cssi/SciSciGPT-SciSciNet huggingface dataset:
Quantitation of normal and formaldehyde‐modiﬁed deoxynucleosides by high‐performance liquid chromatography/UV detection

A sensitive and selective method was developed for the first time to quantify simultaneously the normal and formaldehyde (FA)-modified bases in human placental DNA treated with 100 ppm FA for 20 h at 37 degrees Celsius. Digestion of DNA to deoxynucleosides with DNase I, phosphodiesterase and alkaline phosphatase occurred in that order with centrifugation steps. The normal and FA-modified deoxynucleosides were then resolved from one another and reagent blank interferences to produce selective separation through high performance liquid chromatography-ultraviolet detection at 254 nm. A C(18) reversed-phase column facilitated the resolution using 5 mm ammonium acetate and a gradient of 0-6% methanol at fl ow rates of 0.3-1.4 mL/min before column cleaning. The lower quantifiable limits for deoxyadenosine, deoxyguanosine, deoxycytidine, thymidine, N(6)-hydroxymethyldeoxyadenosine (N(6)-dA), N(2)-hydroxymethyldeoxyguanosine (N(2)-dG) and N(4)-hydroxymethyldeoxycytidine (N(4)-dC) were 11, 7.6, 12, 15, 10, 10 and 22 pmol, respectively. The abundance order of the modified deoxynucleosides was N(6)-dA > N(2)-dG > N(4)-dC. dT did not form hydroxymethyl derivatives. The respective concentrations were about 6.0, 10.0 and 23 pmol of modified deoxynucleosides in 80 micro g of human placental DNA after treatment with 100 micro g/mL of formalin for 20 h at 37 degrees Celsius. The stabilities of N(6)-dA and N(2)-dG were much better at -20 degrees Celsius than at 25 degrees Celsius, where the respective halftimes were about 50.1 and 21.0 h.
On the mark(s): Optimum currency areas in Germany

Abstract In the wake of unification, the former GDR became a member of the DM monetary zone. We evaluate whether unified Germany satisfies the criteria defining an optimal monetary area. We conclude that the primary criterion, similarity of shocks, is not satisfied even by the western states, a reflection of the importance of sector-specific relative to geographic shocks coupled with different sectoral structures. Extending this argument, we conclude that the correlation of shocks to the eastern states with western states is also likely to be small. A case for monetary unification must, in consequence, be based on political rather than narrowly economic calculations.
Top partners at the CERN LHC: Spin and mass measurement

If one takes naturalness seriously and also assumes a weakly coupled extension of the standard model (SM) then there are expectations for phenomenology that can be inferred in a model-independent framework. The first such expectation is that there is likely to be some colored particle with mass $\mathcal{O}(\mathrm{TeV})$ that cancels the top loop contribution to the quadratic divergence of the Higgs mass. In this paper we begin a model-independent analysis of the phenomenology of this ``top partner,'' ${t}^{\ensuremath{'}}$. We make one additional assumption that it is odd under a parity which is responsible for the stability of a WIMP dark matter candidate, $N$. We focus on three questions to be explored at the LHC: discovery opportunities, mass determination, and spin determination of this top partner. We find that within a certain region of masses for the ${t}^{\ensuremath{'}}$ and $N$, ${t}^{\ensuremath{'}}{\overline{t}}^{\ensuremath{'}}$ is easily discovered in the $t\overline{t}+2N$ decay with the tops decaying fully hadronically. We show that without having to rely on other channels for new physics that for a given ${t}^{\ensuremath{'}}$ spin the masses of ${t}^{\ensuremath{'}}$ and $N$ can be measured using kinematic information (e.g. average ${\mathrm{E\ensuremath{\llap{\not\;}}}}_{\mathrm{T}}$ or ${H}_{T}$) and total cross section. A degeneracy due to the spin remains, but with several hundred ${\mathrm{fb}}^{\ensuremath{-}1}$ of luminosity we demonstrate potentially useful new methods for determining the ${t}^{\ensuremath{'}}$ spin over a wide range of masses. Our methods when could be useful for distinguishing supersymmetric and nonsupersymmetric models.
Characterization of the effects of nonspecific xenon-protein interactions on (129)Xe chemical shifts in aqueous solution: further development of xenon as a biomolecular probe.

The sensitivity of 129 Xe chemical shifts to weak nonspecific xenon‐protein interactions has suggested the use of xenon to probe biomolecular structure and interactions. The realization of this potential necessitates a further understanding of how different macromolecular properties influence the 129 Xe chemical shift in aqueous solution. Toward this goal, we have acquired 129 Xe NMR spectra of xenon dissolved in amino acid, peptide, and protein solutions under both native and denaturing conditions. In general, these cosolutes induce 129 Xe chemical shifts that are downfield relative to the shift in water, as they deshield the xenon nucleus through weak, diffusion-mediated interactions. Correlations between the extent of deshielding and molecular properties including chemical identity, structure, and charge are reported. Xenon deshielding was found to depend linearly on protein size under denaturing solution conditions; the denaturant itself has a characteristic effect on the 129 Xe chemical shift that likely results from a change in the xenon solvation shell structure. In native protein solutions, contributions to the overall 129 Xe chemical shift arise from the presence of weak xenon binding either in cavities or at the protein surface. Potential applications of xenon as a probe of biological systems including the detection of conformational changes and the possible quantification of buried surface area at protein‐protein interfaces are discussed. C ∞ 2001 Academic Press
A higher order approximation for non-linear normal modes in two degree of freedom systems

Abstract Explicit approximate expressions for normal modal curves in non-linear two degree of freedom systems are obtained by applying a perturbation method to the modal equation: 2(h − V)y″ + (1 + y′ 2 )(V y − y′V x = 0. The results are not valid in the neighborhood of V = h.
METHYLATION OF THE Z-DNA DECAMER D(GC)5 POTENTIATES THE FORMATION OF A-DNA: CRYSTAL STRUCTURE OF D(GM5CGM5CGCGCGC)

It is well known that methylation of alternating Py x Pu sequences potentiates the formation of Z-DNA. However, we have now observed that methylation of the alternating Z-DNA oligomer d(GCGCGCGCGC), which starts with a 5'-purine, unexpectedly stabilizes the A-DNA conformation. The double methyl derivative d(Gm5CGm5CGCGCGC), which crystallizes as duplex A-DNA in the hexagonal space group P6(1)22, a = b = 39.33 A and c = 77.93 A with one strand per asymmetric unit and six duplexes in the unit cell, refined to an R factor of 19.1 for 204 DNA atoms and 43 solvent molecules. This is the first report of a DNA sequence crystallized in both right and left-handed conformations, allowing structural comparisons not previously possible and, more importantly, this is the first time that methylation has been shown to potentiate the formation of A-DNA from a sequence known to crystallize as Z-DNA. From this study, ten base-pairs appear to be the critical length in determining the handedness of d(GC)n-type sequences in the crystalline state. Because methylation of nuclear DNA is linked to a number of cellular processes, including transcriptional inactivation, this study has important implications for the role of A-DNA in methylated regions of genomic DNA and, thus, in the regulation of gene expression. In this context, the structure of d(Gm5Cm5CGCGCGC) will be compared with that of the alternating A-DNA decamer d(GCACGCGTGC) and the alternating Z-DNA decamer d(GCGCGCGCGC) and discussed in terms of the forces that govern the handedness of duplex DNA oligomers.
Algorithm for the worst error in linear systems with bounded input and its rate of change

Computational worst error algorithm for linear systems and quadratic error criteria, showing flowgraph and computer execution results
Role of computer-assisted visual search in mammographic interpretation

We used eye-position data to develop Computer-Assisted Visual Search (CAVS) as an aid to mammographic interpretation. CAVS feeds back regions of interest that receive prolonged visual dwell (greater than or equal to 1000 ms) by highlighting them on the mammogram. These regions are then reevaluated for possible missed breast cancers. Six radiology residents and fellows interpreted a test set of 40 mammograms twice, once with CAVS feedback (FB), and once without CAVS FB in a crossover, repeated- measures design. Eye position was monitored. LROC performance (area) was compared with and without CAVS FB. Detection and localization of malignant lesions improved 12% with CAVS FB. This was not significant. The test set contained subtle malignant lesions. 65% (176/272) of true lesions were fixated. Of those fixated, 49% (87/176) received prolonged attention resulting in CAVS FB, and 54% (47/87) of FBs resulted in TPs. Test-set difficulty and the lack of reading experience of the readers may have contributed to the relatively low overall performance, and may have also limited the effectiveness of CAVS FB which could only play a role in localizing potential lesions if the reader fixated and dwelled on them.© (2001) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Kinetic model for electrorefining, part II: Model applications and case studies

Abstract The model developed in Part I of the systematic study is applied to identify the kinetic features of materials flow in an electrorefinner. The most recent thermodynamic and electrochemical data reported are used in the present simulations. Both liquid and solid electrodes are considered. The main differences of the kinetics of materials dissolution/deposition between the liquid and solid electrode and the reasons for these differences are identified. The important factors that affect the evolution of electrorefining with operation are identified.
Some distal limb structures develop in mice lacking Sonic hedgehog signaling.

Abstract Patterning of the limb is coordinated by the complex interplay of three signaling regions: the apical ectodermal ridge (AER), the zone of polarizing activity (ZPA), and the non-ridge limb ectoderm. Complex feedback loops exist between Shh in the ZPA, Bmps and their antagonists in the adjacent mesenchyme, Wnt7a in the dorsal ectoderm and Fgfs in the AER. In contrast to the previously reported complete absence of digits in Shh−/− mice, we show that one morphologically distinct digit, with a well-delineated nail and phalanges, forms in Shh−/− hindlimbs, while intermediate structures are severely truncated and fused. The presence of distal autopod elements is consistent with weak expression of Hoxd13 in Shh−/− hindlimbs. Shh−/− forelimbs in contrast have one distal cartilage element, a less-well differentiated nail and fused intermediate bones. Interestingly, Ihh is expressed at the tip of Shh mutant limbs and could account for formation of distal structures. In contrast to previous studies we also demonstrate that Shh signaling is required for maintenance of normal Fgf8 expression, since expression of Fgf8, unlike some other AER marker genes, is rapidly lost from anterior to posterior after E10.5, with only a small domain of Fgf8 expression remaining posteriorly. Furthermore, loss of expanded Fgf8 expression is paralleled by a collapse of the handplate. Our data show that development of most intermediate elements of the hindlimb skeleton are Shh-dependent, and that Shh signaling is required for anterior-posterior expansion of the AER in both limbs and for the subsequent branching of zeugopod and autopod elements. Finally, we show that Shh is also required for outgrowth of the limb ectoderm and thus for the formation of a distinct limb compartment.
Time-dependent Synchrotron and Compton Spectra from Jets of Microquasars

Jet models for the high-energy emission of Galactic X-ray binary sources have regained significant interest with detailed spectral and timing studies of the X-ray emission from microquasars, the recent detection by the HESS collaboration of very high energy γ-rays from the microquasar LS 5039, and the earlier suggestion of jet models for ultraluminous X-ray sources observed in many nearby galaxies. Here we study the synchrotron and Compton signatures of time-dependent electron injection and acceleration, and adiabatic and radiative cooling in the jets of Galactic microquasars. Synchrotron, synchrotron self-Compton, and external Compton radiation processes with soft photons provided by the companion star and the accretion disk are treated. An analytical solution is introduced to the electron kinetic equation for general power-law geometries of the jets for Compton scattering in the Thomson regime. We pay particular attention to predictions concerning the rapid flux and spectral variability signatures expected in a variety of scenarios, making specific predictions concerning possible spectral hysteresis, similar to what has been observed in several TeV blazars. Such predictions should be testable with dedicated monitoring observations of Galactic microquasars and ultraluminous X-ray sources using Chandra and/or XMM-Newton.
EATING DISORDERS: EFFICACY OF PHARMACOLOGICAL AND PSYCHOLOGICAL INTERVENTIONS

Abstract Eating disorders represent a spectrum of overlapping conditions that combine disturbances in eating with various forms of traditional psychopathology. Medications are often helpful in the management of the psychopathology associated with anorexia nervosa but no compound has been shown to assist weight gain reliably or alter other core features of the condition. Contingency management and other behavior therapy procedures are effective in promoting weight gain in anorexia nervosa. The limited effectiveness of cognitive interventions for anorexia nervosa may be due to the complex of physical symptoms associated with low body weight. Antidepressants reduce binging and purging in bulimia nervosa and binge eating disorder, although this action appears to be independent of any antidepressant effect. Cognitive/behavioral interventions also reduce binging and purging, and comparisons of this therapy with medication indicate that psychotherapy alone is more effective than medication alone. Moreover, changes produced by cognitive/behavioral interventions endure longer than medication where higher relapse rates are common. Most studies also reveal no advantage of medication over cognitive/behavioral therapy alone in the reduction of bulimic symptoms.
Cellular electrophysiologic properties of old canine atria provide a substrate for arrhythmogenesis

Objective: The incidence of atrial fibrillation increases with age. We hypothesized that aging-associated changes in the atrial action potential (AP) and conduction velocity provide a substrate for abnormal conduction and arrhythmogenesis. Methods: We used microelectrode techniques to record AP from the endocardium of the right atrial wall of dogs aged 1–5 (adult) and >8 years (old). Conduction velocity was measured between two microelectrodes 3–10 mm apart. Histological study was carried out to assess fibrosis. Results: Whereas resting potential, AP amplitude and V max did not differ with age, the plateau was more negative and AP duration was longer in old tissue. The L-type calcium current ( I Ca,L) agonist Bay K8644 (10−8–10−6 mol/l) elevated the plateau and shortened APD more in old than in adult, such that AP contour in old atria approached that of adult. In contrast, the I Ca,L blocker nisoldipine (10−8–10−5 mol/l) depressed the plateau in adult and had no effect in old. There was no difference between the two groups in conduction velocity of normal beats, whereas for early premature impulses, reduced conduction velocity and a wider time window manifesting slow conduction were detected in old in comparison to adult tissue. A twofold increase in the amount of fibrous tissue was detected in old atria. Conclusions: Our data show significant differences in contour of AP in adult and old atria. The responses to Bay K8644 and nisoldipine suggest a decreased I Ca,L in old atrial tissue. The alterations in AP contour and increased fibrosis may be responsible for slower conduction of early premature beats in old atria. The age-related changes in conduction of premature beats are consistent with those observed in patients with paroxysmal atrial fibrillation and may contribute to the greater propensity to atrial fibrillation in the aged.
Time of origin of unipolar brush cells in the rat cerebellum as observed by prenatal bromodeoxyuridine labeling

Abstract Unipolar brush cells (UBCs) are a class of excitatory, glutamatergic interneurons occurring at high density in the granular layer of the vestibulo-cerebellum. UBCs are intermediate in size between granule cells, which in rat originate postnatally from precursors in the external granular layer, and Golgi cells, which are generated prenatally and postnatally from precursors in the ventricular zone that continue to divide while they migrate toward the cortex. The origin of the UBCs is still poorly understood. In this study, we set forth to ascertain the possible prenatal origin of UBCs, taking advantage of the immunocytochemical 5-bromo-2′-deoxyuridine (BrdU) method to label dividing cells in combination with antisera to cell population markers, that distinguish UBCs from granule and Golgi cells. Pregnant rat dams received six i.p. injections of BrdU (total 36 mg/animal) over 2 successive days at different stages of prenatal development (embryonic day [E]14/15–E20/21). Adult offspring were analyzed for histology. Using antibodies against the ionotropic glutamate receptor GluR2 and the calcium binding protein calretinin we found two populations of UBCs. A subset of about 30% of UBCs was calretinin and GluR2 positive, while the majority of the UBCs were calretinin negative and GluR2 positive. Results indicate that UBCs originate from precursors proliferating between E16 and E21. However, UBCs defined by calretinin immunoreactivity were primarily born in a narrow time window at E17–18. UBCs immunostained with antiserum to GluR2, but not labeled with calretinin were generated later, from E19 to E21. Our data also indicate that a part of GluR2 positive UBCs are born around and after E22. The subset of later born, calretinin negative UBCs may coincide with the pale cells, a group of cerebellar interneurons previously identified by [3H]thymidine labeling.
Fulminant cerebellitis with radiological recurrence in an adult patient with Crohn's disease

There are few reports of cerebellitis in adults and reports of recurrent cerebellitis are extremely rare. This report highlights both the fulminant course that may follow cerebellitis and a potentially important association with Crohn's disease. A 41-year-old man presented with headache and cerebellar dysfunction a month after ileo-colonic resection for Crohn's disease. MRI demonstrated T2-signal abnormalities, pial enhancement and cerebellar enlargement. His course was complicated by obstructive hydrocephalus, intraventricular hemorrhage associated with external ventricular drain placement and left transverse sinus venous thrombosis. Treatment with high-dose intravenous steroids and anti-coagulation resulted in improvement. Asymptomatic radiological worsening 13 months after initial presentation occurred during a relapse of Crohn's disease. He was treated with intravenous steroids and maintenance azathioprine for his Crohn's and suspected immune mediated cerebellitis. At last follow-up 4 years after initial presentation his clinical status remained unchanged and radiological changes had stabilized. Adult onset cerebellitis may be fulminant and recurrent. Early immunotherapy in acute relapsing cerebellitis may speed recovery and prevent recurrence. Onset and radiological relapse of cerebellitis during Crohn's disease flare-ups as in our case possibly suggests a shared autoimmune pathogenesis.
Specificity of Distalless Repression and Limb Primordia Development by Abdominal Hox Proteins

In Drosophila, differences between segments, such as the presence or absence of appendages, are controlled by Hox transcription factors. The Hox protein Ultrabithorax (Ubx) suppresses limb formation in the abdomen by repressing the leg selector gene Distalless, whereas Antennapedia (Antp), a thoracic Hox protein, does not repress Distalless. We show that the Hox cofactors Extradenticle and Homothorax selectively enhance Ubx, but not Antp, binding to a Distalless regulatory sequence. A C-terminal peptide in Ubx stimulates binding to this site. However, DNA binding is not sufficient for Distalless repression. Instead, an additional alternatively spliced domain in Ubx is required for Distalless repression but not DNA binding. Thus, the functional specificities of Hox proteins depend on both DNA binding-dependent and -independent mechanisms.
Experimental carcinogenesis of pyrolysis fuel oil

In the manufacture of ethylene by high-temperature cracking of hydrocarbons, certain high-boiling materials known as pyrolysis fuel oil result as residues. Two samples of these residues produced skin carcinomas upon lifespan application to the skin of mice. Similar results have been previously reported from other carbonaceous materials subjected to high temperatures and pressures. It should be noted that these tests exposed mice to conditions different from those of working humans but do serve as warning of a possible health risk.
Wheat germ phosphoglycerate mutase: evidence for a metalloenzyme

Wheat germ phosphoglycerate mutase, exposed to 3.4 M guanidinium chloride at 22 degrees C and pH 7.8, slowly undergoes time-dependent inactivation which can be fully reversed by adding excess Co2+ or Mn2+ to a 50-fold dilution of the denaturing medium. Titration of the denatured enzyme with either Co2+ or Mn2+ shows that wheat germ mutase preferentially binds Co2+. Assuming 1:1 complexation between metal atom and protein, the apparent dissociation constants (Kd) for E Co2+ and E Mn2+ at 22 degrees C and pH 8.7 are approximately 1.06 and 1.84, respectively. Other metal atoms (e.g., Cr2+, Cu2+, Fe2+, Fe3+, Mg2+, and Ni2+) have no effect in restoring the apoenzyme's catalytic activity. At low concentrations (0.11-0.23 mM) Zn2+ partially restores activity, but promotes protein precipitation at elevated concentrations. Evidence suggests that all bisphosphoglycerate-independent phosphoglycerate mutases require either an intra- or an extramolecular metal atom in order to function. Attempts to characterize wheat germ mutase as a glycoprotein have yielded negative results.
Effects of optic primordium removal on the development of the isthmo-optic nucleus in the duck (Anas platyrhynchos)

Abstract The development of the isthmo-optic nucleus in the absence of its peripheral field of innervation (eye) was studied from day 8 of incubation through hatching in duck embryos. Unilateral extirpation of the optic primordia usually on the right side was performed on the fourth day of incubation. Cell counts from alternate sections indicate that early and total eye removal has no effect upon cellular proliferation, migration and differentiation of the neuroblasts up to day 18. Between days 18 and 21, the nucleus undergoes a massive cellular degeneration presumably due to failure on the part of outgrowing axons to establish appropriate peripheral connections. This exaggerated cell loss continues through the rest of the incubation period and the nucleus shows a complete cell loss by the time of hatching.
AN INVESTIGATION OF WAXES ISOLATED FROM HEAVY OILS PRODUCED FROM NORTHWEST ASPHALT RIDGE TAR SANDS

ABSTRACT During the late 1970's, the Laramie Energy Technology Center operated two in-situ combustion projects in the Northwest Asphalt Ridge tar sand deposit of Utah. Some of the heavy oils produced were observed to have high pour points, which resulted in handling problems in cold weather. These heavy oils contain waxes, which were found to be n-alkane homologues ranging past carbon number 60. These alkanes seem to have been derived from what are probably Ozokerite veins, which are found in the tar sand deposit. Samples from these veins and waxes derived from produced heavy oils were studied using 13C NMR, IR, and chemical ionization mass spectrometry.
Hematopoietic potential of murine skeletal muscle–derived CD45−Sca-1+c-kit− cells

Abstract Objective Somatic stem cells, which are poorly defined in postnatal mammalian tissues, are attractive candidates for examination of stem cell plasticity. Our goal was to determine the identity of neonatal muscle-derived cells that contain hematopoietic potential and to explore the status of CD45 expression on these cells. Materials and Methods Skeletal muscle from thighs of 4- to 7-day-old mice was harvested, enzymatically digested, and flow cytometrically sorted to yield CD45 − Sca-1 + c-kit − cells. These cells were examined in hematopoietic colony-forming assays and competitive repopulation assays, and were expanded ex vivo. Additionally, CD45, c-kit, PU.1, and β globin major expression was tracked over time in cultured cells to assess the possibility of manipulating stem cell differentiation in vitro. Results Freshly isolated CD45 − Sca-1 + c-kit − cells were devoid of hematopoietic lineage markers and contained no colony-forming activity but displayed superior long-term competitive repopulating ability when compared to freshly isolated muscle-derived CD45 + Sca-1 + c-kit + cells. CD45 − Sca-1 + c-kit − cells expanded ex vivo in 5 ng/mL murine stem cell factor, mFlt-3L, and megakaryocyte growth and development factor (MGDF) for 9 days increased their in vivo hematopoietic repopulating potential 5.3-fold relative to fresh cells. Although fresh cells did not transcribe mRNA of several hematopoietic genes, a small fraction of cells cultured for 9 days acquired cell surface c-kit, and only these cells expressed c-kit and PU.1 mRNA and maintained competitive repopulating ability, suggesting at least myeloid and perhaps lymphoid developmental potential. Conclusion Neonatal murine muscle-derived cells expressing the phenotype CD45 − Sca-1 + c-kit − are putative adult somatic stem cells with in vitro and in vivo hematopoietic differentiation potential.
Abstract A49: Circulating tumor cell (CTC) assay development for detection of H2AX as a clinical pharmacodynamic (PD) marker for Chk1 kinase inhibitors.

Circulating tumor cells are prognostic of survival in metastatic breast, colon, and prostate cancers. Additionally, CTCs are of interest because they may be representative of the phenotype/genotype of the primary and metastatic tumors, and a useful tool (e.g. patient stratification) for drug development. CTCs, as “liquid biopsies” are potentially useful as a pharmacodynamic marker allowing easy repeat sampling before and after drug treatment. We describe the development of a CTC assay measuring H2AX induction, a marker of DNA damage. The CTC assay was developed using the FDA cleared Veridex/CellSearch™ instrument and reagents for enumeration of CTCs from blood. CellSearch defines CTCs as EpCam+/DAPI+/CK 8,18,19+/CD45−. For assay development, cells from tumor cell lines representing major solid tumor types were chosen, cultured, treated with inhibitors of checkpoint kinase 1 (Chk1, LY2603618, LY2606368) or with various standard-of-care (SOC) chemotherapeutics. These treated cells were then spiked into whole blood drawn into CellSave™ (preservative+EDTA). LY2603618 and LY2606368 are inhibitors of Chk1 kinase currently in clinical development. LY2603618 is meant to be used in combination with a DNA damaging agent, while LY2606368 has potent single agent activity. Inhibition of Chk1 in cells with DNA damage allows the cells to progress into mitosis without DNA repair, leading to cell death. In tumor xenograft mouse models, treatment reduced tumor volume with elevation of γH2AX in tumors and anagen hair follicles at drug exposure levels similar to concentrations used for the CTC γH2AX development assay. For initial assay development, mouse whole blood was used and results reproduced subsequently with human whole blood from healthy subjects. The spiked tumor cells in blood samples were recovered using the CellSearch Mouse/Rat CTC kit (for mouse blood) or human CXC kit (for human blood), supplemented with the R-PE conjugated anti-γH2AX antibody. γH2AX in the recovered tumor cells was detected in the open/fourth channel on the CellSearch instrument. Results were confirmed by flow analysis. Without drug treatment, only about 0.2–2% of all cultured tumor cells were γH2AX positive. The magnitude of the induction of γH2AX in the cells after treatment was dose and cell-line dependent. Significant induction of H2AX (>20% cells) was observed after 24 hour treatment with only a few SOC agents (cisplatin, etoposide) in sensitive tumor cell lines; the majority induced moderate to low levels (usually Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr A49.
Synthesis of feedback controls using optimization theory--An example

This paper illustrates the use of optimization theory in the synthesis of a linear time-varying feedback control by carrying out the design of an aircraft landing system. The optimization method employed is the Parametric Expansion Method. A number of different controls are synthesized by selecting different functional forms for the weighting factors appearing in the error index formulated from the performance requirements. These controls are compared by presenting the landing trajectories of the aircraft.
Differing patterns of aberrant neuronal sprouting in Alzheimer's disease with and without Lewy bodies

Abstract About one quarter of Alzheimer's disease patients have been found to have concomitant subcortical and neocortical Lewy bodies (LBs). We compared the aberrant neuronal sprouting and the extent of neuritic and synaptic damage in these Lewy body variant of Alzheimer's disease (LBV), with the same pathologic alterations in Alzheimer's disease without LBs (AD). More of the thioflavine-S-positive senile plaques of the LBVs contained growth associated protein 43 (GAP-43), a marker of neuritic growth and sprouting. Compared to AD, the LBVs had 39% more GAP-43-positive plaques in the frontal cortex, and 53% more in the hippocampus. These neuritic alterations were accompanied by an accumulation of amyloid precursor protein and phosphorylate neurofilaments.. Synapse loss was the same in LBV and AD. These results suggest more extensive aberrant neuronal sprouting in LBV than in AD.
Biochemical correlates of longevity in two closely related rodent species

The objective of this study was to explore the basis of variations in the life span and metabolic potential, i.e., total amount of energy consumed during life, between different species, in context of the free radical hypothesis of aging. A comparison was made between the house mouse (Mus musculus) and the white-footed mouse (Peromyscus leucopus): the latter has >2-fold greater life span and metabolic potential than the former. Longer life span and higher metabolic potential of Peromyscus were associated with low rates of mitochondrial O.−2 and H2O2 generation, higher activities of catalase and glutathione peroxidase and low levels of protein oxidative damage as well as low susceptibility to oxidative damage in response to experimental oxidative stress. Results support the role of oxidative stress in aging.
Towards scalable authentication in health services

Over the last two decades, many attempts have been made to computerize the management of patient records using advanced computing and networking facilities across healthcare providers such as hospitals, clinics, and clearing agencies. In addition to this transition from a disparate and paper-based infrastructure to a consolidated and digital medium-based one, we have been confronted with privacy and security requirements since the advent of the Health Insurance Portability and Accountability Act (HIPPA). The problem we seek to address in this paper is to provide authentication of individual identity in the context of accessing critical information in Web-based e-health systems including secure transmission of data across the Internet. These problems have technical solutions that are well known, but the solutions in general are strongly biased toward a single individual interacting with a single application. In this paper, we propose a scalable token-based authentication architecture and demonstrate how we can implement this architecture using commercial-off-the-set technologies. Our approach focuses on vendor-neutral specifications. The proof-of-concept prototype has been implemented so that the pilot testing may be conducted at various sites.
Who's on First? Listing Authors by Relative Contribution Trumps the Alphabet

Political science as a discipline lacks any convention on the order in which authors should be listed in co-authored publications. As a result, the order of authors' surnames currently provides no information to other scholars, hiring and promotion committees, and other reviewers about the relative contributions of each collaborator. This lack of information impedes the allocation of proper credit for scholarly contributions. Moreover, in collaborations between junior and senior colleagues, or other asymmetric status hierarchies, the absence of both information and any convention tends to favor more established scholars; this makes it more difficult for graduate students, untenured professors, and other vulnerable co-authors to negotiate for and receive appropriate credit. Listing authors by relative contribution is both more informative and fair. In publications where one author provides the necessary research funding, or a faculty member is not only a co-author but also a dissertation or other academic advisor, it is also appropriate to designate that collaborator as “last” or “senior author.” In all cases, articles should carry a short statement indicating the division of labor between the co-authors, even or especially if the contributions are equal.
Where's the FEEB? the effectiveness of instruction set randomization

Instruction Set Randomization (ISR) has been proposed as a promising defense against code injection attacks. It defuses all standard code injection attacks since the attacker does not know the instruction set of the target machine. A motivated attacker, however, may be able to circumvent ISR by determining the randomization key. In this paper, we investigate the possibility of a remote attacker successfully determining an ISR key using an incremental attack. We introduce a strategy for attacking ISR-protected servers, develop and analyze two types of attack, and present a technique for packaging the worm with a miniature virtual machine that reduces the number of key bytes an attacker must acquire to 128. Our attacks can break enough key bytes to infect an ISR-protected server in under 7 minutes. Our results provide insights into properties necessary for ISR implementations to be secure.
Imagery in cognitive architecture: Representation and control at multiple levels of abstraction

In a cognitive architecture, intelligent behavior is contingent upon the use of an appropriate abstract representation of the task. When designing a general-purpose cognitive architecture, two basic challenges related to abstraction arise, which are introduced and examined in this article. The perceptual abstraction problem results from the difficulty of creating a single perception system able to induce appropriate abstract representations in any task the agent might encounter, and the irreducibility problem arises because some tasks are resistant to being abstracted at all. The first contribution of this paper is identifying these problems, and the second contribution is showing a means to address them. This is accomplished through the use of mental imagery. To support imagery, a concrete (highly detailed) representation of the spatial state of the problem is maintained as an intermediate between the external world and an abstract representation. Actions can be simulated (imagined) in terms of this concrete representation, and the agent can derive abstract information by applying perceptual processes to the resulting concrete state. Imagery works to mitigate the perceptual abstraction problem by allowing a given perception system to work in a wider variety of tasks, since perception can be dynamically combined with imagery, and works to mitigate the irreducibility problem by allowing internal simulation of low-level control processes. To demonstrate these benefits, an implementation is described, which is an extension of the Soar architecture. An agent in this architecture that uses reinforcement learning and imagery to play an arcade game and an agent that performs sampling-based motion planning for a car-like vehicle are described, demonstrating the perceptual abstraction and irreducibility problems and the associated use of imagery to mitigate those problems in complex AI tasks. Previous AI systems have incorporated imagery-like processes, however, the functional benefit of imagery in those systems has typically been characterized as the ability to perform more efficient inference through the use of a specialized representation. The use of imagery here shows further benefits related to the perceptual abstraction and irreducibility problems, enriching the broader understanding of the role of imagery in cognitive systems.
Beckman Coulter access creatine kinase MB assay.

A recent article by Apple et al. (1) presents plasma 99th percentile reference limits and analytical …
Seastacks Buried Beneath Newly Reported Lower Miocene Sandstone, Northern Santa Barbara County, California: ABSTRACT

Three large, isolated exposures of a light-gray, coarse-grained, thick-bedded sandstone unit occur in the northern San Rafael Mountains of Santa Barbara County, California. These rocks are moderately fossiliferous and contain Vertipecten bowersi, Amussiopecten vanvlecki, Aequipecten andersoni, Otrea howelli, shark teeth, whale bones, and regular echinoid spines. The fossils indicate that the sandstone unit, although previously reported as upper(?) Miocene, correlates best with the lower Miocene Vaqueros Formation. This unit was deposited in angular unconformity on a Cretaceous, greenish-gray turbidite sequence of interbedded sandstone and shale, and onlaps the unconformity erosion surface from west to east, the unit being thicker in the west and older at its base. The underlying Cretaceous sandstone beds are well indurated, and during the eastward transgression of the early Miocene sea, they resisted wave erosion and stood as seastacks offshore of the advancing coastline, thus creating a very irregular topographic surface upon which the Vaqueros Formation was deposited. Some seastacks were as much as 4 m tall, as indicated by inliers of Cretaceous rock surrounded by 4-m thick sections of the Vaqueros Formation. End_of_Article - Last_Page 665------------
Prevalence of abnormal ankle-brachial index among individuals with low or intermediate Framingham Risk Scores.

Purpose: To determine the prevalence of an abnormal ankle-brachial index (ABI) among subjects not considered to be at high risk for cardiovascular disease (CVD) based on the Framingham Risk Score (FRS). Materials and Methods: Data from the Population-Based Examinations to Determine Ankle-brachiaL index (PEDAL) Study (2007–2009), a cross-sectional study at 23 U.S. sites, in conjunction with Legs for Life, a national ABI screening program, were analyzed. This study includes data from 822 participants (average age 64.3 years 11.6, 69.7% women, 89.7% non-Hispanic white) without known CVD or diabetes, who were screened for peripheral artery disease (PAD) with an ABI and for whom all FRS variables were available. Participants’ 10-year coronary heart disease (CHD) risk was estimated from the FRS, and three risk categories were defined: low ( 10%), intermediate (10%–19%), and high ( 20%). ABI 0.90 or 1.4 in either leg was considered abnormal. Results: The prevalence of abnormal ABI was 14.2% (95%confidence interval [CI] 11.9%–16.8%). According to the FRS, 463 (56.3%) participants were at low risk, 212 (25.8%) were at intermediate risk, and 147 (17.9%) were at high risk. Among participants with a low FRS (n 463; without CVD or diabetes or both) and an intermediate FRS (n 212; without CVD or diabetes or both), 12.3% and 12.2% had an abnormal ABI. Conclusions: The prevalence of abnormal ABI, a CHD equivalent, is high among individuals not identified as high risk by conventional Framingham-based risk assessment.
Nutrition of algal-invertebrate symbiosis. II. Effects of exogenous nitrogen sources on growth, photosynthesis and the rate of excretion by algal symbionts in vivo and in vitro

The effect of increasing concentrations of ammonia, nitrate and urea was tested on (1) axenic cultures of the symbiont Gymnodinium microadriaticum, (2) symbionts freshly isolated from the tissues of the staghorn coral Acropora cervicornis, and (3) symbionts in vivo in this same host. Rates of symbiont photosynthesis and excretion were measured by using H$^{14}$CO$_{3}^{-}$. Rates of skeletogenesis in A. cervicornis were measured using $^{45}$Ca$^{2+}$. Growth was determined by cell count. Analysis of growth rates in established cultures and freshly isolated symbionts, shows no apparent stimulation by these nitrogen additions at the concentrations used. Growth is comparable to controls. Ammonia, in concentrations ranging between 20 and 200 $\mu $M, increases the photosynthetic rate of symbionts in vivo and in vitro. The rate of excretion of labelled photosynthate is also stimulated. Calcification by the host is increased proportionally in these same experiments. Ammonia addition has no measurable effect in the dark or in the presence of 10$^{-5}$ M 3,3:4-dichlorophenyl-1:1-dimethyl urea (DCMU). Similar results are obtained with urea additions in vivo. Increasing concentrations of nitrate in vivo and in vitro and urea in vitro do not stimulate photosynthesis, excretion or calcification (nitrate only) in these experiments.
αMβ2‐integrin‐intercellular adhesion molecule‐1 interactions drive the flow‐dependent trafficking of Guillain–Barré syndrome patient derived mononuclear leukocytes at the blood–nerve barrier in vitro

The mechanisms of hematogenous leukocyte trafficking at the human blood-nerve barrier (BNB) are largely unknown. Intercellular adhesion molecule-1 (ICAM-1) has been implicated in the pathogenesis of Guillain-Barre syndrome (GBS). We developed a cytokine-activated human in vitro BNB model using primary endoneurial endothelial cells. Endothelial treatment with 10 U/ml tissue necrosis factor-α and 20 U/ml interferon-γ resulted in de novo expression of pro-inflammatory chemokines CCL2, CXCL9, CXCL11, and CCL20, with increased expression of CXCL2-3, CXCL8, and CXCL10 relative to basal levels. Cytokine treatment induced/enhanced ICAM-1, E- and P-selectin, vascular cell adhesion molecule-1 and the alternatively spliced pro-adhesive fibronectin variant, fibronectin connecting segment-1 expression in a time-dependent manner, without alterations in junctional adhesion molecule-A expression. Lymphocytes and monocytes from untreated GBS patients express ICAM-1 counterligands, α(M)- and α(L)-integrin, with differential regulation of α(M) -integrin expression compared to healthy controls. Under flow conditions that mimic capillary hemodynamics in vivo, there was a >3-fold increase in total GBS patient and healthy control mononuclear leukocyte adhesion/migration at the BNB following cytokine treatment relative to the untreated state. Function neutralizing monoclonal antibodies against human α(M)-integrin (CD11b) and ICAM-1 reduced untreated GBS patient mononuclear leukocyte trafficking at the BNB by 59% and 64.2%, respectively. Monoclonal antibodies against α(L)-integrin (CD11a) and human intravenous immunoglobulin reduced total leukocyte adhesion/migration by 22.8% and 17.6%, respectively. This study demonstrates differential regulation of α(M)-integrin on circulating mononuclear cells in GBS, as well as an important role for α(M)-integrin-ICAM-1 interactions in pathogenic GBS patient leukocyte trafficking at the human BNB in vitro.
Management of supraglottic squeeze in adductor spasmodic dysphonia: a new technique.

Objectives: Spasmodic dysphonia is a disabling disorder of the voice characterized primarily by involuntary disruptions of phonation. Botulinum toxin injections of the thyroarytenoid muscles have been the treatment of choice for adductor spasmodic dysphonia (ADSD). We describe a new technique to address the problem of compensatory or supraglottic hyperadduction in some of these patients. Study Design: Case series. Methods: Four patients with ADSD with sphincteric supraglottic contraction were seen for evaluation of botulinum toxin injection. On fiberoptic exam, it was noted that they had type I hyperadduction of the true vocal cords with a significant type III, and/or type IV hyperadduction of the supraglottis. After standard management of the thyroarytenoid muscles, the strained/strangled voice continued. On fiberoptic exam it was noted that the vocal folds were weakened, but the supraglottic hyperfunction persisted. The patients were treated by speech therapists to unload their supraglottis without success. All patients then had their oblique portion of the lateral cricoarytenoid muscles injected with botulinum toxin A through a thyrohyoid approach. This was done in the office under electromyographic control. Results: On follow-up, all patients demonstrated improvement in the quality of their voices (as compared to thyroarytenoid injections alone). Conclusions: We describe a new technique for injection of the supraglottic portion of the lateral cricoarytenoid muscles. We demonstrate this can be done safely and successfully in an office setting with electromyography control.
C2B polylysine motif of synaptotagmin facilitates a Ca2+-independent stage of synaptic vesicle priming in vivo.

Synaptotagmin I, a synaptic vesicle protein required for efficient synaptic transmission, contains a highly conserved polylysine motif necessary for function. Using Drosophila, we examined in which step of the synaptic vesicle cycle this motif functions. Polylysine motif mutants exhibited an apparent decreased Ca2+ affinity of release, and, at low Ca2+, an increased failure rate, increased facilitation, and increased augmentation, indicative of a decreased release probability. Disruption of Ca2+ binding, however, cannot account for all of the deficits in the mutants; rather, the decreased release probability is probably due to a disruption in the coupling of synaptotagmin to the release machinery. Mutants exhibited a major slowing of recovery from synaptic depression, which suggests that membrane trafficking before fusion is disrupted. The disrupted process is not endocytosis because the rate of FM 1-43 uptake was unchanged in the mutants, and the polylysine motif mutant synaptotagmin was able to rescue the synaptic vesicle depletion normally found in sytnull mutants. Thus, the polylysine motif functions after endocytosis and before fusion. Finally, mutation of the polylysine motif inhibits the Ca2+-independent ability of synaptotagmin to accelerate SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor)-mediated fusion. Together, our results demonstrate that the polylysine motif is required for efficient Ca2+-independent docking and/or priming of synaptic vesicles in vivo.
What is security and security studies?: Lessons from the cold war

(1992). What is security and security studies?: Lessons from the cold war. Arms Control: Vol. 13, No. 1, pp. 1-31.