cssi/SciSciGPT-SciSciNet huggingface dataset:
Uncovering Androgen Responsive Regulatory Networks in Prostate Cancer

An important goal for prostate cancer therapy is to identify novel mechanisms of androgen signaling that may provide new targets for androgen blockade therapy. Androgen regulated target genes continue to be identified, and include genes with regulatory regions containing 1) classical dimeric androgen receptor elements, or 2) sites for other transcription factors that tether androgen receptor to a regulatory region lacking androgen receptor binding sites, or 3) non-canonical half-sites. The latter category of half-sites is becoming increasingly important, because up to 80% of potential androgen receptor regulatory regions identified by chromatin immunoprecipitation microarray technology contain these monomeric half-sites [1-3]. Determining which of these predicted target genes and androgen pathways are functional is very important, as they contribute to our understanding of prostate cancer progression. Microarray analyses were used to identify genes expressed in laser captured prostate cancer epithelial cells [4], leading to identification of pathways of co-regulated genes. It is expected that important regulatory regions would be conserved between mammalian genomes, thus, comparative evolutionary analyses were used to identify evolutionary conserved transcription factor binding sites [5]. Notably, non-canonical androgen receptor half-sites were identified in a majority of the gene promoters analyzed, and these sites were adjacent to evolutionary conserved zinc finger transcription factor sites. Subsequent ChIP assays showed that indeed SP1, WT1 and AR proteins all bind to a common regulatory region, indicating potential for interaction between these transcription factors that in turn can modulate hormone responsiveness. Overall, our bioinformatics screening coupled with experimental validation has revealed critical components of regulatory networks important in prostate cancer cells and disease progression.
Choosing the best knowledge base system for large semantic web applications

We present an evaluation of four knowledge base systems with respect to use in large Semantic Web applications. We discuss the performance of each system. In particular, we show that existing systems need to place a greater emphasis on scalability.
The Use of Network Analysis to Strengthen Community Partnerships

Community partnerships or networks of collaborating public and nonprofit organizations are an important way of addressing a wide range of problems and needs that communities face. In the academic literature, network analysis has been used to analyze and understand the structure of the relationships that make up multiorganizational partnerships. But this tool is not well-known outside the small group of researchers who study networks, and it is seldom used as a method of assisting communities. This article briefly discusses network analysis and how community leaders can use the results generated by this tool to strengthen relationships among public and nonprofit organizations, thereby building the community's capacity to address critical needs in areas such as health, human services, social problems, and economic development.
On representation of Poisson mixtures as Poisson sums and a characterization of the gamma distribution

A necessary and sufficient condition for a Poisson mixture with an exponential type mixing distribution to be equivalently represented as a Poisson sum is obtained. The problem of deriving a similar condition under any mixing distribution on (0, ∞) is discussed. Finally, a characterization of the gamma distribution is obtained.
Footprint modeling for vegetation atmosphere exchange studies: a review and perspective

The footprint of a turbulent flux measurement defines its spatial context. With the onset of long-term flux measurement sites over forests and other inherently inhomogeneous areas, and the development of the FLUXNET program, the need for flux footprint estimations has grown dramatically. This paper provides an overview of existing footprint modeling approaches in the critical light of hindsight and discusses their respective strengths and weaknesses. The second main objective of this paper is to establish a formal connection between micrometeorological measurements of scalar fluxes and their mass conservation equation, in a surface–vegetation–atmosphere volume. An important focus is to identify the limitations of the footprint concept and to point out situations where the application of footprint models may lead to erroneous conclusions, as much as to demonstrate its utility and power where warranted. Finally, a perspective on the current state-of-the-art of footprint modeling is offered, with a list of challenges and suggestions for future directions. © 2002 Elsevier Science B.V. All rights reserved.
Amorphous silicon carbide films by plasma-enhanced chemical vapor deposition

Plasma-enhanced chemical vapor deposition (PECVD) of amorphous silicon carbide ( alpha -SiC) is studied. PECVD allows deposition of alpha -SiC on a variety of substrates at low temperatures. The index of refraction of the deposited alpha -SiC films was in the range of 1.9 to 2.4 depending on the SiH/sub 4//CH/sub 4/ gas flow ratio and RF power. The deposition rate of alpha -SiC films, averaging 45 AA/min, increased with increasing RF power and pressure, and with decreasing substrate temperature. The quality of the deposited films could be improved by high-temperature annealing. The HF etch rate of the PECVD SiC films in HF is small enough (i.e., 5 AA/s on the average) to enable utilization of these films in surface micromachining processes which use silicon dioxide as a sacrificial layer. >
Annulusmagnus and Ascitendus, two new genera in the Annulatascaceae

Two pyrenomycetes in the Annulatascaceae described from freshwater, Annulatascus triseptatus and Ascolacicola austriaca, are reported from North and South America for the first time. Both species occur commonly on submerged wood in the U.S.A. The two taxa are similar morphologically in having black coriaceous ascomata, cylindrical necks, septate paraphyses, cylindrical pedicellate asci with prominent apical rings and three-septate ascospores. Molecular data demonstrates that Annulatascus is polyphyletic, with A. triseptatus on a clade widely separated from the type species of the genus, A. velatisporus. Ascolacicola austriaca is on a monophyletic clade within the Annulatascaceae as sister taxon of A. triseptatus. Based on morphological data and phylogenetic analyses of 28S rDNA sequence data, new genera Annulusmagnus and Ascitendus are established for Annulatascus triseptatus and Ascolacicola austriaca, respectively.
18O labeled nucleosides. 1. A general method for the synthesis of specifically labeled pyrimidine deoxyribosides

A facile method for the preparation of 18O labeled pyrimidine deoxyribosides is described. The method provides a means of selectively labeling the base, sugar or both the base and sugar moieties with high levels of 18O. Thymidine is used as a model to illustrate the method. The site and level of label was established using mass spectrometry.
An integrative theory of prefrontal cortex function

▪ Abstract The prefrontal cortex has long been suspected to play an important role in cognitive control, in the ability to orchestrate thought and action in accordance with internal goals. Its neural basis, however, has remained a mystery. Here, we propose that cognitive control stems from the active maintenance of patterns of activity in the prefrontal cortex that represent goals and the means to achieve them. They provide bias signals to other brain structures whose net effect is to guide the flow of activity along neural pathways that establish the proper mappings between inputs, internal states, and outputs needed to perform a given task. We review neurophysiological, neurobiological, neuroimaging, and computational studies that support this theory and discuss its implications as well as further issues to be addressed
Interaction between insect strain and artificial diet in diamondback moth development and reproduction

The economical production of physiologically and behaviorally competent diamondback moth (DBM), Plutella xylostella (L.) (Lepidoptera: Plutellidae), is critical to most research and control programs against this insect. Although a few laboratory-adapted colonies are currently maintained on artificial diets, the establishment and adaptation of feral DBM onto semi-synthetic diets is often difficult. Understanding the interactions between insect strain and diet may be critical to the process of laboratory adaptation as well as to the successful use of laboratory-reared insects in the field. As such, the objective of this study was to investigate the interaction between several DBM colonies/strains and different natural and semi-synthetic diets. Specifically, we examined the effect of different diets on the length of development, percent survival, adult weight, female fecundity, and adult longevity for two feral and one laboratory-adapted strain of DBM. Significant interactions were observed between diet and laboratory-adapted and feral strains, and also between diet and different feral strains with respect to many of the growth and development parameters tested. Therefore, the performance of one strain of DBM on a particular diet was not necessarily predicted by the performance of another DBM strain on the same diet. However, the soy-based diet developed and reported herein performed well for all three DBM strains tested. In future efforts to colonize feral DBM, we suggest that researchers assay different diet formulations in order to identify a semi-synthetic diet that is most suitable for the particular DBM strain under consideration.
Geoacoustic Models of the Seabed to Support Range-Dependent Propagation Studies on the Scotian Shelf

Joint long-range propagation experiments were performed at two sites in the Western North Atlantic by the Applied Research Laboratory (ARL) of The Pennsylvania State University, and the Defence Research Establishment Atlantic (DREA) of Dartmouth, Nova Scotia. One result of this program was the development of geoacoustic models of the seabed along the propagation tracks between the shallow (ARL) and deep (DREA) receiving arrays. The seabed models are based on profiling performed with the Huntec Deep-Tow System, grab sample data supplied by the Bedford Institute of Oceanography of Dartmouth, Nova Scotia, and dispersion and seismic refraction analysis. Each track is divided into a number of regions, with each region characterized by a geoacoustic model of two to four layers. Compressional wave attenuation values are predicted for each layer, from Huntec and grab sample data, by the Biot-Stoll Sediment model and by historical data. Using the seabed models as inputs to an adiabatic, normal-mode propagation model, transmission loss is predicted and compared with experimental losses measured at the ARL array.
Behavior of Electrodeposited Cd and Pb Schottky Junctions on CH3-Terminated n-Si(111) Surfaces

n-Si/Cd and n-Si/Pb Schottky junctions have been prepared by electrodeposition of Cd or Pb from acidic aqueous solutions onto H-terminated and CH3-terminated n-type Si(111) surfaces. For both nondegenerately (n-) and degenerately (n+-) doped H–Si(111) electrodes, Cd and Pb were readily electroplated and oxidatively stripped, consistent with a small barrier height (Phib) at the Si/solution and the Si/metal junctions. Electrodeposition of Cd or Pb onto degenerately doped CH3-terminated n+-Si(111) electrodes occurred at the same potentials as Cd or Pd electrodeposition onto H-terminated n+-Si(111). However, electrodeposition on nondegenerately doped CH3-terminated n-Si(111) surfaces was significantly shifted to more negative applied potentials (by −130 and −347 mV, respectively), and the anodic stripping of the electrodeposited metals was severely attenuated, indicating large values of Phib for contacts on nondegenerately doped n-type CH3–Si(111) surfaces. With either Cd or Pb, current–voltage measurements on the dry, electrodeposited Schottky junctions indicated that much larger values of Phib were obtained on CH3-terminated n-Si(111) surfaces than on H-terminated n-Si(111) surfaces. Chronoamperometric data indicated that CH3–Si(111) surfaces possessed an order-of-magnitude lower density of nucleation sites for metal electrodeposition than did H–Si(111) surfaces, attesting to the high degree of structural passivation afforded by the CH3–Si surface modification.
Nkx6 genes pattern the frog neural plate and Nkx6.1 is necessary for motoneuron axon projection

Neuronal subtypes originate from an undifferentiated neural epithelium that is progressively divided into progenitor domains by homeodomain transcription factors such as members of the Nkx family. Here we report the functional analysis of Nkx6.1 and Nkx6.2 in Xenopus. While Nkx6.2 is expressed early in a large region of the medial neural plate, Nkx6.1 is restricted to a region overlapping with the region of motor neuron formation. By mRNA injection we show that both can inhibit primary neurogenesis as well as expression of intermediate neural plate markers. However, they do not form auto-regulatory loops and fail to induce ectopic motor neurons as they do in the chick. Using morpholino-mediated knockdown in Xenopus laevis and Xenopus tropicalis we show that Nkx6.1 knockdown results in paralyzed tadpoles. Using DiI labeling and immunohistochemistry we show that the underlying mechanism is a failure of spinal motor neurons to extend axons to their targets. Analysis of neural pattern reveals that ventral Lhx3+ and Pax2+ interneurons are dependent on Nkx6.1 function, but overall neural patterning is not. This study illustrates that while important aspects of Nkx6 gene function are conserved in vertebrate neural patterning, others are not.
An introduction to randomized algorithms

CA 94720, USA; and Karp, R.M., An introduction to randomized algorithms, Discrete Applied Mathematics 34 (1991) 165-201. Research conducted over the past fifteen years has amply demonstrated the advantages of algorithms that make random choices in the course of their execution. This paper presents a wide variety of examples intended to illustrate the range of applications of randomized algorithms, and the general principles and approaches that are of greatest use in their construction. The examples are drawn from many areas, including number theory, algebra, graph theory, pattern matching, selection, sorting, searching, computational geometry, combinatorial enumeration, and parallel and distributed computation. 1. Foreword
Energy-delay optimization of thin-body MOSFETs for the sub-15 nm regime

This work presents the design of enhancement-mode and accumulation-mode thin-body MOSFETs optimized in terms of energy vs. delay (E-D), and assesses the effectiveness of back-gate biasing to adjust the leakage current. It is shown that back-gated FETs (BG-FETs) can provide power savings over double-gate FETs. Since BG-FETs span a wide range in E-D space, they can provide a single-device solution for high-performance and low-power applications through adaptive supply-voltage and threshold-voltage biasing.
Learner-Generated Attention to Form.

Results of recent studies, some of which appear in this volume, suggest that the incorporation of some degree of focus on form (FonF) into meaning-centered instruction can lead to improved performance in processing input and increased accuracy in production. Long (1983) originally defined FonF as a brief turning of attention to some formal feature while the overriding focus of the interaction remains on meaning. Ideally, this focus should arise incidentally, in response to some problem in comprehension or production. The incidental nature of the interaction would be more likely to result in focus on a form to which the learner is attending and is ready to notice. However, to ascertain the effect of such a focus in an experimental setting, it becomes necessary to manipulate the situation somewhat, in particular, to predetermine the formal focus and to ensure that it will occur. As a result, in most studies the focus is provided by the researcher and delivered intentionally, and usually extensively, through the teacher or special materials. Thus, the focus no longer arises incidentally, potentially vitiating the effectiveness of the intervention. This study differs from previous studies in two ways. First, it is set in intact classrooms, so all episodes involving focus on form arise incidentally. Second, it examines only such episodes as are initiated by learners. The justification for this is an extension of the argument for incidental FonF. If the effectiveness of FonF is ultimately determined by learner need, then it is essential to examine the episodes in which the learners themselves choose to focus on formal aspects of language. The study addresses the following research questions: Do learners initiate attention to form, as requests for assistance, feedback on error, modeling, or fine tuning, that is, repetitions, recasts, and requests for clarification? If so, on what kinds of forms do they choose to focus? The results suggest that learners can and do attend to form, though relatively infrequently. The most frequent way that they do this is t o request assistance from their teachers. Learner-generated attention to form increases considerably with rising proficiency and during specific activities. In general, the likelihood of learner-generated attention to form seems to be linked to learners' perception of the goals of the activity. In addition, as learners' proficiency increases, they are less likely to rely on their teachers for help. Finally, episodes that involve learners-generated attention to form revolve largely around lexis. More than anything else, learners want to know about words.
Variations in PET/CT Methodology for Oncologic Imaging at U.S. Academic Medical Centers: An Imaging Response Assessment Team Survey

In 2005, 8 Imaging Response Assessment Teams (IRATs) were funded by the National Cancer Institute (NCI) as supplemental grants to existing NCI Cancer Centers. After discussion among the IRATs regarding the need for increased standardization of clinical and research PET/CT methodology, it became apparent that data acquisition and processing approaches differ considerably among centers. To determine the variability in detail, a survey of IRAT sites and IRAT affiliates was performed. Methods: A 34-question instrument evaluating patient preparation, scanner type, performance approach, display, and analysis was developed. Fifteen institutions, including the 8 original IRATs and 7 institutions that had developed affiliate IRATs, were surveyed. Results: The major areas of variation were 18F-FDG dose (259–740 MBq [7–20 mCi]) uptake time (45–90 min), sedation (never to frequently), handling of diabetic patients, imaging time (2–7 min/bed position), performance of diagnostic CT scans as a part of PET/CT, type of acquisition (2-dimensional vs. 3-dimensional), CT technique, duration of fasting (4 or 6 h), and (varying widely) acquisition, processing, display, and PACS software—with 4 sites stating that poor-quality images appear on PACS. Conclusion: There is considerable variability in the way PET/CT scans are performed at academic institutions that are part of the IRAT network. This variability likely makes it difficult to quantitatively compare studies performed at different centers. These data suggest that additional standardization in methodology will be required so that PET/CT studies, especially those performed quantitatively, are more comparable across sites.
Characterization of a New and Complete Lead-Free Thick Film Resistor System for the Hybrid Circuit Market

The move to lead-free thick film technology, including resistors does not necessarily mean a move away from performance. There have been many recent developments in the area of lead-free glasses, thick film dielectrics, and conductor materials. However, the development of lead-free resistor materials has been slower to enter the market. This slower evolution is due, in part, to the need to develop a series of discrete compositions that are compatible with each other and cover a wide range of resistance values. There can be 8–10 individual members in such a series. The primary goal of this development was to achieve resistor performance on par with, or superior to an existing and popular premium lead based resistor system. This paper describes a new series of lead-free thick film resistor compositions that cover a complete range of decade values from 1 Ohm/square to 10 MegOhms/square. Each member is compatible and blendable with adjacent members to cover all possible resistivity needs. This system provides...
Addressing the Language Classroom Competencies of the European Higher Education Area Through the Use of Technology

This chapter focuses upon the use of technology to address the language classroom competencies of the European Higher Education Area (EHEA). Through an exploration of previous research into the intersection of technology and language learning, the authors identify a variety of ways that these core competencies can be addressed. The authors contextualize these suggestions within pedagogical practice that is focused upon project-based learning with attention paid to tasks in an array of contexts. The practices are presented within frameworks for both telecollaboration and local collaboration. The authors focus upon addressing both the general and discipline-specific competency frameworks within the EHEA.
Congress, the Commander-in-Chief, and the Separation of Powers After Hamdan

In Hamdan v. Rumsfeld, the U.S. Supreme Court held that military tribunals established by President Bush were unlawful because they were inconsistent with the Uniform Code of Military Justice, concluding that, Whether or not the President has independent power, absent congressional authorization, to convene military commissions, he may not disregard limitations that Congress has, in proper exercise of its own war powers, placed on his powers. Moreover, the Court reached this conclusion notwithstanding debates in recent years over the Commander-in-Chief override, and the considerable questions as to Congress's power to interpose substantive limitations on the President's war powers. In this Essay, I compare the rationale behind Justice Stevens's majority opinion in Hamdan with two early Supreme Court decisions - Little v. Barreme and Brown v. United States - and suggest that Hamdan is, or at least appears to be, the reaffirmation of a formalist approach to separation of powers cases in fields where Congress has legislated. Thus, although the key passage from Hamdan cites Justice Jackson's canonical concurrence, the logic of the opinion is more comparable to the forgotten concurrence of Justice Clark. But the harder question is whether Hamdan's separation-of-powers formalism is anything more than sui generis. Thus, the Essay concludes by suggesting that the common thread, in Little, Brown, Youngstown, and Hamdan, is the strength of the textual argument in favor of Congress's regulatory power. After Hamdan, then, courts and commentators alike may well need to pay far closer attention to the specific congressional powers implicated in each case where the Executive Branch argues that Congress cannot interfere.
A Paired Comparison Nested Logit Model of Individual Preference Structures

Models that rely on the assumption of simple scalability have dominated multiattribute choice and preference modeling for almost 20 years, despite the fact that simple scalability is violated in ma...
Financial Literacy in the Czech Republic

This paper analyses the need to deal with the issue of financial literacy and financial knowledge not only by adults, but also by youth and young adults. This paper is focused on research into the knowledge and understanding of the financial literacy of young people, mostly between the ages of 16 to 33 years, via a questionnaire. The survey, undertaken in the Czech Republic, is based on a sample of 329 students from high schools and 329 students from the University of South Bohemia in Ceske Budějovice [658].
485 APURINIC/APYRIMIDINIC ENDONUCLEASE ACTIVITY CONTRIBUTES TO RESISTANCE IN EPENDYMOMAS.

Background Ependymomas are brain tumors with a 10-year recurrence rate of 90-95% with local distribution; 5-year progression-free survival rates in children currently are approximately at around 14%. Apurinic/apyrimidinic endonuclease (Ap endo) is a key DNA repair enzyme that confers resistance to radiation-induced cytoxic abasic sites in human cells. We assayed Ap endo activity in ependymomas to establish correlates with tumor and patient characteristics and with response to adjuvant radiation therapy. Study Design and Methods In cell lines Ap endo activity was suppressed by transfection with antisense siRNA and exposed to radiation. Suppression of Ap endo activity was accompanied by increased sensitivity to radiation. In vivo, Ap endo activity was assayed from 21 ependymomas from patients at Children9s Hospital and Regional Medical Center of which 11 tumors progressed following radiation. Cox proportional hazards regression models were used to analyze the association of activity with time to tumor progression (TTP). Results In a multivariate model, with Ap endo activity entered as a continuous variable, the hazard ratio for progression after radiation treatment in 21 individuals increased by a factor of 1.34 for every 0.01 unit increase in activity ( p Conclusion Our results suggest that apurinic endonuclease activity may provide resistance to radiation therapy and serve as a predictive marker to treatment response and suggest that the use of Ap endo inhibitors has the ability to be clinically efficacious in overcoming resistance.
A paradigm for the evaluation and management of spinal coccidioidomycosis

Background Coccidioidomycosis is a fungal infection that is endemic to parts of the Southwestern United States. When infection involves the spine, the treatment strategies can be challenging. We have devised a management protocol for spinal coccidioidomycosis based on a review of the literature and our experience. Methods The electronic literature search of National Library of Medicine for publications from 1964 to 2014 was performed using the following keywords: Coccidioidomycosis and spine. The search yielded 24 papers. Treatment strategies were summarized into a treatment protocol. Results A total of 164 cases of spinal coccidioidomycosis were identified, ranging in age from 80 years. Males (n = 131) and African-Americans (n = 79) were strikingly over-represented. Medical therapy: Once a diagnosis of spinal coccidioidomycosis is established, antifungal therapy should always be started. Antifungal therapy with amphotericin B or azoles like fluconazole. Medical therapy needs to be continued for many years and sometimes indefinitely to reduce disease recurrence or progression. Surgical management is indicated in cases with mechanical instability, neurologic deficit, medically intractable pain, or progression of infection despite antifungal therapy. Conclusions This work provides a working protocol involving assessment and reassessment for the management of spinal coccidioidomycosis. Medical management with antifungal agents in some cases can provide satisfactory disease control. However, in patients with mechanical instability, neurologic deficit, medically intractable pain or disease progression disease control may only be achieved with surgical debridement and stabilization.
Diagnostic challenges in ALS

Although the essential requirements for diagnosis of amyotrophic lateral sclerosis (ALS) are clearly defined by the El Escorial criteria, many physicians, including neurologists, still miss the diagnosis. Physician misdiagnosis of ALS relates to lack of knowledge about ALS and skill and to diagnostic difficulty. The differential diagnosis must exclude nonmotor neuron diseases and other adult-onset motor neuron diseases with restricted presentations, e.g., progressive bulbar palsy (pure bulbar), progressive muscular atrophy (pure lower motor neuron) and primary lateral sclerosis (pure upper motor neuron), ALS-like syndromes and ALS variants, and adult-onset spinal muscular atrophies. Although the diagnosis of ALS remains a clinical one, laboratory testing can be used to exclude other diseases and to confirm the diagnosis. Such tests include EMG and nerve conduction studies, MRI and CT of the spine and brain, identification of biochemical markers in blood and CSF, and muscle or nerve biopsy. Genetic testing can identify gene defects in some types of familial ALS and in certain other inherited motor neuron diseases that mimic ALS. At present there is no widely accepted protocol for laboratory testing in cases of suspected ALS, but it is hoped that laboratory tests will improve in the future to facilitate earlier confirmation of a diagnosis of ALS. However, correct and early diagnosis of ALS can only be achieved when the first, second, or third physician who sees the patient knows about ALS and includes it in a differential diagnosis.
‘There were ethical dilemmas all day long!’: harrowing tales of ethnographic researchers in criminology and criminal justice

AbstractWhile there have been many ethnographies published within the disciplines of criminology and criminal justice, very few studies have examined actual field researchers who have successfully employed this qualitative technique. In this exploratory study, we identified and conducted phone interviews with a sample of eight scholars who have used variations of the ethnographic method to study aspects of life which relate to crime, deviant behavior, and social control. Respondents revealed to us their colorful stories, as well as the risks, rewards, and ethical dilemmas they experienced while attempting to balance the delicate roles of being insiders, outsiders, researchers, and participants. They specifically discussed how they negotiated the personal and professional obstacles of being thrust into criminal worlds (as well as criminal justice worlds) and ultimately managed to thrive while conducting fieldwork in perilous places.
Optimizing Outcome in Autism Spectrum Disorders

Autism spectrum disorders (ASDs) are usually lifelong with wide ranging functional outcomes. Intensive behavioral intervention, implemented early, can improve outcome significantly. Some individual...
The Mechanism of MnTE-2-PyP Functioning Differently in Cancer Cells and Normal Cells

Rationale: Radiotherapy reduces prostate cancer growth but patients suffer from side effects caused by the accumulation of reactive oxygen species. MnTE-2-PyP5+ reduces radiation induced side effects, while simultaneously inhibiting cancer progression. We hypothesize that MnTE-2-PyP increases H2O2 levels in cancer cells but not normal cells due to the difference in redox capacities between the two cell types. Methods Three cell lines, PC3, LNCaP, primary mouse fibroblasts(PMF) were treated with PBS or 30µM MnTE-2-PyP. A Ros-Glo assay was performed to measure H2O2 levels in MnTE-2- PyP treated or untreated cells. In order to measure protein oxidation in PC3 cells treated with MnTE-2-PyP, biotinylated iodoacetamide (BIAM) probe was used which binds only to reduced thiol groups. A western for streptavidin was performed to identify proteins containing reduced thiols. Mass Spec was performed to determine protein contents difference in both drug treated or untreated cells. An in gel catalase activity assay was performed for cells treated with or without MnTE-2-PyP. The EPR assay was conducted to detect the basal levels of O2– in 3 cell lines. Results MnTE-2-PyP significantly increased H2O2 level in PC3 cells and LNCaP cells as compared to PBS treated cells but no in normal primary fibroblasts. Accordingly, we found that the increased H2O2 in the cancer cells caused global oxidation of thiols in many different proteins. MnTE-2-PyP treatment increased the amount of oxidized proteins in PC3 cells but not in PMF. Mass spectrometry was performed to identify oxidized proteins in the presence of MnTE-2-PyP. Preliminary results have identified two proteins that are oxidized with MnTE-2-PyP treatment: serine/threonine-protein phosphatase PP1-beta catalytic subunit and Pre-mRNA-processing factor 19. One explanation for why more H2O2 is produced in cancer cells vs. normal cells is that normal cells may have more active H2O2 removing enzymes than cancer cells, like catalase. However, we found that LNCaP cells have the highest catalase activity than PMF and PC3. But MnTE-2-PyP did not change the catalase activity in any kind of cell line. We also measured basal levels of superoxide production in cancer vs. normal cells, since MnTE-2-PyP scavenges superoxide to produce H2O2. We found that PMF have higher basal superoxide radicals than PC3 cells and LNCaP cells. Conclusion MnTE-2-PyP increases H2O2 levels in cancer cells but not normal cells, which leads to the oxidation of proteins in PC3 cells. We hypothesized that this difference in H2O2 production could be due to the fact that cancer cells have a reduced ability to remove H2O2; however, our preliminary data do not support this hypothesis. There are other important H2O2 removing enzymes that we still need to measure to obtain the over antioxidant capacity of the cells.
Using tumor-associated antigen (TAA) chip technology to enhance antibody detection in immunodiagnosis of hepatocellular carcinoma

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA 3972 Liver cancer, especially hepatocellular carcinoma (HCC), is one of the most malignant tumors, which affects the Hispanic population of the United States at a rate double that of the white population. The majority of people with HCC will die within 1 year of its detection. This high case fatality rate can in part be attributed to lack of diagnostic methods that allow early detection. Therefore, there is an urgent need for the development of more HCC sensitive and specific approaches in the early detection of this cancer. In the present study, the proteomic approach was applied to identify HCC-related TAAs as markers in HCC. Twenty HCC sera and 10 normal human sera were collected from the US-Mexico border region, and further used in proteomic approach to identify potential TAAs. A total of 34 immunoreactive protein spots of interest were excised from the 2-DE gel, digested with trypsin, and subsequently analyzed by mass spectrometry (LC-MS/MS). Of 34 immunoreactive protein spots, 29 were finally identified. In particularly, four proteins were reported to be associated with HCC, and 14 with other type of cancers. In order to evaluate whether these identified proteins can be used as candidate markers in HCC, we have integrated our TAA array with protein chip technology to develop a novel TAA chip for further screening HCC serum samples. A total of 19 TAAs which includes 17 TAAs used in previous studies, and 2 TAAs identified in the above study were printed on microscope slide using a robotic arrayer. In the subsequent study, this TAA chip was used to screen 20 HCC sera and 10 normal sera for evaluating the potential application of this approach. The results indicated that different HCC serum had a different anti-TAA profile. For example, one HCC serum had immunoreactions with cyclin D, cyclin E, p62, koc, c-myc, survivin, wnt, and RalA, and another serum had immunoreactions with p16, cyclin D, cyclin E, koc, c-myc, survivin, wnt, and RalA. Of ten normal sera screened, only one had weak immunoreactions with cyclin D and wnt protein. Of 20 HCC sera tested, six sera showed a much higher intensity value compared to normal controls, indicating that antibody responses to 19 TAAs in some cancer patients were quite robust, and not just mildly elevated. This preliminary study also provides a possibility that a customized TAA chip can be developed in the future for immunodiagnosis of certain type of cancer.
Role of endothelial nitric oxide in control of peripheral vascular conductance during muscle metaboreflex activation

The muscle metaboreflex is a powerful pressor reflex induced by the activation of chemically sensitive muscle afferents as a result of metabolite accumulation. During submaximal dynamic exercise, t...
Mechanical demands on the lower back in patients with non-chronic low back pain during a symmetric lowering and lifting task.

Abstract There is limited information in the literature related to the lower back loading in patients with LBP, particularly those with non-chronic LBP. Toward addressing such a research gap, a case-control study was conducted to explore the differences in lower back mechanical loads between a group of females (n = 19) with non-chronic, non-specific LBP and a group of asymptomatic females (n = 19). The differences in lower back mechanical loads were determined when participants completed one symmetric lowering and lifting of a 4.5 kg load at their preferred cadence. The axial, shearing, and moment components of task demand at the time of peak moment component as well as measures of peak trunk kinematics were analyzed. Patient vs. asymptomatic group performed the task with smaller peak thoracic rotation and peak lumbar flexion. While no differences in the moment component of task demand on the lower back between the patients and controls were found, the shearing (40–50 age group) and axial components of task demand were, respectively, larger and smaller in patients vs. controls. Whether alterations in lower back loads in patients with non-chronic LBP are in response to pain or preceded the pain, the long-term exposure to abnormal lower back mechanics may adversely affect spinal structure and increase the likelihood of further injury or pain. Therefore, the underlying reason(s) as well as the potential consequence(s) of such altered lower back mechanics in patients with non-chronic LBP should to be further investigated.
Whole-exome sequencing for RH genotyping and alloimmunization risk in children with sickle cell anemia

RH genes are highly polymorphic and encode the most complex of the 35 human blood group systems. This genetic diversity contributes to Rh alloimmunization in patients with sickle cell anemia (SCA) and is not avoided by serologic Rh-matched red cell transfusions. Standard serologic testing does not distinguish variant Rh antigens. Single nucleotide polymorphism (SNP)–based DNA arrays detect many RHD and RHCE variants, but the number of alleles tested is limited. We explored a next-generation sequencing (NGS) approach using whole-exome sequencing (WES) in 27 Rh alloimmunized and 27 matched non-alloimmunized patients with SCA who received chronic red cell transfusions and were enrolled in a multicenter study. We demonstrate that WES provides a comprehensive RH genotype, identifies SNPs not interrogated by DNA array, and accurately determines RHD zygosity. Among this multicenter cohort, we demonstrate an association between an altered RH genotype and Rh alloimmunization: 52% of Rh immunized vs 19% of non-immunized patients expressed variant Rh without co-expression of the conventional protein. Our findings suggest that RH allele variation in patients with SCA is clinically relevant, and NGS technology can offer a comprehensive alternative to targeted SNP-based testing. This is particularly relevant as NGS data becomes more widely available and could provide the means for reducing Rh alloimmunization in children with SCA.
Does neoadjuvant/perioperative chemotherapy improve overall survival for T2N0 gastric adenocarcinoma?

BACKGROUND The purpose of this study was to determine whether neoadjuvant and/or perioperative chemotherapy (NAC) has an overall survival (OS) benefit for patients with T2N0 gastric adenocarcinoma. STUDY DESIGN We performed retrospective analyses using the National Cancer Data Base, 2004-2013. Patients with T2N0 gastric adenocarcinoma were divided into two treatment groups: (1) NAC plus surgery (NA + S) and (2) surgery alone (S). RESULTS Of 1,704 patients included, 277 (16.3%) received NAC, and 1,427 (83.7%) were treated with surgery alone. Patients in the NA + S group were more likely to be younger, have fewer comorbidities, and have larger tumors located in the proximal stomach. Although in an unadjusted analysis of OS, the NA + S group had improved survival compared to the S group (HR = 0.81, 95% CI 0.67-0.99, P < 0.0001), this was not maintained in a propensity adjusted analysis (HR = 0.89, 95% CI 0.68-1.18, P = 0.42). Similarly, propensity adjusted analyses accounting for potential bias from clinical misstaging or treatment effect from NAC did not show any OS benefit from NAC. CONCLUSION Based on the largest cohort of clinically staged T2N0 gastric adenocarcinoma, there was no OS benefit derived from NAC compared to surgery alone. For select patients with reliable preoperative staging, NAC may be omitted.
An activity theory perspective of how scenario-based simulations support learning: a descriptive analysis

The dominant frameworks for describing how simulations support learning emphasize increasing access to structured practice and the provision of feedback which are commonly associated with skills-based simulations. By contrast, studies examining student participants’ experiences during scenario-based simulations suggest that learning may also occur through participation. However, studies directly examining student participation during scenario-based simulations are limited. This study examined the types of activities student participants engaged in during scenario-based simulations and then analyzed their patterns of activity to consider how participation may support learning. Drawing from Engestrom’s first-, second-, and third-generation activity systems analysis, an in-depth descriptive analysis was conducted. The study drew from multiple qualitative methods, namely narrative, video, and activity systems analysis, to examine student participants’ activities and interaction patterns across four video-recorded simulations depicting common motivations for using scenario-based simulations (e.g., communication, critical patient management). The activity systems analysis revealed that student participants’ activities encompassed three clinically relevant categories, including (a) use of physical clinical tools and artifacts, (b) social interactions, and (c) performance of structured interventions. Role assignment influenced participants’ activities and the complexity of their engagement. Importantly, participants made sense of the clinical situation presented in the scenario by reflexively linking these three activities together. Specifically, student participants performed structured interventions, relying upon the use of physical tools, clinical artifacts, and social interactions together with interactions between students, standardized patients, and other simulated participants to achieve their goals. When multiple student participants were present, such as in a team-based scenario, they distributed the workload to achieve their goals. The findings suggest that student participants learned as they engaged in these scenario-based simulations when they worked to make sense of the patient’s clinical presentation. The findings may provide insight into how student participants’ meaning-making efforts are mediated by the cultural artifacts (e.g., physical clinical tools) they access, the social interactions they engage in, the structured interventions they perform, and the roles they are assigned. The findings also highlight the complex and emergent properties of scenario-based simulations as well as how activities are nested. Implications for learning, instructional design, and assessment are discussed.
The eyes have it: influenza virus infection beyond the respiratory tract.

Summary Avian and human influenza A viruses alike have shown a capacity to use the eye as a portal of entry and cause ocular disease in human beings. However, whereas influenza viruses generally represent a respiratory pathogen and only occasionally cause ocular complications, the H7 virus subtype stands alone in possessing an ocular tropism. Clarifying what confers such non-respiratory tropism to a respiratory virus will permit a greater ability to identify, treat, and prevent zoonotic human infection following ocular exposure to influenza viruses; especially those within the H7 subtype, which continue to cause avian epidemics on many continents.
Applications of Gait Analysis

The applications of gait analysis are divided into two categories: clinical gait analysis and scientific gait analysis. One problem with this distinction is that it implies that clinical gait analysis is not scientific, and that scientific gait analysis has no clinical value, neither of which is necessarily true. However, there are considerable differences in approach, and even larger differences in equipment, between the clinician who observes gait subjectively, with no technological aids, and the university biomechanics laboratory that uses the techniques of scientific gait analysis as a research tool. Clinical gait analysis has the aim of helping individual patients directly, whereas scientific gait analysis aims to improve the understanding of gait, either as an end in itself, or to improve medical diagnosis or treatment in the future. Clinical applications include decision making in a number of patient groups, especially children with cerebral palsy, and the use of gait analysis in the documentation of a patient's condition. Scientific gait analysis is divided into clinical and fundamental research, the former concentrating on disease processes and methods of treatment, the latter on methods of measurement, and the advancement of knowledge in biomechanics, human performance, and physiology.
Elder Financial Exploitation: A Strategy for Advancing Research, Theory and Policy

In 2012, Attorney General Eric Holder reported that as many as 1 in 5 elder Americans were victims of financial exploitation which is defined as the illegal use or appropriation of an elder citizen’s resources. Importantly, this 1 in 5 figure does not capture the full extent of elder financial exploitation because numerous cases go unreported. For example, U.S. Secretary of Health and Human Services Kathleen Sebelius reported that for every single report of elder abuse or financial exploitation there are 24 actual cases that were not reported. Clearly, elder financial exploitation is a serious social problem that will grow in the future as the proportion of population of elder citizens continues to expand. While research has increased in recent years, empirical and theoretical understanding of this social problem remains fragmented and inconclusive. As a result, our prevention and intervention polices are without the necessary evidence-based understanding required for effectiveness. Among the major empirical, theoretical and policy questions are: What is the prevalence of various types of elder financial exploitation? What factors contribute to victimization? How do we account theoretically for such victimization? And, what can be done to prevent and reduce it? This paper responds to these questions with a review of the relevant literature on elder financial exploitation toward the end of articulating a research strategy that would advance our theoretical and empirical knowledge of this important social problem, and notably, provide the necessary evidence-based understanding needed for more effective prevention policies and practices.
SETI: Assessing Imaginative Proposals

Supposedly one of the strengths of the search for extraterrestrial intelligence (SETI) community “is its imaginative capacity to take seriously things that most people dismiss out of hand.” That phrase, as we will see, was prompted, not by a speculative proposal, but by rash action that outraged some. It was followed by an editorial call for discussion and assessment as to how to proceed in the particular matter. As related to SETI, this chapter will broadly consider the question “How seriously should imaginative proposals be taken?” It shall provide guidelines for evaluating them and deciding “When does imaginative become outrageous?”