366 research outputs found
The gauge theory of dislocations: static solutions of screw and edge dislocations
We investigate the T(3)-gauge theory of static dislocations in continuous
solids. We use the most general linear constitutive relations bilinear in the
elastic distortion tensor and dislocation density tensor for the force and
pseudomoment stresses of an isotropic solid. The constitutive relations contain
six material parameters. In this theory both the force and pseudomoment
stresses are asymmetric. The theory possesses four characteristic lengths l1,
l2, l3 and l4 which are given explicitely. We first derive the
three-dimensional Green tensor of the master equation for the force stresses in
the translational gauge theory of dislocations. We then investigate the
situation of generalized plane strain (anti-plane strain and plane strain).
Using the stress function method, we find modified stress functions for screw
and edge dislocations. The solution of the screw dislocation is given in terms
of one independent length l1=l4. For the problem of an edge dislocation, only
two characteristic lengths l2 and l3 arise with one of them being the same
l2=l1 as for the screw dislocation. Thus, this theory possesses only two
independent lengths for generalized plane strain. If the two lengths l2 and l3
of an edge dislocation are equal, we obtain an edge dislocation which is the
gauge theoretical version of a modified Volterra edge dislocation. In the case
of symmetric stresses we recover well known results obtained earlier.Comment: 33 pages, 17 figure
Atorvastatin pretreatment diminishes the levels of myocardial ischemia markers early after CABG operation: an observational study
<p>Abstract</p> <p>Background</p> <p>Statin pretreatment has been associated with a decrease in myocardial ischemia markers after various procedures and cardiovascular events. This study examined the potential beneficial effects of preoperative atorvastatin treatment among patients undergoing on-pump CABG operation.</p> <p>Methods</p> <p>Twenty patients that had received atorvastatin treatment for at least 15 days prior to the operation and 20 patients who had not received any antihyperlipidemic agent prior to surgery were included in this study. CK-MB and troponin I levels were measured at baseline and 24 hours after the operation. Perioperative variables were also recorded.</p> <p>Results</p> <p>Twenty-four hours after the operation, troponin I and CK-MB levels were significantly lower in the atorvastatin group: for CK-MB levels, 12.9 ± 4.3 versus 18.7 ± 7.4 ng/ml, p = 0.004; for troponin I levels, 1.7 ± 0.3 versus 2.7 ± 0.7 ng/ml, p < 0.001. In addition, atorvastatin use was associated with a decrease in the duration of ICU stay.</p> <p>Conclusions</p> <p>Preoperative atorvastatin treatment results in significant reductions in the levels of myocardial injury markers early after on-pump CABG operation, suggesting a reduction in perioperative ischemia in this group of patients. Further studies are needed to elucidate the mechanisms of these potential benefits of statin pretreatment.</p
Point process time–frequency analysis of dynamic respiratory patterns during meditation practice
Respiratory sinus arrhythmia (RSA) is largely mediated by the autonomic nervous system through its modulating influence on the heart beats. We propose a robust algorithm for quantifying instantaneous RSA as applied to heart beat intervals and respiratory recordings under dynamic breathing patterns. The blood volume pressure-derived heart beat series (pulse intervals, PIs) are modeled as an inverse Gaussian point process, with the instantaneous mean PI modeled as a bivariate regression incorporating both past PIs and respiration values observed at the beats. A point process maximum likelihood algorithm is used to estimate the model parameters, and instantaneous RSA is estimated via a frequency domain transfer function evaluated at instantaneous respiratory frequency where high coherence between respiration and PIs is observed. The model is statistically validated using Kolmogorov–Smirnov goodness-of-fit analysis, as well as independence tests. The algorithm is applied to subjects engaged in meditative practice, with distinctive dynamics in the respiration patterns elicited as a result. The presented analysis confirms the ability of the algorithm to track important changes in cardiorespiratory interactions elicited during meditation, otherwise not evidenced in control resting states, reporting statistically significant increase in RSA gain as measured by our paradigm.National Institutes of Health (U.S.) (Grant R01-HL084502)National Institutes of Health (U.S.) (Grant R01-DA015644)National Institutes of Health (U.S.) (Grant DP1-OD003646)National Institutes of Health (U.S.) (Grant K01-AT00694-01
Drugs in early clinical development for the treatment of osteosarcoma
Introduction: Osteosarcomas are the main malignant primary bone tumours found in children
and young adults. Conventional treatment is based on diagnosis and resection surgery,
combined with polychemotherapy. This is a protocol that was established in the 1970s.
Unfortunately, this therapeutic approach has reached a plateau of efficacy and the patient
survival rate has not improved in the last four decades. New therapeutic approaches are thus
required to improve the prognosis for osteosarcoma patients.
Areas covered: From the databases available and published scientific literature, the present
review gives an overview of the drugs currently in early clinical development for the
treatment of osteosarcoma. For each drug, a short description is given of the relevant
scientific data supporting its development.
Expert opinion: Multidrug targeted approaches are set to emerge, given the heterogeneity of
osteosarcoma subtypes and the multitude of therapeutic responses. The key role played by the
microenvironment in the disease increases the number of therapeutic targets (such as
macrophages or osteoclasts), as well as the master proteins that control cell proliferation or
cell death. Ongoing phase I/II trials are important steps, not only for identifying new therapies
with greater safety and efficacy, but also for better defining the role played by the
microenvironment in the pathogenesis of osteosarcoma
Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses
The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined
Components of SurA Required for Outer Membrane Biogenesis in Uropathogenic Escherichia coli
Background: SurA is a periplasmic peptidyl-prolyl isomerase (PPIase) and chaperone of Escherichia coli and other Gramnegative bacteria. In contrast to other PPIases, SurA appears to have a distinct role in chaperoning newly synthesized porins destined for insertion into the outer membrane. Previous studies have indicated that the chaperone activity of SurA rests in its ‘‘core module’ ’ (the N- plus C-terminal domains), based on in vivo envelope phenotypes and in vitro binding and protection of non-native substrates. Methodology/Principal Findings: In this study, we determined the components of SurA required for chaperone activity using in vivo phenotypes relevant to disease causation by uropathogenic E. coli (UPEC), namely membrane resistance to permeation by antimicrobials and maturation of the type 1 pilus usher FimD. FimD is a SurA-dependent, integral outer membrane protein through which heteropolymeric type 1 pili, which confer bladder epithelial binding and invasion capacity upon uropathogenic E. coli, are assembled and extruded. Consistent with prior results, the in vivo chaperone activity of SurA in UPEC rested primarily in the core module. However, the PPIase domains I and II were not expendable for wild-type resistance to novobiocin in broth culture. Steady-state levels of FimD were substantially restored in the UPEC surA mutant complemented with the SurA N- plus C-terminal domains. The addition of PPIase domain I augmented FimD maturation into the outer membrane, consistent with a model in which domain I enhances stability of and/or substrat
Mutation analysis of genes that control the G1/S cell cycle in melanoma: TP53, CDKN1A, CDKN2A, and CDKN2B
BACKGROUND: The role of genes involved in the control of progression from the G1 to the S phase of the cell cycle in melanoma tumors in not fully known. The aim of our study was to analyse mutations in TP53, CDKN1A, CDKN2A, and CDKN2B genes in melanoma tumors and melanoma cell lines METHODS: We analysed 39 primary and metastatic melanomas and 9 melanoma cell lines by single-stranded conformational polymorphism (SSCP). RESULTS: The single-stranded technique showed heterozygous defects in the TP53 gene in 8 of 39 (20.5%) melanoma tumors: three new single point mutations in intronic sequences (introns 1 and 2) and exon 10, and three new single nucleotide polymorphisms located in introns 1 and 2 (C to T transition at position 11701 in intron 1; C insertion at position 11818 in intron 2; and C insertion at position 11875 in intron 2). One melanoma tumor exhibited two heterozygous alterations in the CDKN2A exon 1 one of which was novel (stop codon, and missense mutation). No defects were found in the remaining genes. CONCLUSION: These results suggest that these genes are involved in melanoma tumorigenesis, although they may be not the major targets. Other suppressor genes that may be informative of the mechanism of tumorigenesis in skin melanomas should be studied
The effect of tight glycaemic control, during and after cardiac surgery, on patient mortality and morbidity: A systematic review and meta-analysis
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