cssi/SciSciGPT-SciSciNet huggingface dataset:
Physical phantom studies of helical cone-beam CT with exact reconstruction.

Purpose: Onboard cone-beam computed tomography(CBCT) connected to radiotherapy linear accelerators suffers CT number consistency and uniformity problems in addition to limited longitudinal coverage. Such problems have prevented CBCT from being fully utilized in many quantitative applications including tumor response evaluation and daily radiationdose computation. This paper presents a feasibility study on the helical CBCT scan with exact reconstruction that could be a potential solution. Methods: A Varian TrueBeam treatment machine was programmed in the research mode to accomplish helical scans that required synchronized gantry circular rotation and couch table linear motion. Two physical phantoms were scanned in both 360° and 720° helical trajectories. A Katsevich exact reconstruction algorithm was implemented and tested with digital phantom simulations. It was further optimized to account for mechanical instabilities of both gantry rotation and couch table motion from the physical phantom measurements. Preprocessing was employed to correct photon scattering, beam hardening, and bowtie filtration. The reconstructed images were compared to those reconstructed from the FDK approximate reconstruction algorithm using the same phantom projections. Comparisons have also been made with the clinical circular CBCTimages and the diagnostic helical CTimages of the same physical phantoms. Results: Satisfactory reconstruction results were obtained for the Katsevich algorithm in digital phantom study. Physical phantom results demonstrated that a 360° helical scan could provide up to 19 cm longitudinal coverage, which could be increased to 54 cm with a 720° helical scan. Imagespatial resolution and soft tissue contrast were sufficient. The Q-value, which combined the spatial frequency response (modulation transfer function) and the imagenoise, was calculated, and suggested that the Katsevich algorithm was superior to the FDK algorithm. Conclusions: A helical CBCT scan is useful to extend the longitudinal coverage. The Katsevich exact reconstruction algorithm could provide additional advantages in image qualities over the traditional FDK approximate algorithm. The combination of helical CBCT scan with exact reconstruction was proved feasible and would render CBCT more useful in image-guided radiation therapy.
Computation of Dense Optical Flow with a Parametric Smoothness Model

A new algorithm is presented for the computation of dense optical flow and motion boundaries from an image sequence using two or more frames. The algorithm is based on a novel parametric smoothness model; it decomposes optical flow into irrotational and solenoidal fields, and imposes the smoothness constraint on each field separately. This model implies smooth translation and rotation of the underlying motion process. In contrast, the smoothness constraints used in all previous work do not distinguish the translational and rotational components but simply combine them as a whole. The derivation of the parametric smoothness model sheds new light on the interpretation of the conventional membrane model. The problem of oversmoothing across motion boundaries can be resolved to a high degree by successively improving the estimate of the parameters of the smoothness model. Significant improvements over classical gradient based methods have been obtained for a class of test problems by the proposed new algorithm.
Comprehensive management of type 2 diabetes.

Knowing which tests and treatment each patient needs is only one aspect of successful management of type 2 diabetes. lt is equally important to know which treatment the patient is willing to undertake, and to have in place a system for remembering when to test and for tracking what already has been done.
Pazopanib in sarcomas: expanding the PALETTE.

Purpose of review After failure of standard therapy, few effective treatment options exist for adult patients with metastatic sarcomas, and median survival remains dismal at approximately 1 year. Pazopanib, a multitargeted tyrosine kinase inhibitor, has recently been approved for nonadipocytic soft tissue sarcomas refractory to chemotherapy. In this review, we will revisit the efficacy of pazopanib in sarcomas, and present a patient case that illustrates two of many unanswered questions: which sarcoma patients are most likely to benefit from pazopanib therapy, and what criteria are best suited to accurately detect benefit in clinical trials?
Anxiety and Panic in Recreational Scuba Divers

Scuba diving is a high-risk sport; it is estimated that 3 to 9 deaths per 100 000 divers occur annually in the US alone, in addition to increasing numbers of cases of decompression illness each year. However, there has been a tendency within the diving community to de-emphasise the risks associated with scuba diving. While there are numerous factors responsible for the injuries and fatalities occurring in this sport, there is general consensus that many of these cases are caused by panic. There is also evidence that individuals who are characterised by elevated levels of trait anxiety are more likely to have greater state anxiety responses when exposed to a stressor, and hence, this sub-group of the diving population is at an increased level of risk. Efforts to demonstrate that selected interventions such as hypnosis, imagery, meditation and relaxation can reduce stress responses in anxious divers has not yielded consistent findings, and there is a need for systematic research dealing with the efficacy of selected intervention strategies.
Biomechanical Effects of Chiropractic-Based Distraction Therapy on the Behavior of Healthy and Degenerated Cervical Discs: A Finite Element Model Analysis

Many neck pain complaints are associated with degenerated discs in cervical spine. Disc degeneration (DD) consists of cascading stages of events with complex changes in disc tissue properties. This results in deterioration of the ability of the disc to perform its function normally. Several biomechanical and biochemical changes occur in the disc with degeneration. Increase in motion segment stiffness and peak stresses in the posterior annulus are some of the gross changes that occur in the disc with degeneration.Copyright © 2009 by ASME
Three-dimensional photoelastic investigations of circular cylinders with spherical cavities in axial loading: The experimental procedures, the stress distributions along different lines, as well as the comparison of the results with existing analytical solutions are included

This paper presents three-dimensional photoelastic studies of the stress distributions in circular cylinders with spherical cavities on their centerlines under tension and compression loadings. The experimental procedures, the stress distributions along different lines as well as the comparison of the results with existing analytical solutions are included.
Distinguishing depressive and negative symptoms in chronic schizophrenia.

In rating negative symptoms in chronic schizophrenia the Scale for the Assessment of Negative Symptoms showed less overlap with the Hamilton Rating Scale for Depression than the withdrawal-retardation subscale of the Brief Psychiatric Rating Scale. The distinction between depression and negative symptoms is best made by a careful evaluation of the patients’ mood and thoughts.
A RE-EVALUATION OF THE MASTOID REGION OF CONTEMPORARY AND FOSSIL MAN.

This study points out a heretofore unrecognized range of variation in the mastoid area, between modern and ancient man. The mastoid region of modern man was re-investigated and found to present a very different picture from fossil man. A trend was noted in modern man toward the enlargement of the mastoid process, the eruption of the juxtamastoid process in the digastric fossa and the absence of a pronounced occipitomastoid crest. The conditios were considerably differnt in Neanderthal man. In this group the area consisted of a small mastoid process, a spacious digastric fossa with no intervening juxtamastoid process and an occipitomastoid crest which exceeded or at least equaled, the projection of its mastoid process. This additional data emphasizes the cranial differences between modern man and Neanderthal man and suggests that the region should be re-evaluated in light of this new data.
DNA adducts as biomarkers for oxidative and genotoxic stress from pesticides in crop plants.

Plant studies have been carried out to identify the nature and extent of the formation of adducts with DNA bases when treated with pesticide formulations. DNA extracted from crop plants after treatment with pesticide formulations has yielded evidence of adduct formation. The extent of DNA modification has been established by 32P postlabeling studies. The radiochromatograms from 32P postlabeling of isolated plant DNA from grapes, bush beans, soybeans, pumpkins, and cucumbers show elevated adduct levels in treated vegetable plants as compared with untreated controls. A number of different adduct spots appear, likely indicating adduct formation with pesticide molecules or their metabolites. The DNA adducts from hexenal and 4-hydroxy-2-nonenal were clearly observed, indicating oxidative stress and lipid peroxidation in the plant.
Railway Time and Rubber Time

This article addresses the co-existence of rigid punctuality and a rubber-like flexibility in the Japanese conception of time. It examines how the clock and social norms shape the everyday use of time related to railways, work, and appointments in Japan. It demonstrates that multiple discourses of time and the complicated interactions among them create temporal complexity in which the seeming contradiction between rigidity and flexibility is compromised. The data derive from long-term participant-observation research among Japanese in Japan and abroad.
Ab initio study of aspartic and glutamic acid: Supplementary evidence for structural requirements at position 9 for glucagon activity

Abstract Our previous work established that position 9 aspartic acid in glucagon was a critical residue for transduction of the hormone response. An uncoupling of the binding interaction from adenylate cyclase activation was demonstrated by the observation that amino acid replacements at position 9 resulted in peptides that had no measurable adenylate cyclase activity yet were still recognized by the glucagon receptor. It was also later shown that His1 played a major role in activation, and it was suggested that an electrostatic interaction between the aspartic acid carboxylate and the histidine imidazole occurred as part of the activation mechanism. This did not preclude intermolecular interactions of this aspartic acid with other residues within the receptor binding site. The observation that a conservative substitution of glutamic acid for aspartic acid at position 9 was sufficient to result in the potent antagonist, des-His1d[Glu9]glucagon amide, implied that even glutamic acid possessed the minimum properties necessary for inhibition, and that the precise position of the carboxyl group at position 9 in glucagon was an absolute requirement for full agonist activity. The present investigation was conducted with ab initio calculations and molecular modeling to shed some light on the source of this phenomenon.
Convective instability of ferromagnetic fluids

Convective instability of a ferromagnetic fluid is predicted for a fluid layer heated from below in the presence of a uniform vertical magnetic field. Convection is caused by a spatial variation in magnetization which is induced when the magnetization of the fluid is a function of temperature and a temperature gradient is established across the layer. A linearized convective instability analysis predicts the critical temperature gradient when only the magnetic mechanism is important, as well as when both the magnetic and buoyancy mechanisms are operative. The magnetic mechanism predominates over the buoyancy mechanism in fluid layers about 1 mm thick. For a fluid layer contained between two free boundaries which are constrained flat, the exact solution is derived for some parameter values and oscillatory instability cannot occur. For rigid boundaries, approximate solutions for stationary instability are derived by the Galerkin method for a wide range of parameter values. It is shown that in this case the Galerkin method yields an eigenvalue which is stationary to small changes in the trial functions, because the Galerkin method is equivalent to an adjoint variational principle.
In vivo interactions of acrylonitrile with macromolecules in rats

Abstract The irreversible binding of [2,3- 14 C]acrylonitrile (VCN) to proteins, RNA and DNA of various tissues of male Sprague—Dawley rats after a single oral dose of 46.5 mg/kg (0.5 LD 50 ) has been studied. Proteins were isolated by chloroform-isoamyl alcohol-phenol extraction. RNA and DNA were separated by hydroxyapatite chromatography. Binding of VCN to proteins was extensive and was time dependent. Radioactivity in nucleic acids was registered in the liver and the target organs, stomach and brain. DNA alkylation, which increased by time, was significantly higher in the target organs, brain and stomach (119 and 81 pmol/mg, respectively, at 24 h) than that in the liver. The covalent binding indices for the liver, stomach and brain at 24 h after dosing were, 5.9, 51.9 and 65.3, respectively. These results suggest that VCN is able to act as a multipotent carcinogen by alkylation of DNA in the extrahepatic target tissues, stomach and brain.
Extrapair copulations reduce inbreeding for female red-backed fairy-wrens, Malurus melanocephalus

In many socially monogamous species, females copulate with and produce offspring sired by males other than their social mates, yet it remains controversial whether or how females benefit from these ‘extrapair’ copulations. Recently, it has been suggested that females might benefit if they are able to copulate with extrapair males that are genetically dissimilar to themselves, thereby potentially increasing the heterozygosity and/or reducing the level of inbreeding of the resulting offspring. However, empirical tests of this hypothesis have been criticized because a low number of molecular markers can lead to biased estimates of relatedness among individuals, and because all studies to date have been correlational and therefore unable to rule out potentially confounding factors. The red-backed fairy-wren is a bird with very limited dispersal, and hence the risks of inbreeding are high. We used a panel of microsatellite markers to examine paternity and relatedness between mates in this species, and also conducted an experiment that manipulated relatedness between a female and her social mate. Results from both approaches showed that females paired to genetically similar males were more likely to produce young sired by extrapair males, and that those offspring were less inbred (more heterozygous) than within-pair offspring. Thus, female fairy-wrens are able to avoid the potential costs of close inbreeding through extrapair copulations.
Association of laminin and other basement membrane components with regions of high acetylcholine receptor density on cultured myotubes.

Abstract The distribution of immunoreactivity to basement membrane components in cultures of rat skeletal myotubes was compared to acetylcholine receptor distribution by fluorescence microscopy. Laminin occurred in patches on the myotube surface, and most laminin patches coincided or overlapped with acetylcholine receptor aggregates. Almost all receptor aggregates coincided with laminin patches. Most of the heparan sulfate proteoglycan and fibronectin was associated with non-muscle cells, but some patches coincided with receptor aggregates on myotubes. In cultures treated with l -ascorbate, collagen types IV and V covered much of the myotube surface and receptor aggregates often coincided with intense collagen patches. When receptor aggregation was induced by treatment of cultures with soluble neural factors, the newly formed receptor aggregates coincided with laminin patches. The results suggest that each of the basement membrane components studied has a distinct distribution pattern in primary rat muscle cell cultures. The striking association of laminin immunoreactivity with receptor aggregates, together with the enhancement of receptor aggregation by laminin reported previously (Vogel et al., J. Neurosci . 3 , 1058–1068, 1983) suggests that laminin could have a role in the organization of acetylcholine receptors on developing muscle fibers.
The effect of linagliptin on glycaemic control and tolerability in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

Aim: Linagliptin is a new dipeptidyl peptidase-4 inhibitor recently approved for use in the USA. The objective of this systematic review and meta-analysis was to assess effect of linagliptin on glycaemic control, biomarkers and incidence of adverse events (AEs) in patients with type 2 diabetes mellitus. Methods: Five published and four unpublished randomized, clinical trials were identified from multiple databases. Qualitative assessments and quantitative analyses were performed. Results: Nine studies included 4246 participants with 53% men, 59.4% Caucasians, 38.7% Asians, and age range 45–69 years. Linagliptin was given as monotherapy (vs. placebo) or combined with metformin (vs. metformin + placebo), sulphonylurea (vs. sulphonylurea + placebo) or pioglitazone (vs. pioglitazone + placebo). Linagliptin 5 mg/day for 12–24 weeks, significantly reduced haemoglobin A1c (HbA1c) (−0.63%, p < 0.00001), fasting plasma glucose (FPG) (−1.01 mmol/l, p < 0.00001) and improved disposition index (DI, product of insulin sensitivity and acute insulin secretion) (p = 0.0001). Linagliptin monotherapy was not more effective than metformin at reducing HbA1c or FPG. Similar proportion of patients in linagliptin and placebo groups reported AEs including upper respiratory tract infections, headaches, nausea, hypertension and back pain. Conclusions: Linagliptin was associated with modest but significant reduction in HbA1c and FPG and improved DI after 12–24 weeks. Patients who would probably benefit most are those with HbA1c <9%, already on an active agent, compliant with weight reduction strategies, and can recognize and manage hypoglycaemia, fluid retention and upper respiratory tract infections. Long-term studies are needed to determine durability of response, incidence of microvascular and macrovacular complications, cost-effectiveness and safety.
Genetically Engineered Cells with Regulatable GABA Production Can Affect Afterdischarges and Behavioral Seizures After Transplantation into the Dentate Gyrus

Abstract Intractable seizures originating in the mesial temporal lobe can often be controlled by resection. An alternative to removing hippocampal tissue may be transplantation of GABA-producing cells. Neural cell transplantation has been performed in hundreds of patients, including some with temporal lobe epilepsy. This study evaluates the seizure-suppressing capabilities of engineered GABA-producing cells transplanted into the dentate gyrus. Immortalized neurons were engineered to produce GABA under the control of doxycycline. The cells were characterized for GABA production in vitro and for their ability to raise GABA concentrations in vivo . Cells were transplanted bilaterally into the dentate gyrus of rats and tested in two separate paradigms. Afterdischarge thresholds and durations were tested with granule cell stimulation, and the development of behavioral seizures, induced by daily electrical stimulation of the major excitatory input pathway into the dentate gyrus, was assessed in the presence, or the absence, of doxycycline. GABA production was under the tight control of doxycycline. Cells engineered to produce GABA raised tissue GABA concentrations in the hippocampus compared with non GABA-producing cells, and this was abolished when doxycycline was administered. GABA-producing cells raised the threshold, and shortened the duration of hippocampal afterdischarges elicited by granule cell stimulation. Lastly, the appearance of stage 5 seizures was slowed in the kindling paradigm, compared with a group that received non-GABA-producing cells, and compared with a group that received GABA-producing cells but was administered doxycycline. This study shows that targeted hippocampal implants of genetically engineered cells have the potential to raise GABA levels and to affect seizure development. The ability to suppress the production of GABA, and to modulate the physiological effects of the transplanted cells provides an important level of experimental control. These techniques, combined with stem cell technology, may advance cell-based therapies for epilepsy and other diseases of the CNS.
The impulse response and time dependent force on a baffled circular piston and a sphere

The time dependent force on the surface of an acoustic radiator which is vibrating with a uniform velocity is expressed as the convolution of the surface velocity with an appropriately defined impulse response. Since the impulse response is equivalent to the inverse Fourier transform of the acoustic radiation impedance, the impulse response for particular vibrators whose radiation impedance is known can be obtained directly from the impedance. To illustrate the approach the impulse response for a baffled circular piston and a pulsating sphere are obtained from their respective radiation impedances. Both impulse responses exhibit the same initial behavior, i.e., a Dirac delta function at time zero; however, their subsequent time histories are considerably different. The time dependent forces on both the piston and sphere are investigated for pulsed velocities and the results are compared to classical steady-state results.
Malate dehydrogenase isozymes of the marine snail, Ilyanassa obsoleta

Abstract Malate dehydrogenase (MDH) exists in several isozymic forms in the marine snail, Ilyanassa obsoleta. The isozymes may be classified in two distinct groups, mitochondrial and supernatant. The kinetic properties of these two groups of MDH's resemble those reported for mammalian and avian MDH's except that the relative electrophoretic mobilities of the two groups of isozymes are reversed. The organs of I. obsoleta all contain the same MDH isozymes as revealed by starch gel electrophoresis of organ homogenates. However, quantitative differences in relative abundance were commonly observed, but these differences may be artifacts of preparation since they were not repeatable. All of the supernatant MDH isozymes were apparently of the same molecular weight and were all convertible to a single form by prolonged exposure to 2-mercaptoethanol. This conversion was reversible by removal of the mercaptoethanol. However, the mitochondrial MDH isozymes were not affected by mercaptoethanol. Comparisons of Ilyanassa and pig heart mitochondrial and supernatant MDH isozymes showed parallel responses to mercaptoethanol by the homologous preparations from the two species.
Depressurization of natural gas hydrates in berea sandstone cores

D. W. Davidsonet al. [7] were among the first to recognize significant deposits of natural gas clathrate hydrates in the Western Hemisphere. This work discusses the recovery of gas from such deposits, through laboratory measurement and modeling of a depressurization scheme. The work provides a determination of the volume of gas produced and the position of the hydrate interface, as a function of time when a hydrate-containing core is depressurized. A moving boundary model is shown to provide a satisfactory fit to hydrate dissociation measurements. Qualitative information is provided concerning hydrate formation in Berea Sandstone cores.
Plant Biotechnology Patents: Applications in Agriculture and Medicine

Recent advances in agricultural biotechnology have enabled the field of plant biology to move forward in great leaps and bounds. In particular, recent breakthroughs in molecular biology, plant genomics and crop science have brought about a paradigm shift of thought regarding the manner by which plants can be utilized both in agriculture and in medicine. Besides the more well known improvements in agronomic traits of crops such as disease resistance and drought tolerance, plants can now be associated with topics as diverse as biofuel production, phytoremediation, the improvement of nutritional qualities in edible plants, the identification of compounds for medicinal purposes in plants and the use of plants as therapeutic protein production platforms. This diversification of plant science has been accompanied by the great abundance of new patents issued in these fields and, as many of these inventions approach commercial realization, the subsequent increase in agriculturally-based industries. While this review chapter is written primarily for plant scientists who have great interest in the new directions being taken with respect to applications in agricultural biotechnology, those in other disciplines, such as medical researchers, environmental scientists and engineers, may find significant value in reading this article as well. The review attempts to provide an overview of the most recent patents issued for plant biotechnology with respect to both agriculture and medicine. The chapter concludes with the proposal that the combined driving forces of climate change, as well as the ever increasing needs for clean energy and food security will play a pivotal role in leading the direction for applied plant biotechnology research in the future.
Integrating Computational and Biochemical Studies to Explore Mechanisms in NF-κB Signaling

Signal transduction networks regulate cellular function and respond to changes in intra- and intercellular environments. They control both homeostatic and stimulus-induced responses. However, the role and importance of individual network components in the function of the network are often difficult to discern. This is evident when a genetic deletion or mutation does not show an expected phenotype or when a pharmacological treatment has surprising effects. Computational simulations with networks reconstructed in silico as mathematical equations enable functional analysis of network behavior and are well suited to complement in vivo and in vitro studies (1–4). The utility of integrating experimental and computational methodologies derives from the iterative application of each approach to inform the other. Experimental analyses provide critical insight to select the components and reactions to include in the computational model and to constrain the simulation parameters. In turn, the computational analyses provide mechanistic insights to drive further experimental analyses. Studies of the lac operon in Escherichia coli are often cited as original examples of this integrated approach wherein a simple set of mathematical equations was sufficient to account for the transcriptional negative feedback of the lac operon (5). In eukaryotic systems, developmental, cell cycle control, and circadian rhythm processes in several organisms have been examined and validated in silico (6–10). Models of protein kinase cascades have produced important insights such as amplification and temporal fidelity, bistability, and signaling cross-talk (11). More recently, advances in systems biology have produced increasingly complete cellular parts lists that have enabled statistical modeling to reconstruct large scale molecular networks (12, 13). However, the resulting models are largely non-quantitative and do not consider the temporal dimension, although these aspects are essential to biological regulation (4). With top-down network reconstruction efforts identifying functional modules, traditional biochemical bottom-up approaches are critical for providing mechanistic detail. This is where kinetic computational modeling of molecular networks may function as an important bridge for these distinct approaches.
Differentiating Germline vs Somatic Variants in Cancer Tissue: Are Large-Panel Genetic Tests Helping or Hurting the Cancer Patient?

The increased use of next-generation sequencing (NGS)2 and increased understanding of tumor genetics have led to the identification of safer and more effective anticancer therapies. Unfortunately, solid tumors are genetically diverse, limiting the efficacy of targeted therapies to subsets of patients having specific genomic profiles. As a result, comprehensive genetic testing using NGS gene panels is becoming more common to help clinicians select appropriate therapies. A recent article in Science Translational Medicine (1) suggests that testing only tumor DNA and not germline DNA may lead to inappropriate administration of cancer therapies, resulting in patient safety concerns and increased healthcare costs. This study assessed 815 tumor-normal paired samples using either exome sequencing or a targeted 111-gene panel from patients with 15 different tumor types. …
Deconvolution Technique For The Improvement Of Contrast Of Image Intensifiers

A mathematical filter which improves the contrast response of image intensifiers is derived. The filter is obtained by inverting the point spread function (PSF) of the system. A point spread function which takes into account the spread of light in the image intensi-fier system is proposed using physical arguments. The PSF has two parameters which are the range and the fraction of light which spreads. These two parameters are determined by a least squares fit to the experimentally measured data. The inverse filter is used in the deconvolution of video images. The results indicate that a substantial improvement in the contrast ratio of the system can be achieved by this technique.*
Standard Of Measurement For Student Evaluation Instruments

For colleges and universities, the expectation for excellence in teaching and learning has made development of a system for measuring teaching effectiveness critical. Teaching effectiveness is generally assessed with a comprehensive review of skills including instructional design, instructional delivery and course management. This requires student feedback usually in the form of Student Evaluation Instruments (SEIs). Since SEIs are an important part of measuring teaching effectiveness to assess excellence, and excellence in the classroom is expected when considering promotion and tenure, it follows that they play an integral role in the promotion and tenure process. In fact, faculty promotions and the issuance of tenure may hinge on the results of these vital evaluations. Our study investigates the use of SEIs at our university’s School of Business. Unlike many other prior studies, limited to a single course or department and a single semester, we examined data collected from the use during six semesters (three years) of our Student Evaluation Instrument for the entire School of Business. The results yielded nearly 30,000 useable responses across all business majors. If SEIs are to be used effectively and fairly then one must have a clear understanding as to what should be the appropriate standard used to evaluate faculty teaching effectiveness. Should a global value – the mean for the entire school or university – be used or should it be based on the mean for each department? We believe this to be a critical consideration given the potential for differences in mean ratings amongst departments.
A Model of DNA Repeat-Assembled Mitotic Chromosomal Skeleton

Despite intensive investigation for decades, the principle of higher-order organization of mitotic chromosomes is unclear. Here, I describe a novel model that emphasizes a critical role of interactions of homologous DNA repeats (repetitive elements; repetitive sequences) in mitotic chromosome architecture. According to the model, DNA repeats are assembled, via repeat interactions (pairing), into compact core structures that govern the arrangement of chromatins in mitotic chromosomes. Tandem repeat assemblies form a chromosomal axis to coordinate chromatins in the longitudinal dimension, while dispersed repeat assemblies form chromosomal nodes around the axis to organize chromatins in the halo. The chromosomal axis and nodes constitute a firm skeleton on which non-skeletal chromatins can be anchored, folded, and supercoiled.
Incidental Findings in Genetics Research Using Archived DNA

There are countless variations on this theme. The call can come from one of your own physicians who was called by the investigator. Your physician may or may not be well informed on what the reported finding about Disease Y means or how to respond. DNA testing can reveal more than susceptibility to disease. People can learn that they do not have the biological connections — parentage or evidence of ethnic origin — that they thought they did. Colleagues who serve on the Institutional Review Board (IRB) in my institution tell me that they currently do not permit “cold calls” of the type portrayed in the opening paragraph. Such direct contacts have, however, occurred in the past, with or without the blessing of an IRB. Sharing findings with the individual’s physician, who is then supposed to serve as a learned and wise intermediary, is not without problems either, given that many physicians understand little about complex genetics. Yet the very existence of this project on managing incidental findings in research demonstrates that some people believe that some research findings ought to be available to participants.
Fibroblast growth factor inducible 14 as potential target in patients with alcoholic hepatitis

Alcoholic hepatitis is a distinct clinical entity characterised by jaundice and liver failure that generally occurs after decades of heavy alcohol use. Recovery from alcoholic hepatitis is determined by abstinence from alcohol, the presence of mild clinical symptoms and the implementation of appropriate therapy. Unfortunately, patients with severe alcoholic hepatitis have a high mortality rate of about 40% to 50% despite optimal medical management.1 A significant percentage of patients succumb to bacterial infections with infection-attributed mortality of 12% to 54%2 underscoring the importance of bacterial translocation and an impaired immune response. Moreover, patients with alcoholic hepatitis have a profound, often sepsis-like hyper-inflammatory state which suggests the possibility that proinflammatory mediators such as cytokines contribute to alcoholic hepatitis by promoting systemic inflammation and systemic inflammatory response syndrome. Tumour necrosis factor α (TNFα) has been proposed to be the critical cytokine involved in the pathogenesis of alcoholic hepatitis, which is mostly based on animal models of experimental alcoholic liver disease.3 Inhibition of TNFα attenuates alcoholic liver injury in rats.4 Elevated plasma TNFα is a significant predictor of decreased long-term survival in patients with severe alcoholic hepatitis.5 However, clinical trials using an anti-TNFα strategy resulted in disappointing outcomes.6 ,7 In patients with moderate to severe alcoholic hepatitis, etanercept was associated …
Pre-calculated protein structure alignments at the RCSB PDB website

Summary: With the continuous growth of the RCSB Protein Data Bank (PDB), providing an up-to-date systematic structure comparison of all protein structures poses an ever growing challenge. Here, we present a comparison tool for calculating both 1D protein sequence and 3D protein structure alignments. This tool supports various applications at the RCSB PDB website. First, a structure alignment web service calculates pairwise alignments. Second, a stand-alone application runs alignments locally and visualizes the results. Third, pre-calculated 3D structure comparisons for the whole PDB are provided and updated on a weekly basis. These three applications allow users to discover novel relationships between proteins available either at the RCSB PDB or provided by the user. Availability and Implementation: A web user interface is available at http://www.rcsb.org/pdb/workbench/workbench.do. The source code is available under the LGPL license from http://www.biojava.org. A source bundle, prepared for local execution, is available from http://source.rcsb.org Contact:[email protected]; [email protected]
Evaluation of a brief intervention designed to increase CPR training among pregnant pool owners

This study evaluated whether a brief videotape could motivate pregnant pool owners to be trained in infant/child cardiopulmonary resuscitation (CPR). Women were recruited from prenatal classes in South Florida. Eligible volunteers were randomized to view a video or receive standard treatment, after completing a questionnaire. The video explained toddler drowning risk, as well as the value of isolation pool fencing and CPR training. Women were contacted by phone 6 months after giving birth to complete a follow-up survey. Sixty-one percent of eligible mothers agreed to study enrollment and 92% of those completed a follow-up interview (n = 101). At baseline, there was no significant difference between the proportion of mothers with current CPR training in the treatment and control groups. At follow-up, 48% of those in the intervention group reported CPR instruction versus 28% of the control group (x(2) = 3.93, P = 0.03). Video viewers were also more likely to report significant changes in perceptions that favored CPR training. Health care facilities located in communities with high rates of toddler drowning may want to screen prenatal students for pool ownership and encourage at-risk families to be trained in infant/child CPR. Such programs should, however, emphasize the primacy of isolation fencing as a preventive measure. Language: en
Modeling and 6-DOF vibration reduction for a spacecraft with precision sensors

A mathematical model of a six-degree-of-freedom hexapod system for vibration isolation was derived in the discretetime domain on the basis of the experimental data obtained from a satellite. Using Box-Jenkins model structure, the transfer functions between six piezoelectric actuator input voltages and six geophone sensor output voltages are identified empirically. The 6x6 transfer function matrix is symmetric, and its off-diagonal terms indicate the coupling among different inputJoutput channels. A model of transmissibility matrix relating tri-axial geophones on the base and the platform was also developed to identify other important comer frequencies. Using multi-input multi-output control techniques such as Linear Quadratic Gaussian and H", high-order controllers were developed. The simulation results using these controllers obtain 33 dB, and 12 dB vibration attenuation at 5, and 25 Hz corner frequencies, respectively.
Structure of an LDLR-RAP Complex Reveals a General Mode for Ligand Recognition by Lipoprotein Receptors

Proteins of the low-density lipoprotein receptor (LDLR) family are remarkable in their ability to bind an extremely diverse range of protein and lipoprotein ligands, yet the basis for ligand recognition is poorly understood. Here, we report the 1.26 A X-ray structure of a complex between a two-module region of the ligand binding domain of the LDLR and the third domain of RAP, an escort protein for LDLR family members. The RAP domain forms a three-helix bundle with two docking sites, one for each LDLR module. The mode of recognition at each site is virtually identical: three conserved, calcium-coordinating acidic residues from each LDLR module encircle a lysine side chain protruding from the second helix of RAP. This metal-dependent mode of electrostatic recognition, together with avidity effects resulting from the use of multiple sites, represents a general binding strategy likely to apply in the binding of other basic ligands to LDLR family proteins.
Abnormal papillary muscle morphology is independently associated with increased left ventricular outflow tract obstruction in hypertrophic cardiomyopathy

Background: Abnormal papillary muscles (PM) are often found in hypertrophic cardiomyopathy (HCM). Objective: To assess the relationship between morphological alterations of PM in patients with HCM and left ventricular outflow tract (LVOT) obstruction, using magnetic resonance imaging (MRI) and echocardiography. Methods: Fifty-six patients with HCM (mean age 42 years (interquartile range 27, 51), 70% male) and 30 controls (mean age (42 (30, 53) years, 80% male) underwent MRI on a 1.5 T scanner (Siemens, Erlangen, Germany). Standard cine images were obtained in short-axis (base to apex), along with two-, three- and four-chamber views. The presence of bifid PM (none, one or both) and anteroapical displacement of anterolateral PM was recorded by MRI and correlated with resting LVOT gradients obtained by echocardiography. Results: Double bifid PM (70% vs 17%) and anteroapical displacement of anterolateral PM (77% vs 17%) were more prevalent in patients with HCM than in controls (p Conclusions: Patients with HCM with abnormal PM have a higher degree of resting LVOT gradient, which is independent of septal thickness.
From biochemical and structural studies of soluble guanylate cyclase toward drug design

The heterodimeric haemoprotein soluble guanylate cyclase (sGC) is the direct sensor and mediator of nitric oxide (NO) signal transduction via the NO-sGC-cGMP pathway. Aberrant sGC-dependent signalling may be fundamental to the aetiology of a wide variety of cardiovascular pathologies. As a consequence, compounds that activate cGMP production by sGC have a considerable therapeutic potential. To date, x-ray structures of independent sGC domains HNOX, HNOX-A and GC have been solved. Nevertheless, the determination of the full-length sGC x-ray structure would provide additional clues to understand the structural basis for the mechanism of sGC assembly and regulation and should facilitate the design of these therapeutic agents. To achieve this goal, I developed a heterologous expression system of full-length bovine sGC (Fl-sGC). Early attempts to produce recombinant bovine sGC in E. coli resulted in misfolded protein accumulation. Indeed, producing soluble protein in Escherichia coli is still a major difficulty in the sGC field. By using fusion technology, I successfully overexpressed both α and β subunits in a soluble heme-bound active form. Optimization of expression levels by varying bacterial growth conditions including temperature, media, additives and induction, will be followed by purification and characterization of Fl-sGC. So, a crucial step has been achieved, allowing us to pursue structural studies to probe the structure and mechanism of sGC and promote the discovery of stimulators of this physiologically important enzyme.
A two-stage algorithm for enhancement of reverberant speech

Room reverberation causes two perceptual distortions on clean speech: coloration and long-term reverberation. These two effects correspond to two physical variables: signal-to-reverberant energy ratio (SRR) and reverberation time, respectively. Based on this observation, we propose a two-stage algorithm that enhances reverberant speech from one-microphone recordings. In the first stage, an inverse filter is estimated to reduce coloration effects or increase SRR. The second stage employs spectral subtraction to minimize the influence of long-term reverberation. The proposed algorithm significantly improves the quality of reverberant speech. A comparison with a recent one-microphone enhancement algorithm shows that our system produces significantly better results.
WS-trustworthy: a framework for Web services centered trustworthy computing

The emerging paradigm of Web services has been gaining significant momentum in the recent years since it offers a promising way to facilitate business-to-business (B2B) collaboration. However, it is not clear that this new model of Web services provides any measurable increase in computing trustworthiness. We propose a generic framework to control the trustworthiness of computing in the domain of Web services. A layered model is established to highlight four key elements: resources, policies, validation processes, and management. The robustness of this model exhibits its flexibility and extensibility. Examples utilizing our framework are reported.
Raising the intelligence stakes: Corporate information warfare and strategic surprise

In war as in business, surprise can be a powerful strategic weapon. This article draws parallels between military and business planning, and explores the role of strategic intelligence in achieving and preempting surprise in the commercial marketplace. Sherman Kent (1949) defined strategic intelligence as the “kind of knowledge a state must possess regarding other states in order to assure itself that its causes will not suffer nor its undertakings fail because its statesmen and soldiers plan and act in ignorance.” With one or two word changes (business/organization for state; executives/managers for statesmen/soldiers), this definition could apply equally well to the world of business. In highly competitive global markets, ignorance of other players' actions or of developments in the wider business environment can prove costly. The chances of achieving, and/or being subjected to, strategic surprise have increased correlatively with the growth of networked, multinational organizations and electronic commerce. In an age of information warfare, strategic surprise has become virtually synonymous with technological surprise, thereby putting a premium on high-grade intelligence and threat assessment. © 1999 John Wiley & Sons, Inc.
Costal2, a Novel Kinesin-Related Protein in the Hedgehog Signaling Pathway

The Hedgehog (HH) signaling proteins control cell fates and patterning during animal development. In Drosophila, HH protein induces the transcription of target genes encoding secondary signals such as DPP and WG proteins by opposing a repressor system. The repressors include Costal2, protein kinase A, and the HH receptor Patched. Like HH, the kinase Fused and the transcription factor Cubitus interruptus (CI) act positively upon targets. Here we show that costal2 encodes a kinesin-related protein that accumulates preferentially in cells capable of responding to HH. COS2 is cytoplasmic and binds microtubules. We find that CI associates with COS2 in a large protein complex, suggesting that COS2 directly controls the activity of CI.
The Effect of Fingolimod on Conversion of Acute Gadolinium-Enhancing Lesions to Chronic T1 Hypointensities in Multiple Sclerosis

BACKGROUND Brain lesions converting to chronic T1 hypointensities (“chronic black holes” [CBH]), indicate severe tissue destruction (axonal loss and irreversible demyelination) in multiple sclerosis (MS). Two mechanisms by which fingolimod could limit MS lesion evolution include sequestration of lymphocytes in the periphery or direct neuroprotective effects. We investigated the effect of fingolimod on the evolution of acute gadolinium-enhancing (Gd+) brain lesions to CBH in patients with MS. METHODS This was a retrospective nonrandomized comparison of patients with Gd+ brain lesions at the time of starting oral fingolimod [.5 mg/day, n = 26, age (mean ± SD) 39.2 ± 10.6 years, Expanded Disability Status Scale (EDSS) score - median (range): 1.75 (0, 6.5)] to those on no therapy [n = 30, age 41.7 ± 9.3 years; EDSS 1.0 (0, 6)]. Each lesion was classified by whether it converted to a CBH in the year following treatment. RESULTS In the fingolimod group, 99 Gd+ baseline lesions (mean ± SD, range: 3.8 ± 5.1; 1, 21 per patient) were identified of which 25 (25%) evolved to CBH (1.0 ± 2.0; 0, 10 per patient). The untreated group had 62 baseline Gd+ lesions (2.1 ± 2.3; 1, 13), 26 (42%) of which evolved to CBH (.9 ± 1.4; 0, 7) (P = .063). Thirteen patients (50%) receiving fingolimod and 17 untreated patients (57%) developed CBH (P = .79). CONCLUSION This pilot study shows a trend of fingolimod on reducing the conversion rate from acute to chronic destructive MS lesions. Such an effect awaits verification in larger randomized prospective studies.