Strong ultrafast demagnetization due to the intraband transitions.

Demagnetization in ferromagnetic transition metals driven by a femtosecond laser pulse is a fundamental problem in solid state physics, and its understanding is essential to the development of spintronic devices.Ab initiocalculation of time-dependent magnetic moment in the velocity gauge so far has not been successful in reproducing the large amount of demagnetization observed in experiments. In this work, we propose a method to incorporate intraband transitions within the velocity gauge through a convective derivative in the crystal momentum space. Our results for transition-element bulk crystals (bcc Fe, hcp Co and fcc Ni) based on the time-dependent quantum Liouville equation show a dramatic enhancement in the amount of demagnetization after the inclusion of an intraband term, in agreement with experiments. We also find that the effect of intraband transitions on each ferromagnetic material is distinctly different because of their band structure and spin property differences. Our finding has a far-reaching impact on understanding of ultrafast demagnetization.

An adaptive method of defining negative mutation status for multi-sample comparison using next-generation sequencing.

BACKGROUND: Multi-sample comparison is commonly used in cancer genomics studies. By using next-generation sequencing (NGS), a mutation's status in a specific sample can be measured by the number of reads supporting mutant or wildtype alleles. When no mutant reads are detected, it could represent either a true negative mutation status or a false negative due to an insufficient number of reads, so-called "coverage". To minimize the chance of false-negative, we should consider the mutation status as "unknown" instead of "negative" when the coverage is inadequately low. There is no established method for determining the coverage threshold between negative and unknown statuses. A common solution is to apply a universal minimum coverage (UMC). However, this method relies on an arbitrarily chosen threshold, and it does not take into account the mutations' relative abundances, which can vary dramatically by the type of mutations. The result could be misclassification between negative and unknown statuses. METHODS: We propose an adaptive mutation-specific negative (MSN) method to improve the discrimination between negative and unknown mutation statuses. For a specific mutation, a non-positive sample is compared with every known positive sample to test the null hypothesis that they may contain the same frequency of mutant reads. The non-positive sample can only be claimed as "negative" when this null hypothesis is rejected with all known positive samples; otherwise, the status would be "unknown". RESULTS: We first compared the performance of MSN and UMC methods in a simulated dataset containing varying tumor cell fractions. Only the MSN methods appropriately assigned negative statuses for samples with both high- and low-tumor cell fractions. When evaluated on a real dual-platform single-cell sequencing dataset, the MSN method not only provided more accurate assessments of negative statuses but also yielded three times more available data after excluding the "unknown" statuses, compared with the UMC method. CONCLUSIONS: We developed a new adaptive method for distinguishing unknown from negative statuses in multi-sample comparison NGS data. The method can provide more accurate negative statuses than the conventional UMC method and generate a remarkably higher amount of available data by reducing unnecessary "unknown" calls.

All-optical spin switching under different spin configurations.

All-optical spin switching represents a new frontier in femtomagnetism. However, its underlying principles are quite different from traditional thermal activated spin switching. Here, we employ an atomic spin model and present a systematic investigation from a single spin to a large system of over a million spins. We find that for a single spin without an external perturbation, the conservation of total angular momentum requires that the spin change, if any, exactly matches the orbital momentum change, but a laser pulse significantly alters this relation, where the spin change does not necessarily follow the orbital change. This is reflected in the strong dependence of switching on laser polarization. To have an efficient spin switching, the electron initial momentum direction must closely follow the spin's orientation, so the orbital angular momentum is transverse to the spin and consequently the spin-orbit torque lies in the same direction as the spin. The module of the spin-orbit torque is [Formula: see text], where [Formula: see text] is the angle between spin [Formula: see text] and position [Formula: see text] (momentum [Formula: see text]) and [Formula: see text] is the angle between [Formula: see text] and [Formula: see text]. These findings are manifested in a much larger system. We find that the spin response depends on underlying spin structures. A linearly polarized laser pulse creates a dip in a uniform inplane-magnetized thin film, but has little effects on Néel and Bloch walls. Both right- and left- circularly polarized light ([Formula: see text] and [Formula: see text]) have stronger but different effects in both uniform spin domains and Néel walls. While [Formula: see text] light creates a basin of spins pointing down, [Formula: see text] light creates a mound of spins pointing up. In the vicinity of the structure spins are reversed, similar to the experimental observation. [Formula: see text] light has a dramatic effect, disrupting spins in Bloch walls. By contrast, [Formula: see text] light has a small effect on Bloch walls because [Formula: see text] only switches down spins up and once the spins already point up, there is no major effect. These findings are expected to have important implications in the future.

Quantum mechanical interpretation of the ultrafast all optical spin switching.

The all-optical spin switching induced by an intense (∼TW cm-2), near-infrared (775 nm), ultrashort (∼100 fs) circularly-polarized laser pulse is studied based on the spin-orbit coupled Heisenberg model. We find that the magnetic spin momentum undergoes an oscillation in time during the interaction with a driving laser pulse, which can be explained as a classical counterpart of the Rabi oscillation associated with a spin-orbit coupling. The optimal spin reversal is achieved by adjusting the pulse duration to one half the Rabi oscillation period. A successive spin reversal by a delayed pulse is possible if it has the opposite helicity and a shorter duration relative to the first pulse. Moreover, inclusion of an exchange interaction term in the Hamiltonian leads to a precession of the magnetic spin momentum that lasts even after the driving laser pulse turns off. This spin precession is stronger in antiferromagnets than ferrimagnets.

Genomic profiling is predictive of response to cisplatin treatment but not to PI3K inhibition in bladder cancer patient-derived xenografts.

PURPOSE: Effective systemic therapeutic options are limited for bladder cancer. In this preclinical study we tested whether bladder cancer gene alterations may be predictive of treatment response. EXPERIMENTAL DESIGN: We performed genomic profiling of two bladder cancer patient derived tumor xenografts (PDX). We optimized the exome sequence analysis method to overcome the mouse genome interference. RESULTS: We identified a number of somatic mutations, mostly shared by the primary tumors and PDX. In particular, BLCAb001, which is less responsive to cisplatin than BLCAb002, carried non-sense mutations in several genes associated with cisplatin resistance, including MLH1, BRCA2, and CASP8. Furthermore, RNA-Seq analysis revealed the overexpression of cisplatin resistance associated genes such as SLC7A11, TLE4, and IL1A in BLCAb001. Two different PIK3CA mutations, E542K and E545K, were identified in BLCAb001 and BLCAb002, respectively. Thus, we tested whether the genomic profiling was predictive of response to a dual PI3K/mTOR targeting agent, LY3023414. Despite harboring similar PIK3CA mutations, BLCAb001 and BLCAb002 exhibited differential response, both in vitro and in vivo. Sustained target modulation was observed in the sensitive model BLCAb002 but not in BLCAb001, as well as decreased autophagy. Interestingly, computational modelling of mutant structures and affinity binding to PI3K revealed that E542K mutation was associated with weaker drug binding than E545K. CONCLUSIONS: Our results suggest that the presence of activating PIK3CA mutations may not necessarily predict in vivo treatment response to PI3K targeted therapies, while specific gene alterations may be predictive for cisplatin response in bladder cancer models and, potentially, in patients as well.

SCNVSim: somatic copy number variation and structure variation simulator.

BACKGROUND: Somatically acquired structure variations (SVs) and copy number variations (CNVs) can induce genetic changes that are directly related to tumor genesis. Somatic SV/CNV detection using next-generation sequencing (NGS) data still faces major challenges introduced by tumor sample characteristics, such as ploidy, heterogeneity, and purity. A simulated cancer genome with known SVs and CNVs can serve as a benchmark for evaluating the performance of existing somatic SV/CNV detection tools and developing new methods. RESULTS: SCNVSim is a tool for simulating somatic CNVs and structure variations SVs. Other than multiple types of SV and CNV events, the tool is capable of simulating important features related to tumor samples including aneuploidy, heterogeneity and purity. CONCLUSIONS: SCNVSim generates the genomes of a cancer cell population with detailed information of copy number status, loss of heterozygosity (LOH), and event break points, which is essential for developing and evaluating somatic CNV and SV detection methods in cancer genomics studies.

Whole-genome sequencing of a malignant granular cell tumor with metabolic response to pazopanib.

Granular cell tumors are an uncommon soft tissue neoplasm. Malignant granular cell tumors comprise <2% of all granular cell tumors, are associated with aggressive behavior and poor clinical outcome, and are poorly understood in terms of tumor etiology and systematic treatment. Because of its rarity, the genetic basis of malignant granular cell tumor remains unknown. We performed whole-genome sequencing of one malignant granular cell tumor with metabolic response to pazopanib. This tumor exhibited a very low mutation rate and an overall stable genome with local complex rearrangements. The mutation signature was dominated by C>T transitions, particularly when immediately preceded by a 5' G. A loss-of-function mutation was detected in a newly recognized tumor suppressor candidate, BRD7. No mutations were found in known targets of pazopanib. However, we identified a receptor tyrosine kinase pathway mutation in GFRA2 that warrants further evaluation. To the best of our knowledge, this is only the second reported case of a malignant granular cell tumor exhibiting a response to pazopanib, and the first whole-genome sequencing of this uncommon tumor type. The findings provide insight into the genetic basis of malignant granular cell tumors and identify potential targets for further investigation.