Design, fabrication and control of soft robots

Conventionally, engineers have employed rigid materials to fabricate precise, predictable robotic systems, which are easily modelled as rigid members connected at discrete joints. Natural systems, however, often match or exceed the performance of robotic systems with deformable bodies. Cephalopods, for example, achieve amazing feats of manipulation and locomotion without a skeleton; even vertebrates such as humans achieve dynamic gaits by storing elastic energy in their compliant bones and soft tissues. Inspired by nature, engineers have begun to explore the design and control of soft-bodied robots composed of compliant materials. This Review discusses recent developments in the emerging field of soft robotics.National Science Foundation (U.S.) (Grant IIS-1226883

The effects of sheep manure application time and rates on yield and botanical composition of secondary succession rangeland

This experimental study was conducted in Samsun/Turkey on a secondary succession rangeland during 2006 - 2008. Botanical composition of the experimental area consists of 28% legumes, 64% grasses, and 8% of other species. Target rates of sheep manure were 0, 25.0, 50.0, 75.0, and 100 kg total N ha–1, based on the manure analyses results (according to N rates in sheep manure). The sheep manure was applied at two different times. Means of 3 years of experimental period and total dry matteryield was obtained from the manure treatment of 75.0 kg N ha-1 and 50 + 50 kg N ha-1 (4153 kg ha-1, and 3813 kg ha-1, respectively). With respect to the three-year average, ratios of legumes, grasses, and otherplants ranged from 20.8 to 40.7%, 41.6 to 66.9%, and 10.7 to 20.7%, respectively. Although ratios of legumes, and other plants increased in the all of the treatments, grass ratios decreased. The crude protein content of obtained rangeland hay ranged between 107.0 and 143.0 g kg-1 in 2006, 93.0 and 123.4 g kg-1 in 2007, 116.3 and 166.4 g kg-1 in 2008. The maximum benefit was provided from the application of 75.0 kg N ha-1 with a sum of 971.2 ha-1

A Soft Robotic Wearable Wrist Device for Kinesthetic Haptic Feedback

Advances in soft robotics provide a unique approach for delivering haptic feedback to a user by a soft wearable device. Such devices can apply forces directly on the human joints, while still maintaining the safety and flexibility necessary for use in close proximity to the human body. To take advantage of these properties, we present a new haptic wrist device using pressure-driven soft actuators called reverse pneumatic artificial muscles (rPAMs) mounted on four sides of the wrist. These actuators are originally pre-strained and release compressive stress under pressure, applying a safe torque around the wrist joints while being compact and portable, representing the first soft haptic device capable of real-time feedback. To demonstrate the functional utility of this device, we created a virtual path-following task, wherein the user employs the motion of their wrist to control their embodied agent. We used the haptic wrist device to assist the user in following the path and study their performance with and without haptic feedback in multiple scenarios. Our results quantify the effect of wearable soft robotic haptic feedback on user performance. Specifically, we observed that our haptic feedback system improved the performance of users following complicated paths in a statistically significant manner, but did not show improvement for simple linear paths. Based on our findings, we anticipate broader applications of wearable soft robotic haptic devices toward intuitive user interactions with robots, computers, and other users

Antigen-Displaying Lipid-Enveloped PLGA Nanoparticles as Delivery Agents for a Plasmodium vivax Malaria Vaccine

The parasite Plasmodium vivax is the most frequent cause of malaria outside of sub-Saharan Africa, but efforts to develop viable vaccines against P. vivax so far have been inadequate. We recently developed pathogen-mimicking polymeric vaccine nanoparticles composed of the FDA-approved biodegradable polymer poly(lactide-co-glycolide) acid (PLGA) “enveloped” by a lipid membrane. In this study, we sought to determine whether this vaccine delivery platform could be applied to enhance the immune response against P. vivax sporozoites. A candidate malaria antigen, VMP001, was conjugated to the lipid membrane of the particles, and an immunostimulatory molecule, monophosphoryl lipid A (MPLA), was incorporated into the lipid membranes, creating pathogen-mimicking nanoparticle vaccines (VMP001-NPs). Vaccination with VMP001-NPs promoted germinal center formation and elicited durable antigen-specific antibodies with significantly higher titers and more balanced Th1/Th2 responses in vivo, compared with vaccines composed of soluble protein mixed with MPLA. Antibodies raised by NP vaccinations also exhibited enhanced avidity and affinity toward the domains within the circumsporozoite protein implicated in protection and were able to agglutinate live P. vivax sporozoites. These results demonstrate that these VMP001-NPs are promising vaccines candidates that may elicit protective immunity against P. vivax sporozoites.United States. Dept. of Defense (contract W911NF-07-D-0004)Ragon Institute of MGH, MIT and Harvar

Synthetic Nanoparticles for Vaccines and Immunotherapy

The immune system plays a critical role in our health. No other component of human physiology plays a decisive role in as diverse an array of maladies, from deadly diseases with which we are all familiar to equally terrible esoteric conditions: HIV, malaria, pneumococcal and influenza infections; cancer; atherosclerosis; autoimmune diseases such as lupus, diabetes, and multiple sclerosis. The importance of understanding the function of the immune system and learning how to modulate immunity to protect against or treat disease thus cannot be overstated. Fortunately, we are entering an exciting era where the science of immunology is defining pathways for the rational manipulation of the immune system at the cellular and molecular level, and this understanding is leading to dramatic advances in the clinic that are transforming the future of medicine.1,2 These initial advances are being made primarily through biologic drugs– recombinant proteins (especially antibodies) or patient-derived cell therapies– but exciting data from preclinical studies suggest that a marriage of approaches based in biotechnology with the materials science and chemistry of nanomaterials, especially nanoparticles, could enable more effective and safer immune engineering strategies. This review will examine these nanoparticle-based strategies to immune modulation in detail, and discuss the promise and outstanding challenges facing the field of immune engineering from a chemical biology/materials engineering perspectiveNational Institutes of Health (U.S.) (Grants AI111860, CA174795, CA172164, AI091693, and AI095109)United States. Department of Defense (W911NF-13-D-0001 and Awards W911NF-07-D-0004

Evaluation Of Clinical And Follow-up Results Of Patients With Congenital Nephrotic Syndrome

Introduction:  Congenital nephrotic syndrome (CNS) is characterized by severe proteinuria, hypoalbuminemia, and edema within the first three months of life. CNS can occur due to perinatal infections or mutation of genes encoding structural or regulatory proteins of the glomerular filtration barrier. Treatment includes albumin infusions, nephrectomy, dialysis, and transplantation. Objective: In this study, we aimed to evaluate the demographic, clinical, and follow-up results of patients with CNS followed up in our center between 2010 and 2020. Patients and method:  Demographic, clinical, laboratory values of 8 patients diagnosed with CNS between 2010 and 2020, kidney biopsy results, genetic examinations, and follow-up results were retrospectively evaluated. Results: A total of 8 patients (4 girls) were included in this study. The median age at diagnosis was 36 days (3 days-8 months) and the follow-up period was 34 months (7-114 months). There was a history of prematurity and consanguinity in 5 patients. Edema was detected at the admission of all patients. Albumin infusion and captopril therapy were started from the diagnosis. No pathology was seen in the tests for perinatal infection, and Ultrasonographic examinations were normal. In the genetic analysis, NPHS1 (Nephrin) homozygous mutation was detected in six patients, and coenzyme Q2 mutation was detected in one patient. Peritoneal dialysis treatment was performed in four patients during the follow-up, and unilateral nephrectomy was completed in one patient. During the follow-up, four of eight patients (three due to sepsis while on dialysis, one on the postoperative after the first day of transplantation) died. Three patients are followed up with kidney transplantation and one with supportive treatment. Conclusion: According to our results, most CNS cases are genetic, and nephrin mutation is the most common cause. Management of complications in CNS is crucial for patient survival

The prevalence and consequences of burnout on a group of preclinical dental students

Objective: The aim of this study is to investigate the prevalence of burnout among a group of Turkish preclinical dental students, to compare the level of burnout and to determine the consequences in structural equation model. Materials and Methods: Preclinical dental students (n = 329, 50.5% of females and 49.5% of males) aged between 18 and 24 took part in the study. Maslach burnout inventory student version, academic satisfaction scale, and personal information sheet were used to gather data. Pearson correlation analyses, t-test, and one-way ANOVA were used for statistical analysis. The proposed theoretical model was tested via observed variable path analysis using maximum likelihood parameter estimation with AMOS 7.0. Results: About 22.3% of students had high level of emotional exhaustion, 16.7% of students had high level of cynicism, and 17.9% of students suffered from high level of reduced academic efficacy. While the students attending the first grade reported higher level of reduced academic efficacy, the students in the third grade reported higher level of emotional exhaustion. Academic workload played an important role in the development of burnout. As consequences of burnout, students with high levels of burnout intended to change their current major and did not to plan to continue to postgraduate education. Students with high level of burnout reported less level of academic satisfaction and academic achievement. Conclusions: Creating awareness on the burnout of dental students from the preclinical period may be useful for prevention and more compatible dental education environment. © 2015 European Journal of Dentistry

Mitochondrial targeted antioxidants, mitoquinone and SKQ1, not vitamin C, mitigate doxorubicin-induced damage in H9c2 myoblast: pretreatment vs. co-treatment

BACKGROUND: Preconditioning of the heart ameliorates doxorubicin (Dox)-induced cardiotoxicity. We tested whether pretreating cardiomyocytes by mitochondrial-targeted antioxidants, mitoquinone (MitoQ) or SKQ1, would provide better protection against Dox than co-treatment. METHODS: We investigated the dose-response relationship of MitoQ, SKQ1, and vitamin C on Dox-induced damage on H9c2 cardiomyoblasts when drugs were given concurrently with Dox (e.g., co-treatment) or 24 h prior to Dox (e.g., pretreatment). Moreover, their effects on intracellular and mitochondrial oxidative stress were evaluated by 2,7-dichlorofluorescin diacetate and MitoSOX, respectively. RESULTS: Dox (0.5-50 μM, n = 6) dose-dependently reduced cell viability. By contrast, co-treatment of MitoQ (0.05-10 μM, n = 6) and SKQ1 (0.05-10 μM, n = 6), but not vitamin C (1-2000 μM, n = 3), significantly improved cell viability only at intermediate doses (0.5-1 μM). MitoQ (1 μM) and SKQ1 (1 μM) significantly increased cell viability to 1.79 ± 0.12 and 1.59 ± 0.08 relative to Dox alone, respectively (both p \u3c 0.05). Interestingly, when given as pretreatment, only higher doses of MitoQ (2.5 μM, n = 9) and SKQ1 (5 μM, n = 7) showed maximal protection and improved cell viability to 2.19 ± 0.13 and 1.65 ± 0.07 relative to Dox alone, respectively (both p \u3c 0.01), which was better than that of co-treatment. Moreover, the protective effects were attributed to the significant reduction in Dox-induced intracellular and mitochondrial oxidative stress. CONCLUSION: The data suggest that MitoQ and SKQ1, but not vitamin C, mitigated DOX-induced damage. Moreover, MitoQ pretreatment showed significantly higher cardioprotection than its co-treatment and SKQ1, which may be due to its better antioxidant effects

Variant‐specific effects of GBA1 mutations on dopaminergic neuron proteostasis

Glucocerebrosidase 1 (GBA1) mutations are the most important genetic risk factors for Parkinson's disease (PD). Clinically, mild (e.g., p.N370S) and severe (e.g., p.L444P and p.D409H) GBA1 mutations have different PD phenotypes, with differences in age at disease onset, progression, and the severity of motor and non‐motor symptoms. We hypothesize that GBA1 mutations cause the accumulation of α‐synuclein by affecting the cross‐talk between cellular protein degradation mechanisms, leading to neurodegeneration. Accordingly, we tested whether mild and severe GBA1 mutations differentially affect the degradation of α‐synuclein via the ubiquitin–proteasome system (UPS), chaperone‐mediated autophagy (CMA), and macroautophagy and differentially cause accumulation and/or release of α‐synuclein. Our results demonstrate that endoplasmic reticulum (ER) stress and total ubiquitination rates were significantly increased in cells with severe GBA1 mutations. CMA was found to be defective in induced pluripotent stem cell (iPSC)‐derived dopaminergic neurons with mild GBA1 mutations, but not in those with severe GBA1 mutations. When examining macroautophagy, we observed reduced formation of autophagosomes in cells with the N370S and D409H GBA1 mutations and impairments in autophagosome–lysosome fusion in cells with the L444P GBA1 mutation. Accordingly, severe GBA1 mutations were found to trigger the accumulation and release of oligomeric α‐synuclein in iPSC‐derived dopaminergic neurons, primarily as a result of increased ER stress and defective macroautophagy, while mild GBA1 mutations affected CMA, which is mainly responsible for the degradation of the monomeric form of α‐synuclein. Overall, our findings provide new insight into the molecular basis of the clinical variability in PD associated with different GBA1 mutations