Stepwise membrane binding of extended synaptotagmins revealed by optical tweezers.

Extended synaptotagmins (E-Syts) mediate lipid exchange between the endoplasmic reticulum (ER) and the plasma membrane (PM). Anchored on the ER, E-Syts bind the PM via an array of C2 domains in a Ca2+- and lipid-dependent manner, drawing the two membranes close to facilitate lipid exchange. How these C2 domains bind the PM and regulate the ER-PM distance is not well understood. Here, we applied optical tweezers to dissect PM binding by E-Syt1 and E-Syt2. We detected Ca2+- and lipid-dependent membrane-binding kinetics of both E-Syts and determined the binding energies and rates of individual C2 domains or pairs. We incorporated these parameters in a theoretical model to recapitulate salient features of E-Syt-mediated membrane contacts observed in vivo, including their equilibrium distances and probabilities. Our methods can be applied to study other proteins containing multiple membrane-binding domains linked by disordered polypeptides.

Speckle wavemeter based on a multi-core fiber and compressive imaging.

Random speckle patterns contain valuable information about the incident light. Researchers have successfully constructed spectrometers and wavemeters by utilizing the speckles generated by inter-mode interferences of a multimode fiber (MMF). However, cameras were often employed to record the speckle data in previous reports. The camera's high cost (especially in the near-infrared range), large size, and low response speed limit the applications in optical communications, metrology, and optical sensing. A seven-core fiber (SCF) was fused with an MMF to capture the speckle pattern, where each core coupled part of the speckle field. Furthermore, we take advantage of the space division multiplexing capability of the SCF by incorporating an optical switch. This allows the variety of speckles generated by the incidence of different cores into the MMF. A convolutional neural network (CNN) regression algorithm was designed to analyze the complicated speckle data. The experimental results show that the proposed wavemeter can resolve adjacent wavelengths of 1 pm with an error of about 0.2 pm. We also discussed how different lengths of MMF influence the wavelength resolution. In conclusion, our research presents a robust and cost-effective approach to a wavelength measurement device by use of a seven-core optical fiber.

Inverse design of polarization conversion metasurfaces by deep neural networks.

To address the problem of multiple solutions and improve the calculating speed, we construct a tandem architecture consisting of a forward modeling network and an inverse design network. Using this combined network, we inversely design the circular polarization converter and analyze the effect of different design parameters on the prediction accuracy of the polarization conversion rate. The average mean square error of the circular polarization converter is 0.00121 at an average prediction time of 1.56×10-2 s. If only the forward modeling process is considered, it takes 6.15×10-4 s, which is 2.1×105 times faster than that using the traditional numerical full-wave simulation method. By slightly resizing the network input and output layers, the network is adaptable to the design of both the linear cross-polarization and linear-to-circular polarization converters.

Multi-source Seq2seq guided by knowledge for Chinese healthcare consultation.

Online healthcare consultation offers people a convenient way to consult doctors. In this paper, we aim at building a generative dialog system for Chinese healthcare consultation. As the original Seq2seq architecture tends to suffer the issue of generating low-quality responses, the multi-source Seq2seq architecture generating more informative responses is much more preferred in this task. The multi-source Seq2seq architecture takes advantage of retrieval techniques to obtain responses from the database, and then takes these responses alongside the user-issued question as input. However, some of the retrieved responses might be not much related to the user-issued question, resulting in the generation of unsatisfying responses that are not correct in diagnosis or instead provide inappropriate advice on prevention or treatment. Therefore, this paper proposes multi-source Seq2seq guided by knowledge (MSSGK) to handle this problem. MSSGK differs from the multi-source Seq2seq architecture in that domain knowledge, including disease labels and topic labels about prevention and treatment, is introduced into the response generation via a multi-task learning framework. To better exploit the domain knowledge, we propose three attention mechanisms to provide more appropriate guidance for response generation. Experimental results on a dataset of real-world healthcare consultation show the effectiveness of the proposed method.

Cross domains adversarial learning for Chinese named entity recognition for online medical consultation.

Deep learning methods have been applied to Chinese named entity recognition for the online medical consultation. They require a large number of marked samples. However, no such database is available at present. This paper begins with constructing a larger labelled Chinese texts database for the online medical consultation. Second, a basic framework unit is proposed, which is pre-trained by the transfer learning from both Bidirectional language model and Mask language model trained on the larger unlabelled data. Finally, cross domains adversarial learning (CDAL) for Chinese named entity recognition is proposed to further improve the performance, which not only uses the pre-trained basic framework unit, but also uses the adversarial multi-task learning on both electronic medical record texts and online medical consultation texts. Experimental results validate the effectiveness of CDAL.

Effects of aberrations on effective point spread function in STED microscopy.

Like other imaging techniques, stimulated emission depletion (STED) microscopy suffers from aberrations. While their effects on depletion patterns have been explicitly investigated, the study on how aberrations affect the effective point spread function (PSF) in STED microscopy is still missing. For STED researchers, however, this study is beneficial, as it directly bridges image qualities and aberrations. In this paper, we quantitatively analyze the effects of primary aberrations, including astigmatism, coma, trefoil, and spherical aberration, in two-dimensional (2D) and three-dimensional (3D) STED microscopy, and further discuss the corresponding aberration tolerance. Specifically, attention is given to the modification of the shape, the size, and the peak intensity of the effective PSF in the presence of these aberrations.

[Study on the Preparation of Ba3Si6O9N4 : Eu(2+) Phosphor and the Characterization of Their Luminescence Properties].

Ba3Si6O9N4 : Eu(2+) phosphors were synthesized by two-step synthesis processes based on high temperature solid phase using BaSiO3 as a precursor. The influence mechanism of the Eu(2+) doping concentration to the luminescence properties of Ba3Si6O9N4 : Eu(2+) phosphors were mainly investigated. This paper made a comparison between the luminescence properties of Ba3Si6ON4 : Eu(2+) phosphors prepared by two-step processes and solid- state reaction method. The results showed that the Ba3Si6O9N4 : Eu(3+) phosphors synthesized by two-step processes had higher purity and higher crystallinity. There exists concentration quenching in Ba3Si6O9N4 : Eu(2+) phosphors for both two-step processes and solid-state reaction when the doping concentration x is more than 9%. Both the concentration quenching mechanism of Ba3 Si 09 N4 : EuI+ phosphor prepared by solid-state reaction and two-step processes is electric dipole-dipole interaction. The emission peak of Ba3Si6O9N4 : Eu(2+) phosphors (peak 489 nm) prepared by two-step processes had a blue shift compared to the emission peak of Ba3Si6O9N4 : Eu2+ phosphors (peak 512nm) prepared by solid-state reaction. The emission peak of Ba3Si6O9N4 : Eu2+ phosphors prepared by two-step processes relatively close to the theoretical value (480 nm). The spectrum analysis result showed that the element component of Ba3Si6O3N4 : Eu2+ phosphors prepared by two-step processes was closer to the theoretical value, it means that the two-step processes can effectively reduce the lattice defects. The Ba3Si6O9N4 : Eu(2+) phosphors synthesized by two-step processes had better thermal stability, which demonstrates to be a highly promising phosphor for white-LED applications.

Rugate notch filter fabricated by atomic layer deposition.

A Rugate notch filter is fabricated by atomic layer deposition. By regulating the thickness ratio of TiO2 and Al2O3 in a nanoscale layer, the refractive index is tailored between the refractive indices of the two materials. With the method of equivalent refractive index, the continuously variable refractive index of the designed Rugate filter is dispersed into several discrete ones, so that it can be realized by the refractive index tailoring. To coincide with the thickness, the nanoscale layer is iteratively deposited in the equivalent layer. The experimental reflectance matches the designed one well, and the average reflectance is 86.7% (510-590 nm).

Investigation on multi-parameter of hydrate-bearing synthetic sediment during hydrate replacement process: A in-situ X-ray computed tomography study.

Carbon sequestration can be achieved by carbon dioxide replacement in natural gas hydrate exploitation, which reducing greenhouse gas emissions and providing an effective solution to address climate change, while simultaneously protecting the environment and promoting sustainable energy development. Gas replacement can achieve gas exploitation, gas storage, and stability enhancement simultaneously. However, time-varying microstructure evolution of the hydrate-bearing sediment (HBS) during this process remain a large amount of uncertainty. In this study, with microfocus computer tomography, hydrate replacement process is realized using xenon gas to replace krypton hydrate. During this period, the initial hydrate saturation and effective confining pressure were 63 % and 1 MPa respectively, the results were obtained as follows: 1. Hydrate occurrence dynamically adjusted during replacement process due to the "barrier effect" and "diffusion effect". 2. Dissociated water migration occurred in the sediment, and this induced local hydrate enrichment temporarily and blockages, but the blockages were eventually dredged with the dissociation of the Kr hydrate. 3. The sphericity and surface roughness of the hydrate particles were slightly improved, the pore space connectivity was well enhanced, and both tortuosity and absolute permeability was better strengthened after replacement process, where the absolute permeability was increased by 225.23 %, though the blockage occurrence temporarily weakened this strengthener.

Evanescent-wave-induced frequency shift for optical superresolution imaging.

We propose a method to enhance the resolution and break the diffraction limit. The superresolution imaging is realized by incorporating total internal reflection (TIR) illumination with a passive spatial frequency shift mechanism. Meanwhile, TIR supplies a surface field with a limited penetration depth, which demonstrates that the axial resolution can be improved simultaneously. The superresolution capability is confirmed both theoretically and experimentally. Compared with microfiber-based former work, this idea possesses promising merits, providing a wider viewing field and a simpler configuration for variable illumination orientations, thereby implying abundant application potentials.

Continuous manipulation of doughnut focal spot in a large scale.

We theoretically demonstrate that the doughnut focal spot can continuously be manipulated by synthetically using various beam modulation techniques. Comparatively, a more evident effect can be expected by different orders of phase modulation, while accurate manipulation stems from changing the phase diversity between two arms in an image inverting interferometer (III). The size of central dark spot can thus be continuously adjusted in a theoretically infinite scale, although it may actually be limited by resolution of Spatial Light Modulator (SLM). This approach brings additional flexibility to many applications, such as optical tweezers.

Manipulation of doughnut focal spot by image inverting interferometry.

Based on image inverting interference combined with phase modulation, we theoretically demonstrate that the doughnut focal spot can readily be manipulated, and either shrinkage or expansion of size of the central dark spot is possible in a large scale (peak-to-peak value: 0.555λ-0.830λ, or 93.3%-140.8% compared with the standard one). As the interference and phase modulation can both be achieved by a double Porro prism, it is feasible to introduce this approach into optical tweezers to improve their performance. As much as 33.9% intensity of stimulated emission depletion (STED) beam can be reduced if the further optimized configuration is utilized in STED microscopy.

Fast Peel-Off Ultrathin, Transparent, and Free-Standing Films Assembled from Low-Dimensional Materials Using MXene Sacrificial Layers and Produced Bubbles.

Ultrathin, transparent, and free-standing films assembled from low-dimensional nanomaterials (LDMs) are promising for various applications, including transparent heaters and membranes. However, the intact separation of the assembled films, especially those with controlled ultrathin thickness from deposited substrates, is a tremendous challenge, particularly for fast peeling off via self-detaching. Herein, we propose a versatile method to rapidly peel off ultrathin assembled LDM films, including three types of carbon nanotubes, vermiculite, Ag nanowires, and carbon nanotube@graphene, by dissolving the MXene interlayer from the layer-by-layer filtered MXene/LDM Janus films using diluted H2 O2 . The MXene sacrificial interlayers play dual roles, including physical isolation of LDM films from filter membranes and the production of bubbles that buoy ultrathin LDM films, making them free-standing. The integrality and self-detaching rate of the LDM films are determined by the loading and reactivity of the MXene interlayers. The intact LDM films can self-detach in 80 s by dissolving the optimized MXene interlayer and producing bubbles. The as-made free-standing ultrathin LDM films can be transferred to arbitrary substrates and exhibit outstanding performance as transparent heaters. This scalable method provides an efficient and versatile method to produce ultrathin, transparent, and free-standing LDM films and finds new applications for the growing MXene family.

Mechanical behaviors of hydrate-bearing sediment with different cementation spatial distributions at microscales.

Unlike the conceptual models, the natural hydrate spatial distribution in sediments is multitype and presents different coalescence degrees. In this study, we present pore-scale triaxial test results for hydrate-bearing sediments with different hydrate spatial distributions for the first time. It shows that the specimen with a more dispersed hydrate distribution yields later and exhibits larger peak strength. Correspondingly, the localized deformation develops more slowly, and the shear band is steeper and thinner. The cementation failure in the specimen with a more dispersed hydrate distribution develops more slowly. However, the changing rate of the pore space characteristic does not seem to be affected by the hydrate spatial distribution. Moreover, the specimen with a more dispersed hydrate distribution has a larger hydrate-sand interfacial area, and further axial loading would increase it rapidly firstly, and then the increasing rate would be slowed down since the cementation structure failure.

Identification of a mimotope of an infectious bronchitis virus S1 protein.

The S1 protein of the infectious bronchitis virus (IBV) is a major structural protein that induces the production of the virus-neutralization antibodies. The monoclonal antibody against the IBV M41 S1 protein was used as a target for biopanning. After three rounds of biopanning, randomly selected phages bound to the monoclonal antibody. Sequence analysis showed that the dominant sequence was SFYDFEMQGFFI. Indirect competitive enzyme-linked immunosorbent assay showed that SFYDFEMQGFFI is a mimotope of the S1 protein that was predicted by PepSurf. The mimotope may provide information for further structural and functional analyses of the S1 protein.

Induction of anti-Zearalenone immune response with mimotopes identified from a phage display peptide library.

Zearalenone (ZEN), a type of non-steroidal estrogenic mycotoxin, is mainly produced by several species of Fusarium molds. It is ubiquitous in contaminated grains and grain products all over the world, posing a serious threat to animal and human health. This study aims to screen the mimotopes of ZEN from a phage display random 12-mer peptide library and explore their immunogenicity. A monoclonal antibody (mAb) against ZEN was employed as the target for mimotope selection from a phage display random peptide library. After four rounds of panning, six mimotopes that could specifically bind to ZEN mAb were obtained. In order to explore the immunogenicity of these mimotopes, Balb/c mice were immunized with phages Z8, Z21, Z35, Z8:Z21:Z35(1:1:1) and the conjugate of ZEN-bovine serum albumin (ZEN-BSA), respectively. The titers of antibodies in the mice immunized with mimotopes were 1:3200 (Z8), 1:3200 (Z21), 1:6400 (Z35), 1:6400 (1:1:1 mixture of Z8, Z21 and Z35), and the binding between serum antibodies and ZEN-OVA could be blocked by ZEN standards. These results demonstrated that the mimotopes of ZEN could induce specific antibodies against ZEN, suggesting that these displayed peptides were immunogenic.

Personalized Body Constitution Inquiry Based on Machine Learning.

Background: Body constitution (BC) is the abstract concept indicating the state of a person's health in Traditional Chinese Medicine (TCM). The doctor identifies the body constitution of the patient through inspection and inquiry. Previous research simulates doctors to identify BC types according to a patient's objective physical indicators. However, the lack of subjective feeling information can reduce the accuracy of the machine to imitate the doctor's diagnosis. The Constitution in Chinese Medicine Questionnaire (CCMQ) is used to collect subjective information but suffers from low acquisition efficiency. Methods: This paper presents a personalized body constitution inquiry method based on a machine learning technique. It employs a random generator, a feature extractor, and a classifier to simulate the doctor inquiry and generate a personalized questionnaire. Specifically, the feature extractor evaluates and sorts the question of the constitution in the CCMQ based on the recognition results of the tongue coating image of patients. The sorted questions and relevant BC label are inputted into the classifier; the best questions are screened out for patients. Results: The experimental results show that our method can select personalized questions from the CCMQ for the patients, significantly reducing the time and the number of questions to answer. It also improves the accuracy of recognizing BC. Compared with the CCMQ, patients had 68.3% fewer questions to answer and the time occupied by answering is reduced by 80.3%. Conclusions: The proposed method can simulate the doctor's inquiry and pick out personalized questions for patients. It can act as auxiliary diagnosis tools to collect subjective patient feelings and help make further judgments on the patient's BC types.

A microfocus x-ray computed tomography based gas hydrate triaxial testing apparatus.

Gas hydrate-bearing sediment shows complex mechanical characteristics. Its macroscopic deformation process involves many microstructural changes such as phase transformation, grain transport, and cementation failure. However, the conventional gas hydrate triaxial testing apparatus is not possible to obtain the microstructure in the samples. In this study, a novel, low-temperature (-35 to 20 °C), high-pressure (>16 MPa confining pressure and >95.4 MPa vertical stress) triaxial testing apparatus suitable for X-ray computed tomography scanning is developed. The new apparatus permits time-lapse imaging to capture the role of hydrate saturation, effective stress, strain rate, hydrate decomposition on hydrate-bearing sediment characteristic, and cementation failure behavior. The apparatus capabilities are demonstrated using in situ generation of hydrate on a xenon hydrate-bearing glass bead sample. In the mentioned case, a consolidated drained shear test was conducted, and the imaging reveals hydrate occurrence with a saturation of 37.3% as well as the evolution of localized strain (or shear band) and cementation failure along with axial strain.

Alveolar paratesticular rhabdomyosarcoma mimicing epididymitis: Case report and literature review.

RATIONALE: Most patients with paratesticular rhabdomyosarcoma may typically present as a unilateral, painless palpable scrotum mass. However, only a few cases of RMS presenting as painful edema of the scrotum mimicing epididymitis. We herein report an unusual case of alveolar paratesticular rhabdomyosarcoma misdiagnosed as epididymitis. PATIENT CONCERNS: A 19-year-old adolescent, presented to urologist with painful swelling of the scrotum on the left side over the preceding several days. Antibiotics were administered by physician for two months and the pain improved, but the swelling did not fade. DIAGNOSES: Alveolar praratesticular rhabdomyosarcoma. INTERVENTIONS: A left, soft tissue mass in the scrotum without definite metastasis or lymphadenopathy was confirmed by computed tomography (CT) and magnetic resonance imaging. A radical left orchiectomy via the inguinal approach was performed successfully. OUTCOME: The patient received 8 cycles of adjuvant chemotherapy, the patient remains recurrence- and metastasis-free at 13 months after surgery. LESSONS: When paratesticular RMS is presenting with symptoms of epididymitis, this malignant tumor is usually overlooked. When patients complain of painful scrotal swelling, RMS arise from paratesticular tissue should be considered.

Single-molecule force spectroscopy of protein-membrane interactions.

Many biological processes rely on protein-membrane interactions in the presence of mechanical forces, yet high resolution methods to quantify such interactions are lacking. Here, we describe a single-molecule force spectroscopy approach to quantify membrane binding of C2 domains in Synaptotagmin-1 (Syt1) and Extended Synaptotagmin-2 (E-Syt2). Syts and E-Syts bind the plasma membrane via multiple C2 domains, bridging the plasma membrane with synaptic vesicles or endoplasmic reticulum to regulate membrane fusion or lipid exchange, respectively. In our approach, single proteins attached to membranes supported on silica beads are pulled by optical tweezers, allowing membrane binding and unbinding transitions to be measured with unprecedented spatiotemporal resolution. C2 domains from either protein resisted unbinding forces of 2-7 pN and had binding energies of 4-14 kBT per C2 domain. Regulation by bilayer composition or Ca2+ recapitulated known properties of both proteins. The method can be widely applied to study protein-membrane interactions.