DWRSeg: Rethinking Efficient Acquisition of Multi-scale Contextual Information for Real-time Semantic Segmentation

Many current works directly adopt multi-rate depth-wise dilated convolutions to capture multi-scale contextual information simultaneously from one input feature map, thus improving the feature extraction efficiency for real-time semantic segmentation. However, this design may lead to difficult access to multi-scale contextual information because of the unreasonable structure and hyperparameters. To lower the difficulty of drawing multi-scale contextual information, we propose a highly efficient multi-scale feature extraction method, which decomposes the original single-step method into two steps, Region Residualization-Semantic Residualization. In this method, the multi-rate depth-wise dilated convolutions take a simpler role in feature extraction: performing simple semantic-based morphological filtering with one desired receptive field in the second step based on each concise feature map of region form provided by the first step, to improve their efficiency. Moreover, the dilation rates and the capacity of dilated convolutions for each network stage are elaborated to fully utilize all the feature maps of region form that can be achieved.Accordingly, we design a novel Dilation-wise Residual (DWR) module and a Simple Inverted Residual (SIR) module for the high and low level network, respectively, and form a powerful DWR Segmentation (DWRSeg) network. Extensive experiments on the Cityscapes and CamVid datasets demonstrate the effectiveness of our method by achieving a state-of-the-art trade-off between accuracy and inference speed, in addition to being lighter weight. Without pretraining or resorting to any training trick, we achieve an mIoU of 72.7% on the Cityscapes test set at a speed of 319.5 FPS on one NVIDIA GeForce GTX 1080 Ti card, which exceeds the latest methods of a speed of 69.5 FPS and 0.8% mIoU. The code and trained models are publicly available

Fusion with extracellular domain of cytotoxic T-lymphocyte-associated-antigen 4 leads to enhancement of immunogenicity of Hantaan virus DNA vaccines in C57BL/6 mice

<p>Abstract</p> <p>Background</p> <p>Hantaan virus (HTNV) is the causative agent of the most severe form of a rodent-borne disease known as hemorrhagic fever with renal syndrome (HFRS). A safe and effective HTNV vaccine is needed. Vaccination with DNA constructs expressing fused antigen with bioactive factors, has shown promising improvement of immunogenicity for viral agents in animal models, but the effect of fusion strategy on HTNV DNA vaccine has not been investigated.</p> <p>Results</p> <p>DNA plasmids encoding the HTNV nucleocapsid protein (N) and glycoprotein (Gn and Gc) in fusion to the extracellular domain of cytotoxic T-lymphocyte-associated-antigen 4 (eCTLA-4) targeting to antigen presenting cells (APCs) were constructed. Intramuscular immunization of mice with plasmids expressing eCTLA-4-HTNV-N/GP fusion proteins leads to a significant enhancement of the specific antibody response as well as cytotoxic T-lymphocyte (CTL) response in C57BL/6 mice. Moreover, this effect could be further augmented when co-administered with CpG motifs.</p> <p>Conclusions</p> <p>Modification of viral antigen in fusion to bioactive factor will be promising to confer efficient antigen presentation and improve the potency of DNA vaccine in mice.</p

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR210005172

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

cDNA cloning and expression of a novel cell surface-expressed heparan sulfate/heparin interacting protein (HIP) from human cell lines and functional studies of a synthetic HIP peptide

Heparan sulfate proteoglycans and their corresponding binding sites have been suggested to play an important role during the initial attachment of blastocysts to uterine epithelium and human trophoblastic cell lines to uterine epithelial cell lines. Previous studies on RL95 cells, a human uterine epithelial cell line, characterized a single class of cell surface heparin/heparan sulfate (HP/HS)-binding sites. Three major HP/HS-binding peptide fragments were isolated from RL95 cell surfaces by tryptic digestion and partial amino-terminal amino acid sequence from each peptide fragment was obtained. In the current study, using the approaches of reverse transcription-polymerase chain reaction and cDNA library screening, a novel cell surface $\rm\underline{H}$P/HS $\rm\underline{i}$nteracting $\rm\underline{p}$rotein (HIP) has been isolated from RL95 cells. The full-length cDNA of HIP encodes a protein of 259 amino acids with a calculated molecular weight of 17,754 Da and pI of 11.75. Transfection of HIP cDNA into NIH-3T3 cells demonstrated cell surface expression and a size similar to that of HIP expressed by human cells. Predicted amino acid sequence indicates that HIP lacks a membrane spanning region and has no consensus sites for glycosylation. Northern blot analysis detected a single transcript of 1.3 kb in both total RNA and poly(A\sp+) RNA. Examination of human cell lines and normal tissues using both Northern blot and Western blot analysis revealed that HIP is differentially expressed in a variety of human cell lines and normal tissues, but absent in some cell lines examined. HIP has about 80% homology, at the level of both mRNA and protein, to a rodent protein, designated as ribosomal protein L29. Thus, members of the L29 family may be displayed on cell surfaces where they participate in HP/HS binding events. Studies on a synthetic peptide derived from HIP demonstrate that HIP peptide binds HS/HP with high selectivity and has high affinity (Kd = 10 nM) for a subset of polysaccharides found in commercial HIP preparations. Moreover, HIP peptide also binds certain forms of cell surface, but not secreted or intracellular. HS expressed by RL95 and JAR cells. This peptide supports the attachment of several human trophoblastic cell lines and a variety of mammalian adherent cell lines in a HS-dependent fashion. Furthermore, studies on the subset of HP specifically recognized by HIP peptide indicate that this high-affinity HP (HA-HP) has a larger median MW and a greater negative charge density than bulk HP. The minimum size of oligosaccharide required to bind to HIP peptide with high affinity is a septa- or octasaccharide. HA-HP also quantitatively binds to antithrombin-III (AT-III) with high affinity, indicating that HIP peptide and AT-III may recognize the same or similar oligosaccharide structure(s). Furthermore, HIP peptide antagonizes HP action and promotes blood coagulation in both factor Xa- and thrombin-dependent assays. Finally, HA-HP recognized by HP peptide is highly enriched with anticoagulant activity relative to bulk HP. Collectively, these results demonstrate that HIP may play a role in the HP/HS-involved cell-cell and cell-matrix interactions and recognizes a motif in HP similar or identical to that recognized by AT-III and therefore, may modulate blood coagulation

A heparin-binding synthetic peptide of heparin/heparan sulfateinteracting protein modulates blood coagulation activities

We have previously identified and characterized a heparin-binding cell surface protein (heparin/heparan sulfate-interacting protein, or HIP) present on epithelial and endothelial cells. A synthetic peptide mimicking a heparin-binding domain of HIP is now shown to bind a small subset of heparin molecules with high affinity and, therefore, presumably recognizes a specific structural motif in the heparin molecule. Further analyses revealed that the heparin molecules exhibiting a high affinity for the HIP peptide also show an extremely high affinity for antithrombin III (AT-III), a cofactor required for heparin’s anticoagulant activity. The HIP peptide was shown to compete with AT-III for binding to heparin and to neutralize the anticoagulant activity of heparin in blood plasma assays. Furthermore, the heparin subfraction that binds to the HIP peptide with high affinity exhibits an extremely high anticoagulant activity. We conclude that although the HIP peptide shows no sequence similarity with AT-III, the two proteins recognize the same or similar structural motifs in heparin

Hydrocarbon formation and accumulation of the deep Paleogene of the Jiyang Depression, Shengli Oilfield

Using geochemistry, sedimentary and petroleum geology methods, and based on the analysis of spatial distribution of deep source rocks and sedimentary organic facies, the favorable exploration prospects in the Jiyang Depression, Shengli Oilfield are studieded. There are 4 types of sedimentary organic facies (including anoxic organic facies, anaerobic organic facies, dysaerobic organic facies and aerobic organic facies) in deep source rocks of Kongdian Formation - Sha-4 Member, Paleogene. The source rocks of Anoxic facies and anaerobic facies are discovered in the Sha-4 Member and are proved as excellent source rocks, while the Kongdian Formation source rocks compose mainly of the dysaerobic facies and aerobic facies and served as common source rocks. The whole hydrocarbon expulsion process is divided into 3 stages, including free water expulsion, hydrocarbon generation and energy accumulation, and hydrocarbon expulsion from microfractures. The hydrocarbon expulsion from deep source rocks mainly occurs in the stage of hydrocarbon expulsion from microfractures, during which there are three oil and gas migration modes with different geologic conditions, including vertical migration, lateral migration and downward migration. The studies indicated that the hydrocarbons in shallow and medium formations from the Sha-4 Member excellent source rocks of anoxic and anaerobic facies are mainly accumulated through vertical migration along the faults, while the reservoirs formed by lateral migration and downward migration are still waiting to be revealed. So there is great exporation potential for the deep Paleogene of the Jiyang Depression. Key words: Jiyang Depression, Paleogene, organic facies, hydrocarbon generation and expulsion mechanism, hydrocarbon migration, accumulatio

Control of pressure system development on reservoir formation in the Dongying Sag, Shengli Oilfield, East China

The zonality of abnormal pressure is closely correspondent to the breakthrough pressure (or pressure preservative ability) of mudstones in the Dongying Sag. The breakthrough pressures and formation fluid pressure coefficients rise with increasing depth. The preservation of isolated mudstone intervals is also important to the abnormal pressure formation. Based on the episodic difference of pressure buildup mechanism, source dynamic (fluid pressure in source rocks) fields of critical geologic times were analyzed in lateral plane and vertical profiles in the Dongying Sag. Source dynamic of major source rocks occurs in disequilibrium with time and space, which affects oil-gas sources and reservoir formation and controls the direction of oil-gas migration as a whole. The present reservoirs are distributed along the pressure decreasing directions. The distribution of the reservoirs is successional to the evolution of source dynamic. On the other hand, oil-gas migration and accumulation affect the distribution of formation pressure fields. The isolated mudstone intervals preserve the fluid pressures to different extents. Due to the equilibrium between pressure buildup and pressure relief, source dynamic creates different conditions in various pressure systems during its transference, which cause the differences in types and features of oil-gas reservoirs. Based on the evolutionary history of source dynamic, the reservoir forming process in the Dongying Sag was analyzed. The deep layers of the Shahejie Formation are important targets for us to discover light hydrocarbon and natural gas reservoirs with high pressures. 摘 要: 东营凹陷异常压力的分带性与泥岩的突破压力（或保存能力）具有明显的对应关系，随着深度增加，泥岩突破压力及地层流体压力系数均增大，泥岩封隔层对流体压力的保存也是形成异常压力的重要条件。基于增压机制的阶段性差异，对东营凹陷平面上及典型剖面中重要地质历史时期源动力（烃源岩流体压力）场进行了分析，主力烃源岩的源动力在时间和空间上发育不均衡，从整体上影响了储集层油气来源及油藏的形成，控制了油气运移的方向。现今油藏总体沿地质历史时期源动力场降低的方向分布，表现出油藏的分布与源动力的演化具有一定的继承性；油气运移和成藏也影响了地层压力场的分布，高压油气运移到储集层后，其泥岩封隔层不同程度地保存了流体压力。由于增压-卸压的平衡关系，源动力传递过程中在不同压力系统中构成了不同的动力条件，造成了各压力系统中油气成藏类型和特征具有一定的差异性。根据源动力的演化史，指出沙河街组深层是寻找高压轻质油藏及天然气藏的重要目标。 Key words: Dongying Sag, palaeopressure, petroleum accumulation, controlling, fillin

Transmembrane domain helix packing stabilizes integrin aIIb beta 3 in the low affinity state

Regulated changes in the affinity of integrin adhesion receptors ("activation") play an important role in numerous biological functions including hemostasis, the immune response, and cell migration. Physiological integrin activation is the result of conformational changes in the extracellular domain initiated by the binding of cytoplasmic proteins to integrin cytoplasmic domains. The conformational changes in the extracellular domain are likely caused by disruption of intersubunit interactions between the alpha and beta transmembrane (TM) and cytoplasmic domains. Here, we reasoned that mutation of residues contributing to alpha/beta interactions that stabilize the low affinity state should lead to integrin activation. Thus, we subjected the entire intracellular domain of the beta3 integrin subunit to unbiased random mutagenesis and selected it for activated mutants. 25 unique activating mutations were identified in the TM and membrane-proximal cytoplasmic domain. In contrast, no activating mutations were identified in the more distal cytoplasmic tail, suggesting that this region is dispensable for the maintenance of the inactive state. Among the 13 novel TM domain mutations that lead to integrin activation were several informative point mutations that, in combination with computational modeling, suggested the existence of a specific TM helix-helix packing interface that maintains the low affinity state. The interactions predicted by the model were used to identify additional activating mutations in both the alpha and beta TM domains. Therefore, we propose that helical packing of the alpha and beta TM domains forms a clasp that regulates integrin activation