gebhart/patrepeval huggingface dataset:
Associate toxin-antitoxin with CRISPR-Cas to kill multidrug-resistant pathogens (2023)

CreTA, CRISPR-regulated toxin-antitoxin (TA), safeguards CRISPR-Cas immune systems by inducing cell dormancy/death upon their inactivation. Here, we characterize a bacterial CreTA associating with the I-F CRISPR-Cas in Acinetobacter. CreT is a distinct bactericidal small RNA likely targeting several essential RNA molecules that are required to initiate protein synthesis. CreA guides the CRISPR effector to transcriptionally repress CreT. We further demonstrate a proof-of-concept antimicrobial strategy named ATTACK, which AssociaTes TA and CRISPR-Cas to Kill multidrug resistant (MDR) pathogens. In this design, CRISPR-Cas is programed to target antibiotic resistance gene(s) to selectively kill MDR pathogens or cure their resistance, and when CRISPR-Cas is inactivated or suppressed by unwanted genetic or non-genetic events/factors, CreTA triggers cell death as the last resort. Our data highlight the diversity of RNA toxins coevolving with CRISPR-Cas, and illuminate a combined strategy of CRISPR and TA antimicrobials to 'ATTACK' MDR pathogens.
Reductive dechlorination of chlorinated ethene DNAPLs by a culture enriched from contaminated groundwater (1999)

A microbial culture enriched from a trichloroethene-contaminated groundwater aquifer reductively dechlorinated trichloroethene (TCE) and tetrachloroethene (PCE) to ethene. Initial PCE dechlorination rate studies indicated a first-order dependence with respect to substrate at low PCE concentrations, and a zero-order dependence at high concentrations. Studies of TCE and vinyl chloride (VC) dechlorination indicated a first-order dependence at all substrate concentrations. VC had little or no effect on the initial rate of TCE dechlorination. With subsaturating concentrations of chlorinated ethenes, nearly stoichiometric amounts of the toxic intermediate vinyl chloride accumulated prior to its dechlorination to ethene. In contrast, under saturating conditions, in which a dense, nonaqueous-phase liquid existed in equilibrium with the aqueous phase, the chlorinated ethene was dechlorinated to ethene, at a rapid rate, with the accumulation of relatively small amounts of chlorinated intermediates.
Quasiparticle semiconductor band structures including spin–orbit interactions (2013)

We present first-principles calculations of the quasiparticle band structure of the group IV materials Si and Ge and the group III-V compound semiconductors AlP, AlAs, AlSb, InP, InAs, InSb, GaP, GaAs and GaSb. Calculations are performed using the plane wave pseudopotential method and the 'one-shot' GW method, i.e. G(0)W(0). Quasiparticle band structures, augmented with the effects of spin-orbit, are obtained via a Wannier interpolation of the obtained quasiparticle energies and calculated spin-orbit matrix. Our calculations explicitly treat the shallow semicore states of In and Ga, which are known to be important in the description of the electronic properties, as valence states in the quasiparticle calculation. Our calculated quasiparticle energies, combining both the ab initio evaluation of the electron self-energy and the vector part of the pseudopotential representing the spin-orbit effects, are in generally very good agreement with experimental values. These calculations illustrate the predictive power of the methodology as applied to group IV and III-V semiconductors.
High-Power-Density Annular Fuel for Pressurized Water Reactors: Manufacturing Costs and Economic Benefits (2007)

Annular fuel can be used as a means to upgrade the power density in future and current reactors. This study determined the economic impact of the manufacturing and use of this higher energy density fuel. An evaluation of the manufacturing costs associated with annular fuel indicated that there should be minimal if any manufacturing cost impacts. While each rod would use more material (uranium and zirconium) than a standard solid-pellet-based fuel, fewer rods are required for each assembly.Several uprate options were compared to a new build of a Generation III 1117-MW(electric) plant (option 1) on the basis of rate of return (ROR) on investment, which was calculated at 6.9%. Option 2 was the uprate of an operating Generation II power plant from 1200 to 1800 MW(electric) including steam generator replacements, which resulted in an ROR of 6.3%. Option 2 was also evaluated assuming that a shutdown to upgrade was coordinated with a previously scheduled replacement of steam generators. Assuming that 3 of the 12 months required for uprating the plant are already paid for by the steam generator replacement, the ROR of this option then rises to 13.0%, which makes it the best option available. Option 3 was the building of a new Generation III plant with an output of 1717 MW(electric) using annular fuel, which had an ROR of 11.5%. This was compared to a new 1717-MW(electric) Generation III plant with low energy density standard fuel, which yielded an ROR of 10.8%.It was concluded that the use of annular fuel, when complemented with other changes in the fuel such as longer rod lengths, higher fuel density, and core reflectors that would increase the amount of fuel in the core and increase its neutron efficiency, could improve the rate of return on invested capital for new plants by getting more capacity from a smaller-sized nuclear island, which reduces the capital cost per installed kilowatt.Note that this study did take into account replacement power and unused fuel value at the time of transition from standard to annular fuel, but not costs associated with the changes required to the power system outside of the plant boundary, which would be site dependent. When replacement power and fuel displacement costs were not included, the ROR for the 600-MW(electric) uprate option 2 rose to 11.6%. This result indicates that large 50% uprates may make sense if low-cost replacement power during the transition outage is readily available and if a fuel management program before the uprate can minimize the residual value of the displaced standard fuel. It is also clear that with sufficient lifetime, uprating plants, regardless of the method used, results in better plant economics because of the economy of scale effect.
Effects of Yaw Motion on Driving Behaviour, Comfort and Realism (2012)

The use of large displacement yaw cueing is becoming more common as a part of the motion cueing in driving simulators. It is expected that driving behaviour, comfort and realism will be positively affected by adding a yaw table, especially during low-speed turning manoeuvres. We used TNO's advanced motion platform Desdemona to explore the effects of yaw motion during highway and urban turning manoeuvres: 14 participants drove the simulator with and without yaw motion. Questionnaires results showed that the simulation was rated as quite realistic. Effects of yaw motion on the subjective ratings were not found. In terms of driving behaviour, we found statistically significant effects of yaw motion in curve driving, especially in small-radius curves. With yaw motion present, driving behaviour became more cautious, and (compared against the literature) more realistic. This suggests that adding yaw motion to a driving simulator improves the external validity for low-speed corner driving manoeuvres.
HiPerRF: A Dual-Bit Dense Storage SFQ Register File (2022)

Single Flux Quantum (SFQ) superconducting technology provides significant power and performance benefits in the era of diminishing CMOS scaling. Recent advances in design tools and fabrication facilities have brought SFQ based computing to the forefront. One challenge faced by SFQ technology is to have a compact and robust on-chip memory, which can be used for implementing register files and cache memory. While dense memories are being investigated through the development of three-terminal devices such as Nanocryotrons, in this work, we build on a novel memory cell built using traditional Josephson junctions (JJs). In particular, we design a high capacity register file, called HiPerRF, that builds on a High Capacity Destructive ReadOut (HC-DRO) cell in SFQ technology. HC-DRO design can store up to three fluxon pulses, thereby providing the equivalent of 2-bit storage in a single cell. However, these cells provide only destructive readout capability, namely each value can be read only once. However, CPU register file contents are read multiple times in any program, and hence a destructive readout complicates register file design. HiPerRF provides the non-destructive property using a loopback write mechanism, thereby preserving the higher density of HC-DRO cells without compromising the multi-read demands of a register file. HiPerRF reduces the JJ count of the register file design, after accounting for all the peripheral access circuitry costs, by 56.1% and reduces the static power by 46.2%. Furthermore, HiPerRF reduces the JJ count by 16.3% even when considering an entire in-order RISC-V CPU core.
Urokinase-type plasminogen activator (uPA) is critical for progression of tuberous sclerosis complex 2 (TSC2)-deficient tumors (2017)

Lymphangioleiomyomatosis (LAM) is a fatal lung disease associated with germline or somatic inactivating mutations in tuberous sclerosis complex genes (<i>TSC1</i> or <i>TSC2</i>). LAM is characterized by neoplastic growth of smooth muscle-α-actin-positive cells that destroy lung parenchyma and by the formation of benign renal neoplasms called angiolipomas. The mammalian target of rapamycin complex 1 (mTORC1) inhibitor rapamycin slows progression of these diseases but is not curative and associated with notable toxicity at clinically effective doses, highlighting the need for better understanding LAM's molecular etiology. We report here that LAM lesions and angiomyolipomas overexpress urokinase-type plasminogen activator (uPA). <i>Tsc1</i><sup>-/-</sup> and <i>Tsc2</i><sup>-/-</sup> mouse embryonic fibroblasts expressed higher uPA levels than their WT counterparts, resulting from the TSC inactivation. Inhibition of uPA expression in <i>Tsc2</i>-null cells reduced the growth and invasiveness and increased susceptibility to apoptosis. However, rapamycin further increased uPA expression in TSC2-null tumor cells and immortalized TSC2-null angiomyolipoma cells, but not in cells with intact TSC. Induction of glucocorticoid receptor signaling or forkhead box (FOXO) 1/3 inhibition abolished the rapamycin-induced uPA expression in TSC-compromised cells. Moreover, rapamycin-enhanced migration of TSC2-null cells was inhibited by the uPA inhibitor UK122, dexamethasone, and a FOXO inhibitor. uPA-knock-out mice developed fewer and smaller TSC2-null lung tumors, and introduction of uPA shRNA in tumor cells or amiloride-induced uPA inhibition reduced tumorigenesis <i>in vivo</i> These findings suggest that interference with the uPA-dependent pathway, when used along with rapamycin, might attenuate LAM progression and potentially other TSC-related disorders.
NF-κB Is Active in Mcl-1 Promoter Regulation in Human CLL. (2008)

Abstract The NF-κB family of transcription factors is linked to neoplasia due to its role in increasing cell proliferation as well as inhibiting apoptosis. NF-κB has been reported to be constitutively active in chronic lymphocytic leukemia (CLL), but the mechanism underlying this this activation is not fully understood and the critical target genes involved have not been identified. To further define the mechanism(s) by which NF-κB promotes survival in CLL, we investigated the role of this transcription factor in the regulation of the myeloid cell leukemia 1 (Mcl-1) gene. The promoter region of Mcl-1 contains a putative NF-κB binding site, and increased expression of the Mcl-1 protein has been related to rapid disease progression and resistance to apoptosis in CLL. However, a direct link between NF-κB and Mcl-1 transcriptional regulation has not yet been established in B-cells or human CLL. We demonstrate here that NF-κB binding is a critical event in the transcriptional regulation of Mcl-1, as deletion of the NF-κB binding site in the promoter results in decreased activity of an Mcl-1-luciferase reporter construct. In addition, pharmacological inhibition of NF-κB reduced p65 nuclear localization and binding of NF-κB to the Mcl-1 promoter. Interestingly, when CLL patient samples were exposed to an IKK inhibitor, Bay-11, the extent of Mcl-1 inhibition varied in patients. We therefore examined whether the effect on Mcl-1 correlated with in vitro cell survival, a result that might be expected given that NF-κB expression has been previously reported to correlate with CLL cell survival. We found that CLL patient cells more sensitive to Bay-11-induced apoptosis also showed a larger decrease in Mcl-1 mRNA, suggesting that Mcl-1 message level may be a useful diagnostic to predict patients that will respond to NF-κB targeted therapy. Furthermore, different inducers of the NF-κB signaling pathway (CD40L, immune stimulatory CpG-ODN and TNF-α), promote differential effects on Mcl-1 regulation in CLL patient cells. Although all three treatments increase NF-κB nuclear localization and DNA binding, Mcl-1 RNA and protein increased with CpG and CD40L treatment, but not TNFα. This result provides evidence of stimulus-specific regulation of Mcl-1 by NF-κB. Based on these observations, we hypothesize that there is a direct link between NF-κB DNA binding and transcriptional control of Mcl-1, and that this gene could serve as a pharmacodynamic endpoint to monitor the efficacy of NF-κB inhibitors in CLL cells. Additionally, a direct link of NF-κB activity to Mcl-1 expression and cell survival provide further justification for targeting this transcription factor for treatment in CLL.
Combustion of Chlorinated VOC on Nanostructured Chromia Aerogel as Catalyst and Catalyst Support (2005)

The chromia-based catalysts have been reported to combine the high activity and resistance to deactivation in oxidative removal of chlorinated VOC. However, their activity is limited by the low amount of chromia that can be deposited on supports maintaining the optimal state of surface species and high surface area. The pure nanostructured chromia was used as a catalytically active support for noble metals and transition-metal oxide oxidation catalysts. High efficiency of Pt-promoted CrOOH aerogel with surface area of 500 m2*g(-1) was demonstrated in full combustion of 1,2-dichloroethane (DCE) and chlorobenzene (CB). At gas hour space velocity (GHSV) of 46 000 h(-1), the total conversion to CO2/H2O/HCl was achieved at 330 degrees C (DCE) and 380 degrees C (CB). The combustion rate constants measured at standard conditions with 0.5% Pt/CrOOH catalyst were 1 or 2 orders of magnitude higher than measured with 15%Cr2O3/Al2O3 or 0.5%Pt/Al2O3, respectively. The effects of Pt, Au, Mn, and Ce additives on the performance of CrOOH aerogel in combustion of chlorinated VOC were analyzed related to the materials structure.
Heavy–light chain interrelations of MS-associated immunoglobulins probed by deep sequencing and rational variation (2014)

The mechanisms triggering most of autoimmune diseases are still obscure. Autoreactive B cells play a crucial role in the development of such pathologies and, in particular, production of autoantibodies of different specificities. The combination of deep-sequencing technology with functional studies of antibodies selected from highly representative immunoglobulin combinatorial libraries may provide unique information on specific features in the repertoires of autoreactive B cells. Here, we have analyzed cross-combinations of the variable regions of human immunoglobulins against the myelin basic protein (MBP) previously selected from a multiple sclerosis (MS)-related scFv phage-display library. On the other hand, we have performed deep sequencing of the sublibraries of scFvs against MBP, Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1), and myelin oligodendrocyte glycoprotein (MOG). Bioinformatics analysis of sequencing data and surface plasmon resonance (SPR) studies have shown that it is the variable fragments of antibody heavy chains that mainly determine both the affinity of antibodies to the parent autoantigen and their cross-reactivity. It is suggested that LMP1-cross-reactive anti-myelin autoantibodies contain heavy chains encoded by certain germline gene segments, which may be a hallmark of the EBV-specific B cell subpopulation involved in MS triggering.
A rapid method for the generation of uniform acellular bone explants: a technical note (2010)

To summarize, we present a freeze-thaw method for the creation of acellular bone explants, which is easy to perform, not time-consuming and provides consistent results.
Optically Tunable Tin Oxide-Coated Hollow Gold–Silver Nanorattles for Use in Solar-Driven Applications (2020)

Core@shell metal nanoparticles have emerged as promising photocatalysts because of their strong and tunable plasmonic properties; however, marked improvements in photocatalytic efficiency are needed if these materials are to be widely used in practical applications. Accordingly, the design of new and functional light-responsive nanostructures remains a central focus of nanomaterial research. To this end, we report the synthesis of nanorattles comprising hollow gold-silver nanoshells encapsulated within vacuous tin oxide shells of adjustable thicknesses (∼10 and ∼30 nm for the two examples prepared in this initial report). These composite nanorattles exhibited broad tunable optical extinctions ranging from ultraviolet to near-infrared spectral regions (i.e., 300-745 nm). Zeta potential measurements showed a large negative surface charge of approximately -35 mV, which afforded colloidal stability to the nanorattles in aqueous solution. We also characterized the nanorattles structurally and compositionally using scanning electron microscopy, transmission electron microscopy, and energy-dispersive X-ray spectroscopy. Futhermore, finite-difference time-domain simulation and photoluminescence properties of the composited nanoparticles were investigated. Collectively, these studies indicate that our tin oxide-coated hollow gold-silver nanorattles are promising candidates for use in solar-driven applications.
A straightforward electro-optic polymer covered titanium dioxide strip line modulator with a low driving voltage (2014)

An electro-optic (EO) modulator composed of an EO polymer/titanium dioxide (TiO2) hybrid waveguide has been designed and fabricated. By using a TiO2 strip line (0.3 × 0.3 μm2 cross-section) as the core, the confinement factor in the EO polymer is optimized, thus achieving a high EO activity. The coplanar electrode spacing is tuned to enable an effective poling and a small propagation loss. The measured in-device EO coefficient is 100 pm/V at 1550 nm, with a driving voltage (Vπ) 3.2 V for the 12 mm-electrode length. The results also predict a possible Vπ of ∼1 V in a push-pull MZI structure. The EO activity of the modulator exhibited an excellent temporal stability at 85 °C for 500 h due to the high glass transition temperature of the EO polymer and the temperature-insensitive TiO2 strip line.
Comparative degradation of oomycete, ascomycete, and basidiomycete cell walls by mycoparasitic and biocontrol fungi (2002)

Fourteen fungi (primarily representing mycoparasitic and biocontrol fungi) were tested for their ability to grow on and degrade cell walls (CWs) of an oomycete (Pythium ultimum), ascomycete (Fusarium equisetii), and basidiomycete (Rhizoctonia solani), and their hydrolytic enzymes were characterized. Protein was detected in the cultural medium of eleven of the test isolates, and these fungi significantly degraded CWs over the 14-day duration of the experiment. In general, a greater level of CW degradation occurred for F. equisetii and P. ultimum than for R. solani. Fungi that degraded F. equisetii CWs were Coniothyrium minitans, Gliocladium roseum, Myrothecium verrucaria, Talaromyces flavus, and Trichoderma harzianum. Taxa degrading P ultimum CWs included Chaetomium globosum, Coniothyrium minitans, M. verrucaria, Seimatosporium sp., Talaromyces flavus, Trichoderma hamatum, Trichoderma harzianum, and Trichoderma viride. Production of extracellular protein was highly correlated with CW degradation. Considerable variation in the molecular weights of CW-degrading enzymes were detected among the test fungi and the CW substrates in zymogram electrophoresis. Multivariate analysis between CW degradation and hydrolysis of barley beta-glucan (beta1,3- and beta1,4-glucanases), laminarin (beta1,3- and beta1,6-glucanases), carboxymethyl cellulose (endo-beta1,4-glucanases), colloidal chitin (chitinases), and chitosan (chitosanases) was conducted. For F. equisetii CWs, the regression model accounted for 80% of the variability, and carboxymethyl cellulases acting together with beta-glucanases contributed an R2 of 0.52, whereas chitinases and beta-glucanases alone contributed an R2 of 0.11 and 0.12, respectively. Only 61% of the variability observed in the degradation of P. ultimum CWs was explained by the enzyme classes tested, and primarily beta-glucanases (R2 of 0.53) and carboxymethyl cellulases (R2 of 0.08) alone contributed to CW break down. Too few of the test fungi degraded R. solani CWs to perform multivariate analysis effectively. This study identified several fungi that degraded ascomyceteous and oomyceteous, and to a lesser extent, basidiomycetous CWs. An array of enzymes were implicated in CW degradation.
Severe Pain in Chronic Pancreatitis Patients: Considering Mental Health and Associated Genetic Factors (2021)

Pain is the most distressing and disruptive feature of recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) resulting in low quality of life (QOL) and disabilities. There is no single, characteristic pain pattern in patients with RAP and CP. Abdominal imaging features of CP accurately reflect morphologic features but they do not correlate with pain. Pain is the major driver of poor quality of life (QOL) and it is the constant pain, rather than intermittent pain that drives poor QOL. Furthermore, the most severe constant pain experience in CP is also a complex condition. The ability to target the etiopathogenesis of severe pain requires new methods to detect the exact pain mechanisms in an individual at cellular, tissue, system and psychiatric levels. In patients with complex and severe disease, it is likely that multiple overlapping mechanisms are simultaneously driving pain, anxiety and depression. Quantitative sensory testing (QST) shows promise in detecting alterations in central processing of pain signals and to classify patients for mechanistic and therapeutic studies. New genetic research suggests that genetic loci for severe pain in CP overlap with genetic loci for depression and other psychiatric disorders, providing additional insights and therapeutic targets for individual patients with severe CP pain. Well-designed clinical trials that integrate clinical features, QST, genetics and psychological assessments with targeted treatment and assessment of responses are required for a quantum leap forward. A better understanding of the context and mechanisms contributing to severe pain experiences in individual patients is predicted to lead to better therapies and quality of life.