gebhart/patrepeval huggingface dataset:
Identification and characterization of the WYL BrxR protein and its gene as separable regulatory elements of a BREX phage restriction system (2021)

ABSTRACT Bacteriophage exclusion (‘BREX’) phage restriction systems are found in a wide range of bacteria. Various BREX systems encode unique combinations of proteins that usually include a site-specific methyltransferase; none appear to contain a nuclease. Here we describe the identification and characterization of a Type I BREX system from Acinetobacter and the effect of deleting each BREX ORF on growth, methylation, and restriction. We identified a previously uncharacterized gene in the BREX operon that is dispensable for methylation but involved in restriction. Biochemical and crystallographic analyses of this factor, which we term BrxR (‘BREX Regulator’), demonstrate that it forms a homodimer and specifically binds a DNA target site upstream of its transcription start site. Deletion of the BrxR gene causes cell toxicity, reduces restriction, and significantly increases the expression of BrxC. In contrast, the introduction of a premature stop codon into the BrxR gene, or a point mutation blocking its DNA binding ability, has little effect on restriction, implying that the BrxR coding sequence and BrxR protein play independent functional roles. We speculate that the BrxR coding sequence is involved in cis regulation of anti-phage activity, while the BrxR protein plays an additional regulatory role, perhaps during horizontal transfer.
Thick-Film Electrochemical Detectors for Poly(dimethylsiloxane)-based Microchip Capillary Electrophoresis (2002)

A new poly(dimethylsiloxane) (PDMS)-based microchip capillary electrophoresis (CE) device, with a thick-film electrochemical detector, is described. The end-column design relies on screen-printing the amperometric carbon working electrode on the base plate of a PDMS microchip (opposite to the exit of the microchannel). Since the channel depth and electrode height are quite similar, this is a flow-onto/flow-by hybrid arrangement. The influence of relevant experimental variables, such as the separation and detection potentials, is reported along with the attractive analytical performance. Flat baselines and extremely low noise levels are observed even at high separation fields (approaching 700 V/cm), reflecting the effective electrical isolation of the detector. The resulting detection limits (150 nM for epinephrine and 280 nM for catechol) compare favorably with those obtained by other PDMS-based electrochemical detectors. Such coupling of low-cost and versatile PDMS chips and thick-film electrochemical detectors holds great promise for high-volume production of disposable microfluidic analytical devices.
Inflated false negative rates undermine reproducibility in task-based fMRI (2017)

Abstract Reproducibility is generally regarded as a hallmark of scientific validity. It can be undermined by two very different factors, namely inflated false positive rates or inflated false negative rates. Here we investigate the role of the second factor, i.e. the degree to which true effects are not detected reliably. The availability of large public databases and also supercomputing allows us to tackle this problem quantitatively. Specifically, we estimated the reproducibility in task-based fMRI data over different samples randomly drawn from a large cohort of subjects obtained from the Human Connectome Project. We use the full cohort as a standard of reference to approximate true positive effects, and compute the fraction of those effects that was detected reliably using standard software packages at various smaller sample sizes. We found that with standard sample sizes this fraction was less than 25 percent. We conclude that inflated false negative rates are a major factor that undermine reproducibility. We introduce a new statistical inference algorithm based on a novel test statistic and show that it improves reproducibility without inflating false positive rates.
In vivo lentiviral vector gene therapy to cure hereditary tyrosinemia type 1 and prevent development of precancerous and cancerous lesions (2022)

Conventional therapy for hereditary tyrosinemia type-1 (HT1) with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) delays and in some cases fails to prevent disease progression to liver fibrosis, liver failure, and activation of tumorigenic pathways. Here we demonstrate cure of HT1 by direct, in vivo administration of a therapeutic lentiviral vector targeting the expression of a human fumarylacetoacetate hydrolase (FAH) transgene in the porcine model of HT1. This therapy is well tolerated and provides stable long-term expression of FAH in pigs with HT1. Genomic integration displays a benign profile, with subsequent fibrosis and tumorigenicity gene expression patterns similar to wild-type animals as compared to NTBC-treated or diseased untreated animals. Indeed, the phenotypic and genomic data following in vivo lentiviral vector administration demonstrate comparative superiority over other therapies including ex vivo cell therapy and therefore support clinical application of this approach.
3D Integrated Water Cooling of a Composite Multilayer Stack of Chips (2010)

New generation supercomputers with three dimensional stacked chip architectures pose a major challenge with respect to removal of dissipated heat which can reach currently as high as 250 W/cm2 in multilayer chip stacks of less than 0.3 cm3 volume. Interlayer integrated water cooling [1] is a very promising approach for such high heat flux removal due to much larger thermal capacity and conductivity of water compared to air, the traditional cooling fluid. In the current work, a multiscale conjugate heat transfer model is developed for integrated water cooling of chip layers and validated with experimental measurements on a specially designed thermal test vehicle that simulates a four tier chip stack with a footprint of 1 cm2. The cooling heat transfer structure, which consists of microchannels with cylindrical pin fins, is conceived in such a way that it can be directly integrated with the device layout in multilayer chips. Every composite layer is cooled by water flow in microchannels (height: 100 μm), which are arranged in 2 port water inlet-outlet configuration. The total power removed in the stack is 390 W at a temperature gradient budget of 60 K from liquid inlet to maximal junction temperature, corresponding to about 1.3 kW/cm3 volumetric heat flow. The computational cost and complexity of detailed CFD modeling of heat transfer in stacked chips with integrated cooling can be prohibitive. Therefore, the heat transfer structure is modeled using a porous medium approach, where the model parameters of heat transfer and hydrodynamic resistance are derived from averaging the results of the detailed 3D-CFD simulations of a single stream-wise row of fins. The modeling results indicate that an isotropic porous medium model does not accurately predict the measured temperature fields. The variation of material properties due to temperature gradients are found to be large, therefore variable properties are used in the model. It is also shown that the modeling of the heat transfer in the cooling sublayers requires the implementation of a porous medium approach with a local thermal non-equilibrium as well as orthotropic heat conduction and hydrodynamic resistance. The improved model reproduces the temperatures measured in the stack within 10%. The model is used to predict the behavior of multilayer stacks mimicking the change of heat fluxes resulting from variations in the computational load of the chips during their operation.
Secure remote sensing and communication using digital pufs (2014)

Small form, mobile, and remote sensor network systems require secure and ultralow power data collection and communication solutions due to their energy constraints. The physical unclonable function (PUF) has emerged as a popular modern low power security primitive. However, current designs are analog in nature and susceptible to instability and difficult to integrate into existing circuitry. In this paper, we present the digital PUF which is stable in the same sense that digital logic is stable, has a very small footprint and very small timing overhead, and can be easily integrated into existing designs. We demonstrate the use of the digital PUF on two applications that are crucial for sensor networks: trusted remote sensing and logic obfuscation. We present our security analysis using standard randomness tests and confusion and diffusion analysis, and apply our new obfuscation approach on a set of standard design benchmarks.
Serum‐free, chemically defined medium with TGF‐β3 enhances functional properties of nucleus pulposus cell‐laden carboxymethylcellulose hydrogel constructs (2009)

Degeneration of the nucleus pulposus (NP) has been implicated as a major cause of low back pain. Tissue engineering strategies may provide a viable NP replacement therapy; however, culture conditions must be optimized to promote functional tissue development. In this study, a standard serum-containing medium formulation was compared to a chemically defined, serum-free medium to determine the effect on matrix elaboration and functional properties of NP cell-laden carboxymethylcellulose (CMC) hydrogels. Additionally, both media were further supplemented with transforming growth factor-beta 3 (TGF-beta(3)). Glycosaminoglycan (GAG) content increased in both TGF-beta(3)-treated groups and was highest for treated, serum-free constructs (9.46 +/- 1.51 microg GAG/mg wet weight), while there were no quantifiable GAGs in untreated serum-containing samples. Histology revealed uniform, interterritorial staining for chondroitin sulfate proteoglycan throughout the treated, serum-free constructs. Type II collagen content was greater in both serum-free groups and highest in treated, serum-free constructs. The equilibrium Young's modulus was highest in serum-free samples supplemented with TGF-beta(3) (18.54 +/- 1.92 kPa), and the equilibrium weight swelling ratio of these constructs approached that of the native NP tissue (22.19 +/- 0.46 vs. 19.94 +/- 3.09, respectively). Taken together, these results demonstrate enhanced functional matrix development by NP cells when cultured in CMC hydrogels maintained in serum-free, TGF-beta(3) supplemented medium, indicating the importance of medium formulation in NP construct development.
Managing Human-Robot Engagement with Forecasts and... um ... Hesitations (2014)

We explore methods for managing conversational engagement in open-world, physically situated dialog systems. We investigate a self-supervised methodology for constructing forecasting models that aim to anticipate when participants are about to terminate their interactions with a situated system. We study how these models can be leveraged to guide a disengagement policy that uses linguistic hesitation actions, such as filled and non-filled pauses, when uncertainty about the continuation of engagement arises. The hesitations allow for additional time for sensing and inference, and convey the system's uncertainty. We report results from a study of the proposed approach with a directions-giving robot deployed in the wild.
Mesenchymal Transitions in Development and Disease (2016)

The ability of epithelial cells and endothelial cells to transform into mesenchymal cells is one of the most basic cellular mechanisms in biology. This process, referred to as epithelial-mesenchymal transition (EMT) or endothelial-mesenchymal transition (EndMT), regulates various stages of embryonic development and contributes to the progression of a wide array of diseases and in tissue repair [1, 2].

During embryogenesis, EMT is essential for gastrulation, primitive streak formation, somite dissociation, neural crest development, and palate and lip fusion [3]. EndMT is critical for cardiac development, particularly in the formation of the valves and septa of the heart [4] and the generation of mesodermal cells and multipotent progenitors [5].

In the adult organism, EMT and EndMT are usually dormant until pathological stimuli awaken this embryonic mechanism. For example, EMT is the primary mechanism of cancer metastasis [6, 7], whereas EndMT forms cancer-associated fibroblasts in the tumor microenvironment [8]. Also, both EMT and EndMT have been shown to generate fibroblasts that cause the formation of scar tissue after tissue injury or in association with inflammatory and fibrotic diseases [9–11].

Mesenchymal transitions have traditionally been considered to have a positive effect in development and a negative effect in disease. However, novel findings regarding the stem cell phenotype generated by EMT and EndMT [12, 13] suggest that they may have therapeutic potential for the treatment of various degenerative diseases. This marks an exciting period in this field of research, which may provide new methods for tissue engineering and regeneration by harnessing the power of this embryonic mechanism.

In this special issue, the articles focus on the cutting-edge research on EMT/EndMT, including the role of this mechanism in regenerative medicine, peritoneal fibrosis, liver fibrosis, systemic sclerosis, and angiogenesis. This issue also explores how factors such as mechanical force, vitamin D signaling, and noncoding RNAs regulate mesenchymal transitions, which may provide novel insight into future avenues of research and therapeutic development.


Damian Medici

Pura Munoz-Canoves

Pan-Chyr Yang

Silvia Brunelli
Towards self-adaptable, scalable, dependable and energy efficient networks: the self-growing concept (2010)

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Spirocyclic Lignans from Guaiacum (Zygophyllaceae) Induce Apoptosis in Human Breast Cancer Cell Lines (2011)

We investigated the composition of extracts derived from Guaiacum spp. (Zygophyllaceae), a group of neotropical tree species with varied uses in Central and South American traditional medicine. Activity-guided fractionation of Guaiacum heartwood extracts led to the identification of four new spirocyclic lignans, named ramonanins A-D (1-4). The ramonanins exhibit cytotoxic activity against human breast cancer cell lines with an IC50 value of 18 μM and induce cell death via apoptotic mechanisms. The ramonanins are derived from four units of coniferyl alcohol and feature an unusual spirocyclic ring system.
Oxygen-molecule spin-nanotubes constructed by physisorption into a nanoporous medium (2008)

We succeeded in controlling gas-liquid-solid transitions and in constructing ``spin-nanotubes (SNTs)'' based on antiferromagnetic correlations by physisorbing oxygen molecules $({\text{O}}_{2})$ into the nanosize pores of a mesoporous medium MCM-41 while also manipulating the adsorption quantity. The phase diagram of ${\text{O}}_{2}$ physisorbed into MCM-41 presents many common characteristics with that of ${\text{O}}_{2}$ layers physisorbed on graphite substrates. In the present case, experimental verification of the antiferromagnetic square lattice in the liquid phase of the monolayer proved the formation of ${\text{O}}_{2}$ SNTs. The present ${\text{O}}_{2}$ SNT is an experimental example of the successful construction of SNT.
Dynamic Reliability Management in Neuromorphic Computing (2021)

Neuromorphic computing systems uses non-volatile memory (NVM) to implement high-density and low-energy synaptic storage. Elevated voltages and currents needed to operate NVMs cause aging of CMOS-based transistors in each neuron and synapse circuit in the hardware, drifting the transistor's parameters from their nominal values. Aggressive device scaling increases power density and temperature, which accelerates the aging, challenging the reliable operation of neuromorphic systems. Existing reliability-oriented techniques periodically de-stress all neuron and synapse circuits in the hardware at fixed intervals, assuming worst-case operating conditions, without actually tracking their aging at run time. To de-stress these circuits, normal operation must be interrupted, which introduces latency in spike generation and propagation, impacting the inter-spike interval and hence, performance, e.g., accuracy. We propose a new architectural technique to mitigate the aging-related reliability problems in neuromorphic systems, by designing an intelligent run-time manager (NCRTM), which dynamically destresses neuron and synapse circuits in response to the short-term aging in their CMOS transistors during the execution of machine learning workloads, with the objective of meeting a reliability target. NCRTM de-stresses these circuits only when it is absolutely necessary to do so, otherwise reducing the performance impact by scheduling de-stress operations off the critical path. We evaluate NCRTM with state-of-the-art machine learning workloads on a neuromorphic hardware. Our results demonstrate that NCRTM significantly improves the reliability of neuromorphic hardware, with marginal impact on performance.
Humanized anti-CEACAM6 PEGylated scFv: A promising novel therapy for pancreatic cancer (2007)

3042 Background: Novel Therapies for pancreatic cancer (PC) based on biological insight are urgently needed. CEACAM6, a member of the carcinoembryonic antigen (CEA) family, is a cell surface oncogene on PC cells. It is a glycoprotein composed of 3 Ig-like domains (Mr ∼35.2kD) and is linked to the plasma membrane via a glycophospholipid linked anchor. It is over-expressed on ≥95% PC patients’ found irrespective of stage of disease and represents a target for antibody therapy. Methods: Murine anti-CEACAM6 monoclonal antibody (Mab) 13–1 was humanized by a structure-based approach and single chain variable fragments (scFv) designed consisting of a Gly/Ser-linker which includes a cysteine residue for PEGylation. Murine scFv and 4 humanized scFv fragments (Version.1, 2, 7, 8) were bacterially expressed, purified, PEGylated and evaluated for activity alone or in combination with gemcitabine in human PC cell lines and mouse xenograft tumors. Cell viability, apoptosis and in-cell Westerns were done for efficacy and binding. Mouse xenograft tumors were treated with scFv or PEGylated scFv or combination with gemcitabine. Tumors (treated Vs untreated) were analyzed by immunohistochemistry for Ki-67, CD31, CEACAM6 and Caspase 3 Results: Mab 13–1, murine and 4 humanized scFvs’ were cytotoxic to CEACAM6 expressing PC cells (BxPC-3, HPAF-2) and not to PC cells that lack CEACAM6 (CaPan-2) with increased PARP-cleavage that was dose dependent (IC 50 =10μg/mL). Western blotting of culture media and serum from xenograft mice showed that CEACAM6 is not shed. In-cell Western confirmed humanized V.7 to be the best binder (K D =1–10μg/mL) confirming protein-protein interaction studies performed in silico with homology models of murine and humanized scFvs’ and CEACAM6. The murine scFv alone or the humanized scFV (V.8) in combination with gemcitabine delayed tumor growth by &gt;50%. This tumor reduction correlated well with the immunohistochemical markers of response. Conclusions: We have demonstrated that CEACAM6 is a clinically relevant target in PC and that a PEGylated humanized scFv is a novel effective therapy alone and/or in combination with gemcitabine. Humanized scFv V.7 is undergoing mouse xenograft evaluation and expect will be the most effective agent to take forward into clinical development. No significant financial relationships to disclose.
Printed assemblies of ultrathin, microscale inorganic light emitting diodes for deformable and semitransparent displays (2023)

Described herein are printable structures and methods for making, assembling and arranging electronic devices. A number of the methods described herein are useful for assembling electronic devices where one or more device components are embedded in a polymer which is patterned during the embedding process with trenches for electrical interconnects between device components. Some methods described herein are useful for assembling electronic devices by printing methods, such as by dry transfer contact printing methods. Also described herein are GaN light emitting diodes and methods for making and arranging GaN light emitting diodes, for example for display or lighting systems.
Nucleophilic character of alkyl radicals. Part 17. Absolute rate constants and the alternating effect in the addition of alkyl radicals to styrene and acrylic monomers (1978)

The absolute rate constants for the addition of alkyl radicals to styrene and acrylic monomers are determined by two kinetic models. The first evaluates the ratio of electron-transfer oxidation by copper(II) acetate and addition to the double bonds, and the second determines the relative rates of alternating addition to acrylic monomers. The results are compared with the values in gas-phase reactions and are discussed in terms of polar effects and frontier orbital theory. The synthetic interest of the reactions involved is emphasized.
Fluoromorphic Substrates for Fatty Acid Metabolism: Highly Sensitive Probes for Mammalian Medium‐Chain Acyl‐CoA Dehydrogenase (2005)

Nicht pingelig: Eine systematische Studie ergab eine beachtliche Substrattoleranz der mittelkettenspezifischen Acyl-CoA-Dehydrogenase (MCAD), eines Elements des β-Oxidationsweges beim Abbau von Fettsäuren. Mithilfe dreier fluorogener Reportersubstrate ist ein selektives, empfindliches und kontinuierliches Aufzeichnen der MCAD-Aktivität in Gewebe-Homogenaten möglich.
Mast cell targeted therapy with imatinib mesylate or sodium cromoglycate : a novel approach to inhibit angiogenesis and prostate tumour growth (2008)

Mast cell targeted therapy with imatinib mesylate or sodium cromoglycate : a novel approach to inhibit angiogenesis and prostate tumour growth
Design and Optimization of a Switched Reluctance Motor Driving a Compressor for a PEM Fuel-Cell System for Automotive Applications (2010)

This paper describes the design of a high-speed three-phase switched reluctance machine to drive a compressor for the air management of a fuel-cell system for automotive applications. The machine geometry is optimized by means of a finite-element method coupled to a genetic algorithm. The performance of the optimized machine is evaluated, taking into account the iron and air-friction losses. Some theoretical and numerical results are sustained by the measured ones in the same operating conditions.