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Background K1 capsular polysaccharide (CPS)-associated Klebsiella pneumoniae is the primary cause of pyogenic liver abscesses (PLA) in Asia. Patients with PLA often have serious complications, ultimately leading to a mortality of ~ 5%. This K1 CPS has been reported as a promising target for development of glycoconjugate vaccines against K. pneumoniae infection. The pyruvylation and O-acetylation modifications on the K1 CPS are essential to the immune response induced by the CPS. To date, however, obtaining the fragments of K1 CPS that contain the pyruvylation and O-acetylation for generating glycoconjugate vaccines still remains a challenge. Methods We analyzed the digested CPS products with NMR spectroscopy and mass spectrometry to reveal a bacteriophage-derived polysaccharide depolymerase specific to K1 CPS. The biochemical and biophysical properties of the enzyme were characterized and its crystal structures containing bound CPS products were determined. We also performed site-directed mutagenesis, enzyme kinetic analysis, phage absorption and infectivity studies, and treatment of the K. pneumoniae-infected mice with the wild-type and mutant enzymes. Results We found a bacteriophage-derived polysaccharide lyase that depolymerizes the K1 CPS into fragments of 1–3 repeating trisaccharide units with the retention of the pyruvylation and O-acetylation, and thus the important antigenic determinants of intact K1 CPS. We also determined the 1.46-Å-resolution, product-bound crystal structure of the enzyme, revealing two distinct carbohydrate-binding sites in a trimeric β-helix architecture, which provide the first direct evidence for a second, non-catalytic, carbohydrate-binding site in bacteriophage-derived polysaccharide depolymerases. We demonstrate the tight interaction between the pyruvate moiety of K1 CPS and the enzyme in this second carbohydrate-binding site to be crucial to CPS depolymerization of the enzyme as well as phage absorption and infectivity. We also demonstrate that the enzyme is capable of protecting mice from K1 K. pneumoniae infection, even against a high challenge dose. Conclusions Our results provide insights into how the enzyme recognizes and depolymerizes the K1 CPS, and demonstrate the potential use of the protein not only as a therapeutic agent against K. pneumoniae, but also as a tool to prepare structurally-defined oligosaccharides for the generation of glycoconjugate vaccines against infections caused by this organism.

The purpose of this article was to explore the adaptation to an implantable cardioverter defibrillator (ICD) of a survivor of sudden death due to fatal arrhythmia. Owing to medical urgency, the case patient, a woman, did not have sufficient time to get prepared mentally. Therefore, the case had difficulty coping and ultimately rejected the ICD device. During the period of hospital care (November 10th to 19th, 2015), in-depth interview and clinical observation were used to obtain information from the case. The interview was transcribed and analyzed by repeated reading. The analysis found the following major post-ICD-implantation-associated health problems: confusion about the necessity of ICD, changes in body image due to ICD device implantation, and maladaptation in post-ICD daily life. In addition to providing ICD-related information and to strengthening her support system, we explored with the case the meanings of the ICD device in order to resolve her confusion. In addition, we recognized her perception regarding the ICD device without judgement and discussed the impact on her body of having the ICD. Concurrently, we encouraged the case to re-examine her self-value and life goals. In addition, we reconstructed the picture of the appearance of wound and made her realized the merit of the ICD. In terms of broader application, we hope that patients may learn to understand the worth and meanings of the ICD device and to restore positive attitudes with regard to body image. Furthermore, these interventions help encourage patients to re-examine their self-worth and goals and to internalize the ICD device, thereby minimizing the psychological impact of implantation. Ultimately, this case adapted well to the ICD device. Finally, we hope to share this experience as a reference for improving quality of care. These results may specifically help sudden death survivors to adapt to ICD implantation.致命性心律不整導致猝死後裝置體內去顫器病人之調適歷程.本文主要在探討致命性心律不整導致猝死後，裝置體內去顫器病人之調適歷程。此個案是經歷猝死急救後存活者，在無充分時間心理準備下，迫切地決定裝置體內去顫器（implantable cardioverter defibrillator, ICD），導致個案不知如何應對，進而對植入的ICD產生排斥想法。筆者於2015年11月10日至11月19日照護期間，藉由深入訪談與臨床觀察進行資料收集，並將訪談撰寫成行為過程實錄，經過反覆閱讀內容與分析，發現個案面臨裝置ICD後的相關健康問題為：對ICD存在感到困惑、ICD植入後身體心像改變及日後生活的調適障礙。照護期間除了提供ICD自我照護的相關訊息與強化支持系統運作之外，以不批判態度瞭解個案裝置ICD後看法，藉由共同探索裝置ICD的意義，來解除ICD存在之困惑，並共同討論裝置ICD對其影響，促進個案重新審視自我價值及人生目標。同時，重新建立傷口外觀圖像，體認ICD存在價值，轉變ICD植入後身體心像，以協助個案將ICD裝置內化，進而降低裝置後的心理衝擊，最終達到對ICD的正向調適。冀望將此經驗提供日後臨床照護上之參考，並協助裝置ICD個案之調適。.

This work demonstrates that a complete description of the interaction of matter and all forces, gravitational and non-gravitational, can in fact be realized within a quantum affine algebraic framework. Using the affine group formalism, we construct elements of a physical Hilbert space for full, Lorentzian quantum gravity coupled to the Standard Model in four spacetime dimensions. Affine algebraic quantization of gravitation and matter on equal footing implies a fundamental uncertainty relation which is predicated upon a non-vanishing cosmological constant., Comment: 9 pages

The Quantum Wheeler-DeWitt operator can be derived from an affine commutation relation via the affine group representation formalism for gravity, wherein a family of gauge-diffeomorphism invariant affine coherent states are constructed from a fiducial state. In this article, the role of the fiducial state is played by a regularized Gaussian peaked on densitized triad configurations corresponding to 3-metrics of constant spatial scalar curvature. The affine group manifold consists of points in the upper half plane, wherein each point is labeled by two local gravitational degrees of freedom from the Yamabe construction. From this viewpoint, here we show that the translational subgroup of affine coherent states constitute a set of exact solutions of the Wheeler-DeWitt equation. The affine translational parameter $b$ admits a physical interpretation analogous to a continuous plane wave energy spectrum, where the curvature constant $k$ plays the role of the energy. This result shows that the affine translational subgroup generates transformations in the curvature constant $k$ from the Yamabe problem, while $k$ is inert under the kinematic symmetries of gravity., 9 pages