Mustafa Kemal'in Boğazlara dair görüşü

Taha Toros Arşivi, Dosya Adı: Milli Mücadele İstiklal Harbi GazetesiUnutma İstanbul projesi İstanbul Kalkınma Ajansı'nın 2016 yılı "Yenilikçi ve Yaratıcı İstanbul Mali Destek Programı" kapsamında desteklenmiştir. Proje No: TR10/16/YNY/010

PRAME and CTCFL-reactive TCRs for the treatment of ovarian cancer

Recurrent disease emerges in the majority of patients with ovarian cancer (OVCA). Adoptive T-cell therapies with T-cell receptors (TCRs) targeting tumor-associated antigens (TAAs) are considered promising solutions for less-immunogenic 'cold' ovarian tumors. In order to treat a broader patient population, more TCRs targeting peptides derived from different TAAs binding in various HLA class I molecules are essential. By performing a differential gene expression analysis using mRNA-seq datasets, PRAME, CTCFL and CLDN6 were selected as strictly tumor-specific TAAs, with high expression in ovarian cancer and at least 20-fold lower expression in all healthy tissues of risk. In primary OVCA patient samples and cell lines we confirmed expression and identified naturally expressed TAA-derived peptides in the HLA class I ligandome. Subsequently, high-avidity T-cell clones recognizing these peptides were isolated from the allo-HLA T-cell repertoire of healthy individuals. Three PRAME TCRs and one CTCFL TCR of the most promising T-cell clones were sequenced, and transferred to CD8+ T cells. The PRAME TCR-T cells demonstrated potent and specific antitumor reactivity in vitro and in vivo. The CTCFL TCR-T cells efficiently recognized primary patient-derived OVCA cells, and OVCA cell lines treated with demethylating agent 5-aza-2 '-deoxycytidine (DAC). The identified PRAME and CTCFL TCRs are promising candidates for the treatment of patients with ovarian cancer, and are an essential addition to the currently used HLA-A*02:01 restricted PRAME TCRs. Our selection of differentially expressed genes, naturally expressed TAA peptides and potent TCRs can improve and broaden the use of T-cell therapies for patients with ovarian cancer or other PRAME or CTCFL expressing cancers.Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

Thermal properties of AlN-based atom chips

We have studied the thermal properties of atom chips consisting o high thermal conductivity Aluminum Nitride (AlN) substrates on which gold microwires are directly deposited. We have measured the heating of wires of several widths and with different thermal couplings to the copper mount holding the chip. The results are in good agreement with a theoretical model where the copper mount is treated as a heat sink and the thermal interface resistance between the wire and the substrate is vanishing. We give analytical formulas describing the different transient heating regimes and the steady state. We identify criteria to optimize the design of a chip as well as the maximal currents $I_c$ that can be fed in the wires. For a 600 $\mu$m thick-chip glued on a copper block with Epotek H77, we find $I_c=16$ A for a 3 $\mu$m high, 200 $\mu$m wide-wire

One-dimensional Bose gas on an atom chip

We describe experiments investigating the (coherence) properties of a finite-temperature one-dimensional (1D) Bose gas with repulsive interactions. The confining magnetic field is generated with a micro-electronic circuit. This microtrap for atoms or `atom chip' is particularly suited to generate a tight waveguide for atoms close to the chip surface. In contrast to the usual case of Bose-Einstein condensation in 3D, in 1D the system is not characterized by long-range phase coherence. Further interest in the 1D Bose gas stems from the fact that it forms the textbook example for the many-body quantum-mechanical systems that can be exactly solved using the Bethe Ansatz. Moreover, using a method developed by Yang and Yang, exact expressions for the thermodynamics of this system can be given. We summarize the theoretical background that is relevant to describe the (nearly) 1D gas in our experiments. The design and construction of our microtrap is described in some detail. We discuss the technique of Bose-gas focusing, in particular how it applies to our 1D system, and demonstrate that it can be used to probe the momentum distribution of the 1D gas. Finally, we perform a direct comparison of the measured in situ density distribution to the predictions of a model based on the exact Yang-Yang thermodynamics and find very good agreement

Ultrasound guided lumpectomy is superior to wire guided resection of nonpalpable breast cancer: a prospective randomised trial.

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Ultrasound-guided lumpectomy of nonpalpable breast cancer versus wire-guided resection: a randomized clinical trial.

Contains fulltext : 143598.pdf (publisher's version ) (Closed access)BACKGROUND: The wire-guided excision of nonpalpable breast cancer often results in tumor resections with inadequate margins. This prospective, randomized trial was undertaken to investigate whether intraoperative ultrasound (US) guidance enables a better margin clearance than the wire-guided technique in the breast-conserving treatment of nonpalpable breast cancers. METHODS: Patients with a preoperative histological diagnosis of nonpalpable breast cancer that could be visualized both with US and mammography were included. Patients were randomized to undergo either a wire-guided or a US-guided excision. Adequate margins were defined as >/=1 mm. RESULTS: Of 49 included patients, 23 were assigned to undergo wire-guided excision and 26 to undergo US-guided excision. One patient crossed over to US-guided excision after inadvertent wire displacement. Mean tumor diameter, specimen weight, and operating time were similar in both groups. The excision was adequate in 24 (89%) of 27 US-guided excisions and 12 (55%) of 22 wire-guide excisions (P =.007). CONCLUSIONS: US-guided excision seems to be superior to wire-guided excision with respect to margin clearance of mammographically detected and US-visible nonpalpable breast cancers. Patients do not have to undergo the unpleasant wire placement before surgery

A general approach to detect folding intermediates from steady-state and time-resolved fluorescence of single tryptophan-containing proteins

During denaturant-induced equilibrium (un)folding of wild-type apoflavodoxin from Azotobacter vinelandii, a molten globule-like folding intermediate is formed. This wild-type protein contains three tryptophans. In this study, we use a general approach to analyze time-resolved fluorescence and steady-state fluorescence data that are obtained upon denaturant-induced unfolding of a single-tryptophan-containing variant of apoflavodoxin [i.e., W74/F128/F167 (WFF) apoflavodoxin]. The experimental data are assembled in matrices, and subsequent singular-value decomposition of these matrices (i.e., based on either steady-state or time-resolved fluorescence data) shows the presence of three significant, and independent, components. Consequently, to further analyze the denaturation trajectories, we use a three-state protein folding model in which a folding intermediate and native and unfolded protein molecules take part. Using a global analysis procedure, we determine the relative concentrations of the species involved and show that the stability of WFF apoflavodoxin against global unfolding is ∼4.1 kcal/mol. Analysis of time-resolved anisotropy data of WFF apoflavodoxin unfolding reveals the remarkable observation that W74 is equally well fixed within both the native protein and the molten globule-like folding intermediate. Slight differences between the direct environments of W74 in the folding intermediate and native protein cause different rotameric populations of the indole in both folding species as fluorescence lifetime analysis reveals. Importantly, thermodynamic analyses of the spectral denaturation trajectories of the double-tryptophan- containing protein variants WWF apoflavodoxin and WFW apoflavodoxin show that these variants are significantly more stable (5.9 kcal/mol and 6.8 kcal/mol, respectively) than WFF apoflavodoxin (4.1 kcal/mol) Hence, tryptophan residues contribute considerably to the 10.5 kcal/mol thermodynamic stability of native wild-type apoflavodoxin. © 2011 American Chemical Society

A general approach for detecting folding intermediates from staedy-state and time-resolved fluorescence of single-tryptophan-containing proteins

During denaturant-induced equilibrium (un)folding of wild-type apoflavodoxin from Azotobacter vinelandii, a molten globule-like folding intermediate is formed. This wild-type protein contains three tryptophans. In this study, we use a general approach to analyze time-resolved fluorescence and steady-state fluorescence data that are obtained upon denaturant-induced unfolding of a single-tryptophan-containing variant of apoflavodoxin [i.e., W74/F128/F167 (WFF) apoflavodoxin]. The experimental data are assembled in matrices, and subsequent singular-value decomposition of these matrices (i.e., based on either steady-state or time-resolved fluorescence data) shows the presence of three significant, and independent, components. Consequently, to further analyze the denaturation trajectories, we use a three-state protein folding model in which a folding intermediate and native and unfolded protein molecules take part. Using a global analysis procedure, we determine the relative concentrations of the species involved and show that the stability of WFF apoflavodoxin against global unfolding is 4.1 kcal/mol. Analysis of time-resolved anisotropy data of WFF apoflavodoxin unfolding reveals the remarkable observation that W74 is equally well fixed within both the native protein and the molten globule-like folding intermediate. Slight differences between the direct environments of W74 in the folding intermediate and native protein cause different rotameric populations of the indole in both folding species as fluorescence lifetime analysis reveals. Importantly, thermodynamic analyses of the spectral denaturation trajectories of the double-tryptophan-containing protein variants WWF apoflavodoxin and WFW apoflavodoxin show that these variants are significantly more stable (5.9 kcal/mol and 6.8 kcal/mol, respectively) than WFF apoflavodoxin (4.1 kcal/mol) Hence, tryptophan residues contribute considerably to the 10.5 kcal/mol thermodynamic stability of native wild-type apoflavodoxi

5-Fluorotryptophan as dual probe for ground-state heterogeneity and excited-state dynamics in apoflavodoxin

The apoflavodoxin protein from Azotobacter vinelandii harboring three tryptophan (Trp) residues, was biosynthetically labeled with 5-fluorotryptophan (5-FTrp). 5-FTrp has the advantage that chemical differences in its microenvironment can be sensitively visualized via 19F NMR. Moreover, it shows simpler fluorescence decay kinetics. The occurrence of FRET was earlier observed via the fluorescence anisotropy decay of WT apoflavodoxin and the anisotropy decay parameters are in excellent agreement with distances between and relative orientations of all Trp residues. The anisotropy decay in 5-FTrp apoflavodoxin demonstrates that the distances and orientations are identical for this protein. This work demonstrates the added value of replacing Trp by 5-FTrp to study structural features of proteins via 19F NMR and fluorescence spectroscopy.