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.

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.

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.

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.

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.

High dose rate brachytherapy for carcinoma of the uterine cervix: comparison of two different fractionation regimens.

PURPOSE: There is no consensus as to the best dose-fractionation regimen in high dose rate (HDR) brachytherapy for cervix cancer. Since 1983, two fractionation regimens have been used in different time periods at National Cancer Center Hospital, and their treatment results have been compared in terms of 5-year survival, local control, and complication rate to find the better therapeutic regimen. METHODS AND MATERIALS: From November 1983 to October 1990, 130 patients with uterine cervix carcinoma were treated with HDR intracavitary brachytherapy using a remote afterloading system. There were 21 Stage Ib patients, 5 Stage IIa, 29 Stage IIb, 2 Stage IIIa, 68 Stage IIIb, and 5 Stage IVa. The median age was 64 years. The median follow-up time was 50 months. Radiotherapy consisted of external beam irradiation to the pelvis (mean dose of 50 Gy), combined with HDR brachytherapy (mean dose of 20 Gy to point A) given 5 Gy per session twice weekly (group A: 54 patients) or 6 Gy once weekly (group B: 76 patients). RESULTS: The overall 5-year survival was 52% in group A and 72% in group B. Local recurrence rate was 11%, and distant failure rate was 21%, with no difference between the two groups. The complication rate was significantly lower in group B (37%) than in group A (55%). Multivariate analysis has shown that factors affecting survival were stage, brachytherapy dose, and local control status. No factor was predictive of local control, but the external beam radiation dose significantly influenced the risk of complications. CONCLUSION: The once-weekly HDR intracavitary applications combined with properly adjusted external beam pelvic irradiation is a safe and effective treatment for patients with uterine cervix cancer.

Carcinoma of the uterine cervix treated with external irradiation alone.

One hundred and four out of 2701 patients with carcinoma of the uterine cervix were treated with a curative intent by external irradiation alone at the National Cancer Center Hospital from 1962 to 1979. All patients were judged inappropriate for the combined treatment of intracavitary and external irradiation, which was the treatment of choice for patients with advanced carcinoma of the uterine cervix in the hospital. The 5-year survival rate was 17% overall and 36, 17, and 5% for patients with Stage II, III, and IV disease, respectively. The local control rate was 20%, at 2 years, for all patients. Major complications were observed in five patients. There were no major complications in patients given a total dose of less than 115 in the Time Dose Fractionation factor (TDF). External irradiation combined with interstitial irradiation and/or hyperthermia is being considered to improve the results.

High-dose-rate intracavitary irradiation in the treatment of carcinoma of the uterine cervix: early experience with 84 patients.

Eighty-four patients with previously untreated invasive carcinoma of the uterine cervix were treated by high-dose-rate intracavitary irradiation using a remotely controlled afterloading system (Ralstron) with or without external irradiation at the National Cancer Center Hospital, Tokyo, between 1977 and 1981. Survival rates and local control rates were comparable to those for 372 patients treated by low-dose-rate intracavitary irradiation with or without external irradiation from 1972 to 1981 at the hospital. The incidence of major complications was 5.1 and 2.4% for the patients treated by low-dose-rate intracavitary irradiation and by high-dose-rate irradiation, respectively. The results are comparable to those reported by other institutions. We have abandoned the conventional low-dose-rate intracavitary irradiation with the impression that the high-dose-rate remotely controlled afterloading system is a good alternative to the conventional one.

Distribution of a gelsolin-like 74,000 mol. wt protein in neural and endocrine tissues.

A Ca2(+)-dependent actin binding protein with a molecular weight of 74,000, was purified from bovine adrenal medulla by using deoxyribonuclease I affinity chromatography followed by ion-exchange chromatography and gel filtration. This protein broke actin filaments into fragments and promoted nucleation of actin polymerization in a Ca2(+)-dependent manner as effectively as gelsolin. Proteolytic and immunological comparison with gelsolin which is widely distributed actin-severing protein, indicated that the 74,000 mol. wt protein is a distinct protein, but its domain structure resembles that of gelsolin. Immunoblotting using antibody against this protein showed a tissue-specific distribution. The protein was detected in various endocrine, neuroendocrine and nervous tissues, but not in muscle tissues and plasma which contained relatively large amounts of cytoplasmic and plasma gelsolin. This fact might indicate that this actin-severing protein is involved in the regulation of the secretory process of endocrine and nervous tissues. In the exocytotic process regulated by Ca2+, this protein probably plays a role to free secretory organelles like vesicles from the cytoskeletal network, mainly F-actin, which prevents the movement of secretory vesicles in the resting state.

Characterization of alpha 1-adrenoceptors expressed in a novel vascular smooth muscle cell line cloned from p53 knockout mice, P53LMAC01 (AC01) cells.

1. We pharmacologically studied the alpha 1-adrenoceptor (AR) subtype(s) involved in receptor-mediated signalling in a novel vascular smooth muscle cell line cloned from p53 knockout mice, P53LMAC01 (AC01) cells. 2. Radioligand binding studies with [125I]-HEAT showed the existence of a homogeneous population of binding site with an affinity (Kd value) of 0.4 nM and a maximum number of binding sites (Bmax) of 100 fmol mg-1 protein. Catecholamines competed for [125I]-HEAT binding stereospecifically and with the characteristic alpha 1-AR potency series. 3. Displacement curves for BMY-7378 and KMD-3213 best fitted a one-site model with a pKi value (-log10 (equilibrium inhibition constant)) of 6.06 and 7.07, respectively. 4. Reverse transcription-polymerase chain reaction (RT-PCR) assay detected alpha 1B- and alpha 1D-AR, but not alpha 1A-AR transcript. 5. Chlorethylclonidine (CEC) treatment nearly abolished (-)noradrenaline (NA) (10 microM)-induced inositol[1,4,5]trisphosphate (IP3) production, and BMY-7378 inhibited the response with a Ki value of 0.3 nM, which value was similar to that obtained in the cells expressing alpha 1D-AR. In both AC01 cells and cells expressing alpha 1D-AR, BMY-7378 protected alpha 1-ARs from CEC alkylation while it had little protective effect on CEC alkylation and NA-induced IP3 production in cells expressing alpha 1B-AR. 6. The results indicate that AC01 cells contain predominantly alpha 1B-ARs and a small population of alpha 1D-ARs; however, phosphoinositide (PI)/Ca2+ signalling is mainly mediated through the minor population of alpha 1D-ARs, rather than the alpha 1B-ARs.

Peritoneal cytology in endometrial cancer - an investigation of the source of endometrial cancer-cells in the peritoneal-cavity.

In order to identify the source of endometrial cancer cells in the peritoneal cavity, the incidence of positive peritoneal cytology was assessed according to pTNM classification. In 74 cases free peritoneal fluid in the pelvic cavity was aspirated. In the absence of fluid smears of the cul-de-sac was made by scraping (45 cases). Five of 15 positive aspirated cases were pT1N0 or pT2N0. These five cases underwent surgery alone and are still alive with no evidence of disease. Malignant cells which supposedly gain access to the pelvic cavity via the fallopian tube have low potential for implantation.

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.

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.

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.

Analysis of the interaction of reserpine with actin by the photoaffinity labelling method.

The interaction of reserpine with one of the cytoskeletal proteins, actin, was analyzed by the photoaffinity labelling method using [3H]reserpine. Reserpine bound sufficiently to G- or oligomeric actin, but hardly to F-actin under the same experimental conditions. This result could be explained if reserpine binds to a specific region of the G-actin molecule that is responsible for actin-actin interactions. It is concordant with this idea that [3H]reserpine bound only to specific proteolytic fragments of actin. When reserpine was mixed with crude extracts of two kinds of tissues, chicken gizzard smooth muscle and bovine adrenal medulla, it bound to the 42 kDa protein of sodium dodecyl sulfate-polyacrylamide gel electrophoresis in both cases. Its molecular size and abundance suggest strongly that this 42 kDa protein is actin. The binding of reserpine to actin was inhibited by dopamine in a dose-dependent manner. These results suggest that actin could be one of the target molecules of reserpine.

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.

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.

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.

Evaluation of alpha-fetoprotein in early infancy.

Serum AFP concentrations of normal subjects were statistically analyzed in order to obtain the normal ranges in early infancy. The 95% prediction band would seem to offer a convenient means of evaluating serum AFP in the age range 0-300 days of life. Some illustrative cases, whose AFP values were formerly considered to be abnormally high but later proved to be within normal range, are presented.

[Randomized controlled study of high-dose metoclopramide (2 mg/kg x 4:H) vs moderate-dose metoclopramide (1 mg/kg x 4:M) in the prevention of CDDP-induced emesis].

A comparison of the antiemetic effects of (H) and (M) was carried out by randomized control study in gynecologic cancer patients receiving CDDP (35-110 mg/m2). Metoclopramide was given at a dosage of 2 mg/kg (H) or 1 mg/kg (M), intravenously, 30 minutes before and 2.5 hours, 5.0 hours, and 7.5 hours following chemotherapy. Treatment with (H) resulted in 3.3 episodes of vomiting (range 0-5) whereas the episodes of vomiting noted with (M) were 3.4 (range 1-5). In patients receiving CDDP (H) or (M) dosage of metoclopramide gives similar antiemetic protection.