Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers.

Passive administration of HIV neutralizing antibodies (nAbs) can protect macaques from hard-to-neutralize (tier 2) chimeric simian-human immunodeficiency virus (SHIV) challenge. However, conditions for nAb-mediated protection after vaccination have not been established. Here, we selected groups of 6 rhesus macaques with either high or low serum nAb titers from a total of 78 animals immunized with recombinant native-like (SOSIP) Env trimers. Repeat intrarectal challenge with homologous tier 2 SHIVBG505 led to rapid infection in unimmunized and low-titer animals. High-titer animals, however, demonstrated protection that was gradually lost as nAb titers waned over time. An autologous serum ID50 nAb titer of ∼1:500 afforded more than 90% protection from medium-dose SHIV infection. In contrast, antibody-dependent cellular cytotoxicity and T cell activity did not correlate with protection. Therefore, Env protein-based vaccination strategies can protect against hard-to-neutralize SHIV challenge in rhesus macaques by inducing tier 2 nAbs, provided appropriate neutralizing titers can be reached and maintained.

Electron-Microscopy-Based Epitope Mapping Defines Specificities of Polyclonal Antibodies Elicited during HIV-1 BG505 Envelope Trimer Immunization.

Characterizing polyclonal antibody responses via currently available methods is inherently complex and difficult. Mapping epitopes in an immune response is typically incomplete, which creates a barrier to fully understanding the humoral response to antigens and hinders rational vaccine design efforts. Here, we describe a method of characterizing polyclonal responses by using electron microscopy, and we applied this method to the immunization of rabbits with an HIV-1 envelope glycoprotein vaccine candidate, BG505 SOSIP.664. We detected known epitopes within the polyclonal sera and revealed how antibody responses evolved during the prime-boosting strategy to ultimately result in a neutralizing antibody response. We uncovered previously unidentified epitopes, including an epitope proximal to one recognized by human broadly neutralizing antibodies as well as potentially distracting non-neutralizing epitopes. Our method provides an efficient and semiquantitative map of epitopes that are targeted in a polyclonal antibody response and should be of widespread utility in vaccine and infection studies.

A survey of ficolin-3 activity in Systemic Lupus Erythematosus reveals a link to hematological disease manifestations and autoantibody profile.

The complement system plays a central role in the pathogenesis of Systemic Lupus Erythematosus (SLE), but most studies have focused on the classical pathway. Ficolin-3 is the main initiator of the lectin pathway of complement in humans, but its role in systemic autoimmune disease has not been conclusively determined. Here, we combined biochemical and genetic approaches to assess the contribution of ficolin-3 to SLE risk and disease manifestations. Ficolin-3 activity was measured by a functional assay in serum or plasma samples from Swedish SLE patients (n = 786) and controls matched for age and sex (n = 566). Genetic variants in an extended 300 kb genomic region spanning the FCN3 locus were analyzed for their association with ficolin-3 activity and SLE manifestations in a Swedish multicenter cohort (n = 985). Patients with ficolin-3 activity in the highest tertile showed a strong enrichment in an SLE cluster defined by anti-Sm/DNA/nucleosome antibodies (OR 3.0, p < 0.001) and had increased rates of hematological disease (OR 1.4, p = 0.078) and lymphopenia (OR = 1.6, p = 0.039). Genetic variants associated with low ficolin-3 activity mapped to an extended haplotype in high linkage disequilibrium upstream of the FCN3 gene. Patients carrying the lead genetic variant associated with low ficolin-3 activity had a lower frequency of hematological disease (OR 0.67, p = 0.018) and lymphopenia (OR 0.63, p = 0.031) and fewer autoantibodies (p = 0.0019). Loss-of-function variants in the FCN3 gene were not associated with SLE, but four (0.5 %) SLE patients developed acquired ficolin-3 deficiency where ficolin-3 activity in serum was depleted following diagnosis of SLE. Taken together, our results provide genetic and biochemical evidence that implicate the lectin pathway in hematological SLE manifestations. We also identify lectin pathway activation through ficolin-3 as a factor that contributes to the autoantibody response in SLE.

A Multi-Modal Under-Sensorized Wearable System for Optimal Kinematic and Muscular Tracking of Human Upper Limb Motion.

Wearable sensing solutions have emerged as a promising paradigm for monitoring human musculoskeletal state in an unobtrusive way. To increase the deployability of these systems, considerations related to cost reduction and enhanced form factor and wearability tend to discourage the number of sensors in use. In our previous work, we provided a theoretical solution to the problem of jointly reconstructing the entire muscular-kinematic state of the upper limb, when only a limited amount of optimally retrieved sensory data are available. However, the effective implementation of these methods in a physical, under-sensorized wearable has never been attempted before. In this work, we propose to bridge this gap by presenting an under-sensorized system based on inertial measurement units (IMUs) and surface electromyography (sEMG) electrodes for the reconstruction of the upper limb musculoskeletal state, focusing on the minimization of the sensors' number. We found that, relying on two IMUs only and eight sEMG sensors, we can conjointly reconstruct all 17 degrees of freedom (five joints, twelve muscles) of the upper limb musculoskeletal state, yielding a median normalized RMS error of 8.5% on the non-measured joints and 2.5% on the non-measured muscles.

Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA.

OBJECTIVE: To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). METHODS: Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. RESULTS: PR3-ANCA+ AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 × 10-61, odds ratio (OR) 0.10; rs9277341, P = 1.5 × 10-44, OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 × 10-10, OR 2.9). MPO-ANCA+ AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 × 10-25, OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 × 10-7, OR 3.0), the latter a novel susceptibility locus for MPO-ANCA+ granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. CONCLUSION: We identified a novel susceptibility locus for MPO-ANCA+ AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.

A computational framework for post-TAVR cardiac conduction abnormality (CCA) risk assessment in patient-specific anatomy.

BACKGROUND: Cardiac conduction abnormality (CCA)- one of the major persistent complications associated with transcatheter aortic valve replacement (TAVR) may lead to permanent pacemaker implantation. Localized stresses exerted by the device frame on the membranous septum (MS) which lies between the aortic annulus and the bundle of His, may disturb the cardiac conduction and cause the resultant CCA. We hypothesize that the area-weighted average maximum principal logarithmic strain (AMPLS) in the MS region can predict the risk of CCA following TAVR. METHODS: Rigorous finite element-based analysis was conducted in two patients (Balloon expandable TAVR recipients) to assess post-TAVR CCA risk. Following the procedure one of the patients required permanent pacemaker (PPM) implantation while the other did not (control case). Patient-specific aortic root was modeled, MS was identified from the CT image, and the TAVR deployment was simulated. Mechanical factors in the MS region such as logarithmic strain, contact force, contact pressure, contact pressure index (CPI) and their time history during the TAVR deployment; and anatomical factors such as MS length, implantation depth, were analyzed. RESULTS: Maximum AMPLS (0.47 and 0.37, respectively), contact force (0.92 N and 0.72 N, respectively), and CPI (3.99 and 2.86, respectively) in the MS region were significantly elevated in the PPM patient as compared to control patient. CONCLUSION: Elevated stresses generated by TAVR devices during deployment appear to correlate with CCA risk, with AMPLS in the MS region emerging as a strong predictor that could be used for preprocedural planning in order to minimize CCA risk.

The interaction between motion and texture in the sense of touch.

Besides providing information on elementary properties of objects, like texture, roughness, and softness, the sense of touch is also important in building a representation of object movement and the movement of our hands. Neural and behavioral studies shed light on the mechanisms and limits of our sense of touch in the perception of texture and motion, and of its role in the control of movement of our hands. The interplay between the geometrical and mechanical properties of the touched objects, such as shape and texture, the movement of the hand exploring the object, and the motion felt by touch, will be discussed in this article. Interestingly, the interaction between motion and textures can generate perceptual illusions in touch. For example, the orientation and the spacing of the texture elements on a static surface induces the illusion of surface motion when we move our hand on it or can elicit the perception of a curved trajectory during sliding, straight hand movements. In this work we present a multiperspective view that encompasses both the perceptual and the motor aspects, as well as the response of peripheral and central nerve structures, to analyze and better understand the complex mechanisms underpinning the tactile representation of texture and motion. Such a better understanding of the spatiotemporal features of the tactile stimulus can reveal novel transdisciplinary applications in neuroscience and haptics.

Molecular pathways in patients with systemic lupus erythematosus revealed by gene-centred DNA sequencing.

OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease with extensive heterogeneity in disease presentation between patients, which is likely due to an underlying molecular diversity. Here, we aimed at elucidating the genetic aetiology of SLE from the immunity pathway level to the single variant level, and stratify patients with SLE into distinguishable molecular subgroups, which could inform treatment choices in SLE. METHODS: We undertook a pathway-centred approach, using sequencing of immunological pathway genes. Altogether 1832 candidate genes were analysed in 958 Swedish patients with SLE and 1026 healthy individuals. Aggregate and single variant association testing was performed, and we generated pathway polygenic risk scores (PRS). RESULTS: We identified two main independent pathways involved in SLE susceptibility: T lymphocyte differentiation and innate immunity, characterised by HLA and interferon, respectively. Pathway PRS defined pathways in individual patients, who on average were positive for seven pathways. We found that SLE organ damage was more pronounced in patients positive for the T or B cell receptor signalling pathways. Further, pathway PRS-based clustering allowed stratification of patients into four groups with different risk score profiles. Studying sets of genes with priors for involvement in SLE, we observed an aggregate common variant contribution to SLE at genes previously reported for monogenic SLE as well as at interferonopathy genes. CONCLUSIONS: Our results show that pathway risk scores have the potential to stratify patients with SLE beyond clinical manifestations into molecular subsets, which may have implications for clinical follow-up and therapy selection.

Genetic and clinical basis for two distinct subtypes of primary Sjögren's syndrome.

OBJECTIVES: Clinical presentation of primary Sjögren's syndrome (pSS) varies considerably. A shortage of evidence-based objective markers hinders efficient drug development and most clinical trials have failed to reach primary endpoints. METHODS: We performed a multicentre study to identify patient subgroups based on clinical, immunological and genetic features. Targeted DNA sequencing of 1853 autoimmune-related loci was performed. After quality control, 918 patients with pSS, 1264 controls and 107 045 single nucleotide variants remained for analysis. Replication was performed in 177 patients with pSS and 7672 controls. RESULTS: We found strong signals of association with pSS in the HLA region. Principal component analysis of clinical data distinguished two patient subgroups defined by the presence of SSA/SSB antibodies. We observed an unprecedented high risk of pSS for an association in the HLA-DQA1 locus of odds ratio 6.10 (95% CI: 4.93, 7.54, P=2.2×10-62) in the SSA/SSB-positive subgroup, while absent in the antibody negative group. Three independent signals within the MHC were observed. The two most significant variants in MHC class I and II respectively, identified patients with a higher risk of hypergammaglobulinaemia, leukopenia, anaemia, purpura, major salivary gland swelling and lymphadenopathy. Replication confirmed the association with both MHC class I and II signals confined to SSA/SSB antibody positive pSS. CONCLUSION: Two subgroups of patients with pSS with distinct clinical manifestations can be defined by the presence or absence of SSA/SSB antibodies and genetic markers in the HLA locus. These subgroups should be considered in clinical follow-up, drug development and trial outcomes, for the benefit of both subgroups.

Whole-genome genotyping and resequencing reveal the association of a deletion in the complex interferon alpha gene cluster with hypothyroidism in dogs.

BACKGROUND: Hypothyroidism is a common complex endocrinopathy that typically has an autoimmune etiology, and it affects both humans and dogs. Genetic and environmental factors are both known to play important roles in the disease development. In this study, we sought to identify the genetic risk factors potentially involved in the susceptibility to the disease in the high-risk Giant Schnauzer dog breed. RESULTS: By employing genome-wide association followed by fine-mapping (top variant p-value = 5.7 × 10- 6), integrated with whole-genome resequencing and copy number variation analysis, we detected a ~ 8.9 kbp deletion strongly associated (p-value = 0.0001) with protection against development of hypothyroidism. The deletion is located between two predicted Interferon alpha (IFNA) genes and it may eliminate functional elements potentially involved in the transcriptional regulation of these genes. Remarkably, type I IFNs have been extensively associated to human autoimmune hypothyroidism and general autoimmunity. Nonetheless, the extreme genomic complexity of the associated region on CFA11 warrants further long-read sequencing and annotation efforts in order to ascribe functions to the identified deletion and to characterize the canine IFNA gene cluster in more detail. CONCLUSIONS: Our results expand the current knowledge on genetic determinants of canine hypothyroidism by revealing a significant link with the human counterpart disease, potentially translating into better diagnostic tools across species, and may contribute to improved canine breeding strategies.

Exploiting upper-limb functional principal components for human-like motion generation of anthropomorphic robots.

BACKGROUND: Human-likeliness of robot movements is a key component to enable a safe and effective human-robot interaction, since it contributes to increase acceptance and motion predictability of robots that have to closely interact with people, e.g. for assistance and rehabilitation purposes. Several parameters have been used to quantify how much a robot behaves like a human, which encompass aspects related to both the robot appearance and motion. The latter point is fundamental to allow the operator to interpret robotic actions, and plan a meaningful reactions. While different approaches have been presented in literature, which aim at devising bio-aware control guidelines, a direct implementation of human actions for robot planning is not straightforward, still representing an open issue in robotics. METHODS: We propose to embed a synergistic representation of human movements for robot motion generation. To do this, we recorded human upper-limb motions during daily living activities. We used functional Principal Component Analysis (fPCA) to extract principal motion patterns. We then formulated the planning problem by optimizing the weights of a reduced set of these components. For free-motions, our planning method results into a closed form solution which uses only one principal component. In case of obstacles, a numerical routine is proposed, incrementally enrolling principal components until the problem is solved with a suitable precision. RESULTS: Results of fPCA show that more than 80% of the observed variance can be explained by only three functional components. The application of our method to different meaningful movements, with and without obstacles, show that our approach is able to generate complex motions with a very reduced number of functional components. We show that the first synergy alone accounts for the 96% of cost reduction and that three components are able to achieve a satisfactory motion reconstruction in all the considered cases. CONCLUSIONS: In this work we moved from the analysis of human movements via fPCA characterization to the design of a novel human-like motion generation algorithm able to generate, efficiently and with a reduced set of basis elements, several complex movements in free space, both in free motion and in case of obstacle avoidance tasks.

The Sensor-Based Biomechanical Risk Assessment at the Base of the Need for Revising of Standards for Human Ergonomics.

Due to the epochal changes introduced by "Industry 4.0", it is getting harder to apply the varying approaches for biomechanical risk assessment of manual handling tasks used to prevent work-related musculoskeletal disorders (WMDs) considered within the International Standards for ergonomics. In fact, the innovative human-robot collaboration (HRC) systems are widening the number of work motor tasks that cannot be assessed. On the other hand, new sensor-based tools for biomechanical risk assessment could be used for both quantitative "direct instrumental evaluations" and "rating of standard methods", allowing certain improvements over traditional methods. In this light, this Letter aims at detecting the need for revising the standards for human ergonomics and biomechanical risk assessment by analyzing the WMDs prevalence and incidence; additionally, the strengths and weaknesses of traditional methods listed within the International Standards for manual handling activities and the next challenges needed for their revision are considered. As a representative example, the discussion is referred to the lifting of heavy loads where the revision should include the use of sensor-based tools for biomechanical risk assessment during lifting performed with the use of exoskeletons, by more than one person (team lifting) and when the traditional methods cannot be applied. The wearability of sensing and feedback sensors in addition to human augmentation technologies allows for increasing workers' awareness about possible risks and enhance the effectiveness and safety during the execution of in many manual handling activities.

SoftHand at the CYBATHLON: a user's experience.

BACKGROUND: Roughly one-quarter of upper limb prosthesis users reject their prosthesis. Reasons for rejection range from comfort, to cost, aesthetics, function, and more. This paper follows a single user from training with and testing of a novel upper-limb myoelectric prosthesis (the SoftHand Pro) for participation in the CYBATHLON rehearsal to training for and competing in the CYBATHLON 2016 with a figure-of-nine harness controlled powered prosthesis (SoftHand Pro-H) to explore the feasibility and usability of a flexible anthropomorphic prosthetic hand. METHODS: The CYBATHLON pilot took part in multiple in-lab training sessions with the SoftHand Pro and SoftHand Pro-H; these sessions focused on basic control and use of the prosthetic devices and direct training of the tasks in the CYBATHLON. He used these devices in competition in the Powered Arm Prosthesis Race in the CYBATHLON rehearsal and 2016 events. RESULTS: In training for the CYBATHLON rehearsal, the subject was able to quickly improve performance with the myoelectric SHP despite typically using a body-powered prosthetic hook. The subject improved further with additional training using the figure-of-nine harness-controlled SHPH in preparation for the CYBATHLON. The Pilot placed 3rd (out of 4) in the rehearsal. In the CYBATHLON, he placed 5th (out of 12) and was one of only two pilots who successfully completed all tasks in the competition, having the second-highest score overall. CONCLUSIONS: Results with the SoftHand Pro and Pro-H suggest it to be a viable alternative to existing anthropomorphic hands and show that the unique flexibility of the hand is easily learned and exploited.

Heterosubtypic antibodies to influenza A virus have limited activity against cell-bound virus but are not impaired by strain-specific serum antibodies.

UNLABELLED: The majority of influenza virus-specific antibodies elicited by vaccination or natural infection are effective only against the eliciting or closely related viruses. Rare stem-specific heterosubtypic monoclonal antibodies (hMAbs) can neutralize multiple strains and subtypes by preventing hemagglutinin (HA)-mediated fusion of the viral membrane with the endosomal membrane. The epitopes recognized by these hMAbs are therefore considered promising targets for the development of pan-influenza virus vaccines. Here, we report the isolation of a novel human HA stem-reactive monoclonal antibody, hMAb 1.12, with exceptionally broad neutralizing activity encompassing viruses from 15 distinct HA subtypes. Using MAb 1.12 and two other monoclonal antibodies, we demonstrate that neutralization by hMAbs is virtually irreversible but becomes severely impaired following virus attachment to cells. In contrast, no interference by human anti-influenza virus serum antibodies was found, indicating that apically binding antibodies do not impair access to the membrane-proximal heterosubtypic epitopes. Our findings therefore encourage development of new vaccine concepts aiming at the induction of stem-specific heterosubtypic antibodies, as we provide support for their effectiveness in individuals previously exposed to influenza virus. IMPORTANCE: The influenza A virus hemagglutinin (HA) can easily accommodate changes in its antigenic structures to escape preexisting immunity. This variability restricts the breadth and long-term efficacy of influenza vaccines. Only a few heterosubtypic antibodies (hMAbs), i.e., antibodies that can neutralize more than one subtype of influenza A virus, have been identified. The molecular interactions between these heterosubtypic antibodies and hemagglutinin are well characterized, yet little is known about the functional properties of these antibodies. Using a new, extraordinarily broad hMAb, we show that virus neutralization by hMAbs is virtually irreversible and that efficient neutralization is possible only if stem-specific hMAbs bind to HA before the virus attaches to the cell surface. No interference between strain-specific human serum immunoglobulin and hMAbs was found, indicating that preexisting humoral immunity to influenza virus does not limit the efficacy of stem-reactive heterosubtypic antibodies. This knowledge supports the development of a pan-influenza virus vaccine.

cgmisc: enhanced genome-wide association analyses and visualization.

UNLABELLED: High-throughput genotyping and sequencing technologies facilitate studies of complex genetic traits and provide new research opportunities. The increasing popularity of genome-wide association studies (GWAS) leads to the discovery of new associated loci and a better understanding of the genetic architecture underlying not only diseases, but also other monogenic and complex phenotypes. Several softwares are available for performing GWAS analyses, R environment being one of them. RESULTS: We present cgmisc, an R package that enables enhanced data analysis and visualization of results from GWAS. The package contains several utilities and modules that complement and enhance the functionality of the existing software. It also provides several tools for advanced visualization of genomic data and utilizes the power of the R language to aid in preparation of publication-quality figures. Some of the package functions are specific for the domestic dog (Canis familiaris) data. AVAILABILITY AND IMPLEMENTATION: The package is operating system-independent and is available from: https://github.com/cgmisc-team/cgmisc CONTACT: marcin.kierczak@imbim.uu.se. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Effect of Balloon-Expandable Transcatheter Aortic Valve Replacement Positioning: A Patient-Specific Numerical Model.

Transcatheter aortic valve replacement (TAVR) has emerged as a life-saving and effective alternative to surgical valve replacement in high-risk, elderly patients with severe calcific aortic stenosis. Despite its early promise, certain limitations and adverse events, such as suboptimal placement and valve migration, have been reported. In the present study, it was aimed to evaluate the effect of various TAVR deployment locations on the procedural outcome by assessing the risk for valve migration. The deployment of a balloon-expandable Edwards SAPIEN valve was simulated via finite element analysis in a patient-specific calcified aortic root, which was reconstructed from CT scans of a retrospective case of valve migration. The deployment location was parametrized in three configurations and the anchorage was quantitatively assessed based on the contact between the stent and the native valve during the deployment and recoil phases. The proximal deployment led to lower contact area between the native leaflets and the stent which poses higher risk for valve migration. The distal and midway positions resulted in comparable outcomes, with the former providing a slightly better anchorage. The approach presented might be used as a predictive tool for procedural planning in order to prevent prosthesis migration and achieve better clinical outcomes.

A Synergy-Based Optimally Designed Sensing Glove for Functional Grasp Recognition.

Achieving accurate and reliable kinematic hand pose reconstructions represents a challenging task. The main reason for this is the complexity of hand biomechanics, where several degrees of freedom are distributed along a continuous deformable structure. Wearable sensing can represent a viable solution to tackle this issue, since it enables a more natural kinematic monitoring. However, the intrinsic accuracy (as well as the number of sensing elements) of wearable hand pose reconstruction (HPR) systems can be severely limited by ergonomics and cost considerations. In this paper, we combined the theoretical foundations of the optimal design of HPR devices based on hand synergy information, i.e., the inter-joint covariation patterns, with textile goniometers based on knitted piezoresistive fabrics (KPF) technology, to develop, for the first time, an optimally-designed under-sensed glove for measuring hand kinematics. We used only five sensors optimally placed on the hand and completed hand pose reconstruction (described according to a kinematic model with 19 degrees of freedom) leveraging upon synergistic information. The reconstructions we obtained from five different subjects were used to implement an unsupervised method for the recognition of eight functional grasps, showing a high degree of accuracy and robustness.

Prevalence and predictors for homo- and heterosubtypic antibodies against influenza a virus.

BACKGROUND: The effectiveness of trivalent influenza vaccination has been confirmed in several studies. To date, it is not known whether repeated exposure and vaccination to influenza promote production of cross-reactive antibodies. Furthermore, how strains encountered earlier in life imprint the immune response is currently poorly understood. METHODS: To determine the prevalence for human homo- and heterosubtypic antibody responses, we scrutinized serum samples from 305 healthy volunteers for hemagglutinin-binding and -neutralizing antibodies against several strains and subtypes of influenza A. Statistical analyses were then performed to establish the association of measured values with potential predictors. RESULTS: It was found that vaccination not only promoted higher binding and neutralizing antibody titers to homosubtypic influenza isolates but also increased heterosubtypic human immune responses. Both binding and neutralizing antibody titers in relation with age of the donors mirrored the course of the different influenza strain circulation during the last century. Advanced age appeared to be of advantage for both binding and neutralizing titers to most subtypes. In contrast, the first virus subtype encountered was found to imprint to some degree subsequent antibody responses. Antibodies to recent strains, however, primarily seemed to be promoted by vaccination. CONCLUSIONS: We provide evidence that vaccinations stimulate both homo- and heterosubtypic immune responses in young and middle-aged as well as more senior individuals. Our analyses suggest that influenza vaccinations not only prevent infection against currently circulating strains but can also stimulate broader humoral immune responses that potentially attenuate infections with zoonotic or antigenically shifted strains.

Tactile Perception in Upper Limb Prostheses: Mechanical Characterization, Human Experiments, and Computational Findings.

Tactile feedback is essential for upper-limb prostheses functionality and embodiment, yet its practical implementation presents challenges. Users must adapt to non-physiological signals, increasing cognitive load. However, some prosthetic devices transmit tactile information through socket vibrations, even to untrained individuals. Our experiments validated this observation, demonstrating a user's surprising ability to identify contacted fingers with a purely passive, cosmetic hand. Further experiments with advanced soft articulated hands revealed decreased performance in tactile information relayed by socket vibrations as hand complexity increased. To understand the underlying mechanisms, we conducted numerical and mechanical vibration tests on four prostheses of varying complexity. Additionally, a machine-learning classifier identified the contacted finger based on measured socket signals. Quantitative results confirmed that rigid hands facilitated contact discrimination, achieving 83% accuracy in distinguishing index finger contacts from others. While human discrimination decreased with advanced hands, machine learning surpassed human performance. These findings suggest that rigid prostheses provide natural vibration transmission, potentially reducing the need for tactile feedback devices, which advanced hands may require. Nonetheless, the possibility of machine learning algorithms outperforming human discrimination indicates potential to enhance socket vibrations through active sensing and actuation, bridging the gap in vibration-transmitted tactile discrimination between rigid and advanced hands.