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Yardımcı üreme teknolojisi sikluslarında gonadotropin salgılayıcı hormon agonistleri ile ovulasyonun tetiklenmesi
No full textGonadotropin-releasing hormone agonists (GnRHa) have gained increasing attention in the last decade as an alternative trigger for oocyte maturation in patients at high risk for ovarian hyperstimulation syndrome (OHSS). They provide a short luteinizing hormone (LH) peak that limits the production of vascular endothelial growth factor, which is the key mediator leading to increased vascular permeability, the hallmark of OHSS. Initial studies showed similar oocyte yield and embryo quality compared with conventional human chorionic gonadotropin (hCG) triggering; however, lower pregnancy rates and higher miscarriage rates were alarming in GnRHa triggered groups. Therefore, two approaches have been implemented to rescue the luteal phase in fresh transfers. Intensive luteal phase support (iLPS) involves administiration of high doses of progesterone and estrogen and active patient monitoring. iLPS has been shown to provide satisfactory fertilization and clinical pregnancy rates, and to be especially useful in patients with high endogenous LH levels, such as in polycystic ovary syndrome. The other method for luteal phase rescue is low-dose hCG administiration 35 hours after GnRHa trigger. Likewise, this method results in statistically similar ongoing pregnancy rates (although slightly lower than) to those of hCG triggered cycles. GnRHa triggering decreased OHSS rates dramatically, however, none of the rescue methods prevent OHSS totally. Cases were reported even in patients who underwent cryopreservation and did not receive hCG. GnRH triggering induces a follicle stimulating hormone (FSH) surge, similar to natural cycles. Its possible benefits have been investigated and dual triggering, GnRHa trigger accompanied by a simultaneous low-dose hCG injection, has produced promising results that urge further exploration. Last of all, GnRHa triggering is useful in fertility preservation cycles in patients with hormone sensitive tumors. In conclusion, GnRHa triggering accompanied by appropriate luteal phase rescue protocols is a relatively safe option for patients at high risk for OHSS. / Gonadotropin salgılayıcı hormon agonistleri (GnRHa), ovaryan hiperstimülasyon sendromu (OHSS) açısından yüksek riskli olan hastalarda oosit matürasyonunun tetiklenmesi için bir alternatif olarak dikkat çekmişlerdir. Kısa süren bir lüteinizan hormon (LH) piki yarattıkları için OHSS’nin patogenezinde yatan artmış damar geçirgenliğinin sorumlusu vasküler endoteliyal büyüme faktörünün üretimini sınırlandırırlar. İnsan koryonik gonadotropin (hCG) ve GnRHa ile oosit matürasyonunun tetiklenmesini karşılaştıran ilk çalışmalarda, elde edilen oosit sayısı ve embryo kalitesi açısından iki grup arasında fark yokken, GnRHa kullanılan grupta gebelik oranlarının daha düşük ve gebelik kaybı oranlarının daha yüksek olduğu gözlenmiştir. Bu nedenle, taze transfer sikluslarında luteal fazın kurtarılması için iki yöntem geliştirilmiştir. Bunların ilki yoğun luteal faz desteği (iLPS) olup, yüksek doz progesteron ve östrojen verilmesini luteal fazing aktif takibini gerektirir. iLPS ile tatminkar fertilizasyon ve klinik gebelik oranları sağlanmış, polikistik ove sendromu gibi endojen LH seviyeleri yüksek olan hastalarda özellikle faydalı bulunmuştur. Luteal fazın kurtarılması için önerilen diğer yöntem ise GnRHa’dan 35 saat sonra düşük doz hCG uygulanmasıdır. Bu yöntemle, konvansiyonel hCG’dekine yakın (fakat bir miktar daha düşük) gebelik oranları elde edilmiştir. GnRHa kullanımı OHSS oranlarını belirgin biçimde düşürmekle birlikte, hiç bir yöntemin OHSS’yi tamamen ortadan kaldıramadığı bilinmelidir. hCG almayan ve doğrudan kriyoprezervasyon yapılan hastalarda dahi OHSS olguları bildirilmiştir. GnRHa ile oosit matürasyonunun tetiklenmesi sırasında, doğal sikluslardakine benzer bir folikül stimulan hormone artışı sağlanır. Bu artışın olası faydaları göz önüne alınarak ikili tetikleme (dual triggering) metodu geliştirilmiştir. GnRHa ile tetikleme sırasında düşük doz hCG uygulanmış, umut vadeden sonuçlar alınmıştır. Ayrıca, GnRHa ile oosit matürasyonu sağlanmasının, hormonlara duyarlı kanseri olan hastalarda fertilite korunmasında faydalı olabileceği gösterilmiştir. Sonuçta, GnRHa ile tetiklemeyi takiben uygun luteal faz kurtarma protokollerinin uygulanması OHSS açısından yüksek risk taşıyan hastalarda büyük ölçüde güvenli bir yöntemdir
Estimation of global lightning activity and observations of atmospheric electric field
No full textVariations in the global atmospheric electric circuit are investigated using a wide range of globally spaced instruments observing VLF (similar to 10 kHz) waves, ELF (similar to 300 Hz) waves, Schumann resonances (4-60 Hz), and the atmospheric fair weather electric field. For the ELF/VLF observations, propagation effects are accounted for in a novel approach using established monthly averages of lightning location provided by the Lightning Image Sensor (LIS) and applying known frequency specific attenuation parameters for daytime/nighttime ELF/VLF propagation. Schumann resonances are analyzed using decomposition into propagating and standing waves in the Earth-ionosphere waveguide. Derived lightning activity is compared to existing global lightning detection networks and fair weather field observations. The results suggest that characteristics of lightning discharges vary by region and may have diverse effects upon the ionospheric potential
A stochastic representation for mean curvature type geometric flows
No full textA smooth solution {Gamma(t)}(tis an element of[0,T]) subset of R-d of a parabolic geometric flow is characterized as the reachability set of a stochastic target problem. In this control problem the controller tries to steer the state process into a given deterministic set T with probability one. The reachability set, V(t), for the target problem is the set of all initial data x from which the state process X-X(v)(t) is an element of T for some control process v. This representation is proved by studying the squared distance function to Gamma(t). For the codimension k mean curvature flow, the state process is dX(t) = root2P dW(t), where W(t) is a d-dimensional Brownian motion, and the control P is any projection matrix onto a (d - k)-dimensional plane. Smooth solutions of the inverse mean curvature flow and a discussion of non smooth solutions are also given
Superior oblique anterior transposition with horizontal recti recession-resection for total third-nerve palsy
No full textAims. To report the results of lateral rectus muscle recession, medial rectus muscle resection, and superior oblique muscle transposition in the restoration and maintenance of ocular alignment in primary position for patients with total third-nerve palsy. Methods. The medical records of patients who underwent surgery between March 2007 and September 2011 for total third-nerve palsy were reviewed. All patients underwent a preoperative assessment, including a detailed ophthalmologic examination. Results. A total of 6 patients (age range, 14-45 years) were included. The median preoperative horizontal deviation was 67.5 Prism Diopter (PD) (interquartile range [IQR] 57.5-70) and vertical deviation was 13.5 PD (IQR 10-20). The median postoperative horizontal residual exodeviation was 8.0 PD (IQR 1-16), and the vertical deviation was 0 PD (IQR 0-4). The median correction of hypotropia following superior oblique transposition was 13.5 +/- 2.9 PD (range, 10-16). All cases were vertically aligned within 5 PD. Four of the six cases were aligned within 10 PD of the horizontal deviation. Adduction and head posture were improved in all patients. All patients gained new area of binocular single vision in the primary position after the operation. Conclusion. Lateral rectus recession, medial rectus resection, and superior oblique transposition may be used to achieve satisfactory cosmetic and functional results in total third-nerve palsy
Reliefs of Southern Gate, Alacahöyük
No full textReliefs of Southern Gate, Alacahöyük. They were made inside the Sphinx Gate and located on the right of the two great sphinxes of the southern outer monumental gateway which was set between two towers. In the doorjambs are two 13 foot hight monoliths which were carved to create 7 foot high sphinxes. Inside this Sphinx Gate was a large Hittite building complex. An important city in pre-Hittite times, Alacahöyük was overshadowed by the nearby capital Hattusa of the Hittites after the Hittite conquest. Alacahöyük located 36 km to the northeast of the Hattusa (Boğazköy), in the Çorum province of Turkey. Although the most important findings are the artifacts from the pre-Hittite royal tombs dating from about 2500 BC, the outstanding monuments today are from the Hittite period.Black & white photograph
Burial finding with bull figure, Pre-Hittite Hattic religious standard, Alacahöyük
No full textImage of one of the burial findings, cult object found in the royal tombs of pre-Hittite (Hatti) times from 3rd millenium BC, represented to gods. Hieroglyphs also seen in the background. It is currently housed in Anatolian Civilization Museum in Ankara.Black & white photograph
Time-resolved local strain tracking microscopy for cell mechanics
No full textA uniaxial cell stretching technique to measure time-resolved local substrate strain while simultaneously imaging adherent cells is presented. The experimental setup comprises a uniaxial stretcher platform compatible with inverted microscopy and transparent elastomer samples with embedded fluorescent beads. This integration enables the acquisition of real-time spatiotemporal data, which is then processed using a single-particle tracking algorithm to track the positions of fluorescent beads for the subsequent computation of local strain. The present local strain tracking method is demonstrated using polydimethylsiloxane (PDMS) samples of rectangular and dogbone geometries. The comparison of experimental results and finite element simulations for the two sample geometries illustrates the capability of the present system to accurately quantify local deformation even when the strain distribution is non-uniform over the sample. For a regular dogbone sample, the experimentally obtained value of local strain at the center of the sample is 77%, while the average strain calculated using the applied cross-head displacement is 48%. This observation indicates that considerable errors may arise when cross-head measurement is utilized to estimate strain in the case of non-uniform sample geometry. Finally, the compatibility of the proposed platform with biological samples is tested using a unibody PDMS sample with a well to contain cells and culture media. HeLa S3 cells are plated on collagen-coated samples and cell adhesion and proliferation are observed. Samples with adherent cells are then stretched to demonstrate simultaneous cell imaging and tracking of embedded fluorescent beads
Cyclophilin40 isomerase activity is regulated by a temperature-dependent allosteric interaction with Hsp90
No full textCyclophilin 40 (Cyp40) comprises an N-terminal cyclophilin domain with peptidyl-prolyl isomerase (PPIase) activity and a C-terminal tetratricopeptide repeat (TPR) domain that binds to the C-terminal -EEVD sequence common to both heat shock protein 70 (Hsp70) and Hsp90. We show in the present study that binding of peptides containing the MEEVD motif reduces the PPIase activity by similar to 30%. CD and fluorescence assays show that the TPR domain is less stable than the cyclophilin domain and is stabilized by peptide binding. Isothermal titration calorimetry (ITC) shows that the affinity for the -MEEVD peptide is temperature sensitive in the physiological temperature range. Results from these biophysical studies fit with the MD simulations of the apo and holo (peptide-bound) structures which show a significant reduction in root mean square (RMS) fluctuation in both TPR and cyclophilin domains when -MEEVD is bound. The MD simulations of the apo-protein also highlight strong anti-correlated motions between residues around the PPIase-active site and a band of residues running across four of the seven helices in the TPR domain. Peptide binding leads to a distortion in the shape of the active site and a significant reduction in these strongly anti-correlated motions, providing an explanation for the allosteric effect of ligand binding and loss of PPIase activity. Together the experimental and MD results suggest that on heat shock, dissociation of Cyp40 from complexes mediated by the TPR domain leads to an increased pool of free Cyp40 capable of acting as an isomerase/chaperone in conditions of cellular stress
Classification of drug molecules considering their IC(50) values using mixed-integer linear programming based hyper-boxes method
No full textBackground: A priori analysis of the activity of drugs on the target protein by computational approaches can be useful in narrowing down drug candidates for further experimental tests. Currently, there are a large number of computational methods that predict the activity of drugs on proteins. In this study, we approach the activity prediction problem as a classification problem and, we aim to improve the classification accuracy by introducing an algorithm that combines partial least squares regression with mixed-integer programming based hyper-boxes classification method, where drug molecules are classified as low active or high active regarding their binding activity (IC(50) values) on target proteins. We also aim to determine the most significant molecular descriptors for the drug molecules. Results: We first apply our approach by analyzing the activities of widely known inhibitor datasets including Acetylcholinesterase (ACHE), Benzodiazepine Receptor (BZR), Dihydrofolate Reductase (DHFR), Cyclooxygenase-2 (COX-2) with known IC(50) values. The results at this stage proved that our approach consistently gives better classification accuracies compared to 63 other reported classification methods such as SVM, Naive Bayes, where we were able to predict the experimentally determined IC50 values with a worst case accuracy of 96%. To further test applicability of this approach we first created dataset for Cytochrome P450 C17 inhibitors and then predicted their activities with 100% accuracy. Conclusion: Our results indicate that this approach can be utilized to predict the inhibitory effects of inhibitors based on their molecular descriptors. This approach will not only enhance drug discovery process, but also save time and resources committed
Is there any association between cognitive status and functional capacity during exacerbation of chronic obstructive pulmonary disease?
No full textThe aim of this study is to screen the cognitive function during exacerbation of chronic obstructive pulmonary disease (COPD) and investigate whether there is any association between cognitive function and functional impairment, disease severity, or other clinical parameters. Age and sex-matched 133 subjects with COPD exacerbation, 34 stable COPD subjects, and 34 non-COPD subjects were enrolled in this study. For the purpose of this study, mini-mental state examination (MMSE) and Hospital Anxiety and Depression scale were performed. Six-minute walk distance (6MWD) was recorded, and BODE index was calculated. COPD subjects with exacerbation had the lowest MMSE scores (p = 0.022). Frequency of subjects with MMSE score lower than 24 is 22.6, 8.8, and 8.8% in the COPD subjects with exacerbation, stable COPD, and non-COPD control subjects, respectively. The COPD subjects with exacerbation who had MMSE scores lower than 24 were older and less educated. Subjects with COPD exacerbation had shorter 6MWD than that of stable COPD and non-COPD subjects. After controlling for the impact of age and educational level on MMSE, there was no association between 6MWD and MMSE scores in subjects with COPD exacerbation. Cognitive impairment is an important comorbidity during COPD exacerbation. Functional capacity is also lower in exacerbation. However, no association was found between cognitive impairment and functional capacity during exacerbation