Stem cells and cancer immunotherapy: Arrowhead’s 2nd annual cancer immunotherapy conference

Investigators from academia and industry gathered on April 4 and 5, 2013, in Washington DC at the Arrowhead’s 2nd Annual Cancer Immunotherapy Conference. Two complementary concepts were discussed: cancer “stem cells” as targets and therapeutic platforms based on stem cells

A high resolution spallation driven facility at the CERN-PS to measure neutron cross sections in the interval from 1 eV to 250 MeV : a relative performance assessment - Add. 1

In the proposed facility with 24 GeV PS beam on a Lead target, the number of produced neutrons exceeds 760 per proton. In comparison, with a LINAC (GELINA) one currently obtains only about 0.05 neutrons per electron of about 100 MeV. An additional factor of 2.5 for the CERN facility is due to the strong, forward peaking of the neutron flux, arising from the high proton energy and corresponding longitudinal boost. This huge factor in neutron yield per incident particle, namely 2.5 x 760/0.05 = 3.8 x 10^4, is only partially off-set by the higher, time averaged current of the LINAC e.g. 100 mA vs . 2 mA of the CERN-PS. Therefore the useful, initial neutron rate at the CERN facility is about three orders of magnitude larger than in the most performing electron LINACs, GELINA in Belgium and ORELLA in the US. The time duration of the PS pulse is presently Deltat|_r.m.s.=13.5 ns and we believe it could be reduced to Deltat|_r.m.s.= 6.75 ns. The electron LINAC has much shorter pulses Deltat| _r.m.s.= 1 ns, to which however the resolution of the counters has to be added. But for neutron energy 1 MeV, is not affecting the actual TOF energy resolution, dominated by the fluctuations of moderation. Since these time fluctuations are largely independent of the chosen mechanism to produce the initial neutrons, the initial flux difference between the two methods, e.g. electrons vs. protons, reflects directly in the counting rate for a given TOF resolution at the measuring station. Furthermore the CERN PS (< 1/2.4 sec^-1) has a much smaller repetition rate than the LINAC (1 /800 sec-1) and it presents no problems of time overlaps at the measuring station due to successive bunches. The accidental background due to radio-active targets is also much better suppressed. Finally the gamma-prompt flash is considerably smaller for a proton machine than in the case of an electron LINAC and no gamma-filters are required

Maintenance of spermatogenesis requires TAF4b, a gonad-specific subunit of TFIID

The establishment and maintenance of spermatogenesis in mammals requires specialized networks of gene expression programs in the testis. The gonad-specific TAF4b component of TFIID (formerly TAFII105) is a transcriptional regulator enriched in the mouse testis. Herein we show that TAF4b is required for maintenance of spermatogenesis in the mouse. While young Taf4b-null males are initially fertile, Taf4b-null males become infertile by 3 mo of age and eventually exhibit seminiferous tubules devoid of germ cells. At birth, testes of Taf4b-null males appear histologically normal; however, at post-natal day 3 gonocyte proliferation is impaired and expression of spermatogonial stem cell markers c-Ret, Plzf, and Stra8 is reduced. Together, these data indicate that TAF4b is required for the precise expression of gene products essential for germ cell proliferation and suggest that TAF4b may be required for the regulation of spermatogonial stem cell specification and proliferation that is obligatory for normal spermatogenic maintenance in the adult

A CERN-PS Experimental Campaign to Measure Neutron Cross Sections from 1 e V to 250 MeV with High Resolution.

Abstract not availableJRC.D-Institute for Reference Materials and Measurements (Geel

Ran GTPase Cycle and Importins α and β Are Essential for Spindle Formation and Nuclear Envelope Assembly in Living Caenorhabditis elegans Embryos

The small GTPase Ran has been found to play pivotal roles in several aspects of cell function. We have investigated the role of the Ran GTPase cycle in spindle formation and nuclear envelope assembly in dividing Caenorhabditis elegans embryos in real time. We found that Ran and its cofactors RanBP2, RanGAP, and RCC1 are all essential for reformation of the nuclear envelope after cell division. Reducing the expression of any of these components of the Ran GTPase cycle by RNAi leads to strong extranuclear clustering of integral nuclear envelope proteins and nucleoporins. Ran, RanBP2, and RanGAP are also required for building a mitotic spindle, whereas astral microtubules are normal in the absence of these proteins. RCC1(RNAi) embryos have similar abnormalities in the initial phase of spindle formation but eventually recover to form a bipolar spindle. Irregular chromatin structures and chromatin bridges due to spindle failure were frequently observed in embryos where the Ran cycle was perturbed. In addition, connection between the centrosomes and the male pronucleus, and thus centrosome positioning, depends upon the Ran cycle components. Finally, we have demonstrated that both IMA-2 and IMB-1, the homologues of vertebrate importin α and β, are essential for both spindle assembly and nuclear formation in early embryos