Characterizing strongly correlated matter is an increasingly central challenge in quantum science, where structure is often obscured by massive entanglement. It is becoming clear that in the quantum regime, state preparation and characterization should not be treated separately-entangling the two processes provides a quantum advantage in information extraction. Here, we present an approach that we term "manybody Ramsey interferometry" that combines adiabatic state preparation and Ramsey spectroscopy: Leveraging our recently developed one-to-one mapping between computational-basis states and manybody eigenstates, we prepare a superposition of manybody eigenstates controlled by the state of an ancilla qubit, allow the superposition to evolve relative phase, and then reverse the preparation protocol to disentangle the ancilla while localizing phase information back into it.
View Article and Find Full Text PDFImproving cancer immunotherapy efficacy hinges on identifying key T-cell populations critical for tumor control and response to Immune Checkpoint Blockade (ICB). We have recently reported that while the co-expression of PD-1 and CD28 is associated with impaired functionality in peripheral blood, it significantly enhances T-cell fitness in the tumor site of non-small cell lung cancer (NSCLC) patients. To uncover the underlying mechanisms, we explored the role of CD26, a key player in T-cell activation through its interaction with adenosine deaminase (ADA), a crucial intra/extracellular enzyme able to neutralize local adenosine (ADO).
View Article and Find Full Text PDFBackground: Tertiary Lymphoid Structures (TLS) correlate with positive outcomes in patients with NSCLC and the efficacy of immune checkpoint blockade (ICB) in cancer. The actin regulatory protein hMENA undergoes tissue-specific splicing, producing the epithelial hMENA linked to favorable prognosis in early NSCLC, and the mesenchymal hMENAΔv6 found in invasive cancer cells and pro-tumoral cancer-associated fibroblasts (CAFs). This study investigates how hMENA isoforms in tumor cells and CAFs relate to TLS presence, localization and impact on patient outcomes and ICB response.
View Article and Find Full Text PDFBackground: Immune checkpoint blockade (ICB) has significantly prolonged survival of non-small cell lung cancer (NSCLC) patients, although most patients develop mechanisms of resistance. Recently single-cell RNA-sequencing (scRNA-Seq) revealed a huge T-cell phenotypic and (dys)functional state variability. Accordingly, T-cell exhaustion is recognized as a functional adaptation, with a dynamic progression from a long-lived "pre-exhausted stem-like progenitor" to a "terminally exhausted" state.
View Article and Find Full Text PDFBackground: Understanding how cancer signaling pathways promote an immunosuppressive program which sustains acquired or primary resistance to immune checkpoint blockade (ICB) is a crucial step in improving immunotherapy efficacy. Among the pathways that can affect ICB response is the interferon (IFN) pathway that may be both detrimental and beneficial. The immune sensor retinoic acid-inducible gene I (RIG-I) induces IFN activation and secretion and is activated by actin cytoskeleton disturbance.
View Article and Find Full Text PDFThe impact of radiotherapy (RT) on immune cell status in prostate cancer (PCa) is only partially determined. The aim of this study was to assess the effect of different RT strategies on peripheral B, T, and Natural killer (NK) lymphocytes at precise longitudinal time-points in PCa. 18 patients treated with stereotactic body radiation therapy (SBRT) (40 Gy/3FRX), definitive moderate-hypofractionation (62 Gy/20FRX), or post-operative conventional-fractionation RT (66-69 Gy/30FRX) were prospectively evaluated for the immune cell profile in terms of immune cell composition, differentiation stage, cytokine production and inhibitory receptor (IR) expression.
View Article and Find Full Text PDFGuiding many-body systems to desired states is a central challenge of modern quantum science, with applications from quantum computation to many-body physics and quantum-enhanced metrology. Approaches to solving this problem include step-by-step assembly, reservoir engineering to irreversibly pump towards a target state and adiabatic evolution from a known initial state. Here we construct low-entropy quantum fluids of light in a Bose-Hubbard circuit by combining particle-by-particle assembly and adiabatic preparation.
View Article and Find Full Text PDFThe eruption of the Hunga-Tonga volcano in the South Pacific Ocean on January 15, 2022, at about 4:15 UTC, generated a violent explosion, which created atmospheric pressure disturbances in the form of Rayleigh-Lamb waves detected all over the globe. Here we discuss the observation of the Hunga-Tonga shock-wave performed at the Ny-Ålesund Research Station on the Spitsbergen island, by the detectors of the PolarquEEEst experiment and their ancillary sensors. Online pressure data as well as the results of dedicated offline analysis are presented and discussed in details.
View Article and Find Full Text PDFIntroduction: The structural validity and reliability of the Short-Form Health Survey 12 (SF-12) has not yet been tested in adults with the Marfan syndrome (MFS). This gap could undermine an evidence-grounded practice and research, especially considering that the need to assess health-related quality of life in patients with MFS has increased due to the improved life expectancy of these patients and the need to identify their determinants of quality of life. For this reason, this study aimed to confirm the dimensionality (structural validity) of the SF-12, its concurrent validity, and its reliability (internal consistency).
View Article and Find Full Text PDFWe report a measurement of the energy spectrum of cosmic rays above 2.5×10^{18} eV based on 215 030 events. New results are presented: at about 1.
View Article and Find Full Text PDFThe dynamic interplay between cancer cells and cancer-associated fibroblasts (CAFs) is regulated by multiple signaling pathways, which can lead to cancer progression and therapy resistance. We have previously demonstrated that hMENA, a member of the actin regulatory protein of Ena/VASP family, and its tissue-specific isoforms influence a number of intracellular signaling pathways related to cancer progression. Here, we report a novel function of hMENA/hMENAΔv6 isoforms in tumor-promoting CAFs and in the modulation of pro-tumoral cancer cell/CAF crosstalk via GAS6/AXL axis regulation.
View Article and Find Full Text PDFHere, we developed an unbiased, functional target-discovery platform to identify immunogenic proteins from primary non-small cell lung cancer (NSCLC) cells that had been induced to apoptosis by cisplatin (CDDP) treatment in vitro, as compared with their live counterparts. Among the multitude of proteins identified, some of them were represented as fragmented proteins in apoptotic tumor cells, and acted as non-mutated neoantigens (NM-neoAgs). Indeed, only the fragmented proteins elicited effective multi-specific CD4 and CD8 T cell responses, upon a chemotherapy protocol including CDDP.
View Article and Find Full Text PDFThe magnitude and the quality of T-cell response are critical endpoints in the immune-monitoring of cancer patients. The release of cytokines and lytic factors by T cells operate in each phase of the cancer immunity cycle. The simultaneous cytokine production, defined as T-cell polyfunctionality, is a dynamic state of different T-cell subsets and may represent a surrogate biomarker of response to immune-mediated therapies.
View Article and Find Full Text PDFChloroform is a recognised cause of acute liver injury, although now rarely encountered in clinical practice. We present a case of inhalational chloroform self-poisoning in a 47-year-old man that presented to hospital initially with reduced conscious level and later developed acute liver injury that was treated with intravenous acetylcysteine. This paper reviews the existing literature and presents a summary of the mechanisms of chloroform hepatotoxicity.
View Article and Find Full Text PDFWe developed novel techniques to fabricate atomically thin Bi_{2.1}Sr_{1.9}CaCu_{2.
View Article and Find Full Text PDFWe have recently described that DNA-damage inducing drug DTIC, administered before peptide (Melan-A and gp100)-vaccination, improves anti-tumor CD8 Melan-A-specific T-cell functionality, enlarges the Melan-A TCR repertoire and impacts the overall survival of melanoma patients. To identify whether the two Ags employed in the vaccination differently shape the anti-tumor response, herein we have carried out a detailed analysis of phenotype, anti-tumor functionality and TCR repertoire in treatment-driven gp100-specific CD8 T cells, in the same patients previously analyzed for Melan-A. We found that T-cell clones isolated from patients treated with vaccination alone possessed an Early/intermediate differentiated phenotype, whereas T cells isolated after DTIC plus vaccination were late-differentiated.
View Article and Find Full Text PDFThis study evaluated the surface microhardness of Lucirin-TPO (TPO) containing resin based composite (RBC) cured with three light-emitting diode (LED) light curing units (LCUs) (two single-peak LED and one multi-peak LED), and two different energy density (ED) (8 J/cm and 16 J/cm). Ninety specimens (8 mm wide and 2 mm thick) (n=5), were prepared with three different shades: translucent (T), A2 dentin (A2d), and A4 dentin (A4d). Specimens were subjected to micro-hardness Vickers measurements (Vickers Hardness Number, VHN) on both top and bottom surfaces.
View Article and Find Full Text PDFIL-18 is an inflammasome-related cytokine, member of the IL-1 family, produced by a wide range of cells in response to signals by several pathogen- or damage-associated molecular patterns. It can be highly represented in tumor patients, but its relevance in human cancer development is not clear. In this study, we provide evidence that IL-18 is principally expressed in tumor cells and, in concert with other conventional Th1 cell-driven cytokines, has a pivotal role in establishing a pro-inflammatory milieu in the tumor microenvironment of human non-small cell lung cancer (NSCLC).
View Article and Find Full Text PDFRecent advances in the targeted modification of complex eukaryotic genomes have unlocked a new era of genome engineering. From the pioneering work using zinc-finger nucleases (ZFNs), to the advent of the versatile and specific TALEN systems, and most recently the highly accessible CRISPR/Cas9 systems, we now possess an unprecedented ability to analyze developmental processes using sophisticated designer genetic tools. In this Review, we summarize the common approaches and applications of these still-evolving tools as they are being used in the most popular model developmental systems.
View Article and Find Full Text PDFEmbryology can be a rich component of early scientific experiences, and the zebrafish (Danio rerio) is an outstanding model for the study of life science. Most often, the production and maintenance of embryos is left to professional scientists. In this work, we describe a set of experiments performed together by all of the students of Lincoln K-8 Choice School in Rochester, MN.
View Article and Find Full Text PDFEthnopharmacological Relevance: Verbascum xanthophoeniceum is a representative of mullein species with a strong tradition of use in folk medicine as a remedy in inflammatory and infectious contexts. This plant accumulates phenylethanoid and iridoid metabolites with a partially characterized bioactivity.
Materials And Methods: Here, we compared anti-inflammatory effects of Verbascum xanthophoeniceum crude extract, its fractions, isolated iridoid glycosides, including aucubin, ajugol, harpagide, harpagoside, nigroside III and nigroside VI, and phenylethanoid glycosides verbascoside and forsythoside B in primary cultures of normal human keratinocytes (NHK).
Meckel's diverticulum (MD) is the most common congenital anomaly of the gastro-intestinal tract (approximately 2% of population), and arises from improper closure and absorption of the omphalomesenteric duct. Very few cases of Meckel's diverticulitis on the mesenteric side have been reported in the surgical literature, and no reported cases have been documented on preoperative imaging. We report a 65-year-old woman presenting symptoms and signs of acute abdomen with an initial suspicion of acute appendicitis.
View Article and Find Full Text PDFEvidence by functional imaging studies suggests the role of left dorsolateral prefrontal cortex (DLPFC) in the inhibitory control of nociceptive transmission system. Repetitive transcranial magnetic stimulation (rTMS) is able to modulate pain response to capsaicin. In the present study, we evaluated the effect of DLPFC activation (through rTMS) on nociceptive control in a model of capsaicin-induced pain.
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