The emission of γ-Ray beams with orbital angular momentum in laser-driven micro-channel plasma target.

We investigated the emission of multi-MeV γ-Ray beams with orbital angular momentum (OAM) from the interaction of an intense circularly polarized (CP) laser with a micro-channel plasma target. The driving laser can generate high energy electrons via direct laser acceleration within the channel. By attaching a plasma foil as the reflecting mirror, the CP laser is reflected and automatically colliding with the electrons. High energy gamma-photons are emitted through inverse Compton scattering (ICS) during collision. Three-dimensional particle-in-cell simulations reveal that the spin angular momentum (SAM) of the CP laser can be transferred to the OAM of accelerated electrons and further to the emitted gamma-ray beam. These results may guide future experiments in laser-driven gamma-ray sources using micro-structures.

New Optical Manipulation of Relativistic Vortex Cutter.

A new relativistic vortex cutter driven by the Laguerre-Gaussian (LG) mode is carried out for the first time in three-dimensional particle-in-cell simulations. Studies show that the electric fields periodically concentrate and emanate within every laser wavelength for the reflected circularly polarized LG_{p}^{l} (p=0, l=1, σ_{z}=-1) laser, which works just like a vortex cutter, resulting in a relativistic ultrashort collimated electron cluster with a constant period in space. A single particle model is given and verifies that the cluster formation has a close relation with the parameters of orbital angular momentum (l) and spin angular momentum (σ_{z}). Such a relativistic vortex cutter potentially can be applied for the accelerator, generating high-flux particle and coherent radiation sources, and so on.

Magnetic Field Generation in Plasma Waves Driven by Copropagating Intense Twisted Lasers.

We present a new magnetic field generation mechanism in underdense plasmas driven by the beating of two, copropagating, Laguerre-Gaussian orbital angular momentum laser pulses with different frequencies and also different twist indices. The resulting twisted ponderomotive force drives up an electron plasma wave with a helical rotating structure. To second order, there is a nonlinear rotating current leading to the onset of an intense, static axial magnetic field, which persists over a long time in the plasma (ps scale) after the laser pulses have passed by. The results are confirmed in three-dimensional particle-in-cell simulations and also theoretical analysis. For the case of 300 fs duration, 3.8×10^{17} W/cm^{2} peak laser intensity we observe magnetic field of up to 0.4 MG. This new method of magnetic field creation may find applications in charged beam collimation and microscale pinch.

Collisionless Shock Acceleration of High-Flux Quasimonoenergetic Proton Beams Driven by Circularly Polarized Laser Pulses.

We present experimental studies on ion acceleration using an 800-nm circularly polarized laser pulse with a peak intensity of 6.9×10^{19} W/cm^{2} interacting with an overdense plasma that is produced by a laser prepulse ionizing an initially ultrathin plastic foil. The proton spectra exhibit spectral peaks at energies up to 9 MeV with energy spreads of 30% and fluxes as high as 3×10^{12} protons/MeV/sr. Two-dimensional particle-in-cell simulations reveal that collisionless shocks are efficiently launched by circularly polarized lasers in exploded plasmas, resulting in the acceleration of quasimonoenergetic proton beams. Furthermore, this scheme predicts the generation of quasimonoenergetic proton beams with peak energies of approximately 150 MeV using current laser technology, representing a significant step toward applications such as proton therapy.

Complement activation promotes colitis-associated carcinogenesis through activating intestinal IL-1ß/IL-17A axis.

Colitis-associated colorectal cancer (CAC) is the most serious complication of inflammatory bowel disease (IBD). Excessive complement activation has been shown to be involved in the pathogenesis of IBD. However, its role in the development of CAC is largely unknown. Here, using a CAC model induced by combined administration of azoxymethane (AOM) and dextran sulfate sodium (DSS), we demonstrated that complement activation was required for CAC pathogenesis. Deficiency in key components of complement (e.g., C3, C5, or C5a receptor) rendered tumor repression in mice subjected to AOM/DSS. Mechanistic investigation revealed that complement ablation dramatically reduced proinflammatory cytokine interleukin (IL)-1ß levels in the colonic tissues that was mainly produced by infiltrating neutrophils. IL-1ß promoted colon carcinogenesis by eliciting IL-17 response in intestinal myeloid cells. Furthermore, complement-activation product C5a represented a potent inducer for IL-1ß in neutrophil, accounting for downregulation of IL-1ß levels in the employed complement-deficient mice. Overall, our study proposes a protumorigenic role of complement in inflammation-related colorectal cancer and that the therapeutic strategies targeting complement may be beneficial for the treatment of CAC in clinic.

Cloning and functional identification of a novel BCA3 splice.

The human breast cancer-associated gene (BCA3) was first discovered in breast and prostate cancer cells lines. In vivo studies have shown that BCA3 is mainly expressed in breast tumor cells and not in normal breast and prostate tissues. To date, 3 splice variants of BCA3 have been reported: a double-absent variant lacking exon 3 and exon 5 (BCA3-1), an exon 3-absent variant (BCA3-2), and full-length BCA3. In this study, we investigated whether a novel BCA3 splice variant exists that lacks only the exon 5-encoding sequence. BCA3 variant splices were subcloned and sequenced using reverse transcription-polymerase chain reaction. The preliminary biological functions of the splices were identified using confocal microscopy and a luciferase assay. The absence of exon 3 and exon 5 influenced the subcellular localization of BCA3 and nuclear factor kappa B (NF-kB)-dependent gene expression. Exon 3 and exon 5 of BCA3 may function together to provide a nuclear localization signal or transport sequence to enter the nucleus, and exon 3 may contain specific sequence(s) or domain(s) that influence the NF-κB signal cascade. The discovery of novel BCA3 splicing indicates a new cancer research area, which may increase the understanding of cancer generation and development.

Radiation-reaction trapping of electrons in extreme laser fields.

A radiation-reaction trapping (RRT) of electrons is revealed in the near-QED regime of laser-plasma interaction. Electrons quivering in laser pulse experience radiation reaction (RR) recoil force by radiating photons. When the laser field reaches the threshold, the RR force becomes significant enough to compensate for the expelling laser ponderomotive force. Then electrons are trapped inside the laser pulse instead of being scattered off transversely and form a dense plasma bunch. The mechanism is demonstrated both by full three-dimensional particle-in-cell simulations using the QED photonic approach and numerical test-particle modeling based on the classical Landau-Lifshitz formula of RR force. Furthermore, the proposed analysis shows that the threshold of laser field amplitude for RRT is approximately the cubic root of laser wavelength over classical electron radius. Because of the pinching effect of the trapped electron bunch, the required laser intensity for RRT can be further reduced.

Neutrophil infiltration favors colitis-associated tumorigenesis by activating the interleukin-1 (IL-1)/IL-6 axis.

Neutrophil infiltration is a key event in chronic intestinal inflammation and associated colorectal cancer, but how these cells support cancer development is poorly understood. In this study, using a mouse model of colitis-associated cancer (CAC), we have demonstrated that infiltrated neutrophils produce large amounts of interleukin-1 (IL)-1ß that is critical for the development of CAC. Depletion of neutrophil or blockade of IL-1ß activity significantly reduced mucosal damage and tumor formation. This protumorigenic function of IL-1ß was mainly attributed to increased IL-6 secretion by intestine-resident mononuclear phagocytes (MPs). Furthermore, commensal flora-derived lipopolysaccharide (LPS) was identified to trigger IL-1ß expression in neutrophils. Importantly, accumulation of IL-1ß-expressing neutrophils was seen in lesions of patients suffering from ulceratic CAC and these infiltrated neutrophils induced IL-6 production by intestinal MPs in an IL-1ß-dependent manner. Overall, these findings reveal that in CAC milieu, infiltrating neutrophils secrete IL-1ß that promotes tumorigenesis by inducing IL-6 production by intestinal MPs.

Absence of SH2B3 mutation in nonobese diabetic mice.

Type 1 diabetes is a chronic progressive autoimmune disease characterized by mononuclear cell infiltration, with subsequent destruction of insulin-producing ß-cells. Studies have identified strong associations between type 1 diabetes and several chromosome regions, including 12q24. Association between type 1 diabetes and 12q24 arises from SNP rs3184504; rs3184504 is a nonsynonymous SNP in exon 3 of SH2B3 (also known as LNK). Nonobese diabetic (NOD) mice recapitulate many aspects of the pathogenesis of type 1 diabetes in humans and are therefore frequently used in studies addressing the cellular and molecular mechanisms of this disease. It is of interest to know whether there is a similar mutation of SH2B3 in NOD mice. We found that the SH2B3 mutation is absent in NOD mice. To our knowledge, this is the first report of the sequence and the protein levels of SH2B3 in NOD mice.

Determination of carrier-envelope phase of relativistic few-cycle laser pulses by Thomson backscattering spectroscopy.

A method is proposed to determine the carrier-envelope phase (CEP) of a relativistic few-cycle laser pulse via the frequency of the Thomson backscattering (TBS) light. We theoretically investigate the generation of a flying mirror when a few-cycle drive pulse with relativistic intensity interacts with a target combined with a thin and a thick foil. The frequency of the TBS light generated from the flying mirror shows a sensitive dependence on the CEP of the drive pulse. The obtained results are verified by one-dimensional particle-in-cell simulations and are explained by an analytical model.

Relativistic single-cycled short-wavelength laser pulse compressed from a chirped pulse induced by laser-foil interaction.

By particle-in-cell simulation and analysis, we propose a plasma approach to generate a relativistic chirped pulse based on a laser-foil interaction. When two counterpropagating circularly polarized pulses interact with an overdense foil, the driving pulse (with a larger laser field amplitude) will accelerate the whole foil to form a double-layer structure, and the scattered pulse (with a smaller laser field amplitude) is reflected by this flying layer. Because of the Doppler effect and the varying velocity of the layer, the reflected pulse is up-shifted for frequency and chirped; thus, it could be compressed to a nearly single-cycled relativistic laser pulse with a short wavelength. Simulations show that a nearly single-cycled subfemtosecond relativistic pulse can be generated with a wavelength of 0.2 µm after dispersion compensation.

Laser-driven inertial ion focusing.

A Hohlraum-like configuration is proposed for realizing a simple compact source for neutrons. A laser pulse enters a tiny thin-shelled hollow-sphere target through a small opening and is self-consistently trapped in the cavity. The electrons in the inner shell-wall region are expelled by the light pressure. The resulting space-charge field compresses the local ions into a thin layer that becomes strongly heated. An inward expansion of ions into the shell cavity then occurs, resulting in the formation at the cavity center of a hot spot of ions at high density and temperature, similar to that in inertial electrostatic confinement.

Generating quasi-single-cycle relativistic laser pulses by laser-foil interaction.

A scheme for producing nearly single-cycle relativistic laser pulses is proposed. When a laser pulse interacts with an overdense thin foil, because of self-consistent nonlinear modulation, the latter will be more transparent to the more intense part of the laser, so that a transmitted pulse can be much shorter than the incident pulse. Using two-dimensional particle-in-cell simulation and analytical modeling, it is found that a transmitted pulse of duration 4 fs and peak intensity 3 x 10{20} W/cm{2} can be generated from a circularly polarized laser pulse. The intensity of the resulting pulse is only limited by that of the incident pulse, since this scheme involves only laser-plasma interaction.

Structural analysis of the epitopes on erbB2 interacted with inhibitory or non-inhibitory monoclonal antibodies.

erbB2 oncogene encodes a growth factor receptor. The overexpression of erbB2 was correlated with more aggressive tumors and a poorer prognosis. Some antibodies directed to this molecule have an antitumor effect in vivo, but some antibodies do not. In an attempt to understand the molecular basis of the anti-erbB2 antibody interaction with erbB2 ectodomain (ECD), we analyzed binding epitopes on erbB2 for inhibitory and non-inhibitory antibodies, Herceptin and HF by computer-guided protein engineering and site-directed mutagenesis. Two different interaction domains were identified by molecular docking, computer graphics and distance geometry method and confirmed through studies on a series of mutants of erbB2 ECD. Non-inhibitory antibody HF only recognized N-terminal portion of erbB2 ECD, but inhibitory antibody Herceptin bound to C-terminal portion of it exclusively. The region interacted with inhibitory antibody Herceptin can be an important target for anticancer therapies.

Association between Lyn protein tyrosine kinase (p53/56lyn) and the beta subunit of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors in a GM-CSF-dependent human megakaryocytic leukemia cell line (M-07e).

The role of the lyn product (p53/p56lyn), a membrane-associated protein tyrosine kinase in the signaling pathway used by granulocyte macrophage-CSFR (GM-CSFR) was investigated by using the GM-CSF-dependent human megakaryoblastic leukemia cell line M-07e. M-07e cells express GM-CSFR and are dependent on GM-CSF for survival and proliferation in vitro. Treatment with anti-lyn Abs coimmunoprecipitated, along with lyn product, the beta subunit of GM-CSFR and a phosphoprotein with a molecular mass of 120 kDa (p120) in the lysates of M-07e cells but not in the lysates of human monocyte-derived macrophages (HMDM) or human lymphoid leukemia cells. That the 120-kDa phosphoprotein coimmunoprecipitated by anti-lyn Abs is the beta subunit of GM-CSFR was confirmed in the immunoprecipitates (IP) of M-07e cells with the use of an agarose-conjugated anti-p-tyr mAb. The formation of GM-CSF/GM-CSFR/lyn signaling complexes was verified in an autoradiographic study with anti-lyn IP of M-07e cells that had been bound with 125I-labeled recombinant human (rh)GM-CSF. The p120 protein (beta subunit) was not detected in the IP of M-07e cells with anti-fyn or anti-PI3 Abs. A direct association of Lyn kinase with the beta subunit of GM-CSFR was illustrated with a reversed approach showing the recovery of Lyn protein in anti-beta (CRS1) but not anti-alpha IP of M-07e cells that had been starved for a prolonged period. Finally, the interaction of Lyn kinase with the GM-CSFR complexes was further corroborated using anti-GM-CSF (G133) mAb, which coimmunoprecipitated both the p120 beta subunit and lyn product in the lysates of M-07e cells that had been bound with rhGM-CSF before cell lysis. Removal of rhGM-CSF from culture medium for 10 to 12 h resulted in a marked decrease in lyn-associated kinase activity but not the beta subunit/lyn kinase complex formation. Taken together, our results showed that, in M-07e cells, Lyn protein tyrosine kinase (p53/p56lyn) is stably associated with a constitutively phosphorylated beta subunit of the GM-CSFR in a manner that seems to be independent of lyn kinase activity.

Cryopreservation of human bone marrow after purging T-cells or tumor cells.

Bone marrow transplantation (BMT) is a valuable measure for treatment of leukemia. In order to reduce, even to eliminate, the graft versus host disease after allogenic BMT and prevent the reinfusion of tumor cells during autologous BMT, the cryopreservation of human BM after purging T-cells with immunotoxin or purging tumor cells with monoclonal antibody 55 (McAb55) was studied. Results demonstrated that: (1) treatment with McAb55 and rabbit complement (RC) did not affect the GM-CFU of BM, but treatment with immunotoxin slightly decreased the GM-CFU of BM; (2) a freeze-thawing procedure obviously decreased the GM-CFU number of BM, the GM-CFU numbers of frozen BM samples were lower than those of the nonfrozen samples; (3) there were no differences in GM-CFU numbers between normal BM and BM treated with McAb55 and RC when the cooling rate used was the same; (4) there was a negative linear correlation between cooling rates and GM-CFU numbers of BM in the cooling rate range used and the optimal cooling rate for the cryopreservation of normal BM and BM treated with McAb55 and RC or immunotoxin was the same, namely, 0.5 degrees C/min.

Preparation and characterization of monoclonal antibodies against recombinant human tumor necrosis factor alpha.

Tumor necrosis factor (TNF alpha) plays an important role in cytotoxicity and inhibition of tumor cells. Further studies on the structure, function and clinical application of TNF alpha will be useful. Nine clones of hybridoma secreting monoclonal antibodies against recombinant human tumor necrosis factor alpha (rHTNF alpha) were obtained by using cell fusion technology. None of the monoclonal antibodies cross-reacted with rIL-1, rIL-2, rIFN gamma, rIFN alpha and E. coli lysates. Western blot demonstrated that they specifically recognized the rHTNF antigen of M. W. 17000 daltons. Some of the antibodies can also recognize native rHTNF. These antibodies neutralized the cytotoxicity of rHTNF alpha to different extents. They will be utilized as immunoaffinity column to purify rHTNF alpha from recombinant E. coli lysates.

[Complications associated with soft hydrophilic contact lenses].

The authors report 89 cases of ocular complications associated with soft hydrophilic contact lenses, including corneal abrasions, corneal ulcers, punctate corneal epithelial erosions, aphakic corneal edema, and superior limbal keratoconjunctivitis. Soft contact lenses interfere with the integrity and function of the tear film, so that corneal metabolism is affected, predisposing the cornea to infections by Pseudomonas, Acanthamoebia, fungus and virus. The incidence of the complications is high; therefore, due attention should be devoted to their prevention and treatment.

Nucleotide sequences and expression in Escherichia coli of the in-phase overlapping Pseudomonas aeruginosa plcR genes.

The translation products of chromosomal DNAs of Pseudomonas aeruginosa encoding phospholipase C (heat-labile hemolysin) have been examined in T7 promoter plasmid vectors and expressed in Escherichia coli cells. A plasmid carrying a 4.7-kilobase (kb) DNA fragment was found to encode the 80-kilodalton (kDa) phospholipase C as well as two more proteins with an apparent molecular mass of 26 and 19 kDa. Expression directed by this DNA fragment with various deletions suggested that the coding region for the two smaller proteins was contained in a 1-kb DNA region. Moreover, the size of both proteins was reduced by the same amount by an internal BglII-BglII DNA deletion, suggesting that they were translated from overlapping genes. Similar results were obtained with another independently cloned 6.1-kb Pseudomonas DNA, which in addition coded for a 31-kDa protein of opposite orientation. The nucleotide sequence of the 1-kb region above revealed an open reading frame with a signal sequence typical of secretory proteins and a potential in-phase internal translation initiation site. Pulse-chase and localization studies in E. coli showed that the 26-kDa protein was a precursor of a secreted periplasmic 23-kDa protein (PlcR1) while the 19-kDa protein (PlcR2) was mostly cytoplasmic. These results indicate the expression of Pseudomonas in-phase overlapping genes in E. coli.