cssi/SciSciGPT-SciSciNet huggingface dataset:
Phase I trials as valid therapeutic options for patients with cancer.

For many years, oncology phase I trials have been referred to as ‘toxicity trials’ and have been believed to have low clinical utility other than that of establishing the adverse event profile of novel therapeutic agents. The traditional distinction of clinical trials into three phases has been challenged in the past few years by the introduction of targeted therapies and immunotherapies into the routine management of patients with cancer. This transformation has especially affected early phase trials, leading to the current situation in which response rates are increasingly reported from phase I trials. In this Perspectives, we highlight key elements of phase I trials and discuss how each one of them contributes to a new paradigm whereby preliminary measurements of the clinical benefit from a novel treatment can be obtained in current phase I trials, which can therefore be considered to have a therapeutic intent. Oncology phase I trials have been traditionally referred to as ‘toxicity trials’. The distinction of clinical trials into three phases has been challenged in the past few years, leading to the current situation in which response rates are increasingly reported from phase I trials. The authors dissect the ethical dilemmas surrounding the therapeutic intent of phase I trials and provide evidence of contemporary phase I trials as a therapeutic option for patients with cancer.
Comparing inpatient versus emergency department clinician perceptions of personal protective equipment for different isolation precautions

Adherence to isolation precaution practices, including use of personal protective equipment (PPE), remains a challenge in most hospitals. We surveyed inpatient and emergency department clinicians about their experiences and opinions of various isolation policies, specifically those related to wearing PPE. Our findings show several differences between inpatient and emergency department clinicians involving perceptions related to safety, and the difficulty associated with using PPE for certain types of organisms.
Ocean Acidification: The Other CO2 Problem

Summary The overall goal of this lecture is to provide an overview of the process and progress of ocean acidification in the global oceans and its impacts on marine organisms over time scales of days to centuries. Examples of acidification impacts on corals, shellfish, and zooplankton are given to show how acidification can affect different kinds of life processes. This lecture describes what we know and what we don't know about ecosystem responses to acidification and the socio-economic implications for our society. Finally, we discuss the future implications of increased CO2 levels on the health of our ocean ecosystems and related ocean-based economies.
Chapter 144 – Japanese Beetle

Publisher Summary This chapter focuses on the Japanese beetle, Popillia japonica Newman. It is among the most polyphagous of plant-feeding insects. The adults skeletonize the foliage or feed on the flowers or fruits, of nearly 300 species of wild or cultivated plants. The larvae, or grubs, develop in the soil where they feed on roots of turf and pasture grasses, vegetables, nursery seedlings, and field crops. It belongs to the family Scarabaeidae, subfamily Rutelinae. Adults are broadly oval, 8–11 mm in length, metallic green, with coppery-brown elytra that do not quite cover the end of the abdomen. The abdomen bears five patches of white hairs on both side, and another pair near its tip. Females, which tend to be slightly larger than males, have an elongate, spatula-shaped spur on the fore tibia, used for digging. This spur is shorter and pointed in males. Japanese beetles have a 1-year life cycle in most parts of their range. Adults occur from June to August. Upon emergence from the soil, virgin females emit a volatile sex pheromone that attracts clusters of males. Subsequent mating occurs on food plants. The beetles typically feed from the upper surface of leaves, chewing out the tissue between the veins and leaving a lace-like skeleton.
Secular State and Religious Education in Public Schools: The Brazilian Case

The present work is about religion classes in the elementary schools of the Brazilian public education system, a controversial topic since the 1988 Federal Constitution first enlists it in Article 210. Even though the enrollment in the religious education class is optional, the classes are conducted on regular school hours, according to what the constitutional text determines, as an expression of the fundamental right to freedom of religion. Apart from the Constitution, there are also statutes that regulate religion teaching. That is precisely the case of the National Education Guidelines Act (federal statute n. 9394/1996), which ensures respect for religious and cultural diversity and prohibits any form of proselytism. Article 33 of such statute establishes that each State should determine the content of the religious education classes, as well as set the rules for the admission of teachers. The treaty signed by Brazil and the Holy See in 2008 also deals with religious education. Article 11 of the treaty allows for both catholic and other religions education classes. The Attorney General challenged all these statutes in the Supreme Court. In 2010, it filed an Action of Unconstitutionality, alleging that the statutes in regard to religious education classes in public schools violate Article 19 of the 1988 Federal Constitution, which defines Brazil as a secular State. In 2017, the Supreme Court of Justice, by a majority, dismissed the case, deeming the Action of Unconstitutionality devoid of legal grounds, and ruled that the government, observing the binomial State secularity (CF, Section 19,I)/acknowledgment of religious freedom (CF, Section 5th, VI), shall act in full regulation of compliance with the constitutional provision set forth in Section 210, §1st, authorizing the public school system, under equal conditions (CF, Article 5th, caput), to offer religious education of various beliefs by means of formal requirements previously set by the Brazilian Ministry of Education. The anxiety generated by the case depicts the dynamic religious pluralism that exists in Brazil, and exposes the dispute for the public arena, in a polarized environment in which fundamentalism speeches are not uncommon. The text concludes that as long as the Government is not excessively involved, neither confessional nor nonconfessional religious classes violate the Constitution.
Catalytic Metal-free Allylic C-H Amination of Terpenoids.

The selective replacement of C–H bonds in complex molecules, especially natural products like terpenoids, is a highly efficient way to introduce new functionality and/or couple fragments. Here, we ...
Mast Cells Promote Nonalcoholic Fatty Liver Disease Phenotypes and Microvesicular Steatosis in Mice Fed a Western Diet.

BACKGROUND AND AIMS Nonalcoholic fatty liver disease (NAFLD) is simple steatosis but can develop into nonalcoholic steatohepatitis (NASH), characterized by liver inflammation, fibrosis, and microvesicular steatosis. Mast cells (MCs) infiltrate the liver during cholestasis and promote ductular reaction (DR), biliary senescence, and liver fibrosis. We aimed to determine the effects of MC depletion during NAFLD/NASH. APPROACH AND RESULTS Wild-type (WT) and KitW-sh (MC-deficient) mice were fed a control diet (CD) or a Western diet (WD) for 16 weeks; select WT and KitW-sh WD mice received tail vein injections of MCs 2 times per week for 2 weeks prior to sacrifice. Human samples were collected from normal, NAFLD, or NASH mice. Cholangiocytes from WT WD mice and human NASH have increased insulin-like growth factor 1 expression that promotes MC migration/activation. Enhanced MC presence was noted in WT WD mice and human NASH, along with increased DR. WT WD mice had significantly increased steatosis, DR/biliary senescence, inflammation, liver fibrosis, and angiogenesis compared to WT CD mice, which was significantly reduced in KitW-sh WD mice. Loss of MCs prominently reduced microvesicular steatosis in zone 1 hepatocytes. MC injection promoted WD-induced biliary and liver damage and specifically up-regulated microvesicular steatosis in zone 1 hepatocytes. Aldehyde dehydrogenase 1 family, member A3 (ALDH1A3) expression is reduced in WT WD mice and human NASH but increased in KitW-sh WD mice. MicroRNA 144-3 prime (miR-144-3p) expression was increased in WT WD mice and human NASH but reduced in KitW-sh WD mice and was found to target ALDH1A3. CONCLUSIONS MCs promote WD-induced biliary and liver damage and may promote microvesicular steatosis development during NAFLD progression to NASH through miR-144-3p/ALDH1A3 signaling. Inhibition of MC activation may be a therapeutic option for NAFLD/NASH treatment.
A scheme for data compression in supercomputers

A compression algorithm that is tailored to utilize the enormous speed and memory size of supercomputers is presented. It utilizes an enhanced arithmetic coding scheme. Efficient VLSI designs for the enhanced scheme are given. The designs are suitable for inclusion in disk and communication controllers of supercomputers and would provide a practical way to increase thresholds of data transfer rates and communication bandwidth effectively.
Optimal Scheduling of Integrated Microgrids with High Resolution Islanding

As renewable energy integration has been developing fast in recent years, it can not only bring economic benefits but also improve reliability compared to the traditional form of transmission and distribution. Microgrid has been widely used in the world, bringing a new type of transaction energy between the main grid and dispatchable units. This paper aims to develop a new transaction energy and model between the main grid and integrated microgrids, to save the total energy cost, as well as the economic improvement among each microgrid. Lagrangian relaxation method has been used to decompose each microgrid problem, and high-resolution islanding consideration has been used to operate each microgrid in their islanded mode. Simulation results have been developed both in grid-connected mode and islanded mode.
Imaging (Cost, Radiation)

Periodic imaging of the recurrent stone former is an important component of their management. Imaging can help monitor for stone activity and the effectiveness of preventative strategies. There are a number of factors to take into consideration when choosing the appropriate imaging modality to follow a stone patient. These factors include whether the stones will be radio-opaque, as well as the amount of radiation the imaging study exposes patients to. In addition, cost is an important consideration when choosing a study. Non-contrast computed tomography remains the most sensitive imaging study for the evaluation of nephrolithiasis; however it is associated with relatively high cost and radiation. New low dose protocols reduce the radiation exposure. Renal ultrasound does not expose patients to any radiation and may be useful for the follow-up of radio-lucent stones. Plain abdominal radiography is both inexpensive and associated with minimal radiation exposure. Its use should be limited to patients with radio-opaque stones. Finally, new technologies, such as digital tomosynthesis may prove to be useful in the follow-up of recurrent stone formers. Digital tomosynthesis has improved sensitivity for stone detection compared to plain radiography with less cost and radiation than low dose computed tomography.
Conjugate Gradient Approach to Parallel Processing in Dynamic Simulation of Power Systems

In this paper we present a new approach to solving the power system dynamic simulation problem using the Generalised Minimal Residual (GMRES) algorithm. This is one of the several methods in the family of Conjugate Gradient methods for solving systems of equations of the form Ax = b. Although some of these methods require A be symmetric positive definite, GMRES has no such restriction. The technique is illustrated on a 39 bus, 10 machine power system using the Cray Y-MP.
Evidence-based treatment for justice-involved youth

This chapter pinpoints the conceptual foundations and treatment strategies for early intervention and community-based treatment programs, and provides case examples illustrating the unique features of each approach. In addition, it presents two promising transition programs with implications for treatment of youth in secure programs prior to their participation in community-based aftercare treatments. Early intervention and community-based treatment programs are intended to provide alternatives to secure facilities for juveniles involved in criminal activity. These approaches are analogous to strategies used in public health to prevent, control, and reduce the impact of illness on quality of life, morbidity, and mortality. Two examples of early intervention programs include diversion programs and mentoring programs. All of the common characteristics of evidence-based programs highlighted in the chapter must be attended to and fulfilled, including: qualities of effective providers; training and protocol adherence; clinical supervision; and collaboration with stakeholders in the system.
BMCP1: a mitochondrial uncoupling protein in neurons which regulates mitochondrial function and oxidant production

Outside the nervous system, members of the mitochondrial uncoupling protein (UCP) family have been proposed to contribute to control of body temperature and energy metabolism, and regulation of mitochondrial production of reactive oxygen species (ROS). However, the function of brain mitochondrial carrier protein 1 (BMCP1), which is highly expressed in brain, remains to be determined. To study BMCP1 expression and function in the nervous system, a high-affinity antibody to BMCP1 was generated and used to analyze tissue expression of BMCP1 protein in mouse. BMCP1 protein was highly expressed in heart and kidney, but not liver or lung. In the nervous system, BMCP1 was present in cortex, basal ganglia, substantia nigra, cerebellum, and spinal cord. Both BMCP1 mRNA and protein expression was almost exclusively neuronal. To study the effect of BMCP1 expression on mitochondrial function, neuronal (GT1-1) cell lines with stable overexpression of BMCP1 were generated. Transfected cells had higher State 4 respiration and lower mitochondrial membrane potential (ψm), consistent with greater mitochondrial uncoupling. BMCP1 expression also decreased mitochondrial production of ROS. These data suggest that BMCP1 can modify mitochondrial respiratory efficiency and mitochondrial oxidant production, and raise the possibility that BMCP1 might alter the vulnerability of brain to both acute injury and to neurodegenerative conditions.
Termination, Stabilization, and Continuity of Care

Termination and stabilization are vital components to the social work practice. More than just the ending point of services, termination and stabilization are integral to the overall therapeutic and problem-solving process and provide the end to the formal clinical relationship for client. For the purposes of this chapter, termination and stabilization are understood to be interrelated processes. This chapter will discuss definitions and understandings of this phase of treatment, place these within a transtheoretical model, outline perspectives on both, and empirical research related to this phase of services within differing models. Keywords: stabilization; termination; social work practice
Monte Carlo Simulation of Adaptive Stated Preference Survey with a case study: Effects of Aggregate Mode Shares on Individual Mode Choice

Monte Carlo experiments are used to study the unbiasedness of several common random utility models for a proposed adaptive stated preference survey. This survey is used to study the influence of the knowledge of existing mode shares on travelers mode choice. Furthermore, the survey is applied to a sample of subjects selected from the University of Minnesota. The results indicate that the presence of mode shares in the mode choice model does influence the decision of travelers. The estimates are found to be biased by the Monte Carlo experiments.
Using Social Media in Rulemaking: Possibilities and Barriers

“Web 2.0” is characterized by interaction, collaboration, non-static web sites, use of social media, and creation of user-generated content. In theory, these Web 2.0 tools can be harnessed not only in the private sphere but as tools for an e-topia of citizen engagement and participatory democracy. Notice-and-comment rulemaking is the pre-digital government process that most approached (while still falling far short of) the e-topian vision of public participation in deliberative governance. The notice-and-comment process for federal agency rulemaking has now changed from a paper process to an electronic one. Expectations for this switch were high; many anticipated a revolution that would make rulemaking not just more efficient, but also more broadly participatory, democratic, and dialogic. In the event, the move online has not produced a fundamental shift in the nature of notice-and-comment rulemaking. At the same time, the online world in general has come to be increasingly characterized by participatory and dialogic activities, with a move from static, text-based websites to dynamic, multi-media platforms with large amounts of user-generated content. This shift has not left agencies untouched. To the contrary, agencies at all levels of government have embraced social media – by late 2013 there were over 1000 registered federal agency twitter feeds and over 1000 registered federal agency Facebook pages, for example – but these have been used much more as tools for broadcasting the agency’s message than for dialogue or obtaining input. All of which invites the questions whether agencies could or should directly rely on social media in the rulemaking process.This study reviews how federal agencies have been using social media to date and considers the practical and legal barriers to using social media in rulemaking, not just to raise the visibility of rulemakings, which is certainly happening, but to gather relevant input and help formulate the content of rules. The study was undertaken for the Administrative Conference of the United States and is the basis for a set of recommendations adopted by ACUS in December 2013. Those recommendations overlap with but are not identical to the recommendations set out herein.
Molecular Genetics of Metastasis

Metastasis is the spread of cancer cells throughout the body. Although it is frequently the cause of death from malignant growths, it is the most poorly understood aspect of carcinogenesis. The underlying process of cancer cell dissemination is controlled by genetic programs in the tumour cells and in the host. The tumour cell-intrinsic genetic programs of metastasis confer invasiveness and anchorage-independence. The responsible genes are typically deregulated by aberrant expression or splicing. Organ preference of metastasis depends on more complex tumour–host interactions. Metastasis suppressor genes, when expressed, can negatively regulate tumour spread. The molecular genetics of metastasis has led to the development of diagnostic tests, based on gene expression profiles that help predict metastatic potential. Further, it has opened prospects for the targeting of key culprit genes in antimetastasis therapy. Key Concepts: Cancer invasiveness constitutes the breaking of tumour cells through tissue barriers and represents the earliest manifestation of metastasis. The genetic basis of metastasis formation is the aberrant expression or splicing of stress response genes. The biologic activity of metastasis-mediating gene products is extensively regulated by posttranscriptional mechanisms. Cancer metastasis is guided by two intrinsic characteristics of cancer cells, invasiveness and anchorage-independent survival. Cancer cell invasiveness is mediated by secreted proteases, homing receptors, cytokine ligands and associated signalling molecules. The acquisition of invasiveness by tumour cells is accompanied by a characteristic, reversible remodelling, called the epithelial-mesenchymal transition. Cancers shed their tumour cells into the blood or lymph stream from the earliest stages of growth on; most cells die in the circulation. Fully transformed cells can survive without anchorage for extended periods of time. Genetic programs of metastasis encode consistent patterns of organ preference by individual malignancies. Like other functions within cancer cells, the ability to metastasise is under positive and negative genetic control. Keywords: metastasis; invasion; anoikis; homing receptor; cytokine; protease
Preclinical Performance Evaluation of Percutaneous Glucose Biosensors: Experimental Considerations and Recommendations

The utility of continuous glucose monitoring devices remains limited by an obstinate foreign body response (FBR) that degrades the analytical performance of the in vivo sensor. A number of novel materials that resist or delay the FBR have been proposed as outer, tissue-contacting glucose sensor membranes as a strategy to improve sensor accuracy. Traditionally, researchers have examined the ability of a material to minimize the host response by assessing adsorbed cell morphology and tissue histology. However, these techniques do not adequately predict in vivo glucose sensor function, necessitating sensor performance evaluation in a relevant animal model prior to human testing. Herein, the effects of critical experimental parameters, including the animal model and data processing methods, on the reliability and usefulness of preclinical sensor performance data are considered.
Are Demographics Adequate Controls for Cell-Phone-Only Coverage Bias in Mass Communication Research?:

Cell-phone-only (CPO) households differ along key variables from non-CPO households, creating potential coverage biases in landline-only random-digit-dialing (RDD) surveys. Researchers have attempted to correct for this by weighting their data based on demographic differences. Previous research, however, has not examined CPO coverage biases in media-use surveys—an important oversight as cell phone use is itself a media choice. This article presents a secondary analysis of Pew’s 2012 media consumption survey and concludes that demographics alone are not adequate controls for the CPO bias in media-use surveys.
Memory-monitoring accuracy as influenced by the distribution of retrieval practice

An experiment was done to determine whether retrieval practice improved judgment-of-learning (JOL) accuracy when degree of learning was controlled. Fifty undergraduate students were asked to learn a long list of unrelated facts, with critical items presented either once or four times. The repetitions of critical items were retrieval prompts for half of the subjects (study-test) and additional study presentations (study-only) for the other half of the subjects. The subjects made JOL ratings after the last occurrence of critical items. Immediately after the study list, they were given a cued-recall test. Recall was comparable for once-presented items and repeated items across the two groups, but JOL accuracy was higher for repeated items in the study-test group. These results confirm that retrieval practice enhances JOL accuracy even when degree of learning is controlled.
Predicting drug interactions using cultured human hepatocytes

In previous papers we demonstrated that cyclosporin A (CsA) was specifically oxidized in rabbit and human liver by cytochrome P-450IIIA. We therefore anticipated that any drug that is an inducer or an inhibitor of this cytochrome should lead to interaction with CsA when given in association with it. In order to confirm this hypothesis, primary cultures of human hepatocytes and human liver microsomes were used to “reproduce” in vitro clinically significant interactions observed between CsA and drugs known either as specific inducers (i.e., rifampicin) or as specific inhibitors (i.e., erythromycin) of P-450IIIA. Our results were in close agreement with the clinical reports. Human hepatocytes maintained in primary cultures for 72 hr in the presence of 50 μM rifampicin exhibited increased levels of P-450IIIA, determined by Western blot using specific antibodies, and concomitant increase in CsA oxidase activity, determined by HPLC analysis of extra and intracellular media. Conversely, these cultures exhibited erythromycin concentrationdependent decreases in CsA oxidase activity when incubated in the presence of 5, 20, and 100 μM erythromycin. In addition, a Lineweaver-Burk analysis of the erythromycin-mediated inhibition of CsA oxidase activity in human liver microsomes revealed competitive inhibition (with Ki of 75 μM) as expected, this macrolide being a specific substrate of P-450IIIA. Using this experimental approach, 59 molecules representative of 17 different therapeutic classes were screened for inducers and inhibitors of CsA oxidase activity. Our results allowed us to elucidate the molecular mechanism of previously observed, but unexplained, drug interactions involving CsA, and to detect drugs that should interfere with CsA metabolism as inducers or inhibitors. Drugs detected as potential inducers of CsA oxidase included: rifampicin, sulfadimidine, phenobarbital, phenytoin, phenylbutazone, dexamethasone, sulfinpyrazone, and carbamazepine. Drugs detected as potential competitive inhibitors included: triacetyloleandomycin, erythromycin, josamycin, midecamycin, ketoconazole, miconazole, midazolam, nifedipin, diltiazem, verapamil, nicardipine, ergotamine, dihydroergotamine, glibenclamide, bromocryptine, ethynylestradiol, progesterone, cortisol, prednisone, prednisolone, and methylprednisolone. Finally cefoperazone, cefotaxime, ceftazidime, isoniazide, doxycycline, spiramycin, sulfamethoxazole, norfloxacin, pefloxacin, vancocin, trimethoprime, amphotericine B, valproic acid, quinidine, cimetidine, ranitidine, omeprazole, diclofenac, aspirin, paracetamol, debrisoquine, guanoxan, captopril, furosemide, acetazolamide, sparteine, gliclazide, and imipramine were found not to interfere with the hepatic metabolism of CsA.
Musical Intervention in Family Therapy

The family therapy approach to treatment is an outgrowth of individual therapy and can present optimal opportuni­ ties for the use of music therapy. Three major schools of thought in family therapy--systemic, structural, and stra­ tegic-provide treatment objectives that lend themselves to musical intervention. The structural family therapy school of thought in particular lends itself to music inter­ vention due to its concern with balance of power, limits, boundaries, and family roles, which can be addressed through various musical exercises and techniques. Musical intervention within a family therapy context is a new and relatively unexplored avenue of treatment deserving of further research. Origins of Family Therapy While individual therapy examines pathology in a setting exclu­ sive of social context, family therapy directly explores the function of pathology within the confines of the family as a social system. Traditional Freudian therapy utilizes the dynamics of a private, one-on-one relationship to elicit the transfer of habitual reactions and attitudes toward principal family figures onto the therapist. In this way, dynamics of the patient’s family interactions are indirectly brought into treatment for examination. Family therapy
Analysis of brain fMRI time-series using HRF knowledge-based correlation classifier on unsupervised self-organizing neural network map

Brain imaging and particular functional MRI (fMRI), which acquires brain volumes in time, reveals new understanding of the functional/structural relation in neuroscience. During fMRI imaging physiological state changes occur in the brain regions activated from the task paradigm which the subject performs in the scanner. These state changes can be depicted in the small veins of the activated region due to the blood oxygen level dependent (BOLD) effect. For each brain voxel in the fMRI experiment one accumulates a time series vector which has to be analyzed for similarity to the original task paradigm vector and its characteristic hemodynamic response function (HRF). Various analysis methods have been discussed for fMRI analysis, model-based statistical or unsupervised data-driven techniques. The purpose of this paper is to introduce a new method which combines two different approaches. We use an unsupervised self-organizing map (SOM) neural network to reduce the time series vector space by non-linear pattern recognition into a 2D table of representative time series wave-forms. Using a-priori knowledge of the HRF, either derived from a theoretical wave-form model or estimated from a brain region of interest (ROI), one can use correlation analysis between the time series patterns of the SOM table and the HRF to depict regions of activation specific to the HRF. An optional second SOM training with a reduce number of neurons of the best-matching time series to the HRF classification refines the second neural network pattern table. The learned time series pattern of each neuron and the corresponding brain voxels are superimposed onto the subject's brain image for visual investigation.
Perceptions of Neighborhood Disorder: The Role of Individual and Neighborhood Characteristics.

Objectives The study of neighborhood effects on health and wellbeing has regained prominence in recent years. Most authors have relied on Census data and other administrative data sources to assess neighborhood characteristics. Less commonly employed, but gaining in popularity, are measures from surveys which ask neighborhood residents about various aspects of their neighborhood environment. Such surveys are a potentially attractive alternative or augmentation to administrative data sources.
Change in microbial communities in acetate- and glucose-fed microbial fuel cells in the presence of light.

Abstract Power densities produced by microbial fuel cells (MFCs) in natural systems are changed by exposure to light through the enrichment of photosynthetic microorganisms. When MFCs with brush anodes were exposed to light (4000 lx), power densities increased by 8–10% for glucose-fed reactors, and 34% for acetate-fed reactors. Denaturing gradient gel electrophoresis (DGGE) profiles based on the 16S rRNA gene showed that exposure to high light levels changed the microbial communities on the anodes. Based on 16S rRNA gene clone libraries of light-exposed systems the anode communities using glucose were also significantly different than those fed acetate. Dominant bacteria that are known exoelectrogens were identified in the anode biofilm, including a purple nonsulfur (PNS) photosynthetic bacterium, Rhodopseudomonas palustris , and a dissimilatory iron-reducing bacterium, Geobacter sulfurreducens . Pure culture tests confirmed that PNS photosynthetic bacteria increased power production when exposed to high light intensities (4000 lx). These results demonstrate that power production and community composition are affected by light conditions as well as electron donors in single-chamber air-cathode MFCs.
Regulation of MMP-9 Production by Human Corneal Epithelial Cells

The matrix metalloproteinases, MMP-2 and MMP-9, are known to be critical extracellular-remodeling enzymes in wound healing and other diseases of the ocular surface. This study investigated the regulation of MMP-2 and MMP-9 in human corneal epithelial cells by growth factors and pro-inflammatory cytokines (IL-1beta and TNF-alpha) they are exposed to, and by doxycycline, a medication used to treat ocular surface disease. Primary human corneal epithelial cell cultures were treated with one of the following cytokines (IL-1alpha, IL-1beta, IL-6, IL-8, TNF-alpha) or growth factors (EGF, HGF, KGF, PDGF-BB, TGF-alpha, TGF-beta), with or without their corresponding inhibitors. The conditioned media were collected after 24 hr for gelatin zymography and MMP-9 activity assay. Total RNA was extracted from the cells treated for 6 hr and was subjected to RT-PCR and Northern hybridization. Between the two gelatinases, MMP-2 and MMP-9, detected by zymography, the 92 kDa MMP-9 in the conditioned medium was markedly up-regulated by the pro-inflammatory cytokines, IL-1beta and TNF-alpha. The MMP-9 protein and activity were dose-dependently stimulated by IL-1beta or TNF-alpha at 0.1, 1.0 and 10 ng ml(-1). This up-regulation was nearly abolished by neutralizing antibodies (IL-1beta and TNF-alpha) and by IL-1 receptor antagonist. Semi-quantitative RT-PCR and Northern hybridization disclosed that the MMP-9 transcript was also markedly up-regulated in a dose-dependent manner by IL-1beta and TNF-alpha. Doxycycline (10 microg ml(-1)) suppressed MMP-9 protein level and activity, but not its mRNA, that was stimulated by IL-1beta and TNF-alpha (1 ng ml(-1)). In contrast, the 72 kDa MMP-2 was not significantly modulated by any of these cytokines. In conclusion, production of MMP-9 is stimulated by the pro-inflammatory cytokines, IL-1beta and TNF-alpha. These factors may play a role in the pathogenesis of MMP-9 mediated corneal matrix degradation. The efficacy of doxycycline in treating ocular surface diseases may be related to its ability to suppress MMP-9 production in the corneal epithelium.
A Filter-Based Approach to Detect End-of-Utterances from Prosody in Dialog Systems

We propose an efficient method to detect end-of-utterances from prosodic information in conversational speech. Our method is based on the application of a large set of binary and ramp filters to the energy and fundamental frequency signals obtained from the speech signal. These filter responses, which can be computed very efficiently, are used as input to a learning algorithm that generates the final detector. Preliminary experiments using data obtained from conversations show that an accurate classifier can be trained efficiently and that good results can be obtained without requiring a speech recognition system.
Power integrity analysis for core timing models

An improved framework of power integrity analysis for core logic timing analysis is presented in this paper. Due to ever increasing power consumption of core digital blocks, jitter due to supply noise contributes a significant timing error, and on-chip logic timing analysis requires accurate modeling of supply noise induced jitter. Jitter information provides additional information to define precise power distribution network (PDN) requirements. The formulation to predict the jitter due to core noise is first presented in this paper followed by the modeling flow that can conveniently be incorporated into existing static timing analysis (STA) analysis. The presented method accounts for potential jitter tracking or anti-tracking between data and clock paths and any AC noise behavior. It covers a general topology including unbalanced clock trees, multi-cycle data paths, and multiple-power domains.
DYNAMICS OF TRANSVERSELY VIBRATING BEAMS USING FOUR ENGINEERING THEORIES

Abstract In this paper, the full development and analysis of four models for the transversely vibrating uniform beam are presented. The four theories are the Euler–Bernoulli, Rayleigh, shear and Timoshenko. First, a brief history of the development of each beam model is presented. Second, the equation of motion for each model, and the expressions for boundary conditions are obtained using Hamilton's variational principle. Third, the frequency equations are obtained for four sets of end conditions: free–free, clamped–clamped, hinged–hinged and clamped–free. The roots of the frequency equations are presented in terms of normalized wave numbers. The normalized wave numbers for the other six sets of end conditions are obtained using the analysis of symmetric and antisymmetric modes. Fourth, the orthogonality conditions of the eigenfunctions or mode shape and the procedure to obtain the forced response using the method of eigenfunction expansion is presented. Finally, a numerical example is shown for a non-slender beam to signify the differences among the four beam models.
Critical issues confronting the advancement of applied sport psychology

Abstract Despite considerable progress over the last 10 years, applied sport psychology confronts several persistent issues that continue to limit the growth and development of the field. Specifically, issues requiring more comprehensive and proactive attention and initiatives include: the training of graduate students, the accreditation of graduate programs, the job market, and the establishment of systematic educational outreach programs. Suggestions are offered regarding how enhancements in each of the aforementioned issues can be initiated, and potential benefits gained by students, faculty, and the general public are identified and discussed. Given the climate in many academic institutions emphasizing program downsizing, sport psychology may be approaching and confronting one of the most crucial crossroads in its existence. Without direct efforts to assure academic credibility and public confidence in the standards of training and practice, sport psychology may fail to actualize a meaningful future r...
Chemotherapy of non-small cell lung cancer: Clinical trials at the Memorial Sloan-Kettering Cancer Center

Bronchogenic carcinoma is one of the most difficult and pressing problems in cancer therapy. Overall survival of 799 primary cases at Memorial Sloan-Kettering Cancer Center was 7.8%, reflecting the advanced nature of most lung cancer at the time of presentation and the inadequacy of current local therapies as potential cures. The need for effective systemic therapy having acceptable toxicity is obvious. From 1972 to 1975, four combination drug regimens were tested at the Center: MAV, MFC, CAMF, and VAB. Despite the lack of significant responses, the median survival was 2.5 to 6 months. A subsequent study of the effect of high doses of cyclophosphamide, followed by high doses of methotrexate with leukovorin rescue, produced significant toxicity; partial responses were seen in 5/20 patients. Other agents tested have included pyrazofurin, vindesine, chlorozotocin, PCNU, PALA, m-AMSA, and interferon. Only vindesine has shown promise. Recent trials of cisplatin (DDP) in combination with vindesine have been encouraging. Eighty-one patients with measurable inoperable non-small cell lung cancer have been treated with this combination. Toxicity has been easily managed. Complete or partial responses have been demonstrated in 43 percent of 35 patients. Duration of response has been significantly greater for patients receiving high-dose DDP as compared to low-dose DDP. Addition of cyclophosphamide to the regimen appeared to offer no obvious advantages. Future studies include a clinical trial of the DDP-vindesine combination in the adjuvant setting.
Stabilization of Low-Frequency Oscillations of Liquid Propellant Rockets with Fuel Line Stabilizer

Chugging oscil lations of a liquid propellant rocket may be explained by using a feedback system principle in which the dynamic characteristics of the fuel supply sys tem play an important role. Suitable modification of the fuelsupply system performance can stabilize the chugging act ion. In the chugging-frequency range, this dynamic performance approaches those of a first-order system. The use of a high injector restriction factor can give a stabil ization effect equivalent to that of a lead-lag ne t work used in a servo sys tem, but it is undesirable because of the large supply pressure required. Two basic types of stabilizer that can modify the dynamic characteristics of the fuel supply sys tem sufficiently to give a stabil ization effect wi thout the need of high supply pressure are introduced. The various dynamic and static characteristics of these stabilizers are analyzed. The design problems are also discussed.
Metabolism and excretion of aminopyrine by cows

Abstract The metabolism and excretion of aminopyrine were studied in normal lactating dairy cattle. Cows were placed in a stall and catheters for blood and urine collection were fixed in place. Loading doses of aminopyrine ranging from 11.3 to 35.3 mg/kg were given intravenously. Plasma, milk, and urine samples were taken simultaneously for 24 hours. Evidence is presented which indicates that aminopyrine is metabolized to aminoantipyrine and N-acetyl-4-aminoantipyrine. Small amounts of conjugated 4-hydroxyantipyrine were also recovered from the urine. Hydroxylation and conjugation of either aminopyrine or 4-aminoantipyrine occur in the cow. Cows given 4-aminoantipyrine showed significant levels of N-acetyl-4-aminoantipyrine in the plasma and urine. When N-acetyl-4-aminoantipyrine was infused, no aminopyrine or 4-aminoantipyrine could be detected in urine or plasma. An average of 32.4, 9.2, 24.5, and 0.57% of the aminopyrine given was excreted in the urine as unchanged aminopyrine, aminoantipyrine, acetylaminoantipyrine, and 4-hydroxyantipyrine, respectively.
The Database of Court Officers

T history of courts has too often focused on individuals who knew the king, wrote for him or painted him. While such work is of obvious value, it neglects one of the most important and interesting of the implications of Norbert Elias's The Court Society: that courts were societies or communities in their own right, however inter-connected with the larger societies over which they presided. To understand how courts worked and what it was like to attend them, to evoke the experience of those who served in them, it is necessary to understand courts from top to bottom. It is necessary, in short, to confront the experience of all those who served at courts, from lords chamberlain and steward to stable groom or chamber maid. Unfortunately, this is easier said (or urged upon others) than done. Stable grooms and chamber maids are unlikely to have left collections of correspondence, diaries or personal account books. They figure in official documentation, household ordinances or advice books, much as they figure in contemporary painting: as part of a necessary, but ultimately anonymous and undifferentiated, cast of characters, lurking in the background, the individual members of which were virtually interchangeable. Is there no way to engage with their experience and use it to enhance our understanding of the court as a whole? I would ,submit that, within the British historiographical tradition, at least, the way forward was shown long ago in the work of scholars like Sir Lewis Namier and his successors at the History of Parliament; Gerald Aylmer in his two great books on the personnel of seventeenth-century government, The King s Servants and The State s Servants; 1 and the army of demographic, social and local historians who have, over the last half-century, attempted to reconstruct the English metropolis, county, town and village. Each of these historians or groups of historians has sought to understand the structure, the experience and even the ethos of particular communities or institutions, through a composite picture built up from the biographical details of the individuals who composed them. In short, each has sought to understand the whole through the particular experiences of its individual parts. The purpose of this article is to inform readers of The Court Historian of a project currently in progress, which attempts to apply some of the techniques of the demographic, social and local historian, not to a county or a village community, but to the English Court in the period 1660-1837. The Database of Court Officers (DCO) is a computer database which will, upon completion, contain the career particulars of every officer and servant of the royal household who was sworn into service between the restoration of Charles II and the accession of Queen Victoria. Before explaining what this means and assessing its potential to enhance our understanding of the English Court, it is necessary to explain the genesis of and sources for the project.
Boron Neutron Capture Therapy: Cellular Targeting of High Linear Energy Transfer Radiation:

Boron neutron capture therapy (BNCT) is based on the preferential targeting of tumor cells with (10)B and subsequent activation with thermal neutrons to produce a highly localized radiation. In theory, it is possible to selectively irradiate a tumor and the associated infiltrating tumor cells with large single doses of high-LET radiation while sparing the adjacent normal tissues. The mixture of high- and low-LET dose components created in tissue during neutron irradiation complicates the radiobiology of BNCT. Much of the complexity has been unravelled through a combination of preclinical experimentation and clinical dose escalation experience. Over 350 patients have been treated in a number of different facilities worldwide. The accumulated clinical experience has demonstrated that BNCT can be delivered safely but is still defining the limits of normal brain tolerance. Several independent BNCT clinical protocols have demonstrated that BNCT can produce median survivals in patients with glioblastoma that appear to be equivalent to conventional photon therapy. This review describes the individual components and methodologies required for effect BNCT: the boron delivery agents; the analytical techniques; the neutron beams; the dosimetry and radiation biology measurements; and how these components have been integrated into a series of clinical studies. The single greatest weakness of BNCT at the present time is non-uniform delivery of boron into all tumor cells. Future improvements in BNCT effectiveness will come from improved boron delivery agents, improved boron administration protocols, or through combination of BNCT with other modalities.
Competition between Species: Frequency Dependence

Whether two species competing for the same limited resources can stably coexist has been subject to controversy for several decades. The relative fitnesses of two species of Drosophila under competition in laboratory populations are shown to be inversely related to the relative frequencies of these species. This frequency-dependent fitness leads to a stable coexistence of the two species in spite of their competition for limited resources.
Accumulation of Non-steroidal Anti-inflammatory Drugs by Gingival Fibroblasts

Non-steroidal anti-inflammatory drugs (NSAIDs) are used to manage pain and inflammatory disorders. We hypothesized that gingival fibroblasts actively accumulate NSAIDs and enhance their levels in gingival connective tissue. Using fluorescence to monitor NSAID transport, we demonstrated that cultured gingival fibroblasts transport naproxen in a saturable, temperature-dependent manner with a K(m) of 127 mug/mL and a V(max) of 1.42 ng/min/mug protein. At steady state, the intracellular/extracellular concentration ratio was 1.9 for naproxen and 7.2 for ibuprofen. Naproxen transport was most efficient at neutral pH and was significantly enhanced upon cell treatment with TNF-alpha. In humans, systemically administered naproxen attained steady-state levels of 61.9 mug/mL in blood and 9.4 mug/g in healthy gingival connective tissue, while ibuprofen attained levels of 2.3 mug/mL and 1.5 mug/g, respectively. Thus, gingival fibroblasts possess transporters for NSAIDs that are up-regulated by an inflammatory mediator, but there is no evidence that they contribute to elevated NSAID levels in healthy gingiva.
Ab initio Study of the Structural, Tautomeric, Pairing, and Electronic Properties of Seleno-Derivatives of Thymine

The structural, tautomeric, hydrogen-bonding, stacking, and electronic properties of a seleno-derivative of thymine (T), denoted here as 4SeT and created by replacing O4 in T with Se, are investiga...