Pharmacologic blockade of the myostatin (Mstn)/activin receptor pathway is being pursued as a potential therapy for several muscle wasting disorders. The functional benefits of blocking this pathway ...are under investigation, in particular given the findings that greater muscle hypertrophy results from Mstn deficiency arising from genetic ablation compared to post‐developmental Mstn blockade. Using high‐resolution MS coupled with SILAC mouse technology, we quantitated the relative proteomic changes in gastrocnemius muscle from Mstn knockout (Mstn−/−) and mice treated for 2‐weeks with REGN1033, an anti‐Mstn antibody. Relative to wild‐type animals, Mstn−/− mice had a two‐fold greater muscle mass and a >1.5‐fold change in expression of 12.0% of 1137 quantified muscle proteins. In contrast, mice treated with REGN1033 had minimal changes in muscle proteome (0.7% of 1510 proteins >1.5‐fold change, similar to biological difference 0.5% of 1310) even though the treatment induced significant 20% muscle mass increase. Functional annotation of the altered proteins in Mstn−/− mice corroborates the mutiple physiological changes including slow‐to‐fast fiber type switch. Thus, the proteome‐wide protein expression differs between Mstn−/− mice and mice subjected to specific Mstn blockade post‐developmentally, providing molecular‐level insights to inform mechanistic hypotheses to explain the observed functional differences.
Pancreatic cancer is projected to become the second leading cause of cancer-related death in the United States by 2020. A familial aggregation of pancreatic cancer has been established, but the cause ...of this aggregation in most families is unknown. To determine the genetic basis of susceptibility in these families, we sequenced the germline genomes of 638 patients with familial pancreatic cancer and the tumor exomes of 39 familial pancreatic adenocarcinomas. Our analyses support the role of previously identified familial pancreatic cancer susceptibility genes such as BRCA2, CDKN2A, and ATM, and identify novel candidate genes harboring rare, deleterious germline variants for further characterization. We also show how somatic point mutations that occur during hematopoiesis can affect the interpretation of genome-wide studies of hereditary traits. Our observations have important implications for the etiology of pancreatic cancer and for the identification of susceptibility genes in other common cancer types.
The genetic basis of disease susceptibility in the majority of patients with familial pancreatic cancer is unknown. We whole genome sequenced 638 patients with familial pancreatic cancer and demonstrate that the genetic underpinning of inherited pancreatic cancer is highly heterogeneous. This has significant implications for the management of patients with familial pancreatic cancer.
Quantum key distribution (QKD) and quantum message encryption protocols promise a secure way to distribute information while detecting eavesdropping. However, current protocols may suffer from ...significantly reduced eavesdropping protection when only a subset of qubits are observed by an attacker. In this paper, we present two quantum cryptographic protocols leveraging the quantum Fourier transform (QFT) and show their higher effectiveness even when an attacker measures only a subset of the transmitted qubits. The foremost of these protocols is a novel QKD method that leverages this effectiveness of the QFT while being more practical than previously proposed QFT-based protocols, most notably by not relying on quantum memory. We additionally show how existing quantum encryption methods can be augmented with a QFT-based approach to improve eavesdropping detection. Finally, we provide equations to analyze different QFT-based detection schemes within these protocols so that protocol designers can make custom schemes for their purpose.
Reductive Quantum Phase Estimation Papadopoulos, Nicholas J C; Reilly, Jarrod T; John Drew Wilson ...
arXiv (Cornell University),
07/2024
Paper, Journal Article
Open access
Estimating a quantum phase is a necessary task in a wide range of fields of quantum science. To accomplish this task, two well-known methods have been developed in distinct contexts, namely, Ramsey ...interferometry (RI) in atomic and molecular physics and quantum phase estimation (QPE) in quantum computing. We demonstrate that these canonical examples are instances of a larger class of phase estimation protocols, which we call reductive quantum phase estimation (RQPE) circuits. Here we present an explicit algorithm that allows one to create an RQPE circuit. This circuit distinguishes an arbitrary set of phases with a fewer number of qubits and unitary applications, thereby solving a general class of quantum hypothesis testing to which RI and QPE belong. We further demonstrate a trade-off between measurement precision and phase distinguishability, which allows one to tune the circuit to be optimal for a specific application.
The DAMIC-M (DArk Matter In CCDs at Modane) experiment employs thick, fully depleted silicon charged-coupled devices (CCDs) to search for dark matter particles with a target exposure of 1 kg-year. A ...novel skipper readout implemented in the CCDs provides single electron resolution through multiple non-destructive measurements of the individual pixel charge, pushing the detection threshold to the eV-scale. DAMIC-M will advance by several orders of magnitude the exploration of the dark matter particle hypothesis, in particular of candidates pertaining to the so-called “hidden sector.” A prototype, the Low Background Chamber (LBC), with 20g of low background Skipper CCDs, has been recently installed at Laboratoire Souterrain de Modane and is currently taking data. We will report the status of the DAMIC-M experiment and first results obtained with LBC commissioning data.
The major histocompatibility complex class I complex consists of a heavy chain and a light chain (β2- microglobulin, β2m, which assemble with a short endogenously derived peptide in the endoplasmic ...reticulum. The class I peptide can be directly exchanged, either at the cell surface or, as recently described, in vesicles of the endocytic compartments, thus allowing exogenous peptides to enter the class I presentation pathway. To probe the interactions between the components of the class I molecule, we analyzed the exchange of peptide and β2m by using purified, recombinant H2-Kb/peptide complexes in a cell-free in vitro system. The exchange of competitor peptide was primarily dependent on the off-rate of the original peptide in the class I binding groove. Peptide exchange was not enhanced by the presence of exogenous β2m, as exchange occurred to the same extent in its absence. Thus, the exchange of peptide and β2m are independent events. The exchange rate of β2m also was not affected by the dissociation rates of the original peptides. Furthermore, peptides could substantially exchange into class I molecules over a pH range of 5.5 to 7.5, conditions prevalent in certain endocytic compartments. We conclude that the dynamic properties of the components of class I molecules explain its function as a highly peptide-receptive molecule. The major histocompatibility complex class I can readily receive peptides independent of the presence of exogenous β2m, even at a low pH. Such properties are relevant to class I peptide acquisition, which can occur at the cell surface, as well as in specialized endosomes.
Innovation in Histopathology Teaching Danks, Janine A.; Papadopoulos, Roula; Vardaxis, Nicholas J.
Journal of histotechnology,
09/2009, Volume:
32, Issue:
3
Journal Article
Peer reviewed
The utilization of a computerized system of classroom teaching (Netop) for improving undergraduate histopathology teaching is described. The system allows for a blended learning laboratory ...environment where "wet laboratory" tasks (e.g., staining and microscopic examination of tissue sections) are combined with a virtual laboratory workspace (e.g., accessing of visual databases, manuals and records). An advantage of the system is control of the student classroom experience by the instructor and sharing of data amongst instructor, the whole class, groups of students or individual students. The system is used with great success in the teaching of Laboratory Medicine students in their four-year Bachelor of Applied Science degree. Other improvements in laboratory teaching in this course are described and it is reported that these improvements, together with the computerized teaching system, have been responsible for increased student engagement and improved student learning outcomes. (The J Histotechnol 32(3):119-121, 2009)
Submitted March 3, 2009; accepted August 11, 2009
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