Angular Momentum of Twisted Radiation from an Electron in Spiral Motion.

We theoretically demonstrate for the first time that a single free electron in circular or spiral motion emits twisted photons carrying well-defined orbital angular momentum along the axis of the electron circulation, in adding to spin angular momentum. We show that, when the electron velocity is relativistic, the radiation field contains harmonic components and the photons of lth harmonic carry lℏ total angular momentum for each. This work indicates that twisted photons are naturally emitted by free electrons and are more ubiquitous in laboratories and in nature than ever thought.

Coherent Beam-Beam Instability in Collisions with a Large Crossing Angle.

In recent years the "crab-waist collision" scheme [P. Raimondi, Proceedings of 2nd SuperB Workshop, Frascati, 2006.; M. Zobov et al., Phys. Rev. Lett. 104, 174801 (2010)PRLTAO0031-900710.1103/PhysRevLett.104.174801] has become popular for circular e^{+} e^{-} colliders. The designs of several future colliders are based on this scheme. So far the beam-beam effects for collisions under a large crossing angle with or without crab waist were mostly studied using weak-strong simulations. We present here strong-strong simulations showing a novel strong coherent head-tail instability, which can limit the performance of proposed future colliders. We explain the underlying instability mechanism starting from the "cross-wake force" induced by the beam-beam interaction. Using this beam-beam wake, the beam-beam head tail modes are studied by an eigenmode analysis. The instability may affect all collider designs based on the crab-waist scheme. We suggest an experimental verification at SuperKEKB during its commissioning phase II.

Observation of vertical betatron sideband due to electron clouds in the KEKB low energy ring.

The effects of electron clouds on positively charged beams have been an active area of research in recent years at particle accelerators around the world. Transverse beam-size blowup due to electron clouds has been observed in some machines and is considered to be a major limiting factor in the development of higher-current, higher-luminosity electron-positron colliders. The leading proposed mechanism for beam blowup is the excitation of a fast head-tail instability due to short-range wakes within the electron cloud. We present here observations of betatron oscillation sidebands in bunch-by-bunch spectra that may provide direct evidence of such head-tail motion in a positron beam.

Mechanism of electron multipacting with a long-bunch proton beam.

The energy gain and motion of electrons can quantitatively describe the mechanism of electron multipacting in a long-bunched proton machine. Strong multipacting usually happens around the bunches' tails due to the high energy of electrons when they hit the chamber surface. We investigated several important parameters of electron multipacting, proving that it is sensitive to the beam's intensity, the shape of its longitudinal profile, its transverse size, the secondary emission yield, and the energy at peak secondary emission yield. Our analyses, simulations, and experiments are all in agreement.

Beam-beam limit in e+e- circular colliders.

Beam-beam effects limit the luminosity of circular colliders. Once the bunch population exceeds a threshold, the luminosity increases at a slower rate. This phenomenon is called the beam-beam limit. Onset of the beam-beam limit has been analyzed with various simulation methods based on the weak-strong and strong-strong models. We have observed that an incoherent phenomenon is mainly concerned in the beam-beam limit. The simulation have shown that equilibrium distributions of the two colliding beams are distorted from Gaussians when the luminosity is limited. The beam-beam limit is estimated to be xi approximately 0.1 for a B factory with damping time of several thousand turns.

Prognostic significance of positive peritoneal cytology in endometrial carcinoma confined to the uterus.

A retrospective analysis was performed to evaluate the prognostic significance of peritoneal cytology in patients with endometrial carcinoma limited to the uterus. A total of 280 patients with surgically staged endometrial carcinoma that was histologically confined to the uterus were examined clinicopathologically. The median length of follow-up was 62 (range, 12-135) months. All patients underwent hysterectomy and salpingo-oophorectomy with selective lymphadenectomy, and only three patients received adjuvant postoperative therapy. No preoperative adjuvant therapy was employed. In all, 48 patients (17%) had positive peritoneal cytology. The 5-year survival rate among patients with positive or negative peritoneal cytology was 91 or 95%, respectively, showing no significant difference (log-rank, P=0.42). The disease-free survival rate at 36 months was 90% among patients with positive cytology, compared with that of 94% among patients with negative cytology, and the difference was not significant (log-rank, P=0.52). Multivariate proportional hazards model revealed only histologic grade to be an independent prognostic factor of survival (P=0.0003, 95% CI 3.02 - 40.27) among the factors analysed (age, peritoneal cytology, and depth of myometrial invasion). Multivariate analysis revealed that histologic grade (P=0.02, 95% CI 1.21-9.92) was also the only independent prognostic factor of disease-free survival. We concluded that the presence of positive peritoneal cytology is not an independent prognostic factor in patients with endometrial carcinoma confined to the uterus, and adjuvant therapy does not appear to be beneficial in these patients.

Immature glandular features in squamous cell carcinoma of the uterine cervix as an independent indicator of resistance to radiotherapy.

The aim of this study was to evaluate the significance of "immature glandular features" in cervical squamous cell carcinoma (SCC) as an indicator of tumor radioresistance. Pretreatment biopsied tissue specimens of cervical SCC from 100 patients who were uniformly treated with radiotherapy alone were classified into clinically radioresistant (cR) and radiosensitive (cS) groups. Seven histologic parameters comprising glassy cells, signet ring cells, squamous differentiation, recognizable gland, nuclear atypia, stromal response, and mitotic counts were examined. Glassy cells and signet ring cells were regarded as "immature glandular features". The correlation of these seven parameters with tumor response to radiotherapy and patient prognosis was analyzed by univariate and multivariate analyses. As objective indicators of glandular differentiation, alcian-blue staining and immunostaining of cytokeratins 7 and 20 were also performed. It was revealed that immature glandular features, absence of squamous differentiation, and low nuclear atypia were significant indicators of radioresistance of the tumor and of poorer patient prognosis. Combining those histological parameters, the present SCC cases were classified into 26 pathologically radioresistant (pR) and 74 radiosensitive (pS) groups. In the pR group, 54% (14 of 26) were clinically radioresistant, whereas 20% (15 of 74) of the pS group were clinically radioresistant (P = 0.002). The overall prognosis of the pR group was much poorer than that of the pS group (P < 0.0001). This correlation also held true in cases of identical stage and age. We could not show objectively glandular differentiation of "immature glandular features". Nonetheless, the identification of "immature glandular features" was effective in predicting the radiotherapy resistance of cervical SCC and poorer patient prognosis.

Wake-field and fast head-tail instability caused by an electron cloud.

In positron and proton storage rings, electrons produced by photoemission, ionization, and secondary emission accumulate in the vacuum chamber during multibunch operation with close spacing. A positron or proton bunch passing through this "electron cloud" experiences a force similar to a short-range wake field. This effective wake field can cause a transverse-mode-coupling instability, if the electron-cloud density exceeds a threshold value. In this report, we compute the electron-cloud induced wake in a region without external magnetic field both analytically and via computer simulation, for parameters representing the low-energy positron ring of KEKB and the LHC proton beam in the CERN SPS. We study the linearity and time dependence of the wake function and its variation with the size of the electron cloud. Using a broadband resonator model for the electron-cloud wake field, we then evaluate theoretical expressions for the transverse-mode-coupling instability based on the linearized Vlasov equation, and for the instability threshold of fast transverse blow up including its dependence on chromaticity.

Primary epithelioid sarcoma of the vulva.

A case of a 31-year-old woman with epithelioid sarcoma of the vulva which metastasized to the regional lymph node 8 years after onset of the disease is reported here. The patient first noticed a painless subcutaneous mass of 5 mm in diameter in the right labium majus at age of 21. This was excised locally at age 23, but recurred 17 months later. Although local excision was again performed, the tumor recurred and continued to enlarge very slowly. At this stage, based on the pathology of both the initial and second tumors, the diagnosis was of a benign inflammatory process. However, local recurrence and inguinal lymph node swelling occurred at age 29, and biopsy was taken. The pathology report indicated benign granulomatous changes. The slides were reconsidered and re-interpreted as epithelioid sarcoma, whereupon radical vulvectomy was performed at age 31. Vulvar epithelioid sarcoma with inguinal lymph node metastasis was first diagnosed at that time. Epithelioid sarcoma of the vulva is an exceedingly rare tumor, and only 15 cases have been reported thus far in the literature. Early diagnosis and curative treatment of this tumor may be problematic for gynecologists because of its rarity and therefore little-known characteristic clinical behavior and histology. Radical vulvectomy or extensive local excision with inguinal lymphadenectomy at the time of diagnosis is recommended as the treatment of choice.

The proliferative response of p53 knock-out mouse-derived vascular smooth muscle cell line, P53LMAC01, to PDGF, when compared with human aortic smooth muscle cells.

To develop an in vitro experimental model of vascular smooth muscle cell hyperplasia, a major feature in chronic cardiac rejection, we studied a novel vascular smooth muscle cell line, P53LMAC01 (AC01), which was established from aortic smooth muscles of p53 knock-out mice, to determine its response to a platelet-derived growth factor (PDGF) and to Cyclosporin A (CsA). The responses were compared with those of human aortic smooth muscle cells (AOSMC). The AC01 exhibited a distinct proliferative response to PDGF similar to that of AOSMC under serum-free conditions. 10 ng/ml of PDGF-BB increased by a factor of 4.5 and PDGF-AB doubled the thymidine uptake, but PDGF-AA caused only a slight increase. The proliferation was markedly inhibited by 10(-6) M of CsA but less affected by 10(-7) M. These results indicate that the AC01 cell line could provide a convenient experimental system for investigating chronic rejection in vitro and that the system might work as a screening model of agents for treating transplant-related arteriosclerosis.

Acceleration of actin polymerization and rapid microfilament reorganization in cultured hepatocytes by cyclochlorotin, a hepatotoxic cyclic peptide.

Cyclochlorotin (= chloropeptide, CC) is a hepatotoxic mycotoxin of Penicillium islandicum Sopp. The effect of CC on actin polymerization was examined by the measurement of changes in fluorescence intensity using pyrene-labeled actin and high shear viscosity. In the presence of CC, the time course of actin polymerization was accelerated in a dose dependent manner (2.5 ng/ml-2.5 microg/ml), without affecting the final level of viscosity. CC exerted a strong stabilizing effect on actin, enabling it to maintain its filamentous form in the presence of members of actin-binding proteins, including those of the gelsolin family prepared from hepatocytes. Microscopic observation revealed that in cultured hepatocytes, 1.0 microg/ml of CC induced bleb formation and changes in the microfilament. These observations indicated that after contact of the hepatocyte with CC, the following events were probable. The toxin passed through the cell membrane by a transport system and immediately reacted with the actin-actin binding proteins underlying the lipid bilayer. Bleb formation and hepatotoxicity were thus induced.

Prominent immunogenicity of monosialosyl galactosylgloboside, carrying a stage-specific embryonic antigen-4 (SSEA-4) epitope in the ACHN human renal tubular cell line-a simple method for producing monoclonal antibodies against detergent-insoluble microdomains/raft.

The binding of Shiga toxin (Stx) to Gb3Cer in detergent-insoluble microdomains (DIM)/raft of the ACHN human renal tubular cell line causes the temporal activation of the Src-family kinase Yes [1]. As a strategy for examining signaling mechanisms in DIM/raft, monoclonal antibodies (MAbs) are reliable tools for characterizing the constituent molecules in these microdomains. Thus, we employed DIM/raft suspensions of ACHN cells as an immunogen to develop MAbs. Simply subcutaneous injections of ACHN DIM/raft could elevate the serum titer after several boosts. The first screening was performed using dot-blot immunostaining with culture supernatants on a polyvinylidene difluoride (PVDF) membrane, on which DIM/raft or their chloroform/methanol (C/M) (2:1, v/v) extracts were dot-blotted. The next screening was performed by flowcytometric analysis of ACHN cells treated with or without a permeabilizing reagent. Many of the clones (21/31 clones=68%) thus obtained were also found to recognize to lipid fractions of the DIM/raft. Strikingly, all of the 21 clones that reacted to the lipid fraction were found to recognize monosialosyl galactosylgloboside (MSGG) or GL7, which carries the SSEA-4 epitope. Using DIM/raft as immunogens may enable us to easily obtain MAbs for glycolipids.

Nitrobenzylthioinosine (NBT), a nucleoside transport inhibitor, protects against Shiga toxin cytotoxicity in human microvascular endothelial cells.

Infections with Shiga toxin (Stx)-producing Escherichia coli (STEC) cause microvascular endothelial cell damage, resulting in hemorrhagic colitis and hemolytic uremic syndrome. The prevention of endothelial cell damage is therefore a crucial step in overcoming this disorder. Here, we report that nitrobenzylthioinosine (NBT), a nucleoside transport inhibitor, has a protective effect against the cytotoxicity of Stxs in human microvascular endothelial cells (HMVECs). The relative viability of cells treated with 1.5-15 pM of Stx1 was reduced to 10-20% of that without Stx1. However, the viability of cells treated with NBT (10-100 microM) remained higher than 80%, even in the presence of Stx1. NBT also protected against Stx1 cytotoxicity in sodium butyrate-treated hypersensitive HMVECs. The protective effect of NBT against Stx cytotoxicity may be due to the depletion of ATP in the cells, thereby inhibiting the entry of Stx1.

Simulation of beam-beam effects in a circular e(+)e(-) collider

We have carried out a strong-strong simulation to study the beam-beam effect in a circular electron-positron collider. In the simulation, both the positron and electron beams are represented by macroparticles, and the interaction between the two beams is obtained by solving the Poisson equation for the charge distribution of the macroparticles. Using the simulation, we investigate the beam-beam limit and the coherent beam-beam tune shift, two characteristic phenomena of the beam-beam effect. We also study collision with a finite crossing angle, and verify its feasibility for the KEKB factory. Our results for KEKB yield an estimated luminosity of 8.5x10(33) cm(-2) s(-1), only slightly lower than the design value of 1x10(34) cm(-2) s(-1).

Globotriaosyl ceramide (CD77/Gb3) in the glycolipid-enriched membrane domain participates in B-cell receptor-mediated apoptosis by regulating lyn kinase activity in human B cells.

The role of CD77 expressed on a fraction of germinal center B cells, also known as glycosphyngolipid Gb3, and as a functional receptor for Shiga toxins (Stx) in B-cell receptor (BCR)-mediated apoptosis was investigated. Using Stx1-sensitive Burkitt's lymphoma Ramos cells as an in vitro model of CD77(+) germinal center B cells, intracellular signaling events mediated by either Stx1 or anti-CD77 antibody were examined immunobiochemically and immunocytologically. We observed prompt activation of Lyn and Syk kinases leading to increased binding of these proteins to surface IgM (sIgM) in Ramos cells after Stx1 treatment. We also observed microscopic colocalization of CD77 and sIgM after stimulation with Stx1. Along with the synergism between the cross-linking of CD77 and that of sIgM in their effect on apoptosis induction, it was highly probable that CD77 cross-linking induces activation of the BCR signaling cascade. Analysis using sucrose density gradient centrifugation suggested that Stx1 binding to CD77 induced recruitment and activation of Lyn in the glycolipid-enriched membrane (GEM) fractions. Once activated, however, Lyn seemed to acquire an increased detergent solubility and moved outside of the GEM fractions. This study describes the participation of the GEM domain in BCR-signaling cascade and suggests a possible role of CD77 as a regulator of BCR-induced apoptosis in human B cells.

Head-tail instability caused by electron clouds in positron storage rings

In positron or proton storage rings with many closely spaced bunches, an electron cloud can build up in the vacuum chamber due to photoemission or secondary emission. We discuss the possibility of a single-bunch two-stream instability driven by this electron cloud. Depending on the strength of the beam-electron interaction, the chromaticity and the synchrotron oscillation frequency, this instability either resembles a linac beam breakup or a head-tail instability. We present computer simulations of the instabilities, and compare the simulation results with analytical estimates.

Functional conservation of platelet glycoprotein V promoter between mouse and human megakaryocytes.

OBJECTIVE: In an attempt to clarify the megakaryo-specific regulatory mechanism of GPV gene transcription, we characterized the 5'-flanking region of the mouse GPV gene. MATERIALS AND METHODS: The promotor activity of a -481/+22 5'-fragment of the mouse GPV gene was examined in normal mouse bone marrow cells (BMC) and various human cell lines using two distinct reporter gene assay systems, luciferase and green fluorescence protein (GFP). RESULTS: When a DNA construct consisting of this fragment and a GFP reporter gene were transiently expressed in thrombopoietin-supported mouse BMC culture, GFP was identified only in megakaryocytes. The same construct expressed high levels of GFP in the human megakaryocytic Dami line. When assessed by dual luciferase assay, the full -481/+22 fragment could drive variable promoter activity in human as well as mouse megakaryocytic lines but did not work in non-megakaryocytic cells. Sufficient transcriptional activation of this fragment was restricted to the cells expressing apparent GPV mRNA. A deletion and point mutation study indicated that GATA and Ets motifs, typical cis-acting elements for platelet-specific genes, located of -75 and -46, respectively, were essential for promoter function. CONCLUSION: The GPV promoter has the general characteristics found in platelet-specific genes, and the mechanism for megakaryocyte-specific, maturation-dependent regulation of GPV gene transcription is highly conserved between mouse and human. Analysis of GPV transcription mechanism utilizing human lines as well as BMC should provide new information on the final maturational process of megakaryocytes.

Assembly of smooth muscle myosin by the 38k protein, a homologue of a subunit of pre-mRNA splicing factor-2.

Smooth muscle myosin in the dephosphorylated state does not form filaments in vitro. However, thick filaments, which are composed of myosin and myosin-binding protein(s), persist in smooth muscle cells, even if myosin is subjected to the phosphorylation- dephosphorylation cycle. The characterization of telokin as a myosin-assembling protein successfully explained the discrepancy. However, smooth muscle cells that are devoid of telokin have been observed. We expected to find another ubiquitous protein with a similar role, and attempted to purify it from chicken gizzard. The 38k protein bound to both phosphorylated and dephosphorylated myosin to a similar extent. The effect of the myosin-binding activity was to assemble dephosphorylated myosin into filaments, although it had no effect on the phosphorylated myosin. The 38k protein bound to myosin with both COOH-terminal 20 and NH(2)-terminal 28 residues of the 38k protein being essential for myosin binding. The amino acid sequence of the 38k protein was not homologous to telokin, but to human p32, which was originally found in nuclei as a subunit of pre-mRNA splicing factor-2. Western blotting showed that the protein was expressed in various smooth muscles. Immunofluorescence microscopy with cultured smooth muscle cells revealed colocalization of the 38k protein with myosin and with other cytoskeletal elements. The absence of nuclear immunostaining was discussed in relation to smooth muscle differentiation.

[Experimental study on direct toxicity of combined cisplatin and methotrexate for normal and neoplastic cell lines].

The combination effect of cisplatin (CDDP) and methotrexate (MTX) on the cytotoxicity against normal fibroblast and malignant cell line were investigated utilizing MTT assay. In case of normal fibroblast, the optical density (OD) value in CDDP + MTX was significantly higher and remained at a consistently higher value in various mixture rates than that in CDDP alone. Such low cytotoxicity may be due to MTX because the addition of Leucovorin resulted in an apparent decrease in the OD value. The combination of the two drugs was thought to alleviate the toxicity of CDDP on fibroblast, in contrast to its increase on cancer cells.