gebhart/patrepeval huggingface dataset:
“Energetic” Cancer Stem Cells (e-CSCs): A New Hyper-Metabolic and Proliferative Tumor Cell Phenotype, Driven by Mitochondrial Energy (2019)

Here, we provide the necessary evidence that mitochondrial metabolism drives the anchorage-independent proliferation of CSCs. Two human breast cancer cell lines, MCF7 [ER(+)] and MDA-MB-468 (triple-negative), were used as model systems. To directly address the issue of metabolic heterogeneity in cancer, we purified a new distinct sub-population of CSCs, based solely on their energetic profile. We propose the term "energetic" cancer stem cells (e-CSCs), to better describe this novel cellular phenotype. In a single step, we first isolated an auto-fluorescent cell sub-population, based on their high flavin-content, using flow-cytometry. Then, these cells were further subjected to a detailed phenotypic characterization. More specifically, e-CSCs were more glycolytic, with higher mitochondrial mass and showed significantly elevated oxidative metabolism. e-CSCs also demonstrated an increased capacity to undergo cell cycle progression, as well as enhanced anchorage-independent growth and ALDH-positivity. Most importantly, these e-CSCs could be effectively targeted by treatments with either (i) OXPHOS inhibitors (DPI) or (ii) a CDK4/6 inhibitor (Ribociclib). Finally, we were able to distinguish two distinct phenotypic sub-types of e-CSCs, depending on whether they were grown as 2D-monolayers or as 3D-spheroids. Remarkably, under 3D anchorage-independent growth conditions, e-CSCs were strictly dependent on oxidative mitochondrial metabolism. Unbiased proteomics analysis demonstrated the up-regulation of gene products specifically related to the anti-oxidant response, mitochondrial energy production, and mitochondrial biogenesis. Therefore, mitochondrial inhibitors should be further developed as promising anti-cancer agents, to directly target and eliminate the "fittest" e-CSCs. Our results have important implications for using e-CSCs, especially those derived from 3D-spheroids, (i) in tumor tissue bio-banking and (ii) as a new cellular platform for drug development.
Optical Stimulation of Peripheral Nerves In Vivo (2004)

A novel method of stimulation of neural tissue using pulsed, low-energy laser light is presented. Optical stimulation elicits compound nerve and muscle action potentials, with resultant muscle contraction, similar to responses obtained with conventional electrical stimulation of the nerve. Results indicate wavelength dependence of optical stimulation and stimulation thresholds from 0.312 J/cm2 (λ=3μm) to 1.02 J/cm2 (λ=4μm) with the largest ratio of damage/stimulation threshold (>5) at absorption valleys in soft tissue (4 and 2.1 μm).
Managing Temporal Data (2009)

In general, databases store current data. However,the capability to maintain temporal data is a crucial requirement for many organizations and provides the base for organizational intelligence. A temporal database maintains time-varying data, that is, past, present, and future data. In this chapter, we focus on the relational data model and address the subtle issues in modeling and designing temporal databases. A common approach to handle temporal data within the traditional relational databases is the addition of time columns to a relation. Though this appears to be a simple and intuitive solution, it does not address many subtle issues peculiar to temporal data, that is, comparing database states at two different time points, capturing the periods for concurrent events and accessing times beyond these periods, handling multi-valued attributes, coalescing and restructuring temporal data, and so forth, [Gadia 1988, Tansel and Tin 1997]. There is a growing interest in temporal databases. A first book dedicated to temporal databases [Tansel at al 1993] followed by others addressing issues in handling time-varying data [Betini, Jajodia and Wang 1988, Date, Darwen and Lorentzos 2002, Snodgrass 1999].
Intrinsic Toxin-Derived Peptides Destabilize and Inactivate <i>Clostridium difficile</i> TcdB (2017)

<i>Clostridium difficile</i> infection (CDI) is a major cause of hospital-associated, antibiotic-induced diarrhea, which is largely mediated by the production of two large multidomain clostridial toxins, TcdA and TcdB. Both toxins coordinate the action of specific domains to bind receptors, enter cells, and deliver a catalytic fragment into the cytosol. This results in GTPase inactivation, actin disassembly, and cytotoxicity. TcdB in particular has been shown to encode a region covering amino acids 1753 to 1851 that affects epitope exposure and cytotoxicity. Surprisingly, studies here show that several peptides derived from this region, which share the consensus sequence <sub>1769</sub>NVFKGNTISDK<sub>1779</sub>, protect cells from the action of TcdB. One peptide, PepB2, forms multiple interactions with the carboxy-terminal region of TcdB, destabilizes TcdB structure, and disrupts cell binding. We further show that these effects require PepB2 to form a higher-order polymeric complex, a process that requires the central GN amino acid pair. These data suggest that TcdB<sub>1769-1779</sub> interacts with repeat sequences in the proximal carboxy-terminal domain of TcdB (i.e., the CROP domain) to alter the conformation of TcdB. Furthermore, these studies provide insights into TcdB structure and functions that can be exploited to inactivate this critical virulence factor and ameliorate the course of CDI.<b>IMPORTANCE</b><i>Clostridium difficile</i> is a leading cause of hospital-associated illness that is often associated with antibiotic treatment. To cause disease, <i>C. difficile</i> secretes toxins, including TcdB, which is a multidomain intracellular bacterial toxin that undergoes conformational changes during cellular intoxication. This study describes the development of peptide-based inhibitors that target a region of TcdB thought to be critical for structural integrity of the toxin. The results show that peptides derived from a structurally important region of TcdB can be used to destabilize the toxin and prevent cellular intoxication. Importantly, this work provides a novel means of toxin inhibition that could in the future develop into a <i>C. difficile</i> treatment.
Direct waveform synthesis with continuous variable level multilevel converter using extended commutation cells (2016)

The extended commutation cell is a four-port, four-switch cell that allows for bidirectional energy transport in two orthogonal directions throughout the cell. The voltage across each cell capacitor can be adjusted independently of the load, resulting in high flexibility in output levels. By placing the capacitors in (anti-) series while adjusting their voltage level a continuous waveform can be constructed. The analysis is given for a single and two-cell converter including load current correction. Additionally the waveform synthesis is simulated and experimentally verified on a 3.7 kW two-cell prototype.
Epitaxial relationship between wurtzite GaN and β-Ga2O3 (2007)

The epitaxial relationship between wurtzite GaN and monoclinic β-Ga2O3 is studied by transmission electron microscopy. GaN is grown on β-Ga2O3 by molecular beam epitaxy without any low-temperature buffer layer, obtaining c plane GaN on a plane β-Ga2O3. The effect of the surface nitridation, which is necessary for the epitaxial growth, is analyzed at the atomic level. The lattice mismatch has a minimum of 2.6% for the in-plane epitaxial relationship ⟨011⟩Ga2O3‖⟨101¯0⟩GaN.
Aromatase P450 Gene Expression in Human Adipose Tissue. ROLE OF A Jak/STAT PATHWAY IN REGULATION OF THE ADIPOSE-SPECIFIC PROMOTER (1995)

In the present report we describe a heretofore unrecognized role for a Jak/STAT signaling pathway, namely the stimulation of expression of the aromatase P450 (CYP19) gene, and hence of estrogen biosynthesis, in human adipose tissue. Expression of this gene in adipose tissue as well as in adipose stromal cells maintained in the presence of serum and glucocorticoids is regulated by a distal TATA-less promoter, I.4, which contains a glucocorticoid response element, an Sp1 binding site, and an interferon-gamma activation site (GAS) element. The stimulatory action of serum (in the presence of dexamethasone) can be replaced by interleukin (IL)-11, leukemia inhibitory factor, and oncostatin-M, as well as by IL-6, providing the IL-6 soluble receptor is also present. Stimulation of the cells by these factors led to rapid phosphorylation of Jak1, but not Jak2 or Jak3, on tyrosine residues. STAT3 but not STAT1 was also phosphorylated and bound to the GAS element in the I.4 promoter region. When regions of this promoter were fused upstream of the chloramphenicol acetyltransferase reporter gene and transfected into the cells, mutagenesis or deletion of the GAS element led to complete loss of reporter gene expression. Since adipose tissue is the major site of estrogen biosynthesis in men and in postmenopausal women, this pathway involving a Jak/STAT signaling mechanism acting together with glucocorticoids and Sp1 appears to be the principal means whereby estrogen biosynthesis is regulated in the elderly.
Extending the threshold and frequency range for phase-based frequency estimation (1999)

Standard phase-based frequency estimation has a threshold that is high, is frequency dependent, and does not decrease with increasing signal length. These problems are solved by processing the signal with a highly overlapped filter bank before applying phase-based frequency estimation. By exploiting decimation, a closed-form matrix inversion, and cascades of simple filter banks, the computational complexity is kept low.
Proteomic Analysis of Calcium/Calmodulin-dependent Protein Kinase I and IV in Vitro Substrates Reveals Distinct Catalytic Preferences (2003)

The multifunctional calcium/calmodulin-dependent protein kinases I and IV (CaMKI and CaMKIV) are closely related by primary sequence and predicted to have similar substrate specificities based on peptide studies. We identified a fragment of p300-(1-117) that is a substrate of both kinases, and through both mutagenesis and Edman phosphate ((32)P) release sequencing, established that CaMKI and CaMKIV phosphorylate completely different sites. The CaMKI site, Ser(89) ((84)LLRSGSSPNL(93)), fits the expected consensus whereas the CaMKIV site, Ser(24) ((19)SSPALSASAS(28)), is novel. To compare kinase substrate preferences more generally, we employed a proteomic display technique that allowed comparison of complex cell extracts phosphorylated by each kinase in a rapid in vitro assay, thereby demonstrating substrate preferences that overlapped but were clearly distinct. To validate this approach, one of the proteins labeled in this assay was identified by microsequencing as HSP25, purified as a recombinant protein, and examined as a substrate for both CaMKI and CaMKIV. Again, CaMKI and CaMKIV were different, this time in kinetics and stoichiometry of the phosphorylation sites, with CaMKI preferring Ser(15) ((10)LLRTPSWGPF(19)) to Ser(85) ((80)LNRQLSSGVS(89)) 3:1, but CaMKIV phosphorylating the two sites equally. These differences in substrate specificities emphasize the need to consider these protein kinases independently despite their close homology.
The Role of Ephs and Ephrins in Memory Formation (2015)

The ability to efficiently store memories in the brain is a fundamental process and its impairment is associated with multiple human mental disorders. Evidence indicates that long-term memory formation involves alterations of synaptic efficacy produced by modifications in neural transmission and morphology. The Eph receptors and their cognate ephrin ligands have been shown to be involved in these key neuronal processes by regulating events such as presynaptic transmitter release, postsynaptic glutamate receptor conductance and trafficking, synaptic glutamate reuptake, and dendritic spine morphogenesis. Recent findings show that Ephs and ephrins are needed for memory formation in different organisms. These proteins participate in the formation of various types of memories that are subserved by different neurons and brain regions. Ephs and ephrins are involved in brain disorders and diseases with memory impairment symptoms, including Alzheimer's disease and anxiety. Drugs that agonize or antagonize Ephs/ephrins signaling have been developed and could serve as therapeutic agents to treat such diseases. Ephs and ephrins may therefore induce cellular alterations mandatory for memory formation and serve as a target for pharmacological intervention for treatment of memory-related brain diseases.
Helical Oligourea Foldamers as Powerful Hydrogen Bonding Catalysts for Enantioselective C–C Bond-Forming Reactions (2017)

Substantial progress has been made toward the development of metal-free catalysts of enantioselective transformations, yet the discovery of organic catalysts effective at low catalyst loadings remains a major challenge. Here we report a novel synergistic catalyst combination system consisting of a peptide-inspired chiral helical (thio)urea oligomer and a simple tertiary amine that is able to promote the Michael reaction between enolizable carbonyl compounds and nitroolefins with excellent enantioselectivities at exceptionally low (1/10 000) chiral catalyst/substrate molar ratios. In addition to high selectivity, which correlates strongly with helix folding, the system we report here is also highly amenable to optimization, as each of its components can be fine-tuned separately to increase reaction rates and/or selectivities. The predictability of the foldamer secondary structure coupled to the high level of control over the primary sequence results in a system with significant potential for future catalyst design.
Hardware trojan detection through information flow security verification (2017)

Semiconductor design houses are increasingly becoming dependent on third party vendors to procure intellectual property (IP) and meet time-to-market constraints. However, these third party IPs cannot be trusted as hardware Trojans can be maliciously inserted into them by untrusted vendors. While different approaches have been proposed to detect Trojans in third party IPs, their limitations have not been extensively studied. In this paper, we analyze the limitations of the state-of-the-art Trojan detection techniques and demonstrate with experimental results how to defeat these detection mechanisms. We then propose a Trojan detection framework based on information flow security (IFS) verification. Our framework detects violation of IFS policies caused by Trojans without the need of white-box knowledge of the IP. We experimentally validate the efficacy of our proposed technique by accurately identifying Trojans in the trust-hub benchmarks. We also demonstrate that our technique does not share the limitations of the previously proposed Trojan detection techniques.
Neuronal expression of a single‐chain variable fragment antibody against Aβ oligomers protects synapses and rescues memory in Alzheimer models (2020)

Abstract Background Alzheimer's disease (AD) is the main cause of dementia in the elderly and is characterized by abnormal accumulation of the beta‐amyloid peptide (Aß) in the brain. Considerable evidence has shown that soluble Abeta oligomers (AßOs) are the main neurotoxins involved in synaptic dysfunction and the memory loss. Method We evaluated the therapeutic potential of NUsc1, a single chain variable Fragment (scFv) antibody isolated from a screen to identify scFv’s targeting AβOs. Using an adeno‐associated virus derived vector (AAV) we analyzed its protective effects both in vitro and in vivo models of AD. AAV‐NUsc1 capability to induce NUsc1 expression and secretion in humans was tested using human brain slices in culture. Result We here show that recombinant NUsc1, a single‐chain variable fragment (scFv) antibody that selectively targets a subset of neurotoxic AβOs, prevented AβO‐induced inhibition of long‐term potentiation in hippocampal slices, and blocked memory impairment induced by intracerebroventricular infusion of AβOs in mice. We next developed an adeno‐associated virus vector to drive neuronal expression of NUsc1 (AAV‐NUsc1) as a novel therapeutic approach for AD. Importantly, transduction by AAV‐NUsc1 induced NUsc1 expression and secretion in adult human brain slices. In primary hippocampal cultures, transduction by AAV‐NUsc1 reduced AβO binding to neurons and prevented AβO‐induced loss of dendritic spines. Remarkably, AAV‐NUsc1 prevented memory impairment caused by AβO infusion in mice and reversed memory deficits in APPswe/PS1ΔE9 AD mice. Conclusion AAV‐NUsc1 represents a potential tool for gene therapy in AD by using an AAV vector to induce in vivo sustained expression of a single chain variable fragment antibody to neutralize AβOs.
Advanced method for efficient functionalization of polymers by intermediate free-radical formation with vacuum-ultraviolet radiation and producing superhydrophilic surfaces (2023)

An efficient approach for tailoring surface properties of polymers is presented, which enables rapid modification leading to superhydrophilic properties. The approach is based on vacuum-ultraviolet radiation (VUV) pretreatment of the surface to create reactive dangling bonds. This step is followed by a second treatment using neutral oxygen atoms that react with the dangling bonds and form functional groups. The beneficial effect of VUV pretreatment for enhanced functionalization was clearly demonstrated by comparing VUV pretreatment in plasmas created in different gases, i.e., hydrogen, nitrogen, and oxygen, which differ in the intensity of VUV/UV radiation. The emission intensity of VUV radiation for all gases was measured by vacuum ultraviolet spectroscopy. It was shown that VUV has a strong influence on the treatment time and final surface wettability. A superhydrophilic surface was obtained only if using VUV pretreatment. Furthermore, the treatment time was significantly reduced to only a second of treatment. These findings show that such an approach may be used to enhance the surface reaction efficiency for further grafting of chemical groups.
Conversion of an inactive xylose isomerase into a functional enzyme by co-expression of GroEL-GroES chaperonins in Saccharomyces cerevisiae (2017)

Based on our results, we elaborate an extensive discussion concerning the uncertainties that surround heterologous expression of xylose isomerases in S. cerevisiae. Probably, a correct folding promoted by GroEL-GroES could solve some issues regarding a limited or absent XI activity in S. cerevisiae. The strains developed in this work have promising industrial characteristics, and the designed strategy could be an interesting approach to overcome the non-functionality of bacterial protein expression in yeasts.
Adaptive decision feedback turbo equalization (2003)

We present an adaptive iterative (turbo) decision feedback equalizer (DFE) for channels with intersymbol interference (ISI). The filter coefficients are computed directly from the soft decisions and the received data to minimize a least squares cost function. This method performs better than a turbo DFE with perfect channel knowledge, where the filters are selected to minimize mean squared error (MSE) assuming perfect feedback. We also present adaptive reduced-rank algorithms, which can further improve performance and reduce complexity.
Design and development of a soft robotic octopus arm exploiting embodied intelligence (2012)

The octopus is a marine animal whose body has no rigid structures. It has eight arms mainly composed of muscles organized in a peculiar structure, named muscular hydrostat, that can change stiffness and that is used as a sort of a modifiable skeleton. Furthermore, the morphology of the arms and the mechanical characteristics of their tissues are such that the interaction with the environment, namely water, is exploited to simplify the control of movements. From these considerations, the octopus emerges as a paradigmatic example of embodied intelligence and a good model for soft robotics. In this paper the design and the development of an artificial muscular hydrostat are reported, underling the efforts in the design and development of new technologies for soft robotics, like materials, mechanisms, soft actuators. The first prototype of soft robot arm is presented, with experimental results that show its capability to perform the basic movements of the octopus arm (like elongation, shortening, and bending) and demonstrate how embodiment can be effective in the design of robots.
Reverse-mode AD in a functional framework (2008)

We show that reverse-mode AD (Automatic Differentiation)—a generalized gradient-calculation operator—can be incorporated as a first-class function in an augmented lambda calculus, and therefore into a functional-programming language. Closure is achieved, in that the new operator can be applied to any expression in the augmented language, yielding an expression in that language. This requires the resolution of two major technical issues: (a) how to transform nested lambda expressions, including those with free-variable references, and (b) how to support self application of the AD machinery. AD transformations preserve certain complexity properties, among them that the reverse phase of the reverse-mode AD transformation of a function have the same temporal complexity as the original untransformed function. First-class unrestricted AD operators increase the expressive power available to the numeric programmer, and may have significant practical implications for the construction of numeric software that is robust, modular, concise, correct, and efficient.
Cellular Location of HNF4α is Linked With Terminal Liver Failure in Humans (2020)

Hepatocyte nuclear factor 4 alpha (HNF4α) is a transcription factor that plays a critical role in hepatocyte function, and HNF4α-based reprogramming corrects terminal liver failure in rats with chronic liver disease. In the livers of patients with advanced cirrhosis, HNF4α RNA expression levels decrease as hepatic function deteriorates, and protein expression is found in the cytoplasm. These findings could explain impaired hepatic function in patients with degenerative liver disease. In this study, we analyzed HNF4α localization and the pathways involved in post-translational modification of HNF4α in human hepatocytes from patients with decompensated liver function. RNA-sequencing analysis revealed that AKT-related pathways, specifically phospho-AKT, is down-regulated in cirrhotic hepatocytes from patients with terminal failure, in whom nuclear levels of HNF4α were significantly reduced, and cytoplasmic expression of HNF4α was increased. cMET was also significantly reduced in failing hepatocytes. Moreover, metabolic profiling showed a glycolytic phenotype in failing human hepatocytes. The contribution of cMET and phospho-AKT to nuclear localization of HNF4α was confirmed using Spearman's rank correlation test and pathway analysis, and further correlated with hepatic dysfunction by principal component analysis. HNF4α acetylation, a posttranslational modification important for nuclear retention, was also significantly reduced in failing human hepatocytes when compared with normal controls. <i>Conclusion:</i> These results suggest that the alterations in the cMET-AKT pathway directly correlate with HNF4α localization and level of hepatocyte dysfunction. This study suggests that manipulation of HNF4α and pathways involved in HNF4α posttranslational modification may restore hepatocyte function in patients with terminal liver failure.