cssi/SciSciGPT-SciSciNet huggingface dataset:
Results of retroviral and adenoviral approaches to cancer gene therapy.

ABSTRACT Genetic modification for cancer treatment solid tumor neoplasms. This paper will has involved the introduction of chemothera- review the use of multidrug resistance-1 py protection and sensitization genes into retroviral vectors and cytosine deami- normal and tumor cells, respectively, for the nase adenoviral prodrug activation vec- purpose of improving the outcome of con- tors for this purpose. Stem Cells 1998;16 ventional approaches to the treatment of (suppl 1):247-250 METHODS AND RESULTS MDR-lA, Retroviral Vectors for Chemoprotection Michael Gottesman and his coworkers had first created transgenic mice carrying the multidrug resistance-1 (MDR-1) cDNA driven by a Harvey Sarcoma Virus long-terminal repeat [l]. This pro- moter is active in the more mature cells of the bone marrow, in contrast to the endogenous promoter, which is downregulated during myeloid maturation [2]. Gottesman’s data showed that the bone marrow cells in MDR-1 transgenic mice exhibited high levels of p-glycoprotein, and that these cells were resistant to the toxic effects of drugs recognized and transported by the p-glycoprotein transporter [I].
Structural Basis of Allosteric Activation of Sterile α Motif and Histidine-Aspartate Domain-containing Protein 1 (SAMHD1) by Nucleoside Triphosphates

Sterile α motif and histidine-aspartate domain-containing protein 1 (SAMHD1) plays a critical role in inhibiting HIV infection, curtailing the pool of dNTPs available for reverse transcription of the viral genome. Recent structural data suggested a compelling mechanism for the regulation of SAMHD1 enzymatic activity and revealed dGTP-induced association of two inactive dimers into an active tetrameric enzyme. Here, we present the crystal structures of SAMHD1 catalytic core (residues 113–626) tetramers, complexed with mixtures of nucleotides, including dGTP/dATP, dGTP/dCTP, dGTP/dTTP, and dGTP/dUTP. The combined structural and biochemical data provide insight into dNTP promiscuity at the secondary allosteric site and how enzymatic activity is modulated. In addition, we present biochemical analyses of GTP-induced SAMHD1 full-length tetramerization and the structure of SAMHD1 catalytic core tetramer in complex with GTP/dATP, revealing the structural basis of GTP-mediated SAMHD1 activation. Altogether, the data presented here advance our understanding of SAMHD1 function during cellular homeostasis.
Compact encoding of stationary Markov sources

We treat the problem of encoding the outputs from a controllable rate source whose output statistics can be accurately described as a stationary finite-state Markov process. The class of encoding schemes considered is restricted to those in which each output from the source is encoded as a separate, uniquely decodable codeword. We present a uniquely decodable scheme in this class which minimizes the ensemble average length of the transmitted message corresponding to any number of outputs from the source, i.e., a compact encoding scheme. The code used will vary with time as a function of the entire past history of the source. The future encoding of the outputs from a sample source with any given past history will be compact also. Although the efficiency of the encoding scheme can be improved by enlarging the class of schemes considered, e.g., by applying the technique presented herein to higher order extensions of the source, this topic is not pursued.
Single-Molecule and Ensemble Fluorescence Study of Cryptic Disorder and Oligomerization in Nucleophosmin

Nucleophosmin (Npm) takes part in several important cellular processes including ribosome biogenesis and centrosome duplication. Past studies have shown that the Arf tumor suppressor protein interacts with the N-terminal region of Npm to form MDa sized complexes in vivo (1, 2). Npm shuttles between the nucleolus and cytoplasm and mediates assembly and maturation of ribosomal particles. We hypothesize that this shuttling activity is influenced by Npm's oligomeric state. Recently, the N-terminal region of Npm (residues 1-130, Npm-N) containing the oligomerization domain and a conserved disordered acidic stretch, was shown to interconvert between a monomeric disordered state and a folded, pentameric state, in response to changes in its ionic environment (3). However, the structural biophysics of the Npm/Arf system is not well understood, in part due to its complexity and high aggregation propensity. Here, we use the strengths of single-molecule (SM) and ensemble fluorescence in combination to study the folding and structural interconversion of Npm-N. In addition, we studied the interaction of Npm-N with various Arf fragments. These experiments shed light on the kinetics and mechanism of salt- and Arf-induced coupled folding and oligomerization of Npm-N, revealing multiple steps and the associated timescales. Moreover, our results suggest that Arf might arrest Npm-N in the oligomeric form, thus modulating the structural equilibrium of Npm-N, which we speculate is the underlying mechanism of inhibition of Npm's role in ribosome biogenesis by Arf. Thus, our high-resolution fluorescence studies of folding and oligomerization of Npm-N provide key biophysical insights into how Npm's shuttling and ribosome biogenesis functions are controlled.(1) Ithana, K. et al. (2003), Mol. Cell., 12, 1151-1164(2) Bertwistle, D. et al. (2004), Mol. Cell. Biol., 24, 985-996(3) Mitrea, DM. et al, manuscript in preparation
NFATc3 Regulates Kv2.1 Expression in Arterial Smooth Muscle

Voltage-gated K+ (Kv) channels control the excitability of arterial smooth muscle. However, the molecular mechanisms regulating Kv channel function in smooth muscle remain unclear. We examined the hypothesis that the vasoactive peptide angiotensin II (Ang II) regulates arterial smooth muscle Kv channel function via calcineurin-dependent activation of the transcription factor NFAT. We found that sustained administration of Ang II decreased Kv currents (IKv) by reducing the expression of Kv2.1 K+ channel subunits. This effect of Ang II was independent of pressure but required Ca2+ influx through L-type Ca2+ channels. Consistent with our hypothesis, we found that calcineurin and NFATc3 are obligatory components of the signaling cascade mediating reduced IKv by Ang II. We conclude that sustained Ang II exposure increases smooth muscle Ca2+, which leads to activation of calcineurin and NFATc3, culminating in decreased Kv2.1 expression and reduced IKv function. These results support the novel concept that NFATc3 controls the excitability of arterial smooth muscle by regulating Kv2.1 expression.
Sensitivity of Strained and Unstrained Structure Growthon GaAs (111)B

Compared with traditional (100) surfaces, the growth window for achieving high-quality photonic device structures on (111) GaAs by conventional molecular beam epitaxy (MBE) is very narrow. However, strained and unstrained structures produced on (111) substrates offer a new class of electronic and optoelectronic devices that benefit from the piezoelectric effect—a feature not accessible on symmetric (100) orientations—and additional material choices, such as InAs and InGaAs. In this work, we report on a series of investigations of strained and unstrained structures that include GaAs, AlGaAs/GaAs, and InAs/GaAs quantum layers deposited on epi-ready GaAs (111)B 2° → [\( 2\bar{1}\bar{1} \)] Si-doped substrates by conventional MBE.
Glutaraldehyde-fixed erythrocytes for indirect haemagglutination with Mycoplasma.

Mycoplasma pneumoniae (Eaton agent) is an important cause of respiratory disease in adults and children1–4. Immunological response to infection can be measured by a variety of serological procedures5–7. Of these, complement fixation and indirect haemagglutination are most useful for the required differential diagnosis from viral infection, and for epidemiological studies. Both procedures have the disadvantage of requiring considerable time and the preparation of several reagents. The applicability of the indirect haemagglutination test would be greatly extended and the test made very simple if a source of antigen-coated cells were available.
The Fundamental Noise Limit of Linear Amplifiers

If the uncertainty principle of quantum mechanics is applied to the process of signal measurement, two theorems relating to amplifier noise performance can be deduced. First, it can be shown that it is impossible to construct a linear noiseless amplifier. Second, if the amplifier is characterized as having additive white Gaussian noise, it can be shown that the minimum possible noise temperature of any linear amplifier is T.= In 2 -IIG -hv 1-1/ IG k In the limit of high gain G this expression reduces to that previously derived for the ideal maser and parametric amplifier. It is shown that the minimum noise amplifier does not degrade the signal but rather allows the use of an inaccurate detector to make measurements on an incoming signal to the greatest accuracy consistent with the uncertainty principle.
Resource Utilization Among Neonatologists in a University Children’s Hospital

Objective . We studied factors affecting length of hospital stay and resulting hospital charges among patients managed by two separate groups of neonatologists in the same academic health science center. Design. Retrospective analysis of clinical and financial data base information. Methods. Neonatal intensive care was provided in the same acute care nursery in a large university children’s hospital by: (1) neonatologists in a full-time academic division (group A) and (2) a group associated with a private managed care organization (group B). Clinical and financial parameters of all neonates admitted in fiscal year 1994 were compared for the two provider groups. Stepwise regression analysis was used to evaluate factors influencing hospital charges and length of hospital stay (LOS) and to adjust for differences in clinical variables between the two groups. Results. Group A physicians provided care for 340 infants, while 137 were treated by those of group B. Group A included older patients, more outborns, more level III patients, more sepsis, more intermittent positive pressure ventilation, and more patent ductus arteriosus. The incidence of transient tachypnea of the newborn was higher among group B patients. Hospital charges were primarily determined by LOS, which was similar for the two groups. When the data were corrected for differences in risk and patient acuity, however, a significant relationship between physician group and LOS was demonstrated, with LOS being an average of 7.8 days shorter for group A. A net reduction of $3 114 969 in hospital charges might have been realized had group A physicians provided care for all study patients. Conclusions. Hospital charges were determined by LOS. In this setting, academic neonatologists produced shorter LOS and comparable clinical outcomes, despite caring for a population at greater risk. The reduction in LOS could have resulted in more than $3.1 million in annualized savings had the academic group provided care for all of the study patients. resource utilization, hospital changes, length of stay, neonatologists.
Can a short film impact HIV-related risk and stigma perceptions? Results from an experiment in Abuja, Nigeria.

HIV/AIDS-related stigma is believed to result in negative social consequences for people with the disease and to be a deterrent to HIV serostatus testing. The ability of communicators to change people's stigma perceptions and subsequently impact decisions to test, however, is not well understood. Based on the entertainment–education approach, this article presents the results of a field experiment conducted in Abuja, Nigeria, testing a mediated intervention designed to reduce HIV-related stigma and risk perceptions. The results indicate that the intervention was effective relative to a control in impacting perceptions of the severity of HIV and some stigma-related attitudes, particularly for male participants; and that for this sample, risk and stigma perceptions significantly impact intentions to test for HIV. It also showed that severity perceptions mediated the relationship between viewing the film and testing intent.
Left Ventricular Performance Following Digitalization in Patients with and without Heart Failure

Nine patients, three with left ventricular failure and six with compensated heart disease, were studied by means of right and transseptal left heart catheterization during acute digitalization with acetyl strophanthidin. One of the patients with heart failure and a compensated subject with the Wolff-Parkinson-White syndrome were also studied during supine left leg exercise. In the decompensated group, digitalization produced a decrease in heart rate and increases in stroke index, stroke work, mean stroke power, mean systolic ejection rate, and the rate of pressure rise in the left ventricle. Left ventricular end-diastolic pressures were markedly lowered after digitalization. In the compensated group, no significant changes in cardiac index, stroke index, or mean systolic ejection rate were observed. Although there were small increases in stroke work and power and moderate decreases in left ventricular diastolic pressures, the most striking finding was an increase in the rate of rise of left ventricular sy...
Gestational choriocarcinoma arising from a cornual ectopic pregnancy: a case report and review of the literature.

Gestational choriocarcinoma associated with ectopic pregnancy is an extremely rare event. We report a case of a choriocarcinoma arising from a cornual pregnancy. The patient is a 35-year-old G8 P2052 who was referred to our department due to failure of treatment for a suspected ectopic pregnancy. The patient had initially been treated with methotrexate injection but her β-hCG levels reached a plateau 3 weeks later and, despite another two methotrexate injections, started to rise. The patient underwent dilation and curettage that did not reveal any trophoblastic tissue. A diagnostic hysteroscopy that followed demonstrated occluded ostia of the left tube. The patient subsequently underwent diagnostic laparoscopy that revealed a mass in the left cornua, which was removed with wedge-wide resection. Histologic evaluation revealed choriocaricnoma. Appropriate monitoring of β-hCG titers following conservative management of suspected ectopic pregnancy is important, not only to diagnose persistent ectopic gestation, but also to rule out the presence of malignant trophoblastic disease, albeit the latter is a rare diagnosis.
Pineal gland structure and respiration as affected by age and hypocaloric diet

Abstract The effect of age and underfeeding on pineal gland structure and metabolism was determined in male rats. Both chronic and acute caloric restriction was imposed on selected groups of these animals to determine the process by which pineal cell number is altered. Oxygen consumption of single pineal glands was greatest in the tissues removed from neonatal animals and declined thereafter. Pineal respiration was enhanced in the chronically undefed animals when compared with similar tissue from their littermates, but was uneffected when food was withheld for a short period of time. Mitotic indices of pineal cells similarly decreased with age, but were not enhanced by either underfeeding schedule. Pineal cell number, which also decreased as time progressed, was significantly higher in chronically underfed rats than in controls. No such increase was evident in short term underfed animals. It is concluded that the enhanced metabolism of pineal glands from chronically underfed rats occurs due to the increased number of cells present. This increase results from a reduced loss of pineal cells rather than an enhanced production by stimulation of mitotic activity. Based upon the capacity of pineal compounds to alter neuroendocrine feedback sensitivities, life prolongation resulting from feed restriction may in part be due to the persistence of a juvenile type pineal gland in the chronically underfed rat.
Diagnostic accuracy of sentinel node identification is maintained with the addition of local lidocaine and subareolar radioactive colloid injection.

Preoperative sentinel node localization (SNL) using a subareolar injection of radiotracer technetium-99m-sulfur colloid (Tc99mSC) is associated with significant pain. Lidocaine use during SNL is not widely adopted partly due to a concern that it can obscure sentinel node identification and reduce its diagnostic accuracy. We prospectively identified women with a biopsy-proven infiltrating breast cancer who were awaiting a SNL. The women completed the McGill pain questionnaire, Visual Analog Scale, and Wong–Baker FACES Pain Rating Scale prior to and following SNL. We identified a retrospective cohort of women with similar demographic and tumor characteristics who did not receive lidocaine before SNL. We compared sentinel lymph node identification rates in the two cohorts. We used Wilcoxon rank sum tests to compare continuous measures and Fisher’s exact test for categorical measures. Between January 2011 to July 2012, 110 women consented, and 105 were eligible for and received lidocaine prior to Tc99mSC injection. The post-lidocaine identification rate of SNL was 95 % with Tc99mSC, and 100 % with the addition of intraoperative methylene blue dye/saline. Pain range prior to and following the SNL was unchanged (P = 0.703). We identified 187 women from 2005 to 2009 who did not receive lidocaine during preoperative SNL. There was no significant difference in the success rate of SNL, with or without lidocaine (P = 0.194). The administration of lidocaine during SNL prevents pain related to isotope injection while maintaining the success rate. We have changed our practice at our center to incorporate the use of lidocaine during all SNL.
Septate uterus with cervical duplication and longitudinal vaginal septum: a report of five new cases.

Abstract Objective To describe a unique congenital mullerian anomaly. Design Case report. Setting A university-based reproductive endocrine center. Patient(s) Five reproductive-age, nulligravida patients who underwent clinical, radiologic, and surgical work-up. Intervention(s) Retrospective review of prior medical records and studies. Main outcome measure(s) Definition of abnormal pelvic anatomy. Result(s) Five patients from a university-based, reproductive endocrine center were found to have cervical duplication with a longitudinal vaginal septum, uterine septum, and a normal fundus. The patients most often presented initially to their primary obstetrician–gynecologists with symptomatic complaints secondary to their vaginal septums. Diagnoses were obtained with physical examinations, ultrasound imaging, hysterosalpingograms, magnetic resonance imaging, and surgical evaluation. Conclusion(s) These findings call into question the classic hypothesis of unidirectional (caudal to cranial) mullerian development and supports an alternative embryologic hypothesis of Muller et al., which states that fusion and resorption begins at the isthmus and proceeds simultaneously in both the cranial and caudad directions. The high number of cases reported here might be due to the increased accessibility and accuracy of such imaging modalities as magnetic resonance imaging. These patients will be followed longitudinally so that it can be determined whether this anomaly affects fertility and so that the optimal treatment plans can be developed.
Geographic discrepancies between global and local rarity richness patterns and the implications for conservation

The emerging interest in the biological and conservation significance of locally rare species prompts a number of questions about their correspondence with other categories of biodiversity, especially global rarity. Here we present an analysis of the correspondence between the distributions of globally and locally rare plants. Using biological hotspots of rarity as our framework, we evaluate the extent to which conservation of globally rare plants will act as a surrogate for conservation of locally rare taxa. Subsequently, we aim to identify gaps between rarity hotspots and protected land to guide conservation planning. We compiled distribution data for globally and locally rare plants from botanically diverse Napa County, California into a geographic information system. We then generated richness maps highlighting hotspots of global and local rarity. Following this, we overlaid the distribution of these hotspots with the distribution of protected lands to identify conservation gaps. Based on occupancy of 1 km2 grid cells, we found that over half of Napa County is occupied by at least one globally or locally rare plant. Hotspots of global and local rarity occurred in a substantially smaller portion of the county. Of these hotspots, less than 5% were classified as multi-scale hotspots, i.e. they were hotspots of global and local rarity. Although, several hotspots corresponded with the 483 km2 of protected lands in Napa County, some of the richest areas did not. Thus, our results show that there are important conservation gaps in Napa County. Furthermore, if only hotspots of global rarity are preserved, only a subset of locally rare plants will be protected. Therefore, conservation of global, local, and multi-scale hotspots needs serious consideration if the goals are to protect a larger variety of biological attributes, prevent extinction, and limit extirpation in Napa County.
A Model for Segmentation and Analysis of Noisy Images

Abstract This article proposes a statistical model for image generation that provides automatic segmentation of images into intensity-differentiated regions and facilitates the quantitative assessment of uncertainty associated with identified image features. The model is specified hierarchically within the Bayesian paradigm. At the lowest level in the hierarchy, a Gibbs distribution is used to specify a probability distribution on the space of all possible partitions of the discretized image scene. An important feature of this distribution is that the number of partitioning elements, or image regions, is not specified a priori. At higher levels in the hierarchical specification, random variables representing emission intensities are associated with regions and pixels. Observations are assumed to be generated from exponential family models centered about these values.
Experimental Induction of Chronic Aflatoxicosis in Chickens by Purified Aflatoxin B1 and Its Reversal by Activated Charcoal, Phenobarbital, and Reduced Glutathione

Abstract Aflatoxin B1 (AFB1) caused dose-dependent reductions in weight gain and feed consumption when day-old Hubbard × Hubbard broiler type chicks were maintained on a diet contaminated with either 0, 2.5, 5, or 10 ppm purified AFB1 for 8 weeks. Although changes in these parameters were detected at the 2.5 and 5 ppm, the most profound changes were evident at 10 ppm contamination. The concentration of cytochrome P-450 in hepatic microsomes, measured at the end of 8 weeks, also showed dose-dependent decreases. Cytochrome P-450 content in chickens receiving 2.5, 5, and 10 ppm AFB1 was 16, 28, and 65%, respectively, less than the control. Microsomal benzphetamine N-demethylase activity was not inhibited by 2.5 or 5 ppm, but ingestion of 10 ppm AFB1 reduced its activity by more than 40%. Serum glutamic oxalacetic transaminase (SGOT) levels of chickens receiving 10 ppm AFB1 increased by more than 100%, indicating substantial liver damage. However, birds simultaneously receiving 10 ppm AFB1 and activated charcoal (.1% in the feed) or either reduced glutathione (.05%) or phenobarbital (.05%, given intermittently) in their drinking water showed a trend of improvement in feed consumption (
Characterization and comparison of 128x128 element nuclear optical dynamic display system resistive arrays

Dynamic infrared scene projection is a common technology used to provide end to end testing and characterization of infrared sensor systems. Scene projection technology will play an increasing role in infrared system evaluation and development as the cost and risk of flight testing increases and new display technologies begin to emerge. This paper describes a series of tests performed in the Seeker Experimental System (SES) at MIT Lincoln Laboratory (MIT LL). A small collection of 128×128 element Nuclear Optical Dynamic Display System (NODDS) resistive arrays were tested and compared using FIESTA drive electronics developed by ATK Mission Research. The residual spatial nonuniformity of the NODDS arrays were calculated after applying a sparse grid based nonuniformity correction algorithm developed at MIT LL. The nonuniformity correction algorithm is a slightly modified version of the industry standard sparse grid technique and is outlined in this paper. Additional metrics used to compare the arrays include emitter temporal response, raw nonuniformity, transfer function smoothness, dynamic range, and bad display pixel characteristics.
Predicting the brain response to treatment using a Bayesian hierarchical model with application to a study of schizophrenia

In vivo functional neuroimaging, including functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), is becoming increasingly important in defining the pathophysiology of psychiatric disorders such as schizophrenia, major depression, and Alzheimer's disease. Furthermore, recent studies have begun to investigate the possibility of using functional neuroimaging to guide treatment selection for individual patients. By studying the changes between a patient's pre- and post-treatment brain activity, investigators are gaining insights into the impact of treatment on behavior-related neural processing traits associated with particular psychiatric disorders. Furthermore, these studies may shed light on the neural basis of response and nonresponse to specific treatments. The practical limitation of such studies is that the post-treatment scans offer little guidance to treatment selection in clinical settings, since treatment decisions precede the availability of post-treatment brain scans. This shortcoming represents the impetus for developing statistical methodology that would provide clinicians with predictive information concerning the effect of treatment on brain activity and, ultimately, symptom-related behaviors. We present a prediction algorithm that uses a patient's pretreatment scans, coupled with relevant patient characteristics, to forecast the patient's brain activity following a specified treatment regimen. We derive our predictive method from a Bayesian hierarchical model constructed on the pre- and post-treatment scans of designated training data. We perform estimation using the expectation-maximization algorithm. We evaluate the accuracy of our proposed prediction method using K-fold cross-validation, quantifying the error using two new measures that we propose for neuroimaging data. The proposed method is applicable to both PET and fMRI studies. We illustrate its use with a PET study of working memory in patients with schizophrenia and an fMRI data example is also provided.
Mathematical analysis of hemoglobin spectrophotometry in microvessels.

Spectrophotometry of hemoglobin in microvessels is commonly performed by collecting light either from a small region around the vessel centerline or from the entire lumen of the vessel. In the latter instance, parallel rays of light may not encounter the same amount of absorbing species. Hence, a phenomenon similar to the sieve effect reported in the literature on hemoglobin spectrophotometry may be expected to occur. Although it has been observed that under such circumstances nonlinearities in calibration characteristics arise, the implications of this effect on the interpretation of the spectrophotometric mean concentration have never been addressed so far. Mathematical analysis of hemoglobin spectrophotometry in microvessels, performed in this study, reveals that for practical situations the calibration curve is indeed nonlinear. Moreover, the spectrophotometric mean oxygen saturation is an overestimate of the mean oxygen saturation during oxygenation and an underestimate of the mean oxygen saturation during deoxygenation. These deviations depend upon the manner in which the total heme concentration is distributed within the lumen. Application of the analysis to artificial microvessels showed that the observed superior oxygen transport characteristics of flowing erythrocyte suspensions and hemoglobin solution mixtures could in part be due to the assumptions underlying the procedure used to interpret the experimental results. The implications of this result on models for oxygen transport in microvessels are discussed along with possible resolutions.
Abdominal aortic calcification, BMD, and bone microstructure: a population-based study.

To better define the relationship between vascular calcification and bone mass/structure, we assessed abdominal aortic calcification (AAC), BMD, and bone microstructure in an age-stratified, random sample of 693 Rochester, MN, residents. Participants underwent QCT of the spine and hip and high-resolution pQCT (HRpQCT) of the radius to define volumetric BMD (vBMD) and microstructural parameters. AAC was quantified with the Agatston scoring method. In men, AAC correlated with lower vertebral trabecular and femoral neck vBMD (p < 0.001), but not after age or multivariable (age, body mass index, smoking status) adjustment. Separation into <50 and ≥50 yr showed this pattern only in the older men. BV/TV and Tb.Th inversely correlated with AAC in all men (p < 0.001), and Tb.Th remained significantly correlated after age adjustment (p < 0.05). Tb.N positively correlated with AAC in younger men (p < 0.001) but negatively correlated in older men (p < 0.001). The opposite was true with Tb.Sp (p = 0.01 and p < 0.001, respectively). Lower Tb.N and higher Tb.Sp correlated with AAC in older men even after multivariable adjustment. Among all women and postmenopausal women, AAC correlated with lower vertebral and femoral neck vBMD (p < 0.001) but not after adjustment. Lower BV/TV and Tb.Th correlated with AAC (p = 0.03 and p = 0.04, respectively) in women, but not after adjustment. Our findings support an age-dependent association between AAC and vBMD. We also found that AAC correlates with specific bone microstructural parameters in older men, suggesting a possible common pathogenesis for vascular calcification and deterioration in bone structure. However, sex-specific differences exist.
Whole-Genome Single-Nucleotide-Polymorphism Analysis for Discrimination of Clostridium botulinum Group I Strains

ABSTRACT Clostridium botulinum is a genetically diverse Gram-positive bacterium producing extremely potent neurotoxins (botulinum neurotoxins A through G [BoNT/A-G]). The complete genome sequences of three strains harboring only the BoNT/A1 nucleotide sequence are publicly available. Although these strains contain a toxin cluster (HA+ OrfX−) associated with hemagglutinin genes, little is known about the genomes of subtype A1 strains (termed HA− OrfX+) that lack hemagglutinin genes in the toxin gene cluster. We sequenced the genomes of three BoNT/A1-producing C. botulinum strains: two strains with the HA+ OrfX− cluster (69A and 32A) and one strain with the HA− OrfX+ cluster (CDC297). Whole-genome phylogenic single-nucleotide-polymorphism (SNP) analysis of these strains along with other publicly available C. botulinum group I strains revealed five distinct lineages. Strains 69A and 32A clustered with the C. botulinum type A1 Hall group, and strain CDC297 clustered with the C. botulinum type Ba4 strain 657. This study reports the use of whole-genome SNP sequence analysis for discrimination of C. botulinum group I strains and demonstrates the utility of this analysis in quickly differentiating C. botulinum strains harboring identical toxin gene subtypes. This analysis further supports previous work showing that strains CDC297 and 657 likely evolved from a common ancestor and independently acquired separate BoNT/A1 toxin gene clusters at distinct genomic locations.
The effect of foliage phenotype and seed size on the crop growth of Pisum sativum (L)

Studies have been made of the growth of three foliage phenotypes of pea during the early growth of the pea crop prior to the onset of plant-plant interaction. These phenotypes were conventional (AfAfStSt), ‘semi-leafless’ (afafStSt) and ‘leafless’ (afafstst). The ‘leafless’ type had a lower growth rate compared with the conventional type, after 24 days from sowing and had a reduced relative growth rate (RGR) during the sampling period. The growth of the ‘semi-leafless’ type, however, was similar to that of the conventional phenotype. The reduced RGR of the ‘leafless’ plant was due to a reduced RGR of the stem portion of the plant, whereas the RGR of the remainder of the plant was similar in all three phenotypes. For each phenotype, two seed weight classes were sown and their growth compared. RGR was similar for these pairs of seed weight classes in each phenotype but the heavier seed weight class had a significantly superior growth rate in two of the three phenotypes. This is discussed in relation to the difference in the size of the embryonic axis. Results are discussed with regard to the development of a new phenotype for the dried pea crop.
Chromosomal localization of human haemoglobin structural genes: techniques queried.

Price, Conover and Hirschhorn1 have reported the in situ hybridization of haemoglobin mRNA to diploid chromosomes. We think such a conclusion to be impossible because the specific activity of their mRNA was 6 × 10−7 disintegrations per mRNA molecule during the two week exposure of their autoradiographs. As a genome has been reported to contain less than five haemoglobin cistrons2, even if hybridization and autoradiographic efficiencies were 100%, then at most only 6 × 10−6 silver grains would have been produced over the diploid cell's haemoglobin loci.
Thermal Stress Analysis of Reentry Vehicle Nosetips at Angle of Attack.

Abstract The ASAAS (Asymmetric Stress Analysis of Axisymmetric Solids) computer program is applied to the prediction of thermal stresses in a reentry vehicle nosetip subjected to asymmetric temperature distributions and angle-of-attack loadings during reentry. This three-dimensional stress analysis computer program has the unique capability of properly accounting for the circumferential variation of temperature dependent material properties. It is based on a meridional finite element discretization of an axisymmetric solid combined with a Fourier series representation of circumferentially dependent variables. In contrast with similar methods where material properties cannot be expressed as a function of temperature, this method requires that the large system of equations be solved simultaneously. This is handled efficiently in ASAAS by several newly developed approaches to stiffness matrix generation and simultaneous equation solution. The nosetip analyzed is fabricated from an orthotropic, temperature dependent graphite material that is susceptible to thermal shock. Analyses are performed at several points in a trajectory and the effects of both aerodynamic heating and pressure loading are considered. The complete states of temperature, stress, strain and displacement throughout the graphite material are obtained as a product of ASAAS. Results are presented in the form of meridional contour plots at selected circumferential stations. The usefulness of ASAAS in performing angle-of-attack analysis of nosetips is evaluated by comparison to an axisymmetric analysis based on single ray heating. In addition, the convergence of solutions with increasing numbers of harmonics is demonstrated and computer run times are discussed.
Does Powerlessness Explain the Relationship Between Intimate Partner Violence and Depression

The current study aimed to test whether relationship power could act as a mediator of the relationship between intimate partner violence and depression. The proposed mediation model was based on the theory of gender and power and on previous research of intimate partner violence and depression. Survey results from a sample of 327 single undergraduate women lent support to the hypothesis stating that relationship power accounts for some of the association between intimate partner violence and depression. Results revealed that women who felt powerless had higher rates of intimate violence victimization and higher levels of depression; a mediation analysis revealed that sexual relationship power mediated the relationship between intimate partner violence and depression. Future interventions targeting the prevention of intimate partner violence among young women may want to utilize an empowerment approach to decrease their likelihood of experiencing dating violence victimization and their subsequent risk for depression.
Adhesive surface design using topology optimization

Tailoring adhesive properties between surfaces is of great importance for micro-scale systems, ranging from managing stiction in MEMS devices to designing wall-scaling gecko-like robots. A methodology is introduced for designing adhesive interfaces between structures using topology optimization. Structures subjected to external loads that lead to delamination are studied for situations where displacements and deformations are small. Only the effects of adhesive forces acting normal to the surfaces are considered. An interface finite element is presented that couples a penalty contact formulation and a Lennard–Jones model of van der Waals adhesive forces. Two- and three dimensional design optimization problems are presented in which adhesive force distributions are designed such that load-displacement curves of delaminating structures match target responses. The design variables describe the adhesive energy per area of the interface between the surfaces, as well as the geometry of the delaminating structure. A built-in length scale in the formulation of the adhesion forces eliminates the need for filtering to achieve comparable optimal adhesive designs over a range of mesh densities. The resulting design problem is solved by gradient based optimization algorithms evaluating the design sensitivities by the adjoint method. Results show that the delamination response can be effectively manipulated by the method presented. Varying simultaneously both adhesive and geometric parameters yields a wider range of reachable target load-displacement curves than in the case varying adhesive energy alone.
Police uniforms, attitudes, and citizens

Abstract This study focuses on identifying the relationship between the citizen's attitude toward the police and the police uniform and authoritarian attitude. The perceived authority associated with the police uniform has been an essential ingredient of the police role. Consequently, the police uniform influences attitudes and behaviors of the wearers as well as the citizens with whom they interact. The citizen's attitude is negatively affected by the traditional military style police uniform in conjunction with the authoritarian attitude exhibited by police officers in performance of their duties. Consequently, when the uniform and officer's attitude are altered, there will be a corresponding change in the citizen's attitude toward the police. The attitude of the officer, in conjunction with the uniform, exerts considerably more influence on the citizen's attitude than does the uniform, officer's attitude, or any additional factor acting independently.
Retargeting mobile group II introns to repair mutant genes.

Retroposable elements such as retroviral and lentiviral vectors have been employed for many gene therapy applications. Unfortunately, such gene transfer vectors integrate genes into many different DNA sequences and unintended integration of the vector near a growth-promoting gene can engender pathological consequences. For example, retroviral vector-mediated gene transfer induced leukemia in 2 of 11 children treated for severe combined immunodeficiency, raising significant safety issues for gene transfer strategies that cannot be targeted to specific sequences. Here, we examine the use of a mobile retroposable genetic element that can be targeted to introduce therapeutic sequences site specifically into mutant genes. The data demonstrate that the mobile group II intron from Lactococcus lactis can be targeted to insert into and repair mutant lacZ (approved gene symbol GLB1) and β-globin (approved gene symbol HBB) genes with high efficiency and fidelity in model systems in bacteria. These results suggest that these mobile genetic elements represent a novel class of agents for performing targeted genetic repair.
DUCTUS ARTERIOSUS ENDOTHELIAL CELLS AND SMOOTH MUSCLE CELLS ALTER THEIR INTEGRIN EXPRESSION TO PRODUCE PERMANENT POSTNATAL CLOSURE. • 1198

Following muscular constriction of the ductus arteriosus in the first hours after delivery, extensive neointimal thickening is required to produce permanent occlusion of the ductus lumen. In premature infants, despite, smooth muscle constriction, neointimal mounds frequently fail to develop, resulting in vessel reopening. Neointimal mounds are formed by luminal endothelial cells(ECs) and medial smooth muscle cells (SMCs) that migrate into the subendothelial space. The migration of ECs and SMCs requires the presence of cell surface receptors (integrins) that interact with the surrounding extracellular matrix (ECM). The ability of the integrin receptors to bind to different ECM molecules is determined by the combination of α and β subunits that make up the integrin receptor. Using immunohistochemical techniques, we examined ductus arteriosus obtained from 4 fetal and 11 four-day-old newborn (3 full-term and 8 preterm [78% gestation]) rhesus monkeys to determine the effects of gestational age on postnatal integrin expression and ductus remodeling. In the fetal ductus, ECs lining the vessel's lumen have a limited repertoire of integrins (weak expression ofα1β1 and minimal to negligible expression of otherβ1, β3, β4, β5, andβ6 integrins). In contrast, ECs of capillaries invading the ductus adventitial layer strongly express several integrins(α1β1, α2β1,α3β1, α6β1,αVβ5, α6β4). During postnatal closure, luminal ECs of the full-term ductus change their phenotype and express the identical repertoire of integrins found on migrating capillary endothelial cells. Similarly, after birth, SMCs in the closing ductus change their phenotype and express 2 additional integrins(α5β1 and αVβ3) that we have previously shown to be necessary for SMC migration in vitro. Among the 8 preterm ductus, 3 had lumens that were occluded by neointimal formation; the integrin profiles of the ECs and SMCs of these 3 ductus were identical to those expressed by cells of the full-term postnatal closed ductus. In contrast, 5 preterm newborns with persistently patent ductus lumen failed to develop these postnatal changes in integrin expression and failed to develop neointimal mounds. No evidence of intimal thickening occurred in the absence of changes in integrin expression. These findings show that during ductus closure, ECs and SMCs change their phenotype and express integrins found on migrating cells; this enables them to produce the neointimal mounds necessary for permanent closure.
Pathogenicity of A and B morphotypes of Sphaeropsis sapinea confirmed on American larch (tamarack) and European larch

Summary Fungi identified as Sphaeropsis sapinea (or synonyms) have been reported from Larix. Lack of pathogenicity tests, confusion about the identity of isolates mentioned in previous literature, and existence of distinct populations (A and B morphotypes) of the pathogen indicated the need to evaluate the ability of S. sapinea to cause disease of larch. Elongating snoot tips of Larix decidua, Larix laricina, and known hosts of the pathogen, Pinus banksiana and Pinus resinosa, were inoculated with water-agar plugs colonized with an A or a B isolate, or sterile plugs (controls). Each of five replications included five seedlings for each treatment-species combination. After 6 weeks, no symptoms had developed on control seedlings, but two-way analyses of variance revealed significant effects of isolate morpnotype and host on both incidence and severity of disease (values of p ≤ 0.01). The A isolate killed almost all shoot tips, but the B isolate killed from no P. resinosa shoots to 56% of L. laricina shoots. The average length of shoot killed by the A isolate was also greater than that killed by the B isolate. Response to the B isolate again varied among species, with greater average lengths of shoot killed on the larches (compared with the pines). Both A and B morphotypes of 5. sapinea should be considered among the fungi encountered on L. decidua and L. laricina.
Treatment of metastatic breast cancer--economic and ethical considerations.

(1997). Bioethics: Treatment of Metastatic Breast Cancer—Economic and Ethical Considerations. Cancer Investigation: Vol. 15, No. 4, pp. 335-341.
Limited hydrologic response to Pleistocene climate change in deep vadose zones - Yucca Mountain, Nevada

Abstract Understanding the movement of water through thick vadose zones, especially on time scales encompassing long-term climate change, is increasingly important as societies utilize semi-arid environments for both water resources and sites viewed as favorable for long-term disposal or storage of hazardous waste. Hydrologic responses to Pleistocene climate change within a deep vadose zone in the eastern Mojave Desert at Yucca Mountain, Nevada, were evaluated by uranium-series dating of finely layered hyalitic opal using secondary ion mass spectrometry. Opal is present within cm-thick secondary hydrogenic mineral crusts coating floors of lithophysal cavities in fractured volcanic rocks at depths of 200 to 300 m below land surface. Uranium concentrations in opal fluctuate systematically between 5 and 550 μg/g. Age-calibrated profiles of uranium concentration correlate with regional climate records over the last 300,000 years and produce time-series spectral peaks that have distinct periodicities of 100- and 41-ka, consistent with planetary orbital parameters. These results indicate that the chemical compositions of percolating solutions varied in response to near-surface, climate-driven processes. However, slow (micrometers per thousand years), relatively uniform growth rates of secondary opal and calcite deposition spanning several glacial–interglacial climate cycles imply that water fluxes in the deep vadose zone remained low and generally buffered from the large fluctuations in available surface moisture during different climates.
Behavior of the Gibbs Sampler When Conditional Distributions Are Potentially Incompatible.

The Gibbs sampler has been used extensively in the statistics literature. It relies on iteratively sampling from a set of compatible conditional distributions and the sampler is known to converge to a unique invariant joint distribution. However, the Gibbs sampler behaves rather differently when the conditional distributions are not compatible. Such applications have seen increasing use in areas such as multiple imputation. In this paper, we demonstrate that what a Gibbs sampler converges to is a function of the order of the sampling scheme. Besides providing the mathematical background of this behaviour, we also explain how that happens through a thorough analysis of the examples.
Assurance of Learning and the MFT: Closing the Loops With an Online Review

The authors describe the four stages of the closing the loop process undertaken by a college of business (COB) over a 6-year period. The COB developed and offered an online, noncredit review course to help students prepare for the Major Field Test in Business (MFT). Early results demonstrated the efficacy of the course as student scores rose from the 40th percentile to the 65th percentile. The authors analyze stage 4 data to determine the relationship between the online review and MFT performance. Results suggest the impact of the online review course diminishes as overall performance increases. Assessment outcomes may be influenced by the number of Hispanic and international students taking the MFT.