cssi/SciSciGPT-SciSciNet huggingface dataset:
Punishment and Respect The Sacralization of the Person and Its Endangerment

Discussions of punishmentin the modern era turn on the question of the definition and importance of human rights. To understand this linkage, it is important to examine critically two narratives of the origin and development of modern Western forms of punishment, namely that of the Enlightenment, and that of the process of ‘disciplination’ to be found in the work of Foucault. In this article, I suggest an alternative to both these narratives, namely a Durkheimian attention to the process of the ‘sacralization of the person’ which indicates the importance ofreading thedevelopment ofmodernpunishment aspart of a larger process of ‘inclusion’ in which more and more people were included within the category of human personhood. A focus on the sacrality of the person as central to the notion of punishment also helps us to understand the ambiguity of punishment in the modern era, as well as threats posed to human rights by certain contemporary punishment regimes.
The Attraction and Repulsion caused by the Radiation of Heat

WILL you allow me to say a few words in reference to the report of Mr. Crookes's paper which appeared in NATURE, vol. xi. p. 494. Apparently Mr. Crookes does not understand the nature of the forces which I have shown to result from the communication of heat between a gas and a surface; otherwise he would not bring forward as conclusive against the supposition that the phenomena which he has discovered are due to these forces, experiments which show entirely the other way. As I have previously explained, it follows as a direct result of the kinetic theory of gas, that if such forces as I have supposed exist for a certain tension of the gas surrounding the surface, they will not be diminished by diminishing the tension of the gas; and consequently no amount of pumping would destroy such forces where they once existed. Whereas the smaller the tension of the gas the freer the surface will be to move, and the less its motion would be opposed by convection currents; hence, on the supposition that the motion is due to these forces, the only effect of improving the vacuum would be to intensify the action. An this being the case, it is clear that Mr. Crookes's experiments, in which he finds that the action still remains in the most perfect vacuum which he has obtained, tend to support and not to upset my conclusion that the actions are due to these forces. The fact that Mr. Crookes finds it impossible to conceive this only shows, as I have said, that he does not comprehend the nature of the forces; for it certainly presents no greater difficulty than the fact that the velocity of sound is independent of the tension of the gas through which it is transmitted.
Evaluation of the performance of a fiber-bundle-based optical wireless link

This paper reports on a simulation-based investigation of an optical wireless system using fiber-bundle based transmitters and receivers. The simulation incorporates both beam propagation theory and experimental data from evaluations of the individual components. The coverage area at the receiver is evaluated as a function of transmitter power, link length, misalignment, and the number of transmitter fibers employed. An optimum coverage area is achievable with proper selection of transmitter parameters for a given link length. Trade-offs between the number of fibers employed and the transmitter power are explored.
Comparison of the three large polymerase proteins of influenza A, B, and C viruses

The three large RNA segments of influenza C virus C/JJ/50 were cloned and sequenced, and the deduced amino acid sequences were compared with those of the polymerase (P) proteins of influenza A and B viruses. The coding strategy of the C virus RNA segments is the same as that for the large A and B virus segments as one long open reading frame is present in each segment. RNA segment 1 of influenza C virus encodes the equivalent of the PB2 protein; it has an approximate 25% sequence identity with the corresponding (cap binding) influenza A and B virus PB2 proteins. The PB1 protein of influenza C virus, coded for by segment 2, has an approximate 40% sequence identity with the corresponding proteins of influenza A and B viruses including the Asp-Asp sequence motif found in many RNA polymerase molecules. The PB1 polymerase is thus the most highly conserved protein among the influenza A, B, and C viruses. Although the protein coded for by RNA 3 of influenza C virus shows an approximate 25% sequence identity with the acid polymerase (PA) proteins of the A and B viruses, its sequence does not display any acid charge features at neutral pH. This protein is thus referred to as the P3 (rather than the PA) protein of influenza C virus.
Atomic-resolution scanning-tunneling-microscopy investigations of alkali-metal – graphite intercalation compounds

The scanning tunneling microscope has been used to image stage-1 and stage-2 potassium, rubidium, and cesium graphite intercalation complexes with atomic resolution. Images of the stage-1 materials exhibit a 2a modulation for a wide range of tunneling currents (0.5 to 10 nA) and bias voltages (-750 to +750 mV). This new superlattice is also ordered over large (g500\ifmmode\times\else\texttimes\fi{}500 A${\r{}}^{2}$) areas. Images of the stage-2 materials are dominated by a centered hexagonal structure typical of graphite. The vertical corrugation determined for the stage-2 materials is, however, significantly smaller than observed for graphite. These results are discussed with respect to theoretical explanations of the anomalous features observed in images of graphite.
Field systems analysis: A tactical guide for exploring temporal relationships in classroom settings

Abstract Many research paradigms are currently competing for acceptance in teacher effectiveness research, all striving to lend greater insight into the ecological and behavioral intricacies of expert instruction. One alternative, titled field systems analysis, is presented from conceptual and technical perspectives. This approach primarily focuses upon the temporal relationships among organismic behaviors and contextual elements in classroom settings, providing for the discovery of contiguous chains of behaviors. Driven by induction and description, the strategy de-emphasizes claims of independent causality. The methodology includes: (a) verbal description, (b) exhaustive category system construction, (c) alternative forms of data presentation, and (d) alternative dimensions of data interpretation. Selected results of an exemplary study with one teacher are provided to demonstrate the nature and benefits of the paradigm. Several chains of instructional behavior were apparent, and insight was gained into the temporal relationships among instructional, interpersonal, and managerial teacher behaviors.
A molecular theory of polymer chain folding

A molecular theory is proposed to account for the regular folding of polymer chains during crystallization. It predicts that an isolated polymer chain greater than some critical length can lower its energy by crystallizing into a regular folded-chain conformation. Similarly, a single molecular chain crystallizing upon an infinitely large substrate will also lower its free energy by regular folding. In a crystal composed of polymer molecules all having the same length the lowest free energy occurs when all chains are completely extended; however, there also exists a whole series of metastable states corresponding to one, two, three, etc. folds per molecules. When the crystal is composed of a distribution of molecular lengths, the lowest free energy corresponds to a folded-chain crystal whose thickness is a sensitive function of the distribution. If the low end of the molecular length distribution is assumed to be truncated at the observed length of extended-chain crystals, the theory satisfactorily predicts the observed thicknesses of folded-chain crystals obtained by melt crystallization of both fractions and whole polymer. I never saw a folded chain. I never hope to see one But I can tell you anyhow. I'm damn near sure there be one.
Molecular phylogeny and biogeography of Linanthus (Polemoniaceae)

To better understand the evolutionary history of Linanthus (Polemoniaceae) and its relatives, molecular phylogenies based on DNA sequence data from the internal transcribed spacer (ITS) region of nrDNA and the chloroplast gene matK were estimated using several methods. Our data suggest two separate and well-supported lineages of Linanthus in close association with two other genera— Leptodactylon and Phlox. These results agree with previous molecular systematic work on the Polemoniaceae, but do not support the traditional classification of the genus as a natural group, nor do they support the sectional classification within the genus. With a distribution centered primarily in western North America and a high degree of endemism in the California Floristic Province, it has been suggested by Raven and Axelrod that the origin and diversification of Linanthus and its relatives were tied to the development of a summer-dry climate in western North America, which began around 13‐15 million years ago (mya). Increased drying during the Pliocene (1.2‐5 mya) has also been hypothesized by Axelrod to have led to an increase in plant speciation in California and adjacent areas. Divergence times within the Linanthus lineages were estimated from the ITS and matK gene trees. A log-likelihood ratio test could not reject clock-like evolution for the matK data; however, the clock was strongly rejected for the ITS data set. Although ITS molecular evolution was not clock-like, the estimated times of divergence were similar to those of the matK data set. Within both lineages of Linanthus there seems to have been considerable diversification that has occurred since the Pliocene.
Democratization and Land Reform Accomplishment in the Philippines

Does democratization lead to land reform accomplishment? In the literature, there is no consensus. Three possibilities exist: democracy causes increased land redistributions, is merely correlated with it, or is not associated with the transfer of physical assets at all. To choose between possibilities, I conduct a detailed qualitative analysis of land-tenure patterns and reform initiatives from colonial times to the present. I also compile a dataset from original and secondary sources in order to report Philippine land-redistribution accomplishment. I have descriptive statistics of accomplishment from 1960 to the present and more comprehensive data from 1972 to 2003. The descriptive statistics that I collected show a pattern that is consistent with a positive relationship between democracy and land redistribution. I then turn my attention to the mechanism. Is it plausible that elections explain reform? Do peasants insist upon land transfers? I find evidence to suggest that this is, in fact, the case. My first set of results tests whether land transfers are correlated with agricultural population. Due to data limitations, this analysis is conducted in cross section. Consistent with the idea that a democratic government would be responsive to the interests of the public, results show that the government redistributed a greater share of the targeted land in provinces in which a greater share of the population worked in agriculture. My second set of results exploits the availability of time-series cross-sectional data for leaseholds. My analysis shows that as agriculture becomes more important to the regional economy — and to regional voters — the government responds by increasing the rate at which leaseholds are created above the rate that might be expected from the rate seen the previous year.
Identification and biological evaluation of a novel and potent small molecule radiation sensitizer via an unbiased screen of a chemical library.

For patients with solid tumors, the tolerance of surrounding tissues often limits the dose of radiation that can be delivered. Thus, agents that preferentially increase the cytotoxic effects of radiation toward tumor cells would significantly alter the therapeutic ratio and improve patient survival. Using a highthroughput, unbiased screening approach, we have identified 4¶-bromo-3¶-nitropropiophenone (NS-123) as a radiosensitizer of human glioma cells in vitro and in vivo. NS-123 radiosensitized U251 glioma cells in a dose-dependent and timedependent manner, with dose enhancement ratios ranging from 1.3 to 2.0. HT-29 colorectal carcinoma and A549 lung adenocarcinoma cells were also radiosensitized by NS-123 in vitro, whereas NS-123 did not increase the radiation sensitivity of normal human astrocytes or developmental abnormalities or lethality of irradiated Zebrafish embryos. In a novel xenograft model of U251 cells implanted into Zebrafish embryos, NS-123 enhanced the tumor growth-inhibitory effects of ionizing radiation (IR) with no apparent effect on embryo development. Similar results were obtained using a mouse tumor xenograft model in which NS-123 sensitized U251 tumors to IR while exhibiting no overt toxicity. In vitro pretreatment with NS-123 resulted in accumulation of unrepaired IR-induced DNA strand breaks and prolonged phosphorylation of the surrogate markers of DNA damage H2AX, ataxia telangiectasia mutated protein, DNA-dependent protein kinase, and CHK2 after IR, suggesting that NS-123 inhibits a critical step in the DNA repair pathway. These results show the potential of this cell-based, high-throughput screening method to identify novel radiosensitizers and suggest that NS-123 and similar nitrophenol compounds may be effective in antiglioma modalities. [Cancer Res 2007; 67(18):8791–9]
Elder Abuse Some African American Views

To gain a greater understanding of what “elder abuse” means to the American public, a random sample of adults from seven culturally diverse counties in North Carolina was interviewed. Included in the sample were African Americans from four different counties and regions of the state. The four African American groups' responses were compared with each other, and with the views of a panel of elder mistreatment experts. There were areas of agreement and disagreement. The relevance of the findings is discussed in relation to research, practice, education, and policy.
Studies on the supracallosal mesial cortex of unanesthetized, conscious mammals. II. Monkey. A. Movements elicited by electrical stimulation.

Abstract 1. 1. The supracallosal mesial cortex of alert, unanesthetized cats was stimulated by bidirectional pulses and mapped for movement. 2. 2. The bidirectional pulse separates well the thresholds for movement (lower) and electrical epileptiform after-discharge (higher). An increase in the pulse duration of a unidirectional pulse brings these two thresholds closer together. 3. 3. The threshold for movement during the sleeping state is approximately twice as high as that found during the waking state for all frequencies of stimulation. 4. 4. Two “felunculi” (feline equivalent of homunculus) are found: the anterior felunculus has a lower threshold than the posterior one. The face is represented at the anterior and posterior portion of the mesial region with the extremities in the middle. The majority (86 per cent) of all observed responses from the mesial cortex involve movements of the face and head. 5. 5. Ipsilateral and bilateral responses are prominently represented on the posterior felunculus. 6. 6. Evidence is shown to suggest that functions of the entire supracallosal mesial cortex of the cat may include a motor representation.
Late Miocene to Pleistocene paleoceanographic records from the Feni and Gardar Drifts: Pliocene reduction in abyssal flow

Magnetic fabric analyses from two North Atlantic drift deposits provide proxies for determining relative variations in the strength of abyssal flow over the last 10 my. The data show a cessation of current-controlled sedimentation at the shallower Feni Drift (2417 m) at the time of onset of Northern Hemisphere glaciation (2.6 Ma). Drift formation ended nearly 2 my earlier (4.2 Ma) at the deeper Gardar Drift (3220 m), implying stepwise reduction in deep-water flow. Relatively light d 18 O values at the deeper Gardar Drift indicate a warmer, thus also more salty, water mass site prior to 6 Ma. We interpret this as representing Mediterranean Sea water, which flowed north at depths greater than that of the Feni Drift Site. The supply of Mediterranean Water to the North Atlantic was shut off as the Gibraltar Straits closed, causing the Messinian salinity crisis, and never returned to that position in the water column after the Mediterranean opened again. D 2005 Elsevier B.V. All rights reserved.
The zeroth law of thermodynamics and volume-preserving conservative system in equilibrium with stochastic damping

Abstract We propose a mathematical formulation of the zeroth law of thermodynamics and develop a stochastic dynamical theory, with a consistent irreversible thermodynamics, for systems possessing sustained conservative stationary current in phase space while in equilibrium with a heat bath. The theory generalizes underdamped mechanical equilibrium: d x = g d t + { − D ∇ ϕ d t + 2 D d B ( t ) } , with ∇ ⋅ g = 0 and { ⋯ } respectively representing phase-volume preserving dynamics and stochastic damping. The zeroth law implies stationary distribution u s s ( x ) = e − ϕ ( x ) . We find an orthogonality ∇ ϕ ⋅ g = 0 as a hallmark of the system. Stochastic thermodynamics based on time reversal ( t , ϕ , g ) → ( − t , ϕ , − g ) is formulated: entropy production e p # ( t ) = − d F ( t ) / d t ; generalized “heat” h d # ( t ) = − d U ( t ) / d t , U ( t ) = ∫ R n ϕ ( x ) u ( x , t ) d x being “internal energy”, and “free energy” F ( t ) = U ( t ) + ∫ R n u ( x , t ) ln u ( x , t ) d x never increases. Entropy follows d S d t = e p # − h d # . Our formulation is shown to be consistent with an earlier theory of P. Ao. Its contradistinctions to other theories, potential-flux decomposition, stochastic Hamiltonian system with even and odd variables, Klein–Kramers equation, Freidlin–Wentzellʼs theory, and GENERIC, are discussed.
Heterodimerization and functional interaction between EGF receptor family members: a new signaling paradigm with implications for breast cancer research

The EGF receptor (EGFR) and HER2 are members of a growth factor receptor family. Overexpression of either protein in advanced breast cancer correlates with poor prognosis. EGF stimulates growth by binding to EGFR, activating the receptor's intracellular tyrosine kinase. The initial consequence is phosphorylation of specific tyrosine-containing sequences in the receptor's carboxyl terminus. These phosphotyrosines serves as high affinity recognition sites for proteins that, in turn, transmit the growth signal inside the cell. Mechanistic studies suggest that EGF binds to a single EGFR, triggering dimerization with another like receptor molecule. This dimerization is thought to initiate the tyrosine kinase activation. The EGF receptor family was recently expanded with the sequencing of HER3 and HER4. Each of the four family members was postulated to regulate a unique growth or differentiation signaling repertoire when activated by a receptor-specific ligand. However, new data from numerous laboratories suggest that EGFR family members may play a complex and ultimately more flexible role in signaling by forming heterodimers between family members, e.g. EGFR:HER2 or HER4:HER2. These heterodimers may form even when only one member of the pair binds its ligand. This review summarizes current work on heterodimerization and attempts to predict the consequences for downstream signaling. In brief, when compared to ligand-dependent receptor homodimers comprised of two proteins with the same internalization sequence and phosphorylated tyrosine residues, heterodimers are likely to: i) expand substrate selection and downstream signaling pathway activation; ii) promote interaction between sets of substrates in the mixed receptor complexes that would not ordinarily be physically juxtaposed; iii) alter the duration of receptor signaling by changing rates of receptor internalization, ligand loss, kinase inactivation, recycling, etc.; and iv) alter rates of receptor and substrate dephosphorylation. In addition to understanding interactions of heterodimers with the internalization machinery, identification of receptor-specific substrates and binding proteins for each EGFR family member will be necessary to explicate the role of heterodimers in growth and differentiation.
Minimum register requirements for a module schedule

Module scheduling is an efficient technique for exploiting instruction level parallelism in a variety of loops, resulting in high performance code but increased register requirements. We present a combined approach that schedules the loop operations for minimum register requirements, given a module reservation table. Our method determines optimal register requirements for machines with finite resources and for general dependence graphs. This method demonstrates the potential of lifetime-sensitive module scheduling and is useful in evaluating the performance of lifetime-sensitive module scheduling heuristics.
TRANSPORTABLE NATURAL-LANGUAGE INTERFACES: PROBLEMS AND TECHNIQUES

I will address the questions posed to the panel from wlthln the context of a project at SRI, TEAM [Grosz, 1982b], that is developing techniques for transportable natural-language interfaces. The goal of transportability is to enable nonspeciallsts to adapt a natural-language processing system for access to an existing conventional database. TEAM is designed to interact with two different kinds of users. During an acquisition dlalogue, a database expert (DBE) provides TEAM with information about the files and fields in the conventlonal database for which a natural-language interface is desired. (Typlcally this database already exists and is populated, but TEAM also provides facillties for creating small local databases.) This dlalogue results in extension of the language-processlng and data access components that make it possible for an end user to query the new database in natural language.
Numerical Simulation of Subduction Zone Pressure-Temperature-Time Paths: Constraints on Fluid Production and Arc Magmatism

The location and sequence of metamorphic devolatilization and partial melting reactions in subduction zones may be constrained by integrating fluid and rock pressure-temperature-time (P-T-t) paths predicted by numerical heat-transfer models with phase diagrams constructed for metasedimentary, metabasaltic, and ultramafic bulk compositions. Numerical experiments conducted using a two-dimensional heat transfer model demonstrate that the primary controls on subduction zone P-T-t paths are: (1) the initial thermal structure; (2) the amount of previously subducted lithosphere; (3) the location of the rock in the subduction zone; and (4) the vigour of mantle wedge convection induced by the subducting slab. Typical vertical fluid fluxes out of the subducting slab range from less than 0.1 to 1 (kg fluid) m$^{-2}$ a$^{-1}$ for a convergence rate of 3 cm a$^{-1}$. Partial melting of the subducting, amphibole-bearing oceanic crust is predicted to only occur during the early stages of subduction initiated in young (less than 50 Ma) oceanic lithosphere. In contrast, partial melting of the overlying mantle wedge occurs in many subduction zone experiments as a result of the infiltration of fluids derived from slab devolatilization reactions. Partial melting in the mantle wedge may occur by a two-stage process in which amphibole is first formed by H$_{2}$O infiltration and subsequently destroyed as the rock is dragged downward across the fluid-absent `hornblende-out' partial melting reaction.
FACTORS INVOLVED IN THE INDUCTION OF NON-SPECIFIC RESISTANCE TO STREPTOCOCCAL INFECTION IN MICE BY ENDOTOXIN

Endotoxins derived from several species of Gram-negative bacteria, while inducing non-specific resistance to typhoid bacilli in mice, failed to increase the resistance of these animals to infection with virulent strains of Group A streptococci. However, if administration of endotoxin was followed by injection of minute amounts of type-specific antiserum, a substantial degree of protection against the streptococcal pathogen was obtained. The same amount of type-specific antiserum given to the animals by itself did not have any effect on the outcome of the streptococcal infection. Fresh rabbit blood, obtained from animals pretreated with endotoxin, together with anti-M protein immune serum, was found strongly bactericidal for streptococci. These observations suggest that, at least with regard to streptococcal infection, both humoral and cellular factors are required for induction of non-specific resistance.
Parallel phylogeographic structure in ecologically similar sympatric sister taxa

Present-day phylogeographic patterns have been shaped by the dual histories of lineages and places, producing a diversity of relationships that may challenge discovery of general rules. For example, the predicted positive correlation between dispersal ability and gene flow has been supported inconsistently, suggesting unaccounted complexity in theory or the comparative framework. Here, I extend the sympatric sister-species approach, in which variance between lineages and places is minimized, to sister clades and test a fundamental assumption of comparative genetic studies of dispersal: that taxa which evolved at the same time and in the same place will, if they have similar life histories and ecologies, have essentially the same phylogeographic structure. Phylogenetic analyses of 197 Stigmatopora pipefishes using two nuclear (creatine kinase intron 6, α-tropomyosin) and two mitochondrial (16S, noncoding region) loci revealed largely synchronous parallel diversification of sister clades that are codistributed from Western Australia to New Zealand, supporting the null hypothesis. Only one comparison, however, yielded a sympatric sister-species pair (the two stem species), so I also explored the potential for extant species sharing a substantial proportion of their evolutionary histories in sympatry to substitute for sister taxon comparisons. In eastern Australia, where strong environmental structure is lacking, phylogeographic differences between species that have been codistributed for ∼85% of their evolutionary histories were consistent with tendencies favoured by their modest life-history differences, that is the larger, rarer species had lower genetic diversity. In contrast, in New Zealand, two species codistributed for ∼70% of their evolutionary histories were both structured similarly by a strong biogeographic filter despite differences in life history. Rigorously quantifying the influence of intrinsic and extrinsic factors on phylogeographic structure may advance most efficiently through meta-analyses of contemporaneously codistributed taxa, including but not limited to sympatric sister species.
Interaction of Muscle and Brain Sodium Channels with Multiple Members of the Syntrophin Family of Dystrophin-Associated Proteins

Syntrophins are cytoplasmic peripheral membrane proteins of the dystrophin-associated protein complex (DAPC). Three syntrophin isoforms, α1, β1, and β2, are encoded by distinct genes. Each contains two pleckstrin homology (PH) domains, a syntrophin-unique (SU) domain, and a PDZ domain. The name PDZ comes from the first three proteins found to contain repeats of this domain (PSD-95,Drosophila discs large protein, and the zona occludens protein 1). PDZ domains in other proteins bind to the C termini of ion channels and neurotransmitter receptors containing the consensus sequence (S/T)XV-COOH and mediate the clustering or synaptic localization of these proteins. Two voltage-gated sodium channels (NaChs), SkM1 and SkM2, of skeletal and cardiac muscle, respectively, have this consensus sequence. Because NaChs are sarcolemmal components like syntrophins, we have investigated possible interactions between these proteins. NaChs copurify with syntrophin and dystrophin from extracts of skeletal and cardiac muscle. Peptides corresponding to the C-terminal 10 amino acids of SkM1 and SkM2 are sufficient to bind detergent-solubilized muscle syntrophins, to inhibit the binding of native NaChs to syntrophin PDZ domain fusion proteins, and to bind specifically to PDZ domains from α1-, β1-, and β2-syntrophin. These peptides also inhibit binding of the syntrophin PDZ domain to the PDZ domain of neuronal nitric oxide synthase, an interaction that is not mediated by C-terminal sequences. Brain NaChs, which lack the (S/T)XV consensus sequence, also copurify with syntrophin and dystrophin, an interaction that does not appear to be mediated by the PDZ domain of syntrophin. Collectively, our data suggest that syntrophins link NaChs to the actin cytoskeleton and the extracellular matrix via dystrophin and the DAPC.
Ovarian Dysgenesis Due to 45 X, 0/46 Dic (X) Mosaicism

A 16 year old girl was evaluated for short stature, primary amenorrhea, and lack of development of secondary sex characteristics. She did not have the classical phenotypic signs of Turner's syndrome. However, she was short, had infantile genitalia and the adnexa were not palpable. There was a minor bone malformation and no signs of visceral abnormalities. The hormonal studies showed hypergonadotropic hypogonadism and borderline hypothyroidism. The rest of the endocrine functions was normal. The Barr bodies on the buccal smear were decreased and in part abnormal, large or bipartite. The karyotype showed mosaicism of about equal proportions of 45 X, 0/46, X, die (X). The large dicentric chromosome was due to the end to end fusion of two X chromosomes by their short arms. Sequential binding studies were performed and failed to document any loss of genetic material of the dicentric X. It is speculated that the fusion of X chromosomes during an early mitotic division was responsible for the 45 X, 0 cell line, ...
Pharmacologically Increasing Mdm2 Inhibits DNA Repair and Cooperates with Genotoxic Agents to Kill p53-Inactivated Ovarian Cancer Cells

The Mdm2 oncogene is a negative regulator of the p53 tumor suppressor and recently identified inhibitor of DNA break repair. Nutlin-3 is a small-molecule inhibitor of Mdm2–p53 interaction that can induce apoptosis in cancer cells through activation of p53. Although this is a promising therapy for those cancers with wild-type p53, half of all human cancers have inactivated p53. Here, we reveal that a previously unappreciated effect of Nutlin is inhibition of DNA break repair, stemming from its ability to increase Mdm2 protein levels. The Nutlin-induced increase in Mdm2 inhibited DNA double-strand break repair and prolonged DNA damage response signaling independent of p53. Mechanistically, this effect of Nutlin required Mdm2 and acted through Nbs1 of the Mre11–Rad50–Nbs1 DNA repair complex. In ovarian cancer cells, where >90% have inactivated p53, Nutlin combined with the genotoxic agents, cisplatin or etoposide, had a cooperative lethal effect resulting in increased DNA damage and apoptosis. Therefore, these data demonstrate an unexpected consequence of pharmacologically increasing Mdm2 levels that when used in combination with genotoxic agents induces synthetic lethality in ovarian cancer cells, and likely other malignant cell types, that have inactivated p53. Implications: Data reveal a therapeutically beneficial effect of pharmacologically increasing Mdm2 levels combined with chemotherapeutic agents for malignancies that have lost functional p53. Mol Cancer Res; 13(8); 1197–205. ©2015 AACR . This article is featured in Highlights of This Issue, [p. 1161][1] [1]: /lookup/volpage/13/1161?iss=8
[18F]2-fluoro-2-deoxy-D-glucose positron emission tomography demonstration of estrogen negative and positive feedback on luteinizing hormone secretion in women.

Context: Precise regulation of the neuroendocrine components of the female reproductive axis involves both negative and positive feedback of estrogen on gonadotropin secretion. Objective: Our objective was to determine the hypothalamic and/or pituitary sites of estrogen negative and positive feedback using neuroimaging techniques. Design and Setting: A graded estrogen infusion protocol was administered at a General Clinical Research Center in an academic medical center. Subjects: Healthy postmenopausal women (n = 11) were recruited for study. Interventions: Serum samples were measured every 4 h. A structural magnetic resonance imaging was performed at baseline, and [18F]2-fluoro-2-deoxy-d-glucose (18FDG) positron emission tomography was performed at baseline and 24 and 72 h. FDG positron emission tomography was co-registered with magnetic resonance imaging scans, and region of interest analysis was performed. Main Outcome Measures: Serum LH and estradiol were assessed. Normalized values for glucose uptake were extracted from each region of interest for each subject at each time point. Results: A decrease in normalized 18FDG uptake was apparent in the hypothalamus at 24 h (P < 0.02) associated with decreased LH (P < 0.0005). The increase in LH at 72 h (P < 0.0005) was associated with increased pituitary 18FDG uptake (P < 0.02) but no change in hypothalamic uptake. Conclusions: Changes in 18FDG uptake as a measure of metabolic activity can be demonstrated in the hypothalamus and pituitary in association with discrete hormonal events. Results are consistent with mediation of estrogen negative feedback on LH at the hypothalamus, whereas estrogen positive feedback occurs at the pituitary with no evidence of increased hypothalamic activity in women.
Parasite loss and introduced species: a comparison of the parasites of the Puerto Rican tree frog, ( Eleutherodactylus coqui ), in its native and introduced ranges

The Puerto Rican frog, Eleutherodactylus coqui has invaded Hawaii and reached densities far exceeding those in their native range. One possible explanation for the success of E. coqui in its introduced range is that it lost its co-evolved parasites in the process of the invasion. We compared the parasites of E. coqui in its native versus introduced range. We collected parasite data on 160 individual coqui frogs collected during January-April 2006 from eight populations in Puerto Rico and Hawaii. Puerto Rican coqui frogs had higher species richness of parasites than Hawaiian coqui frogs. Parasite prevalence and intensity were significantly higher in Hawaii, however this was likely a product of the life history of the dominant parasite and its minimal harm to the host. This suggests that the scarcity of parasites may be a factor contributing to the success of Eleutherodactylus coqui in Hawaii.
Effect of Faraday rotation on L-band interferometric and polarimetric synthetic-aperture radar data

Electromagnetic waves traveling through the ionosphere undergo a Faraday rotation of the polarization vector, which modifies the polarization and phase characteristics of the electromagnetic signal. Using L-band (/spl lambda/=24 cm), polarimetric synthetic aperture radar (SAR) data from the shuttle imaging radar C (SIR-C) acquired in 1994, the author simulates the effect of a change in the Faraday rotation angle /spl psi/ on spaceborne interferometric and polarimetric data. In one experiment, it was found that phase coherence is reduced by up to 33% when /spl psi/ changes between successive data acquisitions. If /spl psi/ changes by more than 40/spl deg/, a differential phase signal, which varies from field to field, appears in the interferogram and impairs the mapping of surface topography and/or the detection of ground deformation. This signal is caused by phase differences between horizontal-polarized and vertical-polarized radar signals from intermediate levels of vegetation canopy, similar to the phase difference measured between H-polarized and V-polarized signals on a single date. In a second experiment, data from the Japanese Earth Resources Satellite (JERS-1) L-band radar acquired in an area of active deforestation in Rondonia, Brazil, are compared with SIR-C L-band polarimetric data acquired at the same incidence, two weeks later, but from a lower orbiting altitude. Large differences in scattering behavior are recorded between the two datasets in the areas of slash and burn forest, which are difficult to reconcile with surface changes. A simulation with SIR-C polarimetric data, however, suggests that those differences are consistent with a Faraday rotation angle of about 30/spl plusmn/10/spl deg/ in the JERS-1 data and 0/spl deg/ in the SIR-C data. Based on these two experiments and on Global Positioning System (GPS) records of ionospheric activity, it is concluded that Faraday rotation should not affect the analysis of L-band spaceborne data during periods of low ionospheric activity (solar minima).
Conversation with Noam Chomsky about Social Justice and the Future

Leading intellectual Noam Chomsky offers historical perspectives, insight and critique regarding recent social movements. His views on the Occupy movement, in particular, resonate with some key themes in Jesuit higher education. An interview with Chomsky, conducted by Chris Steele, centers on seven questions, presented here in both text and video, that can be used to spark reflection and discussion in university classrooms.
A Power-Aware Run-Time System for High-Performance Computing

For decades, the high-performance computing (HPC) community has focused on performance, where performance is defined as speed. To achieve better performance per compute node, microprocessor vendors have not only doubled the number of transistors (and speed) every 18-24 months, but they have also doubled the power densities. Consequently, keeping a large-scale HPC system functioning properly requires continual cooling in a largemachine room, thus resulting in substantial operational costs. Furthermore, the increase in power densities has led (in part) to a decrease in system reliability, thus leading to lost productivity. To address these problems, we propose a power-aware algorithm that automatically and transparently adapts its voltage and frequency settings to achieve significant power reduction and energy savings with minimal impact on performance. Specifically, we leverage a commodity technology called "dynamic voltage and frequency scaling" to implement our power-aware algorithm in the run-time system of commodity HPC systems.
Simultaneous determination of 3-mercaptopyruvate and cobinamide in plasma by liquid chromatography–tandem mass spectrometry

The current suite of Food and Drug Administration (FDA) approved antidotes (i.e., sodium nitrite, sodium thiosulfate, and hydroxocobalamin) are effective for treating cyanide poisoning, but individually, each antidote has major limitations (e.g., large effective dosage or delayed onset of action). To mitigate these limitations, next-generation cyanide antidotes are being investigated, including 3-mercaptopyruvate (3-MP) and cobinamide (Cbi). Analytical methods capable of detecting these therapeutics individually and simultaneously (for combination therapy) are essential for the development of 3-MP and Cbi as potential cyanide antidotes. Therefore, a liquid chromatography-tandem mass-spectrometry method for the simultaneous analysis of 3-MP and Cbi was developed. Sample preparation of 3-MP consisted of spiking plasma with an internal standard ((13)C3-3-MP), precipitation of plasma proteins, and derivatizing 3-MP with monobromobimane to produce 3-mercaptopyruvate-bimane. Preparation of Cbi involved denaturing plasma proteins with simultaneous addition of excess cyanide to convert each Cbi species to dicyanocobinamide (Cbi(CN)2). The limits of detection for 3-MP and Cbi were 0.5μM and 0.2μM, respectively. The linear ranges were 2-500μM for 3-MP and 0.5-50μM for Cbi. The accuracy and precision for 3-MP were 100±9% and <8.3% relative standard deviation (RSD), respectively. For Cbi(CN)2, the accuracy was 100±13% and the precision was <9.5% RSD. The method presented here was used to determine 3-MP and Cbi from treated animals and may ultimately facilitate FDA approval of these antidotes for treatment of cyanide poisoning.
Regulation of nuclear factor κB activation by G-protein-coupled receptors

Accumulating evidence indicates that G-protein-coupled receptors (GPCRs) play an active role in transcriptional regulation. In leukocytes, activation of receptors for several chemokines and classic chemoattractants has been associated with enhanced expression of proinflammatory cytokines and chemokines. GPCRs in endothelial and epithelial cells also regulate transcription and contribute to the expression of cytokines, adhesion molecules, and growth factors that are essential for extravasation of leukocytes and tissue repair. Nuclear factor (NF) kappaB is one of the most important transcription factors responsible for the expression of these proinflammatory genes. Recent studies have shown that GPCRs utilize several different pathways to activate NF-kappaB. These pathways differ from the ones induced by classic cytokines in that they are initiated by heterotrimeric G-proteins, but they converge to IkappaB phosphorylation and nuclear translocation/modification of the NF-kappaB proteins. GPCR-induced NF-kappaB activation provides an effective means for local expression of cytokine and growth factor genes due to the wide distribution of these receptors. Chemokine-induced, GPCR-mediated production of chemokines constitutes an autocrine regulatory mechanism for the growth of certain malignant tumors and enhances the recruitment of leukocytes to sites of inflammation.
Levodopa in the treatment of Parkinson's disease.

Levodopa is the most efficacious drug to treat the symptoms of Parkinson’s disease (PD) and is widely considered the “gold standard” by which to compare other therapies, including surgical therapy. Response to levodopa is one of the criteria for the clinical diagnosis of PD. A major limiting factor in levodopa therapy is the development of motor complications, namely dyskinesias and motor fluctuations. The ELLDOPA study was designed to determine if levodopa affected the progression of PD. This double-blind randomized study showed that the subjects treated with levodopa for 40 weeks had less severe parkinsonism than the placebo treated subjects even after a 2-week washout of medications, with the highest dose group showing the greatest benefit. Thus, levodopa may actually have neuroprotective value, but the result was not conclusive of slowing disease progression, because the same result could have arisen from a very long-lasting symptomatic benefit of levodopa.
Social Cooperation and the Apparent Tension between Personal and Impersonal Exchange

Experimental research provides evidence for both agents as noncooperatively self-interested and cooperatively other-regarding. Drawing on the work of F.A. Hayek, Vernon Smith attempts to resolve this apparent tension by distinguishing between two spheres of human interaction. According to V. Smith, in the personal sphere individuals are psychologically hardwired for cooperation and in the impersonal sphere they are hardwired for noncooperative behavior. Building on the solution offered by V. Smith, this paper offers a rational choice approach to seemingly anomalous experimentally observed behavior. Using the Ricardian Law of Association, I reconstitute trust game decision trees to resolve the apparent tension in experimental results.
Examination of type specimens for Colliculoamphora reichardtiana (Grunow) Williams and Reid, with a description of a new species, Colliculoamphora johnwrightii nov. sp.

In the original description of the diatom genus Colliculoamphora, the type species of Colliculoamphora reichardtiana (Grunow) Williams and Reid (= Amphora reichardtiana Grunow) was mistakenly said to be from Honduras. Inspection of relevant specimens and manuscript material of Amphora reichardtiana in Grunow's collection (held in W) has permitted a re-evaluation of the species. Type material has been identified and, after examination, a new species, Colliculoamphora johnwrightii, is separated from Colliculoamphora reichardtiana.
An Output-Based Adaptive Hybridized Discontinuous Galerkin Method on Deforming Domains

In this paper we present an output-based adaptive method for unsteady simulations of convection-dominated flows on deformable domains. The target discretization is the hybridized discontinuous Galerkin method (HDG), which offers potential computational savings at high order compared to the discontinuous Galerkin (DG) method. Mesh deformation is achieved through an arbitrary Lagrangian-Eulerian transformation with an analytical mapping. We present details of this transformation applied to the HDG system of equations, with focus on the auxiliary gradient equation, viscous stabilization, and output calculation. The temporal discretization for adaptive runs is DG in time, which lends itself to rigorous a posteriori error estimation using a fine-space discrete adjoint solution. We present modifications to the approximate factorization technique that enables an efficient DG-in-time solution for HDG. Space-time error estimates drive metric-based static spatial refinement on unstructured spatial meshes and slab-based temporal nodalizations. We show accuracy and cost comparisons between adaptive DG and HDG simulations of two-dimensional flows governed by the compressible Navier-Stokes equations on deforming domains.
Comparison of Fast Gas Chomatography–Surface Acoustic Wave (FGC-SAW) Detection and GC-MS for Characterizing Blueberry Cultivars and Maturity

A novel analytical method using fast gas chromatography-surface acoustic wave detection (FGC-SAW) was employed to rapidly characterize blueberry volatile profiles according to genotypes and fruit maturity. Fourteen FGC-SAW peaks were observed and 11 peaks were tentatively identified in the 15 s chromatogram. Peak identifications were confirmed by matching retention index values with similar values from GC-MS analyses of the same samples. Eighty peaks were observed in the 40 min GC-MS analysis of identical samples. Principal component analysis (PCA) score plots of FGC-SAW and GC-MS data both differentiated blueberries according to genotype, maturity stage, and harvest date even though FGC-SAW PCA's used far fewer peak area values. PCA plots clearly separated 'FL02-40', 'Snowchaser', 'Jewel', and 'Primadonna' blueberry cultivars into four quarters using two-dimensional PCA projections. FGC-SAW was also successful in differentiating three berry maturity stages in PCA score plots for both 'Jewel' and 'Primadonna' cultivars. FGC-SAW is an effective technique for rapid analysis of major blueberry volatiles, but could not determine many mid- and low-level volatiles as they were often coeluted with higher concentration volatiles.
Polymyxin B Treatment Improves Bactofection Efficacy and Reduces Cytotoxicity

Improvements to bacterial vectors have resulted in nonviral gene therapy vehicles that are easily prepared and can achieve high levels of transfection efficacy. However, these vectors are plagued b...
Systems of quadratic equations: Efficient solution algorithms and conditions for solvability

We study multivariate systems of quadratic equations of the form F (x) = s where F ∶ ℝn ↦ ℝn and Fi a quadratic function of x for i = 1, …, n. These types of equations arise across a variety of applications including sensor network localization, power systems and matrix factorization. In general, solving systems of quadratic equations is a challenging task, and in its most general form is NP-hard. In this paper, we approach this problem from a different perspective: We characterize domains over which the problem can be solved efficiently. For any such domain, we develop an efficient algorithm that terminates with: a) a solution in the domain, or b) a certificate of non-existence of the solution in the domain. Further, we derive conditions on s that guarantee the existence of a solution in the domain. We show how this result can be used to construct convex inner approximations to the feasible set of a Quadratically Constrained Quadratic Program (QCQP). Finally, we illustrate the results on simple examples from these application domains.
Comparison of Sensitivity of Serum and CSF Samples in Immunodiagnosis of Neurocysticercosis

Paired serum and CSF samples were obtained from 91 patients with neurocysticercosis (NCC) for detection of Taenia solium (TS) antibodies and antigens, in a study at centers in Lima, Peru, Belgium, and the USA.