Miracle-dz/UniFAR-FTUs huggingface dataset:
Direct Association of Csk Homologous Kinase (CHK) with the Diphosphorylated Site Tyr568/570 of the Activated c-KIT in Megakaryocytes*

The Csk homologous kinase (CHK), formerly MATK, has previously been shown to bind to activated c-KIT. In this report, we characterize the binding of SH2CHK to specific phosphotyrosine sites on the c-KIT protein sequence. Phosphopeptide inhibition of the in vitro interaction of SH2CHK-glutathione S-transferase fusion protein/c-KIT from SCF/KL-treated Mo7e megakaryocytic cells indicated that two sites on c-KIT were able to bind SH2CHK. These sites were the Tyr568/570 diphosphorylated sequence and the monophosphorylated Tyr721 sequence. To confirm this, we precipitated native CHK from cellular extracts using phosphorylated peptides linked to Affi-Gel 15. In addition, purified SH2CHK-glutathione S-transferase fusion protein was precipitated with the same peptide beads. All of the peptide bead-binding studies were consistent with the direct binding of SH2CHK to phosphorylated Tyr568/570 and Tyr721 sites. Binding of FYN and SHC to the diphosphorylated Tyr568/570 site was observed, while binding of Csk to this site was not observed. The SH2CHK binding to the two sites is direct and not through phosphorylated intermediates such as FYN or SHC. Site-directed mutagenesis of the full-length c-KIT cDNA followed by transient transfection indicated that only the Tyr568/570, and not the Tyr721, is able to bind SH2CHK. This indicates that CHK binds to the same site on c-KIT to which FYN binds, possibly bringing the two into proximity on associated c-KIT subunits and leading to the down-regulation of FYN by CHK.
Gastric gland mucin‐specific O‐glycan expression decreases with tumor progression from precursor lesions to pancreatic cancer

Pancreatic cancer is lethal, as it is often detected late. Thus, novel biomarkers of precursor lesions are needed to devise timely therapies. Pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN) are major precursors of pancreatic cancer. In normal gastric mucosa, gastric gland mucin‐specific O‐glycans are unique in having α1,4‐linked N‐acetylglucosamine (αGlcNAc) residues attached to MUC6. Recently we reported that αGlcNAc functions as a tumor suppressor for differentiated‐type gastric adenocarcinoma (Karasawa et al., J Clin Invest 122, 923, 2012). MUC6 is also expressed in pancreatic neoplasms, including PanIN and IPMN, but the role of αGlcNAc expression in pancreatic neoplasms remains unknown. Here, we analyze expression patterns of αGlcNAc, MUC6 and MUC5AC in pancreatic neoplasms and compare them with progression from PanIN to invasive ductal adenocarcinoma (IDAC) (the PanIN‐IDAC sequence; 20 cases) and from IPMN to IPMN with associated invasive carcinoma (IPMNAIC) (the IPMN‐IPMNAIC sequence; 20 cases). At both sequences, the frequency of MUC6‐positive and αGlcNAc‐positive lesions decreased with tumor progression. We then compared expression levels of αGlcNAc and MUC6 at each step of the progression. At the PanIN‐IDAC sequence, αGlcNAc expression significantly decreased relative to MUC6 in low‐grade PanIN (P = 0.021), high‐grade PanIN/intraductal spread of IDAC (P = 0.031) and IDAC (P = 0.013). At the IPMN‐IPMNAIC sequence, decreased αGlcNAc expression was also observed in low‐grade IPMN exhibiting gastric‐type morphology (P = 0.020). These results suggest that decreased expression of αGlcNAc relative to MUC6 occurs early and marks the initiation of tumor progression to pancreatic cancer.
Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials.

PURPOSE To determine aggregate outcomes and prognostic covariates in patients with recurrent glioma enrolled onto phase II chemotherapy trials. PATIENTS AND METHODS Patients from eight consecutive phase II trials included 225 with recurrent glioblastoma multiforme (GBM) and 150 with recurrent anaplastic astrocytoma (AA). Their median age was 45 years (range, 15 to 82 years) and their median Karnofsky performance score was 80 (range, 60 to 100). Prognostic covariates were analyzed with respect to tumor response, progression-free survival (PFS), and overall survival (OS) by multivariate logistic and Cox proportional hazards regression analyses. RESULTS Overall, 34 (9%) had complete or partial response, whereas 80 (21%) were alive and progression-free at 6 months (APF6). The median PFS was 10 weeks and median OS was 30 weeks. Histology was a robust prognostic factor across all outcomes. GBM patients had significantly poorer outcomes than AA patients. The APF6 proportion was 15% for GBM and 31% for AA, whereas the median PFS was 9 weeks for GBM and 13 weeks for AA. Results were also significantly poorer for patients with more than two prior surgeries or chemotherapy regimens. CONCLUSION Histology is a dominant factor in determining outcome in patients with recurrent glioma enrolled onto phase II trials. Future trials should be designed with separate histology strata.
Physicochemical Decellularization of Composite Flexor Tendon–Bone Interface Grafts

Background: Extremity injuries involving tendon attachment to bone are difficult to address. Clinically, tendon-bone interface allografts must be decellularized to reduce immunogenicity. Composite grafts are difficult to decellularize because chemical agents cannot reach cells between tissues. In this study, the authors attempted to optimize tendon-bone interface graft decellularization. Methods: Human flexor digitorum profundus tendons with attached distal phalanx were harvested from cadavers and divided into four groups. Group 1 (control) was untreated. Group 2 (chemical) was chemically treated with 5% peracetic acid, 0.1% ethylenediaminetetraacetic acid, and 0.1% sodium dodecyl sulfate. Group 3 (low-power) underwent targeted ultrasonication for 3 minutes (22,274 J, 126W) followed by chemical decellularization. Group 4 (high-power) underwent targeted ultrasonication for 10 minutes (88,490 J, 155W) followed by chemical decellularization. Decellularization was assessed histologically with hematoxylin and eosin stain and stains for major histocompatibility complex I stains. Cell counts were performed. The ultimate tensile load of decellularized grafts (group 4) were compared with pair-matched untreated grafts (group 1). Results: Average cell counts were 100 ± 41, 27 ± 10, 12 ± 11, and 6 ± 11 per high-power field for groups 1, 2, 3, and 4, respectively (p < 0.001). Decellularization using physical and chemical treatments (groups 3 and 4) resulted in substantial reduction of cells and major histocompatibility complex I molecules. There was no difference in ultimate tensile load between treated (group4) and untreated (group 1) samples (p > 0.5). Conclusions: Physicochemical decellularization of tendon-bone interface grafts using targeted ultrasonication and chemical treatment resulted in near-complete reduction in cellularity and maintenance of tensile strength. In the future, these decellularized composite scaffolds may be used for reconstruction of tendon-bone injuries.
School-Based Team Research to Address Grand Challenges Through P–12 Physical Education Programs

One of the grand challenges of our time is to educate children and youth to live physically active and healthy lives today and into adulthood. To do so, we must first agree that the highest mission priority for physical education programs in schools is that of public health promotion through physical activity. Under that mission, school physical education programs from preschool to Grade 12 (P–12) would be designed, implemented, resourced, and evaluated to help children meet the recommended 60 min of daily physical activity. From there, the worth of those programs would be judged on their success in accomplishing that mission. This article outlines an agenda for conducting longitudinal, cross-disciplinary team research on exemplary physical education programs that have demonstrated the capacity to help more children achieve the recommended daily level for physical activity. Once those exemplars have been studied and documented, the final step in this agenda is for researchers to disseminate their findings beyond the traditional audiences who read scholarly journals. Those new audiences would include school leaders, parents, other physical activity professionals and organizations, and, ultimately, policymakers. The article ends with a description of a 2-year research project that achieved many of the goals aligned with comprehensive school physical activity programs and that would promote SHAPE America – The Society of Health and Physical Educators' 50 Million Strong by 2029 initiative.
N‐Acylated Alanine Methyl Esters (NAMEs) from Roseovarius tolerans, Structural Analogs of Quorum‐Sensing Autoinducers, N‐Acylhomoserine Lactones

The Roseobacter clade is one of the most important bacteria group living in the ocean. Liquid cultures of Roseovarius tolerans EL 164 were investigated for the production of autoinducers such as N‐acylhomoserine lactones (AHLs) and other secondary metabolites. The XAD extracts were analyzed by GC/MS. Two AHLs, Z7‐C14 : 1‐homoserine lactone (HSL) and C15 : 1‐HSL, were identified. Additionally, the extract contained five compounds with molecular‐ion peaks at m/z 104, 145, and 158, thus exhibiting mass spectra similar to those of AHLs with corresponding peaks at m/z 102, 143, and 156. Isolation of the main compound by column chromatography, NMR analysis, dimethyl disulfide derivatization for the determination of the location of the CC bond and finally synthesis of the compound with the proposed structure confirmed the compound to be (Z)‐N‐(hexadec‐9‐enoyl)alanine methyl ester. Four additional minor compounds were identified as C14 : 0‐, C15 : 0‐, C16 : 0‐, and C17 : 1‐N‐acylated alanine methyl esters (NAMEs). All NAMEs have not been described from natural sources before. A BLASTp search showed the presence of AHL‐producing luxI genes, but no homologous genes potentially responsible for the structurally closely related NAMEs were found. The involvement of the NAMEs in chemical communication processes of the bacteria is discussed.
A Panel Logit Analysis Research on the Choice of Donate Behavior: Using 2006~2015 Data of Korea Welfare Panel

This study aims to examine the causality between socio-economic factors and Donate Behaviour. With the 10 years data in Korea Welfare Panel and Panal logit analysis, the analysis has done on the basis of household and sampled 134,500 data. The results of this research as follows: First, in demographic variables, women revealed as they donate more than men(β=.223, p<.05). And the more the age grows, the less they donate or volunteer periodically(β=-.009, p<.001). Second, in working conditions, paid workers showed less donate behavior than self-employment workers and economically inactive population(β=-.578, p<.001). Third, Self-esteem(β=1.673, p<.001)and Life satisfaction(β=1.01, p<.001) showed significant effect on donate behavior. Lastly, scholarship of father(β=.211, p<.001) revealed as significant on donate behavior. However, scholarship of mother did not showed significant effect. Also, the research had some limitations. First, the precision of the variables were not tested. Second, some variables to analyze were not in the data. Therefore, proper considerations on testing the precision of the variables and the method for measuring the missed variables are needed. ■ keyword :∣Donation∣Donate Behavior∣Volunteer∣Panel Logit Analysis∣Korea Welfare Panel∣ 접수일자 : 2017년 11월 01일 수정일자 : 2018년 02월 23일 심사완료일 : 2018년 03월 21일 교신저자 : 황정은, e-mail : niriri@hanmail.net 기부 행위 선택에 대한 패널 로짓 분석: 2006~2015년 한국 복지 패널 자료를 중심으로 19
In Vivo Intervertebral Disc Characterization Using Magnetic Resonance Spectroscopy and T1&rgr; Imaging: Association With Discography and Oswestry Disability Index and Short Form-36 Health Survey

Study Design. An in vivo study of intervertebral disc degeneration by using quantitative magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Objective. To quantify water and proteoglycan (PG) content in the intervertebral disc by using in vivo MRS and to evaluate the relationship between MRS-quantified water/PG content, T1&rgr;, Pfirrmann score, clinical self-assessment, and discography. Summary of Background Data. Previous in vitro studies have investigated the relationship between MRS-quantified water/PG content and degenerative grade by using cadaveric intervertebral discs. T1&rgr; has been shown to relate to Pfirrmann grade and clinical self-assessment. However, the associations between MRS-quantified water/PG content, MRI-based T1&rgr;, self-assessment of health status, and clinical response to discography have not been studied in vivo. Methods. MRS and MRI were performed in 26 patients (70 discs) with symptomatic intervertebral degenerative disc (IVDD) and 23 controls (41 discs). Patients underwent evaluation of intervertebral discs with provocative discography. All subjects completed the Short Form-36 Health Survey and Oswestry Disability Index questionnaires. Results. The water/PG peak area ratio was significantly elevated in (a) patients (compared with controls) and in (b) discs with positive discography (compared with negative discography). Magnetic resonance (MR) T1&rgr; exhibited similar trends. A significant association was found between T1&rgr; and normalized PG content (R2 = 0.61, P < 0.05) but not between T1&rgr; and normalized water content (R2 = 0.24, P > 0.05). The water/PG peak area ratio, normalized water, normalized PG, and Pfirrmann grade were significantly associated with patient self-assessment of disability and physical composite score, while disc height was not. Conclusion. This study demonstrated a relationship between in vivo MRS spectroscopy (water content and PG content), imaging parameters (T1&rgr; and Pfirrmann grade), discography results, and clinical self-assessment, suggesting that MRS-quantified water, PG, and MR T1&rgr; relaxation time may potentially serve as biomarkers of symptomatic IVDD.
Comparative Effect of Gromwell (Lithospermum erythrorhizon) Extract and Borage Oil on Reversing Epidermal Hyperproliferation in Guinea Pigs

To compare the systemic efficacy of borage oil (Borago officinalis: BO) and gromwell (Lithospermum erythrorhizon), two plant species of the Boraginaceae family, epidermal hyperproliferation was induced in guinea pigs by a hydrogenated coconut oil diet for 8 weeks. Subsequently, guinea pigs were fed diets of BO (group HBO), organic extract (group HGO), or water extract (group HGW) of gromwell for 2 weeks. In groups HGO and HGW, proliferation scores and the level of ceramides, the major lipid maintaining epidermal barrier, were similar with those in normal control group BO fed BO diet for 10 weeks. Despite accumulation of 15-hydroxyeicosatrienoic acid (15-HETrE), the potent anti-proliferative metabolite of γ-linolenic acid (GLA: major polyunsaturated fatty acid in BO), the reversal of epidermal hyperproliferation and the ceramide level of group HBO were less than those of groups HGO and HGW. Taken together, our data demonstrate that gromwell is more effective in reversing epidermal hyperproliferation with a marked increase in ceramides.
Triple Immunofluorolabeling with Two Rabbit Polyclonal Antibodies and a Mouse Monoclonal Antibody Allowing Three-dimensional Analysis of Cotton Wool Plaques in Alzheimer Disease

We established a triple-labeling method with two rabbit polyclonal antibodies and a mouse monoclonal antibody and examined autopsied brain tissue with cotton wool plaques (CWPs). One of the polyclonal antibodies was so diluted (anti-Aβ42 or anti-Aβ40/1:30,000 or anti-von Willebrand factor/1:1000) that its visualization was possible only after amplification with the catalyzed reporter deposition (CARD) method. The other polyclonal antibody (anti-Aβ40 or anti-Ap42/1:1000) was visualized with a fluorochrome conjugated to an anti-rabbit antibody that specifically visualized the latter polyclonal antibody because of its lower sensitivity. A monoclonal antibody, AT8, was superimposed to yield triple immunofluorolabeling. Serial optical sections with an interval of 0.3 μm were reconstructed to allow three-dimensional (3D) observation of these three epitopes. Aβ40 was localized to core-like structures, mainly in layers I–III, and was sometimes in contact with the vascular wall, both without neuritic reactions. CWPs, present in layers I–VI, were labeled with anti-Aβ42 and were accompanied by neuritic reactions. These differences suggest that mechanisms of Aβ deposition and its relation to neuritic reactions or to blood vessels differ according to the lesion, even in the same microscopic field.
Characterization and Use in Immunoradiometric Assay of Monoclonal Antibodies Directed Against Human Proinsulin

Proinsulin in human serum is heterogenous. Existing assay methods do not distinguish between the various forms intermediate on the pathway of processing from proinsulin to insulin. We report the production of mouse monoclonal antibodies against human proinsulin with biosynthetic human proinsulin (produced by recombinant DNA technology) as immunogen. Four monoclonal antibody-producing cell lines were obtained from two separate fusions. Two of the antibodies had affinity constants for intact proinsulin of 3.1 × 1010 and 5.6 × 1010 L/mol and bound all forms of proinsulin and insulin. Crossreactivity with intact proinsulin was greater than with 65-66 and 32-33 split proinsulins and des 64-65 and des 31-32 proinsulins. The third antibody had an affinity constant for intact proinsulin of 6.3 × 1010 L/mol and reacted only with intact proinsulin, 65-66 split proinsulin, and des 64-65 proinsulin; there was no reaction with 32-33 split proinsulin, des 31-32 proinsulin, or C-peptide. The fourth antibody reacted only with intact proinsulin and had an affinity constant of 4.1 × 108 L/mol. We report the use of two antibodies in a sensitive two-site immunoradiometric assay for intact proinsulin. Insulin, C-peptide, and 32-33 split proinsulin did not react in the assay up to a concentration of 100 pM. The 65-66 split proinsulin and des 64-65 proinsulin reacted with a potency of ∼55% relative to intact proinsulin. Serum proinsulin concentrations measured with this assay were compared with those determined by an alternative method that detects only split proinsulins. The results suggest that both intact and split proinsulins occur in human serum but that the forms differ in their kinetics of release and removal in response to an oral glucose load.
Cell cycle-specific and cell type-specific expression of Rb in the developing human retina.

PURPOSE To define the pattern of Rb expression relative to cell cycle position and cell type in the developing human retina. METHODS Cryosections of fetal week 11-18 retinas were immunostained for Rb and cell cycle- or cell type-specific markers. RESULTS Rb was prominent in retinal progenitor cells (RPCs) expressing the cyclin D1, cyclin A, and cytoplasmic cyclin B markers of G1, S, and early to mid G2 phases, but not in RPCs expressing the phosphohistone H3 marker of late G2 and M. Rb was not detected in the earliest postmitotic ganglion, amacrine, horizontal, and bipolar cell precursors migrating away from the ventricular layer, but was detected as such cells underwent further differentiation. Among photoreceptors, Rb was not detected in the earliest RXRgamma(+) cone precursors or in the earliest Nrl(+) rod precursors, but subsequently rose to high levels in cones and to low levels in rods. Rb was prominent at the time when Müller glia exit the cell cycle and was generally expressed in a pattern complementary to p27(Kip1). CONCLUSIONS Rb exhibits cell cycle-specific expression in RPCs, with loss in late G2-M and restoration in G1. Rb is re-expressed after postmitotic ganglion, amacrine, horizontal, and bipolar cell precursors migrate away from the ventricular layer; after the appearance of early cone and rod markers; but coinciding with Müller glia cell cycle withdrawal. The results suggest that Rb does not mediate the initial proliferative arrest of retinal neurons, but may indirectly induce arrest in RPCs or maintain an arrest in postmitotic precursors.
Effect of macrolide antibiotics on uptake of digoxin into rat liver

The objective of this study was to examine the effect of macrolide antibiotics, clarithromycin, erythromycin, roxithromycin, josamycin and azithromycin, on the hepatic uptake of digoxin. The uptake of [3H]digoxin was studied in rats in vivo, using the tissue‐sampling single‐injection technique, and in isolated rat hepatocytes in vitro. The uptake of [3H]digoxin into rat hepatocytes was concentration‐dependent with a Michaelis constant (Km) of 445 nM. All the macrolide antibiotics inhibited the uptake of [3H]digoxin into rat hepatocytes in a concentration‐dependent manner. However, clarithromycin did not affect the in vivo hepatic uptake of digoxin in rats. The in vivo permeability–surface area product of digoxin for hepatic uptake (PSinf) was estimated to be 12.5 ml/min/g liver from the present in vitro data, which is far larger than the hepatic blood flow rate (1.4 ml/min/g liver). Macrolide antibiotics at clinically relevant concentrations inhibit digoxin uptake by rat hepatocytes in vitro, but not in vivo, probably because hepatic uptake of digoxin in rats is blood flow‐limited. Clinically observed digoxin–macrolide interaction in humans could be due to macrolide inhibition of hepatic digoxin uptake, if the uptake is permeation‐limited. Copyright © 2007 John Wiley & Sons, Ltd.
A Bayesian Sparse Reconstruction Framework for Mitigation of Non-Linear Effects in OFDM Systems

The mitigation of nonlinear distortion caused by power amplifiers (PA) in Orthogonal Frequency Division Multiplexing (OFDM) systems is an essential issue to enable energy efficient operation. We propose a new algorithm for receiver-based clipping estimation in OFDM systems that combines the existing Iterative Hard Thresholding method with a novel Bayesian framework to estimate clipping parameters at the receiver. We avoid the use of pilots and formulate the recovery problem solely on reliably detected sub-carriers. We also develop a new criterion for selecting these reliable carriers that takes into account the channel code. Through simulations, we show that the proposed technique outperforms the existing methods both in terms of BER and speed.
Performance analysis of powerline communication for local area networking

The integration of power line communication with that of visible light communication is being considered in this paper. At the physical layer, the existing integrated system degrades in its performance in the presence of power line noises. In this paper a modified integrated system that utilizes the advantage of turbo codes is proposed. Also in the modified integrated system the effect of multipath in power line channel is considered. The simulation results show that our proposed system provides a coding gain of about 6dB. At the data link layer, the media access control (MAC) protocol has to provide large flexibility and scalability to match the heterogeneous requirements such as voice, video and data. The MAC analysis using hybrid protocol, which is based on virtual slot multiple access (VSMA) with a novel backoff mechanism is extended to the PLC and its throughput and delay characteristics are studied.