To Invest or Not to Invest: Using Vocal Behavior to Predict Decisions of Investors in an Entrepreneurial Context

Entrepreneurial pitch competitions have become increasinglypopular in the start-up culture to attract prospective investors. As theultimate funding decision often follows from some form of social interaction,it is important to understand how the decision-making processof investors is influenced by behavioral cues. In this work, we examinewhether vocal features are associated with the ultimate funding decisionof investors by utilizing deep learning methods.We used videos of individualsin an entrepreneurial pitch competition as input to predict whetherinvestors will invest in the startup or not. We proposed models that combinedeep audio features and Handcrafted audio Features (HaF) and feedthem into two types of Recurrent Neural Networks (RNN), namely LongShort-Term Memory (LSTM) and Gated Recurrent Units (GRU). Wealso trained the RNNs with only deep features to assess whether HaFprovide additional information to the models. Our results show that it ispromising to use vocal behavior of pitchers to predict whether investorswill invest in their business idea. Different types of RNNs yielded similarperformance, yet the addition of HaF improved the performance

To Invest or Not to Invest: Using Vocal Behavior to Predict Decisions of Investors in an Entrepreneurial Context

Entrepreneurial pitch competitions have become increasinglypopular in the start-up culture to attract prospective investors. As theultimate funding decision often follows from some form of social interaction,it is important to understand how the decision-making processof investors is influenced by behavioral cues. In this work, we examinewhether vocal features are associated with the ultimate funding decisionof investors by utilizing deep learning methods.We used videos of individualsin an entrepreneurial pitch competition as input to predict whetherinvestors will invest in the startup or not. We proposed models that combinedeep audio features and Handcrafted audio Features (HaF) and feedthem into two types of Recurrent Neural Networks (RNN), namely LongShort-Term Memory (LSTM) and Gated Recurrent Units (GRU). Wealso trained the RNNs with only deep features to assess whether HaFprovide additional information to the models. Our results show that it ispromising to use vocal behavior of pitchers to predict whether investorswill invest in their business idea. Different types of RNNs yielded similarperformance, yet the addition of HaF improved the performance

An Fc-modified monoclonal antibody as novel treatment option for pancreatic cancer

Pancreatic cancer is a highly lethal disease with limited treatment options. Hence, there is a considerable medical need for novel treatment strategies. Monoclonal antibodies (mAbs) have significantly improved cancer therapy, primarily due to their ability to stimulate antibody-dependent cellular cytotoxicity (ADCC), which plays a crucial role in their therapeutic efficacy. As a result, significant effort has been focused on improving this critical function by engineering mAbs with Fc regions that have increased affinity for the Fc receptor CD16 expressed on natural killer (NK) cells, the major cell population that mediates ADCC in humans. Here we report on the preclinical characterization of a mAb directed to the target antigen B7-H3 (CD276) containing an Fc part with the amino acid substitutions S239D/I332E to increase affinity for CD16 (B7-H3-SDIE) for the treatment of pancreatic cancer. B7-H3 (CD276) is highly expressed in many tumor entities, whereas expression on healthy tissues is more limited. Our findings confirm high expression of B7-H3 on pancreatic cancer cells. Furthermore, our study shows that B7-H3-SDIE effectively activates NK cells against pancreatic cancer cells in an antigen-dependent manner, as demonstrated by the analysis of NK cell activation, degranulation and cytokine release. The activation of NK cells resulted in significant tumor cell lysis in both short-term and long-term cytotoxicity assays. In conclusion, B7-H3-SDIE constitutes a promising agent for the treatment of pancreatic cancer

Strigolactone- and Karrikin-Independent SMXL Proteins Are Central Regulators of Phloem Formation

Plant stem cell niches, the meristems, require long-distance transport of energy metabolites and signaling molecules along the phloem tissue. However, currently it is unclear how specification of phloem cells is controlled. Here we show that the genes SUPPRESSOR OF MAX2 1-LIKE3 (SMXL3), SMXL4, and SMXL5 act as cell-autonomous key regulators of phloem formation in Arabidopsis thaliana. The three genes form an uncharacterized subclade of the SMXL gene family that mediates hormonal strigolactone and karrikin signaling. Strigolactones are endogenous signaling molecules regulating shoot and root branching [1] whereas exogenous karrikin molecules induce germination after wildfires [2]. Both activities depend on the F-box protein and SCF (Skp, Cullin, F-box) complex component MORE AXILLARY GROWTH2 (MAX2) [3-5]. Strigolactone and karrikin perception leads to MAX2-dependent degradation of distinct SMXL protein family members, which is key for mediating hormonal effects [6-12]. However, the nature of events immediately downstream of SMXL protein degradation and whether all SMXL proteins mediate strigolactone or karrikin signaling is unknown. In this study we demonstrate that, within the SMXL gene family, specifically SMXL3/4/5 deficiency results in strong defects in phloem formation, alteredsugar accumulation, and seedling lethality. By comparing protein stabilities, we show that SMXL3/4/5 proteins function differently to canonical strigolactone and karrikin signaling mediators, although being functionally interchangeable with those under low strigolactone/karrikin signaling conditions. Our observations reveal a fundamental mechanism of phloem formation and indicate that diversity of SMXL protein functions is essential for a steady fuelling of plant meristems.Peer reviewe

Zalecenia Polskiego Towarzystwa Nefrologii Dziecięcej (PTNFD) dotyczące postępowania z dzieckiem z zakażeniem układu moczowego

W związku z brakiem jednolitego stanowiska w literaturze Polskie Towarzystwo Nefrologii Dziecięcej podjęło decyzję o opracowaniu standardów postępowania z dzieckiem z zakażeniem układu moczowego (ZUM). Celem standardów jest ujednolicenie rodzajów świadczeń dla pacjenta, jak również optymalizacja sposobów i kosztów leczenia. Poniższe zalecenia są skierowane nie tylko do nefrologów dziecięcych, ale również do lekarzy pediatrów i lekarzy rodzinnych, którzy najwcześniej podejmują decyzję o sposobie postępowania diagnostycznego i leczenia dziecka z ZUM. Należy zaznaczyć, że poniższe zalecenia, opracowane przez zespół ekspertów na podstawie dostępnych opracowań naukowych, powinny stanowić jedynie praktyczne wskazówki dla lekarzy. Należy je traktować jako hipotezę wymagającą sprawdzenia w badaniach aktualnie prowadzonych i tych zaplanowanych na przyszłość. Wytyczne w żadnym wypadku nie są bezwzględnym nakazem. Postępowanie zgodne ze standardami nie gwarantuje terapeutycznego sukcesu i może też nie zahamować postępu choroby

Lack of Matrilin-2 Favors Liver Tumor Development via Erk1/2 and GSK-3 beta Pathways In Vivo

Matrilin-2 (Matn2) is a multidomain adaptor protein which plays a role in the assembly of extracellular matrix (ECM). It is produced by oval cells during stem cell-driven liver regeneration. In our study, the impact of Matn2 on hepatocarcinogenesis was investigated in Matn2(-/-) mice comparing them with wild-type (WT) mice in a diethylnitrosamine (DEN) model. The liver tissue was analyzed macroscopically, histologically and immunohistochemically, at protein level by Proteome Profiler Arrays and Western blot analysis. Matn2(-/-) mice exhibited higher susceptibility to hepatocarcinogenesis compared to wild-type mice. In the liver of Matn2(-/-) mice, spontaneous microscopic tumor foci were detected without DEN treatment. After 15 mu g/g body weight DEN treatment, the liver of Matn2(-/-) mice contained macroscopic tumors of both larger number and size than the WT liver. In contrast with the WT liver, spontaneous phosphorylation of EGFR, Erk1/2 GSK-3 alpha/beta and retinoblastoma protein (p-Rb), decrease in p21/CIP1 level, and increase in beta-Catenin protein expression were detected in Matn2(-/-) livers. Focal Ki-67 positivity of these samples provided additional support to our presumption that the lack of Matn2 drives the liver into a pro-proliferatory state, making it prone to tumor development. This enhanced proliferative capacity was further increased in the tumor nodules of DEN-treated Matn2(-/-) livers. Our study suggests that Matn2 functions as a tumor suppressor in hepatocarcinogenesis, and in this process activation of EGFR together with that of Erk1/2, as well as inactivation of GSK-3 beta, play strategic roles

Decorin deficiency promotes hepatic carcinogenesis

Hepatocellular carcinoma represents one of the most-rapidly spreading cancers in the world. In the majority of cases, an inflammation-driven fibrosis or cirrhosis precedes the development of the tumor. During malignant transformation, the tumor microenvironment undergoes qualitative and quantitative changes that modulate the behavior of the malignant cells. A key constituent for the hepatic microenvironment is the small leucine-rich proteoglycan decorin, known to interfere with cellular events of tumorigenesis mainly by blocking various receptor tyrosine kinases (RTK) such as EGFR, Met, IGF-IR, PDGFR and VEGFR2. In this study, we characterized cell signaling events evoked by decorin deficiency in two experimental models of hepatocarcinogenesis using thioacetamide or diethyl nitrosamine as carcinogens. Genetic ablation of decorin led to enhanced tumor occurrence as compared to wild-type animals. These findings correlated with decreased levels of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 and a concurrent elevation in retinoblastoma protein phosphorylation via cyclin dependent kinase 4. Decreased steady state p21Waf1/Cip1 levels correlated with enhanced expression of transcription factor AP4, a known transcriptional repressor of p21Waf1/Cip1, and enhanced c-Myc protein levels. In addition, translocation of beta-catenin was a typical event in diethyl nitrosamine-evoked tumors. In parallel, decreased phosphorylation of both c-Myc and beta-catenin was observed in Dcn-/- livers likely due to the hindered GSK3beta-mediated targeting of these proteins to proteasomal degradation. We discovered that in a genetic background lacking decorin, four RTKs were constitutively activated (phosphorylated), including three known targets of decorin such as PDGFRalpha, EGFR, IGF-IR, and a novel RTK MSPR/RON. Our findings provide powerful genetic evidence for a crucial in vivo role of decorin during hepatocarcinogenesis as lack of decorin in the liver and hepatic stroma facilitates experimental carcinogenesis by providing an environment devoid of this potent pan-RTK inhibitor. Thus, our results support future utilization of decorin as an antitumor agent in liver cancer

Caveolae in Rabbit Ventricular Myocytes: Distribution and Dynamic Diminution after Cell Isolation

Caveolae are signal transduction centers, yet their subcellular distribution and preservation in cardiac myocytes after cell isolation are not well documented. Here, we quantify caveolae located within 100 nm of the outer cell surface membrane in rabbit single-ventricular cardiomyocytes over 8 h post-isolation and relate this to the presence of caveolae in intact tissue. Hearts from New Zealand white rabbits were either chemically fixed by coronary perfusion or enzymatically digested to isolate ventricular myocytes, which were subsequently fixed at 0, 3, and 8 h post-isolation. In live cells, the patch-clamp technique was used to measure whole-cell plasma membrane capacitance, and in fixed cells, caveolae were quantified by transmission electron microscopy. Changes in cell-surface topology were assessed using scanning electron microscopy. In fixed ventricular myocardium, dual-axis electron tomography was used for three-dimensional reconstruction and analysis of caveolae in situ. The presence and distribution of surface-sarcolemmal caveolae in freshly isolated cells matches that of intact myocardium. With time, the number of surface-sarcolemmal caveolae decreases in isolated cardiomyocytes. This is associated with a gradual increase in whole-cell membrane capacitance. Concurrently, there is a significant increase in area, diameter, and circularity of sub-sarcolemmal mitochondria, indicative of swelling. In addition, electron tomography data from intact heart illustrate the regular presence of caveolae not only at the surface sarcolemma, but also on transverse-tubular membranes in ventricular myocardium. Thus, caveolae are dynamic structures, present both at surface-sarcolemmal and transverse-tubular membranes. After cell isolation, the number of surface-sarcolemmal caveolae decreases significantly within a time frame relevant for single-cell research. The concurrent increase in cell capacitance suggests that membrane incorporation of surface-sarcolemmal caveolae underlies this, but internalization and/or micro-vesicle loss to the extracellular space may also contribute. Given that much of the research into cardiac caveolae-dependent signaling utilizes isolated cells, and since caveolae-dependent pathways matter for a wide range of other study targets, analysis of isolated cell data should take the time post-isolation into account

Elucidating the small regulatory RNA repertoire of the sea anemone Anemonia viridis based on whole genome and small RNA sequencing

Cnidarians harbor a variety of small regulatory RNAs that include microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs), but detailed information is limited. Here, we report the identification and expression of novel miRNAs and putative piRNAs, as well as their genomic loci, in the symbiotic sea anemone Anemonia viridis. We generated a draft assembly of the A. viridis genome with putative size of 313 Mb that appeared to be composed of about 36% repeats, including known transposable elements. We detected approximately equal fractions of DNA transposons and retrotransposons. Deep sequencing of small RNA libraries constructed from A. viridis adults sampled at a natural CO2 gradient off Vulcano Island, Italy, identified 70 distinct miRNAs. Eight were homologous to previously reported miRNAs in cnidarians, whereas 62 appeared novel. Nine miRNAs were recognized as differentially expressed along the natural seawater pH gradient. We found a highly abundant and diverse population of piRNAs, with a substantial fraction showing ping–pong signatures. We identified nearly 22% putative piRNAs potentially targeting transposable elements within the A. viridis genome. The A. viridis genome appeared similar in size to that of other hexacorals with a very high divergence of transposable elements resembling that of the sea anemone genus Exaiptasia. The genome encodes and expresses a high number of small regulatory RNAs, which include novel miRNAs and piRNAs. Differentially expressed small RNAs along the seawater pH gradient indicated regulatory gene responses to environmental stressors