Immune development in HIV-exposed uninfected children born to HIV-infected women

Immunological and clinical findings suggestive of some immune dysfunction have been reported among HIV-exposed uninfected (HEU) children and adolescents. Whether these defects are persistent or transitory is still unknown. HEU pediatric population at birth, 12 months, 6-12 years were evaluated in comparison to healthy age-matched HIV-unexposed controls. Plasma levels of LPS, sCD14, cytokines, lymphocyte immunophenotyping and T-cell receptor excision circles (TREC) were assessed. HEU and controls had similar LPS levels, which remained low from birth to 6-12 years; for plasma sCD14, IL-2, IL-6, IL-7, IL-10, IL-12p70, IL-13, IL-17, IFN-γ, TNF-α, G-CSF, GM-CSF and MCP-1, which increased from birth to 12 months and then decreased at 6-12 years; and for TREC/106 PBMC at birth in HEU and controls. By contrast, plasma MIP-1β levels were lower in HEU than in controls (p=0.009) at 12 months, and IL-4 levels were higher in HEU than controls (p=0.04) at 6-12 years. Immune activation was higher in HEU at 12 months and at 6-12 years than controls based on frequencies of CD38+HLA-DR+CD8+T cells (p=0.05) and of CD38+HLA-DR+CD4+T cells (p=0.006). Resting memory and activated mature B cells increased from birth to 6-12 years in both groups. The development of the immune system in vertically HEU individuals is comparable to the general population in most parameters, but subtle or transient differences exist. Their role in influencing clinical incidences in HEU is unknown

Emotion regulation strategies and psychological health across cultures

Emotion regulation is important for psychological health and can be achieved by implementing various strategies. How one regulates emotions is critical for maximizing psychological health. Few studies, however, tested the psychological correlates of different emotion regulation strategies across multiple cultures. In a preregistered cross-cultural study (N = 3,960, 19 countries), conducted during the COVID-19 pandemic, we assessed associations between the use of seven emotion regulation strategies (situation selection, distraction, rumination, cognitive reappraisal, acceptance, expressive suppression, and emotional support seeking) and four indices of psychological health (life satisfaction, depressive symptoms, perceived stress, and loneliness). Model comparisons based on Bayesian information criteria provided support for cultural differences in 36% of associations, with very strong support for differences in 18% of associations. Strategies that were linked to worse psychological health in individualist countries (e.g., rumination, expressive suppression) were unrelated or linked to better psychological health in collectivist countries. Cultural differences in associations with psychological health were most prominent for expressive suppression and rumination and also found for distraction and acceptance. In addition, we found evidence for cultural similarities in 46% of associations between strategies and psychological health, but none of this evidence was very strong. Cultural similarities were most prominent in associations of psychological health with emotional support seeking. These findings highlight the importance of considering the cultural context to understand how individuals from diverse backgrounds manage unpleasant emotions. (PsycInfo Database Record (c) 2023 APA, all rights reserved

Root tip-dependent, active riboflavin secretion by Hyoscyamus albus hairy roots under iron deficiency

Hyoscyamus albus hairy roots with/without an exogenous gene (11 clones) were established by inoculation of Agrobacterium rhizogenes. All clones cultured under iron deficient condition secreted riboflavin from root tips into the culture medium and the productivity depended on the number and size of root tips among the clones, although the addition of sucrose was essential for riboflavin production. A decline of pH was observed before riboflavin production and root development using either a root tip or propagated roots: propagated roots were employed for further work due to their lesser variation. Additions of proton-pump inhibitors, N,N’-dicyclohexylcarbodiimide (DCCD) at 100 and 10 μM and erythrosine B at 100 μM, suppressed the pH decline at 100 and 10 μM accompanied by inhibition of riboflavin secretion and root growth; at 10 μM of erythrosine B, pH decline occurred with a moderate delay, but both growth and riboflavin efflux were inhibited. Neither inhibition of the pH decline nor riboflavin production was observed at 1 μM. To examine the necessity of acidification and riboflavin secretion by the roots themselves, artificial pH reduction of culture medium with organic acids and the addition of exogenous riboflavin with/without pH reduction were performed. When hairy roots were cultured in iron-deficient medium acidified with citric acid (pH 4.0) or malic acid (pH 3.7), pH increased rapidly to around 5 overnight, following which riboflavin production and root growth occurred. Addition of riboflavin did not affect riboflavin secretion by the roots, but acidification with citric acid (pH 4.0) helped achiever greater riboflavin production and earlier pH elevation. These results indicate that riboflavin efflux does not directly connected to active pH reduction, and more significantly active riboflavin secretion occurs by internal requirement in H. albus hairy roots under iron deficiency

Strong HIV-1-Specific T Cell Responses in HIV-1-Exposed Uninfected Infants and Neonates Revealed after Regulatory T Cell Removal

BACKGROUND: In utero transmission of HIV-1 occurs on average in only 3%–15% of HIV-1-exposed neonates born to mothers not on antiretroviral drug therapy. Thus, despite potential exposure, the majority of infants remain uninfected. Weak HIV-1-specific T-cell responses have been detected in children exposed to HIV-1, and potentially contribute to protection against infection. We, and others, have recently shown that the removal of CD4(+)CD25(+) T-regulatory (Treg) cells can reveal strong HIV-1 specific T-cell responses in some HIV-1 infected adults. Here, we hypothesized that Treg cells could suppress HIV-1-specific immune responses in young children. METHODOLOGY/PRINCIPAL FINDINGS: We studied two cohorts of children. The first group included HIV-1-exposed-uninfected (EU) as well as unexposed (UNEX) neonates. The second group comprised HIV-1-infected and HIV-1-EU children. We quantified the frequency of Treg cells, T-cell activation, and cell-mediated immune responses. We detected high levels of CD4(+)CD25(+)CD127(−) Treg cells and low levels of CD4(+) and CD8(+) T cell activation in the cord blood of the EU neonates. We observed HIV-1-specific T cell immune responses in all of the children exposed to the virus. These T-cell responses were not seen in the cord blood of control HIV-1 unexposed neonates. Moreover, the depletion of CD4(+)CD25(+) Treg cells from the cord blood of EU newborns strikingly augmented both CD4(+) and CD8(+) HIV-1-specific immune responses. CONCLUSIONS/SIGNIFICANCE: This study provides new evidence that EU infants can mount strong HIV-1-specific T cell responses, and that in utero CD4(+)CD25(+) T-regulatory cells may be contributing to the lack of vertical transmission by reducing T cell activation

The DOCK Protein Sponge Binds to ELMO and Functions in Drosophila Embryonic CNS Development

Cell morphogenesis, which requires rearrangement of the actin cytoskeleton, is essential to coordinate the development of tissues such as the musculature and nervous system during normal embryonic development. One class of signaling proteins that regulate actin cytoskeletal rearrangement is the evolutionarily conserved CDM (C. elegans Ced-5, human DOCK180, Drosophila Myoblast city, or Mbc) family of proteins, which function as unconventional guanine nucleotide exchange factors for the small GTPase Rac. This CDM-Rac protein complex is sufficient for Rac activation, but is enhanced upon the association of CDM proteins with the ELMO/Ced-12 family of proteins. We identified and characterized the role of Drosophila Sponge (Spg), the vertebrate DOCK3/DOCK4 counterpart as an ELMO-interacting protein. Our analysis shows Spg mRNA and protein is expressed in the visceral musculature and developing nervous system, suggesting a role for Spg in later embryogenesis. As maternal null mutants of spg die early in development, we utilized genetic interaction analysis to uncover the role of Spg in central nervous system (CNS) development. Consistent with its role in ELMO-dependent pathways, we found genetic interactions with spg and elmo mutants exhibited aberrant axonal defects. In addition, our data suggests Ncad may be responsible for recruiting Spg to the membrane, possibly in CNS development. Our findings not only characterize the role of a new DOCK family member, but help to further understand the role of signaling downstream of N-cadherin in neuronal development

T cell metabolism drives immunity

Lymphocytes must adapt to a wide array of environmental stressors as part of their normal development, during which they undergo a dramatic metabolic remodeling process. Research in this area has yielded surprising findings on the roles of diverse metabolic pathways and metabolites, which have been found to regulate lymphocyte signaling and influence differentiation, function and fate. In this review, we integrate the latest findings in the field to provide an up-to-date resource on lymphocyte metabolism

Research and Design of a Routing Protocol in Large-Scale Wireless Sensor Networks

无线传感器网络，作为全球未来十大技术之一，集成了传感器技术、嵌入式计算技术、分布式信息处理和自组织网技术，可实时感知、采集、处理、传输网络分布区域内的各种信息数据，在军事国防、生物医疗、环境监测、抢险救灾、防恐反恐、危险区域远程控制等领域具有十分广阔的应用前景。 本文研究分析了无线传感器网络的已有路由协议，并针对大规模的无线传感器网络设计了一种树状路由协议，它根据节点地址信息来形成路由，从而简化了复杂繁冗的路由表查找和维护，节省了不必要的开销，提高了路由效率，实现了快速有效的数据传输。 为支持此路由协议本文提出了一种自适应动态地址分配算——ADAR（AdaptiveDynamicAddre...As one of the ten high technologies in the future, wireless sensor network, which is the integration of micro-sensors, embedded computing, modern network and Ad Hoc technologies, can apperceive, collect, process and transmit various information data within the region. It can be used in military defense, biomedical, environmental monitoring, disaster relief, counter-terrorism, remote control of haz...学位：工学硕士院系专业：信息科学与技术学院通信工程系_通信与信息系统学号：2332007115216

Comfort Women and Sexual Slavery in International Law: Seeking Justice and Reparations

Programa de Doctorat en Dret i Ciència Política[eng] During World War II, the Imperial Japanese Army forced over 200,000 women into sexual slavery in comfort stations across Asia. It is estimated that 80% of the ‘comfort women’ were from Korea, and the rest were from countries such as China, Japan, the Philippines, Taiwan, the Dutch East Indies and East Timor. The research carried out until now on the ‘comfort women’ has revealed the extent to which these women were deprived of personal freedom and control over their sexual autonomy and body and subjected to regulations on a chattel-like basis of their reproductive health. Despite this, the International Military Tribunal For the far East, established after the World War II, merely delivered the ‘victor’s justice’, and it failed to sufficiently prosecute crimes related to the ‘comfort women’. About 50 years later, in 1990s, the concern over the issue of the sexual violence in international law emerged from the prosecutions of sexual offenders tried in the ad hoc International Criminal Tribunals for the former Yugoslavia and Rwanda. In this context, the injustice for the ‘comfort women’ and its consideration as crimes of sexual slavery became an object of debate and was actively discussed within the international organisations. From 1991 to 2001, the ‘comfort women’ filed 10 lawsuits against the Japanese government before the domestic tribunals, but all the cases were eventually dismissed. In 1996, the Japanese government established an Asian Women’s Fund to provide compensation, medical welfare and letters of apology to the ‘comfort women’. However, the Asian Women’s Fund has been criticised by the United Nations, because the reparations were implemented without the admission of the state responsibility. The debate over the ‘comfort women’, lasting more than 80 years since the end of World War II, has shown the complexity of the legal and political problems, causing continuing suffering and violation of human rights of the ‘comfort women’. Therefore, this contribution will analyse to what extent the development of international law in relation to the crime of sexual slavery can contribute to promote the right to justice and the right to reparation of the ‘comfort women’. To this end, I will investigate the Japan’s international responsibility for the ‘comfort women’ as sexual slavery and examine the evolving principles of the international law in relation to the right to an effective remedy and the right to reparation. I argue that Japan has been in complete disregard for jus cogens norm of prohibition of slavery and should acknowledge that it bears the state responsibility for the systematic sexual slavery of the ‘comfort women’. I also argue that not only material reparation, but also symbolic and transformative reparation together with structural changes should be provided for the ‘comfort women’, adopting victims-oriented and gendered approach which has lacked to date.[cat] Durant la Segona Guerra Mundial, l'exèrcit imperial japonès va obligar a més de 200.000 dones a ser esclaves sexuals en estacions de confort a tota Àsia. Es calcula que el 80% de les “dones de consol” eren de Corea, i la resta eren de països com la Xina, el Japó, les Filipines, Taiwan, les Índies Orientals Holandeses i Timor Oriental. La investigació realitzada fins ara sobre les "dones de consol" ha posat de manifest fins a quin punt aquestes dones estaven privades de la llibertat personal i del control sobre la seva autonomia sexual i corporal i sotmeses a les regulacions sobre la seva salut reproductiva sobre una base de tipus mobiliari. Malgrat això, el Tribunal Militar Internacional per a l'Extrem Orient, establert després de la Segona Guerra Mundial, es va limitar a lliurar la "justícia del vencedor" i no va processar prou els crims relacionats amb les "dones de consol". Uns 50 anys més tard, a la dècada de 1990, la preocupació per la qüestió de la violència sexual en el dret internacional va sorgir dels processaments dels delinqüents sexuals jutjats als Tribunals Penals Internacionals ad hoc per a l'antiga Iugoslàvia i Ruanda. En aquest context, la injustícia per a les "dones de consol" i la seva consideració com a delictes d'esclavitud sexual es va convertir en objecte de debat i es va discutir activament dins les organitzacions internacionals. Del 1991 al 2001, les "dones de consol" van presentar 10 querelles contra el govern japonès davant els tribunals interns, però finalment tots els casos van ser desestimats. El 1996, el govern japonès va establir un Fons de Dones Asiàtiques per oferir compensacions, benestar mèdic i cartes de disculpa a les "dones de consol". No obstant això, el Fons de Dones Asiàtiques ha estat criticat per les Nacions Unides perquè les reparacions es van implementar sense l'admissió de la responsabilitat de l'estat. El debat sobre les 'dones de consol', que ha durat més de 80 anys des del final de la Segona Guerra Mundial, ha posat de manifest la complexitat dels problemes legals i polítics, provocant un patiment continuat i la vulneració dels drets humans de les 'dones de consol'. Per aquest motiu aquesta tesi analitzarà fins a quin punt el desenvolupament del dret internacional en relació amb el delicte d'esclavitud sexual pot contribuir a promoure el dret a la justícia i el dret a la reparació de les “dones de consol”. Amb aquesta finalitat, investigaré la responsabilitat internacional del Japó per les "dones de consol" com a esclavitud sexual i examinaré els principis en evolució del dret internacional en relació amb el dret a un recurs efectiu i el dret a la reparació. Argumento que el Japó ha ignorat completament la norma de jus cogens de prohibició de l'esclavitud i hauria de reconèixer que té la responsabilitat estatal de l'esclavitud sexual sistemàtica de les "dones de consol". També argumento que no només s'hauria d'oferir una reparació material, sinó també una reparació simbòlica i transformadora, juntament amb canvis estructurals, per a les "dones de consol", adoptant un enfocament orientat a les víctimes i de gènere que ha mancat fins ara.[spa] Durante la Segunda Guerra Mundial, el Ejército Imperial Japonés obligó a más de 200.000 mujeres a la esclavitud sexual en estaciones de confort en toda Asia. Se estima que el 80% de las 'mujeres de solaz' eran de Corea y el resto de países como China, Japón, Filipinas, Taiwán, las Indias Orientales Holandesas y Timor Oriental. Las investigaciones realizadas hasta ahora sobre las 'mujeres de solaz' han puesto de manifiesto hasta qué punto estas mujeres estaban privadas de libertad personal y de control sobre su autonomía sexual y corporal y sometidas a regulaciones sobre la base de bienes muebles de su salud reproductiva. A pesar de esto, el Tribunal Militar Internacional para el Lejano Oriente, establecido después de la Segunda Guerra Mundial, simplemente dictó la 'justicia del vencedor' y no procesó suficientemente los delitos relacionados con las 'mujeres de solaz'. Aproximadamente 50 años después, en la década de 1990, la preocupación por el tema de la violencia sexual en el derecho internacional surgió a partir de los procesos de los delincuentes sexuales juzgados en los Tribunales Penales Internacionales ad hoc para la ex Yugoslavia y Ruanda. En este contexto, la injusticia para las 'mujeres de solaz' y su consideración como delitos de esclavitud sexual se convirtió en objeto de debate y se discutió activamente en el seno de las organizaciones internacionales. De 1991 a 2001, las 'mujeres de solaz' presentaron 10 demandas contra el gobierno japonés ante los tribunales nacionales, pero todos los casos fueron finalmente desestimados. En 1996, el gobierno japonés estableció un Fondo de Mujeres Asiáticas para proporcionar compensación, bienestar médico y cartas de disculpa a las 'mujeres de consuelo'. Sin embargo, el Fondo de Mujeres Asiáticas ha sido criticado por las Naciones Unidas, porque las reparaciones se implementaron sin la admisión de la responsabilidad del Estado. El debate sobre las 'mujeres de solaz', que dura más de 80 años desde el final de la Segunda Guerra Mundial, ha mostrado la complejidad de los problemas legales y políticos, causando continuo sufrimiento y violación de los derechos humanos de las 'mujeres de solaz'. Por este motivo, esta tesis analizará en qué medida el desarrollo del derecho internacional en relación con el delito de esclavitud sexual puede contribuir a promover el derecho a la justicia y el derecho a la reparación de las 'mujeres de solaz'. Con este fin, investigaré la responsabilidad internacional de Japón por las 'mujeres de solaz' como esclavitud sexual y examinaré los principios en evolución del derecho internacional en relación con el derecho a un recurso efectivo y el derecho a reparación. Argumento que Japón ha hecho caso omiso de la norma jus cogens de prohibición de la esclavitud y debería reconocer que tiene la responsabilidad estatal por la esclavitud sexual sistemática de las 'mujeres de solaz'. También sostengo que no solo debe proporcionarse una reparación material, sino también una reparación simbólica y transformadora junto con cambios estructurales para las 'mujeres de solaz', adoptando un enfoque orientado a las víctimas y de género del que ha carecido hasta la fecha

Comfort Women and Sexual Slavery in International Law: Seeking Justice and Reparations

[eng] During World War II, the Imperial Japanese Army forced over 200,000 women into sexual slavery in comfort stations across Asia. It is estimated that 80% of the ‘comfort women’ were from Korea, and the rest were from countries such as China, Japan, the Philippines, Taiwan, the Dutch East Indies and East Timor. The research carried out until now on the ‘comfort women’ has revealed the extent to which these women were deprived of personal freedom and control over their sexual autonomy and body and subjected to regulations on a chattel-like basis of their reproductive health. Despite this, the International Military Tribunal For the far East, established after the World War II, merely delivered the ‘victor’s justice’, and it failed to sufficiently prosecute crimes related to the ‘comfort women’. About 50 years later, in 1990s, the concern over the issue of the sexual violence in international law emerged from the prosecutions of sexual offenders tried in the ad hoc International Criminal Tribunals for the former Yugoslavia and Rwanda. In this context, the injustice for the ‘comfort women’ and its consideration as crimes of sexual slavery became an object of debate and was actively discussed within the international organisations. From 1991 to 2001, the ‘comfort women’ filed 10 lawsuits against the Japanese government before the domestic tribunals, but all the cases were eventually dismissed. In 1996, the Japanese government established an Asian Women’s Fund to provide compensation, medical welfare and letters of apology to the ‘comfort women’. However, the Asian Women’s Fund has been criticised by the United Nations, because the reparations were implemented without the admission of the state responsibility. The debate over the ‘comfort women’, lasting more than 80 years since the end of World War II, has shown the complexity of the legal and political problems, causing continuing suffering and violation of human rights of the ‘comfort women’. Therefore, this contribution will analyse to what extent the development of international law in relation to the crime of sexual slavery can contribute to promote the right to justice and the right to reparation of the ‘comfort women’. To this end, I will investigate the Japan’s international responsibility for the ‘comfort women’ as sexual slavery and examine the evolving principles of the international law in relation to the right to an effective remedy and the right to reparation. I argue that Japan has been in complete disregard for jus cogens norm of prohibition of slavery and should acknowledge that it bears the state responsibility for the systematic sexual slavery of the ‘comfort women’. I also argue that not only material reparation, but also symbolic and transformative reparation together with structural changes should be provided for the ‘comfort women’, adopting victims-oriented and gendered approach which has lacked to date.[cat] Durant la Segona Guerra Mundial, l'exèrcit imperial japonès va obligar a més de 200.000 dones a ser esclaves sexuals en estacions de confort a tota Àsia. Es calcula que el 80% de les “dones de consol” eren de Corea, i la resta eren de països com la Xina, el Japó, les Filipines, Taiwan, les Índies Orientals Holandeses i Timor Oriental. La investigació realitzada fins ara sobre les "dones de consol" ha posat de manifest fins a quin punt aquestes dones estaven privades de la llibertat personal i del control sobre la seva autonomia sexual i corporal i sotmeses a les regulacions sobre la seva salut reproductiva sobre una base de tipus mobiliari. Malgrat això, el Tribunal Militar Internacional per a l'Extrem Orient, establert després de la Segona Guerra Mundial, es va limitar a lliurar la "justícia del vencedor" i no va processar prou els crims relacionats amb les "dones de consol". Uns 50 anys més tard, a la dècada de 1990, la preocupació per la qüestió de la violència sexual en el dret internacional va sorgir dels processaments dels delinqüents sexuals jutjats als Tribunals Penals Internacionals ad hoc per a l'antiga Iugoslàvia i Ruanda. En aquest context, la injustícia per a les "dones de consol" i la seva consideració com a delictes d'esclavitud sexual es va convertir en objecte de debat i es va discutir activament dins les organitzacions internacionals. Del 1991 al 2001, les "dones de consol" van presentar 10 querelles contra el govern japonès davant els tribunals interns, però finalment tots els casos van ser desestimats. El 1996, el govern japonès va establir un Fons de Dones Asiàtiques per oferir compensacions, benestar mèdic i cartes de disculpa a les "dones de consol". No obstant això, el Fons de Dones Asiàtiques ha estat criticat per les Nacions Unides perquè les reparacions es van implementar sense l'admissió de la responsabilitat de l'estat. El debat sobre les 'dones de consol', que ha durat més de 80 anys des del final de la Segona Guerra Mundial, ha posat de manifest la complexitat dels problemes legals i polítics, provocant un patiment continuat i la vulneració dels drets humans de les 'dones de consol'. Per aquest motiu aquesta tesi analitzarà fins a quin punt el desenvolupament del dret internacional en relació amb el delicte d'esclavitud sexual pot contribuir a promoure el dret a la justícia i el dret a la reparació de les “dones de consol”. Amb aquesta finalitat, investigaré la responsabilitat internacional del Japó per les "dones de consol" com a esclavitud sexual i examinaré els principis en evolució del dret internacional en relació amb el dret a un recurs efectiu i el dret a la reparació. Argumento que el Japó ha ignorat completament la norma de jus cogens de prohibició de l'esclavitud i hauria de reconèixer que té la responsabilitat estatal de l'esclavitud sexual sistemàtica de les "dones de consol". També argumento que no només s'hauria d'oferir una reparació material, sinó també una reparació simbòlica i transformadora, juntament amb canvis estructurals, per a les "dones de consol", adoptant un enfocament orientat a les víctimes i de gènere que ha mancat fins ara.[eng] Durante la Segunda Guerra Mundial, el Ejército Imperial Japonés obligó a más de 200.000 mujeres a la esclavitud sexual en estaciones de confort en toda Asia. Se estima que el 80% de las 'mujeres de solaz' eran de Corea y el resto de países como China, Japón, Filipinas, Taiwán, las Indias Orientales Holandesas y Timor Oriental. Las investigaciones realizadas hasta ahora sobre las 'mujeres de solaz' han puesto de manifiesto hasta qué punto estas mujeres estaban privadas de libertad personal y de control sobre su autonomía sexual y corporal y sometidas a regulaciones sobre la base de bienes muebles de su salud reproductiva. A pesar de esto, el Tribunal Militar Internacional para el Lejano Oriente, establecido después de la Segunda Guerra Mundial, simplemente dictó la 'justicia del vencedor' y no procesó suficientemente los delitos relacionados con las 'mujeres de solaz'. Aproximadamente 50 años después, en la década de 1990, la preocupación por el tema de la violencia sexual en el derecho internacional surgió a partir de los procesos de los delincuentes sexuales juzgados en los Tribunales Penales Internacionales ad hoc para la ex Yugoslavia y Ruanda. En este contexto, la injusticia para las 'mujeres de solaz' y su consideración como delitos de esclavitud sexual se convirtió en objeto de debate y se discutió activamente en el seno de las organizaciones internacionales. De 1991 a 2001, las 'mujeres de solaz' presentaron 10 demandas contra el gobierno japonés ante los tribunales nacionales, pero todos los casos fueron finalmente desestimados. En 1996, el gobierno japonés estableció un Fondo de Mujeres Asiáticas para proporcionar compensación, bienestar médico y cartas de disculpa a las 'mujeres de consuelo'. Sin embargo, el Fondo de Mujeres Asiáticas ha sido criticado por las Naciones Unidas, porque las reparaciones se implementaron sin la admisión de la responsabilidad del Estado. El debate sobre las 'mujeres de solaz', que dura más de 80 años desde el final de la Segunda Guerra Mundial, ha mostrado la complejidad de los problemas legales y políticos, causando continuo sufrimiento y violación de los derechos humanos de las 'mujeres de solaz'. Por este motivo, esta tesis analizará en qué medida el desarrollo del derecho internacional en relación con el delito de esclavitud sexual puede contribuir a promover el derecho a la justicia y el derecho a la reparación de las 'mujeres de solaz'. Con este fin, investigaré la responsabilidad internacional de Japón por las 'mujeres de solaz' como esclavitud sexual y examinaré los principios en evolución del derecho internacional en relación con el derecho a un recurso efectivo y el derecho a reparación. Argumento que Japón ha hecho caso omiso de la norma jus cogens de prohibición de la esclavitud y debería reconocer que tiene la responsabilidad estatal por la esclavitud sexual sistemática de las 'mujeres de solaz'. También sostengo que no solo debe proporcionarse una reparación material, sino también una reparación simbólica y transformadora junto con cambios estructurales para las 'mujeres de solaz', adoptando un enfoque orientado a las víctimas y de género del que ha carecido hasta la fecha