cssi/SciSciGPT-SciSciNet huggingface dataset:
Intracellular Trafficking of the JNCL Protein CLN3

Juvenile neuronal ceroid lipofuscinosis is a lysosomal storage disease that causes visual impairment, progressive mental deterioration, and eventually death. A predominant 1.02-kb deletion as well as other mutations have been described in the CLN3 gene. Lacking significant identity with proteins of known function and no overt targeting signals within the primary amino acid sequence, accurate predictions of the intracellular location and function could not be made. Further, recent conflicting reports identified CLN3 as either a lysosomal or a mitochondrial protein. Transfection experiments using native and epitope-tagged fusion proteins were evaluated to help delineate CLN3 localization. We confirmed by immunohistochemistry and brefeldin A treatment that NH2-terminal green fluorescence protein (GFP)-CLN3 fusion proteins were retained in the Golgi apparatus, with no colocalization with mitochondrial markers. Anti-CLN3 antibodies directed against amino acids 67-90 of CLN3 were generated and shown to be specific for a 50-kDa protein in HEK 293 cells and GFP-CLN3 in transfected cells. However, cells transfected with nontagged CLN3 or carboxyl-terminal-tagged CLN3 were not immunoreactive with anti-CLN3 antibodies, suggesting that normally, the amino terminus interacts with other molecules. Thus, tags on the NH2-terminus probably inhibited these interactions and movement of CLN3 from the Golgi to more distal compartments. Also, CLN3 tagged at the COOH-terminus with either GFP or FLAG epitopes were retained in the ER, indicating a role for the COOH-terminus in trafficking. Taken together, these data confirm that CLN3 traffics through the ER and Golgi.
Finger-like projections of plasma membrane in the most senescent fiber cells of human lenses

PURPOSE. To corroborate the findings of finger-like membrane projections in monkey and baboon lenses, in human lens fiber cells. METHODS. Normal human lenses, two months to 76 years old, as well as age-related nuclear cataracts, were immersion fixed in 2% paraformaldehyde-0.2% glutaraldehyde in 0.1 M sodium cacodylate buffer pH 7.2 for 24 h at room temperature, cut into 200–500 µm thick sections along the equatorial axis, fixed for an additional 12–18 h at room temperature, dehydrated in an ascending ethanol series and embedded in Lowicryl K4M. Semi-thick sections (0.25–1.0 µm) were cut, absorbed onto 75 or 100 nickel slotted grids, labeled with anti-MIP 26 or phalloidin, stained with 2% uranyl acetate and viewed by transmission electron microscopy at 100 kV. RESULTS. Transmission electron microscopy micrographs demonstrated the presence of finger-like plasma membrane projections measuring 0.16–0.25 µm in diameter and 1.0–6.5 µm in length with bulbous terminal tips in the most senescent fiber cells in two...
Ziram activates mitogen-activated protein kinases and decreases cytolytic protein levels in human natural killer cells

Human natural killer (NK) cells are central in immune defense with their ability to lyse tumor cells and virally infected cells. Tumor formation and viral infection may increase if NK cytotoxic function is disrupted. Ziram (zinc dithiocarbamate) is used as an accelerating agent in the production of latex and to protect various fruits and vegetables from fungal infection. Previously, we have shown that exposure to ziram inhibits NK lytic function. Butyltin environmental contaminants, which also inhibit NK lytic function, cause rapid activations of mitogen-activated protein kinases (MAPKs) and decreases in expression of the cytolytic proteins granzyme B and perforin (after 24 h) in exposed NK cells. MAPKs are important regulators of the lytic response of NK cells, and spurious activation of these enzymes by contaminants would leave the NK cells unable to respond to appropriate targets. This study examined the effects of ziram exposures on MAPKs (p44/42, p38, and c-jun-N-terminal kinase) and on levels of cyt...
Particle size interconversion of human low density lipoproteins during incubation of plasma with phosphatidylcholine vesicles.

Incubation of plasma (37°C, 6hr) in the presence of increasing amounts of phosphatidylcholine (PC) vesicles, above a threshold concentration, results in an increase in particle diameter of LDL relative to that from nonincubated plasma. With further PC addition, the major peak of LDL in the gradient gel electrophoretic pattern is transformed, first, into a bimodal and, subsequently, into a single peak distribution. PC-induced interconversion of LDL requires factors(s) in the d > 1.20 g/ml fraction and, at PC concentrations below approximately 2 mg/ml, is not inhibited by p-chloromercuriphenylsulfonic acid. Plasma incubation with increasing PC levels also leads to characteristic particle size transformations in HDL3 species, with the transformation products ultimately converging to form a single peak pattern within the HDL2a size interval. In certain subjects, incubation of plasma, in the absence of added PC, shifts the particle size distribution of LDL towards smaller species; this can be prevented by addition of PC. We propose that incubation-induced shifts of LDL towards larger or smaller species result from changes in phospholipid (PL) content of LDL.
Manifestations of interference fluctuations of phase functions and backscattering cross sections for ice crystals with specific orientations

The ray-by-ray integration technique is applied to investigate the effect of the phase interference between rays on the scattering phase functions and backscattering cross sections of pristine hexagonal ice plates and columns with specific orientations. Numerical computations are carried out at 0.532 and 1.064 µm wavelengths. The results demonstrate that strong fluctuations of the phase function as a function of scattering angle are inherent for oriented particles. In addition, constructive fluctuation patterns are noted for particle backscattering cross sections, and are a function of particle size. These fluctuations, which are absent from the conventional ray-tracing computations, are caused by phase interference.
C5L2, a Nonsignaling C5A Binding Protein†

C5a anaphylatoxin, a potent inflammatory mediator, is known to act through a specific G protein coupled receptor. However, some of the complex effects of C5a in vivo may not be explained solely by the deletion of the known receptor. Here, we show that an orphan receptor, identified as C5L2, is a high affinity C5a binding protein. Unlike the previously described C5aR, C5L2 is obligately uncoupled from heterotrimeric G proteins, in part by virtue of an amino acid alteration in the so-called DRY sequence at the end of the third transmembrane segment. Both human and murine C5L2 bear a leucine for arginine replacement at this site. C5L2, when transfected into several cell types, is weakly phosphorylated in transfected cells following binding of C5a but does not induce significant activation of MAP kinases, mediate calcium flux, or stimulate chemotaxis. Bone marrow cells from wild type respond robustly to C5a with induction and suppression of a number of inflammation related genes. In contrast, C5a receptor deficient mice, which bear C5L2 alone, do not respond to C5a with changes in gene transcription by microarray analyses. Biophysical properties of the C5L2, including slow ligand on and off rates, absence of internalization, and relatively high affinity for the C5a des Arg metabolite, suggest that this receptor may serve to modulate C5a biological functions in vivo. Finally, in contrast to previous reports, we find absolutely no interaction of C5L2 with other anaphylatoxins C3a and C4a.
Adenine nucleotide pool size, adenine nucleotide translocase activity, and respiratory activity in newborn rabbit liver mitochondria

Abstract The adenine nucleotide content (ATP+ADP+AMP) of newborn rabbit liver mitochondria was 6.0±0.5 nmol/mg mitochondrial protein at birth, increased rapidly to 14.5±1.7 nmol/mg protein by 2 h postnatal, peaked at 6 h, then decreased gradually to 7.8±0.6 nmol/mg protein by 4 days postnatal. There was a strong positive correlation ( r =0.82) between the total adenine nucleotide pool size and adenine nucleotide translocase activity in these mitochondria. In contrast, glutamate + malate-supported State 3 respiratory rates remained constant from birth through the first week of life. State 4 rates also remained constant, as did the respiratory control index and uncoupled respiratory rates. The following conclusions are suggested: (1) The maximum rate of translocase activity is limited by the intramitochondrial adenine nucleotide pool size. (2) In newborn rabbit liver mitochondria, the State 3 respiratory rate is not limited by either the adenine pool size or the maximum capacity for translocase-mediated adenine exchange. (3) In contrast to rat, rabbit liver mitochondria are fully functional at birth with regard to respiratory rates and oxidative phosphorylation. (4) The rapid postnatal accumulation of adenine nucleotides by liver mitochondria, now documented in two species, may be a general characteristic of normal metabolic adjustment in neonatal mammals.
Innovative insulations for spacecraft on-surface monitoring system in harsh environments

In this paper, innovative multilayer insulation coatings are investigated to eliminate the environmental effects of spacecraft on-surface monitoring system in harsh environments and ultimately adjust the sensitivity the sensors towards the parameters needed to be sensed. The design of the composite insulation is guided through theoretical and numerical modeling analysis of heat transfer and thermal stress progressing. Detail theoretic, numerical, and experimental analysis proved the feasibility of the proposed multilayer structure of the insulation to work up to 700°C without inducing significant deformation on the top of sensor surface from heat.
Evolution of uranium dioxide structure during irradiation of fuel rods

The characteristic microstructure of UO2 observed in irradiated fuel rods is interpreted as resulting from a particular sequence of events. These are: initial melting of the central region; rapid columnar grain formation adjacent to the molten region; subsequent solidification of the core; and upon long exposure, slow continued columnar grain formation. Quantitative analyses of four irradiation test capsules reveal that the observed structure is consistent with this hypothesis.
Phototherapy for neonatal jaundice: Optimal wavelengths of light*

Phototherapy results in transformation of bilirubin to more water-soluble isomers. The efficacy of monochromatic visible light from 350 to 550 mm in the fastest photoisomerization reaction was quantitated by high-pressure liquid chromatography. The most effective wavelengths in vitro (i.e., leading to >25% photoisomer) were in the blue spectrum from ∼390 to 470 nm. Green light (530 nm) was not only ineffective for production of photoisomer, but capable of reversing the reaction. The results indicate that any clinically useful phototherapy unit must include the blue portion of the visible spectrum, and suggest that the effectiveness of phototherapy may be increased by elimination of green light.
Extracellular vesicles as a platform for ‘liquid biopsy’ in glioblastoma patients

Extracellular vesicles (EVs) are cell-secreted vesicles that range from 30-2000 nm in size. These vesicles are secreted by both normal and neoplastic cells. Physiologically, EVs serve multiple critical biologic functions, including cellular remodeling, intracellular communication, modulation of the tumor microenvironment and regulation of immune function. Because EVs contain genetic and proteomic contents that reflect the cell of origin, it is possible to detect tumor-specific material in EVs secreted by cancer cells. Importantly, EVs secreted by cancer cells transgress anatomic compartments and can be detected in the blood, cerebrospinal fluid, and other biofluids of cancer patients. In this context, there is a growing interest in analyzing EVs from the biofluid of cancer patients as a means of disease diagnosis and therapeutic monitoring. In this article, we review the development of EVs as a diagnostic platform for the most common form of brain cancer, glioblastoma, discuss potential clinical translational opportunities and identify the central challenges associated with future clinical applications.
Application of a new structural theory to polymers. ii. transition states for amorphous polymers and copolymers

Abstract A recently developed nonequilibrium thermodynamic theory of continuum rheology is combined with a generalized definition of thermomechanical transitions, to produce a single equation for interrelating the basic variables (stress o, strain rate ∊, pressure p, temperature T, and structure ) at a transition. Specialization of  to represent uncrosslinked polymers leads to incorporation of molecular weight M as a variable. New predictions are thus made for the glass transition [Tg(M), Tg(p), Tg(∊) and others] and compared successfully with data. Particularly remarkable are the results that 1/Tg is a piecewise linear function of In M, and T is piecewise linear with p. Comparable results and confirmation with data arise when applying the theory to the liquid-liquid transition, T ll (M). For random copolymers, application of a single mixing rule to the transition equation leads to a prediction of Tg as a function of composition and the Tgi for the homopolymers (components i). This relationship reduces,...
Resmethrin and Permethrin Sprays to Reduce Annoyance from a Deer Fly, Chrysops atlanticus

Resmethrin and permethrin were applied to reduce annoyance from Chrysops atlanticus Pechuman in agricultural areas of southern New Jersey. Resmethrin was applied at rates of 0.015 to 0.112 kg/ha by mist blower. Spray was directed from the edge of the fields into the vegetative wooded barrier between cultivated fields and the salt marsh. At the aforementioned rates, deer fly annoyance (except in 1 application) was reduced by more than 95% 1 h posttreatment, by 27–97% after 8 h, and by 0–96.% after 24 h. Resmethrin in 2 applications by ULV and 2 applications with low volume mist blower at 0.0078 and 0.041 kg/ha, respectively, also was effective. Permethrin in limited tests similarly reduced annoyance.
Social Learning Interventions in a Developmental Disabilities Partial Hospital Program

Social learning interventions have been widely applied to the treatment of psychiatric symptoms. However, treatments for individuals with developmental disabilities and coexisting mental illness have routinely emphasized reinforcement-based contingency strategies rather than cognitive approaches. The slower rate of integrating cognitive strategies may be due to several factors including adherence to widely accepted behavior modification models, failure to acknowledge the coexistence of mental illness with mental retardation, and the difficulty of adapting social learning strategies for the developmentally delayed. Treatment outcomes following the application of social learning interventions were observed in a psychiatric partial hospital program for persons with developmental disabilities and mental illness. Three cases are presented to illustrate the application of social learning interventions and highlight specific adaptations of treatment strategies to the cognitive functioning level and developmental...
Na+-K+ ATPase distribution in frog and bovine lenses

Na+-K+ ATPase activity was measured in the capsule-epithelium and decapsulated frog and bovine lens. The decapsulated lens contained approximately 20% of the whole lens activity in the frog and 30% in the bovine. These values were measured from the aqueous homogenate of the entire decapsulated lens, an approach which may have underestimated the activity by diluting the ouabain-sensitive component in the preparation. Subsequent determinations were done on separate portions of superficial (2 to 3 mm) anterior-equatorial, and posterior bovine cortex. The activities per gram of tissue were enriched with respect to the values for the entire decapsulated bovine lens. These activities were further enriched by a sucrose density gradient centrifugation. The anterior-equatorial cortical segment contained 1.6 times the activity found in the capsule-epithelium. The posterior cortex had a much smaller but statistically significant level of Na+-K+ ATPase. It is unlikely that the observed asymmetry of the anterior-equat...
Acute Elbow Dislocations in Athletes

Elbow dislocation in the athletic population is not an uncommon injury. The literature does not clearly establish treatment guidelines, with treatment being extrapolated from the experience in the general population. A short period of immobilization with early range of motion exercises limits disability and allows return to sports participation within 6 weeks.
Opioid inhibition of Ih via adenylyl cyclase

Abstract Opioids are coupled through G proteins to both ion channels and adenylyl cyclase. This study describes opioid modulation of the voltage-dependent cation channel, I h , in cultured guinea pig nodose ganglion neurons. Forskolin, PGE 2 , and cAMP analogs shifted the voltage dependence of activation of I h to more depolarized potentials and increased the inward current at −60 mV. Opioids had no effect on In alone, but reversed the effect of forskolin on I h . This action of opioids was blocked by naloxone. Opioids had no effect on In in the presence of CAMP analogs, suggesting that modulation occurs at the level of adenylyl cyclase. The shift in the voltage dependence of I h by agents that induce inflammation (i.e., PGE 2 ), is one potential mechanism to mediate an increased excitability. Opioid inhibition of adenylyl cyclase and subsequent inhibition of In may be a mechanism by which opioids inhibit primary afferent excitability and relieve pain.
Imaging Ejecta and Debris Cloud Behavior Using Laser Side-lighting

Abstract The Caltech Small Particle Hypervelocity Impact Range (SPHIR Facility) utilizes a two-stage, light gas gun to accelerate Nylon 6/6 right cylinders (d = 1.8 mm, L/D=1, 5.5 mg) and spheres (d = 1.8 mm, 3.6 mg) to impact speeds of 5 km/s and above. The projectiles impact aluminum 6061-T6 plate targets. An optical technique was employed to produce images of the hypervelocity impact event with short exposure times (20 ns) and short inter-frame times (
Assessment of calcium sparks in intact skeletal muscle fibers.

Maintaining homeostatic Ca2+ signaling is a fundamental physiological process in living cells. Ca2+ sparks are the elementary units of Ca2+ signaling in the striated muscle fibers that appear as highly localized Ca2+ release events mediated by ryanodine receptor (RyR) Ca2+ release channels on the sarcoplasmic reticulum (SR) membrane. Proper assessment of muscle Ca2+ sparks could provide information on the intracellular Ca2+ handling properties of healthy and diseased striated muscles. Although Ca2+ sparks events are commonly seen in resting cardiomyocytes, they are rarely observed in resting skeletal muscle fibers; thus there is a need for methods to generate and analyze sparks in skeletal muscle fibers. Detailed here is an experimental protocol for measuring Ca2+ sparks in isolated flexor digitorm brevis (FDB) muscle fibers using fluorescent Ca2+ indictors and laser scanning confocal microscopy. In this approach, isolated FDB fibers are exposed to transient hypoosmotic stress followed by a return to isotonic physiological solution. Under these conditions, a robust Ca2+ sparks response is detected adjacent to the sarcolemmal membrane in young healthy FDB muscle fibers. Altered Ca2+ sparks response is detected in dystrophic or aged skeletal muscle fibers. This approach has recently demonstrated that membrane-delimited signaling involving cross-talk between inositol (1,4,5)-triphosphate receptor (IP3R) and RyR contributes to Ca2+ spark activation in skeletal muscle. In summary, our studies using osmotic stress induced Ca2+ sparks showed that this intracellular response reflects a muscle signaling mechanism in physiology and aging/disease states, including mouse models of muscle dystrophy (mdx mice) or amyotrophic lateral sclerosis (ALS model).
Vertebral Artery Blood flow Velocity Changes Associated with Cervical Spine rotation: A Meta-Analysis of the Evidence with implications for Professional Practice

Many studies of vertebral artery (VA) blood flow changes related to cervical spine rotation have been published, but the findings are controversial and the evidence unconvincing. Recent Doppler measurements suggest that contralateral VA blood flow is compromised on full rotation in both healthy subjects and patients. More rigorous research is needed, and it was the aim of this study to conduct a meta-analysis of published data to inform professional practice. A systematic literature search, including only Doppler studies of VA blood flow velocity associated with cervical spine rotation in adults, yielded nine reports with published data. Using weighted means of the pooled data, the magnitude of the effect size (Cohen's d) was calculated for differences between patients and subjects, sitting or lying supine for testing, the parts of the VA insonated, and the changes recorded after cervical spine rotation. From this meta-analysis, VA blood flow velocity was found to be compromised more in patients than healthy individuals, on contralateral rotation, with the subject sitting, and more in the intracranial compared to the cervical part of the VA. Possible reasons for these findings are suggested, and it is advised that sustained end-of-range rotation and quick-thrust rotational manipulations be avoided until there is a stronger evidence base for clinical practice.
Preparation of II-VI Quantum Dot Composites by Electrospray Omcvd

A novel technique combining electrospray and organometallic chemical vapor deposition (OMCVD) has been developed for synthesis of VI-II quantum dot composites. CdSe nanocrystallites dispersed in a mixture of pyridine and acetonitrile were electrosprayed into the gas-phase in the growth zone of an OMCVD reactor and then incorporated into a ZnSe matrix grown by OMCVD. Hydrogen selenide and diethylzinc were used to deposit the ZnSe matrix at temperatures of 150 - 240°C. The ZnSe/CdSe quantum dot composites were characterized by visible absorption spectroscopy, room temperature photoluminescence and Auger electron spectroscopy. The optical properties of the composites are determined by the size of the original CdSe nanocrystallites.
Is It Possible to Manage Hypertension and Evaluate Therapy Without Ambulatory Blood Pressure Monitoring

In the management of patients with hypertension, blood pressure (BP) has been traditionally measured in the physician’s office. The contribution of ambulatory BP monitoring (ABPM) to the management of hypertensive patients has been increasingly recognized through clinical and epidemiological research. Ambulatory BP monitoring can enhance the ability to detect white-coat or masked hypertension, determine the absence of nocturnal dipping status, and evaluate BP control in patients on antihypertensive therapy. Recently, the United Kingdom National Clinical Guideline Centre published guidelines for the clinical management of primary hypertension in adults, recommending the routine use of ABPM to make the initial diagnosis of hypertension. While the advantages of ABPM are apparent from a clinical perspective, its use should be considered in relation to the cost of the equipment, data evaluation, and staff training as well as the possible inconvenience to the patient. In this review, we summarize the clinical importance of ABPM and discuss the current guidelines for establishing the diagnosis of hypertension.
Religious coping and caregiver well-being in Mexican-American families

Objective: We sought to explore the association of religious and spiritual coping with multiple measures of well-being in Latinos caring for older relatives with long-term or permanent disability, either with or without dementia. Methods: Using a multi-dimensional survey instrument, we conducted in-home interviews with 66 predominantly Mexican-American Catholic family caregivers near the US–Mexico border. We assessed caregivers’ intrinsic, organizational and non-organizational religiosity with the Duke Religiosity Index, as well as Pargament's brief positive and negative spiritual coping scale to determine the association of religiosity with caregivers’ mental and physical health, depressive symptomatology and perceived burden. Results: Using regression analysis, we controlled for sociocultural factors (e.g. familism, acculturation), other forms of formal and informal support, care recipients’ functional status and characteristics of the caregiving dyad. Intrinsic and organizational religiosity was associ...
The role of reversibility in the enantioselective conjugate addition of α,α-disubstituted aldehydes to nitro-olefins catalyzed by primary amine thioureas

Kinetic and spectroscopic studies probing the conjugate addition of 2-phenylpropanal to nitro-olefins catalyzed by two different primary amine thiourea catalysts reveal the nature of the catalyst resting state and demonstrate that reversibility of the reaction is implicated in cases of low enantio- and diastereoselectivity.
Africa, Asia, Europe and Latin America

Bibliographie des rapports officiels publies par les etats d'Afrique, d'Asie, d'Europe et d'Amerique Latine, de juin 1986 a juin 1987
Influence of dobutamine or exercise stress on the results of pulsed-wave Doppler assessment of myocardial velocity.

Background Pulsed-wave Doppler assessment of myocardial velocity (MDV) may permit a more quantitative interpretation of stress echocardiography. This technique has been used with dobutamine echo (DbE), but exercise echo (ExE) may be preferred in patients who are able to exercise maximally. The influence of these stressors on the results of MDV are undefined. Purpose This study sought to determine whether differences between the physiology of DbE and ExE could influence the MDV responses to stress and whether interpretative criteria should be different with exercise or dobutamine stress. Methods DbE or ExE was performed in 105 patients tested for known or suspected coronary artery disease. Pulsed-wave MDV was obtained in basal segments of anteroseptal, septal, anterior, posterior, lateral, and inferior walls in the apical views at rest and at peak doses of dobutamine or immediately after exercise. Segments were classified as normal or abnormal (ischemia or scar) according to results of 2-dimensional echocardiography, and MDV obtained at rest and stress was compared by using analysis of variance. Results Resting heart rate was similar before both dobutamine and exercise, but heart rate at peak dobutamine exceeded that after exercise (137 +/- 10 vs 115 +/- 22, P < .01). For both ExE and DbE, MDV was significantly greater at rest and stress in normal than in abnormal segments. Stress MDV in both normal and abnormal segments was greater with DbE than with ExE (17.0 +/- 4.8 cm/s vs 10.3 +/- 3.4 cm/s, P < .001 for normal segments and 10.7 +/- 4.4 cm/s vs 7.9 +/- 3.3 cm/s, P < .001 for abnormal segments, Increase in MDV/Delta heart rate induced by DbE was greater than by ExE in normal (0.14 +/- 0.07 cm/s . beat for DbE and 0.09 +/- 0.08 cm/s . beat for ExE; P < .05) but similar in abnormal segments (0.06 +/- 0.07 cm/s . beat for DbE and 0.05 +/- 0.09 cm/s . beat for ExE). MDV correlated better with peak heart rate at ExE (r = 0.56, P < .01) than at DbE (r = 0.28, P < .01). Conclusions MDV responses to exercise and pharmacologic stress appear to be different, reflecting differences in inotropy, loading, and the timing of imaging. These findings may influence the ability of MDV to differentiate normal from abnormal stress echocardiography responses.
A study on the scheduling problem of goods pictures in an online store

An integer programming model is given to deal with the problem that an online store wants to arrange the display time of goods pictures within the given scheduling horizon and space in order to maximize its profits. In this model, two characters that goods pictures have effect on demands and there are no inventories in many online stores are considered. It is explained that the problem discussed is equivalent to a special multiple-choice knapsack problem, so a dynamic programming algorithm with a complexity of pseudo polynomial time is provided; the properties of the objective function are studied, a greedy-like heuristic algorithm based on them with a complexity of polynomial time is proposed, and an example is given to demonstrate that the greedy-like heuristic method is effective.
Pharmacokinetics and metabolism of darifenacin in the mouse, rat, dog and man

1. Followingintravenousadministrationto animals at 2 5 mg kg, darifenacinexhibited terminal plasma half-lifes < 2 h due to high plasma clearance (with respect to blood flow) and volumes of distribu...
The disinfectant dilemma revisited.

INTRODUCTION Medical instruments that come in contact with patients' blood and body fluids during invasive procedures should be sterilized after use. Some instruments, however, are too delicate to tolerate autoclave temperatures, even the lower temperature required by ethylene oxide sterilization. Chemical sterilants are an acceptable alternative but present a different problem because they require prolonged soaking time from six and three-quarters to ten hours. This long exposure to liquids may adversely affect the components of some instruments. Therefore, the manufacturer should always be consulted when prolonged soaking is contemplated. Another disadvantage to prolonged sterilization cycles is the increased number of instruments that may be required to compensate for the lag in availability. As an acceptable alternative, the Centers for Disease Control (CDC) and others have divided instruments into three categories:1-3 instruments that enter normally sterile tissue and the vascular system (these must be sterilized); instruments that contact nonintact skin and mucous membranes (these should receive high-level disinfection); and items that contact only intact skin such as blood pressure cuffs (these require a lower level of disinfection and will not be discussed here). Importantly, it should be noted that the Environmental Protection Agency (EPA), which registers chemical disinfectants/sterilants, does not recognize these categorizations. They register solutions for sterilization or disinfection. As described previously, EPA-registered chemical disinfectants were used widely and without misgivings as to their efficacy until 1984.4 At that time, Surgikos, the manufacturer of a glutaraldehydebased product, changed its instructions for the disinfection of instruments contaminated with tubercle bacilli from ten minutes to 45 minutes, and most importantly, introduced a temperature requirement of 25'C (771F).5 Surgikos claimed that tuberculocidal (TB) efficacy could not be confirmed by the standard test developed by the Association of Official Analytical Chemists (AOAC). A previous article by Rutala and Cole also described the inability to reproduce manufacturers' bactericidal claims for six disinfectants tested against three other AOAC test bacteria. Three of four laboratories failed their own products in this blind test.6 At a national symposium in Washington, DC in 1987, it became apparent that the only point of agreement between the scientific community, the AOAC, the CDC and some manufacturers was that the gold standard for testing the efficacy of disinfectants, the AOAC test, was tarnished and that a new test was needed. There was, however, no agreement about the type of test that would be reliable and reproducible. To this day there is no such universally accepted test.
A trivariate box macroelement

Given a rectangular box which has been split into 24 tetrahedra, we show how to construct a C1 macroelement using polynomial pieces of degree 6.
An athymic rat model of cutaneous radiation injury designed to study human tissue-based wound therapy

To describe a pilot study for a novel preclinical model used to test human tissue-based therapies in the setting of cutaneous radiation injury. A protocol was designed to irradiate the skin of athymic rats while sparing the body and internal organs by utilizing a non-occlusive skin clamp along with an x-ray image guided stereotactic irradiator. Each rat was irradiated both on the right and the left flank with a circular field at a 20 cm source-to-surface distance (SSD). Single fractions of 30.4 Gy, 41.5 Gy, 52.6 Gy, 65.5 Gy, and 76.5 Gy were applied in a dose-finding trial. Eight additional wounds were created using the 41.5 Gy dose level. Each wound was photographed and the percentage of the irradiated area ulcerated at given time points was analyzed using ImageJ software. No systemic or lethal sequelae occurred in any animals, and all irradiated skin areas in the multi-dose trial underwent ulceration. Greater than 60% of skin within each irradiated zone underwent ulceration within ten days, with peak ulceration ranging from 62.1% to 79.8%. Peak ulceration showed a weak correlation with radiation dose (r = 0.664). Mean ulceration rate over the study period is more closely correlated to dose (r = 0.753). With the highest dose excluded due to contraction-related distortions, correlation between dose and average ulceration showed a stronger relationship (r = 0.895). Eight additional wounds created using 41.5 Gy all reached peak ulceration above 50%, with all healing significantly but incompletely by the 65-day endpoint. We developed a functional preclinical model which is currently used to evaluate human tissue-based therapies in the setting of cutaneous radiation injury. Similar models may be widely applicable and useful the development of novel therapies which may improve radiotherapy management over a broad clinical spectrum.
Technologies for wireless computing

Introduction A.P. Chandrakasan, R.W. Brodersen. Hardware-Software Architecture of the SWAN Wireless ATM Network P. Agrawal, et al. An Integrated Testbed for Wireless Multimedia Computing C. Chien, et al. Design of a Low Power Video Decompression Chip Set for Portable Applications B.M. Gordon, et al. IC Implementation Challenges of a 2.4 GHz Wireless LAN Chipset M. Chian, et al. Flat Panel Displays for Portable Systems K.R. Sarma, T. Akinwande. Threshold-Voltage Control Schemes through Substrate-Bias for Low-Power High-Speed CMOS LSI Design T. Kuroda, T. Sakurai. Processor Design for Portable Systems T.D. Burd, R.W. Brodersen. Instruction Level Power Analysis and Optimization of Software V. Tiwari, et al. Low-Power Architectural Synthesis and the Impact of Exploiting Locality R. Mehra, et al. Techniques for Power Estimation and Optimization at the Logic Level: A Survey J. Monteiro, S. Devadas.
Capturing Articulation in Assemblies from Component Geometry

This paper presents a method to extract instantaneous articulation from part geometry, based on surface mating constraints as well as constraints imposed by other incidental contacts. Many assemblies contain joints, each of which have degrees of freedom associated with them. These joints allow the relative positions of parts in the mechanism to change as the joints are articulated. Being able to represent these joints and their behavior is important from the designers perspective because it enables him or her to verify whether kinematic requirements have been met.Therefore, it is useful to be able to obtain such joint information directly from part geometry and contact physics. The method presented here handles all lower pairs of kinematic joints. Surface mating contacts are classied into one of three types: planar, spherical and cylindrical. The contacts are represented by algebraic inequalities describing the translational and angular velocities at the contact. Non-penetration conditions are written for a nite set of points on the boundary of each contact face, and it is shown that the nite set of conditions is representative of the entire boundary and the region enclosed by the boundary. Simultaneous satisfaction of the non-penetration conditions at all the contact surfaces between a pair of bodies is represented by a 6-dimensional simplex, which can be solved using linear programming.
Solution of the generalized eigenvalue equation perturbed by a generalized low rank perturbation

The problem of finding eigenvalues and eigenstates of the generalized perturbed eigenvalue equation \(\left( {\mathbb{B} + \mathbb{V}} \right)\)Ψ = g3(ℂ+ℙ)Ψ is considered. The eigenvalues and the eigenstates of the unperturbed eigenvalue equation \(\mathbb{B}\)φ = λℂφ are assumed to be known. Matrices \(\mathbb{B},\mathbb{V}\), ℂ and ℙ can be arbitrary, except for the requirement that ℂ be nonsingular and that the eigenstates of the unperturbed equation be complete. It is shown that the eigenvalues and the eigenstates of the perturbed equation can be easily obtained if the rank of the generalized perturbation \(\left\{ {\mathbb{V},\mathbb{P}} \right\}\), ℙ is small. A special case of low rank perturbations are piecewise local perturbations which are common in physics and chemistry. If the perturbation is piecewise local with fixed localizability, the operation count for the derivation of a single eigenvalue and/or a single eigenstate is \(\mathcal{O}\)(n). If the perturbation has a fixed rank, the operation count for the derivation of all eigenvalues and/or all eigenstates is \(\mathcal{O}\)(n2).
Optimal vitamin D status attenuates the age-associated increase in systolic blood pressure in white Americans: results from the third National Health and Nutrition Examination Survey

Background: The prevalences of both hypertension and vitamin D insufficiency are high in the United States. Recent clinical trials and animal studies have suggested that vitamin D insufficiency may be associated with elevated blood pressure. Objective: With cross-sectional data, we sought to determine whether vitamin D concentrations were related to systolic blood pressure (SBP) in the third National Health and Nutrition Examination Survey (1988–1992). Design: Blood pressure was classified with 5 categories from the Joint National Committee 7 with a sixth category added to distinguish participants with normotensive SBP (110 mm Hg) from those with high-normal SBP (110–119 mm Hg). We used predicted marginalstoestimatetheconditionalmeansofserum25hydroxyvitamin D [25(OH)D] and to test for trend across blood pressure categories. We used linear regression to explore the association between vitamin D, blood pressure, and age. Results: Lower 25(OH)D concentrations were associated with a higher blood pressure category in whites (P 0.001); however, when controlling for age, the association was no longer significant. Concentrations of 25(OH)D80 nmol/L decreased the age-related increase in SBP by 20% compared with participants having 25(OH)D concentrations 50 nmol/L (P 0.001). Only 8% of blacks had 25(OH)D concentrations 80 nmol/L. Conclusions: SBP is inversely associated with serum vitamin D concentrations in nonhypertensive white persons in the United States. This observation provides a rationale for studies on the potential effects of vitamin D supplementation as a method to reduce SBPinpersonsatriskofhypertension. AmJClinNutr2008;87: 136–41.
Intraspecific variation in production of astringent phenolics over a vegetation-resource availability gradient

The chemical constituency of flowering dogwood (Cornus florida L.) and red maple (Acer rubrum L.) foliage was analyzed over a species compositional gradient to test the hypothesis that over subtle gradients of moisture and nutrient availability production of phenolic compounds will be increased on sites of greatest stress. Calcium and nitrogen concentrations declined along the gradient in both species, while phosphorus showed a significant decline only in red maple. Lignin concentrations in both species were unrelated to the vegetation gradient, but astringent phenolics increased by 156% and 159% in dogwood and red maple, respectively. The correlation between production of polyphenolds and site quality supports previous observations that under conditions of environmental stress production of many secondary compounds is increased, and suggests that this relationship is significant over subtle environmental gradients.
Model Diffuse Attenuation Coefficient Profiles

Abstract : Light transport through water is controlled by the properties of dissolved substances, particulate matter, and water itself. The rate at which the light field decays can be measured by optical instrumentation and parameterized by the apparent optical property of the water, the diffuse attenuation coefficient, k. The diffuse attenuation coefficient is known to vary with depth near the surface. However, as the light field penetrates to greater depths, the value of k approaches an asymptotic value which can be treated as a quasi- inherent property of the water mass. Generally, the actual depth at which k approaches an asymptotic value is the bottom of the euphotic zone (1% level) for all but the clearest waters. The primary optical parameter of interest in this study is the downwelling diffuse attenuation coefficient, k sub d, which we will designate simply as 'k'. The objective of this work is to develop methods or algorithms for computing vertical, or depth, profiles of k given a surface k value. Lasers, Models, Optics, Surveillance.
Prospective memory deficits are associated with poorer everyday functioning in Parkinson's disease

Although individuals with Parkinson's disease (PD) evidence moderate deficits in prospective memory (PM), it is not known whether PM deficits confer an increased risk of poorer everyday functioning. In the current study, 33 individuals with PD and 26 demographically similar normal controls (NC) were administered performance-based and self-report measures of PM and everyday functioning, including medication and financial management. As compared to NC, PD participants demonstrated significantly lower scores on performance-based measures of PM and financial capacity, worse performance at a trend level on performance-based medication management and endorsed significantly greater self-reported declines in PM and instrumental activities of daily living (iADLs). In the PD sample, the laboratory measure of PM significantly correlated with performance-based measures of financial capacity and medication management and a self-report measure of medication management. Self-reported PM failures significantly correlated with perceived declines in iADLs, worse medication management, and poorer health-related quality of life. Although future studies are needed to examine the incremental ecological validity of PM in PD, findings from this study extend prior research by providing preliminary evidence that PM impairment may play a significant role in a range of critical everyday functions in PD.
Rate Limits of On-Beat and Off-Beat Tapping With Simple Auditory Rhythms: 1. Qualitative Observations

The accuracy of on-beat and off-beat synchronized finger tapping was examined as a function of sequence rate in musically trained individuals. Auditory sequences consisted of cyclically repeated, underlyingly isochronous patterns of the form T0, TT0, or TTT0, where T denotes a tone onset and 0 denotes its absence. In different conditions, participants attempted to tap in synchrony with one of the possible T (“onbeat”) or 0 (“off-beat”) positions in each pattern while the sequence rate increased from trial to trial. It was hypothesized that on-beat tapping would be easier with tones that carry a rhythmic grouping accent (T 2 in TT0, T 1 and T 3 in TTT0) than with tones that do not (T 1 in TT0, T 2 in TTT0), according to findings of Povel and colleagues. The hypothesis was strongly supported for TTT0, but there were considerable individual differences with regard to TT0. Off-beat tapping was generally difficult and often switched to on-beat tapping at fast tempi. The findings reveal rate limits of sensorimotor coordination that may be relevant to music performance in ensembles.
Targeted expression of the dominant-negative FGFR4a in the eye using Xrx1A regulatory sequences interferes with normal retinal development

Molecular analysis of vertebrate eye development has been hampered by the availability of sequences that can selectively direct gene expression in the developing eye. We report the characterization of the regulatory sequences of the Xenopus laevis Rx1A gene that can direct gene expression in the retinal progenitor cells. We have used these sequences to investigate the role of Fibroblast Growth Factor (FGF) signaling in the development of retinal cell types. FGFs are signaling molecules that are crucial for correct patterning of the embryo and that play important roles in the development of several embryonic tissues. FGFs and their receptors are expressed in the developing retina, and FGF receptor-mediated signaling has been implicated to have a role in the specification and survival of retinal cell types. We investigated the role of FGF signaling mediated by FGF receptor 4a in the development of retinal cell types in Xenopus laevis. For this purpose, we have made transgenic Xenopus tadpoles in which the dominant-negative FGFR4a (ΔFGFR4a) coding region was linked to the newly characterized regulatory sequences of the Xrx1A gene. We found that the expression ofΔ FGFR4a in retinal progenitor cells results in abnormal retinal development. The retinas of transgenic animals expressing ΔFGFR4a show disorganized cell layering and specifically lack photoreceptor cells. These experiments show that FGFR4a-mediated FGF signaling is necessary for the correct specification of retinal cell types. Furthermore, they demonstrate that constructs using Xrx1A regulatory sequences are excellent tools with which to study the developmental processes involved in retinal formation.
Quantifying validation of discrete event simulation models

Simulation model validation and its rigorous assessment is known to be a difficult task. Quantification of validation is necessary to answer the question "how much validation is adequate?" One can answer this question by developing adequacy criteria to measure the validation performed on a simulation model. Developing test adequacy criteria for verifying computer programs has been useful for improving the quality and increasing confidence of regular software systems. We argue that from the validation and verification (V&V) perspective, simulation models are no different than software that are generally termed as "non-testable" due to the absence of a test oracle. There has been little research to develop V&V related adequacy criteria for this type of software. We present a validation coverage criterion, show in detail how it applies to discrete-event simulation models (DES), and discuss how it can be extended to develop V&V coverage criteria for other "non-testable" software.
Patterns of Failure after Trimodality Therapy for Pancreatic and Duodenal Cancers

Materials/Methods:We reviewed the records of patientswho underwent pancreaticoduodenectomyand chemoradiation for pancreatic and duodenal cancers at the Hospital of the University of Pennsylvania between 1982 and 2006. A total of 116 patients had data available to evaluate for patterns of failure. Time was calculated from the date of surgery to first documented failure, death without failure, or last contact without failure. A cumulative incidence analysis was performed to estimate failure rates by site of first failure.