cssi/SciSciGPT-SciSciNet huggingface dataset:
Adulthood residential ultraviolet radiation, sun sensitivity, dietary vitamin D, and risk of lymphoid malignancies in the California Teachers Study

To lend clarity to inconsistent prior findings of an inverse association between ultraviolet radiation (UVR) exposure and risk of lymphoid malignancies, we examined the association of prospectively ascertained residential ambient UVR exposure with risk of non-Hodgkin lymphomas (NHLs), multiple myeloma (MM), and classical Hodgkin lymphoma in the California Teachers Study cohort. Among 121 216 eligible women, 629 were diagnosed with NHL, 119 with MM, and 38 with Hodgkin lymphoma between 1995-1996 and 2007. Cox proportional hazards regression was used to estimate incidence rate ratios (RRs) with 95% confidence intervals (CIs). Residential UVR levels within a 20-km radius were associated with reduced risk of overall NHL (RR for highest vs lowest statewide quartile of minimum UVR [≥ 5100 vs < 4915 W-h/m2], 0.58; 95% CI, 0.42-0.80), especially diffuse large B-cell lymphoma (RR, 0.36; 95% CI, 0.17-0.78) and chronic lymphocytic leukemia/small lymphocytic lymphoma (RR, 0.46; 95% CI, 0.21-1.01), and MM (RR for maximum UVR, 0.57; 95% CI, 0.36-0.90). These associations were not modified by skin sensitivity to sunlight, race/ethnicity, body mass index, or neighborhood socioeconomic status. Dietary vitamin D also was not associated with risk of lymphoid malignancies. These results support a protective effect of routine residential UVR exposure against lymphomagenesis through mechanisms possibly independent of vitamin D.
Method for measuring total cross sections with neutrons having energies from 2.5 to 15 MeV

Abstract Pulsed-beam time-of-flight techniques, used in a transmission measurement with a continuous spectrum of neutron energies, permit moderate resolution (2.5 to 4.5 percent, without gaps) and moderate precision (1 to 3 percent) to be obtained in an investigation of neutron total cross sections between 2.5 and 15 MeV. Neutrons are produced by bombarding a thick lithium target with deuterons and are detected by a liquid scintillation counter. The use of small-diameter samples close to the source minimises inscattering and permits the use of scarce samples. Calculations relative to the best position, diameter and thickness for the samples are summarized. Sharp structure in the spectrum introduces some difficulties into the reduction of data and may cause systematic errors above 11 MeV. Tests for other systematic errors have shown them to be less than two percent.
Density of liquid He 4 at freezing and entropy of solid He 4 at low temperatures

The density of liquid $^{4}\mathrm{He}$ has been measured along the melting curve in the temperature range 0.1-0.82 K by observing the change with temperature of the resonant frequency of a superconducting microwave cavity immersed in the liquid. Relative changes in density as small as 4 \ifmmode\times\else\texttimes\fi{} ${10}^{\ensuremath{-}9}$ could be resolved. From the results the entropy of solid $^{4}\mathrm{He}$ was obtained by using the Clausius-Clapeyron equation in conjunction with values for the isobaric-thermal-expansion coefficient and entropy of the liquid calculated from other data. No evidence for an anomalous linear temperature term in the entropy of the solid was found. The data are shown to be in good agreement with published measurements of the Debye temperature of the solid by Gardner, Hoffer, and Phillips.
Modelling population dynamics of Sinapis arvensis in organically grown spring wheat production systems

Summary Although we know that alterations in crop density, crop spatial pattern and inclusion of more selective weed control can improve weed suppression for organic growers, it is unknown whether these result in changes to the weed seedbank that increase cropping system profitability over time. Data collected from field trials conducted in 2009 and 2010 in Maine, USA, comparing regional grower practices (Standard) with management that aimed to (i) facilitate better physical weed control through the use of wide row spacing and inter-row cultivation (Wide) or (ii) enhance crop–weed competition through increased seeding rate and narrow inter-row spacing (Narrow HD), were used to construct a matrix population model with an economic sub-model. Using field measurements of grain yield and weed survival and fecundity, we investigated the lasting implications of employing alternative organic spring wheat (Triticum aestivum) production practices on Sinapis arvensis population dynamics. In most scenarios, the model indicated that regional production practices were not sufficient to prevent an increase in the weed seedbank, even with excellent weed control. The two alternative methods, on the other hand, were able to limit weed population growth when initial densities were low or cultivation efficacy was >80%. Due to higher seed costs in the Narrow HD system, net returns were still lower after 10 years of simulation in this system compared with wide rows with cultivation, despite a lower weed seedbank.
Comparison of health-related quality of life and prostate-associated symptoms after primary and salvage cryotherapy for prostate cancer

Recent advances in cryosurgery of the prostate have led to the ability to treat tumors successfully with decreased morbidity. The patients’ perspectives of this relatively new technique, however, have not yet been addressed. The purpose of this study was to compare health related quality of life (QoL) as well as prostate-associated symptoms in patients after primary and salvage cryoablation for clinically localized prostate cancer using a self-administered questionnaire. A total of 131 consecutive patients who underwent cryoablation of the prostate between 1997 and 2001 were included in this confidential mailing study. The patients were either (a) patients with localized prostate cancer with contraindications for radical surgery, including patients refusing other forms of therapy, or (b) had locally recurrent prostate cancer after failure of radiation therapy. All patients received 3 months of neoadjuvant androgen deprivation therapy prior to cryosurgery and were surgically treated by the same surgeon using an argon-based system. We used the EORTC QLQ-C30, a commonly used, multidimensional instrument together with a supplementing, prostate-cancer-specific module. Eighty-one of the 131 patients (response rate 62%) returned the questionnaires. The two groups were comparable regarding age (mean age 72.8 vs 70.1 for the primary and the salvage group, respectively; p=0.22). The overall QoL scores were high in both groups. Primary cryotherapy patients fared significantly better regarding physical (p=0.005) and social (p=0.024) functioning compared with salvage cryotherapy patients. The most prominent prostate-related symptom in both patient groups was sexual dysfunction, followed by urinary symptoms, which were significantly more severe in the salvage group (p=0.001). Incontinence rates were 5.9 and 10% in the primary and the salvage group, respectively. Severe erectile dysfunction was reported in 86 and 90% of the primary and the salvage group, respectively. The present study demonstrates that, in selected patients, cryotherapy is a treatment option which has a functional outcome comparable to traditionally used prostate cancer treatments. More information regarding QoL is necessary for appropriate patient counseling and individual decision-making in the presence of various treatment alternatives.
Gender: a critical factor in a couples group

Couples group therapy should be considered as a primary treatment for marital couples whose dysfunctional interaction is rigidified and chronic. A gender-linked perspective for treatment is developed which expands a psychodynamic approach underscoring power as one of the central issues in marital conflict. Clinical vignettes from couples groups illustrate this model. A gender orientation facilitates the psychodynamic group process, decreases unrealistic expectations of the spouse, and encourages greater acceptance of male/female and individual differences. In this setting, individuals are able to develop new and more functional modes of interaction with their spouses, which generate an increased sense of empowerment.
Photoabsorption Cross Sections of Organophosphonates at 120-180 nm

In the course of studying the reactivity of three organophosphonate compounds with air discharge products, it became desirable to determine the VUV absorption cross sections for these materials [DMMP, (CH3O)2PO(CH3); DEMP, (C2H5O)2PO(CH3); O,S-DEMP, (C2H5O)(C2H5S)PO(CH3)]. Both O2 and O2(a1Δg) are conveniently monitored by VUV absorption, and it was thus necessary to determine the degree of interference that the organophosphonates might cause. To our knowledge, there is no information available on their VUV absorption below 200 nm, whereas significant O2 absorption does not take place above 175 nm.
The influence of preceramic binders on the microstructural development of silicon nitride

A number of polymeric precursors to silicon nitride were prepared and evaluated as binders in cold pressing/pressureless sintering operations. These polymers exhibited ceramic yields in excess of 75% by weight, and powder compacts made using them as binders displayed improved green handling properties. Compacts pyrolysed at 800 °C exhibited unusual microstructures, including the development of whiskers in situ. Based on microstructural observation, compacts sintered under pressureless conditions appeared to show enhanced densification relative to those processed without preceramic binders. Preceramic binders appeared to enhance the formation of β-Si3N4 and may enhance densification of compacts sintered under pressureless conditions.
Interfacial Three-Phonon Processes and Anomalous Interfacial Energy Transport

This work was done in collaboration with my former graduate student, M. E. Lumpkin. 1,2 It was motivated by the phonon pulse measurements of Wyatt et al, 3 who observed that high-frequency phonons can break the so-called “critical cone” on passing across the interface between NaF and liquid 4He. A simple mechanism for cone-breaking is presented by the interfacial three-phonon process: a phonon incident from, e.g., NaF splits into two phonons emergent in liquid 4He.
Zionism and jewish identity

stories show that all the survivors found some way to flee. However, not all who fled survived. In a situation of extreme helplessness, denial and hopelessness must have been widespread. Comforting those unable to flee seems as heroic to me as fighting in die forests. We will debate these issues for a long time. These books are all of value to their professional audiences. Non-spe cialists will find them interesting as well. However, for me, die testimony of child survivors offers an unusually immediate, powerful, and moving win dow into their experience. I regret that it is not possible to have a follow-up on their memories and situation today.
Quantitative Radiocardiography in Major Pulmonary Thromboembolism

Cardiac index (CI) and pulmonary blood volume index (PVBI) were measured by quantitative radiocardiographic studies using radioactive 113m indium and a scintillation probe in 37 patients with confirmed major pulmonary thromboembolism. The mean PBVI was 185 ± 11 ml/sq m (SE) and was significantly less than normal (310 ± 5 ml/sq m [SE]; P 2 SD), and the mean pulmonary vascular occlusion was 21 percent in these patients. Eighteen patients (49 percent) died, and the most significant correlate of mortality was CI, which was depressed (less than 2.7 L/min/sq m) in all but two. Twenty-three serial determinations of pulmonary blood volume (PBV) ranging from 1 to 18 days after the initial study showed a mean increase in PBV of 27 ml/day in ten survivors. Quantitative radiocardiographic studies provide a means of diagnosing major pulmonary thromboembolism by measuring decreases in PBVI; it can assess the magnitude of major pulmonary thromboembolism and can assess CI and, thereby, predict risk of mortality; and it provides a means of following the resolution rate of major pulmonary thromboembolism.
Effect of fire-retardant treatment on plywood pH and the relationship of pH to strength properties

This paper investigates the relationship between wood pH and the strength properties of fire-retardant-treated (FRT) plywood, as it is affected by fire-retardant (FR) formulations, processing variables, and extended high temperature exposure conditions. The objectives of this study were to (1) identify the effect of post-treatment kiln-drying temperature, followed by high temperature exposure, on wood pH; (2) identify the effect of various mixtures of FR components, followed by high temperature exposure, on wood pH; (3) determine if treatment effects on strength and pH are affected by plywood thickness; and (4) quantify the relationship between changes in wood pH and strength loss and whether pH can be used as a predictor of strength loss. Results indicate that the differences in pH resulting from the initial redry temperature became insignificant after extended periods of high temperature exposure. All FR treatments studied caused large, rapid decreases in pH, with the most rapid decreases occurring with formulations containing phosphoric acid. Additions of borate compounds, especially disodium octaborate tetrahydrate (Timbor), produced a measurable buffering effect that slowed or lessened the decreases in pH. No differences in the effect of FRT on the wood pH-strength relationship were noted between the two plywood thicknesses evaluated. A strong relationship was noted between changes in pH of the plywood and reductions in strength and energy-related properties. These findings suggest that the pH of FRT plywood is a good indicator of its current condition and may have potential as a predictor of future strength loss as the plywood is subjected to elevated in-service temperatures.
Replication of defective and competent forms of murine sarcoma virus in mouse cell cultures.

Abstract The propagation of each of the known constituents of murine sarcoma virus stocks—competent MSV, defective MSV, and endogenous MuLV—was studied in three different mouse cell culture systems: Swiss mouse embryo, the established 3T3 cell line, and neonatal Swiss mouse kidney secondary cultures. All the viral components of the MSV complex adsorbed to the same degree to all three cell types. MuLV alone grew well in the embryo culture, grew poorly in the 3T3 cell line and very poorly in the kidney cultures. A defective MSV-MuLV mixture propagated rapidly in the embryo cultures and eventually yielded some competent MSV progeny. Propagation of the defective MSV-MuLV mixture was poor in the 3T3 cell line and and barely detectable in the kidney cultures. In the 3T3 cell, the slow rate of defective MSV growth was not enhanced by the addition of exogenous MuLV. In contrast, virus stocks consisting predominantly of competent MSV propagated rapidly and well in all three cell systems. In embryo cells competent MSV gave rise to virus progeny composed of a mixture of defective and competent MSV. Infection of 3T3 cells with competent virus resulted in initially defective, and later in some competent, MSV. In mouse kidney cells the progeny of competent MSV consisted of predominantly defective MSV, a small amount of competent virus, and very little MuLV. These findings define the superior infective capacity of competent MSV and the modulation of the composition of the sarcoma-leukemia virus complex during propagation in various mouse cell systems.
Cationic, Helical Antimicrobial Peptoids with Biomimetic Antimicrobial Activity

Increasingly prevalent resistance of pathogenic bacteria to conventional small-molecule antibiotic drugs is creating an urgent need for the discovery of new classes of antibiotics that are active against biofilms. Bacteria that are multidrug resistant (MDR) are of increasing concern for infectious disease. Current treatment of these infections that involve resistant organisms may require 6-12 months of antibiotic treatment, creating difficulties with compliance.We are continuing to develop oligo-N-substituted glycine (peptoid) mimics of cationic, helical antimicrobial peptides (AMPs), and some of our recently acquired data indicate that peptoids could address the problem of growing resistance. Peptoids have been shown to have extremely broad-spectrum activity, and certain peptoids function well in the presence of serum proteins. Their biophysical mechanism of action makes it difficult for bacteria to evolve resistance to them. We have tested our most promising peptoids, peptides and commercial antibiotics in vitro against bacterial biofilms of a variety of important bacterial organisms. We show that certain peptoids can be as active as the preferred conventional antibiotics against bacterial infections, even at low micromolar doses. Small, structured biomimetic oligomers such as our antimicrobial peptoids may offer a new class of drugs that are useful in treating persistent bacterial infections.
Formamidine group transfer in extracts of human pancreas, liver, and kidney.

Abstract Extracts of human pancreas, liver, and kidney catalyze transfer of the formamidine (-C(NH)NH2) group from certain donor compounds to hydroxylamine. Amidinotransferase activity of human liver is approximately equal to that of kidney; human pancreas has 5 times the activity of liver and kidney. No significant amidinotransferase activity was observed in extracts from livers of rat, rabbit, or dog; monkey liver has half the activity of human liver. Formamidine donors include, in descending order of activity: arginine, guanidinoacetate, 4-guanidinobutyrate, and 3-guanidinopropionate. l -2-Amino-4-guanidinobutyrate and l -2-amino-3-guanidinopropionate have no donor activity. The most effective inhibitors of each of these transamidinations are, in descending order, ornithine, glycine, and norvaline. It is suggested that most, if not all, of the foregoing reactions are catalyzed by l -arginine: glycine amidinotransferase (EC 2.6.2.1) and that, unlike the case of certain lower mammals, the liver of primates can catalyze the first step in creatine biosynthesis. Several methods of assaying for amidinotransferase in the presence of high levels of arginase (EC 3.5.3.1) are illustrated. To explain the observed enzyme inhibitions, two tentative models of the enzymic site of human pancreatic amidinotransferase are considered: one involving partially overlapping acceptor-specific sites, the other involving acceptor sites which are spacially separated but subject to distortion by adsorbed acceptors.
Analysis of antigen-antibody reactions of two plant viruses by density-gradient centrifugation and electron microscopy.

Abstract Electron microscopy and density-gradient centrifugation were used for a sensitive and specific detection of serological reactions of plant viruses. Addition of a limited amount of homologous antiserum to tobacco mosaic and southern bean mosaic viruses aggregated only part of the virus. The unaggregated virus sedimented at a normal rate and could be measured by density-gradient centrifugation. The amount of unaggregated virus was nearly a linear function of the logarithm of the antiserum concentrations in the 20% to 80% reaction range. The amount of antiserum necessary to aggregate 50% of the virus could be determined by interpolation. This 50% point depended upon the initial concentration of virus. Removal of a zone by a specific antiserum could be used to identify zones, to determine relations between antigenic materials of different zones, and to provide a specific measure of one antigen-antibody combination in the presence of other nonrelated antigens. Centrifugation of mixtures with antibody excess gave no zones that could be attributed to “soluble antigen” or to antibody-coated virus. Density-gradient centrifugation gave an accurate determination of the precipition reaction and indicated that virus was aggregated with dilutions of antiserum beyond the end point of visible precipitation. Electron microscopy confirmed that low concentrations of virus were aggregated by low concentrations of antiserum.
Experiences with a large-scale deployment of Stanford Peer-to-Peer Multicast

Traditionally, a large number of dedicated media servers have been deployed to serve a large population of viewers for a single streaming event. However, maintaining media servers is not only costly but also usually requires over-provisioning due to the difficulty of predicting the peak size of an audience. Peer-to-Peer (P2P) streaming is a new approach to overcome these difficulties inherent in server-based streaming. We have developed the Stanford Peer-to-Peer Multicast (SPPM) protocol for live multicast streaming. SPPM constructs multiple multicast trees to push media streams to the population of peers, thereby achieving low end-to-end transmission delay. The degradation of video quality due to peer churn and packet loss in the network is reduced by video-aware packet scheduling and retransmission. In this paper, we present lessons we acquired from the deployment of a commercial variant of SPPM for a large-scale streaming event which attracted more than 33,000 viewers. We collected server logs and analyzed user statistics as well as the system performance. The results show that our system can achieve low end-to-end delay of only a few seconds with an average packet loss ratio of around 1%. We also found that improving peer-to-peer connectivity can substantially enhance the aggregate uplink capacity of P2P systems.
Effects of stimulus repetition rate and frequency on the auditory brainstem response in normal cochlear-impaired, and VIII nerve/brainstem-impaired subjects.

The effects of signal repetition rate and frequency on the auditory brainstem responses of normal listeners, of persons with cochlear lesions, and of persons with VIII nerve/brainstem lesions were ...
Visions of Glory: The Place of the Azusa Street Revival in Pentecostal History

As news of the great Welsh Revival of 1904 reached Southern California, Frank Bartleman, an itinerant evangelist and pastor living in Los Angeles, became convinced that God was preparing to revitalize his beloved holiness movement with a powerful, even apocalyptic, spiritual awakening. Certain that events in Wales would be duplicated in California, Bartleman reported in 1905 that “the Spirit is brooding over our land.… Los Angeles, Southern California, and the whole continent shall surely find itself ere long in the throes of a mighty revival.” In 1906 he speculated that theSan Francisco earthquake “was surely the voice of God to the people on the Pacific Coast.” Bartleman indeed witnessed such a revival, for in early April 1906, this “Latter Rain” outpouring had begun to fall on a small gathering of saints led by William J. Seymour, a black holiness preacher. At a vacant AME mission at 312 Azusa Street, countless pentecostals received the baptism of the Holy Spirit evidenced by speaking in other tongues—a “second Pentecost” replicating the first recorded in Acts 2. Bartleman, who also experienced this, would soon become integral to the revival's growth by reporting the events at Los Angeles within a vast network of holiness and higher life periodicals. As during other religious awakenings, such reports not only generated the perception of widespread divine activity but also provided an interpretive scheme for understanding the meaning of such activity. For Bartleman, Azusa was the starting point of a worldwide awakening that would initiate Christ's return. He reported: “Los Angeles seems to be the place, and this the time, in the mind of God, for the restoration of the church to her former place.”
Monte Carlo study of electronic transport in Al 1 − x Ga x As/GaAs single-well heterostructures

A study of electronic transport in ${\mathrm{Al}}_{1\mathrm{\ensuremath{-}}\mathrm{x}}$${\mathrm{Ga}}_{\mathrm{x}}$As/GaAs single-well structures including multisubband conduction at 77 and 300 K has been performed. The electronic states of the quantum well are calculated self-consistently taking the five lowest subbands into account. The numerically obtained wave functions and energy levels are used to obtain the major two-dimensional scattering rates in each subband. Polar optical- and acoustic-phonon (via deformation-potential) scattering are considered including intersubband transitions. For ionized impurity scattering, the screening effects due to the five lowest subbands are taken into account to obtain the Fourier-transformed Coulomb potential. The steady-state and transient behavior of the electrons in the well are studied through a Monte Carlo particle simulation. It is shown that high transient velocities [(3--8)\ifmmode\times\else\texttimes\fi{}${10}^{7}$ cm/sec] can be expected at low and intermediate fields.
Environmental effects of techno-economic systems: A systems engineering interpretation of the input-output approach

The basic principles of Leontief's input-output analysis to assess environmental effects[1] can be derived from a systems engineering viewpoint, using multivariable block diagrams. The advantage of the systems engineering interpretation is to make the input-output analysis intuitively clear and to suggest, and facilitate certain extensions of Leontief's results.
THE CONTINENTAL MARGIN OFF THE ATLANTIC COAST OF THE UNITED STATES: CARBONATE IN SEDIMENTS, NOVA SCOTIA TO HUDSON CANYON1

SUMMARY A joint survey by the Woods Hole Oceanographic Institution and the U. S. Geological Survey, begun in 1962, aims at the geologic exploration of the Atlantic continental margin. This report describes the distribution of carbonate in the surface sediments between Nova Scotia and Hudson Canyon. Samples of surface sediment on a 10-mile grid reveal that over more than 90% of its area the shelf sediment contains less than 5% calcium carbonate. These low values are due to low production by aquatic organisms, a consequence of low average water temperatures. A few locales on the shelf have high carbonate concentration owing to a prolific sessile or nearly sessile fauna. Seaward of the shelf concentrations of calcium carbonate increase regularly with depth to about 30% on the upper continental rise; this increase reflects a greater relative abundance of planktonic Foraminifera due to a decrease in the rate of deposition of land derived detritus. Limestone outcrops are very rare in the area.
Vocational interests and personality

The field of vocational counselling lacks consensus regarding the dimensions common to a vocational guidance test battery and the appropriate methodology to employ in the analysis of the internal structure of vocational guidance test data. In this study we sought to clarify these issues by testing the hypothesis that vocational interest and personality tests measure a common domain. The MMPI, EPPS, and KPR-C were administered to 489 high school and college men aged 15 to 34 (X = 21.2) years and 137 females aged 16 to 35 (X = 22.6) years randomly chosen from a larger population seeking vocational guidance. The data provide evidence that there are six dimensions which describe a common domain of personality and vocational interest. Canonical correlational analysis best combined the personality and interest scales when compared with hierarchical cluster analysis, principal component analysis, and multimethod factor analysis. Implications of the findings to vocational counselling are discussed in terms of relative importance of personality and interest measures, amount of information provided by these instruments, and contribution of test data to the guidance process.
Contributions of the Histidine Side Chain and the N-Terminal α-Amino Group to the Binding Thermodynamics of Oligopeptides to Nucleic Acids as a Function of pH

Interactions of histidine with nucleic acid phosphates and histidine pKa shifts make important contributions to many protein−nucleic acid binding processes. To characterize these phenomena in simplified systems, we quantified binding of a histidine-containing model peptide HWKK (+NH3-His-Trp-Lys-Lys-NH2) and its lysine analogue KWKK (+NH3-Lys-Trp-Lys-Lys-NH2) to a single-stranded RNA model, polyuridylate (polyU), by changes in tryptophan fluorescence as a function of salt concentration and pH. For both HWKK and KWKK, equilibrium binding constants, Kobs, and magnitudes of log−log salt derivatives, SKobs ≡ (∂logKobs/∂log[Na+]), decreased with increasing pH in the manner expected for a titration curve model in which deprotonation of the histidine and α-amino groups weakens binding and reduces its salt-dependence. Fully protonated HWKK and KWKK exhibit the same Kobs and SKobs within uncertainty, and these SKobs values are consistent with limiting-law polyelectrolyte theory for +4 cationic oligopeptides bindin...
Corrections in the Measurement of Fluorescence Polarization

Abstract Blank corrections in polarization measurements with single beam spectrofluorometers are straightforward and permit characterization of polarization spectra of samples having quantum yields of less than 0.01. Few samples require no such correction. Problems in determining what is a suitable blank are discussed. Such blanks have unfortunately been ignored in many studies, and dual phototube instruments have been advocated in which it is difficult to apply such corrections. G, the grating correction factor, is shown to vary sharply with emission wavelength, in contrast to other reports, but is independent of slit width. Therefore, a calibration curve of G vs. emission wavelength may be obtained for a given instrument, thus avoiding the need to determine G for each sample.
Age-related efficacy with an AAV vector in Fabry disease mice.

1096-7192/$ see front matter 2008 Elsevier Inc. A doi:10.1016/j.ymgme.2008.10.014 * Corresponding author. Fax: +1 (919) 684 0983. E-mail address: dwight.koeberl@duke.edu When gene therapy is under development for genetic diseases, especially those diseases with available therapy, long-term efficacy clearly must be considered. Preclinical experiments must be done in the most relevant animal disease model, considering all relevant factors including immune competence, age, genotype, and dose requirements. The results of preclinical experiments should be reported whenever significant data are generated, even if these constitute ‘‘negative results”. A well-known, if poorly studied phenomenon consists of the under-reporting of negative results, which is more likely attributable to self-censoring by investigators than to editorial decisions [1]. The failure to publish all significant results handicaps the pace of advances in research, wastes resources, and handicaps research careers due to redundant efforts in multiple laboratories. An example of the reporting of negative, as well as positive, results appears in this issue. Ogawa et al. evaluated an adeno-associated virus (AAV) vector in the mouse model for Fabry disease, administering the vector to neonatal and adult mice of both sexes [2]. A differential response to the vector was demonstrated, because efficacy was observed in neonatal mice and to a lesser extent in adult male mice. The implications for clinical trial planning are evident, if this vector was under consideration for gene therapy in humans (and related vectors certainly are being considered). Of note, a related vector containing a ubiquitously active regulatory cassette provoked immune responses in adult Fabry mice that precluded efficacy when pseudotyped as AAV2. However, the currently described vector achieved partial efficacy in adult male mice when pseudotyped as AAV1. Therefore the choice of regulatory cassette and serotype seemed to have reduced the impact of immune responses and enhanced efficacy, at least in adult mice. The high degree of efficacy of this AAV vector in neonatal mice is no surprise, because AAV vectors have demonstrated high efficacy in neonatal mice of several different lysosomal storage disease models [3–5]. It should be noted that neonatal mice are at an
Major and Massive Hemoptysis: Reassessment of Conservative Management

The etiologic factors of major (greater than or equal to 200 ml/24 hr) and massive (greater than or equal to 1,000 ml/24 hr) hemoptysis may well affect the outcome and, therefore, the treatment of this often life-threatening problem. the decline in the incidence of tuberculosis (TB) and bronchiectasis, along with the increase in bronchitis and neoplasia, have led to a strong institutional bias against operating on patients with major and massive hemoptysis. A retrospective case study and an extensive literature review were undertaken to critically evaluate this policy. Fifty-nine consecutive patients with major hemoptysis, 26 of whom had massive hemoptysis, were identified from 887 patients seen in our institution over a 10-year period. Only four of these 59 patients underwent surgery, while 55 were managed conservatively. Etiologic factors, operability, and bleeding rate all appeared to play a major role in outcome. No patients with bronchitis, bronchiectasis, tuberculosis, or who were on anticoagulation therapy died compared to a mortality rate of 59% in patients with carcinoma (CA) of the lung and 71% in patients with leukemia. Eleven percent of operable patients treated conservatively died compared to a 46% mortality rate for nonoperable patients. And, 9% of patients with bleeding rates less than 1,000 ml/24 hr died compared to 58% of those with greater than or equal to 1,000 ml/24 hr. Conservative management appears to have a low mortality in patients with non-tuberculosis-related major hemoptysis as well as in many patients with massive hemoptysis, especially those patients who are operable and those without neoplastic disease.
Mechanobiological Response of Tendon Stem Cells: Implications of Tendon Homeostasis and Pathogenesis of Tendinopathy

Tendons are constantly subjected to mechanical loading in vivo. Recently, stem cells were identified in human, mouse, and rabbit tendons, but the mechanobiological responses of tendon stem cells (TSCs) are still undefined. Using an in vitro system capable of mimicking in vivo loading conditions, it was determined that mechanical stretching increased TSC proliferation in a stretching magnitude-dependent manner. Moreover, low mechanical stretching at 4% ("clamp-to-clamp" engineering strain) promoted differentiation of TSCs into tenocytes, whereas large stretching at 8% induced differentiation of some TSCs into adipogenic, chondrogenic, and osteogenic lineages, as indicated by upregulated expression of marker genes for adipocytes, chondrocytes, and osteocytes. Thus, low mechanical stretching may be beneficial to tendons by enabling differentiation of TSCs into tenocytes to maintain tendon homeostasis. However, large mechanical loading may be detrimental, as it directs differentiation of TSCs into non-tenocytes in tendons, thus resulting in lipid accumulation, mucoid formation, and tissue calcification, which are typical features of tendinopathy at later stages.
Fuchs endothelial corneal dystrophy: a neurodegenerative disorder?

First described more than a century ago, Fuchs endothelial corneal dystrophy (FECD) is a common disease characterized by progressive loss of endothelial cells, thickening of the Descemet membrane, and deposition of extracellular matrix in the form of guttae. Advanced cases result in corneal edema and vision loss occurring in patients aged 60 years or older.1 Genetic studies have identified associated genes and chromosomal loci, while proteomic and genomic studies are elucidating molecular pathogenesis. These recent findings suggest a new context in which FECD may be considered–as a neurodegenerative disorder. In this Viewpoint, we explore parallels between FECD and neurodegenerative diseases with better-understood pathogenic mechanisms such as Huntington disease, Fragile Xsyndrome, and Alzheimer disease. By comparing FECD with this group, we propose some mechanistic themes that may give insight into pathophysiology and possible nonsurgical treatments.
Resident duty hour regulation and patient safety: Establishing a balance between concerns about resident fatigue and adequate training in neurosurgery - Special topic

Postgraduate training in medicine has been under scrutiny over the past 10 years with a major focus on physician personal health and patient safety. The culmination of a series of events led to the 80-hour work week instituted by the Accreditation Council on Graduate Medical Education in 2003. The effect this mandate has had on surgical education, and specifically training in neurological surgery, has been incompletely evaluated. Nevertheless, external pressure has prompted the Institute of Medicine to issue a new report on resident work hours and patient safety. In this report, the authors focus on the unique aspects of neurosurgical training in which physicians are trained to safely and effectively carry out complex high-risk tasks, the experience from abroad where work hours are reduced to well below 80 hours/week, and the risk that further reduction in work hours poses to the public. The authors conclude that there must be an adequate balance between the risks associated with resident fatigue and those associated with an inexperienced neurosurgical work force for public health.
Topological coarsening of symmetric diblock copolymer films: Model 2D systems.

Films of diblock copolymers with thicknesses less than a lamellar period on a noninteracting surface were found to be model systems for studying the late stages of two dimensional phase separation. It was found under conditions of constant surface coverage that the average particle size , the inverse of the total number of particles N(t) -1 , and the correlation length ξ(t) varied as t a , t 2a , and t a , respectively, where a=0.23±0.03
Loline alkaloid production by fungal endophytes of Fescue species select for particular epiphytic bacterial microflora

The leaves of fescue grasses are protected from herbivores by the production of loline alkaloids by the mutualist fungal endophytes Neotyphodium sp. or Epichloe sp. Most bacteria that reside on the leaf surface of such grasses can consume these defensive chemicals. Loline-consuming bacteria are rare on the leaves of other plant species. Several bacterial species including Burkholderia ambifaria recovered from tall fescue could use N-formyl loline as a sole carbon and nitrogen source in culture and achieved population sizes that were about eightfold higher when inoculated onto plants harboring loline-producing fungal endophytes than on plants lacking such endophytes or which were colonized by fungal variants incapable of loline production. In contrast, mutants of B. ambifaria and other bacterial species incapable of loline catabolism achieved similarly low population sizes on tall fescue colonized by loline-producing Neotyphodium sp. and on plants lacking this endophytic fungus. Lolines that are released onto the surface of plants benefiting from a fungal mutualism thus appear to be a major resource that can be exploited by epiphytic bacteria, thereby driving the establishment of a characteristic bacterial community on such plants.
An Ly-like specificity with extensive nonlymphoid expression.

The characteristics of a strong mouse alloantigen with renal, bone marrow, and lymphoid expression were studied. This antigen is probably identical to that currently designated Ly-6.2. It was defined by the high-titered (1:1000) cytotoxic activity of three different antisera against peripheral lymphocyte target cells from DBA/2, DBA/1, and a variety of other strains. In the F2 and four backcross generations the genetic control of this specificity segregated as a single autosomal dominant gene. In lymphoid tissues the predominant expression was on T cells but 10–30% of B cells were lysed by these antisera. The specificity was expressed strongly in kidney, as shown by sequential absorption, in amounts equal to or greater than the amount in lymphoid tissues. Comparison to the rate of absorption of H-2 by kidney indicated that this antigen may be expressed in amounts comparable to an H-2 antigen in kidney. Immunization with kidney tissue resulted in a strong cytotoxic antibody response. The number of bone marrow cells expressing this antigen (40–50%) was well beyond what could be accounted for by T lymphocytes in bone marrow. In addition, a nonlymphoid tumor, the P815Y mastocytoma, was positive by cytotoxicity and by absorption. The extensive nonlymphoid expression and antigenic strength of Ly-6.2 raises the possibility that this serologically defined lymphocyte alloantigen will have histocompatibility effects when allografts of the appropriate tissues are examined.
HYPOTHALAMIC UNIT ACTIVITY. II. CENTRAL AND PERIPHERAL INFLUENCES.

Abstract 1. 1. In 26 acute experiments the firing rates of single hypothalamic and ventral thalamic units were analyzed during individual and paired visceral and central stimulation and somatic and central stimulation. Visceral stimulation involved distention of the urinary bladder. Somatic stimulation consisted of electrical stimulation of the sciatic nerve, adjusted to minimize A-delta and C fiber volleys. Central stimulation consisted of electrical stimulation of a variety of rhinencephalic and striatal regions with the emphasis on amygdaloid, prepyriform and pyriform sites. 2. 2. Two hundred and seventeen units were subjected to all the stimulation procedures. Fifty-seven per cent of these were responsive to at least one of the peripheral stimuli and the central stimulus or their paired effect. Thirteen per cent were only responsive to a peripheral stimulus and 6 per cent to a central stimulus. Two topographic trends emerged from stimulation of the various central structures. First, there was a vast reduction in the number of spontaneously active hypothalamic units during and for 15 min following brief stimulation of the dorsal hippocampus. Second, there was a paucity of unit responses to basal forebrain stimulation. 3. 3. Analysis of unitary firing patterns during individual visceral and somatic stimulation and during paired central-peripheral stimulation illustrated two principles. First, the direction of effect ( i.e. , augmentation or reduction in firing rate) exterted by the central stimulus was similar for central-visceral and central-somatic stimulation procedures. Second, the firing pattern of those units which responded in one direction to peripheral stimulation and in the other direction to central stimulation tended to reflect the peripheral influence when the opposing stimuli were paired. 4. 4. The firing patterns of 98 units were analyzed during two sets of paired central-peripheral stimuli involving stimulation of different rhinencephalic or striatal structures ( e.g. forebrain septum and basal forebrain, caudate nucleus and globus pallidus). For 49 per cent of this group, both central stimuli exerted an almost identical effect during paired central-peripheral stimulation. In only one case did the central stimuli exert opposite effects when paired with a peripheral stimulus. 5. 5. These results were considered in support of the concept that the afferent input to the hypothalamus is a major determinant of the susceptibility of hypothalamic neurons to rhinencephalic and striatal influences.
The respiratory syncytial virus polymerase has multiple RNA synthesis activities at the promoter.

Respiratory syncytial virus (RSV) is an RNA virus in the Family Paramyxoviridae. Here, the activities performed by the RSV polymerase when it encounters the viral antigenomic promoter were examined. RSV RNA synthesis was reconstituted in vitro using recombinant, isolated polymerase and an RNA oligonucleotide template representing nucleotides 1–25 of the trailer complement (TrC) promoter. The RSV polymerase was found to have two RNA synthesis activities, initiating RNA synthesis from the +3 site on the promoter, and adding a specific sequence of nucleotides to the 3′ end of the TrC RNA using a back-priming mechanism. Examination of viral RNA isolated from RSV infected cells identified RNAs initiated at the +3 site on the TrC promoter, in addition to the expected +1 site, and showed that a significant proportion of antigenome RNAs contained specific nucleotide additions at the 3′ end, demonstrating that the observations made in vitro reflected events that occur during RSV infection. Analysis of the impact of the 3′ terminal extension on promoter activity indicated that it can inhibit RNA synthesis initiation. These findings indicate that RSV polymerase-promoter interactions are more complex than previously thought and suggest that there might be sophisticated mechanisms for regulating promoter activity during infection.
Social dynamics and the quantifying of social forces.

Social and industrial evolutionary processes are considered to be a sequence of replacements or substitutions: new ideas for old, new labor patterns for old, new technologies for old. The logistic equation has often been used to describe population growth processes and replacement processes. It sometimes suffers from contradicting observational data. It is shown here that the deviations are often associated with unusual intermittent events—wars, strikes, economic panics, etc.—and that in many cases a few years after the event it can be abstracted as an instantaneous δ function impulse. After the event, the evolutionary process continues along its normal course. A formula is derived to use the observational data to determine the strength of the impulse modeling an event.
Single-stage balloon valvuloplasty for critical pulmonary valve stenosis in the neonate

Balloon valvuloplasty (BV) in neonates with critical pulmonary valve stenosis (CPVS) is limited by technical considerations, mainly the difficulty of traversing the stenotic valve. To simplify the procedure we used a 4F Cobra Type I catheter to cross the pulmonary valve (PV) without the aid of a guidewire, and performed single-stage BV, using low-profile balloons, in 12 neonates with CPVS. Procedure and total fluoroscopy times were 69 ± 33 min (42–125 min) and 34 ± 19 min (20–58 min), respectively. Following BV, right ventricular systolic pressure (RVSP) decreased from 102 ± 17 mm Hg to 56 ± 15 mm Hg (p < 0.001); and the ratio of RVSP to aortic systolic pressure decreased from 1.39 ± 0.22 to 0.73 ± 0.21 (p < 0.001). No significant complications were observed. BV failed in two patients, who subsequently had surgery. At follow-up (a mean of 19 months), Doppler gradient was 19 ± 12 mm Hg (0–50 mm Hg). BV was repeated in one patient. We conclude that in neonates with CPVS, the use of the 4F Cobra type I catheter facilitates crossing of the PV and allows performance of BV in a single stage; this enhances safety and time-efficiency, and shortens exposure to radiation. Cathet. Cardiovasc. Diagn. 40:322–325, 1997. © 1997 Wiley-Liss, Inc.
Weaning from ventilatory support.

Purpose of reviewIn intubated patients, mechanical ventilation offers essential ventilatory support, while the respiratory system recovers from acute respiratory failure. Yet, invasive mechanical ventilation is associated with risks and complications that prolong the duration of mechanical ventilati