently derived a kinematic description for the motion of a deformable body that was constructed out of a Gram-Schmidt factorization of the deformation gradient. Specifically, the metric tensor that associates with a convected co-ordinate system was quantified in terms of the physical attributes that arise from an upper-triangular deconstruction of the deformation gradient. It is within a rectangular, Cartesian, co-ordinate system, created by this Gram-Schmidt factorization, that a frame of reference exists wherein the physical components for convected vector and tensor fields are realized. In this paper the authors derive two sets of thermodynamically admissible stress-strain pairs. They are quantified in terms of physical components extracted from a convected stress and a convected velocity gradient, with elastic models being presented for both sets. The first model supports two modes of deformation: elongation and shear. The second model supports three modes of deformation: dilatation, squeeze and shear. These models are distinguished by their pure- and simple-shear responses. They contain the coupling effects of Lord Kelvin (Thomson, 1878; Poisson, 1827; Poynting, 1909). Furthermore, we show that the Lodge-Meissner (Lodge and Meissner, 1972) effect from rheology and the Poynting (Poynting, 1909) effect from solid mechanics are the same physical phenomenon.
On mechanisms of light-induced deformations in photoreceptors

Abstract Photoreceptors in the retina convert light into electrical signals through a phototransduction cycle that consists of multiple electrical and biochemical events. Phase-resolved optical coherence tomography (pOCT) measurements of the optical path length (OPL) change in the cone photoreceptor outer segments after a light stimulus (optoretinogram) reveal a fast, ms-scale contraction by tens of nm, followed by a slow (hundreds of ms) elongation reaching hundreds of nm. Ultrafast measurements with a line-scan pOCT system show that the contractile response amplitude increases logarithmically with the number of incident photons, and its peak shifts earlier at higher stimulus intensities. We present a model that accounts for these features of the contractile response. Conformational changes in opsins after photoisomerization result in the fractional shift of charge across the disk membrane, leading to a transmembrane voltage change, known as the early receptor potential (ERP). Lateral repulsion of the ions on both sides of the membrane affects its surface tension and leads to its lateral expansion. Since the volume of the disks does not change much on a ms time scale, their lateral expansion leads to an axial contraction of the outer segment. With increasing stimulus intensity and resulting tension, the area expansion coefficient of the disk membrane also increases as thermally-induced fluctuations are pulled flat, resisting further expansion. This results in a logarithmic saturation of the deformation and a peak shift to earlier with brighter stimuli. Slow expansion of the photoreceptors is explained by the influx of water due to osmotic changes during phototransduction. Both effects closely match measurements in healthy human volunteers.
Discovering How Community Organizing Leads to Social Change: Developing Formal Practice Theory for Social Workers Engaged in Empowering Community Organizing

DISCOVERING HOW COMMUNITY ORGANIZING LEADS TO SOCIAL CHANGE: DEVELOPING FORMAL PRACTICE THEORY FOR SOCIAL WORKERS ENGAGED IN EMPOWERING COMMUNITY ORGANIZING By Shane R. Brady A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2012 Major Director: Dr. Mary Katherine O’Connor Professor, School of Social Work Community organizing as an area of social work practice has historic roots in challenging inequality, building capacity, and meeting the needs of local peoples through taking collective action. While the literature of community organizing is rich in conceptual frameworks, practice approaches, and case studies, it lacks the level of formal theory that exists in clinical social work. Formal practice theories provide social workers with evidence informed guidance about “what to do”, “how to do it”, and “what to expect”; however, social workers engaging in community organizing have little formal practice theory. The results of this study build the beginning foundation for a direct practice theory of community organizing that can be utilized by social workers engaged in community organizing to better inform practice. In this study, I used Delphi methodology to build formal practice theory by exploring the perspectives of nine community-organizing experts with an average of nearly 30 years of experience from the union organizing and civil rights organizing traditions. Through three waves of data collection, I learned that community organizing is a dialectical process that includes three distinct stages: community building, plan, and mobilize. These distinct stages do not operate solely in a linear or cyclical fashion, but work dynamically with the ever changing social environment to achieve social change. My findings support the idea that community organizing is dependent upon the participation and inclusion of local peoples. While practitioners have distinct roles in organizing efforts, community members determine many aspects of what and how the organizing process unfolds. My findings provide the beginning foundation for a direct social work practice theory of community organizing that can be utilized to guide professional practice as well as provide a basis for further research. It is through further research that community organizing can be better understood and utilized to create evidence informed interventions that are both respectful and inclusive of community members as well as empirical and evidence informed.
VASCULAR COMPLICATIONS RELATED TO PHYSICAL THERAPY: WALKING ON ECMO

Early and progressive mobility in patients in an intensive care (ICU) setting is associated with decreased delirium, decreased length of stay, and more favorable surgical outcomes. The purpose of this study is to quantify the incidence of vascular complications in patients requiring Venous-Venous (
Steroid-sparing agents for the treatment of inflammation in complicated neurocysticercosis (15)

Objective: To describe 3 patients followed at a single hospital for neurocysticercosis-associated inflammation requiring steroid-sparing agents (SSAs). Background: Neurocysticercosis is a major cause of neurologic disease and epilepsy worldwide. Clinical manifestations of NCC are primarily due to the inflammatory response against degenerating cysts. Patients may also develop chronic inflammation requiring long-term immunosuppression. Corticosteroids are first-line anti-inflammatory agents in neurocysticercosis, however, prolonged treatment is associated with toxicity. While recent guidelines recommend methotrexate as an SSA, when to initiate SSAs and alternatives to methotrexate in case of failure or intolerance remain unspecified. Design/Methods: NA Results: Patient 1: A 64-year-old Cape Verdean woman presented with headaches, seizures, and multiple subarachnoid cysts on brain MRI. She was treated with a prolonged course of albendazole and prednisone with recurrent disease following prednisone taper. Methotrexate was tried but resulted in ulcerative stomatitis and leukopenia. Prednisone was resumed without antiparasitic therapy and was tapered slowly with resolution of her symptoms and MRI findings. Patient 2: A 48-year-old Guatemalan man presented with headaches and multiple cysts in the pre-pontine and lumbar cisterns. He was treated with albendazole and dexamethasone for 6 months, complicated by lumbar vertebral fracture. Because of persistent inflammation on his brain MRI, he was transitioned to methotrexate with clinical stability. Patient 3: A 43-year-old Cape Verdean man presented with headache and parenchymal cysts on brain MRI. He was treated with praziquantel, albendazole, and dexamethasone and was re-treated several months later because of persistent perilesional edema. Because of ongoing perilesional edema on high-dose prednisone, he initiated methotrexate. Perilesional edema persisted, and he was started on adalimumab with clinical and radiographic resolution. Conclusions: We describe 3 cases of persistent neurocysticercosis-associated inflammation that highlight both the efficacy and complications of SSAs use in neurocysticercosis. Our series emphasizes the need for further study on the use of SSAs in the treatment of neurocysticercosis-related inflammation. Disclosure: Dr. Anand has nothing to disclose. Dr. Mukerji has nothing to disclose. Dr. Thon has nothing to disclose. Dr. Gunaratne has nothing to disclose. Dr. Cho has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Optum. Dr. Venna has nothing to disclose.
The determination of alternative hospital classifications.

Abstract The problem of determining alternative hospital classifications when explicit constraints are recognized in the classification process is discussed. It is argued that such constraints are an integral part of most hospital classification processes and should be handled directly. A methodology based on cluster analysis, which can directly accommodate any number of specific constraints that might be imposed on the classification process, is described. A number of these possible constraints are presented. To illustrate the process, the methodology is applied to a data set of 200 short-term general hospitals; empirical results are presented that demonstrate the potential effects of various constraints on the hospital classification process.
The Quality Versus Quantity Trade-Off: Why and When Choices for Self Versus Others Differ.

The trade-off between quality and quantity pervades many domains of life, including that of making product choices for ourselves and others, whether as gifts or as everyday favors. In five studies ...
Outcomes of superior segmentectomy versus lower lobectomy for superior segment Stage I non-small-cell lung cancer are equivalent: An analysis of 196 patients at a single, high volume institution.

Objectives To determine if superior segmentectomy has equivalent overall (OS), disease-free (DFS), and locoregional-recurrence-free survival (LRFS) to lower lobectomy for early-stage non-small-cell lung cancer (NSCLC) in the superior segment. Methods We retrospectively reviewed all Stage 1 lower lobectomies for superior segment lesions and superior segmentectomies at our hospital from 2000 to 2018. Comparison statistics and Cox hazard modeling were performed to determine differences between groups and attempt to identify risk factors for OS, DFS, and LRFS. Results Superior segmentectomy patients, compared with lower lobectomy patients, had more current smokers, worse forced expiratory volume in 1 s percentage, radiologic emphysema scores, clinically and pathologically smaller tumors, and more occurrences of 0 lymph nodes examined. Outcomes for superior segmentectomy compared with lower lobectomy were equivalent for 5-year OS (67.0% vs. 75.1%, p = 0.70), DFS (56.9% vs. 60.4%, p = 0.59), and LRFS (87.9% vs. 91.3%, p = 0.46). Multivariable Cox modeling lacked utility due to no outcome differences. Conclusions In well-selected patients, superior segmentectomies can have equivalent OS, DFS, and LRFS compared with lower lobectomies of superior segment tumors for early stage lung cancer. Further data are needed to provide better risk estimates.
Relaxation capacity of cartilage is a critical factor in rate- and integrity-dependent fracture.

Articular cartilage heals poorly but experiences mechanically induced damage across a broad range of loading rates and matrix integrity. Because loading rates and matrix integrity affect cartilage mechanical responses due to poroviscoelastic relaxation mechanisms, their effects on cartilage failure are important for assessing and preventing failure. This paper investigated rate- and integrity-dependent crack nucleation in cartilage from pre- to post-relaxation timescales. Rate-dependent crack nucleation and relaxation responses were obtained as a function of matrix integrity through microindentation. Total work for crack nucleation increased with decreased matrix integrity, and with decreased loading rates. Critical energy release rate of intact cartilage was estimated as 2.39 ± 1.39 to 2.48 ± 1.26 kJ m−2 in a pre-relaxation timescale. These findings showed that crack nucleation is delayed when cartilage can accommodate localized loading through poroviscoelastic relaxation mechanisms before fracture at a given loading rate and integrity state.
Signal-precision Uncertainty and Trading Volume

Traditional models of market reactions to signals about a firm's value predict that trading volume is a V-shaped function of the signal. These models also imply that investors' posterior beliefs converge after the signal is released. However, empirical and anecdotal evidence suggest that trading volume is not V-shaped and that investors' posterior beliefs seem to diverge following the release of certain types of information. We reconcile the conflicting theoretical predictions and empirical evidence by developing a generalized model in which investors have both heterogeneous beliefs about a firm's prospects and uncertainty about the signal-precision. In contrast to traditional models, we show that some signals cause investors' beliefs to diverge and trading volume, in turn, becomes an M-shaped function of the signal. We document empirical evidence that corroborates this prediction: we show that trading volume is indeed an M-shaped function. We also develop a measure of signal-precision uncertainty and show that trading volume's M-shaped pattern is more pronounced in an environment with high signal-precision uncertainty.
Navigating without vision: spontaneous use of terrain slant in outdoor place learning

The topography of the land provides a suite of spatial information for navigation. In an outdoor field experiment, we examined terrain slant as a nonvisual cue. Without being told which cue to use,...
Planning for Future Fire: Scenario Analysis of an Accelerated Fuel Reduction Plan for the Western United States

Abstract Recent fire seasons brought a new fire reality to the western US, and motivated federal agencies to explore scenarios for augmenting current fuel management and forest restoration in areas where fires might threaten critical resources and developed areas. To support this effort, we modeled the scheduling of an accelerated forest and fuel management scenario on 76 western US national forests. Specifically, we modeled a 10-year ramp up of current forest and fuel management that targeted the source of wildfire exposure to developed areas and simulated treatment in areas that accounted for 77% of the predicted exposure. We used a sample of 30 future fire seasons to understand how the plan might be impacted by wildfires and treatment. We found that once fully implemented more than 20% of simulated fires on national forests overlapped fuel treatments, and that roughly 20% of the projects were burned prior to their implementation, suggesting that any plan will undergo significant revision during implementation. Treated areas intersected by wildfire accounted for twice the exposure than non-treated areas that also burned. The study demonstrates the use of scenario planning to design a fuel treatment program that targets wildfire exposure to developed areas, and the methods pave the way for expanded use of scenario planning science to analyze and communicate large scale expansion of current forest and fuel management initiatives.
Pseudomonas aeruginosa Reduces VX-809 Stimulated F508del-CFTR Chloride Secretion by Airway Epithelial Cells.

Background P. aeruginosa is an opportunistic pathogen that chronically infects the lungs of 85% of adult patients with Cystic Fibrosis (CF). Previously, we demonstrated that P. aeruginosa reduced wt-CFTR Cl secretion by airway epithelial cells. Recently, a new investigational drug VX-809 has been shown to increase F508del-CFTR Cl secretion in human bronchial epithelial (HBE) cells, and, in combination with VX-770, to increase FEV1 (forced expiratory volume in 1 second) by an average of 3-5% in CF patients homozygous for the F508del-CFTR mutation. We propose that P. aeruginosa infection of CF lungs reduces VX-809 + VX-770- stimulated F508del-CFTR Cl secretion, and thereby reduces the clinical efficacy of VX-809 + VX-770. Methods and Results F508del-CFBE cells and primary cultures of CF-HBE cells (F508del/F508del) were exposed to VX-809 alone or a combination of VX-809 + VX-770 for 48 hours and the effect of P. aeruginosa on F508del-CFTR Cl secretion was measured in Ussing chambers. The effect of VX-809 on F508del-CFTR abundance was measured by cell surface biotinylation and western blot analysis. PAO1, PA14, PAK and 6 clinical isolates of P. aeruginosa (3 mucoid and 3 non-mucoid) significantly reduced drug stimulated F508del-CFTR Cl secretion, and plasma membrane F508del-CFTR. Conclusion The observation that P. aeruginosa reduces VX-809 and VX-809 + VX-770 stimulated F508del CFTR Cl secretion may explain, in part, why VX-809 + VX-770 has modest efficacy in clinical trials.
Combining power management and power control in multihop IEEE 802.11 ad hoc networks

Power-saving is a major topic in mobile network research. MAC and network level power-saving schemes can be divided into two categories. One is power management, which tries to put as many idle stations into sleep mode as possible. The other is power control, whose goal is to minimize the transmission power by reducing the transmitting range. However, the two catagories of schemes do not take advantage of each other. In this paper, we propose an algorithm which integrates and balances both of the two approaches to get maximal power conservation, and closely combines power-saving and routing in the wireless ad hoc networks. Using power consumption figures measured and reported by other researchers, a simulation of power control, power management and the proposed combined algorithms has been set up and results are presented.
Degradation and resynthesis of adenine nucleotides in adult rat heart myocytes.

The degradation and short-term resynthesis of adenine nucleotides have been examined in a preparation of isolated rat heart myocytes. These myocyte preparations are essentially free of vascular and endothelial cells, contain levels of adenine nucleotides quite comparable to those of intact heart tissue, and retain these components remarkably well for up to 2 h of aerobic incubation in the presence of 1 mM Ca2+. When the cells are rapidly and synchronously de-energized by addition of uncoupler, an inhibitor of respiration and iodoacetate, cellular ATP is degraded almost quantitatively to AMP. The AMP is then converted to either intracellular adenosine, which accumulates to high concentrations before release to the cell exterior, or to IMP. The relative contribution of these two pathways depends on the metabolic state of the cells just prior to de-energization, with IMP production favored when respiring cells are de-energized and adenosine formation predominant when glycolyzing myocytes are subjected to this treatment. Cells de-energized by anaerobiosis in the absence of glucose lose ATP and adenine nucleotides with the production of IMP and adenosine. Upon reoxygenation, these cells restore a high adenylate energy charge and about 60% of control levels of GTP. There is a net resynthesis of 5-7 nmol of adenine nucleotides.mg-1 protein with a corresponding decline in IMP. Added [14C]adenosine labels the adenine nucleotide pool, but little net resynthesis of adenine nucleotides via adenosine kinase can be detected. It therefore appears that a rapid regeneration of adenine nucleotides can occur via the enzymes of the purine nucleotide cycle in heart myocytes and is limited by the size of the IMP pool retained.
Building loyal relationships between customers and providers: a focus on resource investments.

Abstract The increasingly competitive tourism industry has led to a paradigm shift in marketing philosophy from a focus on discrete transactions to one of long-term relationships. This paper proposes a conceptual model of the antecedents of customer loyalty; a construct central to relationship marketing. The model proposed draws from Resource Theory, and the notions of reciprocity and customer equity. According to the proposed model, when customers and providers invest specific profiles of resources in each other, the customers tend to develop a bond with the customer and become dedicated to maintaining a stable relationship. The model is used to discuss the mixed results of current loyalty programs and to outline future research efforts.
Sonographic appearance of a dermoid cyst (mature cystic teratoma) of the spleen

Splenic dermoids are rare, with few published case reports and no ultrasound images in the English literature. We report the case of a 57-year-old woman with that diagnosis and illustrate it with ultrasound, CT, and pathology images. We discuss the differential diagnosis of solid splenic lesions. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound, 43:132–134, 2015
Antepartum fetal evaluation: Development of a fetal biophysical profile

Five fetal biophysical variables, fetal breathing movements, fetal movements, fetal tone, qualitative amniotic fluid volume, and the nonstress test, were measured in the same observation period in 216 patients with high-risk pregnancies. All delivered within one week of the last observation. The relationship between individual biophysical variables and combinations of variables to the outcome of pregnancy as judged by five-minute Apgar score, fetal distress in labor, and perinatal mortality rate (PMN) was determined. For any single test, the false negative rate was low and was similar between tests, but the false positive rate was high (greater than 50%) and varied significantly between tests. Combining tests resulted in a significant change in both the false negative and false positive rates as compared to any single test. The most accurate differentiation of the normal from the compromised fetus was obtained when all five variables were studied. The PNM ranged from 0 when all variables were normal to 600 per 1,000 when all were abnormal. These data suggest that combined fetal biophysical testing is a more accurate method of antepartum fetal evaluation than any single method.
Quantum Mechanics in a Rotating Frame

The rotating frame is considered in quantum mechanics on the basis of the position dependent boost relating this frame to the non rotating inertial frame. We derive the Sagnac phase shift and the spin coupling with the rotation in the non relativistic limit by a simple treatment. By taking the low energy limit of the Dirac equation with a spin connection, we obtain the Hamiltonian for the rotating frame, which gives rise to all the phase shifts discussed before. Furthermore, we obtain a new phase shift due to the spin-orbit coupling.
Assessment of Mitochondrial Dysfunction Arising from Treatment with Hepatotoxicants

Studies demonstrate that mitochondrial dysfunction is a key causative factor in liver disease. Indeed, defects in mitochondrial energy metabolism, disrupted calcium handling, and increased reactive oxygen/nitrogen species production are observed in many metabolic disorders and diseases induced by toxicants. Mitochondria have emerged as a main research focus through work defining new functions of this key organelle in normal cellular physiology and pathophysiology. Specifically, studies show a critical role of mitochondrial reactive oxygen/nitrogen species production in regulating cellular signaling pathways involved in cell survival and death. Given this, along with advances made in proteomics technologies, mitochondria are recognized as top candidates for proteomics analysis. However, assessment of mitochondrial function and it’s proteome following toxicant exposure are not trivial undertakings. In this chapter a technique used to isolate mitochondria from liver tissue is presented along with methods needed to assess mitochondria functionality. The methods described include measurement of mitochondrial respiration, calcium accumulation, and reactive oxygen species production. A presentation of proteomics approaches is also included to allow researchers the basic tools needed to identify alterations in the mitochondrial proteome that contribute to toxicant-mediated diseases. Specifically, methods are presented that demonstrate how thiol labeling reagents in combination with electrophoresis and western blotting can be used to detect oxidant-mediated alterations in mitochondrial protein thiols. A few select pieces data are presented highlighting the power of proteomics to identify mitochondrial targets that contribute to mitochondrial dysfunction and hepatotoxicity in response to specific toxicant exposures and metabolic stressors such as alcohol and environmental tobacco smoke.
Conditional Mutator Gene in Escherichia coli: Isolation, Mapping, and Effector Studies

A mutator gene, mutD5, whose phenotype is conditional, has been identified in Escherichia coli. By P1 transduction it has been shown to lie at about 5.7 min on the chromosome, being co-transduced with proA and argF. In rich medium, streptomycin- and nalidixic acid-resistant mutation frequencies are 50 to 100 times higher than those in minimal medium. In minimal medium, the mutD5-induced mutation frequencies are still 50 to 100 times above co-isogenic wild-type (mut+) levels. Similar results were obtained with all markers tested. Mutant frequencies can be raised by thymidine in the medium at concentrations as low as 0.04 μM, or by the endogenous generation of thymidine from thymine plus a deoxyribosyl donor. Deoxyadenosine, various ribonucleosides, thymine, and 2-deoxyribose do not stimulate mutation. None of these effects are related to growth rate, since growth rate and mutation rate can be decoupled completely.
Calculation of Transmutation in Copper and Comparison with Measured Electrical Properties

Calculations of the transmutation of pure cooper have been performed for the Fast Flux Test Facility/Materials Open Test Assembly (FFTF/MOTA) and for the STARFIRE first-wall fusion reactor. The principal transmutation products in decreasing order of importance are nickel, zinc, and cobalt. Contrary to previously published calculations, nickel and zinc are produced at nearly equal rates in FFTF, but cobalt is insignificant. The fusion reactor case shows much higher transmutation rates and produces about twice as much nickel as zinc. Transmutation rates for FFTF were determined using adjusted neutron energy spectra based on dosimetry measurements at various positions in the MOTA. The predicted transmutation rates were compared directly with nickel concentrations measured by Energy Dispersive X-Ray Spectrometry (EDS) microchemistry and with measurements of the electrical conductivity of copper and two copper alloys irradiated in the MOTA. Measurements and calculations agree within {+-}15%.
Semiconductor laser-based optoelectronics oscillators

We demonstrate the realization of coupled opto-electronic oscillators (COEO) with different semiconductor lasers, including a ring laser, a Fabry-Perot laser, and a colliding pulse mode-locked laser. Each COEO can simultaneously generate short optical pulses and spectrally pure RF signals. With these devices, we obtained optical pulses as short as 6 picoseconds and RF signals as high in frequency as 18 GHz with a spectral purity comparable with a HP8561B synthesizer. These experiments demonstrate that COEOs are promising compact sources for generating low jitter optical pulses and low phase noise RF/millimeter wave signals.
First Report of Sclerotinia sclerotiorum Infection on Cuphea.

Species of the genus Cuphea (family Lythraceae) are being developed as potential domestic sources of medium length fatty acids (lauric and capric) for use in industrial lubricants and detergents. During September 2004, patches of dead plants were observed in test plots of Cuphea sp. cv. PSR-23 (1) (Cuphea viscosissima Jacq. × C. lanceolata W.T. Aiton) near Morris, MN and Prosper, ND, approximately 200 km apart. Seed yield in the diseased Morris field was 78 kg/ha compared with 516 kg/ha in nearby, nonaffected fields of the same variety, for an 85% yield reduction. Stems were split open to reveal long, cylindrical sclerotia as much as 8 mm long. Isolations from diseased stem tissue and sclerotia were identified as Sclerotinia sclerotiorum (Lib.) de Bary and produced typical sized sclerotia (4 to 6 mm in diameter) after 7 days growth on potato dextrose agar (PDA). Cuphea PSR-23 plants were grown in the greenhouse in individual pots for 5 weeks and then inoculated. Three inoculation methods were used. For th...
C64x VelociTI.2 extensions support media-rich broadband infrastructure and image analysis systems

This paper describes the new C64x DSP core including instruction set extensions that enhance performance for image and video processing. Key features include packed data processing and special instructions to accelerate algorithms such as motion estimation. Devices based on the C64x will be ideally suited for key target applications including video infrastructure and image analysis.
Blimp-1 Orchestrates Plasma Cell Differentiation by Extinguishing the Mature B Cell Gene Expression Program

Blimp-1, a transcriptional repressor, drives the terminal differentiation of B cells to plasma cells. Using DNA microarrays, we found that introduction of Blimp-1 into B cells blocked expression of a remarkably large set of genes, while a much smaller number was induced. Blimp-1 initiated this cascade of gene expression changes by directly repressing genes encoding several transcription factors, including Spi-B and Id3, that regulate signaling by the B cell receptor. Blimp-1 also inhibited immunoglobulin class switching by blocking expression of AID, Ku70, Ku86, DNA-PKcs, and STAT6. These findings suggest that Blimp-1 promotes plasmacytic differentiation by extinguishing gene expression important for B cell receptor signaling, germinal center B cell function, and proliferation while allowing expression of important plasma cell genes such as XBP-1.
Some explicit solutions of the additive Deligne–Simpson problem and their applications

Abstract In this paper we construct three infinite series and two extra triples (E8 and E 8 ) of complex matrices B, C, and A=B+C of special spectral types associated to Simpson's classification in Amer. Math. Soc. Proc. 1 (1992) 157 and Magyar et al. classification in Adv. Math. 141 (1999) 97. This enables us to construct Fuchsian systems of differential equations which generalize the hypergeometric equation of Gauss–Riemann. In a sense, they are the closest relatives of the famous equation, because their triples of spectral flags have finitely many orbits for the diagonal action of the general linear group in the space of solutions. In all the cases except for E8, we also explicitly construct scalar products such that A, B, and C are self-adjoint with respect to them. In the context of Fuchsian systems, these scalar products become monodromy invariant complex symmetric bilinear forms in the spaces of solutions. When the eigenvalues of A, B, and C are real, the matrices and the scalar products become real as well. We find inequalities on the eigenvalues of A, B, and C which make the scalar products positive-definite. As proved by Klyachko, spectra of three hermitian (or real symmetric) matrices B, C, and A=B+C form a polyhedral convex cone in the space of triple spectra. He also gave a recursive algorithm to generate inequalities describing the cone. The inequalities we obtain describe non-recursively some faces of the Klyachko cone.
Plasma fibrinogen patterns in patients with coronary atherosclerosis.

Plasma fibrinogen determinations in 46 coronary patients and 49 healthy individuals were made over a period of about 33 months. The mean fibrinogen levels were calculated and shown to increase with age. The fibrinogen levels in the younger patient group were elevated and resembled the levels of the older control subjects. The statistical test of the variance was significantly greater in the patient group. The inclusion of episodes of infections, bleeding, and surgery, all of which are known to raise the plasma fibrinogen levels, did not significantly alter the greater fibrinogen variance in the patient group. Comparison of a group of patients receiving anticoagulant orally to a group not receiving the drugs failed to indicate that the anticoagulants restored the lower variance seen in the controls. Of the four patients whose deaths were documented as due to recurrent coronary events, all had greater fibrinogen variances than a comparable group of patients who survived. The fibrinogen variance may not only reflect an unstable clotting mechanism in patients with coronary thrombosis but may also have prognostic significance for the recurrence of myocardial infarction.
Methods for evaluating the reference value in laboratory intercomparisons of dimensional measurements

A number of methods have been proposed to evaluate the reference value for intercomparisons of laboratory measurements. Methods for establishing the reference value include the arithmetic mean, weighted mean (with weights proportional to the reciprocals of the squared uncertainties), median, and total median. In addition, it has been suggested that it might be possible to modify the weighted mean, using iterative approaches to automatically eliminate outliers or to modify the weights in light of the results of the intercomparison. No single one of the analysis methods is best for all circumstances, nor can the efficiency of any method be determined without making assumptions about the underlying nature of the intercomparison. (How well do the participants evaluate their uncertainties? What is the underlying distribution of errors, including outliers? Are the errors correlated between one laboratory and the next?) Although there is considerable divergence of opinion as to what constitutes realistic assumptions, completed international comparisons can begin to provide at least rough guidance for constructing models. In this paper, I will try to construct models that are consistent with what we have learned thus far from CCL (Consultative Committee for Length) key comparisons in the field of dimensional metrology. Based on such models, I have explored various methods for establishing a reference value, to determine which methods are likely to produce a reference value with a low uncertainty. As would be expected, there is no single method that is always superior; results depend on both the underlying assumptions and on the spread and distribution of claimed uncertainties of the participating laboratories.
New approach in correcting for multipath interference including the use of fuzzy logic

This paper describes a new way for recovering FM stereo signals after being subjected to multipath interference. This approach relies on the detection of out-of-band noise to signal the occurrence of multipath events. The correction is done by controlling the cutoff frequencies of two adaptive lowpass filters used to pass the desired left and right stereo signals simultaneously. The cutoff frequency of each filter is determined by the measurement of the peak frequency found in the in-band audio signal falling within a moving time window. This measurement is only enabled in the absence of interference. The duration of correction is initially determined by the energy of the out-of-band noise but later controlled by a Fuzzy controller whose inputs are the current duration and the duration error.
Evaluation Challenges for Bridging Semantic Gap: Shape Disagreements on Pulmonary Nodules in the Lung Image Database Consortium

Evaluating the success of prediction and retrieval systems depends upon a reliable reference standard, a ground truth. The ideal gold standard is expected to result from the marking, labeling, and rating of domain experts. However experts disagree and lack of agreement challenges the development and evaluation of image-based feature prediction. This paper addresses the success and limitations in bridging the semantic gap between CT-based pulmonary nodule image features and radiologistsâ€™ ratings of diagnostic characteristics. The prediction of diagnostic characteristics promises to automatically annotate images with medically meaningful descriptions usable for indexing and retrieving in content-based image retrieval (CBIR) and computer aided diagnosis (CADx). Successful results in predicting texture characteristics will be contrasted with less successful results for boundary shapes. The two primary differences in agreement between radiologists will be discussed; the first concerns agreement about the existence of a nodule, while the second considers the variability in radiologistsâ€™ ratings.
Isolation and preliminary characterization of clathrin-associated proteins.

Clathrin-associated proteins were separated from clathrin under various clathrin-denaturing conditions, i.e. heating, freezing and isoelectric precipitation. The proteins retained biological activity; they were purified further by affinity chromatography on calmodulin-conjugated CNBr-Sepharose 4B and used for antibody purification. The affinity-purified anti-(clathrin-associated proteins) antibodies gave a fluorescent dotted pattern in cultured fibroblasts consistent with the known distribution of clathrin. Chemical cross-linking of pure clathrin-associated proteins indicated that these polypeptides exist as monomers in solution, each possessing Ca2+-dependent affinity for calmodulin to which they bind in a 1:1 molar ratio. Chymotryptic treatment of coated vesicles selectively cleaved the clathrin-associated proteins into a 15 000-18 000-Mr doublet polypeptide. These subfragments retained their Ca2+-dependent affinity for calmodulin. Our results support a regulatory role for clathrin-associated proteins in clathrin assemblies.
Performance evaluation of a new algorithm for the detection of remote homologs with sequence comparison

A detailed analysis of the performance of hybrid, a new sequence alignment algorithm developed by Yu and coworkers that combines Smith Waterman local dynamic programming with a local version of the maximum-likelihood approach, was made to access the applicability of this algorithm to the detection of distant homologs by sequence comparison. We analyzed the statistics of hybrid with a set of nonhomologous protein sequences from the SCOP database and found that the statistics of the scores from hybrid algorithm follows an Extreme Value Distribution with lambda ∼1, as previously shown by Yu et al. for the case of artificially generated sequences. Local dynamic programming was compared to the hybrid algorithm by using two different test data sets of distant homologs from the PFAM and COGs protein sequence databases. The studies were made with several score functions in current use including OPTIMA, a new score function originally developed to detect remote homologs with the Smith Waterman algorithm. We found OPTIMA to be the best score function for both both dynamic programming and the hybrid algorithms. The ability of dynamic programming to discriminate between homologs and nonhomologs in the two sets of distantly related sequences is slightly better than that of hybrid algorithm. The advantage of producing accurate score statistics with only a few simulations may overcome the small differences in performance and make this new algorithm suitable for detection of homologs in conjunction with a wide range of score functions and gap penalties. Proteins 2002;48:367–376. © 2002 Wiley-Liss, Inc.
Quantitative optical spectroscopy for pancreatic cancer detection

We report novel optical diagnostic algorithms for clinical pancreatic tissue classification, including a photon-tissue interaction model developed to extract biophysical parameters from reflectance and fluorescence spectra to distinguish pancreatic adenocarcinoma from normal tissue and pancreatitis.
Fast lithium-ion conducting thin-film electrolytes integrated directly on flexible substrates for high-power solid-state batteries.

By utilizing an equilibrium processing strategy that enables co-firing of oxides and base metals, a means to integrate the lithium-stable fast lithium-ion conductor lanthanum lithium tantalate directly with a thin copper foil current collector appropriate for a solid-state battery is presented. This resulting thin-film electrolyte possesses a room temperature lithium-ion conductivity of 1.5 × 10(-5) S cm(-1) , which has the potential to increase the power of a solid-state battery over current state of the art.