High-Order Adiabatic Approximation for Non-Hermitian Quantum System and Complexization of Berry's Phase

In this paper the evolution of a quantum system drived by a non-Hermitian Hamiltonian depending on slowly-changing parameters is studied by building an universal high-order adiabatic approximation(HOAA) method with Berry's phase ,which is valid for either the Hermitian or the non-Hermitian cases. This method can be regarded as a non-trivial generalization of the HOAA method for closed quantum system presented by this author before. In a general situation, the probabilities of adiabatic decay and non-adiabatic transitions are explicitly obtained for the evolution of the non-Hermitian quantum system. It is also shown that the non-Hermitian analog of the Berry's phase factor for the non-Hermitian case just enjoys the holonomy structure of the dual linear bundle over the parameter manifold. The non-Hermitian evolution of the generalized forced harmonic oscillator is discussed as an illustrative examples.Comment: ITP.SB-93-22,17 page

Planetary bearing defect detection in a commercial helicopter main gearbox with vibration and acoustic emission

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Helicopter gearboxes significantly differ from other transmission types and exhibit unique behaviors that reduce the effectiveness of traditional fault diagnostics methods. In addition, due to lack of redundancy, helicopter transmission failure can lead to catastrophic accidents. Bearing faults in helicopter gearboxes are difficult to discriminate due to the low signal to noise ratio (SNR) in the presence of gear vibration. In addition, the vibration response from the planet gear bearings must be transmitted via a time-varying path through the ring gear to externally mounted accelerometers, which cause yet further bearing vibration signal suppression. This research programme has resulted in the successful proof of concept of a broadband wireless transmission sensor that incorporates power scavenging whilst operating within a helicopter gearbox. In addition, this paper investigates the application of signal separation techniques in detection of bearing faults within the epicyclic module of a large helicopter (CS-29) main gearbox using vibration and Acoustic Emissions (AE). It compares their effectiveness for various operating conditions. Three signal processing techniques including an adaptive filter, spectral kurtosis and envelope analysis, were combined for this investigation. In addition, this research discusses the feasibility of using AE for helicopter gearbox monitoring

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

Estimation of GFR in South Asians: a study from the general population in Pakistan.

BACKGROUND: South Asians are at high risk for chronic kidney disease. However, unlike those in the United States and United Kingdom, laboratories in South Asian countries do not routinely report estimated glomerular filtration rate (eGFR) when serum creatinine is measured. The objectives of the study were to: (1) evaluate the performance of existing GFR estimating equations in South Asians, and (2) modify the existing equations or develop a new equation for use in this population. STUDY DESIGN: Cross-sectional population-based study. SETTING & PARTICIPANTS: 581 participants 40 years or older were enrolled from 10 randomly selected communities and renal clinics in Karachi. PREDICTORS: eGFR, age, sex, serum creatinine level. OUTCOMES: Bias (the median difference between measured GFR [mGFR] and eGFR), precision (the IQR of the difference), accuracy (P30; percentage of participants with eGFR within 30% of mGFR), and the root mean squared error reported as cross-validated estimates along with bootstrapped 95% CIs based on 1,000 replications. RESULTS: The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation performed better than the MDRD (Modification of Diet in Renal Disease) Study equation in terms of greater accuracy at P30 (76.1% [95% CI, 72.7%-79.5%] vs 68.0% [95% CI, 64.3%-71.7%]; P \u3c 0.001) and improved precision (IQR, 22.6 [95% CI, 19.9-25.3] vs 28.6 [95% CI, 25.8-31.5] mL/min/1.73 m(2); P \u3c 0.001). However, both equations overestimated mGFR. Applying modification factors for slope and intercept to the CKD-EPI equation to create a CKD-EPI Pakistan equation (such that eGFRCKD-EPI(PK) = 0.686 × eGFRCKD-EPI(1.059)) in order to eliminate bias improved accuracy (P30, 81.6% [95% CI, 78.4%-84.8%]; P \u3c 0.001) comparably to new estimating equations developed using creatinine level and additional variables. LIMITATIONS: Lack of external validation data set and few participants with low GFR. CONCLUSIONS: The CKD-EPI creatinine equation is more accurate and precise than the MDRD Study equation in estimating GFR in a South Asian population in Karachi. The CKD-EPI Pakistan equation further improves the performance of the CKD-EPI equation in South Asians and could be used for eGFR reporting