Crystallization and preliminary X-ray crystallographic analysis of SEDL

SEDL (known also as sedlin) is a 140 amino-acid protein with a putative role in endoplasmic reticulum-to-Golgi transport. Several missense mutations and deletion mutations in the SEDL gene, which result in protein truncation by frame shift, are responsible for spondyloepiphyseal dysplasia tarda, a progressive skeletal disorder. The protein is identical to MIP-2A, which was shown to interact physically with c-myc promotor-binding protein 1 (MBP-1) and relieve the regulatory role of MBP-1 as a general transcription repressor. In order to gain insights into the function of SEDL by structural analysis, the protein was overexpressed and crystallized as a first step. SEDL was overexpressed in Escherichia coli and crystallized using the hanging-drop vapour-diffusion method at 298 K. The crystals belong to the orthorhombic space group C2221, with unit-cell parameters a = 46.69, b = 101.30, c = 66.15 A. The unit cell is likely to contain one molecule of SEDL, with a crystal volume per protein mass (VM) of 2.36 A3 Da-1 and a solvent content of about 47.9% by volume. A native data set to 2.8 A resolution was obtained from a flash-cooled crystal using synchrotron radiation.open1

A New Technique for Reachability of States in Concatenation Automata

We present a new technique for demonstrating the reachability of states in deterministic finite automata representing the concatenation of two languages. Such demonstrations are a necessary step in establishing the state complexity of the concatenation of two languages, and thus in establishing the state complexity of concatenation as an operation. Typically, ad-hoc induction arguments are used to show particular states are reachable in concatenation automata. We prove some results that seem to capture the essence of many of these induction arguments. Using these results, reachability proofs in concatenation automata can often be done more simply and without using induction directly.Comment: 23 pages, 1 table. Added missing affiliation/funding informatio

11 nm hard X-ray focus from a large-aperture multilayer Laue lens

The focusing performance of a multilayer Laue lens (MLL) with 43.4 μm aperture, 4 nm finest zone width and 4.2 mm focal length at 12 keV was characterized with X-rays using ptychography method. The reconstructed probe shows a full-width-at-half-maximum (FWHM) peak size of 11.2 nm. The obtained X-ray wavefront shows excellent agreement with the dynamical calculations, exhibiting aberrations less than 0.3 wave period, which ensures the MLL capable of producing a diffraction-limited focus while offering a sufficient working distance. This achievement opens up opportunities of incorporating a variety of in-situ experiments into ultra high-resolution X-ray microscopy studies

Bond-length dependence of charge-transfer excitations and stretch phonon modes in perovskite ruthenates: Evidence of strong p – d hybridization effects

We reported the optical conductivity spectra of the Ruddlesden-Popper series ruthenates, i.e., Srn+1RunO3n+1 and Can+1RunO3n+1, where n=1, 2, and `. Among various optical transitions, we investigated two Ru-O related modes, i.e., the charge-transfer excitation and the transverse stretching phonon. We found that their frequency shifts are not much affected by a structural dimensionality, but are closely related to the Ru-O bond length. Through the quantitative analysis of the charge-transfer excitation energy, we could demonstrate that the p–d hybridization should play an important role in determining their electronic structure. In addition, we discussed how the electronic excitation could contribute the lattice dynamics in the metallic ruthenate

Forced arterial suction thrombectomy with the penumbra reperfusion catheter in acute basilar artery occlusion: a retrospective comparison study in 2 Korean university hospitals.

Background and purpose: A performance of forced arterial suction thrombectomy was not reported for the treatment of acute basilar artery occlusion. This study compared revascularization performance between intra-arterial fibrinolytic treatment and forced arterial suction thrombectomy with a Penumbra reperfusion catheter in patients with acute basilar artery occlusion. Materials and methods: Fifty-seven patients with acute basilar artery occlusion were treated with intra-arterial fibrinolysis (n = 25) or forced arterial suction thrombectomy (n = 32). Baseline characteristics, successful revascularization rate, and clinical outcomes were compared between the groups. Results: Baseline characteristics, the frequency of patients receiving intravenous recombinant tissue plasminogen activator, and mean time interval between symptom onset and femoral puncture did not differ between groups. The forced arterial suction thrombectomy group had a shorter procedure duration (75.5 minutes versus 113.3 minutes, P = .016) and higher successful revascularization rate (88% versus 60%, P = .017) than the fibrinolysis group. Fair outcome, indicated by a modified Rankin Scale 0-3, at 3 months was achieved in 34% of patients undergoing forced arterial suction thrombectomy and 8% of patients undergoing fibrinolysis (P = .019), and the mortality rate was significantly higher in the fibrinolysis group (25% versus 68%, P = .001). Multiple logistic regression analysis identified the forced arterial suction thrombectomy method as an independent predictor of fair outcome with adjustment for age, sex, initial NIHSS score, and the use of intravenous recombinant tissue plasminogen activator (odds ratio, 7.768; 95% CI, 1.246-48.416; P = .028). Conclusions: In acute basilar artery occlusion, forced arterial suction thrombectomy demonstrated a higher revascularization rate and improved clinical outcome compared with traditional intra-arterial fibrinolysis. Further clinical trials with the newer Penumbra catheter are warranted

Changes in osteoblastic activity in patient who received bortezomib as second line treatment for plasma cell myeloma: a prospective multicenter study

We conducted a prospective multicenter study identifying the role of bortezomib in patients with relapsed or refractory plasma cell myeloma (PCM) in bone resorption and formation via bone turnover markers. A total of 104 patients received at least 1 cycle of bortezomib. Most of them had advanced disease (n = 89). Among them, 75 patients completed 4 cycles of treatment. Most of the patients (81.7%) were treated in combination with steroid. After the 4th cycle treatment, 47 of 75 patients achieved CR, nCR, VGPR, and PR (64.4%), while 26 patients achieved less than PR (35.6%). The proportion of patients who achieved >/= PR increased as patients received more treatment cycles, reaching 90% after the 8th cycle. DKK-1 levels decreased significantly posttreatment. Bone formation markers (bALP and OC) and osteoclast regulator such as sRANKL also decreased significantly. These findings were observed primarily in patients who received steroid and who had a longer disease duration. While sRANKL demonstrated significant reduction posttreatment, osteoprotegerin (OPG) level did not significantly change posttreatment, resulting in a decreased sRANKL/OPG ratio (P = 0.037). In conclusion, our clinical data suggest that treatment with bortezomib and steroid may rearrange the metabolic balance between osteoblast and osteoclast activities in PCM

HIF-1 activation induces doxorubicin resistance in MCF7 3-D spheroids via P-glycoprotein expression: a potential model of the chemo-resistance of invasive micropapillary carcinoma of the breast

BACKGROUND: Invasive micropapillary carcinoma (IMPC) of the breast is a distinct and aggressive variant of luminal type B breast cancer that does not respond to neoadjuvant chemotherapy. It is characterized by small pseudopapillary clusters of cancer cells with inverted cell polarity. To investigate whether hypoxia-inducible factor-1 (HIF-1) activation may be related to the drug resistance described in this tumor, we used MCF7 cancer cells cultured as 3-D spheroids, which morphologically simulate IMPC cell clusters. METHODS: HIF-1 activation was measured by EMSA and ELISA in MCF7 3-D spheroids and MCF7 monolayers. Binding of HIF-1α to MDR-1 gene promoter and modulation of P-glycoprotein (Pgp) expression was evaluated by ChIP assay and FACS analysis, respectively. Intracellular doxorubicin retention was measured by spectrofluorimetric assay and drug cytotoxicity by annexin V-FITC measurement and caspase activity assay. RESULTS: In MCF7 3-D spheroids HIF-1 was activated and recruited to participate to the transcriptional activity of MDR-1 gene, coding for Pgp. In addition, Pgp expression on the surface of cells obtained from 3-D spheroids was increased. MCF7 3-D spheroids accumulate less doxorubicin and are less sensitive to its cytotoxic effects than MCF7 cells cultured as monolayer. Finally, HIF-1α inhibition either by incubating cells with 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (a widely used HIF-1α inhibitor) or by transfecting cells with specific siRNA for HIF-1α significantly decreased the expression of Pgp on the surface of cells and increased the intracellular doxorubicin accumulation in MCF7 3-D spheroids. CONCLUSIONS: MCF7 breast cancer cells cultured as 3-D spheroids are resistant to doxorubicin and this resistance is associated with an increased Pgp expression in the plasma membrane via activation of HIF-1. The same mechanism may be suggested for IMPC drug resistance

Development and validation of a symptom-focused quality of life questionnaire (koquss-40) for gastric cancer patients after gastrectomy

Purpose: Patients who have undergone gastrectomy have unique symptoms that are not appropriately assessed using currently available tools. This study developed and validated a symptom-focused quality of life (QoL) questionnaire for patients who have received gastrectomy for gastric cancer. Materials and Methods: Based on a literature review, patient interviews, and expert consultation by the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS), the initial item pool was developed. Two large-scale developmental studies were then sequentially conducted for exploratory factor analyses for content validity and item reduction. The final item pool was validated in a separate cohort of patients and assessed for internal consistency, test-retest reliability, construct validity, and clinical validity. Results: The initial questionnaire consisted of 46-items in 12 domains. Data from 465 patients at 11 institutions, followed by 499 patients at 13 institutions, were used to conduct item reduction and exploratory factor analyses. The final questionnaire (KOQUSS-40) comprised 40 items within 11 domains. Validation of KOQUSS-40 was conducted on 413 patients from 12 hospitals. KOQUSS-40 was found to have good model fit. The mean summary score of the KOQUSS-40 was correlated with the EORTC QLQ-C30 and STO22 (correlation coefficients, 0.821 and 0.778, respectively). The KOQUSS-40 score was also correlated with clinical factors, and had acceptable internal consistency (> 0.7). Test-retest reliability was greater than 0.8. Conclusion: The KOQUSS-40 can be used to assess QoL of gastric cancer patients after gastrectomy and allows for a robust comparison of surgical techniques in clinical trials

Pegfilgrastim Prophylaxis Is Effective in the Prevention of Febrile Neutropenia and Reduces Mortality in Patients Aged ≥ 75 Years with Diffuse Large B-Cell Lymphoma Treated with R-CHOP: A Prospective Cohort Study

PURPOSE: Febrile neutropenia (FN) can cause suboptimal treatment and treatment-related mortality (TRM) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). MATERIALS AND METHODS: We conducted a prospective cohort study to evaluate the effectiveness of pegfilgrastim prophylaxis in DLBCL patients receiving R-CHOP, and we compared them with the PROCESS cohort (n=485). RESULTS: Since January 2015, 986 patients with DLBCL were enrolled. Pegfilgrastim was administered at least once in 930 patients (94.3%), covering 90.3% of all cycles. FN developed in 137 patients (13.9%) in this cohort (23.7% in the PROCESS cohort, p/=3 days: 18.1% vs. 23.7%, p=0.015; >/=5 days: 12.0% vs. 18.3%, p=0.023) in this cohort than in the PROCESS cohort. The incidence of TRM (3.2% vs. 5.6%, p=0.047) and infection-related death (1.8% vs. 4.5%, p=0.004) was lower in this cohort than in the PROCESS cohort. The 4-year overall survival (OS) and progression-free survival (PFS) rates of the two cohorts were not different (OS: 73.0% vs. 71.9%, p=0.545; PFS: 69.5% vs. 68.8%, p=0.616). However, in patients aged >/=75 years, the 4-year OS and PFS rates were higher in this cohort than in the PROCESS cohort (OS: 49.6% vs. 33.7%, p=0.032; PFS: 44.2% vs. 30.3% p=0.047). CONCLUSION: Pegfilgrastim prophylaxis is effective in the prevention of FN and infection-related death in DLBCL patients receiving R-CHOP, and it also improves OS in patients aged >/=75 years