Consistent and Truthful Interpretation with Fourier Analysis

For many interdisciplinary fields, ML interpretations need to be consistent with what-if scenarios related to the current case, i.e., if one factor changes, how does the model react? Although the attribution methods are supported by the elegant axiomatic systems, they mainly focus on individual inputs, and are generally inconsistent. To support what-if scenarios, we introduce a new notion called truthful interpretation, and apply Fourier analysis of Boolean functions to get rigorous guarantees. Experimental results show that for neighborhoods with various radii, our method achieves 2x - 50x lower interpretation error compared with the other methods

Disorder enabled band structure engineering of a topological insulator surface

Three dimensional topological insulators are bulk insulators with $\mathbf{Z}_2$ topological electronic order that gives rise to conducting light-like surface states. These surface electrons are exceptionally resistant to localization by non-magnetic disorder, and have been adopted as the basis for a wide range of proposals to achieve new quasiparticle species and device functionality. Recent studies have yielded a surprise by showing that in spite of resisting localization, topological insulator surface electrons can be reshaped by defects into distinctive resonance states. Here we use numerical simulations and scanning tunneling microscopy data to show that these resonance states have significance well beyond the localized regime usually associated with impurity bands. At native densities in the model Bi$_2$X$_3$ (X=Bi, Te) compounds, defect resonance states are predicted to generate a new quantum basis for an emergent electron gas that supports diffusive electrical transport

Immunotherapy for Renal Cell Carcinoma

Despite the rapid development of therapeutic modalities for advanced or metastatic renal cell carcinoma (mRCC) over the past decade to include traditional immunotherapy, such as high-dose interleukin-2 and interferon-α, as well as a number of targeted antiangiogenic therapies, mRCC continues to be associated with poor prognosis. Currently, immunotherapy has seen tremendous development in the form of immune checkpoint inhibition and vaccines at a dizzying pace, which are being studied in mRCC and are showing promise as important steps in the management of this disease. With so many drugs available to clinicians and patients, properly integrating immunotherapy especially immune checkpoint blockade (ICB) into the treatment paradigm is challenging. Emerging research with additional ICB agents and novel combination strategies is likely to further impact clinical decision-making. The further development of biomarkers for predicting a response is required to achieve optimal efficacy with these therapeutic interventions. This chapter summarizes the current landscape of standard and emerging immune therapeutics and other modalities for mRCC

PexRAP inhibits PRDM16-mediated thermogenic gene expression

How the nuclear receptor PPARγ regulates the development of two functionally distinct types of adipose tissue, brown and white fat, as well as the browning of white fat, remains unclear. Our previous studies suggest that PexRAP, a peroxisomal lipid synthetic enzyme, regulates PPARγ signaling and white adipogenesis. Here, we show that PexRAP is an inhibitor of brown adipocyte gene expression. PexRAP inactivation promoted adipocyte browning, increased energy expenditure, and decreased adiposity. Identification of PexRAP-interacting proteins suggests that PexRAP function extends beyond its role as a lipid synthetic enzyme. Notably, PexRAP interacts with importin-β1, a nuclear import factor, and knockdown of PexRAP in adipocytes reduced the levels of nuclear phospholipids. PexRAP also interacts with PPARγ, as well as PRDM16, a critical transcriptional regulator of thermogenesis, and disrupts the PRDM16-PPARγ complex, providing a potential mechanism for PexRAP-mediated inhibition of adipocyte browning. These results identify PexRAP as an important regulator of adipose tissue remodeling

Irreversible proliferation of magnetic moments at cleaved surfaces of the topological Kondo insulator SmB6

The compound SmB$_6$ is the best established realization of a topological Kondo insulator, in which a topological insulator state is obtained through Kondo coherence. Recent studies have found evidence that the surface of SmB$_6$ hosts ferromagnetic domains, creating an intrinsic platform for unidirectional ballistic transport at the domain boundaries. Here, surface-sensitive X-ray absorption (XAS) and bulk-sensitive resonant inelastic X-ray scattering (RIXS) spectra are measured at the Sm N$_{4,5}$-edge, and used to evaluate electronic symmetries, excitations and temperature dependence near the surface of cleaved samples. The XAS data show that the density of large-moment atomic multiplet states on a cleaved surface grows irreversibly over time, to a degree that likely exceeds a related change that has recently been observed in the surface 4f orbital occupation

SiO2 nanoparticles induce cytotoxicity and protein expression alteration in HaCaT cells

<p>Abstract</p> <p>Background</p> <p>Nanometer silicon dioxide (nano-SiO₂) has a wide variety of applications in material sciences, engineering and medicine; however, the potential cell biological and proteomic effects of nano-SiO₂exposure and the toxic mechanisms remain far from clear.</p> <p>Results</p> <p>Here, we evaluated the effects of amorphous nano-SiO₂(15-nm, 30-nm SiO₂). on cellular viability, cell cycle, apoptosis and protein expression in HaCaT cells by using biochemical and morphological analysis, two-dimensional differential gel electrophoresis (2D-DIGE) as well as mass spectrometry (MS). We found that the cellular viability of HaCaT cells was significantly decreased in a dose-dependent manner after the treatment of nano-SiO₂and micro-sized SiO₂particles. The IC₅₀value (50% concentration of inhibition) was associated with the size of SiO₂particles. Exposure to nano-SiO₂and micro-sized SiO₂particles also induced apoptosis in HaCaT cells in a dose-dependent manner. Furthermore, the smaller SiO₂particle size was, the higher apoptotic rate the cells underwent. The proteomic analysis revealed that 16 differentially expressed proteins were induced by SiO₂exposure, and that the expression levels of the differentially expressed proteins were associated with the particle size. The 16 proteins were identified by MALDI-TOF-TOF-MS analysis and could be classified into 5 categories according to their functions. They include oxidative stress-associated proteins; cytoskeleton-associated proteins; molecular chaperones; energy metabolism-associated proteins; apoptosis and tumor-associated proteins.</p> <p>Conclusions</p> <p>These results showed that nano-SiO₂exposure exerted toxic effects and altered protein expression in HaCaT cells. The data indicated the alterations of the proteins, such as the proteins associated with oxidative stress and apoptosis, could be involved in the toxic mechanisms of nano-SiO₂exposure.</p

JARVIS-1: Open-World Multi-task Agents with Memory-Augmented Multimodal Language Models

Achieving human-like planning and control with multimodal observations in an open world is a key milestone for more functional generalist agents. Existing approaches can handle certain long-horizon tasks in an open world. However, they still struggle when the number of open-world tasks could potentially be infinite and lack the capability to progressively enhance task completion as game time progresses. We introduce JARVIS-1, an open-world agent that can perceive multimodal input (visual observations and human instructions), generate sophisticated plans, and perform embodied control, all within the popular yet challenging open-world Minecraft universe. Specifically, we develop JARVIS-1 on top of pre-trained multimodal language models, which map visual observations and textual instructions to plans. The plans will be ultimately dispatched to the goal-conditioned controllers. We outfit JARVIS-1 with a multimodal memory, which facilitates planning using both pre-trained knowledge and its actual game survival experiences. JARVIS-1 is the existing most general agent in Minecraft, capable of completing over 200 different tasks using control and observation space similar to humans. These tasks range from short-horizon tasks, e.g., "chopping trees" to long-horizon tasks, e.g., "obtaining a diamond pickaxe". JARVIS-1 performs exceptionally well in short-horizon tasks, achieving nearly perfect performance. In the classic long-term task of $\texttt{ObtainDiamondPickaxe}$, JARVIS-1 surpasses the reliability of current state-of-the-art agents by 5 times and can successfully complete longer-horizon and more challenging tasks. The project page is available at https://craftjarvis.org/JARVIS-1Comment: update project pag

Observation of a topological insulator Dirac cone reshaped by non-magnetic impurity resonance

The massless Dirac electrons found at topological insulator surfaces are thought to be influenced very little by weak, non-magnetic disorder. However, a resonance effect of strongly perturbing non-magnetic impurities has been theoretically predicted to change the dispersion and physical nature of low-energy quasiparticles, resulting in unique particle-like states that lack microscopic translational symmetry. Here we report the direct observation of impurities reshaping the surface Dirac cone of the model three-dimensional topological insulator bismuth selenide. A pronounced kink-like dispersion feature is observed in disorder-enriched samples, and found to be closely associated with the anomaly caused by impurity resonance in the surface state density of states, as observed by dichroic angle-resolved photoemission spectroscopy. The experimental observation of these features, which closely resemble theoretical predictions, has significant implications for the properties of topological Dirac cones in applied scenarios that commonly feature point-defect disorder at surfaces or interfaces. Topological insulators - influence of surface impurities: The electronic properties of topological insulators are robust against perturbations, including the presence of non-magnetic impurities. However, surface impurities can give rise to resonant states near the Dirac point, and if their density becomes sufficiently high it is predicted that they can substantially modify the dispersion of the Dirac cone and develop a collective behaviour that results in the formation of particle-like states that lack microscopic translational symmetry. L. Andrew Wray at Purdue University and at the New York University Shanghai, and colleagues, used angle-resolved photoemission spectroscopy to experimentally observe the reshaping of the surface Dirac cone in a defect-rich sample of the topological insulator Bi2Se3. These results indicate that surface impurities can provide a useful handle to control the properties of topological insulators