cssi/SciSciGPT-SciSciNet huggingface dataset:
Statistical significance for hierarchical clustering in genetic association and microarray expression studies.

Background With the increasing amount of data generated in molecular genetics laboratories, it is often difficult to make sense of results because of the vast number of different outcomes or variables studied. Examples include expression levels for large numbers of genes and haplotypes at large numbers of loci. It is then natural to group observations into smaller numbers of classes that allow for an easier overview and interpretation of the data. This grouping is often carried out in multiple steps with the aid of hierarchical cluster analysis, each step leading to a smaller number of classes by combining similar observations or classes. At each step, either implicitly or explicitly, researchers tend to interpret results and eventually focus on that set of classes providing the "best" (most significant) result. While this approach makes sense, the overall statistical significance of the experiment must include the clustering process, which modifies the grouping structure of the data and often removes variation.
Estimation of a model of cumulative pregnancy following infertility therapy

Life-table estimation of cumulative pregnancy curves following infertility therapy is an important tool for evaluating the effectiveness of therapy. However, a satisfactory method for summarizing an entire cumulative pregnancy curve in terms of a small number of clinically useful parameters is currently lacking. In the present paper, a model is developed in which cumulative pregnancy is expressed as a function of two parameters: the cure rate and the instantaneous probability of pregnancy among those cured. This model is applied to data on endometriosis and polycystic ovary syndrome, and the resulting predicted cumulative pregnancy curves almost perfectly follow the observed data.
A New Paradigm for Biochemical Energy Coupling SALMONELLA TYPHIMURIUM NICOTINATE PHOSPHORIBOSYLTRANSFERASE

The pncB gene of Salmonella typhimurium was used to develop an overexpression system for nicotinate phosphoribosyltransferase (NAPRTase, EC 2.4.2.11), which forms nicotinate mononucleotide (NAMN) and PPi from nicotinate and alpha-D-5-phosphoribosyl-1-pyrophosphate (PRPP). NAPRTase hydrolyzes ATP in 1:1 molar stoichiometry to NAMN synthesis. Hydrolysis of ATP alters the ratio of products/substrates for the reaction nicotinate + PRPP NAMN + PPi from its equilibrium value of 0.67 to a steady-state value of 1100. The energy for the maintenance of this ratio must come from ATP hydrolysis. However, in contrast to other ATP-utilizing enzymes, when all ATP is hydrolyzed the unfavorable product/substrate ratio collapses. ATP/ADP exchange results suggest that the overall reaction involves a phosphoenzyme (E-P) arising from E.ATP. Km values for nicotinate and PRPP each decreased by 200-fold when ATP was present to phosphorylate the enzyme. PPi stimulated the ATPase activity of the enzyme to Vmax values, suggesting that PPi formation during catalysis provides a trigger for cleavage of the putative E-P in the overall reaction and regenerates the low affinity form of the enzyme. A model is presented in which alternation of high and low affinity forms of NAPRTase provides a "steady-state" coupling between ATP hydrolysis and NAMN formation.
EXPERIMENTAL PRIMARY CUTANEOUS COCCIDIOIDOMYCOSIS IN THE MONKEY.

Converse, John L. (U.S. Army Biological Laboratories, Fort Detrick, Frederick, Md.), Steven P. Pakes, Ernest M. Snyder, and Merida W. Castleberry. Experimental primary cutaneous coccidioidomycosis in the monkey. J. Bacteriol. 87:81–85. 1964.—Primary cutaneous coccidioidomycosis was studied in the monkey (Macaca mulatta) to find a suitable strain of Coccidioides immitis for use as a viable vaccine. Intradermal inoculation (medial surface of the right forearm) produced more severe vaccination reactions (draining vaccination site and axillary lymph node hypertrophy) than did subcutaneous injection. A subcutaneous vaccine dose of 10 arthrospores resulted in less reaction than a 100-spore dose. Moreover, dissemination beyond the regional lymph nodes did not occur after injection of ten spores of even the most virulent strains of C. immitis. Two of the five strains tested (Silveira, M-11, D-76, Cash, and a colonial isolate from Cash designated CW1) exhibited very mild vaccination reactions and appeared to have been cleared from the tissues upon necropsy at 10 months postvaccination. These two strains (Cash and CW1) appear promising for further immunological studies with a viable vaccine.
Immune events associated with inflammatory bowel disease.

Immunologic abnormalities have been implicated in the etiology of inflammatory bowel disease (IBD). Defects of systemic immunity and of local (intestinal) immunity have been studied. The numbers of T and B lymphocytes and their characteristics seem to vary with the disease, but no cause-and-effect relationship has been established. The presence of anticolon antibodies in patients with ulcerative colitis suggests that these antibodies could be involved in IBD, but they have also been found in other conditions. In the peripheral blood, abnormalities of cell-mediated immunity are inconsistent and suggest that they are not fundamental defects of the disease. The hypothesis that the inflammatory process is a result of immune-mediated intestinal tissue damage is being extensively studied. The high familial incidence of the disease suggests a role of histocompatibility locus antigens, but no reproducible association can be established. In vivo and in vitro studies of mucosal mononuclear cells have revealed abnor...
Mineralocorticoid and glucocorticoid receptors in the amygdala regulate distinct responses to colorectal distension

Previously we found that exposure of the amygdala to elevated levels of corticosterone (CORT) induces anxiety-like behavior coupled to colonic hypersensitivity to distension, however, the specific corticoid receptor mediating the CORT responses remains controversial. In this study we investigated, through the use of selective antagonists, the relative role of amygdaloid mineralocorticoid (MR) versus glucocorticoid receptors (GR) in CORT-mediated spinal and cardiovascular pseudoaffective reflex responses to colorectal distension (CRD). Micropellets containing, CORT and a selective MR antagonist (spironolactone) or GR antagonist (mifepristone) were implanted stereotaxically onto the dorsal margin of the amygdala in rats. On day 7 post-implantation in response to graded CRD we measured: (i) changes in the electrical activity of dorsal horn neurons in the L6-S1 spinal cord and (ii) the cardiovascular depressor responses. Exposure of the amygdala to CORT-releasing micropellets increased the proportion of spinal neurons showing high-threshold and/or long-lasting responses and potentiated the magnitude of excitation. Elevated levels of amygdala CORT also increased the magnitude of the cardiovascular depressor response to CRD. MR but not GR antagonism prevented the increase in spinal cord neuronal excitation, whereas either the MR or GR antagonist decreased the magnitude of the depressor cardiovascular response to CRD. We conclude that MR in the amygdala trigger descending pathways facilitating viscero-nociceptive processing in the spinal cord, whereas MR and GR have a non-redundant role in CORT-induced potentiation of the autonomic pseudoaffective responses to colorectal stimuli.
Radiation-hardened microelectronics for space applications

Abstract Radiation-hardened technology for space applications will be evaluated in light of its survivability in the total-dose, cosmic-ray, and solar flare environments normally encountered in space. Several examples of technology development programs will be summarized, including Sandia programs over the last two decades. Techniques for optimizing the radiation hardnes of CMOS technologies for space will be discussed. For total-dose hardness, these techniques provide information about the number of radiation-induced defects and their microscopic nature, and are used to identify manufacturing processes that play an important role in the fabrication of radiation-hardened integrated circuits (ICs). For examples, the roles of high-temperature anneals, hydrogen and interfacial strain in the buildup of radiation-induced defects have received a great deal of attention, and many CMOS process flows have been designed to minimize hydrogen incorporation and reduce interfacial stress. Techniques for ensuring the tolerance of ICs to single-event phenomena (SEP) will be addressed, including the manufacture and control of high-resistivity polysilicon feedback resistors. Finally, some future trends in hardness assurance and testing that support more cost-effective qualification of ICs used in space will be covered. For total-dose, trends include wafer-level testing and X-ray irradiations; while for EP, trends include Cf-252 and laser testing
OBSERVATIONS ON THE EUGLENOID COLACIUM WITH SPECIAL REFERENCE TO THE FORMATION AND MORPHOLOGY OF ATTACHMENT MATERIAL1

SUMMARY Certain taxonomic features of Colacium Ehrb. are evaluated from field, clone, and literature studies. A main character, morphology of the attachment material, is shown to be partially nutritionally controlled: stalks and cushion holdfasts are produced in soil-water but rarely in plain Euglena medium; ferric and manganouns compounds influence the, formation of stalks in C. vesiculosum; single clones of C. vesiculosum produce holdfast characteristics of C. arbuscula, C. steinii, C. sideropus, and C. simplex when grown in soil-water medium. Stalk formation is rare in C. vesiculosum but common in C. mucronatum and Colacium sp. (from the rectum of damselflies). Some questionable negative observations, incompleteness of certain species descriptions, and overlapping of species characteristics lead us to believe that C. sequabile, C. stentorinum, C. calvum, C. multoculata, C. elongatum, C. ovale, C. arcuatum, C. cyclopicola, and C. pyrenophorum = C. vesiculosum. Our C. vesiculosum attached to Mougeotia and Volvox tertius, suggesting that the epiphytic species of Colacium, C. epiphyticum, and C. parasiticum need to be studied in clonal culture to determine if they have substrate specificity, and if they represent valid species. Recommendations are made for identifying and naming species.
Tumor Amylase: The Effect of Various Hormones and Chemical Agents

In the preceding paper (1), we described a method whereby the amylolytic activity of mouse sarcoma could be measured. It is the purpose of this paper to present the results of experiments performed upon mice in an attempt to alter the amylolytic activity of such tumors. This activity is expressed in terms of an α-value, the significance of which has been discussed in the previous paper. Possible Factors Affecting Amylolytic Activityof Sarcoma The α-value for amylase in tumors carried by inbred mice was fairly constant, the usual variation being between 9 and 13 per gram of tumor. Occasionally a single tumor with no obvious gross pathological difference from the others would be as low as 6 or as high as 15. The age of the tumor and the rapidity of its growth (the latter probably dependent to some degree on the size of the original implant) had some bearing on the glycogenolytic activity. In general, the older the tumor and the slower its growth, the higher was its α-value. The actual figures may be seen in the control groups presented in Tables I and II. In consequence of these variations, every experiment had its own controls, with mice of approximately the same age, kept under identical conditions, and with tumors of similar size which had been inoculated at the same time as those of the experimental animals. The tumors were all from eighteen to twenty-eight days old when used.
ELECTRON MICROSCOPE STUDIES OF CRYSTAL-COLLAGEN RELATIONSHIPS IN BONE : IV. THE OCCURRENCE OF CRYSTALS WITHIN COLLAGEN FIBRILS

Crystals are seen occasionally within the diameter of transversely sectioned collagen fibrils near the calcification front of newly formed bone.
Specificity in chaperonin-mediated protein folding.

CHAPERONINS are ubiquitous multisubunit toroidal complexes that aid protein folding in an ATP-dependent manner1–6. Current models of folding by the bacterial chaperonin GroEL depict its role as unfolding and releasing molecules that have misfolded, so that they can return to a potentially productive folding pathway in solution 7,8. Accordingly, a given target polypeptide might require several cycles of binding and ATP-driven release from different chaperonin complexes before reaching the native state. Surprisingly, cycling of a target protein does not guarantee its folding, and we report here that unfolded β-actin or α-tubulin both form tight complexes when presented to either GroEL or its mitochondria! homologue, and both undergo cycles of release and rebinding upon incubation with ATP, but no native protein is produced. We conclude that different chaperonins produce distinctive spectra of folding intermediates.
Beet western yellows virus in phloem of pennycress

The effects of beet western yellows virus on pennycress phloem were investigated using electron microscopy and collecting at intervals after aphid inoculation. Particles were seen in mature sieve elements from the earliest collection date, but they became less numerous in sieve elements of older leaves as the infection progressed. The first cytopathological effect in phloem parenchyma cells was the appearance of virus vesicles that became enclosed in ER membranes and attached to the outer layer of the nuclear envelope. At the time of vesicle attachment and thereafter, virions appeared in phloem parenchyma cell nuclei. In some instances virions appeared in the cytoplasm, but in many cases they remained in nuclei, often occupying a perinucleolar position. Aspects of the virus invasion and distribution in pennycress phloem are compared to effects of other luteo-viruses.
How lysenkoism became pseudoscience: dobzhansky to velikovsky.

At some point in America in the 1940s, T. D. Lysenko’s neo-Lamarckian hereditary theories transformed from a set of disputed doctrines into a prime exemplar of “pseudoscience.” This paper explores the context in which this theory acquired this pejorative status by examining American efforts to refute Lysenkoism both before and after the famous August 1948 endorsement of Lysenko’s doctrines by the Stalinist state, with particular attention to the translation efforts of Theodosius Dobzhansky. After enumerating numerous tactics for combating perceived pseudoscience, the Lysenko case is then juxtaposed with another American case of alleged pseudoscience: the notorious 1950 scandal surrounding Immanuel Velikovsky’s Worlds in Collision (1950, Worlds in Collision. New York: Macmillan). On several levels, the characterization of Lysenkoism as pseudoscientific served as a template for casting other rejected theories, including Velikovsky’s, in the same light.
Navigating Mobile Robot With A Supervisory Vision System

Among the various schemes for navigating mobile robot, the control of robot vehicle under a supervisory vision system is a simple and flexible one. In this paper, a design of such system is presented. The human operator can easily specify the planned route of the mobile robot on a monitor which shows the site image taken by the supervisory camera. Our design allows the user to specify the route, the dwelling time at each stop along the route, and the multi-route, multi-robot scheduling. In addition to the interactive human interface, several vision techniques used to achieve real-time mobile robot locating are presented. Together with the image-to-world coordinate transformation, the accuracy of this vision-based navigation system is analyzed.
Wear debris pseudotumor following total knee arthroplasty: a case report

Introduction In patients who have undergone a total joint replacement, any mass occurring in or adjacent to the joint needs thorough investigation and a wear debris-induced cyst should be suspected.
In-Service Safety Performance Evaluation of Roadside Concrete Barriers

Safety-shaped concrete barriers have been the most widely used rigid roadside barriers to shield errant motorists from roadside hazards or obstacles. These barriers are designed to lift impacting vehicles up and thereby extend the duration of impact and reduce the peak decelerations on the vehicle. However, safety-shaped concrete barriers tend to produce rollovers due to excessive vehicle climbing. Vertical concrete barriers, on the other hand, do not have the advantage of reducing impact forces by lifting the vehicle up, but they do produce lower roll angles. The objective of this research was to evaluate which of these two barrier profiles is the safest based on real-world vehicle crash data. The safest profile was defined as the one that produced lower driver injury severity levels and rollover propensity. It was found that safety-shaped barriers are more likely to produce rollovers as compared to vertical barriers. It was also found that crashes involving safety-shaped barriers tended to result in more severe driver injury levels. This finding was not statistically significant though. However, rollovers were found to significantly increase driver injury severity levels. Therefore, it is believed that the expanded use of vertical concrete barriers should improve overall highway safety.
Morphologic diversity of the minor salivary glands of the rat: fertile ground for studies in gene function and proteomics

In this article the locations and histologic and ultrastructural features of all of the minor salivary glands of the rat are presented; similarities and differences among them are highlighted. These glands are almost as diverse morphologically as the major salivary glands of the rat. The acini of von Ebner's glands are serous; those of the anterior and posterior buccal glands and minor sublingual glands are mucous; and those of the glossopalatal, palatal, and Weber's glands are mucous with serous demilunes. The anterior buccal, minor sublingual and von Ebner's glands have striated and stratified columnar ducts, while only the minor sublingual and von Ebner's glands have intercalated ducts. The glossopalatal, palatal, posterior buccal and Weber's glands have none of these ducts; the tubulo-acini drain abruptly into short terminal ducts composed of stratified squamous epithelium. All of the mucous acini react with an antibody to a mucin (Muc19) of the rat major sublingual gland, but in some of the glands the reaction varies in intensity among the acinar cells. Ultrastructurally, the mucous secretory granules of the anterior buccal, glossopalatal, palatal and Weber's glands are biphasic, while those of the minor sublingual and posterior buccal glands are monophasic. Although there is a considerable body of literature concerning the development, innervation, physiology and proteomics of von Ebner's glands, investigation of the other minor salivary glands of the rat ranges from modest to nearly nonexistent.
Human γδ-T cells in adoptive immunotherapy of malignant and infectious diseases

Human γδ-T cells are capable of mediating both innate antitumor and antiviral activity, functions that theoretically might be exploitable in the treatment of a variety of malignant or infectious diseases. Nonetheless, experimental therapies incorporating the adoptive transfer of human γδ-T cells have remained unfeasible to date owing largely to the difficulty of isolating or expanding sufficient numbers of γδ-T cells. It is in this context that recent discoveries from our laboratory are presented. By identifying specific signaling pathways that selectively inhibit activation-induced apoptosis in apoptosis-prone γδ-T cells, we have been able to expand large numbers of viable and functional human γδ-T cells, an undertaking until now not possible. As important, these apoptosis-resistant γδ-T cells appear to retain major histocompatibility complex-unrestricted (innate) anti-tumor activity against a wide variety of human tumor cells both in vitro and in vivo. Moreover, apoptosis-resistant γδ-T cells also display potent innate antiviral activity in vitro against human immunodeficiency virus-1. Both the biologic and practical implications of these findings are considered and discussed particularly as they relate to the development of future adoptive immunotherapy strategies.
Temporal and receptor correlates of the estrogen response in sheep

Uterine blood flow and uterine cytosol and nuclear estrogen receptors were measured at critical times during estradiol-induced vasodilatation in acute anesthetized and chronic conscious sheep preparations at estradiol bolus injection frequencies from 1 to 24 hours. During acute experiments, the uterine blood flow response was muted and cytosol estrogen receptor replenishment did not occur whereas full replenishment occurred in 12 hours in conscious ewes. In ewes treated with daily estradiol that had a stable daily uterine blood flow response, the uterine blood flow response 24 hours after uterine biopsy was similar to the preoperative one. Analysis of the duration of peak uterine blood flow levels and the rate of uterine blood flow descent from peak levels showed that an interval of 18 hours between estradiol injections was necessary for the uterine blood flow response to approximate that observed after 24 hours. These observations suggest: (1) that uterine vascular receptor replenishment is delayed compared with that of the total uterus; (2) that operative stress compromises cytosol estrogen receptor metabolism and possibly nuclear estrogen receptor function; (3) that the delayed maximum uterine blood flow response to estradiol in ewes previously untreated with estradiol is due to a trophic uterine effect of daily estradiol stimulation.
Dietary fat, sugar, and fiber predict body fat content

Abstract Objective This study was conducted to determine the relationships among the specific components of dietary fat and carbohydrate and body fatness in lean and obese adults. Design Body composition determination was performed on each subject by hydrostatic weighing at residual volume. Subsequently, the individual components of dietary fat and carbohydrate were examined relative to body fatness using a 3-day food diary and a food frequency questionnaire. Subjects Subjects were 23 lean (11.1±2.9% body fat) men, 23 obese (29.2±3.8% body fat) men, 17 lean (16.7±3.3% body fat) women, and 15 obese (42.7±3.9% body fat) women who volunteered for free diet and body composition analyses. Inclusion criteria were 15% body fat for lean men, 25% for obese men, 20% for lean women, and 35% for obese women. Statistical analysis performed Group comparisons for dietary variables were made with a multivariate analysis of variance. Results No differences were found between lean and obese subjects for energy intake or total sugar intake, but obese subjects derived a greater of their energy from fat (33.1±2.6% and 36.3±2.3% for obese men and women, respectively, vs 29.1±1.3% and 29.6±2.0%, lean men and women, respectively). Percent of fat intake for saturated, monounsaturated, and polyunsaturated fats was not different among groups. Obese subjects derived a greater percentage of their sugar intake from added sugars than lean subjects (38.0±3.5% vs 25.2±2.0%, respectively, for men; 47.9±8.0% vs 31.4±3.4%, respectively, for women). Dietary fiber was lower for obese men (20.9±1.8 g) and women (15.7±1.1 g) than for lean men (27.0±1.8 g) and women (22.7±2.1 g). Applications/conclusions Obesity is maintained primarily by a diet that is high in fat and added sugar and relatively low in fiber. Alterations in diet composition rather than energy intake may be a weight control strategy for overweight adults.
A spectral study of the second-order exceptional X1-Jacobi differential expression and a related non-classical Jacobi differential expression

Abstract The exceptional X 1 -Jacobi differential expression is a second-order ordinary differential expression with rational coefficients; it was discovered by Gomez-Ullate, Kamran and Milson in 2009. In their work, they showed that there is a sequence of polynomial eigenfunctions { P ˆ n ( α , β ) } n = 1 ∞ called the exceptional X 1 -Jacobi polynomials. There is no exceptional X 1 -Jacobi polynomial of degree zero. These polynomials form a complete orthogonal set in the weighted Hilbert space L 2 ( ( − 1 , 1 ) ; w ˆ α , β ) , where w ˆ α , β is a positive rational weight function related to the classical Jacobi weight. Among other conditions placed on the parameters α and β, it is required that α , β > 0 . In this paper, we develop the spectral theory of this expression in L 2 ( ( − 1 , 1 ) ; w ˆ α , β ) . We also consider the spectral analysis of the ‘extreme’ non-exceptional case, namely when α = 0 . In this case, the polynomial solutions are the non-classical Jacobi polynomials { P n ( − 2 , β ) } n = 2 ∞ . We study the corresponding Jacobi differential expression in several Hilbert spaces, including their natural L 2 setting and a certain Sobolev space S where the full sequence { P n ( − 2 , β ) } n = 0 ∞ is studied and a careful spectral analysis of the Jacobi expression is carried out.
Defects in the two-dimensional electron solid and implications for melting

We have calculated the energies of formation for various defects in a two-dimensional electron lattice. Included are vacancies and interstitials, dislocation pairs, and grain boundaries. From the results, we have extracted the dislocation core energy, and an approximate formula for the grain boundary energy as a function of angle. We discuss some possible implications for melting, and for dynamic processes such as electron diffusion and dislocation migration.
Locally adaptive smoothing splines

Locally adaptive smoothing splines combine features of variable kernel estimators and smoothing splines allowing for local adaptive fitting of a nonparametric regression function with splines. Basically, one presmooths the raw data with a local bandwidth kernel estimator, and then computes a global fit to the presmoothed data using a penalized likelihood. The resulting estimator is a locally adaptive smoothing spline easily computed for any point in the domain of the regression function from the values of the locally adaptive kernel estimator on a grid. We present some asymptotic properties of this estimator and study its finite sample behavior through simulations.
Third Harmonic Generation in Polycrystalline Anatase Titanium Dioxide Nanowaveguides

We experimentally demonstrate third-harmonic generation in polycrystalline anatase titanium dioxide nano-waveguides, using ultrashort optical pulses centered around 1550 nm. Phase matching is achieved using higher order optical modes at the third harmonic wavelength.
Crossover analysis of the heat capacity of YBa2Cu3O7-x near Tc: Evidence for XY-like critical behavior.

The heat-capacity anomaly of a largely untwinned single crystal of YBa 2 Cu 3 O 7-x is reanalyzed by means of a crossover model. The conventional Gaussian-corrected BCS shape is shown to be inadequate to fit the data within ±4 K of T c , a range much larger than estimated from the Ginzburg criterion. Improved fits in the vicinity of T c were obtained using the approach of Chen, Albright, and Sengers, who introduced a crossover function to interpolate smoothly between critical and mean-field behavior
Does Whole-Body 2-[18F]-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography Have an Advantage Over Thoracic Positron Emission Tomography for Staging Patients With Lung Cancer?

Background: Whole-body (WB) positron emission tomography (PET) with 2-[ 18 F]-fluoro-2-deoxy-D-glucose (FDG) is more accurate than other imaging studies for detecting lung cancer and extrathoracic metastatic disease. Thoracic PET (from the skull base through the kidneys) may be equally as useful as WB PET (skull base to mid-thigh). With the recent introduction of hybrid CT-PET systems, use of thoracic PET would minimize radiation dose. Methods: A retrospective review of a series of WB PET scans performed in our department was performed to identify patients evaluated for a solitary pulmonary nodule or newly diagnosed lung cancer who had distant extracranial and extrathoracic metastases detected by PET. All patients with true extrathoracic metastases were documented by ancillary radiologic and clinical data. Patients were staged according to the American Joint Committee on Cancer TNM system based on findings within the confines of a thoracic PET and WB PET. Comparison was made between staging based on thoracic and WB PET to determine if there was a significant difference. Results: Of 1,026 studies, distant extracranial metastases were described in 35 patients with lung cancer. Findings were determined to be false-positive in nine patients. Of the 26 patients with true metastases on WB PET, 25 patients had metastatic lesions within the confines of thoracic PET. Relative to WB PET, the sensitivity of thoracic PET is 96.2% (95% confidence interval, 1 to 99.3%) for detection of distant metastases. Only one patient had an isolated metastasis that was detected only by WB PET. This patient would have been staged IIIB by thoracic PET as opposed to stage IV by WB PET. Conclusions: Thoracic PET, when compared to WB PET, is 96.2% sensitive for detecting extrathoracic metastases in patients with newly diagnosed non-small cell lung cancer.
Comparison of Research Designs for Two Controlled Trials of Mass Media Interventions

This paper compares two controlled trials of mass media interventions, factors influencing their designs, and design lessons learned from these experiences. Mass media evaluations based on a scientific research model are motivated by gaps in knowledge. The results of such research are intended to serve the needs of consensus development processes through which confident recommendations can be made for intervention strategies that should be more widely applied. For these purposes, the scientific research context emphasizes internal validity of evaluation design, such as controlled experiments. This paper describes two such trials, implemented at different times with differing social contexts for youth cigarette smoking, smoking prevention research evidence bases, and tobacco control environments. Common and unique features of the two trials are reviewed, and observations are noted about the conditions under which controlled trials of mass media interventions might be warranted.
Considerations in designing and analyzing surgical adjuvant study in resected stage I and II carcinoma of the lung.

An in-depth retrospective statistical analysis was performed on 115 consecutive Stage I and Stage II cases of carcinoma of the lung. One hundred and nine cases were found to be acceptable for evaluation. Since there were eight postoperative deaths, 101 cases were analyzed for the purpose of establishing statistical models to be utilized in the planning of multi-institutional surgical adjuvant studies. Factors analyzed included surgical stage, histologic type, mode of curative surgery, age, sex, race, surgical complications, the use of radiotherapy, time to disease recurrence, location of the relapses, and survival. The histologic type and the surgical stage were found to be the most significant variables influencing both the length of disease-free interval and the ultimate survival with disease. The median disease-free intervals were 44+ months for Stage I adenocarcinoma, 23 months for Stage I epidermoid, 12 months for Stage II adenocarcinoma, and 21 months for Stage II epidermoid carcinoma. The median survival was 44+ months for Stage I adenocarcinoma, 42 months for Stage I epidermoid, 22 months for Stage II adenocarcinoma, and 28 months for Stage II epidermoid carcinoma. Postoperative radiation therapy failed to show any prolonging of either disease-free interval or survival time. Analyses helped identify an early failure component that was approximately associated with a constant relapse rate for specific time intervals. There was a recurrence rate of 1.7% per month for 18 months in Stage I adenocarcinoma, 2.9% per month for 24 months in Stage II adenocarcinoma, and 2.7% per month for 26 months in both Stage I and II epidermoid carcinoma. The surgical cure rate, as suggested from the plateauing of the disease-free curves, was found to be 55% (±12%) for Stage I adenocarcinoma, 30% (±10%) for Stage I epidermoid, 22% (±11%) for Stage II adenocarcinoma and 13% (±9%) for Stage II epidermoid carcinoma. Inferior periods for disease-free interval for survival in small (oat) cell carcinoma were felt to be consistent with the concept of the presence of microscopic metastatic disease at the time of surgery. Inclusion of this group of patients into surgical adjuvant studies is not recommended. Absence of a higher cure rate in epidermoid and adenocarcinoma was also attributed to the presence of micrometastasis at the time of resection based on the analysis of the location of the initial clinical appearance of recurrence. Also, the period of time from recurrence until death in each group was found to be associated with multiple variables and thus it will be difficult to interpret the effect of adjuvant therapy on survival in this group unless the therapy following recurrence is standardized. A simple statistical model consisting of early and late component is proposed for use in studies designed to test the efficacy of surgical adjuvant programs in resected lung cancer.
Nonlinear estimation analysis of the kinetics of catalytic ethanol dehydrogenation

Abstract In previous work, F ranckaerts and F roment analyzed the kinetics of the catalytic dehydrogenation of ethanol in an integral flow reactor. This analysis involved the initial rate method combined with parameter estimation by linear regression. In the present study, nonlinear estimation has been applied directly to the integral conversion data. For this purpose an experimental computer program has been used which features a kinetics input language, a numerical integration solver and a nonlinear estimation algorithm. The results of this study are in substantial agreement with those of F ranckaerts and F roment . An adequate representation of the data is given by a Langmuir-Hinshelwood form in which surface-reaction on dual sites without dissociation is controlling. Moreover, discrimination among alternative models is shown to be possible due in large part to the experimental design in which measurements were made at different total pressures as well as at various initial feed concentrations and space velocities.
Sign notation in ferroelectric free energy functions

Abstract The sign notation of the elastic and electrostrictive terms in the free energy density function of nonlinear polarizable deformable solids is not unique. Four possible, commonly used sign combinations have been analyzed, and their implication on the associated elastic boundary conditions is described.
Mutational analysis of βCOP (Sec26p) identifies an appendage domain critical for function

The appendage domain of the γCOP subunit of the COPI vesicle coat bears a striking structural resemblance to adaptin-family appendages despite limited primary sequence homology. Both the γCOP appendage domain and an equivalent region on βCOP contain the FxxxW motif; the conservation of this motif suggested the existence of a functional appendage domain in βCOP. Sequence comparisons in combination with structural prediction tools show that the fold of the COOH-terminus of Sec26p is strongly predicted to closely mimic that of adaptin-family appendages. Deletion of the appendage domain of Sec26p results in inviability in yeast, over-expression of the deletion construct is dominant negative and mutagenesis of this region identifies residues critical for function. The ArfGAP Glo3p was identified via suppression screening as a potential downstream modulator of Sec26p in a manner that is independent of the GAP activity of Glo3p but requires the presence of the COOH-terminal ISS motifs. Together, these results indicate an essential function for the predicted βCOP appendage and suggest that both COPI appendages perform a biologically active regulatory role with a structure related to adaptin-family appendage domains.
Temporal effects of tumor necrosis factor-α on intracellular survival of Mycobacterium paratuberculosis

The causative agent in Johne's disease is Mycobacterium paratuberculosis, an intracellular pathogen which causes enteritis in ruminants. Little is known about interactions between the host cell (macrophage) and M. paratuberculosis; however, this bacterium is able to evade normal host immune defenses and cause a chronic infective state. In the present study, we evaluated whether activation of a murine macrophage cell line (J774.16) by pretreatment with recombinant murine tumor necrosis factor alpha (TNF) prior to infection with M. paratuberculosis would affect their ability to restrict growth and kill the ingested bacteria. A murine cell line was utilized owing to difficulty in obtaining bovine reagents and lack of a continuous bovine macrophage cell line for repeated experimentation. After 4 h of infection, numbers of viable bacteria in cell lysates were significantly lower for macrophages pretreated with 1000 IU TNF ml-1. The rate of bacterial growth as assessed by BACTEC radiometric culture system was also reduced at this time point. Upon further extension of the infection period to 72 h, we observed that moderate doses of TNF (10-1000 IU ml-1) significantly increased the number of viable M. paratuberculosis recovered whereas the highest dose of TNF (4000 IU ml-1) effectively reduced bacterial numbers. These data indicate that TNF can either enhance or reduce macrophage mycobactericidal and mycobacteriostatic activity depending upon both the level of TNF to which cells are exposed and the duration of infection.
Iron depletion without anemia is not associated with impaired selenium status in college-aged women

Iron-deficiency anemia has been shown to alter body mineral concentrations and activities of iron- and non-iron-containing enzymes, especially those with antioxidant functions. These effects, however, have been less studied in nonanemic iron-depleted individuals. Thus, this study assessed indices of selenium status in 12 college-aged females with adequate iron stores and 15 college-aged females with low iron stores before and after iron therapy. Blood samples were drawn at baseline for both groups and following iron supplementation in the low-iron-stores group. Hematocrit, hemoglobin, and serum ferritin concentrations of the low-iron-stores group were significantly lower than those of the control group. The serum transferrin receptor-to-serum ferritin ratio in the low-iron-stores group was significantly greater than that of the control group. Serum selenium and glutathione peroxidase concentrations of the low-iron-stores group were not significantly different from those of the controls. Iron supplementation significantly increased hemoglobin, hematocrit, and serum ferritin concentrations and significantly decreased the serum transferrin receptor concentration and serum transferrin receptor:serum ferritin ratio in the low-iron-stores group posttreatment compared to pretreatment. Serum selenium and glutathione peroxidase concentrations did not differ significantly from pretreatment to posttreatment in the low-iron-stores group. Results of this study indicate that low iron stores without anemia are not associated with impaired selenium status in college-aged females.
Inhibition of catalysed thermal decomposition of DDT

In the laboratory, picolinic acid and salicylal-amino-guanidine have been found to inhibit the iron catalysed thermal (110–120° for twenty-four hours) decomposition of technical grade DDT very effectively at concentrations as low as 2% of the inhibitor. Under similar conditions the technical grade DDT decomposed (dehydro-halogenated) quantitatively.
Is the Ability to Integrate Parts into Wholes Affected in Autism Spectrum Disorder

There is considerable debate about whether people with autism spectrum disorder (ASD) are biased toward local information and whether this disrupts their ability to integrate two complex shapes elements into a single figure. Moreover, few have examined the relationship between integration ability and ASD symptom severity. Adolescent/adult males with ASD and age and IQ-matched controls were compared on their performance of a simple silhouette-to-shape matching task and a higher-order shape-integration task. Relative to basic silhouette-to-shape matching, ASD participants were disproportionately slower than controls on shape-integration. Moreover, this relative slowing correlated with increased symptom severity in ASD participants. These findings support the notion that integrating local information is disproportionately more challenging in ASD; this weakness may play a role in ASD symptomatology.
Development of a preclinical PK/PD model to assess antitumor response of a sequential aflibercept and doxorubicin-dosing strategy in acute myeloid leukemia.

Timing of the anti-angiogenic agent with respect to the chemotherapeutic agent may be crucial in determining the success of combination therapy in cancer. We investigated the effects of sequential therapy with the potent VEGF inhibitor, aflibercept, and doxorubicin (DOX) in preclinical acute myeloid leukemia (AML) models. Mice were engrafted with human HL-60 and HEL-luciferase leukemia cells via S.C. and/or I.V. injection and treated with two to three doses of aflibercept (5–25 mg/kg) up to 3–7 days prior to doxorubicin (30 mg/kg) administration. Leukemia growth was determined by local tumor measurements (days 0–16) and systemic bioluminescent imaging (days 0–28) in animals receiving DOX (3 mg/kg) with or without aflibercept. A PK/PD model was developed to characterize how prior administration of aflibercept altered intratumoral DOX uptake. DOX concentration–time profiles were described using a four-compartment PK model with linear elimination. We determined that intratumoral DOX concentrations were 6-fold higher in the aflibercept plus DOX treatment group versus DOX alone in association with increased drug uptake rates (from 0.125 to 0.471 ml/h/kg) into tumor without affecting drug efflux. PD modeling demonstrated that the observed growth retardation was mainly due to the combination of DOX plus TRAP group; 0.00794 vs. 0.0043 h−1. This PK/PD modeling approach in leukemia enabled us to predict the effects of dosing frequency and sequence for the combination of anti-VEGF and cytotoxic agents on AML growth in both xenograft and marrow, and may be useful in the design of future rational combinatorial dosing regimens in hematological malignancies.
Mammalian Sly1 Regulates Syntaxin 5 Function in Endoplasmic Reticulum to Golgi Transport

Members of the syntaxin gene family are components of protein complexes which regulate vesicle docking and/or fusion during transport of cargo through the secretory pathway of eukaryotic cells. We have previously demonstrated that syntaxin 5 is specifically required for endoplasmic reticulum to Golgi transport (Dascher, C., Matteson, J., and Balch, W. E. (1994) J. Biol. Chem. 269, 29363-29366). To extend these observations we have now cloned a protein from rat liver membranes which forms a native complex with syntaxin 5. We demonstrate that this protein is the mammalian homologue to yeast Sly1p, previously identified as a protein which genetically and biochemically interacts with the small GTPase Ypt1p and Sed5p, proteins involved in docking/fusion in the early secretory pathway of yeast. Using transient expression we find that overexpression of rat liver Sly1 (rSly1) can neutralize the dominant negative effects of excess syntaxin 5 on endoplasmic reticulum to Golgi transport. These results suggest that rSly1 functions to positively regulate syntaxin 5 function.
Binding of 2-acetylpyridine-5-[(2-chloroanilino)thiocarbonyl] thiocarbonohydrazone (BW348U87) to human serum albumin

Dissociation constants and rate constants for the binding of 2-acetylpyridine-5-[(2-chloroanilino)thiocarbonyl]thiocar bonohydrazone (I, BW348U87), an agent that enhances the antiherpetic efficacy of acyclovir, to human serum albumin have been determined. I quenched the fluorescence of human serum albumin, whereas the absorbance of I at 370 nm increased upon binding to the protein. The absorbance change was attributed to preferential binding of anionic I (pKa 7.0). Titration data indicated multiple binding sites for I. The dissociation constant of the high-affinity site was 0.11 microM. The time course for binding of I to 100 nM human serum albumin was biphasic. The early and late phases were described by first-order rate constants that had maximal values of 100 and 11 sec-1, respectively. The rate constant for the dissociation of I from human serum albumin was estimated to be 6 sec-1. Dodecyl sulfate and octanoate displaced I from human serum albumin.I with rate constants of 4.5 and 7.3 sec-1, respectively. Since the fluorescence emission spectrum of human serum albumin and the absorption spectrum of I overlapped significantly (the spectral overlap integral, J, was 2.6 x 10(-14) M-1 cm3), the possibility of Forster dipole-dipole energy transfer was considered. However, a significant fraction of the fluorescence quenching by I resulted from a conformational change in the protein upon binding of I and was not the result of dipole-dipole energy transfer. Nonetheless, the distance between one of the binding regions for I on human serum albumin and a tryptophan residue in the protein was estimated to be 31 A by this method. The high affinity of I for albumin could be related to its low hematological toxicity.
Posture mirroring and interactional involvement: Sex and sex typing effects

This study investigated the effects of sex (male-male vs. female-female) and sex typing (sex typed-sex typed, sex typed-androgynous, and androgynous-androgynous) on dyadic posture mirroring between strangers in a “waiting room” context. Results revealed a significant interaction between sex composition and sex-typing composition such that among sex-typed pairs, females displayed more posture mirroring than males but among androgynous pairs, the effect was reversed with male dyads showing more posture sharing than female dyads. Results also showed a surprising negative relation between mirroring and rapport as well as a negative correlation between mirroring and verbalization. The suggestion made is that individual action in the form of talk and communal engagement in the form of mirroring may represent different modes of being involved in an interaction.
Regulating the onset of mitosis

In eukaryotes, G2/M progression is mediated by activation of mitosis promoting factor (MPF). To ensure faithful chromosome segregation, the activity of key mitotic inducers and inhibitors are coupled with chromosome replication, spindle pole duplication, morphogenesis, and DNA damage. Evidence gathered in the past two years has underscored the importance of positioning MPF and its regulators in the proper place at the proper time to ensure orderly progression through the G2/M transition. Altering the spatial organization of G2/M regulators also contributes to prevention of mitosis following DNA damage.