Panaxadiol carbamate derivatives: Synthesis and biological evaluation as potential multifunctional anti-Alzheimer agents.

It is reported that panaxadiol has neuroprotective effects. Previous studies have found that compound with carbamate structure introduced at the 3-OH position of 20 (R) -panaxadiol showed the most effective neuroprotective activity with an EC50 of 13.17 µM. Therefore, we designed and synthesized a series of ginseng diol carbamate derivatives with ginseng diol as the lead compound, and tested their anti-AD activity. It was found that the protective effect of compound Q4 on adrenal pheochromocytoma was 80.6 ±â€¯10.85 % (15 µM), and the EC50 was 4.32 µM. According to the ELISA results, Q4 reduced the expression of Aß25-35 by decreasing ß-secretase production. Molecular docking studies revealed that the binding affinity of Q4 to ß-secretase was -49.67 kcal/mol, indicating a strong binding affinity of Q4 to ß-secretase. Western blotting showed that compound Q4 decreased IL-1ß levels, which may contribute to its anti-inflammatory effect. Furthermore, compound Q4 exhibits anti-AD activities by reducing abnormal phosphorylation of tau protein and activation of the mitogen activated protein kinase pathway. The learning and memory deficits in mice treated with Q4in vivo were significantly alleviated. Therefore, Q4 may be a promising multifunctional drug for the treatment of AD, providing a new way for anti-AD drugs.

Effects of seawater acidification and warming on morphometrics and biomineralization-related gene expression during embryo-larval development of a lightly-calcified echinoderm.

CO2-induced ocean acidification and warming pose ecological threats to marine life, especially calcifying species such as echinoderms, who rely on biomineralization for skeleton formation. However, previous studies on echinoderm calcification amid climate change had a strong bias towards heavily calcified echinoderms, with little research on lightly calcified ones, such as sea cucumbers. Here, we analyzed the embryo-larval development and their biomineralization-related gene expression of a lightly calcified echinoderm, the sea cucumber (Apostichopus japonicus), under experimental seawater acidification (OA) and/or warming (OW). Results showed that OA (- 0.37 units) delayed development and decreased body size (8.58-56.25 % and 0.36-19.66 % decreases in stage duration and body length, respectively), whereas OW (+3.1 °C) accelerated development and increased body size (33.99-55.28 % increase in stage duration and 2.44-14.41 % enlargement in body length). OW buffered the negative effects of OA on the development timing and body size of A. japonicus. Additionally, no target genes were expressed in the blastula stage, and only two biomineralization genes (colp3α, cyp2) and five TFs (erg, tgif, foxN2/3, gata1/2/3, and tbr) were expressed throughout the embryo-larval development. Our findings suggest that the low calcification in A. japonicus larvae may be caused by biomineralization genes contraction, and low expression of those genes. Furthermore, this study indicated that seawater acidification and warming affect expression of biomineralization-related genes, and had an effect on body size and development rate during the embryo-larval stage in sea cucumbers. Our study is a first step toward a better understanding of the complexity of high pCO2 on calcification and helpful for revealing the adaptive strategy of less-calcified echinoderms amid climate change.

Analysis of the utilization value of different tissues of Taxus×Media based on metabolomics and antioxidant activity.

BACKGROUND: Taxaceae, is a class of dioecious and evergreen plant with substantial economic and ecology value. At present many phytochemical analyses have been performed in Taxus plants. And various biological constituents have been isolated from various Taxus species. However, the difference of compounds and antioxidant capacity of different tissues of T. media is not clear. RESULTS: In the present study, we investigated the metabolites and antioxidant activity of four tissues of T. media, including T. media bark (TB), T. media fresh leaves (TFL), T. media seeds (TS), T. media aril (TA). In total, 808 compounds, covering 11 subclasses, were identified by using UPLC-MS/MS. Paclitaxel, the most popular anticancer compound, was found to accumulate most in TS, followed by TB, TFL and TA in order. Further analysis found that 70 key differential metabolites with VIP > 1.0 and p < 0.05, covering 8 subclasses, were screened as the key differential metabolites in four tissues. The characteristic compounds of TFL mainly included flavonoids and tanninsis. Alkaloids and phenolic acids were major characteristic compounds of TS and TB respectively. Amino acids and derivatives, organic acids, saccharides and lipids were the major characteristic compounds of TA. Additionally, based on FRAP and ABTS method, TS and TFL exhibited higher antioxidant activity than TB and TA. CONCLUSION: There was significant difference in metabolite content among different tissues of T. media. TFL and TS had higher metabolites and antioxidant capacity than other tissues, indicating that TFL and TS were more suitable for the development and utilization of T. media in foods and drinks.

Arabidopsis HOPS subunit VPS41 carries out plant-specific roles in vacuolar transport and vegetative growth.

The homotypic fusion and protein sorting (HOPS) complex is a conserved, multi-subunit tethering complex in eukaryotic cells. In yeast and mammalian cells, the HOPS subunit vacuolar protein sorting-associated protein 41 (VPS41) is recruited to late endosomes after Ras-related protein 7 (Rab7) activation and is essential for vacuole fusion. However, whether VPS41 plays conserved roles in plants is not clear. Here, we demonstrate that in the model plant Arabidopsis (Arabidopsis thaliana), VPS41 localizes to distinct condensates in root cells in addition to its reported localization at the tonoplast. The formation of condensates does not rely on the known upstream regulators but depends on VPS41 self-interaction and is essential for vegetative growth regulation. Genetic evidence indicates that VPS41 is required for both homotypic vacuole fusion and cargo sorting from the adaptor protein complex 3, Rab5, and Golgi-independent pathways but is dispensable for the Rab7 cargo inositol transporter 1. We also show that VPS41 has HOPS-independent functions in vacuolar transport. Taken together, our findings indicate that Arabidopsis VPS41 is a unique subunit of the HOPS complex that carries out plant-specific roles in both vacuolar transport and developmental regulation.

MIZU-KUSSEI1 (MIZ1) and GNOM/MIZ2 control not only positive hydrotropism but also phototropism in Arabidopsis roots.

In response to unilateral blue light illumination, roots of some plant species such as Arabidopsis thaliana exhibit negative phototropism (bending away from light), which is important for light avoidance in nature. MIZU-KUSSEI1 (MIZ1) and GNOM/MIZ2 are essential for positive hydrotropism (i.e. in the presence of a moisture gradient, root bending towards greater water availability). Intriguingly, mutations in these genes also cause a substantial reduction in phototropism. Here, we examined whether the same tissue-specific sites of expression required for MIZ1- and GNOM/MIZ2-regulated hydrotropism in Arabidopsis roots are also required for phototropism. The attenuated phototropic response of miz1 roots was completely restored when a functional MIZ1-green fluorescent protein (GFP) fusion was expressed in the cortex of the root elongation zone but not in other tissues such as root cap, meristem, epidermis, or endodermis. The hydrotropic defect and reduced phototropism of miz2 roots were restored by GNOM/MIZ2 expression in either the epidermis, cortex, or stele, but not in the root cap or endodermis. Thus, the sites in root tissues that are involved in the regulation of MIZ1- and GNOM/MIZ2-dependent hydrotropism also regulate phototropism. These results suggest that MIZ1- and GNOM/MIZ2-mediated pathways are, at least in part, shared by hydrotropic and phototropic responses in Arabidopsis roots.

c-Myc inhibits LAPTM5 expression in B-cell lymphomas.

Myc is a pivotal protooncogenic transcription factor that contributes to the development of almost all Burkitt's lymphomas and about one-third of diffuse large B-cell lymphomas. How B-cells sustain their uncontrolled proliferation due to high Myc is not yet well defined. Here, we found that Myc trans-represses the expression of murine LAPTM5, a gene coding a lysosome-associated protein, by binding to two E-boxes in the LAPTM5 promoter. While the product of intact mRNA (CDS+3'UTR) of LAPTM5 failed to suppress the growth of B-lymphomas, either the protein coded by coding sequence (CDS) itself or the non-coding 3'-untranslated region (3'UTR) mRNA was able to inhibit the growth of B-lymphomas. Moreover, Myc trans-activated miR-17-3p, which promoted tumor growth. Strikingly, LAPTM5 3'UTR contains 11 miR-17-3p-binding sites through which the LAPTM5 protein synthesis was inhibited. The functional interplay between low LAPTM5 mRNA and high miR-17-3p due to high Myc in B-lymphomas leads to further dampening of tumor-suppressive LAPTM5 protein, which promotes tumor progression. Our results indicate that Myc inhibits LAPTM5 expression in B-lymphoma cells by transcriptional and post-transcriptional modifications.

Na Cocations and Hydrothermal Aging Cooperatively Boost the Regeneration of Phosphorus-Poisoned Pd/SSZ-13 for Passive NOx Adsorption.

Pd/SSZ-13 has been proposed as a passive NOx adsorber (PNA) for low-temperature NOx adsorption. However, it remains challenging for Pd/SSZ-13 to work efficiently when suffering from phosphorus poisoning. Herein, we report a simple and efficient strategy to regenerate the phosphorus-poisoned Pd/SSZ-13 based on the cooperation between hydrothermal aging treatment and Na cocations. It was found that hydrothermal aging treatment enabled the redispersion of Pd and P-containing species in phosphorus-poisoned Pd/SSZ-13. Meanwhile, the presence of Na cocations significantly reduced the formation of AlPO4 and retained more paired Al sites for highly dispersed Pd2+ ions, which was of great importance for the recovery of adsorption performance. To our satisfaction, the restoration ratio of the adsorption capacity of poisoned Pd/SSZ-13 was >90% after regeneration. Strikingly, the NOx adsorption activities of phosphorus-poisoned Pd/SSZ-13 with phosphorus loadings of 0.2 and 0.4 mmol g-1 almost completely recovered upon regeneration. This study demonstrates the promoting effect of Na cocations on the regeneration of phosphorus-poisoned Pd/SSZ-13 by hydrothermal aging treatment, which provides useful guidance for the design of PNA materials with excellent durability for cold-start application.

Construction and evaluation of a column chart model and a random forest model for predicting the prognosis of hydrodistention surgery in BPS/IC patients based on preoperative CD117, P2X3R, NGF, and TrkA levels.

OBJECTIVE: This study seeks to investigate independent risk factors affecting the prognoses of patients with bladder pain syndrome/interstitial cystitis (BPS/IC) following hydrodistention surgery and to develop a column chart model and a random forest model to help predict clinical outcomes. METHOD: A retrospective analysis was conducted on the clinical data of 1006 BPS/IC patients who visited the urology department of the Fifth Hospital of Shanxi Medical University (Shanxi Provincial People's Hospital) between June 2012 and June 2022. The patients were randomly divided into a model group (n = 704) and a validation group (n = 302). In the model group, logistic regression analysis was used to identify independent risk factors, which were used to construct a prognostic nomogram. The nomogram was evaluated by analyzing the area under the curve (AUC), calibration curve, and decision curve. These results were subsequently validated via consistency analysis (n = 302). And based on the random forest algorithm, we calculate the same data and construct a random forest model. RESULT: Multivariate logistic regression analysis revealed that age and the expression of the biomarkers CD117, P2X3R, NGF, and TrkA were independent prognostic factors for patients with BPS/IC (P < 0.05). Using these five indicators, a nomogram was developed to predict the risk factors for BPS/IC (scores ranged from 0 to 400). Based on the indicators, the nomogram demonstrated good prognostic performance (AUC = 0.982 and 95% confidence interva is 0.960-0.100). The correction curve indicated a high level of differentiation in the model, and the decision curve suggested positive clinical benefits. The random forest model has high accuracy and good calibration in predicting the prognosis of patients with interstitial cystitis after hydrodistention surgery. CONCLUSION: Age, CD117, P2X3R, NGF, and TrkA are independent prognostic factors for bladder pain syndrome/interstitial cystitis. The column chart model and random forest model constructed based on these indicators have good predictive performance for patient prognosis.

Automatic Registration of Homogeneous and Cross-Source TomoSAR Point Clouds in Urban Areas.

Building reconstruction using high-resolution satellite-based synthetic SAR tomography (TomoSAR) is of great importance in urban planning and city modeling applications. However, since the imaging mode of SAR is side-by-side, the TomoSAR point cloud of a single orbit cannot achieve a complete observation of buildings. It is difficult for existing methods to extract the same features, as well as to use the overlap rate to achieve the alignment of the homologous TomoSAR point cloud and the cross-source TomoSAR point cloud. Therefore, this paper proposes a robust alignment method for TomoSAR point clouds in urban areas. First, noise points and outlier points are filtered by statistical filtering, and density of projection point (DoPP)-based projection is used to extract TomoSAR building point clouds and obtain the facade points for subsequent calculations based on density clustering. Subsequently, coarse alignment of source and target point clouds was performed using principal component analysis (PCA). Lastly, the rotation and translation coefficients were calculated using the angle of the normal vector of the opposite facade of the building and the distance of the outer end of the facade projection. The experimental results verify the feasibility and robustness of the proposed method. For the homologous TomoSAR point cloud, the experimental results show that the average rotation error of the proposed method was less than 0.1°, and the average translation error was less than 0.25 m. The alignment accuracy of the cross-source TomoSAR point cloud was evaluated for the defined angle and distance, whose values were less than 0.2° and 0.25 m.

A Lightweight YOLOv5-MNE Algorithm for SAR Ship Detection.

Unlike optical satellites, synthetic aperture radar (SAR) satellites can operate all day and in all weather conditions, so they have a broad range of applications in the field of ocean monitoring. The ship targets' contour information from SAR images is often unclear, and the background is complicated due to the influence of sea clutter and proximity to land, leading to the accuracy problem of ship monitoring. Compared with traditional methods, deep learning has powerful data processing ability and feature extraction ability, but its complex model and calculations lead to a certain degree of difficulty. To solve this problem, we propose a lightweight YOLOV5-MNE, which significantly improves the training speed and reduces the running memory and number of model parameters and maintains a certain accuracy on a lager dataset. By redesigning the MNEBlock module and using CBR standard convolution to reduce computation, we integrated the CA (coordinate attention) mechanism to ensure better detection performance. We achieved 94.7% precision, a 2.2 M model size, and a 0.91 M parameter quantity on the SSDD dataset.

Geochemical Characteristics and Significance of Organic Matter in Hydrate-Bearing Sediments from Shenhu Area, South China Sea.

Rock-Eval pyrolysis and the biomarker composition of organic matter were systematically studied in hydrate-bearing sediments from the Shenhu area, South China Sea. The n-alkane distribution patterns revealed that the organic matter in the sediments appeared to originate from mixed sources of marine autochthonous input, terrestrial higher plants, and ancient reworked organic matter. The low total organic carbon contents (average < 0.5%) and the low hydrogen index (HI, <80 mg HC/g TOC) suggested the poor hydrocarbon-generation potential of the deposited organic matter at a surrounding temperature of <20 °C in unconsolidated sediments. The abnormally high production index and the fossil-originated unresolved complex mixture (UCM) accompanied by sterane and hopane of high maturity indicated the contribution of deep hydrocarbon reservoirs. Preliminary oil-to-source correlation for the extracts implied that the allochthonous hydrocarbons in the W01B and W02B sediments might have originated from the terrestrial source rocks of mature Enping and Wenchang formations, while those of W03B seem to be derived from more reduced and immature marine source rocks such as the Zhuhai formation. The results of the organic extracts supported the previous identification of source rocks based on the isotopic composition of C2+ hydrate-bound gases. The biomarker of methanogens, squalane, was recognized in the sediments of this study, possibly suggesting the generation of secondary microbial gases which are coupled with the biodegradation of the deep allochthonous hydrocarbons.

Joint Sparsity for TomoSAR Imaging in Urban Areas Using Building POI and TerraSAR-X Staring Spotlight Data.

Synthetic aperture radar (SAR) tomography (TomoSAR) can obtain 3D imaging models of observed urban areas and can also discriminate different scatters in an azimuth-range pixel unit. Recently, compressive sensing (CS) has been applied to TomoSAR imaging with the use of very-high-resolution (VHR) SAR images delivered by modern SAR systems, such as TerraSAR-X and TanDEM-X. Compared with the traditional Fourier transform and spectrum estimation methods, using sparse information for TomoSAR imaging can obtain super-resolution power and robustness and is only minorly impacted by the sidelobe effect. However, due to the tight control of SAR satellite orbit, the number of acquisitions is usually too low to form a synthetic aperture in the elevation direction, and the baseline distribution of acquisitions is also uneven. In addition, artificial outliers may easily be generated in later TomoSAR processing, leading to a poor mapping product. Focusing on these problems, by synthesizing the opinions of various experts and scholarly works, this paper briefly reviews the research status of sparse TomoSAR imaging. Then, a joint sparse imaging algorithm, based on the building points of interest (POIs) and maximum likelihood estimation, is proposed to reduce the number of acquisitions required and reject the scatterer outliers. Moreover, we adopted the proposed novel workflow in the TerraSAR-X datasets in staring spotlight (ST) work mode. The experiments on simulation data and TerraSAR-X data stacks not only indicated the effectiveness of the proposed approach, but also proved the great potential of producing a high-precision dense point cloud from staring spotlight (ST) data.

Abnormal Detection of Cash-Out Groups in IoT Based Payment.

With the rise of online/mobile transactions, the cost of cash-out has decreased and the cost of detection has increased. In the world of online/mobile payment in IoT, merchants and credit cards can be applied and approved online and used in the form of a QR code but not a physical card or Point of Sale equipment, making it easy for these systems to be controlled by a group of fraudsters. In mainland China, where the credit card transaction fee is, on average, lower than a retail loan rate, the credit card cash-out option is attractive for people for an investment or business operation, which, after investigation, can be considered unlawful if over a certain amount is used. Because cash-out will incur fees for the merchants, while bringing money to the credit cards' owners, it is difficult to confirm, as nobody will declare or admit it. Furthermore, it is more difficult to detect cash-out groups than individuals, because cash-out groups are more hidden, which leads to bigger transaction amounts. We propose a new method for the detection of cash-out groups. First, the seed cards are mined and the seed cards' diffusion is then performed through the local graph clustering algorithm (Approximate PageRank, APR). Second, a merchant association network in IoT is constructed based on the suspicious cards, using the graph embedding algorithm (Node2Vec). Third, we use the clustering algorithm (DBSCAN) to cluster the nodes in the Euclidean space, which divides the merchants into groups. Finally, we design a method to classify the severity of the groups to facilitate the following risk investigation. The proposed method covers 145 merchants from 195 known risky merchants in groups that acquire cash-out from four banks, which shows that this method can identify most (74.4%) cash-out groups. In addition, the proposed method identifies a further 178 cash-out merchants in the group within the same four acquirers, resulting in a total of 30,586 merchants. The results and framework are already adopted and absorbed into the design for a cash-out group detection system in IoT by the Chinese payment processor.

Surgical efficacy analysis of tarsal tunnel syndrome: a retrospective study of 107 patients.

Tarsal tunnel syndrome (TTS) is an entrapment neuropathy of the posterior tibial nerve or its terminal branches compressed by its fibro-osseous tunnel beneath the flexor retinaculum on the medial side of the ankle. The current study was a retrospective study of 107 cases of patients with TTS, in which the onset characteristics were summarized, the factors that might affect the surgical treatment effects of TTS were discussed and analyzed. The syndrome diagnoses and treatment experiences of TTS were extracted and analyzed. In our cohort, TTS was more often found in middle-aged and older women. And the medial plantar nerve bundle was the most frequently affected nerve structure. The efficacy of surgical treatment were correlated to the causes of the disease, involved nerve bundles, methods of operation, and whether neurolysis of the epineurium was performed. Neurolysis of the epineurium is was recommended for patients with an enlarged tibial nerve due to impingement. The Singh method was recommended to release the tibial nerve and its branches. Patients with negative preoperative EMG results should carefully be cautious when considering their decision to undergo surgical treatment.

The Effect of Age on the Immunogenicity of the Live Attenuated Zoster Vaccine Is Predicted by Baseline Regulatory T Cells and Varicella-Zoster Virus-Specific T Cell Immunity.

Older age is associated with increased infectious morbidity and decreased immune responses to vaccines, but the mechanisms that mediate this effect are incompletely understood. The efficacy and immunogenicity of the live attenuated zoster vaccine (ZVL) have a very-well-described negative association with the age of the vaccinee. In a study of 600 ZVL recipients 50 to >80 years of age, we investigated immunological factors that might explain the effect of age on the immunogenicity of ZVL. Using FluoroSpot assays and flow cytometry, we determined that varicella-zoster virus (VZV)-specific peak T helper 1 (VZV-Th1) responses to ZVL were independently predicted by prevaccination VZV-Th1 responses, regulatory T cells (Treg), and PD1-expressing immune checkpoint T cells (Tcheck) but not by the age of the vaccinee. Persistence of VZV-Th1 1 year after vaccination was independently predicted by the factors mentioned above, by peak VZV-Th1 responses to ZVL, and by the age of the vaccinee. We further demonstrated by ex vivo blocking experiments the mechanistic role of PD1 and CTLA4 as modulators of decreased VZV-Th1 responses in the study participants. VZV-specific cytotoxic T cell (VZV-CTL) and T follicular helper responses to ZVL did not correlate with age, but similar to other Th1 responses, VZV-CTL peak and baseline responses were independently correlated. These data expand our understanding of the factors affecting the magnitude and kinetics of T cell responses to ZVL in older adults and show the importance of prevaccination Treg and Tcheck in modulating the immunogenicity of ZVL. This presents new potential interventions to increase vaccine responses in older adults.IMPORTANCE Vaccination is the most effective method to protect older adults against viral infections. However, the immunogenicity of viral vaccines in older adults is notoriously poor. The live attenuated zoster vaccine (ZVL) provides the best example of a gradual decrease of vaccine immunogenicity with every 10-year age increase above 50 years. Here we show that the abundance of regulatory T cells before vaccine administration to older adults has a significant inhibitory effect on immune responses to ZVL and, together with baseline immunity to varicella-zoster virus, explains the effect of age on the immunogenicity of ZVL. Moreover, in vitro blockade of regulatory T cell mechanisms of action with biologic modulators restores immune responses to varicella-zoster virus in vaccinees. Collectively, these observations suggest that immune modulators that block regulatory T cell activity may increase responses to viral attenuated vaccines in older adults.

Adsorption Properties of Pd3-Modified Double-Vacancy Defect Graphene toward SF6 Decomposition Products.

In this study, we investigate Pd3-cluster-modified 555-777 graphene (Pd3-graphene) as a novel resistor-type gas sensor to detect SF6 decomposition products based on density functional theory calculations. We obtained and minutely analyzed the relevant parameters of each most stable adsorption configuration to explore the microscopic mechanism during gas adsorption. Theoretical results reveal that Pd3-graphene shows great adsorption capacity and sensitivity toward those decompositions. High adsorption energies and abundant charge transfer amounts could guarantee a stable adsorption structure of decomposition gases on Pd3-graphene surface. The complex change of density of states verifies a strong chemical reaction between the gases and the surface. Moreover, the conductivity of Pd3-graphene would improve due to the decrease of energy gap, and the sensitivity was calculated as SOF2 > H2S > SO2 > SO2 F2. This work provides an effective method to evaluate the operation status of SF6 gas-insulated equipment.

Real-time Concealed Object Detection from Passive Millimeter Wave Images Based on the YOLOv3 Algorithm.

The detection of objects concealed under people's clothing is a very challenging task, which has crucial applications for security. When testing the human body for metal contraband, the concealed targets are usually small in size and are required to be detected within a few seconds. Focusing on weapon detection, this paper proposes using a real-time detection method for detecting concealed metallic weapons on the human body applied to passive millimeter wave (PMMW) imagery based on the You Only Look Once (YOLO) algorithm, YOLOv3, and a small sample dataset. The experimental results from YOLOv3-13, YOLOv3-53, and Single Shot MultiBox Detector (SSD) algorithm, SSD-VGG16, are compared ultimately, using the same PMMW dataset. For the perspective of detection accuracy, detection speed, and computation resource, it shows that the YOLOv3-53 model had a detection speed of 36 frames per second (FPS) and a mean average precision (mAP) of 95% on a GPU-1080Ti computer, more effective and feasible for the real-time detection of weapon contraband on human body for PMMW images, even with small sample data.

Persistence of Varicella-Zoster Virus Cell-Mediated Immunity After the Administration of a Second Dose of Live Herpes Zoster Vaccine.

Protection against zoster conferred by zoster vaccine live (ZVL; Zostavax) wanes over time. We compared varicella-zoster virus cell-mediated immunity (VZV-CMI) of adults ≥70 years who received a second dose of ZVL ≥10 years after the initial dose with de novo-immunized age-matched controls. Before and during the first year after vaccination, VZV-CMI was significantly higher in reimmunized compared with de novo vaccinees. At 3 years, VZV-CMI differences between groups decreased and only memory responses remained marginally higher in reimmunized participants. In conclusion, the increase in VZV-CMI generated by reimmunization with ZVL is at least equally persistent compared with de novo immunization.

Inactivated varicella zoster vaccine in autologous haemopoietic stem-cell transplant recipients: an international, multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Recipients of autologous haemopoietic stem-cell transplants (auto-HSCT) have an increased risk of herpes zoster and herpes zoster-related complications. The aim of this study was to establish the efficacy and safety of an inactivated varicella zoster vaccine for the prevention of herpes zoster after auto-HSCT. METHODS: In this randomised, double-blind, placebo-controlled phase 3 trial, participants were recruited from 135 medical centres (ie, stem-cell transplant centres and hospitals) in North America, South America, Europe, and Asia. Patients were eligible if they were aged 18 years or older, scheduled to receive an auto-HSCT within 60 days of enrolment, and had a history of varicella infection or were seropositive for antibodies to varicella zoster virus, or both. Exclusion criteria included a history of herpes zoster within the previous year of enrolment, and intended antiviral prophylaxis for longer than 6 months after transplantation. Participants were randomly assigned according to a central randomisation schedule generated by the trial statistician, to receive either the inactivated-virus vaccine from one of three consistency lots, a high-antigen lot, or placebo, stratified by age (<50 vs ≥50 years) and intended duration of antiviral prophylaxis after transplantation (≤3 months vs >3 to ≤6 months). Participants, investigators, trial staff, and the funder's clinical and laboratory personnel were masked to group assignment. Participants were given four doses of inactivated vaccine or placebo, with the first dose 5-60 days before auto-HSCT, and the second, third, and fourth doses at about 30, 60, and 90 days after transplantation. The primary efficacy endpoint was the incidence of herpes zoster, confirmed by PCR or adjudication by a masked clinical committee, or both, assessed in all participants randomly assigned to the vaccine consistency lot group or placebo group who received at least one dose of vaccine and had auto-HSCT. Safety was assessed in all randomised participants who received at least one dose of vaccine and had follow-up data. A prespecified vaccine efficacy success criterion required the lower bound of the 95% CI be higher than 25% for the relative reduction of the hazard ratio of herpes zoster infection in participants given the vaccine from one of the consistency lots compared with those given placebo. This trial is registered on ClinicalTrials.gov (NCT01229267) and EudraCT (2010-020150-34). FINDINGS: Between Dec 7, 2010, and April 25, 2013, 560 participants were randomly assigned to the vaccine consistency lot group, 106 to the high-antigen lot group, and 564 to the placebo group. 249 (44%) of patients in the vaccine consistency lot group, 35 (33%) in the high-antigen lot group, and 220 (39%) in the placebo group discontinued before study end, mostly because of death or withdrawal. 51 participants were excluded from the primary efficacy endpoint analyses because they did not undergo auto-HSCT or were not vaccinated, or both (22 [4%] in the vaccine consistency lot group, and 29 [5%] in the placebo group). Mean follow-up for efficacy was 2·4 years (SD 1·3) in the vaccine consistency lot group and 2·3 years (SD 1·3) in the placebo group. 42 (8%) of 538 participants in the vaccine consistency lot group (32·9 per 1000 person-years) and 113 (21%) of 535 in the placebo group (91·9 per 1000 person-years) had a confirmed case of herpes zoster. The estimated vaccine efficacy was 63·8% (95% CI 48·4-74·6), meeting the pre-specified success criterion. For the combined vaccine groups versus the placebo group, the proportion of patients with serious adverse events (216 [33%] of 657 vs 181 [33%] of 554; risk difference 0·2%, 95% CI -5·1 to 5·5) and serious vaccine-related adverse events (five [1%] vs five [1%]; risk difference 0·1%, -1·4 to 1·1) were similar. Vaccine-related injection-site adverse events occurred more frequently in participants given vaccine than those given placebo (191 [29%] vs 36 [7%]; risk difference 22·6%, 95% CI 18·5-26·6; p<0·0001). INTERPRETATION: This study shows for the first time in a large phase 3 trial that early vaccination of auto-HSCT recipients during the peri-transplant period can be effective for the prevention of an opportunistic infection like herpes zoster and that the vaccine is well tolerated. FUNDING: Merck & Co., Inc.

Hough Transform and Clustering for a 3-D Building Reconstruction with Tomographic SAR Point Clouds.

Tomographic synthetic aperture radar (TomoSAR) produces 3-D point clouds with unavoidable noise or false targets that seriously deteriorate the quality of 3-D images and the building reconstruction over urban areas. In this paper, a Hough transform was adopted to detect the outline of a building; however, on one hand, the obtained outline of a building with Hough transform is broken, and on the other hand, some of these broken lines belong to the same segment of a building outline, but the parameters of these lines are slightly different. These problems will lead to that segment of a building outline being represented by multiple different parameters in the Hough transform. Therefore, an unsupervised clustering method was employed for clustering these line parameters. The lines gathered in the same cluster were considered to correspond to a same segment of a building outline. In this way, different line parameters corresponding to a segment of a building outline were integrated into one and then the continuous outline of the building in cloud points was obtained. Steps of the proposed data processing method were as follows. First, the Hough transform was made use of to detect the lines on the tomography plane in TomoSAR point clouds. These detected lines lay on the outline of the building, but they were broken due to the density variation of point clouds. Second, the lines detected using the Hough transform were grouped as a date set for training the building outline. Unsupervised clustering was utilized to classify the lines in several clusters. The cluster number was automatically determined via the unsupervised clustering algorithm, which meant the number of straight segments of the building edge was obtained. The lines in each cluster were considered to belong to the same straight segment of the building outline. Then, within each cluster, which represents a part or a segment of the building edge, a repaired straight line was constructed. Third, between each two clusters or each two segments of the building outline, the joint point was estimated by extending the two segments. Therefore, the building outline was obtained as completely as possible. Finally, taking the estimated building outline as the clustering center, supervised learning algorithm was used to classify the building cloud point and the noise (or false targets), then the building cloud point was refined. Then, our refined and unrefined data were fed into the neural network for building the 3-D construction. The comparison results show the correctness and the effectiveness of our improved method.