Antigenic Heterogeneity in Cell Populations of Cloned Polyoma,Virus-induced Tumour Lines

WALLS and Negroni¹ isolated in tissue culture two cell clones from a polyoma virus-induced fibrosarcoma of H₃B/Bi mice. One (malignant cell line 7₁) produced transplantable tumours in adult syngeneic mice; the other (transformed non-malignant line 7₂) was not tumorigenic but induced resistance to the growth of the malignant cells. We have now confirmed these results and extended them to show that other malignant cells (tissue culture clones C₄ and C₅) from a polyoma virus-induced parotid tumour of syngeneic mice are also inhibited by pre-immunization with a non-malignant line (7₂). The number of cells required to induce tumours in 50% of the animals is ten times higher in the preimmunized mice than in the controls, for both fibrosarcoma and parotid malignant lines (Table 1).     

Rapidarc联合呼吸门控在非小细胞肺癌放疗中的应用

目的：探讨RapidArc联合呼吸门控技术在非小细胞肺癌放射治疗中的应用。方法：选取未能手术的ⅢA-ⅢB期非小细胞肺癌患者19例,分别在自由呼吸（FB）和呼吸门控系统RC状态下为每例患者设计FB下的IMRT（IMRT-FB）、双弧RapidArc（Arc-FB）和RC下的IMRT（IMRT-RC）、双弧RapidArc（Arc-RC）4种放疗计划。评价四种计划和Arc-RC治疗的疗效及副反应。结果：除1例患者由于经济原因中途退出,其他患者均顺利完成治疗。PTV的平均体积由FB下的296 cm3减少到了RC下的210.2cm3;RC下的双肺平均体积为3817.4 cm3,较FB增加了34%;Arc-RC计划靶区的CI、HI及D2%、D98%、V95,与IMRT-FB、Arc-FB、IMRT-RC计划差异无统计学意义,但双肺的V20、V30、V40、V50、及平均剂量（Dmean）明显低于后三者（P〈0.05）。总有效率为72.23%（13例）。急性放射性食管炎1、2级发生率分别为61.1%、16.7%,急性放射性肺炎1、2级发生率分别为77.8%、11.1%,骨髓抑制1、2、3级分别为61.1%、22.2%、11.1%,急性心脏损伤1、2级发生率分别为83.3%、16.7%。结论：RapidArc联合呼吸门控在非小细胞肺癌精确放疗中具有减少正常组织受照剂量体积和提高放疗精度的作用。     

Rapid arc 联合呼吸门控在非小细胞肺癌放疗中的应用

目的：探讨RapidArc 联合呼吸门控技术在非小细胞肺癌放射治疗中的应用。方法：选取未能手术的ⅢA-ⅢB 期非小细胞肺 癌患者19 例,分别在自由呼吸(FB) 和呼吸门控系统RC 状态下为每例患者设计FB 下的IMRT (IMRT-FB)、双弧RapidArc (Arc-FB)和RC 下的IMRT(IMRT-RC)、双弧RapidArc(Arc-RC)4种放疗计划。评价四种计划和Arc-RC 治疗的疗效及副反应。结 果：除1 例患者由于经济原因中途退出,其他患者均顺利完成治疗。PTV 的平均体积由FB 下的296 cm3减少到了RC 下的210.2 cm3;RC下的双肺平均体积为3817.4 cm3,较FB 增加了34%;Arc-RC计划靶区的CI、HI及D2%、D98%、V95,与IMRT-FB、Arc-FB、 IMRT-RC 计划差异无统计学意义,但双肺的V20、V30、V40、V50、及平均剂量(Dmean)明显低于后三者(P<0.05)。总有效率为72.23％(13 例)。急性放射性食管炎1、2 级发生率分别为61.1%、16.7%,急性放射性肺炎1、2 级发生率分别为77.8%、11.1%,骨髓抑制1、2、3 级分别为61.1%、22.2%、11.1%,急性心脏损伤1、2 级发生率分别为83.3%、16.7%。结论：RapidArc 联合呼吸门控在非小细胞肺癌 精确放疗中具有减少正常组织受照剂量体积和提高放疗精度的作用。     

Gating of ventilatory activity in the cave-cricket, Troglophilus cavicola

ABSTRACT. The rhythm of 'abdominal respiratory movements' (ARMs) in partly tethered cave-crickets was recorded via correlated hindleg movements associated with abdominal ventilation, and analysed with respect to postural changes (cricket placed horizontally or vertically) under the following stimulus regimes: touch stimuli of constant duration but varying rates were presented to the hind legs independently of the ARM rhythm; touch stimuli with constant delays were triggered by the previous ARM; and light stimuli were presented, preceding the touch stimuli. With constantly spaced touch stimuli, on- and off-effects are visible in the number of ARMs per time unit and this is more pronounced in the horizontal than in the vertical position. Continuous modulations of ARMs patterning (tonic effects) are revealed in free run cycles which are intercalated in rhythmic driving series: at intertouch lengths of 20 s such free run cycling is faster under vertical than under horizontal conditions. With the vertical stance it is delayed by additional light. Even the kind of vertical orientation causes tonic effects. Thus crickets that face downward exhibit a slower ARM rhythm than those facing upward. Under entrainment to constantly delayed touches, two parameters of ARM rhythm ('basic period' and 'consecutive period') were studied to elucidate the hypothetical cycling of the pacemaker under different stances. Under horizontal conditions the 'basic periods' are shortened if the delay of touch does not exceed 0.2 periods of free run cycling. However, in the vertical position, the 'basic periods' are prolonged. With delay times exceeding 0.5 periods of free run cycle, the 'consecutive periods' are lengthened if the cricket is oriented vertically, but remain unaffected under horizontal conditions. On the basis of these results, a model for resetting and sensory modulation of ARM control is presented.     

Gating of locomotor activity in the cave-cricket, Troglophilus cavicola

ABSTRACT. Cave-crickets of the genus Troglophilus exhibit a slope dependent gating of locomotor behaviour (Kastberger, 1982), which is mainly expressed by a suppression of evasive jumping on inclined surfaces. A similar dependence of the jumpting rate on the ground inclination to that seen in the cave-cricket can be shown in the African cricket Phaeophyllacris and in the grasshopper Chorthippus. They differ only in the basic motivation for jumping. In this study, free-moving and tethered cave-crickets were studied to elucidate the inclination-sensitive control of gating locomotor activity. Cave-crickets with cauterized tarsal nerves exhibit only a 20% reduction in jumpting rate at slopes up to 45 compared with intact crickets. Freely moving crickets with compensated body weights show a suppression of evasive jumping which is complete if the vertical force overrides the body weight. Dorsally tethered cave-crickets which contact a rotary globe with their tarsi, show a significant increase in the latency of jerking beyond 60 inclination. Crickets placed on a floating boat and partially fixed respond to both static and dynamic forces applied to the longitudinal axis of the cricket. Static towing forces induce passive movements and the rate of active balancing are linearly correlated to the force applied. Under dynamic forces the rate of balancing is dependent on the longitudinal position of the legs and on the direction of force. This basic relation is changed by additional stimulation such as light and vibration. Locomotor activity is gated in a different mode, if the light interval is placed during forward or during backward forcing. Light-off suppresses locomotor activity. The results of dynamic forcing suggest the existence of a gain control which might be responsible for modal and temporal effects in gating locomotion.     

Visualisation and Quantification of Morphogen Gradient Formation in the Zebrafish

During embryonic development, signalling molecules known as morphogens act in a concentration-dependent manner to provide positional information to responding tissues. In the early zebrafish embryo, graded signalling by members of the nodal family induces the formation of mesoderm and endoderm, thereby patterning the embryo into three germ layers. Nodal signalling has also been implicated in the establishment of the dorso-ventral axis of the embryo. Although one can infer the existence of nodal gradients by comparing gene expression patterns in wild-type embryos and embryos in which nodal signalling is diminished or augmented, real understanding can only come from directly observing the gradients. One approach is to determine local ligand concentrations in the embryo, but this is technically challenging, and the presence of inhibitors might cause the effective concentration of a ligand to differ from its actual concentration. We have therefore taken two approaches to visualise a direct response to nodal signalling. In the first, we have used transgenic embryos to study the nuclear accumulation of a Smad2-Venus fusion protein, and in the second we have used bimolecular fluorescence complementation to visualise the formation of a complex between Smad2 and Smad4. This has allowed us to visualise, in living embryos, the formation of a graded distribution of nodal signalling activity. We have quantified the formation of the gradient in time and space, and our results not only confirm that nodal signalling patterns the embryo into three germ layers, but also shed light on its role in patterning the dorso-ventral axis and highlight unexpected complexities of mesodermal patterning.     

On the Structure and Gating Mechanism of the Mitochondrial Channel, VDAC

There is considerable evidence that the voltage-gated mitochondrial channel VDAC forms a -barrel pore. Inferences about the number and tilt of -strands can be drawn from comparisons with bacterial -barrel pores whose structures have been determined by x-ray crystallography. A structural model for VDAC is proposed (based on sequence analysis and electron crystallography) in which the open state is like that of bacterial porins with several important differences. Because VDAC does not occur as close-packed trimers, there are probably fewer interpore contacts than in the bacterial porins. VDAC also appears to lack a large, fixed intraluminal segment and may not have as extensive a region of uniformly 35°-tilted -strands as do the bacterial porins. These structural differences would be expected to render VDAC's -barrel less stable than its bacterial counterparts, making major conformational changes like those associated with gating more energetically feasible. A possible gating mechanism is suggested in which movement of the N-terminal -helix out of the lumen wall triggers larger-scale structural changes.     

Role of Ion Distribution and Energy Barriers for Concerted Motion of Subunits in Selectivity Filter Gating of a K+ Channel

Most potassium channels have two main gate locations, hosting an inner gate at the cytosolic entrance and a filter gate in the selectivity filter; the function of these gates is in many channels coupled. To obtain exclusive insights into the molecular mechanisms that determine opening and closing of the filter gate, we use a combination of single-channel recordings and gating analysis in the minimal viral channel Kcv_NTS. This channel has no inner gate, and its fast closing at negative voltages can therefore be entirely assigned to the filter gate. We find that mutations of S42 in the pore helix severely slow down closing of this filter gate, an effect which is not correlated with hydrogen bond formation by the amino acid at this position. Hence, different from KcsA, which contains the critical E71 in the equivalent position forming a salt bridge, the coupling between selectivity filter and surrounding structures for filter gating must in Kcv_NTS rely on different modes of interaction. Quantitative analysis of concatemers carrying different numbers of S42T mutations reveals that each subunit contributes the same amount of ～ 0.4 kcal/mol to the energy barrier for filter closure indicating a concerted action of the subunits. Since the mutations have neither an influence on the unitary current nor on the voltage dependency of the gate, the data stress that the high subunit cooperativity is mediated through conformational changes rather than through changes in the ion occupation in the selectivity filter.     

Evaluation of Breathing Pattern: Comparison of a Manual Assessment of Respiratory Motion (MARM) and Respiratory Induction Plethysmography

Altered breathing pattern is an aspect of dysfunctional breathing but few standardised techniques exist to evaluate it. This study investigates a technique for evaluating and quantifying breathing pattern, called the Manual Assessment of Respiratory Motion (MARM) and compares it to measures performed with Respiratory Induction Plethysmography (RIP). About 12 subjects altered their breathing and posture while 2 examiners assessed their breathing using the MARM. Simultaneous measurements with RIP were taken. Inter-examiner agreement and agreement between MARM and RIP were assessed. The ability of the measurement methods to differentiate between diverse breathing and postural patterns was compared. High levels of agreement between examiners were found with the MARM for measures of the upper rib cage relative to lower rib cage/abdomen motion during breathing but not for measures of volume. The measures of upper rib cage dominance during breathing correlated with similar measures obtained from RIP. Both RIP and MARM measures methods were able to differentiate between abdominal and thoracic breathing patterns, but only MARM was able to differentiate between breathing changes occurring as result of slumped versus erect sitting posture. This study suggests that the MARM is a reliable clinical tool for assessing breathing pattern.     

The Relative Biological Effectiveness for Carbon and Oxygen Ion Beams Using the Raster-Scanning Technique in Hepatocellular Carcinoma Cell Lines

BackgroundAim of this study was to evaluate the relative biological effectiveness (RBE) of carbon (12C) and oxygen ion (16O)-irradiation applied in the raster-scanning technique at the Heidelberg Ion beam Therapy center (HIT) based on clonogenic survival in hepatocellular carcinoma cell lines compared to photon irradiation.MethodsFour human HCC lines Hep3B, PLC, HepG2 and HUH7 were irradiated with photons, 12C and 16O using a customized experimental setting at HIT for in-vitro trials. Cells were irradiated with increasing physical photon single doses of 0, 2, 4 and 6 Gy and heavy ionsingle doses of 0, 0.125, 0.5, 1, 2, 3 Gy (12C and 16O). SOBP-penetration depth and extension was 35 mm +/−4 mm and 36 mm +/−5 mm for carbon ions and oxygen ions respectively. Mean energy level and mean linear energy transfer (LET) were 130 MeV/u and 112 keV/um for 12C, and 154 MeV/u and 146 keV/um for 16O. Clonogenic survival was computated and realtive biological effectiveness (RBE) values were defined.ResultsFor all cell lines and both particle modalities α- and β-values were determined. As expected, α-values were significantly higher for 12C and 16O than for photons, reflecting a steeper decline of the initial slope of the survival curves for high-LET beams. RBE-values were in the range of 2.1–3.3 and 1.9–3.1 for 12C and 16O, respectively.ConclusionBoth irradiation with 12C and 16O using the rasterscanning technique leads to an enhanced RBE in HCC cell lines. No relevant differences between achieved RBE-values for 12C and 16O were found. Results of this work will further influence biological-adapted treatment planning for HCC patients that will undergo particle therapy with 12C or 16O.     

Dosimetric comparison of left-sided whole-breast irradiation with 3DCRT,forward-planned IMRT,inverse-planned IMRT,helical tomotherapy,and volumetric arc therapy

PurposeThis study evaluated the dose distribution and homogeneity of four different types of intensity-modulated radiotherapy (IMRT) in comparison with standard wedged tangential-beam three-dimensional conformal radiotherapy (3DCRT) of the left breast in patients who had undergone lumpectomy.Materials and methodsFive radiotherapy treatment plans, including 3DCRT, forward-planned IMRT (for-IMRT), inverse IMRT (inv-IMRT), helical tomotherapy (HT) and volumetric-modulated arc therapy (VMAT), were created for 15 consecutive patients.ResultsAll modalities presented similar target coverage. Target max doses were reduced with for-IMRT compared to 3DCRT, and these doses were further reduced with inv-IMRT and HT. HT resulted in the lowest max doses delivered to the heart, left anterior descending artery (LAD), and ipsilateral lung, but had higher mean, max, and low doses delivered to contralateral breast. HT resulted in increased low doses to a large volume of healthy tissue. Compared to other techniques, all inverse-planned modalities significantly improved conformity number; however, VMAT had worse homogeneity. The for-IMRT plan significantly lowered monitor unit (MU) compared to the inverse-planned techniques.ConclusionAll modalities evaluated provide adequate coverage of the whole breast. For-IMRT improves target homogeneity compared with 3DCRT, but to a lesser degree than the inverse-planned inv-IMRT and HT. HT decreases the ipsilateral OAR volumes receiving higher and mean doses with an increase in the volumes receiving low doses, which is known to lead to an increased rate of radiation-induced secondary malignancies.     

Influence of Visual Motion,Suggestion, and Illusory Motion on Self-Motion Perception in the Horizontal Plane

A moving visual field can induce the feeling of self-motion or vection. Illusory motion from static repeated asymmetric patterns creates a compelling visual motion stimulus, but it is unclear if such illusory motion can induce a feeling of self-motion or alter self-motion perception. In these experiments, human subjects reported the perceived direction of self-motion for sway translation and yaw rotation at the end of a period of viewing set visual stimuli coordinated with varying inertial stimuli. This tested the hypothesis that illusory visual motion would influence self-motion perception in the horizontal plane. Trials were arranged into 5 blocks based on stimulus type: moving star field with yaw rotation, moving star field with sway translation, illusory motion with yaw, illusory motion with sway, and static arrows with sway. Static arrows were used to evaluate the effect of cognitive suggestion on self-motion perception. Each trial had a control condition; the illusory motion controls were altered versions of the experimental image, which removed the illusory motion effect. For the moving visual stimulus, controls were carried out in a dark room. With the arrow visual stimulus, controls were a gray screen. In blocks containing a visual stimulus there was an 8s viewing interval with the inertial stimulus occurring over the final 1s. This allowed measurement of the visual illusion perception using objective methods. When no visual stimulus was present, only the 1s motion stimulus was presented. Eight women and five men (mean age 37) participated. To assess for a shift in self-motion perception, the effect of each visual stimulus on the self-motion stimulus (cm/s) at which subjects were equally likely to report motion in either direction was measured. Significant effects were seen for moving star fields for both translation (p = 0.001) and rotation (p<0.001), and arrows (p = 0.02). For the visual motion stimuli, inertial motion perception was shifted in the direction consistent with the visual stimulus. Arrows had a small effect on self-motion perception driven by a minority of subjects. There was no significant effect of illusory motion on self-motion perception for either translation or rotation (p>0.1 for both). Thus, although a true moving visual field can induce self-motion, results of this study show that illusory motion does not.     

Changes in Physiological Properties and Respiratory Pathway of the New Lines of Wheat Introduced Exogenous DNA Under Salt Stress

New lines of wheat (Triticum aestivum L.) was obtained by introducing the DNA of sorghum ( Sorghum vulgare Pers.) into wheat cultivar “Longchun 13”. The changes of respiratory pathway, contents of protein, Na+ and K+ in the leaves and roots of the new lines of wheat under salt stress were determined and compared with the control cultivar, “Longchun 13”. The decrease of the content of K+ was observed with the increase of NaCl concentrations, but the decrease was more in the control than that in the new lines, and more in roots than in leaves. Content of proline and Na+ in both two wheats lines increased greatly, but the former increased more significantly in the new lines and the latter more significantly in control both in leaves and roots. The operation of the cyanide-resistant pathway of respiration was enhanced at different degrees after salt stress and it increased much more in roots and leaves of the control plant than that in the new lines, but the cytochrome pathway of electron transport was still the main one consistently. The possible significance of these changes was discussed.     

Tridimensional dose evaluation of the respiratory motion influence on breast radiotherapy treatments using conformal radiotherapy,forward IMRT,and inverse IMRT planning techniques

PurposeTo evaluate the respiratory motion influence on the tridimensional (3D) dose delivery to breast-shaped phantoms using conformal radiotherapy (3D-RT), Field-in Field (FiF), and IMRT planning techniques.MethodsThis study used breast-shaped phantoms filled with MAGIC-f gel dosimeter to simulate the breast, and an oscillation platform to simulate the respiratory motion. The platform allowed motion in the anterior-posterior direction with oscillation amplitudes of 0.34 cm, 0.88 cm, and 1.22 cm. CT images of the static phantom were used for the 3D-RT, FiF, and IMRT treatment planning. Five phantoms were prepared and irradiated for each planning technique evaluated. Phantom 1 was irradiated static, phantoms 2–4 were irradiated moving with the three different motion amplitudes, and phantom 5 was used as a reference. The 3D dose distributions were obtained by relaxometry of magnetic resonance imaging, and the respiratory motion influence in the doses distribution was accessed by gamma evaluations (3%/3mm/15% threshold) comparing the measurements of the phantoms irradiated under movement with the static ones.ResultsThe mean gamma approvals for three oscillatory amplitudes were 96.44%, 93.23%, and 91.65%; 98.42%, 95.66%, and 94.31%; and 94.49%, 93.51%, and 86.62% respectively for 3D-RT, FiF and IMRT treatments. A gamma results profile per slice along the phantom showed that for FiF and IMRT irradiations, most of the failures occurred in the central region of the phantom.ConclusionsBy increasing the respiratory motion movement, the dose distribution variations for the three planning techniques were more pronounced, being the FiF technique variations the smallest one.     

Dosimetric Comparison of the Simultaneous Integrated Boost in Whole-Breast Irradiation after Breast-Conserving Surgery: IMRT,IMRT plus an Electron Boost and VMAT

Objectives

To compare the target volume coverage and doses to organs at risks (OARs) using three techniques that simultaneous integrated boost (SIB) in whole-breast irradiation (WBI) after breast-conserving surgery, including intensity-modulated radiation therapy (IMRT), IMRT plus an electron boost (IMRT-EB), and volumetric-modulated arc therapy (VMAT).

Methods

A total of 10 patients with early-stage left-sided breast cancer after breast-conserving surgery were included in this study. IMRT, IMRT-EB and VMAT plans were generated for each patient.

Results

The conformity index (CI) of the planning target volumes evaluation (PTV-Eval) of VMAT was significantly superior to those of IMRT and IMRT-EB (P < 0.05). The CI of the PTV Eval-boost of VMAT was better than that of IMRT (P = 0.018) and IMRT-EB (P < 0.001), while the CI of the PTV Eval-boost of IMRT was better than that of IMRT-EB (P = 0.002). The V5, V10 and Dmean in ipsilateral lung with VMAT were significantly higher than IMRT (P < 0.05) and IMRT-EB (P < 0.05). The Dmean, V5 and V10 in heart with VMAT were significantly greater than those of IMRT and IMRT-EB (P < 0.05). There was no significant difference in the OARs between IMRT and IMRT-EB (P > 0.05).

Conclusions

Considered the target volume coverage and radiation dose delivered to the OARs (especially the heart and lung), IMRT may be more suitable for the SIB in WBI than IMRT-EB and VMAT. Additional clinical studies with a larger sample size will be needed to assess the long-term feasibility and efficacy of SIB using different radiotherapy techniques.     

盐胁迫下导入外源DNA小麦新品系生理特性与呼吸途径的变化

测定了将高粱（Sorghum vulgare Pers.）DNA导入小麦（Triticum aestivum L.）“陇春13号”后得到的耐盐新品系根和叶中不同盐浓度胁迫条件下呼吸途径、脯氨酸、Na^ 和K^ 含量的变化,并以“陇春13号”作为对照进行比较。结果表明：K^＋含量均随盐浓度的提高而不断下降,但新品系与对照相比,叶的下降速率明显低于根;脯氨酸和Na^ 的含量则均呈持续上升趋势,且对照叶和根中脯氨酸增加幅度不及新品系,但其叶和根中Na^ 积累显地高于新品系;抗氰呼吸实际运行均不 同程度地加强了,但对照的叶和根的运行程度分别强于新品系,且在整个胁迫过程中细胞色素途径仍是线粒体呼吸中电子传递的主要途径。