cssi/SciSciGPT-SciSciNet huggingface dataset:
Enhancement of t-PA Induced Fibrinolysis with Laser Energy: In-Vitro Observations

The solid-state, pulsed-wave, holmium:YAG laser operates within strong water absorption peaks at the mid-infrared optical wavelength. This laser has been shown to be capable of inducing a mechanical, photoacoustic dissolution of fibrin, a major constituent of thrombi. It is not known whether this laser's energy combined with pharmacologic therapy can enhance the rate of fibrinolysis. The aims of this study were (1) to test the hypothesis that mid-infrared laser emission can enhance tissue-type plasminogen-activator (t-PA) mediated fibrinolysis and (2) to test the combined effect of these two methods of fibrinolysis on fibrin clots varying in age. Three in vitro experimental protocols were used. (1) Fibrin clots were treated with 116 000 IU t-PA for 1, 6 and 12 h, respectively, and then exposed to mid-infrared laser energy (solid-state, pulsed-wave, holmium:YAG, 2.1 μm wavelength 250 ms pulse length, 5 Hz repetition rate, 500 mJ/pulse (33 J/cm2)). (2) Fibrin gels layered with t-PA were exposed to either 25, 50, 75 or 100 J laser energy. t-PA was then allowed to interact with the lased gels for an additional 4 h. (3) The effects of varying clot age (1, 4 or 8 h) on laser (75 J) augmentation of t-PA induced fibrinolysis were tested. Each experimental protocol had control gels and following each experimental manoeuvre, 20 μl of the plasmin inhibitor e-amino-n caproic acid was added and fibrin degradation products (FDPs), an indicator of fibrinolysis, were measured by latex agglutination. In fibrin clots exposed to t-PA for 6 h, the addition of laser energy significantly increased FDPs released (t-PA alone 40±0 μg/ml, laser plus t-PA 160±0 μg/ml, p 300 μg/ml, p=0.001). The rise in FDPs was significantly greater with 75 J of laser energy compared to 25 J (160±0 μg/ml vs. 80±0 μg/ml, p=0.0001), however, energy levels greater than 75 J did not further increase the amount of FDPs indicating a plateau phenomenon in dose–response relationship. t-PA had a decreased fibrinolytic effect on 4 and 8 h-old clots (FDPs of 60±20 μg/ml and 30±10 μg/ml, respectively). Laser energy reversed this trend and enhanced fibrinolysis in both 4 and 8 h-old clots. In 4 h-old clots, laser plus t-PA resulted in FDP release of 160±0 μg/ml compared to 60±20 μg/ml for t-PA alone (p=0.007). In 8 h-old clots, FDP release with laser plus t-PA was 160±0 μg/ml compared to 30±10 μg/ml with t-PA alone (p=0.0004). It was concluded that in vitro application of mid-infrared laser energy significantly enhances fibrinolysis in fibrin clots initially treated by t-PA. The in vitro interaction between mid-infrared laser and t-PA is energy dependent, however, at energy levels exceeding 75 J there is a plateau phenomenon in dose–response relationship. This wavelength photoacoustic energy also augments the decreased response of ageing clots to t-PA.
Meaningfulness, Commitment, and Engagement:The Intersection of a Deeper Level of Intrinsic Motivation:

The problem and the solution. The work motivation literature suggests the existence of a level of motivation that goes beyond the commonly known typologies of intrinsic and extrinsic motivation. Th...
Heterogeneous NOx chemistry in the polluted PBL

Abstract The significance of heterogeneous mechanisms in controlling gas-phase NO x (NO, NO 2 ) mixing ratios in polluted urban air, especially during nighttime, is not well established. Several recent studies have suggested that carbon soot can provide an effective surface for mediating the inter conversion among several NO y members. However, a number of such reactions reported in the literature have widely varying reaction probabilities and often conflicting pathways. We evaluated several of these reactions and choose the NO 2 conversion to HONO on the surface of soot particles for further analysis with a box photochemical model. These calculations show that the conversion of NO 2 to HONO on particle surfaces produces a large, measurable signal (up to several parts per billion) in nighttime HONO mixing ratios. Inclusion of this reaction was also shown to have significant impacts on ozone, OH and HO 2 in the polluted planetary boundary layer (PBL). The sensitivity of these results to the different reaction rate probabilities ( γ ) and particle surface areas was also examined. Results are then evaluated to find the combination of γ and surface areas that would mostly likely occur in the PBL within the limitations of the model.
Ability of Chelators to Alter the Physical Location and Prooxidant Activity of Iron in Oil-in-Water Emulsions

: Our research determined whether chelators could influence physical location and prooxidative activity of lipid-phase iron in oil-in-water emulsions. Corn oil saturated with ferric ions was used to produce polyoxyethylene 10 lauryl ether-stabilized oil-in-water emulsions. Continuous-phase iron concentrations increased with increasing chelator concentrations (10 to 100 μM) and storage time (1 to 7 d). At pH 3.0, the concentration of continuous-phase iron was higher in the presence of EDTA and sodium tripolyphosphate (STPP) than citrate. STPP and EDTA were more effective than citrate at inhibiting lipid oxidation at pH 3.0. These results indicate that chelators can increase the transfer of iron in lipid to the aqueous phase, thus altering its prooxidant activity in oil-in-water emulsions.
An Improved HPLC Method for the Determination of Furosemide in Plasma and Urine

Abstract A sensitive HPLC method with minimal sample preparation and good reproducibility for the determination of furosemide in plasma and urine is described. Acidified plasma samples were extracted using CH2Cl2 containing desmethylnaproxen as internal standard (IS). Fresh urine samples were incubated with β-gluc-uronidase for 15 minutes and then treated with CH3CN containing IS. Chromatography was performed on a C18 column with 10 mcl sample injection, Mobile phases were: a) for plasma: 0.01 M NaH2PO4, pH 3.5 - CH3OH (65:35), and b) for urine: acetic acid, pH 3.5 - CHS3OH (60:40) at 3 ml/min and fluorescence detection at Ex 235/Em 389 nm. The plasma standard curve was linear from 0.01 to 15.0 mcg/ml and the urine from 0.5 to 200.0 mcg/ml. The within run CV's were 3,2% at 0.74 mcg/ml plasma and 2.0% at 10.7 mcg/ml urine. Recovery from plasma was 69.9% at 2.0 mcg/ml and 98.6% from urine at 5.0 mcg/ml. The stability of furosemide and its glucuronide were studied. Both methods have been applied to the analy...
Requirements for a practical network event recognition language

Abstract We propose a run-time monitoring and checking architecture for network protocols called Network Event Recognition. Our framework is based on passively monitoring the packet trace produced by a protocol implementation and checking it for properties written in a formal specification language, NERL. In this paper, we describe the design requirements for NERL. We show how the unique requirements of network protocol monitoring impact design and implementation options. Finally we outline our prototype implementation of NERL and discuss two case studies: checking the correctness of network protocol simulations and privacy issues in packet-mode surveillance.
The effects of high and low doses of methadone on cigarette smoking

The effect of methadone dose on the cigarette smoking of five methadone maintenance subjects was studied in a clinical setting. Following a two-week baseline period, daily doses of methadone were either increased (50-80 mg) or decreased (80-50 mg) every two weeks according to an A-B-A-B study design. Continuous self-monitoring was used to collect data on natural smoking behavior, and expired air carbon monoxide (CO) levels were measured at each clinic visit. The predicted methadone dose-related changes in smoking were found in three of the five subjects. Fine-grained analysis of self-monitoring records showed that the proportion of total daily smoking was highest within 4 h after taking methadone for three subjects. CO levels were not significantly associated with smoking rate. The results further support and extend previous reports that methadone may produce dose-related increases in smoking. No reactive effects of self-monitoring were observed, and compliance with this procedure was extremely high, supporting the usefulness of this method for assessing natural smoking behavior in this population.
The use of the case-crossover design in studying illicit drug use.

The case-crossover design was developed to study time-varying exposures that cause transient excess risk of acute health events. It is a variant of case-control and subject-as-own-control research designs, involving use of information about exposure history of each case to estimate the transient effect. This kind of self-control design can help to reduce sampling bias otherwise introduced in the selection of controls, as well as confounding bias that might be derived from enduring individual characteristics, especially personality traits and other long-standing inherited or acquired vulnerabilities. When the subject is used as his or her own control, these personal vulnerabilities are matched. In this paper we discuss strengths and weaknesses of the case-crossover design and suggest applications of the case-crossover design in epidemiologic studies on suspected hazards of illicit drug use, and in studies of drug use and co-occurring psychiatric disturbances. We conclude that the case-crossover design can ...
Decision Support for Planning and Resource Allocation in Hierarchical Organizations

Planning in hierarchical organizations frequently involves interpreting objectives assigned by a superordinate, developing objectives to assign to subordinates, and allocating resources to subordinates for the accomplishment of their objectives. The planning problem is to develop a program of objectives that is feasible within the resource constraints, and which provides the best possible contribution to the superordinate's plan. Resource allocation is computation intensive and is a prime candidate for mathematical programming decision support. The principal difficulty in applying mathematical programming techniques is the lack of a suitable structure defining the relationship between resource allocations and contribution to the overarching objectives of the superordinate. A decision support methodology for planning and resource allocation in hierarchical organizations is presented. The methodology employs a goal-reduction model based on logical principles for the decomposition of objectives. The model has a natural mathematical interpretation of the composition effects of accomplishing subgoals. The same principles used in reducing the abstraction of the objectives are used in aggregating the contributions of allocated resources to the objectives. The notion of archetype objectives used as intermediate steps in goal reduction is developed. An interactive optimization procedure is described in which an optimization algorithm is used to develop trial solutions, and in which user preferences and priorities are elicited in the context of the trial solutions. The goal structure is the basis for the optimization function and the interactions with the user. Fire support planning in combined arms operations is used to illustrate the approach.
New opportunities in ultrasonic transducers emerging from innovations in piezoelectric materials (Invited Paper)

Piezoelectric materials lie at the heart of ultrasonic transducers. These materials convert electrical energy into mechanical form when generating an interrogating acoustic pulse and convert mechanical energy into an electric signal when detecting its echoes. This paper first surveys the piezoelectric materials in current use: piezoceramics, such as barium titanate, lead zirconate titanate, and modified lead titanate; piezopolymers, such as polyvinylidene difluoride and its copolymer with trifluroethylene; and piezocomposites, consisting of piezoceramic rods in a passive polymer matrix. Each material system has properties which commend them for use in the present single element transducers, annular arrays, sequenced linear arrays, and steered phased arrays. Looking to the future, new transducer possibilities are opening up due to recent piezoelectric material developments, such as, for example, synthesis techniques for fine-grained high-density piezoceramics, electrostrictive relaxor ferroelectric ceramics, novel piezoceramic forming methods, piezoceramic fiber synthesis, piezoceramic/metal multilayer structures, composite acoustoelectric materials, ferroelectric thin film growth and processing, and new piezopolymers. These innovations lead to fabrication of conventional transducers at high frequencies, fine-scale piezocomposites, 11/2-D and 2-D arrays, small intravascular transducers, as well as provide opportunities for new ultrasonic imaging techniques, using pitch-catch and non-resonant traveling wave transducers.
Strategic Implications of Electronic Linkages

Abstract In this article, senior executives comment on the strategic issues involved in EDI. Trading partner relationships and the balance of power are critical issues when firms participate in electronic commerce. the relationships between trading partners who exchange data electronically are very important to these executives. the participants in the study also are concerned about the relative power between their firm and other members of the supply chain.
Perinatal size and maturation of the olfactory and vomeronasal neuroepithelia in lorisoids and lemuroids

Explanations for the chemosensory abilities of newborn mammals focus primarily on food (milk) acquisition and communication (e.g., maternal–infant bonding). However, the relative importance of the main and accessory (vomeronasal) olfactory systems is hypothesized to differ at birth between altricial and precocial mammals. Strepsirrhines (lemurs and lorises) possess main and accessory olfactory systems, and vary in life-history traits related to infant dependency and maturation. Accordingly, this study examines the size and maturational characteristics of vomeronasal (VNNE) and olfactory (OE) neuroepithelia in strepsirrhines. Serially sectioned heads of 18 infant cadavers were examined microscopically for neuroepithelial distribution. Measurements were taken on the length of the nasal fossa on one side that was occupied by VNNE and OE. The data were corrected for body size using the cranial length or body mass, and were then examined for correlation with several life-history variables, as well as activity pattern. In addition, immunohistochemistry was used to identify cells in the VNNE and OE that express olfactory marker protein (OMP), a marker of mature olfactory neurons. Relative OE extent was not significantly correlated with any of the life-history variables. Relative VNNE length was negatively correlated with relative gestation length and relative neonatal mass (P<0.05). However, when we corrected for phylogenetic relationships, we found no significant correlations between either of the neuroepithelial measurements and life-history variables. Immunohistochemical findings suggest that OE has more OMP-reactive cells than VNNE in all species. OMP-reactive cells appear to be less numerous in diurnal species compared to most nocturnal species. These results indicate that the VNNE may be relatively longer at birth in altricial species. However, it remains uncertain how phylogeny and/or ontogeny may explain these findings. Am. J. Primatol. 69:74–85, 2007. © 2006 Wiley-Liss, Inc.
A Design Oriented Reliability Methodology for Fatigue Life Under Stochastic Loadings

Fatigue damage analysis is critical for systems under stochastic loadings. To estimate the fatigue reliability at the design level, a hybrid reliability analysis method is proposed in this work. The First Order Reliability Method (FORM), the inverse FORM, and the peak distribution analysis are integrated for the fatigue reliability analysis at the early design stage. Equations for the mean value, the zero upcrossing rate, and the extreme stress distributions are derived for problems where stationary stochastic processes are involved. Then the fatigue damage is analyzed with the peak counting method. The developed methodology is demonstrated by a simple mathematical example and is then applied to the fatigue reliability analysis of a shaft under stochastic loadings. The results indicate the effectiveness of the proposed method in predicting fatigue damage and reliability.Copyright © 2013 by ASME
Aldosterone-induced proteins in renal epithelia

Similar aldosterone-induced proteins have been demonstrated in two renal epithelia, the urinary bladder of the toad, Bufo marinus, and epithelia formed by cells of the A6 line derived from the kidney of the toad, Xenopus laevis. The proteins are induced along with the stimulation of Na+ transport but their synthesis is not dependent on Na+ transport per se. In view of the similar characteristics of the aldosterone-induced proteins in these two different epithelia, we suggest that they may have an important role in aldosterone-induced Na+ transport.
Perspectives from the Dark Side: The career transition from faculty to administrator

A number of challenges mark the transition from full-time faculty member to academic administrator.
A SUGGESTED SOLUTION TO LINE VERSUS STAFF PROBLEMS IN ORGANIZATION THEORY

Suggests a solution to the conflict between the role of line executives and staff executives in organization theory. Areas of conflict; Description of several examples; Details of the approach to t...
Analysis of Job Satisfaction of the Federal White-Collar Work Force: Findings from the Survey of Federal Employees:

The purpose of this study is to extend previous work on job satisfaction to identify major job and organizational factors as well as individual characteristics that affect employee job satisfaction...
CACHEXIA HYPOPHYSEOPRIVA (SIMMONDS' DISEASE)

Cachexia hypophyseopriva or Simmonds' disease is due to atrophy of the anterior lobe of the pituitary gland. The onset of this disease is insidious, usually in the third or fourth decade, and occurs chiefly in women, the picture being characterized by marked emaciation, precocious senescence, gastro-intestinal distress, loss of the secondary sexual characteristics and intense debility. In addition, hypothermia, bradycardia accompanied by hypotension, a reduced metabolic rate and diminished salt and water excretion are present, with death terminating the syndrome. There may be marked somnolence, diminished mental powers and a tendency to melancholia (1, 2). Anterior pituitary extracts have been used in the treatment of this condition with improvement as reported by Herman (3) and Dunn (4). In this paper we wish to report a typical case of Simmons' disease in which treatment with anterior pituitary extracts was not beneficial.
Analysis of spatial open-loop system by means of direction cosine transformation matrices

In this paper, an analytical approach for the displacement analysis of spatial openloop systems by means of direction cosine transformation matrices is presented. Two local coordinate systems at each joint are designated to formulate the direction cosine matrices, in recursive form, of the joint axis and link vector. Elements of the 3×3 direction cosine transformation matrices are computed based on the geometry of successive link elements, the unit vectors of preceding joint axis and link vector, and the cofactors of direction cosine matrix. The analysis using direction cosine matrix method will provide the “exact” joint positions in space. A computer algorithm is developed to investigate the workspaces of spatial n-R open-loop systems that projected onto the X-Y, Y-Z, and Z-X coordinate planes, respectively. Numerical examples for the workspaces of an industrial robot and the human upper extremity are illustrated.
Aberrant expression of Cks1 and Cks2 contributes to prostate tumorigenesis by promoting proliferation and inhibiting programmed cell death.

The mammalian Cks family consists of 2 well-conserved small proteins, Cks1 and Cks2. Cks1 has been shown to promote cell-cycle progression by triggering degradation of p27kip1. The function of Cks2 in somatic mammalian cells is not well understood although it is required for the first metaphase/anaphase transition during the meiosis. Emerging evidence shows that elevated expression of Cks1 and Cks2 is often found in a variety of tumors, and is correlated with poor survival rate of the patients. Here we demonstrated that expression of Cks1 and Cks2 were elevated in prostate tumors of human and animal models, as well as prostatic cancer cell lines. Forced expression of Cks1 and Cks2 in benign prostate tumor epithelial cells promoted cell population growth. Knockdown of Cks1 expression in malignant prostate tumor cells inhibited proliferation, anchorage-independent growth, and migration activities, whereas knockdown of Cks2 expression induced programmed cell death and inhibited the tumorigenicity. Collectively, the data suggest that elevated expression of Cks1 contributes to the tumorigenicity of prostate tumor cells by promoting cell growth and elevated expression of Cks2 protects the cells from apoptosis. Thus, the finding suggests a novel therapeutic strategy for prostatic cancer based on inhibiting Cks1 and Cks2 activity. © 2008 Wiley-Liss, Inc.
Functional computations in logic programs

Although the ability to simulate nondeterminism and to compute multiple solutions for a single query is a powerful and attractive feature of logic programming languages, it is expensive in both time and space. Since programs in such languages are very often functional, that is, they do not produce more than one distinct solution for a single input, this overhead is especially undesirable. This paper describes how programs may be analyzed statically to determine which literals and predicates are functional, and how the program may then be optimized using this information. Our notion of “functionality” subsumes the notion of “determinacy” that has been considered by various researchers. Our algorithm is less reliant on language features such as the cut, and thus extends more easily to parallel execution strategies, than others that have been proposed.
A Qualitative Research Study of Oral Communication Performance.

This paper focuses on the qualitative methods used to examine one teacher's instructional practice and his students' performance. The qualitative nature of this study reveals insights into teaching and learning through its focus on emerging themes and patterns that developed over time. Methods used included participation-observation; collection of field notes and documents; administration of a pre/post-survey; interviews with teacher and students; and analysis of analytic memos. Analysis of the data reveals interesting themes regarding preparation, practice, and performance. The participants included advanced-level science students and their high school science teacher whose goal was to combine skills-based instruction (oral communication) with course content (chemistry). Implications for this study provide one example of a qualitative research study of oral communication performance that outlines the various methods used to conduct research in a naturalistic and interpretive setting.
Suppressor Scanning at Positions 177 and 236 in the Escherichia coli Lactose/H+ Cotransporter and Stereotypical Effects of Acidic Substituents That Suggest a Favored Orientation of Transmembrane Segments Relative to the Lipid Bilayer

Acidic substituents for Ala-177 (helix 6) or Tyr-236 (helix 7) in LacY cause effects on sugar recognition and cosubstrate coupling that are stereotypical of neutral substituents. Thus, helices 6 and 7 are probably oriented to produce little side-chain contact with the low dielectric lipid bilayer at positions 177 and 236.
Methodology for Analyzing Ranges of Uncertain Model Parameters and Their Impact on Total Maximum Daily Load Process

A methodology for analyzing uncertain parameter ranges prior to model calibration or uncertainty analysis is presented. The method considers parameters that exist in complex models and are typically difficult to set using site-specific data (i.e., parameters that have suggested ranges, national average ranges, or ranges set with land characteristic data). The method applies Monte Carlo runs and an interval-spaced sensitivity analysis to determine the parts of parameter ranges that will most likely cause unrealistic model results. An application of the method is presented using the Soil and Water Assessment Tool model as applied to the Cannonsville Reservoir system watershed for hydrology and sediment simulations. Results indicate that after parameter range reduction, the model output range was reduced by an order of magnitude, thereby reducing the uncertainty of the model and aiding the calibration effort. Sediment transport is difficult to monitor and model in its many stages of transport so significant uncertainty in the sediment erosion and transport parameters for this model still exist. This uncertainty will impact the application of the model for Total Maximum Daily Load development and management decisions.
Acid and alkaline phosphatases of Capnocytophaga species. III. The relationship of the enzymes to the cell wall

Acid (AcP) and alkaline phosphatase (AlP) were localized by physicobiochemical techniques. Greater than 53% of the phosphatases were detected, following sonication, in a low speed centrifugation pellet while osmotically shocked and spheroplasted Capnocytophaga species released only 9-28% and 11-43% of the cellular phosphatases, respectively. French pressure cell disruption was more effective in releasing the phosphatases. Cell fragments were separated into cell wall, cytoplasmic membrane, and soluble fractions as determined by marker enzyme, chemical composition, transmission electron microscopy, sodium dodecyl sulphate - polyacrylamide gel electrophoresis (SDS-PAGE) protein analysis, and gel diffusion. AcP and AlP was partitioned between the isolated cell wall (31-46%) and soluble material (33-61%), with greater than 60% of the phosphatases remaining with the cell wall following Triton X-100 treatment. The amount of phosphatase at the surface of intact C. ochracea was quantitated by specific 125I-protein labelling.
Unique T Cell Antagonist Properties of the Exact Self-Correlate of a Peptide Antigen Revealed by Self-Substitution of Non-Self-Positions in the Peptide Sequence

Abstract The role of self-peptides in shaping the T cell receptor (TCR) repertoire remains to be established. While TCR reactive to certain self-peptides are thought to be deleted in the thymus, the selection of TCR specificity for foreign peptide reactivity appears to require recognition of self-peptide(s) bound to the groove of thymic major histocompatibility complex (MHC) molecules. This dichotomy suggests that different TCR affinities, accessory signals, and/or different sets of self-peptides dictate the eventual fate of any given TCR-bearing clone. Recently, it has been established for several T cell epitopes that derivatives with substitutions in TCR-contact residues can antagonize the proliferation of T cell clones against the wild-type peptide antigen. Moreover, these altered peptide ligands have demonstrated activity in the positive selection of thymocytes with TCR reactive to the wild-type peptide antigen. We have investigated the specificity of T cell antagonism with step-wise substitution of self-amino acids into each nonconserved position of a 12-amino-acid foreign peptide antigen. Our data demonstrate that the ability to antagonize proliferation without competition for MHC binding is unique to the exact self-derivative, where all five of the self-substitutions are inserted. These properties may specifically allow certain self-peptides to downregulate T cell activation to the foreign ligand and/or provide a source of stimulation for immunologic memory.
Regulation of adherens junctions and epithelial paracellular permeability: a novel function for polyamines

Maintenance of intestinal mucosal epithelial integrity requires polyamines that are involved in the multiple signaling pathways controlling gene expression and different epithelial cell functions. ...
Chirality: a blueprint for the future

The chirality that is inherent in the enzyme systems of living organisms results in an abundance of enantiopure organic molecules in the living world. In addition to the optical properties first noticed by Pasteur, stereospecific interactions at recognition sites result in differences in both biological and toxicological effects. This fact underlies the continuing growth in chiral chemistry, rooted as it is in fundamental biochemistry. The pharmaceutical industry has undergone a strategic shift and embraced the wide spectrum of asymmetrical synthetic methods now available. The use of these processes in developmental synthesis and large-scale manufacturing has provided new challenges in drug discovery, motivated by a desire to improve industrial efficacy and decrease the time from the conception of a new drug to the market. The economic impact of the industrial production of chiral drugs is now huge--more than 50% of the 500 top-selling drugs were single-enantiomers in 1997. Sales have continued to increase by more than 20% for the past 6 yr and worldwide annual sales of enantiomeric drugs exceeded US$100 billion for the first time in the year 2000, chiral drugs representing close to one-third of all sales worldwide. While some 'chiral switches' may be of less apparent benefit, or indeed detrimental in some cases, encouragement by the regulatory agencies and the ability to extend the life cycle of a drug coming off patent promotes the trend. However, it may turn out to be the ability to provide chiral templates, and thereby attack the key targets of selectivity and specificity, that will lead to the greatest benefits. Research into new chemical entities that can interact specifically with enzyme families may potentially lead to new therapies for complex disease processes. As Richards has stated, the approach is designed to create a made to measure product, rather than one off the peg.
Association of mitral annular calcium with symptomatic peripheral arterial disease in older persons.

R1 has suggested that mitral annular calcium (MAC) is a form of atherosclerosis. Coronary risk factors are more prevalent in patients with MAC than in those without MAC.2–4 Patients with MAC have a higher prevalence of coronary artery disease5,6 and new coronary events7,8 than patients without MAC. Extracranial carotid arterial disease9 and stroke7,10–12 are also more prevalent in patients with MAC than in those without MAC. We report the association of MAC with peripheral arterial disease (PAD) in 924 older men and in 1,881 older women. • • • In a prospective study, technically adequate 2-dimensional echocardiograms of the mitral valve for diagnosing MAC8 were obtained in 924 men (mean age 80 6 8 years, range 60 to 100), and in 1,881 women (mean age 81 6 8 years, range 60 to 103) in a long-term health care facility. The subjects in this study were unselected patients $60 years of age who were not terminally ill at admission. Symptomatic PAD was diagnosed if the patient had a documented history of surgery for PAD or if the patient had ischemic pain at rest, ulceration or gangrene in an extremity, intermittent claudication, numbness, coldness, cyanosis, or pallor in an extremity, or trophic changes with dry, scaly, and shiny atrophic skin, diminished hair growth, thickened, brittle toenails, or subcutaneous atrophy in an extremity associated with absent or weak arterial pulses.13 PAD was also documented by Doppler studies, arteriograms, and/or surgical confirmation in 769 of 782 patients (98%) with clinical manifestations consistent with PAD. For analyses comparing the 2 groups, chi-square analyses were used for dichotomous variables. MAC was present in 336 of 924 older men (36%) and in 985 of 1,881 older women (52%) (p ,0.0001). Symptomatic PAD was present in 306 of 924 older men (33%) and in 476 of 1,881 older women (25%) (p ,0.0001). Table 1 shows the prevalence of symptomatic PAD in older men and women with and without MAC and also lists levels of statistical significance. In the 98% of patients with symptomatic PAD documented by Doppler studies, arteriograms, and/or surgical confirmation, the association of symptomatic PAD with MAC in older men and women was the same as that listed in Table 1. Patients with MAC have a higher prevalence of coronary risk factors,2–4 coronary artery disease,5,6 new coronary events,7,8 extracranial carotid arterial disease,9 and stroke7,10–12 than patients without MAC. Chronic hypercalcemia predisposes to MAC.14 MAC is also more prevalent in older patients with chronic renal insufficiency than in older patients with normal renal function.15
CompOSE|Q-a QoS-enabled customizable middleware framework for distributed computing

Advances in networking, communication, storage and computing technologies coupled with emerging novel application areas is enabling the widespread use of large scale distributed computing systems. These systems exhibit constant evolution as new applications place specialized requirements from the computing and communication infrastructure. Many applications provide QoS (quality of service) parameters that define the extent to which performance specifications such as responsiveness, reliability, availability, security and cost-effectiveness may be violated. These requirements are often implemented via resource management mechanisms in the middleware. We develop a QoS-enabled customizable middleware framework called CompOSE|Q that can safely and effectively manage change in large scale distributed systems. We illustrate how to achieve flexible, safe and efficient composability of resource management services in the middleware layer while ensuring QoS to the application.
Small bowel sarcoma: Tumor biology and advances in therapeutics

Spindle cell neoplasms are rare mesenchymal tumors of the gastrointestinal tract. GIST (Gastrointestinal stromal tumor) and leiomyosarcoma share similar clinical presentations, gross and microscopic characteristics making distinction difficult in the absence of immunohistochemical (IHC) studies. A multidisciplinary approach is required for treatment planning and ensuring best outcomes. Surgery remains the mainstay of curative treatment for both tumors. Significant advances in targeted molecular therapies have occurred in the past decade in the treatment of GIST with improvement in morbidity and mortality. Similar newer discoveries for treatment of leiomyosarcoma have failed to show any significant survival benefits as yet. Early diagnosis and R0 surgical resection offers the best long term outcome for leiomyosarcoma. Here in we review and discuss the concepts of genetic alterations, newer markers, possible cancer pathways and advances in treatment strategies for these sarcomas.
Differentiated Instruction, Professional Development, and Teacher Efficacy:

Teachers often struggle to provide all students access to specific learning activities that work best for them—and what works best for some students will not work for others. Differentiating instruction makes sense because it offers different paths to understanding content, process, and products, considering what is appropriate given a child’s profile of strengths, interests, and styles. This study focused on teacher efficacy as a way to explain teacher willingness to differentiate instruction. We found that a greater number of professional development hours in differentiation of instruction was positively associated with both teacher efficacy and the teacher’s sense of efficacy beliefs. This study demonstrated that teacher efficacy is an important dimension in implementing the process of differentiation regardless of what level or what content area the teacher taught (elementary, middle, or high school). Implications and future directions for research are also discussed.
A server centric authentication protocol for a RFID system

A large scale implementation of RFID technology in many practical applications including supply chain and retail stores require the resolution of the either-or dichotomy between low-cost RFID tags and secure RFID systems. This research proposes an approach in which the complexity and hence the cost of RFID tags can be drastically reduce by eliminating the security-assuring computational resources from the RFID tags and placing the security burden on the data processing server. This approach can make it possible to carry out secure transactions even with simple and inexpensive RFID tags. This research investigates a multiple ID authentication protocol based on this approach. The paper presents an empirical formula for the prediction of the performance of the protocol in terms of the number of spoofs per transaction for a given protocol configuration.
Nutraceuticals: Pharmacy's Challenge and Opportunity

The rapid increase in the use of nutraceuticals by large segments of the American population presents both a challenge and professional opportunity for pharmacists. Nutraceuticals include dietary s...
Technique for the R‐Curve Determination of Y‐TZP Using Indentation‐Produced Flaws

A technique was developed to estimate the R-curve behavior of Y-TZP using indentation-produced flaws. This technique allows crack-growth resistance to be determined for short crack extensions (micrometers). For Y-TZP samples sintered at 1600°C for 1 h (mean grain size, 0.7 μm), the crackgrowth resistance increases rapidly over the first 10 μm. Peak toughness values determined from this technique correlate with chevron-notch fracture toughness if the ellipticity of the indentation-produced flaw is considered.
Distinguishing primary central nervous system lymphoma from other central nervous system diseases: a neurosurgical perspective on diagnostic dilemmas and approaches.

Object. White matter diseases, including demyelinating or inflammatory disorders, may be indistinguishable clinically and radiologically from some central nervous system (CNS) tumors. In such situations, determination of the final diagnosis is difficult. An example is the differential diagnosis of non-acquired immunodeficiency syndrome‐related primary central nervous system lymphoma (PCNSL) and multiple sclerosis (MS), a demyelinating disease. Unfortunately, delayed diagnosis and treatment of PCNSL can negatively affect prognosis. Methods. The authors reviewed the cases of eight patients with PCNSL or MS. In each case, the initial diagnosis (PCNSL or MS) was equivocal. In these cases, conventional diagnostic approaches were not definitive, thus further delaying diagnosis. The initial symptoms, the selected diagnostic tests, and the presumptive as well as final diagnosis for each case are discussed. The final diagnosis was PCNSL in six cases and MS in two. The uncertainty about the clinical or initial pathological presentation required further diagnostic evaluation in all cases. Two important neurosurgical guidelines are the avoidance of corticosteroid agents and performance of biopsy sampling rather than volumetric tumor resection. Highvolume lumbar puncture, slit-lamp examination/vitrectomy, new CNS imaging techniques, and repeated biopsy procedures also proved helpful. Conclusions. In PCNSL, early definitive diagnosis and treatment are the keys to successful outcomes. Knowledge of strategies essential to early diagnosis lessens the need for brain biopsy sampling, but this procedure is still usually necessary. In such selected cases, biopsy sampling is appropriate even when pathological investigation shows MS rather than PCNSL. Complete resection is not indicated in PCNSL and can lead to additional sequelae.
Protein-coat dynamics and cluster phases in intracellular trafficking

Clustering of membrane proteins is a hallmark of biological membranes' lateral organization and crucial to their function. However, the physical properties of these protein aggregates remain poorly understood. Ensembles of coat proteins, the example considered here, are necessary for intracellular transport in eukaryotic cells. Assembly and disassembly rates for coat proteins involved in intracellular vesicular trafficking must be carefully controlled: their assembly deforms the membrane patch and drives vesicle formation, yet the protein coat must rapidly disassemble after vesiculation. Motivated by recent experimental findings for protein-coat dynamics, we study a dynamical Ising-type model for coat assembly and disassembly, and demonstrate how simple dynamical rules generate a robust, steady-state distribution of protein clusters (corresponding to intermediate budded shapes) and how cluster sizes are controlled by the kinetics. We interpret the results in terms of both vesiculation and the coupling to cargo proteins.
Intravitreous anti-raf-1 kinase antisense oligonucleotide as an angioinhibitory agent in porcine preretinal neovascularization.

Purpose. To test the efficacy of a synthetic antisense oligonucleotide inhibitor of an intracellular signal transduction protein, C-raf-1 kinase, as an inhibitor of ocular neovascularization. Methods. A 2'methoxyethyl, 2'deoxy chimeric 20-nucleotide sequence containing a uniform phosphorothioate backbone was synthesized which targets the 3'untranslated region of porcine C-raf-1mRNA (ISIS 107189). Efficacy of mRNA inhibition was tested in vitro in porcine vascular endothelial cells and treated pigs by Northern blotting. In a pig model of intraocular neovascularization induced by branch retinal vein occlusion, intravitreal injection of ISIS 107189 compound (8µM calculated intraocular concentration) at baseline and on days 14, 42, and 70, was tested against vehicle as control for inhibition of neovascularization. After enucleation on day 84, ocular tissues were analyzed for ISIS 107189 content by solid-phase extraction and capillary gel electrophoresis. Cryostat sections were immunostained for C-raf-1 kinase...
Risk Adjusted Identification of Wiener Systems

This paper addresses the problem of identification of Wiener systems from a set-membership standpoint. Its main result shows that, by pursuing a risk-adjusted approach, the problem can be reduced to a convex LMI optimization form that can be efficiently solved. These results are illustrated with a non-trivial problem arising in computer vision: tracking a human in a sequence of frames, where the challenge here arises from the changes in appearance undergone by the target and the large number of pixels to be tracked.
Variability in the measurement of C-reactive protein in healthy subjects: implications for reference intervals and epidemiological applications

We developed a reproducible ELISA for C-reactive protein (CRP), calibrated with WHO Reference Material, for which intra- and interassay CVs were 3.0% and 6.0%, respectively. Analytical recovery was 97.9%. The distribution of CRP in a healthy blood donor population (n = 143) was nongaussian, with 2.5th, 50th, and 97.5th percentile values of 0.08, 0.64, and 3.11 mg/L, respectively. There was no sex-related difference, and the association with age was weak. In a study of variability [by the method of Fraser and Harris (Crit Rev Clin Lab Sci 1989;27:409-37)], the analytical variability was 5.2%; the within-subject variability, CVI, was 42.2%; and the between-subject variability, CVG, was 92.5%. The critical difference for sequential values significant at P < or =0.05 (i.e., the smallest percentage change unlikely to be due to analytical variability or CVI) was calculated as 118%, and the index of individuality, CVI/CVG, was 0.46. This suggests that CRP, like many clinical chemistry analytes, has limited usefulness in detecting early disease-associated changes when used in conjunction with a healthy reference interval. From a molecular epidemiological standpoint, the usefulness of CRP in longitudinal studies is suggested by the small index of individuality and by observations that (a) short-term fluctuations were infrequent, (b) all data stayed within the reference interval, and (c) relative rankings of the subjects over 6 months only moderately deteriorated.
DNA Y structure: a versatile, multidimensional single molecule assay.

Optical trapping is a powerful single molecule technique used to study dynamic biomolecular events, especially those involving DNA and DNA-binding proteins. Current implementations usually involve only one of stretching, unzipping, or twisting DNA along one dimension. To expand the capabilities of optical trapping for more complex measurements would require a multidimensional technique that combines all of these manipulations in a single experiment. Here, we report the development and utilization of such a novel optical trapping assay based on a three-branch DNA construct, termed a "Y structure". This multidimensional assay allows precise, real-time tracking of multiple configura- tional changes. When the Y structure template is unzipped under both force and torque, the force and extension of all three branches can be determined simultaneously. Moreover, the assay is readily compatible with fluorescence, as demonstrated by unzipping through a fluorescently labeled, paused transcription complex. This novel assay thus allows for the visualization and precision mapping of complex interactions of biomechanical events.
Abstract 3232: Oligonucleotide-selective sequencing (OS-Seq): a rapid and efficient targeting technology for ultra-deep detection of cancer mutations and rearrangements.

Somatic mutations, chromosomal rearrangements and other genomic aberrations in cancer genomes are critical events in the development of cancer and increasingly used in identifying oncogenic events that may be indicators for targeted therapies. For rapid and high accuracy analysis of targeted candidate genes and regions from cancer genomes, we developed OS-Seq that can be used to simultaneously discover cancer point mutations, copy number variants and rearrangements. For this new sequencing technology, we re-engineer the immobilized oligonucleotide primer lawn on a solid phase support (e.g. Illumina flow cell) with capture “primer-probes” such that it functions for both genomic target capture and sequencing (Myllykangas et al. 2011, Nature Biotech). As a result, in a matter of days we can rapidly sequence target regions in cancer genomes. We designed an in-silico exome capture probe set, enabling rapid design of disease-specific targeted capture primer probe sets. Subsequently, we designed assays to cover 313 and 1,400 cancer genes. Using the 313-gene assay targeting 5,000 exons, we can routinely sequence cancer genomes with on-target coverage greater than 500X, including for the entire length of exons as large as 1 Mb regions. Using a smaller gene set we have established coverage depths over 8,000 that enables the investigation of tumor evolution via mutations with low allelic fractions. In addition, we have designed OS-Seq assays for characterizing loci that are involved in rearrangements. We design capture probes positioned on opposing strands upstream and downstream of suspected rearrangement breakpoints and by localized assembly were able to confirm certain rearrangements, including a long deletion and inversions. For our current studies, we are using OS-Seq to identify cancer mutations in colorectal adenocarcinoma and determine the extent of genetic heterogeneity prevalent in these tumors. OS-Seq provides high-depth, high quality cancer genome sequence data, opening the door to potential diagnostic analysis of cancer genetic heterogeneity as seen in tumor evolution and cancer rearrangements. Citation Format: Erik S. Hopmans, Georges Natsoulis, Jason Buenrostro, Sue Grimes, John Bell, Hanlee P. Ji. Oligonucleotide-selective sequencing (OS-Seq): a rapid and efficient targeting technology for ultra-deep detection of cancer mutations and rearrangements. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3232. doi:10.1158/1538-7445.AM2013-3232