Graphene Strain-Effect Transistor with Colossal ON/OFF Current Ratio Enabled by Reversible Nanocrack Formation in Metal Electrodes on Piezoelectric Substrates.

Extraordinarily high carrier mobility in graphene has led to many remarkable discoveries in physics and at the same time invoked great interest in graphene-based electronic devices and sensors. However, the poor ON/OFF current ratio observed in graphene field-effect transistors has stymied its use in many applications. Here, we introduce a graphene strain-effect transistor (GSET) with a colossal ON/OFF current ratio in excess of 107 by exploiting strain-induced reversible nanocrack formation in the source/drain metal contacts with the help of a piezoelectric gate stack. GSETs also exhibit steep switching with a subthreshold swing (SS) < 1 mV/decade averaged over ∼6 orders of magnitude change in the source-to-drain current for both electron and hole branch amidst a finite hysteresis window. We also demonstrate high device yield and strain endurance for GSETs. We believe that GSETs can significantly expand the application space for graphene-based technologies beyond what is currently envisioned.

An Ultra-steep Slope Two-dimensional Strain Effect Transistor.

We introduce a high-performance and ultra-steep slope switch, referred to as strain effect transistor (SET), with a subthreshold swing < 0.68 mV/decade at room temperature for 7 orders of magnitude change in the source-to-drain current based on atomically thin 1T'-MoTe2 as the channel material, piezoelectric lead zirconate titanate (PZT) as the gate dielectric, and nickel (Ni) as the source/drain contact metal. We exploit gate-voltage induced strain transduction in PZT leading to abrupt and reversible cracking of the metal contacts to achieve the abrupt switching. The SET also exhibits a low OFF-state current < 1 pA/µm, a high ON-state current > 1.8 mA/µm at a supply voltage of 1 V, a large current ON/OFF ratio > 1 × 109, and a high transconductance of > 100 µS/µm. The switching delay for the SET was found to be < 5 µs, and no device failure was observed even after 1 million (1 × 106) switching cycles.

Comparative genome analysis of mycobacteria focusing on tRNA and non-coding RNA.

BACKGROUND: The Mycobacterium genus encompasses at least 192 named species, many of which cause severe diseases such as tuberculosis. Non-tuberculosis mycobacteria (NTM) can also infect humans and animals. Some are of emerging concern because they show high resistance to commonly used antibiotics while others are used and evaluated in bioremediation or included in anticancer vaccines. RESULTS: We provide the genome sequences for 114 mycobacterial type strains and together with 130 available mycobacterial genomes we generated a phylogenetic tree based on 387 core genes and supported by average nucleotide identity (ANI) data. The 244 genome sequences cover most of the species constituting the Mycobacterium genus. The genome sizes ranged from 3.2 to 8.1 Mb with an average of 5.7 Mb, and we identified 14 new plasmids. Moreover, mycobacterial genomes consisted of phage-like sequences ranging between 0 and 4.64% dependent on mycobacteria while the number of IS elements varied between 1 and 290. Our data also revealed that, depending on the mycobacteria, the number of tRNA and non-coding (nc) RNA genes differ and that their positions on the chromosome varied. We identified a conserved core set of 12 ncRNAs, 43 tRNAs and 18 aminoacyl-tRNA synthetases among mycobacteria. CONCLUSIONS: Phages, IS elements, tRNA and ncRNAs appear to have contributed to the evolution of the Mycobacterium genus where several tRNA and ncRNA genes have been horizontally transferred. On the basis of our phylogenetic analysis, we identified several isolates of unnamed species as new mycobacterial species or strains of known mycobacteria. The predicted number of coding sequences correlates with genome size while the number of tRNA, rRNA and ncRNA genes does not. Together these findings expand our insight into the evolution of the Mycobacterium genus and as such they establish a platform to understand mycobacterial pathogenicity, their evolution, antibiotic resistance/tolerance as well as the function and evolution of ncRNA among mycobacteria.

Comparative genomics of Mycobacterium mucogenicum and Mycobacterium neoaurum clade members emphasizing tRNA and non-coding RNA.

BACKGROUND: Mycobacteria occupy various ecological niches and can be isolated from soil, tap water and ground water. Several cause diseases in humans and animals. To get deeper insight into our understanding of mycobacterial evolution focusing on tRNA and non-coding (nc)RNA, we conducted a comparative genome analysis of Mycobacterium mucogenicum (Mmuc) and Mycobacterium neoaurum (Mneo) clade members. RESULTS: Genome sizes for Mmuc- and Mneo-clade members vary between 5.4 and 6.5 Mbps with the complete MmucT (type strain) genome encompassing 6.1 Mbp. The number of tRNA genes range between 46 and 79 (including one pseudo tRNA gene) with 39 tRNA genes common among the members of these clades, while additional tRNA genes were probably acquired through horizontal gene transfer. Selected tRNAs and ncRNAs (RNase P RNA, tmRNA, 4.5S RNA, Ms1 RNA and 6C RNA) are expressed, and the levels for several of these are higher in stationary phase compared to exponentially growing cells. The rare tRNAIleTAT isoacceptor and two for mycobacteria novel ncRNAs: the Lactobacillales-derived GOLLD RNA and a homolog to the antisense Salmonella typhimurium phage Sar RNA, were shown to be present and expressed in certain Mmuc-clade members. CONCLUSIONS: Phages, IS elements, horizontally transferred tRNA gene clusters, and phage-derived ncRNAs appears to have influenced the evolution of the Mmuc- and Mneo-clades. While the number of predicted coding sequences correlates with genome size, the number of tRNA coding genes does not. The majority of the tRNA genes in mycobacteria are transcribed mainly from single genes and the levels of certain ncRNAs, including RNase P RNA (essential for the processing of tRNAs), are higher at stationary phase compared to exponentially growing cells. We provide supporting evidence that Ms1 RNA represents a mycobacterial 6S RNA variant. The evolutionary routes for the ncRNAs RNase P RNA, tmRNA and Ms1 RNA are different from that of the core genes.

Quantification of stochastic noise of splicing and polyadenylation in Entamoeba histolytica.

Alternative splicing and polyadenylation were observed pervasively in eukaryotic messenger RNAs. These alternative isoforms could either be consequences of physiological regulation or stochastic noise of RNA processing. To quantify the extent of stochastic noise in splicing and polyadenylation, we analyzed the alternative usage of splicing and polyadenylation sites in Entamoeba histolytica using RNA-Seq. First, we identified a large number of rarely spliced alternative junctions and then showed that the occurrence of these alternative splicing events is correlated with splicing site sequence, occurrence of constitutive splicing events and messenger RNA abundance. Our results implied the majority of these alternative splicing events are likely to be stochastic error of splicing machineries, and we estimated the corresponding error rates. Second, we observed extensive microheterogeneity of polyadenylation cleavage sites, and the extent of such microheterogeneity is correlated with the occurrence of constitutive cleavage events, suggesting most of such microheterogeneity is likely to be stochastic. Overall, we only observed a small fraction of alternative splicing and polyadenylation isoforms that are unlikely to be solely stochastic, implying the functional relevance of alternative splicing and polyadenylation in E. histolytica is limited. Lastly, we revised the gene models and annotated their 3'UTR in AmoebaDB, providing valuable resources to the community.

Cardiac biopsies reveal differences in transcriptomics between left and right ventricle in patients with or without diagnostic signs of heart failure.

New or mild heart failure (HF) is mainly caused by left ventricular dysfunction. We hypothesised that gene expression differ between the left (LV) and right ventricle (RV) and secondly by type of LV dysfunction. We compared gene expression through myocardial biopsies from LV and RV of patients undergoing elective coronary bypass surgery (CABG). Patients were categorised based on LV ejection fraction (EF), diastolic function and NT-proBNP into pEF (preserved; LVEF ≥ 45%), rEF (reduced; LVEF < 45%) or normal LV function. Principal component analysis of gene expression displayed two clusters corresponding to LV and RV. Up-regulated genes in LV included natriuretic peptides NPPA and NPPB, transcription factors/coactivators STAT4 and VGLL2, ion channel related HCN2 and LRRC38 associated with cardiac muscle contraction, cytoskeleton, and cellular component movement. Patients with pEF phenotype versus normal differed in gene expression predominantly in LV, supporting that diastolic dysfunction and structural changes reflect early LV disease in pEF. DKK2 was overexpressed in LV of HFpEF phenotype, potentially leading to lower expression levels of ß-catenin, α-SMA (smooth muscle actin), and enhanced apoptosis, and could be a possible factor in the development of HFpEF. CXCL14 was down-regulated in both pEF and rEF, and may play a role to promote development of HF.

Genetic heterogeneity revealed by sequence analysis of Mycobacterium tuberculosis isolates from extra-pulmonary tuberculosis patients.

BACKGROUND: Tuberculosis remains a major public health problem. Clinical tuberculosis manifests often as pulmonary and occasionally as extra-pulmonary tuberculosis. The emergence of drug resistant tubercle bacilli and its association with HIV is a formidable challenge to curb the spread of tuberculosis. There have been concerted efforts by whole genome sequencing and bioinformatics analysis to identify genomic patterns and to establish a relationship between the genotype of the organism and clinical manifestation of tuberculosis. Extra-pulmonary TB constitutes 15-20 percent of the total clinical cases of tuberculosis reported among immunocompetent patients, whereas among HIV patients the incidence is more than 50 percent. Genomic analysis of M. tuberculosis isolates from extra pulmonary patients has not been explored. RESULTS: The genomic DNA of 5 extra-pulmonary clinical isolates of M. tuberculosis derived from cerebrospinal fluid, lymph node fine needle aspirates (FNAC) / biopsies, were sequenced. Next generation sequencing approach (NGS) was employed to identify Single Nucleotide Variations (SNVs) and computational methods used to predict their consequence on functional genes. Analysis of distribution of SNVs led to the finding that there are mixed genotypes in patient isolates and that many SNVs are likely to influence either gene function or their expression. Phylogenetic relationship between the isolates correlated with the origin of the isolates. In addition, insertion sites of IS elements were identified and their distribution revealed a variation in number and position of the element in the 5 extra-pulmonary isolates compared to the reference M. tuberculosis H37Rv strain. CONCLUSIONS: The results suggest that NGS sequencing is able to identify small variations in genomes of M. tuberculosis isolates including changes in IS element insertion sites. Moreover, variations in isolates of M. tuberculosis from non-pulmonary sites were documented. The analysis of our results indicates genomic heterogeneity in the clinical isolates.

Digital Keying Enabled by Reconfigurable 2D Modulators.

Energy, area, and bandwidth efficient communication primitives are essential to sustain the rapid increase in connectivity among internet-of-things (IoT) edge devices. While IoT edge-sensing, edge-computing, and edge-storage have witnessed innovation in materials and devices, IoT edge communication is yet to experience such transformation. The aging silicon (Si)-based complementary metal-oxide-semiconductor (CMOS) technology continues to remain the mainstay of communication devices where they are used to implement amplitude, frequency, and phase shift keying (amplitude-shift keying [ASK]/frequency-shift keying [FSK]/phase-shift keying [PSK]). Keying allows digital information to be communicated over a radio channel. While CMOS-based keying devices have evolved over the years, their hardware footprint and energy consumption are major concerns for resource constrained IoT communication. Furthermore, separate circuit designs and hardware elements are needed for each keying scheme and achieving multibit modulation to improve bandwidth efficiency remains a challenge. Here, a reconfigurable modulator is introduced that exploits unique ambipolar transport and programmable Dirac voltage in ultrathin MoTe2 field-effect transistors to achieve ASK, FSK, and PSK modulation. Furthermore, by integrating two programmed MoTe2 field-effect transistors, multibit data modulation is demonstrated, which improves the bandwidth efficiency by 200%. Finally, a frequency quadrupler is also realized exploiting the unique "double-well" transfer characteristic.

An Annealing Accelerator for Ising Spin Systems Based on In-Memory Complementary 2D FETs.

Metaheuristic algorithms such as simulated annealing (SA) are often implemented for optimization in combinatorial problems, especially for discreet problems. SA employs a stochastic search, where high-energy transitions ("hill-climbing") are allowed with a temperature-dependent probability to escape local optima. Ising spin glass systems have properties such as spin disorder and "frustration" and provide a discreet combinatorial problem with a high number of metastable states and ground-state degeneracy. In this work, subthreshold Boltzmann transport is exploited in complementary 2D field-effect transistors (p-type WSe2 and n-type MoS2 ) integrated with an analog, nonvolatile, and programmable floating-gate memory stack to develop in-memory computing primitives necessary for energy- and area-efficient hardware acceleration of SA for Ising spin systems. Search acceleration of >800× is demonstrated for 4 × 4 ferromagnetic, antiferromagnetic, and spin glass systems using SA compared to an exhaustive search using a brute force trial at miniscule total energy expenditure of ≈120 nJ. The hardware-realistic numerical simulations further highlight the astounding benefits of SA in accelerating the search for larger spin lattices.

A biomimetic neural encoder for spiking neural network.

Spiking neural networks (SNNs) promise to bridge the gap between artificial neural networks (ANNs) and biological neural networks (BNNs) by exploiting biologically plausible neurons that offer faster inference, lower energy expenditure, and event-driven information processing capabilities. However, implementation of SNNs in future neuromorphic hardware requires hardware encoders analogous to the sensory neurons, which convert external/internal stimulus into spike trains based on specific neural algorithm along with inherent stochasticity. Unfortunately, conventional solid-state transducers are inadequate for this purpose necessitating the development of neural encoders to serve the growing need of neuromorphic computing. Here, we demonstrate a biomimetic device based on a dual gated MoS2 field effect transistor (FET) capable of encoding analog signals into stochastic spike trains following various neural encoding algorithms such as rate-based encoding, spike timing-based encoding, and spike count-based encoding. Two important aspects of neural encoding, namely, dynamic range and encoding precision are also captured in our demonstration. Furthermore, the encoding energy was found to be as frugal as ≈1-5 pJ/spike. Finally, we show fast (≈200 timesteps) encoding of the MNIST data set using our biomimetic device followed by more than 91% accurate inference using a trained SNN.

ABWGAT: anchor-based whole genome analysis tool.

SUMMARY: Large numbers of genomes are being sequenced regularly and the rate will go up in future due to availability of new genome sequencing techniques. In order to understand genotype to phenotype relationships, it is necessary to identify sequence variations at the genomic level. Alignment of a pair of genomes and parsing the alignment data is an accepted approach for identification of variations. Though there are a number of tools available for whole-genome alignment, none of these allows automatic parsing of the alignment and identification of different kinds of genomic variants with high degree of sensitivity. Here we present a simple web-based interface for whole genome comparison named ABWGAT (Anchor-Based Whole Genome Analysis Tool) that is simple to use. The output is a list of variations such as SNVs, indels, repeat expansion and inversion. AVAILABILITY: The web server is freely available to non-commercial users at the following address http://abwgc.jnu.ac.in/_sarba. Supplementary data are available at http://abwgc.jnu.ac.in/_sarba/cgi-bin/abwgc_retrival.cgi using job id 524, 526 and 528. CONTACT: dsarbashis@gmail.com; alok.bhattacharya@gmail.com

Author Correction: Extensive genomic diversity among Mycobacterium marinum strains revealed by whole genome sequencing.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A biomimetic 2D transistor for audiomorphic computing.

In this article, we introduce a biomimetic audiomorphic device that captures the neurobiological architecture and computational map inside the auditory cortex of barn owl known for its exceptional hunting ability in complete darkness using auditory cues. The device consists of multiple split-gates with nanogaps on a semiconducting MoS2 channel connected to the source/drain contacts for imitating the spatial map of coincidence detector neurons and tunable RC circuits for imitating the interaural time delay neurons following the Jeffress model of sound localization. Furthermore, we use global back-gating capability to demonstrate neuroplasticity to capture behavioral and/or adaptation related changes in the barn owl. Finally, the virtual source model for current transport is combined with finite element COMSOL multiphysics simulations to explain and project the performance of the biomimetic audiomorphic device. We find that the precision of the biomimetic device can supersede the barn owl by orders of magnitude.

Extended insight into the Mycobacterium chelonae-abscessus complex through whole genome sequencing of Mycobacterium salmoniphilum outbreak and Mycobacterium salmoniphilum-like strains.

Members of the Mycobacterium chelonae-abscessus complex (MCAC) are close to the mycobacterial ancestor and includes both human, animal and fish pathogens. We present the genomes of 14 members of this complex: the complete genomes of Mycobacterium salmoniphilum and Mycobacterium chelonae type strains, seven M. salmoniphilum isolates, and five M. salmoniphilum-like strains including strains isolated during an outbreak in an animal facility at Uppsala University. Average nucleotide identity (ANI) analysis and core gene phylogeny revealed that the M. salmoniphilum-like strains are variants of the human pathogen Mycobacterium franklinii and phylogenetically close to Mycobacterium abscessus. Our data further suggested that M. salmoniphilum separates into three branches named group I, II and III with the M. salmoniphilum type strain belonging to group II. Among predicted virulence factors, the presence of phospholipase C (plcC), which is a major virulence factor that makes M. abscessus highly cytotoxic to mouse macrophages, and that M. franklinii originally was isolated from infected humans make it plausible that the outbreak in the animal facility was caused by a M. salmoniphilum-like strain. Interestingly, M. salmoniphilum-like was isolated from tap water suggesting that it can be present in the environment. Moreover, we predicted the presence of mutational hotspots in the M. salmoniphilum isolates and 26% of these hotspots overlap with genes categorized as having roles in virulence, disease and defense. We also provide data about key genes involved in transcription and translation such as sigma factor, ribosomal protein and tRNA genes.

Transcriptomics of cardiac biopsies reveals differences in patients with or without diagnostic parameters for heart failure with preserved ejection fraction.

Heart failure affects 2-3% of adult Western population. Prevalence of heart failure with preserved left ventricular (LV) ejection fraction (HFpEF) increases. Studies suggest HFpEF patients to have altered myocardial structure and functional changes such as incomplete relaxation and increased cardiac stiffness. We hypothesised that patients undergoing elective coronary bypass surgery (CABG) with HFpEF characteristics would show distinctive gene expression compared to patients with normal LV physiology. Myocardial biopsies for mRNA expression analysis were obtained from sixteen patients with LV ejection fraction ≥45%. Five out of 16 patients (31%) had echocardiographic characteristics and increased NTproBNP levels indicative of HFpEF and this group was used as HFpEF proxy, while 11 patients had Normal LV physiology. Utilising principal component analysis, the gene expression data clustered into two groups, corresponding to HFpEF proxy and Normal physiology, and 743 differentially expressed genes were identified. The associated top biological functions were cardiac muscle contraction, oxidative phosphorylation, cellular remodelling and matrix organisation. Our results also indicate that upstream regulatory events, including inhibition of transcription factors STAT4, SRF and TP53, and activation of transcription repressors HEY2 and KDM5A, could provide explanatory mechanisms to observed gene expression differences and ultimately cardiac dysfunction in the HFpEF proxy group.

Extensive genomic diversity among Mycobacterium marinum strains revealed by whole genome sequencing.

Mycobacterium marinum is the causative agent for the tuberculosis-like disease mycobacteriosis in fish and skin lesions in humans. Ubiquitous in its geographical distribution, M. marinum is known to occupy diverse fish as hosts. However, information about its genomic diversity is limited. Here, we provide the genome sequences for 15 M. marinum strains isolated from infected humans and fish. Comparative genomic analysis of these and four available genomes of the M. marinum strains M, E11, MB2 and Europe reveal high genomic diversity among the strains, leading to the conclusion that M. marinum should be divided into two different clusters, the "M"- and the "Aronson"-type. We suggest that these two clusters should be considered to represent two M. marinum subspecies. Our data also show that the M. marinum pan-genome for both groups is open and expanding and we provide data showing high number of mutational hotspots in M. marinum relative to other mycobacteria such as Mycobacterium tuberculosis. This high genomic diversity might be related to the ability of M. marinum to occupy different ecological niches.

The Mycobacterium phlei Genome: Expectations and Surprises.

Mycobacterium phlei, a nontuberculosis mycobacterial species, was first described in 1898-1899. We present the complete genome sequence for theM. phlei CCUG21000(T)type strain and the draft genomes for four additional strains. The genome size for all five is 5.3 Mb with 69.4% Guanine-Cytosine content. This is ≈0.35 Mbp smaller than the previously reported M. phlei RIVM draft genome. The size difference is attributed partly to large bacteriophage sequence fragments in theM. phlei RIVM genome. Comparative analysis revealed the following: 1) A CRISPR system similar to Type 1E (cas3) in M. phlei RIVM; 2) genes involved in polyamine metabolism and transport (potAD,potF) that are absent in other mycobacteria, and 3) strain-specific variations in the number of σ-factor genes. Moreover,M. phlei has as many as 82 mce(mammalian cell entry) homologs and many of the horizontally acquired genes in M. phlei are present in other environmental bacteria including mycobacteria that share similar habitat. Phylogenetic analysis based on 693 Mycobacterium core genes present in all complete mycobacterial genomes suggested that its closest neighbor is Mycobacterium smegmatis JS623 and Mycobacterium rhodesiae NBB3, while it is more distant toM. smegmatis mc2 155.

Characterization of Three Mycobacterium spp. with Potential Use in Bioremediation by Genome Sequencing and Comparative Genomics.

We provide the genome sequences of the type strains of the polychlorophenol-degrading Mycobacterium chlorophenolicum (DSM43826), the degrader of chlorinated aliphatics Mycobacterium chubuense (DSM44219) and Mycobacterium obuense (DSM44075) that has been tested for use in cancer immunotherapy. The genome sizes of M. chlorophenolicum, M. chubuense, and M. obuense are 6.93, 5.95, and 5.58 Mb with GC-contents of 68.4%, 69.2%, and 67.9%, respectively. Comparative genomic analysis revealed that 3,254 genes are common and we predicted approximately 250 genes acquired through horizontal gene transfer from different sources including proteobacteria. The data also showed that the biodegrading Mycobacterium spp. NBB4, also referred to as M. chubuense NBB4, is distantly related to the M. chubuense type strain and should be considered as a separate species, we suggest it to be named Mycobacterium ethylenense NBB4. Among different categories we identified genes with potential roles in: biodegradation of aromatic compounds and copper homeostasis. These are the first nonpathogenic Mycobacterium spp. found harboring genes involved in copper homeostasis. These findings would therefore provide insight into the role of this group of Mycobacterium spp. in bioremediation as well as the evolution of copper homeostasis within the Mycobacterium genus.

Comparative Sigma Factor-mRNA Levels in Mycobacterium marinum under Stress Conditions and during Host Infection.

We have used RNASeq and qRT-PCR to study mRNA levels for all σ-factors in different Mycobacterium marinum strains under various growth and stress conditions. We also studied their levels in M. marinum from infected fish and mosquito larvae. The annotated σ-factors were expressed and transcripts varied in relation to growth and stress conditions. Some were highly abundant such as sigA, sigB, sigC, sigD, sigE and sigH while others were not. The σ-factor mRNA profiles were similar after heat stress, during infection of fish and mosquito larvae. The similarity also applies to some of the known heat shock genes such as the α-crystallin gene. Therefore, it seems probable that the physiological state of M. marinum is similar when exposed to these different conditions. Moreover, the mosquito larvae data suggest that this is the state that the fish encounter when infected, at least with respect to σ-factor mRNA levels. Comparative genomic analysis of σ-factor gene localizations in three M. marinum strains and Mycobacterium tuberculosis H37Rv revealed chromosomal rearrangements that changed the localization of especially sigA, sigB, sigD, sigE, sigF and sigJ after the divergence of these two species. This may explain the variation in species-specific expression upon exposure to different growth conditions.

Draft Genome Sequence of Saccharopolyspora rectivirgula.

We have sequenced the genome of Saccharopolyspora rectivirgula, the causative agent of farmer's lung disease. The draft genome consists of 182 contigs totaling 3,977,051 bp, with a GC content of 68.9%.