cssi/SciSciGPT-SciSciNet huggingface dataset:
Advantages of the lipoprotein-associated phospholipase A2 activity assay.

Abstract Objectives: Lipoprotein-associated phospholipase A2 (Lp-PLA 2 ) is increased in circulation in patients at higher risk of coronary heart disease (CHD) events and stroke. Therefore, measurement of Lp-PLA 2 can be used as an adjunct to traditional cardiovascular risk factors for identifying individuals at higher risk of cardiovascular events. Recently, a reagent for measuring Lp-PLA 2 activity (diaDexus, San Francisco, CA) received FDA approval. Here we evaluate the assay performance of the Lp-PLA 2 activity assay. Methods: Lp-PLA 2 activity assay reagent performance was evaluated on an open user-defined channel on a Cobas 6000/c501 (Roche Diagnostics, Indianapolis, IN) using a 5-point calibration curve (0–400 nmol/min/mL). Analytical performance was established for the following parameters: precision, linearity, accuracy, analytical sensitivity, analytical specificity, reference interval, reagent lot-to-lot comparison, specimen type, on-board reagent stability, and sample stability. Results: Assay limit of detection was determined to be 7.8 nmol/min/mL with an average %CV of 2.8%. Precision studies revealed a coefficient of variation ≤ 1.6% between 79 and 307 nmol/min/mL and accuracy was demonstrated between 4.8–368.7 nmol/min/mL. Comparable results were generated in paired SST serum and EDTA plasma. No age association was found with Lp-PLA 2 activity at the 95th percentile however a gender association was identified resulting in gender-specific 95th percentile limits in a healthy reference population. No bias was found when comparing results from several different lots of assay reagent. Lp-PLA 2 activity results are extremely stable in both serum and EDTA plasma under refrigerate and frozen storage conditions up to 31 days. Conclusions: Lp-PLA 2 activity assay displays accurate and precise performance characteristics on the Cobas c501 platform. The assay performance is significantly improved over the predecessor immunoassay allowing for adoption of Lp-PLA 2 activity in clinical practice.
Subpicomolar Diphenyleneiodonium Inhibits Microglial NADPH Oxidase with High Specificity and Shows Great Potential as a Therapeutic Agent for Neurodegenerative Diseases

Activation of microglial NADPH oxidase (NOX2) plays a critical role in mediating neuroinflammation, which is closely linked with the pathogenesis of a variety of neurodegenerative diseases, including Parkinson's disease (PD). The inhibition of NOX2-generated superoxide has become an effective strategy for developing disease-modifying therapies for PD. However, the lack of specific and potent NOX2 inhibitors has hampered the progress of this approach. Diphenyleneiodonium (DPI) is a widely used, long-acting NOX2 inhibitor. However, due to its non-specificity for NOX2 and high cytotoxicity at standard doses (µM), DPI has been precluded from human studies. In this study, using ultra-low doses of DPI, we aimed to: (1) investigate whether these problems could be circumvented and (2) determine whether ultra-low doses of DPI were able to preserve its utility as a potent NOX2 inhibitor. We found that DPI at subpicomolar concentrations (10−14 and 10−13 M) displays no toxicity in primary midbrain neuron-glia cultures. More importantly, we observed that subpicomolar DPI inhibited phorbol myristate acetate (PMA)-induced activation of NOX2. The same concentrations of DPI did not inhibit the activities of a series of flavoprotein-containing enzymes. Furthermore, potent neuroprotective efficacy was demonstrated in a post-treatment study. When subpicomolar DPI was added to neuron-glia cultures pretreated with lipopolysaccharide, 1-methyl-4-phenylpyridinium or rotenone, it potently protected the dopaminergic neurons. In summary, DPI's unique combination of high specificity toward NOX2, low cytotoxicity and potent neuroprotective efficacy in post-treatment regimens suggests that subpicomolar DPI may be an ideal candidate for further animal studies and potential clinical trials. GLIA 2014;62:2034–2043
In vivo electron paramagnetic resonance imaging of differential tumor targeting using cis‐3,4‐di(acetoxymethoxycarbonyl)‐2,2,5,5‐tetramethyl‐1‐pyrrolidinyloxyl

Purpose EPR spectroscopy promises quantitative images of important physiologic markers of animal tumors and normal tissues, such as pO2, pH, and thiol redox status. These parameters of tissue function are conveniently reported by tailored nitroxides. For defining tumor physiology, it is vital that nitroxides are selectively localized in tumors relative to normal tissue. Furthermore, these paramagnetic species should be specifically taken up by cells of the tumor, thereby reporting on both the site of tumor formation and the physiological status of the tissue. This study investigates the tumor localization of the novel nitroxide, cis-3,4-di(acetoxymethoxycarbonyl)-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl 3 relative to the corresponding di-acid 4.
Candidacidal activity of myeloperoxidase: characterization of myeloperoxidase-yeast complex formation.

Abstract We have previously demonstrated the ability of human neutrophil myeloperoxidase to bind to cell wall mannan polysaccharide isolated from Candida albicans . This binding capacity provides for association of the enzyme with target yeast which is essential for efficient candidacidal activity. In this report, we further consider the role of the mannan-binding property of myeloperoxidase in the candidacidal activity of the enzyme. Solubilized mannan antagonizes binding of the enzyme to yeast, suggesting that mannan may be a primary component of the fungal cell wall which serves as a target for binding of myeloperoxidase. Myeloperoxidase is shown to form complexes with both solubilized mannan and Candida yeast, with Kds of 0.97 × 10−5 M and 1.2 × 10−5 M, respectively. The interaction between myeloperoxidase and mannan does not allow the enzyme to readily dissociate from the surface of target yeast. As a result, the enzyme may be unable to dissociate from dead yeast to become available for binding to additional fungal targets.
Clinical and Laboratory Investigations of some of the Newer Sex Hormone Preparations.

AFTER the biological chemists had determined the structure of natural estrogens,androgens and progesterone, their efforts were directed, with surprising JL JJL. success, to synthesizing these hormones as well as to the development and investigation of chemical compounds of stronger potency, particularly those absorbed through the intestinal tract. In addition, numerous laboratories have been busy in attempts to purify the gonadotropic factors whose chemical structure is still unknown, and if possible, to separate the follicle stimulating from the luteinizing factors as well as to determine whether or not these reactions are due to separate and distinct entities. We have been engaged in studying the clinical effect of some of these compounds, with control of the changes in hormone excretions resulting from such therapy. Stilbestrol is a synthetic substancewhich has strong estrogenic action. It has but a faint structural resemblance to the natural estrogens. Synthesized and prepared by Dodds and his group (...
Shifting the Blame: Racial Ideology and Politics in the Post-Civil Rights Era

In the post-civil rights era, critics on the right have indicted liberal social policies for exacerbating the very problems of racism and poverty they purport to alleviate. In vastly distinct ways,...
Simultaneous analysis of multiple fluorescent probes in single cells by microspectroscopic imaging

Simultaneous Analysis of Multiple Fluorescent Probes in SingleCells by Microspectroscopic Imaging.Raul Martinez—Zaguilan, Linda S. Tompkins and Ronald M. LynchDepartments of Biochemistry, Physiology and PharmacologyUniversity of Arizona, Health Sciences Center, Tucson, AZ 85724ABSTRACTA spectrograph based imaging system attached to a microscope is described for use inmonitoring the fluorescence of multiple probes loaded into single cells. Movements ofions, important in regulating cell function, are inter-related under many conditions.Since we are interested in the mechanisms underlying coupling between ion movementsand metabolism, we required a microscope based system to analyze these parameters at
Effect of clinician applied maneuvers on fetal brachial plexus strain during shoulder dystocia delivery

516 517 EFFECT OF CLINICIAN APPLIED MANEUVERS ON FETAL BRACHIAL PLEXUS STRAIN DURING SHOULDER DYSTOCIA DELIVERY BERNARD GONIK, RICHARD COSTELLO, NING ZHANG, MICHELE GRIMM, Wayne State University, Ob/Gyn, Detroit, MI Wayne State University, Biomedical Engineering, Detroit, MI OBJECTIVE: To objectively study the impact of suprapubic pressure (SPP), oblique fetal shoulder displacement (OSD), and posterior arm delivery (PAD) on brachial plexus (BP) strain during a shoulder dystocia (SD) event. STUDY DESIGN: A computer software crash dummy model (MADYMO) was modified based on establishedmaternal and fetal anatomic specifications to simulate vaginal delivery after anterior impaction of the fetal shoulder behind the symphysis pubis. The BP was modeled as a spring, using mechanical properties from previously reported data. Exogenously applied axial loading force was used to accomplish delivery. SPP was modeled by a compressive force applied superior to the anterior fetal shoulder. OSD was modeled by repositioning of the fetal torso within the maternal pelvis prior to applying extraction force. PAD was modeled by circumducting the fetal posterior arm prior to applying force. BP deformation was assessed as percent strain in the nerve (change in length/original length3100). RESULTS: With lithotomy pelvic positioning, 75 N of exogenous force was required to achieve delivery. This was associated with 14% BP strain. Applying graded SPP reduced the needed delivery forces and subsequent BP strain. An 80 N SPP resulted in a delivery force of 60 N and a BP strain of 9.8%. Rotating the fetal shoulders to an oblique position decreased delivery force to 50 N and BP strain to 9.8%. Delivering the posterior arm decreased the bisacromial diameter resulting in a reduction in required force to 30 N and a BP strain of 5.3%. CONCLUSION: Vaginal delivery associated with SD results in measurable BP strain. Use of established maneuvers for the management of SD such as SPP, OSD or PAD can result in an objective reduction in needed exogenous delivery force and BP strain. Although computer modeling did not allow for interexperiment variability and therefore statistical comparisons of strain differences, overall BP strain was reduced from 30-62 % with these maneuvers. December 2003 Am J Obstet Gynecol S200 SMFM Abstracts
Cell properties after repeated transplantation of spontaneously and of SV40 virus transformed mouse cell lines. I. Growth in culture.

“Spontaneously” or SV40 virus transformed AL/N mouse cell lines were passed repeatedly through syngeneic mice. Cell lines were re-established in culture from minced pieces of tumors in the presence of concentrated fetal calf serum or from tumor cells dispersed by trypsin. The aim of this study was to compare the two cell lines in regard to the selection processes which operate during such procedures by characterization of the resulting cell lines. Measurements of growth in tissue culture on substratum showed no significant difference between any of the transformed cell lines. The SV40 transformed cells and its derivative cells had a low anchorage requirement for growth. The greatest anchorage requirement for growth was in the normal untransformed cells and in the derivative cells from the “spontaneously” transformed cells which were established from minced tumors. The spontaneously transformed cells and all derivative cells had high tumorigenicity in vivo (TD50 108), except when injected into irradiated mice (TD50 = 107). The derivative cell lines obtained from such a tumor had increased tumorigenicity (TD50 = 1–5 × 105 in the immunocompetent mice, 5 × 104 in the irradiated mice). The SV40 transformed derivative cells maintained their SV40 specific T antigen and their susceptibility to lysis by specific antiserum.
Robust Univariate Test of Symmetry

Abstract This paper presents a test of symmetry based on the gaps of the order statistics. This test is sensitive to small skewed transformations of symmetric random variables and is adjusted for the apparent long-tailedness of the sample. A comparison of this adjusted test, the usual skewness test g 1, and Gupta's asymptotically nonparametric procedure shows that the procedure presented here has the best performance as a test of symmetry.
Towards efficiency and portability: programming with the BSP model

The Bulk-Synchronous Parallel (BSP) model was proposed by Valiant as a model for general-purpose parallel computation. The objective of the model is to allow the design of parallel programs that can be executed efficiently on a variety of architectures. While many theoretical arguments in support of the BSP model have been presented, the degree to which the model can be efficiently utilized on existing parallel machines remains unclear. To explore this question, we implemented s small library of BSP functions, called the Green BSP library, on several parallel platfotms. We also created a number of parallel applications based on this library. Here, we report on the performance of six of these applications on three different parallel platforms. Our preliminary results suggest that the BSP model can be used to develop efficient and portable programs for a range of machines and applications.
A measurement technique of time-dependent dielectric breakdown in MOS capacitors

Abstract The statistical nature of time-dependent dielectric breakdown characteristics in MOS capacitors was evidenced by testing large numbers of capacitors fabricated on single wafers. A multi-point probe and automatic electronic visual display technique are introduced that will yield statistical results which are necessary for the investigation of temperature, electric field, thermal annealing, and radiation effects in the breakdown characteristics, and an interpretation of the physical mechanisms involved. It is shown that capacitors of area greater than 2 × 10 −3 cm 2 may yield worst-case results, and that a multi-point probe of capacitors of smaller sizes can be used to obtain a profile of non-uniformities in the SiO 2 films.
Late effects of head and neck radiation therapy and patient/dentist compliance with recommended dental care

Head and neck radiation therapy patients have permanent damage to their salivary glands, tissue, and bone. This damage may result in late effects such as: xerostomia, rampant dental caries, demineralization, trismus, and osteoradionecrosis. Therefore, a pretherapy dental evaluation and treatment and compliance with a long-term oral care regimen are necessary. This retrospective study was designed to assess the late effects of radiation therapy and compliance with long-term care recommendations of patients seen in the Oncology Dental Support Clinic at the University of Missouri-Kansas City School of Dentistry during 1981 to 1989. Telephone interviews of patients and their dentists were conducted, and a written questionnaire to the dentists provided further data. Late effects were consistent with those reported in the literature. A compliance rate of approximately 50% was reported. Several measures have been implemented in an attempt to increase compliance.
Use of ketorolac is associated with decreased pneumonia following rib fractures.

Abstract Background The effectiveness of the nonsteroidal anti-inflammatory drug ketorolac in reducing pulmonary morbidity after rib fractures remains largely unknown. Methods A retrospective cohort study was conducted spanning January 2003 to June 2011 assessing pneumonia within 30 days and potential adverse effects of ketorolac among all patients with rib fractures who received ketorolac Results Among 202 patients who received ketorolac and 417 who did not, ketorolac use was associated with decreased pneumonia (odds ratio, .14; 95% confidence interval, .04 to .46) and increased ventilator-free days (difference, 1.8 days; 95% confidence interval, 1.1 to 2.5) and intensive care unit–free days (difference, 2.1 days; 95% confidence interval, 1.3 to 3.0) within 30 days. The rates of acute kidney injury, gastrointestinal hemorrhage, and fracture nonunion were not different. Conclusions Early administration of ketorolac to patients with rib fractures is associated with a decreased likelihood of pneumonia, without apparent risks.
First-Year College Students' Attitudes about End-of-Life Decision-Making

This study analyzes attitudes about treatment of the terminally ill among a group of first-year undergraduate students—a cohort that was in high school when intense publicity and extensive political and judicial involvement in the Terri Schiavo case occurred. Data for the study were collected by structured personal interviews with 201 randomly selected, first-year students in the first half of fall semester, 2005. Students clearly make distinctions in the propriety of active euthanasia, passive euthanasia, and physician-assisted death. Presented with a situation of a terminally ill patient in considerable pain, 65.1% of the students supported or strongly supported withdrawal of life-sustaining technology (passive euthanasia), 34.3% supported the physician providing the means of death to the patient (physician-assisted death), and 28.3% supported the physician actually administering a lethal injection (active euthanasia). A review of the literature of correlates of euthanasia attitudes in a variety of samp...
Developmentally dictated expression of heat shock factors: Exclusive expression of HSF4 in the postnatal lens and its specific interaction with αB-crystallin heat shock promoter

The molecular cascade of stress response in higher eukaryotes commences in the cytoplasm with the trimerization of the heat shock factor 1 (HSF1), followed by its transport to the nucleus, where it binds to the heat shock element leading to the activation of transcription from the down-stream gene(s). This well-established paradigm has been mostly studied in cultured cells. The developmental and tissue-specific control of the heat shock transcription factors (HSFs) and their interactions with heat shock promoters remain unexplored. We report here that in the rat lens, among the three mammalian HSFs, expression of HSF1 and HSF2 is largely fetal, whereas the expression of HSF4 is predominantly postnatal. Similar pattern of expression of HSF1 and HSF4 is seen in fetal and adult human lenses. This stage-specific inverse relationship between the expression of HSF1/2 and HSF4 suggests tissue-specific management of stress depending on the presence or absence of specific HSF(s). In addition to real-time PCR and immunoblotting, gel mobility shift assays, coupled with specific antibodies and HSE probes, derived from three different heat shock promoters, establish that there is no HSF1 or HSF2 binding activity in the postnatal lens nuclear extracts. Using this unique, developmentally modulated in vivo system, we demonstrate 1) specific patterns of HSF4 binding to heat shock elements derived from αB-crystallin, Hsp70, and Hsp82 promoters and 2) that it is HSF4 and not HSF1 or HSF2 that interacts with the canonical heat shock element of the αB-crystallin gene.
Rock 67015: A feldspathic fragmental breccia with KREEP‐rich melt clasts

The feldspathic fragmental breccia (FFB) 67015, from the rim of North Ray Crater, contains a wider range of clast lithologies than have previously been described for FFBs. The present petrological and chemical study reveals two components of major importance: a dark, vesicular, KREEP-rich melt rock of very high alumina basalt composition common at the Apollo 16 site, and a large clast of medium-grained ferroan anorthositic norite which composition falls among the most magnesian members of the ferroan anorthosite suite of pristine cumulate rocks. This latter material constitutes a previously missing member of certain mixing models, which were designed to account for the North Ray Crater melt rocks and bulk breccias.
Micro and semimicro determination of arsenate using ion-selective electrodes

An indirect method for the microestimation of 0.75 to 15 ppm (1−10−5 to 2·10−4M) of As(V) has been described: Arsenate is precipitated with lanthanum nitrate at a pH of 8.65. The excess of lanthanum is titrated with standard fluoride, using a fluoride ion-selective electrode. Equivalence points are located on volume-corrected Gran's plot paper. This method can also be used to estimate the sum of arsenate and phosphate. For larger amounts of arsenate and for increased precision and accuracy, potentiometric titration with lead perchlorate, using a lead ion-selective electrode, is recommended. Other possibilities for determining arsenate and a method for estimating tungstate are suggested.
Culture of intact Sertoli/germ cell units and isolated Sertoli cells from Squalus testis. II. Stimulatory effects of insulin and IGF-I on DNA synthesis in premeiotic stages.

To investigate growth control mechanisms during spermatogenesis in vitro, [3H]thymidine incorporation into acid-insoluble macromolecules was used to quantify DNA synthesis in cultured spermatocysts (intact Sertoli cell/germ cell clones) derived from premeiotic (PrM), meiotic (M), and postmeiotic (PoM) regions of dogfish (Squalus acanthias) testis. Forty-eight hours after seeding in basal medium, DNA synthesis was > 7-fold higher in PrM cysts than in other stages, thus verifying the staging procedure. In autoradiograms, germ cells of PrM cysts (e.g., spermatogonial and preleptotene stages) were labeled all-or-none, but not all cysts were labeled, and later developmental stages (e.g., cysts with round or elongating spermatids) were never labeled. Fetal bovine serum (FBS, 10%) and insulin-transferrin-selenite (ITS, 10 micrograms-10 ng/ml) doubled DNA synthesis in PrM cyst cultures but had no effect at other stages. Bovine insulin (10 micrograms/ml) and human recombinant insulin-like growth factor-I (IGF-I, 15 ng/ml) also doubled [3H]thymidine uptake in PrM cultures, but lower doses were less effective and estradiol-17 beta, transferrin, adult shark serum, purified shark relaxin, and a variety of other known growth factors were neither stimulatory nor inhibitory at the doses and conditions tested. Sertoli cell monolayers derived from PrM- or M-stage spermatocysts displayed a dose-response increase in DNA synthesis after addition of IGF-I (15-75 ng/ml), with a maximal increment significantly greater than with 10% FBS. Using [3H]thymidine incorporation by PrM cysts as an end-point, stimulatory bioactivity was detected in the < 30,000 kDa fraction of spent media from PrM Sertoli cells, whereas the low molecular weight fraction of M-stage Sertoli cells was inhibitory. Gel electrophoretic analysis of the two fractions revealed qualitative and quantitative differences in protein banding patterns, reinforcing the view that secretory activity of Sertoli cells is stage related. Results of these studies implicate insulin/IGF-I in mechanisms governing proliferation of male germ cells and support the view that Sertoli cells have an autocrine or paracrine role as both targets and sources of growth regulatory factors.
Respiratory motion effects on whole breast helical tomotherapy

The effects of intrafraction respiratory motion on nonhelical intensity-modulated radiotherapy have been well addressed in the literature, both theoretically and experimentally. However, the consequences of respiratory motion on helical tomotherapy, for patient-specific treatment plans, are less well known. Parameters specific to this treatment modality such as pitch, gantry speed, and degree of modulation may play prominent roles in radiation delivery with respect to intrafraction respiratory motion. This phantom-based study specifically addressed the effects of intrafraction respiratory motion on whole breast helical tomotherapy. A device capable of driving an acrylic phantom with reproducible, one-dimensional, anterior-posterior motion resembling a sinusoid of 4.6 mm crest-trough amplitude was developed. A plan to irradiate the corner of an acrylic phantom using parameters typical of a whole breast helical tomotherapy technique was developed using the TomoTherapy Hi-Art-II System®. The treatment was delivered to the phantom, with Kodak EDR2 film in the axial plane, for each of the following conditions: (i) phantom at 270 ° initial sinusoidal phase and 12 cycles/min motion, (ii) phantom at 270 ° initial sinusoidal phase and 18 cycles/min motion, and (iii)–(v) phantom at 18 cycles/min motion with 0 ° , 90 ° , and 180 ° initial sinusoidal phases. A measure of technique reproducibility was also performed for several irradiations with the phantom static at 270 ° initial sinusoidal phase. Films were processed using a Kodak MIN-R mammography film processor, scanned with a Vidar NXR-16 Dosimetry Pro scanner and analyzed with RIT113 v.4.2 software. Films were compared to a reference film irradiated under the conditions of no motion and 270 ° sinusoidal phase. For all comparisons, 5 % dose difference threshold, 3 % dose difference and 2 mm distance-to-agreement gamma analysis, and isodose plots were generated. The results of this study show a small area of greater than 5 % decrease in dose at the phantom’s anterior surface and a 1.5 − 3 mm posterior-medial shift of isodose lines in the penumbral and apex regions of the PTV. Frequency and phase effects are apparent within the PTV where dose varies with high spatial frequency. As the reference film was produced by delivering the treatment plan to the phantom static and in the position corresponding to maximum expiration, results are representative of extreme deviations between planned and delivered dose with respect to sinusoidal motion of clinically relevant magnitudes and frequencies.
Improving interconnect characteristics of thin film MEMS processes

One problem faced by designers utilizing polysilicon based surface micromaching processes is the poor conductivity of polysilicon. Process factors preclude inclusion of metal layers in these processes before the final polysilicon layer is annealed. Adding metal after anneal but before release restricts the metal to only the top layer of the design, making it much less useful for interconnect, and restricting reflective surfaces to the top layer. We present techniques for adding metal after release which avoid some of the usual pitfalls. Application areas for which these techniques could prove useful include RF, Microwave, Optical MEMS, and MEMS devices used in high-speed digital communications. Creating a multilayer metal interconnect is enabled by utilizing a self-masking approach to avoid shorting, and applying e-beam evaporation from a variety of angles. Using this approach, even lower level polysilicon lines can be metallized. Results using two deposition angle recipes on test structures and devices fabricated in a thin film MEMS process are presented.
A theory of scar unemployment

Abstract A job search model of scar unemployment is presented wherein it is demonstrated that the escape rate from unemployment decreases with unemployment duration, under fairly general conditions on the offer distribution. A striking and counter intuitive result is that the current reservation wage for a scarred worker and an unscarred worker is the same, when faced with identical search environments.
Crystal structure of epidoxorubicin-formaldehyde virtual crosslink of DNA and evidence for its formation in human breast-cancer cells.

Epidoxorubicin and daunorubicin are proposed to be cytotoxic to tumor cells by catalyzing production of formaldehyde through redox cycling and using the formaldehyde for covalent attachment to DNA at G bases. The crystal structure of epidoxorubicin covalently bound to a d(CGCGCG) oligomer was determined to 1.6 A resolution. The structure reveals slightly distorted B-form DNA bearing two molecules of epidoxorubicin symmetrically intercalated at the termini, with each covalently attached from its N3′ to N2 of a G base via a CH2 group from the formaldehyde. The structure is analogous to daunorubicin covalently bound to d(CGCGCG) determined previously, except for additional hydrogen bonding from the epimeric O4′ to O2 of a C base. The role of drug–DNA covalent bonding in cells was investigated with synthetic epidoxorubicin–formaldehyde conjugate (Epidoxoform) and synthetic daunorubicin–formaldehyde conjugate (Daunoform). Uptake and location of drug fluorophore in doxorubicin-resistant human breast-cancer cells (MCF-7/ADR cells) was observed by fluorescence microscopy and flow cytometry. The fluorophore of Daunoform appeared more rapidly in cells and was released more rapidly from cells than the fluorophore of Epidoxoform over a 3 h exposure period. The fluorophore appeared predominantly in the nucleus of cells treated with both conjugates. The difference in uptake is explained in terms of the slower rate of hydrolysis of Epidoxoform to the species reactive with DNA and a proposed slower release from DNA based upon the crystal structures.
Characterization of Poly-SiC Pressure Sensors for High Temperature and High Pressure Applications

We report two improvements of our all-silicon carbide (SiC) micromachined capacitive diaphragm-based pressure sensors: Ti/TaSi2/Pt contact metallization to enhance temperature cycling durability and a 0.5 μm-thin sensing gap to further improve sensor sensitivity. Three sensors with 0.5 μm and 1.5 μm sensing gaps were packaged individually in high temperature ceramic packages and characterized to designed (static) pressures of 2.1 MPa (300 psi), 3.4 MPa (500psi) and 6.9 MPa (1000 psi) up to 550°C. For the 3.4 MPa range sensor (0.5 μm gap, 70 μm diaphragm radius), a sensitivity of 0.06 fF/Pa and a nonlinearity of 2.0% was obtained at 550°C in contact mode operation. In comparison, the 2.1 MPa range sensor (1.5 μm gap, 95 μm diaphragm radius) demonstrated a sensitivity of 0.07 fF/Pa and a nonlinearity of 4.6% at 550°C in contact mode operation. The 6.9 MPa range sensor (1.5 μm gap, 70 μm diaphragm radius) demonstrated a sensitivity of 0.03 fF/Pa and a nonlinearity of 4.0% at 500°C, also in contact mode.
Cardiopulmonary sympathetic and vagal afferents excite C1–C2 propriospinal cells in rats

The purpose of this study in anesthetized rats was to determine the effects of stimulating cardiopulmonary sympathetic afferents (CPSA) and vagal afferents on C1-C2 descending propriospinal neurons. We hypothesized that inhibition of spinal sensory neurons produced by CPSA or vagus activation might relay in C1-C2 spinal segments. Extracellular action potentials were recorded from 73 C1-C2 neurons whose axons were antidromically activated in lumbar segments. CPSA input excited 22 cells, inhibited two cells and excited/inhibited one cell, whereas vagal input excited eight cells and inhibited two cells. Results are consistent with the hypothesis that CPSA input can be processed in C1-C2 segments to produce neural modulation in distant spinal segments.
Effects op high rates op fertilizer N, P, and K on corn, Zea Mays L., leaf nutrient concentrations

Abstract The leaf concentrations of N, P, and K were primarily influenced by the respective fertilizer nutrient, except P, vhich also was influenced by the fertilizer N. Increasing rates of the nutrients well above those recommended for normal corn production increased the leaf nutrient concentrations, but not yields after the first increment of fertilizer. The effect of dry veather reduced yields 0.7 quintals per hectare per day and also vas negatively correlated with the leaf N and leaf P concentrations (0.01 probability level).
Feedback stabilization of connected nonlinear oscillators with uncontrollable linearization

A nonlinear system with uncontrollable linearization is under investigation. The uncontrollable part of the linearization is assumed to have no eigenvalues in the right half-plane and have eigenvalues with zero real and nonzero imaginary part. A nonlinear feedback loop is assumed to carry out a connection between the controllable part of the system and the uncontrollable one. The control law of the controllable part is defined to be a linear function of the state variables. This linear feedback loop can maintain the stability of a whole control system provided its feedback law coefficients satisfy a system of algebraic inequalities. The consistence of this system of inequalities is proved.
Specialization, fan-out, and multi-human/multi-robot supervisory control

This paper explores supervisory control of multiple, heterogeneous, independent robots by operator teams. Experimental evidence is presented which suggests that two cooperating operators may have free capacity that can be used to improve primary task performance without increasing average fan-out.
Satellite cells from dystrophic (mdx) mouse muscle are stimulated by fibroblast growth factor in vitro

Satellite cells cultured from dystrophic (mdx) and from control mouse hindlimb muscles grow and fuse to form muscle fibers within 4-5 days. Total cell number and muscle-fiber formation are stimulated by bovine fibroblast growth factor (FGF). At low FGF levels (0.02-0.20 ng/ml) control satellite cells as well as fibroblasts are unresponsive, while mdx satellite cells show three- to four-fold increases in growth. Control cells do not begin to respond until FGF levels reach 1-5 ng/ml. Heparin, a major constituent of muscle fiber basal lamina, inhibits myogenesis in these mouse muscle cultures. The heightened sensitivity of mdx satellite cells to FGF may permit high rates of new fiber formation in vivo without a parallel hyperplasia in the muscle fibroblast population. This finding may be important in explaining successful regeneration in mdx muscle in vivo and the fact that mdx animals escape the catastrophic symptoms seen in the related human Duchenne muscular dystrophy.
Activation of Skeletal Muscle Satellite Cells and the Role of Fibroblast Growth Factor Receptors

Specific, high-affinity binding of FGF2 was evaluated in cultured skeletal muscle satellite cells from young (3- to 4-week-old) and adult (9- to 12-month-old) rats prior to the first division in culture. Specific binding of FGF2 was detected on satellite cells from young rats at 18 h postplating, the earliest time examined, but specific binding was not detectable until 42 h on satellite cells from old rats. This correlates well with the delayed entry into the cell cycle exhibited by adult satellite cells and with the ability of satellite cells from rats of these ages to proliferate in response to FGF2. Patterns of tyrosine phosphorylation in whole cell extracts, following stimulation by FGF2, indicated specific FGF2 phosphorylation of proteins of 150/145, 90, 42, and 35 kDa in cells from both age groups. Several growth factors were evaluated for their ability to stimulate early entry of adult satellite cells into the cell cycle, and none of the following growth factors were able to activate proliferation of these cells: FGF2, IGF-1, IGF-2, PDGF-BB, TGF-beta 1, or TGF-beta 2. In addition, specific binding of FGF2 to 48-h cultures of adult satellite cells was not stimulated by FGF2, IGF-1, IGF-2, PDGF-BB, or TGF-beta 2, and specific binding was significantly decreased (P < 0.05) by FGF2 and TGF-beta 2. Specific binding was significantly lower in cells treated with PDGF-BB than in cells treated with either form of IGF but was greater than in cells treated with FGF2 or TGF-beta 2. The results of these experiments suggest that expression of functional FGF receptors on the surface of satellite cells may represent an important step in the activation of quiescent satellite cells.
Huntingtin: a single bait hooks many species

Cloning of the Huntington's disease gene uncovered huntingtin, which is remarkable for its lack of similarity with known proteins despite its large size, approximately 350 kDa. Subsequent experiments established that huntingtin has an as yet unknown function, crucial for embryonic development and neurogenesis. Recent protein trapping to identify huntingtin interactors now reveals that many different prey fall victim to huntingtin bait.
17β-Estradiol eye drops protect the retinal ganglion cell layer and preserve visual function in an in vivo model of glaucoma

Neuroprotection in glaucoma as a curative strategy complementary to current therapies to lower intraocular pressure (IOP) is highly desirable. This study was designed to investigate neuroprotection by 17β-estradiol (E2) to prevent retinal ganglion cell (RGC) death in a glaucoma model of surgically elevated IOP in rats. We found that daily treatment with E2-containing eye drops resulted in significant E2 concentration in the retina with concomitant profound neuroprotective therapeutic benefits, even in the presence of continually elevated IOP. The number of apoptotic cells in the RGC layer was significantly decreased in the E2-treated group, when compared to the vehicle-treated controls. Deterioration in visual acuity in these animals was also markedly prevented. Using mass spectrometry-based proteomics, beneficial changes in the expression of several proteins implicated in the maintenance of retinal health were also found in the retina of E2-treated animals. On the other hand, systemic side effects could not be avoided with the eye drops, as confirmed by the measured high circulating estrogen levels and through the assessment of the uterus representing a typical hormone-sensitive peripheral organ. Collectively, the demonstrated significant neuroprotective effect of topical E2 in the selected animal model of glaucoma provides a clear rationale for further studies aiming at targeting E2 into the eye while avoiding systemic E2 exposure to diminish undesirable off-target side effects.
Production of antibody to human osteosarcoma associated antigens by continuous human lymphoblastoid cell lines

Human lymphoblastoid cell lines that produce specific antibody against human osteosarcoma associated plasma membrane antigens have been established by preselecting OSAA binding human B lymphocytes from an osteosarcoma patient followed by Epstein-Barr virus (EBV) transformation. Four cell lines ( Kla -1, Kla -2, Kla -3, Kla -4) were obtained and cloned. The antibodies were lambda light containing IgM. The specificities of the antibodies were confirmed by immunofluorescence assays using tumor cell lines of various histologic types. Positive immunofluorescence was observed with all human osteosarcoma cell lines tested except one but not with tumor cell lines of other histologic types.
Effects of hydrogen bonding and structure of the accessory bacteriochlorophylls on charge separation in Rb. capsulatus reaction centers

Histidine residues have been introduced into Rb. capsulatus reaction centers at M-polypeptide position 201 and at L-polypeptide position 174 to engender hydrogen bonds to the ring-V keto groups of the accessory bacteriochlorophyll cofactors BA and BB, respectively. Resonance Raman studies indicate that both mutations result in hydrogen-bonding interactions, as well as significant perturbations to the structure of the bacteriochlorophyll macrocycles. Nonetheless, ultrafast transient absorption measurements show that the structural/energetic effects of the mutations cause only minor changes in the primary photochemistry.
Towards individualized medicine: flies lead the way

While the search for the genetic foundation of complex diseases receives a great deal of attention in the popular scientific press, it is merely the first step in a very long journey from gene identification to therapeutic options. Unexpectedly, even diseases that are caused by mutations in a single gene have a collection of diverse possible symptoms that variably affect each patient. What is becoming more obvious is the need to correlate specific endophenotypes, or subsets of disease symptoms, with specific genetic and/or environmental factors that differ from patient to patient. Surprisingly, Drosophila melanogaster, the common fruit fly, may be a key player in making these assignments, and in the drug-discovery process that necessarily follows. In this review, we discuss the issues that are emerging in neurological disease research, and why Drosophila’s role in the pathway towards pharmacological solutions is likely to increase.
Insulin hypoglycemia and hypothalamic hyperphagia

Adult female rats were subjected to bilateral lesions of varying extent in the ventromedial nuclei of the hypothalamus. On reaching asymptote, Ss were given subcutaneous injections of protamine zinc insulin, daily, for 10 days. Obesity asymptote attained by brain damage was positively correlated with judged extent of lesions, while insulin-induced superobesity was negatively correlated with hypothalamic obesity asymptote. No relationship was found between the time taken to reach hypothalamic obesity asymptote and the asymptotic weight.
Beyond the manual: The flexible use of cognitive behavioral therapy for bulimia nervosa

The treatment manual applying cognitive behavioral therapy principles for bulimia nervosa originally was used in early treatment outcome studies and was later expanded and enhanced by Fairburn, et al, 1993 , Fairburn, et al, 1993 , Fairburn, et al, 1993 for broader clinical use. The manual is well researched as an effective treatment and currently is advocated as the first-line treatment for bulimia nervosa. However, despite the research data supporting its use, these manual-based techniques are still not widely practiced in the treatment of eating disorders outside of academic research settings. This article aims to elaborate on aspects of the manual that may have hindered some therapists in its use. We focus on clarifying aspects of the treatment process that may assist clinicians to flexibly apply the treatment manual's specific techniques by emphasizing stylistic approaches to help facilitate treatment adherence, diminish risks of treatment dropout, and address behaviors that interfere with treatment.
Alloy Disorder Effects In Molecular Beam Epitaxically Grown Al x Ga 1-x As Examined Via Raman And Rayleigh Scattering And Near Edge Luminescence

Raman scattering, Rayleigh scattering and band edge photoluminescence are employed to examine the behavior of alloy disorder in AlxGa1-xAs alloys grown on GaAs(100) under reflection high energy electron diffraction determined growth conditions in molecular beam epitaxy. Evidence is found for the dependence of the short and long range disorder effects on the growth kinetics attendant to chosen growth conditions and on the Al concentration. At high Al concentration (xAl~0.8) evidence is found for the occurrence of atomic scale GaAs-like and AlAs-like regions. In addition, the "AlAs-like" TO mode is observed in the forbidden back scattering geometry and is likely due to strain and/or disorder related breakdown of the usual selection rules.© (1988) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Adiabatic, Isothermal, and Intermediate Pressure Derivatives of the Elastic Constants for Cubic Symmetry. I. Basic Formulae

The thermodynamic relations between the adiabatic pressure derivatives of the adiabatic elastic constants, the isothermal pressure derivatives of the isothermal elastic constants, and the isothermal pressure derivatives of the adiabatic elastic constants that can be measured ultrasonically are compiled and correctly proved for cubic symmetry. Also, the corresponding relations between the linear combinations of the third-order elastic constants that can be determined from these pressure coefficients are derived. Die thermodynamischen Beziehungen zwischen den adiabatischen Druckkoeffizienten der adiabatischen elastischen Konstanten, den isothermen Druckkoeffizienten der isothermen elastischen Konstanten und den mittels Ultraschall direkt mesbaren isothermen Druckkoeffizienten der adiabatischen elastischen Konstanten werden fur kubische Symmetrie zusammengestellt und korrekt begrundet. Auserdem werden die entsprechenden Beziehungen zwischen den aus diesen Druckkoeffizienten bestimmbaren Linearkombinationen der elastischen Konstanten dritter Ordnung abgeleitet.
Directly Administered Antiretroviral Therapy in an Urban Methadone Maintenance Clinic: A Nonrandomized Comparative Study

Methadone-maintenance treatment clinics are strategically appealing sites for provision of directly administered antiretroviral therapy (DAART) to human immunodeficiency virus type 1 (HIV-1)-infected injection drug users (IDUs). We initiated an ongoing DAART protocol at a university-associated methadone clinic in April 2001, which continues to enroll participants. Participants ingested antiretroviral medications under direct supervision on days they attended the clinic; evening doses and doses on "methadone take-home days" were self-administered. Comparison IDUs receiving either standard care or treatment-adherence support were randomly selected from the population of the HIV-1 clinic where DAART participants received their primary care for HIV-1 infection, with frequency matching by sex, prior antiretroviral exposure, and receipt of methadone therapy. In an intention-to-treat analysis, 79% of DAART participants achieved HIV-1 RNA levels of <400 copies/mL by month 6 of therapy, compared with 54% in the standard care group (P=.035) and 48% in the adherence support group (P=.008). The preliminary results of this study both suggest that DAART can be feasible and acceptable to patients in a methadone clinic setting and provide impetus for further study of this treatment strategy in randomized controlled trials.
Input variable selection for water resources systems using a modified minimum redundancy maximum relevance (mMRMR) algorithm

Input variable selection (IVS) is a necessary step in modeling water resources systems. Neglecting this step may lead to unnecessary model complexity and reduced model accuracy. In this paper, we apply the minimum redundancy maximum relevance (MRMR) algorithm to identifying the most relevant set of inputs in modeling a water resources system. We further introduce two modified versions of the MRMR algorithm (α-MRMR and β-MRMR), where α and β are correction factors that are found to increase and decrease as a power-law function, respectively, with the progress of the input selection algorithms and the increase of the number of selected input variables. We apply the proposed algorithms to 22 reservoirs in California to predict daily releases based on a set from a 121 potential input variables. Results indicate that the two proposed algorithms are good measures of model inputs as reflected in enhanced model performance. The α-MRMR and β-MRMR values exhibit strong negative correlation to model performance as depicted in lower root-mean-square-error (RMSE) values.
The evolution of clinical applications of biodegradable implants in arthroscopic surgery

Arthroscopic surgery is the most recent orthopaedic discipline to embrace biodegradable implant technology. Osteochondral fractures have been shown to be amenable to arthroscopic fixation with biodegradable pins. The areas of most recent interest have been biodegradable interference screw fixation for ACL reconstruction in the knee, biodegradable suture anchors for rotator cuff repair and capsulolabral repair in the shoulder. Biodegradable implants have allowed a paradigm shift away from bionic (mechanical replacement) engineering and toward true biologic solutions to reconstructive problems in arthroscopic surgery.