Temperature Modulation of Electric Fields in Biological Matter

Pulsed electric fields (PEF) have become an important minimally invasive surgical technology for various applications including genetic engineering, electrochemotherapy and tissue ablation. This study explores the hypothesis that temperature dependent electrical parameters of tissue can be used to modulate the outcome of PEF protocols, providing a new means for controlling and optimizing this minimally invasive surgical procedure. This study investigates two different applications of cooling temperatures applied during PEF. The first case utilizes an electrode which simultaneously delivers pulsed electric fields and cooling temperatures. The subsequent results demonstrate that changes in electrical properties due to temperature produced by this configuration can substantially magnify and confine the electric fields in the cooled regions while almost eliminating electric fields in surrounding regions. This method can be used to increase precision in the PEF procedure, and eliminate muscle contractions and damage to adjacent tissues. The second configuration considered introduces a third probe that is not electrically active and only applies cooling boundary conditions. This second study demonstrates that in this probe configuration the temperature induced changes in electrical properties of tissue substantially reduce the electric fields in the cooled regions. This novel treatment can potentially be used to protect sensitive tissues from the effect of the PEF. Perhaps the most important conclusion of this investigation is that temperature is a powerful and accessible mechanism to modulate and control electric fields in biological tissues and can therefore be used to optimize and control PEF treatments

Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2

Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1 , JAK3 , STAT3 , and SOCS1 . We also identified mutations in KRAS , TP53 , and TERT . Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. We modeled the effects of SETD2 loss in vivo by developing a T cell–specific knockout mouse. These mice manifested an expansion of γδ T cells, indicating novel roles for SETD2 in T cell development and lymphomagenesis. Our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease and may inform future classification schemes

Identifying Heated Rocks Through Feldspar Luminescence Analysis (pIRIR (290) ) and a Critical Evaluation of Macroscopic Assessment

Throughout (pre)history, non-flint rocks have been used to structure fireplaces, to retain heat, to boil liquids, and to cook food. Thus far, the identification of heated non-flint rocks in archaeological contexts largely depends on a visual (macroscopic) assessment using criteria thought to be diagnostic for thermal alteration. However, visual identification can be subject to observer bias, and some heat-induced traces can be quite difficult to distinguish from other types of weathering or discolouration. In this paper, we present feldspar luminescence analysis as an independent, objective way to identify heated non-flint rocks and to evaluate the results against the established visual macroscopic method for the identification of such pieces. This is done by submitting manuported rocks with and without inferred macroscopic characteristics of heating, originating from the Last Interglacial, Middle Palaeolithic site Neumark-Nord 2/2 (Germany), to feldspar luminescence analysis (pIRIR (290) ). Results of the feldspar luminescence analysis are compared with the visual assessments. This proof of concept study demonstrates the potential of luminescence analyses as an independent, quantitative method for the identification of heated rocks-and their prehistoric applications like hot-stone cooking, specifically for cases where macroscopic assessment cannot provide reliable determinations

Use of red ochre by early Neandertals

The use of manganese and iron oxides by late Neandertals is well documented in Europe, especially for the period 60–40 kya. Such finds often have been interpreted as pigments even though their exact function is largely unknown. Here we report significantly older iron oxide finds that constitute the earliest documented use of red ochre by Neandertals. These finds were small concentrates of red material retrieved during excavations at Maastricht-Belvédère, The Netherlands. The excavations exposed a series of well-preserved flint artifact (and occasionally bone) scatters, formed in a river valley setting during a late Middle Pleistocene full interglacial period. Samples of the reddish material were submitted to various forms of analyses to study their physical properties. All analyses identified the red material as hematite. This is a nonlocal material that was imported to the site, possibly over dozens of kilometers. Identification of the Maastricht-Belvédère finds as hematite pushes the use of red ochre by (early) Neandertals back in time significantly, to minimally 200–250 kya (i.e., to the same time range as the early ochre use in the African record)