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Phosphorylation switches Bax from promoting to inhibiting apoptosis thereby increasing drug resistance
No full textAkt is a pro-survival kinase frequently activated in human cancers and is associated with more aggressive tumors that resist therapy. Here, we connect Akt pathway activation to reduced sensitivity to chemotherapy via Akt phosphorylation of Bax at residue S184, one of the pro-apoptotic Bcl-2 family proteins required for cells to undergo apoptosis. We show that phosphorylation by Akt converts the pro-apoptotic protein Bax into an anti-apoptotic protein. Mechanistically, we show that phosphorylation (i) enables Bax binding to pro-apoptotic BH3 proteins in solution, and (ii) prevents Bax inserting into mitochondria. Together, these alterations promote resistance to apoptotic stimuli by sequestering pro-apoptotic activator BH3 proteins. Bax phosphorylation correlates with cellular resistance to BH3 mimetics in primary ovarian cancer cells. Further, analysis of the TCGA database reveals that 98% of cancer patients with increased BAX levels also have an upregulated Akt pathway, compared to 47% of patients with unchanged or decreased BAX levels. These results suggest that in patients, increased phosphorylated anti-apoptotic Bax promotes resistance of cancer cells to inherent and drug-induced apoptosis
Çok projeli kaynak kısıtlı proje çizelgeleme problemi: Bir yazılım firmasında uygulama çalışması
No full textProje yönetimi temel olarak projenin hedeflerine ulaşması için planlama ve çizelgeleme faaliyetlerinin birlikte ele alındığı faaliyetler bütünüdür. Proje çizelgeleme problemleri günümüzde proje temelli üretim yapan firmaların ortak problemi olup birtakım kısıtlar altında en kısa zamanda veya en az maliyetle projelerin tamamlanmasını amaçlayan çizelgeleme problemidir. Bu çalışmada proje bazlı çalışan ve aynı anda birden fazla projeyi eş zamanlı yürüten bir yazılım firmasındaki projelerin çizelgelenmesi için bir çözüm yolu önerilmiştir. Firmanın karşı karşıya kaldığı problemde öncüllük ilişkileri olan farklı faaliyetlere ve kısıtlı kaynaklara sahip birden çok projenin en kısa tamamlanma süresinin bulunması amaçlanmaktadır. Problemin çözümü için literatürde yer alan doğrusal karar modelleri araştırılmış ve ele alınan karar modeli optimizasyon programlama dili (OPL) yardımıyla kodlanmıştır. Karar modeli CPLEX çözücüsü ile çözdürülerek sonuçları incelenmiştir. Ayrıca firmanın proje çizelgeleme probleminin karar modeli ile çözümü kolaylaştırmak adına JAVA programlama dilinde bir yazılım geliştirilerek ara yüz tasarlanmıştır. Tasarlanan ara yüz sayesinde firma çalışanlarının önerilen yöntemi daha etkin kullanması sağlanmıştır. Sonuç bölümünde yapılan tez çalışması değerlendirilerek, ileride yapılabilecek çalışmalardan bahsedilmiştir.
Project management is basically a combination of planning and scheduling activities with the aim to meet project‟s targets. Nowadays project scheduling is a very common problem in project based production companies. The problem is aim to complete the projects with the shortest time or minimum cost under some constraints. In this thesis, a new method was proposed for generating a schedule for a software company which runs multiple projects simultaneously. The problem faced by the company is aimed at finding the smallest completion time of multi-projects which has different precedence and constrained resources in different activities. In order to solve the problem, the linear decision models were investigated and the chosen decision model was coded using Optimization Programming Language (OPL). The results of the decision model were investigated with the help of CPLEX Optimizer solver. In order to ease the use of the decision model and the solver, a user interface was added using JAVA programming language. As a result, the end users were able to use the proposed scheduling method more affectively. In the conclusion section, the current thesis was evaluated and the possible future studies were called out
Post-traumatic Delayed Peripheral Facial Palsy
Get PDFPeripheral facial palsy in children is very rare in comparison to adults. The most common cause is idiopathic. Another rare cause of peripheral facial palsy in children is trauma. It occurs after head trauma, mostly due to temporal bone fracture as an early onset paralysis after trauma. Early onset facial palsy is usually due to direct damage to the facial nerve whereas there is some controversy about the etiology of late onset facial palsy. In this article, a child patient whose peripheral facial palsy developed six days after a head injury is presented, and the etiopathogenesis and the treatment of delayed traumatic facial palsy after temporal bone fracture is discussed
Smoothed one-core and core-multi-shell regular black holes
Get PDFWe discuss the generic properties of a general, smoothly varying, spherically symmetric mass distribution D(r,theta), with no cosmological term (. is a length scale parameter). Observing these constraints, we show that (1.) the de Sitter behavior of spacetime at the origin is generic and depends only on D(0,theta), (2.) the geometry may posses up to 2(k + 1) horizons depending solely on the total mass M if the cumulative distribution of D(r,theta) has 2k + 1 inflection points, and (3.) no scalar invariant nor a thermodynamic entity diverges. We define new two-parameter mathematical distributions mimicking Gaussian and step-like functions and reduce to the Dirac distribution in the limit of vanishing parameter.. We use these distributions to derive in closed forms asymptotically flat, spherically symmetric, solutions that describe and model a variety of physical and geometric entities ranging from noncommutative black holes, quantumcorrected black holes to stars and dark matter halos for various scaling values of.. We show that the mass-to-radius ratio pi c(2)/G is an upper limit for regular-black-hole formation. Core-multi-shell and multi-shell regular black holes are also derived
Tissue engineering and its application areas
No full textTissue engineering is a multidisciplinary area that has been put forward to offer solutions to the problems arising from limiting factors, especially the lack of donors and the formation of immunological response in organ transplantation. This approach finds application in the field of regenerative medicine by demonstrating the appropriate tissue and/or organ model. Basically, tissue engineering involves the construction of scaffolds suitable for the target tissue and/or organ, the factors that make up this scaffold, and the cells to be added to this scaffold. Nowadays, especially stem cell studies can be applied in three dimensional (3D) structures by using cell culture conditions in scaffold construction. In recent years, regenerative medicine approaches have focused on areas where stem cell and three dimensional structures are studied. Today, stem cell studies in which three dimensional culture conditions are applied instead of two dimensional (2D) culture conditions and these three dimensional culture media can be found in dynamic culture conditions with elements such as bioreactors gain increasing importance in terms of tissue engineering and renewable medicine. Depending on the developing technology, tissue engineering products have a wide clinical coverage. Some of the tissue engineering products designed for tissue and organ regeneration, displacing damaged tissue or organ have an important place in life sciences today, including research and some clinical use. Especially in recent years, regenerative medicine studies, which have gained significant momentum due to improvements in stem cell technology and biomolecularization, have made tissue engineering an important part of life sciences. In this review, the elements that make up the tissue engineering will be explained with examples of the literature. © 2018 by Türkiye Klinikleri
Bone Cement Leakage in Transpedicular Percutaneous Vertebroplasty: Analysis of 20 Patients
Get PDFObjective: Percutaneous vertebroplasty (PVP) is one of the frequently preferred interventional methods in spinal surgery. Although it is classified as minimally invasive, the most common complication of this procedure is bone cement leakage. Leakage of bone cement is often asymptomatic, but can lead to serious complications such as paraplegia and pulmonary embolism. In this study, we aimed to investigate the complications and consequences of cement leakage in the percutaneous vertebroplasty procedure.
Methods: Between 2009 and 2015, 20 (14 female and 6 male, mean age 69.7) patients who underwent percutaneous vertebroplasty to 26 vertebrae were included in the study. 17 vertebrae were treated for osteoporotic compression (65.3%), 4 vertebrae for pathologic compression fractures (15.3%), 4 vertebrae for traumatic compression fractures (15.3%) and 1 vertebrae for painful hemangioma (3.8%). Leakage localizations of bone cement were classified as venous plexus, paravertebral soft tissue, spinal canal, intervertebral foramen, into the niddle channel and intervertebral disc space.
Results: Twelve vertebrae showed no leakage (46.1%). 5 vertebrae had leakage into the niddle channel (19.2%), and 3 had leakage to vertebra disc space leakage (11.5%) and 2 vertebrae had to venous plexus and paravertebral tissue leakage (7.6%) Foraminal and spinal canal leakage (3.8%) was observed in one patient on single level. Radicular pain was seen in one patient. Partial pain control was observed in 20% of the patients while 80% of the patients had complete pain control on follow ups.
Conclusion: Major complications following percutaneous vertebroplasty are mostly due to bone cement leaks. In order to prevent major complications, it is necessary to determine the possible causes of leakage. Performing the application with the correct technique with properly prepared bone cement is essential. Also usage of contast dye may be useful for pre-injection risk of leakage complications
Fetal HLA-G alleles and their effect on miscarriage
No full textBackground. Immunosuppression at the feto-maternal interface is crucial for a successful pregnancy outcome. Human leukocyte antigen-G (HLA-G) seems to be a major contributor to fetal tolerance. The HLA-G expression is seen in cytotrophoblasts and in maternal blood. Fetal HLA-G acts on decidual antigen-presenting cells (APCs), natural killers (NKs) and T cells. Recent findings revealed that defects in placentation and their consequences are associated with maternal HLA-G variants and their expression levels.
Objectives. The objective of this article is to investigate the relationship between fetal HLA-G alleles and miscarriage, which has not been investigated to date.
Material and methods. The present study includes 204 recurrent miscarriage (RM) cases who were admitted to our clinic between 2012 and 2016. Twenty-eight miscarriage products without maternal cell contamination and any known pathology were analyzed by HLA-G typing. In addition, 3' untranslated region (UTR) 14-base pair (bp) insertion/deletion polymorphism was also investigated by Sanger sequencing.
Results. For our population, the most frequent HLA-G type was G*01:01, both in the study group (30.3%) and in the control group (47%). The study revealed that the G*01:04 allele was significantly associated with miscarriage (p = 0.007). The 3' UTR 14bp deletion was more frequent in the miscarriage group, but there was no significant correlation.
Conclusions. HLA-G alleles seem to be related with miscarriage and should be considered in RM cases
Developmental delays and psychiatric diagnoses are elevated in offspring staying in prisons with their mothers
No full textThe aim of the study was to describe the sociodemographic and clinical features of the mothers and their offspring staying with them in prison. The study was planned as a cross-sectional, single-center study of mothers residing in Tarsus Closed Women's Prison of Turkish Ministry of Justice along with their 0 to 6 years old offspring. Mothers were evaluated via Structured Clinical Interview for DSM-IV Axis I Disorders. A psychologist blind to maternal evaluations applied the Denver Developmental Screening Test II (DII-DST). Children/mothers were also evaluated by a child and adolescent psychiatrist via K-SADS-PL. Twenty-four mothers with a mean age of 29.3 years were included. Most common diagnoses in mothers were nicotine abuse (n = 17, 70.8%), specific phobia (n = 8, 33.3%), alcohol abuse (n = 7, 29.2%) and substance abuse (n = 5, 20.8%). Twenty-six children (53.9% female) were living with their mothers in prison, and the mean age of those was 26.3 months. Results of the D-II-DST were abnormal in 33.3% of the children. Most common diagnoses in children were adjustment disorder (n = 7, 26.9%) separation anxiety disorder (n = 3, 11.5%) and conduct disorder (n = 2, 7.7%). A multi-center study is necessary to reach that neglected/under-served population and address the inter-generational transmission of abuse, neglect, and psychopathology
Hounsfield unit value has null effect on thyroid nodules at F-18-FDG PET/CT scans
Get PDFObjective: Detection rate of thyroid nodules is increasing with the use of new imaging modalities, especially in screening for malignancies. Positron emission tomography/computed tomography (PET/CT)-positive thyroid nodules should be differentiated for malignancy to avoid unnecessary operations and further follow-up. Most trials evaluate the role of SUVmax, but there is no definitive information about the utility of Hounsfield unit (HU) values for prediction of malignancy. This study aimed to evaluate the HU values beside SUVmax for detecting malignancy risk of PET/CT-positive thyroid nodules. Subjects and methods: Results of 98 cancer patients who had fine needle aspiration biopsy (FNAB) for thyroid nodules detected on PET/CT between January 2011 and December 2015 were assessed. The FNABs and surgical pathological results were recorded. Results: FNABs revealed benign results in 32 patients (32.7%), malignant in 18 (18.4%), non-diagnostic in 20 (20.4%), and indeterminate in 28 (28.5%). Twenty-four patients underwent thyroidectomy. The mean HU values were not significantly different in benign and malignant nodules (p = 0.73). However, the mean SUVmax was significantly higher (p < 0.001) in malignant ones. Area under curve (AUC) was 0.824 for SUVmax; the cut-off value was over 5.55 (p < 0.001), with 80% sensitivity, 84.5% specificity. Conclusions: Our current study demonstrated that HU value does not add any additional valuable information for discriminating between malignant and benign thyroid nodules. We also defined a SUVmax cut-off value of 5.55 for malignant potential of thyroid nodules detected on PET/CT
Comparison of Three Surgical Techniques in Pilonidal Sinus Surgery
Get PDFOur study aims to compare the surgical outcome of Limberg transposition flap, Karydakis flap, and primary closure after excision to treat sacrococcygeal pilonidal sinus disease. A total of 634 patients with pilonidal sinus who underwent surgery were evaluated retrospectively from January 2014 to January 2016. The patients were divided into three groups. Limberg transposition flap (LTF) was performed in 131 patients (group 1), Karydakis flap (KF) was performed in 232 patients (group 2) and primary closure (PC) after excision was performed in 271 patients (group 3). Patient demographics, operative and postoperative outcomes were recorded and analyzed retrospectively. The mean age (p=0.98), sex ratio (p=0.74) and removed sinus volume (p=0.67) were not statistically different between groups. Mean operative time was 54.3 ± 6.4 min for group 1, 46.8 ± 10.5 min for group 2, and 26.9 ± 5.8 min for group 3 respectively (p=0.01). When the length of hospital stay was compared, there was a significant difference in favor of primary closure (p=0.01). Regarding early surgical complication, Karydakis flap technique was superior to other groups (p<0.001). The recurrent rate was higher in the primary closure group (p<0.001). In our study, the primary closure method regarding the duration of surgery and hospitalization; Karydakis method regarding postoperative complications (seroma, hematoma, wound dissociation, infection, recurrence) were superior to the other two methods