Miracle-dz/UniFAR-FTUs huggingface dataset:
Use of Glycerol in Biotechnological Applications

Since decades the limited access to petroleum oil is a major concern and substitutions for fossil fuels are needed. One promising substitute is biodiesel, which is widely produced from vegetable oils, e.g. from rape seeds, soybeans, sunflower seeds or animal fats. In the synthesis of biodiesel, oils and fats are transesterified to fatty acid methyl ester in the presence of sodium hydroxide or potassium hydroxide. In this process, glycerol is generated as stoichiometric byproduct with a ratio of 10% (w/w) with respect to biodiesel produced. In 2009, the biodiesel production of the world reached 16 million tons (Licht, 2010), with the lion's share produced by the European Union with 9 million tons (EBB, European Biodiesel Board 2010), followed by the United States with a production of 2.7 million tons (Licht, 2010). Hence, 1.6 million tons of glycerol were produced as obligatory by-product. Glycerol finds applications as an ingredient of various products, such as creams, food, feed, and pharmaceuticals, but the demand for glycerol in these processes is limited. Integrated conversion of raw glycerol from the biodiesel process to value-added products is a driver towards higher cost efficiency of biodiesel production. Glycerol is a good source of carbon and energy for growth of several microorganisms and may be suitable for the biotechnological production of a number of chemicals in fermentative processes. To date several microbiological productions have been adjusted to glycerol as carbon and energy source or, if glycerol is close to the desired product, are based on glycerol as substrate anyway. For instance, the biotechnological production of 1,3propanediol and dihydroxyacetone has predominantly been carried out from glycerol, since these processes are catalyzed in a two and one step reaction, respectively. Bacterial 1,3propanediol production from glycerol is involving two enzymes. First glycerol is dehydrated by glycerol dehydratase to 3-hydroxypropionaldehyde, which is subsequently converted to 1,3-propanediol by 1,3-propanediol dehydrogenase. Predominantly, 1,3propanediol production has been approved with Clostridium strains, Klebsiella pneumoniae, or Escherichia coli (Zhu et al. 2002, Biebl et al. 1998, Forsberg, 1987). 1,3-propanediol finds application in the production of the polyester polytrimethylene terephthalate. Strains of Gluconobacter oxydans are used for producing dihydroxyacetone (glycerone) from glycerol (Flickinger & Perlman, 1977). Dihydroxyacetone is used as a building block in organic chemistry and as a skin tanning agent in cosmetics. Besides products that can be derived from glycerol in one or two reactions further products requiring more complex conversions have been investigated, e.g. succinic acid production
An Extension of Path Coupling and Its Application to the Glauber Dynamics for Graph Colorings

A new method for analyzing the mixing time of Markov chains is described. This method is an extension of path coupling and involves analyzing the coupling over multiple steps. The expected behavior of the coupling at a certain stopping time is used to bound the expected behavior of the coupling after a fixed number of steps. The new method is applied to analyze the mixing time of the Glauber dynamics for graph colorings. We show that the Glauber dynamics has O(n log(n)) mixing time for triangle-free $\Delta$-regular graphs if k colors are used, where $k\geq (2-\eta)\Delta$, for some small positive constant $\eta$. This is the first proof of an optimal upper bound for the mixing time of the Glauber dynamics for some values of k in the range $k\leq 2\Delta$.
Desmoglein 2 Is Less Important than Desmoglein 3 for Keratinocyte Cohesion

Desmosomes provide intercellular adhesive strength required for integrity of epithelial and some non-epithelial tissues. Within the epidermis, the cadherin-type adhesion molecules desmoglein (Dsg) 1–4 and desmocollin (Dsc) 1–3 build the adhesive core of desmosomes. In keratinocytes, several isoforms of these proteins are co-expressed. However, the contribution of specific isoforms to overall cell cohesion is unclear. Therefore, in this study we investigated the roles of Dsg2 and Dsg3, the latter of which is known to be essential for keratinocyte adhesion based on its autoantibody-induced loss of function in the autoimmune blistering skin disease pemphigus vulgaris (PV). The pathogenic PV antibody AK23, targeting the Dsg3 adhesive domain, led to profound loss of cell cohesion in human keratinocytes as revealed by the dispase-based dissociation assays. In contrast, an antibody against Dsg2 had no effect on cell cohesion although the Dsg2 antibody was demonstrated to interfere with Dsg2 transinteraction by single molecule atomic force microscopy and was effective to reduce cell cohesion in intestinal epithelial Caco-2 cells which express Dsg2 as the only Dsg isoform. To substantiate these findings, siRNA-mediated silencing of Dsg2 or Dsg3 was performed in keratinocytes. In contrast to Dsg3-depleted cells, Dsg2 knockdown reduced cell cohesion only under conditions of increased shear. These experiments indicate that specific desmosomal cadherins contribute differently to keratinocyte cohesion and that Dsg2 compared to Dsg3 is less important in this context.
Activated Carbon Production from Agricultural Biomass Using Response Surface Method (RSM) for Cd (II) Removal

The production of activated carbon (AC) from sugarcane bagasse (SCB) was carried out using central composite design of response surface method to run a limited number of experiments with the possibility of revealing the interaction of three selected factors of temperature, time and nitrogen/steam flowrate at different levels. Two second order quadratic regression model equations were developed using statistical analysis with Design Expert ® software. The models were used for the prediction of removal of Cd 2+ and carbon yield. Correlation coefficients (R 2 ) were 0.957 for removal and 0.985 for yield, showing the sufficiency of the model in predicting response within 13 experimental runs. Characterization of the product with optimal performance which was produced at 900 o C, with nitrogen/steam flow of 100 mL/min and activation time of 30 minutes, was carried out. The performance showed this AC sample was able to remove 62.42% Cd 2+ from an aqueous solution with concentration 2 mg/L within 2 hours at optimized conditions. Experimental results indicated that AC from SCB had good prospect for Cd 2+ removal.
Theoretical analysis of fluorescence signals in filamentation of femtosecond laser pulses in nitrogen molecular gas

We study numerically and analytically the role of the combined effect of self-focusing, geometrical focusing, and the plasma defocusing in the formation of the fluorescence signal during the filamentation of a Ti:sapphire laser pulse in nitrogen molecular gas. Results of numerical simulations are used to estimate the number of excited ions in the focal volume, which is proportional to the fluorescence signal. We find good agreement between the theoretical results and the experimental data, showing that such data can be used to get further insight into the effective focal volume during filamentation of femtosecond laser pulses in transparent media.
A model predictive framework of Ground Source Heat Pump coupled with Aquifer Thermal Energy Storage System in heating and cooling equipment of a building

This paper presents a complete model of a building heating and cooling equipment and a ground source heat pump (GSHP) coupled with an aquifer thermal energy storage (ATES) system. This model contains detailed mathematical representations of building thermal dynamics, ATES system dynamics, heat exchanger (HE), and GSHP together with heating and cooling circulated water pipelines. In particular, we derive a static (steadystate) model for a countercurrent HE and an electrical GSHP as a function of water flow rates and input/output water temperatures in both sides of HE and GSHP to determine the amount of heat transfer from ATES to HE then HE to GSHP, and vice versa. We then develop a model predictive control framework to keep track of the desired building zone temperature, while meeting operational constraints. In such a framework, a finite-horizon mixed-integer nonlinear optimization problem is solved at each sampling time. A simulation study illustrates the functioning of our proposed predictive model.
The guanylate binding protein‐1 GTPase controls the invasive and angiogenic capability of endothelial cells through inhibition of MMP‐1 expression

Expression of the large GTPase guanylate binding protein‐1 (GBP‐1) is induced by inflammatory cytokines (ICs) in endothelial cells (ECs), and the helical domain of the molecule mediates the repression of EC proliferation by ICs. Here we show that the expression of GBP‐1 and of the matrix metalloproteinase‐1 (MMP‐1) are inversely related in vitro and in vivo, and that GBP‐1 selectively inhibits the expression of MMP‐1 in ECs, but not the expression of other proteases. The GTPase activity of GBP‐1 was necessary for this effect, which inhibited invasiveness and tube‐forming capability of ECs in three‐dimensional collagen‐I matrices. A GTPase‐deficient mutant (D184N‐GBP‐1) operated as a transdominant inhibitor of wild‐type GBP‐1 and rescued MMP‐1 expression in the presence of ICs. Expression of D184N‐GBP‐1, as well as paracrine supplementation of MMP‐1, restored the tube‐forming capability of ECs in the presence of wild‐type GBP‐1. The latter finding indicated that the inhibition of capillary formation is specifically due to the repression of MMP‐1 expression by GBP‐1, and is not affected by the anti‐proliferative activity of the helical domain of GBP‐1. These findings substantiate the role of GBP‐1 as a major regulator of the anti‐angiogenic response of ECs to ICs.
Laparoscopic Elective Colonic Operation and Concomitant Abdominall Wall Hernia Prosthetic Repair: Safe and Feasible?

S ince the introduction of laparoscopic surgery, the promise of lower postoperative morbidity and improved cosmesis has been achieved. Continuous technological developments in instrumentation, access, and optics devices were necessary to allow better surgical results and patient’s safety. In recent times, innovative techniques of natural orif ice transluminal endoscopic surgery (NOTES), laparoendoscopic surgery (LESS), and single-incision laparoscopic surgery (SILS) have been applied as a step toward even more less-invasive procedures. [1] The f inal promises of minimally invasive surgery are improved cosmetic results and earlier postoperative recovery with the same oncological and functional results in comparison to standard laparoscopic methods. Despite this, many hurdles to widespread adoption of these techniques exist, including technical challenges, such as decreased triangulation and unfamiliar viewing angles, and more philosophical issues, such as the necessity of demonstrating benefits of these techniques over conventional laparoscopy. Future research will seek to overcome these obstacles.
Farnesoid X Receptor Deficiency Induces Nonalcoholic Steatohepatitis in Low-Density Lipoprotein Receptor-Knockout Mice Fed a High-Fat Diet

Nonalcoholic steatohepatitis (NASH) comprises dysregulation of lipid metabolism and inflammation. Identification of the various genetic and environmental susceptibility factors for NASH may provide novel treatments to limit inflammation and fibrosis in patients. This study utilized a mouse model of hypercholesterolemia, low-density lipoprotein receptor knockout (LDLr-/-) mice fed a high-fat diet for 5 months, to test the hypothesis that farnesoid X receptor (FXR) deficiency contributed to NASH development. Either the high-fat diet or FXR deficiency increased serum alanine aminotransferase activity, whereas only FXR deficiency increased bile acid and alkaline phosphatase levels. FXR deficiency and high-fat feeding increased serum cholesterol and triglycerides. Although high fat led to macrosteatosis and hepatocyte ballooning in livers of mice regardless of genotype, no inflammatory infiltrate was observed in the livers of LDLr-/- mice. In contrast, in the livers of LDLr-/-/FXR-/- mice, foci of inflammatory cells were observed occasionally when fed the control diet and were greatly increased when fed the high-fat diet. Consistent with enhanced inflammatory cells, hepatic levels of tumor necrosis factor α and intercellular adhesion molecule-1 mRNA were increased by the high-fat diet in LDLr-/-/FXR-/- mice. In agreement with elevated levels of procollagen 1α1 and TGF-β mRNA, type 1 collagen protein levels were increased in livers of LDLr-/-/FXR-/- mice fed a high-fat diet. In conclusion, FXR deficiency induces pathologic manifestations required for NASH diagnosis in a mouse model of hypercholesterolemia, including macrosteatosis, hepatocyte ballooning, and inflammation, which suggest a combination of FXR deficiency and high-fat diet is a risk factor for NASH development, and activation of FXR may be a therapeutic intervention in the treatment of NASH.
NOTCH1 Can Initiate NF-κB Activation via Cytosolic Interactions with Components of the T Cell Signalosome

T cell stimulation requires the input and integration of external signals. Signaling through the T cell receptor (TCR) is known to induce formation of the membrane-tethered CBM complex, comprising CARMA1, BCL10, and MALT1, which is required for TCR-mediated NF-κB activation. TCR signaling has been shown to activate NOTCH proteins, transmembrane receptors also implicated in NF-κB activation. However, the link between TCR-mediated NOTCH signaling and early events leading to induction of NF-κB activity remains unclear. In this report, we demonstrate a novel cytosolic function for NOTCH1 and show that it is essential to CBM complex formation. Using a model of skin allograft rejection, we show in vivo that NOTCH1 acts in the same functional pathway as PKCθ, a T cell-specific kinase important for CBM assembly and classical NF-κB activation. We further demonstrate in vitro NOTCH1 associates physically with PKCθ and CARMA1 in the cytosol. Unexpectedly, when NOTCH1 expression was abrogated using RNAi approaches, interactions between CARMA1, BCL10, and MALT1 were lost. This failure in CBM assembly reduced inhibitor of kappa B alpha phosphorylation and diminished NF-κB–DNA binding. Finally, using a luciferase gene reporter assay, we show the intracellular domain of NOTCH1 can initiate robust NF-κB activity in stimulated T cells, even when NOTCH1 is excluded from the nucleus through modifications that restrict it to the cytoplasm or hold it tethered to the membrane. Collectively, these observations provide evidence that NOTCH1 may facilitate early events during T cell activation by nucleating the CBM complex and initiating NF-κB signaling.
Eradication of Large Solid Tumors by Gene Therapy with a T-Cell Receptor Targeting a Single Cancer-Specific Point Mutation

Purpose: Cancers usually contain multiple unique tumor-specific antigens produced by single amino acid substitutions (AAS) and encoded by somatic nonsynonymous single nucleotide substitutions. We determined whether adoptively transferred T cells can reject large, well-established solid tumors when engineered to express a single type of T-cell receptor (TCR) that is specific for a single AAS. Experimental Design: By exome and RNA sequencing of an UV-induced tumor, we identified an AAS in p68 (mp68), a co-activator of p53. This AAS seemed to be an ideal tumor-specific neoepitope because it is encoded by a trunk mutation in the primary autochthonous cancer and binds with highest affinity to the MHC. A high-avidity mp68-specific TCR was used to genetically engineer T cells as well as to generate TCR-transgenic mice for adoptive therapy. Results: When the neoepitope was expressed at high levels and by all cancer cells, their direct recognition sufficed to destroy intratumor vessels and eradicate large, long-established solid tumors. When the neoepitope was targeted as autochthonous antigen, T cells caused cancer regression followed by escape of antigen-negative variants. Escape could be thwarted by expressing the antigen at increased levels in all cancer cells or by combining T-cell therapy with local irradiation. Therapeutic efficacies of TCR-transduced and TCR-transgenic T cells were similar. Conclusions: Gene therapy with a single TCR targeting a single AAS can eradicate large established cancer, but a uniform expression and/or sufficient levels of the targeted neoepitope or additional therapy are required to overcome tumor escape. Clin Cancer Res; 22(11); 2734–43. ©2015 AACR. See related commentary by Liu, p. 2602
A classification scheme for human polyomavirus JCV variants based on the nucleotide sequence of the noncoding regulatory region

The human polyomavirus JCV is responsible for the central nervous system (CNS) demyelination observed in cases of progressive multifocal leukoencephalopathy (PML). Lytic infection of oligodendrocytes, the cells that constitute the basis of myelin in the CNS, is established by JCV in conjunction with immunosuppressive conditions. Beyond this, however, many questions related to JCV pathogenesis remain unanswered. The JCV regulatory region is a hypervariable noncoding sequence positioned between the early and late protein-coding regions. The particular nucleotide sequence of a JCV regulatory region affects levels of viral transcription and replication. Modifications to this promoter/enhancer structure can alter the cellular host range and may be responsible for switching JCV between states of lytic and latent infection. The regulatory region structure has, therefore, been used to distinguish JCV variants. Nucleotide sequencing studies have uncovered numerous variations of regulatory region structure. Until now, however, no inclusive nomenclature existed that linked variants by regulatory region structure and/or activity. We have arranged all known variant JCV regulatory regions into quadrants according to the integration of particular sequence sections and repetition of sequence section groups. This arrangement of regulatory regions results in an updated nomenclature that is well-suited for describing the relationships between JCV variants. Four distinct structural forms (I-S, I-R, II-S, and II-R) are defined along with tissue tropisms. This design provides logical connections between the variant regulatory regions and may be useful for elucidating crucial steps in JCV pathogenesis.
Human metapneumovirus bronchiolitis in infancy is an important risk factor for asthma at age 5

Human metapneumovirus (hMPV) infection plays an important role in the pediatric respiratory infections. However, little is known about the relationship between hMPV‐bronchiolitis and the development of subsequent wheezing. The aim of this study was to evaluate the outcome at third to fifth year after admission for hMPV‐bronchiolitis and to compare it with children admitted for respiratory syncytial virus (RSV)‐bronchiolitis and with children without lower respiratory disease in the first 2 years of life.
Proteasome inhibitor-induced apoptosis is mediated by positive feedback amplification of PKCδ proteolytic activation and mitochondrial translocation

Emerging evidence implicates impaired protein degradation by the ubiquitin proteasome system (UPS) in Parkinson's disease; however cellular mechanisms underlying dopaminergic degeneration during proteasomal dysfunction are yet to be characterized. In the present study, we identified that the novel PKC isoform PKCδ plays a central role in mediating apoptotic cell death following UPS dysfunction in dopaminergic neuronal cells. Inhibition of proteasome function by MG‐132 in dopaminergic neuronal cell model (N27 cells) rapidly depolarized mitochondria independent of ROS generation to activate the apoptotic cascade involving cytochrome c release, and caspase‐9 and caspase‐3 activation. PKCδ was a key downstream effector of caspase‐3 because the kinase was proteolytically cleaved by caspase‐3 following exposure to proteasome inhibitors MG‐132 or lactacystin, resulting in a persistent increase in the kinase activity. Notably MG‐132 treatment resulted in translocation of proteolytically cleaved PKCδ fragments to mitochondria in a time‐dependent fashion, and the PKCδ inhibition effectively blocked the activation of caspase‐9 and caspase‐3, indicating that the accumulation of the PKCδ catalytic fragment in the mitochondrial fraction possibly amplifies mitochondria‐mediated apoptosis. Overexpression of the kinase active catalytic fragment of PKCδ (PKCδ‐CF) but not the regulatory fragment (RF), or mitochondria‐targeted expression of PKCδ‐CF triggers caspase‐3 activation and apoptosis. Furthermore, inhibition of PKCδ proteolytic cleavage by a caspase‐3 cleavage‐resistant mutant (PKCδ‐CRM) or suppression of PKCδ expression by siRNA significantly attenuated MG‐132‐induced caspase‐9 and ‐3 activation and DNA fragmentation. Collectively, these results demonstrate that proteolytically activated PKCδ has a significant feedback regulatory role in amplification of the mitochondria‐mediated apoptotic cascade during proteasome dysfunction in dopaminergic neuronal cells.
Ontology Evolution Under Semantic Constraints

The dynamic nature of ontology development has motivated the formal study of ontology evolution problems. This paper presents a logical framework that enables fine-grained investigation of evolution problems at a deductive level. In our framework, the optimal evolutions of an ontology O are those ontologies O' that maximally preserve both the structure of O, and its entailments in a given preservation language. We show that our framework is compatible with the postulates of Belief Revision, and we investigate the existence of optimal evolutions in various settings. In particular, we present first results on TBox-level revision and contraction in the EL and FL0 families of Description Logics.
Task-dependent and distinct roles of the temporoparietal junction and inferior frontal cortex in the control of imitation

The control of neurological networks supporting social cognition is crucially important for social interaction. In particular, the control of imitation is directly linked to interaction quality, with impairments associated with disorders characterized by social difficulties. Previous work suggests inferior frontal cortex (IFC) and the temporoparietal junction (TPJ) are involved in controlling imitation, but the functional roles of these areas remain unclear. Here, transcranial direct current stimulation (tDCS) was used to enhance cortical excitability at IFC and the TPJ prior to the completion of three tasks: (i) a naturalistic social interaction during which increased imitation is known to improve rapport, (ii) a choice reaction time task in which imitation needs to be inhibited for successful performance and (iii) a non-imitative control task. Relative to sham stimulation, stimulating IFC improved the context-dependent control of imitation—participants imitated more during the social interaction and less during the imitation inhibition task. In contrast, stimulating the TPJ reduced imitation in the inhibition task without affecting imitation during social interaction. Neither stimulation site affected the non-imitative control task. These data support a model in which IFC modulates imitation directly according to task demands, whereas TPJ controls task-appropriate shifts in attention toward representation of the self or the other, indirectly impacting upon imitation.