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At least 235 records · Page 13Linked to original sources
PubMed1993

Crystal structure of TGF-beta 2 refined at 1.8 A resolution.

The crystal structure of TGF-beta 2 has been refined using data collected with synchrotron radiation (CHESS) to 1.8 A resolution with a residual R (= sigma magnitude of Fo-magnitude of Fc/sigma magnitude of Fo) factor of 17.3%. The model consists of 890 protein atoms from all 112 residues and 59 water molecules. The monomer of TGF-beta 2 assumes a rather extended conformation and lacks a well-defined hydrophobic core. Surface accessibility calculations show only 44% of the nonpolar surface is buried in the monomer. In contrast, 55.8% of the nonpolar surface area is buried when the two monomers form a dimer, a typical value for globular proteins. This includes a 1300 A2 buried interface area that is largely hydrophobic. Sequence comparisons using a profile derived from the refined TGF-beta 2 structure suggest that the cluster of four disulfides (three intramonomeric disulfide bonds 15-78, 44-109, 48-111 forming a disulfide knot, and one intermonomeric disulfide 77-77) together with the extended beta strand region constitutes the conserved structural motif for the TGF-beta superfamily. This structural motif, without the 77-77 disulfide bond, defines also the common fold for a general family of growth factors, including the nerve growth factor and platelet-derived growth factor families. The fold is conserved only at the monomer level, while the active forms are dimers, suggesting that dimerization plays an important role in regulating the binding of these cytokines to their receptors and in modulating the biological responses.

Crystallography, X-Ray↗
PubMed2000

Rapid MR imaging of cryoprotectant permeation in an engineered dermal replacement.

Magnetic resonance (MR) imaging is a powerful technique for monitoring the permeation of cryoprotective agents (CPAs) inside tissues. However, the techniques published until now suffer from inherently long imaging times, limiting the application of these techniques to slow diffusion processes and large CPA concentrations. In this study, we present a rapid MR imaging technique based on a CHESS-FLASH scheme combined with Keyhole image acquisition. This technique can image the fast permeation of Me(2)SO solutions into freeze-dried artificial dermal replacements for concentrations down to 10% v/v. Special attention is given to evaluating the technique for quantitative analysis.

Cryopreservation↗
PubMed1996

Atomic structure of the degraded procapsid particle of the bacteriophage G4: induced structural changes in the presence of calcium ions and functional implications.

Bacteriophage G4 and phiX174 are members of the Microviridae family. The degree of similarity of the structural proteins ranges from 66% identity of the F protein to 40% identity of the G protein. The atomic structure of the phiX174 virion had previously been determined by X-ray crystallography. Bacteriophage G4 procapsids, consisting of the structural proteins F, G, D, B, H, and small traces of J but no DNA, were set up for crystallization. However, the resultant crystals were of degraded procapsid particles, which had lost the assembly scaffolding proteins D and B, resulting in particles that resembled empty virions. The structure of the degraded G4 procapsid has been determined to 3.0 angstrom resolution. The particles crystallized in the hexagonal space group P6(3)22 with unit cell dimensions a=b=414.2(5) angstrom and c=263.0(3) angstrom. The diffraction data were collected at the Cornell High Energy Synchrotron Source (CHESS) on film and image plates using oscillation photography. Packing considerations indicated there were two particles per unit cell. A self-rotation function confirmed that the particles were positioned on 32 point group special positions in the unit cell. Initial phases were calculated to 6 angstrom resolution, based on the known phiX174 virion model. Phase information was then extended in steps to 3.0 angstrom resolution by molecular replacement electron density modification and particle envelope generation. The resulting electron density map was readily interpretable in terms of the F and G polypeptides, as occur in the mature capsid of phiX174. In a few regions of the electron density map there were inconsistencies between the density and the published amino acid sequence. Redetermining the amino acid sequence confirmed that the density was correct. The r.m.s. deviation between the Calpha backbone of the mature capsid of phiX174 and the degraded G4 procapsid was 0.36 angstrom for the F protein and 1.38 angstrom for the G protein. This is consistent with the greater conservation of the F protein compared to the G protein sequences among members of the Microviridae family. Functionally important features between phiX174 and G4 had greater conservation. Calcium ions (Ca2+) were shown to bind to G4 at a general site located near the icosahedral 3-fold axis on the F protein capsid, equivalent to sites found previously in phiX174. Binding of Ca2+ also caused the ordering of the conserved region of the DNA binding protein J, which was present in the degraded procapsid particle in the absence of DNA.

Amino Acid Sequence↗
PubMed2001

Low-power water suppression by hyperbolic secant pulses with controlled offsets and delays (WASHCODE).

A class of chemical-shift-selective (CHESS) water suppression (WS) schemes is presented in which the characteristic frequency-domain excitation profiles of "adiabatic" full-passage (AFP) RF pulses are utilized for frequency-selective excitation of the water resonance. In the proposed WS schemes, dubbed WASHCODE, hyperbolic secant (HS) pulses were used as the AFP pulses. Besides the high immunity of WS efficiency toward B(1) inhomogeneity, these sequences also exhibit extraordinary insensitivity to the dispersion of the water T(1) relaxation times. The actual performance of the proposed WS schemes was achieved in particular by optimizing the frequency offsets of WS HS pulses and the time intervals between them. To reduce the RF power requirements of these WS sequences for in vivo applications, HS pulses with the minimum possible frequency bandwidths were employed, which also substantially reduced the adverse effects on the observed proton MR spectra. The proposed WS schemes were evaluated by simulations based on the Bloch equations. Several WS sequences which looked particularly promising were verified experimentally on the human brain on a 3 T MR scanner using very short echo-time STEAM for volume selection and a standard single-loop surface coil for both signal transmission and reception. Routinely, water-suppression factors ranging from 2000 to 4000 were achieved in vivo without additional adjustment of parameters for individual subjects and without violating legal safety limits.

Brain↗
PubMed1998

The endovascular treatment of brain arteriovenous malformations.

Advances in superselective microcatheterization techniques, which took place in the past decade, established superselective endovascular exploration as an integral and indispensable tool in the pretherapeutic evaluation of brain AVMs. The strict and routine application of superselective angiography furthered our knowledge on the angioarchitecture of brain AVMs, including vascular composition of the nidus, types of feeding arteries and types and patterns of venous drainage. In addition, various types of weak angioarchitectural elements, such as flow-related aneurysms, intranidal vascular cavities and varix formation proximal to high-grade stenosis of draining veins, could be identified as factors predisposing for AVM rupture. A wide spectrum of secondary angiomorphological changes induced by the arteriovenous shunt of the nidus and occurring up- and downstream of the nidus have been identified as manifestations of high-flow angiopathy. These data help to better predict the natural history, understand the widely variable clinical presentation and to define therapeutic targets of brain AVMs. Correlation of the topography of the AVM as demonstrated by MR with the angioarchitecture as demonstrated by superselective angiography provided a system for topographic-vascular classification of brain AVMs, which proved very useful for patient selection and definition of therapeutic goals. This study showed, that 40% of patients with brain AVMs can be cured by embolization alone with a severe morbidity of 1.3% and a mortality of 1.3%. Part of theses patients can, however, be cured equally effective by microsurgery or radiosurgery. Which modality will be chosen for a particular patient will mainly depend on the locally available expertise and experience, but also on the preference of the patient following its comprehensive information about the chances for cure and the risks associated with each of these therapeutic modalities. Embolization has a significant role in the multimodality treatment of brain AVMs, by either enabling or facilitating subsequent microsurgical or radiosurgical treatment. Appropriately targeted embolization in otherwise untreatable AVMs represents a reasonable form of palliative treatment of either ameliorating the clinical condition of the patient or reducing the potential risk of hemorrhage. Regarding the practical aspects of the endovascular treatment the following conclusions could be drawn from the experience obtained with this series of 387 patients with a brain AVM: (1) The goal of endovascular treatment should be defined prior to the procedure. This does not preclude a change in the goal, if additional information obtained during the procedure make this necessary. (2) The result of endovascular treatment of a brain AVM in terms of the degree of obliteration achieved and complication rate depends mainly on the endovascular strategy developed and the technique applied. These depend on the specific angioarchitecture and topography of the individual AVM, on the past history and clinical presentation of the patient and on the predefined goal of embolization. The strategy should include the definition of embolization targets, the selection of the most appropriate approach for endovascular navigation, the determination of the sequence of catheterization of individual feeding arteries, the selection of the type of catheters and microcatheters, the selection of the appropriate embolic materials as well as the site and mode of their delivery. Thereafter, every endovascular move should be, as in a chess game, the result of a logical plan. (3) Atraumatic superselective microcatheterization is a key point in the endovascular treatment of brain AVMs. It requires manual skills, knowledge of anatomy and respect for the vascular wall. (4) All locations of brain AVMs should be regarded as eloquent, and no distinction should be made between eloquent and non-eloquent areas of the brain when deciding on the execution of embolizatio

Adolescent↗
PubMed1987

Darwinian evolution in games with perfect information.

We consider a model of Darwinian evolution in games with perfect information like chess or checkers. The evolution is viewed as a sequence of strategies, each of which wins over its immediate predecessor. We argue that the intelligence level of strategies need not necessarily increase during this type of evolution.

Algorithms↗
PubMed1989

Model of respiratory sinus arrhythmia in man.

The first section of the model delineates the parasympathetic signal as a function of the interaction between the respiratory and the vagal neurones of the common brainstem network. The second section is a version of Chess and Calaresu's description of the vagus/heart period system in the sympathetically blocked cat. The sympathetic influence is introduced in the third section, taking into account the autonomic effects on the transmembrane potential of the sinoatrial pacemaker as found in the rabbit. The model was implemented on a dedicated analogue computer with an accuracy of 1 per cent. The concordance between the analogue and the breathing/respiratory sinus arrhythmia (RSA) system in humans was studied using simulated respiratory signals. The results confirm the central origin of the RSA as a meaningful modelling premise and indicate the dependence of the RSA amplitude on the operating point of the vagus.

Animals↗
PubMed1991

Structure of bovine prothrombin fragment 1 refined at 2.25 A resolution.

The structure of bovine prothrombin fragment 1 has been refined at 2.25 A resolution using high resolution measurements made with the synchrotron beam at CHESS. The synchrotron data were collected photographically by oscillation methods (R-merge = 0.08). These were combined with lower order diffractometer data for refinement purposes. The structure was refined using restrained least-squares methods with the program PROLSQ to a crystallographic R-value of 0.175. The structure includes 105 water molecules with occupancies of greater than 0.6. The first 35 residues (Ala1-Leu35) of the N-terminal gamma-carboxy glutamic acid-domain (Ala1-Cys48) of fragment 1 are disordered as are two carbohydrate chains of Mr approximately 5000; the latter two combine to render 40% of the structure disordered. The folding of the kringle of fragment 1 is related to the close intramolecular contact between the inner loop disulfide groups. Half of the conserved sequence of the kringle forms an inner core surrounding these disulfide groups. The remainder of the sequence conservation is associated with the many turns of the main chain. The Pro95 residue of the kringle has a cis conformation and Tyr74 is ordered in fragment 1, although nuclear magnetic resonance studies indicate that the comparable residue of plasminogen kringle 4 has two positions. Surface accessibility calculations indicate that none of the disulfide groups of fragment 1 is accessible to solvent.

Amino Acid Sequence↗
PubMed1993

A multiparametric data analysis showing the potential of localized proton MR spectroscopy of the brain in the metabolic characterization of neurological diseases.

We conducted an extended clinical evaluation of localized proton magnetic resonance spectroscopy (MRS) of the brain, performed on various brain diseases using short stimulated echo times. Pathologies studied were mainly multiple sclerosis, stroke, leukoaraiosis, AIDS-related leukoencephalopathies and glial tumors. Other miscellaneous pathologies were also studied. Magnetic resonance examination of the brain was conducted on a Siemens Magnetom SP63 (equipped with a 1.5 T magnet). Localized proton MRS was performed on a routine basis immediately after imaging, using the STEAM (stimulated echo acquisition mode) with a short echo time (20 ms) combined with a CHESS (chemical shift selective excitation) sequence. One or two VOI (8 ml) were examined. Data on 125 spectra were processed by principal component analysis (PCA) and conventional variance analysis. The following metabolite resonances were studied: inositol-glycine, taurine-scyllo-inositol, choline derivatives, phosphocreatine-creatine, aspartate, glutamine glutamate, N-acetylaspartate, acetate and lactate. PCA demonstrates that the different metabolic variables are independent. The analysis of groups of spectra clearly demonstrates that the metabolic profiles detected by localized MRS in various pathologies (i) differ significantly from controls, and (ii) allow a metabolic discrimination between groups of pathologies. Results of PCA are confirmed by variance analysis. Strokes are characterized by an increase in lactate concentration and leukoaraiosis by a decrease in inositol-glycine resonance. AIDS-related leukodystrophies are characterized by increases in lactate and choline concentrations. Reduction in N-acetylaspartate which is observed in most pathologies is not significant in the small lesions of white matter. Lactate has often been found in MS plaques, but no variation in the choline/phosphocreatine ratio was observed. GABA was tentatively assigned in the spectrum of a patient with epilepsy under sodium valproate treatment. This study illustrates the clinical feasibility of the technique, the value of a multiparametric data analysis in the definition of the pertinent variables characterizing the metabolic impairment, and the impact of localized proton MR spectroscopy of the brain in the assessment of cerebral suffering.

AIDS Dementia Complex↗
PubMed1980

Antidepressant potentiation of 5-hydroxytryptophan by L-deprenil in affective illness.

In an open trial study, L-Deprenil, an irreversible selective MAO-B inhibitor without 'chesse effect' was given to 14 patients with unipolar and bipolar depression receiving L-5-Hydroxytryptophan (L-5-HTP) and benzerazide. Ten out of 14 patients showed a good response to the combination of drugs and a correlation was found between the degree of platelet MAO inhibition and clinical response. In a double-blind controlled study, 18 affectively ill patients were randomly allocated to L-Deprenil plus L-5-HTP and benzerazide, 21 patients were treated with L-5-HTP and benzerazide and 19 patients with placebo only. Patients treated with the combination of L-Deprenil and L-5-HTP showed a significantly greater clinical improvement than placebo patients but this was not the case for patients treated with 5-HTP alone. A positive relationship was demonstrated between mood improvement and degree of platelet MAO inhibition in patients treated with L-Deprenil.

5-Hydroxytryptophan↗
PubMed1989

Reconstruction of postburn sequelae with expanded flaps.

The reconstruction of important skin shortages can only be done with local tissue after expansion has provided the skin demanded by the procedure. None the less, it is pointed out that the most important commitment is the planning of all the steps in the reconstruction, like a chess game, and the management of the expanded skin in the classical way as rotation, transposition, and advancement flaps. Nineteen patients with extensive alopecia and three patients with deformities of body contour and scars, were treated with a Radovan-type expander. The results exceeded all the predictable results with other techniques because all of them were 'impossible' cases for the classical reconstructive techniques. The complications are outlined, some of which are related to technical aspects.

Adolescent↗
PubMed1993

Selective 19F MR imaging of 5-fluorouracil and alpha-fluoro-beta-alanine.

A 19F MR chemical shift imaging (CSI) technique is presented which enables selective imaging of the antineoplastic drug 5-fluorouracil (5-FU) and its major catabolite alpha-fluoro-beta-alanine (FBAL). The CSI sequence employs a chemical shift selective (CHESS) saturation pulse to suppress either the 5-FU or the FBAL resonance before the other component of the two-line 19F MR spectrum is measured. Because the transmitter frequency can always be set to the Larmor frequency of the 19F resonance to be imaged, this approach yields 5-FU and FBAL MR images free of chemical shift artifacts in read-out and slice-selection direction. In phantom experiments, selective 5-FU and FBAL images with a spatial resolution of 15 x 15 x 20 mm3 (4.5 ml) were obtained in 30 min from a model solution, whose drug and catabolite concentrations were similar to those estimated in the liver of tumor patients undergoing IV chemotherapy with 5-FU. The drug-specific MR imaging technique developed is, therefore, well-suited for the direct and noninvasive monitoring of the up-take and trapping of 5-FU in liver tumors in vivo.

Artifacts↗
PubMed2004

Novelty seekers and impulsive subjects are low in morningness.

The bipolar dimension of morningness-eveningness refers to the preferred times of day for achieving various activities (i.e. the phase of the circadian clock). It is validated from a biological point of view, associated with at least one gene and heritable through an epistatic mechanism. It has been used as a proxy to study the relationships between the circadian system, personality and psychopathology: there is a correlation between the evening orientation and depression, extraversion and, probably, impulsivity. Furthermore, there is a possible relationship with temperament in children as theorized by Thomas and Chess. In this paper, we expanded on the hypothesis that impulsive subjects are low in morningness by performing a factor analysis of the Composite Scale of Morningness, Cloninger's temperament and character inventory, and Spielberger's trait anxiety inventory in a sample of 129 males. The results can probably be extended to women. Morningness is negatively correlated with novelty seeking (which includes an impulsivity facet), positively correlated with persistence, and independent of character dimensions and trait anxiety. Future research may focus in the involvement of the circadian system in these personality dimensions and facets, and the benefits of adding chronotherapic manipulations in the treatment of the personality disorders.

Adolescent↗
PubMed2006

Doctor-patient relationship as motivation and outcome: examining uses of an Interactive Cancer Communication System.

OBJECTIVE: To examine how the pre-existing doctor-patient relationship predicts conceptually distinct service use within an Interactive Cancer Communication System (ICCS) for underserved women with breast cancer and in turn how service utilization influences the doctor-patient relationship. METHODS: Study sample included 231 recently diagnosed, lower income breast cancer patients. Participants were provided a free computer, Internet access and training in how to use an ICCS called the Comprehensive Health Enhancement Support System (CHESS) "Living with Breast Cancer" program. Survey data was collected at pre-test and 4-months after using the system, and use data about how women used the system was also collected. RESULTS: The only statistically significant predictor of service use was that patients with a more negative appraisal about the doctor-patient relationship used the Ask an Expert service more frequently, and there were trends toward a more negative appraisal of the doctor-patient relationship being associated with higher use of Information and Interactive services. Conversely, there was a trend toward a more positive appraisal predicting higher use of the Discussion Group service. In terms of statistically significant effects, more frequent utilization of Information services was associated with a more positive appraisal of the doctor relationship. CONCLUSION: While a more negative perception of the doctor-patient relationships at pre-test was associated with higher use of most of the conceptually distinct services within this ICCS, use of the Information services was associated with having a more positive appraisal of the doctor-patient relationship at post-test suggesting that high-quality information on the Internet can serve to improve patients' satisfaction with their doctor.

Adult↗
PubMed2003

Selection of an adsorbent for lead removal from drinking water by a point-of-use treatment device.

The removal of lead from drinking water was investigated to develop a point-of-use water filter that could meet the regulation imposed by the new European Directive 98-83 lowering lead concentration in drinking water below 10 microgL(-1). The objective of this research was to assess the potential of different adsorbents (zeolites, resins, activated carbon, manganese oxides, cellulose powder) to remove lead from tap water with a very short contact time. To begin, the repartition of the lead species in a tap water and a mineral water was computed with the computer model CHESS. It showed that in bicarbonated waters lead is mainly under lead carbonate form, either in the aqueous or in the mineral phase. Batch experiments were then conducted to measure the equilibrium adsorption isotherms of the adsorbents. Then, for five of them, dynamic experiments in micro-columns were carried out to assess the outlet lead concentration level. Three adsorbents gave rise to a leakage concentration lower than 10 microgL(-1) and were then selected for prototypes experiments: chabasite, an activated carbon coated with a synthetic zeolite and a natural manganese oxide. The proposed method clearly showed that the measurement of equilibrium isotherms is not sufficient to predict the effectiveness of an adsorbent, and must be coupled with dynamic experiments.

Adsorption↗
PubMed1994

X-ray diffraction measurements of the extensibility of actin and myosin filaments in contracting muscle.

We have used a small angle scattering system assembled on the high flux multipole wiggler beam line at CHESS (Cornell) to make very accurate spacing measurements of certain meridional and layer-line reflections from contracting muscles. During isometric contraction, the actin 27.3 A reflection increases in spacing from its resting value by approximately 0.3%, and other actin reflections, including the 59 and 51 A off-meridional reflections, show corresponding changes in spacing. When tension is augmented or diminished by applying moderate speed length changes to a contracting muscle, changes in spacing in the range of 0.19-0.24% (when scaled to full isometric tension) can be seen. The larger difference between the resting and isometric spacings suggests either nonlinearity at low tension levels or the presence of a component related to activation itself. Myosin filaments also show similar increases in axial period during slow stretch, in addition to the well known larger change associated with activation. An actin spacing change of 0.25-0.3% can also be measured during a 2 ms time frame immediately after a quick release, showing that the elastic behavior is rapid. These observations of filament extensions totaling 2-3 nm per half-sarcomere may necessitate some significant revision of the interpretation of a number of mechanical experiments in muscle, in which it has usually been assumed that virtually all of the elasticity resides in the cross-bridges.

Actins↗
PubMed1985

Chemical-shift-selective magnetic-resonance imaging of avascular necrosis of the femoral head.

Chemical-shift-selective (CHESS) nuclear-magnetic-resonance (NMR) imaging is a new method for separating "water" and "fat" (CH2) resonances in proton NMR imaging. Its major advantage over conventional composite NMR imaging is the contrast enhancement, which in particular allows the detection of small water-containing structures, such as vessels or joint surfaces, normally obscured by fat signals. First clinical findings in the femoral head with avascular necrosis are reported.

Adipose Tissue↗
PubMed1997

Evolution's 'missing link': a hypothesis upon neural plasticity, prefrontal working memory and the origins of modern cognition.

Many activities such as reading, mathematics and chess depend upon cognitive processes which arose after our evolution. Why could they arise if not evolved? I argue four things fortuitously came together to make our nonevolved cognitive skills possible: (i) neural plasticity; (ii) large functionally uncommitted prefrontal, temporal and parietal cerebral cortices; (iii) the ability of their neural circuits (due to neural plasticity), if trained, to take on novel symbolic and nonsymbolic skills; and (iv) a large prefrontal cortex which could use its working memory as a tuition management sketch pad in which to train them. Pre-evolved for other reasons, these four (together with invented symbolic systems and technology) together enable modern humans to 'upgrade' our already evolved cognitive skills to do new and nonevolved things.

Animals↗