Relative pose measurement for noncooperative objects is an important part of 3D shape recognition and motion tracking. The methods based on scanning point clouds have better environmental ...adaptability and stability than image-based methods. However, the discrete points obtained from a continuous surface are sparse, which leads to point-to-point dislocations in the overlapping area and seriously reduces the accuracy. Therefore, this paper proposed a relative-pose-measurement algorithm based on double-constrained intersurface mutual projections. First, the initial corresponding set was constructed using mutual projections between the areas with similar feature descriptors, and then the final corresponding set was determined through the rigid-transformation-consistency constraint to improve the accuracy of the matchings and achieve a high-accuracy relative pose measurement. In the Stanford dataset, the rotation error and translation error were reduced by 19.3% and 13.4%, respectively. Furthermore, based on the proposed evaluation method, which separated the error of the pose-measurement algorithm from that of the instrument, the experiments were carried out with a self-made swept-frequency interferometer. The rotation error was reduced by 39.8%, and the surface deviation was reduced by 4.9%, which further proved the advancement of the method.
Trastuzumab (Herceptin
®
) is currently used as a treatment for patients whose breast tumors overexpress HER2/ErbB2. Trastuzumab-DM1 (T-DM1, trastuzumab emtansine) is designed to combine the clinical ...benefits of trastuzumab with a potent microtubule-disrupting drug, DM1 (a maytansine derivative). Currently T-DM1 is being tested in multiple clinical trials. The mechanisms of action for trastuzumab include inhibition of PI3K/AKT signaling pathway, inhibition of HER-2 shedding and Fcγ receptor mediated engagement of immune cells, which may result in antibody-dependent cellular cytotoxicity (ADCC). Here we report that T-DM1 retains the mechanisms of action of unconjugated trastuzumab and is active against lapatinib resistant cell lines and tumors.
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•Panshi nephrite is of dolomite-related origin.•Panshi nephrite samples all exhibited very low total rare earth element contents.•Panshi nephrite was formed in many stages during the ...Variscan–Indosinian epoch.
Nephrite is an important variety of jade that is of great significance in prospecting management. Little research has been carried out on the newly discovered nephrite deposit in Panshi, Jilin Province, Northeast China. This paper presents the first systematic study of this new deposit. The mineralogical, petrological, and geochemical characteristics along with the petrogenesis of samples from this deposit were evaluated by microscopic observation, scanning electron microscopy, electron probe microanalysis, and laser ablation inductively coupled plasma mass spectrometry. The main mineral component of the Panshi nephrite was determined to be tremolite, and diopside, chlorite, apatite, calcite, and dolomite were observed as secondary minerals. The tremolite presented two microstructures: feltlike and fibroblastic. All the examined tremolite samples contained low amounts of FeO (0.006–0.249 wt%), Cr2O3 (0.000–0.047 wt%), and NiO (0.000–0.053 wt%) along with high values (>0.99) of Mg2+/(Mg2++Fe2+) relative to dolomite-related nephrites. The nephrite samples all exhibited very low total rare earth element contents ranging from 1.831 to 5.121 ppm and were characterized by positive and negative Eu anomalies (0.267–4.446), negative Ce anomalies (0.283–0.650), positive U anomalies, and negative Ba, Nb, Ti, and Ce anomalies. These characteristics indicate a multistage, superimposed mineralization formation mechanism for the Panshi nephrite. The test results and regional geological survey results indicate that the Panshi nephrite deposit was likely formed by intermediate-felsicmagmas that intruded into dolomitic marble in many stages during the Variscan–Indosinian epoch. Generally, the genesis of the Panshi nephrite can be ascribed to two typical processes, contact metasomatism and late metamorphism, and the Panshi nephrite is of dolomite-related origin. The results of this study provide theoretical guidance for the search for nephrite deposits of dolomite-related origin.
Targeting HER2 with multiple HER2-directed therapies represents a promising area of treatment for HER2-positive cancers. We investigated combining the HER2-directed antibody-drug conjugate ...trastuzumab emtansine (T-DM1) with the HER2 dimerization inhibitor pertuzumab (Perjeta).
Drug combination studies with T-DM1 and pertuzumab were performed on cultured tumor cells and in mouse xenograft models of HER2-amplified cancer. In patients with HER2-positive locally advanced or metastatic breast cancer (mBC), T-DM1 was dose-escalated with a fixed standard pertuzumab dose in a 3+3 phase Ib/II study design.
Treatment of HER2-overexpressing tumor cells in vitro with T-DM1 plus pertuzumab resulted in synergistic inhibition of cell proliferation and induction of apoptotic cell death. The presence of the HER3 ligand, heregulin (NRG-1β), reduced the cytotoxic activity of T-DM1 in a subset of breast cancer lines; this effect was reversed by the addition of pertuzumab. Results from mouse xenograft models showed enhanced antitumor efficacy with T-DM1 and pertuzumab resulting from the unique antitumor activities of each agent. In patients with mBC previously treated with trastuzumab, lapatinib, and chemotherapy, T-DM1 could be dosed at the maximum tolerated dose (MTD; 3.6 mg/kg every 3 weeks) with standard dose pertuzumab. Adverse events were mostly grade 1 and 2, with indications of clinical activity.
Dual targeting of HER2 with the combination of T-DM1 and pertuzumab in cell culture and mouse xenograft models resulted in enhanced antitumor activity. In patients, this combination showed an encouraging safety and tolerability profile with preliminary evidence of efficacy.
Direct sunlight in complex environmental conditions severely interferes with the light intensity response for imaging Polarization Sensor (PS), leading to a reduction in polarization orientation ...accuracy. Addressing this issue, this article analyzes the impact mechanism of direct sunlight on polarization sensor detection in a complex environment. The direct sunlight interference factor is introduced into the intensity response model of imaging polarization detection, enhancing the accuracy of the polarization detection model. Furthermore, a polarization state information analytical solution model based on direct sunlight compensation is constructed to improve the accuracy and real-time performance of the polarization state information solution. On this basis, an improved bio-orientation method based on direct sunlight compensation for imaging polarization sensor is proposed. The outdoor dynamic reorientation experiment platform is established to validate the effectiveness of the proposed method. Compared with the traditional methods, the experimental results demonstrate a 23% to 47% improvement in the polarization orientation accuracy under various solar zenith angles.
Recent study shows that recommendation system not only relys on user's static preference, but also dynamic preference. Consequently, it leads to the emergence of session-based recommendation. With ...the development of recurrent neural network, this kind of method can capture representations of users' sequential behaviors from a large number of sessions. However it is prone to spurious dependency problem. Recently, convolutional neural network has also shown its potential in modelling session, especially in extracting complex local pattern of subsequence. Therefore, we propose a hybrid neural model, called SGPD, for learning sequential general pattern and dependency for session-based recommendation. In SGPD, we propose recurrent residual convolution network to extract general pattern of subsequence in a session. Furthermore, the SGPD scans sequence from forward and reverse direction by bidirectional recurrent neural network, and learns sequential dependency of a session. Finally, the objective function is constructed by cross entropy and the model parameters are learned. The experimental results show that the precision rate, recall rate and mean reciprocal ranking of SGPD are greatly improved compared with the state-of-art methods. It has good application prospect.
Antibody drug conjugates (ADCs) combine the ideal properties of both antibodies and cytotoxic drugs by targeting potent drugs to the antigen-expressing tumor cells, thereby enhancing their antitumor ...activity. Successful ADC development for a given target antigen depends on optimization of antibody selection, linker stability, cytotoxic drug potency, and mode of linker-drug conjugation to the antibody. Here, we systematically examined the in vitro potency as well as in vivo preclinical efficacy and safety profiles of a heterogeneous preparation of conventional trastuzumab-mcc-DM1 (TMAb-mcc-DM1) ADC with that of a homogeneous engineered thio-trastuzumab-mpeo-DM1 (thioTMAb-mpeo-DM1) conjugate.
To generate thioTMAb-mpeo-DM1, one drug maytansinoid 1 (DM1) molecule was conjugated to an engineered cysteine residue at Ala114 (Kabat numbering) on each trastuzumab-heavy chain, resulting in two DM1 molecules per antibody. ThioTMAb-mpeo-DM1 retained similar in vitro anti-cell proliferation activity and human epidermal growth factor receptor 2 (HER2) binding properties to that of the conventional ADC. Furthermore, it showed improved efficacy over the conventional ADC at DM1-equivalent doses (μg/m(2)) and retained efficacy at equivalent antibody doses (mg/kg). An improved safety profile of >2-fold was observed in a short-term target-independent rat safety study. In cynomolgus monkey safety studies, thioTMAb-mpeo-DM1 was tolerated at higher antibody doses (up to 48 mg/kg or 6,000 μg DM1/m(2)) compared with the conventional ADC that had dose-limiting toxicity at 30 mg/kg (6,000 μg DM1/m(2)).
The engineered thioTMAb-mpeo-DM1 with broadened therapeutic index represents a promising antibody drug conjugate for future clinical development of HER2-positive targeted breast cancer therapies.
Antibody–drug conjugates (ADCs) have become an important therapeutic modality for oncology, with three approved by the FDA and over 60 others in clinical trials. Despite the progress, improvements in ...ADC therapeutic index are desired. Peptide-based ADC linkers that are cleaved by lysosomal proteases have shown sufficient stability in serum and effective payload-release in targeted cells. If the linker can be preferentially hydrolyzed by tumor-specific proteases, safety margin may improve. However, the use of peptide-based linkers limits our ability to modulate protease specificity. Here we report the structure-guided discovery of novel, nonpeptidic ADC linkers. We show that a cyclobutane-1,1-dicarboxamide-containing linker is hydrolyzed predominantly by cathepsin B while the valine–citrulline dipeptide linker is not. ADCs bearing the nonpeptidic linker are as efficacious and stable in vivo as those with the dipeptide linker. Our results strongly support the application of the peptidomimetic linker and present new opportunities for improving the selectivity of ADCs.
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