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Biomedical subjects

S Chen

Publications and source records attributed to S Chen.

At least 37 records · Page 2Linked to original sources

Measurement of two- and three-nucleon short-range correlation probabilities in nuclei.

The ratios of inclusive electron scattering cross sections of 4He, 12C, and 56Fe to 3He have been measured at 1 < xB <. At Q2 > 1.4 GeV2, the ratios exhibit two separate plateaus, at 1.5 < xB < 2 and at xB > 2.25. This pattern is predicted by models that include 2- and 3-nucleon short-range correlations (SRC). Relative to A = 3, the per-nucleon probabilities of 3-nucleon SRC are 2.3, 3.1, and 4.4 times larger for A = 4, 12, and 56. This is the first measurement of 3-nucleon SRC probabilities in nuclei.

Journal Article↗

Eta' photoproduction on the proton for photon energies from 1.527 to 2.227 GeV.

Differential cross sections for the reaction gamma p --> eta' p have been measured with the CLAS spectrometer and a tagged photon beam with energies from 1.527 to 2.227 GeV. The results reported here possess much greater accuracy than previous measurements. Analyses of these data suggest for the first time the coupling of the eta'N channel to both the S11(1535) and P11(1710) resonances, known to couple strongly to the etaN channel in photoproduction on the proton, and the importance of J = 3/2 resonances in the process.

Journal Article↗

Modification of the p53 transgene of a replication-competent adenovirus prevents mdm2- and E1b-55kD-mediated degradation of p53.

Clinical efficacy of adenovirus-mediated cancer gene therapy has been limited thus far. To improve its oncolytic effect, a replication-competent adenoviral vector was previously constructed to express high levels of p53 at a late time point in the viral life cycle. p53 expression from this vector improved tumor cell killing and viral spread in vitro. However, p53 function is antagonized by cellular mdm2 and adenoviral E1b-55kD, both of which are known to bind to and inactivate p53. Therefore, a new vector (Adp53W23S) that expresses a modified p53 transgene, which does not bind to E1b-55kd and mdm2, was constructed. The modified p53 protein was demonstrated to have a substantially prolonged half-life, and its localization was predominantly nuclear. Viral replication was unaffected by expression of the modified p53 and cancer cell killing was improved in vitro. However, in a xenograft model, efficacy was not significantly different from control virus. In conclusion, expression of a degradation-resistant p53 transgene late in the life cycle of a replication-competent adenovirus improves p53 stability and cancer cell killing in vitro. However, other factors, such as the adenoviral E1b-19kD and E1a proteins, which oppose p53 function, and limitations to viral spread need to be addressed to further improve in vivo efficacy.

Adenoviridae↗

Search for Theta+ (1540) Pentaquark in High-Statistics Measurement of gammap-->K0K+n at CLAS.

The exclusive reaction gammap-->K0K+n was studied in the photon energy range between 1.6 and 3.8 GeV searching for evidence of the exotic baryon Theta+ (1540)-->nK+. The decay to nK+requires the assignment of strangeness S=+1 to any observed resonance. Data were collected with the CLAS detector at the Thomas Jefferson National Accelerator Facility corresponding to an integrated luminosity of 70 pb-1. No evidence for the Theta+ pentaquark was found. Upper limits were set on the production cross section as function of center-of-mass angle and nK+ mass. The 95% C.L. upper limit on the total cross section for a narrow resonance at 1540 MeV was found to be 0.8 nb.

Journal Article↗

Superplastic carbon nanotubes.

The theoretical maximum tensile strain--that is, elongation--of a single-walled carbon nanotube is almost 20%, but in practice only 6% is achieved. Here we show that, at high temperatures, individual single-walled carbon nanotubes can undergo superplastic deformation, becoming nearly 280% longer and 15 times narrower before breaking. This superplastic deformation is the result of the nucleation and motion of kinks in the structure, and could prove useful in helping to strengthen and toughen ceramics and other nanocomposites at high temperatures.

Journal Article↗

The enantioseparation of amino acids on a teicoplanin chiral stationary phase using non-aqueous mobile phases after pre-column derivatization with sulfur-containing reagents: the considerations of mobile phase composition and analyte structure variation on resolution enhancement.

Amino acids were derivatized with sulfur-containing reagents in alkaline medium and enantioresolved by HPLC on a teicoplanin chiral stationary phase. Much better resolution was achieved using methanol-based mobile phase compared with elution with acetonitrile-based solvent mixture. The value of selectivity factor for many derivatives examined in the study can be easily several tenths of 100 or even exceed 100 in some cases. This magnitude of resolution is suitable for the preparative-scale application of isolating alpha-amino acid enantiomers in the derivatized form using a short column. The resolution is believed to be a result of the hydrogen bonding and steric hindrance by the nitrogen and sulfur atoms from the isothiocyanatyl fragment of the reagent, respectively, and is enhanced as the fragment is structurally phenylated (e.g. 2,4-difluorophenyl isothiocyanate and others examined in this study). The enhancement is even more significant if the aromatic moiety of the reagent becomes more acidic through halogenation with chlorine or fluorine for the stronger pi-pi interaction. However, this type of enhancement is offset to some extent and sometimes obscured by a chlorinated reagent that is relatively large in size as compared with the fluorinated one. Judging from the chromatographic data and the elution profile, the mechanisms leading to the resolutions are believed to be different under the elution of polar-organic mobile phases (i.e. methanol- and acetonitrile-based mobile phases).

Amino Acids↗

Organogenesis of pancreatic anlagen allografted in rats.

AIMS: To study the possibility of revascularization, growth, and differentiation of embryonic pancreatic anlagen transplanted to adult hosts. While transplantations of pancreas and islets are the main methods to cure diabetes mellitus, the donor source is in shortage. So it's necessary to find a new source for transplantation. METHODS: The pancreas from embryonic day 14.5 (E14.5) and 15.5 (E15.5) Lewis rat embryos were implanted into either intraperitoneal or subrenal capsular site of healthy Lewis rats. at 3 weeks or 6 weeks after implantation, the pancreatic anlagen in the host rats were resected for size measurements, as well as histopathologic and immunohistochemical examinations. RESULTS: Three weeks after implantation into the renal-capsular site, the size of both E14.5 and E15.5 pancreatic anlagen had enlarged 10- to 15-fold with differentiation of acinar components upon histological examination. Moreover, increasing numbers of beta cells and islets stained positive for insulin, and newly generated vessels were observed around the tissues. Continued proliferation of the endocrine islets in E14.5 pancreatic anlagen grafts was observed after another 3 weeks, whereas further proliferation in the E15.5 pancreatic anlagen graft was not seen. Additionally fibrosis appeared in the exocrine component of both E14.5 and E15.5 pancreatic anlagen at this time point. When implanted into intraperitoneal site, enlarged E15.5 pancreatic anlagen with proliferatels beta cells were also observed after 3 weeks. However, both the size of the pancreatic anlagen and the proliferation of the beta cells were much less than that in the subrenal capsular site. CONCLUSIONS: The allografted E14.5 and E15.5 pancreatic anlagen revascularised and grew into tissues that were structurally similar to normal mature rats pancreatic tissue. Adequate embryonic age for the transplantation of pancreatic anlagen is 14.5 and 15.5 days old. Subrenal capsula is a more suitable site than the peritoneal cavity for implantation of pancreatic anlagen.

Animals↗

Prolonged cardiac allograft survival in presensitized rats after a high activity Yunnan-cobra venom factor therapy.

UNLABELLED: Complement-dependent antibody-mediated acute humoral rejection is the major obstacle of clinical transplantation across ABO incompatibility and human leukocyte antigen presensitization. We previously demonstrated that Yunnan-cobra venom factor (Y-CVF) could almost completely abrogate complement activity and successfully prevent hyperacute rejection in some xenotransplant models without any obvious toxicity. In this study we investigated whether depletion of complement by Y-CVF prevented acute humoral allograft rejection in presensitized rats thereby prolonging graft survival. METHODS: Presensitization was achieved in Lewis rats by sequential grafting of three full-thickness skin pieces from Brown Norway rats. Serum cytotoxic alloantibody titers were determined by a modified in vitro complement-dependent microcytotoxicity assay. After presensitization, each Lewis rat received a heterotopic Brown Norway cardiac allograft. Fifteen recipients were divided into two groups: (1) no treatment control (n = 7); (2) Y-CVF therapy group (86 u/kg, IV, day -1) (n = 8). After cessation of the heart beat, allograft rejection was confirmed by pathologic as well as IgG and C3 immunohistochemical examinations. RESULTS: The mean graft survival time was significantly prolonged to 99.50 +/- 38.72 hours among rats that received Y-CVF vs 12.71 +/- 13.94 hours in nontreated controls (P < .001). Upon pathological and immunohistochemical examination, acute humoral rejection was mainly exhibited in the control group, whereas acute cellular rejection was mainly displayed in the Y-CVF therapy group. CONCLUSIONS: Our study demonstrated that complement depletion by Y-CVF significantly inhibited acute humoral allograft rejection in presensitized rats. As a therapeutic immunointervention tool for complement, Y-CVF has shown potential efficacy across ABO incompatible and positive cross-match barriers.

Animals↗

Sertoli cells induce xenolymphocyte apoptosis in vitro.

BACKGROUND: Testicular Sertoli cells can protect pancreatic islet grafts from allo- and autoimmune destruction; however, the mechanisms underlying immune privilege of the testicle are not well understood, especially in xenotransplantation. The purpose of this study was to investigate whether rat Sertoli cells could induce mouse lymphocyte apoptosis in vitro. METHODS: Testis was isolated from 2- to 4-week-old Sprague Dawley (SD) rats. Sertoli cells were successfully prepared by digestion with collagenase type V, trypsin, and DNase I, and then identified by electron microscope. Viability and apoptosis of cultured cells were measured by flow cytometry. We examined the apoptosis rates of Balb/c mouse lymphocytes, which were cocultured with SD rat Sertoli cells by FACS. The expression of Fas ligand (Fasl), transforming growth factor (TGF)-beta1 and clusterin on Sertoli cells were detected by immunocytochemistry. RESULTS: In the cocultured system, Sertoli cells accounted for more than 93%. With our isolation method, the viability of Sertoli cells was more than 95% and the apoptosis rate was 10.87% +/- 3.87%. The lymphocyte apoptosis ratio was 15.52 +/- 0.17 (P < .01, compared with the control groups). SABC immunochemistry staining showed that the sertoli cells could express FasL, TGF-beta, and clusterin. CONCLUSIONS: In our coculture in vitro, rat Sertoli cells expressed FasL and TGF-beta1 as well as induced the apoptosis of mouse lymphocytes. These results indicated that the expression of FasL and TGF-beta1 on Sertoli cells might relate to immune privilege in xenotransplantation.

Animals↗

Induction of accommodation model by combined RNA interference targeting 1,3-galactosyltransferase gene and low-dose GS-IB4 lectin in vitro.

OBJECTIVE: This study sought to mimic the interaction of xenograft endothelial cells and human serum in vitro after successfully silencing the expression of porcine alpha1,3-galactosyltransferase (alpha1,3GT) gene by RNA interference (RNAi), and to investigate the possibility of inducing accommodation in vitro by stimulation of alpha-Gal-specific binding lectin, Griffonia simplicifolia isolectin B4 (GS-IB4) and RNAi. MATERIALS AND METHODS: Various alpha-Gal expression patterns on a pig endothelial cell immortalized line (PED) was achieved by serial doses of small interfering RNA (siRNA) targeting porcinc alpha1,3GT gene. alpha1,3GT-siRNA transfected PEDs were exposed to increasing doses of GS-IB4 lectin (0.5, 2, and 8 microg/mL) for 4 hours before incubation with normal human serum (NHS). Accommodation phenomenon of PEDs in NHS was observed by 51Cr release and antibody/complement binding assays. RESULTS: With combined RNAi and low-dose GS-IB4 stimulation, PEDs remarkably inhibited complement-mediated cytotoxicity, which showed a better protective effect than using RNAi alone. At a concentration of 2 mug/mL, GS-IB4 exhibited the maximum protective effect. The expression of E-selectin on alpha1,3GT-siRNA transfected PEDs did not differ from that on parental PEDs with heat-inactivated NHS (HINHS) stimulation. Combined with GS-IB4 stimulation, however, it inhibited expression of E-selectin, which was GS-IB4 dose dependent, resulting in mean fluorescence intensity values of 98.5, 42.0, and 36.3 at 0.5, 2, and 8 microg/mL. The mRNA expression of the protective gene HO-1 was significantly up-regulated after treatment with RNAi and low-dose of GS-IB4. CONCLUSIONS: Combined RNAi and low-dose GS-IB4 induced pig endothelial cell accommodation in vitro. The level of alpha-Gal expression played an important role in the induction of accommodation.

Animals↗

A study of soluble HLA-G1 protecting porcine endothelial cells against human natural killer cell-mediated cytotoxicity.

UNLABELLED: Human natural killer (NK) cells, which can mediate direct lysis of porcine endothelial cells, play an important role in xenograft rejection. HLA-G, which is a critical molecule in maintaining maternal immune tolerance of semi-allogenic fetus, is able to protect susceptible target cells from lysis induced by NK cells. In this study, we investigated whether soluble HLA-G1 (sHLA-G1) protected porcine xenogeneic cells against human NK cell-mediated lysis. METHODS: The human sHLA-G1 genomic DNA (pcDNA3-sHLA-G1) was transfected into a B lymphoblastoid cell line 721.221 (LCL721.221) by nucleofector. The sHLA-G1 expression of the transfected LCL721.221 cells was identified by RT-PCR and Dot-ELISA. The sHLA-G1 protein was purified by affinity chromatography on anti-HLA-ImAb W6/32 coupled to cyanogen-bromide-activated Sepharose 4B from culture supernates of transfectants. Various concentrations of sHLA-G(1) protein (0, 2, 4, 6, or 8 microg/mL) were added to a NK cell-mediated xenogenic cell lysis system with either NK92 cells or fresh human peripheral blood mononuclear cells (PBMCs) cocultured with the porcine endothelial cells line. A LDH release assay was used to evaluate NK cell-mediated cytotoxicity. RESULTS: sHLA-G1 provided significant protection of porcine endothelial cells against human NK-mediated cytotoxicity in a dose-dependent manner. The rates of NK92 cell-mediated cytotoxicity were reduced to 83.4 +/- 5.7% (2 microg/mL), 56.6 +/- 9.3% (4 microg/mL), 39.3 +/- 10.2% (6 microg/mL), and 31.2 +/- 4.9% (8 microg/mL) versus 96.9 +/- 3.0% in the control group (P < .01). Similarly, adding 6 microg/mL sHLA-G1 reduced the mean rate of PBMC-mediated cytotoxicity (n = 4) to 5.8 +/- 1.6% from 23.9 +/- 1.3% in the control group (P < .01). CONCLUSIONS: These results indicated that sHLA-G1 protected xenogeneic porcine endothelial cells against attack by human NK cells, thus providing a new approach to overcome NK-mediated immunity to xenografts.

Animals↗

Real-time observation of tubule formation from amorphous carbon nanowires under high-bias Joule heating.

The tubule formation process from amorphous carbon nanowires under high-bias-caused Joule heating was observed in real time in a high-resolution transmission electron microscope. The crystallization of the amorphous carbon nanowires occurred in two distinct ways: the formation of tubular graphitic basal planes parallel to the nanowire axis on the surface and the formation of nano-onions in the interior of the nanowire. The tubule formation mechanism is a process of solid-state atom diffusion at high temperatures. Energetically, the tubule formation is caused by the exceptionally low surface energy of the (0002) plane of graphite. Higher input power to the amorphous nanowires generally leads to improved graphitization and, in turn, to increased conductance. The results suggest that nanotube formation in the arc-discharge growth process may involve the formation and crystallization of amorphous carbon.

Computer Systems↗

Coupling endoplasmic reticulum stress to the cell-death program: a novel HSP90-independent role for the small chaperone protein p23.

The endoplasmic reticulum (ER) is the principal organelle for the biosynthesis of proteins, steroids and many lipids, and is highly sensitive to alterations in its environment. Perturbation of Ca(2+) homeostasis, elevated secretory protein synthesis, deprivation of glucose or other sugars, altered glycosylation and/or the accumulation of misfolded proteins may all result in ER stress, and prolonged ER stress triggers cell death. Studies from multiple laboratories have identified the roles of several ER stress-induced cell-death modulators and effectors through the use of biochemical, pharmacological and genetic tools. In the present work, we describe the role of p23, a small chaperone protein, in preventing ER stress-induced cell death. p23 is a highly conserved chaperone protein that modulates HSP90 activity and is also a component of the steroid receptors. p23 is cleaved during ER stress-induced cell death; this cleavage, which occurs close to the carboxy-terminus, requires caspase-3 and/or caspase-7, but not caspase-8. Blockage of the caspase cleavage site of p23 was associated with decreased cell death induced by ER stress. Immunodepletion of p23 or inhibition of p23 expression by siRNA resulted in enhancement of ER stress-induced cell death. While p23 co-immunoprecipitated with the BH3-only protein PUMA (p53-upregulated modulator of apoptosis) in untreated cells, prolonged ER stress disrupted this interaction. The results define a protective role for p23, and provide further support for a model in which ER stress is coupled to the mitochondrial intrinsic apoptotic pathway through the activities of BH3 family proteins.

Animals↗

Kernel classifier construction using orthogonal forward selection and boosting with Fisher ratio class separability measure.

A greedy technique is proposed to construct parsimonious kernel classifiers using the orthogonal forward selection method and boosting based on Fisher ratio for class separability measure. Unlike most kernel classification methods, which restrict kernel means to the training input data and use a fixed common variance for all the kernel terms, the proposed technique can tune both the mean vector and diagonal covariance matrix of individual kernel by incrementally maximizing Fisher ratio for class separability measure. An efficient weighted optimization method is developed based on boosting to append kernels one by one in an orthogonal forward selection procedure. Experimental results obtained using this construction technique demonstrate that it offers a viable alternative to the existing state-of-the-art kernel modeling methods for constructing sparse Gaussian radial basis function network classifiers that generalize well.

Algorithms↗

A novel index for analysing the response of a microbial culture to changes in the environmental variables during cultivation.

AIMS: To analyse the sensitivity of a microbial culture to variations in the cultivation conditions by using the motile intensity of the cells. METHODS AND RESULTS: Batch cultures of Bacillus thuringiensis were used to study the sensitivity of the cells to pulse changes in pH, temperature and oxygen supply. A droplet of the culture sample was visualized under an optical microscope and the image of the moving cells was captured with a computer controlled display camera attached to the microscope. Motile intensity was computed directly using an image analysis programme. The results showed that the different phases of cell growth exhibited different motile intensities. The motile intensity changed remarkably at the high level of the motile intensity, when the environmental variables are changed. CONCLUSIONS: The product formation was considerably reduced when a disturbance was applied at the high magnitude of motile intensity. SIGNIFICANCE AND IMPACT OF STUDY: Monitoring the motile intensity by image analysis is simple and makes it an attractive method for assessing the effect of environmental variables on the growth and product formation of microbial cultures.

Bacillus thuringiensis↗

Polymorphism of HLA class II genes in Miao and Yao nationalities of Southwest China.

In the present study, the polymorphism of human leucocyte antigen class II genes was investigated by the sequence-based typing method in two Chinese populations: the Miaos (n = 85) from Guizhou province and the Yaos (n = 66) from Yunnan province. These two populations exhibited certain similarity in their allelic distributions. Among 24 DRB1 alleles detected, DRB1*150101, DRB1*140101, DRB1*160201 and DRB1*090102 in Miao and DRB1*120201, DRB1*140101, DRB1*150101 and DRB1*090102 in Yao were highly predominant. Sixteen DQB1 alleles in total were found in these two populations among which DQB1*050201, DQB1*060101/060103 and DQB1*030101/0309 in both Miao and Yao and DQB1*050301 in Yao were commonly observed. In the 13 DPB1 alleles detected, the most frequent allele was DPB1*0501 in Miao and Yao followed by DPB1*02 and DPB1*1301. Frequent comparisons with other Chinese populations suggested the southern Chinese feature for both the Miao and Yao nationalities.

Alleles↗

Human immunodeficiency virus test-seeking motivation in blood donors, São Paulo, Brazil.

BACKGROUND AND OBJECTIVE: Previous studies have shown that volunteer, community-recruited donors have a higher prevalence of human immunodeficiency virus (HIV) infection in São Paulo, Brazil, than replacement donors. One hypothesis which may explain this unexpected finding is that some individuals donate blood because they are seeking HIV testing. The objective of this study was to characterize test-seeking blood donors and to determine whether they are at higher risk for HIV infection compared with other donors. MATERIALS AND METHODS: Subjects presenting for blood donation were asked to participate in a study assessing their motivations (including test seeking) to donate, as measured by perceiving donation as a means to obtain infectious disease test results. Participants completed the standard blood bank predonation screening questions plus our additional survey, and were tested for HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell lymphocytotrophic virus (HTLV) I/II, syphilis and Chagas' disease. As a result of anticipated low statistical power to directly measure the association between test-seeking motivation and HIV infection, we tested for herpes simplex virus type 2 (HSV-2) as a marker of sexual risk for HIV. Our survey includes accepted donors as well as persons whose risk-behaviour histories would result in their exclusion from donation according to routine screening procedures. RESULTS: Of 1,720 potential blood donors randomly selected and approached, 1,600 (93.0%) participated. Overall, 141 (8.8%) were classified as test seekers; 15.6% of these were HSV-2 positive. The proportion of test seekers was the same among community-recruited and replacement donors. Test seekers had a higher prevalence of HSV-2 [adjusted odds ratio (AOR) 1.66; 95% confidence interval (CI): 1.06-2.59] adjusting for age, gender and prior donation. The association was significant among community-recruited blood donors whose previous donation was more than 1 year ago (i.e. 'lapsed donors') (AOR 2.55; 95% CI: 1.20-5.44). Test seekers were not more likely to be rejected from blood donation as a result of health reasons, self-reported HIV risk-related behaviour, or by their own confidential unit exclusion. We found no difference in HSV-2 prevalence between persons accepted for donation (15.7%) and those rejected because of self-reported sexual risk (16.7%). CONCLUSIONS: We did not detect a difference in the proportion of test seekers across different types of blood donors; however, we did detect an association between HSV-2 infection and test seeking, especially among community-recruited lapsed blood donors. Of note, questions on test-seeking behaviour detected donors with increased prevalence of HSV-2, but the self-reported sexual risk behaviours currently used for deferral criteria did not. Incentives to get tested at sites other than blood banks may decrease the residual risk of HIV in the blood supply.

Adult↗