cssi/SciSciGPT-SciSciNet huggingface dataset:
Genetic testing in patients with nonsyndromic autism spectrum disorder and EEG abnormalities with or without epilepsy: Is exome trio-based testing the best clinical approach?

Abstract Objectives The association between autism spectrum disorder (ASD) and epilepsy is well-known. Abnormalities on electroencephalography (EEG) studies have been reported in patients with ASD without a history of seizures, and these patients have lower functional scores on adaptive measures than patients with ASD with normal EEG studies. The purpose of the study was to evaluate the genetic test approach in children with ASD and abnormal EEGs. Methods Data were collected from medical records at Cincinnati Children’s Hospital Medical Center (CCHMC) of a previously published cohort of patients with well-characterized ASD based on evaluation by Developmental Pediatrics. Patients were subdivided into two groups: ASD without epilepsy, but with abnormal EEG results, and ASD with epilepsy. EEG data were abstracted from reports. In this follow-up study, we analyzed genetic testing data, namely the proportion of this cohort that received genetic testing, and the specific type of genetic testing that was ordered to analyze if there were any differences between groups. Results Analysis was performed on 173 patients with ASD. Ninety-five patients had a diagnosis of epilepsy. Seventy-eight patients did not have a diagnosis of epilepsy but did have abnormal EEGs. In both groups, approximately three quarters of all subjects received routine neurodevelopmental genetic testing (77% versus 72% p = 0.15) without significant differences between groups. The ASD + epilepsy group was more likely to receive additional second-tier genetic testing outside of a routine neurodevelopmental workup (35% versus 15% p = 0.007). The ASD + epilepsy group was more likely to receive phenotype specific panels, most often an epilepsy gene panel of less than 250 genes (15% versus 3% p = 0.008). However, the ASD + epilepsy group was less likely to receive a genetic diagnosis from testing than the ASD + abnormal EEG group (9% versus 33%, p = 0.047). Conclusions Patients with ASD along with a formal epilepsy diagnosis received more genetic testing; but had an overall lower diagnostic rate than patients with ASD with abnormal EEGs but without a formal epilepsy diagnosis. Patients in this cohort without a diagnosis of epilepsy were more likely to get broad trio-based exome testing instead of targeted epilepsy gene panel testing. A higher diagnostic rate was found in patients when a broad genetic test strategy was implemented.
Is Menière's Disease a Contraindication to Stapedectomy?

OBJECTIVE Review surgical outcomes of stapedectomy for otosclerosis in patients with Meniere's disease. STUDY DESIGN Retrospective case review. SETTING Tertiary referral center. PATIENTS Patients with otosclerosis and Meniere's disease undergoing stapedectomy between 2010 and 2017. INTERVENTION Stapedectomy. MAIN OUTCOME MEASURES Pre- and postoperative hearing and complications. Hearing was measured by air conduction (AC) and bone conduction (BC) pure-tone frequency, pure-tone averages (PTA), air-bone gap (ABG), and word recognition scores (WRS). RESULTS Among 1,499 patients with otosclerosis, the incidence of concomitant Meniere's disease was 1.7%. Fifteen patients with otosclerosis and Meniere's disease underwent stapedectomy, 12 primary and three revisions. Mean AC PTA was 43 dB preoperatively, and 25 dB postoperatively (p = 0.0007), while the ABG improved on average from 20 to 5 dB (p = 0.0001). There was no significant difference in BC PTA or WRS postoperatively. Two patients experienced fluctuation of hearing in the postoperative period, one of which resolved with a course of steroids. The mean follow-up time was 41 months. CONCLUSIONS In patients with otosclerosis and Meniere's disease, stapedectomy provides excellent hearing outcomes in a majority of patients. As is characteristic of Meniere's disease, some patients will continue to experience fluctuating hearing postoperatively, which may progress to severe sensorineural hearing loss. Meniere's disease may not be an absolute contraindication to stapes surgery.
Salto a conclusiones y formación de delirios en psicosis: un análisis crítico

Resumen Los delirios son uno de los sintomas mas complejos de la psicosis en la esquizofrenia. El enfoque de los dos factores —uno de los enfoques neuropsiquiatricos mas populares para la etiologia de los delirios en la actualidad— propone la existencia de alteraciones experienciales (factor 1) y sesgos cognitivos (factor 2) que, en interaccion, producirian el sintoma. Una de las alteraciones cognitivas mas aludidas por este enfoque es la de «salto a conclusiones», esto es, la tendencia de ciertos sujetos a generar conclusiones apresuradas a pesar de no tener suficiente evidencia para ello. Este trabajo ofrece una revision narrativa que, luego de clarificar la estructura explicativa del modelo de los dos factores, examina y evalua criticamente los estudios y la evidencia utilizada por el enfoque para establecer al sesgo de salto a conclusiones como uno de los principales factores cognitivos anormales en el proceso de formacion de delirios en psicosis y, por lo tanto, como una de las principales evidencias empiricas en favor del modelo.
Baseline pathogenic mutations in non-AR/non-TP53 genes and prediction of response to high-dose testosterone.

146Background: The fact that high dose of testosterone (HDT) elicits positive responses in a subset of prostate cancer patients (pts) is surprising and puzzling. Genomics data differentiating respo...
Melphalan Transport, Glutathione Levels, and Glutathione-S-transferase Activity in Human Medulloblastoma

Abstract Melphalan transport, glutathione levels, and glutathione- S -transferase activity were measured in two continuous human medulloblastoma cell lines and transplantable xenografts in athymic nude mice, TE-671 and Daoy. In vitro mean glutathione levels were 10.06 nmol/10 6 cells in TE-671 and 2.96 nmol/10 6 cells in Daoy. In vitro mean glutathione- S -transferase values were 91.52 nmol/min/mg protein in TE-671 and 50.31 nmol/min/mg protein in Daoy. Transport studies revealed kinetic parameters of K m = 108.3 µm, V max = 363.1 pmol/10 6 cells/min in TE-671 and K m = 111.7 µm, V max = 180.6 pmol/10 6 cells/min in Daoy. Melphalan transport was inhibited by both dl-α-2-aminobicyclo[2.2.1]heptane-2-carboxylic acid and sodium ion depletion in TE-671 and Daoy cells in vitro , indicating that both systems of amino acid transport are functional in these medulloblastoma lines. In vivo s.c. xenograft glutathione values were lower (7.79 nmol/mg protein) in TE-671 than in Daoy (13.68 nmol/mg protein). The mean plasma concentration in mice given a 10% lethal dose (71.3 mg/m 2 ) of melphalan i.p. was 50.3 µm at 10 min, with the half-life of 29.9 min. At this dose, s.c. xenograft levels were 2- to 3-fold higher in TE-671 than in Daoy tumors for the 3-h period measured. These studies demonstrate transport parameters confirming facilitated transport of melphalan in human medulloblastoma, a mean murine plasma melphalan concentration (following treatment with melphalan) above the in vitro drug dose at which there is a 90% reduction in the number of colonies in comparison to controls for TE-671 and Daoy for 2 h, and glutathione and glutathione- S -transferase levels in the same range previously reported in other melphalan-sensitive and melphalan-resistant human tumors. Future work with spontaneous and acquired melphalan-resistant human medulloblastoma cell lines and xenografts will define the role of these mechanisms in mediating drug resistance.
NMR Studies of Zinc, Copper, and Iron Binding to Histidine, the Principal Metal Ion Complexing Site of Amyloid-β Peptide

Amyloid-beta (Abeta), the major component of senile plaques in Alzheimer's disease, is known to complex transition metal ions mainly through histidine residues. In this study, using 1H NMR titration experiments, we show that histidine binds strongly to Zn(II), Cu(II), and Fe(III) ions at a biologically relevant pH (pH 7.4), with a stoichiometry of Zn(II): histidine binding of 1:2. The observed deshielding of the chemical shifts and relative line broadening indicate that Fenton-active Cu(II) and Fe(III) bind to histidine relatively more efficiently as compared to Zn(II). Parallel studies showed that glutamic acid and aspartic acid are relatively inefficient in metal ion binding. From these studies, we suggest that Abeta-chelated Zn(II) is readily displaced by Cu(II) and Fe(III) ions and leads to a propagation of oxidative stress.
Progress in a replicated selection for elevated blood ethanol concentrations in HDID mice.

Drinking in the dark (DID) is a limited access ethanol-drinking phenotype in mice. High Drinking in the Dark (HDID-1) mice have been bred for 27 selected generations (S27) for elevated blood ethanol concentrations (BECs) after a 4-h period of access to 20% ethanol. A second replicate line (HDID-2) was started later from the same founder population and is currently in S20. An initial report of response to selection in HDID-1 was published after S11. This article reports genetic and behavioral characteristics of both lines in comparison with the HS controls. Heritability is low in both replicates (h(2) = 0.09) but the lines have shown 4-5 fold increases in BEC since S0; 80% of HDID-1 and 60% of HDID-2 mice reach BECs greater than 1.0 mg/ml. Several hours after a DID test, HDID mice show mild signs of withdrawal. Although not considered during selection, intake of ethanol (g/kg) during the DID test increased by approximately 80% in HDID-1 and 60% in HDID-2. Common genetic influences were more important than environmental influences in determining the similarity between BEC and intake for HDID mice. Analysis of the partitioning of intake showed that 60% of intake is concentrated in the last 2 h of the 4 h session. However, this has not changed during selection. Hourly BECs during the DID test reach peak levels after 3 or 4 h of drinking. HDID mice do not differ from HS mice in their rate of elimination of an acute dose of alcohol.
Messungen an Lichtbogengeneratoren

In der Anordnung Abb. 151 auf Seite 189 wird eine Geislersche Rohre langs eines Radius einer schwarzen Scheibe angebracht und durch Vermittlung von Schleifringkontakten von dem Lichtbogenkreise erregt.
Use of the Newton-Raphson iteration to eliminate low frequency dipoles

Amplifiers with closely-spaced low-frequency pole-zero pairs (dipoles) are normally avoided for applications that require fast settling because they have slow-settling components in the transient response. In this work, an algorithm that involves a Newton-Raphson iteration is utilized to tune an amplifier with multiple low-frequency dipoles and facilitate pole-zero cancellation. The tuned structure is more suitable for fast settling applications.
Ontology-extended component-based workflows: a framework for constructing complex workflows from semantically heterogeneous software components

Virtually all areas of human endeavor involve workflows – that is, coordinated execution of multiple tasks. In practice, this requires the assembly of complex workflows from semantically heterogeneous components. In this paper, we develop ontology-extended workflow components and semantically consistent methods for assembling such components into complex ontology-extended component-based workflows. The result is a sound theoretical framework for assembly of semantically well-formed workflows from semantically heterogeneous components.
Bid-deficient mice are resistant to Fas-induced hepatocellular apoptosis

The protein Bid is a participant in the pathway that leads to cell death (apoptosis), mediating the release of cytochrome c from mitochondria in response to signals from 'death' receptors known as TNFR1/Fas on the cell surface. It is a member of the proapoptotic Bcd-2 family and is activated as a result of its cleavage by caspase 8, one of a family of proteolytic cell-death proteins. To investigate the role of Bid in vivo, we have generated mice deficient for Bid. We find that when these mice are injected with an antibody directed against Fas, they nearly all survive, whereas wild-type mice die from hepatocellular apoptosis and haemorrhagic necrosis. About half of the Bid-deficient animals had no apparent liver injury and showed no evidence of activation of the effector caspases 3 and 7, although the initiator caspase 8 had been activated. Other Bid-deficient mice survived with only moderate damage: all three caspases (8 and 37) were activated but their cell nuclei were intact and no mitochondrial cytochrome c was released. We also investigated the effects of Bid deficiency in cultured cells treated with anti-Fas antibody (hepatocytes and thymocytes) or with TNFalpha. (fibroblasts). In these Bid-/- cells, mitochondrial dysfunction was delayed, cytochrome c was not released, effector caspase activity was reduced and the cleavage of apoptosis substrates was altered. This loss-of-function model indicates that Bid is a critical substrate in vivo for signalling by death-receptor agonists, which mediates a mitochondrial amplification loop that is essential for the apoptosis of selected cells.
Water Resources Implications of Global Warming: A U.S. Regional Perspective

The implications of global warming for the performance of six U.S. water resource systems are evaluated. The six case study sites represent a range of geographic and hydrologic, as well as institutional and social settings. Large, multi-reservoir systems (Columbia River, Missouri River, Apalachicola-Chatahoochee-Flint (ACF) Rivers), small, one or two reservoir systems (Tacoma and Boston) and medium size systems (Savannah River) are represented. The river basins range from mountainous to low relief and semi-humid to semi-arid, and the system operational purposes range from predominantly municipal to broadly multi-purpose. The studies inferred, using a chain of climate downscaling, hydrologic and water resources systems models, the sensitivity of six water resources systems to changes in precipitation, temperature and solar radiation. The climate change scenarios used in this study are based on results from transient climate change experiments performed with coupled ocean-atmosphere General Circulation Models (GCMs) for the 1995 Intergovernmental Panel on Climate Change (IPCC) assessment. An earlier doubled-CO2 scenario from one of the GCMs was also used in the evaluation. The GCM scenarios were transferred to the local level using a simple downscaling approach that scales local weather variables by fixed monthly ratios (for precipitation) and fixed monthly shifts (for temperature). For those river basins where snow plays an important role in the current climate hydrology (Tacoma, Columbia, Missouri and, to a lesser extent, Boston) changes in temperature result in important changes in seasonal streamflow hydrographs. In these systems, spring snowmelt peaks are reduced and winter flows increase, on average. Changes in precipitation are generally reflected in the annual total runoff volumes more than in the seasonal shape of the hydrographs. In the Savannah and ACF systems, where snow plays a minor hydrological role, changes in hydrological response are linked more directly to temperature and precipitation changes. Effects on system performance varied from system to system, from GCM to GCM, and for each system operating objective (such as hydropower production, municipal and industrial supply, flood control, recreation, navigation and instream flow protection). Effects were generally smaller for the transient scenarios than for the doubled CO2 scenario. In terms of streamflow, one of the transient scenarios tended to have increases at most sites, while another tended to have decreases at most sites. The third showed no general consistency over the six sites. Generally, the water resource system performance effects were determined by the hydrologic changes and the amount of buffering provided by the system's storage capacity. The effects of demand growth and other plausible future operational considerations were evaluated as well. For most sites, the effects of these non-climatic effects on future system performance would about equal or exceed the effects of climate change over system planning horizons.
Fatal Acute Lymphoblastic Leukemia in Mice Transgenic for B Cell-Restricted bcl-xL and c-myc

Expression of the c-myc gene is frequently dysregulated in malignant tumors and translocations of c-myc into the Ig H chain locus are associated with Burkitt's-type lymphoma. There is indirect evidence that bcl-x, an anti-apoptotic member of the bcl-2 gene family, may also contribute to a variety of B lymphoid tumors. In this study, we show that mice transgenic for both B cell-restricted c-myc and bcl-x(L) developed aggressive, acute leukemias expressing early B lineage and stem cell surface markers. Of interest, the tumor cells proliferated and differentiated down the B cell developmental pathway following in vitro treatment with IL-7. Analysis of sorted leukemic cells from spleen indicated constitutive expression of sterile micro and kappa transcripts in combination with evidence for D-J(H) DNA rearrangements. Several B cell-specific genes were either not expressed or were expressed at low levels in primary tumor cells and were induced following culture with IL-7. IL-7 also increased V-Jkappa and V-DJ(H) rearrangements. These data demonstrate oncogenic synergy between c-myc and bcl-x(L) in a new mouse model for acute lymphoblastic leukemia. Tumors in these animals target an early stage in B cell development characterized by the expression of both B lineage and stem cell genes.
PROSTATE CANCER : FLOW CYTOMETRIC METHODS FOR DETECTION OF BONE MARROW MICROMETASTASES

Up to 60% of patients with clinically localized prostate cancer will relapse despite potentially curative local treatment. Current staging tests have been limited in adequately identifying individual patients who are at a high risk for future relapse. Detection of bone marrow micrometastases may identify individuals destined to develop clinically detectable systemic metastases. Although immunohistochemistry and molecular approaches are being investigated, the most ideal test(s) are yet to be determined. In this report we describe methods for specific detection and isolation of prostate cancer micrometastases by multi-parameter rare event flow cytometric analysis. A model was developed and validated using three human prostate cancer cell lines, healthy donor marrow, dual marker labeling for cytokeratin (epithelial-specific marker) and CD45 (bone marrow-specific marker). The detection sensitivity of this model was at the level of one prostate cancer cell in 100,000 nucleated bone marrow cells. As a part of an ongoing clinical study, bone marrow aspirates from 15 patients with newly diagnosed prostate cancer have been analyzed. Six patients were found to have cytokeratin positive/CD45 negative cells in their bone marrow aspirates. We conclude that flow cytometric rare event analysis provides a sensitive and specific assay for detection of bone marrow micrometastases in patients with clinically localized prostate cancer.
Mast cell heterogeneity in dog skin

The degree of metachromasia of mast cell granules is known to vary with the type of tissue fixation and among different tissues and species. The present study sought to determine whether mast cells in dog skin are heterogeneous with respect to fixation and staining properties. We performed skin biopsies in six anesthetized, atopic dogs and one mongrel dog. One biopsy was fixed in formalin and a second, from a parallel abdominal site, was fixed in basic lead acetate (Mota's solution). Adjacent sections from each biopsy were stained with alcian blue (1%, pH 0.5) or for chloroacetate esterase activity. In alcian blue-stained sections, one-third fewer mast cells were detected in skin fixed in formalin (1,836 +/- 454 mast cells/mm3, mean +/- SEM) than in skin fixed in basic lead acetate (2,684 +/- 527 mast cells/mm3) (P less than 0.05). The chloroacetate esterase reaction detected the larger number of mast cells regardless of the fixative used. We conclude that mast cell heterogeneity, as demonstrated by metachromatic staining following different types of tissue fixation, exists in dog skin. "Typical" mast cells stain with alcian blue regardless of fixation; however, "atypical" mast cells exhibit metachromasia only after fixation in basic lead acetate. Both the typical and atypical types of mast cells have chloroacetate esterase activity.
FATIGUE CRACK TIP MECHANICS OF A POWDER METALLURGY ALUMINUM ALLOY IN VACUUM AND HUMID AIR

— Fatigue crack tip opening displacements and strains in the material very close to the crack tip have been determined from measured displacements for cracks grown in both vacuum and humid air environments. The environment alters both the relations between crack tip opening displacement and crack tip strain, and the effect of cyclic stress intensity on these factors. Results of dynamic observation of intermittent crack growth are correlated with fractographic evidence. The relationships between crack tip parameters are used in a previously developed mathematical model. The effect of wet air on fatigue crack growth is found to be a reduction in crack tip plasticity.
LIGHT-DEFLECTION EFFECTS IN THE INTERFEROMETRY OF ONE-DIMENSIONAL REFRACTIVE-INDEX FIELDS.

Distortions in interferograms of refractive-index fields due to deviations from straight-line propagation have been analyzed numerically. Quantitative refractive-index profiles can often not be derived in a simple way from interferograms. The choice of the plane of focus and the alignment of the object with respect to the light direction are found to affect the distortions greatly. Results for typical examples of refractive-index fields encountered in different electrochemical systems are given.
Microbiological properties of pork cheek meat as affected by acetic acid and temperature.

Our objective was to determine the effect of acetic acid (AA) and temperature in inhibiting Salmonella typhimurium, aerobic plate counts (APCs) and total coliforms on pork cheek meat. Compared with initial APCs of control cheeks, a reduction in log10 CFU/cm2 APC by more than 78.6% was found in all samples that were treated with 20 and 40° acetic acid (P < 0.05). Additionally, total coliforms for acidtreated cheeks were lower for both AA treatments (P < 0.05). Cheeks (n = 10/treatment) were also sprayed in a commercial pork slaughter facility carcass wash with 2% AA (25°) and compared to control (non-treated) cheeks. The incidence of Salmonella decreased by 67% for acid-treated cheeks (P < 0.05). A significant decrease in APCs and coliforms occurred for the acid-treated cheeks (P < 0.05).
Effects of tungsten oxide addition on the electrochemical performance of nanoscale tantalum oxide-based electrocatalysts for proton exchange membrane (PEM) fuel cells

Abstract In the present study, the properties of non-platinum based nanoscale tantalum oxide/tungsten oxide-carbon composite catalysts were investigated for potential use in catalyzing the oxygen reduction reaction on the cathode side of a PEM fuel cell. All of the tantalum oxide-based catalysts exhibit high ORR on-set potentials, comparable with the commercial Pt/C catalyst even though oxygen reduction current was limited. The tungsten oxide doping to tantalum oxide improved catalytic performance. The performance enhancement was due to a decrease in resistance polarization with increasing tungsten content mainly due to the decrease in resistance polarization. XPS results indicate that the oxidation state of tungsten is +6 and that of the tantalum is +5, suggesting that excess oxygen is generated in the resulting oxide structure. This compositional effect seems to reduce resistance polarization by altering the surface chemistry of the tantalum oxide and enhancing the reaction steps such as surface diffusion. Maximum performance was achieved with a catalyst containing 32 mol% of tungsten oxide, reaching a mass specific current density of ∼7% that of the commercial Pt/C catalyst at 0.6 V vs. NHE and ∼35% at 0.2 V vs. NHE. In term of area-specific current density, five-fold increase in loading of the doped catalyst leads to a 4–4.5 fold increase in area specific current density at 0.6 V vs. NHE, reaching 66% that of the Pt/C catalyst at 100 rpm and 35% at 2400 rpm.
Marfan's syndrome with massive calcification of the mitral annulus at age twenty-six.

Abstract A 26 year old white man with a typical Marfan's syndrome and massive calcification of the mitral annulus unaccompanied by obvious involvement of the mitral leaflets is presented. He underwent surgical correction of an ascending aortic aneurysm with a Teflon graft, and the replacement of an incompetent aortic valve with a No. 12 Starr-Edwards prosthesis. His postoperative course was uneventful. No murmurs were associated with the calcified annulus. It is not clear whether the calcified annulus can be included as a connective tissue defect characteristic of Marfan's syndrome or whether it occurred as an isolated finding typical of a noninflammatory degenerative aging process.
Visual illusions in neural networks: Line neutralization, tilt after effect, and angle expansion

Abstract Certain visual illusions occur in neural networks that are capable of storing partially contrasted enhanced spatial patterns in short term memory (STM), and whose feature detectors are interconnected by nontrivial generalization gradients. These include neutralization, or adaptation, of nearly vertical or horizontal lines, tilt after-effect of successively viewed lines, and perceived angle expansion. Neutralization can be achieved by networks whose vertical and horizontal representations have higher saturation levels, broader tuning curves, or stronger input pathways. Tilt after-effect and angle expansion can be achieved by shunting lateral inhibition that causes an outward peak shift in the orientationally-coded STM pattern. The amount of outward peak shift is also dependent on the size of the potassium equilibrium point. Differences between the directions of tilt aftereffect (successive contrast) and angle expansion (simultaneous contrast) are ascribed to a normalization of total activity in the STM buffer whereby present stimuli and representations in STM of past stimuli interact to form a consistent action-oriented consensus.
Allelotype of colorectal carcinomas

To examine the extent and variation of allelic loss in a common adult tumor, polymorphic DNA markers were studied from every nonacrocentric autosomal arm in 56 paired colorectal carcinoma and adjacent normal colonic mucosa specimens. This analysis was termed an allelotype, in analogy with a karyotype. Three major conclusions were drawn from this analysis: (i) Allelic deletions were remarkably common; one of the alleles of each polymorphic marker tested was lost in at least some tumors, and some tumors lost more than half of their parental alleles. (ii) In addition to allelic deletions, new DNA fragments not present in normal tissue were identified in five carcinomas; these new fragments contained repeated sequences of the variable number of tandem repeat type. (iii) Patients with more than the median percentage of allelic deletions had a considerably worse prognosis than did the other patients, although the size and stage of the primary tumors were very similar in the two groups. In addition to its implications concerning the genetic events underlying tumorigenesis, tumor allelotype may provide a molecular tool for improved estimation of prognosis in patients with colorectal cancer.
Research methods in language learning

Research Methods in Language Learning helps readers understand and critique research. This book is intended to help readers understand and critique research in language learning. It presents a balanced and objective view of a range of methods - including formal experiments, introspective methods, interaction and transcript analysis, ethnography, and case studies. The book is highly accessible and does not assume specialist or technical knowledge. This volume will be of interest to students of applied linguistics and educational researchers, in addition to classroom teachers and teachers-in-training. Throughout the book, theoretical issues are drawn from published studies and reports. The book emphasizes the professional and practical value of reading published research.
Observations of prolonged use of oral emcyt in prostatic cancer patients

Abstract Experiences resulting from Emcyt therapy in patients with both newly diagnosed and hormone refractory advanced prostate cancer, as well as an adjuvant to surgery or radiotherapy in earlier disease are presented. Data from trials of the National Prostatic Cancer Project (NPCP) and a series from Roswell Park Memorial Institute (RPMI) were divided into short-term (up to twenty weeks and up to fifty-two weeks in adjuvant trials) and long-term therapy. Baseline disease and patient characteristics and toxicities encountered in these two treatment-duration groups were compared. Patients in a more favorable health or disease status and/or responded to therapy were more frequently in the long-term group. Patients in the long-term group tended to have higher over-all incidences of toxicity; and although many had occurrences begin as early as those in the short-term group, they were able to tolerate the therapy for relatively long periods. The agent is thus both effective and can be given safely for long periods of time.
Our Cosmic Origins: From the Big Bang to the Emergence of Life and Intelligence

Our Cosmic Origins, first published in 1998, traces the remarkable story of the emergence of life and intelligence right through the complex evolutionary history of the Universe. Armand Delsemme weaves together a rich tapestry of science, bringing together cosmology, astronomy, geology, biochemistry and biology in this wide-ranging book. In following the complex, chronological story, we discover how the first elements formed in the early Universe, how stars and planets were born, how the first bacteria evolved towards a plethora of plants and animals, and how the coupling of the eye and brain led to the development of self-awareness and, ultimately, intelligence. Professor Delsemme concludes with the tantalising suggestion that the existence of alien life and intelligence is likely, and examines our chances of contacting it. This provocative book provides the general reader with an accessible and wide-ranging account of how life evolved on Earth and how likely it is to exist elsewhere in the Universe.
Kinetic theory of gelation: Numerical simulation and comparison with analytical results

Abstract Aerosol evolution with an apparent gelation transition (formation of an infinite size particle) is studied numerically. It is found that the numerical results agree well with the analytical results in both the pre- and the postgel transition periods. The reasons for the apparent success of the numerical technique, despite the lack of provision for gel formation, are discussed.
Effect of storage temperature on crystal formation rate and growth rate of calcium lactate crystals on smoked Cheddar cheeses.

Abstract Previous studies have shown that storage temperature influences the formation of calcium lactate crystals on vacuum-packaged Cheddar cheese surfaces. However, the mechanisms by which crystallization is modulated by storage temperature are not completely understood. The objectives of this study were to evaluate the effect of storage temperature on smoked Cheddar cheese surfaces for (1) the number of discrete visible crystals formed per unit of cheese surface area; (2) growth rate and shape of discrete crystals (as measured by area and circularity); (3) percentage of total cheese surface area occupied by crystals. Three vacuum-packaged, random weight (~300g) retail samples of naturally smoked Cheddar cheese, produced from the same vat of cheese, were obtained from a retail source. The samples were cut parallel to the longitudinal axis at a depth of 10mm from the 2 surfaces to give six 10-mm-thick slabs, 4 of which were randomly assigned to 4 different storage temperature treatments: 1, 5, 10°C, and weekly cycling between 1 and 10°C. Samples were stored for 30wk. Following the onset of visible surface crystals, digital photographs of surfaces were taken every other week and evaluated by image analysis for number of discrete crystal regions and total surface area occupied by crystals. Specific discrete crystals were chosen and evaluated biweekly for radius, area, and circularity. The entire experiment was conducted in triplicate. The effects of cheese surface, storage temperature, and storage time on crystal number and total crystal area were evaluated by ANOVA, according to a repeated-measures design. The number of discrete crystal regions increased significantly during storage but at different rates for different temperature treatments. Total crystal area also increased significantly during storage, at rates that varied with temperature treatment. Storage temperature did not appear to have a major effect on the growth rates and shapes of the individual crystals that were chosen for analysis. The data indicated that the effect of storage temperature was complex, likely involving solubility changes, the formation of d(−) and l(+) lactic acid, and the occurrence of syneresis, which in turn affected the number of crystal formation sites and total crystal area on the cheese surface.
In vitro fluid dynamics of the St Jude valve prosthesis in steady and pulsatile flow.

The flow downstream from the St Jude valve prosthesis is studied in vitro in both steady and pulsatile flow. Conditions for the pulsatile flow studies approximate the in vivo resting state. Laser-Doppler anemometry (LDA) is used to measure instantaneous point velocities at numerous locations pre-selected to conform to a systematic, flow-mapping measurement methodology. Overall, the results for the St Jude valve indicate a relatively undisturbed forward flow through the prosthesis. The acceleration ratios, defined as the maximum mean axial velocity for the St Jude valve divided by that for no valve obstructing the flow, are small, being 1.2 and 1.4 for steady and pulsatile flow, respectively. Both the secondary flow structure and the flow disturbance produced by this valve are minimal. Maximum mean velocities in the radial and azimuthal directions are only about 5-10 per cent of that in the axial direction. There is. however, notable evidence of flow wakes generated by the valve’s opened leaflets. Velocity defects caused by these wakes are found to be as much as 50 per cent. The bulk flow through this valve is in this sense quite unlike that reported by others for the natural aortic valve studied in vitro.
Reflection from a periodically perforated plane using a subsectional current approximation

The scattering from a zero thickness plane having finite sheet resistance and perforated periodically with apertures is calculated for arbitrary plane wave illumination. The surface current density within the unit cell is approximated by a finite number of current elements having rooftop spatial dependence. The transverse electric field is expressed in terms of the current, and the electric field boundary condition is satisfied in an integral sense over the conductor, generating a finite dimension matrix equation whose solution is the current density. Since the conductor shape is defined through the locations of subsectional current elements, arbitrary shaped apertures can be handled. The reflection coefficient and current distribution are calculated for square apertures in both perfectly conducting and resistive sheets, and for cross-shaped apertures. Finite resistivity is shown to cause the magnitude of the transverse magnetic (TM) reflection coefficient to decrease more rapidly and its phase to decrease less rapidly, as the angle of incidence approaches glancing. Through detailed plots of the current density, the current crowding around the apertures is made clearly evident.
The SLAC Mark II Upgrade Drift Chamber Front End Electronics

The SLAC Mark II detector is being improved by the addition of a new main drift chamber and associated electronics to prepare it for operation as the first detector at SLC. Presented here are the initial signal processing electronics, the preamplifiers, amplifiers and discriminators for the 5832 sense wires, which are located on the detector itself. The performance of the detector is established almost entirely by the drift chamber and this electronics.
Impairment in family caregiving: a biological perspective

This paper focuses on patterns in the care of children and dependent elders, providing a new perspective to understand impairment in family caregiving. One concept from evolutionary theory, kin selection, has promise for providing a broad framework for understanding patterns of family caregiving. We present an application of the evolutionary model to the issue of family care decisions in the face of potential conflicts of interest. Specifically, a mathematical biological model, which was developed to understand self-preservation motivation, is applied to the kin investment decision. Using the evolutionary model, the main predictors of investment would be relatedness, reproductive value, and expected benefit from the care invested. The biological model accounts very simply for decisions between caring for an elder parent or caring for your own child, and for decisions by two daughters (one with a child, one childless) to care for an elder parent. The factors that form the basis of an evolutionary model (relatedness, reproductive value, and benefit from care) have not been widely investigated in family care studies, however, and this absence reveals new directions for future research.
Tectonic forcing of late Cenozoic climate

Global cooling in the Cenozoic, which led to the growth of large continental ice sheets in both hemispheres, may have been caused by the uplift of the Tibetan plateau and the positive feedbacks initiated by this event. In particular, tectonically driven increases in chemical weathering may have resulted in a decrease of atmospheric C02 concentration over the past 40 Myr.
Why Cold, Dense Quark Matter could be “Quarkyonic”

I give a pedagogical review of how cold, dense quark matter can be viewed as “Quarkyonic”, at least when the number of colors is large (and the number of flavors, small). This provides a different way of viewing the excitation spectrum of dense quarks. While the free energy is, up to power law corrections, close to that of free quarks, the excitation spectrum is very different, dominated by confined, collective excitations near the Fermi surface.
Lack of Efficacy of Angiotensin-Converting Enzyme Inhibitors in Reducing Interdialytic Weight Gain

Angiotensin-converting enzyme inhibitors (ACEIs) have been suggested to reduce interdialytic fluid weight gain, presumably via suppression of the dipsogenic angiotensin II. We retrospectively studied 25 (76% black) chronic hemodialysis patients who received ACEIs for blood pressure control. The mean arterial blood pressure decreased from 115.4 +/- 10.4 mm Hg to 112.7 +/- 9.0 mm Hg (mean +/- SD; P = NS) and there was no change in the interdialytic weight gain (3.74 +/- 1.5 kg v 3.72 +/- 1.5 kg; P = NS). Only 10 (40%) patients had some reduction in their interdialytic weight gain; in four of them the reduction was more than 20% of the pre-ACEI weight gain. When nine patients who had no decline in blood pressure were excluded due to possible noncompliance, the mean arterial blood pressure in the remaining 16 patients (75% black) declined from 119.3 +/- 9.9 mm Hg to 111.6 +/- 9.9 mm Hg (P < 0.0001), but there was no change in the interdialytic fluid weight gain (3.7 +/- 1.4 kg v 3.8 +/- 1.4 kg; P = NS). There was no correlation between age, race, etiology of renal failure, or blood pressure response and change in the interdialytic weight gain after ACEI treatment. Our results do not support the previous report that ACEIs significantly decrease the interdialytic weight gain in chronic hemodialysis patients. The multifactorial nature of excessive fluid intake in the hemodialysis patients and the differences in patient population and study design may account for this discrepancy.
Pattern recognition in nucleic acid sequences. I. A general method for finding local homologies and symmetries

We present an algorithm--a generalization of the Needleman-Wunsch-Sellers algorithm--which finds within longer sequences all subsequences that resemble one another locally. The probability that so close a resemblance would occur by chance alone is calculated and used to classify these local homologies according to statistical significance. Repeats and inverted repeats may also be found. Results for both random and biological nucleic acid sequences are presented. Fourteen complete genomes are analyzed for dyad symmetries.
A Second-Order Moments Method for Uncertainty Analysis

The system moments approach is extended to combine random variables for large systems. A computer code, COSMOS, has been developed to propagate uncertainties for systems which contain up to 100 components. Extension of the method to very large systems is possible by modular evaluation. An example illustrates the method for evaluating the distribution of the top event unavailability for a fault tree. Advantages of the method include small required execution times and the avoidance of random number generation. Application of the method to Boolean sum-of-products representations of fault trees provides results which are consistent with the Monte Carlo method since, for this special case, higher order derivatives are zero. Serious limitations to the method include: unquantifiable accuracy for functions whose higher derivatives are non-zero (as is often the case), inability to model s-dependent failures as the moments equations assume s-independence, and difficulty in improving the accuracy of the method (compared with Monte Carlo evaluation which may be arbitrarily improved).
Apurinic/Apyrimidinic Endonuclease/Redox Effector Factor-1(APE/Ref-1): A Unique Target for the Prevention and Treatment of Human Melanoma

Management of melanoma is a growing and challenging public health issue requiring novel and multidisciplinary approaches to achieve more efficient prevention and therapeutic benefits. The aim of this article is to show the critical role of APE/Ref-1 on melanomagenesis and progression. APE/Ref-1 serves as a redox-sensitive node of convergence of various signals as well as a DNA-repair enzyme, and its activation protects melanocytes and melanoma cells from chronic oxidative stress and promotes cell survival via mediation of downstream pathways. APE/Ref-1 is a strong candidate as a potential drug-treatable target for the prevention and treatment of human melanoma. Lead compounds exhibiting inhibitory effects on APE/Ref-1 are also reviewed. We anticipate potential clinical benefit in the future through inhibition of APE/Ref-1 and/or Ref-1-mediated signaling.
Stimulation of lens cell differentiation by gap junction protein connexin 45.6.

PURPOSE The present study was undertaken to explore the roles gap junctions play in lens epithelial cell differentiation. METHODS Recombinant retroviruses expressing three chick lens connexins (Cx)-Cx43, Cx45.6, and Cx56-were prepared and used to infect isolated chick lens primary cultures. The expression and distribution of proteins was determined using immunoblots and confocal immunofluorescence microscopy. Intercellular couplings were assessed by single cell microinjection and scrape-loading dye transfer, and cell proliferation was evaluated by [(3)H]thymidine labeling. RESULTS Of the three lens connexins, only the cultures overexpressing exogenous Cx45.6 displayed the advancement of lens epithelial-fiber cell differentiation. The lentoids, a unique morphologic structure that is an indicative of lens fiber formation, were formed earlier in Cx45.6 overexpressed cultures; however, the rate of lens cell proliferation was not affected. The expression of the lens differentiation marker proteins, major intrinsic protein (MIP) and delta-crystallin, was also increased in Cx45.6-overexpressing cells. The cells overexpressing Cx45.6 displayed similar levels of intercellular couplings as did the controls. Moreover, exogenously expressed connexins were mostly colocalized with their endogenous counterparts and the overexpression of Cx45.6 had no impact on the expression of endogenous Cx43 and Cx56. CONCLUSIONS These results suggest that Cx45.6 plays an important role in stimulating lens cell differentiation and fiber formation, which is different from the other lens connexins, Cx43 and Cx56. This stimulatory effect is independent of gap junction-mediated intercellular communication and lens cell proliferation.
Relation of Kidney Function and Albuminuria With Atrial Fibrillation (from the Heart and Soul Study)

Atrial fibrillation (AF) is common in end-stage renal disease, but the relation between more modest decrements in kidney function or albuminuria with AF is uncertain. Among 956 outpatients with coronary artery disease, kidney function was assessed using 3 methods (cystatin C–based estimated glomerular filtration rate [eGFR cys ], creatinine-based eGFR [eGFR Cr ], and the urinary albumin/creatinine ratio [ACR]) and prevalent AF using surface electrocardiography. Multivariate logistic regression was used to evaluated the association of each measure of kidney function with AF. The mean eGFR cys was 71 ± 23 ml/min/1.73 m 2 , and the median ACR was 10 mg/g (interquartile range 6 to 19). Forty subjects (4%) had prevalent AF. Compared to participants with eGFR cys in the highest tertile (eGFR cys >79), those with eGFR cys in the lowest tertile (eGFR cys Cr but did not reach statistical significance (OR 1.59, 95% CI 0.57 to 4.40). Participants with ACRs in the highest tertile (ACR >15 mg/g) had more than fourfold greater odds of AF compared to participants in the lowest ACR tertile (ACR cys (OR 4.36, 95% CI 1.45 to 13.05) or eGFR Cr (OR 4.61, 95% CI 1.56 to 13.66). In conclusion, among outpatients with coronary artery disease, lower eGFR cys and higher ACR were associated with prevalent AF, independent of each other.
Excited states of a dilute Bose-Einstein condensate in a harmonic trap

The low-lying hydrodynamic normal modes of a dilute Bose-Einstein gas in an isotropic harmonic trap determine the corresponding Bogoliubov amplitudes. In the Thomas-Fermi limit, these modes have large low-temperature occupation numbers and they permit an explicit construction of the dynamic structure function $S(\mathbf{q},\ensuremath{\omega})$. The total noncondensate number ${N}^{\ensuremath{'}}(0)$ at zero temperature increases like ${R}^{6}$, where $R$ is the condensate radius measured in units of the oscillator length. The lowest dipole modes are constructed explicitly in the Bogoliubov approximation.
Equilibrium and Dynamics at Microparticle/Liquid Interfaces

Second harmonic studies of:time dependent imaging of live neuron membrane potential, molecular ion transport across a liposome bilayer in real time, and ultrafast interfacial electron transfer, will be discussed.
Monoclonal antibodies and reagents for botulinum research

Botulinum neurotoxin (BoNT) is produced by Clostridium botulinum as a dichain protein of ~ 150 kDa that blocks acetylcholine release resulting in muscular paralysis. Diagnosis of BoNT often relies on the mouse bioassay that has a detection limit of 10–20 pg/mL and can take up to four days to complete. Rapid in vitro methods for toxin detection are needed and to date, most rely on either immunoassay or endopeptidase activity. In the latter, many also use specific antibodies to concentrate the toxin. We have developed panels of monoclonal antibodies (mAbs) to purified toxin, serotypes A, B and E, as well as mAbs to the non-toxic associated proteins. Application of these mAbs in sandwich ELISAs and assay performance in milk and other foods is discussed. The assays described here are able to detect toxin in a few hours, at levels lower than the mouse bioassay.