Candida albicans is the most common cause of serious fungal disease in humans. Creation of isogenic null mutants of this diploid organism, which requires sequential gene targeting, allows dissection of virulence mechanisms. Published analyses of such mutants show a near-perfect correlation between C. albicans pathogenicity and the ability to undergo a yeast-to-hypha morphological switch in vitro. However, most studies used mutants constructed with a marker that is itself a virulence determinant and therefore complicates their interpretation. Using alternative markers, we created ~3000 homozygous deletion strains affecting 674 genes or roughly 11% of the C. albicans genome. Screening for infectivity in a mouse model and for morphological switching and cell proliferation in vitro, we identified 115 infectivity-attenuated mutants, of which nearly half demonstrated normal morphological switching and proliferation. Analysis of such mutants identified the glycolipid, glucosylceramide, as the first small molecule synthesized by this pathogen to be required specifically for virulence.

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Advanced data encryption requires the use of true random number generators (TRNGs) to produce unpredictable sequences of bits. TRNG circuits with high degree of randomness and low power consumption may be fabricated by using the random telegraph noise (RTN) current signals produced by polarized metal/insulator/metal (MIM) devices as entropy source. However, the RTN signals produced by MIM devices made of traditional insulators, i.e., transition metal oxides like HfO2 and Al2O3, are not stable enough due to the formation and lateral expansion of defect clusters, resulting in undesired current fluctuations and the disappearance of the RTN effect. Here, the fabrication of highly stable TRNG circuits with low power consumption, high degree of randomness (even for a long string of 224 − 1 bits), and high throughput of 1 Mbit s−1 by using MIM devices made of multilayer hexagonal boron nitride (h‐BN) is shown. Their application is also demonstrated to produce one‐time passwords, which is ideal for the internet‐of‐everything. The superior stability of the h‐BN‐based TRNG is related to the presence of few‐atoms‐wide defects embedded within the layered and crystalline structure of the h‐BN stack, which produces a confinement effect that avoids their lateral expansion and results in stable operation.

Heterogeneous integration of nanomaterials has enabled advanced electronics and photonics applications. However, similar progress has been challenging for thermal applications, in part due to shorter wavelengths of heat carriers (phonons) compared to electrons and photons. Here, we demonstrate unusually high thermal isolation across ultrathin heterostructures, achieved by layering atomically thin two-dimensional (2D) materials. We realize artificial stacks of monolayer graphene, MoS2, and WSe2 with thermal resistance greater than 100 times thicker SiO2 and effective thermal conductivity lower than air at room temperature. Using Raman thermometry, we simultaneously identify the thermal resistance between any 2D monolayers in the stack. Ultrahigh thermal isolation is achieved through the mismatch in mass density and phonon density of states between the 2D layers. These thermal metamaterials are an example in the emerging field of phononics and could find applications where ultrathin thermal insulation is desired, in thermal energy harvesting, or for routing heat in ultracompact geometries.

Semiconducting MoTe2 is one of the few two-dimensional (2D) materials with a moderate band gap, similar to silicon. However, this material remains underexplored for 2D electronics due to ambient instability and predominantly p-type Fermi level pinning at contacts. Here, we demonstrate unipolar n-type MoTe2 transistors with the highest performance to date, including high saturation current (>400 µA/µm at 80 K and >200 µA/µm at 300 K) and relatively low contact resistance (1.2 to 2 kΩ•µm from 80 to 300 K), achieved with Ag contacts and AlOx encapsulation. We also investigate other contact metals, extracting their Schottky barrier heights using an analytic subthreshold model. High-resolution X-ray photoelectron spectroscopy reveals that interfacial metal-Te compounds dominate the contact resistance. Among the metals studied, Sc has the lowest work function but is the most reactive, which we counter by inserting monolayer h-BN between MoTe2 and Sc. These metal-insulator-semiconductor (MIS) contacts partly de-pin the metal Fermi level and lead to the smallest Schottky barrier for electron injection. Overall, this work improves our understanding of n-type contacts to 2D materials, an important advance for low-power electronics.

Two-dimensional (2D) semiconducting transition metal dichalcogenides (TMDs) are good candidates for high-performance flexible electronics. However, most demonstrations of such flexible field-effect transistors (FETs) to date have been on the micron scale, not benefitting from the short-channel advantages of 2D-TMDs. Here, we demonstrate flexible monolayer MoS2 FETs with the shortest channels reported to date (down to 50 nm) and remarkably high on-current (up to 470 µA µm -1 at 1 V drain-to-source voltage) which is comparable to flexible graphene or crystalline silicon FETs. This is achieved using a new transfer method wherein contacts are initially patterned on the rigid TMD growth substrate with nanoscale lithography, then coated with a polyimide (PI) film which becomes the flexible substrate after release, with the contacts and TMD. We also apply this transfer process to other TMDs, reporting the first flexible FETs with MoSe2 and record on-current for flexible WSe2 FETs. These achievements push 2D semiconductors closer to a technology for low-power and high-performance flexible electronics.For several years, the "Internet-of-Things" (IoT) has been increasingly prevalent in the forecast of future electronics. From monitoring the environment and machines around us to the human body, IoT envisions electronics physically present in every aspect of our daily lives. While some devices may be realized on rigid silicon, there is a need for electronics with new non-planar form factors 1,2 , which are thin and light, and can be conformally attached to objects with unusual shapes, on the human skin, or even implanted into the human body 1 . With these applications in mind, we need to realize electronics on flexible substrates that are robust to mechanical strain, easy to integrate, and capable of low-power consumption and high performance at the nanoscale 2,3 .Recent studies have suggested that 2D materials are good candidates for flexible substrates, because of their lack of dangling bonds, good carrier mobility in atomically thin (sub-1 nm) layers, reduced

Yeast exonuclease 1 (Exo1) is induced during meiosis and plays an important role in DNA homologous recombination and mismatch correction pathways. The human homolog, an 803-amino acid protein, shares 55% similarity to the yeast Exo1. In this report, we show that the enzyme functionally complements Saccharomyces cerevisiae Exo1 in recombination of direct repeat DNA fragments, UV resistance, and mutation avoidance by in vivo assays. Furthermore, the human enzyme suppresses the conditional lethality of a rad27⌬ mutant, symptomatic of defective RNA primer removal. The purified recombinant enzyme not only displays 5-3 double strand DNA exonuclease activity, but also shows an RNase H activity. This result indicates a back-up function of exonuclease 1 to flap endonuclease-1 in RNA primer removal during lagging strand DNA synthesis.Mutations cause genomic instability and gene dysfunction, many of which affect cell growth and lead to tumorigenesis. Fortunately, in normal cells, mutation rate is low due to the existence of different DNA repair systems such as mismatch, excision, and recombinational DNA repair pathways. In humans, DNA mutation accumulation is a critical step in carcinogenesis. Dysfunctional mutations of DNA mismatch repair genes such as MSH2, MLH1, and PMS2, are the main cause of the hereditary non-polyposis colorectal cancer (1-6). A portion of sporadic cancers is due to acquired mutations in mismatch repair genes as well (7). Mutations of genes encoding nucleotide excision repair proteins including XPG nuclease are linked to xeroderma pigmentosum (8 -17).Nucleases play important roles in several pathways including DNA replication, repair, and recombination. DNA fragments containing a lesion are removed by the combined efforts of a helicase and a nuclease. For instance, in the DNA mismatch repair of E. coli, exonucleases, exo I (3Ј-5Ј excision) and exo VII or Rec J (5Ј-3Ј excision) are responsible for the bidirectional removal of DNA fragments containing mismatched lesions (18,19). For DNA recombination or repair of double strand DNA breaks through recombination, an important step is to generate a 3Ј single-stranded terminus for strand invasion. This step is accomplished by 5Ј-3Ј exonucleases (20 -22). During DNA replication the removal of RNA primers in the lagging strand also requires 5Ј-3Ј nuclease activity (23). In E. coli and other bacteria, the removal of RNA primers is performed by the 5Ј-3Ј exonuclease activity of DNA polymerase I (24 -27). The polA ex1 mutant, defective in 5Ј-3Ј exonuclease activity, exhibits retarded joining of nascent DNA fragments. In eukaryotes, DNA polymerases lack an intrinsic 5Ј-nuclease. Removal of RNA primers is carried out by an independent enzyme, Rad27/FEN-1 nuclease, with both flap endonuclease and 5Ј-3Јexonuclease activities (28 -38). Disruption of the flap endonuclease gene RAD27 in the yeast Saccharomyces cerevisiae resulted in DNA replication defective symptom including the conditional lethality (39 -42). Survival of the null mutant at 30°C suggests that other en...

Ventilation and perfusion MR imaging are able to provide regional pulmonary functional information with high spatial and temporal resolution. The ability of MR imaging to assess both the magnitude and regional distribution of pulmonary functional impairment could have an important effect on the evaluation of lung disease.