cssi/SciSciGPT-SciSciNet huggingface dataset:
Point mutations in the β chain CDR3 can alter the T cell receptor recognition pattern on an MHC class I\peptide complex over a broad interface area

To study how the T cell receptor interacts with its cognate ligand, the MHC/peptide complex, we used site directed mutagenesis to generate single point mutants that alter amino acids in the CDR3beta loop of a H-2Kb restricted TCR (N30.7) specific for an immunodominant peptide N52-N59 (VSV8) derived from the vesicular stomatitis virus nucleocapsid. The effect of each mutation on antigen recognition was analyzed using wild type H-2Kb and VSV8 peptide, as well as H-2Kb and VSV8 variants carrying single replacements at residues known to be exposed to the TCR. These analyses revealed that point mutations at some positions in the CDR3beta loop abrogated recognition entirely, while mutations at other CDR3beta positions caused an altered pattern of antigen recognition over a broad area on the MHC/peptide surface. This area included the N-terminus of the peptide, as well as residues of the MHC alpha1 and alpha2 helices flanking this region. Assuming that the N30 TCR docks on the MHC/peptide with an orientation similar to that recently observed in two different TCR-MHC/peptide crystal structures, our findings would suggest that single amino acid alterations within CDR3beta can affect the interaction of the TCR with an MHC surface region distal from the predicted CDR3beta-Kb/VSV8 interface. Such unique recognition capabilities are generated with minimal alterations in the CDR3 loops of the TCR. These observations suggest the hypothesis that extensive changes in the recognition pattern due to small perturbations in the CDR3 structure appears to be a structural strategy for generating a highly diversified TCR repertoire with specificity for a wide variety of antigens.
Fixed list versus snowball selection of social networks

Abstract Two ways of collecting network data are discussed in the context of interorganizational networks among social service agencies. One method proceeds with a fixed agency list while the other uses a snowball selection procedure. We find that: 1. (i) the agencies included in the two selection procedures differ; 2. (ii) network-based indicators for agencies (such as centrality) differ; 3. (iii) the substantive contents of the included ties differ; and 4. (iv) the structure of the networks differ. The two methods are fundamentally different and cannot be used as surrogates for each other. When data are gathered at multiple points in time, the differences between the methods are more acute. Interagency networks change through time: agencies leave the network while other agencies join. Snowball selection can respond to these changes while fixed list selection does not.
Quantitative Histochemistry: Histologic Sampling of Sections of Frozen-Dried Tissues

Microchemical techniques are available for analyses of many enzymes and other components of tissue for which stains are not available. This paper describes techniques of freeze drying and histological sampling of certain cell groups or structures free from surrounding stroma, fat and other types of cells. Quantitative data can be obtained for many enzymes in 0.5 to 5 μ samples of freeze-dried tissue. For example, glucoses-phosphate dehydrogenase activity was measured and compared in the breast alveoli of mice in estrus, diestrus, gestation and lactation.
Microinjection of Antibody to Mad2 Protein into Mammalian Cells in Mitosis Induces Premature Anaphase

In yeast, the Mad2 protein is required for the M phase arrest induced by microtubule inhibitors, but the protein is not essential under normal culture conditions. We tested whether the Mad2 protein participates in regulating the timing of anaphase onset in mammalian cells in the absence of microtubule drugs. When microinjected into living prophase or prometaphase PtK1 cells, anti-Mad2 antibody induced the onset of anaphase prematurely during prometaphase, before the chromosomes had assembled at the metaphase plate. Anti-Mad2 antibody-injected cells completed all aspects of anaphase including chromatid movement to the spindle poles and pole–pole separation. Identical results were obtained when primary human keratinocytes were injected with anti-Mad2 antibody. These studies suggest that Mad2 protein function is essential for the timing of anaphase onset in somatic cells at each mitosis. Thus, in mammalian somatic cells, the spindle checkpoint appears to be a component of the timing mechanism for normal mitosis, blocking anaphase onset until all chromosomes are aligned at the metaphase plate.
Toroidal coil counter-current chromatography study of the mass transfer rate of proteins in aqueous–aqueous polymer phase system

The cause of excessive band broadening of protein samples in polymer phase partitioning by counter-current chromatography (CCC) was investigated. A simple rotary device was constructed to measure the mass transfer rates of five samples including potassium dichromate, methylene blue, lysozyme, ovalbumin and human serum albumin. The results indicated that the mass transfer rates of these samples are closely correlated with their molecular masses: the higher the molecular mass, the lower the mass transfer rate. These findings are also consistent with the partition efficiencies of these samples in the same solvent system by CCC. The beneficial effect of the Coriolis force demonstrated in protein separations by the toroidal coil centrifuge may be reasonably explained on the basis of the mass transfer resistance of protein molecules through the interface: we speculate that when the Coriolis force acts parallel to the effective coil segment it can produce large interfacial areas by dispersing the mobile phase into the stationary phase, thus accelerating the mass transfer rate of protein samples.
Benzologs of the thiazolo[3,2-a]pyridinium system

By use of concentrated sulfuric acid rather than hydrobromic acid as the cyclizing medium, good yields of the thiazolo[3,2-a]quinolinium ion and its derivatives may be obtained from α-(2-quinolylthio) ketones or acetals. In the same way, α-(1-isoquinolylthio) and α-(6-phenanthridylthio) ketones afford thiazolo[2,3-a]isoquinolinium and thiazolo-[3,2-f]phenanthridinium salts.
Co-operative components, spatial localization and oscillatory cellular dynamics

Abstract The consequences of spatial localization on the dynamic behavior of catalytic components whose outputs control one another's activities but are not the substrates of those activities are explored. For some simple model systems we naturally find limit cycle oscillations, multiple asymptotic states, dependence of the dynamic states upon spatial configuration of the components, and complex switching between dynamic states as a function of external perturbation to the system.
Effects of amino acids and peptides on rumen microbial growth yields

Abstract Experiments were conducted using mixed rumen bacterial cultures to determine which amino acids limited growth. Complete amino acid mixtures stimulated microbial growth alone and when added to casein. Amino acid subgroups did not stimulate growth alone or when added to casein or casein hydrolysates. Results were similar whether growth was limited by periodic addition of low amounts of carbohydrate or when higher amounts were added to batch cultures. Little growth occurred with ammonia as sole N source. Addition of 100 mg/L of amino acids and peptides quadrupled growth. peptides at 10 mg/L resulted in higher growth than the corresponding amount of free amino acids. Apparent saturation of growth occurred when 10 mg/L of a complete amino acid mixture or trypticase was added to cultures. The Michaelis constant values for amino acids and trypticase were determined to be .5 and 1.0 mg/L, respectively. Growth was a linear function of amount of carbohydrate fermented with the coefficient of slope increasing with increasing amino acid concentrations. These experiments demonstrate that growth stimulation from amino acids and proteins is due to the number of amino acids provided in a given mixture rather than specific growth limiting amino acids. Rumen bacterial growth is greatly stimulated by amino acids and peptides, with low affinity constant values, allowing good growth in the concentrations of amino acids and peptides found in vivo.
SPATIALLY EXPLICIT AND STOCHASTIC SIMULATION OF FOREST- LANDSCAPE FIRE DISTURBANCE AND SUCCESSION

Understanding disturbance and recovery of forest landscapes is a challenge because of complex interactions over a range of temporal and spatial scales. Landscape simulation models offer an approach to studying such systems at broad scales. Fire can be simulated spatially using mechanistic or stochastic approaches. We describe the fire module in a spatially explicit, stochastic model of forest landscape dynamics (LANDIS) that in- corporates fire, windthrow, and harvest disturbance with species-level succession. A sto- chastic approach is suited to forest landscape models that are designed to simulate patterns over large spatial and time domains and are not used deterministically to predict individual events. We used the model to examine how disturbance regimes and species dynamics interact across a large (500 000 ha), heterogeneous landscape in northern Wisconsin, USA, with six land types having different species environments, and fire disturbance return intervals varying from 200 to 1000 yr. The model shows that there are feedbacks over time between species, disturbance, and environment, resulting in the re-emergence of patterns that char- acterized the landscape before extensive alteration. Landscape equilibrium of species com- position and age-class structure develops at three scales from the initial, disturbed landscape. Over 100-150 yr, fine-grained successional processes cause gradual disaggregation of the initial pattern of relatively homogenous composition and age classes. Species such as eastern hemlock ( Tsuga canadensis), largely removed from the landscape by past human activities, only slowly re-invade. Next, patterns on the various land types diverge, driven by different disturbance regimes and dominant species. Finally, aging of the landscape causes the prob- abilities of larger and more severe fires to increase, and a coarse-grained pattern develops from the disturbance patches. Influence of adjacent land types is shown as fires spread across land type boundaries, although modified in spread and severity. As found by others, altered landscapes are likely to retain their modified pattern for centuries, suggesting that nonequilibrium conditions between tree species and climate will persist under predicted rates of climate change. The results suggest that this modeling approach can be useful in examining species- level, broad-scale responses of heterogeneous landscapes to changes in landscape distur- bance, such as modified management or land-use scenarios, or effects of global change.
C-reactive protein and development of a prothrombogenic microvasculature in heart transplant recipients

Introduction: Increased C-reactive protein (CRP) serum levels and activation of endothelium have been recognized as risk factors for transplant coronary artery disease (Tx-CAD) and graft failure, suggesting that a proinflammatory microenvironment within the allografts plays a major role in patient’s outcome. Since endothelial activation is associated with a procoagulant status in the microvasculature, we investigated whether elevated levels of high-sensitivity CRP (hs-CRP) were associated with the presence of a procoagulant microvasculature. Methods: hs-CRP levels were determined using ELISA in serial serum samples (Median: 7; Range: 1–7) obtained during the first 3 months following heart transplantation from 120 patients. All patients were evaluated for the presence of a prothrombogenic microvasculature (i.e., lack of microvascular antithrombin, depletion of arteriolar tissue plasminogen activator and presence of microvascular fibrin) within the allografts. Results: Patients (N 120) were grouped according to the hs-CRP percentile levels. Groups under the 25th percentile ( 1.1 mg/L), between the 25th and 75th percentiles (1.1–6.2 mg/L) and over the 75th percentile ( 6.2 mg/L) were compared to evaluate differences in the procoagulant status of the microvasculature. A significant association was found between hs-CRP levels and levels of vascular antithrombin reactivity (p 0.001), arteriolar tissue plasminogen activator reactivity (p 0.001) and microvascular fibrin deposits (p 0.001), indicating that increased levels of hs-CRP were associated with the presence of a procoagulant microvasculature. Each one of these factors was independently associated with development and severity of Tx-CAD (p 0.01). Conclusions: The present data show that elevated levels of hs-CRP are associated with a procoagulant microvasculature and suggest that this vascular environment promotes Tx-CAD and allograft failure. These data emphasize the need to understand the role of CRP in endothelial activation and coagulation in order to further intervene and affect the outcome of heart transplant patients.
REPRESENTING CONDITIONAL INDEPENDENCE RELATIONS BY VALUATION NETWORKS

Valuation networks have been proposed as graphical representations of valuation-based systems. The axiomatic framework of valuation-based systems is able to capture many uncertainty calculi including probability theory, Dempster-Shafer's belief-function theory, Spohn's epistemic belief theory, and Zadeh's possibility theory. In this paper, we show how valuation networks encode conditional independence relations. For the probabilistic case, the class of probability models encoded by valuation networks includes undirected graph models, directed acyclic graph models, directed balloon graph models, and recursive causal graph models.
CYTOLOGY AND MORPHOGENESIS IN THE RHIZOMORPH OF ARMILLARIA MELLEA

A B S T R A C T Aided by the techniques of thin sectioning and electron microscopy, the apical region of the rhizomorph of Armillaria mellea has been examined. This region is composed of concentric zones of morphologically distinct tissues derived from a subapical meristematic zone designated the apical center. Meristematic activity is of two types: (1) primary, localized in the apical center, in which new hyphal elements are formed from apical initials, and (2) secondary, localized in the lateral regions of the apex, in which elaboration of the hyphal elements by means of elongation and secondary crosswall formation takes place. From these meristematic zones the tissuies of the mature rhizomorph are derived and include: (a) peripheral hyphae, (b) cortex, (e) subcortex, and (d) primary and secondary medulla. The manner of differentiation of an apical initial appears unique and involves synchronous nuclear divisions accompanied by segmentation in many planes. The result of this activity is the formation of multinucleate hyphae. Apical initials are usually highly cytoplasmic and possess peculiar non-membrane-bound fibrous butndles, but in all other respects they resemble the hyphae of most Basidiomycetes thus far examined with the electron microscope. FOLLOWING the work of Hartig (1873), which established the relationship between rhizomorphs
Flow and load characteristics of microbearings with slip

The fluid mechanics and operating characteristics of bearings that support rotating surfaces in micromachines are different from their larger cousins. The present study analyzes microbearings represented as an eccentric cylinder rotating in a stationary housing. The flow Reynolds number is assumed small, the clearance between shaft and housing is not small relative to the overall bearing dimensions, and there is slip at the walls due to non-continuum effects. The two-dimensional governing equations are written in terms of the streamfunction in bipolar coordinates and an infinite-series solution is obtained. For high values of the eccentricity and low slip factors the flow may develop a recirculation region. The force and torque on the load-bearing inner cylinder increase with increasing eccentricity and decrease with increasing slip.
Cyclic Polyamidato Dianions as Bridges between Mo24+ Units: Synthesis, Crystal Structures, Electrochemistry, Absorption Spectra, and Electronic Structures

Compounds in which quadruply bonded Mo24+ units, Mo2(DAniF)3 (DAniF = N,N‘-di-p-anisylformamidinate), are linked by cyclic diamidate anions have been synthesized and characterized by X-ray crystallography and spectroscopic methods. As identified by the diamidate linker, these compounds are 4,6-dioxypyrimidinate (2), 2,3-dioxypyrazinate (3), 2,3-dioxyquinoxalinate (4), 2,3-dioxy-5,6-dicyanopyrazinate (5), and cyanurate (6). With uracilate, a dinuclear unlinked 1:1 adduct is formed, Mo2(DAniF)3(uracilate) (1). The cyclic voltammograms of 3−5 reveal significantly larger ΔE1/2 values (258 mV−308 mV) than that of the oxalate linked analogue (212 mV), which is indicative of greater charge delocalization in the mixed valent Mo24+/Mo25+ species and hence greater communication between the two Mo2 units. ΔE1/2 for 2 is substantially lower than those for 3−5. This difference is attributed to the meta disposition of the two amidate groups in 4,6-dioxypyrimidinate as compared to their ortho arrangement in the pyrazina...
Incorporating Protein Environments in Density Functional Theory: A Self-Consistent Reaction Field Calculation of Redox Potentials of [2Fe2S] Clusters in Ferredoxin and Phthalate Dioxygenase Reductase

An approach to calculating molecular electronic structures of active-site clusters in the presence of protein environments has been developed. The active-site cluster is treated by density functional theory. The protein field, together with the reaction field arising mainly from solvent, is obtained from a finite-difference solution to the Poisson−Boltzmann equation with three dielectric regions, and then these are coupled to the density functional calculation by a self-consistent iterative procedure. The method is applied to compute redox potentials of ferredoxin from Anabaena 7120 and phthalate dioxygenase reductase (PDR) from Pseudomonas cepacia, both having similar [Fe2S2(SR)4] active-site clusters. The calculated redox potentials, −1.007 V and −0.812 V in 0.05 M ionic strength for ferredoxin and PDR, respectively, deviate significantly from experimental values of −0.440 and −0.174 V. However, the calculated data reproduce the experimental trend fairly well. The calculated redox potential for PDR is 1...
SAGA and CONDENSE: a two-phase approach for the implementation of recurrence equations on multiprocessor architectures

The automation of parallel implementations of algorithms, specifically those arising in scientific and engineering applications, is investigated. Since many of these computations can be formulated as coupled system of recurrence equations, they exhibit a high degree of repetitiveness and regularity. These properties are utilized to generate efficient, and in certain cases optimal, schedules and processor assignments on particular multiprocessor configurations. The process of determining a parallel implementation consists of two successive stages, named SAGA and CONDENSE. SAGA generates a minimal-time systolic implementation with a number of processors that is likely to be problem-dependent. If the problem size exceeds the size of the target architecture, CONDENSE groups the processors in the array given by SAGA so that each group is assigned, or condensed, to one processor of the target architecture. The condensation is done so as to minimize the total run time and is guided by the systolic array from SAGA. >
Anhedonia as a function of non-affective interpretation of ambiguous stimuli and threshold for affective and neutral stimuli.

A theory that schizophrenic anhedonia–the failure to express pleasure– is associated with a tendency to interpret ambiguous stimuli as neutral rather than emotion-laden and arises from selectively high perceptual thresholds for affective stimuli was tested. Seventy-six schizophrenic males were required to guess whether words presented to them tachistoscopically for extremely short periods were positive, negative or neutral in content. The high-anhedonic Ss were significantly more likely to guess neutral words and less likely to offer pleasant interpretations than the low-anhedonic sample, which suggests that anhedonia is associated with a tendency to interpret one's environment as lacking in positive emotional value. The thresholds of high- and low-anhedonic schizophrenic groups then were compared on pleasant, unpleasant, and neutral tachistoscopically-presented stimuli. In the only two significant differences in the latter analyses, high anhedonics showed greater thresholds for neutral stimuli than low anhedonics. These findings suggest that anhedonia is not mediated by peculiarly high thresholds for affective stimuli.
Mutant p53 forms a complex with Sp1 on HIV-LTR DNA.

Many mutants of p53 activate HIV-LTR driven transcription and promote HIV replication. The region of the HIV-LTR containing Sp1-binding sites is important for this effect. In this study we test the hypothesis that mutant p53 interacts with DNA-bound Sp1 and in this way can increase transcription from Sp1-dependent promoters. We have used the breast cancer cell line MDA-MB-468 that expresses endogenous mutant p53(His273) as our source of p53 protein. First, we demonstrated that this mutant p53 participates in activating transcription from the HIV-LTR by showing that HIV-LTR-directed transcription in MDA-MB-468 cells is inhibited in a dominant-negative manner by p53(Val135). Using HIV-LTR DNA affinity chromatography, we detected coelution of p53(His273) and Sp1. We also demonstrated that this mutant p53 binds sequence specifically to the super consensus sequence (SCS) and that Sp1 coeluted with p53(His273) from a column containing this site. These data indicate that p53(His273) can associate with DNA-bound Sp1 suggesting that activated HIV-LTR transcription associated with mutant p53 occurs through a DNA driven multi-protein complex.
A plastic scintillation detector for beta-ray spectrum measurements

Abstract A scintillation detection system has been built for the determination of beta decay Q-values and ground state branching of short-lived fission products. The beta-ray response of the well-type plastic scintillators was determined by direct measurements of monoenergetic beta rays with energies up to 5 MeV. The beta-ray energy calibration, determined by continuous beta-ray spectra and internal conversion electrons, was found to have a partially quadratic energy dependence. A technique for using gamma-ray Compton spectra to obtain the energy calibration is described. The method of analysis of the distorted beta-ray spectra, which is successful in correcting the distortions down to one-tenth of the maximum beta-ray energy, allows the number of fit parameters to be reduced by application of constraints based on knowledge of the energy level scheme of the daughter nucleus. Sample results, which illustrate the quality of the fits to beta-ray spectra, are presented for 32P and 137Xe.
Concordance testing comparing STR multiplex kits with a standard data set

Abstract Multiple concordance studies have been performed at NIST with a standard sample set (≈1450 U.S. population samples) using various STR multiplex kits from Applied Biosystems, Promega Corporation, and Qiagen, including many of the new generation European kits. Out of 948,301 allele comparisons, differences were observed 1109 times resulting in a concordance rate of 99.88%. These differences were reported to the collaborating commercial vendors, which in many cases lead to revised kits and a reduction in null alleles through the addition of degenerate primers or primer redesign.
Scattering amplitudes in hot gauge theories.

A consistent method for the perturbative calculation of scattering amplitudes in hot gauge theories is developed. It involves the resummation of a subset of thermal fluctuations, termed hard thermal loops, into effective propagators and vertices. The damping rate of a heavy fermion is computed as an example.
Wheelchair Use by Ambulatory Nursing Home Residents

In a survey of wheelchair use in two nursing homes, the authors found a substantial number of cognitively intact nursing home residents who walked, but who also used a wheelchair. Using chart review and interviews with the residents, it was found that multiple physical factors, including pain, strength, endurance, vision and balance, and multiple social and environmental factors, including the fear of falling, were related to the resident's decision to use a wheelchair as an alternative means of mobility. A physical examination focused on aspects of mobility was completed on each resident and was intended to characterize the physical limitations in groups studied. In the nursing home environment, use of the wheelchair is viewed by the residents as a self-initiated choice which the residents believed significantly enhanced their sense of well-being. Finally, there was minimal recognition of mobility as a problem on the part of the medical and nursing staff. The study raises a number of important issues concerning walking versus wheelchair use in the nursing home.
Enhancement of carbonic anhydrase activity by erythrocyte membranes

The human erythrocyte membrane is an efficient enhancer of both high (CA II) and low (CA I) activity isozymes of red blood cell carbonic anhydrase. The presence of membrane increased CO2 hydration catalyzed by bovine CA II 1.6-fold, human CA II 3.5-fold, and human CA I 1.6-fold. With the high activity CA isozymes, maximal stimulation was observed in the presence of 1-3 micrograms membrane protein/ml. The Vmax for bovine CA II (4 nM) rose from 0.302 to 0.839 mM/s, while that for human CA II (6 nM) increased from 0.113 to 0.414 mM/s in the absence and presence of membrane, respectively. The apparent Km for CO2 increased from 13.2 to 51.2 mM for bovine CA II, and from 6.5 to 38.5 mM for human CA II. Mixtures of membrane plus enzyme, upon centrifugation through linear sucrose density gradients, displayed enhanced Ca activity only in membrane-containing gradient fractions, verifying the stimulatory ability of membranes on enzyme activity and indicating tight and stable complex formation. Membrane enhancement of CA activity appears to be a general phenomenon in that mouse hepatocyte membranes also stimulated CA activity, although less efficiently than erythrocyte membranes. Of the many soluble putative effectors assayed, only imidazole enhanced CA II activity to an extent comparable with erythrocyte membranes; imidazole did not, however, stimulate the activity of human CA I. The data are consistent with a model of CA II activation by membrane association that may effect a distortion of the enzyme conformation in such a way as to facilitate intra- and/or intermolecular proton transfer between membrane-bound and enzyme-bound proton shuttling residues (perhaps the imidazole moiety of histidine) and the Zn-bound hydroxide at the catalytic site of the enzyme.
Simulated and experimental performance of a heat pipe assisted solar wall

Abstract Performance was evaluated for a passive solar space heating system utilizing heat pipes to transfer heat through an insulated wall from an absorber outside the building to a storage tank inside the building. The one-directional, thermal diode heat transfer effect of heat pipes make them ideal for passive solar applications. Gains by the heat pipe are not lost during cloud cover or periods of low irradiation. Simplified thermal resistance-based computer models were constructed to simulate the performance of direct gain, indirect gain, and integrated heat pipe passive solar systems in four different climates. The heat pipe system provided significantly higher solar fractions than the other passive options in all climates, but was particularly advantageous in cold and cloudy climates. Parametric sensitivity was evaluated for material and design features related to the collector cover, absorber plate, heat pipe, and water storage tank to determine a combination providing good thermal performance with diminishing returns for incremental parametric improvements. Important parameters included a high transmittance glazing, a high performance absorber surface and large thermal storage capacity. An experimental model of the heat pipe passive solar wall was also tested in a laboratory setting. Experimental variations included fluid fill levels, addition of insulation on the adiabatic section of the heat pipe, and fins on the outside of the condenser section. Filling the heat pipe to 120% of the volume of the evaporator section and insulating the adiabatic section achieved a system efficiency of 85%. Addition of fins on the condenser of the heat pipe did not significantly enhance overall performance. The computer model was validated by simulating the laboratory experiments and comparing experimental and simulated data. Temperatures across the system were matched by adjusting the model conductances, which resulted in good agreement with the experiment.
A reversed-phase high-performance liquid chromatographic method for characterization of biosynthetic human growth hormone.

An isocratic reversed-phase high-performance liquid chromatographic method for the determination of human growth hormone (HGH) purity is described. This method offers superior resolution of HGH-related substances (e.g., sulfoxide and desamido derivatives) from unmodified HGH when compared to a number of alternative chromatographic and electrophoretic techniques.
Radiofrequency ablation of Barrett's esophagus

Barrett's esophagus, a metaplastic change in the esophagus wherein normal squamous epithelium is replaced by specialized columnar epithelium, is a complication of chronic gastroesophageal reflux disease. There is an association between Barrett's esophagus and esophageal adenocarcinoma. Since 1977, esophageal cancer has increased by more than 500% in the United States. The optimal treatment for dysplastic Barrett's esophagus is unclear. One method for treating dysplastic Barrett's esophagus is radiofrequency ablation (RFA). RFA has been shown to effectively induce reversion to neosquamous tissue, and has been demonstrated in a randomized trial to significantly decrease the risk of progression of dysplasia to cancer. Minimal complications have been reported, and the technique can be performed in an outpatient setting. The aim of this article is to outline and discuss the technical aspects of performance of RFA. The basic principles of RFA and the rationale for adapting this technique to the esophagus will be briefly discussed. Next, the equipment and technique will be explained in detail, including suggestions for improved outcomes. Finally, potential complications, follow-up intervals, and expected outcomes will be addressed.
Overexpression of TGF-β1 in the Central Nervous System of Transgenic Mice Results in Hydrocephalus

Transforming growth factor beta (TGF-beta) has been proposed to play a number of roles in central nervous system (CNS) development and response to injury. To test these proposals, transgenic mice were generated which overproduce TGF-beta 1 in the CNS. Surprisingly, these mice developed severe hydrocephalus and died between birth and 3 weeks of age. Ovary transplantation from an affected female founder has permitted perpetuation of one of the lines as a hydrocephalus model whose genetic defect is known. These results also demonstrate that the developing CNS is highly sensitive to TGF-beta, and suggest a role for aberrant expression of TGF-beta in the pathogenesis of developmental disease of the CNS.
ArChiVED: architectural checking via event digests for high performance validation

Simulation-based techniques play a key role in validating the functional correctness of microprocessor designs. A common approach for validating microprocessors (called instruction-by-instruction, or IBI checking) consists of running a RTL and an architectural simulation in lock-step, while comparing processor architectural state at each instruction retirement. This solution, however, cannot be deployed on long regression tests, because of the limited performance of RTL simulators. Acceleration platforms have the performance power to overcome this issue, but are not amenable to the deployment of an IBI checking methodology. Indeed, validation on these platforms requires logging activity on-platform and then checking it against a golden model off-platform. Unfortunately, an IBI checking approach following this paradigm entails a large slowdown for the acceleration platform, because of the sizable amount of data that must be transferred off-platform for comparison against the golden model. In this work we propose a sequence-by-sequence (SBS) checking approach that is efficient and practical for acceleration platforms. Our solution validates the test execution over sequences of instructions (instead of individual ones), thus greatly reducing the amount of data transferred for off-platform checking. We found that SBS checking delivers the same bug-detection accuracy as traditional IBI checking, while reducing the amount of traced data by more than 90%.
Immunological effects of low-fat diets with and without weight loss.

Objective: The immunologic effects of isocaloric reduced- and low-fat diets and a voluntary calorie-restricted low-fat diet resulting in weight loss were compared to the immunologic effects of an average American diet in hyperlipidemic individuals.Methods: Ten hyperlipidemic subjects were studied during three six-week weight maintenance phases: baseline (BL) [35% fat {14% saturated fat (SFA), 13% monounsaturated fat (MUFA), 8% polyunsaturated fat (PUFA)} and 147 mg cholesterol (C)/1000 kcal], reduced-fat (RF) [26% fat (4% SFA, 11% MUFA, 11% PUFA) and 45 mg C/1000 kcal], and low-fat (LF) [15% fat (5% SFA, 5% MUFA, 3% PUFA) and 35 mg C/1000 kcal] diets followed by 12-week, low-fat calorie reduced phase (LFCR).Results: During the last phase, the subjects’ weight significantly decreased (p = 0.005). Cholesterol levels were significantly reduced during all phases, compared to BL diet (p < 0.05). Delayed-type hypersensitivity (DTH) was assessed using Multi-test CMI. Maximum induration diameters were 22.7, 25.4,...
Depressed Adolescents with a History of Sexual Abuse: Diagnostic Comorbidity and Suicidality

ABSTRACT Objective To determine the nature of comorbid psychopathology and suicidality associated with a history of sexual abuse in depressed adolescents. Method Twenty-four depressed adolescent inpatients with a history of sexual abuse were compared with a matched control group of 24 depressed adolescent inpatients on measures of depression, suicidal ideation and behavior, and posttraumatic stress disorder (PTSD) symptoms Results Depressed adolescents with a history of sexual abuse had a higher prevalence of comorbid PTSD than did those without such a history. Chronicity and severity of abuse were significant contributors to a PTSD diagnosis. No differences were found in depression severity, specific depressive symptoms, or suicidal behavior. Conclusion Comorbidity of depressive disorders and PTSD are common among adolescent inpatients with a history of chronic sexual abuse. The need for thorough assessment of depression and PTSD with appropriate interventions for sexually abused adolescents is clear.
Reducing clutter noise in fast ultrasound imaging with transverse high-pass filtering

Clutter noise that appears as line strips in parallel with transducer surface is often seen in fast imaging with plane wave or waves of small divergences. In this paper, spatial high-pass filters of different cut-off frequencies are applied in the transverse direction in Fourier domain to reduce the clutter noise for the high-frame rate (HFR) imaging method developed previously. The noise reduction and contrast enhancement are significant when 11 transmissions (maximum frame rate of 413 frames/s at a speed of sound of 1500 m/s and 165-mm image depth) are used. However, with 91 transmissions (maximum frame rate of 50 frames/s), the method is less effective since the original image already has a low clutter noise and a high contrast.
The 4q subtelomere harboring the FSHD locus is specifically anchored with peripheral heterochromatin unlike most human telomeres

This paper investigates the nuclear localization of human telomeres and, specifically, the 4q35 subtelomere mutated in facioscapulohumeral dystrophy (FSHD). FSHD is a common muscular dystrophy that has been linked to contraction of D4Z4 tandem repeats, widely postulated to affect distant gene expression. Most human telomeres, such as 17q and 17p, avoid the nuclear periphery to reside within the internal, euchromatic compartment. In contrast, 4q35 localizes at the peripheral heterochromatin with 4p more internal, generating a reproducible chromosome orientation that we relate to gene expression profiles. Studies of hybrid and translocation cell lines indicate this localization is inherent to the distal tip of 4q. Investigation of heterozygous FSHD myoblasts demonstrated no significant displacement of the mutant allele from the nuclear periphery. However, consistent association of the pathogenic D4Z4 locus with the heterochromatic compartment supports a potential role in regulating the heterochromatic state and makes a telomere positioning effect more likely. Furthermore, D4Z4 repeats on other chromosomes also frequently organize with the heterochromatic compartment at the nuclear or nucleolar periphery, demonstrating a commonality among chromosomes harboring this subtelomere repeat family.
Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair

Summary Structure-specific endonucleases mediate cleavage of DNA structures formed during repair of collapsed replication forks and double-strand breaks (DSBs). Here, we identify BTBD12 as the human ortholog of the budding yeast DNA repair factor Slx4p and D. melanogaster MUS312. Human SLX4 forms a multiprotein complex with the ERCC4(XPF)-ERCC1, MUS81-EME1, and SLX1 endonucleases and also associates with MSH2/MSH3 mismatch repair complex, telomere binding complex TERF2(TRF2)-TERF2IP(RAP1), the protein kinase PLK1 and the uncharacterized protein C20orf94. Depletion of SLX4 causes sensitivity to mitomycin C and camptothecin and reduces the efficiency of DSB repair in vivo. SLX4 complexes cleave 3′ flap, 5′ flap, and replication fork structures; yet unlike other endonucleases associated with SLX4, the SLX1-SLX4 module promotes symmetrical cleavage of static and migrating Holliday junctions (HJs), identifying SLX1-SLX4 as a HJ resolvase. Thus, SLX4 assembles a modular toolkit for repair of specific types of DNA lesions and is critical for cellular responses to replication fork failure.
Significance of T-cell stimulation by altered peptide ligands in T cell biology

Investigations of T-cell responses to altered peptide ligands have provided functional evidence that a T-cell receptor can interpret subtle structural changes in its ligand, highlighting the complexity of this antigen receptor signaling system. Over the past year, observations from many studies have suggested several roles for such analog peptides in various aspects of immune responses. Collectively, these data strongly suggest the existence of naturally occurring altered peptide ligands in the endogenous peptide repertoire, that can actively participate in the development and shaping of T-cell immunity.
Bilateral Preauricular Pits

A newborn presents with bilateral preauricular pits (Figures 1, 2) Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. Figure 7. ### Prenatal and Birth History ### Presentation The infant was active, feeding well, and vital signs were stable. However, the findings on physical examination prompted admission to the neonatal intensive care unit for further evaluation. ### Vital Signs ### Physical Examination
Sentinel Node Biopsy: Standard of Care

Abstract: Sentinel lymph node biopsy (SLNB) is a less invasive alternative to axillary lymph node dissection (ALND) for staging breast cancer. In appropriate women, this procedure can stage the axilla with less extensive surgery and fewer complications. Sentinel node status is accurate in predicting axillary status based on single institutional experiences and confirmed by large multi-center trials. Non-sentinel nodes are involved very rarely if the sentinel node is tumor-free. SLNB enables intense examination of a single lymph node. However, the use of special stains to detect micrometastases is of uncertain clinical significance and is the subject of large trials. Early follow-up from the John Wayne Cancer Institute experience demonstrates excellent outcome for patients with either micrometastases or tumor-free nodes. Results from techniques with either blue dye or radioisotope colloid tracer and injection locations at peri-areolar, peritumoral, or subcutaneous sites are similar. These findings support the biological concept of a single (or very few) sentinel nodes for the entire breast. The sentinel node is more predictive of axillary status than any other tumor prognostic factor. Axillary lymph node dissection is unlikely to reveal nodal metastases when the sentinel node is tumor-free, and in such cases there is no reason to perform a completion axillary node dissection. Sentinel node biopsy alone without axillary lymph node dissection should now be the standard of care for most clinically node-negative women with breast cancer.
Hallucinating real things

No particular dagger was the object of Macbeth’s hallucination of a dagger. In contrast, when he hallucinated his former comrade Banquo, Banquo himself was the object of the hallucination. Although philosophers have had much to say about the nature and philosophical import of hallucinations (e.g. Macpherson and Platchias, Hallucination, 2013) and object-involving attitudes (e.g. Jeshion, New essays on singular thought, 2010), their intersection has largely been neglected. Yet, object-involving hallucinations raise interesting questions about memory, perception, and the ways in which we have knowledge of the world around us. In this paper, I offer an account of object-involving hallucinations. Specifically, I argue that they are an unusual species of perceptual remembering.
Nomadic enhancers: Tissue-specific cis-regulatory elements of yellow have divergent genomic positions among Drosophila species

cis-regulatory DNA sequences known as enhancers control gene expression in space and time. They are central to metazoan development and are often responsible for changes in gene regulation that contribute to phenotypic evolution. Here, we examine the sequence, function, and genomic location of enhancers controlling tissue- and cell-type specific expression of the yellow gene in six Drosophila species. yellow is required for the production of dark pigment, and its expression has evolved largely in concert with divergent pigment patterns. Using Drosophila melanogaster as a transgenic host, we examined the expression of reporter genes in which either 5′ intergenic or intronic sequences of yellow from each species controlled the expression of Green Fluorescent Protein. Surprisingly, we found that sequences controlling expression in the wing veins, as well as sequences controlling expression in epidermal cells of the abdomen, thorax, and wing, were located in different genomic regions in different species. By contrast, sequences controlling expression in bristle-associated cells were located in the intron of all species. Differences in the precise pattern of spatial expression within the developing epidermis of D. melanogaster transformants usually correlated with adult pigmentation in the species from which the cis-regulatory sequences were derived, which is consistent with cis-regulatory evolution affecting yellow expression playing a central role in Drosophila pigmentation divergence. Sequence comparisons among species favored a model in which sequential nucleotide substitutions were responsible for the observed changes in cis-regulatory architecture. Taken together, these data demonstrate frequent changes in yellow cis-regulatory architecture among Drosophila species. Similar analyses of other genes, combining in vivo functional tests of enhancer activity with in silico comparative genomics, are needed to determine whether the pattern of regulatory evolution we observed for yellow is characteristic of genes with rapidly evolving expression patterns.
Studies on antisense inhibition of translation in vitro. Anomalies and re-evaluation.

Experiments were carried out to better characterize antisense control of translation, Results in an E. coli system confirmed specific inhibition of poly(U) translation. At low concentrations, certain homopolymers (including poly(rA)) stimulated translation, Oligo(dA) was inhibitory at 1158. Translation of globin mRNA in reticulocyte lysates indicated that ssDNA 15-mers targeted at β-globin mRNA inhibited both α- and β-globin production. Sequences targeted immediately downstream of the AUG were the least effective in inhibition. These and other anomalies are discussed here in relation to those of others, emphasizing caution in performing antisense experiments.
A Clear and Present Danger: Endogenous Ligands of Toll-like Receptors

Neurologic disease promoted by microbial pathogens, sterile injury, or neurodegeneration rapidly induces innate immunity in adjacent healthy tissue, which in turn contributes extensively to neurologic injury. With more recent focus on innate immune processes, it appears that necrotic, but not apoptotic, death mechanisms provoke inflammatory responses likely due to the release or production of endogenous ligands that activate resident immune cells of the central nervous system. These ligands comprise a diverse set of proteins, nucleic acids, and glycosaminoglycans, including heat shock proteins, HMGB1, RNA, DNA, hyaluronan, and heparin sulfate, that stimulate innate immune mechanisms largely through Toll-like receptors (TLRs). The blockade of interactions between endogenous ligands and TLRs may enable neuroprotective therapeutic strategies for a variety of neurologic diseases.
Growth behavior of a class of merit functions for the nonlinear complementarity problem

When the nonlinear complementarity problem is reformulated as that of finding the zero of a self-mapping, the norm of the selfmapping serves naturally as a merit function for the problem. We study the growth behavior of such a merit function. In particular, we show that, for the linear complementarity problem, whether the merit function is coercive is intimately related to whether the underlying matrix is aP-matrix or a nondegenerate matrix or anRo-matrix. We also show that, for the more popular choices of the merit function, the merit function is bounded below by the norm of the natural residual raised to a positive integral power. Thus, if the norm of the natural residual has positive order of growth, then so does the merit function.
Response gradient estimation using mathematical programming models of discrete-event system sample paths

This paper illustrates the use of mathematical programming in computing gradient estimators. Consistency property of these estimators is established under the usual assumptions for IPA gradient estimator consistency. A finite difference tolerance limit is introduced. For complex discrete-event systems, more concise linear programming representations are developed. These new representations provide a direct way of calculating gradient estimates.
Regulation and dysregulation of immunoglobulin E: a molecular and clinical perspective

Background Altered levels of Immunoglobulin E (IgE) represent a dysregulation of IgE synthesis and may be seen in a variety of immunological disorders. The object of this review is to summarize the historical and molecular aspects of IgE synthesis and the disorders associated with dysregulation of IgE production.