cssi/SciSciGPT-SciSciNet huggingface dataset:
T-cell non-Hodgkin lymphoma in human immunodeficiency virus-1-infected individuals

We present two patients with human immunodeficiency virus-1 (HIV-1) infection in whom T-cell non-Hodgkin lymphoma developed, based on pathologic diagnosis, immunophenotyping, and T-cell receptor gene rearrangement. Both cases were positive for human immunodeficiency virus-1 by enzyme-linked immunosorbent assay and immunoblot methods. Histologic sections from each patient showed a high-grade pleomorphic T-cell non-Hodgkin lymphoma, and immunophenotyping demonstrated a prevalence of reactivity for CD4 (helper) over CD8 (suppressor) antigens. T-cell receptor beta-chain gene rearrangement studies revealed a rearranged pattern with either the HindIII or BamHI enzymes, whereas immunoglobulin heavy chain genes retained a germ-line configuration. Viral sequences specific for human T-cell leukemia virus-I, human T-cell leukemia virus-II, or HIV-1 were not detected. Thus, although rare, T-cell non-Hodgkin lymphoma may be observed in HIV-1-infected individuals.
Fluorine-18-deoxyglucose SPECT and coincidence imaging for myocardial viability: Clinical and technologic issues.

Beyond myocardial blood flow and contractile function, the clinical practice of nuclear cardiology is on the verge of expanding its procedures to include the characterization of myocardial metabolism in various cardiovascular disorders. FDG provides the opportunity to probe the glucose utilization status of the human heart. This opportunity is no longer confined to a single technology, such as PET, with a dedicated cyclotron facility, or a single disease condition, such as assessment of myocardial viability. The potential of FDG imaging with a modified gamma camera would enable the application of FDG (as well as other positron-labeled tracers in the future) to the daily clinical practice of nuclear cardiology in concert with conventionally used single-photon tracers, such as Tl–201 and Tc–99m–labeled perfusion tracers.
Developmental Effects of Grouping and Recoding on Learning a Movement Series

Organization of information is a strategy used in verbal learning to improve task performance. Developmental trends exist for the use of an organization strategy; young children generally fail to use organizational cues when responding. With age, children use inherent organization followed by an increased ability to restructure input. This study focused on the developmental ability to use a cognitive strategy to recall a series of eight movements. Three conditions were used: experimenter presented organization (movements presented in order from short to long), training group (movements presented randomly with training to organize), and subjective organization (movements presented randomly). The ages selected were 5, 7, 11, and 19 years, since these ages tend to represent major changes in strategy usage. Learning trials were presented specifically for each group, while for transfer trials all subjects were given movements in an unorganized fashion. Results indicated that the younger children (5- and 7- yea...
The legacy of Faster-Better-Cheaper: Too much risk or over-reaction to perceived failure?

From 1992 until 1999, NASA adopted the mission paradigm of Faster-Better-Cheaper (FBC)—i.e., a large number of relatively small, low-cost spacecraft—for its unmanned spacecraft. As many of the early FBC missions met their objectives (at much lower cost than traditional missions), the FBC approach appeared to be viable. However, after two Mars mission failures in 1999, the FBC paradigm was discontinued and came to be viewed by many to be a failed experiment. We reflect on the legacy of this program. In particular, we focus on the organizational learning literature to explore whether FBC, a stretch goal, was a good step for NASA, where a stretch goal is an extreme goal meant to intentionally generate internal crises to spark energy and to spur change. Previous examinations of the achievements of the FBC paradigm have focused on mission failure rates rather than on cost effectiveness, perhaps a more meaningful measure of performance for unmanned space missions. Therefore, we revisit the question of whether the Faster-Better-Cheaper paradigm was a success or a failure by examining all unmanned NASA missions launched between 1974 to 2007. In the analysis, we define mission performance in terms of the science output per dollar of mission cost, finding that FBC missions resulted in more scientific publications (and citation-weighted publications) per dollar of mission cost than did missions developed under other paradigms. In conclusion, we perceive many lasting benefits to current projects today from the adoption of the stretch goal of completing projects “Faster-Better-Cheaper” in the 1990's and perceive that NASA suffers from a bias against learning from the FBC era because of the stigma of the failed projects.
Characterization of lysosomal contribution to whole-cell light scattering by organelle ablation

Angularly resolved light scattering measurements made at visible wavelengths have the ability to quantify subcellular morphology, with particular sensitivity to organelles the size of mitochondria and lysosomes. We have recently reported on a lysosome-staining-based method that provides scattering contrast between stained and unstained cells, and through the use of appropriate models, we extracted a size distribution and contribution to cellular light scattering that we attributed to lysosomes. We provide an independent measurement of the lysosomal size distribution and contribution to cellular light scattering by exploiting photodynamic ablation of lysosomes and observing its effect on angularly resolved light scattering measurements. From these measurements, we conclude that lysosomes scatter approximately 14% of the light from EMT6 cells at 633 nm and that their size distribution has a mean and standard deviation of 0.8 and 0.4 microm, respectively.
Guest editors' introduction to the special issue

Abstract The background and focus of this special issue are described in this Introduction.
Sequential ionization in 3He with a 1.5-ps 1- microm laser pulse.

We have examined the laser ionization of $^{3}\mathrm{He}$ using 1.053-\ensuremath{\mu}m 1.5-ps laser pulses. The use of $^{3}\mathrm{He}$ rather than $^{4}\mathrm{He}$ in the experiment enables the detection of the second charge state separately from a troublesome background contaminant ${\mathrm{H}}_{2}^{+}$. In these experiments, the production of doubly charged ions is dominated by the sequential process rather than by the direct or simultaneous process.
Biochemical and Serologic Relationships of Isolants of Vibrio fetus from Man

Infection with Vibrio fetus is well known in veterinary medicine as a problem in cattle and sheep. In cattle, the disease is manifested in the female by infertility, and only occasionally by abortion. Vibriosis is a true venereal infection in cattle, with the asymptomatic bull acting as the carrier. In sheep, abortion is the main symptom of the infection, with transmission primarily through contaminated feed and v/ater.
Hot spots in energetic materials generated by infrared and ultrasound, detected by thermal imaging microscopy

We have observed and characterized hot spot formation and hot-spot ignition of energetic materials (EM), where hot spots were created by ultrasonic or long-wavelength infrared (LWIR) exposure, and were detected by high-speed thermal microscopy. The microscope had 15-20 μm spatial resolution and 8.3 ms temporal resolution. LWIR was generated by a CO2 laser (tunable near 10.6 μm or 28.3 THz) and ultrasound by a 20 kHz acoustic horn. Both methods of energy input created spatially homogeneous energy fields, allowing hot spots to develop spontaneously due to the microstructure of the sample materials. We observed formation of hot spots which grew and caused the EM to ignite. The EM studied here consisted of composite solids with 1,3,5-trinitroperhydro-1,3,5-triazine crystals and polymer binders. EM simulants based on sucrose crystals in binders were also examined. The mechanisms of hot spot generation were different with LWIR and ultrasound. With LWIR, hot spots were most efficiently generated within the EM crystals at LWIR wavelengths having longer absorption depths of ∼25 μm, suggesting that hot spot generation mechanisms involved localized absorbing defects within the crystals, LWIR focusing in the crystals or LWIR interference in the crystals. With ultrasound, hot spots were primarily generated in regions of the polymer binder immediately adjacent to crystal surfaces, rather than inside the EM crystals.
The prospects for new treatments for prostate cancer.

Since Brenner and Hall suggested in 1999 that the sensitivity to fraction size of prostate tumors might be uniquely high [ / ratio as low as 1.5 Gy (95% CI 0.8–2.2 Gy)], there has been a plethora of papers in this journal (1–6). This culminated recently in two new analyses of clinical data (7, 8), both reporting remarkable agreement with Brenner and Hall: 1.49 Gy (1.25–1.76 Gy) and 1.2 Gy (0.03–4.1 Gy) respectively. The value of 1.49–1.5 Gy comes from comparing results of external beam treatments with those of permanent implants of I-125 and Pd-103. If a higher relative biological effectiveness (RBE) than unity for the implants is considered, then the / ratio could be different (R.G. Dale, personal communication, 2001). The article in the present issue (8) is a first-class analysis of an innovative schedule (9) in which high-dose-rate (HDR) boost doses were escalated from 3 6 Gy to 2 10 Gy, with a pelvic dose of 46 Gy in 1.8–2 Gy fractions. The resulting increase of 3-year bNED (no biochemical evidence of disease) was so large that it could not be consistent with an / ratio larger than about 4 Gy, the estimated value being 1.2 Gy. This latest analysis (8) avoids the problems of multiinstitute, nonprospective data because it comes from a single institute and the same highly experienced clinical team. There is no uncertainty of RBE in the external beam and HDR radiations. The penalty is naturally that the number of patients is small, especially since only two-thirds of all the patients were suitable for analysis, which therefore does not permit narrow confidence intervals. However, during the next 2 years of follow-up the confidence with which we can view the low value of / will increase, ameliorating some of the cautions which have been expressed (6). During this time we anticipate active discussion concerning the prospects and problems of hypofractionated schedules. As has been pointed out, a low / ratio means that fraction-size sensitivity is similar in principle to that of late-responding normal tissues, because they all proliferate slowly. Indeed, such low / ratios as 1.5 to 2 Gy are reported for spinal cord and brain, but generic late complications involving fibrosis, stenosis, fistula, telangiectasia, etc. are considered to have / ratios of about 3 or 4 Gy, well supported by experimental animal data (10). The apparent disparity between / 3–4 Gy and the current value of 1.2–1.5 Gy for prostate tumors raises the obvious prospect that we might be able to widen the therapeutic window by treating prostate cancer with hypofractionation, for the same reason as, but in the opposite direction to, the strategy that has worked out well in hyperfractionation for head and neck tumors (11). This is the point that future clinical trials can be planned to assess.
Focus, pragmatic presupposition, and activated propositions

Abstract Although it is widely recognized that differences in focal accent represent what are in some sense differences in what is given and what is new, there remains considerable confusion in the literature as to what the relevant notion of ‘given’ is. This paper argues that when one distinguishes ‘given’ in the sense of ‘presupposed’ from ‘given’ in the sense of ‘activated’ (in the mind of the hearer), it becomes clear that it is the latter rather than the former which characterizes the complement of focus. While there is literature that assumes this position, there is a considerable body of literature that assumes that the relevant notion is in fact presupposition and little explicit argumentation that it is not presupposition. In addition, some of the literature that recognizes the relevance of activation mistakenly assumes that something that is activated is necessarily presupposed. The reason for this is that much of the literature ignores the distinction between propositions which are mentally represented and propositions which are believed.
Ordering coproducts of groups and semigroups

Abstract A. A. Vinogradov proved that a coproduct of orderable groups is orderable, and R. E. Johnson extended this result to semigroups. A simpler version of their proof is given, and results are obtained on orderability of group coproducts with amalgamation. In particular, it is shown that the coproduct of two or more copies of an orderable group H with amalgamation of a subgroup T ⊆ H is orderable if and only if T is the difference kernel of a pair of homomorphisms from H into another orderable group, equivalently, if and only if T is convex under some one-sided group-ordering of H . For coproducts of families of nonisomorphic overgroups of a group T , partial results are obtained. Some related results are proved for one-sided orderability.
Inherited defects in the DNA glycosylase MYH cause multiple colorectal adenoma and carcinoma

Dr Cheadle has raised issue with a statement in our commentary that the lack of base excision repair enzymes has not so far been linked to cancer. While we should have cited the articles of Cheadle and his colleagues showing a linkage between MYH missense mutations and colorectal cancer in some families, our statement was based on the phenotype of null mouse mutants deficient in damaged base-specific DNA glycosylases. Several laboratories have generated knockout mouse strains lacking individual DNA glycosylases, including oxidatively damaged base-specific DNA glycosylases OGG1 and NTH1. Both published and unpublished results clearly show that, unlike in the case of mismatch repair-deficient mice, glycosylase-deficient mice do not show significantly enhanced susceptibility to cancer. We, therefore, wrote what is generally accepted: that these DNA glycosylases with overlapping substrate ranges provide back-up or redundant functions, so that the absence of one will be covered by another for the repair of a critical mutagenic lesion. The work of Dr Cheadle and his collaborators strongly suggests a critical role for MYH in preventing carcinogenesis in humans. Further studies are needed to reconcile the apparent discrepancy between the human and mouse studies.
The interdependence of household credit constraints, assets and debts: a two-stage cross-section analysis

The joint determination of household assets, debts and credit constraints is explored using data from the 1983 Survey and Consumer Finances. The suggested six-equation framework allows for substitution and complementarity between different asset and debt types, subject to given household characteristics (including income) and endogenous credit constraints. Two-stage estimates suggest that endogeneity of debts, assets and credit constraints may be important for accurate analysis of households' portfolio choices and excess credit demands.
EXPERIMENTAL FANCONI SYNDROME: INTESTINAL TRANSPORT OF SODIUM, AMINO ACIDS AND GLUCOSE

The effects of Na maleate-induced Fanconi Syndrome on intestinal transport were assessed in rats by an in vivo perfusion technique. Na maleate was given i.p. (1.5 or 9.0 mmoles/kg) to 150 g male Wistar rats. Glycosuria and proteinuria ensued in all animals within 30-60 min. After 90-180 min, 20 cm jejunal segments were perfused for 2 hr under urethane anesthesia. The solutions perfused were Krebs-Hanseleit bicarbonate, isotonic, buffers containing 124 mEq/L of Na, 20 or 40 mM glucose and 1 mM of either L-phenylalanine, L-lysine, glycine or α-aminoisobutyric acid. Tracer amounts of 14C or 3H- labelled glucose or amino acids were included, as well as 600 mg% polyethylene glycol, m.w. 3000-3700. The mean ± S. D. transport rates (in μEq/min/cm of jejunum) for Na were, controls: 165.76 ± 39.46; 1.5 mmoles/kg maleate: 93.97 ± 53.62 (p<.001) and 9.0 mmoles/kg maleate: 51.70 ± 22.31 (p<.001). There were no differences in the transport of glucose and amino acids between control and experimental animals, despite multiple tubular transport defects in the latter. These results suggest that maleate-induced Fanconi Syndrome affects only Na intestinal transport, but not that of amino acids or glucose.
Simplicial Models for the Global Dynamics of Attractors

Abstract Given an unknown attractor A in a continuous dynamical system, how we can discover the topology and dynamics of A ? As a practical matter, how can we do so from only a finite amount of information? One way of doing so is to produce a semi-conjugacy from A onto a model system M whose topology and dynamics are known. The complexity of M then provides a lower bound for the complexity of A . In this paper, we use the techniques of the Conley index to construct a simplicial model and a surjective semi-conjugacy for a large class of attractors. The essential features of this construction are that the model M can be explicitly described and that the finite amount of information needed to construct it is computable.
Tire Cornering Properties

Abstract This paper provides a critical review of tire test techniques, test equipment, data processing methods, and mathematical models for obtaining data and describing tire cornering properties. It examines applicability of this data for evaluation of vehicle directional response properties and shows how test and data processing methods influence tire parameters used in simulations with models. Mathematical relationships between tire parameters and vehicle directional response parameters such as steering sensitivity are shown. Fundamental differences between conditions prevailing in testing, hypothetical assumptions used in mathematical models, and actual tire operating conditions on a vehicle are discussed. The need for transient tire measurements and modeling for transient conditions is also shown.
Transient waves in a layered anisotropic elastic medium

Wave propagation in a periodically layered medium is studied in which each period consists of two layers of homogeneous anisotropic elastic materials. The layered medium occupies the half-space x ≥ 0 in which the x -axis is normal to the layers. Transient waves in the layered medium are generated by a unit step load in time applied at x = 0. A general solution that applies to any x is obtained in the form of a Laplace transform. Asymptotic solutions valid for large x are then deduced. If the applied load at x = 0 is in the direction of one of the polarization vectors for the layered medium determined here, the stress components propagate uncoupled asymptotically. For general loadings, there are three ‘heads of the pulses’, each of which is in the form of an Airy integral.
Recovery of the Ozone Layer: The Ozone Depleting Gas Index

The stratospheric ozone layer, through absorption of solar ultraviolet radiation, protects all biological systems on Earth. In response to concerns over the depletion of the global ozone layer, the U.S. Clean Air Act as amended in 1990 mandates that NASA and NOAA monitor stratospheric ozone and ozone-depleting substances. This information is critical for assessing whether the Montreal Protocol on Substances That Deplete the Ozone Layer, an international treaty that entered into force in 1989 to protect the ozone layer, is having its intended effect of mitigating increases in harmful ultraviolet radiation.
Expression of functional bovine cholesterol side chain cleavage cytochrome P450 (P450scc) in Escherichia coli.

Abstract Escherichia coli expression vectors containing the trc promoter and the complete DNA sequence of either the precursor or the mature form of bovine adrenocortical cholesterol side chain cleavage cytochrome P450 (P450scc) were transformed into E. coli strain JM109 and transcription induced with isopropyl-β- d -thiogalactopyranoside (IPTG). Immunoreactive cytochrome P450scc was produced using the plasmid containing the mature P450scc sequence but not with the plasmid containing the sequence of the precursor form of P450scc, even though P450scc RNA was detectable in both cases. The mature form of P450scc was detected spectrophotometrically in a reduced CO-difference spectrum in E. coli (40–60 nmol/liter culture). Cholesterol and hydroxylated derivatives (22-hydroxycholesterol and 25-hydroxycholesterol) produce a type 1 substrate-binding spectrum in IPTG-induced, transformed E. coli . The P450scc was found to be associated with the E. coli membrane fraction and the enzymatic activity of side chain cleavage of 25-hydroxycholesterol was reconstituted using solubilized membranes, in the presence of purified bovine adrenocortical adrenodoxin and NADPH-adrenodoxin reductase (turnover number; 15.4 nmol/min/nmol P450). This bacterial expression system provides functional P450scc, in the absence of other forms of P450, which can be used for evaluation of enzymatic and spectral properties of this mitochondrial P450 by site-directed mutagenesis.
Additional techniques to reduce heatsink emissions utilizing RF absorbers

This paper compares the electromagnetic interference (EMI) reduction of several radio-frequency (RF) absorber configurations with integrated circuits (IC) and associated heatsinks.
A Controllable Membrane-Type Humidifier for Fuel Cell Applications—Part I: Operation, Modeling and Experimental Validation

For temperature and humidity control of proton exchange membrane fuel cell (PEMFC) reactants, a membrane based external humidification system was designed and constructed. Here we develop and validate a physics based, low-order, control-oriented model of the external humidification system dynamics based on first principles. This model structure enables the application of feedback control for thermal and humidity management of the fuel cell reactants. The humidification strategy posed here deviates from standard internal humidifiers that are relatively compact and cheap but prohibit active humidity regulation and couple reactant humidity requirements to the PEMFC cooling demands. Additionally in developing our model, we reduced the number of sensors required for feedback control by employing a dynamic physics based estimation of the air-vapor mixture relative humidity leaving the humidification system (supplied to the PEMFC) using temperature and pressure measurements. A simple and reproducible methodology is then employed for parameterizing the humidification system model using experimental data.
Evaluation of Monoclonal Antibodies to Human Immunodeficiency Virus Type 1 Primary Isolates by Neutralization Assays: Performance Criteria for Selecting Candidate Antibodies for Clinical Trials

A collaborative study was organized to identify monoclonal antibodies (MAbs) that may be broadly and potently neutralizing for a panel of human immunodeficiency virus type 1 (HIV-1) low-passaged adult and pediatric primary isolates in peripheral blood mononuclear cells. Five laboratories evaluated a coded panel of seven human MAbs to HIV-1 subtype B envelope V3, CD4 binding region, gp41, and other conformationally sensitive determinants. Each laboratory measured neutralizing activity of the MAbs against the laboratory isolate HIV(MN) and a panel of 9 subtype B primary isolates. Antibodies were classified as suitable candidates for future clinical studies if they could neutralize at least half of the 9 primary isolates at a concentration of < or = 25 microg/mL for 90% viral inhibition. The study identified three MAbs that met stated performance criteria: IgG1b12, 2G12, and 2F5. These results may provide a rationale for examining the clinical efficacy, either singly or in combination, of the three MAbs.
Characterization and tribology of PEG-like coatings on UHMWPE for total hip replacements

A crosslinked hydrogel coating similar to poly(ethylene glycol) (PEG) was covalently bonded to the surface of ultrahigh molecular weight polyethylene (UHMWPE) to improve the lubricity and wear resistance of the UHWMPE for use in total joint replacements. The chemistry, hydrophilicity, and protein adsorption resistance of the coatings were determined, and the wear behavior of the PEG-like coating was examined by two methods: pin-on-disk tribometry to evaluate macroscale behavior, and atomic force microscopy (AFM) to simulate asperity wear. As expected, the coating was found to be highly PEG-like, with ∼83% ether content by x-ray photoelectron spectroscopy and more hydrophilic and resistant to protein adsorption than uncoated UHMWPE. Pin-on-disk testing showed that the PEG-like coating could survive 3 MPa of contact pressure, comparable to that experienced by total hip replacements. AFM nanoscratching experiments uncovered three damage mechanisms for the coatings: adhesion/microfracture, pure adhesion, and delamination. The latter two mechanisms appear to correlate well with wear patterns induced by pin-on-disk testing and evaluated by attenuated total reflection Fourier transform infrared spectroscopy mapping. Understanding the mechanisms by which the PEG-like coatings wear is critical for improving the behavior of subsequent generations of wear-resistant hydrogel coatings. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010
The inevitability of conflict between buyers and sellers

Examines the source of conflict between buyers and sellers as it relates to the price of goods purchased for use in production. Focuses on management’s understanding and application of the term “maximize shareholder value”, which is found to result in business decisions that marginalize suppliers’ capabilities and interests. Concludes that conflict between buyers and sellers is an inevitable outcome when buyers make decisions principally centered upon the literal interpretation of management’s role as agents of the board whose primary responsibility is to maximize shareholder value. This finding has widespread implications for both academics and practitioners, as making this linkage explicit defines the challenge for improving purchasing and supply chain management practices in a new way.
A fluoroorotic acid-resistant mutant of Arabidopsis defective in the uptake of uracil

A fluoroorotic acid (FOA)-resistant mutant of Arabidopsis thaliana was isolated by screening M2 populations of ethyl methane sulphonate (EMS)-mutagenized Columbia seed. FOA resistance was due to a nuclear recessive gene, for1-1, which locates to a 519 kb region in chromosome 5. Assays of key regulatory enzymes in de novo pyrimidine synthesis (uridine monophosphate synthase) and salvage biochemistry (thymidine kinase) confirmed that FOA resistance in for1-1/for1-1 plants was not due to altered enzymatic activities. Uptake studies using radiolabelled purines, pyrimidines, and [ 14 C]FOA reveal that for1-1/for1-1 plants were specifically defective in the uptake of uracil or uracil-like bases. To confirm such specificity, genetic crosses show that FOR1 is a distinct locus from FUR1 which encodes a deoxyuridine nucleoside transporter. In addition, for1-1/for1-1 plants were restored to FOA sensitivity by transformation with the Escherichia coli uracil transporter gene uraA driven by the cauliflower mosaic virus (CaMV) 35S promoter. Molecular mapping studies reveal that FOR1 does not correspond to loci belonging to any of the six known nucleobase transporter families identified in the Arabidopsis genome. Moreover, FOR1 does not appear to regulate the transcript levels of either uracil transporter-encoding loci At2g03590 or At2g03530. The above results strongly suggest that the for1-1 mutant allele affects a transport mechanism that is specific for the uptake of uracil.
The neurobiology of decision-making and responsibility: reconciling mechanism and mindedness.

This essay reviews recent developments in neurobiology which are beginning to expose the mechanisms that underlie some elements of decision-making that bear on attributions of responsibility. These “elements” have been mainly studied in simple perceptual decision tasks, which are performed similarly by humans and nonhuman primates. Here we consider the role of neural noise, and suggest that thinking about the role of noise can shift the focus of discussions of randomness in decision-making away from its role in enabling alternate possibilities and toward a potential grounding role for responsibility.
The Influence of Breeding Experience on Nest Success in Red-Winged Blackbird

Abstract. The Red-winged Blackbird (Agelaius phoeniceus) is a polygynous species, and females are typically responsible for the majority of parental care. Despite their limited involvement, males can contribute to reproduction through nest defense and the feeding of nestlings. Some aspects of nest defense may be learned, and older males are more likely to feed young, suggesting that males with previous breeding experience may enjoy higher nest success than their naive counterparts. We manipulated territory ownership on 10 wetlands in central North Dakota in order to examine the influence of breeding experience on reproductive success. We found no evidence that breeding experience increased nest survival ( = 23.0%) or increased the number of fledglings per nest ( = 2.2). In this population, territory quality may contribute more to nesting success than male parental contributions.
The 1993 Walter Hubert Lecture: the role of the p53 tumour-suppressor gene in tumorigenesis

The p53 tumour-suppressor gene is mutated in 60% of human tumours, and the product of the gene acts as a suppressor of cell division. It is thought that the growth-suppressive effects of p53 are mediated through the transcriptional transactivation activity of the protein. Overexpression of the p53 protein results either in arrest in the G1 phase of the cell cycle or in the induction of apoptosis. Both the level of the protein and its transcriptional transactivation activity increase following treatment of cells with agents that damage DNA, and it is thought that p53 acts to protect cells against the accumulation of mutations and subsequent conversion to a cancerous state. The induction of p53 levels in cells exposed to gamma-irradiation results in cell cycle arrest in some cells (fibroblasts) and apoptosis in others (thymocytes). Cells lacking p53 have lost this cell cycle control and presumably accumulate damage-induced mutations that result in tumorigenesis. Thus, the role of p53 in suppressing tumorigenesis may be to rescue the cell or organism from the mutagenic effects of DNA damage. Loss of p53 function accelerates the process of tumorigenesis and alters the response of cells to agents that damage DNA, indicating that successful strategies for radiation therapy may well need to take into account the tissue of origin and the status of p53 in the tumour.
Progressive severe kyphosis as a complication of multilevel cervical percutaneous facet neurotomy: a case report

Abstract Background context Percutaneous facet neurotomy is a procedure commonly used for the treatment of pain thought to originate from zygoapophyseal joint dysfunction. Some practitioners have also used this technique to treat cervicogenic headache. Previously reported complications for this procedure have been minimal and have included dysthesias and local pain. Study design Case report. Methods Bilateral multilevel cervical percutaneous facet neurotomies were used to treat a patient suffering from a chronic headache and neck pain that had failed to respond to extensive medical management. Results Within days of completing the bilateral facet neurotomies, the patient developed head drop. Subsequent electromyography revealed denervation of the patient's paraspinous muscles. Initially the patient was managed conservatively in a cervical collar with the hope that he would recover some function. After few years, the patient developed fixed kyphotic deformity. Correction of the patient's deformity required multilevel anterior cervical discectomy and fusion followed by posterior instrumented fusion. Conclusions When performing multilevel percutaneous cervical facet neurotomies, there is a risk of paraspinous muscle denervation, and subsequent kyphotic deformity may occur. The likelihood of this rare and previously unreported complication can probably be reduced by proper needle positioning and by minimizing the number of levels at which the procedure is performed.
End-point diameter and total length coarse woody debris models for the United States

Abstract Coarse woody debris (CWD) may be defined as dead and down trees of a certain minimum size that are an important forest ecosystem component (e.g., wildlife habitat, carbon stocks, and fuels). Due to field efficiency concerns, some natural resource inventories only measure the attributes of CWD pieces at their point of intersection with a sampling transect (e.g., transect diameter) although measurements of large-end diameter, small-end diameter, and length are often required by natural resource managers. The goal of this study was to develop a system of empirical models that predict CWD dimensions (e.g., large-end diameter) based on CWD attributes measured at the point of intersection with a sample transect and ancillary data (e.g., ecological province). Results indicated that R-squared (R2) values exceeded 0.60 for most of this study's CWD large-end diameter and small-end diameter with only fair results for the length models. The mean residuals of numerous CWD models were within the measurement tolerance expected of actual field crews. Despite remaining unexplained variation, these CWD models may provide foresters with an alternative to the time-consuming activity of measuring all CWD dimensional attributes of interest during large-scale forest inventories.
Low dose elective brain irradiation in small cell carcinoma of the lung

Abstract Elective brain irradiation (EBI) in a dosage of 3000 rad (midplane) in 2 weeks (nominal standard dose (NSD) = 1314 ret) has proven highly effective in preventing initial brain relapse in small cell lung carcinoma. However, the optimal radiation dose for EBI is unknown. 55 patients (31 with regional disease, 24 with extensive disease) without brain metastases were treated with a 4 drug chemotherapy program, (lomustine (CCNU), methotrexate, cyclophosphamide, vincristine) plus radiotherapy (R.T.), 3000 rad in 2 weeks to the primary chest lesion and were randomized to EBI or a control group. The EBI consisted of 2400 rad whole brain, midplane, in 8 fractions, 10 days (NSD = 1130 ret) given at the same time as the R. T. to the primary (3 weeks post-initial chemotherapy). Though all 54 evaluable patients received CCNU 50 Mg/M 2 q. 6 weeks, there were 5 initial brain relapses among 31 control patients (16%) vs none in the 23 EBI patients. The time at risk for recurrence was similar in the two groups, i.e. 31 weeks median in the EBI and 32 weeks in the no-EBI patients. Brain relapses occurred in 2/17 with limited disease and 3/14 with extensive disease. It appears that 2400 rad in 8 fractions is as effective for EBI as larger doses. Toxicity was limited to alopecia. Survival was not significantly affected by EBI, though there is a suggestion of improvement in the regional group.
Pathways for GnRH control of elasmobranch reproductive physiology and behavior

In elasmobranchs, seasonal and developmental changes in reproduction and sexual behavior appear to be regulated by gonadotropin-releasing hormone (GnRH). Circumstantial evidence indicates that GnRH control is primarily via the systemic circulation to pituitary gonadotrophs in the ventral lobe. Additional GnRH effects on other pituitary gonadotrophs and the gonads may also be important. Several forms of GnRH have been reported in sharks and rays; however, the functional significance of the different types is unknown. While immunoreactive-GnRH is present in the preoptic area and hypothalamus, there appears to be little GnRH-staining in the median eminence region. The observations are consistent with a major nonportal distribution of GnRH. Recent studies suggest that the terminal nerve (TN) may be a major source of GnRH. The TN extends from the olfactory sac to the basal telencephalon. It contains abundant immunoreactive-GnRH and has endings in cerebral blood vessels where processes packed with dense-cored vesicles sit adjacent to endothelial cells with active vesicle formation indicative of transcytosis. The TN also projects centrally into the septopreoptic area. The structure may distribute GnRH, both directly to brain nuclei and the olfactory epithelium via synaptic connections and indirectly to brain areas and peripheral reproductive tissues via systemic blood. TN activity may be modulated either through afferent chemical stimulation or via synaptic output from the brain. The results are summarized in a model of suggested neural and endocrine pathways involved in elasmobranch reproduction.
Quality measurement and improvement in upper endoscopy

One consequence of recent health care reform efforts has been an increasing focus on defining and delivering high-quality care. Esophagogastroduodenoscopy (EGD) is a fundamental procedure for endoscopists and quality indicators for measurement have been proposed. These indicators are classified temporally as preprocedural, intraprocedural, and postprocedural. Although some indicators are evidence based, many are derived from expert consensus and may require further validation. An ideal quality indicator is easy to measure at the time of service, correlates well with patient outcome and experience, and has enough variation in practice to allow differentiation between good and poor performers. Among the many proposed quality measurements, it remains uncertain which best meet such criteria. Beyond compliance with reporting quality indicators for EGD, successful endoscopy practices will embrace quality improvement initiatives that collect, organize, and analyze their performance data to improve patient outcomes and the patient endoscopic experience. In recognition of these forthcoming changes, organizations have developed national repositories to assist endoscopy groups in this effort. These initiatives to first gauge and then improve the quality of EGD must lead in parallel to the development of standardized criteria for competency that can be adopted by all programs in which endoscopy is taught, regardless of specialty.
Implementing a Banking Front End Processor in Taiwan Using SOA

This paper presents a Proof Of Concept (POC) experience sharing on how to deploy the Front End Processor (FEP) based on banking requirements in Taiwan. New services usually take several months to materialize as existing IT systems lack compatibility. If banking IT can catch the tempo of business planning; it is the key to save costs while increasing new revenue and profit from higher customer satisfaction and responsiveness. Currently, many banks implement Enterprise Application Integration (EAI) as a bridge between front end and existing systems. Through using Service Oriented Architecture (SOA) - WebSphere Process Server (WPS), the development cycles can be reduced from months to weeks.
Lifelong exposure to methylmercury disrupts stress-induced corticosterone response in zebra finches (Taeniopygia guttata).

Mercury can disrupt the endocrine systems of mammals and fish, but little is known about its effects on avian hormones. The authors employed an experimental manipulation to show that methylmercury suppresses the stress-induced corticosterone response in birds, an effect previously unreported in the literature. Corticosterone regulates many normal metabolic processes, such as the maintenance of proper blood glucose levels during stressful daily fasting; an inability to increase corticosterone levels in response to stressors renders a bird less able to face a wide array of environmental challenges. The authors studied reproductively mature zebra finches that had been exposed to 0.0 µg/g, 0.3 µg/g, 0.6 µg/g, 1.2 µg/g, or 2.4 µg/g (wet wt) dietary methylmercury throughout their life (i.e., from the egg onward). In contrast to some field studies, the present study found no significant change in baseline plasma corticosterone concentrations attributable to chronic methylmercury exposure. However, a comparison between the baseline corticosterone levels and levels after 30 min of handling stress revealed that the ability of birds to mount a stress response was reduced with increasing blood total mercury concentration. These results are consistent with adrenal corticoid disruption caused by chronic mercury exposure and mirror a similar study on free-living nestling songbirds exposed to environmental mercury. Environ Toxicol Chem 2014;33:1072–1076. © 2014 SETAC
Adrenocorticotropic hormone-secreting pancreatic islet cell carcinoma.

A a 3 l t c A g t h p m t 43-year-old woman was diagnosed with adrenocoricotropic hormone (ACTH)–dependent Cushing’s yndrome at another institution about 5 years ago after eveloping major depressive symptoms and then typical linical signs and symptoms of hypercortisolism. The iagnosis was established by serial 24-hour urinary free ortisol measurements in the range of 600 to 1,000 g/24 h (normal 10 to 90 g/24 h), and a cortisol level f 37 g/dL after an oral 1-mg overnight dexamethaone suppression test (normal 1.8 g/dL). An ACTH evel of 161 pg/mL confirmed the diagnosis of ACTHependent hypercortisolism. MRI of her pituitary reealed a slightly prominent gland without evidence of a icroadenoma. Inferior petrosal venous sinus sampling as done before and after intravenous corticotrophineleasing hormone (CRH) administration. The absence f a central-to-peripheral ACTH gradient ( 2 before nd 3 after CRH injection) suggested an ectopic CTH secreting source, but CT imaging revealed no istinct masses or organ abnormalities in her chest, abomen, or pelvis. The patient chose medical treatment with ketoconzole, which effectively controlled her adrenal steroid roduction. Her Cushingoid features regressed, but ever fully subsided, and her 24-hour UFC remained in he mid-to-upper normal range. Imaging studies were 1 2
Dual-task interference and brain structural connectivity in people with Parkinson's disease who freeze.

Background Freezing of gait in people with Parkinson9s disease (PD) is likely related to attentional control (ie, ability to divide and switch attention). However, the neural pathophysiology of altered attentional control in individuals with PD who freeze is unknown. Structural connectivity of the pedunculopontine nucleus has been related to freezing and may play a role in altered attentional control; however, this relationship has not been investigated. We measured whether dual-task interference, defined as the reduction in gait performance during dual-task walking, is more pronounced in individuals with PD who freeze, and whether dual-task interference is associated with structural connectivity and/or executive function in this population. Methods We measured stride length in 13 people with PD with and 12 without freezing of gait during normal and dual-task walking. We also assessed asymmetry of pedunculopontine nucleus structural connectivity via diffusion tensor imaging and performance on cognitive tests assessing inhibition and set-shifting, cognitive domains related to freezing. Results Although stride length was not different across groups, change in stride length between normal and dual-task gait (ie, dual-task interference) was more pronounced in people with PD who freeze compared to non-freezers. Further, in people with PD who freeze, dual-task interference was correlated with asymmetry of pedunculopontine nucleus structural connectivity, Go-NoGo target accuracy (ability to release a response) and simple reaction time. Conclusions These results support the hypothesis that freezing is related to altered attentional control during gait, and suggest that differences in pedunculopontine nucleus connectivity contribute to poorer attentional control in people with PD who freeze.
GroupWear: nametags that tell about relationships

We have built a set of computationally-augmented nametags capable of providing information about the relationship between two people engaged in a face-to-face conversation. This paper puts forward criteria useful for the design of such interpersonal augmentation, experiences that inform the principles, and initial evidence of their success.
Microdetermination of bilirubin concentration by autoanalyzer.

A microdetermination of neonatal serum bilirubin concentration by AutoAnalyzer consumes less than 100 μliters of sample for two tests, requires less than 15 minutes to equilibrate the instrument and less than six minutes between time of sampling and time of read-out. It provides especially accurate data between 10 and 25 mg bilirubin/100 ml and useful data between zero and 40 mg bilirubin/100 ml. The instrument is sufficiently simple to permit its operation on a 24-hour basis by blood bank technologists not previously experienced in clinical chemistry.
Systematic analysis of machine learning algorithms on EEG data for brain state intelligence

Electroencephalography (EEG) is a highly promising medium for brain-computer interfaces (BCI) with potentially extraordinary applications such as the direct control of prosthetics and exoskeletons. However, effective analysis and modeling of EEG data has been limited by its poor spatial resolution. EEG's low amplitude, brief and sporadic nature, compounded by extra-cranial noise, contribute to the difficulty of this problem. This systematic analysis provides strong evidence to guide future research in machine learning applied to real-time analysis of brain states using EEGs. The main goal of this research is to understand how the construction of data sets used in training models affects the accuracy of prominent machine learning algorithms, specifically: Random Forest, Boosting, Naive Bayesian Classifier, k-Nearest Neighbors (KNN) and Support Vector Machine (SVM). Herein, we present a systematic method (N = 153) to test the accuracy of prominent machine learning algorithms when varying three main components of the training data set: the permutations of subjects, the number of unique data sets used to generate the training data set, and the number of samples in each training data set. Our results strongly indicate that Random Forest consistently yields superior results when analyzing EEG data compared to other prominent machine learning algorithms. Furthermore, a pilot investigation was conducted on a mean-normalized feature for EEG data analysis. The pilot analysis (N = 28) confirmed Random Forest's analytical superiority in EEG data, shows signs of improved accuracy, and identifies a distinctive correlation between beta and delta waves and their respective active or idle brain states.
Case 80: An Example of Murphy’s Law

Today you are in the intensive care unit (ICU) as the attending anesthesiologist. It is late at night. A 17-year-old female has been ventilated for several days, following a motor vehicle accident (MVA). You notice that the patient is now requiring high inflation pressures to maintain her oxygenation. Copious amount of purulent sputum are sucked out of her endotracheal tube (ETT) with minimal improvement in the peak airway pressures.
Biology of Chrysopa lanata (Neuroptera: Chrysopidae),

The life history was studied using 151 individual green lacewings under laboratory conditions of 26.5°C, 80% RH, and 14L:10D photoperiod. Eggs required 5.3 days to hatch; the 1st instar lasted 3.5 days, the 2nd 3.0 days, and the 3rd 3.8 days, giving a larval stage of 10.3 days. The combined pre-pupal and pupal stages lasted 9.9 days. Larval size and head capsule widths were measured for each instar. Males lived a mean of 55 days and females a mean of 65 days. The pre-oviposition period averaged 5.4 days. A mean of 687 eggs was laid by each female, the maximum being 1,175 eggs. Most eggs were laid 10–40 days after emergence; oviposition was almost entirely nocturnal. Larvae fed freely on noctuid eggs, and adults were predaceous on cabbage looper eggs, Trichoplusia ni (Hubner), but not the cabbage aphid, Brevicoryne brassicae (L.).