cssi/SciSciGPT-SciSciNet huggingface dataset:
CA19-9 Does Not Predict cholangiocarcinoma in Patients With Primary Sclerosing Cholangitis Undergoing Liver Transplantion

The results of liver transplantation in patients with cholangiocarcinoma have been poor. It has been suggested that elevated serum CA19-9 levels predict cholangiocarcinoma in patients with primary sclerosing cholangitis. We analyzed the predictive value of CA19-9 antigen as a marker of cholangiocarcinoma in patients with primary sclerosing cholangitis evaluated for liver transplantation. We reviewed the charts of 26 patients with primary sclerosing cholangitis (stage IV) in whom preoperative serum CA19-9 levels were determined; 22 of 26 underwent liver transplant. Explant specimens were serially sectioned and examined for tumor. In 3 of the 26 patients, cholangiocarcinoma was diagnosed during pretransplantation evaluation; exploratory laparotomy on the last patient showed no evidence of cholangiocarcinoma, and this patient is awaiting transplantation. Twelve of the 26 patients had CA19-9 levels more than double the laboratory reference range (0-37 U/mL) (mean 183.1 +/- 103 U/mL, range 77-415 U/mL). Two of the 12 patients with elevated CA19-9 levels had cholangiocarcinoma. Of the 14 patients with normal levels, two had cholangiocarcinoma. No correlation between elevated CA19-9 and bile duct dysplasia was noted. Sensitivity for serum CA19-9 levels more than twice the reference range is 50%, specificity is 54.5%, positive predictive value is 16.6%. An elevated serum CA19-9 level in a patient with stage IV primary sclerosing cholangitis does not reliably predict coexisting cholangiocarcinoma. Persistently high or rising serum CA19-9 levels do not indicate more urgent need for liver transplantation.
Passport, a native Tc1 transposon from flatfish, is functionally active in vertebrate cells

The Tc1/mariner family of DNA transposons is widespread across fungal, plant and animal kingdoms, and thought to contribute to the evolution of their host genomes. To date, an active Tc1 transposon has not been identified within the native genome of a vertebrate. We demonstrate that Passport, a native transposon isolated from a fish (Pleuronectes platessa), is active in a variety of vertebrate cells. In transposition assays, we found that the Passport transposon system improved stable cellular transgenesis by 40-fold, has an apparent preference for insertion into genes, and is subject to overproduction inhibition like other Tc1 elements. Passport represents the first vertebrate Tc1 element described as both natively intact and functionally active, and given its restricted phylogenetic distribution, may be contemporaneously active. The Passport transposon system thus complements the available genetic tools for the manipulation of vertebrate genomes, and may provide a unique system for studying the infiltration of vertebrate genomes by Tc1 elements.
Can agency theory justify the regulation of insider trading

The insider trading debate traditionally discusses the pros and cons of insider trading and draws a conclusion about the desirability or undesirability of public regulation of insider trading. One of the most important arguments against insider trading is that it generates agency problems that shareholders cannot resolve and that, therefore, insider trading should be publicly regulated. We have challenged this argument for failing to engage in comparative institutional analysis. We argued that when the negative aspects of insider trading, namely, the agency problems that it may create, are considered, it is necessary to engage in comparative institutional analysis and how these problems can be resolved under two different economic systems: the market economy and interventionism.
In Vitro Analysis of Nuclear Transport Mediated by the C-terminal Shuttle Domain of Tap

The Tap protein of higher eukaryotes is implicated in the nuclear export of type D retroviral mRNA and some cellular mRNAs. Here we have developed an in vitroassay to study nuclear export mediated by the C-terminal shuttle domain of Tap involving the rapamycin-induced attachment of this transport domain to a nuclear green fluorescent protein-containing reporter. We found that export by the Tap transport domain does not involve cytosolic transport factors including the GTPase Ran. The transport domain directly binds to several nucleoporins positioned in different regions of the nuclear pore complex. These results argue that a direct interaction of the Tap transport domain with nucleoporins is responsible for its nucleocytoplasmic translocation. We found that the karyopherin β-related export receptor CRM1 competes with the Tap transport domain for binding to Nup214 but not for binding to Nup62 or Nup153, suggesting that the Tap and CRM1 nuclear export pathways converge at the cytoplasmic periphery of the nuclear pore complex. Because the rates of in vitro nuclear import and export by the Tap transport domain are very similar, the directionality of mRNA export mediated by Tap probably is determined by mechanisms other than simple binding of the Tap transport domain to nucleoporins.
Generals die in friendly fire, or modeling immune response to HIV

We develop a kinetic model for CD8 T lymphocytes (CTL) whose purpose is to kill cells infected with viruses and intracellular parasites. Using a set of first-order nonlinear differential equations, the model predicts how numbers of different cell types involved in CTL response depend on time. The model postulates that CTL response requires continuous presence of professional antigen-presenting cells (APC) comprised of macrophages and dendritic cells. It assumes that any virus present in excess of a threshold level activates APC that, in turn, activate CTL that expand in number and become armed ''effector'' cells. In the end, APC are deactivated after virus is cleared. The lack of signal from APC causes effector cells to differentiate, by default, into ''transitory cells'' that either die, or, in a small part, become long-lived memory cells. Viruses capable of infecting APC will cause premature retirement of effector CTL. If transitory cells encounter virus, which takes place after the premature depletion, CTL become anergic (unresponsive to external stimuli). The model is designed to fit recent experiments on primary CTL response to simian immunodeficiency virus closely related to HIV and lymphocytic choriomeningitis virus. The two viruses are known to infect APC and make them targets for CTL they are supposed to control. Both viruses cause premature depletion and anergy of CTL and persist in the host for life.
Repression of Wnt/β-catenin signaling in the anterior endoderm is essential for liver and pancreas development

The liver and pancreas are specified from the foregut endoderm through an interaction with the adjacent mesoderm. However, the earlier molecular mechanisms that establish the foregut precursors are largely unknown. In this study, we have identified a molecular pathway linking gastrula-stage endoderm patterning to organ specification. We show that in gastrula and early-somite stage Xenopus embryos, Wnt/beta-catenin activity must be repressed in the anterior endoderm to maintain foregut identity and to allow liver and pancreas development. By contrast, high beta-catenin activity in the posterior endoderm inhibits foregut fate while promoting intestinal development. Experimentally repressing beta-catenin activity in the posterior endoderm was sufficient to induce ectopic organ buds that express early liver and pancreas markers. beta-catenin acts in part by inhibiting expression of the homeobox gene hhex, which is one of the earliest foregut markers and is essential for liver and pancreas development. Promoter analysis indicates that beta-catenin represses hhex transcription indirectly via the homeodomain repressor Vent2. Later in development, beta-catenin activity has the opposite effect and enhances liver development. These results illustrate that turning Wnt signaling off and on in the correct temporal sequence is essential for organ formation, a finding that might directly impact efforts to differentiate liver and pancreas tissue from stem cells.
Properties of Enzyme Fraction A from Chlorella and Copurification of 3′(2′),5′-Bisphosphonucleoside 3′(2′)-Phosphohydrolase, Adenosine 5′-Phosphosulfate Sulfohydrolase and Adenosine- 5′-Phosphosulfate Cyclase Activities

Enzyme fraction A from Chlorella which catalyzes the formation of adenosine 5′-phosphosulfatc from adenosine 3′-phosphate 5′-phosphosulfate is further characterized. Fraction A is found to Contain an Mg2+ -activated and Ca2+ -inhibited 3′(2′)-nucleotidase specific for 3′(2′),5′-biphosphonucleosides. This activity has been named 3′(2),5′-biphosphonucleoside 3′(2′)-phosphohydrolase. The A fraction is also found to contain an activity which catalyzes the formation of adenosine 3′: 5′monophosphate (cyclic AMP) from adenosine 5′-phosphosulfate (adenosine 5′-phosphosulfate cyclase). Under the same conditions of assay, 5′-ATP and 5′-ADP are not substrates for cyclic AMP formation. Unlike the 3′(2′),5′-biphosphonucleoside 3′(2′)-phosphohydrolase activity, the adenosine 5′-phosphosulfate cyclase activity does not require Mg2+, requires NH4+ or Na+, and is not inhibited by Ca2+. The A fraction also contains an adenosine 5′-phosphosulfate sulfohydrolase activity which forms 5′-AMP and sulfate. The three activities remain together during purification and acrylamidc gel electrophoresis of the purified preparation yields a pattern where only one protein band has all three activities. The phosphohydrolase can be separated from the other two activities by affinity chromatography on agarose-hexyl-adenosine 3′,5′-bisphosphate yielding a phosphohydrolase preparation showing a single band on gel electrophoresis. The adenosine 5′-phosphosulfate cyclase may provide an alternate route of cyclic AMP formation from sulfate via ATP sulfurylase, but its regulatory significance in Chlorella, if any, remains to be demonstrated. In sulfate reduction, the phosphohydrolase may serve to provide a readily utilized pool of adenosine 5′-phosphosulfate as needed by the adenosine 5′-phosphosulfate sulfotransferase. The cyclase and sulfohydrolase activities would he regarded as side reactions incidental to this pathway, but may be of importance in other metabolic and regulatory reactions.
What Matters Most to Nursing Home Elders: Quality of Life in the Nursing Home

Abstract Objective A growing number of nursing homes across the country are embarking on culture change transformations that focus on maximizing elder residents’ quality of life (QOL). Challenges to culture change implementation include the wide range of possible interventions as well as a lack of research-based evidence to guide these choices. The purpose of this study was to determine those components of nursing home QOL that are associated with elder satisfaction so as to provide direction in the culture change journey. Design A cross-sectional study using a survey administered face-to-face. Setting Three large urban nursing homes within a long term care system in New York State. Participants Sixty-two elder nursing home residents participated in face-to-face interviews. All elders had resided in their nursing communities for at least 3 months before participation. Measurements The survey included the Quality of Life Scales for Nursing Home Residents, which examines elder QOL in 11 domains: autonomy, dignity, food enjoyment, functional competence, individuality, meaningful activity, physical comfort, privacy, relationships, security, and spiritual well-being. Elder satisfaction with the nursing home and nursing home staff were also examined. Results After accounting for cognitive and physical functioning, among the QOL domains, dignity, spiritual well-being, and food enjoyment remained predictors of overall nursing home satisfaction. Additionally, dignity remained a significant predictor of elder satisfaction with staff. Conclusion These results provide one possible path in the culture change journey based on empirical findings.
A GASP IV model of steel ingot processing

This paper describes a GASP IV model of part of a steel mill. The processes modeled include pouring molten steel into molds, removing (stripping) the hot ingots from the molds, and sending them to the soaking pits and finally to the primary rolling mill. Molds move from a preparation area to the furnaces, thence to the stripping cranes, and back to the pre paration area. Rail trains transport ingots and molds.The major problem is how to dispatch a limited number of rail engines to pull trains so that materials and molds are at the right places at the right times for efficient operation. A set of 32 experiments (indi vidual simulation runs) was devised to find an opti mum combination of number of engines, number of transportation zones, and dispatching rules for a particular steel mill.The set of experiments showed (not surprisingly) that the use of a single transportation zone (so that all engines were able to go wherever they were needed) and a larger number of engines resulted in the greatest percentage...
Laboratory Reporting of 25-Hydroxyvitamin D Results: Potential for Clinical Misinterpretation

Vitamin D deficiency is a common health problem, and healthcare providers frequently measure circulating 25-hyroxyvitamin D concentration, the accepted standard for clinical assessment of vitamin D status (1). In the past, assay of this analyte was mainly performed by RIA in which the sum of 25(OH)D3 and 25(OH)D2 was measured (2). Newer HPLC and liquid chromatography mass spectroscopy (LC-MS) assays can measure the 2 forms separately (3)(4). Although the number of laboratories using HPLC or LC-MS for clinical 25(OH)D determination is not known, 17 of 153 laboratories participating in a recent QC survey used these methods, and some large commercial laboratories, which may analyze as many as 30 000 clinical specimens per month, use …
Maternal-fetal immunity: presence of specific cellular hyporesponsiveness and humoral suppressor activity in normal pregnancy and their absence in preeclampsia.

The hypothesis that aberrant maternal-fetal immunity might lead to the development of preeclampsia was examined using mixed lymphocyte culture reactions (MLC) as an in vitro analogue of maternal-fetal immunity. Maternal lymphocytes and serum from five normal pregnant women differed significantly from lymphocytes and serum from five preeclamptics. Maternal cells from normal pregnancy responded appropriately to unrelated control cells, but demonstrated selective hyporesponsiveness to fetal cells in the MLC. Serum from normal pregnancy suppressed MLCs when maternal cells were responder cells (RC) and maternal cells or fetal cells were stimulator cells (SC), and did not inhibit MLCs where maternal cells were RC and control cells were SC. Maternal lymphocytes and serum from preeclamptics did not demonstrate cellular hyporesponsiveness or humoral suppressor activity. Our findings support the notion that specific cellular hyporesponsiveness and humoral suppressor activity is responsible for normal pregnancy; abs...
Viral RNA is required for the association of APOBEC3G with human immunodeficiency virus type 1 nucleoprotein complexes.

APOBEC3G (APO3G) is a host cytidine deaminase that is incorporated into human immunodeficiency virus type 1 (HIV-1) particles. We report here that viral RNA promotes stable association of APO3G with HIV-1 nucleoprotein complexes (NPC). A target sequence located within the 5′-untranslated region of the HIV-1 RNA was identified to be necessary and sufficient for efficient APO3G packaging. Fine mapping revealed a sequence normally involved in viral genomic RNA dimerization and Gag binding to be important for APO3G packaging and association with viral NPC. Our data suggest that packaging of APO3G into HIV-1 NPC is enhanced by viral RNA.
Toward the Scientific Evaluation of Social Attitudes and Ideologies

(1951). Toward the Scientific Evaluation of Social Attitudes and Ideologies. The Journal of Psychology: Vol. 31, No. 1, pp. 97-104.
Adaptive visual tracking of moving objects modeled with unknown parameterized shape contour

The paper presents a new approach to establish a visual tracking system which can automatically detect the shape contours of moving objects, extract their shape parameters, and continuously track locations of these moving objects in the shape parameter space. The system consists of a robust shape detection algorithm based on the randomized Hough transform (RHT) method and an adaptive object tracking algorithm. The paper demonstrates that, through the combination of a motion detector and the RHT method, the resultant shape detection algorithm is computationally efficient and is robust to noise and object occlusion. On the other hand, the tracking algorithm tracks the shape contours and updates the shape parameters corresponding to the translational, rotational, and scaling motion of moving objects. The tracking algorithm uses a decomposition of the parameter space into lower dimensional subspaces for computational efficiency. Finally the paper provides several simulation and experiment results to validate the new approach.
Dispersion effects of fiber Bragg gratings on true-time-delay beamforming networks

Fiber Bragg gratings (FBGs) are key components in wideband true-time-delay beamforming networks. Different time delays are obtained when an RF modulated optical signal is reflected by an array of FBGs located at different physical locations of an optical delay line. In this paper, we report the study of dispersion effects of uniform FBGs on FBG-based true-time-delay beamforming networks. The RF signal is modulated on an optical carrier using double-side-band (DSB) modulation and single-side-band (SSB) modulation. The results indicate that the time delay performance is affected greatly by the dispersion induced by the FBGs. The results also show that the dispersion effect is reduced by four times if an SSB modulation scheme is employed.
Environmentally friendly disposable sensors with microfabricated on-chip planar bismuth electrode for in situ heavy metal ions measurement

Abstract This paper presents an environmentally friendly disposable heavy metal ion sensor for in situ and online monitoring in the nature and physiological systems. The miniaturized sensor chip consists of a non-toxic microfabricated bismuth (Bi) working electrode that replaces the conventional mercury electrodes, an integrated Ag/AgCl reference electrode, a gold counter electrode, and microfluidic channels. In this work, the electrochemical behavior of the Bi working electrode was characterized in several non-deaerated buffer solutions using cyclic voltammetry. The detection and quantification of Pb (II) and Cd (II) were statically performed using anodic stripping voltammetry inside the microchannels, in the Pb (II) concentration range of 25–400 ppb (R2 = 0.991) with limit of detection of 8 ppb for 60 s deposition, and in the Cd (II) concentration range of 28–280 ppb (R2 = 0.986) with limit of detection of 9.3 ppb for 90 s deposition. Particularly, the applications of this sensor chip have been reported with the examples of in situ measurement of Cd (II) concentration in soil pore and ground water and online direct measurement of Cd (II) concentration in cell culture media in its native environment.
Analysis of the LIV System of Campylobacter jejuni Reveals Alternative Roles for LivJ and LivK in Commensalism beyond Branched-Chain Amino Acid Transport

Campylobacter jejuni is a leading cause of diarrheal disease in humans and an intestinal commensal in poultry and other agriculturally important animals. These zoonotic infections result in significant amounts of C. jejuni present in the food supply to contribute to disease in humans. We previously found that a transposon insertion in Cjj81176_1038, encoding a homolog of the Escherichia coli LivJ periplasmic binding protein of the leucine, isoleucine, and valine (LIV) branched-chain amino acid transport system, reduced the commensal colonization capacity of C. jejuni 81-176 in chicks. Cjj81176_1038 is the first gene of a six-gene locus that encodes homologous components of the E. coli LIV system. By analyzing mutants with in-frame deletions of individual genes or pairs of genes, we found that this system constitutes a LIV transport system in C. jejuni responsible for a high level of leucine acquisition and, to a lesser extent, isoleucine and valine acquisition. Despite each LIV protein being required for branched-chain amino acid transport, only the LivJ and LivK periplasmic binding proteins were required for wild-type levels of commensal colonization of chicks. All LIV permease and ATPase components were dispensable for in vivo growth. These results suggest that the biological functions of LivJ and LivK for colonization are more complex than previously hypothesized and extend beyond a role for binding and acquiring branched-chain amino acids during commensalism. In contrast to other studies indicating a requirement and utilization of other specific amino acids for colonization, acquisition of branched-chain amino acids does not appear to be a determinant for C. jejuni during commensalism.
Snipping the thread of life. Antimuscarinic side effects of medications in the elderly.

• Drugs with antimuscarinic activity are used for a wide variety of medical conditions. Unfortunately, side effects that develop as a result of muscarinic blockade are common and their frequency and clinical significance appear to increase with advanced age. Nevertheless, such drugs are frequently prescribed to elderly persons, particularly to those living in nursing homes. This review details the prevalence of antimuscarinic drug use in the elderly, the classes of drugs that exhibit antimuscarinic activity, organ-specific effects of muscarinic blockade, side effects identified in elderly individuals, and strategies to prevent or treat complications of antimuscarinic therapy, including recent advances in the development of drugs with selective activity for specific subclasses of muscarinic receptors. (Arch Intern Med. 1989;149:2414-2420)
Nails in systemic disease

Nail plate and nail unit abnormalities may be helpful as diagnostic tools or as a part of the puzzle for confirmation of systemic disease. There are specific and nonspecific nail signs, which can be seen involving one or more nails, that occur simultaneously or secondary to systemic disease. Occasionally these clues can be diagnostic, while most are nonspecific reaction patterns. Nail changes occur in the nail plate as a result of nail matrix abnormalities caused by systemic disease and other systemic insults such as reactions to medications. In this article we review some of the more common nail signs that can be used to help diagnose systemic disease.
Theme creation for digital collections

This paper presents an approach for integrating multiple sources of semantics for the creating metadata. A new framework is proposed to define topics and themes with both manually and automatically generated terms. The automatically generated terms include: terms from a semantic analysis of the collections and terms from previous user's queries. An interface is developed to facilitate the creation and use of such topics and themes for metadata creation. The framework and the interface promote human-computer collaboration in metadata creation. Several principles underlying such approach are also discussed.
Effect of El Niño (1997–98) on Beaches of the Peninsular Gulf Coast of Florida

Abstract During the winter of 1997–98, the El Nino weather pattern was a major influence on the beaches of the Gulf Coast of the Florida peninsula. Cyclonic storm patterns influenced by El Nino moved across the Gulf of Mexico from the southwest, approaching the coast of Florida from the southwest, a direction that differs from that of the usual winter frontal passage direction. The El Nino effects along the Florida Gulf Coast are in the form of subtropical, low-pressure systems including mild temperatures, frequent storms with sustained winds, high wave energy, and record amounts of rainfall. The winds and waves generated by these systems initially came from the south or west. As the storm passed over the coast, barometric pressure increased and winds shifted to the west or northwest. Ten occurrences of this weather pattern took place from late December 1997 through March 1998. An atypical south to north littoral drift was recognized in localized areas along the Florida Gulf Coast during the winter of 199...
Gene expression patterns in cell lines from patients with 18q- syndrome.

Some studies have suggested that for trisomies, some genes are expressed far in excess of the expected 150% level and that this “dysregulation” is one of the mechanisms for the pathogenesis of trisomies. In an attempt to generalize this result to a monosomy, we examined mRNA isolated from lymphoblastoid cell lines derived from patients with 18q– syndrome, a deletion syndrome involving loss of the distal long arm of chromosome 18. Expression levels of ten chromosome 18 genes were compared between cell lines from eight patients with 18q– syndrome and four diploid controls. Gene expression was investigated by a quantitative reverse-transcription polymerase chain reaction (RT-PCR) method. With the exception of the transcription factor NFATC1, which shows a tendency towards gene dosage compensation (the expression pattern correlates with IgA deficiency), all of the other genes were expressed at a level proportional to their gene copy number. This was true regardless of mRNA abundance or different patterns of gene expression (ubiquitous versus tissue-specific gene expression). These results indicate that, unlike dysregulated gene expression apparent in some trisomies, this monosomic syndrome is largely due to consequences of reduced gene expression.
(Invited) Growth and Processing Techniques for Fabricating Ultra Broadband High-Power Low-Cross-Talk Semiconductor Optical Amplifiers

Recent development of fibers with very low losses over the entire spectral range between 1200 and 1700 nm has laid a foundation for future ultra-broadband (UBB) optical communications. To fully utilize this potential it is expected that next generation photonic components will be able to cover such broad windows for interconnect, switching and networking applications. Currently the major obstacle on the path towards UBB optical communications is lack of a gain material that operates over the entire 500 nm spectrum, rather than just the narrow 40-nm portion covered by the EDFA. To achieve such a broad gain spectrum one needs to combine materials with different effective bandgaps within one waveguide. This can be done either longitudinally (when bandgap is graded along the waveguide) or vertically (when the bandgap is graded in the direction of growth). We have explored both methods and achieved very promising results. Using selective area growth (SAG) technique1 we can grow multiple quantum well (MQW) materials with variable effective bandgaps on the same substrate. This is achieved by grading both MQW composition and sizes. Fig. 1 shows the SAG mask, a fabricated and bonded device, and it electroluminescence (EL) spectra with and without AR coating. An alternative method of getting broad gain is to stack different gain regions vertically and connecting them via tunnel junctions. Such a cascaded UBB SOA is shown in Fig. 2and it incorporates multiple different gain regions ranging from 1200 to 1700nm.
Kif5B and Kifc1 Interact and Are Required for Motility and Fission of Early Endocytic Vesicles in Mouse Liver

Early endocytic vesicles loaded with Texas Red asialoorosomucoid were prepared from mouse liver. These vesicles bound to microtubules in vitro, and upon ATP addition, they moved bidirectionally, frequently undergoing fission into two daughter vesicles. There was no effect of vanadate (inhibitor of dynein) on motility, whereas 5'-adenylylimido-diphosphate (kinesin inhibitor) was highly inhibitory. Studies with specific antibodies confirmed that dynein was not associated with these vesicles and that Kif5B and the minus-end kinesin Kifc1 mediated their plus- and minus-end motility, respectively. More than 90% of vesicles associated with Kifc1 also contained Kif5B, and inhibition of Kifc1 with antibody resulted in enhancement of plus-end-directed motility. There was reduced vesicle fission when either Kifc1 or Kif5B activity was inhibited by antibody, indicating that the opposing forces resulting from activity of both motors are required for fission to occur. Immunoprecipitation of native Kif5B by FLAG antibody after expression of FLAG-Kifc1 in 293T cells indicates that these two motors can interact with each other. Whether they interact directly or through a complex of potential regulatory proteins will need to be clarified in future studies. However, the present study shows that coordinated activity of these kinesins is essential for motility and processing of early endocytic vesicles.
Single-stage single-switch PFC converter with low output voltage

A new type of single-stage single-switch converter with low output voltage and power factor correction is proposed. The lower turns ratio for the isolation transformer is the main feature. The proposed converter is suitable for designing high efficiency, high power factor and low cost power supplies for new generation high-speed integrated circuits.
Reduction of Curd Tension of Milk by the Addition of Sodium Salts

Summary A method has been presented for producing milk with reduced curd tension by the addition of certain sodium salts. It is indicated that there is need for further nutritional study of the product before recommending adoption of the method by the industry.
Studies on the turnover of exogenous mannose-terminal glucocerebrosidase in rat liver lysosomes

Mannose-terminal glucocerebrosidase prepared by exoglycosidase digestion of human placental glucocerebrosidase is reported effective in the treatment of patients with type 1 Gaucher's disease [Barton et al. (1991); N Engl J Med 324:1464-1470]. However, the amount of enzyme that is necessary for therapeutic effect is much higher than would be predicted from in vitro activity measurements. We have investigated the fate of infused enzyme following intravenous administration in Sprague-Dawley rats. In this model system, the enzyme is rapidly cleared from the plasma compartment by receptor-mediated endocytosis via the mannose-specific receptor present on reticuloendothelial cells. Enzyme activity measured in rat liver biopsy specimens at various times post-infusion revealed a rapid initial loss of approximately one-half of the maximum delivered enzyme in the first hour followed by a slower decay with a half-life of approximately 6-8 h. The loss in enzyme activity is paralleled by a loss in enzyme protein when analyzed by Western blots. There is no evidence for return of enzyme activity or inactive enzyme protein to the plasma. Incomplete integration into the lysosomal membrane was demonstrated by the use of differential extraction of purified rat liver lysosomes to distinguish between lumenal and membrane bound enzyme. Immunoelectron microscopy of rat liver following infusion of mannose-terminal glucocerebrosidase confirmed localization of the delivered enzyme primarily within the lumen of the lysosomes of Kupffer cells and to a lesser extent associated with the lysosomal membrane. Enzyme activity was stable in isolated rat liver lysosomes preloaded with mannose-terminal glucocerebrosidase and incubated in the absence or presence of ATP. Acidification of the lysosomes to pH 3 results in a rapid loss of enzyme activity and protein; however, the relationship between the in vitro loss and the loss in enzyme activity in intact liver is not clear. We conclude from these studies that rapid intracellular degradation of administered glucocerebrosidase is the prime factor responsible for the high dose required for effective treatment of Gaucher's disease.
Phase Shift Modulations for Stable, Oscillatory, Traveling, Strongly Nonlinear Waves

Oscillatory dispersive waves propagating in a slowly varying medium are analyzed for Klein-Gordon equations with perturbations. The method of multiple scales is extended to include two fast scales, the usual traveling-wave phase and time, in order to allow initial conditions not usually permitted. An exact wave-action equation is introduced if the traveling wave is stable, involving averages over the periodic wave as well as time. This is equivalent to an extended averaged Lagrangian principle. The equation for the slow modulations of the phase shift of the traveling wave is derived from the higher order terms in the exact action equation and is shown to be the same as in earlier more restrictive studies.
The Perils of Integrating Wellness and Safety and Health and the Possibility of a Worker-Oriented Alternative:

Integration of workplace wellness with safety and health has gained momentum on the initiative of the state allied with a segment of large employers and some health and safety professionals. Integration has a dual potential: to fundamentally reshape occupational health in ways that profoundly benefit workers, or to serve neoliberal corporate goals. A focus on the workplace and the ways work and health interact broaden the definition of a work-related injury or illness and emphasize and challenge the employer decisions that create hazards and determine risk. However, the implementation of integration is taking place in a context of corporate dominance and the aggressive pursuit of a neoliberal agenda. Consequently, in practice, integration efforts have emphasized individual worker responsibility for health and fail to actually integrate wellness with safety and health in a meaningful way. Can an alternative be envisioned and pursued that realizes the promise of integration for workers?
What does it take to improve existing fluorescent proteins for in vivo imaging applications

Although fluorescent proteins are ubiquitously used as genetic tracers and imaging agents, there is significant room for improvement. This chapter discusses how new improved fluorescent proteins can be designed. It focuses on the design of far-red and infrared fluorescent proteins, since the currently-available red fluorescent proteins are not optimal for in vivo applications.
Persistence Mapping Using EUV Solar Imager Data

We describe a simple image processing technique that is useful for the visualization and depiction of gradually evolving or intermittent structures in solar physics extreme-ultraviolet imagery. The technique is an application of image segmentation, which we call "Persistence Mapping," to isolate extreme values in a data set, and is particularly useful for the problem of capturing phenomena that are evolving in both space and time. While integration or "time-lapse" imaging uses the full sample (of size N ), Persistence Mapping rejects (N - 1)/N of the data set and identifies the most relevant 1/N values using the following rule: if a pixel reaches an extreme value, it retains that value until that value is exceeded. The simplest examples isolate minima and maxima, but any quantile or statistic can be used. This paper demonstrates how the technique has been used to extract the dynamics in long-term evolution of comet tails, erupting material, and EUV dimming regions.
Surprisal-Driven Feedback in Recurrent Networks

Recurrent neural nets are widely used for predicting temporal data. Their inherent deep feedforward structure allows learning complex sequential patterns. It is believed that top-down feedback might be an important missing ingredient which in theory could help disambiguate similar patterns depending on broader context. In this paper, we introduce surprisal-driven recurrent networks, which take into account past error information when making new predictions. This is achieved by continuously monitoring the discrepancy between most recent predictions and the actual observations. Furthermore, we show that it outperforms other stochastic and fully deterministic approaches on enwik8 character level prediction task achieving 1.37 BPC.
Overhead Capital: A Study in Development Economics

(1968). Overhead Capital: A Study in Development Economics. Journal of Economic Issues: Vol. 2, No. 2, pp. 261-263.
Stress and Coping of Critical Care Nurses After Unsuccessful Cardiopulmonary Resuscitation

BACKGROUND Participation by a critical care nurse in an unsuccessful resuscitation can create a unique heightened level of psychological stress referred to as postcode stress, activation of coping behaviors, and symptoms of posttraumatic stress disorder (PTSD). OBJECTIVES To explore the relationships among postcode stress, coping behaviors, and PTSD symptom severity in critical care nurses after experiencing unsuccessful cardiopulmonary resuscitations and to see whether institutional support attenuates these repeated psychological traumas. METHODS A national sample of 490 critical care nurses was recruited from the American Association of Critical-Care Nurses' eNewsline and social media. Participants completed the Post-Code Stress Scale, the Brief COPE (abbreviated), and the Impact of Event Scale-Revised, which were administered through an online survey. RESULTS Postcode stress and PTSD symptom severity were weakly associated (r = 0.20, P = .01). No significant associations between coping behaviors and postcode stress were found. Four coping behaviors (denial, self-distraction, self-blame, and behavioral disengagement) were significant predictors of PTSD symptom severity. Severity of postcode stress and PTSD symptoms varied with the availability of institutional support. CONCLUSIONS Critical care nurses show moderate levels of postcode stress and PTSD symptoms when asked to recall an unsuccessful resuscitation and the coping behaviors used. Identifying the critical care nurses most at risk for PTSD will inform the development of interventional research to promote critical care nurses' psychological well-being and reduce their attrition from the profession.
Polypharmacy and Gait Performance in Community-dwelling Older Adults.

Objectives To examine the relationship between polypharmacy and gait performance during simple (normal walk (NW)) and complex (walking while talking (WWT)) locomotion. Design Cross-sectional. Setting Community. Participants Community-dwelling older adults (N = 482). Measurements Polypharmacy, defined as use of five or more medications and a cohort-specific alternate definition of eight or more medications, was examined. Velocity (cm/s) measured quantitatively during NW and WWT conditions. Results The 164 participants (34%) with polypharmacy of five or more medications were older (77.0 ± 6.6 vs 76.0 ± 6.4) and more likely to have hypertension, congestive heart failure, diabetes mellitus, myocardial infarction, and higher body mass index (BMI) and to have fallen within the last year than the remaining 318 without polypharmacy and walked 6 cm/s slower (P = .004) during NW and 4 cm/s slower during WWT (P = .07), adjusting for age, sex, and education. Group differences were not statistically significant after adjusting for comorbidities. Prevalence of polypharmacy of eight or more medications was 10%. This group walked 11 cm/s slower during NW (P < .001) and 8.6 cm/s slower during WWT (P = .01) than those without polypharmacy, adjusted for age, sex, and education. Participants taking eight or more medications had slower NW (8.5 cm/s; P = .01), and WWT (6.9 cm/s; P = .07), compared to those without polypharmacy, adjusting for comorbidities. Adjustments for BMI, high-risk drugs, falls, and comorbidities yielded slower NW (9.4 cm/s, P = .005) and WWT (7.9 cm/s, P = .04 among those with polypharmacy compared to those without polypharmacy). Conclusion These results suggest an association between polypharmacy and locomotion that medical comorbidities only partly explained.
PTH-055 Vitamin b12 deficiency is common in children with ulcerative colitis as well as crohn’s disease

Introduction Patients with Crohn’s Disease (CD) who frequently have ileal involvement are at increased risk of vitamin B12 deficiency. Vitamin B12 deficiency in patients with ulcerative colitis (UC) is not widely reported. The aim of our project is to assess the prevalence of vitamin B12 deficiency in patients with Crohn’s Disease and Ulcerative colitis and to identify risk factors associated with it. Method As part of routine care, patients attending Inflammatory Bowel Disease (IBD) service at Birmingham Children’s Hospital undergo vitamin B12 assessment at least once a year. We included all patients with CD and UC diagnosed who had vitamin B12 measured between 2010–2015. Retrospective review of patient notes and laboratory results were done. Patients with serum vitamin B12 values Results In total 244 patients (157 with CD and 87 with UC) were included. 45/157 (29%) patients with CD had low vitamin B12 levels. 28/87 (32%) patients with UC had low vitamin B12 levels. In patients with Crohn’s disease, disease not being in remission was associated with vitamin B12 deficiency ( p Conclusion Prevalence of Vitamin B12 deficiency is high in patients with Crohn’s Disease and Ulcerative colitis. Vitamin B12 levels need to be checked in all patients with IBD rather than testing based on presence of risk factors. Disclosure of Interest None Declared
Adaptive bitrate video delivery using HTTP/2 over MPTCP architecture

Adaptive bitrate streaming is one of the most popular methods to deliver high definition video content for HTTP clients. Commonly used techniques rely primarily on the estimation of network bandwidth and/or buffer state client-side. Inaccurate estimation leads to performance degradation due to a lack of correct bitrate encoding per chunk, and poor network utilization as a result of inflexible transport protocols. In this paper, we propose a unique approach to removing the client-side estimation of network bandwidth and buffer state. Three modular HTTP/2 server push-based strategies leveraging Multipath TCP are designed to improve the delivery of the video content in lossy environments. The goal is to improve start-up delay and overall performance. Laboratory experiments reveal that the start-up buffering delay is decreased by 40% or more when using HTTP/2 over MPTCP in networks with packet loss rates above 2%.
Neurotrophic Factor Therapy: NGF, BDNF and NT-3

Since the discovery that neurotrophins can stimulate neuronal survival and function and promote axonal growth, there has been speculation that therapeutic application of these proteins could prevent or slow cell death in neurodegenerative diseases such as Alzheimer’s disease and enhance regeneration in the peripheral and central nervous system after injury. Early clinical trials were unsuccessful, however. Over the ensuing years knowledge evolved, indicating that site-specific delivery of growth factors across the blood–brain barrier but limited to regions of degenerating neurons would be required to safely deliver and adequately test their potential to treat neurodegenerative disorders. Recent developments indicate that gene therapy may achieve at least some of the requirements for successful clinical testing of neurotrophin therapy.
Design and rationale of the medical students learning weight management counseling skills (MSWeight) group randomized controlled trial

Physicians have an important role addressing the obesity epidemic. Lack of adequate teaching to provide weight management counseling (WMC) is cited as a reason for limited treatment. National guidelines have not been translated into an evidence-supported, competency-based curriculum in medical schools. Weight Management Counseling in Medical Schools: A Randomized Controlled Trial (MSWeight) is designed to determine if a multi-modal theoretically-guided WMC educational intervention improves observed counseling skills and secondarily improve perceived skills and self-efficacy among medical students compared to traditional education (TE). Eight U.S. medical schools were pair-matched and randomized in a group randomized controlled trial to evaluate whether a multi-modal education (MME) intervention compared to traditional education (TE) improves observed WMC skills. The MME intervention includes innovative components in years 1-3: a structured web-course; a role play exercise, WebPatientEncounter, and an enhanced outpatient internal medicine or family medicine clerkship. This evidence-supported curriculum uses the 5As framework to guide treatment and incorporates patient-centered counseling to engage the patient. The primary outcome is a comparison of scores on an Objective Structured Clinical Examination (OSCE) WMC case among third year medical students. The secondary outcome compares changes in scores of medical students from their first to third year on an assessment of perceived WMC skills and self-efficacy. MSWeight is the first RCT in medical schools to evaluate whether interventions integrated into the curriculum improve medical students' WMC skills. If this educational approach for teaching WMC is effective, feasible and acceptable it can affect how medical schools integrate WMC teaching into their curriculum.
Model predictive control energy dispatch to optimize renewable penetration for a microgrid with battery and thermal storage

As intermittent renewable energy becomes a larger fraction of the overall energy mix in the US, algorithms that efficiently utilize this energy are necessary. In this work, a model predictive control (MPC) method is developed to perform real-time optimization to maximize the power delivery from a renewable supply to a building. An isolated microgrid scenario is considered, consisting of a mixed-use residential and commercial building, renewable power supply, battery storage, hot water tank thermal storage, and a backup supply. The MPC strategy utilizes predictions of the building's electrical and hot water loads, on an hourly basis, along with predictions of the output from the renewable supply. At each time step, these predictions are used to create an optimized power dispatching strategy between the microgrid elements, to maximize renewable energy use. For a fixed size microgrid, the performance of this MPC approach is compared to the performance of a simple non-predictive dispatching strategy.
Arginine vasopressin promotes growth of rat glomerular mesangial cells in culture

Arginine vasopressin (AVP) binds specifically to vascular smooth muscle-like mesangial cells (MCs) and affects contraction. We tested whether this peptide also modulates growth behavior of rat MCs in early subculture (passage 2-5). Subconfluent, serum-starved MCs were exposed to AVP (10(-10)-10(-6) M) in the presence or absence of insulin (5 micrograms/ml). To assess DNA replication, MC uptake of [3H]thymidine (24-h pulse) was determined on days 1, 2, and 3. AVP alone averaged a 1.97-fold increase in DNA synthesis at 24 h, whereas the mean stimulatory effects of AVP at 48 and 72 h were 7.21- and 5.42-fold, respectively. MCs exposed simultaneously to AVP and insulin showed potentiation of the mitogenic response to AVP alone. The V1-receptor antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylene proprionic acid), 2-(O-methyl-Tyr)-Arg]vasopressin (PMP) inhibited only AVP-induced promotion of MC growth (maximal inhibition of -78.3%). The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) acutely stimulated MC proliferation but did not add to the AVP effect. Preincubation of MCs with 600 nM of TPA for 48 h significantly inhibited AVP-induced mitogenesis (-87.2%). By use of fura-2, intracellular calcium (Cai) was assessed by spectrofluorometry. The addition of AVP (10(-12)-10(-6) M) led to a rapid, transient, dose-dependent increase in Cai of 154-383%, respectively. The AVP-induced increase in Cai was greatly inhibited by 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester hydrochloride (TMB-8) (10(-8)-10(-6) M), an inhibitor of Cai release (-23.9 to -72.1%), and it was blunted by the atrial natriuretic peptide AP-28 (-38.3%).(ABSTRACT TRUNCATED AT 250 WORDS)