cssi/SciSciGPT-SciSciNet huggingface dataset:
Tumor expressed PTHrP facilitates prostate cancer-induced osteoblastic lesions

Expression of parathyroid hormone-related protein (PTHrP) correlates with prostate cancer skeletal progression; however, the impact of prostate cancer-derived PTHrP on the microenvironment and osteoblastic lesions in skeletal metastasis has not been completely elucidated. In this study, PTHrP overexpressing prostate cancer clones were stably established by transfection of full length rat PTHrP cDNA. Expression and secretion of PTHrP were verified by western blotting and IRMA assay. PTHrP overexpressing prostate cancer cells had higher growth rates in vitro, and generated larger tumors when inoculated subcutaneously into athymic mice. The impact of tumor-derived PTHrP on bone was investigated using a vossicle co-implant model. Histology revealed increased bone mass adjacent to PTHrP overexpressing tumor foci, with increased osteoblastogenesis, osteoclastogenesis and angiogenesis. In vitro analysis demonstrated pro-osteoclastic and pro-osteoblastic effects of PTHrP. PTHrP enhanced proliferation of bone marrow stromal cells and early osteoblast differentiation. PTHrP exerted a pro-angiogenic effect indirectly, as it increased angiogenesis but only in the presence of bone marrow stromal cells. These data suggest PTHrP plays a role in tumorigenesis in prostate cancer, and that PTHrP is a key mediator for communication and interactions between prostate cancer and the bone microenvironment. Prostate cancer-derived PTHrP is actively involved in osteoblastic skeletal progression.
Lead inhibits the voltage-activated calcium current of Aplysia neurons.

SUMMARY Lead is a potent and reversible inhibitor of the voltage-dependent calcium current of Aplysia neurons in a concentration range (l-1000 PM) similar to that which elicits toxic effects in man. The threshold for inhibition is 1 PM and the dissociation constant about 90 PM. The inhibition is due to reduction of the peak current amplitude, and not due to alteration of the voltage dependence of the activation or inactiva- tion. The effect of lead is specific to the calcium current as the delayed rectifier potassium and the sodium currents are not affected by concentrations of lead (200 PM) which give near-maximal inhibition. The cal- cium current of Aplysia neurons appears similar to the current flowing through the mammalian L-type calcium channel. This suggests that inhibition of the investigated calcium channel may contribute to the toxic effects of lead in mammals.
Crude protein and supplemental dietary tryptophan effects on growth and tissue neurotransmitter levels in the broiler chicken.

Indian River male broiler chickens growing from 7 to 28 d of age were fed on diets containing 120, 210 and 300 g crude protein/kg diet and 0, 1.67 or 16.7 g added tryptophan (TRP)/kg diet. The hypothesis tested was that crude protein levels and TRP would affect both growth and neurotransmitter metabolism. Heart, brain and pancreatic neurotransmitter (noradrenaline (NA), dopamine (DA), serotonin (5-HT) and 5-hydroxy-indole-3-acetic acid (5-HIAA)) concentrations were determined by HPLC separation and electrochemical detection. Malate dehydrogenase (2-oxoglutarate decarboxylating) (NADP+) (MDH(NADP+) ; EC 1.1.1.40), isocitrate dehydrogenase (NADP+) (ICD(NADP+) ; EC 1.1.1.42) and aspartate aminotransferase (AAT ; EC2.6.1.1) activities were also measured. Supplemental TRP decreased growth and feed intake. Increasing dietary crude protein decreased MDH(NADP +), but increased (ICD(NADP +) and AAT activities. Additional dietary TRP decreased MDH(NADP +) activity, but had no effect on other enzyme activities. Cardiac NA concentrations were directly related to dietary crude protein levels while pancreatic levels were inversely related. An increase in dietary crude protein decreased both brain NA and DA. Supplemental dietary TRP increased both 5-HIAA and 5-HT. Changes in feed intake caused by different levels of both dietary crude protein and TRP are accompanied by altered levels of neurotransmitters. The present study indicates that much larger amounts of TRP are required to make simultaneous changes in feed intake and neurotransmitters.
Efficacy of transpupillary thermotherapy (TTT) in the treatment of occult subfoveal choroidal neovascularization in age-related macular degeneration

Purpose. To determine the efficacy of transpupillary thermotherapy (TTT) in the treatment of occult subfoveal choroidal neovascularization in patients with age-related macular degeneration (ARMD). ...
The superior epigastric(RECTUS ABDOMINIS) muscle perforator flap.

The concept of the muscle perforator flap has been proven valid repeatedly, now including the territories of almost all known musculocutaneous flap donor sites. It is well known that the rectus abdominis muscle has a dual vascular supply from 2 dominant source vessels. Yet only the deep inferior epigastric vessels have been used for a relatively long time to supply the well-known D1EP muscle perforator flap. Logically, as previously predicted in this journal, a muscle perforator flap utilizing the cephalic pedicle to the rectus abdominis muscle should also be possible. This prophecy has now become a reality in this first report where a superior epigastric RECFUS ABDOMINIS muscle perforator flap was used successfully as a local flap to close a chest defect.
Nanoparticle Deposition and Convective Transport in Microchannel Heat Exchanger Systems

In the absence of dispersants, surfactants or other deposition inhibiting techniques, nanoparticles contained in a base fluid could potentially deposit on channel walls. Nanoparticle layering has been shown to impact heat transfer coefficient, alter hydrodynamic characteristics including viscosity and flow regime, and influence the onset of boundary layers. The rate of deposition is a function of nanoparticle size, heat flux, microchannel hydraulic diameter, fluid velocity, temperature, adhesion properties and volume fraction. This paper presents an analytical investigation of nanoparticle deposition in microchannel heat exchanger systems. The objective of this study is to correlate the rate of deposition with nanoparticle size, microchannel hydraulic diameter, heat flux and volume fraction for transient flow conditions in which Brownian diffusion and thermophoresis are appreciable slip mechanisms of nanoparticle transport. A two-component four-equation nonhomogeneous thermal equilibrium model for mass, momentum and energy in nanofluids that includes nanoparticle mass transport into the channel walls is used in this analysis. An analytical model representing the transient distribution of nanoparticles in a channel is proposed.Copyright © 2011 by ASME
A survey of graph laplacians

Let G be a graph on n vertices. Its Laplacian is the n-by-n matrix L(G)−D(G)−A(G), where D(G) is the diagonal matrix of vertex degrees and A(G) is the (0,1)-adjacency matrix of G. This article surveys recent results on graph Laplacians.
Flow film boiling from a sphere and a horizontal cylinder embedded in porous medium

This paper focuses on the problem of flow film boiling from a body embedded in a porous medium. Two body geometries are investigated thoroughly: a horizontal cylinder and a sphere. The theoretical model relies on the Brinkman-extended flow model to describe the flow inside the thin vapor layer occupying the neighborhood near the heated surface. Unlike the counterpart of the present problem in classical fluids, it was found that the flow reversal does not occur inside the vapor layer. The effects of subcooling, incoming liquid flow velocity, and Darcy number on the heat and fluid flow characteristics of the problem are thoroughly documented. Finally, the overall and local heat-transfer rates from the surface to the fluid are determined for a wide range of the problem parameters and reported with the help of the conduction referenced Nusselt number. Nomenclature A = dimensionless group, Eq. (.17) B = dimensionless group, Eq. (18) cosh(jc) = hyperbolic cosine of x coth(x) = hyperbolic cotangent of x csch(;c) = hyperbolic cosecant of x D = diameter of sphere or cylinder Da = modified Darcy number, Eq. (9) h — local heat-transfer coefficient hfg = latent heat of vaporization including the effects
Sortase-mediated modification of αDEC205 affords optimization of antigen presentation and immunization against a set of viral epitopes

A monoclonal antibody against the C-type lectin DEC205 (αDEC205) is an effective vehicle for delivery of antigens to dendritic cells through creation of covalent αDEC205–antigen adducts. These adducts can induce antigen-specific T-cell immune responses or tolerance. We exploit the transpeptidase activity of sortase to install modified peptides and protein-sized antigens onto the heavy chain of αDEC205, including linkers that contain nonnatural amino acids. We demonstrate stoichiometric site-specific labeling on a scale not easily achievable by genetic fusions (49 distinct fusions in this report). We conjugated a biotinylated version of a class I MHC-restricted epitope to unlabeled αDEC205 and monitored epitope generation upon binding of the adduct to dendritic cells. Our results show transfer of αDEC205 heavy chain to the cytoplasm, followed by proteasomal degradation. Introduction of a labile dipeptide linker at the N terminus of a T-cell epitope improves proteasome-dependent class I MHC-restricted peptide cross-presentation when delivered by αDEC205 in vitro and in vivo. We also conjugated αDEC205 with a linker-optimized peptide library of known CD8 T-cell epitopes from the mouse γ-herpes virus 68. Animals immunized with such conjugates displayed a 10-fold reduction in viral load.
The Performance of a Bare Machine Email Server

Bare machine applications run directly over the hardware without using an operating system or a hard disk. This paper studies the performance of a bare machine email server whose design and implementation is based on several novel architectural features with a view towards optimizing performance. The results are compared with those for the AxiGen and ShareMailPro email servers, and a lean Java-based email server prototype running on Windows whose application-level operation closely matches that of the bare machine email server. For 80,000 emails in a LAN environment, the bare Machine server processing time is approximately 2 times faster than a Java-based server, and 2.4 times faster than the AxiGen server. For 5,500 emails in a WAN environment, the bare machine server performed at least 1.8 times faster than the Java-based and ShareMailPro servers. The results indicate that the bare machine email server outperforms the conventional email servers in LAN and WAN environments, and demonstrate the capability of using bare machines to build high-performance email servers.
Living with Grandma: A Grandfamily Study.

In recent years, large numbers of grandparents have become full-time surrogate parents to their grandchildren. These grandparents and grandchildren often have serious problems that may require assi...
Compact modeling of environmentally induced radiation effects on electrical devices

This paper presents the feasibility of formalizing a compact modeling methodology for environmentally induced radiation effects, and of implementing that methodology into the Paragon compact modeling tool. For demonstration purposes, the paper focuses on two specific radiation effects implemented in a MOSFET device model. These two effects were chosen in order to illustrate two differing forms of model development. The first form takes existing device models and modifies the equations and/or variables already existing within that model to achieve the required results (behavioral modification). The second form adds completely new equations and variables to existing device models (behavioral augmentation). The MOSFET (1) threshold voltage shift due to total ionizing dosage (TID) and (2) leakage current increase due to TID, are two major device effects that fulfill both of these requirements. Voltage shift and leakage current are critical design issues in rad-hard electronics and space environments. The threshold voltage shift effects are implemented through the modification of device model equations, while leakage current increases are implemented with added behavioral macros to the model topology, thus fulfilling the second requirement. The use of the modified compact MOSFET model is illustrated in the simulation of an op-amp based filter. Gain and frequency shifts can be observed and compared as the circuit absorbs differing amounts of TID.
Proteasomal Regulation of the Hypoxic Response Modulates Aging in C.elegans

The Caenorhabditis elegans von Hippel–Lindau tumor suppressor homolog VHL-1 is a cullin E3 ubiquitin ligase that negatively regulates the hypoxic response by promoting ubiquitination and degradation of the hypoxic response transcription factor HIF-1. Here, we report that loss of VHL-1 significantly increased life span and enhanced resistance to polyglutamine and b-amyloid toxicity. Deletion of HIF-1 was epistatic to VHL-1, indicating that HIF-1 acts downstream of VHL-1 to modulate aging and proteotoxicity. VHL-1 and HIF-1 control longevity by a mechanism distinct from both dietary restriction and insulin-like signaling. These findings define VHL-1 and the hypoxic response as an alternative longevity and protein homeostasis pathway.
Long-term psychosocial adaptation of children who survive burns involving 80% or greater total body surface area

Objective To examine the psychosocial adjustment of survivors of massive pediatric burn injuries, the change in adjustment across time, and the impact on parents. Background Patients/parents were assessed at regular intervals postburn using standardized tests of adjustment. Patients who could not be included in standardized longitudinal assessments were administered questionnaires by mail/telephone. Methods The Child Behavior Checklist, the Teacher Report Form, the Youth Self Report Form, and the Parenting Stress Index were utilized to assess adjustment. Results On all objective measures, the group of survivors and their parents were within normal limits. Adjustment neither improved nor deteriorated over time. Conclusion Children who survive massive burn injuries can achieve positive psychosocial adaptation.
From clausewitz to delbrück and hintze: Achievements and failures of military history

(1980). From clausewitz to delbruck and hintze: Achievements and failures of military history. Journal of Strategic Studies: Vol. 3, Strategy and The Social Sciences, pp. 11-20.
The effects of maternal hypoxia and hyperoxia upon the neonatal pulmonary vasculature.

The fetal and newborn pulmonary artery has thickened media by comparison to that of the older infant. In this study we investigated the proposition that chronic maternal hypoxia during the latter part of gestation might induce further thickening of the neonatal pulmonary artery media. Relative medial thickness was determined by the ratio of the arterial media to external diameter. The mean ratio of small pulmonary arteries of progeny of hypoxic mothers was significantly thicker in each size group between 50 and 150 microns as compared to those born to mothers who spent their gestation in air or hyperoxic environments. Medial hypertrophy was most pronounced in the smaller arteries of the hypoxic group; no intersize variations were found between the control or hyperoxic groups. Medial thickness decreased in all arteries through 2 weeks of age; this decrease was greatest in control and hyperoxic arteries. The possible relationship of hypertrophied pulmonary arterial media and abnormally increased neonatal pulmonary vascular resistance is discussed.
Magnetotelluric evidence for a brittle‐ductile transition, peninsular ranges batholith, southern California?

A magnetotelluric traverse of the Peninsular Ranges in southern California has revealed a pervasive zone of lower resistivity beginning at a uniform depth of 10 km and extending to depths of 60–90 km. Resistivities above 10 km depth are similar to those found in batholiths; very high values correspond to outcrops of crystalline basement. Because seismicity below 11–12 km is sparse, others have concluded that the brittle-ductile transition is shallow beneath the range. The zone of low resistivity in the lower crust corresponds well to the ductile region, and we conclude that the lower values are caused by fluids trapped below the transition. Because the range has experienced vertical uplifts during the Pliocene era and the top of the low resistivity zone is flat, the present brittle-ductile transition must have been formed in the last 5 M.y. A possible source for the fluids is the rift to the east in the Salton Trough.
Morphology of the kidney in a nectarivorous bird, the Anna's hummingbird Calypte anna

The kidneys of Anna's hummingbird (Calypte anna) differ in several significant ways from those of other birds that have been examined. The kidneys of this nectarivore contain very little medullary tissue; 90% of the total volume of the kidneys is cortical tissue, with medulla accounting for only an additional 2%. More than 99% of the nephrons are the so-called ‘reptilian type’), which lack the loop of Henle. The few looped (‘mammalian type’) nephrons are incorporated into only a few medullary cones per kidney. The loopless nephrons are similar to those of other birds. However, the looped nephrons differ in that they lack the thin descending limb of the loop of Henle, which is found in other birds and is thought to play an important role in the countercurrent multiplier system in the avian kidney. Instead, the cells of the nephron segment following the pars recta of the proximal tubule resemble those of the thick ascending limb, with the large populations of mitochondria that are typical of transporting epithelia and no reduction in cell height. The absence of a descending thin limb in Anna's hummingbird is not necessarily a correlate of the hummingbird's liquid diet, because thin limbs have been documented in the kidneys of two other hummingbird species, the rufous hummingbird (Selasphorus rufus) and the broad-tailed hummingbird (Selasphorus platycercus). The functional correlates of the unique renal morphology in Anna's hummingbird warrant further study.
Tack and Related Properties of Isopropyl Azodicarboxylate Modified Polybutadiene

Abstract Polybutadiene has been modified by reaction with isopropyl azodicarboxylate (IAD). The reaction is quite efficient, resulting in a structure in which there are pendant hydrazoester groups dangling from the BR backbone. The Tg's of the modified polymers increase with IAD content. Eventually, at high levels of modification, two Tg's are observed, indicating the presence of two phases. Infrared analysis indicates the presence of H-bonding within the modified polymers. The green strength of these polymers increases with IAD content, whereas, tack passes through a maximum with increasing IAD level. At low IAD levels, the increase in green strength is attributed to increased polar interactions between chains, whereas, at higher IAD levels, there appears to be an additional contribution from strain-induced phase separation (see Reference 1). This type of behavior is favorable for high tack. The initial increase in tack as IAD is incorporated is due, in part, to the enhanced green strength. A more import...
Human-inspired motion primitives and transitions for bipedal robotic locomotion in diverse terrain

SUMMARY In this paper, a control design approach is presented, which uses human data in the development of bipedal robotic control techniques for multiple locomotion behaviors. Insight into the fundamental behaviors of human locomotion is obtained through the examination of experimental human data for walking on flat ground, upstairs, and downstairs. Specifically, it is shown that certain outputs of the human, independent of locomotion terrain, can be characterized by a single function, termed the extended canonical human function. Through feedback linearization, human-inspired locomotion controllers are leveraged to drive the outputs of the simulated robot, via the extended canonical human function, to the outputs from human locomotion. An optimization problem, subject to the constraints of partial hybrid zero dynamics, is presented that yields parameters of these controllers that provide the best fit to human data while ensuring stability of the controlled bipedal robot. The resulting behaviors are stable walking on flat ground, upstairs, and downstairs—these three locomotion modes are termed ‘motion primitives’. A second optimization is presented, which yields controllers that evolve the robot from one motion primitive to another—these modes of locomotion are termed ‘motion transitions’. A directed graph consisting these motion primitives and motion transitions has been constructed for the stable motion planning of bipedal locomotion. A final simulation is given, which shows the controlled evolution of a robotic biped as it transitions through each mode of locomotion over a pyramidal staircase. Copyright © 2013 John Wiley & Sons, Ltd.
Further studies of methamphetamine-induced insulin release.

Abstract In the present study we have evaluated factors that modify methamphetamide-induced insulin secretion. While methamphetamine stimulates insulin secretion in intact rats and mice, it stimulates insulin secretion in vitro only from mouse pancreas. Related drugs such as d -amphetamine, methylphenidate, and tranylcypromine also stimulate insulin secretion in intact rats. Methamphetamine-induced insulin secretion is not altered by α-receptor antagonists or ganglionic blocking agents, but is reduced by β-receptor antagonists. Insulin secretion in response to methamphetamine is significantly increased in the hyperthyroid state and decreased in the hypothyroid state. Chronic methamphetamine administration results in a reduction in the insulin secreted in response to this agent.
Using IR vibrations to quantitatively describe and predict site-selectivity in multivariate Rh-catalyzed C–H functionalization

Achieving selective C–H functionalization is a significant challenge that requires discrimination between many similar C–H bonds. Yet, reaction systems employing Rh2(DOSP)4 and Rh2(BPCP)4 were recently demonstrated to afford high levels of selectivity in the C–H insertion of carbenes into toluene-derived substrates. Herein, we explore the origin of this selectivity through a systematic analysis of substrate and reagent features that alter levels of selectivity from 20 : 1 to 1 : 610 for secondary (or tertiary)-to-primary benzylic C–H functionalization of toluene derivatives. Describing this variation using infrared vibrations and point charges, we have developed a mathematical model from which are identified features of the systems that determine levels of site-selectivity and are applied as predictive factors to describe the selectivity behavior of new substrate/reagent combinations.
Cutaneous Lupus Erythematosus

Lupus erythematosus is an autoimmune disease that presents with either cutaneous or systemic findings. Cutaneous lupus is divided into lupus-specific and -nonspecific skin disease with the former including the acute cutaneous lupus, subacute cutaneous lupus, and chronic cutaneous lupus subtypes. Patients with cutaneous lupus must be evaluated regularly for systemic lupus erythematosus. Treatment for cutaneous lupus erythematosus includes sun exposure avoidance, topical therapies, and oral immunosuppressants. This chapter will review the epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment of cutaneous lupus erythematosus.
THE ASSOCIATION OF AN HLA‘ASTHMA‐ASSOCIATED’ HAPLOTYPE AND IMMEDIATE HYPERSENSITIVITY IN FAMILIAL ASTHMA

SUMMARY Fifty-seven members from ten families in which one parent and at least one child have asthma were studies with dilutional skin tests and RAST to grass pollens after determination of HLA haplotypes. We found no direct evidence for linkage of a hypothetical asthma locus with HLA or for a significant association of asthma with HLA haplotypes. Linkage between the HLA loci and a gene or genes which allow for the expression of clinical asthma could neither be proven nor disproven due to the small sample size. All of the asthmatic children had positive dilutional skin tests and RAST, suggesting that atopic asthma may be genetically controlled by the HLA chromosome (chromosome 6). Nonetheless, determination of the histocompatibility antigens can increase the value of predictive risk analysis for asthma. Such a determination may be important in the early identification of a child born to a family with atopic asthma.
Assessing the Difficulty Level of Math Board Games for Young Children

This study investigated differences in difficulty among three types of math board games used as curricular materials in some preschool classrooms. Difference in performance between low- and middle-income children on the three types of games was also explored. Children drew cards containing one to five large dots; they then attempted to place an equivalent number of counters on a bingo-type board or move an equivalent number of spaces along a short or a long path. The sample consisted of 86 children of diverse race/ethnicity and socioeconomic status, age 3 to 5 years, enrolled in a licensed, urban preschool in the Midwest United States. A mixed-methods design was employed. Repeated measures ANOVA and post hoc testing showed that children scored significantly higher (p < .0001) on grid and short-path games than on longer path games. Head Start children scored significantly lower than middle-income children at age 3, but not at age 4 or 5. Qualitative data revealed mathematical behaviors that indicate when a...
Secondary Structure of Proteins Through Circular Dichroism Spectroscopy

CIRCULAR DICHROISM SPECTROSCOPY .........•.....••......• • 147 Technique .. ...... . . . . .. . . . . . . . . . . . . . . . . . . ...... .... ........ . . . .... 147 Spectrometers.... . . . . . . .... . . . . . . ........ . ...... . . . . . . . . . . . . .... . . . .... . . . ...... . . . . ...... . . . ..... 148 Concentration and Pathlength.. . . . . . . ...... ..... . . . ...... .... ..... . . . .. . . . . ....... .... . . . ... . . . . 149 Noise .. .... . . . . ... . . . . . ....... . . . . . . . . . . . . ... . . ........ ........ ........ . ...... 150 METHODS OF ANALySIS 151 Information Content and Constraints .... . . . . . . . . . . .. . . . .... . ... . . . . ...... ... . ........ . . . . . ... . . 151 Circular Dichroism Spectra for Pure Secondary Structures ...... . . . . . .. . . . . . ... . . . . . . . . . . .. . . . . . 152 Reference Circular Dichroism From Proteins of Known Secondary Structure . . . .... . . . . 154 APPLICATIONS . ......... ..... . . . . . .... . . . . .. . . . ... 159 Analysisfor Secondary Structure......... . . . ..... . . . .. . . . . . ....... .... . . . ....... 159 Proteins With Denatured Circular Dichroism . . . . ..... .. ....... . . . . . . . . .... . 160 Changes in Secondary Structure on Ligand Binding ..... . . . . . . . . . . . . . ... . . . ..... . . ......... 161 Changes in Secondary Structure With Solvent Variation ......... ..... . . ..... . . ..... . ..... . . . ..... 162 Changes in Secondary Structure on Protein Denaturation.... ........ . . . ...... . . .. . . . . . 163 CONCLUSIONS.... ...... ....... ........ 164
An overview of state efforts to improve transfusion medicine. The New York state model.

Abstract Objective.—New York State must provide effective oversight for more than 400 facilities that provide blood services, ensuring the safety of transfusion recipients. Program Structure.—Oversight is based on educated, trained program staff; a council of transfusion medicine experts; regulations governing laboratories and blood banking services; proficiency testing; requirements for reporting transfusion-related errors and incidents; tracking collection, testing, and disposition of all blood; inspections; partnership with the Food and Drug Administration; and investigation of incident reports. Policy letters and guidelines (eg, umbilical cord blood, transfusion-associated infections, intraoperative blood recovery) supplement regulations. Observations.—Standards are maintained through education by a responsive, proactive oversight program. Areas warranting stricter regulation or supplemental educational guidelines are identified by periodic assessment of standards of practice and review of reported in...
Replication and Dissemination of a Cancer Education Model for African American Women

The purpose of this study was to investigate the effectiveness of replicating an evidence-based model, the Witness Project, for increasing breast and cervical cancer screening with African American women in a variety of locations and organizations in the United States. The quantitative and qualitative methods included a cadre of process and outcome measures to evaluate the effectiveness of the four-phase replication process. The intervention was replicated in 25 sites with 401 volunteers, delivering cancer education and screening programs to over 10,000 women. Key components and criteria of successful replication were established, and preliminary screening outcomes demonstrated a 43.4% increase in mammography in women aged 40 and older. This study demonstrates that the Witness Project model can be effectively replicated, that the replication process can be standardized, and that the replication sites were able to obtain positive screening results comparable to the original intervention outcomes. The model was not able to be effectively replicated with just the "turnkey" toolbox approach, but required additional technical assistance.
Targeting DNA mismatches with rhodium metalloinsertors

DNA has been exploited as a biological target of chemotherapeutics since the 1940s. Traditional chemotherapeutics, such as cisplatin and DNA-alkylating agents, rely primarily on increased uptake by rapidly proliferating cancer cells for therapeutic effects, but this strategy can result in off-target toxicity in healthy tissue. Recently, research interests have shifted towards targeted chemotherapeutics, in which a drug targets a specific biological signature of cancer, resulting in selective toxicity towards cancerous cells. Here, we review a family of complexes, termed rhodium metalloinsertors, that selectively target DNA base pair mismatches, a hallmark of mismatch repair (MMR)-deficient cancers. These rhodium metalloinsertors bind DNA mismatches with high specificity and display high selectively in killing MMR-deficient versus MMR-proficient cells. This cell selectivity is unique among small molecules that bind DNA. Current generations of rhodium metalloinsertors have shown nanomolar potency along with high selectivity towards MMR-deficient cells, and show promise as a foundation for a new family of chemotherapeutics for MMR-deficient cancers.
1-Phenyl-3-Trimethylaminopropyl Carbodiimide: A New Inhibitor of Thymidylate Synthase

Thymidylate synthase (EC 2.1.1.45) from methotrexate-resistant Lactobacillus casei was inactivated by 1-phenyl-3-trimethylaminopropyl carbodiimide (PTC), 1-phenyl-3-dimethyl aminopropyl carbodiimide (PDC), and 1-ethyl-3-dimethyl aminopropyl carbodiimide (EDC). In the presence of excess PTC, the inactivation followed pseudo-first order kinetics; the second order rate constant was approximately 200 M-1min-1 at 30 degrees C. The rate of inactivation by PTC was faster than that by either PDC or EDC. Concentrations of the substrate dUMP greater than 0.15 mM, or of the product dTMP greater than 1.6 mM completely protected the enzyme from inactivation by PTC, but 10 mM dUrd provided very little protection. The rate of inactivation of EDC was reduced by only 40% in the presence of 50 mM dUMP. Nucleophiles (sulfanilic acid, glycine methyl ester, or glycine ethyl ester) had no effect on the rate of inactivation by PTC. The complete inactivation of thymidylate synthase by PTC was accompanied by the incorporation of approximately 2 mols of 14C-PTC per mol of enzyme. Although carbodiimides normally modify carboxyl groups in proteins, results from sulfhydryl group titrations and from reversible modification of sulfhydryl groups by methyl methanethiosulfonate suggest that two of the four cysteine residues of thymidylate synthase were modified by PTC.
In-Depth Characterization and Spectral Library Building of Glycopeptides in the Tryptic Digest of a Monoclonal Antibody Using 1D and 2D LC–MS/MS

This work presents a detailed analysis of glycopeptides produced in the tryptic digestion of an IgG1 reference material. Analysis was done by nanospray ESI LC–MS/MS over a wide range of HCD collision energies with both conventional 1D separation for various digestion conditions and a 20 fraction 2D-LC study of a single digest. An extended version of NIST-developed software for analysis of “shotgun” proteomics served to identify the glycopeptides from their precursor masses and product ions for peptides with up to three missed cleavages. A peptide with a single missed cleavage, TKPREEQYNSTYR, was dominant and led to the determination of almost all glycans reported in this study. The 2D studies found a total of 247 glycopeptide ions and 60 glycans of different masses, including 30 glycans found in the 1D studies. This significantly larger number of glycans than found in any other glycoanalysis of therapeutic glycoproteins is due to both the improved separation of sialylated versus asialylated species in the...
Aerodynamic load estimation: Pressure distribution from virtual strain sensors for a pliant membrane wing

The passively adaptive behavior of flexible wings has demonstrated improved performance to that of rigid wings in the presence of low Re flow, near stall angles and flow disturbances. Throughout the natural world proprioceptive sensing is utilized by natural fliers to control their wings during flight. Through proprioceptive sensing of aerodynamic loads, information can be derived that is useful for flight control. Driving at that goal, an approach has been developed to utilize the strain sensed in a membrane wing to estimate aerodynamic loads generated. Hydrostatic pressure tests and wind tunnel tests were conducted to evaluate the capability of the estimation routine. Digital image correlation measurements were take to generate virtual strain sensors on the surface of the membrane. Measurements from a pressure transducer, load cell and CFD simulations were used as a basis of comparison to the estimated loads. Results of the estimation routine were favorable. Estimated pressure distributions closely resembled the actual distributions. The potential for extending this work include, a higher degree of estimate accuracy, estimation of dynamic loads and real-time load estimation.
“Two Functional Groups in One Package”: Using Both Alkyne π-Bonds in Cascade Transformations

Spatial orthogonality of the two independently addressable π-systems in alkynes can be used for the design and control of metal-free cascade transformations. Examples include ionic chemistry of neutral hydrocarbons, preparation of radicals without radical initiators, generation of excited states without light, “1,2-dicarbene reactivity” of alkynes in “boomerang” radical processes, selective conversion of alkynes into carbonyl compounds, and full disassembly of the alkyne moiety.
Scaling Professional Critics: Men and Women Rate Films

Film critic research typically attends to the impact of critics' ratings and reviews on box office receipts. With few exceptions, critics are treated as a homogeneous group. Taking a different appr...
Of sorcerers and thought leaders: marketing the information revolution in the 1960s

AbstractHoopla about the emergence of an information economy was widespread by the 1990s, when academics, politicians and the press celebrated the social transformations brought about by computers. Yet the rhetoric of high-tech revolution long predates Windows 95 or even the World Wide Web. Building on the work of Howard Brick and others on postwar debates over technology and the economy, this article explores how the trope of the “information revolution” entered public discourse in the United States in the 1960s. It considers how the general idea of a post-industrial society – an economy in which manufacturing might play a diminished role – became specifically tied in the public imagination to information technology and intellectual property. Technology firms waged a concerted campaign to assuage anxieties about technological unemployment while extolling the importance of computing and other new technologies to the nation’s economic future. It illustrates how advertisers developed a public relations mess...
To “Feel” and to “Understand” Political Struggle The National-Popular Rhetoric of Podemos

While communication scholars who have invoked the Gramscian concept of hegemony have approached it primarily as a designation for cultural stability and domination, there have been fewer calls for its closer consideration in relation to human agency in the process of social change. Receptive of these calls, in this article, I develop an alternative to the dominant reading of the concept to show its productiveness in the analysis of a political group’s rhetorical situation. I claim that such a conceptualization advances the discussion toward a dimension of rhetorical intervention that passes from an oppressive to an emancipatory understanding of hegemony. I take as my case study the national-popular rhetoric of Podemos, a recently formed political party in Spain, which, in the context of the recent economic crisis, is building hegemony by successfully synthesizing public sentiments and intellectual involvement against austerity policies.
Interactions Between Platelets and the Coagulation System

These events amplify the initating stimulus and lead to explosive thrombin generation and fibrinformation. Platelets can also sustain the procoagulant response by protecting the bound coagulation enzyme complexes from inactivation/inhibition. This overall process provides for rapid and localized clot formation Thrombin generation at the surface of platelets adhered to and activated at sites of vascular injury is central to formation of an insoluble fibrin clot and localized cessation of bleeding. Those platelets that actively regulate thrombin formation can be defined by: (1) a discrete population of young platelets expressing an increased density of adhesion molecules; (2) expression of specific, coagulation protein receptors; and (3) release of a number of hemostatically-active components including a unique and highly procoagulant factor Va molecule.
MODELING OF HUMAN NEAR RESPONSE DISORDERS

ABSTRACT Normally, clear and single binocular vision requires the coordinated turning of the two eyes, called vergence, and focusing of the eyes, called accommodation. It has been shown that static measurements of vergence and accommodation under various open- and closed-loop conditions can be used to calculate accurately parameter values of a normal oculomotor model. Computer simulation using these physiologically justifiable parameters give excellent fit to experimental data. We propose that variation in values of specific parameters in the normal model may be used to simulate oculomotor anomalies. Decrease in accommodative controller gain may result in model behavior similar to the decrease in accommodative response found in amblyopia. Large magnitude vergence bias may be used to model strabismus. Unfortunately, little experimental data on amblyopia and strabismus required for calculation of parameter values is available. Hence, we propose to perform extensive measurements on 15 amblyopic and 15 strabismic subjects. Computer simulation will be used to test parameter values for fit to experimental data. Through development of the model we hope to improve conceptual understanding of major variables related to these ocular conditions and gain insight into the underlying mechanisms. Model testing under different conditions not easily obtainable on patients may lead to development of orthoptics therapy procedures for alleviating manifestations of these two conditions. Finally, data on amblyopia and strabismus resulting from this study will form an empirical basis for future research.
Quantitative accuracy of PET for image-based kinetic analysis

It is essential to achieve quantitative accuracy of radioactivity concentrations (Bq/ml) when performing compartmental modeling and kinetic analysis of dynamic sequences of reconstructed PET images. Dynamic PET data can be acquired in list mode, and often is preferred over frame mode acquisitions due to the flexibility of reformatting the list mode data into different dynamic image sequences after the acquisition is complete. However, most PET data is acquired as static frames. It therefore is important to evaluate the quantitative accuracy of list mode or dynamic PET acquisitions prior to their use for clinical or research applications. We evaluated the quantitative accuracy of list mode acquisitions obtained with a Siemens Biograph 16 PET/CT scanner at our institution; the image data were acquired from an anthropomorphic phantom (Data Spectrum, Hillsborough, NC) filled with an aqueous solution of 18F-fluorodeoxyglucose (FDG). PET data were acquired with the phantom for the following three different configurations: (1) with nonradioactive water in the body compartment, and aqueous solution of 18F-FDG only in a finable cylindrical insert to mimic the first few seconds of highly concentrated radioactivity within the field of view such as that in major venous or pulmonary vessels, or in the right or left cardiac ventricles, (2) with radioactivity throughout the entire body compartment and imaged within 3 min time frames in list mode, and (3) with radioactivity throughout the body compartment and imaged in list mode and reformatted into sequential time frames having intervals of 3, 10, 20, 30, 50, 67 sec, respectively (i.e., total of 180 sec). All measured concentration values were compared against values acquired from static images or against true values calculated from injected dose corrected for physical decay of 18F. These analyses demonstrated that the count rate limitation is minimal or negligible in general as long as there is no more than 370-440 MBq (10-12 mCi) radioactivity entirely within the axial FOV for 1 bed position required for dynamic PET, and the list mode acquisition provides quantitative radioactivity concentration values for all ranges of radioactivity levels. In addition, reformatting a single list mode acquisition into frame data having different time intervals retains quantitative accuracy with respect to static frame data and compared to the known radionuclide concentration in the phantom. Within these constraints, the list mode data acquired with the Biograph 16 PET/CT system is quantitatively accurate for image-based compartmental modeling and kinetic analysis.
Attenuated Hunter Syndrome: A Rare Cause of Simultaneous Retinal and Optic Nerve Disease (P5.300)

OBJECTIVE: To characterize visual pathway involvement in HS. BACKGROUND: Hunter Syndrome (HS) is a multisystem disorder characterized by glycosaminoglycan (GAG) accumulation due to enzyme deficiency of iduronate 2-sulfatase. DESIGN/METHODS: Case report. RESULTS: A 44-year-old man presented with headaches, nausea, and peripheral vision loss. Visual acuities were 20/25 OU with normal color vision. There was no APD; bilateral optic disc edema was noted. Humphrey visual fields (VF) showed pericentric ring scotomas. Full field ERG was normal. Intracranial pressure monitoring was normal. Orbital MRI demonstrated bilateral scleral thickening with a suggestion of scleral canal crowding. Over the next 16 months, VF defects progressed, despite stable acuities and disc appearance. OCT demonstrated microcystic macular edema, thinning of the retinal nerve fiber layer (RNFL: OD 100 / OS 129 microns), ganglion cell layer (GCL), outer nuclear and photoreceptor layers. At 15 months, RNFL thickness declined in OD (by 13 microns), increased in OS (by 9 microns), while macular and retinal changes were stable. CONCLUSIONS: This patient illustrates the complex mechanisms of visual impairment in HS. We hypothesize that the retinal changes and scleral canal crowding with optic disc edema both resulted from GAG deposition. Likewise, the ring scotomas of our patient were pericentral and a full field ERG was normal. Segmentation of the GCL demonstrated a pattern of loss consistent with the field defect. GCL loss could have resulted from trans-synaptic degeneration of the photoreceptor layer, but we think primary injury to the GCL is most likely. The visual acuity preservation and symmetrical pattern of VF loss make a primary optic nerve mechanism unlikely. These findings demonstrate that a combination of retinal and optic nerve changes, including optic disc swelling, optic atrophy and retinopathy, occur in HS. This case emphasizes the potential role for OCT to help delineate the areas of visual pathway involvement. Disclosure: Dr. Narayana has nothing to disclose. Dr. Lau has received personal compensation for activities with Pfizer Inc., Shire, Genzyme, Ultragenyx Pharmaceutical, Amicus Therapeutics, and GlaxoSmithKline. Dr. Nolan has nothing to disclose. Dr. Rucker has nothing to disclose. Dr Balcer received personal compensation from Biogen Idec and consulting for Biogen Idec, Vaccinex and Genzyme. She is on a clinical trial advisory board for Biogen-Idec., Dr. Galetta has received personal compensation for activities with Biogen Idec, Genzyme, and Vaccinex.
High sensitivity troponin and valvular heart disease

Blood-based biomarkers have been extensively studied in a range of cardiovascular diseases and have established utility in routine clinical care, most notably in the diagnosis of acute coronary syndrome (e.g., troponin) and the management of heart failure (e.g., brain-natriuretic peptide). The role of biomarkers is less well established in the management of valvular heart disease (VHD), in which the optimal timing of surgical intervention is often challenging. One promising biomarker that has been the subject of a number of recent VHD research studies is high sensitivity troponin (hs-cTn). Novel high-sensitivity assays can detect subclinical myocardial damage in asymptomatic individuals. Thus, hs-cTn may have utility in the assessment of asymptomatic patients with severe VHD who do not have a clear traditional indication for surgical intervention. In this state-of-the-art review, we examine the current evidence for hs-cTn as a potential biomarker in the most commonly encountered VHD conditions, aortic stenosis and mitral regurgitation. This review provides a synopsis of early evidence indicating that hs-cTn has promise as a biomarker in VHD. However, the impact of its measurement on clinical practice and VHD outcomes needs to be further assessed in prospective studies before routine clinical use becomes a reality.