OPTIMIZATION OF PHOTOLUMINESCENCE-FOLLOWING ELECTRON-TRANSFER WITH TRIS(2,2'-BIPYRIDYL)OS(III) AND APPLICATION TO THE DETERMINATION OF DOPAMINE, SEROTONIN AND CARBIDOPA IN BRAIN MICRODIALYSATE

Biogenic monoamines such as dopamine and serotonin play important roles as major neurotransmitters. Simultaneous determination of the concentration changes is thus crucial to understand brain function. We have developed a capillary HPLC combined with a redox-based postcolumn reaction method, the photoluminescence-following electron-transfer (PFET) technique, for the determination of certain neurotransmitters and their metabolites. Tris(2,2'-bipyridine)osmium was the postcolumn oxidant. The spectroscopic properties of the oxidant changed upon a redox reaction. The change was measured using a laser-induced fluorescence setup to quantify electrochemically active analytes from the chromatographic eluent. Spectroscopic and electrochemical properties of the complex, along with its reaction kinetics were studied in detail to optimize the postcolumn reaction efficiency. The complex was capable of oxidizing and detecting catechols. The spectroscopic properties of the complex were not very advantageous, but careful control of the detection system and reaction conditions enabled sensitive detection of monoamine neurotransmitters in rat brain dialysates. The extent of the postcolumn reaction was predicted by the second-order reaction kinetics in fluidic conditions and experimentally verified. Efficient mixing and reaction of the postcolumn reagent was achieved in a radial diffusion mixer without significant band broadening. The optimized system was capable of detecting biogenic monoamines, such as dopamine, serotonin and 3-methoxytyramine, at about 200 pM concentrations in 500 nL samples. Typical analysis time was less than 10 min. We used this method to monitor neurotransmitter concentrations in rat brain dialysates when the rat was given tetrodotoxin or nomifensine. Changes in neurotransmitter concentrations were observed. Another application of this method was detecting carbidopa in rat brain microdialysates, to study the damage in brain tissues by a microdialysis probe. We observed that carbidopa was present in striatal dialysates after the rat was given i.p. injection of carbidopa

Implicit Kernel Attention

\textit{Attention} computes the dependency between representations, and it encourages the model to focus on the important selective features. Attention-based models, such as Transformers and graph attention networks (GAT) are widely utilized for sequential data and graph-structured data. This paper suggests a new interpretation and generalized structure of the attention in Transformer and GAT. For the attention in Transformer and GAT, we derive that the attention is a product of two parts: 1) the RBF kernel to measure the similarity of two instances and 2) the exponential of $L^{2}$ norm to compute the importance of individual instances. From this decomposition, we generalize the attention in three ways. First, we propose implicit kernel attention with an implicit kernel function, instead of manual kernel selection. Second, we generalize $L^{2}$ norm as the $L^{p}$ norm. Third, we extend our attention to structured multi-head attention. Our generalized attention shows better performance on classification, translation, and regression tasks

Modelling and Simulation of a River-Crossing Operation via Discrete Event Simulation with Engineering Details

From a military standpoint, a river is an area that should be avoided in a potential engagement because of lack of cover and the necessity of dividing the unit while crossing. Thus, a key point of a river-crossing operation is speed. Many efforts have been made to enable faster river crossing by improvement of tactics, techniques, and procedures (TTP). However, improvements in TTP are evaluated by modelling and simulation much less frequently than are the toe-to-toe engagements between two opposing forces, and to our knowledge, this is the first simulation model of brigade-level river crossing with engineering details. This study presents a simulation model of the river-crossing operation, applies real world parameters, and evaluates which tactics are preferable in a particular operational environments. This analysis has led to new operational methods of river crossing that have been suggested by experienced subject-matter experts. For instance, the current Republic of Korea Army Field Manual dictates to rotate river-crossing rafts in all situations, but our experiment suggests that no rotation is preferable when the width of river is less than 400 m based on the statistical analyses, which includes the regression-based meta-modelling and the ANOVA, of our simulation model that embodies the engineering details of river-crossing equipment.Defence Science Journal, Vol. 65, No. 2, March 2015, pp.135-143, DOI:http://dx.doi.org/10.14429/dsj.65.814

CONTRIBUTION OF THE KNEE JOINT TO MECHANICAL ENERGY IN CROUCHING START ACCORDING TO THE BACKWARD BLOCK INCLINED ANGLE INCREASE

The purpose of this study was to analyze the contribution of the knee joint to mechanical energy in crouching start according to the backward block inclined angle increase(F, F1, F2). Using kinetic and kinematic data from 3 university sprinters participating in this study we calculated the energies absorbed and generated by the knee joints. The analysis is limited to a two-dimensional (sagittal plane) exercise. Comparing mean values of the energy absorbed and generated from lower extremity joints of each subjects according to backward block inclined angle increase (F, F1, F2). We generate a ratio of a total energy absorbed and generated from lower extremities to one from knee joints. The generated energy of knee joints during start was the highest for all subjects and the absorbed energy of those was the lowest at 55 degree of backward block angle, or F, for subject 1, 50 degree for subject 2, and 50 degree for subject 3

Refining Generative Process with Discriminator Guidance in Score-based Diffusion Models

The proposed method, Discriminator Guidance, aims to improve sample generation of pre-trained diffusion models. The approach introduces a discriminator that gives explicit supervision to a denoising sample path whether it is realistic or not. Unlike GANs, our approach does not require joint training of score and discriminator networks. Instead, we train the discriminator after score training, making discriminator training stable and fast to converge. In sample generation, we add an auxiliary term to the pre-trained score to deceive the discriminator. This term corrects the model score to the data score at the optimal discriminator, which implies that the discriminator helps better score estimation in a complementary way. Using our algorithm, we achive state-of-the-art results on ImageNet 256x256 with FID 1.83 and recall 0.64, similar to the validation data's FID (1.68) and recall (0.66). We release the code at https://github.com/alsdudrla10/DG.Comment: International Conference on Machine Learning (ICML23

Decomposing Organizational Productivity Changes in Acute Care Hospitals in Tennessee, 2002-2006: A Malmquist Approach

After the passage of the Patient Protection and Affordable Care Act, the survival and the productivity of hospitals are a critical topic in health care management. This study measured the productivity of acute care hospitals in Tennessee, applying the DEA-Malmquist index, which can be decomposed into a technical efficiency and technological change index in relation to factors such as size, ownership, location, and network. This draws on utilization data and financial statements from 144 acute care hospitals in Tennessee from 2002 through 2006. The analysis indicates that community hospitals in Tennessee were generally inefficient. The community hospitals in Tennessee suffered both with respect to technological change and technical efficiency, with the latter playing a relatively more important role. This study finds the bigger-sized, urban, public or nonprofit, strategically allied hospitals to be more productive relatively speaking and suggests that community hospitals in Tennessee need to upsize their facilities or make other adjustments, such as changing their cost structure and the way they operate their facility or bringing in new management to increase productivity. Government and health policy makers also need to develop and enact health policies to ensure that hospitals are both able to make technical progress and improve efficiency and thereby increase productivity.This paper was supported by the National Research Foundation of Korea Grant funded by the Korean Government (NRF-2010-330-B00031 and NRF-2012-330-B00194)

Clinicopathological characteristics of light chain proximal tubulopathy in Korean patients and the diagnostic usefulness of immunohistochemical staining for immunoglobulin light chain

Light chain proximal tubulopathy (LCPT) is a rare paraproteinemic renal disease that has been mostly reported in Western patients. LCPT is characterized by the accumulation of immunoglobulin (Ig)-light chain (LC) in the proximal tubule. Immunohistochemical staining for Ig-LC has not been investigated in the context of LCPT. We reported the clinicopathological characteristics and Ig-LC immunoexpression of patients with LCPT for the first time in Korea. We reviewed the clinicopathological findings of 5 Korean patients diagnosed with LCPT between 2016 and 2018. In addition, immunohistochemical staining for κ-LC and λ-LC was conducted on paraffin-embedded tissues. The median age was 63 years, and the male-to-female ratio was 3:2. The primary renal manifestations were either azotemia or tubular proteinuria. All patients were diagnosed with multiple myeloma with monoclonal κ-LC (#1–2) or λ-LC (#3–5) in the serum and urine. Kidney biopsies revealed diverse and subtle alterations of the proximal tubule, including crystallization, vacuolization, and/or swelling. Electron microscopy revealed crystals in patients #1–2 and non-crystalline particles within numerous/large/dysmorphic lysosomes in patients #3–5. Ig-LC restriction was demonstrated in the proximal tubule as κ-type in patients #1–2 and as λ-type in patients #3–5 by immunohistochemistry and immunofluorescence. Immunohistochemical staining showed diffuse positivity to κ- and λ-LC, although immunofluorescent staining for κ-LC was focal and weak. LCPT has diverse clinicopathological characteristics and subtle morphological alterations, which necessitate ancillary tests for diagnosis. We introduced immunohistochemical staining for Ig-LC as a useful tool for the diagnosis of LCPT, especially in the case of κ-type crystals

Loss of aquaporin-1 expression is associated with worse clinical outcomes in clear cell renal cell carcinoma: an immunohistochemical study

Background Aquaporin (AQP) expression has been investigated in various malignant neoplasms, and the overexpression of AQP is related to poor prognosis in some malignancies. However, the expression of AQP protein in clear cell renal cell carcinoma (ccRCC) has not been extensively investigated by immunohistochemistry with large sample size. Methods We evaluated the AQP expression in 827 ccRCC with immunohistochemical staining in tissue microarray blocks and classified the cases into two categories, high and low expression. Results High expression of aquaporin-1 (AQP1) was found in 320 cases (38.7%), but aquaporin-3 was not expressed in ccRCC. High AQP1 expression was significantly related to younger age, low TNM stage, low World Health Organization/International Society of Urologic Pathology nuclear grade, and absence of distant metastasis. Furthermore, high AQP1 expression was also significantly associated with longer overall survival (OS; p<.001) and progression-specific survival (PFS; p<.001) and was an independent predictor of OS and PFS in ccRCC. Conclusions Our study revealed the prognostic significance of AQP1 protein expression in ccRCC. These findings could be applied to predict the prognosis of ccRCC

Dihydrotestosterone-Inducible IL-6 Inhibits Elongation of Human Hair Shafts by Suppressing Matrix Cell Proliferation and Promotes Regression of Hair Follicles in Mice

Autocrine and paracrine factors are produced by balding dermal papilla (DP) cells following dihydrotestosterone (DHT)-driven alterations and are believed to be key factors involved in male pattern baldness. Herein we report that the IL-6 is upregulated in balding DP cells compared with non-balding DP cells. IL-6 was upregulated 3hours after 10–100nM DHT treatment, and ELISA showed that IL-6 was secreted from balding DP cells in response to DHT. IL-6 receptor (IL-6R) and glycoprotein 130 (gp130) were expressed in follicular keratinocytes, including matrix cells. Recombinant human IL-6 (rhIL-6) inhibited hair shaft elongation and suppressed proliferation of matrix cells in cultured human hair follicles. Moreover, rhIL-6 injection into the hypodermis of mice during anagen caused premature onset of catagen. Taken together, our data strongly suggest that DHT-inducible IL-6 inhibits hair growth as a paracrine mediator from the DP

The Prognostic Implications of Cystic Change in Clear Cell Renal Cell Carcinoma

Background : Cystic renal cell carcinoma has been reported to have a good prognosis. However, previous studies included cases of multilocular cystic renal cell carcinoma, which has an excellent prognosis, and renal cell carcinoma with cystic necrosis, which has an adverse prognosis. Therefore, we analyzed the prognostic influence of cystic change in clear cell renal cell carcinoma after excluding those morphological features. Methods : We identified 225 patients with clear cell renal cell carcinoma who underwent nephrectomy between 2001 and 2003. The clinicopathologic features were compared with clinical outcomes. Results : Cystic change in clear cell renal cell carcinoma (n = 66) was significantly associated with younger patient age (< 55), smaller tumor size (<= 4 cm), lower pT stage (pT1, T2), M0 stage at initial diagnosis, lower tumor, node, and metastasis stage (I, II), and lower nuclear grade (1, 2). Patients with cystic change in clear cell renal cell carcinoma had significantly longer cancer-specific (p = 0.015) and progression-free survival (p = 0.004) than those without cystic change, by univariate analysis. Multivariate analysis revealed that cystic change significantly decreased the risk of cancer progression (risk ratio, 0.27; 95% confidence interval, 0.11 to 0.69). Conclusions : In patients with clear cell renal cell carcinoma, cystic change is a good independent predictor for survival.This work was supported by grant No. 04-2009-007 from the SNUH Research Fund.Jemal A, 2009, CA-CANCER J CLIN, V59, P225, DOI 10.3322/caac.20006Lopez-Beltran A, 2009, INT J UROL, V16, P432, DOI 10.1111/j.1442-2042.2009.02302.xGobbo S, 2008, AM J SURG PATHOL, V32, P1239Gong K, 2008, J CANCER RES CLIN, V134, P433, DOI 10.1007/s00432-007-0302-1Webster WS, 2007, UROLOGY, V70, P900, DOI 10.1016/j.urology.2007.05.029Lopez-Beltran A, 2006, EUR UROL, V49, P798, DOI 10.1016/j.eururo.2005.11.035Suzigan S, 2006, AM J CLIN PATHOL, V125, P217, DOI 10.1039/AH6FC77PYR2V6YAYFrank I, 2005, J UROLOGY, V173, P1889, DOI 10.1097/01.ju.0000158043.94525.d6Patard JJ, 2005, J CLIN ONCOL, V23, P2763, DOI 10.1200/JCO.2005.07.055Kim H, 2004, HUM PATHOL, V35, P1556, DOI 10.1016/j.humpath.2004.06.011Ficarra V, 2004, EUR UROL, V46, P559, DOI 10.1016/j.eururo.2004.07.002Han KR, 2004, UROL ONCOL-SEMIN ORI, V22, P410, DOI 10.1016/S1078-1439(03)00173-XImura J, 2004, APMIS, V112, P183Cheville JC, 2003, AM J SURG PATHOL, V27, P612Frank I, 2002, J UROLOGY, V168, P2395, DOI 10.1097/01.ju.0000035885.91935.d5Nassir A, 2002, UROLOGY, V60, P421GREENE FL, 2002, AJCC CANC STAGING MACorica FA, 1999, J UROLOGY, V161, P408Bielsa O, 1998, BRIT J UROL, V82, P16USUBUTUN A, 1998, INT UROL NEPHROL, V30, P391LYNCH CF, 1995, CANCER, V75, P316HARTMAN DS, 1986, UROLOGY, V28, P145