cssi/SciSciGPT-SciSciNet huggingface dataset:
New Directions for Research on Nonviolence

Like the elephant being approached by the group of blind men for investigation, nonviolence is a concept with many dimensions and many levels that has been approached by many disciplines with their unique methods and theoretical orientations. Anthropologists, historians, political scientists, psychologists, sociologists, and theologians have added insights and knowledge to our understanding of nonviolence and nonviolent action. Much remains for study within each discipline, however more can be learned if interdisciplinary approaches are pursued.
Endothelin modulates chemoreceptor cell function in mammalian carotid body.

The endothelins (ET-1, ET-2, ET-3), a family of unique 21 amino acid peptides, produce a transient vasodilation and protracted vasoconstriction in numerous vascular beds (see Rubanyi and Polokoff, 1994, for review). The synthesis and release of ETs was first described in cultured vascular endothelial cells, but later studies showed that ETs and specific ET receptor sites also exist in the peripheral and central nervous systems, suggesting that in addition to their role as local vasoactive agents, ETs may also function as neuropeptides (Greenberg et al, 1992; Rubanyi and Polokoff, 1994). The tissue distribution of ETs indicates that they frequently co-occur with two other potent vasoactive agents, atrial natriuretic peptide (ANP) and nitric oxide (NO). There are important interactions between these agents, and in some cases ETs are uniquely antagonistic to the physiological effects of NO and ANP (Rubanyi and Polokoff, 1994). Biochemical assessments of the signal transduction mechanisms employed by these agents have shown that the actions of ANP and NO result from increased cyclic GMP (cGMP) production and decreased cellular [Ca2+]i (e.g., see White et al, 1993), whereas the effects of ETs are mediated by elevated inositol phosphate (IPn), protein kinase C (PKc) and sometimes cAMP production, with consequent increases in [Ca2+]i (Simonson & Dunn, 1990; Rubanyi & Polokoff, 1994).
Distributed Device Caching for Information Updating in Emergency Communications

On time information is the basis of coordination and decision making for emergency responses during or after disasters. However, accurate information about disaster scenarios, which usually comes from the monitoring devices or people in disaster areas, is often unavailable since the communication network is congested or even damaged. The information centric network (ICN) paradigm could be employed in this situation to help reduce the download traffic that needs to go through the bottlenecks. However, the regular ICN does not handle frequent information uploading, which posts a new challenge for integrating ICN into the emergency communication network. In this paper, we propose to use edge caches as the foundation of caching systems that support information updating. There are two major design work involved: the local cache placement and across access networks synchronization of the local writing caches in the disaster area. For cache synchronization, we present three different schemes and analyze their system capacity in supporting update traffic from the system's perspective and individual local cache's perspective. For local cache placemen, we propose schemes with flexible scale up and scale down abilities, and present performance analysis on each scheme.
Is This Any Way to Make Civil Rights Law? Judicial Extension of 'Marital Status' Nondiscrimination to Protect Cohabitants

In recent years, civil rights legislation has been the subject of significant attention. In part, this is due to the emergence of novel and contested interpretations of longstanding statutes offering protection against discrimination based upon sex and marital status. Courts and agencies are infusing new meanings into old laws in response to questions provoked by new behaviors. One new question concerns whether to interpret “marital status” nondiscrimination as protecting an unmarried couple’s cohabiting. Four state courts and one federal court have answered “yes.” But these cases work against uniting Americans behind civil rights laws - laws that ought to be a point of national pride. Because of their mistakes in the areas of statutory interpretation and separation of powers, they appear starkly ideological. They also do a poor job reflecting upon the proper balance with religious freedom. Americans may wish to protect cohabiting as a “marital status.” If so, this should be accomplished by a legislative process that can investigate the myriad social welfare questions cohabitation provokes: - especially regarding possible effects on marriage and children’s stability. Cohabitation-protective cases cannot and do not accomplish this. Instead, they play word games and manipulate statutory canons. They tell religious citizens what they are “really” thinking no matter what the citizen believes in her own mind. They also insist, against settled law, that the state, and not the religious citizen, knows the nature of the burden on the free exercise of religion created by a particular civil right. And throughout, such cases fashion social policy, while ignoring the vast amount of data and public opinion necessary to make informed policy. In short, they do civil rights no favor.
(185) A Qualitative Analysis of Pain Meaning: Results from the Oklahoma Study of Native American Pain Risk (OK-SNAP)

Previous research has explored cultural differences concerning the prevalence, response, and treatment preferences of individuals experiencing pain. However, the meaning of these painful experiences has not been comprehensively examined. Research tends to generalize findings from predominantly European American samples and assume universality of their findings across cultures. Numerous studies have demonstrated a significantly higher prevalence of physical pain in Native Americans (NA) compared to non-Hispanic Whites (NHW). Because of this, it is important to consider whether our current understanding of painful experiences is indeed universal. To accomplish this, a semi-structured interview was administered to 156 NAs and 151 NHWs that asked open-ended questions related to: words used to describe physically injurious experiences, the purpose of pain, individual and culture-specific pain meaning, and words for the opposite of pain. Next, themes were generated from transcripts and two raters blind to participants’ racial/ethnic group coded transcripts for the themes. Strong agreement between raters was obtained (Kappa= .75-1.00). Chi-square analyses assessed whether the frequency of responses for themes were different between NHWs and NAs. In general, frequency of themes were similar between groups; nonetheless, a few small group differences were noted. NHWs used the word pain more often to describe physically hurtful experiences (45.3% vs. 42.1%; χ 2 [1, N=309]=4.675, p 2 [1, N=309]=7.320, p 2 [1, N=309]=13.310, p
Craft Breweries and Neighborhood Crime: Are They Related?

In their search for inexpensive real estate, many craft breweries have located in economically distressed neighborhoods. In many cases, breweries have contributed to the revitalization of neighborh...
How are Social Ties Protective

Social ties are the most important resource human beings have. Although other people can be difficult and challenging, they can also provide protection, solace, and social support, among other benefits. However, some relationships can be toxic and because these adverse conditions can be physiologically taxing, they can negatively affect both mental and physical health. Changes such as these can operate in large part through alterations in the sympathetic nervous system, the hypothalamic-pituitary-adrenal system, and the immune system. Much of the benefit of social support is perceptual and stems from the comfort of believing that supportive others can or will be there when times are stressful. The abilities to gain and perceive social support begin early in life and are heavily influenced by the climate of the family. Social support depends, in part, on reciprocity, yet many challenges to receiving support exist. Giving support to others has its own psychological and physiological benefits, although at intense levels, such as demanding caregiving responsibilities, these benefits dwindle. Moreover, social support needs change over time with changing circumstances. Public policy efforts to help people build and capitalize on their potential support networks is essential to maximize the impact of social ties on mental and physical health.
Breaking Bad: Extracellular Vesicles Provoke Tumorigenic Responses Under Oxygen Deprivation.

Intercellular communication is vital to tumor progression. In this issue of Developmental Cell, Bertolini et al. (2020) describe how small extracellular vesicles released from hypoxic mammary tumor cells facilitate intercellular communication, leading to alterations in mitochondrial dynamics and acquisition of invasive phenotypes in normal epithelial cells.
Microstructures and mechanical properties of a modified 9Cr ferritic-martensitic steel in the as-built condition after additive manufacturing

Abstract A newly developed nano-structured high-Mn 9Cr ferritic-martensitic (FM) steel designed for additive manufacturing (Additive-manufactured Nanostructured Alloy, ANA) was fabricated via the direct energy deposition method. The as-printed ANA2 showed tensile properties (strength and elongation) and Charpy impact toughness (upper-shelf energy and ductile-brittle transition temperature) comparable to oxide-dispersion-strengthened (ODS) Eurofer and PM2000. Compared with wrought P91, the as-built ANA2 showed significantly higher yield strength but inferior Charpy impact toughness and ductility. Microstructural characterization revealed uniformly distributed sub-micron pores, an extremely high dislocation density, and a high density of ultrafine nano-structured precipitates in the matrix. The microstructures indicated the dislocations as the dominant strengthening element and the ultrafine precipitates as the primary contribution to estimated irradiation sink density. This work demonstrates the ability to exploit the unique consolidation properties of additive manufacturing to fabricate steels which marry the benefits of both ODS alloys and conventionally processed FM steels.
Perspectives on the receipt of a COVID-19 vaccine: A survey of employees in two large hospitals in Philadelphia.

Abstract Background Health care personnel have been identified by the ACIP as a priority group for COVID-19 vaccination. We conducted a survey in November-December 2020 at two large, academic hospitals in Philadelphia to evaluate the intention of hospital employees to be vaccinated. Methods The survey was sent electronically to all employees (clinical and nonclinical staff) at a children’s hospital and an adult hospital. The survey was voluntary and confidential. Questions focused on plans to receive a COVID-19 vaccine when available, reasons why employees would/would not get vaccinated, when employees planned to be vaccinated, vaccine safety and efficacy features that would be acceptable, and past history of receipt of other vaccines by the employee and family. Responses were analyzed using univariate and multiple logistic regression methods. Results A total of 12,034 hospital employees completed the survey (a 34.5% response rate). Overall, 63.7% of employees reported that they planned to receive a COVID-19 vaccine, 26.3% were unsure, and 10.0% did not plan to be vaccinated. Over 80% of those unsure or unwilling to be vaccinated expressed concerns about vaccine side effects and the vaccines’ newness. In multivariable logistic regression, persons planning to take a COVID-19 vaccine were more likely to be older, male, more educated, Asian or White, up-to-date on vaccinations, without direct patient contact, and tested for COVID-19 in the past. No significant difference in intention to be vaccinated was found between those with higher versus lower levels of exposure to COVID-19 patients or the number of previous exposures to patients with COVID-19. Conclusions While the majority of hospital employees are planning to receive a COVID-19 vaccine, many are unsure or not planning to do so. Further education of hospital employees about the safety, efficacy, and value of the currently available COVID-19 vaccines is critical to vaccine acceptance in this population.
Bar code reader for the THz region

We demonstrate a bar code sensing system for the THz region using leaky parallel plate waveguide and an off-axis parabolic mirror. The bars of the bar code are made from metal with air as gaps between them. We use up to 6 bars in the barcode system which can store up to 64 bits. Because the system employs coherent detection, we can further increase the bit density by adding Teflon strips to the barcode, encoding information in both amplitude and phase delay. These bar codes can be manufactured easily and inexpensively, offering a versatile alternative to RFID tags.
Controlling Spontaneous Emission with Nanohole-Based Phased-Array Metasurfaces

We present metasurfaces made from GaN nanoholes with embedded quantum-well emitters. Using nanolithography, we fabricate 1D beam deflectors and 2D meta-axicons and show that we can manipulate the emitted photoluminescence at will.
Natural language processing versus rule-based text analysis: Comparing BERT score and readability indices to predict crowdfunding outcomes

Abstract We explore how natural language processing can be applied to predict crowdfunding outcomes. Using the Bidirectional Encoder Representations from Transformers (BERT) technique, we find that crowdfunding projects that use a story section description with a higher average BERT score (indicating a lower quality of writing) tend to raise more funding than those with lower average BERT scores. In contrast, risk descriptions that have higher BERT scores tend to receive less funding and attract fewer backers. These relationships remain consistent after controlling for various traditional readability indices, highlighting the potential benefits of incorporating natural language processing techniques in entrepreneurship research.
Proteomic and metabolomic biomarkers of Alzheimer's disease: Opportunities to advance precision medicine and clinical trials

Abstract Medical advances that prolong the lifespan of people with Down Syndrome (DS) have led to increasing incidence of age-related diseases such as Alzheimer's Disease (AD). The scientific community is aggressively working to develop valid and reliable biomarkers of AD that are low cost, noninvasive, and intuitive. It is critical that these biomarkers accurately reflect the heterogeneity of people affected by AD, either those in the general population or those with specific risk factors such as people with DS. Within the framework of systems biology, the proteome and metabolome are most proximate to the endophenotype, thus biomarkers from these omics levels may provide highly accurate information for diagnosis and more precise temporal information for predicting phenoconversion events. These biomarkers would be invaluable for precision medicine and for upcoming clinical trials, useful for enriching participant pools and serving as markers of target engagement, and primary endpoints. Standardization of preanalytical sources of biological noise such as biofluid collection and processing pipelines, and protein and metabolite quantification approaches are hurdles that still need to be overcome.
Age, growth and radiometric age validation of a deep-sea, habitat-forming gorgonian (Primnoa resedaeformis) from the Gulf of Alaska

Sustainable fisheries require (1) viable stock populations with appropriate harvest limits and (2) appropriate habitat for fish to survive, forage, seek refuge, grow and reproduce. Some deep-water habitats, such as those formed by deep-water stands of coral, may be vulnerable to fishing disturbance. The rate at which habitat can be restored is a critical aspect of fishery management. The purpose of this study was to characterize growth rates for a habitatforming deep-sea coral. Two nearly complete colonies of red tree coral (Primnoa resedaeformis) collected from waters off southeast Alaska were used for an analysis of age and growth characteristics. CAT scans revealed that colonies consisted of multiple settlement events, where older basal structures provided for settlement of new colonies. The decay of 210 Pb over the length of the colony was used to validate age estimates from growth ring counts. Age estimates were over 100 yr for sections near the heavily calcified base. Based on validated growth ring counts, growth of red tree coral ranged from 1.60 to 2.32 cm per year in height and was approximately 0.36 mm per year in diameter. These growth rates suggest that the fishery habitat created by red tree coral is extremely vulnerable to bottom fishing activities and may take over 100 years to recover.
Clustering Service Networks with Entity, Attribute, and Link Heterogeneity

Many popular web service networks are content-rich in terms of heterogeneous types of entities and links, associated with incomplete attributes. Clustering such heterogeneous service networks demands new clustering techniques that can handle two heterogeneity challenges: (1) multiple types of entities co-exist in the same service network with multiple attributes, and (2) links between entities have diverse types and carry different semantics. Existing heterogeneous graph clustering techniques tend to pick initial centroids uniformly at random, specify the number k of clusters in advance, and fix k during the clustering process. In this paper, we propose Service Cluster, a novel heterogeneous service network clustering algorithm with four unique features. First, we incorporate various types of entity, attribute and link information into a unified distance measure. Second, we design a Discrete Steepest Descent method to naturally produce initial k and initial centroids simultaneously. Third, we propose a dynamic learning method to automatically adjust the link weights towards clustering convergence. Fourth, we develop an effective optimization strategy to identify new suitable k and k well-chosen centroids at each clustering iteration. Extensive evaluation on real datasets demonstrates that Service Cluster outperforms existing representative methods in terms of both effectiveness and efficiency.
The Wrong Way to Reinvent Media, Part 2: Broadcast Spectrum Taxes to Subsidize Public Media

This essay will discuss proposals to impose a tax on broadcast spectrum licenses to funnel money to public media projects or other “public interest” content or objectives.2 Such a tax would be fundamentally unfair to broadcasters, who are struggling for their very survival in the midst of unprecedented marketplace turmoil. Moreover, such a tax is unnecessary in light of the many other sources of “public interest” programming available today. Finally, even if the government creates or subsidizes wonderful, civic- and culturally-enriching content, there’s no way to force people to consume it. Nor should government force such media choices upon the public. There’s no good reason for government to be socially-engineering media choices through taxes.
Radiative corrections to the decays KL0→e+e- and KL0→μ+μ-

We calculate the rates and lepton ({ital l}) invariant mass distributions for decays of the form 0{sup {minus}+}{r_arrow}l{sup +}l{sup {minus}}{gamma}, which are important radiative corrections to the purely leptonic decays 0{sup {minus}+}{r_arrow}l{sup +}l{sup {minus}}. Our approach uses the loop diagrams which arise by including the two photon intermediate state and we retain the imaginary parts of the loops{emdash}a radiative extension of the {open_quotes}unitarity bound{close_quotes} for the process. These results are compared with those obtained using a model in which the meson couples directly to the leptons. {copyright} {ital 1999} {ital The American Physical Society}
A canonical way to deform a Lagrangian submanifold

We derive some important geometric identities for Lagrangian submanifolds immersed in a K\"ahler manifold and prove that there exists a canonical way to deform a Lagrangian submanifold by a parabolic flow through a family of Lagrangian submanifolds if the ambient space is a Ricci-flat Calabi-Yau manifold.
Turfgrass Management in the United States

Publisher Summary This chapter discusses the management of turfgrass in the United States. Turf is receiving increasingly wide use, for both landscape and sports purposes. Regardless of the use, whether a roadside or a putting green, specifications call for a uniform stand of dense grass. The objectives of turfgrass management encompass the establishment and maintenance of turf stands during the entire year. All turfgrasses require some grooming to keep them attractive and to provide conditions favorable for sod formation. The two requirements of a turf include: density and uniformity. Successful use of grass, for turf purposes, depends on its adjustment to the natural environment and to the microenvironment, created by management practices. Temperature, moisture, fertilizer, shade, lime, and use requirements, all influence the persistence and quality of turfgrass stands Grooming operations normally consist of mowing and thinning. Machinery has contributed, in a vital way, to the upgrading of turfgrass management. Improved machinery has evolved gradually; it can accomplish work adequately, yet at greater speed and with less interference to the users. Many turf managers have been involved not only as innovators of equipment, but also in developing new techniques of using the available equipment.
General-Purpose Computing on a Semantic Network Substrate

This article presents a model of general-purpose computing on a semantic network substrate. The concepts presented are applicable to any semantic network representation. However, due to the standards and technological infrastructure devoted to the Semantic Web effort, this article is presented from this point of view. In the proposed model of computing, the application programming interface, the run-time program, and the state of the computing virtual machine are all represented in the Resource Description Framework (RDF). The implementation of the concepts presented provides a computing paradigm that leverages the distributed and standardized representational-layer of the Semantic Web.
Physicochemical effects of radiation. VII. Effects of high‐speed electrons and gamma radiation on thymus sodium deoxyribonucleate

A sample of thymus sodium deoxyribonucleate has been irradiated with high-speed electrons and with γ-rays in the dry state. Solutions of DNA were irradiated with γ-rays. Higher doses of irradiation in the dry state produced marked reduction in S. At the low doses of electrons and γ-rays, there was an increase in S over the control. This was explained as compensatory. When DNA was irradiated in solution with γ-rays, there was a gradual decrease in S. The decrease in S was greatest when the DNA was irradiated in solution. The decrease in S was greater when DNA was irradiated in the dry state with electrons than when irradiated with γ-rays. The concentration dependence of S20 of DNA was greatly reduced both with irradiation in the dry state with electrons and with γ-rays. In solution with γ-rays, the effect was greater. There was an over-all decrease in intrinsic viscosity with irradiation in the dry state with electrons and with γ-rays. The effect was somewhat greater with electrons for an equivalent dose. Light-scattering measurements indicated the formation of aggregates. In the case of irradiation with γ-rays in the dry state, the maximum formation of aggregates was at 5·106 r. At 20·106 r., the molecular weight was less than at 5·106 r., but still greater than the control. Eine Probe von Natrium-desoxyribonukleat aus Thymus wurde in trockenem Zustand mit Elektronen hoher Geschwindigkeit und mit Gammastrahlen behandelt. Auserdem wurden DNA-Losungen der Wirkung von Gammastrahlen ausgesetzt. Wenn die Trockenpraparate mit hohen Dosen bestrahlt wurden, trat eine deutliche Senkung von S ein. Niedrige Dosen von Elektronen- und Gammastrahlen hatten eine Zunahme von S gegenuber den Kontrollen zur Folge. Wenn gelostes DNA mit Gammastrahlen behandelt wurde nahm S allmahlich ab, die Abnahme erreichte unter diesen Bedingungen ein Maximum. Im trockenen Zustand dagegen wurde S starker durch Elektronen als mit Gammastrahlen reduziert. Die Abhangigkeit von S20 von der DNA-Konzentration wurde im Trockenzustand sowohl durch Gammastrahlen als auch durch Elektronen stark herabgesetzt; in Losung dagegen waren die Gammastrahlen wirkungsvoller. Wenn die trockenen DNA-Praparate behandelt wurden, dann nahm die Viskositat ohne Ruck icht auf die Art der Strahlung zu. Bei aquivalenten Dosen waren die Gammastrahlen etwas besser wirksam als die Elektronen. Lichtstreuungsmessungen wiesen auf Aggregatbildung hin. Maximale Aggregierung wurde mit 5·106 r erzielt (Trockenpraparat). Mit 20·106 r war die Aggregatbildung kleiner, aber immer noch deutlich groser als die der Kontrollen.
Mutational analysis and characterization of the Escherichia coli hya operon, which encodes [NiFe] hydrogenase 1.

Abstract Deletion mutants of Escherichia coli specific for hydrogenase isoenzyme 1 (HYD1) have been constructed and characterized. The hya operon, which contains genes for the two HYD1 structural subunits and four additional genes, was mapped at 22 min on the E. coli chromosome. The total hydrogenase activities of the HYD1-negative mutant and wild-type strains were similar. However, the formate dehydrogenase activity associated with the formate hydrogen lyase pathway was lower in the mutant. The hya mutant (strain AP1), complemented with only the hydrogenase structural genes (hyaAB), produced antigenically identifiable but inactive HYD1 protein. The first five genes of hya (hyaA to hyaE) were required for the synthesis of active HYD1, but wild-type levels of HYD1 activity were restored only when mutant cells were transformed with all six genes of the operon. When AP1 was complemented with hya carried on a high-copy-number plasmid, the HYD1 structural subunits were overexpressed, but the excess protein was unprocessed and localized in the soluble fraction of the cell. The products of hyaDEF are postulated to be involved in the processing of nascent structural subunits (HYAA and HYAB). This processing takes place only after the subunits are inserted into the cell membrane. It is concluded that the biosynthesis of active HYD1 is a complex biochemical process involving the cellular localization and processing of nascent structural subunits, which are in turn dependent on the insertion of nickel into the nascent HYD1 large subunit.
Experimental studies of a gyro-TWT amplifier with a lossy ceramic interaction region

Summary form only given, as follows. Gyrotron traveling wave tube (gyro-TWT) amplifiers are under investigation for radar applications due to their high power and broad bandwidth capabilities in the millimeter wavelength range. The design and experimental study of a 35 GHz gyro-TWT amplifier operating in the circular TEO/sub 01/ mode at the fundamental cyclotron harmonic are presented. The interaction circuit in this experiment consisted of a new type of ceramic loading that provided controlled loading of both the TEO/sub 01/ operating mode and the backward wave oscillations to ensure stable operation. The gyro-TWT circuit consisted of a lossy, linear amplification section that employed ceramic rings spaced to provide the required absorption. The final, nonlinear stage of amplification occurred in a short conducting wall section at the end of the interaction circuit.
Stochastic leadtimes in two-level distribution type networks

Developpement et evaluation de procedures heuristiques pour determiner des delais planifies dans un reseau simple type distribution
Safety profiles and lesion size of different radiofrequency ablation technologies: a comparison of large tip, open and closed irrigation catheters.

Safety Versus Lesion Size of Ablation Catheters. Introduction: Different technologies have been developed for radiofrequency ablation (RFA), which include increasing electrode (tip) size and cooling the tip through irrigation either internally (closed-loop) with D5W or externally (open-loop) with saline. Although these catheters are widely used clinically, the propensity for adverse events and the lesion profiles of each of these catheter technologies have not been directly compared under a wide range of controlled conditions. Methods and Results: Freshly excised canine thigh muscle was placed in a chamber filled with circulating, heparinized blood heated to 37°C. Five different catheters were tested: 4 mm tip, 10 mm tip single thermistor, 10 mm tip multitemperature sensor, 4 mm closed-loop irrigated cooled-tip, and 4 mm open-loop irrigated cooled tip at several different contact and power settings. The catheter and tissue interface was continuously monitored with intracardiac echocardiography (echo) (Acuson). During the RFA, any bubbling generated from the tip and/or popping seen on echo was noted, and after each RFA, the catheter and lesion were examined for the presence of thrombus. For all of the catheters, complications correlated to the electrode tip temperature and power setting. All of the catheters experienced complications at any lesion size except for the open-irrigated catheter, which only had complications at the largest lesions. Overall, the cooled tip catheters experienced an at least sixfold greater odds of popping, bubbling, and impedance rises than the 4 mm, but the majority occurred at power levels greater than 20 W. The open-irrigated catheters created eccentric lesions that extended away from the tissue-catheter interface, in the direction of blood flow. In addition, it produced saline filled blisters at the lesion site in 16.7% of the burns. The 10 mm catheter had an at least twofold greater odds of thrombus, charring, and bubbling, but larger lesions than the 10 mm multitemperature sensor catheter. Conclusions: Catheter type, contact conditions, and power settings all play a role in lesion size and in the frequency of complications that occur during an RFA. Cooling the electrode tip, either internally or externally, does not prevent complications from occurring, especially at the higher power control settings. Adding more temperature sensors to the 10 mm seems to reduce the amount of complications that can occur. (J Cardiovasc Electrophysiol, Vol. 20, pp. 325-335, March 2009)
Involvement of glutamic acid 23 in the catalytic mechanism of T4 endonuclease V

Abstract Bacteriophage T4 endonuclease V has both pyrimidine dimer-specific DNA glycosylase and abasic (AP) lyase activities, which are sequential yet biochemically separable functions. Previous studies using chemical modification and site-directed mutagenesis techniques have shown that the catalytic activities are mediated through the α-amino group of the enzyme forming a covalent (imino) intermediate. However, in addition to the amino-terminal active site residue, examination of the x-ray crystal structure of endonuclease V reveals the presence of Glu-23 near the active site, and this residue has been strongly implicated in the reaction chemistry. In order to understand the role of Glu-23 in the reaction mechanism, four different mutations (E23Q, E23C, E23H, E23D) were constructed, and the mutant proteins were evaluated for DNA glycosylase and AP lyase activities using defined substrates and specific in vitro and in vivo assays. Replacement of Glu-23 with Gln, Cys, or His completely abolished DNA glycosylase and AP lyase activities, while replacement with Asp retained negligible amounts of glycosylase activity, but retained near wild type levels of AP lyase activity. Gel shift assays revealed that all four mutant proteins can recognize and bind to thymine dimers. The results indicate that Glu-23 is the candidate for stabilizing the charge of the imino intermediate that is likely to require an acidic group in the active site of the enzyme.
Idols in the Archive

Is a circumcision, for example, an exterior mark? Is it an archive?Let me begin at the beginning.My left eyebrow has a scar. It is jagged, and usually the droop of the eyebrow hides it from view. I see it sometimes when I look in the mirror. When I see it, I am reminded instantly of my father. He was sitting, reading a newspaper, on the lawn of our Lahore house. It was near to 6:00 p.m.—late evening to dusk. I had recently conquered the art of biking and I was eager to show him how well I rode. I kept going past him on the bike, but he was engrossed in the paper. Finally I decided that to really get his attention, I would need to go really, really fast. I went a ways, and began to pedal furiously. Right as I gathered full speed and came up to him, I looked at him to see if he was watching me. He wasn't. That split second, however, was enough for me to lose control of the bike, which swerved radically to the left, and I went face-first into a column of bricks. He looked up as I stumbled up, my eye covered in blood. I have no memory of this, except for when I “see” my scar.
Pharmacogenetics : A tool for individualising antineoplastic therapy

This article reviews the clinical relevance of pharmacogenetics in cancer chemotherapy, with emphasis on drugs for which genetic differences in enzyme metabolism have been demonstrated to affect patient outcome. About 10% of children with leukaemia are intolerant to mercaptopurine (6-mercaptopurine) because of genetic defects in mercaptopurine inactivation by thiopurine S-methyltransferase. However, mercaptopurine dose intensity, a critical factor for outcome in patients deficient in thiopurine S-methyltransferase, can be maintained by means of thiopurine S-methyltransferase phenotyping or genotyping. Patients with reduced fluorouracil (5-fluorouracil) catabolism are more likely to be exposed to severe toxicity. The measurement of dihydropyrimidine dehydrogenase activity in patients cannot be considered fully predictive, and the role of dihydropyrimidine dehydrogenase gene variants in this syndrome has yet to be clarified. With regard to irinotecan, patients with Gilbert's syndrome phenotype have reduced inactivation of the active topoisomerase I inhibitor 7-ethyl-10-hydroxycamptothecin (SN-38) caused by a mutation in the UDP-glucuronosyltransferase 1A1 gene promoter. This subset of patients is more likely to be exposed to irinotecan toxicity and could be identified by genotyping for gene promoter variants. Finally, the experience with amonafide represents a model for dose individualization approaches that use simple phenotypic probes.
Angle-resolved scatter measurements of laser-damaged DKDP crystals using a bidirectional scatter diagnostics

We built a bi-directional scatter diagnostics to measure and quantify losses due to scattering and absorption of harmonic conversion crystals (DKDP) for the National Ignition Facility (NIF). The main issues to be addressed are (1) amount of total energy reaching the target if the target hole was {+-}200 {micro}rad in size, (2) distribution of energy inside the target hole, (3) collateral damage of other optics by scattered light. The scatter diagnostics enables angle-resolved measurements at 351 nm, and is capable of both near specular transmission and large angle scatter measurements. In the near specular setup, the transmission can be measured within {+-}65 {micro}rad up to {+-}60 mrad acceptance angle. A silicon photo detector and a scientific-grade CCD camera provide total energy and energy distribution. A linear swing arm detection system enables large angle scatter measurements of 360{sup o}, in principal, with step sizes as small as 0.01{sup o} and different collection angle ranging between 1 and 20 mad. In this paper, scatter effects from laser damage and final finishing process of DKDP are discussed.
Diagnosis and management of hypersensitivity reactions related to common cancer chemotherapy agents

Objectives To review clinical hypersensitivity reactions related to common cancer chemotherapy agents and to discuss potential management strategies. Data Sources PubMed searches were performed for articles published from 1970 to 2008 regarding hypersensitivity to cancer chemotherapy and related agents using the keywords hypersensitivity, allergy, chemotherapy, platinums, taxanes, asparaginase, epipodophyllotoxins , and procarbazine . Retrieved articles were surveyed for additional citations. Study Selection Articles were reviewed for relevance to the subject matter, and the most pertinent articles were included in this review. Results Hypersensitivity reactions are commonly associated with the use of certain cancer chemotherapy drugs, including platinums, taxanes, asparaginase, procarbazine, and epipodophyllotoxins. Platinum agents (cisplatin, carboplatin, oxaliplatin) are associated with IgE-mediated hypersensitivity reactions, and skin testing may be indicated. Taxane (paclitaxel, docetaxel)-related reactions are generally non-IgE mediated, and premedication with corticosteroids and antihistamines is usually effective. Asparaginase has a high rate of hypersensitivity reactions that are likely IgE mediated or related to complement activation. Skin testing has been recommended but has not been validated for asparaginase. Procarbazine reactions can be IgE mediated but are also associated with a type III reaction manifested by pulmonary toxicity and cutaneous reactions. Hypersensitivity reactions related to epipodophyllotoxins may involve both immunologic and nonimmunologic factors that may be avoided with a slow infusion and premedication. Conclusion With the increasing use of cancer chemotherapy agents, hypersensitivity reactions are commonly encountered. Knowledge of the presentations of these reactions and management options give the treating physician the means to make an informed decision of how best to proceed.
A BILATERAL GYNANDROMORPH OF THE SNOW CRAB, CHIONOECETES OPILIO, FROM NEWFOUNDLAND, CANADA

In July of 1982 an unusual specimen of the snow crab, Chionoecetes opilio (O. Fabricius, 1788), was caught by a commercial crab fisherman at a position ap proximately 40 km N.E. of St. John's, Newfoundland, at a depth of 185 m. The animal was of 102 mm carapace width, indicating that it was probably sexually mature (Watson, 1970, found that 50% maturity occurred at 57 and 50 mm for males and females, respectively). Its shell condition was classified as new, being hard with very little epibiotic growth, indicating that it had probably molted recently. Further external examination revealed that this animal is apparently a true bilateral gynandromorph. When viewed dorsally (fig. 1) the right side of the animal is typical of mature males while appendages on the left side are greatly reduced in size in proportion to the carapace width. Ventrally the body of the animal was differentiated bilaterally into a male and a female side. The right half exhibits a typical male abdomen which is broad at the base but tapers anteriorally to a slightly rounded tip. The left half exhibits the broad rounded configuration typical of a sexually mature female snow crab (fig. 2). Beneath the abdomen the secondary sexual characteristics are again typical and complete for each sex on their respective sides. On the male half, pleopods are modified so as to effect the transfer of spermatophores into the seminal receptacle while the female half of the animal consists of a seemingly complete seminal receptacle and biramous pleopods used for egg attachment (fig. 3). Although dissection of the animal in order to determine whether or not sper matophores were present in the vas deferens and whether there were mature ova in the ovary could have been informative, this was not attempted as the specimen had been cooked and frozen upon collection in a misguided attempt at preservation.
The potential importance of migratory stopover sites as flight feather molt staging areas: a review for neotropical migrants

The decline of many species of Neotropical migrants has prompted increased research on their ecology on their breeding and wintering grounds. However, studies of their ecology during migration are relatively few. Despite documentation of molt-migration in at least six Neotropical passerine species, this phenomenon has been ignored in current conservation strategies for Neotropical migrants. In this review paper, we suggest that molt studies need to be done as a way to refine and improve conservation plans for Neotropical migrants. We identify three important questions that merit further study: (1) which Neotropical migrant species undergo flight feather molt at migratory-stopover sites; (2) where are molt-migration stopover sites geographically located; and (3) why are these sites preferred as stopover sites during molt? Finding answers to these questions will allow us to protect molt staging areas occupied by Neotropical migrants during migration as many wetland and nearshore oceanic habitats have been protected for molting waterfowl, shorebirds, and seabirds.
Sb-based two-color photodetector fabrication and characterization

Sb-based dual-band detectors were fabricated and characterized. The first band consists of an InGaAsSb pn junction for long wavelength detection, while the second band consists of a GaSb pn junction for shorter wavelength detection. Both bands were grown, lattice-matched to a GaSb substrate, using metal-organic vapor phase epitaxy. Three metal contacts were deposited to access the individual junctions. Spectral response measurements indicated either independent operation of both detectors simultaneously, or bias selective operation for one detector while serially accessing both devices.
Some elementary attempts at numerical modeling of problems concerning rates of evolutionary processes

Abstract An account of numerical work prepared on electronic computers- the problems concerned the ratio at which favorable mutations spread throughout the population subject to a “survival of the fittest” mechanism. Models of asexual reproduction showed the expected linear growth in the number of improvements. The bisexual process greatly accelerated the average acquisition rate.
Reductive detoxification as a mechanism of fungal resistance to singlet oxygen-generating photosensitizers.

Abstract Fungi that are resistant or sensitive to the singlet oxygen-generating toxin cercosporin were assayed for their ability to detoxify it by reduction. Cercosporin reduction was assayed microscopically by using bandpass filters to differentiate between fluorescence emission from cercosporin and reduced cercosporin. Hyphae of the resistant Cercospora and Alternaria species emitted a green fluorescence, indicative of reduced cercosporin. Hyphae of nonviable cultures and of cercosporin-sensitive fungi did not reduce cercosporin. Sensitive fungi occasionally reduced cercosporin when incubated with reducing agents that protect against cercosporin toxicity. Cercosporin could not be efficiently photoreduced in the absence of the fungus. Cercospora species were also resistant to eosin Y but were sensitive to rose bengal. Microscopic observation demonstrated that Cercospora species were not capable of reducing rose bengal but were capable of reducing eosin Y. These observations were supported by in vitro electrochemical measurements that revealed the following order with respect to ease of reduction: cercosporin >> eosin Y > rose bengal. The formal redox potential (E 0') of cercosporin at pH 7.5 was found to be -0.14 V vs. the normal hydrogen electrode. We conclude that Cercospora species protect themselves against cercosporin by the reduction and detoxification of the toxin molecule.
A Standpipe Screen Design to Prevent Fry Loss during Tank Cleaning

Abstract Intensive larviculture of walleye Sander vitreus and other fishes require fine screens over the standpipe to retain the small fish. The high feeding rate of small (<710-μm) microparticulate feed requires that screens be removed for daily cleaning with pressurized water to remove waste feed, oil, and biofilm. Standard screens have an open bottom that can trap fry in the space between the standpipe and the screen when the screen is replaced. Here we describe a modification of a standpipe screen that prevents the fry from entrapment in the space between screen and standpipe. Received April 23, 2010; accepted June 22, 2010
Superresolution imaging in live Caulobacter crescentus cells using photoswitchable enhanced yellow fluorescent protein

Recently, photoactivation and photoswitching were used to control single-molecule fluorescent labels and produce images of cellular structures beyond the optical diffraction limit (e.g., PALM, FPALM, and STORM). While previous live-cell studies relied on sophisticated photoactivatable fluorescent proteins, we show in the present work that superresolution imaging can be performed with fusions to the commonly used fluorescent protein EYFP. Rather than being photoactivated, however, EYFP can be reactivated with violet light after apparent photobleaching. In each cycle after initial imaging, only a sparse subset fluorophores is reactivated and localized, and the final image is then generated from the measured single-molecule positions. Because these methods are based on the imaging nanometer-sized single-molecule emitters and on the use of an active control mechanism to produce sparse sub-ensembles, we suggest the phrase "Single-Molecule Active-Control Microscopy" (SMACM) as an inclusive term for this general imaging strategy. In this paper, we address limitations arising from physiologically imposed upper boundaries on the fluorophore concentration by employing dark time-lapse periods to allow single-molecule motions to fill in filamentous structures, increasing the effective labeling concentration while localizing each emitter at most once per resolution-limited spot. We image cell-cycle-dependent superstructures of the bacterial actin protein MreB in live Caulobacter crescentus cells with sub-40-nm resolution for the first time. Furthermore, we quantify the reactivation quantum yield of EYFP, and find this to be 1.6 x 10-6, on par with conventional photoswitchable fluorescent proteins like Dronpa. These studies show that EYFP is a useful emitter for in vivo superresolution imaging of intracellular structures in bacterial cells.
In vivo tumor cell targeting with "Click" nanoparticles

The in vivo fate of nanomaterials strongly determines their biomedical efficacy. Accordingly, much effort has been invested into the development of library screening methods to select targeting ligands for a diversity of sites in vivo. Still, broad application of chemical and biological screens to the in vivo targeting of nanomaterials requires ligand attachment chemistries that are generalizable, efficient, covalent, orthogonal to diverse biochemical libraries, applicable under aqueous conditions, and stable in in vivo environments. To date, the copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition or "click" reaction has shown considerable promise as a method for developing targeted nanomaterials in vitro. Here, we investigate the utility of "click" chemistry for the in vivo targeting of inorganic nanoparticles to tumors. We find that "click" chemistry allows cyclic LyP-1 targeting peptides to be specifically linked to azido-nanoparticles and to direct their binding to p32-expressing tumor cells in vitro. Moreover, "click" nanoparticles are able to stably circulate for hours in vivo following intravenous administration (>5 h circulation time), extravasate into tumors, and penetrate the tumor interstitium to specifically bind p32-expressing cells in tumors. In the future, in vivo use of "click" nanomaterials should expedite the progression from ligand discovery to in vivo evaluation and diversify approaches toward multifunctional nanoparticle development.