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Summary: Strains from the Cryptococcus gattii species complex (CGSC) have caused the Pacific Northwest cryptococcosis outbreak, the largest cluster of life-threatening fungal infections in otherwise healthy human hosts known to date. In this study, we utilized a pan-phenome-based method to assess the fitness outcomes of CGSC strains under 31 stress conditions, providing a comprehensive overview of 2,821 phenotype-strain associations within this pathogenic clade. Phenotypic clustering analysis revealed a strong correlation between distinct types of stress phenotypes in a subset of CGSC strains, suggesting that shared determinants coordinate their adaptations to various stresses. Notably, a specific group of strains, including the outbreak isolates, exhibited a remarkable ability to adapt to all three of the most commonly used antifungal drugs for treating cryptococcosis (amphotericin B, 5-fluorocytosine, and fluconazole). By integrating pan-genomic and pan-transcriptomic analyses, we identified previously unrecognized genes that play crucial roles in conferring multidrug resistance in an outbreak strain with high multidrug adaptation. From these genes, we identified biomarkers that enable the accurate prediction of highly multidrug-adapted CGSC strains, achieving maximum accuracy and area under the curve (AUC) of 0.79 and 0.86, respectively, using machine learning algorithms. Overall, we developed a pan-omic approach to identify cryptococcal multidrug resistance determinants and predict highly multidrug-adapted CGSC strains that may pose significant clinical concern.

Heterogeneous integration of $\beta $ -Ga2O3 with Si substrate is considered as an effective and low-cost technology for the thermal management of $\beta $ -Ga2O3 electrical devices. In this work, an isotype heterojunction of n-Ga2O3/n+-Si (Ga2O3/Si) was fabricated by surface activated bonding in which an amorphous layer was induced by ion beam bombardment. The current density of Ga2O3/Si Schottky barrier diodes (SBDs) are about two orders of magnitude lower than that of Ga2O3 bulk SBDs at 2.8 V due to the influence of amorphous layer. The results are consistent with the simulation results when $\beta $ -Ga2O3 Mole Fraction (MF $=\,\,\text{n}(\beta $ -Ga2O3)/[ $\text{n}(\beta $ -Ga2O3) + n(SiO2)]) and thickness of amorphous layers (Tox) are set at 0.83 and 3 nm, respectively. Furthermore, devices with different MF and ${\mathrm{ T}}_{\mathrm{ ox}}$ were simulated based on the nonlocal tunneling model by Sentaurus TCAD. The decrease of $\beta $ -Ga2O3 Mole Fraction and increase of amorphous layers thickness in the hetero-interface of Ga2O3/Si SBDs lead to a dramatic degeneration of current density and specific on-resistance in Ga2O3/Si SBDs. These results may provide some guidance for improvement of vertical heterogeneous integration $\beta $ -Ga2O3 devices performance.

Pathogenic fungi of the genus Cryptococcus can undergo bisexual and unisexual reproduction. Here, the authors construct a gene-deletion library for over 100 transcription factor genes in Cryptococcus deneoformans and provide insights into regulatory cascades that are specific for each reproductive mode.

The semiconductor, β-Ga2O3 is attractive for applications in high power electronic devices with low conduction loss due to its ultra-wide bandgap (∼4.9 eV) and large Baliga's figure of merit. However, the thermal conductivity of β-Ga2O3 is much lower than that of other wide/ultra-wide bandgap semiconductors, such as SiC and GaN, which results in the deterioration of β-Ga2O3-based device performance and reliability due to self-heating. To overcome this problem, a scalable thermal management strategy was proposed by heterogeneously integrating wafer-scale single-crystalline β-Ga2O3 thin films on a highly thermally conductive SiC substrate. Characterization of the transferred β-Ga2O3 thin film indicated a uniform thickness to within ±2.01%, a smooth surface with a roughness of 0.2 nm, and good crystalline quality with an X-ray rocking curves (XRC) full width at half maximum of 80 arcsec. Transient thermoreflectance measurements were employed to investigate the thermal properties. The thermal performance of the fabricated β-Ga2O3/SiC heterostructure was effectively improved in comparison with that of the β-Ga2O3 bulk wafer, and the effective thermal boundary resistance could be further reduced to 7.5 m2K/GW by a post-annealing process. Schottky barrier diodes (SBDs) were fabricated on both a β-Ga2O3/SiC heterostructured material and a β-Ga2O3 bulk wafer. Infrared thermal imaging revealed the temperature increase of the SBDs on β-Ga2O3/SiC to be one quarter that on the β-Ga2O3 bulk wafer with the same applied power, which suggests that the combination of the β-Ga2O3 thin film and SiC substrate with high thermal conductivity promotes heat dissipation in β-Ga2O3-based devices.