Human Protection Research Articles

The Elevated Expressions of Anti-lipopolysaccharide Factors After Priming Stimulation Confer Lastingly Humoral Protection in Crab Eriocheir sinensis.

Evidence of immune memory in invertebrates (immune priming) has accumulated in various organisms, and both cellular and humoral immune reactions are speculated to be involved in immune priming. However, there is a lack of understanding of the molecular mechanisms involved. In the present study, the protective effect of primed haemolymph was further validated by the increased survival rate of naïve crabs receiving a transfusion of primed haemolymph. By proteomic analysis, there were 474 proteins identified from the primed haemolymph, and most of them were functionally annotated in transport and metabolism classes. A total of 70 proteins were found to be differentially expressed in haemolymph at 12 hours and 7 days after priming stimulation with Aeromonas hydrophila, among which anti-lipopolysaccharide factor 1 (EsALF-1) and 3 (EsALF-3) were identified as the most significant (p < 0.05). After being challenged with A. hydrophila, EsALF-1 and EsALF-3 were highly expressed at both mRNA (in haemocytes) and protein (in haemolymph) levels compared with blank crabs, and the mRNA expressions of components in the EsTLR1-EsMyd88-EsPelle-EsALF pathway also increased significantly (p < 0.05). The EsALF-3 and EsMyd88 were even significantly higher expressed in response to the second A. hydrophila challenge, but their expressions all decreased (p < 0.05) when EsTLR1 was knocked down by RNAi. After the naïve crabs received an injection with the recombinant protein of EsALF-1 (rEsALF-1) or EsALF-3 (rEsALF-3), their survival rate increased significantly (p < 0.05) upon A. hydrophila stimulation. In contrast, the survival rate of the primed crabs reduced significantly (p < 0.05) after they received an injection with the antibody of EsALF-1 or EsALF-3. The enhanced expressions of EsALF-1 and EsALF-3 after A. hydrophilap riming stimulation could sustain for four weeks. All the results suggested that the EsTLR1-mediated productions of EsALF-1 and EsALF-3 in haemolymph played an indispensable role in the month-long humoral immune protection induced by A. hydrophila, which provides solid evidence of immune priming in crabs and a valuable reference for further understanding immune memory in invertebrates.

10. Quadrivalent M2SR (M2-deficient Single Replication) Live Influenza Vaccine Provides Better Protection Than Inactivated Vaccine Against Drifted Influenza B Virus Challenge in Ferrets

BackgroundQuadrivalent inactivated influenza vaccines (QIV) induce neutralizing antibodies (Abs) against the viral hemagglutinin (HA). Despite annual update of HA vaccine antigens to match circulating strains, current vaccines provide ~60% vaccine effectiveness (VE). QIV VE can be as low as 10% when circulating strains do not match vaccine HA. The live M2SR (M2-deficient single replication) influenza vaccine candidate has previously shown broad humoral, mucosal and cellular immune responses and protection against multiple influenza A subtypes. Here we show similar properties with the Quadrivalent M2SR (Quad M2SR) against drifted influenza B challenge in comparison to QIV.MethodsFerrets pre-infected with influenza H1N1 and B/Yamagata viruses, were immunized intranasally (IN) with PBS (Mock) or Quad M2SR, or intramuscularly with Fluzone QIV. Serum collected post-vaccination was evaluated for Ab responses. Forty-two days after vaccination, ferrets were challenged IN with 106 pfu of B/Brisbane/60/2008 (Victoria lineage) influenza virus. Nasal washes were taken for 7 days post-challenge and evaluated for challenge virus by TCID50 assay. Nasal turbinates, trachea and lungs were also evaluated for virus. ResultsQuad M2SR and QIV elicited high serum Abs against the vaccine strain B/Colorado/06/2017 (Fig. 1A) and against the drifted influenza B challenge strain B/Brisbane/60/2008 (Fig. 1B) in ferrets with preexisting immunity. Like Mock, ferrets who received QIV displayed both weight loss (6.2%, Fig. 2A) and a rise in temperature (1.1oC, Fig. 2B) after challenge. In contrast, the Quad M2SR group did not exhibit any significant weight or temperature changes after challenge. Quad M2SR controlled the drifted challenge virus better than QIV as evidenced by significantly lower or absent post-challenge virus titer in nasal washes (Fig. 3A) and nasal turbinates (Fig. 3B).Figure 1. Serum Neutralization Titers Post-Vaccination Plaque reduction neutralization test (PRNT) antibody titers for Quad M2SR and QIV against matched Influenza B vaccine strain B/Colorado/06/2017 (Fig. 1A) and drifted strain B/Brisbane/60/2008 (Fig. 1B) on pre-study (Day -3), pre-vaccination (Day 28), and 3 weeks post vaccination (Day 51). The detection limit of the assay (horizontal dashed line) was 15 PRNT50.Figure 2. Post-challenge body weight and temperature changes Percent body weight changes (Fig. 2A) and average body temperatures changes (Fig. 2B) following challenge with drifted Influenza B strain B/Brisbane/60/2008 for ferrets vaccinated with Quad M2SR or QIV.Figure 3. Post-challenge virus titers in respiratory tract. Viral titers in nasal washes (Fig. 3A) and nasal turbinates (Fig. 3B) collected post-challenge with Influenza B strain B/Brisbane/60/2008 in ferrets vaccinated with Quad M2SR or QIV. No virus was detected in the trachea or lungs. The detection limit of the assay (horizontal dashed line) was 1.5 log10 TCID50/mL and 20 FFU respectively. Virus titer between groups was significant on day 3 of the nasal washes: one-way analysis of variance (ANOVA) with Multiple t tests to compare between groups, #p<0.05,><0.01,><>ConclusionDespite eliciting similar Ab titers, the Quad M2SR demonstrated superior protection compared to QIV in a drifted influenza B challenge model in ferrets. These results suggest that the intranasal M2SR platform may confer additional advantages over currently available vaccines. Quad M2SR is in late-stage development for testing in a first-in-human clinical study. Disclosures Lindsay Hill-Batorski, PhD, FluGen (Employee) Yasuko Hatta, DVM, PhD, FluGen (Employee) Michael Moser, PhD, FluGen (Employee) David Marshall, BS, FluGen (Employee) Pamuk Bilsel, PhD, FluGen (Employee)

Ecology of aquatic organisms in Ainkurunuru

No living organism can live on earth without water. Today, 70 percent of water is used for agriculture, 20 percent for industrial work and 10 percent for human consumption worldwide. Fish, crocodile, crab, shrimp etc. were found as aquatic organisms during the Sangam period. They describe the nature of the environment in the manner of food chain, spread, space protection, food collection and storage, and coexistence with the law of nature. In 500, news of aquatic organisms and their spreading into a food chain, compliance with the natural law, food conservation, human use methods and environmental contacts have been explored. This article shows that aquatic organisms lived without any pollution and without loss of life during the Sangam period.

EPCT: An Efficient Privacy-Preserving and Collusion-Resisting Top- k Query Processing in WSNs

Data privacy threat arises during providing top- k query processing in the wireless sensor networks. This article presents an efficient privacy-preserving and collusion-resisting top- k (EPCT) query processing protocol. A minimized candidate encrypted dataset determination model is first designed, which is the foundation of EPCT. The model guides the idea of query processing and guarantees the correctness of the protocol. The symmetric encryption with different private key in each sensor is deployed to protect the privacy of sensory data even a few sensors in the networks have been colluding with adversaries. Based on the above model and security setting, two phases of interactions between the interested sensors and the sink are designed to implement the secure query processing protocol. The security analysis shows that the proposed protocol is capable of providing secure top- k queries in the manner of privacy protection and anticollusion, whereas the experimental result indicates that the protocol outperforms the existing works on communication overhead.

Mice with diverse microbial exposure histories as a model for preclinical vaccine testing

Laboratory mice comprise an expeditious model for preclinical vaccine testing; however, vaccine immunogenicity in these models often inadequately translates to humans. Reconstituting physiologic microbial experience to specific pathogen-free (SPF) mice induces durable immunological changes that better recapitulate human immunity. We examined whether mice with diverse microbial experience better model human responses post vaccination. We co-housed laboratory mice with pet-store mice, which have varied microbial exposures, and then assessed immune responses to influenza vaccines. Human transcriptional responses to influenza vaccination are better recapitulated in co-housed mice. Although SPF and co-housed mice were comparably susceptible to acute influenza infection, vaccine-induced humoral responses were dampened in co-housed mice, resulting in poor control upon challenge. Additionally, protective heterosubtypic Tcell immunity was compromised in co-housed mice. Because SPF mice exaggerated humoral and Tcell protection upon influenza vaccination, reconstituting microbial experience in laboratory mice through co-housing may better inform preclinical vaccine testing.

‘Real’ Gerbes and Dirac Cones of Topological Insulators

A time-reversal invariant topological insulator occupying a Euclidean half-space determines a 'Quaternionic' self-adjoint Fredholm family. We show that the discrete spectrum data for such a family is geometrically encoded in a non-trivial 'Real' gerbe. The gerbe invariant, rather than a na\"ive counting of Dirac points, precisely captures how edge states completely fill up the bulk spectral gap in a topologically protected manner.

Mobile Sensing with Smart Wearables of the Physical Context of Distance Learning Students to Consider Its Effects on Learning.

Research shows that various contextual factors can have an impact on learning. Some of these factors can originate from the physical learning environment (PLE) in this regard. When learning from home, learners have to organize their PLE by themselves. This paper is concerned with identifying, measuring, and collecting factors from the PLE that may affect learning using mobile sensing. More specifically, this paper first investigates which factors from the PLE can affect distance learning. The results identify nine types of factors from the PLE associated with cognitive, physiological, and affective effects on learning. Subsequently, this paper examines which instruments can be used to measure the investigated factors. The results highlight several methods involving smart wearables (SWs) to measure these factors from PLEs successfully. Third, this paper explores how software infrastructure can be designed to measure, collect, and process the identified multimodal data from and about the PLE by utilizing mobile sensing. The design and implementation of the Edutex software infrastructure described in this paper will enable learning analytics stakeholders to use data from and about the learners’ physical contexts. Edutex achieves this by utilizing sensor data from smartphones and smartwatches, in addition to response data from experience samples and questionnaires from learners’ smartwatches. Finally, this paper evaluates to what extent the developed infrastructure can provide relevant information about the learning context in a field study with 10 participants. The evaluation demonstrates how the software infrastructure can contextualize multimodal sensor data, such as lighting, ambient noise, and location, with user responses in a reliable, efficient, and protected manner.

PROLONGED COVID-19 IN PATIENTS TREATED WITH RITUXIMAB

TOPIC: Chest Infections TYPE: Fellow Case Reports INTRODUCTION: Patients with COVID-19 who have been prescribed rituximab prior to SARS-CoV-2 infection may be susceptible to an alternative disease course compared to the general population. These patients can develop chronic fatigue, dyspnea, fevers, and persistent radiographic abnormalities after appearing to convalesce from their index infection. CASE PRESENTATION: We report a case series of 3 patients with prolonged COVID-19 infections who had received rituximab prior to their index SARS-CoV-2 infection. They were all successfully treated with a combination of remdesivir and antibody therapy. This report demonstrates and replicates successful application of anti-viral therapy with remdesivir, and the provision of convalescent plasma/monoclonal antibodies to thwart B-cell depletion to treat patients with prolonged COVID-19 symptoms. DISCUSSION: Rituximab can cause B-cell depletion, impairment in humoral immunity, and delayed viral clearance with persistent viremia. Intact humoral and innate immunity appear necessary to eradicate SARS-CoV-2 in some individuals being treated with rituximab. The American Society of Hematology reports on 17 B-cell depleted patients with prolonged COVID-19 who were treated with convalescent plasma. All but 1 patient had symptom improvement within 48 hours. These findings support our experience and suggest that combination antiviral and antibody therapy is a promising treatment strategy. The reporting of successful and safe treatment strategies are crucial to guide clinicians as it is unlikely that there will be large, randomized control trials examining optimal therapeutic strategies for patients with a lack of humoral protection. CONCLUSIONS: Patients with COVID-19 who had been prescribed rituximab prior to infection may be susceptible to chronic symptoms with persistent radiographic features. Combination antiviral and antibody therapy is a promising treatment strategy in this cohort. REFERENCE #1: Hueso T, Pouderoux C, Pere H, et al. Convalescent plasma therapy for B-cell-depleted patients with protracted COVID-19. Blood 2020;136:2290-5 REFERENCE #2: Helleberg M, Niemann CU, Moestrup KS, et al. Persistent COVID-19 in an Immunocompromised Patient Temporarily Responsive to Two Courses of Remdesivir Therapy. J Infect Dis 2020;222:1103-7 DISCLOSURES: No relevant relationships by Rachel Aviv, source=Web Response No relevant relationships by Effie Singas, source=Admin input No relevant relationships by Andrew Weber, source=Web Response

Hydration therapy in oligohydraminos in Ain Shams University Maternity Hospital: Randomized Controlled Clinical Trial

Abstract Background Amniotic fluid surrounds the fetus within first gestational weeks. acts physiologically and anatomically in a protective manner preventing fetal and umbilical cord compressive forces, besides have antibacterial features keeping the fetal temperature stable, and avoiding adhesive attachment to developing fetal membrane system. Amniotic fluid volume and constituents continuously change in a dynamic manner as the gestation progresses. Sufficient amniotic fluid volume is crucial for fetal mechanophysiological well-being adding in normal musculoskeletal wellbeing besides aminiotic fluid consituents refelect physiological integrity of fetal systems particularly the renal and gastrointestinal systems. Objective The aim of this study is to find out if there is significant increase in amniotic fluid index after acute maternal hydration in pregnant women with oligohydraminos and to evaluate therapeutic effectiveness of two different modalities of hydration therapy. Methods We conducted randomized controlled open labeled clinical trial on 300 cases with oligohydraminos admitted to Ain Shams University Maternity Hospital (ASUMH) in the period from September 2019 to March 2020. These patients were classified to three groups, Patients in group A were Oral hydration group: 100 participants while Patients in group B were Intravenous hydration group: 100 participants, patients in Group 3 No hydration group: 100 participants. Results The demographic data analysis of the current study have shown that there was no statistical significant difference between the investigated research groups as regards the demographic characteristics (age, BMI, Parity gestational age p values 0.171,0.370,0.840,0.290 consecutively). The study results also showed that oligoydramnios recurrence frequency was highest among control group, followed by intravenous group and least in oral group, the differences were statistically nonsignificant. Conclusion Hydration can be considered an effective way of decreasing the chance of oligohydraminos because maternal dehydration increases the chance of the condition. Therefore both serum and oral hydration therapies are hypothesized to be effective treatment for oligohydraminos. Previous studies have supported this hypothesis. Maternal hydration may theoretically increase amniotic fluid volume may by causing fetal diuresis.

영화 〈토미리스: 전쟁의 여신〉을 통해 본 스키타이 문화와 샤머니즘 고찰

The purpose of this study is to comprehensively discuss the Scythian culture, the archetypal female hero image, and the shamanistic tradition in the Kazakhstan film The Legend of Tomiris directed by Akan Satayev.<BR> In general, historical and literary works tend to portray women as passive images. In traditional societies, women were portrayed in a distorted form from a man’s point of view. For example, the woman depicted in mythology has the image of a fragile and submissive who needs the protection of men. These distorted images of women were constantly enlarged and reproduced in various literary works and myths.<BR> In particular, in the process of male-centered modernization, prejudices and distorted perceptions of women have deepened. The socio-educational function of the image of women fixed and biased by men since ancient times can be defined as symbolic violence. Distorted images or stereotypes of women undermined women’s subjective abilities and reduced women’s roles to a limited area of role. However, the image of women in ancient society is different from the existing fixed image of women. It is different from the image presented in modern and contemporary society.<BR> The female hero, Tomiris is one of the figures who excelled as a leader and a warrior in the ancient world while standing proudly against men. Tomiris is a real person who actually existed in history, and was a valiant female warrior who prevented the invasion of the great empire of Persia. The necessity of discussing the archetypal female hero is because through the image of the female hero of the ancient nomadic society, it is possible to understand the characteristics and abilities of various women beyond the existing distorted female image.<BR> Tomiris is a female warrior and heroine who overcomes all kinds of adversity and hardships and unites the nomads of the steppe to face the invasion of the Persian Empire. In other words, the movie The Legend of Tomiris breaks down the stereotyped image and prejudice against women and induces a new cognitive awareness of women.

Ingesta de polifenoles y riesgo cardiovascular en el ensayo PREDIMED-Plus. Una comparación de diferentes ecuaciones de riesgo

Introduction and objectivesQuantification of cardiovascular risk has been based on scores such as Framingham, Framingham-REGICOR, SCORE or Life's Simple 7 (LS7). In vitro, animal, and randomized clinical studies have shown that polyphenols may provide benefits to the vascular system and reduce the inflammatory response. However, some clinical-epidemiological studies have yielded inconsistent results. Our aim was to assess the possible association between intake of the various polyphenol classes and established cardiovascular scores. MethodsThis cross-sectional analysis involved 6633 PREDIMED-Plus study participants. Food polyphenol content was estimated by a semiquantitative food frequency questionnaire, adjusted for total energy intake according to the residual method. The association between polyphenol intake and cardiovascular risk was tested using linear regression analyses. ResultsTotal polyphenol and flavonoid intake were directly and significantly associated only with the LS7 scale. Intake of lignans was directly and significantly associated with SCORE and LS7 scales, stilbene intake with SCORE, and phenolic acid intake with Framingham and Framingham-REGICOR scores. Other polyphenol classes were associated in a protective and significant manner in Framingham, SCORE and LS7 scores. In women, intake of all the polyphenol classes, except phenolic acids, showed a protective trend in the results of the Framingham, Framingham-REGICOR scores and LS7 scale. ConclusionsAn inverse association was found between consumption of the ‘other polyphenols’ class and, especially among women, with estimated cardiovascular risk. The results were similar to those of Framingham, Framingham-REGICOR and LS7 (after eliminating the diet component) and differed from those of SCORE, but the predictors included were limited in the latter case.Full English text available from:www.revespcardiol.org/en

The molecular interplay of the establishment of an infection \u2013 gene expression of Diaphorina citri gut and Candidatus Liberibacter asiaticus

BackgroundCandidatus Liberibacter asiaticus (CLas) is one the causative agents of greening disease in citrus, an unccurable, devastating disease of citrus worldwide. CLas is vectored by Diaphorina citri, and the understanding of the molecular interplay between vector and pathogen will provide additional basis for the development and implementation of successful management strategies. We focused in the molecular interplay occurring in the gut of the vector, a major barrier for CLas invasion and colonization.ResultsWe investigated the differential expression of vector and CLas genes by analyzing a de novo reference metatranscriptome of the gut of adult psyllids fed of CLas-infected and healthy citrus plants for 1-2, 3-4 and 5-6 days. CLas regulates the immune response of the vector affecting the production of reactive species of oxygen and nitrogen, and the production of antimicrobial peptides. Moreover, CLas overexpressed peroxiredoxin, probably in a protective manner. The major transcript involved in immune expression was related to melanization, a CLIP-domain serine protease we believe participates in the wounding of epithelial cells damaged during infection, which is supported by the down-regulation of pangolin. We also detected that CLas modulates the gut peristalsis of psyllids through the down-regulation of titin, reducing the elimination of CLas with faeces. The up-regulation of the neuromodulator arylalkylamine N-acetyltransferase implies CLas also interferes with the double brain-gut communication circuitry of the vector. CLas colonizes the gut by expressing two Type IVb pilin flp genes and several chaperones that can also function as adhesins. We hypothesized biofilm formation occurs by the expression of the cold shock protein of CLas.ConclusionsThe thorough detailed analysis of the transcritome of Ca. L. asiaticus and of D. citri at different time points of their interaction in the gut tissues of the host led to the identification of several host genes targeted for regulation by L. asiaticus, but also bacterial genes coding for potential effector proteins. The identified targets and effector proteins are potential targets for the development of new management strategies directed to interfere with the successful utilization of the psyllid vector by this pathogen.

At Death's Door: A Scene of Damnatio ad Bestias on a Key Handle from Leicester

ABSTRACTA decorated copper-alloy key handle was recovered during excavation of a town house in Roman Leicester (Ratae Corieltavorum). The decoration comprises two groups of figures modelled in high relief: a bearded, unarmed man fighting with a lion, arranged above four naked male youths embracing one another in a protective manner. This decoration cannot be paralleled among other similarly elaborate Roman key handles and is best interpreted as a scene of damnatio ad bestias, although it does not directly replicate other known scenes of this punishment and spectacle. Other readings of the image are possible, depending on the context and perspective of the viewer as they handled the object.

Antibody interference by a non-neutralizing antibody abrogates humoral protection against Plasmodium yoelii liver stage.

Both subunit and attenuated whole-sporozoite vaccination strategies against Plasmodium infection have shown promising initial results in malaria-naive westerners but less efficacy in malaria-exposed individuals in endemic areas. Here, we demonstrate proof of concept by using a rodent malaria model in which non-neutralizing antibodies (nNAbs) can directly interfere with protective anti-circumsporozoite protein (CSP) humoral responses. We characterize a monoclonal antibody, RAM1, against Plasmodium yoelii sporozoite major surface antigen CSP. Unlike the canonical PyCSP repeat domain binding and neutralizing antibody (NAb) 2F6, RAM1 does not inhibit sporozoite traversal or entry of hepatocytes invitro or infection invivo. Although 2F6 and RAM1 bind non-overlapping regions of the CSP-repeat domain, pre-treatment with RAM1 abrogates the capacity of NAb to block sporozoite traversal and invasion invitro. Importantly, RAM1 reduces the efficacy of the polyclonal humoral response against PyCSP invivo. Collectively, our data provide a proof of concept that nNAbs can alter the efficacy of malaria vaccination.

Polyphenol intake and cardiovascular risk in the PREDIMED-Plus trial. A comparison of different risk equations

Introduction and objectivesQuantification of cardiovascular risk has been based on scores such as Framingham, Framingham-REGICOR, SCORE or Life's Simple 7 (LS7). In vitro, animal, and randomized clinical studies have shown that polyphenols may provide benefits to the vascular system and reduce the inflammatory response. However, some clinical-epidemiological studies have yielded inconsistent results. Our aim was to assess the possible association between intake of the various polyphenol classes and established cardiovascular scores. MethodsThis cross-sectional analysis involved 6633 PREDIMED-Plus study participants. Food polyphenol content was estimated by a semiquantitative food frequency questionnaire, adjusted for total energy intake according to the residual method. The association between polyphenol intake and cardiovascular risk was tested using linear regression analyses. ResultsTotal polyphenol and flavonoid intake were directly and significantly associated only with the LS7 scale. Intake of lignans was directly and significantly associated with SCORE and LS7 scales, stilbene intake with SCORE, and phenolic acid intake with Framingham and Framingham-REGICOR scores. Other polyphenol classes were associated in a protective and significant manner in Framingham, SCORE and LS7 scores. In women, intake of all the polyphenol classes, except phenolic acids, showed a protective trend in the results of the Framingham, Framingham-REGICOR scores and LS7 scale. ConclusionsAn inverse association was found between consumption of the ‘other polyphenols’ class and, especially among women, with estimated cardiovascular risk. The results were similar to those of Framingham, Framingham-REGICOR and LS7 (after eliminating the diet component) and differed from those of SCORE, but the predictors included were limited in the latter case.

APOE Genotype and Alzheimer's Disease: The Influence of Lifestyle and Environmental Factors.

Alzheimer's disease (AD) is the most common neurodegenerative disorder with obscure pathogenesis and no disease-modifying therapy to date. AD is multifactorial disease that develops from the complex interplay of genetic factors and environmental exposures. The E4 allele of the gene encoding apolipoprotein E (APOE) is the most common genetic risk factor for AD, whereas the E2 allele acts in a protective manner. A growing amount of epidemiological evidence suggests that several lifestyle habits and environmental factors may interact with APOE alleles to synergistically affect the risk of AD development. Among them, physical exercise, dietary habits including fat intake and ketogenic diet, higher education, traumatic brain injury, cigarette smoking, coffee consumption, alcohol intake, and exposure to pesticides and sunlight have gained increasing attention. Although the current evidence is inconsistent, it seems that younger APOE4 carriers in preclinical stages may benefit mostly from preventive lifestyle interventions, whereas older APOE4 noncarriers with dementia may show the most pronounced effects. The large discrepancies between the epidemiological studies may be attributed to differences in the sample sizes, the demographic characteristics of the participants, including age and sex, the methodological design, and potential related exposures and comorbidities as possible cofounding factors. In this Review, we aim to discuss available evidence of the prominent APOE genotype-environment interactions in regard to cognitive decline with a focus on AD, providing an overview of the current landscape in this field and suggesting future directions.

Engineered platforms for topological superconductivity and Majorana zero modes

Among the major avenues that are being pursued for realizing quantum bits, the Majorana-based approach has been the most recent to be launched. It attempts to realize qubits that store quantum information in a topologically protected manner. The quantum information is protected by non-local storage in localized and well-separated Majorana zero modes, and manipulated by exploiting their non-abelian quantum statistics. Realizing these topological qubits is experimentally challenging, requiring superconductivity, helical electrons (created by spin–orbit coupling) and breaking of time-reversal symmetry to all cooperate in an uncomfortable alliance. Over the past decade, several candidate materials systems for realizing Majorana-based topological qubits have been explored, and there is accumulating, though still debated, evidence that zero modes are indeed being realized. This Review surveys the basic physical principles on which these approaches are based, the materials systems that are being developed and the current state of the field. We highlight both the progress that has been made and the challenges that still need to be overcome.

An ACE2 Triple Decoy that neutralizes SARS-CoV-2 shows enhanced affinity for virus variants

The SARS-CoV-2 variants replacing the first wave strain pose an increased threat by their potential ability to escape pre-existing humoral protection. An angiotensin converting enzyme 2 (ACE2) decoy that competes with endogenous ACE2 for binding of the SARS-CoV-2 spike receptor binding domain (S RBD) and inhibits infection may offer a therapeutic option with sustained efficacy against variants. Here, we used Molecular Dynamics (MD) simulation to predict ACE2 sequence substitutions that might increase its affinity for S RBD and screened candidate ACE2 decoys in vitro. The lead ACE2(T27Y/H34A)-IgG1FC fusion protein with enhanced S RBD affinity shows greater live SARS-CoV-2 virus neutralization capability than wild type ACE2. MD simulation was used to predict the effects of S RBD variant mutations on decoy affinity that was then confirmed by testing of an ACE2 Triple Decoy that included an additional enzyme activity-deactivating H374N substitution against mutated S RBD. The ACE2 Triple Decoy maintains high affinity for mutated S RBD, displays enhanced affinity for S RBD N501Y or L452R, and has the highest affinity for S RBD with both E484K and N501Y mutations, making it a viable therapeutic option for the prevention or treatment of SARS-CoV-2 infection with a high likelihood of efficacy against variants.

Toll-like receptor gene polymorphisms in patients with myeloproliferative neoplasms.

Toll-like receptors (TLRs) are a family of transmembrane receptors whose signaling control cellular processes of cell proliferation, survival, apoptosis, angiogenesis, remodeling, and repair of tissues. Polymorphisms in TLR genes can change the balance between pro and anti-inflammatory cytokines, modulating the risk of infection, chronic inflammation, and cancer. Although many studies have demonstrated the direct involvement of TLR signaling in the benefit of tumor cells in certain cancers, little is known about the influence of these gene polymorphisms on myeloproliferative neoplasms (MPNs). In this context, the objective of the study was to investigate a possible association between the TLR polymorphisms and the development of MPNs. 167 patients diagnosed with MPN and 222 healthy controls from the same region were evaluated. Genomic DNA was extracted and the TLR2 (rs5743708), TLR4 (rs4986790, rs4986791), TLR9 (rs5743836, rs187084) and JAK2V617F polymorphisms were genotyped by PCR-RFLP. The statistical analysis was performed by OpenEpi and SNPstat software. The JAK2V617F mutation was found in 68.32% of patients. TLR9-1486C/T CT genotype was less frequent in patients with polycythemia vera (PV) (OR 0.39, 95% CI 0.20-0.78, P = 0.025). When haplotype frequencies were analyzed, -1237T/-1486C (TLR9) was also less frequent in men (OR 0.58, 95% CI 0.36-0.94) and JAK negative men patients (OR 0.43, 95% CI 0.21-0.88). We can infer that the TLR9-1486 CT genotype could be associated with protection for PV and the TLR9-1237T/-1486C haplotype, protection for men, as well as for JAK negative men patients with MPN. There were no associations between TLR2 and TLR4 gene polymorphisms and MPN.

Hysteric Woman: A Study on The Yellow Wallpaper

In an unquestionably patriarchal society, women who dissent, who had a voice of her own, one with strong affiliations towards social change were labelled as hysteric and mad. Their symptoms were thoughtfulness, deviation from social behavior, tendency to shout and express one’s emotion, even getting angry were considered as symptoms of hysteria. A hysteric woman is a hopeless woman, the lost one; who needs to be locked up in an attic. The men had two extreme approaches towards these conditions. They either treated women as fragile beings, who need to be cared and nurtured under the protection of men. Or they termed “women with disease” as monstrous, insane, dangerous and despicable beings. These two approaches were unhealthy and were designed to preserve the superiority of masculine self over the feminine. These tags which were labelled on women came from their existential fear; ‘the castration anxiety’.