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Two-dimensional (2D) materials and heterostructures are promising candidates for nanoelectronics. However, the quality of material interfaces often limits the performance of electronic devices made from atomically thick 2D materials and heterostructures. Atomic force microscopy (AFM) tip-based cleaning is a reliable technique to remove interface contaminants and flatten heterostructures. Here, we demonstrate AFM tip-based cleaning applied to hBN-encapsulated monolayer MoS2 transistors, which results in electrical performance improvements of the devices. To investigate the impact of cleaning on device performance, we compared the characteristics of as-transferred heterostructures and transistors before and after tip-based cleaning using photoluminescence (PL) and electronic measurements. The PL linewidth of monolayer MoS2 decreased from 84 meV before cleaning to 71 meV after cleaning. The extrinsic mobility of monolayer MoS2 field-effect transistors increased from 21 cm2/Vs before cleaning to 38 cm2/Vs after cleaning. Using the results from AFM topography, photoluminescence, and back-gated field-effect measurements, we infer that tip-based cleaning enhances the mobility of hBN-encapsulated monolayer MoS2 by reducing interface disorder. Finally, we fabricate a MoS2 field-effect transistor (FET) from a tip-cleaned heterostructure and achieved a device mobility of 73 cm2/Vs. The results of this work could be used to improve the electrical performance of heterostructure devices and other types of mechanically assembled van der Waals heterostructures.

Summary: Phase change materials (PCMs) having a large latent heat during solid-liquid phase transition are promising for thermal energy storage applications. However, the relatively low thermal conductivity of the majority of promising PCMs (

This paper describes a nickel-based cellular material, which has the strength of titanium and the density of water. The material’s strength arises from size-dependent strengthening of load-bearing nickel struts whose diameter is as small as 17 nm and whose 8 GPa yield strength exceeds that of bulk nickel by up to 4X. The mechanical properties of this material can be controlled by varying the nanometer-scale geometry, with strength varying over the range 90–880 MPa, modulus varying over the range 14–116 GPa, and density varying over the range 880–14500 kg/m3. We refer to this material as a “metallic wood,” because it has the high mechanical strength and chemical stability of metal, as well as a density close to that of natural materials such as wood.

Significance An important limitation of current assays for the detection of SARS-CoV-2 stems from their reliance on time-consuming, labor-intensive, and laboratory-based protocols for viral isolation, lysis, and removal of inhibiting materials. While RT-PCR remains the gold standard for performing clinical diagnostics to amplify the RNA sequences, there is an urgent need for alternative testing platforms that are rapid, accurate, simple, and portable. Here, we demonstrate isothermal RT-LAMP nucleic acid-based detection of SARS-CoV-2 with an additively manufactured cartridge and a smartphone-based instrument for testing that can be performed at the point of sample collection., The COVID-19 pandemic provides an urgent example where a gap exists between availability of state-of-the-art diagnostics and current needs. As assay protocols and primer sequences become widely known, many laboratories perform diagnostic tests using methods such as RT-PCR or reverse transcription loop mediated isothermal amplification (RT-LAMP). Here, we report an RT-LAMP isothermal assay for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and demonstrate the assay on clinical samples using a simple and accessible point-of-care (POC) instrument. We characterized the assay by dipping swabs into synthetic nasal fluid spiked with the virus, moving the swab to viral transport medium (VTM), and sampling a volume of the VTM to perform the RT-LAMP assay without an RNA extraction kit. The assay has a limit of detection (LOD) of 50 RNA copies per μL in the VTM solution within 30 min. We further demonstrate our assay by detecting SARS-CoV-2 viruses from 20 clinical samples. Finally, we demonstrate a portable and real-time POC device to detect SARS-CoV-2 from VTM samples using an additively manufactured three-dimensional cartridge and a smartphone-based reader. The POC system was tested using 10 clinical samples, and was able to detect SARS-CoV-2 from these clinical samples by distinguishing positive samples from negative samples after 30 min. The POC tests are in complete agreement with RT-PCR controls. This work demonstrates an alternative pathway for SARS-CoV-2 diagnostics that does not require conventional laboratory infrastructure, in settings where diagnosis is required at the point of sample collection.

Understanding the atomistic origin of defects in two-dimensional transition metal dichalcogenides, their impact on the electronic properties, and how to control them is critical for future electronics and optoelectronics. Here, we demonstrate the integration of thermochemical scanning probe lithography (tc-SPL) with a flow-through reactive gas cell to achieve nanoscale control of defects in monolayer MoS2. The tc-SPL produced defects can present either p- or n-type doping on demand, depending on the used gasses, allowing the realization of field effect transistors, and p-n junctions with precise sub-μm spatial control, and a rectification ratio of over 104. Doping and defects formation are elucidated by means of X-Ray photoelectron spectroscopy, scanning transmission electron microscopy, and density functional theory. We find that p-type doping in HCl/H2O atmosphere is related to the rearrangement of sulfur atoms, and the formation of protruding covalent S-S bonds on the surface. Alternatively, local heating MoS2 in N2 produces n-character.

The COVID-19 pandemic disrupted the world in 2020 by spreading at unprecedented rates and causing tens of thousands of fatalities within a few months. The number of deaths dramatically increased in regions where the number of patients in need of hospital care exceeded the availability of care. Many COVID-19 patients experience Acute Respiratory Distress Syndrome (ARDS), a condition that can be treated with mechanical ventilation. In response to the need for mechanical ventilators, designed and tested an emergency ventilator (EV) that can control a patient’s peak inspiratory pressure (PIP) and breathing rate, while keeping a positive end expiratory pressure (PEEP). This article describes the rapid design, prototyping, and testing of the EV. The development process was enabled by rapid design iterations using additive manufacturing (AM). In the initial design phase, iterations between design, AM, and testing enabled a working prototype within one week. The designs of the 16 different components of the ventilator were locked by additively manufacturing and testing a total of 283 parts having parametrically varied dimensions. In the second stage, AM was used to produce 75 functional prototypes to support engineering evaluation and animal testing. The devices were tested over more than two million cycles. We also developed an electronic monitoring system and with automatic alarm to provide for safe operation, along with training materials and user guides. The final designs are available online under a free license. The designs have been transferred to more than 70 organizations in 15 countries. This project demonstrates the potential for ultra-fast product design, engineering, and testing of medical devices needed for COVID-19 emergency response.

A scalable technique for making octet microlattice topology mechanical metamaterials with a cell size of 1 mm or less from thin stainless steel sheets is described. The microfabrication process used a perforation operation to form planar truss sheets by the periodic removal of rectangular shaped material. A simultaneous perforation and corrugation operation was also used to create a single layer of trusses with a pyramidal topology. A 3D lattice was then assembled by alternatively stacking the pyramidal and planar truss sheets, taking care to align their nodes to form the octet lattice truss topology. A vacuum brazing method was used to metallurgically bond the assembly. The compressive properties of the microlattices are shown to be comparable to those of much larger cell-size structures of similar material and topology. An assessment of geometric imperfection sensitivity indicates where further mechanical property improvements could be realized by improving the precision of both the perforation and assembly process. Keywords: Octet lattice, Microfabrication, Mechanical metamaterials, Mechanical properties

Osteoarthritis (OA) is a progressive and degenerative disease, which may result in significant pain and decreased quality of life. Recent updates in our understanding of OA have demonstrated that it is a whole joint disease that has many similarities to an unhealed wound containing inflammatory cytokines. The nSTRIDE Autologous Protein Solution (APS) Kit is a medical device under development for the treatment of OA. The APS Kit processes a patient's own blood at the point of care to contain high concentrations of anti-inflammatory cytokines and anabolic growth factors. This study assessed the safety and treatment effects of a single intra-articular injection of APS. Eleven patients were enrolled in this study. Sufficient blood could not be drawn from one patient who was subsequently withdrawn, leaving 10 patients treated. Minor adverse events (AEs) were experienced by seven subjects (63.6%). There was one serious AE (diverticulitis) unrelated to the device or procedure. One subject experienced AEs that were judged “likely” to be procedure related (arthralgia/musculoskeletal discomfort) and all resolved within 6 days of injection. All other AEs were unrelated to the device or procedure. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores improved significantly over time (ANOVA, p

Phase transitions in purple membrane have been a topic of debate for the past two decades. In this work we present studies of a reversible transition of purple membrane in the 50-60 °C range in zeptoliter volumes under different heating regimes (global heating and local heating). The temperature of the reversible phase transition is 52 ± 5 °C for both local and global heating, supporting the hypothesis that this transition is mainly due to a structural rearrangement of bR molecules and trimers. To achieve high resolution measurements of temperature-dependent phase transitions, a new scanning probe microscopy-based method was developed. We believe that our new technique can be extended to other biological systems and can contribute to the understanding of inhomogeneous phase transitions in complex systems.

Objectives: Determine the real-world difference\ud between 2 groups of patients with severe aortic\ud stenosis and similar baseline comorbidities: surgical\ud turn down (STD) patients, who were managed\ud medically prior to the availability of transcatheter aortic\ud valve implantation (TAVI) following formal surgical\ud outpatient assessment, and patients managed with a\ud TAVI implant.\ud Design: Retrospective cohort study from real-world\ud data.\ud Setting: Electronic patient letters were searched for\ud patients with a diagnosis of severe aortic stenosis and\ud a formal outpatient STD prior to the availability of TAVI\ud (1999–2009). The second group comprised the first 90\ud cases of TAVI in South Wales (2009 onwards). 2 years\ud prior to and 5 years following TAVI/STD were assessed.\ud Patient data were pseudoanonymised, using the Secure\ud Anonymized Information Linkage (SAIL) databank, and\ud extracted from Office National Statistics (ONS), PatientEpisode\ud Database for Wales (PEDW) and general\ud practitioner databases.\ud Population: 90 patients who had undergone TAVI in\ud South Wales, and 65 STD patients who were medically\ud managed.\ud Main outcome measures: Survival, hospital\ud admission frequency and length of stay, primary care\ud visits, and cost-effectiveness.\ud Results: TAVI patients were significantly older (81.8 vs\ud 79.2), more likely to be male (59.1% vs 49.3%),\ud baseline comorbidities were balanced. Mortality in TAVI\ud versus STD was 28% vs 70% at 1000 days follow-up.\ud There were significantly more hospital admissions per\ud year in the TAVI group prior to TAVI/STD (1.5 (IQR 1.0–\ud 2.4) vs 1.0 IQR (0.5–1.5)). Post TAVI/STD, the TAVI\ud group had significantly lower hospital admissions (0.3\ud (IQR 0.0–1.0) vs 1.2 (IQR 0.7–3.0)) and lengths of stay\ud (0.4 (IQR 0.0–13.8) vs 11.0 (IQR 2.5–28.5), p

The CD8+ T-cell response comprises terminally differentiated effector cells and antigen-experienced memory T cells. The latter encompass central (TCM) and effector (TEM) memory cells. TCM cells are superior in their protection against viral and bacterial challenges and mediation of antitumor immunity due to their higher proliferative ability upon antigen re-encounter. Defining a mechanism to enhance TCM cells and delay terminal differentiation of CD8+ T cells is crucial for cancer immune therapy, as it can promote a better tumor immune response. The differentiation of CD8+ memory T cells is thought to be coordinated by the phosphoinositide 3-kinase (PI3K)/Akt pathway. We, therefore, investigated the role of Akt isoforms in the differentiation and proliferation of memory CD8+ T cells. We found that Akt1 and Akt2, but not Akt3, drive the terminal differentiation of CD8+ T cells, and their inhibition enhances the therapeutically superior TCM phenotype. Furthermore, the inhibition of Akt1 and Akt2, but not Akt 3, delays CD8+ T-cell exhaustion and preserves naïve and TCM CD8+ T cells, thus enhancing their proliferative ability and survival and prolonging their cytokine and Granzyme B production ability. Here, we define a mechanism in which proliferative potential, function, and survival of CD8+ T cells are enhanced by maintaining a reservoir of TCM and naïve cells using only Akt1 and Akt2 inhibition. Therefore, our findings strongly suggest the utility of using Akt1 and Akt2 inhibitors to modulate CD8+ T cells, both for adoptive cell transfer and vaccine-based cancer immune therapies.

I; Our goal is to understand the evolution of the structure and function of cholinesterases (ChEs) in the deuterostome lineage and in particular to understand the role of paralogous enzymes such as the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) of the vertebrates. We have, in the past, characterized ChEs in two acraniate deuterostomes: amphioxus (a cephalochordate) and Ciona intestinalis (a urochordate). Here we present results on an AChE from a basal deuterostome, a model hemichordate, the acorn worm Saccoglossus kowalevskii. Of the eight genes coding for putative ChE-like proteins possessing Trp84, a characteristic of the choline-binding catalytic subsite of ChEs, we cloned a full length cDNA with a coding sequence typical of an acraniate AChE possessing a C-terminal exon coding for a typical T-peptide. We then used in vitro expression of the cDNA in COS-7 cells to characterize the AChE kinetically, pharmacologically, and biochemically. The cDNA codes for an AChE (AChE1), which is found in monomeric (G(1)), dimeric (G(2)), and tetrameric (G(4)) forms; and interacts with poly-L-proline, PRiMA, and ColQ characteristic of an AChE possessing a T-peptide:The expression of the AChE is temperature dependent, with greater expression at 30 degrees C. We discuss the implications of these data for the evolution of the ChEs in the deuterostomes.

MEMS resonant mass sensors can measure the mass of individual cells, though long-term growth measurements are limited by the movement of cells off the sensor area. Micro-patterning techniques are a powerful approach to control the placement of individual cells in an arrayed format. In this work we present a method for micro-patterning cells on fully suspended resonant sensors through select functionalization and passivation of the chip surface. This method combines high-resolution photolithography with a blanket transfer technique for applying photoresist to avoid damaging the sensors. Cells are constrained to the patterned collagen area on the sensor by pluronic acting as a cell adhesion blocker. This micro-patterning method enables long-term growth measurements, which is demonstrated by a measurement of the change in mass of a human breast cancer cell over 18 h.

The localized temperature-dependent piezoelectric response of ferroelectric barium strontium titanate (BST) thin films is studied using an electro-thermal (ET) nanoprobe. The ET probe provides independent electrical and thermal excitation to a nanometer-scale volume of the specimen and is capable of detecting the phase transition temperature of the BST thin films. The piezoresponse measured by the ET probe follows the temperature dependence of the piezoelectric constant, whereas with bulk heating the response follows the temperature dependence of the spontaneous polarization. The observed differences stem from the localized inhomogeneous electro-thermal field distribution at the specimen. © 2012 American Institute of Physics.

Immunoassays for detection of bacterial pathogens rely on the selectivity and stability of bio-recognition elements such as antibodies tethered to sensor surfaces. The search for novel surfaces that improve the stability of biomolecules and assay performance has been pursued for a long time. However, the anticipated improvements in stability have not been realized in practice under physiological conditions because the surface functionalization layers on commonly used substrates, silica and gold, are themselves unstable on time scales of days. In this paper, we show that covalent linking of antibodies to diamond surfaces leads to substantial improvements in biological activity of proteins as measured by the ability to selectively capture cells of the pathogenic bacterium Escherichia coli O157:H7 Escherichia coli O157:H7 even after exposure to buffer solutions at 37 oC for extended periods of time, approaching 2 weeks. Our results from ELISA, XPS, fl uorescence microscopy, and MD simulations suggest that by using highly stable surface chemistry and controlling the nanoscale organization of the antibodies on the surface, it is possible to achieve signifi cant improvements in biological activity and stability. Our fi ndings can be easily extended to functionalization of micro and nanodimensional sensors and structures of biomedical diagnostic and therapeutic interest.

Writing Conductive Lines with Hot Tips The interface within devices between conductors, semiconductors, and insulators is usually created by stacking patterned layers of different materials. For flexible electronics, it can be advantageous to avoid this architectural constraint. Graphene oxide, formed by chemical exfoliation of graphite, can be reduced to a more conductive form using chemical reductants. Wei et al. (p. 1373 ) now show that layers of graphene oxide can also be reduced using a hot atomic force microscope tip to create materials comparable to those of organic conductors. This process can create patterned regions (down to 12 nanometers in width) that differ in conductivity by up to four orders of magnitude.

Nanoscale chemical patterning of different chemical species (amine, thiol, aldehyde, and biotin) in independent nanopatterns is achieved by the iterative application of thermochemical nanolithography (TCN L) to inscribe amine patterns followed by their chemical conversion to other functional groups. Due to the unique chemical stability of the patterns, the resultant substrates can be stored for weeks and subsequently be used for covalent and molecular-recognition-based attachment of nano-objects using standard chemical protocols. In particular, the ability of this method to attach proteins and DNA to the chemical nanopatterns and to create co-patterns of two distinctive bioactive proteins is demonstrated.

A heater design, used in a micro-calorimetric sensor, has been optimized for temperature uniformity and the sensor has been used for detection of trace amounts of explosives. In this abstract the design, characterization and functionality is described. The performance of the novel heater design is characterized by measuring the Temperature Coefficient of Resistivity (TCR) values and by mapping the temperature distribution using Raman spectroscopy. The new heater design has increased the temperature uniformity and calorimetric measurements on DNT (2,4-Dinitrotoluene) show more reproducible and better defined signals.

Cell-extracellular matrix (ECM) and cell-cell interactions regulate keratinocyte cell fate and differentiation. In the present analysis, we examined the differentiation of primary human keratinocytes cultured on micropatterned substrates that varied the extent of cell-cell contact while maintaining constant cell-ECM areas. Bowtie-shaped micropatterned areas (75-1600 microm(2)) were engineered to either permit or prevent cell-cell contact for pairs of adherent keratinocytes. Cell pairs with direct cell-cell contact exhibited enhanced expression of the differentiation markers involucrin and keratin 10 compared to cells with no cell-cell contact. In contrast, available cell-spreading area, as regulated by pattern size, did not alter keratinocyte involucrin expression. Disruption of E-cadherin binding by either antibody blocking or expression of a dominant-negative receptor diminished the ability of micropattern-regulated cell-cell contact to modulate involucrin expression. These results demonstrate that cadherin-mediated cell-cell contact regulates early keratinocyte differentiation independently from changes in cell shape.

Background There has been debate on which blood components should be included in autologous therapies. Autologous Protein Solution (APS) is a unique blood-derived therapy composed of concentrated white blood cells, platelets, and plasma to contain high concentrations of anti-inflammatory cytokines and anabolic growth factors to potentially address osteoarthritis. The primary aim of the exploratory secondary analysis was to identify characteristics of an Autologous Protein Solution (APS) that may correlate with improved Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and OMERACT-OARSI responder status after treatment of subjects with an intra-articular injection of APS. Methods Eleven subjects were enrolled in a pilot study of a single intra-articular injection of APS in subjects with knee osteoarthritis. Two APS kits were processed per patient. The output of the first APS kit was injected intra-articularly. White blood cell (WBC) and cytokine concentrations were measured from the output of the second APS kit. WOMAC surveys were completed at baseline and at follow up visits. Linear regression analyses were performed on the blood components of APS with subject outcomes. Anderson-Darling analysis was used to determine whether the cytokine concentrations in whole blood and APS had a normal distribution. Either paired t-test analyses or Wilcoxon signed-rank analyses were performed for normal and non-parametrically distributed data, respectively. Results The WBC concentration in APS was significantly (p 0.7) correlated with IL-1ra in APS but not significantly correlated with IL-1β. The ratio of IL-1ra to IL-1β in APS was significantly correlated with improved WOMAC pain scores one week and six months post-injection. 85.7 % of subjects whose APS had a IL-1ra:IL-1β ratio greater than 1000 or a WBC count greater than 30 k/μl were OMERACT-OARSI responders six months post-injection. Conclusions The correlations between the IL-1ra:IL-1β ratio and WBC concentration in a subject’s APS and their WOMAC pain scores and classification as OMERACT-OARSI responders suggest the potential utility of these characteristics as diagnostic markers. Additional studies are ongoing to determine whether APS is safe and effective and to further evaluate the relationship between APS composition and clinical outcomes. Trial Registration (NCT01773226) Electronic supplementary material The online version of this article (doi:10.1186/s40634-016-0043-7) contains supplementary material, which is available to authorized users.

Background Abnormal NF-κB2 activation has been implicated in the pathogenesis of multiple myeloma, a cancer of plasma cells. However, a causal role for aberrant NF-κB2 signaling in the development of plasma cell tumors has not been established. Also unclear is the molecular mechanism that drives the tumorigenic process. We investigated these questions by using a transgenic mouse model with lymphocyte-targeted expression of p80HT, a lymphoma-associated NF-κB2 mutant, and human multiple myeloma cell lines. Methods We conducted a detailed histopathological characterization of lymphomas developed in p80HT transgenic mice and microarray gene expression profiling of p80HT B cells with the goal of identifying genes that drive plasma cell tumor development. We further verified the significance of our findings in human multiple myeloma cell lines. Results Approximately 40% of p80HT mice showed elevated levels of monoclonal immunoglobulin (M-protein) in the serum and developed plasma cell tumors. Some of these mice displayed key features of human multiple myeloma with accumulation of plasma cells in the bone marrow, osteolytic bone lesions and/or diffuse osteoporosis. Gene expression profiling of B cells from M-protein-positive p80HT mice revealed aberrant expression of genes known to be important in the pathogenesis of multiple myeloma, including cyclin D1, cyclin D2, Blimp1, survivin, IL-10 and IL-15. In vitro assays demonstrated a critical role of Stat3, a key downstream component of IL-10 signaling, in the survival of human multiple myeloma cells. Conclusions These findings provide a mouse model for human multiple myeloma with aberrant NF-κB2 activation and suggest a molecular mechanism for NF-κB2 signaling in the pathogenesis of plasma cell tumors by coordinated regulation of plasma cell generation, proliferation and survival.