Image-Specific Information Suppression and Implicit Local Alignment for Text-based Person Search

Text-based person search (TBPS) is a challenging task that aims to search pedestrian images with the same identity from an image gallery given a query text. In recent years, TBPS has made remarkable progress and state-of-the-art methods achieve superior performance by learning local fine-grained correspondence between images and texts. However, most existing methods rely on explicitly generated local parts to model fine-grained correspondence between modalities, which is unreliable due to the lack of contextual information or the potential introduction of noise. Moreover, existing methods seldom consider the information inequality problem between modalities caused by image-specific information. To address these limitations, we propose an efficient joint Multi-level Alignment Network (MANet) for TBPS, which can learn aligned image/text feature representations between modalities at multiple levels, and realize fast and effective person search. Specifically, we first design an image-specific information suppression module, which suppresses image background and environmental factors by relation-guided localization and channel attention filtration respectively. This module effectively alleviates the information inequality problem and realizes the alignment of information volume between images and texts. Secondly, we propose an implicit local alignment module to adaptively aggregate all pixel/word features of image/text to a set of modality-shared semantic topic centers and implicitly learn the local fine-grained correspondence between modalities without additional supervision and cross-modal interactions. And a global alignment is introduced as a supplement to the local perspective. The cooperation of global and local alignment modules enables better semantic alignment between modalities. Extensive experiments on multiple databases demonstrate the effectiveness and superiority of our MANet

Erasing, Transforming, and Noising Defense Network for Occluded Person Re-Identification

Occlusion perturbation presents a significant challenge in person re-identification (re-ID), and existing methods that rely on external visual cues require additional computational resources and only consider the issue of missing information caused by occlusion. In this paper, we propose a simple yet effective framework, termed Erasing, Transforming, and Noising Defense Network (ETNDNet), which treats occlusion as a noise disturbance and solves occluded person re-ID from the perspective of adversarial defense. In the proposed ETNDNet, we introduce three strategies: Firstly, we randomly erase the feature map to create an adversarial representation with incomplete information, enabling adversarial learning of identity loss to protect the re-ID system from the disturbance of missing information. Secondly, we introduce random transformations to simulate the position misalignment caused by occlusion, training the extractor and classifier adversarially to learn robust representations immune to misaligned information. Thirdly, we perturb the feature map with random values to address noisy information introduced by obstacles and non-target pedestrians, and employ adversarial gaming in the re-ID system to enhance its resistance to occlusion noise. Without bells and whistles, ETNDNet has three key highlights: (i) it does not require any external modules with parameters, (ii) it effectively handles various issues caused by occlusion from obstacles and non-target pedestrians, and (iii) it designs the first GAN-based adversarial defense paradigm for occluded person re-ID. Extensive experiments on five public datasets fully demonstrate the effectiveness, superiority, and practicality of the proposed ETNDNet. The code will be released at \url{https://github.com/nengdong96/ETNDNet}

Reduction of voltage gated sodium channel protein in DRG by vector mediated miRNA reduces pain in rats with painful diabetic neuropathy

Abstract Background Painful neuropathy is a common complication of diabetes. Previous studies have identified significant increases in the amount of voltage gated sodium channel isoforms NaV1.7 and NaV1.3 protein in the dorsal root ganglia (DRG) of rats with streptozotocin (STZ)-induced diabetes. We found that gene transfer-mediated release of the inhibitory neurotransmitters enkephalin or gamma amino butyric acid (GABA) from DRG neurons in diabetic animals reduced pain-related behaviors coincident with a reduction in NaV1.7 protein levels in DRG in vivo. To further evaluate the role of NaVα subunit levels in DRG in the pathogenesis of pain in diabetic neuropathy, we constructed a non-replicating herpes simplex virus (HSV)-based vector expressing a microRNA (miRNA) against NaVα subunits. Results Subcutaneous inoculation of the miRNA-expressing HSV vector into the feet of diabetic rats to transduce DRG resulted in a reduction in NaVα subunit levels in DRG neurons, coincident with a reduction in cold allodynia, thermal hyperalgesia and mechanical hyperalgesia. Conclusions These data support the role of increased NaVα protein in DRG in the pathogenesis of pain in diabetic neuropathy, and provide a proof-of-principle demonstration for the development of a novel therapy that could be used to treat intractable pain in patients with diabetic neuropathy.http://deepblue.lib.umich.edu/bitstream/2027.42/112553/1/12990_2011_Article_484.pd

Reduction of Voltage Gated Sodium Channel Protein in DRG by Vector Mediated miRNA Reduces Pain in Rats with Painful Diabetic Neuropathy

BackgroundPainful neuropathy is a common complication of diabetes. Previous studies have identified significant increases in the amount of voltage gated sodium channel isoforms NaV1.7 and NaV1.3 protein in the dorsal root ganglia (DRG) of rats with streptozotocin (STZ)-induced diabetes. We found that gene transfer-mediated release of the inhibitory neurotransmitters enkephalin or gamma amino butyric acid (GABA) from DRG neurons in diabetic animals reduced pain-related behaviors coincident with a reduction in NaV1.7 protein levels in DRG in vivo. To further evaluate the role of NaVα subunit levels in DRG in the pathogenesis of pain in diabetic neuropathy, we constructed a non-replicating herpes simplex virus (HSV)-based vector expressing a microRNA (miRNA) against NaVα subunits.ResultsSubcutaneous inoculation of the miRNA-expressing HSV vector into the feet of diabetic rats to transduce DRG resulted in a reduction in NaVα subunit levels in DRG neurons, coincident with a reduction in cold allodynia, thermal hyperalgesia and mechanical hyperalgesia.ConclusionsThese data support the role of increased NaVα protein in DRG in the pathogenesis of pain in diabetic neuropathy, and provide a proof-of-principle demonstration for the development of a novel therapy that could be used to treat intractable pain in patients with diabetic neuropathy

Glial TNFα in the spinal cord regulates neuropathic pain induced by HIV gp120 application in rats

<p>Abstract</p> <p>Background</p> <p>HIV-associated sensory neuropathy (HIV-SN) is one of the most common forms of peripheral neuropathy, affecting about 30% of people with acquired immune deficiency syndrome (AIDS). The symptoms of HIV-SN are dominated by neuropathic pain. Glia activation in the spinal cord has become an attractive target for attenuating chronic pain. This study will investigate the role of spinal TNFα released from glia in HIV-related neuropathic pain.</p> <p>Results</p> <p>Peripheral gp120 application into the rat sciatic nerve induced mechanical allodynia for more than 7 weeks, and upregulated the expression of spinal TNFα in the mRNA and the protein levels at 2 weeks after gp120 application. Spinal TNFα was colocalized with GFAP (a marker of astrocytes) and Iba1 (a marker of microglia) in immunostaining, suggesting that glia produce TNFα in the spinal cord in this model. Peripheral gp120 application also increased TNFα in the L4/5 DRG. Furthermore, intrathecal administration of TNFα siRNA or soluble TNF receptor reduced gp120 application-induced mechanical allodynia.</p> <p>Conclusions</p> <p>Our results indicate that TNFα in the spinal cord and the DRG are involved in neuropathic pain, following the peripheral HIV gp120 application, and that blockade of the glial product TNFα reverses neuropathic pain induced by HIV gp120 application.</p

Current gene therapy using viral vectors for chronic pain

The complexity of chronic pain and the challenges of pharmacotherapy highlight the importance of development of new approaches to pain management. Gene therapy approaches may be complementary to pharmacotherapy for several advantages. Gene therapy strategies may target specific chronic pain mechanisms in a tissue-specific manner. The present collection of articles features distinct gene therapy approaches targeting specific mechanisms identified as important in the specific pain conditions. Dr. Fairbanks group describes commonly used gene therapeutics (herpes simplex viral vector (HSV) and adeno-associated viral vector (AAV)), and addresses biodistribution and potential neurotoxicity in pre-clinical models of vector delivery. Dr. Tao group addresses that downregulation of a voltage-gated potassium channel (Kv1.2) contributes to the maintenance of neuropathic pain. Alleviation of chronic pain through restoring Kv1.2 expression in sensory neurons is presented in this review. Drs Goins and Kinchington group describes a strategy to use the replication defective HSV vector to deliver two different gene products (enkephalin and TNF soluble receptor) for the treatment of post-herpetic neuralgia. Dr. Hao group addresses the observation that the pro-inflammatory cytokines are an important shared mechanism underlying both neuropathic pain and the development of opioid analgesic tolerance and withdrawal. The use of gene therapy strategies to enhance expression of the anti-pro-inflammatory cytokines is summarized. Development of multiple gene therapy strategies may have the benefit of targeting specific pathologies associated with distinct chronic pain conditions (by Guest Editors, Drs. C. Fairbanks and S. Hao)

The Molecular and Pharmacological Mechanisms of HIV-Related Neuropathic Pain

Infection of the nervous system with the human immunodeficiency virus (HIV-1) can lead to cognitive, motor and sensory disorders. HIV-related sensory neuropathy (HIV-SN) mainly contains the HIV infection-related distal sensory polyneuropathy (DSP) and antiretroviral toxic neuropathies (ATN). The main pathological features that characterize DSP and ATN include retrograde (“dying back”) axonal degeneration of long axons in distal regions of legs or arms, loss of unmyelinated fibers, and variable degree of macrophage infiltration in peripheral nerves and dorsal root ganglia (DRG). One of the most common complaints of HIV-DSP is pain. Unfortunately, many conventional agents utilized as pharmacologic therapy for neuropathic pain are not effective for providing satisfactory analgesia in painful HIV-related distal sensory polyneuropathy, because the molecular mechanisms of the painful HIV-SDP are not clear in detail. The HIV envelope glycoprotein, gp120, appears to contribute to this painful neuropathy. Recently, preclinical studies have shown that glia activation in the spinal cord and DRG has become an attractive target for attenuating chronic pain. Cytokines/chemokines have been implicated in a variety of painful neurological diseases and in animal models of HIV-related neuropathic pain. Mitochondria injured by ATN and/or gp120 may be also involved in the development of HIV-neuropathic pain. This review discusses the neurochemical and pharmacological mechanisms of HIV-related neuropathic pain based on the recent advance in the preclinical studies, providing insights into novel pharmacological targets for future therapy

Applications of Gene Therapy to the Treatment of Chronic Pain

Chronic pain is a highly prevalent condition that impacts adversely on individual quality of life, imposes substantial costs on the healthcare system and a considerable burden on society. Advances in the understanding of pain mechanisms have opened the way for the development of new treatment strategies. The continuous delivery of short-lived potent bioactive molecules to sensory nerves, spinal cord or meninges - achieved by directed gene transfer - offers the possibility to selectively interrupt nociceptive neurotransmission or to interfere with the plastic changes in the nervous system underlying the development or persistence of chronic pain. In this review we describe advances in the use of non-viral and viral vector-based gene transfer for the treatment of pain, with a special focus on the use of recombinant non-replicating herpes simplex virus-based vectors and the prospects for clinical trials