Controlling uncertainty in aptamer selection

The search for high-affinity aptamers for targets such as proteins, small molecules, or cancer cells remains a formidable endeavor. Systematic Evolution of Ligands by EXponential Enrichment (SELEX) offers an iterative process to discover these aptamers through evolutionary selection of high-affinity candidates from a highly diverse random pool. This randomness dictates an unknown population distribution of fitness parameters, encoded by the binding affinities, toward SELEX targets. Adding to this uncertainty, repeating SELEX under identical conditions may lead to variable outcomes. These uncertainties pose a challenge when tuning selection pressures to isolate high-affinity ligands. Here, we present a stochastic hybrid model that describes the evolutionary selection of aptamers to explore the impact of these unknowns. To our surprise, we find that even single copies of high-affinity ligands in a pool of billions can strongly influence population dynamics, yet their survival is highly dependent on chance. We perform Monte Carlo simulations to explore the impact of environmental parameters, such as the target concentration, on selection efficiency in SELEX and identify strategies to control these uncertainties to ultimately improve the outcome and speed of this time- and resource-intensive process.National Cancer Institute (U.S.) (5U01CA177799

Shear Behavior of Non-Persistent Joint under High Normal Load

In this paper, the effect of joint separation on the shear behavior of planar non-persistent joints under high normal load has been investigated using PFC2D. Initially, calibration of PFC was undertaken with respect to the data obtained from experimental laboratory tests to ensure the conformity of the simulated numerical models response. Furthermore, the simulated models were cross checked with the results of direct shear tests performed on non-persistent jointed physical models. Through numerical direct shear tests, the failure process was visually observed, and the failure patterns were found reasonably similar to the experimentally observed trends. The discrete element simulations demonstrated that the failure pattern was mostly influenced by joint separation, while the shear strength was linked to the failure pattern and mechanism.Исследовано влияние разъединения соединения при сдвиге плоского нестабильного соединения под действием интенсивной нормальной нагрузки с использованием программного обеспечения PFC2D. Первоначально калибровка PFC2D проведена на основе экспериментальных данных для согласования с моделируемым числовым результатом. Достоверность моделируемых моделей проверена при сравнении с результатами прямых испытаний на сдвиг, выполненных на нестабильных сочлененных физических моделях. Благодаря числовому прямому испытанию на сдвиг процесс разрушения был отмечен визуально, и разрушенные образцы отбирались подобными экспериментально наблюдаемым тенденциям. Дискретное моделирование элемента показывает, что на разрушение образца главным образом влияет разъединение соединения, в то время как прочность при сдвиге связана с моделью разрушения и механизмом разрушения.Досліджено вплив роз’єднання з’єднання при зсуві плоского нестабільного з’єднання під дією інтенсивного нормального навантаження з використанням програмного забезпечення PFC2D. Спочатку калібрування PFC2D проведено на основі експериментальних даних для узгодження з модельованим числовим результатом. Достовірність модельованих моделей перевірено при порівнянні з результатами прямих випробувань на зсув, що виконані на нестабільних зчленованих фізичних моделях. Завдяки числовому прямому випробуванню на зсув процес руйнування було відмічено візуально, і зруйновані зразки відбиралися подібними експериментально спостережуваним тенденціям. Дискретне моделювання елемента показує, що на руйнування зразка головним чином впливає роз’єднання з’єднання, тоді як міцність при зсуві пов’язана з моделлю руйнування і механізмом руйнування

Platelet Volume Indices in Peripheral Artery Disease

This study aimed to assess the relationship between platelet volume indices (PVI) and peripheral artery disease (PAD). Platelet count (PLT), platelet distribution width (PDW), platelet large cell ratio (P-LCR), and mean platelet volume (MPV) were studied in adult patients with PAD. Two hundred ninety two patients were divided into two groups according to Fontaine classification. Group-1 contained 183 patients with stage I and II with mild symptoms, and the remaining 109 patients referred to the group-2 with severe symptoms. Blood samples were analyzed in a Sysmex SF- 3000 for platelet indices. There were no significant differences between patients in group-1 and group-2 in terms of PVI (P > 0.05). No significant correlation was identified between severity of peripheral vascular disease and PVI in patients with PAD. PVI seem not to associate with severity of PAD

Preanalytical Factors Affecting the Mean Platelet Volume: a Review

Mean platelet volume (MPV) as an indicator of platelet activation is a subject of many studies. Since the introduction of automated hematology analyzers, many authors described mean platelet volume as a marker for different pathologic conditions. It is also known that numerous preanalytical conditions could affect MPV results. Specimens are usually tested several hours after blood collection. There are some specific hematology analyzers which are in use by the majority of hematology laboratories. This review demonstrates some important aspects related to MPV measurement in routine laboratory

The Effect of Activated FXIII, a Transglutaminase, on Vascular Smooth Muscle Cells

Plasma factor XIII (pFXIII) is a heterotetramer of FXIII-A and FXIII-B subunits. The cellular form (cFXIII), a dimer of FXIII-A, is present in a number of cell types. Activated FXIII (FXIIIa), a transglutaminase, plays an important role in clot stabilization, wound healing, angiogenesis and maintenance of pregnancy. It has a direct effect on vascular endothelial cells and fibroblasts, which have been implicated in the development of atherosclerotic plaques. Our aim was to explore the effect of FXIIIa on human aortic smooth muscle cells (HAoSMCs), another major cell type in the atherosclerotic plaque. Osteoblastic transformation induced by Pi and Ca2+ failed to elicit the expression of cFXIII in HAoSMCs. EZ4U, CCK-8 and CytoSelect Wound Healing assays were used to investigate cell proliferation and migration. The Sircol Collagen Assay Kit was used to monitor collagen secretion. Thrombospondin-1 (TSP-1) levels were measured by ELISA. Cell-associated TSP-1 was detected by the immunofluorescence technique. The TSP-1 mRNA level was estimated by RT-qPCR. Activated recombinant cFXIII (rFXIIIa) increased cell proliferation and collagen secretion. In parallel, a 67% decrease in TSP-1 concentration in the medium and a 2.5-fold increase in cells were observed. TSP-1 mRNA did not change significantly. These effects of FXIIIa might contribute to the pathogenesis of atherosclerotic plaques

Cellular Factor XIII, a Transglutaminase in Human Corneal Keratocytes

Cellular factor XIII (cFXIII, FXIII-A2), a transglutaminase, has been demonstrated in a few cell types. Its main function is to cross-link proteins by isopeptide bonds. Here, we investigated the presence of cFXIII in cells of human cornea. Tissue sections of the cornea were immunostained for FXIII-A in combination with staining for CD34 antigen or isopeptide cross-links. Isolated corneal keratocytes were also evaluated by immunofluorescent microscopy and flow cytometry. FXIII-A in the corneal stroma was quantified by Western blotting. FXIII-A mRNA was detected by RT-qPCR. The cornea of FXIII-A-deficient patients was evaluated by cornea topography. FXIII-A was detected in 68 ± 13% of CD34+ keratocytes. Their distribution in the corneal stroma was unequal; they were most abundant in the subepithelial tertile. cFXIII was of cytoplasmic localization. In the stroma, 3.64 ng cFXIII/mg protein was measured. The synthesis of cFXIII by keratocytes was confirmed by RT-qPCR. Isopeptide cross-links were detected above, but not within the corneal stroma. Slight abnormality of the cornea was detected in six out of nine FXIII-A-deficient patients. The presence of cFXIII in human keratocytes was established for the first time. cFXIII might be involved in maintaining the stability of the cornea and in the corneal wound healing process

Reforming Fiscal Institutions in Resource-Rich Arab Economies: Policy Proposals

This paper traces the evolution of fiscal institutions of Resource Rich Arab Economies (RRAEs) over time since their pre-oil days, through the discovery of oil to their build-up of oil exports. It then identifies challenges faced by RRAEs and variations in their severity among the different countries over time. Finally, it articulates specific policy reforms, which, if implemented successfully, could help to overcome these challenges. In some cases, however, these policy proposals may give rise to important trade-offs that will have to be evaluated carefully in individual cases

BILATERAL RENAL ARTERY STENOSIS IN THREE HUNDRED CANDIDATE PATIENTS FOR CORONARY ARTERY ANGIOGRAPHY

Introduction. Renovascular disease is the commonset form of surgically curable hypertension Estimates of the prevalence in general population range from 0.2 percent to 4 percent. It is the most common secondary form of hypertension that is not easily recognizable but curable. We studied the frequency of bilateral renal artery stenosis in patients who had been candidated for coronary artery angiography.
 Methods. Angiography of oronary and renal artery were done in three hundred patients (56.5 percent female and 43.5 percent male), simultaneously. The procedure was done by digital substraction angiography tract in chamran hospital (affiliated ti IUMSHS).
 Results. Fifthy patients had renal artery stenosis. Fourthy six patients had unilateral and four patients had bilateral renal artery stenosis. Only 8 percent of renal stenosis was bilateral.
 Discussion. Atherosclerosis is the most frequent cause of renal artery stenosis. It is often bilateral and progressive, but in this study only 8 percent of patients (1.3 percent of all patients that undergo angiography) had bilateral renal artery stenosis. Therefore in our study bilateral renal artery stenosis was much lower from previous study in other country