cssi/SciSciGPT-SciSciNet huggingface dataset:
Identification of the metal ligands and characterization of a putative zinc finger in methionyl-tRNA synthetase.

Abstract A truncated form of the methionyl-tRNA synthetase (delta MTS), which has been cloned, overproduced, and characterized, was used in an attempt to better understand the role of the enzyme-bound zinc in the amino-acylation process. Apo-, Zn(2+)-, Co(2+)-, and 113Cd(2+)-substituted delta MTS proteins were prepared in vivo and purified to homogeneity. Apo-delta MTS was devoid of enzymatic activity in the aminoacylation of tRNA(fMet) and in the methionine-dependent ATP-pyrophosphate exchange reactions. Kinetic constants in both the aminoacylation and ATP-pyrophosphate exchange reactions for the Co(2+)- and 113Cd(2+)-substituted delta MTS proteins were found to be identical with those of the native Zn2+ protein. The low energy absorption spectrum of Co(2+)-substituted delta MTS resembles the d-d transition bands characteristic of tetrahedrally coordinated Co(2+)-substituted proteins. A strong S-->Co2+ charge transfer absorption at 350 nm was clearly evident having a molar absorptivity consistent with four thiolate ligands. The environment of the metal center was further probed by measuring the 113Cd chemical shift of 113Cd(2+)-substituted delta MTS. A single resonance at 759.6 ppm was observed. This chemical shift is consistent with Cd2+ coordinated to four thiolate ligands. The Escherichia coli methionyl-tRNA synthetase contains a potential metal binding sequence Cys-X2-Cys-X9-Cys-X2-Cys in a connecting polypeptide within the nucleotide fold. Titration of a 21-amino acid peptide corresponding to this putative metal binding site, Cys145-Cys161, was shown to bind Co2+ with a Kd of 120 +/- 11 microM. These results demonstrate that the isolated zinc finger binding domain is capable of specifically forming a stoichiometric complex with the divalent cation. Taken together, our studies identify the 4 cysteine residues in the zinc finger-like domain as the metal binding ligands in the E. coli methionyl-tRNA synthetase. The role of the enzyme-bound metal appears to be structural and not directly involved in catalysis.
Update on Immunofluorescent Testing in Bullous Diseases and Lupus Erythematosus

One of the earliest methods for investigating the immunologic basis of disease was the use of immunofluorescence (IF) on skin biopsy specimens and serum. IF can be used to detect immunoglobulins, complement components, and fibrin. In some diseases, the IF findings are disease specific and diagnostic, especially in certain bullous diseases. The use of IF testing has increased with the recent development of the salt split skin technique. The newer IF findings in some well-established immunodermatologic diseases and several recently described diseases are discussed. A brief description of the techniques involved in direct and indirect IF is also presented.
The Importance of Consumer Behavior Compared to Other Business Courses

Twenty years ago consumer behavior was a new idea in the marketing curriculum of American colleges. Since them the course has increased in popularity. This propensity to install a consumer behavior course has paralleled the acceptance, by scholars and practitioners, of consumer orientation, i.e., the consumer must be satisfied at a profit. One assumes that as the consumer behavior course increased in popularity within marketing departments that the attitude of educators toward its relative importance would change. As a matter of fact, one result appears dependent upon the other.
Kaposi’s Sarcoma Herpesvirus Genome Persistence

Kaposi’s sarcoma-associated herpesvirus (KSHV) has an etiologic role in Kaposi’s sarcoma, primary effusion lymphoma and multicentric Castleman’s disease. These diseases are most common in immunocompromised individuals, especially those with AIDS. Similar to all herpesviruses, KSHV infection is lifelong. KSHV infection in tumor cells is primarily latent, with only a small subset of cells undergoing lytic infection. During latency, the KSHV genome persists as a multiple copy, extrachromosomal episome in the nucleus. In order to persist in proliferating tumor cells, the viral genome replicates once per cell cycle and then segregates to daughter cell nuclei. KSHV only expresses several genes during latent infection. Prominent among these genes, is the latency-associated nuclear antigen (LANA). LANA is responsible for KSHV genome persistence and also exerts transcriptional regulatory effects. LANA mediates KSHV DNA replication and in addition, is responsible for segregation of replicated genomes to daughter nuclei. LANA serves as a molecular tether, bridging the viral genome to mitotic chromosomes to ensure that KSHV DNA reaches progeny nuclei. N-terminal LANA attaches to mitotic chromosomes by binding histones H2A/H2B at the surface of the nucleosome. C-terminal LANA binds specific KSHV DNA sequence and also has a role in chromosome attachment. In addition to the essential roles of N- and C-terminal LANA in genome persistence, internal LANA sequence is also critical for efficient episome maintenance. LANA’s role as an essential mediator of virus persistence makes it an attractive target for inhibition in order to prevent or treat KSHV infection and disease.
EPR OF LASER-ANNEALED, ION-IMPLANTED SILICON

Electron paramagnetic resonance and ion backscattering measurements were made on ion-implanted, pulsed laser annealed silicon. For phosphorus implanted silicon (3×10 13 200 keV P + /cm 2 ) the electrical activity of the implanted donors is restored after laser annealing with ≥1.8 J/cm 2 . Silicon made amorphous with 2×10 15 200 keV Si + /cm 2 and implanted with 3×10 13 200 keV P + /cm 2 can be restored to crystallinity after laser annealing, but electrical activity of the P was not restored due to residual defects for laser energies ≲ 3 J/cm 2 . Electrical activity can be restored, at least in part, for amorphous silicon implanted at lower energies (≈ 50 keV). We also observed that N donors can be present after ion implantation with 28 Si + followed by laser annealing.
Transitioning From Medical Educator to Scholarship in Medical Education

Clinician educators spend most of their time in clinical practice, educating trainees in all types of care settings. Many are involved in formal teaching, curriculum development and learner assessment while holding educational leadership roles as well. Finding time to engage in scholarly work that can be presented and published is an academic expectation, but also a test of efficiency. Just as clinical research originates from problems related to patients, so should educational research originate from issues related to educating the next generation of doctors. Accrediting bodies challenge medical educators to be innovative while faculty already make the best use of the limited time available. One obvious solution is to turn the already existing education work into scholarly work. With forethought, planning, explicit expectations and use of the framework laid out in this article, clinical educators should be able to turn their everyday work and education challenges into scholarly work.
Cocycle and orbit equivalence superrigidity for coinduced actions

We prove a cocycle superrigidity theorem for a large class of coinduced actions. In particular, if
Wireless intraoperative real-time monitoring of neurotransmitters in humans

For decades, Fast Scan Cyclic Voltammetry (FSCV) has been an established method for investigating neurochemical changes in animal models. Various neurotransmitters have been monitored successfully in vivo with high spatial and temporal resolution including dopamine, norepinephrine, adenosine, and serotonin. While FSCV has already provided myriad insights into physiological and pathophysiological neurochemical signaling in the brain, this technique has traditionally been restricted to small animal models. After initial implementations in large animal models, our group and others have recently translated FSCV successfully into humans, showing intraoperative neurochemical monitoring of dopamine and adenosine release in the human brain of patients undergoing deep brain stimulation (DBS) surgery for Parkinson's disease or essential tremor. In this review, we provide an overview of the recent advances in human electrochemistry and current state-of-the-art approach for performing neurochemical recordings in the intraoperative setting in humans. Furthermore, we describe pertinent technological developments such as the WINCS (Wireless Instantaneous Neurotransmitter Concentration Sensing) system and its successor WINCS-Harmoni, a next generation device capable of combining brain stimulation with real-time neurochemical recording in vivo. Finally, we discuss the future potentials of human electrochemistry to advance the understanding of the neurophysiology of the central nervous system, pathological neurochemical changes, and mechanisms of DBS. It is important to note that human neurochemistry is still in its infancy and numerous critical challenges will have to be addressed over the next decades. However, these preliminary studies have shown that DBS surgery offers a unique window of opportunity for performing neurochemical recordings that would be beyond the scope of preclinical research. This technique may thereby provide unprecedented insights into human brain chemistry and myriad neurological and psychiatric conditions.
Preparation of xenon-133 solution for intravenous administration

A method for routine preparation of a solution of /sup 133/Xe gas in saline from commercially available /sup 133/Xe gas ampoules is described and evaluated. At room temperature and atmospheric pressure, about 25% of the /sup 133/Xe gas dissolves in saline. Xenon-133 binds to the syringe wall or may escape into the air when stored in sealed plastic syringes. Preparation immediately prior to use, short-term storage in a properly closed glass vial, and assay of the syringe for activity before and after injection are important considerations for delivering accurate amounts of /sup 133/Xe gas in saline solution.
The Antigenic Structure of the Lipooligosaccharides of Neisseria Gonorrhoeae

The importance of lipooligosaccharide (LOS) (this term which will be used in this chapter in place of “lipopolysacharide” was suggested by Schneider et al. (29) for the lipid A containing glycolipids of pathogenic Neisseria because of the oligosaccharide nature of the saccharide moiety in these organisms) in the pathogenesis and immunobiology of Neisseria gonorrhoeae is unquestioned. Studies by Ward et al. (32), Rice and Kasper (27) and Schneider and co-workers (28) indicate the LOS is a key target on the gonococcal cell surface for human bactericidal antibody. Thus, an understanding of the physicochemical and antigenic structure of gonococcal LOS as well as its characteristics in vivo and in vitro will be important in comprehending the immunobiology of the gonococcus.
A protocol to decrease postoperative chylous effusion duration in children.

ObjectiveOur primary goal was to decrease time to resolution of postoperative chylothorax as demonstrated by total days of chest tube utilisation through development and implementation of a management protocol.MethodsA chylothorax management protocol was implemented as a quality improvement project at a tertiary-care paediatric hospital in July, 2015. Retrospective analysis was completed on patients aged 0–17 years diagnosed with chylothorax within 30 days of cardiac surgery in a pre-protocol cohort (February, 2014 to June, 2015, n=20) and a post-protocol cohort (July, 2015 to March, 2016, n=22).Measurements and resultsPatient characteristics were similar before and after protocol implementation. Duration of mechanical ventilation and cardiac ICU and hospital lengths of stay were unchanged between cohorts. Following protocol implementation, total duration of chest tube utilisation decreased from 12 to 7 days (p=0.047) with a decrease in maximum days of chest tube utilisation from 44 to 13 days. Duration of medium-chain triglyceride feeds decreased from 42 days to 31 days (p=0.01). In total, three patients in the post-protocol cohort underwent additional surgical procedures to treat chylothorax with subsequent resolution of chylothorax within 24 hours. There were no chest tube re-insertions or re-admissions related to chylothorax in either the pre- or post-protocol cohorts. Protocol compliance was 81%.ConclusionsAdoption of a chylothorax management protocol is feasible, and in our small cohort of patients implementation led to a significant decrease in the duration of chest tube utilisation, while eliminating practice variability among providers.
Pathologies Disproportionately Affecting the Underserved

In order to understand the pathologies afflicting the underserved an examination of who this population is key. According to the World Bank’s OVC toolkit, children in general are more vulnerable than adults, and some children are more vulnerable than others (World Bank’s Africa Region and World Bank Institute 2005). The World Bank talks about a downward spiral that may put a child at risk (World Bank’s Africa Region and World Bank Institute 2005). The World Bank OVC Toolkit highlights how changes to the social situation can slowly accumulate resulting in children that are disconnected from the family and without support making them the most vulnerable. These children are then at risk for exploitation, living in poor conditions, poor health outcomes, trauma causing mental health issues and many other problems. This situation occurs in many settings all across the world and affects many children.
Capitalist Production and the Problem of Monopoly

The previous chapters have demonstrated that neither an economic nor a moral case for socialism can be made. Socialism is economically and morally inferior to capitalism. The last chapter examined why socialism is nonetheless a viable social system, and analyzed the socio-psychological characteristics of the state—the institution embodying socialism. Its existence, stability, and growth rest on aggression and on public support of this aggression which the state manages to effect. This it does, for one thing, through a policy of popular discrimination; a policy, that is, of bribing some people into tolerating and supporting the continual exploitation of others by granting them favors; and secondly, through a policy of popular participation in the making of policy, i.e., by corrupting the public and persuading it to play the game of aggression by giving prospective power wielders the consoling opportunity to enact their particular exploitative schemes at one of the subsequent policy changes.
14 – Nutrient Flow and Retention

Publisher Summary This chapter outlines the major nutrient pathways in fishes, emphasizing on the differences among fish species and between fish and terrestrial animals. Fish nutrient metabolism is the sum total of the biochemical reactions in life processes. Fish exhibit subtle differences in genetic isozymes associated with their habitat, but in general, cellular metabolism among fish species is similar. Most fish live in a heat sink and the water temperature governs their metabolism rates. As a result, most fish have adapted enzyme systems to poikilothermic environments and their genetic isozymes, while very similar in structure, combine with the same general substrates to accomplish the digestion, absorption, and subsequent biochemical reactions necessary for energy generation and metabolite incorporation into cell functions. All fish metabolize proteins for amino acid sources for anabolism and growth. Lipid utilization is well developed in most fish, although certain cyprinids have a limited ability to use high-lipid diets without generating liver toxicity and obesity. Fish eliminate most of the nitrogen resulting from amino acid catabolism and other nitrogenous metabolites into the water as ammonia from the gills. Protein retention depends on a number of endogenous and exogenous factors, including the feed intake, dietary protein and energy levels, dietary amino acid leves, dietary amino acid bioavailability, life history stage, and genetically controlled rate of protein turnover.
Taking scientific error and uncertainty seriously

Collections can be treacherous, susceptible to the weaknesses of multiple authorships. When they succeed, however, they can valuably synthesize disparate specialized knowledge. Or at the other extreme, as in this case, they can fruitfully survey and help open a field ripe for further study. The subject here will be familiar to anyone who has heard experimentalists discuss ‘‘sources of error.’’ What happens when investigations ‘‘go amiss’’? In introducing a special 2005 issue of Social Research, Gerald Holton noted:
Interplanetary Gas Dynamics

Observations of the interplanetary medium are considered together with the structure of the solar atmosphere and the kinetic properties of the interplanetary plasma. Methods of gas kinetics and continuum flows are examined, taking into account microscopic and macroscopic representations, the kinetic flow equations, the formal solution of the Vlasov equation, and the continuum flow equations. The collective particle behavior of that interplanetary gas is discussed along with the hydrodynamic coronal expansion, a wave-pump problem, the free expansion phenomenon, and a generalized free expansion problem.
The impact of rural classification systems on a comparison of risky drug-related behaviors in Kentucky and Ohio counties

To analyze county-level differences in injection drug use (IDU) behaviors and overdoses in Kentucky and Ohio, and to assess the impact of using different models to classify counties as rural.Existi...
Systemic overuse of health care in a commercially insured US population, 2010-2015.

Overuse is a leading contributor to the high cost of health care in the United States. Overuse harms patients and is a definitive waste of resources. The Johns Hopkins Overuse Index (JHOI) is a normalized measure of systemic health care services overuse, generated from claims data, that has been used to describe overuse in Medicare beneficiaries and to understand drivers of overuse. We aimed to adapt the JHOI for application to a commercially insured US population, to examine geographic variation in systemic overuse in this population, and to analyze trends over time to inform whether systemic overuse is an enduring problem. We analyzed commercial insurance claims from 18 to 64 year old beneficiaries. We calculated a semiannual JHOI for each of the 375 Metropolitan Statistical Areas and 47 rural regions of the US. We generated maps to examine geographic variation and then analyzed each region’s change in their JHOI quintile from January 2011 to June 2015. The JHOI varied markedly across the US. Across the country, rural regions tended to have less systemic overuse than their MSA counterparts (p < 0.01). Regional systemic overuse is positively correlated from one time period to the next (p < 0.001). Between 2011 and 2015, 53.7% (N = 226) of regions remained in the same quintile of the JHOI. Eighty of these regions had a persistently high or persistently low JHOI throughout study duration. The systemic overuse of health care resources is an enduring, regional problem. Areas identified as having a persistently high rate of systemic overuse merit further investigation to understand drivers and potential points of intervention.
Characterizing Bot Networks on Twitter: An Empirical Analysis of Contentious Issues in the Asia-Pacific

This paper empirically analyzes bot activity in contentious Twitter conversations using case studies from the Asia-Pacific. Bot activity is measured and characterized using a series of interoperable tools leveraging dynamic network analysis and machine learning. We apply this novel and flexible methodological framework to derive insights about information operations in three contexts: the senatorial elections in the Philippines, the presidential elections in Indonesia, and the relocation of a military base in Okinawa. Varying levels of bot prevalence and influence are identified across case studies. The presented findings demonstrate principles of social cyber-security in concrete settings and highlight conceptual and methodological issues to inform further development of analytic pipelines in studying online information operations.
Robust Federated Learning Through Representation Matching and Adaptive Hyper-parameters

Federated learning is a distributed, privacy-aware learning scenario which trains a single model on data belonging to several clients. Each client trains a local model on its data and the local models are then aggregated by a central party. Current federated learning methods struggle in cases with heterogeneous client-side data distributions which can quickly lead to divergent local models and a collapse in performance. Careful hyper-parameter tuning is particularly important in these cases but traditional automated hyper-parameter tuning methods would require several training trials which is often impractical in a federated learning setting. We describe a two-pronged solution to the issues of robustness and hyper-parameter tuning in federated learning settings. We propose a novel representation matching scheme that reduces the divergence of local models by ensuring the feature representations in the global (aggregate) model can be derived from the locally learned representations. We also propose an online hyper-parameter tuning scheme which uses an online version of the REINFORCE algorithm to find a hyper-parameter distribution that maximizes the expected improvements in training loss. We show on several benchmarks that our two-part scheme of local representation matching and global adaptive hyper-parameters significantly improves performance and training robustness.
Simulation 2.0: Integrating Basic Scientists and Clinicians in a Simulation Environment

An increasing number of medical schools are implementing curricular changes that better integrate clinical and basic sciences throughout all four years of medical school. One of the most frequently cited reasons is to improve medical student clinical reasoning skills while simultaneously aiming to decrease the attrition of basic science knowledge. Multiple pedagogical strategies have been explored to achieve this goal. We have found that simulation is a viable medium to integrate basic science within standardized patient encounters for early medical students.
Personality, Retirement, and Cognitive Impairment: Moderating and Mediating Associations.

Objectives: Five-factor model (FFM) personality traits, including higher conscientiousness and lower neuroticism, are associated with lower risk of dementia and cognitive impairment. In this resear...
Examining the Efficacy of E-Service-Learning

E-service-learning is a pedagogical technique in which instruction and/or service occur online. Students in a distance learning section of Atypical Development course created a Google Site with resources for individuals with developmental disabilities. Additionally, students met with youths with developmental disabilities biweekly via Blackboard Collaborate Ultra sessions. At the end of the semester, students completed a questionnaire assessing their e-service-learning experience. Students reported that the e-service-learning experience was related to course content, increased their understanding of individuals with disabilities, increased student engagement, helped them relate the subject matter to everyday life, positively impacted their future academic and career choices, and overall had a positive experience. Students in a face-to-face section of Atypical Development who completed an in-person service-learning project did not significantly differ on any of the aforementioned measures. Course evaluations were also examined for both sections. Students in the e-service-learning section reported greater satisfaction than the in-person service-learning course. Specifically, e-service-learning students reported: the instructor attempted to make the course relevant to students; the assignments helped me learn the subject matter; I enjoyed the class greater than students in the in-person service-learning course. These results indicate that e-service-learning is an efficacious pedagogical practice in distance learning courses.
Teachers’ Enactment of Equity in Alternative Schools: A critical discourse analysis

Purpose: Understanding the needs of at-risk students is thought to be an essential element for educators when they formulate and design alternative educational settings. Yet, it may be difficult for educators to distinguish between responding to the needs of an at-risk student and providing educational equity. The researcher applied equity principles and policy implementation literature to explore how alternative school teachers of at-risk students define, interpret and enact equity. Research Methods: This research was designed as a qualitative cross-case study focusing on five alternative schools in California and Texas. A qualitative thematic analysis was first applied to interviews from fifteen alternative school teachers, followed by a critical discourse analysis of government artifacts, and discursive and social practices. Findings: Teachers’ enactment of equity equated to opportunity; at-risk students were afforded equity by virtue of enrollment in the schools. Implicitly, teachers acted as gate keepers to their classroom and as such only certain students were entitled to attend. Equity arguments emerged when external forces were perceived as creating inequities. Implicit equity arguments emerged by how teachers defined success. Implications: Innovative design and practices used in alternative schools are insufficient for ensuring equity. Enactment of equity through pedagogical choices is reduced by policy procedures. Research is needed in areas: a) that will help teachers reflect on their values and priorities for at-risk students and b) of how efficacy is measured for the alternative school.
Evaluation of physical activity reporting in community Diabetes Prevention Program lifestyle intervention efforts: A systematic review.

Abstract Introduction The Diabetes Prevention Program (DPP) lifestyle intervention has been translated to community settings using the DPP goals of 7% weight loss and 150 min of moderate physical activity (PA) per week. Given that PA is a primary lifestyle goal and has been linked to improvements in metabolic health in the DPP, it is important to understand the role that PA plays in translation effort success. The purpose of this review is to thoroughly evaluate the reporting of PA methodology and results in DPP-based translations in order to guide future prevention efforts. Methods PubMed and Ovid databases were searched to identify peer-reviewed original research articles on DPP-based translations for adults at-risk for developing diabetes or cardiovascular disease, limited to English language publications from January 2002–March 2015. Results 72 original research articles describing 57 translation studies met eligibility criteria. All 57 study interventions included a PA goal, 47 studies (82%) collected participant PA information, and 34 (60%) provided PA results. Conclusions Despite PA being a primary intervention goal, PA methodology and results are under-reported in published DPP translation studies. This absence and inconsistency in reporting PA needs addressed in order to fully understand translation efforts' impact on participant health.
Detecting tourism destinations using scalable geospatial analysis based on cloud computing platform

Abstract The number of geo-tagged digital photos has grown exponentially in the past decades. Increasing numbers of digital photos with geo-tags are available on many photo-sharing websites such as Flickr and Instagram. The proliferation of online photos offers great opportunities to study people's travel experiences and preferences. Mining tourists' behavior and city preferences has become popular in recent geographic information system (GIS) research. However, the huge amount of data also poses challenges in spatial analytics. In this study, we automate the detection of places of interest in multiple cities based on spatial and temporal features of Flickr images from 2007 on. We also speed up the process by running jobs on top of the RHadoop platform. This project provides fast and accurate tourist destination detection by mining large amounts of geo-tagged Flickr images. In addition, this study provides insight in applying the RHadoop platform to strengthen large geospatial data analytics. Our methods can be applied to many other cities, and results are valuable for tourism management.
Towards High‐Resolution Self‐Organizing Maps of Geographic Features

This chapter introduces the use of high-resolution self-organizing maps (SOM) to represent a large number of geographic features on the basis of their attributes. Until now, the SOM method has been applied to geographic data for both clustering and visualization purposes. However, the granularity of the resulting attribute space representations has been far below the resolution at which geographic space is typically represented. We propose to construct SOMs consisting of several hundred thousand neurons, trained with attributes of an equally large number of geographic features, and finally visualized in standard GIS software. This is demonstrated for a data set consisting of climate attributes attached to 200,000+ U.S. census block groups. Further, overlays of point, line, and area features onto such a high-resolution SOM are shown. INTRODUCTION This volume demonstrates the range of approaches currently pursued in the field of geographic visualization. Geographic visualization has clearly captured the public’s imagination. Evolutionary changes in creation, distribution, and interaction with cartographic depictions have powerfully converged in early realizations of the digital earth concept (see chapter by Goodchild in this volume). Further convergence of various technologies and methodologies is likely, including trends towards high-resolution imagery (see preceding chapter by Orford) This is a pre-publication draft only. For the final, published version, please refer to: Skupin, A. and Esperbe, A. (2008) Towards High-Resolution Self-Organizing Maps of Geographic Features. In: Dodge, M., Turner, M., and Derby, M. (Eds.) Geographic Visualization: Concepts, Tools and Applications. Wiley.
Glial-derived neurotrophic factor upregulates expression of functional SNS and NaN sodium channels and their currents in axotomized dorsal root ganglion neurons.

Dorsal root ganglion (DRG) neurons produce multiple sodium currents, including several different TTX-sensitive (TTX-S) currents and TTX-resistant (TTX-R) currents, which are produced by distinct sodium channels. We previously demonstrated that, after sciatic nerve transection, the levels of SNS and NaN sodium channel α-subunit transcripts and protein in small (18–30 μm diameter) DRG neurons are reduced, as are the amplitudes and densities of the slowly inactivating and persistent TTX-R currents produced by these two channels. In this study, we asked whether glial-derived neurotrophic factor (GDNF), which has been shown to prevent some axotomy-induced changes such as the loss of somatostatin expression in DRG neurons, can ameliorate the axotomy-induced downregulation of SNS and NaN TTX-R sodium channels. We show here that exposure to GDNF can significantly increase both slowly inactivating and persistent TTX-R sodium currents, which are paralleled by increases in SNS and NaN mRNA and protein levels, in axotomized DRG neurons in vitro. We also show that intrathecally administered GDNF increases the amplitudes of the slowly inactivating and persistent TTX-R currents, and SNS and NaN protein levels, in peripherally axotomized DRG neurons in vivo. Finally, we demonstrate that GDNF upregulates the persistent TTX-R current in SNS-null mice, thus demonstrating that the upregulated persistent sodium current is not produced by SNS. Because TTX-R sodium channels have been shown to be important in nociception, the effects of GDNF on axotomized DRG neurons may have important implications for the regulation of nociceptive signaling by these cells.
Going Back in Time to Improve Design: The Elemental Function-Failure Design Method

In today’s world it is more important than ever to quickly and accurately satisfy customer needs when launching a new product. It is equally important to design products that adequately accomplish their desired functions with a minimum amount of failures. When failure analysis and prevention are coupled with a product design from its conception, shorter design times and fewer redesigns are necessary to arrive at a final product design. In this article, we explore the potential of a novel design methodology to guide designers toward new designs or redesigns that avoid failures. The Elemental Function-Failure Design Method (EFDM) is based on functional similarity of the product being designed to failed products within a knowledge base. The idea of using component functionality to explore the failure space in design was first introduced as a function-failure analysis approach by Tumer and Stone (2003). The overall approach offers potential improvement over current failure analysis methods (FMEA, etc.), because it can be implemented hand in hand with other conceptual design steps and carried throughout a product’s design cycle. In this paper, this idea is formalized into a systematic methodology that is specifically tailored for use at the conceptual design stage before any physical design choices have been made, hence moving failure analysis earlier in the design cycle. In the following, formalized guidelines for using the EFDM will be outlined for use in new designs and for redesign in existing products. A function-failure knowledge base, derived from actual failure occurrences for Bell 206 rotorcraft will be introduced and used to derive potential failure modes in a comparison of the EFDM and traditional FMEA for two design examples. This comparison will demonstrate the EFDM’s potential in conceptual design failure analysis.Copyright © 2003 by ASME
Matrilysin cleavage of corneal collagen type XVIII NC1 domain and generation of a 28-kDa fragment.

Purpose To localize endostatin and collagen type XVIII in human corneas and to characterize the enzymatic action of matrix metalloproteinases (MMPs) in the cleavage of collagen type XVIII and generation of endostatin in the cornea. Methods Anti-endostatin and anti-hinge antibodies were generated using peptide fragments corresponding to the endostatin region and the adjacent nonendostatin hinge region of collagen XVIII noncollagenous (NC)1 domain, respectively. Confocal immunostaining was performed to localize collagen XVIII in human corneas. SV40-immortalized corneal epithelial cells were immunoprecipitated and incubated with active MMP-1, -2, -3, -7, or -9, and Western blot analysis was performed to study collagen XVIII cleavage. Incubation with MMP-7 was performed at various concentrations (0, 2, 4, and 6 microg/ml) and time intervals (0, 1, 5, and 12 hours). Purified recombinant NC1 fragment of collagen XVIII was also digested with MMP-7, and the cleavage product was sequenced. Results Collagen XVIII was immunolocalized to the human corneal epithelium, epithelial basement membrane, and Descemet membrane. Western blot analysis demonstrated a 180- to 200-kDa band corresponding to collagen XVIII. MMP-7 (but not MMP-1, -2, -3, and -9) cleaved corneal epithelium-derived collagen XVIII to generate a 28-kDa endostatin-spanning fragment in a time- and concentration-dependent fashion. MMP-7 cleaved purified recombinant 34-kDa NC1 fragment of collagen XVIII in the hinge region to generate a 28-kDa fragment. Conclusions Collagen XVIII is present in human cornea. MMP-7 cleaves the collagen XVIII NC1 domain to generate a 28-kDa fragment in the cornea.
Absolute Measurements of Neutron Spectra in High- and Low-Enriched Uranium Materials Test Reactor Fuel

In this paper in-core absolute neutron spectra are measured for high-enriched uranium (HEU) and low-enriched uranium (LEU) materials which test reactor fuel using multiple foil activation. The measurements were made in special fuel elements configured to simulate a regular fuel element but that permitted reproducible insertion of a wide range of samples. The measured subcadmium LEU flux was 14% less than the HEU fuel, which is within the experimental uncertainty of the 19% calculated value. There was no observed difference between the fast spectra. A separate spectral unfolding of just the LEU fast flux yielded reasonable agreement with proton-recoil measurements.
Dynamik von Blut- und Lymphströmung

Die Blutgefase bilden ein geschlossenes Rohrensystem, das Blut vom Herzen ins Gewebe und aus dem Gewebe zuruck zum Herzen transportiert; ein Teil der interstitiellen Flussigkeit gelangt jedoch in die Lymphgefase und uber diese ins Gefassystem. Die Blutstramung kommt vor allem durch die Pumpleistung des Herzens zustande; im grosen Kreislauf sind auserdem die diastolische Ent-Dehnung (Retraktion) der Arterienwande und die Venen-Kompression durch die Skeletmuskulatur bei Arbeit sowie der subatmospharische Druck im Thorax wahrend der Inspiration fur den Ruckflus des Blutes zum Herzen bedeutsam. Der Widerstand, der dem Blutstrom entgegenwirkt, hangt zu einem geringen Grad von der Viscositat, entscheidend aber von der Weite der Gefase, besonders der Arteriolen ab.
An empathy‐humility‐commitment model of forgiveness applied within family dyads

Forgiveness is described as requiring empathy for the offender, the humility to see oneself as being as fallible and needy as the offender, and courage to commit publicly to forgive. Research supports the model in individual therapy and psychoeducational groups in which the forgiver does not have to confront the offender. Family therapy, in which partners, parent–child dyads or siblings must confess their need for forgiveness and forgive face to face provides special challenges. Processes of forgiveness – empathy, humility and commitment – are understood to be the same as in any interpersonal forgiveness context; that is, they are thought to occur within dyads. Techniques compatible with several varieties of family therapies are summarized for applying the model in family therapy to encourage family members to forgive.
Proteomic analysis of nipple aspirate fluid from women with early-stage breast cancer using isotope-coded affinity tags and tandem mass spectrometry reveals differential expression of vitamin D binding protein.

Isotope-coded affinity tag (ICAT) tandem mass spectrometry (MS) allows for qualitative and quantitative analysis of paired protein samples. We sought to determine whether ICAT technology could quantify and identify differential expression of tumor-specific proteins in nipple aspirate fluid (NAF) from the tumor-bearing and contralateral disease-free breasts of patients with unilateral early-stage breast cancer.
Optimized subunit vaccine protects against experimental leishmaniasis

Development of a protective subunit vaccine against Leishmania spp. depends on antigens and adjuvants that induce appropriate immune responses. We evaluated a second generation polyprotein antigen (Leish-110f) in different adjuvant formulations for immunogenicity and protective efficacy against Leishmania spp. challenges. Vaccine-induced protection was associated with antibody and T cell responses to Leish-110f. CD4 T cells were the source of IFN-γ, TNF, and IL-2 double- and triple-positive populations. This study establishes the immunogenicity and protective efficacy of the improved Leish-110f subunit vaccine antigen adjuvanted with natural (MPL-SE) or synthetic (EM005) Toll-like receptor 4 agonists.
NAD(+)-SIRT1 control of H3K4 trimethylation through circadian deacetylation of MLL1

The circadian clock controls the transcription of hundreds of genes through specific chromatin-remodeling events. The histone methyltransferase mixed-lineage leukemia 1 (MLL1) coordinates recruitment of CLOCK-BMAL1 activator complexes to chromatin, an event associated with cyclic trimethylation of histone H3 Lys4 (H3K4) at circadian promoters. Remarkably, in mouse liver circadian H3K4 trimethylation is modulated by SIRT1, an NAD(+)-dependent deacetylase involved in clock control. We show that mammalian MLL1 is acetylated at two conserved residues, K1130 and K1133. Notably, MLL1 acetylation is cyclic, controlled by the clock and by SIRT1, and it affects the methyltransferase activity of MLL1. Moreover, H3K4 methylation at clock-controlled-gene promoters is influenced by pharmacological or genetic inactivation of SIRT1. Finally, levels of MLL1 acetylation and H3K4 trimethylation at circadian gene promoters depend on NAD(+) circadian levels. These findings reveal a previously unappreciated regulatory pathway between energy metabolism and histone methylation.
Investigating the mutual effects of physical training and mu-based brain-computer interface systems

This research seeks to investigate the possible interactions between physical training and mu-based control of brain-computer interface systems. The results of this work will provide new avenues for physical therapy and rehabilitation and spotlight the benefits of neural control of computers for both disabled and able-bodied people.
Retinoblastoma Protein (RB1) Controls Fate Determination in Stem Cells and Progenitors of the Mouse Male Germline

Continual spermatogenesis is the cornerstone of male fertility and relies on the actions of an undifferentiated spermatogonial population comprised of stem cells and progenitors. A foundational spermatogonial stem cell (SSC) pool is established during postnatal development that serves as a self-renewing reservoir from which progenitor spermatogonia arise that transiently amplify in number before committing to terminal differentiation. At present, the underlying molecular mechanisms governing these actions are undefined. Using conditional mutant mouse models, we investigated whether function of the undifferentiated spermatogonial population during postnatal life is influenced by the tumor suppressor protein RB1. Spermatogenesis initiates in mice with conditional inactivation of Rb1 in prospermatogonial precursors, but the germline is progressively lost upon aging due to impaired renewal of the undifferentiated spermatogonial population. In contrast, continual spermatogenesis is sustained following Rb1 inactivation in progenitor spermatogonia, but some cells transform into a carcinoma in situ-like state. Furthermore, knockdown of Rb1 abundance within primary cultures of wild-type undifferentiated spermatogonia impairs maintenance of the SSC pool, and some cells are invasive of the basement membrane after transplant into recipient testes, indicating acquisition of tumorigenic properties. Collectively, these findings indicate that RB1 plays an essential role in establishment of a self-renewing SSC pool and commitment to the spermatogenic lineage within progenitor spermatogonia.
Blazed Holographic Gratings-Formation By Surface Waves And Replication By Metal Electroforming

The formation of a blazed holographic grating, using the interference of an ordinary plane wave with a surface wave is considered. The usual holographic recording arrangement has been modified such that a positive photoresist recording layer is coated on one face of a prism; one of the recording beams is totally reflected from the prism such that the surface wave thus formed enters the photoresist from the back side. The other recording beam also enters from the back side, but is an ordinary plane wave. The resulting interference fringes are inclined with respect to the normal. With this arrangement the profile can be contoured more precisely than usual and many variations in the shape of the profile are possible. Modifications of the method described here allow the formation of gratings on curved surfaces and in some cases correction for aberrations. Once a profile has been formed in this fashion in photoresist it is possible to replicate it exactly in a durable metal layer using electroforming techniques. Such gratings are applicable for use in specrometers where high beam intensities must be taken into account.
Deep PFCB polymer etch development for photonic devices

Dramatic reductions in the size of waveguide bends for materials with low core/clad refractive index contrast can be achieved with single air interface bends (SAIBs) based on total internal reflection. However, high optical efficiency for such bends requires vertical interfaces with low surface roughness. In this presentation we report the development of a highly anisotropic etch for perfluorocyclobutane (PFCB) waveguide structures. We examine the use of inductively coupled plasma reactive ion etching (ICP RIE) based on both oxygen/helium and carbon dioxide/helium etch chemistries to achieve the desired interface quality for high efficiency waveguide bends.
Induction of G2 Arrest and Gene Expression by 2-Aminopurine in Human U937 Promonocyte-Macrophage Cells

The adenine analogue, 2-aminopurine (2-AP), induces G2 arrest in the human promonocyte-macrophage cell line, U937. The arrest is reversible and cells enter mitosis to resume normal logarithmic growth upon removal of the drug. These physiological changes are accompanied by markedly stimulated expression of eukaryotic gene constructs stably integrated in the chromosomes or introduced into the cells by transient transfection. Induction by 2-AP has two components: one involves increased transcription of the introduced genes as shown by run-on transcription experiments. The other involves markedly increased mRNA half-life that affects mRNA transcribed from transiently transfected DNA but apparently does not affect mRNA transcribed from the same chromosomally integrated sequences. Together, these two components could account for the 100- to 1000-fold inductions observed with various transfected gene constructs reported here and elsewhere. Maximum induction by 2-AP is promiscuous with respect to eukaryotic promoter origins or sequences, but appears to require a minimum of two such promoter elements. Thus, G2 cell cycle arrest induced by 2-AP is also associated with transcriptional and post-transcriptional alterations in gene expression. The data also suggest that transiently transfected DNAs may enter spatial or biochemical compartments of the nucleus that are different from those of normal genes in their native locations. These differences may affect the abundance and fate of the transcribed mRNA and, in some circumstances, introduce serious discordances into studies of gene regulation.
On looking at letters within words: Do we "see" them in memory?

Abstract In the context of models of word recognition that assume that word processing is holistic, an interesting paradox emerges to the extent that it is difficult for such models to explain how perceivers can ever “see” the letters within the words in the sense of providing them with specific encodings. It was suggested that one possible explanation is that subjects may decode word codes within memory, and then examine the contents of their memory rather than directly scanning the display itself. Two experiments that explored that issue by comparing the way subjects search for target letters in integratable words as opposed to unintegratable consonant arrays are reported. Although the task in both cases was a visual scan, the results of both experiments indicated that while subjects did appear to visually scan the consonant arrays, their search of the word displays was more characteristic of a memory scan.
Darboux theorem and equivariant Morse lemma

Using supersymmetry differential forms can be studied by methods of the theory of normal forms of smooth functions. Differential forms on M can be considered as functions on a supermanifold M and the De Rham differential on M becomes a vector field on M. This vector field generates an action of the supergroup R0vb1 on M. We prove the equivalent Morse lemma for this action and show that it implies both the ordinary Morse lemma and the Darboux theorem on M.