Solid phase micro extraction for organic contamination control throughout assembly and operational phases of space missions

Space missions concerned with life detection contain highly sensitive instruments for the detection of organics. Terrestrial contamination can interfere with signals of indigenous organics in samples and has the potential to cause false positive biosignature detections, which may lead to incorrect suggestions of the presence of life elsewhere in the Solar System. This study assessed the capability of solid phase micro extraction (SPME) as a method for monitoring organic contamination encountered by spacecraft hardware during assembly and operation. SPME-gas chromatography-mass spectrometry (SPME-GC-MS) analysis was performed on potential contaminant source materials, which are commonly used in spacecraft construction. The sensitivity of SPME-GC-MS to organics was assessed in the context of contaminants identified in molecular wipes taken from hardware surfaces on the ExoMars Rosalind Franklin rover. SPME was found to be effective at detecting a wide range of common organic contaminants that include aromatic hydrocarbons, non-aromatic hydrocarbons, nitrogen-containing compounds, alcohols and carbonyls. A notable example of correlation of contaminant with source material was the detection of benzenamine compounds in an epoxy adhesive analyzed by SPME-GC-MS and in the ExoMars rover surface wipe samples. The current form of SPME-GC-MS does not enable quantitative evaluation of contaminants, nor is it suitable for the detection of every group of organic molecules relevant to astrobiological contamination concerns, namely, large and/or polar molecules such as amino acids. However, it nonetheless represents an effective new monitoring method for rapid, easy identification of organic contaminants commonly present on spacecraft hardware and could thus be utilized in future space missions as part of their contamination control and mitigation protocols

Retrieval of magnetic medical microrobots from the bloodstream

Untethered magnetic microrobots hold the potential to penetrate hard-to-reach areas of the human body and to perform therapy in a controlled way. In the past decade, impressive advancements have been made in this field but the clinical adoption of magnetoresponsive microrobots is still hampered by safety issues. A tool appointed for magnetic microrobots retrieval within body fluids could enable a real paradigm change, fostering their clinical translation.By starting from the general problem to retrieve magnetic microrobots injected into the bloodstream, the authors introduce a magnetic capture model that allows to design retrieval tools for magnetic cores of different diameters (down to 10 nm) and in different environmental conditions (fluid speed up to 7 cms-1). The model robustness is demonstrated by the design and testing of a retrieval catheter. In its optimal configuration, the catheter includes 27 magnets and fits a 12 F catheter. The model provides a good prediction of capture efficiency for 250 nm magnetic particles (experimental data: 77.6%, model prediction: 65%) and a very good prediction for 500 nm particles (experimental data: 93.6%, model prediction: 94%). The results support the proposed model-based design approach, which can be extended to retrieve other magnetoresponsive agents from body compartments

Tumor-on-a-chip platforms to study cancer-immune system crosstalk in the era of immunotherapy

Immunotherapy is a powerful therapeutic approach able to re-educate the immune system to fight cancer. A key player in this process is the tumor microenvironment (TME), which is a dynamic entity characterized by a complex array of tumor and stromal cells as well as immune cell populations trafficking to the tumor site through the endothelial barrier. Recapitulating these multifaceted dynamics is critical for studying the intimate interactions between cancer and the immune system and to assess the efficacy of emerging immunotherapies, such as immune checkpoint inhibitors (ICIs) and adoptive cell-based products. Microfluidic devices offer a unique technological approach to build tumor-on-a-chip reproducing the multiple layers of complexity of cancer-immune system crosstalk. Here, we seek to review the most important biological and engineering developments of microfluidic platforms for studying cancer-immune system interactions, in both solid and hematological tumors, highlighting the role of the vascular component in immune trafficking. Emphasis is given to image processing and related algorithms for real-time monitoring and quantitative evaluation of the cellular response to microenvironmental dynamic changes. The described approaches represent a valuable tool for preclinical evaluation of immunotherapeutic strategies

Tactile sensing and control of robotic manipulator integrating fiber Bragg grating strain-sensor

Tactile sensing is an instrumental modality of robotic manipulation, as it provides information that is not accessible via remote sensors such as cameras or lidars. Touch is particularly crucial in unstructured environments, where the robot’s internal representation of manipulated objects is uncertain. In this study we present the sensorization of an existing artificial hand, with the aim to achieve fine control of robotic limbs and perception of object’s physical properties. Tactile feedback is conveyed by means of a soft sensor integrated at the fingertip of a robotic hand. The sensor consists of an optical fiber, housing Fiber Bragg Gratings (FBGs) transducers, embedded into a soft polymeric material integrated on a rigid hand. Through several tasks involving grasps of different objects in various conditions, the ability of the system to acquire information is assessed. Results show that a classifier based on the sensor outputs of the robotic hand is capable of accurately detecting both size and rigidity of the operated objects (99.36 and 100% accuracy, respectively). Furthermore, the outputs provide evidence of the ability to grab fragile objects without breakage or slippage e and to perform dynamic manipulative tasks, that involve the adaptation of fingers position based on the grasped objects’ condition

The speaking vocabulary of grade two

Thesis (M.A.)--Boston Universit

Conversion of cytochrome c into a peroxidase: inhibitory mechanisms and implication for neurodegenerative diseases.

A further function of cytochrome c (cyt c), beyond respiration, is realized outside mitochondria in the apoptotic program. In the early events of apoptosis, the interaction of cyt c with a mitochondrion-specific phospholipid, cardiolipin (CL), brings about a conformational transition of the protein and acquirement of peroxidase activity. The hallmark of cyt c with peroxidase activity is its partial unfolding accompanied by loosening of the Fe sixth axial bond and an enhanced access of the heme catalytic site to small molecules like H2O2. To investigate the peroxidase activity of non-native cyt c, different forms of the protein were analyzed with the aim to correlate their structural features with the acquired enzymatic activity and apoptogenic properties (wt cyt c/CL complex and two single cyt c variants, H26Y and Y67H, free and bound to CL). The results suggest that cyt c may respond to different environments by changing its fold thus favouring the exertion of different biological functions in different pathophysiological cell conditions. Transitions among different conformations are regulated by endogenous molecules such as ATP and may be affected by synthetic molecules such as minocycline, thus suggesting a mechanism explaining its use as therapeutic agent impacting on disease-associated oxidative and apoptotic mechanisms

OLIMPIC : a 12-month study on the criteria driving retreatment with ranibizumab in patients with visual impairment due to myopic choroidal neovascularization

Purpose: To evaluate criteria driving retreatment with ranibizumab in Italian patients with myopic choroidal neovascularization (mCNV). Methods: OLIMPIC was a 12-month, phase IIIb, open-label study. Patients with active mCNV were treated with ranibizumab 0.5 mg according to the European label. The study assessed local criteria in Italy driving retreatment decisions with ranibizumab; and the efficacy, safety, and tolerability of ranibizumab. Results: The mean (standard deviation [SD]) age of treated patients (N = 200) was 61.8 (12.7) years; range 22\u201385 years. The multivariate regression model indicated that presence of active leakage (odds ratio [OR] 95% confidence interval [CI]: 11.30 [1.03\u2013124.14]), presence of intraretinal fluid (OR [95%CI]: 28.21 [1.55\u2013513.73]), and an improvement in best-corrected visual acuity (BCVA) from baseline < 10 letters (OR [95%CI]: 17.60 [1.39\u2013222.75]) were the factors with the greatest effect on retreatment with ranibizumab. The mean (SD) BCVA gain from baseline to month 12 was 8.4 (12.8) letters (P < 0.0001). The mean (SD) number of injections was 2.41 (1.53); range 1\u20139. Ocular and non-ocular adverse events were reported in 41 (20.5%) and 30 (15.0%) patients, respectively. Conclusions: Individualized treatment with ranibizumab was effective in improving BCVA in patients with mCNV over 12 months. Both anatomical and functional variables had significant effects on causing retreatment. There were no new safety findings. Trial registration: www.ClinicalTrials.Gov (NCT No: NCT02034006)

The key role played by charge in the interaction of cytochrome c with cardiolipin

Cytochrome c undergoes structural variations upon binding of cardiolipin, one of the phospholipids constituting the mitochondrial membrane. Although several mechanisms governing cytochrome c/cardiolipin (cyt c/CL) recognition have been proposed, the interpretation of the process remains, at least in part, unknown. To better define the steps characterizing the cyt c-CL interaction, the role of Lys72 and Lys73, two residues thought to be important in the protein/lipid binding interaction, were recently investigated by mutagenesis. The substitution of the two (positively charged) Lys residues with Asn revealed that such mutations cancel the CL-dependent peroxidase activity of cyt c; furthermore, CL does not interact with the Lys72Asn mutant. In the present paper, we extend our study to the Lys → Arg mutants to investigate the influence exerted by the charge possessed by the residues located at positions 72 and 73 on the cyt c/CL interaction. On the basis of the present work a number of overall conclusions can be drawn: (i) position 72 must be occupied by a positively charged residue to assure cyt c/CL recognition; (ii) the Arg residues located at positions 72 and 73 permit cyt c to react with CL; (iii) the replacement of Lys72 with Arg weakens the second (low-affinity) binding transition; (iv) the Lys73Arg mutation strongly increases the peroxidase activity of the CL-bound protein

The 40s Omega-loop plays a critical role in the stability and the alkaline conformational transition of cytochrome c

The structural and redox properties of a non-covalent complex reconstituted upon mixing two non-contiguous fragments of horse cytochrome c, the residues 1 - 38 heme-containing N-fragment with the residues 57 - 104 C-fragment, have been investigated. With respect to native cyt c, the complex lacks a segment of 18 residues, corresponding, in the native protein, to an omega ( W)loop region. The fragment complex shows compact structure, native-like alpha-helix content but a less rigid atomic packing and reduced stability with respect to the native protein. Structural heterogeneity is observed at pH 7.0, involving formation of an axially misligated low-spin species and consequent partial displacement of Met80 from the sixth coordination position of the heme-iron. Spectroscopic data suggest that a lysine ( located in the Met80-containing loop, namely Lys72, Lys73, or Lys79) replaces the methionine residue. The residues 1 - 38/57 - 104 fragment complex shows an unusual biphasic alkaline titration characterized by a low (pK(a1)= 6.72) and a high pK(a)-associated state transition (pK(a2)= 8.56); this behavior differs from that of native cyt c, which shows a monophasic alkaline transition ( pK(a)= 8.9). The data indicate that the 40s Omega-loop plays an important role in the stability of cyt c and in ensuring a correct alkaline conformational transition of the protein