Partial alignment and measurement of residual dipolar couplings of proteins under high hydrostatic pressure

High-pressure NMR spectroscopy has emerged as a complementary approach for investigating various structural and thermodynamic properties of macromolecules. Noticeably absent from the array of experimental restraints that have been employed to characterize protein structures at high hydrostatic pressure is the residual dipolar coupling, which requires the partial alignment of the macromolecule of interest. Here we examine five alignment media that are commonly used at ambient pressure for this purpose. We find that the spontaneous alignment of Pf1 phage, d(GpG) and a C12E5/n-hexnanol mixture in a magnetic field is preserved under high hydrostatic pressure. However, DMPC/ DHPC bicelles and collagen gel are found to be unsuitable. Evidence is presented to demonstrate that pressure-induced structural changes can be identified using the residual dipolar coupling

Structure and dynamics of Pseudomonas aeruginosa ICP

Pseudomonas aeruginosa inhibitor of cysteine peptidases (PA-ICP) is a potent protein inhibitor of papain-like cysteine peptidases (CPs) identified in Pseudomonas aeruginosa, an opportunistic pathogenic bacteria that can cause severe infections in human. It belongs to the newly characterized natural CP inhibitors of the I42 family, designated the ICP family. The members of this family are present in some protozoa and bacterial pathogens. They can inhibit both parasite and mammalian CPs with high affinity and specificity. Whether the main biological function of the proteins in the pathogens is to regulate the hydrolytic activity of the organisms’ endogenous CPs or exogenous CPs so as to facilitate the pathogens’ invasion or survival is still under investigation. Although Pseudomonas aeruginosa contains a CP inhibitor, no CP genes are found in its genome, suggesting that the targets of PA-ICP may be exogenous. This hypothesis is supported by the presence of a putative secretion signal peptide at the N-terminus of PA-ICP which may be involved in exporting the protein to target exogenous CPs. In order to shed light on the biological function and inhibitory specificity of PA-ICP, the structure and backbone dynamics of this protein were characterised using NMR spectroscopy. In this project, the inhibitory activity of PA-ICP to a range of mammalian model CPs was also studied. Like its previously studied homologs, PA-ICP adopts an immunoglobulin fold comprised of seven β-strands. Three highly conserved sequence motifs located in mobile loop regions form the CP binding site. The inhibitor exhibits higher affinity toward the mammalian CP cathepsin L than cathepsins H and B. Homology modelling of the PA-ICP-cathspin L interaction based on the crystal structure of the chgasin-cathpsin L complex shows that PA-ICP may inhibit the peptidases by blocking the enzyme’s active site and that the interactions between chagasin and CPs may be conserved in PA-ICP-peptidase complexes. The specificity of the inhibitors may be determined by the relative flexibility of the loops bearing the binding site motifs and the electrostatic properties of certain residues near the binding sites

Duszność spowodowana gruźliczakami powstającymi w rdzeniu przedłużonym w czasie leczenia gruźliczego zapalenia opon mózgowo-rdzeniowych

Formation of tuberculoma is a rare response of neurotuberculosis in patients regularly and adequately treated with anti-tuberculous drugs. We report a 13-year-old girl with two tuberculomas which formed in the dorsal part of the medulla oblongata during chemotherapy for tuberculous meningitis. The tuberculomas were both removed via a suboccipital midline approach and were demonstrated by pathological findings but the girl died of cardiac arrest that was thought to be caused by postoperative medulla oblongata oedema. In combination with a literature review, we discuss the clinical features and treatment options of brainstem tuberculomas.Tworzenie się gruźliczaka jest rzadką reakcją w przebiegu właściwie leczonej gruźlicy układu nerwowego. W pracy autorzy opisują przypadek 13-letniej dziewczynki z dwoma gruźliczakami, które utworzyły się w grzbietowej części rdzenia przedłużonego w czasie farmakologicznego leczenia gruźliczego zapalenia opon mózgowo-rdzeniowych. Oba gruźliczaki usunięto z dostępu podpotylicznego w linii środkowej i potwierdzono ich rozpoznanie w badaniu histopatologicznym, ale pacjentka zmarła w wyniku zatrzymania krążenia, przypuszczalnie wskutek pooperacyjnego obrzęku rdzenia przedłużonego. Na podstawie przedstawionego przypadku i przeglądu piśmiennictwa omówiono objawy kliniczne i możliwości leczenia gruźliczaków pnia mózgu

Fabrication of Diamond Nanowires for Quantum Information Processing Applications

We present a design and a top-down fabrication method for realizing diamond nanowires in both bulk single crystal and polycrystalline diamond. Numerical modeling was used to study coupling between a Nitrogen Vacancy (NV) color center and optical modes of a nanowire, and to find an optimal range of nanowire diameters that allows for large collection efficiency of emitted photons. Inductively coupled plasma (ICP) reactive ion etching (RIE) with oxygen is used to fabricate the nanowires. Drop-casted nanoparticles (including $\mathrm{Au}$, $\mathrm{SiO_{2}}$ and $\mathrm{Al_2O_3}$) as well as electron beam lithography defined spin-on glass and evaporated $\mathrm{Au}$ have been used as an etch mask. We found $\mathrm{Al_2O_3}$ nanoparticles to be the most etch resistant. At the same time FOx e-beam resist (spin-on glass) proved to be a suitable etch mask for fabrication of ordered arrays of diamond nanowires. We were able to obtain nanowires with near vertical sidewalls in both polycrystalline and single crystal diamond. The heights and diameters of the polycrystalline nanowires presented in this paper are \unit[\approx1]{\mu m} and \unit[120-340]{nm}, respectively, having a \unit[200]{nm/min} etch rate. In the case of single crystal diamond (types Ib and IIa) nanowires the height and diameter for different diamonds and masks shown in this paper were \unit[1-2.4]{\mu m} and \unit[120-490]{nm} with etch rates between \unit[190-240]{nm/min}.Comment: 11 pages, 26 figures, submitted to Diamond and related Materials; http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TWV-4Y7MM1M-1&_user=10&_coverDate=01%2F25%2F2010&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=6dc58b30f4773a710c667306fc541cc

Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children

Gut microbiota has been implicated as a pivotal contributing factor in diet-related obesity; however, its role in development of disease phenotypes in human genetic obesity such as Prader–Willi syndrome (PWS) remains elusive. In this hospitalized intervention trial with PWS (n = 17) and simple obesity (n = 21) children, a diet rich in non-digestible carbohydrates induced significant weight loss and concomitant structural changes of the gut microbiota together with reduction of serum antigen load and alleviation of inflammation. Co-abundance network analysis of 161 prevalent bacterial draft genomes assembled directly from metagenomic datasets showed relative increase of functional genome groups for acetate production from carbohydrates fermentation. NMR-based metabolomic profiling of urine showed diet-induced overall changes of host metabotypes and identified significantly reduced trimethylamine N-oxide and indoxyl sulfate, host-bacteria co-metabolites known to induce metabolic deteriorations. Specific bacterial genomes that were correlated with urine levels of these detrimental co-metabolites were found to encode enzyme genes for production of their precursors by fermentation of choline or tryptophan in the gut. When transplanted into germ-free mice, the pre-intervention gut microbiota induced higher inflammation and larger adipocytes compared with the post-intervention microbiota from the same volunteer. Our multi-omics-based systems analysis indicates a significant etiological contribution of dysbiotic gut microbiota to both genetic and simple obesity in children, implicating a potentially effective target for alleviation

A Diamond Nanowire Single Photon Antenna

The development of a robust light source that emits one photon at a time is an outstanding challenge in quantum science and technology. Here, at the transition from many to single photon optical communication systems, fully quantum mechanical effects may be utilized to achieve new capabilities, most notably perfectly secure communication via quantum cryptography. Practical implementations place stringent requirements on the device properties, including stable photon generation, room temperature operation, and efficient extraction of many photons. Single photon light emitting devices based on fluorescent dye molecules, quantum dots, and carbon nanotube material systems have all been explored, but none have simultaneously demonstrated all criteria. Here, we describe the design, fabrication, and characterization of a bright source of single photons consisting of an individual Nitrogen-vacancy color center (NV center) in a diamond nanowire operating in ambient conditions. The nanowire plays a positive role in increasing the number of single photons collected from the NV center by an order of magnitude over devices based on bulk diamond crystals, and allows operation at an order of magnitude lower power levels. This result enables a new class of nanostructured diamond devices for room temperature photonic and quantum information processing applications, and will also impact fields as diverse as biological and chemical sensing, opto-mechanics, and scanning-probe microscopy.Comment: 16 pages, 4 figures, v2: Includes improved reference list; modified figure 1 to show a large array of NW and FDTD simulation of field profile; direct experimental comparsion of several bulk/NW devices in figure

Chiang Kai-shek’s “secret deal” at Xian and the start of the Sino-Japanese War

Using newly available archives, particularly the diary and the presidential papers of Chiang Kai-shek, this article challenges the conventional interpretations of the Xian Incident (1936), in particular the widely held belief that the kidnapping of China’s leader Chiang by two rebellious generals forced him to form a united front with the Communist Party to confront Japanese aggression, and of the outbreak of the Sino-Japanese War 7 months later. It puts forth the interpretation that full-scale war between China and Japan was started not by Japan but by Chiang after a Japanese provocation, and the united front was only formed after Chiang ordered his best army units to attack Japanese forces in Shanghai in August 1937 turning it into the largest land battle after the First World War. It must be noted, however, that Japan acted provocatively and aggressively in a local incident outside Beijing a month earlier. Chiang decided on war not because he reached an agreement with the Chinese Communists to form a united front whilst a captive in Xian but because in Xian he received a signal from Josef Stalin that the Soviet Union would support him in a war with Japan. Chiang read Stalin right and the Soviet Union became the largest supplier of weapons to China in the first 4 years of China’s 8-year war with Japan. The hitherto unknown or “secret deal” Chiang made in Xian was an implicit one with Stalin, not with the Chinese Communist Party or its man on the spot Zhou Enlai

Prognostic Analysis of EGFR-TKIs Combined with Gamma Knife in EGFR-mutant Lung Adenocarcinoma with Brain Metastasis

Background and objective Advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma had a high overall incidence of brain metastasis during the full course, and local brain radiotherapy combined with systemic targeted therapy may be a better strategy. This study aimed to identify the prognostic factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients who received EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in combination with gamma knife radiosurgery. Methods Retrospective analysis of EGFR-mutant lung adenocarcinoma patients with brain metastases which developed at initial diagnosis or during EGFR-TKIs treatment period were performed. Intracranial progression free survival (PFS) was statistically analyzed between different subgroups to find out the prognostic factors including gender, age, smoking history, extracranial metastasis, EGFR mutation type, size and number of intracranial lesions, carcino-embryonic antigen (CEA) level, lung-molGPA score and so on. Results A total of 74 EGFR-mutant brain-metastatic lung adenocarcinoma patients were enrolled in this study, with median intracranial PFS of 14.7 months. One-year intracranial-progression-free rate was 58.5%, and two-year rate was 22.2%. Univariate survival analysis showed that patients with lower CEA level at initial diagnosis (3)(15 months vs 12.6 months, P=0.041) were prone to have a superior intracranial PFS. Multivariate analysis showed that CEA≥10 ng/mL and intracranial lesion≥2 cm were the independent risk factors of intracranial PFS. Conclusion EGFR-TKIs in combination with gamma knife radiosurgery was an efficient treatment option to control the cranial tumor lesion. CEA≥10 μg/L at initial diagnosis and intracranial lesion≥2 cm were the risk factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients receiving EGFR-TKIs in combination with gamma knife radiosurgery

Study on Forecasting Break-Up Date of River Ice in Heilongjiang Province Based on LSTM and CEEMDAN

In spring, rivers at middle and high latitudes in the Northern Hemisphere are prone to ice jams, which threaten the safety of hydraulic structures in rivers. Heilongjiang Province is located on the highest latitude in China, starting at 43°26′ N and reaching 53°33′ N. Rivers in Heilongjiang Province freeze in winter and break up in spring. Forecasting the break-up date of river ice accurately can provide an important reference for the command, dispatch, and decision-making of ice flood preventing and shipping. Based on the observed break-up date series of river ice from seven representative hydrological stations in Heilongjiang Province, the complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) was used to decompose the observed break-up date series of river ice into several subsequences, and the long-short term memory neural network (LSTM) was used to forecast the subsequences decomposed by CEEDMAN. Then, the forecast results of each subsequence were summed to obtain the forecasting value for the break-up date of river ice proceeded by CEEMDAN-LSTM. Compared with the LSTM, the forecast accuracy of CEEMDAN-LSTM for the break-up date of river ice had been significantly improved, with the mean absolute error reduced from 0.80–6.40 to 0.75–3.40, the qualification rate increased from 60–100% to 80–100%, the root-mean-square difference reduced from 1.37–5.97 to 0.95–1.69, the correlation coefficient increased from 0.51–0.97 to 0.97–0.98, and the Taylor skill score increased from 0.87–0.99 to 0.99. CEEMDAN-LSTM performed well in forecasting the break-up date of river ice in the Heilongjiang Province, which can provide important information for command, dispatch, and decision-making of ice flood control