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Violence seems deeply rooted in human nature and an endemic potential for such is today frequently associated with differing ethnic, religious or socio-economic backgrounds. Ethnic nepotism is believed to be one of the main causes of inter-group violence in multi-ethnic societies. At the site of Els Trocs in the Spanish Pyrenees, rivalling groups of either migrating early farmers or farmers and indigenous hunter-gatherers collided violently around 5300 BCE. This clash apparently resulted in a massacre of the Els Trocs farmers. The overkill reaction was possibly triggered by xenophobia or massive disputes over resources or privileges. In the present, violence and xenophobia are controlled and sanctioned through social codes of conduct and institutions. So that, rather than representing an insurmountable evolutionary inheritance, violence and ethnic nepotism can be overcome and a sustainable future achieved through mutual respect, tolerance and openness to multi-ethnic societies.

Malignant cells ensure telomere maintenance by the alternative lengthening of telomeres (ALT) in the absence of telomerase activity (TA). The retrotransposons "long interspersed nuclear element-1" (LINE-1, L1) are expressed in malignant cells and are primarily known to contribute to complex karyotypes. Here we demonstrate that LINE-1 ribonucleoprotein particles (L1-RNPs) expression is significantly higher in ALT + - versus in TA + -human glioma. Analyzing a role of L1-RNP in ALT, we show that L1-RNPs bind to telomeric repeat containing RNA (TERRA), which is critical for telomere stabilization and which is overexpressed in ALT + cells. In turn, L1-RNP knockdown (KD) abrogated the nuclear retention of TERRA, resulted in increased telomeric DNA damage, decreased cell growth and reduced expression of ALT characteristics such as c-circles and PML-bodies. L1-RNP KD also decreased the expression of Shelterin- and the ALT-regulating protein Topoisomerase IIIα (TopoIIIα) indicating a more general role of L1-RNPs in supporting telomeric integrity in ALT. Our findings suggest an impact of L1-RNP on telomere stability in ALT + dependent tumor cells. As L1-RNPs are rarely expressed in normal adult human tissue those elements might serve as a novel target for tumor ablative therapy., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Microbial electrosynthesis (MES) is a promising technology to convert CO 2 and electricity into the biofuel methane using methanogens. Until now, most investigations on electro-methanogenesis are "proof-of-principle" studies. In this paper, different strains were quantitatively compared in regard to final methane concentration, yields based on CO 2 -conversion, productivities as well as Coulombic efficiencies in order to identify suitable organisms for MES. Methanococcus vannielii, Methanococcus maripaludis, Methanolacinia petrolearia, Methanobacterium congolense, and Methanoculleus submarinus were able to produce methane via MES at -700 mV vs. standard hydrogen electrode (SHE). Beside methane also biological H 2 production was detected during MES, which might be due to the involvement of hydrogenases. A direct electron transfer pathway is most likely. Obviously, M. maripaludis is the most resource efficient methane producer in microbial electrosynthesis regarding the methane productivity (8.81 ± 0.51 mmol m -2  d -1 ) and the Coulombic efficiency (58.9 ± 0.8%)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Cathode and catholyte are usually optimized to improve microbial electrosynthesis process, whereas the anodic counter reaction was not systematically investigated and optimized for these applications yet. Nevertheless, the anolyte and especially the anode material can limit the cathodic bioelectrochemical process. This paper compares for the first time the performance of different anode materials as counter electrodes for a cathodic bioelectrochemical process, the bioelectromethanogenesis. It was observed that depending on the anode material the cathodic methane production varies from 0.96 µmol/d with a carbon fabric anode to 25.44 µmol/d with a carbon felt anode of the same geometrical surface area. The used anolyte also affected the methane production rate at the cathode. Especially, the pH of the anolyte showed an impact on the system; an anolyte with pH 5 produced up to 2.0 times more methane compared to one with pH 8.5. The proton availability is discussed as one reason for this effect. Although some of the measured effects cannot be explained completely so far this study advises researchers to strongly consider the anode impact during process development and optimization of a cathodic bioelectrochemical synthesis process., Competing Interests: The authors have declared no conflict of interest., (© 2019 The Authors. Engineering in Life Sciences published by Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim.)

Facing energy problems, there is a strong demand for new technologies dealing with the replacement of fossil fuels. The emerging fields of biotechnology, photobiotechnology and electrobiotechnology, offer solutions for the production of fuels, energy, or chemicals using renewable energy sources (light or electrical current e.g. produced by wind or solar power) or organic (waste) substrates. From an engineering point of view both technologies have analogies and some similar challenges, since both light and electron transfer are primarily surface-dependent. In contrast to that, bioproduction processes are typically volume dependent. To allow large scale and industrially relevant applications of photobiotechnology and electrobiotechnology, this opinion first gives an overview over the current scales reached in these areas. We then try to point out the challenges and possible methods for the scale up or numbering up of the reactors used. It is shown that the field of photobiotechnology is by now much more advanced than electrobiotechnology and has achieved industrial applications in some cases. We argue that transferring knowledge from photobiotechnology to electrobiotechnology can speed up the development of the emerging field of electrobiotechnology. We believe that a combination of scale up and numbering up, as it has been shown for several photobiotechnological reactors, may well lead to industrially relevant scales in electrobiotechnological processes allowing an industrial application of the technology in near future., Competing Interests: The authors have declared no conflict of interest., (© 2018 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.)

From the first electromicrobial experiment to a sophisticated microbial electrochemical process - it all takes place in a reactor. Whereas the reactor design and materials used strongly influence the obtained results, there are no common platforms for MES reactors. This is a critical convention gap, as cross-comparison and benchmarking among MES as well as MES vs. conventional biotechnological processes is needed. Only knowledge driven engineering of MES reactors will pave the way to application and commercialization. In this chapter we first assess the requirements on reactors to be used for bioelectrochemical systems as well as potential losses caused by the reactor design. Subsequently, we compile the main types and designs of reactors used for MES so far, starting from simple H-cells to stirred tank reactors. We conclude with a discussion on the weaknesses and strengths of the existing types of reactors for bioelectrochemical systems that are scored on design criteria and draw conclusions for the future engineering of MES reactors.

Objective/background: Carotid bifurcation resection with subsequent reconstruction is performed infrequently. While internal carotid artery (ICA) revascularisation is regarded as mandatory, the external carotid artery (ECA) is severed in most instances. Indications for and results of an autologous bifurcated carotid artery reconstruction are discussed., Methods: This was a single centre retrospective analysis of a consecutive series of patients treated at an academic vascular surgery centre., Results: From December 2006 to August 2015, 47 patients underwent reconstruction of the carotid artery using an autologous bifurcated interposition graft (36 men; median age 68.3 years [range 41-87 years]; 33 asymptomatic [70%]). The indication for reconstruction was recurrent carotid stenosis unfavorable for endovascular treatment/redo patch plasty (n = 29; symptomatic: n = 12), carotid aneurysm (n = 10), neck tumour with vascular involvement (n = 7), and trauma (n = 1). Groups were not different with regard to vascular risk factors. Non-reversed valve depleted saphenous/accessory saphenous vein from the groin was used in 44 (94%), and reversed valve depleted cubital vein bifurcation graft in three patients (6%). Median ICA cross clamp time was 17 min (range 8-30 min). Five patients suffered from intra-operative ischaemic neurological deficits (11%), of which all were temporary except one. One tumour patient died on post-operative day 1 due to bleeding. Median follow up was 28.3 months (range 0.1-97.4 months). Tumour erosion required graft ligation in one patient 7 months after reconstruction. Five significant stenoses of the ICA (11%), nine (19%) stenoses of the ECA, and two (4%) common carotid artery stenoses, with four (8%) re-redo interventions, were observed. Thirteen patients (28%) died after a median follow up of 6.7 months (range 1.7-56.7 months), all unrelated to the vascular procedure., Conclusion: Autologous bifurcated carotid artery interposition graft avoids the use of prosthetic graft material, the ECA remains patent in 80%, and it provides mid-term results comparable with other redo carotid artery procedures. Therefore, this procedure should be reserved for symptomatic patients with no other revascularisation option., (Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Animal resources have been part of hominin diets since around 2.5 million years ago, with sharp-edged stone tools facilitating access to carcasses. How exactly hominins acquired animal prey and how hunting strategies varied through time and space is far from clear. The oldest possible hunting weapons known from the archaeological record are 300,000 to 400,000-year-old sharpened wooden staves. These may have been used as throwing and/or close-range thrusting spears, but actual data on how such objects were used are lacking, as unambiguous lesions caused by such weapon-like objects are unknown for most of human prehistory. Here, we report perforations observed on two fallow deer skeletons from Neumark-Nord, Germany, retrieved during excavations of 120,000-year-old lake shore deposits with abundant traces of Neanderthal presence. Detailed studies of the perforations, including micro-computed tomography imaging and ballistic experiments, demonstrate that they resulted from the close-range use of thrusting spears. Such confrontational ways of hunting require close cooperation between participants, and over time may have shaped important aspects of hominin biology and behaviour.

Since fossil sources for fuel and platform chemicals will become limited in the near future, it is important to develop new concepts for energy supply and production of basic reagents for chemical industry. One alternative to crude oil and fossil natural gas could be the biological conversion of CO 2 or small organic molecules to methane via methanogenic archaea. This process has been known from biogas plants, but recently, new insights into the methanogenic metabolism, technical optimizations and new technology combinations were gained, which would allow moving beyond the mere conversion of biomass. In biogas plants, steps have been undertaken to increase yield and purity of the biogas, such as addition of hydrogen or metal granulate. Furthermore, the integration of electrodes led to the development of microbial electrosynthesis (MES). The idea behind this technique is to use CO 2 and electrical power to generate methane via the microbial metabolism. This review summarizes the biochemical and metabolic background of methanogenesis as well as the latest technical applications of methanogens. As a result, it shall give a sufficient overview over the topic to both, biologists and engineers handling biological or bioelectrochemical methanogenesis.

Ascending aortic aneurysms are mostly asymptomatic and present a great risk of aortic dissection or perforation. Consequently, ascending aortic aneurysms are a source of lethality with increased age. Biological aging results in progressive attrition of telomeres, which are the repetitive DNA sequences at the end of chromosomes. These telomeres play an important role in protection of genomic DNA from end-to-end fusions. Telomere maintenance and telomere attrition-associated senescence of endothelial and smooth muscle cells have been indicated to be part of the pathogenesis of degenerative vascular diseases. This systematic review provides an overview of telomeres, telomere-associated proteins and telomerase to the formation and progression of aneurysms of the thoracic ascending aorta. A better understanding of telomere regulation in the vascular pathology might provide new therapeutic approaches. Measurements of telomere length and telomerase activity could be potential prognostic biomarkers for increased risk of death in elderly patients suffering from an aortic aneurysm., Competing Interests: The authors declare no conflicts of interest.

Randall's plaques (RP) are preferred sites for the formation of calcium oxalate monohydrate (COM) kidney stones. However, although processes of interstitial calcium phosphate (CaP) plaque formation are not well understood, the potential of plaque microstructures as indicators of CaP precipitation conditions received only limited attention. We investigated RP-associated COM stones for structural details of the calcified tissues and microstructural features of plaque-stone interfaces as indicators of the initial processes of stone formation. Significantly increased CaP supersaturation can be expected for interstitial fluid, if reabsorbed ions from the tubular system continuously diffuse into the collagenous connective tissue. Densely packed, fine-grained CaP particles were found in dense textures of basement membranes while larger, laminated particles were scattered in coarse-meshed interstitial tissue, which we propose to be due to differential spatial confinements and restrictions of ion diffusion. Particle morphologies suggest an initial precipitation as metastable amorphous calcium phosphate (ACP). Morphologies and arrangements of first COM crystals at the RP-stone interface ranged from stacked euhedral platelets to skeletal morphologies and even porous, dendritic structures, indicating, in this order, increasing levels of COM supersaturation. Furthermore, these first COM crystals were often coated with CaP. On this basis, we propose that ions from CaP-supersaturated interstitial fluid may diffuse through porous RP into the urine, where a resulting local increase in COM supersaturation could trigger crystal nucleation and, hence, initiate stone formation. Ion-depleted fluid in persistent pores of initial COM layers may get replenished from interstitial fluid, leading to CaP precipitation in porous COM.

Authigenic carbonate build-ups develop at seafloor methane-seeps, where microbially mediated sulphate-dependent anaerobic oxidation of methane facilitates carbonate precipitation. Despite being valuable recorders of past methane seepage events, their role as archives of atmospheric processes has not been examined. Here we show that cyclic sedimentation pulses related to the Indian monsoon in concert with authigenic precipitation of methane-derived aragonite gave rise to a well-laminated carbonate build-up within the oxygen minimum zone off Pakistan (northern Arabian Sea). U-Th dating indicates that the build-up grew during past ~1,130 years, creating an exceptional high-resolution archive of the Indian monsoon system. Monsoon-controlled formation of seep-carbonates extends the known environmental processes recorded by seep-carbonates, revealing a new relationship between atmospheric and seafloor processes.

Background: In geochemically perturbed systems where porewater and mineral assemblages are unequilibrated the processes of mineral precipitation and dissolution may change important transport properties such as porosity and pore diffusion coefficients. These reactions might alter the sealing capabilities of the rock by complete pore-scale precipitation (cementation) of the system or by opening new migration pathways through mineral dissolution. In actual 1D continuum reactive transport codes the coupling of transport and porosity is generally accomplished through the empirical Archie's law. There is very little reported data on systems with changing porosity under well controlled conditions to constrain model input parameters. In this study celestite (SrSO4) was precipitated in the pore space of a compacted sand column under diffusion controlled conditions and the effect on the fluid migration properties was investigated by means of three complementary experimental approaches: (1) tritiated water (HTO) tracer through diffusion, (2) computed micro-tomography (µ-CT) imaging and (3) post-mortem analysis of the precipitate (selective dissolution, SEM/EDX)., Results: The through-diffusion experiments reached steady state after 15 days, at which point celestite precipitation ceased and the non-reactive HTO flux became constant. The pore space in the precipitation zone remained fully connected using a 6 µm µ-CT spatial resolution with 25 % porosity reduction in the approx. 0.35 mm thick dense precipitation zone. The porosity and transport parameters prior to pore-scale precipitation were in good agreement with a porosity of 0.42 ± 0.09 (HTO) and 0.40 ± 0.03 (µ-CT), as was the mass of SrSO4 precipitate estimated by µ-CT at 25 ± 5 mg and selective dissolution 21.7 ± 0.4 mg, respectively. However, using this data as input parameters the 1D single continuum reactive transport model was not able to accurately reproduce both the celestite precipitation front and the remaining connected porosity. The model assumed there was a direct linkage of porosity to the effective diffusivity using only one cementation value over the whole porosity range of the system investigated., Conclusions: The 1D single continuous model either underestimated the remaining connected porosity in the precipitation zone, or overestimated the amount of precipitate. These findings support the need to implement a modified, extended Archie's law to the reactive transport model and show that pore-scale precipitation transforms a system (following Archie's simple power law with only micropores present) towards a system similar to clays with micro- and nanoporosity. Graphical abstract.

In most rodents and some other mammals, the removal of one lung results in compensatory growth associated with dramatic angiogenesis and complete restoration of lung capacity. One pivotal mechanism in neoalveolarization is neovascularization, because without angiogenesis new alveoli can not be formed. The aim of this study is to image and analyze three-dimensionally the different patterns of neovascularization seen following pneumonectomy in mice on a sub-micron-scale. C57/BL6 mice underwent a left-sided pneumonectomy. Lungs were harvested at various timepoints after pneumonectomy. Volume analysis by microCT revealed a striking increase of 143 percent in the cardiac lobe 14 days after pneumonectomy. Analysis of microvascular corrosion casting demonstrated spatially heterogenous vascular densitities which were in line with the perivascular and subpleural compensatory growth pattern observed in anti-PCNA-stained lung sections. Within these regions an expansion of the vascular plexus with increased pillar formations and sprouting angiogenesis, originating both from pre-existing bronchial and pulmonary vessels was observed. Also, type II pneumocytes and alveolar macrophages were seen to participate actively in alveolar neo-angiogenesis after pneumonectomy. 3D-visualizations obtained by high-resolution synchrotron radiation X-ray tomographic microscopy showed the appearance of double-layered vessels and bud-like alveolar baskets as have already been described in normal lung development. Scanning electron microscopy data of microvascular architecture also revealed a replication of perialveolar vessel networks through septum formation as already seen in developmental alveolarization. In addition, the appearance of pillar formations and duplications on alveolar entrance ring vessels in mature alveoli are indicative of vascular remodeling. These findings indicate that sprouting and intussusceptive angiogenesis are pivotal mechanisms in adult lung alveolarization after pneumonectomy. Various forms of developmental neoalveolarization may also be considered to contribute in compensatory lung regeneration.

The development of influenza virus vectors with long insertions of foreign sequences remains difficult due to the small size and instable nature of the virus. Here, we used the influenza virus inherent property of self-optimization to generate a vector stably expressing long transgenes from the NS1 protein ORF. This was achieved by continuous selection of bright fluorescent plaques of a GFP-expressing vector during multiple passages in mouse B16f1 cells. The newly generated vector acquired stability in IFN-competent cell lines and in vivo in murine lungs. Although improved vector fitness was associated with the appearance of four coding mutations in the polymerase (PB2), haemagglutinin and non-structural (NS) segments, the stability of the transgene expression was dependent primarily on the single mutation Q20R in the nuclear export protein (NEP). Importantly, a longer insert, such as a cassette of 1299 nt encoding two Mycobacterium tuberculosis Esat6 and Ag85A proteins, could substitute for the GFP transgene. Thus, the inherent property of the influenza virus to adapt can also be used to adjust a vector backbone to give stable expression of long transgenes.

Newly developed high-speed, synchrotron-based X-ray computed microtomography enabled us to directly image pore-scale displacement events in porous rock in real time. Common approaches to modeling macroscopic fluid behavior are phenomenological, have many shortcomings, and lack consistent links to elementary pore-scale displacement processes, such as Haines jumps and snap-off. Unlike the common singular pore jump paradigm based on observations of restricted artificial capillaries, we found that Haines jumps typically cascade through 10-20 geometrically defined pores per event, accounting for 64% of the energy dissipation. Real-time imaging provided a more detailed fundamental understanding of the elementary processes in porous media, such as hysteresis, snap-off, and nonwetting phase entrapment, and it opens the way for a rigorous process for upscaling based on thermodynamic models.

We combined a noninvasive tomographic imaging technique with an invasive open-system core-flooding experiment and compared the results of the pre- and postflooded states of an experimental sandstone core sample from an ongoing field trial for carbon dioxide geosequestration. For the experiment, a rock core sample of 80 mL volume was taken from the 629 m Stuttgart Formation storage domain of a saline sandstone aquifer at the CCS research pilot plant Ketzin, Germany. Supercritical carbon dioxide and synthetical brine were injected under in situ reservoir p/T-conditions at an average flow rate of 0.1 mL/min for 256 h. X-ray computed microtomographic imaging was carried out before and after the core-flooding experiment at a spatial voxel resolution of 27 μm. No significant changes in microstructure were found at the tomographic imaging resolution including porosity and pore size distribution, except of an increase of depositional heterogeneous distribution of clay minerals in the pores. The digitized rock data were used as direct real microstructure input to the GeoDict software package, to simulate Navier-Stokes flow by a lattice Boltzmann equation solver. This procedure yielded 3D pressure and flow velocity fields, and revealed that the migration of clay particles decreased the permeability tensor probably due to clogging of pore openings.

We studied tracer (Tritiated Water (HTO); Tritium replaces one of the stable hydrogen atoms in the H(2)O molecule) and nanoparticle (quantum dots (QD)) transport by means of column migration experiments and comparison to 3D CFD modeling. Concerning the modeling approach, a natural single fracture was scanned using micro computed tomography (μCT) serving as direct input for the model generation. The 3D simulation does not incorporate any chemical processes besides the molecular diffusion coefficient solely reflecting the impact of fracture heterogeneity on mass (solute and nanoparticles) transport. Complex fluid velocity distributions (flow channeling and flowpath heterogeneity) evolve as direct function of fracture geometry. Both experimental and simulated solute and colloidal breakthrough curves show heavy tailing (non-Fickian transport behavior), respectively. Regarding the type of quantum dots and geochemical conditions prevailing (Grimsel ground water chemistry, QD and diorite surface charge, respectively and porosity of the Äspö diorite drill core) experimental breakthrough of the quantum dots always arrives faster than the solute tracer in line with the modeling results. Besides retardation processes like sorption, filtration, straining or matrix diffusion, the results show that natural 3D fracture heterogeneity represents an important additional retardation mechanism for solutes and colloidal phases. This is clearly verified by the numerical simulations, where the 3D real natural fracture geometry and the resulting complex flow velocity distribution is the only possible process causing solute/nanoparticle retardation. Differences between the experimental results and the simulations are discussed with respect to uncertainties in the μCT measurements and experimental and simulation boundary conditions, respectively., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The typical primary malignancies of the liver are hepatocellular carcinoma and cholangiocarcinoma, whereas colorectal liver metastases are the most frequently occurring secondary tumors. In many cases, only palliative treatment is possible. Boron neutron capture therapy (BNCT) represents a technique that potentially destroys tumor tissue selectively by use of externally induced, locally confined secondary particle irradiation. In 2001 and 2003, BNCT was applied to two patients with colorectal liver metastases in Pavia, Italy. To scrutinize the rationale of BNCT, a clinical pilot study on patients with colorectal liver metastases was carried out at the University of Mainz. The distribution of the (10)B carrier (p-borono-phenylalanine) in the liver and its uptake in cancerous and tumor-free tissue were determined, focusing on a potential correlation between the uptake of p-borono-phenylalanine and the biological characteristics of cancerous tissue. Samples were analyzed using quantitative neutron capture radiography of cryosections combined with histological analysis. Methodological aspects of the combination of these techniques and results from four patients enrolled in the study are presented that indicate that the uptake of p-borono-phenylalanine strongly depends on the metabolic activity of cells.

Aim: Endothelial dysfunction (ED) is the functional prestep in atherosclerosis. Aim of the present study was to evaluate the effects of a potent antioxidant (coenzyme Q(10), CoQ(10)) and of cerivastatin on ED of the brachial artery., Methods and Results: Twenty-five male patients with manifest ED (flow-mediated vasodilation [FMD%]<4.5%) were included in this prospective, randomized, cross-over study. ED of the brachial artery was assessed by the use of high-resolution ultrasound. Each patient had to pass through three treatment phases ((1) single therapy with cerivastatin (C), (2) single therapy with CoQ(10), (3) combination therapy). FMD% significantly improved throughout all treatment phases ((1) 3.50+/-4.05% vs. 8.80+/-6.39%, p=0.009; (2) -0.25+/-4.0% vs. 7.06%+/-4.39%, p=0.004; (3) 3.14+/-3.54% vs. 8.82+/-5.78%, p=0.011). C led to a significant decrease of CoQ(10) plasma levels (1.23+/-0.34 vs. 0.87+/-0.39 microg/ml, p=0.004)., Conclusion: Our results indicate a positive influence of CoQ(10) supplementation on human ED, which appears to be independent of lipid lowering. Although large-scale studies evaluating other antioxidants failed to demonstrate a positive prognostic effect, Q(10) has never been evaluated in larger trials. Experimental as well as clinical results indicate that CoQ(10) warrants further attention in atherosclerosis research.

HB 699 (100 micrograms/ml), almost identical with the left residue of the sulphonylurea glibenclamide, enhanced basal insulin and somatostatin release from the perfused rat pancreas. The compound also augmented both the early and late insulin release stimulated by 6.7 mM glucose, while with 16.7 and 33.3 mM glucose only late insulin release was increased. Furthermore, HB 699 enhanced both phases of glucose induced somatostatin release irrespective of whether 6.7, 16.7 or 33.3 mM glucose were used. As for glucagon release, HB 699 suppressed basal and arginine stimulated glucagon secretion. The present findings imply that the sulphonylurea moiety of glibenclamide is not a prerequisite for its stimulatory action on insulin and somatostatin release. It is suggested that the enhanced somatostatin release mediates the inhibitory effect of the compound on glucagon release.

Employing the test model which we developed for the investigation of platelet adhesiveness and aggregation in vivo, experiments demonstrated that the sulfonyl urea derivatives, glibenclamide, gliclazide, and HB 180, as well as the carboxylic acid derivative, meglitinide, are able to inhibit, in a dose-dependent relationship, the adherence of i.v. injected Walker-256-carcinosarcoma cells to the vascular endothelium of the rat mesentery, as well as to reduce significantly the rate of instantly occurring terminal tumor cell embolism of the lung. Since venous blood platelet count in surviving animals is inversely proportional to the number of the tumor cells which adhere to the vascular endothelium, one can deduce that tumor cell embolism is an immediate result of a massively occurring disseminated intravascular coagulation (DIC) which may be induced by i.v. injection of thromboplastic active carcinosarcoma cells and leads primarily to a drastic platelet count reduction. All four substances inhibit this platelet count reduction as well as the directly correlated tumor cell embolism mortality rate in a linear dose-dependent fashion. Their action can therefore be explained as being mediated via an inhibition of platelet adhesion and aggregation to the circulating tumor cells. Our proof of platelet aggregation in vivo correlates with the results obtained by Klaff et al. (1979), as far as a normalization of the pathologically increased platelet aggregation tendency in vitro in diabetics following 4-6 weeks of therapy with the sulfonyl urea derivatives glibenclamide and gliclazide.

Two fractions with LH releasing activity were obtained from porcine hypothalami by Enzmann et al. (1972). These fractions were designated E 57 and E 203. By comparison with pure natural LH-RH and synthetic LH-RH, E 203 was identified as purified natural LH-RH. E 57, which has only 25% of the activity of E 203, was further evaluated for its biological and immunological activity. E 57 has the same ratio of LH/FSH-releasing activity as natural LH-RH. The binding to a specific LH-RH antiserum is identical with that of natural LH-RH and E 203. It is concluded, that E 57 is an artifact of isolation derived from natural LH-RH. These findings can be considered as additional evidence for the identity of the hypothalamic LH and FSH releasing hormone, since both gonadotrophins are stimulated by the two hypothalamic fractions.