Lightwave-controlled relativistic plasma mirrors.

We report on attosecond-scale control of high-harmonic and fast electron emission from plasma mirrors driven by relativistic-intensity near-single-cycle light waves at a kHz repetition rate. By controlling the waveform of the intense light transient, we reproducibly form a sub-cycle temporal intensity gate at the plasma mirror surface, leading to the observation of extreme ultraviolet spectral continua, characteristic of isolated attosecond pulse (IAP) generation. We also observe the correlated emission of a waveform-dependent relativistic electron beam, paving the way toward fully lightwave-controlled dynamics of relativistic plasma mirrors.

Simple few-shot method for spectrally resolving the wavefront of an ultrashort laser pulse.

We present a novel, to the best of our knowledge, and straightforward approach for the spatio-spectral characterization of ultrashort pulses. This minimally intrusive method relies on placing a mask with specially arranged pinholes in the beam path before the focusing optic and retrieving the spectrally resolved laser wavefront from the speckle pattern produced at focus. We test the efficacy of this new method by accurately retrieving chromatic aberrations, such as pulse-front tilt (PFT), pulse-front curvature (PFC), and higher-order aberrations introduced by a spherical lens. The simplicity and scalability of this method, combined with its compatibility with single-shot operation, make it a strong complement to existing tools for high-intensity laser facilities.

Single-stage few-cycle nonlinear compression of milliJoule energy Ti:Sa femtosecond pulses in a multipass cell.

We report on the nonlinear temporal compression of mJ energy pulses from a Ti:Sa chirped pulse amplifier system in a multipass cell filled with argon. The pulses are compressed from 30 fs down to 5.3 fs, corresponding to two optical cycles. The post-compressed beam exhibits excellent spatial quality and homogeneity. These results provide guidelines for optimizing the compressed pulse quality and further scaling of multipass-cell-based post-compression down to the single-cycle regime.

Immunotherapy guided precision medicine in solid tumors.

Cancer is no longer recognized as a single disease but a collection of diseases each with its defining characteristics and behavior. Even within the same cancer type, there can be substantial heterogeneity at the molecular level. Cancer cells often accumulate various genetic mutations and epigenetic alterations over time, leading to a coexistence of distinct subpopulations of cells within the tumor. This tumor heterogeneity arises not only due to clonal outgrowth of cells with genetic mutations, but also due to interactions of tumor cells with the tumor microenvironment (TME). The latter is a dynamic ecosystem that includes cancer cells, immune cells, fibroblasts, endothelial cells, stromal cells, blood vessels, and extracellular matrix components, tumor-associated macrophages and secreted molecules. The complex interplay between tumor heterogeneity and the TME makes it difficult to develop one-size-fits-all treatments and is often the cause of therapeutic failure and resistance in solid cancers. Technological advances in the post-genomic era have given us cues regarding spatial and temporal tumor heterogeneity. Armed with this knowledge, oncologists are trying to target the unique genomic, epigenetic, and molecular landscape in the tumor cell that causes its oncogenic transformation in a particular patient. This has ushered in the era of personalized precision medicine (PPM). Immunotherapy, on the other hand, involves leveraging the body's immune system to recognize and attack cancer cells and spare healthy cells from the damage induced by radiation and chemotherapy. Combining PPM and immunotherapy represents a paradigm shift in cancer treatment and has emerged as a promising treatment modality for several solid cancers. In this chapter, we summarise major types of cancer immunotherapy and discuss how they are being used for precision medicine in different solid tumors.

Composite coatings of beeswax + naphthalene acetic acid preserved fruit quality and antioxidants in stored lemon fruits.

Lemon fruits are well recognized for their richness in antioxidants. The present study was conducted to maintain the antioxidant properties of lemon fruits under long term cold storage. Fruits were given different treatments of naphthalene acetic acid (NAA) @ 50, 100 and 150 ppm plus beeswax (BW) @ 2% and were stored at 6-8 °C and 90-95% RH for 60 days. At the end of storage, fruits coated with NAA (50 ppm) + BW (2%) retained 42.14 and 34.61% antioxidants, 62.72 and 56.54% phenolic content and 17.72 and 13.80% hydroxyl radical scavenging capacity in peel and pulp, respectively as compared to the control. This treatment also resulted in lesser weight loss (5.27%), higher ascorbic acid content (46.31 mg 100 ml-1 juice) and titratable acidity (5.23%). Hence, NAA + BW coatings were promising for the maintenance of the postharvest antioxidant quality of stored lemons. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01364-4.

Drug response-based precision therapeutic selection for tamoxifen-resistant triple-positive breast cancer.

Breast cancer adaptability to the drug environment reduces the chemotherapeutic response and facilitates acquired drug resistance. Cancer-specific therapeutics can be more effective against advanced-stage cancer than standard chemotherapeutics. To extend the paradigm of cancer-specific therapeutics, clinically relevant acquired tamoxifen-resistant MCF-7 proteome was deconstructed to identify possible druggable targets (N = 150). Twenty-eight drug inhibitors were used against identified druggable targets to suppress non-resistant (NC) and resistant cells (RC). First, selected drugs were screened using growth-inhibitory response against NC and RC. Seven drugs were shortlisted for their time-dependent (10-12 days) cytotoxic effect and further narrowed to three effective drugs (e.g., cisplatin, doxorubicin, and hydroxychloroquine). The growth-suppressive effectiveness of selected drugs was validated in the complex spheroid model (progressive and regressive). In the progressive model, doxorubicin (RC: 83.64 %, NC: 54.81 %), followed by cisplatin (RC: 76.66 %, NC: 68.94 %) and hydroxychloroquine (RC: 68.70 %, NC: 61.78 %) showed a significant growth-suppressive effect. However, in fully grown regressive spheroid, after 4th drug treatment, cisplatin significantly suppressed RC (84.79 %) and NC (40.21 %), while doxorubicin and hydroxychloroquine significantly suppressed only RC (76.09 and 76.34 %). Our in-depth investigation effectively integrated the expression data with the cancer-specific therapeutic investigation. Furthermore, our three-step sequential drug-screening approach unbiasedly identified cisplatin, doxorubicin, and hydroxychloroquine as an efficacious drug to target heterogeneous cancer cell populations. SIGNIFICANCE STATEMENT: Hormonal-positive BC grows slowly, and hormonal-inhibitors effectively suppress the oncogenesis. However, development of drug-resistance not only reduces the drug-response but also increases the chance of BC aggressiveness. Further, alternative chemotherapeutics are widely used to control advanced-stage BC. In contrast, we hypothesized that, compared to standard chemotherapeutics, cancer-specific drugs can be more effective against resistant-cancer. Although cancer-specific treatment identification is an uphill battle, our work shows proteome data can be used for drug selection. We identified multiple druggable targets and, using ex-vivo methods narrowed multiple drugs to disease-condition-specific therapeutics. We consider that our investigation successfully interconnected the expression data with the functional disease-specific therapeutic investigation and selected drugs can be used for effective resistant treatment with higher therapeutic response.

High repetition rate relativistic laser-solid-plasma interaction platform featuring simultaneous particle and radiation detection.

We report on a uniquely designed high repetition rate relativistic laser-solid-plasma interaction platform, featuring the first simultaneous measurement of emitted high-order harmonics, relativistic electrons, and low divergence proton beams. This versatile setup enables detailed parametric studies of the particle and radiation spatio-spectral beam properties under a wide range of controlled interaction conditions, such as pulse duration and plasma density gradient. Its array of complementary diagnostics unlocks the potential to unravel interdependencies among the observables and should aid in further understanding the complex collective dynamics at play during laser-plasma interactions and in optimizing the secondary beam properties for applications.