cssi/SciSciGPT-SciSciNet huggingface dataset:
Proteolysis and binding of myosin subfragment 1 to actin

Abstract Rates of proteolytic cleavage of myosin subfragment 1 were measured in the absence and presence of different amounts of actin. The rates of tryptic digestion at the 50K/20K † junction and papain digestion at the 25K/50K junction of the myosin head were progressively inhibited with increasing substoichiometric molar ratios of actin to myosin subfragment 1. The percentage inhibitions of digestion reactions corresponded precisely to the molar compositions of actin-subfragment 1 solutions and demonstrated that equimolar complexes of these proteins were responsible for the observed changes in the proteolysis of myosin heads.
New surface polariton in spatially dispersive semiconductors.

%e predict a new surface polariton mode in semiconductors with split exciton bands that are linear in the wave vector. It is the only surface polariton whose existence is a result of spatial dispersion (nonlocal effects). Calculated attenuated-total-reflection spectra for the B(n = 1) exciton of Cds exhibit a well-defined minimum corresponding to this mode, in addition to the usual minimum (which persists even in the local
Vasodilator therapy in patients with aortic insufficiency: a systematic review

Background The use of vasodilators to improve long-term outcomes in asymptomatic patients with chronic aortic insufficiency (AI) is controversial. Methods We reviewed MEDLINE, PREMEDLINE, Current Contents, and Cochrane databases to identify relevant clinical trials on asymptomatic patients with chronic AI of at least moderate severity. We included those studies that involved long-term vasodilator therapy (including hydralazine, calcium-channel blockers, and angiotensin-converting enzyme inhibitors) and assessed either hemodynamic and structural parameters or clinical outcomes. Data on patient demographics, study protocols, and outcomes were abstracted. Results Ten studies with 544 asymptomatic patients with chronic AI were identified. Treatment duration with vasodilators ranged from 12 weeks to 7 years. Of these, 8 studies compared vasodilators with placebo or no therapy, with 5 demonstrating improvements in at least 1 hemodynamic or structural parameter with vasodilators and 3 showing little or no apparent benefit. The remaining 2 studies directly compared outcomes between 2 different vasodilators. Both of these studies demonstrated greater improvements in hemodynamic and structural parameters with angiotensin-converting enzyme inhibitors compared with hydralazine and nifedipine. Clinical outcomes were primarily reported in only 2 of the 10 studies. Although one study suggested that the use of vasodilators slowed the rate of progression to surgery for aortic valve replacement, another showed no difference. Conclusions Vasodilators inconsistently improve hemodynamic and structural parameters in asymptomatic patients with chronic AI. In addition, the impact of vasodilators on clinical outcomes is largely uncertain and requires further study.
First AID (activation-induced cytidine deaminase) is needed to produce high affinity isotype-switched antibodies.

An answer to the question "why don't you die when I sneeze?" resides in the ability of higher organisms to mount an aggressive defense in response to an invasion by foreign substances called antigens. In part this defense mechanism is accomplished through the synthesis of high affinity antibody (Ab) 2 proteins that effectively defuse the attack. Initially, lymphoid B cells rearrange immunoglobulin (Ig) genes using V(D)J recombination to generate a diverse repertoire of low affinity Abs. Subsequently these Ig genes undergo somatic hypermutation (SHM) and class switch recombination (CSR) to generate high affinity Ab molecules of different isotypes. Activation-induced cytidine deaminase (AID) is required to initiate both CSR and SHM. The current understanding of immunological diversification can be attributed to the contributions made by cellular and molecular immunologists with biochemical enzymology recently entering the arena. This minireview discusses advances in the understanding ofAb diversification from a biochemical perspective emphasizing the enzymatic properties of AID in initiating SHM and CSR and exploring the role of downstream mutation fixation events mediated by mismatch repair (MMR), basic excision repair (BER), and error-prone DNA polymerases (EP pols).
Zeta (ξ), a growth-related opioid receptor in developing rat cerebellum: identification and characterization

Endogenous opioids and opioid receptors (i.e. endogenous opioid systems) are expressed during neural ontogeny, and play a role in the development of the nervous system. Using [3H][Met5]-enkephalin, a potent ligand involved in neural growth, particularly cell proliferation, specific and saturable binding was detected in homogenates of 6-day-old rat cerebellum; the data were consistent with a single binding site. Scatchard analysis yielded a binding affinity (Kd) of 2.2 nM and a binding capacity (Bmax) of 22.3 fmol/mg protein. Binding was linear with protein concentration, dependent on time, temperature, and pH, and was sensitive to Na+, Mg2+, and guanyl nucleotides. Optimal binding required protease inhibitors, and pretreatment of the homogenates with trypsin markedly reduced binding, suggesting that the binding site was proteinaceous in character. The [Met5]-enkephalin binding site was an integral membrane protein located in the nuclear fraction. Competition experiments indicated that [Met5] enkephalin was the most potent displacer of [3H][Met5]-enkephalin, and that binding was stereospecific. In the adult rat cerebellum, non-opioid receptor binding of [3H][Met5]-enkephalin was recorded, mu and kappa receptors were also found in the developing rat cerebellum, while mu, delta, and kappa receptors were recorded in adult cerebellar tissue. The function, pharmacological and biochemical characteristics, subcellular distribution, and temporal expression of the [Met5]-enkephalin binding site suggest the presence of a unique opioid receptor, termed zeta (zeta), in the developing nervous system.
Hardening and intergranular embrittlement in neutron-irradiated ferritic alloys

Abstract The characteristics of hardening and integranular embrittlement induced during neutron irradiation (0.94 × 10 23 n m −2 at 395 °C) in ferritic alloys doped with copper, phosphorus and/or carbon have been investigated using small punch test techniques. The effect of neutron irradiation on hardening was found to be greater in alloys doped with copper and/or phosphorous than in carbon-containing alloys. It has been shown that the great magnitude of irradiation-induced hardening observed for the copper- and/or phosphorus-containing alloys is attributed to an increase in both the athermal and thermal stress components. The neutron irradiation produced a more substantial increase in the ductile-brittle transition temperature in the copper-doped alloy compared with the other alloys. Intergranular and transgranular fracture occurred in the alloys doped without and with carbon respectively. The neutron irradiation did not alter the fracture mode.
Innovative practices session 5C: Post-silicon debug

Despite advances in design and pre-silicon verification, it is becoming increasingly common for postsilicon validation to discover design errors as well as serious marginalities which threaten a design's economic viability. Consequently, increasingly chip designs are undergoing multiple silicon spins. This is the case not only for high-performance custom and semi-custom chips but also for ASICs. For example, Collett International Research reports that 37% of ASICs require a second spin while 24% of ASICs require more than two spins. Post-silicon validation is hence assuming an increasingly central role in the development of high-performance chips. In this session, we have invited industrial experts in post-silicon validation to share their experiences. In particular, they will share their approach for improving the quality of validation methodology to ensure detection of all possible serious causes of circuit misbehavior which threaten a chip's economic viability. They will also share their experience with diagnosis for identifying underlying root causes to facilitate rapid redesign. They will touch upon how post-silicon validation helps improve our understanding of new processes and facilitates process and design improvements. The invited experts will cover a wide range of high-end designs, including multi-core microprocessors, high-performance special-purpose processors, as well as memory-intensive chips including SoCs.
Stability of visual acuity in amblyopic patients after visual maturity.

One hundred thirty patients with strabismic amblyopia who underwent full-time occlusion therapy (FTO) and were followed through to at least 9 years of age were evaluated to determine the stability of visual acuity after visual maturity (after 9 years of age). Of these 130 patients, 89 are included in this review. At the conclusion of the FTO therapy, 92% (82/89) had attained a visual acuity of 20/40 or better, 6% (5/89) had attained 20/50–20/100, and 2% (2/89) remained at 20/200 or less. Of the nine patients in this series in whom patching was initiated between the ages of 6 and 9 years of age, a good visual result was seen in 89% (8/9), with 63% (5/8) of those attaining 20/20 vision. The final visual acuity in this group of patients was taken at an average patient age of 15.9 years. In 75% of the patients (67/89) there was no change in visual acuity over time, while 17% (15/89) showed a one- or two-line decrease, and in 8% (7/89) vision dropped more than two lines. Of those patients who had ≥ 20/40, 88% (56/64) who had a posttreatment visual acuity of 20/20 showed no change at the final evaluation, but only 50% (9/18) of those whose posttreatment vision was between 20/25 and 20/40 were stable. In those patients who needed part-time occlusion (PTO) to maintain equal visual acuity, their stability appeared to be the same as the vision of those whose vision was maintained without PTO.
Role of pH and Ionic Strength on Water Relationships in Washed Minced Chicken‐breast Muscle Gels

The relationship between pH, ionic strength, and water balance of chicken-breast muscle gels was investigated. An increase in gel pH (pH 6.4 to 7.4) without added NaCl led to dramatic increases in water-holding capacity and water uptake (P < 0.05). Gels at 150 mM NaCl exhibited less ability to adsorb water than salt-free gels (P < 0.05 at pH 6.8 to 7.4) and had lower water-holding capacities (P < 0.05) and fold scores at and below pH 7. Varying salt concentration of the gel-bathing solutions had dramatic effect on the water uptake of the gels. The results show that strong water-absorbing gels can be produced at low ionic strengths and suggest that the negative charge of the muscle proteins is the driving force for water uptake and retention.
The site of origin of electrical responses in visual cells of the leech, Hirudo medicinalis.

In leech visual cells the presumed light-absorbing structures are microvilli arising from the membrane of what would seem to be a large intracellular vacuole. This vacuole, however, is an extracellular compartment, since it communicates with the intercellular spaces through narrow channels. Therefore, the membrane of the microvilli is—as in other invertebrate visual cells—a part of the cell membrane. Visual responses recorded with an electrode within the vacuole were compared with the intracellular recordings. Following illumination the vacuole becomes negative with respect to the outside fluid, while the cells are depolarized. This finding indicates that inward current penetrates the cell through the microvillar membrane. It is concluded, therefore, that the electrical response (receptor potential) originates as a result of changes in the properties of the light-absorbing membrane.
Presence/absence of a keystone species as an indicator of rangeland health

Abstract We examined the relationship between a Chihuahuan Desert grassland keystone species (banner tailed kangaroo rat, Dipodomys spectabilis ) and several vegetation and soil indicators of rangeland health in order to define a threshold indicator value for irreversible change in ecosystem structure and function. The abundance of occupied and/or abandoned D. spectabilis burrow-mounds was assessed at 117 sites in south-central New Mexico where previous studies had reported vegetation cover and composition. The most robust indicator for presence/absence of D. spectabilis was shrub cover. D. spectabilis did not occur at sites with shrub cover >20%. It was concluded that a threshold value of 20% shrub cover could be applied to assessment and monitoring of Chihuahuan Desert rangelands because higher shrub cover results in the local extinction of this keystone species. The combination of data on the presence/absence of a keystone species with vegetation and soil indicators provides a method for identifying thresholds of degradation that may be irreversible.
Capillary Electrophoresis Microchip with a Carbon Nanotube-Modified Electrochemical Detector

Significant improvements in the performance of a capillary electrophoresis (CE) microchip with an electrochemical detector are observed using a carbon nanotube (CNT)-modified working electrode. The CNT-modified electrode allows CE amperometric detection at significantly lower operating potentials and yields substantially enhanced signal-to-noise characteristics. The electrocatalytic detection is coupled to resistance to surface fouling and hence enhanced stability. Such advantages are illustrated in connection with several classes of hydrazine, phenol, purine, and amino acid compounds. Substantial minimization of surface fouling effects has been demonstrated in connection with the monitoring of phenol and tyrosine. Factors affecting the performance of the new CNT detector were assessed and optimized. CNTs from different sources are evaluated, and the effect of an anodic pretreatment is explored. The broad and significant catalytic activity exhibited by CNT-based CE detectors indicates great promise for a wide range of bioanalytical and environmental applications.
Conflict of credentialing: accolade or unfair trade.

The newly appointed chief of surgery at an open-staff hospital received an application for vascular privileges from a senior general surgeon who took a period of additional fellowship in vascular surgery at a nonacademic regional medical center. The fellowship does not make him board eligible in vascular surgery, but he has maintained his general surgery board certification and the pertinent bylaws do not specifically state which certification is required, only that the surgeon must be board certified and have additional training in vascular surgery. He is a member of a large politically powerful group practice that apparently wants to refer their substantial number of vascular cases internally. The chief of surgery finished vascular surgery training locally 3 years ago. The applicant has a checkered past, with multiple lawsuits and in-house investigations of cases with poor outcomes. The credentialing procedure is that the chief of service makes a recommendation to the chief of staff who makes a recommendation to the board of directors for approval. The chief of staff, who will make the final recommendation to the hospital board of directors, is a member of the applicant's group practice. What recommendation should the chief of vascular surgery make to the chief of staff? A Insist that the chief of staff recuse herself and allow him to make the recommendation. B Get an outside review of the applicant's record and have a nonconflicted physician present the conclusions to the hospital board. C Present the chief of surgery's recommendations to the chief of staff and let her decide what to present to the board. D Politic with the chair of the hospital board of directors. E Resign as chief of surgery before you damage your career.
Using the TeraGrid to teach scientific computing

We describe how a new graduate course in scientific computing, taught during Fall 2010 at Louisiana State University, utilized TeraGrid resources to familiarize students with some of the real world issues that computational scientists regularly deal with in their work. The course was designed to provide a broad and practical introduction to scientific computing, creating the basic skills and experience to very quickly get involved in research projects involving modern cyberinfrastructure and complex real world scientific problems. As an integral part of the course, students had to utilize various TeraGrid resources, e.g., by deploying, using and extending scientific software within the national cyberinfrastructure.
Solving regression problems with rule-based ensemble classifiers

We describe a lightweight learning method that induces an ensemble of decision-rule solutions for regression problems. Instead of direct prediction of a continuous output variable, the method discretizes the variable by k-means clustering and solves the resultant classification problem. Predictions on new examples are made by averaging the mean values of classes with votes that are close in number to the most likely class. We provide experimental evidence that this indirect approach can often yield strong results for many applications, generally outperforming direct approaches such as regression trees and rivaling bagged regression trees.
The Valuation of Semiannual Bonds between Interest Payment Dates: A Correction

This note provides a correction to Taylor's 1988 work on the valuation of semiannual coupon bonds between interest payment dates. It shows that the discrepancy in values between Taylor's model and the standard Wall Street pricing formula is much smaller than indicated by Taylor and is unlikely to generate opportunities for arbitrage profits.
Hemodynamic and functional assessment of mechanical aortic valves using combined echocardiography and multidetector computed tomography.

Background Limitations are found in the ability of transthoracic echocardiography to evaluate mechanical aortic valve replacements (AVR). We evaluated the ability of combined echocardiography and computed tomography (CT) to enhance the hemodynamic and functional evaluation of AVR. Methods We performed a retrospective evaluation of 41 consecutive patients with AVR (27 bileaflet, 14 single disc) and both transthoracic echocardiography and 64-detector electrocardiographic-gated CT. Each study was interpreted by 2 independent, blinded readers. The effective orifice area was compared with the corrected energy-loss coefficient area and the geometric orifice area. Patients with an elevated mean pressure gradient (>15mm Hg) were assessed for potential abnormal findings, including patient–prosthesis mismatch, elevated cardiac index, valve dysfunction, significant regurgitation, or pressure recovery effect. Results Significant differences ( P r =0.55–0.98) were observed between the effective orifice area (2.2±0.8cm 2 ), corrected energy-loss coefficient area (3.0±1.5cm 2 ), and geometric orifice area (3.6±0.9cm 2 ). At least one abnormality was observed in 7 of 25 patients with normal gradients and in 14 of 16 patients with elevated gradients ( P P =0.001). Conclusion CT aids in the interrogation of prosthetic valve function, enhancing evaluation for patient prosthesis mismatch, and correction for pressure recovery by the corrected energy-loss coefficient. CT is additive to the assessment of mechanical AVR with transthoracic echocardiography, and the combination permits a more complete assessment of both AVR function and hemodynamics.
Alternate-day micafungin antifungal prophylaxis in pediatric patients undergoing hematopoietic stem cell transplantation: a pharmacokinetic study.

Disseminated fungal infection is a major cause of morbidity and mortality in children undergoing hematopoietic stem cell transplantation (HSCT). Prophylaxis with amphotericin B can be limited by renal toxicity. Oral triazoles can be limited by poor absorption, large interindividual pharmacokinetic (PK) variability, and hepatic toxicity, leading to interruptions in therapy and breakthrough infections. Intravenous (i.v.) micafungin has potential advantages, because of its better safety profile, specifically in terms of hepatic and renal toxicity, and lack of drug-drug interactions with common medications used in the HSCT setting. We hypothesized that higher dose micafungin (3 mg/kg) every other day will provide drug exposure similar to standard dosing (1 mg/kg) given daily, and improve patient compliance in very young children in whom oral medications can be challenging, at reduced administration costs. Both animal and adult patient data support the use of this approach. Fifteen children (M/F = 11/4, aged ≤10 years; mean: 3.9 years, range: 0.6-10 years) with various hematologic, metabolic, and immune deficiency disorders undergoing HSCT received a single dose of micafungin (3 mg/kg) i.v. over 1 hour. Dose selection was based on published PK data in pediatric patients, and exploration of different dosing regimens using Monte Carlo PK/PD simulation. Blood samples were drawn around this dose and PK analysis was conducted using standard noncompartmental methods. Micafungin at 3 mg/kg dose was well tolerated in all patients. Measurable plasma concentrations were present in all cases at 48 hours. Half-life and clearance observed were comparable to previous pediatric PK data, with clearance being higher than adults as expected. Volume of distribution was higher in our patients compared to published pediatric data, likely because of a larger proportion of very young children in our study cohort. After correction for protein binding, concentrations at the end of the dosing interval during maintenance treatment remain above the minimum inhibitory concentration (MIC) of highly susceptible fungal pathogens. These data suggest that alternate day micafungin dosing, as described here, may provide an attractive alternative for antifungal prophylaxis in HSCT patients and merits further evaluation.
Evidence for a GABAergic Projection from the Dorsal Nucleus of the Lateral Lemniscus to the Inferior Colliculus

This study attempts to determine whether the pathways from the guinea pig dorsal nucleus of the lateral lemniscus (DNLL) to the inferior colliculus (IC) use gamma-aminobutyric acid (GABA) as a transmitter. Injections of kainic acid (KA) were used to destroy neurons in the left DNLL. Two to 4 days after the injection, Nissl-stained sections through the lesion site showed destruction of the DNLL neurons. The lesions varied in size; 12-100% of the DNLL neurons were destroyed on the injected side without damage to the ipsilateral IC. Two to 4 days after the injection, the electrically evoked, Ca(2+)-dependent release and high-affinity uptake of [3H]GABA were measured in dissected pieces of the left and right IC. These activities were compared with those in the IC taken from unlesioned controls and from sham controls, which received injections of saline instead of KA. Each IC was divided into a dorsal piece, which contained the dorsal cortex and dorsomedial nucleus, and a ventral piece, which contained the central and lateral nuclei. Lesions of the left DNLL depressed the release and uptake of [3H]GABA in the ventral pieces of the IC, but there was a greater depression in the ventral IC contralateral to the lesioned DNLL. There were good correlations between the percentage of neuronal loss in the left DNLL and deficits in [3H]GABA release and uptake activities in the ipsi- and contralateral ventral IC. By contrast, there was no depression of [3H]GABA release and uptake in the dorsal pieces of the IC. The localization of the deficits in release and uptake appears to match the distribution of the synaptic endings of the DNLL pathways in the IC. This correspondence associates GABA release and uptake activities with the DNLL projections to the IC and, therefore, suggests that GABA may be a transmitter of these pathways. The release and uptake of [14C]glycine was also measured to determine whether glycine might be a transmitter of the DNLL pathways to the IC. Lesions of the left DNLL failed to alter the Ca(2+)-dependent release or the uptake of [14C]-glycine, suggesting that DNLL neurons are unlikely to use this compound as a transmitter.
A non-linear micromechanics-based analysis of metal-matrix composite laminates

Abstract This paper presents a formulation that performs a direct assembly of a set a equations that relates ply stresses to the constituent microstresses and microstrains up through to the laminate level for any ply layup. The basic tenet of the non-linear laminate formulation in this analysis is that assumptions of the classical laminated plate (CLP) theory for the strain variation in the laminate still apply. Complete details of this analysis from the micromechanics level to the laminate level are presented, and appropriate results of the stress/strain response predictions for monotonic and cyclic applied loads are compared to their analytical and experimental counterparts from previous studies. The non-linear effects of viscoplasticity and fiber/matrix debonding are included in the present formulation, and their impact on both crossply and quasi-isotropic laminates of metal-matrix composites undergoing thermomechanical fatigue loads are examined.
Synthesis of benzopentathiepin analogs and their evaluation as inhibitors of the phosphatase STEP

Striatal-enriched protein tyrosine phosphatase (STEP) is a brain specific protein tyrosine phosphatase that has been implicated in many neurodegenerative diseases, such as Alzheimer’s disease. We recently reported the benzopentathiepin TC-2153 as a potent inhibitor of STEP in vitro, cells and animals. Herein, we report the synthesis and evaluation of TC-2153 analogs in order to define what structural features are important for inhibition and to identify positions tolerant of substitution for further study. The trifluoromethyl substitution is beneficial for inhibitor potency, and the amine is tolerant of acylation, and thus provides a convenient handle for introducing additional functionality such as reporter groups.
Otolaryngology Resident In-Service Examination Scores Predict Passage of the Written Board Examination:

ObjectiveThe purpose of this study was to assess the association between the Otolaryngology Training Examination (OTE) and the passage rate of first-time examinees on the American Board of Otolaryngology (ABOto) Written Qualifying Examination (WQE).Study DesignHistorical cohort study.SettingDe-identified database containing information on examinees who took the WQE in 2007 to 2011 and the OTE in 2005 to 2011.Subjects and MethodsOne thousand three hundred nine otolaryngology residents took the WQE for the first time in 2007 to 2011 and the OTE in their final and penultimate years of training in 2005 to 2011. Data were analyzed using 1-way frequencies and table analysis. Logistic regression was used to model the relationship between the pass/fail WQE result and the OTE percentile score in the final and penultimate years of training. Data transformation was used to analyze WQE passage as a function of OTE scores by deciles and quartiles.ResultsThere is a significant relationship between OTE score and passage...
Ionophorous properties of narasin, a new polyether monocarboxylic acid antibiotic, in rat liver mitochondria.

Abstract Narasin, a new polyether monocarboxylic acid antibiotic, inhibits ATPase and reverses swelling and H+ release from liver mitochondria after induction of cation transport. Among alkali metal cations, narasin shows ionophorous activities with a selectivity of Na+ K+ = Rb+ Cs+ Li+. However, narasin also induces permeability of mitochondria to the non-noble gas cation, Tl+ and the polyatomic cation, NH4+. In fact, the polyether monocarboxylic acid ionophores, narasin and monensin, are more appropriate ionophores for NH4+ than for alkali cations. Narasin inhibits 50 per cent of the ATP hydrolysis activated by dinitrophenol, valinomycin-K+ and monazomycin-K+-NH4+ with ic 50 values of 2.5, 200 and 13 nM respectively. The corresponding ic 50 values for monensin are 7, 750 and 45 nM. The polyether monocarboxylic acid ionophores may play an important role in ionophore-producing organisms as NH4+ carriers.
PURINE METABOLISM IN THERAPY OF VON GIERKE'S DISEASE

Recently Green et. al. (N.E.J. Med. 294:423, 1976) have demonstrated that nocturnal infusion of a high carbohydrate diet is effective in treating patients with Von Gierke's disease. We have studied potential factors which may explain the lower serum uric acid with this therapy. Glycine-1-14C incorporation into urine uric acid, fractional renal acid clearance and red cell phosphoribosylpyrophosphate (PRPP) levels were studied during a control period of frequent daily high carbohydrate feedings (hcf) and frequent daily high carbohydrate feedings and nocturnal vivonex infusion (hcfn). Twenty four hours after injection of glycine-1-14C, the specific activity of uric acid was 3 times greater in hcf than in a control with Glycogen Storage Type III, and this was lowered to 2 times greater with hcfn. Total six day incorporation was 0.68% of the injected glycine-1-14C with hcf, 0.40% in hcfn, and 0.18% in the control. Fraction excretion of uric acid increased fron 11.3 per cent in hcf to 26.3 per cent in hcfn. PRPP levels were 8.0 picomoles/mg protein in hcf, 6.4 in hcfn and 6.0 in controls. We conclude additional of nocturnal feedings to hcf 1)decreases the accelerated de novo purine synthesis to a level still higher than control 2)increases fractional renal uric acid excretion by the kidney associated with lowered serum lactic acid, and 3)does not change red cell PRPP levels. Near normalization of purine metabolism with hcfn in Von Gierke's disease should significantly decrease the risk of gout.
PAX6 increases glioma cell susceptibility to detachment and oxidative stress.

Glioblastoma multiforme (GBM) is an incurable malignant glioma which is very resistant to radiation and alkylating agent-based chemotherapy. Necrosis is a hallmark for GBM and the layer surrounding necrotic area is packed with cells which are now believed to be those migrating out of the necrotic area. Oxidative stress is a condition that GBM cells encounter in the necrotic zone, which is one of the stressful conditions that GBM cells need to resist in order to survive. Our previous studies revealed that low PAX6 expression is a favorable molecular trait for survival acquired by GBM cells because PAX6 could suppress cell invasion and tumorigenicity. Since detachment of cells from GBM is an early event for cell migration and subsequent invasion, we examined whether PAX6 is involved in cell survival after detachment. PAX6 over-expression was achieved in glioma cells transiently (by adenoviral-mediated transient over-expression) or stably (by the establishment of stable cell lines after transfection). The effect of PAX6 over-expression on the survival and growth of glioma cells after detachment from the culture was determined. Our data revealed that GBM cells (with their low PAX6 levels) survived the detachment procedure well. However, PAX6 over-expression attenuated GBM cell recovery of growth after detachment-induced stress. Importantly, intracellular reactive oxygen species (ROS) levels increased following cell detachment and that PAX6 over-expressing cells retained higher level of ROS than control cells. This may be partially responsible for the impaird growth rate after cell detachment. Addition of anti-oxidant improved the cell viability of PAX6 over-expressing cells, but did not restore their ability to proliferate. To survive, GBM cells must resist oxidative stress in the necrotic zone as well as the intracellular ROS generated during detachment. Since PAX6 over-expression in low PAX6-expressing glioma cells attenuated cell survival and growth after detachment, these results suggest that a reduced PAX6 expression may be a molecular trait that gives glioma cells a real selection advantage over other cell types to survive in stressful conditions, thus resulting in expansion of their population.
On Wilde's theory of risk homeostasis

This paper is a comment on The Theory of Risk Homeostasis: Implications for Safety and Health by Gerald J. S. Wilde. Language: en
A TERATOLOGICAL TRIO

For those interested in teratology I wish to record three instances of malformations of the antennae of Coleoptera. The beetles presenting these have been kindly given to me by Mr. W. Simpson, an energetic and observant yound collector of this city.
Lessons learned from community-based cancer screening intervention research.

Behaviors associated with cancer screening have been the focus of intensive research over the past 2 decades, primarily in the form of intervention trials to improve screening based in both clinical and community settings. Meta-analyses and literature reviews have synthesized and organized the resulting literature. From the accumulated work, this review distilled lessons learned from cancer screening intervention research in community settings. The authors posed the question, “What do we know about the development of effective community-based interventions (the level of good over harm achieved in real-world conditions)?” Framed around the concept of focal points (the simultaneous combination of target population, behavioral objective, and setting for an intervention), 13 lessons were derived. One lesson was cross-cutting, and the other lessons addressed the three focal-point components and the major intervention categories (access-enhancing strategies, mass media, small media, one-on-one and small-group education, and combinations of these categories). To build more systematically on existing research, recommendations are made for new directions in basic behavioral and intervention research. Cancer 2004. © 2004 American Cancer Society.
Current issues and future directions in simulation-based training in North America

A number of emerging challenges including globalization, economic pressures and the changing nature of work has combined to create a business environment that demands innovative, flexible training solutions. Simulations are a promising tool for creating more realistic, experiential learning environments to meet these challenges. Unfortunately, the current literature on simulation-based training paints a mixed picture as to the effectiveness of simulations as training tools, with most of the previous research focusing on the specific technologies used in simulation design and little theory-based research focusing on the instructional capabilities or learning processes underlying these technologies. This article examines the promise and perils of simulation-based training, reviews research that has examined the effectiveness of simulations as training tools, identifies pressing research needs, and presents an agenda for future theory-driven research aimed at addressing those needs.
Dopamine: mesocortical vs nigrostriatal uptake in isolated fighting mice and controls

Acute isolation-induced fighting in mice produced a striking 'dose-dependent' increase in Km and Vmax for DA uptake in mesocortical nerve endings (synaptosomes) but no significant changes for these uptake constants in nigrostriatal terminals. The selective response of the mesocortical system to fighting is similar to that reported for other affective paradigms and stress. Several controls were carried out simultaneously to sort out neurotransmitter responses due to aggressive behavior from those due to secondary behaviors which accompany fighting. Non-significant or borderline increases in Km and Vmax for mesocortical DA uptake were noted in (i) animals permitted to witness fighting but prevented from participating, (ii) those subjected to the stress of a mock-fighting situation and (iii) animals simply handled by the investigator, but in no case were the control values increased to the magnitude produced by fighting. (iv) Group-housed animals showed no mesocortical response when placed in the arena with isolated mice. They retired to the corners and would not fight. These mild to negative control findings indicate that the marked cortical responses seen in the fighting animals are not due to (i) anticipation of the fight, (ii) physical stress and motor activity, (iii) placing the animals in the combat arena, or (iv) isolation. Significant changes in nigrostriatal DA reactivity were noted only in the isolated animals prevented from fighting where there was a decrease in Km and Vmax for DA uptake.
INVIOLABLE LAWS, IMPOSSIBLE TO KEEP: ORWELL ON EDUCATION, SUFFERING, AND THE LOSS OF CHILDHOOD

Scholars from multiple disciplines have commented on the divided nature of childhood as a historical construction: a period of life to be valued in itself as well as a means to adulthood. In this essay, James Stillwaggon considers George Orwell's “Such, Such Were the Joys,” an autobiographical account of his childhood education, as a site of conflicting views on childhood. On analyzing Orwell's own conflicted memories, Stillwaggon describes education as a process of suffering the loss of childhood and inquires into the adult subject's maintenance of such loss in memory. Drawing from Deborah Britzman and Jacques Lacan, Stillwaggon suggests that the adult subject's maintenance of a childhood state irrevocably lost is a melancholic identification against the transformative powers of the school.
An Integrated Experimental/Numerical Study of the Bubbly Wake Behind a Cavitating Hydrofoil

Since cavitation is often unavoidable, it is crucial to understand how fluid-handling machinery operates under cavitating conditions. The purpose of this research is to investigate two-phase flow structure in the wake of a hydrofoil undergoing unsteady partial cavitation using an integrated experimental and numerical approach. Experiments were conducted systematically in the high-speed water tunnel at the St. Anthony Falls Laboratory to capture the characteristics of the bubbly wake induced by unsteady partial cavitation. The velocity and bubble information were obtained using a TSI color burst LDA/PDA system with a beam splitter and IFA processor. A nominal sampling period of 30 seconds per coordinate point was chosen for the collection of all data sets of LDV measurements. Since the LDV data rate changes with position, the collection period was also controlled by the upper limit of samples, which were 3,000 samples per point. In order to get enough samples, a nominal sampling period of 180 seconds per coordinate point was selected for PDA measurements and 10,000 samples were used as the upper limit. The actual number of samples for each PDA measurement location was between 5,000 and 10,000 with an average data rate of 40 Hz. The averaged bubble size measured in the wake is obtained to be 240 ∼ 300 microns and the estimated maximum void fraction in the wake being in the order of one percent. A virtual single-phase natural cavitation model with the effect of incondensable gas was developed and implemented to better understand the cavitating wake physics. A number of parameters, such as time-averaged velocity distributions both on suction side of the hydrofoil and in the wake, spectral characteristics of unsteady lift oscillations etc., were computed and found in very good agreement with experimental data (Qin 2004), indicating this model can capture the main physics of unsteady cavitating flow. It was also found that the peak of time-averaged incondensable gas in the wake is in the order of one percent, indicating that the majority of vapor bubbles were condensed to water in the wake and hence the bubbles in the wake of unsteady cavitation are mainly gas bubbles.Copyright © 2005 by ASME
Doxorubicin Selectively Inhibits Brain Versus Atrial Natriuretic Peptide Gene Expression in Cultured Neonatal Rat Myocytes

Doxorubicin is an antineoplastic agent with significant cardiotoxicity. We examined the effects of this agent on the expression of the natriuretic peptide (NP) genes in cultured neonatal rat atrial myocytes. Doxorubicin suppressed NP secretion, steady-state NP mRNA levels, and NP gene promoter activity. In each instance, brain NP (BNP) proved to be more sensitive than atrial NP (ANP) to the inhibitory effects of the drug. ICRF-187 and probucol reversed the inhibition by doxorubicin of ANP mRNA accumulation and ANP gene promoter activity while exerting no effect on BNP mRNA levels or promoter activity. This represents the first identification of the NP genes as targets of doxorubicin toxicity in the myocardial cell. This inhibition operates predominantly at a transcriptional locus and has more potent effects on BNP versus ANP secretion/gene expression. Measurement of BNP secretion/gene expression may provide a sensitive marker of early doxorubicin cardiotoxicity.
Sources of cells that contribute to atherosclerotic intimal calcification: an in vivo genetic fate mapping study.

Aims Vascular cartilaginous metaplasia and calcification are common in patients with atherosclerosis. However, sources of cells contributing to the development of this complication are currently unknown. In this study, we ascertained the origin of cells that give rise to cartilaginous and bony elements in atherosclerotic vessels. Methods and results We utilized genetic fate mapping strategies to trace cells of smooth muscle (SM) origin via SM22α-Cre recombinase and Rosa26-LacZ Cre reporter alleles. In animals expressing both transgenes, co-existence within a single cell of β-galactosidase [marking cells originally derived from SM cells (SMCs)] with osteochondrogenic (Runx2/Cbfa1) or chondrocytic (Sox9, type II collagen) markers, along with simultaneous loss of SM lineage proteins, provides a strong evidence supporting reprogramming of SMCs towards osteochondrogenic or chondrocytic differentiation. Using this technique, we found that vascular SMCs accounted for ∼80% of Runx2/Cbfa1-positive cells and almost all of type II collagen-positive cells (∼98%) in atherosclerotic vessels of LDLr−/− and ApoE−/− mice. We also assessed contribution from bone marrow (BM)-derived cells via analysing vessels dissected from chimerical ApoE−/− mice transplanted with green fluorescence protein-expressing BM. Marrow-derived cells were found to account for ∼20% of Runx2/Cbfa1-positive cells in calcified atherosclerotic vessels of ApoE−/− mice. Conclusion Our results are the first to definitively identify cell sources attributable to atherosclerotic intimal calcification. SMCs were found to be a major contributor that reprogrammed its lineage towards osteochondrogenesis. Marrow-derived cells from the circulation also contributed significantly to the early osteochondrogenic differentiation in atherosclerotic vessels.
Gopher Snake Searching Cliff Swallow Nests in East Central Utah

ABSTRACT. We report details of a serendipitous encounter in July 2010 with a gopher snake (Pituophis catenifer) hunting in the mud nests of Cliff Swallows (Petrochelidon pyrrhonota). The swallow nests occurred beneath a deeply overhung sandstone cliff ledge in a box canyon of Ferron Creek in the shale deserts near Ferren, Emery County, Utah. The inaccessibility of the nests and the movement of the snake to and through them attest to both the extraordinary climbing ability of the gopher snake and the nest site selection and nest construction ability of the swallows.
Smart sensor demonstration payload

This paper discusses smart sensors which are a critical element to monitoring, control, and evaluation processes as needed to support ground based testing for rocket engine test. Sensor applications involve tens to thousands of sensors; their reliable performance is critical to achieve overall system goals. These system engineering trade-offs include the familiar constraints of power, signal conditioning, cabling, reliability, and mass, and now include considerations such as spectrum allocation and interference for wireless sensors.
Probing DNA clamps with single-molecule force spectroscopy

Detailed mechanisms of DNA clamps in prokaryotic and eukaryotic systems were investigated by probing their mechanics with single-molecule force spectroscopy. Specifically, the mechanical forces required for the Escherichia coli and Saccharomyces cerevisiae clamp opening were measured at the single-molecule level by optical tweezers. Steered molecular dynamics simulations further examined the forces involved in DNA clamp opening from the perspective of the interface binding energies associated with the clamp opening processes. In combination with additional molecular dynamics simulations, we identified the contact networks between the clamp subunits that contribute significantly to the interface stability of the S.cerevisiae and E. coli clamps. These studies provide a vivid picture of the mechanics and energy landscape of clamp opening and reveal how the prokaryotic and eukaryotic clamps function through different mechanisms.
A high-fibre bean-rich diet versus a low-carbohydrate diet for obesity

Background High-fibre and low-carbohydrate diets may enhance satiety and promote weight loss. We compared a diet rich in beans aiming to increase dietary fibre and promote weight loss with a low-carbohydrate diet in a randomised controlled trial to assess effect and tolerability of the high-fibre bean-rich diet. Methods and results One hundred and seventy-three women and men, with a mean body mass index of approximately 36 kg m(-2) (one-fifth with diabetes type 2) were randomised to a high-fibre bean-rich diet that achieved mean (SD) fibre intakes of 35.5 (18.6) g day(-1) for women and 42.5 (30.3) g day(-1) for men, or a low-carbohydrate diet. Both diets were induced gradually over 4 weeks and included a 3-day feeding phase. Among 123 (71.1%) completers at 16 weeks, mean (SD) weight loss was 4.1 (4.0) kg in the high-fibre versus 5.2 (4.5) kg in the low-carbohydrate group [difference, 1.1 kg, 95% confidence interval (CI) = -2.6 to -0.5; P = 0.2], with results similar to the intent-to-treat population. Low-density lipoprotein (LDL)-cholesterol levels decreased with the high-fibre diet (difference in LDL-cholesterol versus low-carbohydrate diet, 0.2 mmol L(-1) , 95% CI = 0.01-0.44 mmol L(-1) ; P = 0.045), as did total cholesterol (P = 0.038), whereas changes in other lipids and glucose did not differ. After 52 weeks, the low-carbohydrate (n = 24) group tended to retain weight loss better than the high-fibre group (P = 0.06), although total cholesterol remained lower with the bean-rich diet (P = 0.049). Conclusions A high-fibre bean-rich diet was as effective as a low-carbohydrate diet for weight loss, although only the bean-rich diet lowered atherogenic lipids.
GPS-derived total electron content response for the Bastille Day magnetic storm of 2000 at a low mid-latitude station

First steps toward the development of a vertical Total Electron Content (VTEC) storm-time correction empirical ionospheric model, equivalent to the STORM model for the peak concentration of the F2 region (Araujo-Pradere and Fuller-Rowell, 2002, Araujo-Pradere et al ., 2002), are currently in progress in the NOAA’s Space Environment Center (SEC). The program to obtain VTEC, the SEC’s Win TEC Project (Anghel and Codrescu, 2002), use the RINEX (Receiver Independent Exchange format) files to derive the vertical TEC from the delay of the Global Position System (GPS) signals. With a maximum Dst of –287.6 (maximum a p = 400), the storm of July 2000, known as the Bastille Day storm, has been one of the most intense perturbations in the present solar cycle. The response of the TEC at a low mid-latitude station, as obtained from the delay in code and phase of the GPS signals, is analyzed for this storm. The vertical TEC at ccv3 (Cape Canaveral, Florida, latitude 28.46 N, longitude 279.45 E) suffered a sudden increase, over 250% with respect to quiet conditions, for the first day of the storm, followed by a sharp negative gradient, and a slow recovery. The picture is further complicated by the presence of very steep gradients, responsible for the degradation of the GPS positioning accuracy.