A comparative molecular approach to mesodermal patterning in basal deuterostomes: the expression pattern of Brachyury in the enteropneust hemichordate Ptychodera flava

This work concerns the formation of mesoderm in the development of an enteropneust hemichordate, Ptychodera flava, and the expression of the Brachyury gene during this process. Brachyury expression occurs in two distinct phases. In the embryo, Brachyury is transcribed during gastrulation in the future oral and anal regions of the gut, but transcripts are no longer detected by 2 weeks of development. Brachyury expression is not detected during the 5 months of larval planktonic existence. During this time, the adult coeloms begin to develop, originating as coalescences of cells that appear to delaminate from the wall of the gut. Brachyury expression cannot be detected again until metamorphosis, when transcripts appear in the mesoderm of the adult proboscis, collar and the very posterior region of the trunk. It is also expressed in the posterior end of the gut. At no time is Brachyury expressed in the stomochord, the putative homologue of the chordate notochord. These observations illuminate the process of maximal indirect development in Ptychodera and, by comparison with patterns of Brachyury expression in the indirect development of echinoderms, their sister group, they reveal the evolutionary history of Brachyury utilization in deuterostomes

Highly focused supersonic microjets

The paper describes the production of thin, focused microjets with velocities up to 850 m/s by the rapid vaporization of a small mass of liquid in an open liquid-filled capillary. The vaporization is caused by the absorption of a low-energy laser pulse. A likely explanation of the observed phenomenon is based on the impingement of the shock wave caused by the nearly-instantaneous vaporization on the free surface of the liquid. An experimental study of the dependence of the jet velocity on several parameters is conducted, and a semi-empirical relation for its prediction is developed. The coherence of the jets, their high velocity and good reproducibility and controllability are unique features of the system described. A possible application is to the development of needle-free drug injection systems which are of great importance for global health care.Comment: 10 pages, 11figure

Highly focused supersonic microjets

The paper describes the production of thin, focused microjets with velocities up to 850 m/s by the rapid vaporization of a small mass of liquid in an open liquid-filled capillary. The vaporization is caused by the absorption of a low-energy laser pulse. A likely explanation of the observed phenomenon is based on the impingement of the shock wave caused by the nearly-instantaneous vaporization on the free surface of the liquid. An experimental study of the dependence of the jet velocity on several parameters is conducted, and a semi-empirical relation for its prediction is developed. The coherence of the jets, their high velocity and good reproducibility and controllability are unique features of the system described. A possible application is to the development of needle-free drug injection systems which are of great importance for global health care.Comment: 10 pages, 11figure

Enzootic bovine leukosis accompanied by splenomegaly in an 8-month-old calf

ΔΕΝ ΔΙΑΤΙΘΕΤΑΙ ΠΕΡΙΛΗΨΗIn this report, an 8-month-old calf (crossbred, Holstein × Japanese Black) developed fever and accompanied abomasum displacement. Blood chemical test showed remarkably high values of white blood cell count and heteromorphic lymphocytes. In pathological appraisal, enlarged splenomegaly and swelling of the lymph nodes were observed. Histopathological examination revealed invasion of tumor cells derived from B1 cells into systemic lymph nodes, liver and spleen. The provirus loads of bovine leukemia virus (BLV) was 1,439 copies per 10 ng DNA by using real time PCR. In conclusion, this case was diagnosed as bovine leukemia caused by BLV infection with a huge splenomegaly

Review of Salvage Therapy for Biochemically Recurrent Prostate Cancer: The Role of Imaging and Rationale for Systemic Salvage Targeted Anti-Prostate-Specific Membrane Antigen Radioimmunotherapy

Despite local therapy with curative intent, approximately 30% of men suffer from biochemical relapse. Though some of these PSA relapses are not life threatening, many men eventually progress to metastatic disease and die of prostate cancer. Local therapy is an option for some men, but many have progression of disease following local salvage attempts. One significant issue in this setting is the lack of reliable imaging biomarkers to guide the use of local salvage therapy, as the likely reason for a low cure rate is the presence of undetected micrometastatic disease outside of the prostate/prostate bed. Androgen deprivation therapy is a cornerstone of therapy in the salvage setting. While subsets may benefit in terms of delay in time to metastatic disease and/or death, research is ongoing to improve salvage systemic therapy. Prostate-specific membrane antigen (PSMA) is highly overexpressed by the majority of prostate cancers. While initial methods of exploiting PSMA's high and selective expression were suboptimal, additional work in both imaging and therapeutics is progressing. Salvage therapy and imaging modalities in this setting are briefly reviewed, and the rationale for PSMA-based systemic salvage radioimmunotherapy is described

Gravitational wave source populations: Disentangling an AGN component

The astrophysical origin of the over 90 compact binary mergers discovered by the LIGO and Virgo gravitational wave observatories is an open question. While the unusual mass and spin of some of the discovered objects constrain progenitor scenarios, the observed mergers are consistent with multiple interpretations. A promising approach to solve this question is to consider the observed distributions of binary properties and compare them to expectations from different origin scenarios. Here we describe a new hierarchical population analysis framework to assess the relative contribution of different formation channels simultaneously. For this study we considered binary formation in AGN disks along with phenomenological models, but the same framework can be extended to other models. We find that high-mass and high-mass-ratio binaries appear more likely to have an AGN origin compared to the same origin as lower-mass events. Future observations of high-mass black hole mergers could further disentangle the AGN component from other channels.Comment: 7 pages, 4 figures, and 1 tabl

Synthetic DNA immunotherapy in biochemically relapsed prostate cancer

Background: INO-5150 (PSA and PSMA) +/- INO-9012 (IL-12), a synthetic DNA immunotherapy, was assessed for safety, immunogenicity and efficacy in biochemically recurrent prostate cancer patients (pts). Methods: Phase I, open-label, multi-center study in the US included pts with rising PSA after surgery and/or RT, PSA doubling time (PSADT) \u3e3 months (mos), testosterone \u3e150 ng/dL and no concurrent ADT. Safety, immunogenicity and efficacy (PSA kinetics, PFS) were evaluated in 4 treatment arms of 15 pts each. Arms A: 2mg INO-5150, B: 8.5 mg INO-5150, C: 2mg INO-5150 + 1mg INO-9012 and D: 8.5mg INO-5150 + 1mg INO-9012. Pts received 4 IM doses of vaccine followed by electroporation on day 0, wks 3, 12 and 24 and were followed for 72 wks. Results: 50/61 (82%) pts completed all visits and treatments were well tolerated with no safety concerns. Median PFS for overall population [N = 61, baseline (D0) PSADT range (mos) 1.5-217.1, median 9.8] and for a subset of pts with D0 PSADT ≤12mos (N = 36) has not yet been reached (FU 3-19 mos). 86% of pts with D0 PSADT ≤12 mos were progression free through 19mos FU. 27 out of 36 (75%) pts with D0 PSADT≤ 12 mos had disease stabilization at wks 27 evidenced by significant improvement in log2PSA change over time (slope) and PSADT from D0 (Slope=0.19 declined to 0.1, PSADT=5.3 improved to 10.1 mos, p = \u3c0.0001). This effect was maintained at wk 72 (Slope=0.09, PSADT=10.6, p = \u3c0.0001). Immunogenicity was observed in 77% (47/61) of pts by multiple immunologic assessments. Patient immunogenicity to INO-5150 as determined by CD38 and Perforin + CD8 T cell immune reactivity correlated with attenuated % PSA rise compared to pts without reactivity (p = 0.05, n = 50). Conclusions: INO-5150 +/- INO-9012 was safe, well tolerated and immunogenic. Clinical efficacy was observed in the patients with D0 PSADT≤ 12 mos as evidenced by a significant dampening of log2PSA change over time and increased PSADT up to 72 weeks FU. Additional genomic analyses are ongoing to further elucidate the correlation of immunologic efficacy and clinical benefit. (NCT02514213)

Highly focused supersonic microjets: numerical simulations

By focusing a laser pulse inside a capillary partially filled with liquid, a vapour bubble is created which emits a pressure wave. This pressure wave travels through the liquid and creates a fast, focused axisymmetric microjet when it is reflected at the meniscus. We numerically investigate the formation of this microjet using axisymmetric boundaryintegral simulations, where we model the pressure wave as a pressure pulse applied on the bubble. We find a good agreement between the simulations and experimental results in terms of the time evolution of the jet and on all parameters that can be compared directly. We present a simple analytical model that accurately predicts the velocity of the jet after the pressure pulse and its maximum velocity