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Two-dimensional Vlasov solution for a collisionless plasma jet across transverse magnetic field lines with a sheared bulk velocity.

We consider a two-dimensional (2D) stationary stream of a collisionless plasma injected across an external stationary magnetic field and a background stagnant plasma. The solution is found by solving the Vlasov equation for each species (electrons and protons), the Maxwell-Ampere equation for the magnetic vector potential, and the equation of plasma quasineutrality for the electrostatic potential. The solution of the stationary Vlasov equation is given in terms of two constants of motion and one adiabatic invariant. The partial charge and current densities are given by analytical expressions of the moments of the velocity distribution functions for each particle species. The 2D distribution of the plasma bulk velocity, Vx (y,z), is roughly uniform inside the jet. There is no plasma bulk flow in the direction of the magnetic field. Inside the boundary layer interfacing the jet and the stagnant plasma, the bulk velocity has gradients (i.e., shears) in the direction parallel as well perpendicular to the magnetic field. The parallel component of this gradient, inverted Delta parallel) inverted Delta perpendicular, produces a nonzero electric field component parallel to the magnetic field lines, E.B not equal to 0. The parallel electric field within the transition layer is a basic element allowing plasma elements to be transported across magnetic field lines in astrophysical systems as well as in laboratory experiments where plasmoids are injected across magnetic fields.

Journal Article↗

Decay of Loschmidt echo enhanced by quantum criticality.

We study the transition of a quantum system from a pure state to a mixed one, which is induced by the quantum criticality of the surrounding system E coupled to it. To characterize this transition quantitatively, we carefully examine the behavior of the Loschmidt echo (LE) of E modeled as an Ising model in a transverse field, which behaves as a measuring apparatus in quantum measurement. It is found that the quantum critical behavior of E strongly affects its capability of enhancing the decay of LE: near the critical value of the transverse field entailing the happening of quantum phase transition, the off-diagonal elements of the reduced density matrix describing S vanish sharply.

Journal Article↗

Carcinosarcoma of the prostate.

A unique case of carcinosarcoma of the prostate occurring in a 32 year old man is presented. This is the youngest case reported to date among nine well-documented examples. The patient underwent a total prostatectomy under the diagnosis of prostatic sarcoma. Despite adjuvant chemotherapy and full-dose radiotherapy being undertaken, the patient died from multiple lung metastases about 8 months after the operation. The surgically resected primary tumor was composed of two histologically distinct elements, these being an undifferentiated carcinoma and a sarcoma with various mesodermal components. These elements were intimately intermingled and transitional forms were often noticed. The sarcomatous portion contained myxoid areas, spindle cell sarcomas with nuclear palisading, areas of osteoid formation and small islands of chondromatous differentiation. The pathogenesis of this complex neoplasm is discussed, and it is suggested that vestigial embryologic Müllerian mesodermal tissue may be capable of diverse differentiation.

Adult↗

Combined sellar fibrosarcoma and prolactinoma with neuronal metaplasia: report of a case unassociated with radiotherapy.

We report the occurrence of a primary pituitary fibrosarcoma causally unrelated to radiotherapy, admixed in association with a prolactin cell pituitary adenoma showing neuronal metaplasia. These unique findings were associated with multiple endocrine neoplasia type 1 (MEN 1). Primary fibrosarcoma involving the sella is a very rare tumor. The majority of cases have been associated with prior irradiation of either a pituitary adenoma or a craniopharyngioma. Pituitary adenoma with neuronal metaplasia is also rare and usually occurs in the setting of acromegaly. Despite the intimate association of both elements in our lesion, no transition of adenoma to sarcoma was demonstrable by immunohistochemistry or in situ hybridization studies.

Adult↗

Adenosquamous carcinoma of the prostate.

An unusual adenosquamous carcinoma originating in the prostate of a 73-year-old man is described. The histological finding showed a well differentiated squamous cell carcinoma admixed in an adenocarcinomatous area. A transitional area of 2 carcinomatous elements was also noted. Seven months prior to the development of this lesion, a diagnosis of adenocarcinoma had been established by transurethral resection of the prostate and the patient had been treated with bilateral orchiectomy. This is the first case of adenosquamous carcinoma of the prostate reported in Korea. The pathogenesis and previous reports of this lesion will be discussed.

Aged↗

Toward minimalist models of larger proteins: a ubiquitin-like protein.

Our recently developed off-lattice bead model capable of simulating protein structures with mixed alpha/beta content has been extended to model the folding of a ubiquitin-like protein and provides a means for examining the more complex kinetics involved in the folding of larger proteins. Using trajectories generated from constant-temperature Langevin dynamics simulations and sampling with the multiple multi-histogram method over five-order parameters, we are able to characterize the free energy landscape for folding and find evidence for folding through compact intermediates. Our model reproduces the observation that the C-terminus loop structure in ubiquitin is the last to fold in the folding process and most likely plays a spectator role in the folding kinetics. The possibility of a productive metastable intermediate along the folding pathway consisting of collapsed states with no secondary structure, and of intermediates or transition structures involving secondary structural elements occurring early in the sequence, is also supported by our model. The kinetics of folding remain multi-exponential below the folding temperature, with glass-like kinetics appearing at T/T(f) approximately 0.86. This new physicochemical model, designed to be predictive, helps validate the value of modeling protein folding at this level of detail for genomic-scale studies, and motivates further studies of other protein topologies and the impact of more complex energy functions, such as the addition of solvation forces.

Amino Acid Sequence↗

Research in medical education, a challenge to enhance the quality of education and care.

Research in education assumes that every intuition regarding the improvement in the educational process is followed by justification and foundation. Creativeness and rigor with the relative implications in the context of both research and justification are the two main elements. Knowledge characteristic of the transition from a PHOG approach, that is, based on prejudice, hunches, opinions, guess, to evidence-based education is not easy to collect, document, and generalize. This approach is of even more difficult application in a highly complex context, hard to know, control and improve. To achieve high quality education, research is required for the extremely high cost of non-quality and its strong impact on medical care, social prevention and clinical research. At the university level, everyone carries out research within his/her own discipline, however all should be involved in education at large. This is particularly relevant in the medical school where education is a function of continuous improvement in health care as well as in prevention, to be implemented through health-centered educational projects.

Education, Medical↗

The role of soluble acids from oxidative-hydrolytic breakdown of coal in the development of the fibrous process in anthracosis.

The oxidative-hydrolytic mechanism of interaction of coal with tissue medium and the formation of humic acids (HA) and polycarboxylic acids (PCA) from coal in the organism were demonstrated. The composition of PCA obtained from the coal withdrawn from the organism of animals was investigated by gas-liquid chromatography by means of which 28 acids of the aromatic series were identified. The method of elemental spectral analysis revealed the transition of a number of macro- and microelements into the medium of the organism. It has been shown experimentally that the decrease in the mass of coal correlates with the fibrogenic process. The conclusion has been drawn that the soluble products of the oxidative-hydrolytic breakdown of coal in the organism are among the fibrogenic factors of pneumosclerosis in anthracosis. The initial mechanism in the development of fibrosis is the damage caused by polycarboxylic acids to the microcirculatory bed of the lungs and the structures of the aerohematic barrier.

Animals↗

[So-called carcinosarcoma of the breast--report of 4 cases].

Four cases of so-called carcinosarcoma of the breast were studied histopathologically. The patients were females aged 44, 37, 44 and 77 who were admitted to the Cancer Institute Hospital for breast tumors. Histologically, the tumors showed proliferation of sarcomatous cells with relatively small amounts of papillotubular carcinoma or scirrhous carcinoma. There were transitions between the sarcomatous portion and carcinoma. Two cases showed squamous metaplasia merging into the sarcomatous component, whereas the other 2 showed transition from adenocarcinoma to sarcomatous element. Lymph nodal metastases in 2 cases were papillotubular carcinoma. One patient died of lung and brain metastases, and autopsy revealed only sarcomatous element.

Adult↗

Further study of the conformation of nuclease-(1-126) in relation to intrinsic enzymatic activity.

Nuclease-(1-126), although containing 89% of the amino acid sequence which folds to the ordered structure of nuclease A, is disordered and highly flexible (Taniuchi, H., and Anfinsen, C. B. (1969) J. Biol. Chem. 243, 4778-4786). On the other hand, Sachs et al. (Sachs, D. H., Schechter, A. N., Eastlake, A., and Anfinsen, C. B. (1974) Nature 251, 242-244) have demonstrated intrinsic enzymatic activity for nuclease-(1-126). To attempt to learn whether or not the active population of nuclease-(1-126) has the native conformation, we have examined nuclease-(1-126) with respect to enzymatic kinetics with and without the competitive inhibitor deoxythymidine 3',5'-diphosphate (pdTp), effect of temperature on enzymatic activity, binding of pdTp in the presence of Ca2+ and intrinsic viscosity, Stokes radius, CD, and response to trypsin action in the presence and absence of pdTp and Ca2+. The results indicate that the conformation of nuclease-(1-126) bound with pdTp in the presence of Ca2+ is partially constrained but still highly flexible below 30 degrees C, outside the range of thermal transition exhibited by the ordered elements of nuclease-(1-126). Thus, formation or stabilization of active site of nuclease-(1-126) by binding with ligands is not associated with cooperative folding of the entire polypeptide chain. Considering that nuclease-(1-126) does not bind to nuclease-(127-149) but does to nuclease-(111-149), the results are consistent with the idea that the specific cooperative interactions, providing extra stabilizing energy required for maintaining the polypeptide chain in the ordered state of nuclease A, may be disrupted for nuclease-(1-126) primarily due to cleavage of the peptide bond between residues 126 and 127. Then, it may be thought that binding with ligands does not compensate for this disruption.

Circular Dichroism↗

Transitional care: hospital to home.

Contemporary acute hospital care of older adults must include special attention to the transitional, or peridischarge, phase of hospitalization. This article reviews the evidence from outcomes data and economic factors that demonstrate that precise transitional planning is a critical element in the care of older hospitalized adults. Some of the promising initiatives being explored around the country are reviewed.

Aged↗

Bulge-induced bends in RNA: quantification by transient electric birefringence.

Bulges represent one of the most common non-helical elements in RNA, often displaying a strong degree of phylogenetic conservation, both in location and sequence, within larger RNA molecules. Thus, knowledge of the conformation and flexibility of RNA bulges is an important prerequisite for understanding the rules governing the formation of tertiary structure within the larger molecules. In the current investigation, the magnitudes of the bends induced in a 148 base-pair duplex RNA molecule by single, centrally located bulges of varying size (n = 1 to 6) and base composition (An and Un series) have been determined through the use of transient electric birefringence (TEB). The TEB approach is highly sensitive to the changes in the global shape of RNA (or DNA) helices that accompany the introduction of points of bending or flexibility near the center of the helix. In the current instance, bulge angles deduced from TEB measurements ranged from approximately 7 degrees to approximately 93 degrees, with the angle increasing with increasing n for both An and Un series. For both An and Un series in the absence of Mg2+, the angle increment per added nucleotide varied from approximately 20 degrees to approximately 8 degrees as n increased from 1 to 6. These angle increments remained unchanged for the An series in the presence of Mg2+; however, the angle increments for the Un series were reduced by a factor of 2 for all values of n. Thus the current observations have identified structural transitions in one of the simplest non-helical elements in RNA, transitions that are dependent on both sequence and counterion valence. Finally, the measured bend angles are strongly correlated with the degree of reduction in electrophoretic mobility of bulge-containing RNA helices. The observed correlation was used to obtain a semi-empirical relationship between bend angle and mobility in order that additional angles might be assigned, by interpolation, through the use of gel data alone.

Base Sequence↗

Titration properties and thermodynamics of the transition state for folding: comparison of two-state and multi-state folding pathways.

CI2 folds and unfolds as a single cooperative unit by simple two-state kinetics, which enables the properties of the transition state to be measured from both the forward and backward rate constants. We have examined how the free energy of the transition state for the folding of chymotrypsin inhibitor 2 (CI2) changes with pH and temperature. In addition to the standard thermodynamic quantities, we have measured the overall acid-titration properties of the transition state and its heat capacity relative to both the denatured and native states. We were able to determine the latter by a method analogous to a well-established procedure for measuring the change in heat capacity for equilibrium unfolding: the enthalpy of activation of unfolding at different values of acid pH were plotted against the average temperature of each determination. Our results show that the transition state of CI2 has lost most of the electrostatic and van der Waals' interactions that are found in the native state, but it remains compact and this prevents water molecules from entering some parts of the hydrophobic core. The properties of the transition state of CI2 are then compared with the major folding transition state of the larger protein barnase, which folds by a multi-state mechanism, with the accumulation of a partly structured intermediate (Dphys or I). CI2 folds from a largely unstructured denatured state under physiological conditions via a transition state which is compact but relatively uniformly unstructured, with tertiary and secondary structure being formed in parallel. We term this an expanded pathway. Conversely, barnase folds from a largely structured denatured state in which elements of structure are well formed through a transition state that has islands of folded elements of structure. We term this a compact pathway. These two pathways may correspond to the two extreme ends of a continuous spectrum of protein folding mechanisms. Although the properties of the two transition states are very different, the activation barrier for folding (Dphys-->++) is very similar for both proteins.

Hydrogen-Ion Concentration↗

Effect of G:C-->A:T transition, potentially arising from O6-guanine alkylation, in the transcription regulation of c-fos serum response element.

O6-meGs, if not repaired before cell undergo DNA synthesis, can cause erroneous pairing of thymine resulting in a G:C-->A:T transition, after the next DNA replication. It is known that the presence of O6-meG in promoter sequences inhibits the specific binding of transcription factors. Little is known on the effect of G:C-->A:T transitions on this binding. c-fos SRE was used as a model to study the effect of different G:C-->A:T transitions (at the positions -305, -306, -316, -319 and -320) in terms of SRE specific DNA-binding and functional ability to activate transcription of a reporter gene. The electromobility shift assay and a transient transfection assay were used. The G:C-->A:T transition at -320 caused 92% inhibition, while mutations at the positions -305, -306, -316 and -319 caused respectively 55, 43, 19 and 44% inhibition. The findings indicate that some G:C-->A:T transitions, potentially arising from O6-guanine methylation, can impair the regulation of c-fos transcription.

3T3 Cells↗

Ultrastructural modifications of vesicular and Golgi elements in the Saccharomyces cerevisiae sec21 mutant at permissive and non-permissive temperatures.

BACKGROUND: The secretory protein transit between cisternae of endoplasmic reticulum (ER) and Golgi elements is blocked when the yeast Saccharomyces cerevisiae sec21 mutant is shifted from the permissive (24 degrees C) to a non-permissive (37 degrees C) temperature, but 30-50 nm vesicles accumulate in the cytoplasm. At the semi-permissive temperature of 33 degrees C there is no complete block but rather a slowdown of the protein transport between ER and Golgi. The purpose of the present investigation is to analyze the structural expression of these events. METHODS: S. cerevisiae sec21 mutants were maintained for 90 min at semi-restrictive (33 degrees C) or restrictive (37 degrees C) temperatures and then progressively returned to 24 degrees C. Following fixation in glutaraldehyde and a postfixation in potassium ferrocyanide reduced osmium, 0.08 to 0.2 microns thick sections were cut from Epon embedded yeasts. Using the thicker sections, stereopairs of electron microscope photographs were prepared and used to visualize the three-dimensional configuration of the organelles. RESULTS: At permissive temperature, the Golgi elements appeared as isolated networks of membranous tubules dispersed throughout the cytoplasm. The diameter of these membranous tubules varied considerably from one Golgi element to another. Larger tubules showed at their intersections distensions with size and staining intensity comparable with that of the secretory granules seen at proximity of the Golgi networks or at the cell periphery. Small vesicles in the 30-50 nm size range were rarely if ever observed in cells grown at permissive temperature. Golgi networks and secretion granules were less conspicuous in mutant cells maintained at 33 degrees C and completely disappeared at 37 degrees C. In both cases, the main structural feature was the presence in the cytoplasm of numerous small vesicles and of short membranous tubules with a diameter identical to that of the small vesicles. As soon as 5 minutes after shifting mutants from 33 degrees C to 24 degrees C, the small vesicles disappeared from the cytoplasm, while secretory granules were actively produced in extensively developed Golgi network. When mutants were returned from 37 degrees C to 24 degrees C, the disappearance of small vesicles was more progressive and concomitant with the progressive reconstruction of Golgi networks. CONCLUSIONS: It is thus postulated that, in the above mentioned conditions, the small vesicles of the sec21 mutant did not act as intermediate carriers between the endoplasmic reticulum and a pre-existing Golgi apparatus, but rather fused together to produce newly formed Golgi networks.

Golgi Apparatus↗

Sensitivity analysis of Markov models for communities of competing sessile organisms.

1. Communities of competing sessile organisms are often modelled using Markov chains. Sensitivity analysis of the stationary distribution of these models tells us how we expect the abundance of each organism to respond to changes in interactions between species. This is important for conservation and management. 2. Markov models for such communities have usually been formulated in discrete time. Each column of the discrete-time transition matrix must sum to 1 (column stochasticity). Sensitivity analysis therefore involves defining a pattern of compensation that maintains column stochasticity as a single transition probability changes. There is little biological theory about the appropriate compensation pattern, but the usual choices involve changing only the elements of a single column of the transition matrix. 3. I argue that if the underlying dynamics occur in continuous time, each transition probability is the net outcome of direct and many indirect interactions. 4. Determining the consequences of changing a single direct interaction will often be of interest. I show how this can be achieved using a continuous-time model. The resulting discrete-time compensation pattern is quite different from those that have been considered elsewhere, with changes occurring in many columns. 5. I also show how to determine which direct interactions are being changed under any discrete-time compensation pattern.

Ecosystem↗

Case report of a malignant Brenner tumor with hyperestrogenism.

A rare malignant Brenner tumor of the ovary presenting with hyperestrogenism in a 79 year old woman was examined immunohistochemically and by light and electron microscopy. High pre-operative serum and urinary estrogen concentrations, low serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, and histologically confirmed atypical endometrial hyperplasia suggested the presence of hyperestrogenism. The reduction in serum and urinary estrogen and the increase in serum LH and FSH concentrations after tumor removal confirmed that the tumor was synthesizing estrogen. Histologically, the malignant element was predominantly a squamous cell carcinoma. Transitional cell carcinoma was partially found on the cyst wall. There was a spectrum of morphologic changes between benign and malignant elements with an intermediate area with a proliferating Brenner tumor. Immunohistochemically, only the carcinoembryonic antigen was positive exclusively on the malignant element as well as in the microcyst in the benign epithelial cord, whereas all of the markers for germ cell tumors were negative. The ultrastructural features of the stromal cells were of two types: fibroblasts and steroid-producing cells. The latter type of cells might correspond morphologically to estrogen-producing cells. The present case is the fourth report showing a malignant Brenner tumor combined with apparent hyperestrogenism.

Aged↗

A positive GATA element and a negative vitamin D receptor-like element control atrial chamber-specific expression of a slow myosin heavy-chain gene during cardiac morphogenesis.

We have used the slow myosin heavy chain (MyHC) 3 gene to study the molecular mechanisms that control atrial chamber-specific gene expression. Initially, slow MyHC 3 is uniformly expressed throughout the tubular heart of the quail embryo. As cardiac development proceeds, an anterior-posterior gradient of slow MyHC 3 expression develops, culminating in atrial chamber-restricted expression of this gene following chamberization. Two cis elements within the slow MyHC 3 gene promoter, a GATA-binding motif and a vitamin D receptor (VDR)-like binding motif, control chamber-specific expression. The GATA element of the slow MyHC 3 is sufficient for expression of a heterologous reporter gene in both atrial and ventricular cardiomyocytes, and expression of GATA-4, but not Nkx2-5 or myocyte enhancer factor 2C, activates reporter gene expression in fibroblasts. Equivalent levels of GATA-binding activity were found in extracts of atrial and ventricular cardiomyocytes from embryonic chamberized hearts. These observations suggest that GATA factors positively regulate slow MyHC 3 gene expression throughout the tubular heart and subsequently in the atria. In contrast, an inhibitory activity, operating through the VDR-like element, increased in ventricular cardiomyocytes during the transition of the heart from a tubular to a chambered structure. Overexpression of the VDR, acting via the VDR-like element, duplicates the inhibitory activity in ventricular but not in atrial cardiomyocytes. These data suggest that atrial chamber-specific expression of the slow MyHC 3 gene is achieved through the VDR-like inhibitory element in ventricular cardiomyocytes at the time distinct atrial and ventricular chambers form.

Animals↗