Binding Mode Identification for 7-keto-8-Aminopelargonic Acid Synthase (AtKAPAS) Inhibitors

In this study, we determined the 3D structure of Arabidopsis thaliana KAPAS by homology modeling. We then investigated the binding mode of compounds obtained from the in-house library using computational docking methods. From the flexible docking study, we achieved high dock scores for the active compounds denoted in this study as compound 3 and compound 4. Thus, we highlight the flexibility of specific residues, Lys 312 and Phe 172, when used in active sites

Vav1 inhibits RANKL-induced osteoclast differentiation and bone resorption

Vav1 is a Rho/Rac guanine nucleotide exchange factor primarily expressed in hematopoietic cells. In this study, we investigated the potential role of Vav1 in osteoclast (OC) differentiation by comparing the ability of bone marrow mononuclear cells (BMMCs) obtained from Vav1-deficient (Vav1−/−) and wild-type (WT) mice to differentiate into mature OCs upon stimulation with macrophage colony stimulating factor and receptor activator of nuclear kappa B ligand in vitro. Our results suggested that Vav1 deficiency promoted the differentiation of BMMCs into OCs, as indicated by the increased expression of tartrate-resistant acid phosphatase, cathepsin K, and calcitonin receptor. Therefore, Vav1 may play a negative role in OC differentiation. This hypothesis was supported by the observation of more OCs in the femurs of Vav1−/− mice than in WT mice. Furthermore, the bone status of Vav1−/− mice was analyzed in situ and the femurs of Vav1−/− mice appeared abnormal, with poor bone density and fewer number of trabeculae. In addition, Vav1-deficient OCs showed stronger adhesion to vitronectin, an αvβ3 integrin ligand important in bone resorption. Thus, Vav1 may inhibit OC differentiation and protect against bone resorption

E-beam-enhanced solid-state mechanical amorphization of alpha-quartz: Reducing deformation barrier via localized excess electrons as mobile anions

Under hydrostatic pressure, alpha-quartz undergoes solid-state mechanical amorphization wherein the interpenetration of SiO4 tetrahedra occurs and the material loses crystallinity. This phase transformation requires a high hydrostatic pressure of 14 GPa because the repulsive forces resulting from the ionic nature of the Si-O bonds prevent the severe distortion of the atomic configuration. Herein, we experimentally and computationally demonstrate that e-beam irradiation changes the nature of the interatomic bonds in alpha-quartz and enhances the solid-state mechanical amorphization at nanoscale. Specifically, during in situ uniaxial compression, a larger permanent deformation occurs in alpha-quartz micropillars compressed during e-beam irradiation than in those without e-beam irradiation. Microstructural analysis reveals that the large permanent deformation under e-beam irradiation originates from the enhanced mechanical amorphization of alpha-quartz and the subsequent viscoplastic deformation of the amorphized region. Further, atomic-scale simulations suggest that the delocalized excess electrons introduced by e-beam irradiation move to highly distorted atomic configurations and alleviate the repulsive force, thus reducing the barrier to the solid-state mechanical amorphization. These findings deepen our understanding of electron-matter interactions and can be extended to new glass forming and processing technologies at nano- and microscale.Comment: 24 pages, 6 figure

Development of KAISTSAT-4 Expanding the Role of Small Satellite for Scientific Research

The fourth Korean small satellite, KAISTSAT-4, is under development by Satellite Technology Research Center (SaTReC) of the Korea Advanced Institute of Science and Technology (KAIST). The KAISTSAT-4 program was commenced on October 1998 with multiple mission objectives, which include exploring space science, deploying satellite-based data collection system and development of precision star sensor. Despite severe constraints on mass and size, these advanced science and engineering payloads are expected to deliver various useful results and exhibit the unique role of small satellite. We present an overview of the KAISTSAT-4 mission and describe its current status. Finally the prospect of future small satellite programs is briefly introduced

Helical tomotherapy with concurrent capecitabine for the treatment of inoperable pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>Helical tomotherapy, an advanced intensity-modulated radiation therapy with integrated CT imaging, permits highly conformal irradiation with sparing of normal tissue. Capecitabine, a pro-drug of 5-FU that induces thymidine phosphorylase can achieve higher levels of intracellular 5-FU when administered concurrently with radiation. We evaluated the feasibility as well as the clinical outcome of concurrent administration of capecitabine with tomotherapy in patients with advanced pancreatic cancer.</p> <p>Methods</p> <p>Nineteen patients with advanced pancreatic cancer including primarily unresectable disease and recurrence after curative surgery were included in the study. Two planning target volumes (PTV) were entered: PTV1 is gross tumor volume; and PTV2, the volume of the draining lymph nodes. The total doses to target 1 and target 2 were 55 and 50 Gy, respectively. Capecitabine at 1600 mg/m²/day was administered on each day of irradiation.</p> <p>Results</p> <p>Twenty six measurable lesions were evaluated. Overall in-field response rate was 42.3%; partial responses were achieved in 53.3% of the pancreatic masses, 28.6% of distant metastatic lesions and 25.0% of regional lymph nodes. The median duration of follow-up after tomotherapy was 6.5 months. None of the lesions showed in-field progression. Treatment was well tolerated with only minor toxicities such as grade 1 nausea (one patient), grade 1 hand-foot syndrome (one patient) and grade 1/2 fatigue (three patients).</p> <p>Conclusions</p> <p>Helical tomotherapy with concurrent capecitabine is a feasible option without significant toxicities in patients with advanced pancreatic cancer. We achieved excellent conformal distribution of radiation doses and minimal treatment-related toxicities with promising target volume responses.</p

Community-Acquired versus Nosocomial Klebsiella pneumoniae Bacteremia: Clinical Features, Treatment Outcomes, and Clinical Implication of Antimicrobial Resistance

We conducted this study to compare clinical features, outcomes, and clinical implication of antimicrobial resistance in Klebsiella pneumoniae bacteremia acquired as community vs. nosocomial infection. A total of 377 patients with K. pneumoniae bacteremia (191 community-acquired and 186 nosocomial) were retrospectively analyzed. Neoplastic diseases (hematologic malignancy and solid tumor, 56%) were the most commonly associated conditions in patients with nosocomial bacteremia, whereas chronic liver disease (35%) and diabetes mellitus (20%) were the most commonly associated conditions in patients with community-acquired bacteremia. Bacteremic liver abscess occurred almost exclusively in patients with community-acquired infection. The overall 30-day mortality was 24% (91/377), and the mortality of nosocomial bacteremia was significantly higher than that of community-acquired bacteremia (32% vs. 16%, p<0.001). Of all community-acquired and nosocomial isolates, 4% and 33%, respectively, were extended-spectrum cephalosporin (ESC)-resistant, and 4% and 21%, respectively, were ciprofloxacin (CIP)-resistant. In nosocomial infections, prior uses of ESC and CIP were found to be independent risk factors for ESC and CIP resistance, respectively. Significant differences were identified between community-acquired and nosocomial K. pneumoniae bacteremia, and the mortality of nosocomial infections was more than twice than that of community-acquired infections. Antimicrobial resistance was a widespread nosocomial problem and also identified in community-acquired infections