40 research outputs found

    Performing total knee replacement in cases with various degrees of bone loss

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    The paper analyses main factors that effect treatment results of total knee arthroplasties in cases of bone defects, such as a size and types of bone defects, their connection with previous surgeries, existing classification with their benefits and weak points. Authors show various possibilities of surgical treatment of bone defects that can provide better stability for prosthetic devices. The importance of bone grafts is highlighted as their remodeling provides the base for implant stability in late period of outcome

    HDAC4-regulated STAT1 activation mediates platinum resistance in ovarian cancer

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    Ovarian cancer frequently acquires resistance to platinum chemotherapy, representing a major challenge for improving patient survival. Recent work suggests resistant clones exist within a larger drug sensitive cell-population prior to chemotherapy, implying that resistance is selected for rather than generated by treatment. We sought to compare clinically-derived, intra-patient paired models of initial platinum response and subsequent resistant relapse to define molecular determinants of evolved resistance. Transcriptional analysis of a matched cell-line series from three patients with high-grade serous ovarian cancer before and after development of clinical platinum resistance (PEO1/PEO4/PEO6, PEA1/PEA2, PEO14/PEO23) identified 91 up- and 126 down-regulated genes common to acquired resistance. Significantly enhanced apoptotic response to platinum treatment in resistant cells was observed following knockdown of HDAC4, FOLR2, PIK3R1 or STAT1 (p<0.05). Interestingly, HDAC4 and STAT1 were found to physically interact. Acetyl-STAT1 was detected in platinum sensitive but not HDAC4 over-expressing platinum resistant cells from the same patient. In resistant cells, STAT1 phosphorylation/nuclear translocation was seen following platinum exposure, whereas silencing of HDAC4 increased acetyl-STAT1 levels, prevented platinum induced STAT1 activation and restored cisplatin sensitivity. Conversely, matched sensitive cells were refractory to STAT1 phosphorylation on platinum treatment. Analysis of 16 paired tumor biopsies taken before and after development of clinical platinum resistance showed significantly increased HDAC4 expression in resistant tumors (n=7/16[44%]; p=0.04). Therefore, clinical selection of HDAC4 overexpressing tumor cells upon exposure to chemotherapy promotes STAT1 deacetylation and cancer cell survival. Together, our findings identify HDAC4 as a novel, therapeutically tractable target to counter platinum resistance in ovarian cancer

    Frequency of the factor v r485k polymorphism in sickle cell disease: a potential genetic modifier

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    Some mutations in the Factor V (FV) gene cause a hypercoagulable state, primarily through resistance to cleavage and inactivation by activated protein C (APC). FV Leiden is the most common of these, with a frequency of 5-15% in Caucasian populations. In addition, APC resistance has been associated with the so-called HR-2 haplotype. resulting from a polymorphism in exon 13 of the FV gene. FV Leiden is non-existent among subSaharan Africans and rare in black populations of West Indies and the US suggesting a Caucasian origin for this mutation. A novel 0A mutation at nt 1628 in exon 10 of the FV gene resulting in a ArgLys substitution at residue 485 (R485K) was found in high frequency (32%) in sub-Saharan Africans, but less commonly in Europeans (Helley et al. Hum. Genet, 100:245, 1997). More recent reports found an association with the presence of this polymorphism and thrombosis in the Thai population and coronary artery disease in the Chinese. Furthermore, carriers of R485K mutation were found to have a poor response to APC suggesting that this variant may lead to a hypercoagulable state. We studied the frequency of this mutation in SS patients and non-SS controls from various populations. A 347-bp fragment of the exon 10 of FV gene was amplified and digested with Bsm Al. The G1628A mutation abolishes the recognition site for this enzyme resulting in a 347 bp uncut fragment while the wild-type yields two fragments of 198 and 149 bp that could readily be separated on a 29c agarose gel. The results are shown in the table: N -/- +/- +/+ Frequency Non SS Black 40 23(57.5%) 10(25'») 7(17.5%) 0.3 Non SS Caucasian 23 2.1(100) 0 0 0.0 US SS 122 59(48.4%) 55(45.1%! 8(6.6%) 0.29 Kuwaiti SS 41 31(75.6%) 10(24.4%) 0 0.12 Turkish SS 10 9(90%) 1(10%) 0 0.05 Our data indicate that the R485K polymorphism is rather common in the US wickle cell population. The frequency of this polymorphism among Hb SS patients and its possible association with a hypercoagulable state and thrombosis, make it a likely candidate risk factor for certain complications such as AVN and stroke in Hb SS. Studies on the association of R485K with AVN. stroke, and other thrombolic complications in sickle cell disease as well as functional studies on APC resistance are currently underway

    Minimum flexural reinforcement for T-beams made of higher strength concrete

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    Design codes specify minimum flexural reinforcement for reinforced concrete beams. With the extensive use of higher strength concrete, the empirical expressions of the past for minimum flexural reinforcement, in which the concrete strength is not considered, had to be revised. Six reinforced concrete T-beams, having small ratios of flexural reinforcement, were tested to study the behaviour at the positive moment region and to evaluate the code requirements on minimum flexural reinforcement. A criterion was set and evaluations of different minimum reinforcement requirements were made using this criterion and the test data

    Evaluation of minimum shear reinforcement requirements for higher strength concrete

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    This paper presents an evaluation on the minimum shear reinforcement requirements given in the ACI, Canadian, and Turkish codes for high-strength concrete. Thirteen beams having the minimum shear reinforcement required by ACI 318-83, the Turkish Code, and the equations proposed in this paper were tested Concrete strength varied between so and 80 MPa (8700 and 11,600 psi). For high-strength concrete (f(a)' > 69 MPa), the minimum shear reinforcement requirements of the Turkish Code and ACI 318-95 are not very different from one another Similarly, requirements of the 1994 Canadian Code (CSA A23.3-94) are not too different from the proposed equation. In light of the test results, the adequacy of code requirements are discussed. Emphasis is given to reserve strength ductility, and cracking

    Odd surface waves in two-dimensional incompressible fluids

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    We consider free surface dynamics of a two-dimensional incompressible fluid with odd viscosity. The odd viscosity is a peculiar part of the viscosity tensor which does not result in dissipation and is allowed when parity symmetry is broken. For the case of incompressible fluids, the odd viscosity manifests itself through the free surface (no stress) boundary conditions. We first find the free surface wave solutions of hydrodynamics in the linear approximation and study the dispersion of such waves. As expected, the surface waves are chiral and even exist in the absence of gravity and vanishing shear viscosity. In this limit, we derive effective nonlinear Hamiltonian equations for the surface dynamics, generalizing the linear solutions to the weakly nonlinear case. Within the small surface angle approximation, the equation of motion leads to a new class of non-linear chiral dynamics governed by what we dub the {\it chiral} Burgers equation. The chiral Burgers equation is identical to the complex Burgers equation with imaginary viscosity and an additional analyticity requirement that enforces chirality. We present several exact solutions of the chiral Burgers equation. For generic multiple pole initial conditions, the system evolves to the formation of singularities in a finite time similar to the case of an ideal fluid without odd viscosity. We also obtain a periodic solution to the chiral Burgers corresponding to the non-linear generalization of small amplitude linear waves

    ORTA (ÇANKIRI) YÖRESİ KlL YATAKLARININ JEOLOJlSl VE OLUŞUMU

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    Orta (Çankırı) sahasında linyit damadan ile aratabakalı, kaolinitik killer bulunmaktadır. Bu killerin jeolojik oluşumunu anlamak amacıyla kil yatağı ve çevresindeki kayaçtan içeren alanda jeolojik, mineralojik, petrografik ve mikromorfolojik incelemeler yapılmıştır. Kayaç örnekleri optik mikroskop, X-ışını toz difraktometresi, tarama elektron mikroskobu ile incelenmiştir. Kaolinitik killer, temel kayaçlann üzerindeki gölsel çökelme havzasında akarsularla taşınarak çökelen ve killi, siltli Pliyosen yaşlı Orta formasyonunda oluşmuştur. Ortama, başlıca simekütten oluşan detritik malzeme sağlayan temel kayaçlar, piroklastik (Kepezinkaş formasyonu) ve lav akıntısı (Naltepe bazaltı) karakterindedir. Aynca, Simektitin bazı otijenik süreçlere bağlı olarak da gelişimini işaret eden veriler bulunmuştur. Kil tabakaları asit bataklık ortamında Simektitin kaolinite dönüşümü sonucu oluşmuştur

    Occupant friendly seismic retrofit (OFR) of RC framed buildings

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    An innovative non-evacuation retrofitting technique is being developed for RC buildings. The introduction of cast-in-place RC infill walls is very effective, but involves messy construction work and requires evacuation. The proposed method transforms existing hollow masonry infill walls by reinforcing them with precast concrete panels epoxy glued to the wall and frame members. Three tests have so far been performed under reversed cyclic loading. The first specimen was an ordinary RC frame with hollow brick infill walls, to serve as a reference specimen. The infills of the other two specimens were strengthened with epoxy glued precast concrete panels. Both strengthened specimens exhibited superior behaviour and capacity, indicating the potential of the retrofitting technique
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