cssi/SciSciGPT-SciSciNet huggingface dataset:
Protein synthesis and turnover in normal and hypertrophied heart

Abstract This review deals with some aspects of the synthesis, assembly and turnover of mitochondrial and myofibrillar proteins in normal and hypertrophied hearts. The dynamic state of the myocardium, in which intracellular proteins and organelles are constantly being destroyed and synthesized, is emphasized. In normal cardiac muscle, mitochondrial inner membrane cytochromes turn over synchronously with half-lives of 5 to 6 days. The various myofibrillar proteins also turn over; the fact that they do so with identical apparent half-lives of 8 to 10 days suggests that these proteins are assembled and degraded synchronously. In cardiac hypertrophy produced by constriction of the ascending aorta in rats, inner mitochondrial membrane cytochromes increase in parallel. Early in hypertrophy (1 day after aortic constriction) cytochrome content per gram of heart weight increases, indicating a disproportionate increase in mitochondrial cytochrome mass. By the third postoperative day there already is a decrease in cytochrome content per gram of heart weight. The increase in mitochondrial cytochrome content observed in the hypertrophied heart appears to be due to a decreased rate of cytochrome destruction as well as to an increased rate of cytochrome synthesis. The data on myosin accumulation are consistent with either decreased destruction of myosin or increased efficiency of reutilization of labeled amino acids.
Theory Of Enhanced Optical Nonlinearities In Quantum Dots

A discussion of the exciton regime of quantum dots is presented. We predict the possibility of enhancement of the optical nonlinearities due to exciton quantization. Applications to the dynamic Stark effect and two-wave mixing processes are described.
Reactions of alkyl- and aryl(ferrocenyl)phosphines with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone

Abstract Reaction of diphenyl(ferrocenyl)phosphine ( 1 ), tri(ferrocenyl)phosphine ( 2 ) and t butyl(diferrocenyl)phosphine ( 3 ) with one equivalent of 2,3-dichloro-4,5-dicyano-1,4-benzoquinone (DDQ) yields FcPPh 2 • DDQ ( 4 ), Fc 3 P • DDQ ( 5 ) and Fc 2 P t Bu • DDQ ( 6 ), respectively. Infrared, UV–Vis and ESR spectra of 4 – 6 are consistent with formation of DDQ − Mossbauer spectroscopy, however, reveals that 4 – 6 all contain low spin Fe II suggesting that the radical cation is ligand centered rather than iron centered.
Evidence for the Construct Validity and Reliability of the Co-Cultural Theory Scales

Co-cultural theory provides a theoretical framework that examines the ways that members of co-cultural groups communicate when interacting with members of a dominant culture (Orbe, 1998a). The tenants of the theory were inductively derived via phenomenological analyses of focus group and interview data. Two of the central theoretical components, preferred outcome and communication approach, have been conceptualized as general tendencies that influence communication practices by co-cultural group members within interactions with members of dominant cultural groups. This article reports on the design of a self-report measure of these two components of co-cultural theory and provides evidence from two studies for the construct validity and reliability of the co-cultural theory scales (C-CTS).
Scoring formulas and probability considerations

Bayes' theorem of inverse probability is made the basis of a general equation for scoring objective examinations. The equation so obtained is evaluated by assuming a binomial distribution of examinee knowledge and guessing tendency. A graphical illustration of the application of this equation to a hypothetical test situation is presented. The limitations inherent in the use of Bayes' theorem make it inadvisable to recommend the practical use of the equation unless future experimental evidence indicates an increase in scoring validity which more than compensates for the increase in scoring difficulty.
Flurbiprofen treatment of periodontal disease in beagles.

The effect of the non-steroidal anti-inflammatory drug flurbiprofen on the progression of periodontal disease was studied in 12 beagle dogs over a 2-yr period. Standardized radiographs were used to measure the rate of bone loss; bone-seeking radiophormaceutical uptake was used to assess the effect on bone metabolism, and gingival inflammation was scored. Following a 6-month pretreatment baseline period. 6 dogs were dosed daily with 0.02 mg/kg flurbiprofen for a 12-month treatment period. Also, one side of the mouth in each dog was treated with periodontal flap surgery at the beginning of the treatment period. After 12 months, flurbiprofen was discontinued and the dogs were studied for a 6-month post-treatment period. In flurbiprofen-treated dogs the rate of bone loss was significantly decreased about both surgically and non-surgically treated teeth throughout the 12-month treatment period. This decreased rate was sustained through 3 months of the post-treatment period, but was lost 6 months following the termination of flurbiprofen therapy. No similar effect on reducing the rate of bone loss was observed in the placebo-treated dogs. A significant decrease in bone-seeking radiopharmaceutical uptake was observed in the flurbiprofen-treated teeth, which corresponded with the radiographic findings. Changes in gingival inflammation with flurbiprofen treatment were not observed. These data indicate that flurbiprofen is a potent inhibitor of alveolar bone loss in beagles and within 6 months of the termination of flurbiprofen the effect on slowing the rate of bone loss is lost.
Determination of rare earth elements after pre-concentration using NOBIAS-chelate PA-1®resin: Method development and application in the San Francisco Bay plume

Abstract The resin NOBIAS-chelate PA-1® was used to develop an off-line pre-concentration and extraction method for rare earth elements (REEs) in seawater prior to quantification using magnetic sector, high resolution, inductively coupled plasma mass spectrometry (HR ICP-MS). The method employed an off-line manifold that is inexpensive, easy to set-up, and allows simultaneous processing of several samples. The method has low blanks and detection limits, which were in the range of 0.01 pmol kg− 1 to 0.82 pmol kg− 1, and yields quantitative recovery for all REEs (La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu) precluding the need to use isotope dilution. The HR ICP-MS allows an integrated, time-averaged signal of the eluent sample, reducing the HR ICP-MS instrument time relative to an in-line extraction procedure. The applicability of the method was demonstrated in a test of the hypothesis that some REEs are being mobilized by anthropogenic activities and are elevated in San Francisco Bay (SFB) and its discharge plume into coastal waters off Central California. This was done by normalizing REE data from the SFB to those of the GEOTRACES Surface Coastal (GSC) reference sample, collected in the Santa Barbara Basin off Southern California. The normalized REE pattern indicated a substantial Gd anomaly of up to 30-fold higher than GSC in the industrial southern reach of the SFB (Lower South Bay), and to a lesser extent in the plume, indicative of anthropogenic Gd inputs, associated with the medical use of Gd-based contrasting agents in magnetic resonance imagery, from the surrounding metropolitan area. Smaller anomalies for Lu and Yb were also observed in the Lower South Bay and plume, which were tentatively attributed to industrial inputs. However, because of the relatively restricted industrial uses of these elements this hypothesis requires further investigation. Ce and Eu anomalies were observed in the northern reaches of the Bay and appeared to be associated with natural redox mediated behavior of these REEs.
A new stabilization strategy for incomplete LU preconditioning of indefinite matrices

A two step combined preconditioning strategy is proposed to construct stable and accurate incomplete LU factorization of indefinite matrices arising from CFD applications. This preconditioning procedure is divided into two steps, each step is a factorization of a shifted matrix. Numeral experiments show that a preconditioner can be computed with high accuracy and low fill-in, and that the new strategy is robust on some difficult indefinite matrix test problems.
Compact → Extended Helix Transitions of Polyalanine in Vacuo

The relative stabilities of conformations of [Alan + 3H]3+ peptides (where n = 27−39) have been examined in the gas phase using ion mobility/time-of-flight techniques. At room temperature, two series of conformations that do not interconvert during the 10−40-ms experimental time scales are observed: extended helical structures and more compact geometries assigned as hinged helix-coils (Counterman, A. E.; Clemmer, D. E. J. Am. Chem. Soc., 2001, 123, 1490). At elevated temperatures, a single structural transition is observed; the more compact state unfolds and adopts extended helical structures for all sizes. Relative activation energies for the compact → extended helix transitions increase linearly by ∼1 kcal·mol-1·residue-1 over the n = 27−39 size range. Mechanisms that consider important steps in the helix-coil → helix transition are discussed. We propose that release of the hinge might be a difficult step in this transition that is instigated by intramolecular reorganization of protons.
Anti-Tetanus Toxoid Antibodies in Intravenous Gamma Globulin: An Alternative to Tetanus Immune Globulin

The levels of anti-tetanus toxoid IgG antibodies were measured in 29 lots of intravenous gamma globulin (IVIG). The antibody levels varied from 4 to 90 IU/mL (geometric mean, 18.6; 90% confidence interval, 9.7-35.7). The variation from manufacturer to manufacturer accounted for most of the observed differences among lots; there was relatively little variability among multiple lots from a single manufacturer. IVIG may be an acceptable alternative to horse or human tetanus immune globulin.
The relative importance of directional change, random walks, and stasis in the evolution of fossil lineages

The nature of evolutionary changes recorded by the fossil record has long been controversial, with particular disagreement concerning the relative frequency of gradual change versus stasis within lineages. Here, I present a large-scale, statistical survey of evolutionary mode in fossil lineages. Over 250 sequences of evolving traits were fit by using maximum likelihood to three evolutionary models: directional change, random walk, and stasis. Evolution in these traits was rarely directional; in only 5% of fossil sequences was directional evolution the most strongly supported of the three modes of change. The remaining 95% of sequences were divided nearly equally between random walks and stasis. Variables related to body size were significantly less likely than shape traits to experience stasis. This finding is in accord with previous suggestions that size may be more evolutionarily labile than shape and is consistent with some but not all of the mechanisms proposed to explain evolutionary stasis. In general, similar evolutionary patterns are observed across other variables, such as clade membership and temporal resolution, but there is some evidence that directional change in planktonic organisms is more frequent than in benthic organisms. The rarity with which directional evolution was observed in this study corroborates a key claim of punctuated equilibria and suggests that truly directional evolution is infrequent or, perhaps more importantly, of short enough duration so as to rarely register in paleontological sampling.
Dynamic adaptive redundancy for quality-of-service control in wireless sensor networks

In this paper, we develop and evaluate a new concept of adaptive optimal redundancy to efficiently provide wireless sensor network (WSN) users with QoS-aware information services. Our approach to satisfying application QoS requirements while maximizing the system lifetime is to determine dynamically the optimal level of redundancy at the “source” and “path” levels in response to network dynamics and query QoS requirements on a query by query basis. We develop a mathematical model to analyze the performance characteristics of our proposed solution. The obtained results show that dynamically and adaptively identifying and managing optimal redundancy for per-hop data delivery lead to satisfying query QoS requirements in terms of reliability and timeliness, while maximizing the useful lifetime of WSNs. We validate the analytical results with extensive simulation.
Activation of HIF-1α mRNA by hypoxia and iron chelator in isolated rat carotid body

Abstract The hypoxia inducible factor-1α (HIF-1α) protein level is increased by hypoxia and iron chelator (ciclopirox olamine) in isolated rat carotid body (CB) and glomus cells. Reverse transcription and polymerase chain reaction (RT-PCR) are performed to test whether this increase is caused, at least in part, by increased HIF-1α gene transcription. HIF-1α mRNA levels dose-dependently increased and decreased in the rat CBs incubated for 1 h in a medium saturated with O2 levels that were varied around nominally normoxic level of 21% in the 0–95% range. The iron chelator, ciclopirox olamine (5 μM), stimulated HIF-1α mRNA production under normoxic condition. Thus, in the CB, the main systemic O2-sensing organ, HIF-1α transcription is regulated by O2 supply around the normoxic level; this may contribute to cellular and organismal adaptations to chronic changes in ambient O2.
On a theory of equivalent fuzzy logic advisors

A fuzzy logic advisor (FLA) is the interconnection of three subsystems: encoder, fuzzy logic system, and decoder. It is very useful for making social judgments, and provides a nonlinear mapping of the indicators of a social judgment into a linguistic level of that judgment. A cooperative environment is needed to design the fuzzy logic system within the FLA, and this is done by means of surveys. After defining the notion of equivalent FLAs, this paper provides a theoretical answer to the following question: under what conditions will two (or more) FLAs, that have been designed for the same social judgment, be equivalent? It answers the question with conditions that are both necessary and sufficient. These conditions lead to an equivalency diagram and a practical test to establish equivalence of two (or more) FLAs.
An Empirical Test of an Axiomatic Model of the Relationship Between Language Intensity and Persuasion

The study tested six axioms concerning the effect of language intensity on receiver attitudes. The axioms specify source and receiver variables which might moderate the relationship between intensity and attitude change. The results were consistent with an information processing model based on message discrepancy, expectancy and elaboration likelihood theories. Intensity affected attitudes through three routes. First, intensity increased attitude change via message clarity, with clarity acting as a mediator variable. Second, intensity inter acted with discrepancy and perceived source likeability to produce attitude change. Third, the effect of intensity on attitudes was moderated by source expectations. Results showed that intensity enhances persuasiveness for a high credibility source, inhibits persuasiveness for a low credibility source, and has no effect for a moderate credibility source. Receiver anxiety moderated the effect of source gender expectations on the intensity-attitude relationship. A revis...
Challenges with Demographic Disparities in Gastric Cancer Care and Survival: Spectral Rather than Black and White

Commentary on Stessin and Sherr, [p. 223][1] Gastric cancer, although not too common in the United States, remains among the most lethal malignancies despite recent progress in multimodality therapy ([1][2]). Among the reasons, late-stage diagnosis and challenges to the delivery of complex care are
Immunizations in the United States.

Prevention of disease through the use of vaccines is one of the great success stories of public health and preventive medicine in the United States. Our success in reducing morbidity and mortality from diseases preventable by vaccine is comparable to, or better than, that of virtually any other country in the world. Table 1 shows the maximum reported incidence of diseases preventable by vaccine, the year in which that occurred, and the provisional total number of cases reported in 1989. There have been reductions of 90% or more in reported incidence of all of these diseases. Even though the 16 000 cases of measles reported in 1989 is the largest total since 1978, it still is less than 2% of the peak number. Notwithstanding this great success, there are serious deficits in our immunization program, although the situation is not as bad as one might surmise from the background paper, which does not take into account many factors such as differences in data sources, means of assessment, and surveillance systems. First, I describe the current situation, and then discuss some of the problems we face. The current US immunization schedule (Table 2) calls for a total of six visits for immunization between birth and school entry. Children should receive immunization during the first year of life, the second year, and the fifth or sixth year (just before entry to school). Thus, the population in need of services on an annual basis is three birth cohorts, or approximately 11 to 12 million children. Recent recommendations from the American Academy of Pediatrics for a second dose of measles vaccine to be administered at approximately 12 years of age call for another visit for vaccination and increase the number of children to receive vaccine in a given year to 15 to 16 million.
Visualizing coercible simulations

The labor intensive aspects of simulation development and maintenance make exploration of reuse essential. However, reuse is generally difficult to achieve in practice due to inflexible assumptions and changing requirements. This paper discusses a technology for simulation reuse called COERCE and the visualization tools that this technology requires. COERCE addresses techniques to make simulations more flexible (coercibility) and the process of transforming a simulation to meet new objectives (coercion). We address the following question: Given that COERCE is a semi-automated technology, what visualization capabilities are necessary to support it? We address this question empirically by studying the role of visualization in the construction of a new coercible simulation and in the coercion of an existing example simulation. Based on this study, we propose a set of requirements for any visualization toolkit meant to support COERCE.
On the theory of general on-off sources with applications in high-speed networks

A general theory of on-off sources is provided. The basic source model is characterized by alternating independent on (burst) and off (silence) periods, which may have general distributions. Other more complex sources are constructed, and their behavior is characterized in terms of the basic source model. Heterogeneous and homogeneous statistical multiplexers fed by such sources are considered. In the heterogeneous environment, a simple result on the tail behavior of the multiplexer queue length distribution in the heavy traffic is provided. In the homogeneous environment, asymptotic results on the tail behavior of the queue length distribution are provided for all levels of utilization. The results for the heterogeneous environment suggest a new call admission control policy for general on-off sources in high-speed networks, which depends only on the first two moments of the on and off periods of individual sources and their respective peak rates. >
Ethanol as a possible cofactor in the development of murine AIDS.

Chronic ethanol (EtOH) abuse in humans leads to a variety of immunomodulatory events that can alter resistance to a number of infectious agents. Whether alcohol abuse affects the susceptibility to human immunodeficiency virus infection or the subsequent development of acquired immune deficiency syndrome (AIDS) is a matter of extreme importance ; however, available information in humans or animal models is limited. The goal of this study was to evaluate the effect of chronic EtOH feeding in mice on the development of immunodeficiency in the murine model of AIDS (MAIDS). C57BV6 mice were placed on the Lieber-DeCarli liquid EtOH diet (25% or 31% total caloric intake) or a nutrient-matched isocaloric liquid control diet. Seven days later, mice were infected with the LP-BM5 murine leukemia virus mixture, and groups of infected and noninfected mice were assayed at defined time points postinfection for antigen-specific and nonspecific immune responses. In the absence of retroviral infection, chronic EtOH feeding (5-8 weeks) led to reductions in spleen weights, compared with isocaloric controls. In spite of reduced spleen size, mitogenic responses of spleen cells to concanavalin A (ConA) and lipopolysaccharide (LPS) were elevated in EtOH-fed mice, as compared with mice fed the control diet. Chronic EtOH feeding also enhanced the allogeneic mixed lymphocyte response and increased antigen-specific priming of both B-cells and CD4 + T-cells to the antigen, sheep red blood cells. In MAIDS-infected mice, chronic EtOH feeding delayed but did not prevent the onset of virus-induced immunodeficiency and MAIDS-induced autoantibody synthesis. In contrast to mice with MAIDS infection alone, infected mice fed an EtOH diet displayed significant mitogenic responses to ConA and LPS at 4 weeks postinfection ; however, at 8 weeks postinfection, both groups were completely immunosuppressed. Liver damage was detected in all groups of EtOH-fed mice, as indicated by the elevated liver enzymes, ALT and AST ; moreover, MAIDS infection did not alter the extent of liver damage caused by EtOH feeding. These data suggest that chronic feeding of the Lieber-Decarli EtOH diet in mice can lead to immune enhancement and that under these conditions causes a delay in the onset of MAIDS. Whether these results are caused by the effects of chronic exposure of the immune system to EtOH or to elevated nutrient levels in the standard Lieber-Decarli liquid EtOH diet is discussed.
Detection of Multiple Change Points from Clustering Individual Observations

In the preliminary analysis, also called Stage 1 analysis or retrospective analysis, of statistical process control, one may confront multiple shifts and/or outliers, especially with a large number of observations. This paper addresses the analysis of individual observations, and shows that the X-chart and CUSUM chart may fail to detect the presence of any shifts or outliers when multiple shifts and/or outliers are present. A new method is introduced which is effective in detecting single or multiple shifts and/or outliers. The algorithm and an effective stopping rule that controls the false detection rate are described. Suggestions are given for reducing masking and for diagnosing the number of shifts or outliers present.
Climate, demography and lek stability in an Amazonian bird.

Lekking is a rare, but iconic mating system where polygynous males aggregate and perform group displays to attract females. Existing theory postulates that demographic and environmental stability a...
Experimental evaluation of anti-windup extremum seeking control for airside economizers

Abstract The performance of anti-windup extremum seeking control (ESC) as a model free online optimization strategy is evaluated by experimental studies for energy efficient operation of both chilled-water and direct-expansion airside economizers. For the chilled-water based system, the ESC takes the chilled-water valve control signal as the feedback, and controls the outdoor air damper (OAD) position to minimize the cooling coil load. For the direct-expansion system, the ESC takes the total electricity power consumption as the feedback, and controls the OAD position to minimize the power consumption. Experimental results verify the effectiveness of the ESC scheme for model-free operation without temperature and humidity measurements.
Additions to the Phycomycete Flora of the Douglas Lake Region. III. A New Species of Scherffeliomyces

During the Summer of 1954 there was encountered an interesting chytridiaceous fungus in a collection of algae and decaying plant mate? rial from the vicinity of the University of Michigan Biological Station, Cheboygan, Michigan. In this organism the sporangium is produced from an expansion of the epibiotic portion of the germ tube formed by the encysted zoospore, the zoospore cyst and a segment of the germ tube persisting as an appendage on the developing and mature spo? rangium. These features are characteristic of two small and infre? quently observed genera of chytrids, Scherffeliomyces Sparrow (2, 3) and Coralliochytrium Domjan (1). Subsequent investigation indicated that this organism belongs to the genus Scherffeliomyces and that it is distinct from previously described members of the genus. It is, there? fore, described as new.
Additions to the oothecae, uricose glands, ovarioles, and tergal glands of Blattaria

Oothecae, ovarioles, and male uricose glands of cockroaches collected in Brazil and Thailand were studied. The oothecae of 72 species are illustrated for the first time. At oviposition, the water content of the oothecae of Blaberidae is 50%. Male uricose glands occur commonly in many Plectopterinae and Blattellinae, and in some Epilamprinae. At oviposition, the maximum number of oocytes containing yolk in Zone V per ovariole is 2 in Blattidae and Polyphagidae, 1 or 2 in Blattellidae, and 1 in Blaberidae. The presence or absence of male tergal glands was determined for about 90 genera and about 284 species (museum specimens) of Blaberidae. Tergal glands occur in relatively few genera of blaberids and when present are located on the anterior tergites of some Epilamprinae and Oxyhaloinae.
SOLUBILIZATION BY BUTANOL OF RABBIT CELL-ANTIGENS ASSOCIATED WITH THE REJECTION OF TRANSFERRED LYMPH NODE CELLS.

SummaryStudies have been carried out on the solubilization of the rabbit cell-antigen associated with rejection of transferred allogeneic lymph node cells. Using as a preliminary criterion serologic reaction vs cell-suppressive rabbit anti-rabbit-leucocyte sera, soluble antigen has appeared in low concentration in suspensions of liver cell-fragments from normal rabbits kept for some days at 4°C. The antigen was solubilized by the use of butanol at 20% by volume from suspensions of such liver cell-fragments, if the suspensions were previously maintained at 4°C for some time. Butanol extraction could also be applied to Triton-extracted lipoprotein of cell-fragments obtained from normal rabbit lymph node and spleen with serologically active material obtained in solution in about 10 times the yield obtained from liver, relative to mass of tissue. When the butanol-extracted soluble antigen from rabbit lymph node was injected twice into normal rabbits, the sera of the latter showed the property of suppressing a...
User experience and behaviour research based on design information framework

Aim This research addresses the incorporation of this framework in a structured form of scenario generation to facilitate design problem identification and analysis from holistic viewpoints.Methods Design Information Framework(DIF) was introduced as a mechanism to accommodate multiple viewpoints and to represent them for effective management of design information.Results By introducting the DIF as a unified information platform,sharing and interpreting multiple aspects from different discipline was enabled.Conclusion This method can support the resolution,communication of issues,and better describing the users′ behaviour upon contexts.
Special microanatomical features surrounding the intracorpora cavernosa nerves and their probable function during erection

AbstractThe nerves of the corpora cavernosa have anatomical characteristics different from other nerves. The intracavernous nerves are located in fibrous tunnels into which numerous fibrous bundles establish attachments. These bundles are part of the fibrous meshwork included in the corpora cavernosa.We suspect that during erection, when the corpora fill with blood and high intracavernous pressure develops, the aforementioned meshwork of fibrous bundles attached to all fibrous elements of the corpora, including the tunica albuginea and the perineural fibrous tunnels, stretches and prevents compression of the intracavernous nerves.
Rothko's Negative Theology

This paper argues that the progression of Mark Rotho's painting, from his early, surrealist work to his more famous and more abstract Classical paintings, can be read as following the same structure as outlined by Pseudo-Dionysius' apophatic theology. In his Divine Names and Mystical Theology , Pseudo-Dionysius describes a process whereby one speaks, and fails to speak, the divine. He describes a process that begins in sensory experience and ends up, after ascending by way of negation, in an ";unknowing"; beyond the intellect, a ";darkness beyond light."; This ascension is motivated by what he describes as ";yearning"; and ";beauty."; I argue that both Rothko and Pseudo-Dionysius begin their accounts of beauty in corporeality and recognition only to, through negation, move beyond it. That is, I read Rothko's paintings' progress from specifically religious subject matter into almost pure monochromatic abstraction to mirror the progression of the mystic ascending towards God; Rothko, like Pseudo-Dionysius, negates the form of the body, the form of religious imagery, in his attempts to give the viewers of his painting an experience of transcendence.
Matrix Formulation of the Eigenvalue Problem

The earliest published version of modern quantum mechanics was Heisenberg’s formulation, known asmatrix mechanics1 In it, Heisenberg turned away from classical quantities that could not be measured experimentally and considered “observable magnitudes” expressible as elements of two dimensional arrays. Heisenberg’s empirical rules for combining these magnitudes were identical to mathematical rules for combining matrices that were just at that time being developed by the mathematicians at Gottingen in Germany where Heisenberg was working as a physicist.
Whole-Organism Cellular Pathology: A Systems Approach to Phenomics.

Phenotype is defined as the state of an organism resulting from interactions between genes, environment, disease, molecular mechanisms, and chance. The purpose of the emerging field of phenomics is to systematically determine and measure phenotypes across biology for the sake of understanding. Phenotypes can affect more than one cell type and life stage, so ideal phenotyping would include the state of every cell type within the context of both tissue architecture and the whole organism at each life stage. In medicine, high-resolution anatomic assessment of phenotype is obtained from histology. Histology's interpretative power, codified by Virchow as cellular pathology, is derived from its ability to discern diagnostic and characteristic cellular changes in diseased tissues. Cellular pathology is observed in every major human disease and relies on the ability of histology to detect cellular change in any cell type due to unbiased pan-cellular staining, even in optically opaque tissues. Our laboratory has shown that histology is far more sensitive than stereomicroscopy for detecting phenotypes in zebrafish mutants. Those studies have also shown that more complete sampling, greater consistency in sample orientation, and the inclusion of phenotypes extending over longer length scales would provide greater coverage of common phenotypes. We are developing technical approaches to achieve an ideal detection of cellular pathology using an improved form of X-ray microtomography that retains the strengths and addresses the weaknesses of histology as a screening tool. We are using zebrafish as a vertebrate model based on the overlaps between zebrafish and mammalian tissue architecture, and a body size small enough to allow whole-organism, volumetric imaging at cellular resolution. Automation of whole-organism phenotyping would greatly increase the value of phenomics. Potential societal benefits would include reduction in the cost of drug development, a reduction in the incidence of unexpected severe drug and environmental toxicity, and more rapid elucidation of the contributions of genes and the environment to phenotypes, including the validation of candidate disease alleles identified in population and personal genetics.
Unique characteristics of cryptococcosis identified after death in patients with liver cirrhosis: comparison with concurrent cohort diagnosed antemortem

Characteristics of cirrhosis-associated cryptococcosis first diagnosed after death are not fully known. In a multicenter study, data generated as standard of care was systematically collected in 113 consecutive patients with cirrhosis and cryptococcosis followed for 80 patient-years. The diagnosis of cryptococcosis was first established after death in 15.9% (18/113) of the patients. Compared to cases diagnosed while alive, these patients had higher MELD score (33 vs. 22, P = .029) and higher rate of cryptococcemia (75.0% vs. 41.9%, P = .027). Cases diagnosed after death, in comparison to those diagnosed during life were more likely to present with shock (OR 3.42, 95% CI 1.18-9.90, P = .023), require mechanical ventilation at admission (OR 8.5, 95% CI 2.74-26.38, P = .001), less likely to undergo testing for serum cryptococcal antigen (OR 0.07, 95% CI 0.02-0.21, P < .001) and have positive antigen when the test was performed (OR 0.07, 95% CI 0.01-0.60, P = .016). In a subset of cirrhotic patients with advanced liver disease cryptococcosis was first recognized after death. These patients had the characteristics of presenting with fulminant fungemia, were less likely to have positive serum cryptococcal antigen and posed a diagnostic challenge for care providers.
Huisartsen genetica en zeldzame ziekten

Van zorgverleners in de eerste lijn wordt in toenemende mate verwacht dat zij in de dagelijkse praktijk genetische zorg verlenen. Dit vereist een goede voorbereiding, vaardigheden en kennis om patienten die vragen om informatie en advies op dit terrein te kunnen helpen. Zorgverleners kunnen zich via internet op de hoogte stellen van genetica wanneer ze het nodig hebben. Toepassingen van de snelle ontwikkelingen op het gebied van de genetica in de dagelijkse zorgpraktijk zijn voorhanden, doordat steeds updates plaatsvinden. Dit artikel heeft als doel u te laten zien welke online informatiebronnen over genetica voor u als huisarts en voor de patient beschikbaar zijn, bijvoorbeeld op huisartsengenetica.nl, over welke informatie u kunt beschikken, maar ook wat de beperkingen zijn. Het probeert u, bijvoorbeeld als het gaat om zeldzame ziekten in de dagelijkse praktijk, te laten inzien dat u voor de dagelijkse huisartsgeneeskundige zorgpraktijk veel kunt hebben aan informatie over genetica. Hopelijk inspireert het om opgedane kennis en vaardigheden in de dagelijkse praktijk effectief te gaan toepassen. De digitale middelen zijn overzichtelijk bij elkaar gezet in tab. 1 ‘Overzicht aanbod e‑health informatie bij zeldzame (genetische) aandoeningen’ en in tab. 2 ‘Informatie over genetica in het algemeen’. Tijdige verwijzing van nog niet gediagnosticeerde hoogrisicopatienten kan tot preventieve behandeling leiden, ziekten kunnen worden voorkomen en patienten en familieleden kunnen zich zo gesteund voelen door u als huisarts.
Venture Exchange Regulation: Listing Standards, Market Microstructure, and Investor Protection

This chapter from the forthcoming Handbook on Law and Entrepreneurship (Gordon Smith & Christine Hurt eds.) sets out a template for the regulation of venture exchanges — securities markets specifically designed for trading smaller and younger firms. I argue for listing standards that eliminate the smallest and youngest firms, and those where the listing exchange perceives a heightened risk of fraud. I also suggest that market microstructure rules should mandate fully transparent call-auction trading and limit trading to the listing exchange. Finally, I argue that the most efficient and effective way to protect investors is to deemphasize ex ante regulation, in particular, mandated disclosures, much of which retail investors would likely ignore, and instead emphasize ex post regulation, in particular, SEC enforcement of the rules against securities fraud, market manipulation, and insider trading.
Computer-aided drug discovery research at a global contract research organization

Computer-aided drug discovery started at Albany Molecular Research, Inc in 1997. Over nearly 20 years the role of cheminformatics and computational chemistry has grown throughout the pharmaceutical industry and at AMRI. This paper will describe the infrastructure and roles of CADD throughout drug discovery and some of the lessons learned regarding the success of several methods. Various contributions provided by computational chemistry and cheminformatics in chemical library design, hit triage, hit-to-lead and lead optimization are discussed. Some frequently used computational chemistry techniques are described. The ways in which they may contribute to discovery projects are presented based on a few examples from recent publications.
Effect of injectable trace mineral administration on health, performance, and vaccine response of newly received feedlot cattle

ABSTRACT Previous research has established that trace minerals are necessary for optimal growth and immunity, yet challenges exist with intake of dietary trace minerals in cattle newly received at feedlots. A total of 128 crossbred beef bull (n = 40) and steer (n = 88) calves were used for this 42-d receiving study. Cattle were stratified by initial BW (275 ± 9.54 kg) and sex (steer or bull) and then assigned equivalently to treatment pens (n = 8 per treatment). Treatments were (1) negative control (CON) or (2) injectable trace mineral solution containing 60 mg of Zn/mL (as Zn disodium EDTA), 10 mg of Mn/mL (as Mn disodium EDTA), 5 mg of Se/mL (as sodium selenite), and 15 mg of Cu/mL (as Cu disodium EDTA) administered s.c. at 2.2 mL/100 kg of BW on d 0 (ITM). Health was monitored daily by trained personnel blinded to treatment pen assignment. Blood samples and BW were obtained on d 0, 14, 28, and 42 to determine bovine viral diarrhea virus (BVDV) type 1a antibody titer and gain performance. Standard processing procedures were applied on d 0, including administration of a respiratory vaccine containing modified-live BVDV antigens. No difference in overall ADG (P = 0.21) was detected between CON (1.36) and ITM (1.25 kg/d) steers. Overall DMI was not different (P = 0.83) between CON (6.98) and ITM (7.02 kg/d), but G:F tended (P = 0.08) to be less for ITM from d 28 to 42. The morbidity rate observed in this study was low (14% average), and there was no difference (P = 0.71) in morbidity between treatments, which averaged 15.6 and 12.5% for CON and ITM, respectively. There was a treatment × d interaction (P = 0.09) for BVDV-specific antibody titer. On d 14, ITM had a greater (P = 0.02) BVDV antibody titer than CON. These data suggest that ITM did not improve performance or morbidity when the incidence was low; however, the BVDV-specific antibody response to a respiratory vaccine was greater for ITM on d 14.
Unstable Resonator Studies For A 1-Joule Per Pulse KrF Avalanche Discharge Laser

AbstractExperiments on output beam divergence for a 1 -Joule KrF laser with M = 4 and M = 10unstable resonators for 112.5 cm, 187.5 cm and 225 cm separation are presented. Resultsgave beam divergence no better than some 30 times diffraction limited in the best case.IntroductionThe rare gas halide laser systems are extremely high energy coherent ultraviolet sources. The avalanche- discharge- excited lasers are convenient laboratory tools withoverall system efficiencies at the 0.5% to 2% level. Under stable resonator operation theobserved beam divergence ilneasured to be about three milliradiansT2)The use of negative -branch unstable resonators and walk -off mode unstable resonators shows that the beamquality of the exciplex systems can be improved to a few times diffraction limited. Theachievement of near diffraction limited performance is reported on fairly low energydevices that operate between 50 and 100 millijoules per pulse.Our early studies with negative branch unstable resonators show a loss of control ofthe resonator mode at output energy levels near 120 millijoules. These lasers are, how-ever, characterized by a fairly small gain cross -section (2 cm x .6 cm) so that substan-tial improvement in the gain length product appears possible by designing lasers possessinga much larger discharge cross -section.The difficulties of using unstable resonators to control the output beam quality of therare gas halide avalanche discharge lasers are two -fold. These difficulities are attri-buted to the short gain time and short radiative lifetime of the exciplexes. The shortradiative lifetime means an extremely high gain system which results in amplified sponta-neous emission (ASE). The beam quality of the ASE is determined by the geometry of theactive medium. The short gain time (' 25 -30 ns) presents an extreme difficulty in givingenough time for the unstable resonator to establish a low divergence mode in the cavityand to saturate the medium before much of the gain is lost to spontaneous emission and
Echocardiography is a feasible tool for assessing volume responsiveness.

Shock remains a common and lethal syndrome. Despite several scientific advances, administration of intravenous crystalloid remains a key therapy. Inappropriate administration of fluid, however, results in increased mortality and morbidity. Over the past decade, it has become apparent that the conventional methods of assessing fluid responsiveness with static measures, like central venous pressure, are inaccurate. Several small studies have demonstrated the utility of echocardiographic measures that exploit heart-lung interactions to predict fluid responsiveness in selected patients. Vignon and colleagues recently compared multiple echocardiographic indices to predict fluid responsiveness in ventilated patients (1). Their study is commendable for its large size, and its inclusion of several different categories of acute circulatory failure, including sepsis, hypovolemia, and cardiogenic shock. Also commendable is their reporting of feasibility. The inferior vena cava, pulse pressure variation, and aortic velocity could not be measured in 22% of patients due to image acquisition or absence of sinus rhythm, while superior vena cava could be measured in nearly all patients. It also appeared that superior vena cava collapsibility was the most predictive of the echocardiographic measures.
Imaging in Osteoarthritis

With technologic advances and the availability of sophisticated computer software and analytical strategies, imaging plays an increasingly important role in understanding the disease process of osteoarthritis (OA). Radiography has limitations in that it can visualize only limited features of OA, such as osteophytes and joint space narrowing, but remains the most commonly used modality for establishing an imaging-based diagnosis of OA. This article describes the roles and limitations of different imaging modalities and discusses the optimum imaging protocol, imaging diagnostic criteria of OA, differential diagnoses, and what the referring physician needs to know.
SP0017 Shared mechanisms in cancer and autoimmunity

Some rheumatic disease autoantibodies are powerful markers of subgroups of patients who have distinct disease phenotypes and trajectories. Of particular interest are markers of several disease subgroups in whom cancer and rheumatic disease onset are clustered together in time. For example, a subgroup of scleroderma patients have coincident onset of cancer and scleroderma. This is observed in scleroderma patients with autoantibodies against the RNA polymerase-3 (POLR3), and more recently with autoantibodies recognizing the minor spliceosome. In autoimmune myopathies, temporal clustering of diagnosis of cancer and myositis is associated with autoantibodies to NXP2 and components of the TIF1 complex. Interestingly, although the incidence of cancer is higher in patients with these autoantibodies, most patients with these autoantibodies manifest cancer, even with extended periods of follow-up. These observations provide an important opportunity to investigate the potential mechanisms which operate at the cancer-immune interface during development of rheumatic diseases. We have investigated such mechanisms in scleroderma patients with autoantibodies to POLR3 who also had a cancer diagnosed an average of -2.6 years from scleroderma onset. In cancers from these patients, we found genetic alterations of the POLR3A locus in six of eight patients with antibodies to POLR3 but not in eight patients without these antibodies. 3 antibody-positive patients had somatic mutations in POLR3A; 5 patients had loss of heterozygosity at the POLR3A locus. Analyses of peripheral blood lymphocytes and serum suggested that POLR3A mutations sparked cellular immunity and cross-reactive humoral immune responses. These results offer insight into the pathogenesis of scleroderma, and potentially other autoimmune syndromes. They suggest that somatic mutations in autoantigens in different cancers might initiate an immune response to the mutated autoantigen, which spreads to include the wild type version. Tissues (e.g. blood vessels, regenerating muscle) in which specific autoantigens are expressed at high levels, or potentially play critical functional roles, may be particularly susceptible to immune-mediated dysfunction. The results also provide support for the idea that acquired immunity helps to control naturally occurring cancers in patients with autoimmune rheumatic diseases; it is possible that this immune response may sometimes be fully effective, preventing the emergence of cancer. Disclosure of Interest None declared
Emergent livelihoods: A case study in emergent ecologies, diverse economies and the co-production of livelihoods from the Afram Plains, Ghana

Abstract In the far northeastern corner of the Afram Plains, Ghana, a history of large-scale developmental interventions has led to the emergence of a dynamic ecological and economic assemblage that underpins the formation of emergent livelihood strategies among farming and fishing communities in the region. The cornerstone of these livelihood strategies are local bartering institutions, which have been maintained by these communities for over 60 years. This paper combines the diverse economies and emergent ecologies literatures in order to theorize and situate emergent livelihood practices within an emergent socio-ecological system in the context of historical and contemporary processes of developmental change. Using the lens of feminist political ecology to understand the unequal and gendered dimensions of these livelihood strategies, this research proposes the concept of emergent livelihoods as a way of encapsulating a rich empirical case study that draws diverse economies and emergent ecologies into conversation with critical development studies through a co-production of livelihoods framework.