Precise mapping of disordered regions of nucleoporins in situ

The nuclear pore complex (NPC) is an immense structure which functions as a primary gateway for transport of biomolecules in and out of the nucleus. The NPC allows passive diffusion of small molecules (< 40 kDa, < 4 nm) while blocking large cargo molecules unless they are bound to nuclear transport receptors (NTRs). It is composed of roughly 30 different types of proteins called nucleoporins (Nups). The central transport channel is filled with Nups containing numerous phenylalanine-glycine (FG) repeats which play a major role in forming the permeability barrier. Recent advancements in structural biology approaches have greatly contributed to deciphering the structure of the ring-like NPC scaffold. However, insights about the fundamental nature of the FG Nups such as their spatial organization and dynamics in the central transport channel of the NPC still remains challenging. This is mainly due to technical limitations when aiming to study the flexible intrinsically disordered regions of FG Nups. The goal of my thesis was to devise an experimental strategy to study the spatial organization of FG Nups with residue precision in cells using super-resolution microscopy (SRM). One main bottleneck to achieve this goal was to develop a tool to site-specifically label intracellular proteins with synthetic fluorophores (SFs). In this thesis, I developed and established a labeling strategy implementing genetic code expansion (GCE) technology and click-chemistry reaction in order to label FG Nups in situ in mammalian cells with residue specificity. Moreover, I designed a dual-color imaging strategy using spectral demixing coupled to a robust automated custom-written analysis to quantitatively assess and compare different labeling positions along the disordered regions of FG Nups. I validated the developed labeling and analysis strategy by determining the localization of Nup153, which is one of the largest and in terms of function, one of the most debated FG Nups in the NPC of mammalian cells. Ultimately, I fully utilized the new approach to map the spatial organization of distinct Nup98 regions in situ in mammalian cells. I will discuss possible interpretations and pitfalls of the acquired results and also the steps that are needed to make the labeling strategy live-cell compatible. Further application of my developed approach to other FG Nups in the central channel of the NPC will contribute in acquiring a deeper understanding of the molecular mechanisms behind nucleocytoplasmic transport. In general, my work presents a complementary approach to study the structure and dynamics of flexible proteins inside cells and paves the way towards precise in-cell structural biology

Effect of 5-alpha Reductase Inhibitor on Storage Symptoms in Patients with Benign Prostatic Hyperplasia

Purpose Many patients with benign prostatic hyperplasia (BPH) have storage symptoms. The aim of this study was to evaluate the effects of treatment with a 5-alpha reductase inhibitor (5ARI) on storage symptoms in patients with BPH. Methods This study was conducted in 738 patients with lower urinary tract symptoms secondary to BPH. Patients with a prostate volume of higher than 30 mL on the transrectal ultrasound were classified into two groups: group A, in which an alpha blocker was solely administered for at least 12 months, and group B, in which a combination treatment regimen of an alpha blocker plus 5ARI was used. This was followed by an analysis of the changes in parameters such as the total International Prostate Symptom Score (IPSS), voiding symptom subscore, and storage symptom subscore between the two groups. In addition, we examined whether there was a significant difference between the two groups in the degree of change in storage symptoms between before and after the pharmacological treatment. Results Of the 738 men, 331 had a prostate volume ≥30 mL, including 150 patients in group A and 181 patients in group B. Total IPSS, the voiding symptom subscore, and the storage symptom subscore were significantly lower after treatment than before treatment in both groups (P<0.05). A comparison of the degree of change between before and after treatment, however, showed no significant differences in the storage symptom subscore between the two groups (P>0.05). Conclusions Alpha blocker and 5ARI combination treatment is effective for patients with BPH including storage symptoms. However, 5ARI does not exert a significant effect on storage symptoms in BPH patients

Characteristics of DSSC Panels with Silicone Encapsulant

Dye-sensitized solar cells (DSSC) allow light transmission and the application of various colors that make them especially suitable for building-integrated PV (BIPV) application. In order to apply DSSC modules to windows, the module has to be panelized: a DSSC module should be protected with toughened glass on the entire surface. Up to the present, it seems to be common to use double glazing with DSSC modules, with air gaps between the glass pane and the DSSC modules. Few studies have been conducted on the characteristics of various glazing methods with DSSC modules. This paper proposes a paneling method that uses silicone encapsulant, analyzing the performance through experimentation. Compared to a multilayered DSSC panel with an air gap, the encapsulant-applied panel showed 6% higher light transmittance and 7% higher electrical efficiency. The encapsulant also prevented electrolyte leakage by strengthening the seals in the DSSC module

Malakoplakia of the Kidney Extending to the Descending Colon in a Patient with Secondary Adrenal Insufficiency: A Case Report

Malakoplakia is an uncommon but distinctive type of chronic granulomatous inflammation that occurs most commonly in the genitourinary tract, especially the urinary bladder. Most patients have associated conditions characterized by some degree of immunosuppression, as seen in solid-organ transplants, autoimmune diseases requiring steroid use, chemotherapy, chronic systemic diseases, alcohol abuse and poorly controlled diabetes. We report an unusual case of the renal malakoplakia that involved the perirenal space, extending to the descending colon in a 65-year-old Korean woman with secondary adrenal insufficiency and diabetes mellitus

Design Elements and Electrical Performance of a Bifacial BIPV Module

Bifacial BIPV systems have great potential when applied to buildings given their use of a glass-to-glass structure. However, the performance of bifacial solar cells depends on a variety of design factors. Therefore, in order to apply bifacial solar cells to buildings, a bifacial PV module performance analysis should be carried out, including consideration of the various design elements and reflecting a wide range of installation conditions. This study focuses on the performance of a bifacial BIPV module applied to a building envelope. The results here show that the design elements of reflectivity and the transparent space ratio have the greatest impact on performance levels. The distance between the module and the wall had less of an impact on performance. The bifacial BIPV module produced output up to 30% greater than the output of monofacial PV modules, depending on the design elements. Bifacial BIPV modules themselves should have transparent space ratios of at least 30%. When a dark color is used on the external wall with reflectivity of 50% or less, bifacial BIPV modules with transparent space ratios of 40% and above should be used. In order to achieve higher performance through the installation of bifacial BIPV modules, design conditions which facilitate reflectivity exceeding 50% and a transparent space ratio which exceeds 30% must be met

Remifentanil Prevents Tourniquet-Induced Arterial Pressure Increase in Elderly Orthopedic Patients under Sevoflurane/N2O General Anesthesia

Aims: Prolonged tourniquet inflation produces a hyperdynamic cardiovascular response. We investigated the effect of continuous remifentanil infusion on systemic arterial pressure, heart rate, and cardiac output changes during prolonged tourniquet use in elderly patients under sevoflurane/N2O general anesthesia