Low frequency dynamics of the nitrogenase MoFe protein via femtosecond pump probe spectroscopy - Observation of a candidate promoting vibration

We have used femtosecond pump-probe spectroscopy (FPPS) to study the FeMo-cofactor within the nitrogenase (N2ase) MoFe protein from Azotobacter vinelandii. A sub-20-fs visible laser pulse was used to pump the sample to an excited electronic state, and a second sub-10-fs pulse was used to probe changes in transmission as a function of probe wavelength and delay time. The excited protein relaxes to the ground state with a ~1.2ps time constant. With the short laser pulse we coherently excited the vibrational modes associated with the FeMo-cofactor active site, which are then observed in the time domain. Superimposed on the relaxation dynamics, we distinguished a variety of oscillation frequencies with the strongest band peaks at ~84, 116, 189, and 226cm(-1). Comparison with data from nuclear resonance vibrational spectroscopy (NRVS) shows that the latter pair of signals comes predominantly from the FeMo-cofactor. The frequencies obtained from the FPPS experiment were interpreted with normal mode calculations using both an empirical force field (EFF) and density functional theory (DFT). The FPPS data were also compared with the first reported resonance Raman (RR) spectrum of the N2ase MoFe protein. This approach allows us to outline and assign vibrational modes having relevance to the catalytic activity of N2ase. In particular, the 226cm(-1) band is assigned as a potential 'promoting vibration' in the H-atom transfer (or proton-coupled electron transfer) processes that are an essential feature of N2ase catalysis. The results demonstrate that high-quality room-temperature solution data can be obtained on the MoFe protein by the FPPS technique and that these data provide added insight to the motions and possible operation of this protein and its catalytic prosthetic group

On the joint security of signature and encryption schemes under randomness reuse: efficiency and security amplification

Lecture Notes in Computer Science, 7341We extend the work of Bellare, Boldyreva and Staddon on the systematic analysis of randomness reuse to construct multi-recipient encryption schemes to the case where randomness is reused across different cryptographic primitives. We find that through the additional binding introduced through randomness reuse, one can actually obtain a security amplification with respect to the standard black-box compositions, and achieve a stronger level of security. We introduce stronger notions of security for encryption and signatures, where challenge messages can depend in a restricted way on the random coins used in encryption, and show that two variants of the KEM/DEM paradigm give rise to encryption schemes that meet this enhanced notion of security. We obtain the most efficient signcryption scheme to date that is secure against insider attackers without random oracles.(undefined

Entanglement and Density Matrix of a Block of Spins in AKLT Model

We study a 1-dimensional AKLT spin chain, consisting of spins $S$ in the bulk and $S/2$ at both ends. The unique ground state of this AKLT model is described by the Valence-Bond-Solid (VBS) state. We investigate the density matrix of a contiguous block of bulk spins in this ground state. It is shown that the density matrix is a projector onto a subspace of dimension $(S+1)^{2}$. This subspace is described by non-zero eigenvalues and corresponding eigenvectors of the density matrix. We prove that for large block the von Neumann entropy coincides with Renyi entropy and is equal to $\ln(S+1)^{2}$.Comment: Revised version, typos corrected, references added, 31 page

On Traversable Lorentzian Wormholes in the Vacuum Low Energy Effective String Theory in Einstein and Jordan Frames

Three new classes (II-IV) of solutions of the vacuum low energy effective string theory in four dimensions are derived. Wormhole solutions are investigated in those solutions including the class I case both in the Einstein and in the Jordan (string) frame. It turns out that, of the eight classes of solutions investigated (four in the Einstein frame and four in the corresponding string frame), massive Lorentzian traversable wormholes exist in five classes. Nontrivial massless limit exists only in class I Einstein frame solution while none at all exists in the string frame. An investigation of test scalar charge motion in the class I solution in the two frames is carried out by using the Plebanski-Sawicki theorem. A curious consequence is that the motion around the extremal zero (Keplerian) mass configuration leads, as a result of scalar-scalar interaction, to a new hypothetical "mass" that confines test scalar charges in bound orbits, but does not interact with neutral test particles.Comment: 18 page

Block Spin Density Matrix of the Inhomogeneous AKLT Model

We study the inhomogeneous generalization of a 1-dimensional AKLT spin chain model. Spins at each lattice site could be different. Under certain conditions, the ground state of this AKLT model is unique and is described by the Valence-Bond-Solid (VBS) state. We calculate the density matrix of a contiguous block of bulk spins in this ground state. The density matrix is independent of spins outside the block. It is diagonalized and shown to be a projector onto a subspace. We prove that for large block the density matrix behaves as the identity in the subspace. The von Neumann entropy coincides with Renyi entropy and is equal to the saturated value.Comment: 20 page

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Generation of LUMCi041-A-2: equipping a PAX3 reporter iPSC line with doxycycline inducible H2B-mTurquoise2 for live cell imaging

An induced pluripotent stem cell (iPSC) line, in which a H2B-fluorescent protein fusion is temporally expressed, is a valuable tool to track cells and study cell divisions and apoptosis. To this end we introduced a 3rd generation "all-in-one" doxycycline-inducible H2B-mTurquoise2 vector into the AAVS1 locus of PAX3-Venus iPSCs via CRISPR/Cas9. H2B-mTurquoise2 expression is absent but readily induced by doxycycline allowing quantification of cell divisions and imaging of living cells. Besides being a universal reporter in iPSC-based differentiation and toxicity assays, the generated pluripotent and genomically normal LUMCi041-A-2 line is particularly suited to study PAX3-positive stages of development.Therapeutic cell differentiatio

Patients’ perceptions on non‐specific effects of acupuncture: Qualitative comparison between responders and non‐responders

Background: Non-specific effect of acupuncture constitutes part of the overall effect generated via clinical encounter beyond needle insertion and stimulation. It is unclear how responders and non-responders of acupuncture experience non-specific effects differently. We aimed to compare their experiences in a nested qualitative study embedded in an acupuncture randomized trial on functional dyspepsia. Methods: Purposive sampling was used to capture experience of responders (n=15) and non-responders (n=15) to acupuncture via individual in-depth interviews. Design and analysis followed a framework analysis approach, with reference to an existing model on acupuncture non-specific effects. Themes emerging outside of this model were purposefully explored. Results: Responders had a more trusting relationship with acupuncturist in response to their expression of empathy. In turn they were more actively engaged in lifestyle modifications and dietary advice offered by acupuncturists. Non-responders were not satisfied with the level of reassurance regarding acupuncture safety. They were also expecting more peer support from fellow participants, regarded that as an empowerment process for initiating and sustaining lifestyle changes. Conclusions: Our results highlighted key differences in acupuncture non-specific effect components experienced by responders and non-responders. Positive non-specific effects contributing to overall benefits could be enhanced by emphasizing on empathy expression from acupuncturists, trust-building, offering appropriate explanations on safety, and organizing patient support groups. Further research on the relative importance of each component is warranted

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy