cssi/SciSciGPT-SciSciNet huggingface dataset:
Cyclooxygenase-2 expression induces genomic instability in MCF10A breast epithelial cells.

Background Cyclooxygenase-2 (COX-2) is induced in many breast cancers and COX-2 expression correlates with a worse outcome in the clinic. We hypothesized that the induction of genomic instability is a major mechanism through which COX-2 contributes to breast cancer progression. Methods We transfected a normal immortalized breast epithelial cell line of Basal B subtype, MCF10A, with the pSG5-COX-2 vector and established the stably transfected cell line MCF10A/COX-2. We analyzed the genomic instability phenotype by chromosomal analysis of metaphase-arrested MCF10A and MCF10A/COX-2 cells after Giemsa staining. Groups were compared using χ2 tests. To investigate the DNA damage checkpoint signaling, we analyzed the phosphorylation status of CHK1 protein with a phospho-specific antibody. Results Cytogenetic analysis of early passage transfected cells showed that COX-2 expression increased genomic instability compared with the MCF10A cells transfected with a luciferase vector alone. COX-2 overexpression was associated with a significant increase in chromosomal aberrations (fusions, breaks, and tetraploidy). There was a statistically significant increase in the number of polyploid cells in the COX-2 transfected cells versus the control (P = 0.004). We also found that an inhibitory CHK1 phosphorylation at Ser-280 was dramatically increased upon COX-2 overexpression in MCF10A cells, thus explaining the mechanism of inactivation of an important cell cycle checkpoint. Further analysis of the MCF10A/COX-2 cells showed that these cells have acquired a premalignant phenotype characterized by a morphological transformation, a resistance to anoikis, a reduced requirement of epidermal growth factor for growth in culture, but their inability to establish tumors in a nude mouse model of malignancy. Conclusion We found that COX-2 expression in MCF10A breast epithelial cells confers a premalignant phenotype that includes enhanced genomic instability and altered cell-cycle regulation.
Variation in the molecular mass of the Ah receptor among vertebrate species and strains of rats

The Ah receptor in eight vertebrate species was characterized by labeling the cytosolic fraction of tissue with the photoaffinity ligand, [125I]-2-azido-3-iodo-7,8-dibromodibenzo-p-dioxin, and analysis of the products by denaturing gel electrophoresis. The apparent molecular mass of the dominant labeled peptide showed appreciable species variation: mouse-95 kDa; chicken (embryo)-101 kDa; guinea pig-103 kDa; rabbit-104 kDa; rat-106 kDa; human-106 kDa; monkey-113 kDa, and hamster-124 kDa. Seven inbred strains of rats, had a Ah receptor ligand binding peptide of 106 kDa; however outbred Long-Evans rats were shown to be polymorphic expressing a 101 kDa and/or 106 kDa allelic forms. The notable frequency of structural variation in the Ah receptor is in contrast to the analogous highly conserved steroid hormone receptors.
The Social Amplification of Risk: Theoretical Foundations and Empirical Applications

The article presents the framework of social amplification of risk which integrates the technical assessment and the social experience of risk. Risk perception research has revealed that contextual factors shape individual risk estimations and evaluations. Identification of these factors, such as voluntariness, personal ability to influence risks, familiarity with the hazard, and catastrophic potential, provides useful information about the elements that individuals consider in constructing their interpretation of risks. In addition, analyses of people's heuristics in making inferences have shed some light on how risk information is generalized and evaluated intuitively. These psychological studies fail to explain, however, why individuals attend to certain characteristics of risks and ignore others. Furthermore, in focusing only on the individual as an information processor, these studies exclude from the analysis the social and cultural variance of risk interpretations. The social amplification framework postulates that the social and economic impacts of an adverse event are determined not only by the direct physical consequences of the event, but by the interaction of psychological, cultural, social, and institutional processes that amplify or attenuate public experience of risk and result in secondary impacts.
Isolation of Two Forms of the Nitrogenase VFe Protein from Azotobacter vinelandii

When Q-Sepharose was used in the purification of the V nitrogenase proteins from Azotobacter vinelandii, an increase in resolution was observed that resulted in a separation of the nitrogenase comp...
A MEASURE-THEORETIC APPROACH TO URBAN FIELDS WITH APPLICATIONS TO ORIGIN CONSTRAINED TRAVEL

Mathematical formulations of urban structure usually invoke either a strictly continuous or a strictly discrete account of spatial distributions. The arbitrary nature of this dichotomy is illustrated by urban retail and commercial activity, which can be usefully represented as a mixture of discrete and continuous components. This paper exploits concepts from general measure theory to extend the notion of an urban field. The resulting formulation yields discrete and continuous models as special cases. The abstract-field model is interpreted for the case of urban commercial structure, and is applied to develop a generalized extension of the origin-constrained interaction model. The descriptive utility of the formulation is then demonstrated in the case of commercial arterials in Albany, New York.
Role of Bacteria in Decomposition of Injected Liquid Waste at Wilmington, North Carolina: ABSTRACT

In 1968, Hercules Chemical, Inc., Wilmington, North Carolina, began injecting organic waste through wells into a saline-disposal zone at depths of 850-1,000 ft. The waste, which is a by-product of dimethyl terephthalate used in the production of synthetic fiber, is composed of water, with a pH of about 4.0, containing approximately 15,000 ppm acetic acid, 5,000 ppm formic acid, and 500 ppm methanol. The movement and composition of the transformed waste have been monitored by a network of 14 observation wells drilled to various depths. The waste-water analysis and monitoring were performed by the U.S. Geological Survey. In June 1972, waste was detected in observation well 14. The microbial population was periodically sampled as the dissolved organic carbon fraction increased. The dissolved organic content increased to 112 mg/1, and then rapidly decreased to 20 mg/l. This sudden decrease in dissolved organic carbon was accompanied by the appearance of gas composed of approximately 60% methane. Each time a decrease in dissolved organic carbon occurred, gas was found and an increase in the total microbial population was measured. Methane gas production is the result of microbial activity. The injected waste contains adequate carbon and energy substrates for the strictly anaerobic, methane-producing bacteria which have been isolated from well 14. In addition to the methane-producing bacteria, other bacteria have been isolated and identified. Microorganisms such as Agrobacterium, Pseudomonas (especially species fluorescens), Proteus, Bacillus, Arthrobacter, Aerobacter, Corynebacterium, and Staphylococcus have been observed. The total microbial population was found to be 25 × 108 organisms per milliliter in well 14 and 30 × 108 organisms per milliliter in the unpolluted aquifer. The source of these bacteria is the natural aquifer, inasmuch as the injected waste is sterile. The wast alone does not support a microbial population for it contains no nitrogen. Such nitrogen substrate is apparently supplied by the natural water in the aquifer. End_of_Article - Last_Page 1594------------
Is it time for the customizable infobutton

Infobuttons are intended to provide links to context-sensitive information in online resources to support clinical decision making. In this issue, we discuss challenges that impact the maximal effective use of Infobuttons. We also suggest methods to facilitate the role of Infobuttons as a tool to support optimal use of medications.
869 FAMILIAL HISTIOCYTOSIS IN OFFSPRING OF ARTIFICIALLY INSEMINATED PREGNANCIES

With new technology now available for “artificially” inducing pregnancy, responsibilities for the outcome of these pregnancies arise. We report the occurrence of fatal malignant histiocytosis in 2 siblings, the products of pregnancies resulting from insemination by the same sperm donor. The first, a female, became ill at 3 months of age with a constellation of clinical findings including fever, hepatosplenomegaly, pancytopenia, CSF pleocytosis and seizures, dying at 16 months of age. The second, a male, was conceived during his sib's illness which was felt not to be inherited. His illness, beginning at 2 months, was characterized by fever, hepatosplenomegaly, pancytopenia, CSF pleocytosis, and type IV hyperlipoproteinemia. Death occurred at 4 months from Pseudomonas sepsis. Viral cultures from multiple sites in both children were negative. Autopsies demonstrated massive hepatosplenomegaly and lymphohistiocytic meningeal infiltrates in each. The second sib had notable lymphohistiocytic infiltrate in liver and erythrophagocytosis in liver, spleen, and bone marrow. Both are thought to be cases of familial erythrophagocytic lymphohistiocytosis, a rare and frequently fatal disease, presumably transmitted in an autosomal recessive fashion. These cases illustrate the necessity of caution in utilizing the same sperm donor when one sib is affected with an unknown disorder, even if the problem is presumed not to be inherited. Until a diagnosis can be made with certainty, it may be more prudent to delay repeat insemination or to select a different donor.
Doing What Needs to Be Done

I remember when I was a senior resident working in the city-hospital emergency room. Another resident was on the telephone with the chief admitting resident. The conversation concerned a man with a previously known chronic organic brain syndrome and a fever, who was being admitted to the hospital. Although I don't recall the complete history, one comment made by the resident in the emergency room has remained with me for the past five years: "This man has got to be 'tapped.'" I wondered then and still wonder now whether the patient did require a lumbar puncture. Does the elderly patient . . .
The shifting patterns of HIV encephalitis neuropathology.

HIV infected macrophages infiltrate the nervous system early in the progression of HIV infection, leading to a complex set of neuropathological alterations including HIV encephalitis (HIVE), leuko-encephalopathy and vacuolar myelopathy. This in turn results in neurodegeneration of selective cellular populations and pathways involved in regulating cognitive and motor functioning. Rapid progress in the development of highly active antiretroviral therapy (HAART) has changed the patterns of HIV related neuropathology and neurological manifestations in the past 10 years. The prevalence of opportunistic infections and central nervous system (CNS) neoplasms has decreased, and some groups have proposed that the frequency of chronic forms of HIVE have been rising as the HAART-treated HIV population ages. Accordingly, clinical manifestations have shifted from severe dementia forms to more subtle minor cognitive impairment, leading to the suggestion of a classification of HIV associated neurological conditions into an inactive form, a chronic variety, and a ‘transformed’ variant. From a neuropathological point of view these variants might correspond to: a) aggressive forms with severe HIVE and white matter injury, b) extensive perivascular lymphocytic infiltration, c) ‘ burnt-out’ forms of HIVE and d) aging-associated amyloid accumulation with Alzheimer’s-like neuropathology. Factors contributing to the emergence of these variants of HIVE include the development of viral resistance, immune reconstitution, anti-retroviral drug toxicity and co-morbid factors(e.g., methamphetamine, HCV). More detailed characterization of these proposed variants of HIVE is important in order to better understand the pathogenesis of HIV-associated neurological damage and to design more effective treatments to protect the nervous system.
A continuum theory of traffic dynamics for freeways with special lanes

Abstract This paper presents a generalized theory of kinematic waves for freeways with two vehicle types and a set of lanes reserved for one of the vehicle classes. The theory is not restricted to freeways on which the special lanes are clearly identified by signs and pavement markings; e.g. for high occupancy vehicles. It may also apply if the restrictions are self-imposed, such as would occur on a freeway segment upstream of a busy off-ramp where the existing traffic naturally avoids the ‘far-side’ lanes. Of particular interest are oversaturated time periods because the original theory of kinematic waves proposed by Lighthill and Whitham [ Proceedings Royal Society, A 229 , 281–345 (1955)] and Richards (1956) does not recognize that different traffic conditions (queues and speeds) may arise on the two sets of lanes, and that these may affect the two vehicle classes in different ways. It should be intuitive that whether a single coalesced queue forms on both sets of lanes or separate queues form on each set should depend on the traffic composition by vehicle class. In an attempt to furnish a reasonable depiction of these phenomena, a pair of conservation-type partial differential equations in the densities of the two vehicle types is used to model the freeway. In their simplest form, the equations only require the introduction of one additional parameter (representing the fraction of lanes allocated to each vehicle type) over the basic kinematic wave theory. The model is attractive because the nature of its solution can be described in complete physical detail by means of simple intuitive diagrams that show how the simple kinematic wave model is improved. The paper also introduces an exact solution method for problems with piece-wise constant initial data that can either be applied graphically or numerically. For general (piece-wise smooth) data, the numerical technique can be used to approximate the true solution as closely as desired in a way that does not deteriorate with time. A less precise finite-difference approach that always moves vehicles forward is also presented.
The return of elastomer valves

Abstract This paper concerns the heart valves to be used mainly in artificial hearts. Most of our tricusp semilunar valves are made of polyurethane. These valves have functioned in artificial hearts for up to 62 days, and have been implanted in sheep for 1 year without evidence of thromboembolism. Our valves have a wide opening, using redundant leaflets that are "bistable." Accelerated testing by air jet provides 1,000 closures per second. Regurgitation is measured in an apparatus with the help of a competent valve. All polyurethanes change with age, but Silastic does not.
Spatially Organized Films from Bdellovibrio bacteriovorus Prey Lysates

ABSTRACT Bdellovibrio bacteriovorus is a Gram-negative predator of other Gram-negative bacteria. Interestingly, Bdellovibrio bacteriovorus 109J cells grown in coculture with Escherichia coli ML-35 prey develop into a spatially organized two-dimensional film when located on a nutrient-rich surface. From deposition of 10 μl of a routine cleared coculture of B. bacteriovorus and E. coli cells, the cells multiply into a macroscopic community and segregate into an inner, yellow circular region and an outer, off-white region. Fluorescence in situ hybridization and atomic force microscopy measurements confirm that the mature film is spatially organized into two morphologically distinct Bdellovibrio populations, with primarily small, vibroid cells in the center and a complex mixture of pleomorphic cells in the outer radii. The interior region cell population exhibits the hunting phenotype while the outer region cell subpopulation does not. Crowding and high nutrient availability with limited prey appear to favor diversification of the B. bacteriovorus population into two distinct, thriving subpopulations and may be beneficial to the persistence of B. bacteriovorus in biofilms.
Martensite Formation in Conventional and Isothermal Tension of 304 Austenitic Stainless Steel Measured by X-ray Diffraction

The temperature above which neither stress nor plastic strain can cause austenite to transform to martensite is determined for 304 austenitic stainless steel by X-ray diffraction measurements on specimens that were previously subjected to isothermal tension tests. The specimens were tested at 273 K, 298 K, 308 K, 333 K, and 373 K (0 °C, 25 °C, 35 °C, 60 °C, and 100 °C). A new isothermal testing technique was used not only for controlling the testing temperature but also for averting deformation-induced heating. Hence, the effect of temperature on the strain-induced martensite is decoupled from that of strain. The diffraction measurements reveal that the martensite volume fraction decreases linearly with the testing temperature up to a critical temperature, which is found by linearly extrapolating to zero martensite volume fraction.
Effects of Tobacco Smoke Condensate on Estrogen Receptor-α Gene Expression and Activity

Metallo-estrogens are a new class of potent environmental estrogens. This study investigates whether tobacco smoke condensate (TSC), which contains metals and metalloids, elicits estrogen-like effects at environmentally relevant doses. Treatment of human breast cancer cells, MCF-7, with 40 μg/ml TSC resulted in a 2.5-fold stimulation of cell growth. TSC decreased the concentration of estrogen receptor (ER)-α protein and mRNA (63 and 62%, respectively), and increased the expression of the estrogen-regulated genes, progesterone receptor and pS2 (5- and 2-fold, respectively). In addition, TSC activated ER-α in COS-1 or CHO cells transiently transfected with wild-type ER-α and an ERE-CAT or an ERE-luciferase reporter gene (11- and 6-fold, respectively). TSC also activated a chimeric receptor (GAL-ER) containing the hormone binding domain of ER-α (3.5-fold). It blocked the binding of estradiol to the receptor without altering the affinity of estradiol (Kd = 2.2–6.8 × 10−10 m). Transfection assays with ER-α mut...
Experimental analysis and design considerations of virtual environments creation

Selecting the appropriate 3-D capture and modeling technologies to create the contents of a virtual environment (VE) remains a challenging task. One of the objectives of the environment-modeling project in our laboratory is to develop a design strategy for selecting the optimum sensor technology and its configuration to meet the requirements for virtual environment applications. This will be based on experimental evaluation of all performance aspects fa several systems for creating virtual environments. The main problems include: practical sensor calibration, the registration of images particularly in large sites in the absence of GPS and control points, the complete and accurate coverage of all details, and maintaining realistic-look at real-time rate. This paper focuses on the evaluation of the performance of some approaches to virtual environment creation using specifically designed laboratory experimentation. By understanding the potentials and limitations of each method, we are able to select the optimum one for a given application.© (1998) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Acetylcholine receptors at the neuromuscular junction: Developmental change in receptor turnover

Abstract The turnover of acetylcholine receptors labeled with 125I-labeled α-bungarotoxin was measured in the developing posterior latissimus dorsi muscle of the chick. The degradation rates for acetylcholine receptors at the neuromuscular junction and in extrajunctional regions of the muscle cell were determined. One week after hatching, the rates of junctional and extrajunctional receptor degradation are identical ( t 1 2 = 30 hr ). Three weeks weeks after hatching, however, the rate of junctional receptor degradation is considerably slower ( t 1 2 ≥ 5 days ) and different than the rate of extrajunctional receptor degradation ( t 1 2 = 30 hr ). Thus, receptors which are localized at the neuromuscular junction early in embryonic life only become stable several weeks after hatching.
The 20Ne(α, γ)24Mg reaction from 3 to 6 MeV

Abstract The 20 Ne(α, γ) 24 Mg reaction has been studied from 3 to 6 MeV alpha energy using embedded targets. A total of 19 previously unreported resonances has been detected. In many cases the angular distribution of the capture gamma rays has been measured, and the main features of the decay scheme have been established. Several spin and parity assignments can be made to the resonance states and others are suggested. Corresponding resonances in other reactions are suggested for 15 of the new resonances. One (or possibly both) of the resonances at 5.720 and 5.743 MeV and the resonance at 5.796 MeV might correspond to the 6 + and 5 − states observed in the 12 C( 16 O, α) 24 Mg reaction.
Autogenous Bone Grafting

1. Cranial Bone Grafts (Ruiz) 2. Rib Grafts (Costello) 3. Iliac Crest Grafts (Marx) 4. Intra-Oral Grafts (Pikos) 5. Free Bone Flaps (Blanchaert) 6. Tibia Grafts (Kushner)
Laparoscopic splenectomy - A review

Laparoscopic splenectomy has become the standard approach in many institutions when splenectomy is indicated for benign hematologic disease and has gained acceptance in patients with malignant hematologic disease and splenomegaly. It is a technically difficult procedure and is associated with a steep learning curve, with operative times initially longer than those associated with open splenectomy. However, technical advancements such as hand-assisted laparoscopic splenectomy have facilitated increased acceptance of laparoscopy as an approach that is superior to open splenectomy, even in patients with malignant hematologic disease and/or splenomegaly. When compared to open splenectomy, laparoscopic splenectomy is associated with shorter postoperative hospitalization and improved cosmesis.
EFFECTS OF GYPSY MOTH DEFOLIATION ON FOREST BIRDS: AN ASSESSMENT USING BREEDING BIRD CENSUS DATA

Abstract Although the gypsy moth (Lymantria dispar) is a significant insect pest of eastern deciduous forests in the United States, relatively little is known about its effects on forest bird communities. We used six Breeding Bird Census sites from Connecticut, Pennsylvania, and Virginia to assess changes in bird species richness and individual species density in the years surrounding a gypsy moth outbreak. Individual species' responses were variable among states, and only a few species showed consistent responses to outbreaks across sites. Yellow-billed Cuckoos (Coccyzus americanus) and Black-billed Cuckoos (C. erythropthalmus) appeared two years prior to an outbreak and then disappeared immediately after an outbreak on four of the sites and increased in numbers on another site. Indigo Buntings (Passerina cyanea), which are usually associated with open habitat, increased temporarily after outbreaks and then returned to pre-outbreak densities within 5 yrs after the outbreak. At the community or guild leve...
Leading indicators of inflation in market economies

Abstract Inflation rates are cyclical in major market-oriented economies. Recently Geoffrey H. Moore and Stanley Kaish applied the well-known leading indicator approach to the development of a leading index of inflation cycles for the United States. Their index was based on measures of tightness in the labor market, and a measure of tightness in total credit markets, along with a measure of changes in industrial commodity prices. They found that this composite index reflects changes in inflation rate cycles reasonably well, and that it was more reliable than any of the three components taken alone. The present study broadens their study by attempting to duplicate the leading inflation index for forecasting changes in inflation rates in Canada, the United Kingdom, West Germany, France, Italy, and Japan. In general we find that the leading index is useful in anticipating changes in inflation rates in all these countries with the exception of France and Italy. As such we find that the forecasting properties of this index are often as promising in other countries as they have been in the U.S. Where they are not we conclude that there is a need for further research.
Rapid-2-rapid – a collaborative approach to linkage for those recently infected

In light of evolving, 4th generation HIV diagnostics, more effective strategies to test, link, and retain clients in care, are needed. In New Jersey, USA medical facilities are twice as effective at engaging clients into HIV care as alternative screening entities including community based and public health screening facilities. The goal: Complete screening, confirmation, linkage and entry into care within 2 business days.
Efficient computations via scalable sparse kernel partial least squares and boosted latent features

Kernel partial least squares (KPLS) has been known as a generic kernel regression method and proven to be competitive with other kernel regression methods such as support vector machines for regression (SVM) and kernel ridge regression. Kernel boosted latent features (KBLF) is a variant of KPLS for any differentiable convex loss functions. It provides a more flexible framework for various predictive modeling tasks such as classification with logistic loss and robust regression with L1 norm loss, etc. However, KPLS and KBLF solutions are dense and thus not suitable for large-scale computations. Sparsification of KPLS solutions has been studied for dual and primal forms. For dual sparsity, it requires solving a nonlinear optimization problem at every iteration step and its computational burden limits its applicability to general regression tasks.In this paper, we propose simple heuristics to approximate sparse solutions for KPLS and the framework is also applied for sparsifying KBLF solutions. The algorithm provides an interesting "path" from a maximum residual criterion based algorithm with orthogonality conditions to the dense KPLS/KBLF. With the orthogonality, it differentiates itself from many existing forward selection-type algorithms. The computational advantage is illustrated by benchmark datasets and comparison to SVM is done.
Preserving Identity and Planning for Advance Care (PIPAC): preliminary outcomes from a patient-centered intervention for individuals with mild dementia

Objectives: The purpose of this pilot study was to conduct limited-efficacy testing of the newly developed Preserving Identity and Planning for Advance Care (PIPAC) intervention on self-reported and proxy-reported emotional and health-related outcomes of individuals in the early stages of dementia.Method: A two-group comparison design was implemented. Blocked randomization was used to assign individuals with mild dementia and a family contact to either (1) the four-session, multi-component intervention group focused on reminiscence and future planning or (2) the minimal support phone contact comparison group. Of the 19 enrolled dyads, 18completed post-treatment assessments (i.e. 10 intervention and 8 comparison group). Individuals with dementia were M= 82.8 (SD = 6.46) years old; 31.6% were men and 68.4% were women. Participants were predominantly white/Caucasian (n = 18, 94.7%) with one black/African-American (5.3%).Results: Analyses of covariance controlling for baseline differences revealed clinically ...
Photopolarimetric observations of the minor planet Flora.

Review of the rotation period, phase coefficients, and polarization curve of the unusual asteroid Flora. It is an almost spherical asteroid whose period of rotation is probably 13.6 h, but may be only one half of this. Its surface layer consists of a dark material resembling lunar surface soil, but since the polarization curves of Flora and the moon, though generally similar, are not identical the surface of Flora must differ somewhat either in composition or in texture from that of the moon.
Mosaic mapping of foci associated with longevity in the neurological mutants Hk1 and Sh5 of Drosophila melanogaster

Abstract The shaker mutants Hk1 and Sh5affect the nervous system and reduce lifespan, perhaps through activity-related metabolic rate. Three hundred y w Hk1, y w Sh5, and y w mosaics were generated by an unstable ring-X, scored for external male and female tissues, and kept singly to determine the lifespan of each. Because the mosaics did not resolve themselves into distinct long- and short-lived categories, a computer curve-fitting method was developed to transform and combine the appropriate non-mosaic male (short-lived) and female control curves of percent dying per day, into an approximation of the curves observed for mosaics with a given cuticular landmark male on both, one, or neither side. The resulting estimates of long- and short-lived mosaics of each type were used to calculate the distance between each landmark and the developmental focus for Hk1 and Sh5 life-shortening. In both cases the mutant focus was in the ventral anterior part of the thorax, perhaps in the anterior thoracic ganglion; the focus was submissive for Hk1 and domineering for Sh5. At the same time,there was a second focus, independent of the mutant effect, associated with early mosaic death. In both shaker and control mosaics this early death focus mapped laterally in the region of the wing, and is probably the result of incompatible juxtapositions of male tissue in that region, and female tissue anteriorly. The curve-fitting method may be useful for analyzing other quantitative and multi-focus characters.
Therapeutically targeting the SUMOylation, Ubiquitination and Proteasome pathways as a novel anticancer strategy

The ubiquitin (Ub)+proteasome proteolytic pathway is responsible for the selective degradation of the majority of nuclear and cytosolic proteins. The proteasome is a high molecular weight multicatalytic protease that serves as the catalytic core of the complex Ub-dependent protein degradation pathway and is an exciting new target for the development of novel anticancer therapies. Inhibition of the proteasome, and consequently Ub-dependent proteolysis, with the small molecule pharmacologic agent bortezomib led to approval by the US Food and Drug Administration (FDA) for the treatment of multiple myeloma (MM) that has subsequently been extended to other hematologic malignancies. Inhibition of the proteasome results in the intracellular accumulation of many ubiquitinated proteins that control essential cellular functions such as cellular growth and apoptosis. The accumulation of high molecular weight Ub~protein conjugates eventually triggers apoptosis, with tumor cells more susceptible to proteasome inhibition than non-malignant cells. The defined mechanism of action for proteasome inhibitors has not been completely characterized, not all patients respond to proteasome inhibitor-based therapy, and inevitably patients develop resistance to proteasome inhibitors. Further investigation of the Ub+proteasome system (UPS) is needed to develop more effective inhibitors, to develop agents that overcome bortezomib resistance and to avoid adverse effects such as neuropathy. Furthermore, there are newly uncovered pathways, e.g., the SUMOylation and NEDDylation pathways, which similarly attach Ub-like proteins (ULPs) to protein substrates. The functional consequence of these modifications is only beginning to emerge, but these pathways have been linked to tumorigenesis and may similarly provide therapeutic targets. The immunoproteasome is a specialized form of the proteasome that produces peptides that are presented at the cell surface as major histocompatibility complex (MHC) class I antigens. Proteasome inhibitors decrease the presentation of antigenic peptides to reduce tumor cell recognition by cytotoxic T cells (CTLs) but unexpectedly increase tumor cell recognition by natural killer (NK) cells. Inhibitors of the UPS are validated, cytotoxic agents that may be further exploited in immunotherapy since they modulate tumor cell recognition by effectors of the immune system. Targeting the UPS, SUMOylation and NEDDylation pathways offers great promise in the treatment of hematologic and solid malignancies.
Hypoosmotic stress stimulates growth in HepG2 cells via protein kinase B—dependent activation of activator protein-1

Although hypoosmotic stress-induced cell swelling activates phosphatidylinositol-3-kinase, its impact on the downstream signal protein kinase B and cell growth is unknown. Activator protein-1 is in part phosphatidylinositol-3-kinase dependent, and is important in proliferation. We hypothesized that cell swelling modulates proliferation in HepG2 cells via the protein kinase B-dependent activation of activator protein-1. HepG2 cells pretreated with or without LY294002 were exposed for up to 30 minutes to hypoosmotic medium (160 mOsm/L). Tumor necrosis factor-alpha (1.4 nmol/L) or normoosmolar medium (270 mOsm/L) served as positive and negative controls, respectively. Western immunoblots measured cytoplasmic phosphorylated and total protein kinase B. Electromobility shift assays measured nuclear activator protein-1. Methylene blue assays measured cell proliferation at 24, 48, and 72 hours after stimulation. Hypoosmotic stress phosphorylated protein kinase B by 10 minutes. Subsequently, hypoosmotic exposure stimulated activator protein-1 by 30 minutes. Pulse exposure to hypoosmotic stress potentiated HepG2 proliferation by 72 hours as compared to both negative controls and LY-inhibited cells (n = 4 per group, P = 0.009 and P = 0.004, respectively; P <0.001 analysis of variance. All three activation events were abolished with LY294002 pretreatment. In HepG2 cells, hypoosmotic stress-induced swelling stimulates proliferation via protein kinase B-mediated activation of activator protein-1. These data delineate a possible mechanism linking changes in cell volume to growth in human liver cancer.
Photovoltaic retinal prosthesis for restoring sight to the blind: implant design and fabrication

We have designed and fabricated a silicon photodiode array for use as a subretinal prosthesis aimed at restoring sight to patients who lost photoreceptors due to retinal degeneration. The device operates in photovoltaic mode. Each pixel in the two-dimensional array independently converts pulsed infrared light into biphasic electric current to stimulate remaining retinal neurons without a wired power connection. To enhance the maximum voltage and charge injection levels, each pixel contains three photodiodes connected in series. An active and return electrode in each pixel ensure localized current flow and are sputter coated with iridium oxide to provide high charge injection. The fabrication process consists of eight mask layers and includes deep reactive ion etching, oxidation, and a polysilicon trench refill for in-pixel photodiode separation and isolation of adjacent pixels. Simulation of design parameters included TSUPREM4 computation of doping profiles for n + and p + doped regions and MATLAB computation of the anti-reflection coating layers thicknesses. The main process steps are illustrated in detail, and problems encountered are discussed. The IV characterization of the device shows that the dark reverse current is on the order of 10-100 pA-negligible compared to the stimulation current; the reverse breakdown voltage is higher than 20 V. The measured photo-responsivity per photodiode is about 0.33A/W at 880 nm.
Simple treatment of the anomalous interband dielectric constant of zero-gap semiconductors

A simple treatment of the anomalous static and dynamic interband dielectric constant for zero-gap semiconductors is presented. It is based on an approximate form for the interband matrix element which can be inferred from the $f$ sum rule under a single-particle effective-mass approximation. The calculation encompasses as special cases, pure, doped, and strained crystals at finite temperature and in magnetic fields.
An integrated service for Personalised Healthcare and Wellness (PHW)

At the Systems Biology Lab of the University of Florida, we are developing an integrated system, PHW service, for accessing and storing and monitoring information in personalised medicine. We intend to take a practical approach to build such a system in the framework of clinical and translational sciences of the NIH Roadmap.
Quality-Aware Techniques for Reducing Power of JPEG Codecs

This paper presents use of bit truncation and voltage overscaling to reduce the power consumption of JPEG codecs. Both techniques introduce errors which have to be compensated to minimize quality degradation. To handle the errors due to bit truncation, we propose a compensation scheme based on unbiased estimation of the truncation noise. For 4-bit truncation, such a scheme achieves 23% power savings for DCT with only 0.6dB drop in PSNR. To compensate for errors due to aggressive voltage scaling, we introduce an algorithm-specific technique which is based on exploiting the characteristics of the quantized coefficients after zig-zag scan. This technique is very effective in improving the PSNR performance with a small circuit overhead. A combination of the two techniques help achieve even higher power savings with only a modest increase in PSNR. For instance, a combination of 4-bit truncation and operating voltage of 0.78V results in 44% power reduction for DCT with a 1.8dB drop in PSNR performance of the JPEG codec.
Diminished IL-12 production mediates impaired T-cell stimulating capacity of lymph node dendritic cells and macrophages in SIV infection (INC9P.444)

Mononuclear phagocytes are integral components of the innate immune system that sense invading microbes and expand antigen-specific immune responses. Thus far, their roles in progressive HIV infection remain to be clarified. We used the pathogenic simian immunodeficiency virus (SIV) rhesus macaque model to determine the immune stimulating capacity of plasmacytoid dendritic cells (pDC), myeloid DC (mDC), and macrophages (Mϕ) after SIV infection, focusing on the lymph node compartment. By positive selection through live-cell sorting, we measured the ex vivo ability of each subset to respond to uridine-rich ssRNA oligos derived from the infecting strain of SIV and to subsequently drive CD4+ T cell proliferation and IFN-γ production. Isolated pDC and Mϕ from infected macaques were defective at stimulating CD4+ T cells to divide and produce IFN-γ. Co-stimulatory marker upregulation on mononuclear phagocytes remained comparable in naive and infected samples, whereas deficiencies in IFN-α and IL-12 production by pDC and Mϕ were found concurrent with lower CD4+ T cell function. Furthermore, exogenous IFN-α and IL-12 supplementation was able to recover the CD4+ T cell stimulating capacity of isolated mDC and Mϕ from SIV-infected lymphatic tissue. These novel findings suggest that defects in mononuclear phagocyte T cell stimulating capacity through loss of IL-12 production may contribute to the overall immune dysfunction in pathogenic SIV of rhesus macaques and HIV infection of humans.
SwatCS: Combining simple classifiers with estimated accuracy

This paper is an overview of the SwatCS system submitted to SemEval-2013 Task 2A: Contextual Polarity Disambiguation. The sentiment of individual phrases within a tweet are labeled using a combination of classifiers trained on a range of lexical features. The classifiers are combined by estimating the accuracy of the classifiers on each tweet. Performance is measured when using only the provided training data, and separately when including external data.
Agent-oriented embedded electronic measuring systems

Introduction Agent technology has attracted the attention of academia in many domains in the past decade. It is probably due to the fact that computer systems have been becoming complicated with distribution and openness characteristics. Agent-based systems, or multi-agent systems in general, are contemporary paradigm for software development. Ashri et al. claimed that "the underlying concept of decentralized, autonomous control expressed through agents that are able to communicate and cooperate to achieve goals is especially appealing for applications in heterogeneous and dynamic computing environments." Jennings refers agent-oriented software development approach to as "decomposing the problem into multiple, autonomous components that can act and interact in flexible ways to achieve their set objectives." Jennings also advocates that agent-oriented software development approach offers the following advantages: • Decompose a complex problem effectively so that the problem space can be divided into smaller sub-problem space; • A natural way of modelling such systems because they are, most often, decentralized in nature; and • Interaction among agents is appropriate for modelling the dependencies that exist in complex systems. In the instrumentation and measurement domain, application of agent technology is still in its infancy. Dobrowiecki et al. discussed how measuring instruments are related to artificial intelligence, in particular agent technology. They presented a general idea of agent-based system which is "to order a service from an agent and to delegate any responsibility of direct control, rather than to monitor closely the progress of the problem solving". Amigoni et al. claimed that agent techniques have evolved and improved over the years such that "impacts on measurement systems whose nature and conceptual interpretation have radically changed." Real-life applications of agent technology in this domain are not well documented. It is not easy to find a successful application of agent-based instrumentation and measuring system, although PC-based distributed instrumentation and measuring systems are not uncommon. In fact, they are usually configured as client-server systems. In this article, two real-life agent-oriented applications which are embedded measuring systems will be reviewed. In fact, the two cases are commercial products and have already been mass produced. The reasons why such distributed approach is used will be revealed. In fact, one of them is limited by the outlook design so that two individual functional units (which are agents) have to be built for each final product. On the other hand, the other one is decomposed into different independent units to simplify the software development and product design, which is a collaborative work by three independent companies. Main issues, including difficulties, that came across during the course of development of the two cases with respect to agent-oriented design will be addressed in this article.
Surgical Revision After Percutaneous Mitral Repair With the MitraClip Device

Background Percutaneous mitral repair with the MitraClip device (Evalve, Menlo Park, CA) has been reported. Preserving conventional surgical options in the event of percutaneous treatment failure is important. We describe surgical treatment at varying intervals after the MitraClip procedure in 32 patients. Methods One hundred seven patients with moderate-to-severe or severe mitral regurgitation who were either symptomatic (91%) or, if asymptomatic (9%), had evidence of left ventricular dysfunction were enrolled as part of the Endovascular Valve Edge-to-Edge REpair STudy (EVEREST) phase I registry study or as "roll-in" subjects in the EVEREST II study. Thirty-two of the 107 patients (30%) underwent surgery after an attempted MitraClip procedure. Results Of the 32 patients undergoing post-clip mitral valve surgery, 23 patients (72%) had one or more clips implanted and 9 patients (28%) received no clip implant. The indications for mitral valve surgery in the 23 patients with a clip included partial clip detachment (n = 10), residual or recurrent mitral regurgitation greater than 2+ (n = 9), and other (atrial septal defect [n = 2], device malfunction [n = 1], and incorrectly diagnosed mitral stenosis [n = 1]). Twenty-seven of 31 patients (87%) underwent the surgical procedure planned before surgery (planned procedure unknown in 1 patient). Four of 25 patients (16%) with planned repair underwent mitral valve replacement. Conclusions Standard surgical options were preserved in patients who had surgery after percutaneous repair with the MitraClip device. Successful repair was feasible in the majority of patients after the MitraClip procedure, with repair performed as late as 18 months after clip implantation.
Lipopolysaccharide-binding protein (LBP) serum levels in children with OSA and obesity

Introduction Obstructive sleep apnea (OSA) has been linked to obesity and the metabolic syndrome (MetS). All these conditions are further tightly linked to inflammation, the origin of the latter still being under debate. In recent years, the gut microbiota and/or gut permeability have emerged as important factors in the vicious cycle of obesity, MetS and inflammation. The gut microbiota, which serves as reservoir for bacterial lipopolysaccharides (LPS), could be altered by OSA and trigger inflammation. Lipopolysaccharide-binding protein (LBP) is a 65-kDa acute-phase protein derived from the liver which has been viewed as a surrogate marker of underlying low level endotoxemia brought about by LPS from the gut. We hypothesized that systemic LBP levels would be higher in obese children and in those with OSA. Materials and methods Consecutive snoring and non-snoring children (mean age: 6.8 ± 1.3 years) were included after they underwent overnight polysomnographic evaluation and a fasting blood sample was drawn the morning after the sleep study. Children were subidivided into 4 sub-groups based on the presence of obesity (BMI z score > 1.65) or OSA (obstructive AHI > 2/hrTST). Plasma LBP levels were assayed using commercial ELISA kits. Results Of the children studied to date ( n = 56), non-obese controls had lowest levels of LBP, and the presence of obesity without OSA was associated with significant increases in LBP levels ( p 0.03). Non-obese children with OSA exhibited LBP leves that were similar to those of obese children without OSA ( p 0.01 vs. non-obese without OSA), with obese children with OSA demonstrating the highest LBP levels of all 4 groups ( p 0.02 vs. all 3 other groups). Conclusion Systemic low level endotoxemia and resultant systemic inflammation is present in children who are either obese or suffer from OSA, and is particularly prominent when both conditions are present. We postulate that altered sleep and other factors facilitating obesity such as high fat diet may disrupt the gut microbiome, and lead to increased systemic LPS leaks with resultant inflammation. Acknowledgements NIH HL65270.
Surface‐Diffusion Theory for Drying Creep Effect in Portland Cement Paste and Concrete

An attempt is made to introduce quantitative analysis into the complex problems of the mechanism of drying creep in cement paste. The main source of creep is assumed to be the change in thickness of hindered adsorbed water layers caused by diffusion of water, coupled with diffusion of solids dissolved from the confining adsorbent particles. The basic equations of equilibrium and irreversible thermodynamics governing the problem are formulated, reduced to an initial-boundary value problem, and solved numerically. Computer studies have indicated that the drying creep effect is very likely caused by nonlinear coupling between the diffusion of water and that of solids in the hindered adsorbed layers.