cssi/SciSciGPT-SciSciNet huggingface dataset:
Identification of Rhodospirillum rubrum GlnB Variants That Are Altered in Their Ability To Interact with Different Targets in Response to Nitrogen Status Signals

In Rhodospirillum rubrum, NifA, the transcriptional activator for the nif genes, is posttranslationally activated only by the uridylylated form of GlnB, one of three P(II) homologs in the organism. We have used the yeast two-hybrid system to detect variants of GlnB that interact better with NifA than does wild-type GlnB. When examined for physiological effects in R. rubrum, these GlnB* variants activated NifA in the presence of NH(4)(+), which normally blocks NifA activation completely, and in the absence of GlnD, whose uridylylation of GlnB is also normally essential for NifA activation. When these variants were tested in the two-hybrid system for their interaction with NtrB, a receptor that should interact with the nonuridylylated form of GlnB, they were uniformly weaker than wild-type GlnB in that interaction. When expressed in R. rubrum either as single-copy integrants or on multiple-copy plasmids, these variants were also dramatically altered in terms of their ability to regulate several other receptors involved in nitrogen metabolism, including GlnE, NtrB/NtrC, and DRAT (dinitrogenase reductase ADP-ribosyl transferase)-DRAG (dinitrogenase reductase-activating glycohydrolase). The consistent pattern throughout is that these GlnB variants partially mimic the uridylylated form of wild-type GlnB, even under nitrogen-excess conditions and in strains lacking GlnD. The results suggest that the role of uridylylation of GlnB is primarily to shift the equilibrium of GlnB from a "nitrogen-sufficient" form to a "nitrogen-deficient" form, each of which interacts with different but overlapping receptor proteins in the cell. These GlnB variants apparently shift that equilibrium through direct structural changes.
Towards Omni-Tomography -- Grand Fusion of Multiple Modalities for Simultaneous Interior Tomography

We recently elevated interior tomography from its origin in computed tomography (CT) to a general tomographic principle, and proved its validity for other tomographic modalities including SPECT, MRI, and others. Here we propose "omni-tomography", a novel concept for the grand fusion of multiple tomographic modalities for simultaneous data acquisition in a region of interest (ROI). Omni-tomography can be instrumental when physiological processes under investigation are multi-dimensional, multi-scale, multi-temporal and multi-parametric. Both preclinical and clinical studies now depend on in vivo tomography, often requiring separate evaluations by different imaging modalities. Over the past decade, two approaches have been used for multimodality fusion: Software based image registration and hybrid scanners such as PET-CT, PET-MRI, and SPECT-CT among others. While there are intrinsic limitations with both approaches, the main obstacle to the seamless fusion of multiple imaging modalities has been the bulkiness of each individual imager and the conflict of their physical (especially spatial) requirements. To address this challenge, omni-tomography is now unveiled as an emerging direction for biomedical imaging and systems biomedicine.
Evidence for lower variability of coronary artery calcium mineral mass measurements by multi-detector computed tomography in a community-based cohort—Consequences for progression studies

Abstract Purpose To compare the measurement variability for coronary artery calcium (CAC) measurements using mineral mass compared with a modified Agatston score (AS) or volume score (VS) with multi-detector CT (MDCT) scanning, and to estimate the potential impact of these methods on the design of CAC progression studies. Materials and methods We studied 162 consecutive subjects (83 women, 79 men, mean age 51±11 years) from a general Caucasian community-based cohort (Framingham Heart Study) with duplicate runs of prospective electrocardiographically-triggered MDCT scanning. Each scan was independently evaluated for the presence of CAC by four experienced observers who determined a "modified" AS, VS and mineral mass. Results Of the 162 subjects, CAC was detected in both scans in 69 (42%) and no CAC was detected in either scan in 72 (45%). Calcium scores were low in the 21/162 subjects (12%) for whom CAC was present in one but not the other scan (modified AS r >0.96). However, the mean interscan variability was significantly different between mineral mass, modified AS, and VS (coefficient of variation 26±19%, 41±28% and 34±25%, respectively; p p p r =−0.638, −0.614 and −0.577 for AS, VS, and mineral mass, respectively; all p Conclusion There is significantly reduced interscan variability of CAC measurements with mineral mass compared with the modified AS or VS. However, the measurement variability of all quantification methods is predicted by the amount of CAC and is inversely correlated to the extent of partial volume artifacts. Moreover, the improvement of measurement reproducibility leads to a modest reduction in sample size for observational epidemiological studies or randomized clinical trials to assess the progression of CAC.
The Origins of the Occupational Safety and Health Act of 1970

This paper analyzes the emergence of the Occupational Safety and Health Act of 1970 and finds previous explanations of its origin inadequate. I trace the roots of this law to the protests of rank-and-file workers across the United States at a time when the support of these workers was particularly important to the two main political parties. The protest was directed not only at those employers who operated unsafe and unhealthy workplaces, but also at union officials who paid little or no attention to safety and health issues in negotiating new contracts.
Treatment of intrabony defects with resorbable materials, non-resorbable materials and flap debridement.

Abstract Background: Different types of barriers are used in guided tissue regenerative procedures. Aim: This prospective study compared resorbable citric acid ester softened polylactic acid membranes (RM) and non-resorbable expanded polytetrafluoroethylene (ePTFE) barriers (NRM) in GTR treatment of intrabony defects. Methods: 29 subjects were randomly assigned to the RM group or NRM group. Each patient received one GTR procedure. An open flap debridement (FD) was performed at another site 2 weeks later to evaluate healing potential. Clinical treatment outcomes were finally evaluated 12 months after surgery for changes of pocket depth PD, probing attachment level PAL, and probing bone level PBL, and radiographically for bone change using standardised radiographs. Results: No differences in healing patters after surgery were found between patients in the 2 study groups as evaluated from the FD surgical procedures. NRM treated sites showed less signs of post-surgical inflammation during the 1st 4 weeks of healing than did RM treated sites (p<0.05). GTR-treated defects in the RM group, initially 7.0±2.2 mm deep, showed PD reduction of 3.3±2.2 mm, PAL gain of 2.4±1.8 mm, PBL gain of 2.4±3.7 mm (28%) and a radiographic bone fill of 2.3±2.4 mm. Defects treated with the NRM exhibited PD reduction of 3.1±2.1 mm, PAL gain of 2.4±0.8 mm, PBL gain of 2.2±1.7 mm (25%) and a radiographic bone fill of 3.3±2.2 mm. All improvements were statistically significant (p<0.01) but there was no difference between RM and NRM treatments for any of the efficacy variables. The results of this study indicated that there was no clinically significant difference in treatment outcomes following GTR treatment of intrabony defects with citric acid ester softened polylactic acid membranes as compared to ePTFE barriers. The overall mean inter-proximal vertical bone defect fill at 12 months as assessed from intra-oral radiographs was 44% of the original mean defect depth. Conclusions: Thus, no clinically significant difference in treatment outcomes was observed following GTR treatment of intrabony defects with citric acid ester softened polylactic acid membranes or ePTFE barriers.
Regional differences in functional status among the aged

This study investigated regional differences in functional status among aged Medicare beneficiaries in the United States, and the degree to which population risk factors and certain geographic/environmental attributes of communities accounted for the regional differences. Four years of the Medicare Current Beneficiary Survey (1992-1995) were pooled together yielding 37,150 person-year observations of functional status for a sample of aged Medicare beneficiaries residing in the community or nursing homes. Multinomial logit models, estimated on a four-category functional status scale, produced strong empirical evidence of substantial regional differences in the prevalence of functional independence, functional limitations, IADL limitations, and ADL limitations, that could not be attributed to regional population composition, socio-demographic factors, lifestyle characteristics, and chronic medical conditions. Although such population risk factors accounted for much of the regional variations in functional status among older men, the notably higher prevalence of IADL and ADL limitations among older women residing in the Deep South could not be similarly attributed to such risk factors. Rather, the empirical results suggest that a significant portion of the harmful effects associated with residence in the Deep South among older women may be attributed to a higher prevalence of residence in counties characterized by lower population density and/or higher poverty concentration.
Anilide derivatives of an 8-phenylxanthine carboxylic congener are highly potent and selective antagonists at human A(2B) adenosine receptors.

No highly selective antagonists of the A2B adenosine receptor (AR) have been reported; however such antagonists have therapeutic potential as antiasthmatic agents. Here we report the synthesis of p...
Nazis vs. the Rule of Law: Allegory and Narrative Structure in Fritz Lang's M

Since Kracauer, most readings of Fritz Lang's M have tacitly assumed that a proper understanding of the murderer is the key element to any serious reading of the movie. However, a careful analysis of the film's narrative structure reveals that the murderer is little more than a plot function. His actions only trigger and accelerate the action in the fi lm while an allegorical narrative unfolds. The real struggle presented occurs not between the murderer and those trying to catch him, but between two political paradigms that vie for legitimacy vis-a-vis "the people" and in fact played prominent roles in the late Weimar Republic's political crisis: National Socialism (represented by the criminal underworld) and a state ruled by the constitutional principle of the rule of law (represented by the police). Such a reading is able to shed new light on Lang's political Romanticism. (HL)
A critical evaluation of in vitro cell culture models for high-throughput drug screening and toxicity

Drug candidate and toxicity screening processes currently rely on results from early-stage in vitro cell-based assays expected to faithfully represent essential aspects of in vivo pharmacology and toxicology. Several in vitro designs are optimized for high throughput to benefit screening efficiencies, allowing the entire libraries of potential pharmacologically relevant or possible toxin molecules to be screened for different types of cell signals relevant to tissue damage or to therapeutic goals. Creative approaches to multiplexed cell-based assay designs that select specific cell types, signaling pathways and reporters are routine. However, substantial percentages of new chemical and biological entities (NCEs/NBEs) that fail late-stage human drug testing, or receive regulatory "black box" warnings, or that are removed from the market for safety reasons after regulatory approvals all provide strong evidence that in vitro cell-based assays and subsequent preclinical in vivo studies do not yet provide sufficient pharmacological and toxicity data or reliable predictive capacity for understanding drug candidate performance in vivo. Without a reliable translational assay tool kit for pharmacology and toxicology, the drug development process is costly and inefficient in taking initial in vitro cell-based screens to in vivo testing and subsequent clinical approvals. Commonly employed methods of in vitro testing, including dissociated, organotypic, organ/explant, and 3-D cultures, are reviewed here with specific focus on retaining cell and molecular interactions and physiological parameters that determine cell phenotypes and their corresponding responses to bioactive agents. Distinct advantages and performance challenges for these models pertinent to cell-based assay and their predictive capabilities required for accurate correlations to in vivo mechanisms of drug toxicity are compared.
Hematopoietic stem cell homing: The long, winding and adhesive road to the bone marow

Abstract In adult mammals, a rare population of cells that gives rise to the hematopoietic compartment dwells in niches within the bone marrow where they are nourished and protected. These blood stem cells can, however, exit these niches under physiological conditions and, in the context of bone marrow transplantation, migrate to the recipient's marrow to regenerate hematopoiesis. This review will address old and new discoveries regarding the mechanisms that allow these stem cells to find their way home through long and winding roads: From the peripheral circulation, through interactions with the vessel-lining endothelial cells in the bone marrow, and into their niches located in the intramedullary space. It will also address how these discoveries have provided us with new tools to manipulate stem cell trafficking.
The use of left ventricular epicardial surface velocity patterns as a marker of pacing site.

Ectopic ventricular foci were simulated at selected endocardial sites in 15 closed-chest canines using ventricular pacing. During this pacing, a noninvasive x-ray backscatter imaging technique was used to measure epicardial LV displacements at 5-ms intervals during the cardiac cycle. These displacement measurements were used to calculate epicardial surface velocities in each study and were presented as a time sequence of color coded velocity maps. Characteristic patterns in the timing and spatial propagation of LV surface velocities were noted for each pacing site, particularly during the expansion of the LV during isovolumic contraction and the inward motion of the LV during ejection. Average surface velocity maps for the 15 canines were computed for each pacing site. These average maps were used as standards for comparison with individual pacing studies to determine the probable site of pacing. Comparisons were made using a computer algorithm, based upon auto- and cross-correlation techniques in the time domain. This algorithm correctly identified pacing sites with sensitivities of HA 74%, LV 76%, RV 79%, and RVOT 77% and specificities of RA 98%, LV 96%, RV 90%, and RVOT 93%. The results show that this noninvasive mapping procedure has potential for identifying the location of an ectopic ventricular focus.
RELATION OF CERTAIN ENDOCRINE GLANDS TO BODY WEIGHT IN GROWING AND MATURE NEW ZEALAND WHITE RABBITS1,2

IN the course of a series of experiments in this laboratory during the past few years, a considerable number of normal New Zealand White rabbits have served as controls for experiments. When these animals were killed, the pituitary, thyroid, parathyroid and adrenal glandsand the ovaries and testes were weighed. Kibler, Bergman and Turner (1942) have reported a study of the relation of the pituitary weight to body weight in these animals, while Campbell and Turner (1942) similarly studied the parathyroid glands. The present paper reports the relation of body weight to thyroid, adrenals, ovaries and testes weights of these same animals. It has been pointed out that endocrine gland weights do not usually vary directly with body weight, but to some power of body weight (for references see Mixner, Bergman and Turner, 1943). The relative growth equation Y = aXb has been used widely in studies relating organ or gland weight to body weight (Brody and Kibler, 1941).
Photothermal Tuning and Spatial Mapping of Toroidal Optical Microcavities

A new method for controlling resonance wavelengths of ultrahigh-Q toroidal optical microcavities using a focused free-space laser is presented. Tuning range, rate, and spatial dependence is investigated.
Abstract 4482: Novel and selective small molecule inhibitors of 3-phosphoinositide-dependent kinase-1 inhibit the PDK-1/AKT signaling pathway and cell proliferation

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Receptor tyrosine kinases (RTKs), PTEN (phosphatase and tensin homolog deleted on chromosome 10), and PIK3CA (encodes the p110α subunit of phosphatidylinositol 3-kinase [PI3K]) frequently contribute to tumor progression through their ability to regulate the intracellular level of phosphatidylinositol-3,4,5-triphosphate (PIP3). 3-phosphoinositide-dependent kinase-1 (PDK-1), a serine/threonine kinase, activates the catalytic domain of numerous kinases by phosphorylating their T-loop sites. PDK-1 activity is required for activation of AKT, p70S6K, and RSK which lead to cell proliferation and transformation. The interaction of the pleckstrin homology (PH) domain of AKT with the membrane bound PIP3 confers a conformational change in AKT, allowing PDK-1 to phosphorylate AKT at the residue threonine-308 (T308). This T-loop activation at T308, along with the phosphorylation of the serine-473 residue by mTOR, fully activates the AKT pathway. Although the roles of many PDK-1 substrates have yet to be characterized, the oncogenic activity of aberrant PI3K pathway signaling through PDK-1 has been extensively validated. We have developed a series of 3-Carbonyl-4-Amino-Pyrrolopyrimidne (CAP) compounds that are potent inhibitors of human PDK-1 (full length and kinase domain) which demonstrate more than 100-fold selectivity against P70S6K, PI3K, AKT, and mTOR. In this study, representative compounds from the CAP series were used to perform a variety of anti-tumor assays. We demonstrate PDK-1 compounds inhibit the phosphorylation of T308 on AKT as well as downstream molecules of the PI3K pathway, such as S6 ribosomal protein (S6RP) in breast, lung and colon cancer cell lines harboring a PI3KCA mutation. Additionally, blockade of AKT and molecules in the PI3K pathway leads to the inhibition of cell proliferation and cell transformation in cancer cells. Our data suggest that the inhibition of PDK-1 activity is sufficient to induce anti-tumor activity in cancer cells through the PI3K-PDK1-AKT axis, and that a potent and specific PDK-1 inhibitor could potentially be developed as a therapeutic agent against several cancer types. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4482.
Satellite ephemerides for the Voyager Uranus encounter

Uranian satellite ephemerides are needed by the Voyager project to support both navigation and acquisition of scientific data. This paper presents the approach being taken to develop the ephemerides and details the initial phase of the development. That phase involves the analytical modeling of the satellites' motion and the adjustment of the model to fit astronomical observations. The paper describes the model and gives the result of a fit to 71 years of observations.
Influence of accumulation wall and carrier solution composition on lift force in sedimentation/steric field-flow fractionation

Abstract Sedimentation/steric field-flow fractionation is an established analytical technique for characterizing particulate materials by size in the approximate diameter range 1–100 μm. Particles are eluted through a thin, parallel-walled channel by a flow of a carrier liquid while a centrifugal field is applied across the thin dimension perpendicular to the flow. During elution, particles are driven towards equilibrium positions between the channel walls where the force due to the applied field is balanced by hydrodynamic lift forces. These lift forces are not yet fully characterized, and calibration using latex standards is at present a necessary prerequisite for size characterization of unknown materials. A greater understanding of the forces involved will ultimately eliminate this need for calibration. The elution of latex standards under various field strength and carrier flow rate regimes yields information on lift force as a function of particle size, flow velocity, position within the channel, and any other controllable system property. The work presented here examines the influence of channel wall and carrier solution composition (ionic strength and pH) on overall lift. It is shown that the observed lift may be described as the sum of a force due to the effects of fluid inertia, an empirical near-wall lift force inversely dependent on particle distance from the wall, and a force due to electrostatic repulsion.
Post-synthesis annealing effects on SrGa2Se4:Eu2+ phosphors with peak emission wavelength in the green gap

A high-quality white light source requires high luminous efficacy (lumens per input watt). Theoretically, in the "greenyellow" spectral region (with a peak wavelength at around 555 nm), the luminous efficiency (lumens per radiant watt) reaches a maximum based on the luminous efficiency function, V(λ), and can potentially generate high luminous efficacy. Unfortunately, the light-emitting diode (LED) suffers from low external quantum efficiency in the "greenyellow" region, thereby lowering the luminous efficacy value. Researchers have sought solutions such as nonpolar or semipolar InGaN/GaN LEDs. An alternative to generating green light is to use phosphor down-conversion by exciting a green emission phosphor with a near-UV or blue LED of higher external quantum efficiency. In this study, a SrGa2Se4:Eu2+ phosphor with peak emission wavelength at 555 nm was initially synthesized and followed by a systematic study of the post-synthesis annealing. The purpose of this study was to investigate how post-synthesis annealing conditions, including annealing temperature, annealing duration, and annealing ambient atmosphere, can affect phosphor performance. The phosphor performance was characterized in terms of external quantum efficiency and emission properties. How the external quantum efficiency of the phosphor can be further improved is also discussed.
Magnetism of Rare‐Earth Cobalt Phosphides GdCo3P2 and GdCo5P3

Magnetic properties of GdCo3P2 and GdCo5P3 are reported. Both compounds are paramagnetic at room temperature. GdCo3P2 undergoes an antiferromagnetic transition due to the ordering of gadolinium magnetic moments at 16 K. The cobalt atoms do not contribute to the magnetism of this compound. The antiferromagnetic transition is shifted to lower temperatures by an applied magnetic field, reaching 12 K at 0.60 T. Such behavior is attributed to spin canting or spin reorientation at higher fields. No such abrupt transition is observed in GdCo5P3, but the field dependence of magnetization at 1.8 K indicates canted antiferromagnetism. In addition, observation of distinct peaks in the AC magnetic susceptibility at 66 K, 54 K, and 48 K suggests occurrence of successive magnetic state changes. An examination of previously determined crystal structures of these solids reveals common structural elements derived from the [Co2P2] layer present in the structure of RECo2P2 phases (RE = rare earth; ThCr2Si2 structure type). In GdCo3P2 and GdCo5P3, such layers are truncated and form triangular patterns when viewed along the [010] crystallographic direction. Single-crystal X-ray diffraction analysis showed that GdCo5P3 is isostructural to YCo5P3. The gadolinium atoms form chains along [010] with d(Gd–Gd) = 3.683 A. In GdCo3P2, the gadolinium atoms form cobalt-centered trigonal prisms with d(Gd–Gd) approx. 3.7–3.8 A. The prisms share their trigonal faces to form columns along [010].
Assessment of Air vs Helium-Oxygen Flow-Volume Curves as an Epidemiologic Screening Test

Air and helium-oxygen maximum expiratory flow-volume curves were employed in an epidemiologic field study to assess the utility of density dependence as a screening test. Of 1,584 subjects tested, only 54.1 percent were able to perform the test with vital capacities for the two gases that agreed to within 5 percent. Subjects unable to perform the test properly tended to be older, with a greater prevalence of ventilatory function abnormalities and respiratory problems, than those who could perform the test. There was poor concordance between density dependence, or lack thereof, and standard ventilatory function measurements or evidence of respiratory disease. Under field survey conditions, the test of density dependence did not appear to be a useful screening tool.
FEAR RESPONSES OF BOBWHITE QUAIL (COLINUS VIRGINIANUS) TO A MODEL AND A LIVE RED-TAILED HAWK (BUTEO JAMAICENSIS).

Furchtreaktionen gekafigter, von Hand aufgezogener Baumwachteln (Colinus virginianus) wurden mit Hilfe eines handzahmen Bussards der Art Buteo jamaicensis und seiner lebensgrosen Flugattrappe qualitativ und quantitativ untersucht. Dabei beachteten wir Kontrollmasnahmen, die andere Autoren in ahnlichen Untersuchungen bisher vernachlassigt hatten.
Immunofluorescent Monoclonal Antibody Detection of Breast Cancer in Bone Marrow: Sensitivity in a Model System

We have previously shown that occult micrometastases can be detected in the bone marrow of breast cancer patients using a panel of epithelial specific monoclonal antibodies in an indirect immunofluorescent assay. The sensitivity of this assay has been examined using cells from an established human breast cancer cell line (MCF-7) mixed with normal bone marrow at various dilutions from 400 cancer cells/10(6) marrow cells (400:10(6] to 10:10(6). MCF-7 cells were detected at the lowest concentration studied, namely 10:10(6). The number of fluorescent labeled MCF-7 cells counted at each concentration was related to the concentration by a simple nonlinear statistical model. At the concentration of 10:10(6), the model shows that this technique has the sensitivity to detect between two and four MCF-7 cells 95% of the time. Moreover, by extrapolation, the model predicts that even at the very low concentration of 2:10(6), there is a 95% chance of detecting one cancer cell. Therefore, this assay may be a very sensitive method for detecting cancer cells in the bone marrow in vivo.
Experiments in Novelty Detection at Columbia University

This paper describes the method we used for the Novelty Track for the 2002 Text Retrieval Conference (TREC). We tried to adapt tools we are developing for a task closely related to the novelty part of the this track. The system we are building will scan a stream of documents and present to the user only the new information it finds. For the “relevance” part of the TREC, we decided to test the applicability of some of these tools. Since information retrieval is not a focus of our research, we thought it would be more interesting to use something new rather than try to hurriedly catch up. The results were far from satisfactory, but it is clear from the overall results that novelty detection remains a difficult and unsolved problem.
Psychiatric and Physiological Reactions Produced by Over-the-Counter Medications

(1978). Psychiatric and Physiological Reactions Produced by Over-the-Counter Medications. Journal of Psychedelic Drugs: Vol. 10, No. 3, pp. 243-249.
Finding Combinatorial Connections between Concepts in the Biomedical Literature

There are now a multitude of articles published in a diversity of journals providing information about genes, proteins, pathways, and entire processes. Each article investigates particular subsets of a biological process, but to gain insight into the functioning of a system as a whole, we must computationally integrate information across multiple publications. This is especially important in problems such as modeling cross-talk in signaling networks, designing drug therapies for combinatorial selectivity, and unraveling the role of gene interactions in deleterious phenotypes, where the cost of performing combinatorial screens is exorbitant. In this thesis, we present an automated approach to biological knowledge discovery from PubMed abstracts, suitable for unraveling combinatorial relationships. It involves the systematic application of a ‘storytelling’ algorithm followed by a series of filtering and compression operations over the mined stories. Given a start and end publication, typically with little or no overlap in content, storytelling identifies a chain of intermediate publications from one to the other, such that neighboring publications have significant content similarity. Stories discovered thus provide an argued approach to relate distant concepts through compositions of related concepts. The chains of links employed by stories are then mined to find frequently reused sub-stories, which can be compressed to yield compact templates of connections. We demonstrate a successful application of storytelling to finding combinatorial connections between biological concepts using two application case studies.
2003 Schwartz Award. Pitfalls of peer review. The limited protections of state and federal peer review law for physicians.

(2003). Pitfalls of Peer Review The Limited Protections of State and Federal Peer Review Law for Physicians. Journal of Legal Medicine: Vol. 24, No. 4, pp. 541-556.
WALTZ-DB: a benchmark database of amyloidogenic hexapeptides

Accurate prediction of amyloid-forming amino acid sequences remains an important challenge. We here present an online database that provides open access to the largest set of experimentally characterized amyloid forming hexapeptides. To this end, we expanded our previous set of 280 hexapeptides used to develop the Waltz algorithm with 89 peptides from literature review and by systematic experimental characterisation of the aggregation of 720 hexapeptides by transmission electron microscopy, dye binding and Fourier transform infrared spectroscopy. This brings the total number of experimentally characterized hexapeptides in the WALTZ-DB database to 1089, of which 244 are annotated as positive for amyloid formation.
Safety and proof of principle study of cerebellar vermal theta burst stimulation in refractory schizophrenia

Abstract Background Early invasive electrical stimulation studies suggested that enhancement of cerebellar vermal activity might prove valuable in symptomatic treatment of refractory neuropsychiatric diseases via modulation of emotion and affect. This proof of principle study aimed to test this hypothesis using noninvasive brain stimulation, and to explore the safety of this protocol in schizophrenia. Methods Eight treatment-refractory patients with schizophrenia underwent ten sessions of intermittent theta burst stimulation (TBS) to the cerebellar vermis using MRI-guided transcranial magnetic stimulation (TMS). Assessments included side effect questionnaires, cardiovascular monitoring, psychiatric evaluations and comprehensive neuropsychological testing before and after TBS and at one-week follow-up. Results Overall, TBS was tolerated well with mild side effects primarily comprising neck pain and headache. No serious adverse events occurred. Diastolic blood pressure (BP) showed mild decreases for five minutes post-TBS; no significant changes were detected for systolic BP or pulse. PANSS negative subscale showed significant improvements following TBS and during the follow-up. Calgary Depression Scale and self-report visual analog scales for Happiness and Sadness pointed to significant mood elevation. Neuropsychological testing revealed significantly fewer omissions in working memory and interference conditions of a Continuous Performance Test, a longer spatial span and better delay organization on the Rey–Osterrieth Complex Figure during follow-up. No significant worsening in psychiatric or neuropsychological measures was detected. Conclusions Theta burst stimulation of the cerebellar vermis is safe and well-tolerated, while offering the potential to modulate affect, emotion and cognition in schizophrenia. Future randomized, sham-stimulation controlled studies are warranted to support the clinical efficacy of this technique.
Convergences Between Symbolic Interactionism and Systems Theory1,2

This paper explores certain theoretical convergences between symbolic interactionism and systems theory. Important similarities between these two perspectives with respect to their basic ontological and epistemological assumptions are pointed out and discussed. The systems theory concepts of feedback and redundancy are seen to have important counterparts in symbolic interactionism. Finally, the parallel concerns of symbolic interactionism and systems theory with emergence is discussed in terms of the concepts of hierarchical structure and the law of requisite variety.
Dkk-3, a Secreted Wnt Antagonist, Suppresses Tumorigenic Potential and Pulmonary Metastasis in Osteosarcoma

Osteosarcoma (OS) is the most common primary bone malignancy with a high propensity for local invasion and distant metastasis. Despite current multidisciplinary treatments, there has not been a drastic change in overall prognosis within the past 2 decades. Dickkopf-3 protein (Dkk-3/REIC) has been known to inhibit canonical Wnt/β-catenin pathway, and its expression has been shown to be downregulated in OS cell lines. Using in vivo and in vitro studies, we demonstrated that Dkk-3-transfected 143B cells inhibited tumorigenesis and metastasis in an orthotopic xenograft model of OS. Inoculation of Dkk-3-transfected 143B cell lines into nude mice showed significant decreased tumor growth and less metastatic pulmonary nodules (88.7%) compared to the control vector. In vitro experiments examining cellular motility and viability demonstrated less anchorage-independent growth and decreased cellular motility for Dkk-3-transfected 143B and SaOS2 cell lines compared to the control vector. Downstream expressions of Met, MAPK, ALK, and S1004A were also downregulated in Dkk-3-transfected SaOS2 cells, suggesting the ability of Dkk-3 to inhibit tumorigenic potential of OS. Together, these data suggest that Dkk-3 has a negative impact on the progression of osteosarcoma. Reexpressing Dkk-3 in Dkk-3-deficient OS tumors may prove to be of benefit as a preventive or therapeutic strategy.
Electron Induced Surface Reactions of the Organometallic Precursor Trimethyl(methylcyclopentadienyl)platinum(IV)

The effect of 500 eV electrons on nanometer scale thick films of trimethyl(methylcyclopentadienyl)platinum(IV) (MeCpPtIVMe3), were studied in situ, under ultrahigh vacuum conditions using a combination of temperature-programmed desorption (TPD), X-ray photoelectron spectroscopy (XPS), mass spectrometry, and reflection absorption infrared spectroscopy. TPD results revealed the presence of a monolayer state, with a desorption energy >10 kJ mol−1 larger than the multilayer. XPS data indicate that electron beam induced decomposition of adsorbed MeCpPtIVMe3 produced a carbonaceous film that contained Pt atoms in an electronic state intermediate between metallic Pt and Pt(IV). In addition to Pt(IV) reduction, electron beam irradiation was also accompanied by the evolution of methane and hydrogen from the adsorbate layer and the loss of C−H groups. The rate of Pt(IV) reduction and methane production and the loss of C−H groups from the film were all proportional to the MeCpPtIVMe3 coverage and the incident electr...
Characterization of Human Sclera Barrier Properties for Transscleral Delivery of Bevacizumab and Ranibizumab

The objectives of this study were to (a) investigate transscleral permeation of antivascular endothelial growth factor drugs bevacizumab and ranibizumab and (b) examine the effects of molecular structures of macromolecules upon permeation across human sclera using bevacizumab, ranibizumab, fluorescein isothiocyanate (FITC)-labeled bovine serum albumin (FITC-BSA), FITC-labeled ficoll (FITC-ficoll), and FITC-labeled dextrans (FITC-dextrans) in vitro. The hydrodynamic radii of the macromolecules were measured using dynamic light scattering, their partition coefficients to sclera were determined in uptake experiments, and their permeability coefficients and transport lag times across sclera were evaluated in transport experiments of side-by-side diffusion cells. Macromolecules showed relatively low partition coefficients to sclera. The partition coefficient of FITC-BSA was found to be related to its concentration in the equilibration solution, whereas for other macromolecules, no specific concentration dependency was observed. The macromolecules displayed relatively low permeability coefficients and long transport lag times because of their molecular sizes and hindered diffusion. Bevacizumab, ranibizumab, and FITC-BSA exhibited lower transscleral permeability and longer transport lag times than FITC-dextrans and FITC-ficoll of comparable molecular weights possibly because of the flexible structures of the polysaccharides. Thus, the polysaccharides may not be good surrogate permeants to model transscleral transport of therapeutic proteins in transscleral delivery studies.
Security evaluation of ES&S voting machines and election management system

This paper summarizes a security analysis of the DRE and optical scan voting systems manufactured by Election Systems and Software (ES&S), as used in Ohio (and many other jurisdictions inside and outside the US). We found numerous exploitable vulnerabilities in nearly every component of the ES&S system. These vulnerabilities enable attacks that could alter or forge precinct results, install corrupt firmware, and erase audit records. Our analysis focused on architectural issues in which the interactions between various software and hardware modules leads to systemic vulnerabilities that do not appear to be easily countered with election procedures or software updates. Despite a highly compressed schedule (ten weeks) during which we audited hundreds of thousands of lines of source code (much of which runs on custom hardware), we discovered numerous security flaws in the ES&S system that had escaped the notice of the certification authorities. We discuss our approach to the audit, which was part of Project EVEREST, commissioned by Ohio Secretary of State Jennifer Brunner.
Real time closed orbit correction system

A global closed-orbit feedback experiment based upon a real-time harmonic analysis of both the orbit movement and the correction magnetic fields is described. The harmonic feedback system was constructed and tested on the 750 MeV vacuum ultraviolet ring of the NSLS (National Synchrotron Light Source) and implemented on a real-time basis using relatively simple electronics. The feedback forces the coefficients of a few harmonics near the betatron tune to vanish and significantly improves the global orbit stability. The result of the experiment in the ring using four detectors and four trims, in which maximum observed displacement was reduced by a factor of between three and four, is presented. >
Characterization of G-protein Signaling in Ventricular Myocytes From the Adult Mouse Heart: Differences From the Rat

We have developed a high yield technique for isolating ventricular myocytes from adult mouse hearts. This collagenase-trypsin procedure yields 3-6x10(6)cells/heart. The cells are rod-shaped, roughly 20 microM x 100 microM and Ca(++)tolerant, with viability of 65-80%. Binding studies with [(125)I]ICYP demonstrate the presence of beta -adrenergic receptors at a density of 83 fmol/mg membrane protein. Assessment of the effects of the beta(1)-specific antagonist CGP 20712A on [(125)I]ICYP binding and on isoproterenol (ISO)-sensitive adenylyl cyclase activity indicates that 67% of the receptors are beta(1)and 33% are beta(2), compared to 16-20%beta(2)in rat myocytes. Mouse myocytes respond to isoproterenol to produce cyclic AMP with an EC(50) approximately 110+/-20 n M. A functional G(i)pathway is demonstrated by inhibition of ISO-stimulated cyclic AMP accumulation by endothelin, carbachol and ATP and by sensitivity of this inhibition to pertussis toxin. As assessed by inositol phosphate production, endothelin and ATP stimulate the activity of the G(q)-phospholipase C pathway, whereas carbachol, PGF(2 alpha)and alpha(1)-adrenergic receptor agonists show no significant effect. The inability of alpha(1)-adrenergic receptor agonists to induce phosphoinositide hydrolysis in mouse myocytes differs from a several fold alpha(1)-adrenergic activation that occurs in rat. Biochemical and pharmacological profiles, as well as the need for modifications in experimental design, indicate that mouse myocytes differ substantially from rat cardiac myocytes.
Failure of rapid atrial pacing in the conversion of atrial flutter.

Abstract Rapid atrial pacing, at rates of 150 to 600/min with stimulus strength up to 15 ma, was attempted in 15 patients with atrial flutter. In 13 of the patients, atrial capture was achieved with changes in both atrial and ventricular rates. In 7 of these, flutter resumed upon cessation of pacing. In the other 6, rapid atrial pacing produced atrial fibrillation which persisted until cardioversion. In 2 patients, atrial capture could not be obtained because of increased atrial refractoriness secondary to flutter. Thus, rapid atrial pacing was ineffective in converting atrial flutter to normal sinus rhythm in all 15 patients. This was in contrast to direct-current cardioversion which was successful in 12 of the patients, in all of whom stable sinus rhythm developed. The 3 patients who did not undergo cardioversion subsequently experienced spontaneous conversion to sinus rhythm. These results suggest that rapid atrial pacing has little place in the management of atrial flutter.
Initial effects of software process improvement on an experienced software development team

Discusses the initial stages of a long-term case study designed to examine the efforts of an experienced software development team in moving to a more process-driven software development environment. This team has previously produced software that has met functional, scheduling and cost criteria as specified by their customers. The software development manager, as directed by an organizational mandate, has initiated efforts to move this team into a more structured, formalism-based development and testing environment. The Capability Maturity Model (CMM) developed by the Software Engineering Institute (SEI) is being used as the model for this effort. The group dynamic and team development aspects of this effort are being carefully monitored to determine possible sources of resistance to change and to develop intervention "just-in-time" training sessions that can address identified problem areas, particularly those that may directly affect productivity, quality and scheduling. This paper discusses initial findings in this area and addresses them within the CMM framework.
Ionizing radiation and restriction enzymes induce microhomology-mediated illegitimate recombination in Saccharomyces cerevisiae

DNA double-strand breaks can be repaired by illegitimate recombination without extended sequence homology. A distinct mechanism namely microhomology-mediated recombination occurs between a few basepairs of homology that is associated with deletions. Ionizing radiation and restriction enzymes have been shown to increase the frequency of nonhomologous integration in yeast. However, the mechanism of such enhanced recombination events is not known. Here, we report that both ionizing radiation and restriction enzymes increase the frequency of microhomology-mediated integration. Irradiated yeast cells displayed 77% microhomology-mediated integration, compared to 27% in unirradiated cells. Radiation-induced integration exhibited lack of deletions at genomic insertion sites, implying that such events are likely to occur at undamaged sites. Restriction enzymes also enhanced integration events at random non-restriction sites via microhomology-mediated recombination. Furthermore, generation of a site-specific I-SceI-mediated double-strand break induces microhomology-mediated integration randomly throughout the genome. Taken together, these results suggest that double-strand breaks induce a genome-wide microhomology-mediated illegitimate recombination pathway that facilitates integration probably in trans at non-targeted sites and might be involved in generation of large deletions and other genomic rearrangements.
Text-Independent Speaker Verification in Embedded Environments

A low-resource, text-independent speaker verification (SV) system with an efficient voice model compression technique is described, including its implementation exclusively with integer arithmetic. We describe and discuss the individual algorithmic steps, the integer implementation issues and its error analysis. Performance of the system is evaluated on data collected with iPaq devices and the impact of model compression as well as integer approximation on the accuracy is discussed.
Long-Range GasP with Charge Relaxation

GasP circuit modules communicate handshake signals in two directions over a single state wire. The 2008 Infinity test chip demonstrated GasP in 90 nm CMOS operating at four giga data items per second, but revealed that state wires about 5000 lambda long retard operation by about 10%. Simulations reported in this paper show that GasP modules will tolerate surprisingly long state wires, albeit at reduced throughput. The modules appear to operate correctly with state wires whose delay exceeds the drive time. With such long wires, the receiving module waits until passive distribution of charge brings the wire within range of the receiver's switching threshold. Having put enough charge into the wire, or vice-versa removed enough charge from it,the sending module may proceed with its next task. This result applies equally to other single-track signaling methods.This behavior calls for a new kind of relative timing constraint to address when the wire charging or discharging process may cease rather than when the signal reaches the far end of the wire.
Identification of SV40 large T-antigen-associated proteins in cardiomyocytes from transgenic mice

A cell line derived from transgenic mice expressing the SV40 large T-antigen oncogene in the heart was used to identify cardiomyocyte targets for T-antigen binding. A novel protein of molecular mass of 193 kDa was identified as an associated protein by virtue of its ability to be co-immunoprecipitated with multiple anti-T-antigen antibodies. Two previously described proteins, p120 and p53, were also observed to complex with T-antigen in transformed cardiomyocytes. In addition, several proteins that cross-reacted with either anti-T-antigen or anti-p53 antibodies were identified. Two of these proteins, of apparent molecular masses of 250 and 110 kDa, were only observed in cardiomyocytes. Expression of a third cross-reacting protein of a molecular mass of 180 kDa appeared to be dependent on the growth status of the cells. These proteins may be important constituents of the cardiomyocyte cell cycle, as well as potential cellular targets for myocardial regeneration.
“Personal Truth” and the Essential Point of Communication

The analysis of “personal truth” — for is it a question of anything else? — has proved to be dependent on the conditions of human encounter. It seems that four principal modes can be distinguished according to which this encounter attempts to create a path for itself.