gebhart/patrepeval huggingface dataset:
LuxT controls specific quorum-sensing-regulated behaviors in Vibrionaceae spp. via repression of qrr 1, encoding a small regulatory RNA (2021)

Abstract Quorum sensing (QS) is a process of chemical communication bacteria use to transition between individual and collective behaviors. QS depends on the production, release, and synchronous response to signaling molecules called autoinducers (AIs). The marine bacterium Vibrio harveyi monitors AIs using a signal transduction pathway that relies on five small regulatory RNAs (called Qrr1-5) that post-transcriptionally control target genes. Curiously, the small RNAs function redundantly making it difficult to understand the necessity for five of them. Here, we identify LuxT as a transcriptional repressor of qrr 1. LuxT does not regulate qrr 2-5, demonstrating that qrr genes can be independently controlled to drive unique downstream QS gene expression patterns. LuxT reinforces its control over the same genes it regulates indirectly via repression of qrr 1, through a second transcriptional control mechanism. Genes dually regulated by LuxT specify public goods including an aerolysin-type pore-forming toxin. Phylogenetic analyses reveal that LuxT is conserved among Vibrionaceae and sequence comparisons predict that LuxT represses qrr 1 in additional species. The present findings reveal that redundant QS regulatory RNAs can carry out both shared and unique functions to endow bacteria with plasticity in their output behaviors. Author Summary Bacteria communicate and count their cell numbers using a process called quorum sensing (QS). In response to changes in cell density, QS bacteria alternate between acting as individuals and participating in collective behaviors. Vibrio harveyi is used as a model organism to understand QS-mediated communication. Five small RNAs lie at the heart of the V. harveyi QS system, and they regulate the target genes that underlie the QS response. The small RNAs function redundantly making it difficult to understand why V. harveyi requires five of them. Here, we discover a regulator, called LuxT, that exclusively represses the gene encoding one of the QS small RNAs. LuxT regulation of one QS small RNA enables unique control of a specific subset of QS target genes. LuxT is broadly conserved among Vibrionaceae . Our findings show how redundant regulatory components can possess both common and unique roles that provide bacteria with plasticity in their behaviors.
Viscosities and Sintering Rates of Composite Packings of Spheres (1995)

The effective sintering rates and viscosities of three‐dimensional composite packings have been studied using a discrete numerical model. The packings consist of random mixtures of hard and soft spheres of the same size. With increasing substitution of hard particles for soft particles in the packing, the viscosity increases and the sintering rate decreases. This is particularly abrupt at well‐defined rigidity thresholds where there is a transition from softlike to hardlike behavior. The site fraction of hard particles at which the transition occurs depends on the nature of the interaction between hard particles. When the contact between hard particles resists all six relative degrees of freedom (relative velocities and spins), the bonded case, the rigidity threshold coincides with the percolation threshold (site fraction ∼0.32). When the contact between hard particles resists only interpenetration, the sliding case, the threshold occurs at a site fraction of hard particles very close to unity. Results for the variation of effective properties with site fraction of hard particles are presented for these and other cases. These results can also be applied to the study of elastic percolating networks.
Influence of shear on a lamellar triblock copolymer near the order–disorder transition (1997)

The effects of a large strain (600%) reciprocating steady shear on the lamellar orientation and the order–disorder transition of a nearly symmetric poly(ethylene propylene)–poly(ethylethylene)–poly(ethylene propylene) (PEP–PEE–PEP) triblock copolymer have been studied using small-angle neutron scattering and rheological measurements. Shearing in the ordered state produced parallel lamellae under all steady-state conditions investigated, and the lamellar-to-disorder transition temperature decreased dramatically with increasing shear rate. Both phenomena are qualitatively different from the documented behavior of PEP–PEE diblock copolymers. However, cooling the disordered material while shearing at a relatively low deformation rate initially induces perpendicular lamellae, analogous to the diblock response. These observations are considered in the context of theory and other experimental studies.
The Pretreatment and Conventional Wet Painting of Aluminium Extrusions (1980)

SummaryThe growth of the painted aluminium extrusion market is described, with the development of phosphate and chromate conversion coatings and he application of conventional solvent-borne paints. Conversion coatings are compared with anodizing. The properties of the two main pretreatment processes and their control are discussed, together with faults arising from poor control. The particular deoxidising problem of extrusions is highlighted, with mention of full process sequences used and plant designs. Rinsing and effluent factors are also discussed. Types of solvent-borne paints are compared and the performance of the full system discussed in relation to relevant specifications. Application equipment for these paints is referred to and mention made of the more recent organic finishing methods.
Physiological activation of PKC-alpha via the calcium sensing receptor is not required for the Ca2+-regulated secretion of parathyroid hormone in dispersed bovine parathyroid cells (2004)

Physiological activation of PKC-alpha via the calcium sensing receptor is not required for the Ca2+-regulated secretion of parathyroid hormone in dispersed bovine parathyroid cells
Leukemic transformation by the MLL-AF6 fusion oncogene requires the H3K79 methyltransferase Dot1l (2013)

The t(6;11)(q27;q23) is a recurrent chromosomal rearrangement that encodes the MLLAF6 fusion oncoprotein and is observed in patients with diverse hematologic malignancies. The presence of the t(6;11)(q27;q23) has been linked to poor overall survival in patients with AML. In this study, we demonstrate that MLL-AF6 requires continued activity of the histone-methyltransferase DOT1L to maintain expression of the MLL-AF6-driven oncogenic gene-expression program. Using gene-expression analysis and genome-wide chromatin immunoprecipitation studies followed by next generation sequencing, we found that MLL-fusion target genes display markedly high levels of histone 3 at lysine 79 (H3K79) dimethylation in murine MLL-AF6 leukemias as well as in ML2, a human myelomonocytic leukemia cell line bearing the t(6;11)(q27;q23) translocation. Targeted disruption of Dot1l using a conditional knockout mouse model inhibited leukemogenesis mediated by the MLL-AF6 fusion oncogene. Moreover, both murine MLL-AF6-transformed cells as well as the human MLL-AF6-positive ML2 leukemia cell line displayed specific sensitivity to EPZ0004777, a recently described, selective, small-molecule inhibitor of Dot1l. Dot1l inhibition resulted in significantly decreased proliferation, decreased expression of MLL-AF6 target genes, and cell cycle arrest of MLL-AF6-transformed cells. These results indicate that patients bearing the t(6;11)(q27;q23) translocation may benefit from therapeutic agents targeting aberrant H3K79 methylation.
Molecular mechanism of interleukin-8 gene expression (1994)

A potent leukocyte chemotactic and activating cytokine, interleukin-8 (IL-8), is produced by numerous types of cells in response to inflammatory stimuli. Accumulating evidence indicate that the transcription of IL-8 gene requires the activation of either the combination of NF-kappa B and AP-1 or that of NF-kappa B and NF-IL6, depending on the type of cells. Alternatively, the activation of NF-kappa B is indispensable for IL-8 gene activation in any types of cells examined. On the other hand, an immunosuppressant, FK506, and a glucocorticoid inhibit the gene transcription as well as the production of IL-8. Molecular analyses of IL-8 gene repression by these agents revealed that both affected the activity of the transcription factor(s) bound to the NF-kappa B site, albeit in different ways, thereby suppressing IL-8 gene transcription. Collectively, IL-8 production seems to be controlled mainly at the activation step of the transcription factor(s) bound to the NF-kappa B site.
Quantitative Analysis of the Effect of Salt Concentration on Enzymatic Catalysis (2001)

Like pH, salt concentration can have a dramatic effect on enzymatic catalysis. Here, a general equation is derived for the quantitative analysis of salt-rate profiles: k(cat)/K(M) = (k(cat)/K(M))(MAX)/[1+([Na+]/K[Na+])(n')], where (k(cat)/K(M))(MAX) is the physical limit of k(cat)/K(M), K(Na+) is the salt concentration at which k(cat)/K(M) = (k(cat)/K(M))(MAX)/2, and -n' is the slope of the linear region in a plot of log(k(cat)/K(M)) versus log [Na+]. The value of n' is of special utility, as it reflects the contribution of Coulombic interactions to the uniform binding of the bound states. This equation was used to analyze salt effects on catalysis by ribonuclease A (RNase A), which is a cationic enzyme that catalyzes the cleavage of an anionic substrate, RNA, with k(cat)/K(M) values that can exceed 10(9) M(-1) s(-1). Lys7, Arg10, and Lys66 comprise enzymic subsites that are remote from the active site. Replacing Lys7, Arg10, and Lys66 with alanine decreases the charge on the enzyme as well as the value of n'. Likewise, decreasing the number of phosphoryl groups in the substrate decreases the value of n'. Replacing Lys41, a key active-site residue, with arginine creates a catalyst that is limited by the chemical conversion of substrate to product. This change increases the value of n', as expected for a catalyst that is more sensitive to changes in the binding of the chemical transition state. Hence, the quantitative analysis of salt-rate profiles can provide valuable insight into the role of Coulombic interactions in enzymatic catalysis.
Transcutaneous Battery Recharging By Volume Conduction and its Circuit Modeling (2006)

Many implantable devices require large capacity batteries implanted in the body. Transcutaneous battery recharging can effectively maintain the longevity of these implants. Based on this consideration we have developed a transcutaneous battery recharging circuit unit which takes advantages of skin volume conduction. This unit is able to pass 2.8 mA from the outside to the inside of pig skin with a current transmitting efficiency of 27%. Theoretical analysis and experiments have validated that this battery recharging technology is an effective approach. In this research we have constructed an x-type equivalent circuit model of skin volume conduction for battery recharging. The parameters of the x-type equivalent circuit can be easily measured and used to evaluate the battery charging system characteristics, such as the rechargeable prerequisite and the current transmitting efficiency limitation. We have analyzed the transcutaneous current transmitting efficiency by applying the x-type equivalent circuit model and discussed approaches for enhancing current transmitting efficiency.
Synthesis and characterization of poly(arylene ether sulfone) copolymers with sulfonimide side groups for a proton‐exchange membrane (2006)

Abstract A sulfonimide‐containing comonomer derived from 4,4′‐dichlorodiphenylsulfone was synthesized and copolymerized with 4,4′‐dichlorodiphenylsulfone and 4,4′‐biphenol to prepare sulfonimide‐containing poly(arylene ether sulfone) random copolymers (BPSIs). These copolymers showed slightly higher water uptake than disulfonated poly(arylene ether sulfone) copolymer (BPSH) controls, but their proton‐conductivity values were very comparable to those of the BPSH series with similar ion contents. The proton conductivity increased with the temperature for both systems. For samples with 30 mol % ionic groups, BPSI showed less temperature dependence in proton conductivity and slightly higher methanol permeability in comparison with BPSH. The thermal characterization of the sulfonimide copolymers showed that both the acid and salt forms were stable up to 250 °C under a nitrogen atmosphere. The results suggested that the presumed enhanced stability of the sulfonimide systems did not translate into higher protonic conductivity in liquid water. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 6007–6014, 2006
Cas9 interrogates DNA in discrete steps modulated by mismatches and supercoiling (2020)

The CRISPR-Cas9 nuclease has been widely repurposed as a molecular and cell biology tool for its ability to programmably target and cleave DNA. Cas9 recognizes its target site by unwinding the DNA double helix and hybridizing a 20-nucleotide section of its associated guide RNA to one DNA strand, forming an R-loop structure. A dynamic and mechanical description of R-loop formation is needed to understand the biophysics of target searching and develop rational approaches for mitigating off-target activity while accounting for the influence of torsional strain in the genome. Here we investigate the dynamics of Cas9 R-loop formation and collapse using rotor bead tracking (RBT), a single-molecule technique that can simultaneously monitor DNA unwinding with base-pair resolution and binding of fluorescently labeled macromolecules in real time. By measuring changes in torque upon unwinding of the double helix, we find that R-loop formation and collapse proceed via a transient discrete intermediate, consistent with DNA:RNA hybridization within an initial seed region. Using systematic measurements of target and off-target sequences under controlled mechanical perturbations, we characterize position-dependent effects of sequence mismatches and show how DNA supercoiling modulates the energy landscape of R-loop formation and dictates access to states competent for stable binding and cleavage. Consistent with this energy landscape model, in bulk experiments we observe promiscuous cleavage under physiological negative supercoiling. The detailed description of DNA interrogation presented here suggests strategies for improving the specificity and kinetics of Cas9 as a genome engineering tool and may inspire expanded applications that exploit sensitivity to DNA supercoiling.
Usable bootstrapping of secure ad hoc communication (2010)

Many security services rely on trusted third parties (TTPs), such as off-line Certification Authorities (CA-s) or online key servers, to enable authentication and secure communication among devices and their users. However, in many applications it is impractical to assume the existence of such trusted TTPs. In particular, some applications require direct communication between two or more wireless personal devices that have no prior context and no common point of trust or pre-shared secrets.
In this thesis, we look into the problem of establishing secure ad-hoc communication among devices that have no prior security context or a TTP. The main research contributions of this thesis are: (1) Show how to establish secure ad-hoc communication over a short-range wireless communication channel using three new approaches each having some obvious advantages over the currently available solutions. (a) We demonstrate how audio can be utilized in establishing secure communication. Our methods enable secure pairing of devices, such as a cell phone and a bluetooth headset or a smart phone and a laptop. We argue that using audio as the human-perceivable channel in secure communication establishment has some distinct advantages. (b) We introduce a suite of secure pairing protocols tailored for interface-constraint devices. These protocols impose truly minimal user interface constraints: a single button or a means of one-bit output such as an LED. (c) We introduce a new method of bootstrapping secure communication in sensor networks, taking into account unique requirements of the underlying environment. We use the fact that sensors have identical wireless transceivers and symmetrical physical properties of wireless signals between communicating parties can be utilized to derive secrets that are then used to secure communication. (2) Analyze security and usability of various secure bootstrapping methods. After implementing the methods within a common software platform, we conducted extensive user studies. We conducted these studies in two flavors: (a) Bootstrapping secure communication in one-user setting: a single user establishing secure communication between two of his/her devices. (b) Bootstrapping secure communication in social settings: multiple users establishing secure communication among their respective devices. We conducted separate studies for two-user and group scenarios.
Early Diagnosis and Treatment of Medullary Thyroid Carcinoma (1985)

Medullary thyroid carcinoma (MTC) was first described as a distinct clinical entity by Hazard et al<sup>1</sup>in 1959. Although the lesion was previously thought to be a variant of anaplastic thyroid carcinoma, these investigators appreciated that certain histologic characteristics distinguished it from other thyroid neoplasms. Actually, MTC is derived not from follicular or stromal elements but from neural crest cells, which in mammals are incorporated within the thyroid gland. In birds and fish these cells exist as a separate structure called the ultimobranchial body. In retrospect, it is surprising that MTC was not recognized sooner as being different from other thyroid malignant neoplasms because it has certain unique characteristics, including frequent involvement of both thyroid lobes, occurrence in a familial pattern with assocated endocrinopathies (multiple endocrine neoplasia [MEN] types IIa and IIb), the presence in the tumor of a substance with the histochemical staining properties of amyloid, and the
Genetic interstitial lung disease: an unusual case (2018)

Genetic causes of children interstitial lung disease (ChILD) represent close to 20 % of the cases. We present here the first case of ChILD associated with 48, XXYY syndrome. An 11- months-old boy was admitted to investigate a chronic dyspnea with cough and failure to thrive. His medical history was unremarkable with respect of transient neonatal respiratory distress in a full-term baby. Physical exam at presentation revealed chest wall retraction, basolateral scattered wet crackles and mild hypoxemia requiring nocturnal supplemental oxygen. Metabolic and infectious investigations were unremarkable as were thyroid function and cardiologic assessments. High resolution CT (HRCT) scan was performed showing bilateral ground glass opacities. Monthly intravenous methyl prednisolone pulses were initiated. Despite respiratory function improvement with lower respiratory rate, improvement of chest retraction and weaning of oxygen therapy, HRCT worsened with persistent diffuse bilateral ground-glass opacity. Genetic screening for inherited surfactant metabolism disorders was performed. Interestingly, no mutation was detected in surfactant genes, but search for NKX2-1 large rearrangement by MLPA technology, using probes in chromosomes X and Y as controls, highlighted the presence of excessive genetic material suggesting the abnormal karyotype 48, XXYY, which was further confirmed by cytogenetic method. After 16 months of bolus methylprednisolone therapy, respiratory condition and imaging significantly improve. Besides, developmental delay and cognitive problems were noticed. Overexpression of the CSF2RA gene (GMCSF receptor) located in the pseudoautosomal region of the X and Y chromosomes may explain the lung phenotype.
Control of surface wetting via production of graft polymer chains with adaptive behavior (2013)

The paper reviews control of surface wetting via the production of polymer coatings sensitive to changes in external conditions. Graft polymer compositions having the adaptive properties are obtained by method of surface-initiated atom transfer radical polymerization on aluminum surface. The chemical composition of polymer coatings is confirmed by X-ray photoelectron spectroscopy. The morphology of the modified surface is investigated by scanning electron microscopy. The possibility of wetting control of modified aluminum surfaces modified in a wide range with a change in the pH value and temperature is shown.
A prospective, multi-site, cohort study to estimate incidence of infection and disease due to Lassa fever virus in West African countries (the Enable Lassa research programme)–Study protocol (2023)

Data on LASV infection and LF disease incidence in West Africa from this research programme will determine the feasibility of future Phase IIb or III clinical trials for LF vaccine candidates.
Liposomal Bupivacaine (Bupigel) Demonstrates Minimal Local Nerve Toxicity in a Rabbit Functional Model (2021)

We previously reported the development of a novel formulation of an ultra-long-acting local anesthetic based on bupivacaine encapsulated in large multivesicular liposomes (Bupisomes) embedded in hydrogel. This formulation (Bupigel) prolonged bupivacaine release from the formulation in dissolution-like studies in vitro and analgesia in vivo in mouse, rat, and pig models. In this study we assessed Bupigel neurotoxicity on rabbit sciatic nerve using histopathology and electrophysiologic testing. Sciatic nerves of both hind limbs were injected dropwise with different formulations. Nerve conduction studies and needle electromyography two weeks after perineural administration showed signs of neural damage after injection of free lidocaine and bupivacaine, while there was no sign of neural damage after injection with saline, demonstrating the validity of the method. This test also did not show evidence of motor or sensory nerve damage after injection with liposomal bupivacaine at a dose 10-times higher than free bupivacaine. Histologically, signs of neural damage could be observed with lidocaine. Nerves injected with Bupigel showed mild signs of inflammation and small residues of hydrogel in granulomas, indicating a long residence time of the hydrogel at the site of injection, but no histopathological signs of nerve damage. This demonstrated that early signs of neural damage were detected electrophysiologically, showing the usefulness and sensitivity of electrodiagnostic testing in detection of neural damage from new formulations.
Inclusion of relevant tests in the Pharmacopoeia to improve supply chain integrity (2013)

Because current compendial methods are not sufficiently robust, specific or rapid enough for many excipients, compliance with specifications is a complement, not a substitute for supply chain security. Multiple and more specific tests will hinder economically motivated adulteration. Specifications should be improved, supply chain oversight tightened, and caveat emptor!