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Background As the indications for trans-catheter aortic valve replacement (TAVR) expand, it is expected that the number of TAVR patients would increase and the follow-up duration would be longer. It is known that the incidence of leaflet thrombosis is higher in TAVR than in surgical aortic valve replacement (SAVR), but not much is known about the risk factors of late leaflet thrombosis in TAVR. Aim Therefore, in this study, the incidence and risk factors of late leaflet thrombosis at late term after TAVR and the effect on clinical course of late leaflet thrombosis would be investigated. Method There were 176 patients undergone TAVR from January 2015 to October 2020 in one tertiary hospital of south korea. 94 patients had follow-up cardiovascular computed tomography (CT) between 3 months and 2 years after TAVR. Among 94 patients, late leaflet thrombosis was discovered at 20 patients, and risk factors were analyzed by comparing clinical factors, echocardiographic and cardiovascular CT information, and angiographic data between the group with and without late leaflet thrombosis. And the difference in aortic valve hemodynamics between the group with and without leaflet thrombosis was examined and clinical outcomes were compared. Clinical outcome was defined as the composite of all-cause death, stroke, heart failure (HF) admission, redo-aortic valve (AV) replacement and major bleeding after detection of late leaflet thrombosis. Results Indexed mean sinus of Valsalva diameter, AV calcium score and post procedure estimated orifice area (EOA) had predictability of late leaflet thrombosis with AUC value of 0.670 (95% CI [0.546–0.795], p value = 0.020), AUC value of 0.698 (95% CI [0.544–0.851], p value = 0.012) and AUC value of 0.665 (95 percent CI [0.548–0.782], p value = 0.031), respectively (Figure 1). In echocardiography performed at the time of follow-up CT, AV max velocity and AV mean pressure gradient were higher in thrombosis group and EOA and Doppler velocity index were lower in thrombosis group than in no thrombosis group within normal range (Figure 2). Clinical outcome was not significant different between the two groups (log rank p value = 0.560). Conclusion Larger indexed sinus of Valsalva diameter, higher AV calcium score and smaller post procedure AV EOA were risk factors for late leaflet thrombosis after TAVR. Subclinical late leaflet thrombosis have a benign course when properly managed. Funding Acknowledgement Type of funding sources: None.

Background/Introduction Although pericardiectomy is an effective treatment of constrictive pericarditis (CP), clinical outcome is not always successful. Pericardial calcification is a unique finding in CP. However, the amount and localization of calcification vary. Computer tomography (CT) can visualize the pericardial calcification with high sensitivity and provide the anatomical assessment. Purpose We investigated that how the pattern and amount of pericardial calcification affect the mid-term postoperative outcome after pericardiectomy in CP. Methods All of the patients who underwent total pericardiectomy in our hospital from 2010 to 2020 were derived from electrical medical records (n=105). Among them, preoperative CT scans (non-gated non-contrast) of 98 patients were available and, thus, 98 consecutive patients were finally analyzed. Medical records were reviewed in a retrospective manner. Cardiovascular event is defined as cardiovascular death or hospitalization associated with a heart failure symptom and all cause event is defined as all events that require admission. CT scan was analyzed by Aquarius Workstation, and the volume and localization pattern of pericalcification were derived. Pericardium calcium score was given as an Agatston score. Results Of 98 patients, 25 (25.5%) patients were hospitalized with heart failure symptom after pericardiectomy. Median follow up duration of patients is 172 weeks. A group with cardiovascular event had higher NYHA grade (P Conclusion Low burden of pericardial calcification was associated high rate of mid-term clinical event after pericardiectomy CP. Preoperative evaluation of pericardial calcification pattern can be used as predictor of postoperative outcomes. Funding Acknowledgement Type of funding sources: None.

Background Chronic thromboembolic pulmonary disease (CTEPD) without pulmonary hypertension could cause significant exercise limitations. However, interventional or surgical treatments for CTEPD with mild pulmonary hypertension or normal pressure are on controversy. Purpose We aimed to evaluate cardiopulmonary function through cardiopulmonary exercise test (CPET) with stress echocardiography and to determine whether exercise pulmonary hypertension can explain exercise limitations in CTEPD patients with mPAP Methods Patients diagnosed as CTEPD with mPAP less than 30mmHg was derived from our pulmonary hypertension center registry from April 2014 to October 2021.Transthoracic echocardiography (TTE) was performed at baseline (resting state) and immediately after CPET. TTE derived parameters and CPET parameters were compared with hemodynamic parameters measured by right catheterization. Results Total 37 patients were enrolled. Of these, Thirty-five patients had previously been diagnosed with CTEPH and had undergone PEA, BPA, or both. Most of the patients complained dyspnea of WHO functional class II or III. Pulmonary vascular resistance (PVR) was slightly higher than normal (185.0±102.2 dyne sec cm–5). Also VO2max was decreased in CPET (23.1±6.5 mL/kg/min). In correlation analysis, the higher the mPAP and PVR at rest, the lower VO2max during exercise. Meanwhile basal right ventricular (RV) function was normal, an increase in RVSP was notably observed during exercise (RVSP: pre-exercise 36.2±11.9, post-exercise 60.7±19.3, p value Conclusions CTEPD patients with mild or normal PAP showed limited exercise capacity with exercise induced hypertension. Even in the mPAP less than 30mmHg, PVR and mPAP was significantly associated with exercise capacity. CPET with stress echocardiography could help to identify the main cause of exercise limitation in CTEPD patients and possibly provide the guideline for treatment plan. Funding Acknowledgement Type of funding sources: None.

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SETTING: Multicentre retrospective study in South Korea.OBJECTIVE: To longitudinally evaluate changes in lung volume and diffusing capacity for carbon monoxide (DLCO) with forced expiratory volume in 1 sec (FEV1).DESIGN: A total of 155 patients with chronic obstructive pulmonary disease (COPD), whose pulmonary function parameters were measured annually for 5 years, were selected from a prospective cohort in South Korea. A random coefficients model was used to estimate mean annual FEV1, lung volume parameter and DLCO change rates.RESULTS: Patients were classified into four groups based on baseline DLCO and residual volume/total lung capacity (RV/TLC) measurements. The annual FEV1 decline rate was greater in patients with low DLCO than in those with normal DLCO, with the greatest decline occurring in patients with low DLCO and normal RV/TLC. RV and RV/TLC declined in patients with high RV/TLC, whereas these increased in patients with normal RV/TLC. DLCO decreased longitudinally in all four groups, with the greatest decline occurring in patients with normal DLCO and normal RV/TLC.CONCLUSIONS: Different subgroups of patients with COPD exhibited distinctive pulmonary function change patterns. Baseline DLCO and RV/TLC may be used as physiological markers to predict long-term changes in pulmonary function.

The antiinflammatory effect of propolis collected from different geographic regions in South Korea was investigated in the present study. All propolis samples, from six different regions, dose-dependently inhibited the production of nitric oxide and prostaglandin E2 in RAW 264.7 macrophages stimulated with lipopolysaccharide. Propolis also suppressed the expression of inducible nitric oxide synthase and cyclooxygenase-2, stimulated by lipopolysaccharide. Additionally, propolis extracts inhibited ear edema induced by phorbol-12-myristate-13-acetate in mice. Overall, in both in vitro and in vivo studies, Korean propolis extracts showed significant antiinflammatory effects without any geographical variation. In conclusion, Korean propolis could be of the potential for drug development against inflammatory reactions.

Background: APOBEC3B is a cytosine deaminase implicated in host immune defense to virus and mutagenesis in cancer. Germline APOBEC3B deletion is known as risk factors for breast cancer with hypermutation and immune activation from previous database-based studies. This study was aimed to evaluate the incidence of germline APOBEC3B deletion in Korean patients with operable breast cancer. Method: The copy number variants of germline APOBEC3B deletion was analyzed from leukocyte DNA of 103 breast cancer patients whose bloods were collected in 2009 for pharmacogenomic study at Seoul National University Bundang Hospital. Hybrid-capture based next-generation sequencing panel targeting 53 hereditary cancer genes were used. We also measured tumor infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression in tumor or immune cell with a rabbit monoclonal antibody (E1L3N). Results: Median age of breast cancer diagnosis was 46 (25-72). In APOBEC3B deletion analysis, 10 (9.7%), 36 (35.0%), and 57 (55.3%) patients were identified as two-copy deletion (A3Bdel/del), one-one copy deletion (A3Bdel/wt) and no deletion (A3Bwt/wt), respectively. In non-APOBEC3B analysis, 9 (8.7%) patients were identified as pathogenic variant: RAD51D(n=1), GJB2(n=1), BRCA1(n=1), BRCA2 (n=2), ATM(n=1), USH2A(n=1), RET(n=1), BARD1(n=1). We observed no significant association between germline APOBEC3B deletion with any clinicopathologic features of breast cancer such as age, family history of cancer, and bilateral breast cancer. Triple-negative subtype was associated with A3Bwt/wt Tumors (35.1% in A3Bwt/wt vs. 5.6% in A3Bdel/wt vs20% in A3Bdel/del; P=0.018). After a median follow-up time of 92.8 months, APOBEC3B deletion was not predictive of recurrence or survival. In patients with sufficient tumor samples for the assessment of TIL (n=63) and PD-1 (n=71), A3Bdel/del tumor was associated with higher TILs (>10%) than other tumor types (6/7 patients in A3Bdel/del vs. 13/24 in A3Bdel/wt vs. 15/32 in A3Bwt/wt: Fisher's exact test in A3Bdel/del, P=0.029). However, PD-L1 expression was not associated with APOBEC3B deletion status (1/7 patients >1% PD-L1 in A3Bdel/del vs. 4/26 in A3Bdel/wt vs. 8/38 in A3Bwt/wt: P=0.901). Germline APOBEC3B deletion and TILs (n=63) TIL (0-10%)TIL (>10%)TotalA3B(wt/wt)17 (53.1%)15 (46.9%)32A3B(del/wt)11 (45.8%)13 (54.2%)24A3B(del/del)1 (14.3%)6 (85.7%)7 Conclusion: We identified germline APOBEC3B deletion in 9.7% of Korean patients with operable breast cancer. The relationship between A3Bdel/del tumor and high TILs suggests that these tumors might be potential candidates for future immunotherapy. Citation Format: Kim SH, Koung Jin S, Kim YJ, Ahn S, Park SY, Chae SM, Kang E, Kim E-K, Kim IA, Kim JH. Identifying germline APOBEC3B deletion using hereditary cancer panel in Korean patients with operable breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-03-10.

Introduction: Multifocal breast cancers are common, and tend to show more aggressive clinical features than unifocal breast cancers. While each foci of multifocal breast cancers with similar histology shares the same hormone and ERBB2 receptor status in most cases, substantial genomic differences among lesions have been reported. We aimed to investigate the potential genomic differences between multifocal breast cancer lesions. Materials and methods: Twenty-one patients with multifocal breast cancer documented in the resection specimen were included. We selected two lesions with the same histology from each of these 21 patients. Capture-based targeted next generation sequencing was performed using a cancer gene panel consisting of 170 genes for single nucleotide variants (SNV) and small insertions/deletions (Indel), and copy number alterations. Results: The most frequent mutation was TP53 (38.1%), followed by PIK3CA (28.6%). Pathogenic mutations (SNV and Indel) were detected in 13 of 21 patients, of whom 11 shared oncogenic variants in the two lesions. The remaining two patients had different mutation results in TP53 and PIK3CA, respectively. Genomic heterogeneity of copy number alteration was observed in 6 (28.6%) of 21 patients, including difference of FGFR1 status in two patients and difference of FGFR2 status in one patient. Conclusion: Despite similar histologic features of multifocal tumors, genomic inter-lesion heterogeneity was identified in about one-fourth of patients. The spatial genomic heterogeneity in multifocal breast cancers needs to be considered in representative sampling and molecular tests for personalized medicine. Citation Format: Ahn S, Kim HJ, Kang E, Kim E-K, Kim SH, Kim JH, Kim IA, Park SY. Genomic profiling of multifocal breast cancer reveals inter-lesion heterogeneity [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-04-10.

For successful clinical tumor immunotherapy outcomes, strong immune responses against tumor antigens must be generated. Cell-based vaccines compromise one strategy with which to induce appropriate strong immune responses. Previously, we established a natural killer T-cell (NKT) ligand-loaded, adenoviral vector-transduced B-cell-based anticancer cellular vaccine. To enhance tumor antigen delivery to B cells, we established a modified adenoviral vector (Ad-k35) that encoded a truncated form of the breast cancer antigen Her2/neu (Ad-k35HM) in which fiber structure was substituted with adenovirus serotype 35. We observed increased tumor antigen expression with Ad-k35HM in both human and murine B cells. In addition, an Ad-k35HM-transduced B-cell vaccine elicited strong antigen-specific cellular and humoral immune responses that were further enhanced with the additional loading of soluble NKT ligand KBC009. An Ad-k35HM-transduced, KBC009-loaded B-cell vaccine efficiently suppressed the in vivo growth of established tumors in a mouse model. Moreover, the vaccine elicited human leukocyte antigen (HLA)-A2 epitope-specific cytotoxic T-cell responses in B6.Cg (CB)-Tg (HLA-A/H2-D) 2Enge/Jat mice. These findings indicated that the Ad-k35 could be appropriate for the preclinical and clinical development of B-cell-based anticancer immunotherapies.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) can lead to pulmonary hypertension and cor pulmonale, which are predictors of mortality. OBJECTIVE: To identify predictors of increased pulmonary artery pressure (PAP) in COPD patients without resting hypoxaemia, and to characterise COPD patients with increased PAP. DESIGN: A study of 117 COPD patients from the Korean Obstructive Lung Disease (KOLD) cohort who had measurable tricuspid regurgitant flow under transthoracic Doppler echocardiography and no resting hypoxaemia. RESULTS: The mean patient age was 67 years. Mean forced expiratory volume in 1 second (FEV 1 ) was 47% predicted, mean haemoglobin (Hb) concentration was 145 g/l and mean systolic PAP (sPAP) was 33 mmHg. Multiple linear regression analysis showed that Hb was the only factor independently associated with sPAP (beta = ―1.752, P = 0.005). Cluster analysis using FEV 1 % predicted, sPAP and Hb concentration as variables indicated three patient clusters: Cluster 1 (n = 36; mean FEV 1 44% predicted, mean sPAP 39 mmHg, mean Hb 132 g/l), Cluster 2 (n = 45; FEV 1 35% predicted, sPAP 31 mmHg, Hb 154 g/l), and Cluster 3 (n = 36; FEV 1 65% predicted, sPAP 29 mmHg, Hb 148 g/l). CONCLUSION: Elevated PAP was linked to low haemoglobin levels in COPD without resting hypoxaemia.

To investigate the expression of PI3K-p110α, pAkt, PTEN, the signaling molecules from PI3K/Akt signaling pathway, DJ-1, an oncoprotein and HSP90a, a molecular chaperone, and their correlation in uterine cervical neoplasia, in order to elucidate their role in cervical carcinogenesis.Using immunohistochemistry, the authors analyzed the expression of PI3K-p110α, pAkt, PTEN, DJ-1 and HSP90α, and their correlation in ten normal tissues, cervical intraepithelial neoplasia (CIN) including 30 CIN1 and 31 CIN3, and 33 cases of invasive squamous cell carcinoma (SCC).The expression of all proteins significantly increased in CIN3 compared to CIN1, and only the expression of PI3K-p110α significantly increased in invasive SCC compared to CIN3. There was a significant positive correlation between the expression of PI3K-p110α and DJ-1, as well as PI3K-p110α and pAkt in CIN3 and invasive SCC.Overexpression of PI3K-p110α is associated with progression of uterine cervical neoplasia, and the expression of pAkt and DJ-1 is positively correlated with PI3K-p110α expression in this process.

The approach for the synthesis of orotidine (III) is general and not limited to the ribofuranosyl skeleton.

An intramolecular nucleosidation approach provides easy access to orotidine in high yields. Notably, orotate itself is used as a leaving group at the anomeric position. This method has the potential for facile access to derivatives of orotidine of therapeutic interest, with implications for prebiotic formation of nucleosides.

The ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin) regimen has been shown to be effective as an active salvage therapy for lymphoma. Mobilizing stem cells following ESHAP should decrease time to transplantation by making separate mobilizing chemotherapy (MC) unnecessary, while controlling a patient's lymphoma. We therefore assessed the mobilization potential of ESHAP plus G-CSF in 26 patients (ESHAP group) with non-Hodgkin's lymphoma (NHL) and compared these results with those of 24 patients with NHL who received high-dose (4 g/m2l) cyclophosphamide (HDCY) as MC (HDCY group). The age, sex, and radiotherapy to the axial skeleton were well matched between groups, but the number of patients with poor mobilization predictors was higher in the ESHAP group. Significantly higher numbers of CD34+ cells (x 10(6)/kg) (17.1+/-18.8 vs 5.8+/-5.0, P=0.03) and apheresis day 1 CD34+ cells (x 10(6)/kg) (5.5+/-6.6 vs 1.7+/-2.0, P=0.014) were collected from the ESHAP group than from the HDCY group, and the number of patients who achieved an optimal CD34+ cell target of 5 x 10(6)/kg was higher in the ESHAP group (81 vs 50%, P=0.022). Log-rank test revealed that time to target peripheral blood progenitor cell collection (> or =5 x 10(6)/kg) was shorter in the ESHAP group (P=0.007). These results indicate that ESHAP plus G-CSF is an excellent mobilization regimen in patients with relapsed and poor-risk aggressive NHL.

The aim of this study was to correlate MR findings of gallbladder wall thickening with pathologic findings on the basis of the layered pattern and to evaluate the diagnostic value of MR imaging in gallbladder disease. We retrospectively evaluated the source images of HASTE sequences for MR cholangiography in 144 patients with gallbladder wall thickening. The layered pattern of thickened wall was classified into four patterns. Type 1 shows two layers with a thin hypointense inner layer and thick hyperintense outer layer. Type 2 has two layers of ill-defined margin. Type 3 shows multiple hyperintense cystic spaces in the wall. Type 4 shows diffuse nodular thickening without layering. MR findings of a layered pattern of thickened gallbladder were well correlated with histopathology. Chronic cholecystitis matched to type 1, acute cholecystitis corresponded to type 2, adenomyomatosis showed type 3, and the gallbladder carcinomas showed type 4. All four layered patterns were associated with PPV of 73% or greater, sensitivity of 92% or greater and specificity of 95% or greater. Our results indicate that MR findings of gallbladder wall thickening are characteristic in each entity and correlate well with pathologic findings. The classification of the layered pattern may be valuable for interpreting thickened gallbladder wall.

A Web-based, realtime, tele-ultrasound consultation system was designed. The system employed ActiveX control, MPEG-4 coding of full-resolution ultrasound video (640 × 480 pixels at 30 frames/s) and H.320 videoconferencing. It could be used via a Web browser. The system was evaluated over three types of commercial line: a cable connection, ADSL and VDSL. Three radiologists assessed the quality of compressed and uncompressed ultrasound video-sequences from 16 cases (10 abnormal livers, four abnormal kidneys and two abnormal gallbladders). The radiologists' scores showed that, at a given frame rate, increasing the bit rate was associated with increasing quality; however, at a certain threshold bit rate the quality did not increase significantly. The peak signal to noise ratio (PSNR) was also measured between the compressed and uncompressed images. In most cases, the PSNR increased as the bit rate increased, and increased as the number of dropped frames increased. There was a threshold bit rate, at a given frame rate, at which the PSNR did not improve significantly. Taking into account both sets of threshold values, a bit rate of more than 0.6 Mbit/s, at 30 frames/s, is suggested as the threshold for the maintenance of diagnostic image quality.

SummaryTwo types of Balloon Type Bubble Bioreactors (BTBB, air lift type), continuous immersion cultures (with and without raft) and temporary immersion cultures (ebb and flow) were used for mass multiplication of shoots and bulblets of Garlic ‘Danyang’. Murashige and Skoog (1962) liquid medium supplemented with 2% sucrose was used for shoot proliferation and shoot proliferation was recorded after three weeks. MS liquid medium supplemented with 11% sucrose and 0.1 mg l–1 naphthalene acetic acid was used for bulblet induction and growth and bulblet growth was recorded after nine weeks in bioreactor cultures. The continuous immersion types of bioreactors were found suitable for shoot proliferation and 27 shoots were developed from each explant. Biomass of shoots was also highest by this method. Inoculation density of 15 shoots per culture was optimal and aeration of bioreactors with a sparger (0.1 air volume per medium per min) influenced the biomass production. Immersion type (with raft) bioreactor was opt...

A model for non-isothermal Newtonian flow startup in an initially empty modular self-wiping co-rotating twin screw extruder is developed. A viscous Newtonian fluid is considered to gradually fill a modular co-rotating twin screw extruder with viscous heating and heat transfer to the barrel (and screw). The build up of the axial cup mixing temperature profiles with time was calculated for various modular screw configurations.

Frequency mixing (2v1 2 v2) is demonstrated in femtosecond nondegenerate four-wave mixing (FWM) on GaAs multiple quantum wells using two synchronized, independently tunable lasers. The frequency mixing component in the spectrally resolved FWM coexists with the exciton resonance, and it dominates over the exciton component at high intensity and high detuning. This off-resonant component is present only for delays smaller than the temporal pulse width, whereas the resonant exciton component survives for longer delays. [S0031-9007(99)09078-X]

The S0→S1 cavity ring-down (CRD) absorption spectrum of jet-cooled azulene is reported in the spectral region between 14275 and 17300 cm-1. The excess energy dependence of the fast internal conversion rate kic (S1S0) was investigated in the frequency domain by evaluating the linewidths of vibronic states up to excess energies of ∽hc×2500 cm-1. A value for the S1,0 lifetime of ≈2.6±0.4 ps was found. New experimental evidence for a conical intersection of the S0 and S1 potentials at ≈2100±100 cm-1 was found. The possibility of azulene being one of the carriers of the diffuse interstellar bands (DIB) is briefly discussed.

Femtosecond four-wave mixing experiments on GaAs/AlGaAs quantum wells are performed with two independently tunable lasers. Many new results are found, including the heavy-hole-light-hole beating with these two mutually incoherent lasers.

In the near future, upper limb prostheses may interface with peripheral nerves of amputees to help restore vital somatosensory feedback. Achieving that goal requires the transformation of forces artificially sensed in our environment into the depolarization of afferents, by delivering levels of charge adequate for signaling tactile sensory cues yet avoiding tissue damage. The objective of the work herein was to build and test a tactile afferent modulation platform engineered to transform force data input, from an artificial sensor under ramp-and-hold stimuli, into the output of discrete charge-balanced pulses to the rat's acute sural nerve thereby eliciting compound sensory neural action potentials (CSNAPs). In vivo experiments, to stimulate both tactile end organs mechanically and sural nerves electrically, helped fit the model's empirical parameters. Input-output relationships were validated by comparing CSNAPs elicited by the tactile afferent modulation platform with those of natural end organs. The results replicated the natural response where increased force magnitude increased both CSNAP firing rates and waveform amplitudes. Next steps will involve the integration of the engineered platform with a regenerative peripheral nerve interface for the evaluation of its long-term reliability.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field. © 2012 Landes Bioscience.

Microphthalmia associated transcription factor (Mitf) is a key regulatory transcriptional factor of pigmentation-related genes including tyrosinase. Inhibition of tyrosinase transcription by blocking the binding of Mitf with its promoter E-box DNA can control the pigmentation. However, no such chemicals were reported so far.To discover and evaluate the small molecule inhibitors of Mitf-E-box DNA.Candidate chemicals were screened by virtual screening from pharmacophore data followed by Mitf E-box DNA protein chip. After selecting the chemical, its inhibitory activity on binding interaction between Mitf and E-box DNA, electrophoretic mobility shift assay (EMSA) was performed. To evaluate the depigmenting activity of Compound #17, cellular melanin assa, and Western blot were performed in melan-a cells.Among 27 chemicals selected from a pharmacophore data by virtual screening, Compound #17 was screened, which showed the most potent inhibitory activity against Mitf-E-box DNA binding in protein chip. EMSA results confirmed the specific inhibition of Compound #17 on Mitf-E-box DNA binding. In melan-a cells, Compound #17 reduced tyrosinase expression and melanin synthesis (62.5% at 25 μM). The results show that Compound #17 is the first small molecule inhibitor of Mitf-E-box DNA binding with depigmenting activity.

Some of chronic hyperpigmentary diseases, such as melasma, induced by multiple factors including chronic sunlight exposure, can recur even after chemical epidermal removal. Dermal factors may be involved in the pathogenesis of melasma. Changes in dermal fibroblasts resulting from chronic sun exposure might cause melanocytes to synthesize melanin in the epidermis.This study aimed at determining the effects of repetitive ultraviolet (UV) radiation on cultured fibroblasts and the secretion of melanogenic factors.Cultured human fibroblasts were exposed to ultraviolet A (UVA) or ultraviolet B (UVB) for five consecutive days. After each irradiation, the supernatant medium was isolated from each dish and measured for levels of stem cell factor (SCF) and hepatocyte growth factor using an ELISA kit assay. To assess the effect of the keratinocyte-derived factors on fibroblast-secretion of SCF and hepatocyte growth factor, we added supernatants of the UV-irradiated keratinocytes to the non-irradiated fibroblasts. Finally, the irradiated fibroblasts were stained with senescence associated-β-galactosidase to assess their senescent change.Fibroblasts irradiated with UVA or UVB for five consecutive days, secreted SCF at levels that increased with repeated UVA or UVB exposure. Conditioned culture medium from UV-irradiated keratinocytes also induced SCF release from fibroblasts, depending on the number of UV exposures. UVA- or UVB-irradiated fibroblasts stained positive for senescence associated-β-galactosidase, and the staining intensity increased with repeated exposure.These results suggest that fibroblast senescence and increased SCF secretion after repeated UV irradiation may be related to the pathogenesis of recurring hyperpigmentation disorders induced by chronic sun exposure.

Hair greying is an obvious sign of ageing in humans. White (nonpigmented) hair is thicker than black (pigmented) hair. The growth rate of white hair is also significantly higher than that of black hair. However, the mechanism underlying this is largely unknown.To examine the association between hair greying and hair growth patterns by evaluating expression of the genes or proteins related to hair growth in white and black hairs.Morphological characteristics were observed in eyebrow and scalp hairs. The differential expression of genes was analysed in black and white hairs from human scalp by a microarray analysis. Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry for genes and proteins related to hair growth were performed in black and white hairs.Keratin and keratin-associated protein (KRTAP) genes in white hair were upregulated at least two-fold in comparison with black hair in a microarray analysis. Upregulation of selected keratin genes and KRTAP4 isoform genes in white hair was validated by RT-PCR. Immunoreactivity for KRT6, KRT14/16 and KRT25 was increased in the hair follicle of white hair compared with black hair. Gene expression of fibroblast growth factor 5 (FGF5) was downregulated in white hair compared with black hair. However, gene expression of FGF7 was upregulated in white hair compared with black hair.Expression of genes and proteins associated with active hair growth is upregulated in white (nonpigmented) hair compared with black (pigmented) hair. These results suggest that hair greying is associated with active hair growth.

Setting Eleven referring hospitals in South Korea. Objective To compare therapeutic responses in chronic obstructive pulmonary disease (COPD) subgroups, classified by diffusing capacity of the lung for carbon monoxide (DL(CO)) and lung volume. Design A total of 130 stable male COPD patients were classified into four subgroups according to baseline DL(CO) and residual volume/total lung capacity (RV/TLC) ratio. We compared therapeutic responses to short acting β(2)-agonist (SABA) and 3-month combined inhalation of long-acting β(2)-agonist (LABA) and corticosteroid among patients with these subgroups. Results Among the 130 COPD patients, 41 (31.5%) had normal DL(CO) and RV/TLC, 28 (21.5%) low DL(CO) and normal RV/TLC, 31 (23.8%) normal DL(CO) and high RV/TLC, and 30 (23.1%) low DL(CO) and high RV/TLC. The normal DL(CO)/high RV/TLC subgroup showed a significantly larger flow response (changes in forced expiratory volume in 1 s) to salbutamol than the normal DL(CO)/RV/TLC subgroups, and a larger volume response (changes in forced vital capacity) than the two normal RV/TLC subgroups. The normal DL(CO)/high RV/TLC subgroup also showed significantly larger flow and volume response to 3-month combined inhalation of LABA and corticosteroid than the two normal RV/TLC subgroups. Conclusion COPD subgroups classified by DL(CO) and RV/TLC may have different pulmonary function responses to pharmacological treatment.

The recent availability of genetic analyses has demonstrated the shortcomings of the current phenotypic method of corneal dystrophy classification. Abnormalities in different genes can cause a single phenotype, whereas different defects in a single gene can cause different phenotypes. Some disorders termed corneal dystrophies do not appear to have a genetic basis.The purpose of this study was to develop a new classification system for corneal dystrophies, integrating up-to-date information on phenotypic description, pathologic examination, and genetic analysis.The International Committee for Classification of Corneal Dystrophies (IC3D) was created to devise a current and accurate nomenclature.This anatomic classification continues to organize dystrophies according to the level chiefly affected. Each dystrophy has a template summarizing genetic, clinical, and pathologic information. A category number from 1 through 4 is assigned, reflecting the level of evidence supporting the existence of a given dystrophy. The most defined dystrophies belong to category 1 (a well-defined corneal dystrophy in which a gene has been mapped and identified and specific mutations are known) and the least defined belong to category 4 (a suspected dystrophy where the clinical and genetic evidence is not yet convincing). The nomenclature may be updated over time as new information regarding the dystrophies becomes available.The IC3D Classification of Corneal Dystrophies is a new classification system that incorporates many aspects of the traditional definitions of corneal dystrophies with new genetic, clinical, and pathologic information. Standardized templates provide key information that includes a level of evidence for there being a corneal dystrophy. The system is user-friendly and upgradeable and can be retrieved on the website www.corneasociety.org/ic3d .

The study aims to investigate characteristics associated with intent to stay among Quality Improvement (QI) nurses in Korean hospitals.QI nurses have recently emerged as a new specialty area in the nursing profession in Korea. They have played a major role in coordinating and facilitating hospital-wide QI activities. However, their frequent turnover degrades the continuity of overall QI programmes and incurs additional costs in human resource management.A cross-sectional questionnaire survey was administered to 123 QI nurses in 123 general hospitals. The collected data included their hospital and department characteristics, work demand, job satisfaction, organizational commitment and demographics. The response rate was 94.3% (n=116). Multiple logistic regression analysis was performed to determine the factors associated with intent to stay.Only 32.8% intended to stay in their current job. Significant factors associated with intent to stay were affective commitment and work demands. QI nurses with a higher level of affective commitment were more likely to stay [odds ratios (OR)=2.50], whereas those with higher quantitative work demands in QI education and support were less likely to stay (OR=0.40).The findings indicated that intent to stay was closely associated with work environment characteristics. Efforts to enhance their affective commitment and support their workload management are needed to increase the retention of qualified and experienced QI nurses.

The aim of the work is ultimately to establish a theoretical foundation for economical decision making on whether to test; how far to test; whether testing is feasible; and, otherwise, whether there is an alternative to defect tolerance with little or no testing. In this work, a new defect tolerance for the circuits and systems under the circumstances where little or no testing is allowed or feasible, is to be investigated. New methodologies for the design for defect tolerance will be presented and theoretically validated.

The energy states in InAs/GaAs self‐assembled QD system were measured and analyzed by using capacitance‐voltage and deep level transient spectroscopy methods with varying the applied biases and the filling pulse widths. The activation energies of the QD signals were shifted from 0.07 to 0.60 eV by changing the measurement biases, and then these results represent that the QD has many kind of confined energy levels. From the DLTS measurements with varying the filling pulse widths, it was confirmed that the QD has band‐like interacting energy levels.

Although patients with T-cell phenotype lymphomas are generally accepted to have worse prognosis than B-cell phenotype lymphomas, the studies comparing outcomes after autologous stem cell transplantation (ASCT) between peripheral T-cell lymphomas (PTCLs) and with diffuse large B-cell lymphoma (DLBCL) are few. In this study, we compared outcomes after ASCT between 23 patients with PTCLs and 54 patients with DLBCL. Univariate analysis showed that the timing of ASCT, complete response (CR) at ASCT, favorable lactate dehydrogenase/performance/stage, low/low-intermediate (L-LI) International Prognostic Index (IPI) and L-LI age-adjusted IPI (aaIPI) at ASCT were significant predictors of both OS and EFS. Multivariate analysis showed that CR and L-LI aaIPI at ASCT were favorable for both OS (hazard ratio (HR), 0.34; 95% CI, 0.14–0.81; P=0.016 and HR, 0.27; 95% CI, 0.12–0.57; P=0.001) and EFS (HR, 0.38; 95% CI, 0.17–0.85; P=0.020 and HR, 0.36; 95% CI, 0.17–0.77; P=0.008). B-cell or T-cell phenotype, however, had no impact on OS (HR, 0.56; 95% CI, 0.27–1.18; P=0.126) or EFS (HR, 0.62; 95% CI, 0.30–1.30; P=0.206). In conclusion, when compared to patients with DLBCL, patients with PTCLs did not have inferior outcomes after ASCT. T-cell phenotype itself may not have an effect on outcomes of PTCL patients who underwent ASCT.

Rate equations for the vigorous stationary phase fermentation of citric acid by Saccharomycopsis lipolytica were determined using a continuous-stirred-tank-membrane-reactor system. The rate of glucose consumption is independent of fermentation broth glucose concentration for the range of 1-25 g cellulose/L. The rate of glucose consumption is noncompetitively inhibited by citric acid with a product inhibition constant of 235 g citrate/L. The rate of citrate production is proportional to the logarithm of the glucose concentration.

A quantum-dot transistor incorporating silicon self-assembled quantum dots and planar nano-meter sized metal pads (nano-arms) has been fabricated. The current-voltage characteristics measured from the transistor exhibits staircases and oscillations, whose interpretation is consistent with the single electron tunneling through the dots located in between the source and the drain nano-arms.