Lightweight Multilevel Feature Fusion Network for Hyperspectral Image Classification

Hyperspectral images (HSIs), acquired as a 3D data set, contain spectral and spatial information that is important for ground–object recognition. A 3D convolutional neural network (3DCNN) could therefore be more suitable than a 2D one for extracting multiscale neighborhood information in the spectral and spatial domains simultaneously, if it is not restrained by mass parameters and computation cost. In this paper, we propose a novel lightweight multilevel feature fusion network (LMFN) that can achieve satisfactory HSI classification with fewer parameters and a lower computational burden. The LMFN decouples spectral–spatial feature extraction into two modules: point-wise 3D convolution to learn correlations between adjacent bands with no spatial perception, and depth-wise convolution to obtain local texture features while the spectral receptive field remains unchanged. Then, a target-guided fusion mechanism (TFM) is introduced to achieve multilevel spectral–spatial feature fusion between the two modules. More specifically, multiscale spectral features are endowed with spatial long-range dependency, which is quantified by central target pixel-guided similarity measurement. Subsequently, the results obtained from shallow to deep layers are added, respectively, to the spatial modules, in an orderly manner. The TFM block can enhance adjacent spectral correction and focus on pixels that actively boost the target classification accuracy, while performing multiscale feature fusion. Experimental results across three benchmark HSI data sets indicate that our proposed LMFN has competitive advantages, in terms of both classification accuracy and lightweight deep network architecture engineering. More importantly, compared to state-of-the-art methods, the LMFN presents better robustness and generalization.

Hardly visible, highly admired? Youth perceptions of the EU in Kazakhstan

Youth have always been one of the central target audiences of the European Union’s (EU) policies towards Central Asia, which was once again emphasised in the recent EU Strategy for the region. This paper scrutinises how youth representatives in Kazakhstan, Brussels’ closest partner in the region, perceive the EU and its policies. By doing so, the paper shifts the focus from the EU-centric assessment of its external activities, which has long dominated the academic literature, and provides a ‘voice’ to the targets of the EU’s various initiatives. Examining data obtained through the method of pictorial test and focus group discussions with students of leading Kazakhstani universities, the paper argues that the issue Brussels faces among youth is not an image problem, rather it is a visibility issue. Although Kazakhstani youth are aware of the EU’s main ‘attributes’ at the basic level, they have little knowledge that goes beyond stereotypical, yet positive, images of it. This stereotyped admiration towards the EU, however, is not necessarily an outcome of Brussels’ successful policies, rather it is partly inherited from the historically idealised image of Europe. The paper suggests that increasing its visibility and better communicating its policies and messages need to be a priority for the EU in Central Asia.

Sustained Loss of Bdnf Affects Peripheral but Not Central Vestibular Targets

The vestibular system is vital for proper balance perception, and its dysfunction contributes significantly to fall-related injuries, especially in the elderly. Vestibular ganglion neurons innervate vestibular hair cells at the periphery and vestibular nuclei and the uvula and nodule of the cerebellum centrally. During aging, these vestibular ganglion neurons degenerate, impairing vestibular function. A complete understanding of the molecular mechanisms involved in neurosensory cell survival in the vestibular system is unknown. Brain-derived neurotrophic factor (BDNF) is specifically required for the survival of vestibular ganglion neurons, as its loss leads to early neuronal death. Bdnf null mice die within 3 weeks of birth, preventing the study of the long-term effects on target cells. We use Pax2-cre to conditionally knock out Bdnf, allowing mice survival to approximately 6 months of age. We show that a long-term loss of Bdnf leads to a significant reduction in the number of vestibular ganglion neurons and a reduction in the number of vestibular hair cells. There was no significant decrease in the central targets lateral vestibular nucleus (LVN) or the cerebellum at 6 months. This suggests that the connectivity between central target cells and other neurons suffices to prevent their loss despite vestibular hair cell and ganglion neuron loss. Whether the central neurons would undergo eventual degeneration in the absence of Bdnf remains to be determined.

New Therapeutic Targets for Hepatic Fibrosis in the Integrin Family, α8β1 and α11β1, Induced Specifically on Activated Stellate Cells

A huge effort has been devoted to developing drugs targeting integrins over 30 years, because of the primary roles of integrins in the cell-matrix milieu. Five αv-containing integrins, in the 24 family members, have been a central target of fibrosis. Currently, a small molecule against αvβ1 is undergoing a clinical trial for NASH-associated fibrosis as a rare agent aiming at fibrogenesis. Latent TGFβ activation, a distinct talent of αv-integrins, has been intriguing as a therapeutic target. None of the αv-integrin inhibitors, however, has been in the clinical market. αv-integrins commonly recognize an Arg-Gly-Asp (RGD) sequence, and thus the pharmacophore of inhibitors for the 5-integrins is based on the same RGD structure. The RGD preference of the integrins, at the same time, dilutes ligand specificity, as the 5-integrins share ligands containing RGD sequence such as fibronectin. With the inherent little specificity in both drugs and targets, “disease specificity” has become less important for the inhibitors than blocking as many αv-integrins. In fact, an almighty inhibitor for αv-integrins, pan-αv, was in a clinical trial. On the contrary, approved integrin inhibitors are all specific to target integrins, which are expressed in a cell-type specific manner: αIIbβ3 on platelets, α4β1, α4β7 and αLβ2 on leukocytes. Herein, “disease specific” integrins would serve as attractive targets. α8β1 and α11β1 are selectively expressed in hepatic stellate cells (HSCs) and distinctively induced upon culture activation. The exceptional specificity to activated HSCs reflects a rather “pathology specific” nature of these new integrins. The monoclonal antibodies against α8β1 and α11β1 in preclinical examinations may illuminate the road to the first medical agents.

Prophylactic Administration of Antibodies Specific for the HPA-1a Epitope Prevents Alloimmunization and Platelet Destruction in a Murine Model of Fetal Neonatal Alloimmune Thrombocytopenia

Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening bleeding disorder caused by maternal alloantibodies directed against paternally inherited antigens present on the surface of fetal and neonatal platelets. The human platelet alloantigen HPA-1a (formerly known as the Pl A1 alloantigen), is the most frequently implicated HPA for causing FNAIT in Caucasians. A single Leu33Pro amino acid polymorphism near the amino terminus of the integrin b3 subunit (known as GPIIIa in the platelet literature) serves as the central target for alloantibody binding, leading to clearance of both fetal and neonatal platelets, thrombocytopenia, and in the most severe cases, spontaneous- or trauma-induced intracranial hemorrhage. Unlike hemolytic disease of the newborn, which occurs in pregnancies subsequent to parturition-induced alloimmunization, an estimated 25% to 50% of FNAIT cases occur without warning during gestation of the first pregnancy. Though long proposed, there are currently no approved therapies for the prevention of FNAIT. We recently described the development of transgenic mice expressing the human HPA-1a allogeneic epitope on a murine GPIIIa backbone. Transfusion of such platelets into wild-type female mice induced the generation of high-titer anti-HPA-1a alloantibodies that can cross the placenta and recapitulate many of the relevant clinical features of FNAIT. To test the hypothesis that rapid elimination of fetal HPA-1a positive platelets from the circulation of a mother who is HPA-1a negative might prevent maternal alloimmunization and the development of FNAIT, we administered either a hyperimmune plasma-derived polyclonal anti-HPA-1a antibody derived from females having previous cases of FNAIT (termed RLYB211), or a novel human monoclonal antibody directed against the HPA-1a epitope (termed RLYB212), to wild-type female mice prior to challenging them with HPA-1a-positive murine platelets. RLYB211 and RLYB212 were each able to effect the rapid removal of HPA-1a-positive platelets from murine circulation and prevent the development of anti-HPA-1a alloantibodies. Importantly, wild-type female mice pretreated with RLYB211 prior to exposure to HPA-1a-positive platelets, and then impregnated by HPA-1a-positive males, gave birth to HPA-1a-positive pups with significantly improved platelet counts and no bleeding symptoms. These preclinical data establish the potential for prophylactic polyclonal and monoclonal anti-HPA-1a antibody therapy for the prevention of FNAIT in humans. Disclosures Sheridan: Rallybio: Current Employment, Current equity holder in publicly-traded company. Newman: Rallybio: Consultancy, Research Funding.

New Therapeutic Targets for Hepatic Fibrosis in the Integrin Family, α8β1 and α11β1, Induced Specifically on Activated Stellate Cells

Huge effort has been devoted to developing drugs targeting integrins over 30 years, because of the primary roles of integrins in the cell-matrix milieu. Five αv-containing integrins, in the 24 family members, have been a central target of fibrosis. Currently, a small molecule against αvβ1 is undergoing a clinical trial for NASH-associated fibrosis as a rare reagent aiming at fibrogenesis. Latent TGFβ activation, a distinct talent of αv-integrins, has been intriguing as therapeutic target. None of the αv-integrin inhibitors, however, has been in the clinical market. αv-integrins commonly recognize an Arg-Gly-Asp (RGD) sequence, and thus the pharmacophore of inhibitors for the 5-integrins is based on the same RGD structure. The RGD preference of the integrins, at the same time, dilutes ligand specificity, as the 5-integrins share ligands containing RGD sequence such as fibronectin. With the inherent little specificity in both drugs and targets, “disease specificity” has become less important for the inhibitors than blocking as many αv-integrins. In fact, an almighty inhibitor for αv-integrins, pan-αv, was in a clinical trial. On the contrary, approved integrin inhibitors are all specific to target integrins, which are expressed in cell-type specific manner: αIIbβ3 on platelets, α4β1, α4β7 and αLβ2 on leukocytes. Herein, “disease specific” integrins would serve as attractive targets. α8β1 and α11β1 are selectively expressed in hepatic stellate cells (HSCs) and distinctively induced upon culture activation. The exceptional specificity to activated HSCs reflects rather “pathology specific” nature of these new integrins. The monoclonal antibodies against α8β1 and α11β1 in preclinical examinations may illuminate the road to the first medical reagents.

Mitochondrial Quality Control in Cardiac-Conditioning Strategies against Ischemia-Reperfusion Injury

Mitochondria are the central target of ischemic preconditioning and postconditioning cardioprotective strategies, which consist of either the application of brief intermittent ischemia/reperfusion (I/R) cycles or the administration of pharmacological agents. Such strategies reduce cardiac I/R injury by activating protective signaling pathways that prevent the exacerbated production of reactive oxygen/nitrogen species, inhibit opening of mitochondrial permeability transition pore and reduce apoptosis, maintaining normal mitochondrial function. Cardioprotection also involves the activation of mitochondrial quality control (MQC) processes, which replace defective mitochondria or eliminate mitochondrial debris, preserving the structure and function of the network of these organelles, and consequently ensuring homeostasis and survival of cardiomyocytes. Such processes include mitochondrial biogenesis, fission, fusion, mitophagy and mitochondrial-controlled cell death. This review updates recent advances in MQC mechanisms that are activated in the protection conferred by different cardiac conditioning interventions. Furthermore, the role of extracellular vesicles in mitochondrial protection and turnover of these organelles will be discussed. It is concluded that modulation of MQC mechanisms and recognition of mitochondrial targets could provide a potential and selective therapeutic approach for I/R-induced mitochondrial dysfunction.

The Effect of Changing Colours on Central Crowding Reading

Background: Crowding can be defined as the impaired recognition of closely spaced objects. Changing colour and lighting enhance visual comfort and perceptual troubles that influence impaired vision reading. Objective: The current study was aimed to investigate the impact of changing the flanker distance and unflanked targets with colours on central crowding reading for subjects with their distant best correction (BCVA) equal to or greater than 6/6. Methodology: Six native English speakers (age: 18–38) who participated in a cross-section intervention study were asked to identify the orientation of the letter E (flanked or unflanked) in different directions around the central target in different colours (red, green, blue and black) on a white background. Results: Different colours affect central crowding (p<0.05). However, the central crowding reading of red was not affected by changing flankers (P > 0.05). Conclusion: Central reading crowding is visual crowding. Different colours affect central crowding. However, the central crowding reading in red was not affected by changes in flankers.

Molecular Network Approach Reveals Rictor as a Central Target of Cardiac ProtectomiRs

Cardioprotective medications are still unmet clinical needs. We have previously identified several cardioprotective microRNAs (termed ProtectomiRs), the mRNA targets of which may reveal new drug targets for cardioprotection. Here we aimed to identify key molecular targets of ProtectomiRs and confirm their association with cardioprotection in a translational pig model of acute myocardial infarction (AMI). By using a network theoretical approach, we identified 882 potential target genes of 18 previously identified protectomiRs. The Rictor gene was the most central and it was ranked first in the protectomiR-target mRNA molecular network with the highest node degree of 5. Therefore, Rictor and its targeting microRNAs were further validated in heart samples obtained from a translational pig model of AMI and cardioprotection induced by pre- or postconditioning. Three out of five Rictor-targeting pig homologue of rat ProtectomiRs showed significant upregulation in postconditioned but not in preconditioned pig hearts. Rictor was downregulated at the mRNA and protein level in ischemic postconditioning but not in ischemic preconditioning. This is the first demonstration that Rictor is the central molecular target of ProtectomiRs and that decreased Rictor expression may regulate ischemic postconditioning-, but not preconditioning-induced acute cardioprotection. We conclude that Rictor is a potential novel drug target for acute cardioprotection.

VLA-4 as a Central Target for Modulating Neuroinflammatory Disorders

The complex steps leading to the central nervous system (CNS) inflammation and the progress to neuroinflammatory and neurodegenerative disorders have opened up new research and intervention avenues. This review focuses on the therapeutic targeting of the VLA-4 integrin to discuss the clear-cut effect on immune cell trafficking into brain tissues. Besides, we explore the possibility that blocking VLA-4 may have a relevant impact on nonmigratory activities of immune cells, such as antigen presentation and T-cell differentiation, during the neuroinflammatory process. Lastly, the recent refinement of computational techniques is highlighted as a way to increase specificity and to reduce the detrimental side effects of VLA-4 immunotherapies aiming at developing better clinical interventions.