gebhart/patrepeval huggingface dataset:
Rational design of aptazyme riboswitches for efficient control of gene expression in mammalian cells (2016)

Efforts to control mammalian gene expression with ligand-responsive riboswitches have been hindered by lack of a general method for generating efficient switches in mammalian systems. Here we describe a rational-design approach that enables rapid development of efficient <i>cis</i>-acting aptazyme riboswitches. We identified communication-module characteristics associated with aptazyme functionality through analysis of a 32-aptazyme test panel. We then developed a scoring system that predicts an aptazymes's activity by integrating three characteristics of communication-module bases: hydrogen bonding, base stacking, and distance to the enzymatic core. We validated the power and generality of this approach by designing aptazymes responsive to three distinct ligands, each with markedly wider dynamic ranges than any previously reported. These aptayzmes efficiently regulated adeno-associated virus (AAV)-vectored transgene expression in cultured mammalian cells and mice, highlighting one application of these broadly usable regulatory switches. Our approach enables efficient, protein-independent control of gene expression by a range of small molecules.
Structural modifications of highly porous silica aerogels upon densification (1991)

Structural changes during isothermal sintering were studied for two base-catalyzed SiO2 aerogels with initial densities ρ1 = 122 and 256 kg m−3 by means of small-angle X-ray scattering (SAXS). The relevant structural parameters are the specific surface area, which is determined by the size of the compact primary particles, the mean diameter of the secondary particles, which represent the building blocks of the gel network, and finally the size of the macropores within the tenuous tertiary structure. The major finding of our investigations is the observation of two sintering processes with different time scales: a fast reduction of the size of the macropores and a slow increase in the diameter of the secondary particles as well as a relatively small decrease in the specific surface area. For the two samples investigated the changes of these parameters can be unequivocally correlated with the achieved density upon sintering – independent of the initial density.
Stilbene synthase from Scots pine (Pinus sylvestris) (1992)

Stilbene synthases are named according to their substrate preferences. By this definition, enzymes preferring cinnamoyl-CoA are pinosylvin synthases, and proteins with a preference for phenylpropionyl-CoA are dihydropinosylvin synthases. We investigated the assignment of a stilbene synthase cloned from Scots pine (Pinus sylvestris) as dihydropinosylvin synthase and the proposal of an additional pinosylvin synthase [1992, Plant Mol. Biol. 18, 489-503]. The results show that the previous interpretation was misled by several unexpected factors. Firstly, we found that the substrate preference and the activity of the plant-specific protein expressed in E. coli was influenced by bacterial factors. This was reduced by improvement of the expression system, and the subsequent kinetic analysis revealed that cinnamoyl-CoA rather than phenylpropionyl-CoA is the preferred substrate of the cloned stilbene synthase. Secondly, mixing experiments showed that extracts from P. sylvestris contain factor(s) which selectively influenced the substrate preference, i.e. the activity was reduced with phenylpropionyl-CoA, but not with cinnamoyl-CoA. This explained the apparent differences between plant extracts and the cloned enzyme expressed in E. coli. Taken together, the results indicate that the cloned enzyme is a pinosylvin synthase, and there is no evidence for a second stilbene synthase. This study cautions that factors in the natural and in new hosts may complicate the functional identification of cloned sequences.
Clinical impact and diagnosis of human metapneumovirus infection (2004)

Worldwide, hMPV infections account for at least 5 to 7% of the RTI in hospitalized children, but immunocompromised and elderly individuals are also at risk. In the general community hMPV infections account for at least 3% of patients who visit a general practitioner for RTI. The seasonality of hMPV infections resembles that for respiratory syncytial virus and influenza virus infections, with recurrent epidemics during the winter months. Clinical symptoms and laboratory findings associated with hMPV infection exhibit a spectrum virtually indistinguishable from those associated with respiratory syncytial virus disease. The development of diagnostic assays must take into account the existence of two hMPV serotypes.
ISIS-14803 (Isis Pharmaceuticals). (2001)

Isis and Merck are developing an antisense oligonucleotide for the potential treatment of hepatitis C virus (HCV) infection [305306]. As of March 2000, the lead from this program, ISI-14803, was being studied in a phase I/II trial where it was administered in three weekly 2-h infusions for 4 weeks [327913], [357823]. Based on these results Isis plans to evaluate the potential of ISIS-14803 in single-agent trials and in combination studies with PEGylated interferon and ribavirin, and in studies that will examine longer-term dosing with both i.v. and s.c. administration [412920]. In January 2000, Isis signed a binding letter of agreement with Elan to form a new subsidiary of Isis to develop ISIS-14803 [351881], [362727]. In October 2001, Isis reported that it had earned a $1.5 million research milestone payment from Merck for progress in this collaboration [426015].
Light-triggered electrical and optical switching devices (1993)

The functional photoswitchable systems 1–3 and 12–15 display pronounced photochromic properties; the bis-pyridinium derivative 1 represents a prototype of a switched molecular wire which may be converted from an open unconjugated form to a closed electron-conducting state.
Principles for Measurement of Chemical Exposure Based on Recognition-Driven Anchoring Transitions in Liquid Crystals (2001)

The competitive binding of a molecule forming a liquid crystal and a targeted analyte to a common molecular receptor presented at a solid surface possessing nanometer-scale topography is used to trigger an easily visualized surface-driven change in the orientation of a micrometer-thick film of liquid crystal. Diffusion of the targeted analyte from atmosphere to surface-immobilized receptor across the micrometer-thick film of liquid crystal is fast (on the order of seconds), and the competitive interaction of the targeted analyte and liquid crystal with the receptor provides a high level of tolerance to nontargeted species (water, ethanol, acetone, and hexanes). Systems that provide parts-per-billion (by volume) sensitivity to either organoamine or organophosphorus compounds are demonstrated, and their use for imaging of spatial gradients in concentration is reported. This approach does not require complex instrumentation and could provide the basis of wearable personalized sensors for measurement of real-time and cumulative exposure to environmental agents.
[Treatment of chronic viral hepatitis B in secondary membranoproliferative glomerulonephritis using recombinant alfa-2 interferon]. (2000)

A patient suffering from viral hepatitis B and secondary membranoproliferative glomerulonephritis was presented. He was treated with recombinant alfa-2 interferon. The therapy led to clinical and biochemical remission of the liver and kidney lesions. The example of our patient justifies the use of recombinant alfa-2 interferon in the patients with chronic viral hepatitis B and secondary glomerulonephritis.
Oxidation and Reduction of Cerium(IV) Sandwich Complexes with Porphyrin Ligands Linked by Aliphatic Diether Bridges of Variable Chain Length (1998)

Starting from 5-(4-hydroxyphenyl)-10,15,20-tris(4-methylphenyl)porphyrin (2a), the new bis(porphyrinyloxy)alkanes 4a and 4d were synthesized by ether formation with the α,ω-dibromoalkanes Br(CH2)nBr (n = 8, 11; 3a, 3d). 4a was obtained by a two-step reaction with the 5-[4-(8-bromooctyloxy)phenyl]-10,15,20-tris(4-methylphenyl)porphyrin (2b) as an intermediate. The diporphyrins 4a and 4d were metalated with cerium(III) acetylacetonate to yield the new (porphyrin)cerium sandwich complexes 1a and 1d which were characterized by UV/Vis, IR, 1H-NMR, 13C-NMR spectroscopy and cyclic voltammetry. The mono- and dications and the cerium(III) bisporphyrinate anions of 1a-d were produced by electrochemical oxidation and reduction, respectively, and were examined by UV/Vis/NIR spectroscopy. The length of the lateral chains does not have a specific effect on the first and second oxidation potentials of the porphyrin rings and the reduction potentials of the cerium ions in the bisporphyrinate systems, and on the energy of the NIR bands of the monocations.
Loss of the MYC gene amplified in human HL-60 cells after treatment with inhibitors of poly(ADP-ribose) polymerase or with dimethyl sulfoxide. (1989)

In HL-60 cells, a human promyelocytic leukemia cell line, the human c-myc gene, designated MYC, is amplified about 16-fold. On differentiation of the HL-60 cells into granulocytes induced by several inhibitors of poly(ADP-ribose) polymerase [NAD+ poly(adenosine diphosphate D-ribose)ADP-D-ribosyltransferase, EC 2.4.2.30] including benzamide, nicotinamide, coumarin, and 4-hydroxyquinazoline or dimethyl sulfoxide, some MYC loss was observed. In contrast, benzoic acid, a noninhibitory analogue of benzamide, did not induce either granulocytic differentiation or loss of MYC. Loss of MYC seems to be associated with granulocytic differentiation because the time course of its loss was similar to that of appearance of nitroblue tetrazolium-positive cells, mature granulocytes, and its loss was not observed on differentiation of HL-60 cells into macrophages induced by phorbol 12-myristate 13-acetate or teleocidin. The loss of MYC is not the reason for the down regulation of MYC expression observed within 1 hr after addition of inducers, since the loss of MYC was not detected by 1-day treatment with inducers.
Conversion of Xenopus Ectoderm into Neurons by NeuroD, a Basic Helix-Loop-Helix Protein (1995)

Basic helix-loop-helix (bHLH) proteins are instrumental in determining cell type during development. A bHLH protein, termed NeuroD, for neurogenic differentiation, has now been identified as a differentiation factor for neurogenesis because (i) it is expressed transiently in a subset of neurons in the central and peripheral nervous systems at the time of their terminal differentiation into mature neurons and (ii) ectopic expression of neuroD in Xenopus embryos causes premature differentiation of neuronal precursors. Furthermore, neuroD can convert presumptive epidermal cells into neurons and also act as a neuronal determination gene. However, unlike another previously identified proneural gene (XASH-3), neuroD seems competent to bypass the normal inhibitory influences that usually prevent neurogenesis in ventral and lateral ectoderm and is capable of converting most of the embryonic ectoderm into neurons. The data suggest that neuroD may participate in the terminal differentiation step during vertebrate neuronal development.
3D Human Pose Estimation in Video With Temporal Convolutions and Semi-Supervised Training (2019)

In this work, we demonstrate that 3D poses in video can be effectively estimated with a fully convolutional model based on dilated temporal convolutions over 2D keypoints. We also introduce back-projection, a simple and effective semi-supervised training method that leverages unlabeled video data. We start with predicted 2D keypoints for unlabeled video, then estimate 3D poses and finally back-project to the input 2D keypoints. In the supervised setting, our fully-convolutional model outperforms the previous best result from the literature by 6 mm mean per-joint position error on Human3.6M, corresponding to an error reduction of 11%, and the model also shows significant improvements on HumanEva-I. Moreover, experiments with back-projection show that it comfortably outperforms previous state-of-the-art results in semi-supervised settings where labeled data is scarce. Code and models are available at https://github.com/facebookresearch/VideoPose3D.
The different binding modes of Hoechst 33258 to DNA studied by electirc linear dichroism (1993)

The binding mode of the bisbenzimidazole derivative Hoechst 33258 to a series of DNAs and polynucleotides has been investigated by electric linear dichroism. Positive reduced dichroisms were measured for the poly(dA-dT).poly(dA-dT)- and poly(dA).poly(dT)-Hoechst complexes in agreement with a deep penetration of the drug into the minor groove. Similarly, the drug displays positive reduced dichroism in the presence of the DNAs from calf thymus, Clostridium perfringens and Coliphage T4. Conversely, negative reduced dichroisms were obtained when Hoechst 33258 was bound to poly(dG-dC).poly(dG-dC), poly(dA-dC).poly(dG-dT) and poly(dG).poly(dC) as well as with the GC-rich DNA from Micrococcus lysodeikticus indicating that in this case minor groove binding cannot occur. Substitution of guanosines for inosines induces a reversal of the reduced dichroism from negative to positive. Therefore, as anticipated it is the 2-amino group of guanines protruding in this groove which prevents Hoechst 33258 from getting access to the minor groove of GC sequences. The ELD data obtained with the GC-rich biopolymers are consistent with an intercalative binding. Competition experiments performed with the intercalating drug proflavine lend credence to the involvement of an intercalative binding rather than to an external or major groove binding of Hoechst 33258 at GC sequences.
The Pivotal Role of 5-Lipoxygenase Products in the Reaction of Aspirin-sensitive Asthmatics to Aspirin (1993)

A subset of persons with asthma develop bronchospasm, naso-ocular, gastrointestinal, and/or dermal reactions after ingesting aspirin (ASA) or agents with the capacity to inhibit cyclooxygenase. The bronchopulmonary reactions have been associated with a rise in urinary LTE4. We examined the effects of an inhibitor of 5-lipoxygenase, zileuton, in a group of eight asthmatic patients with known sensitivity to ASA accompanied by LTE4 hyperexcretion. We first confirmed ASA sensitivity and an increase in urinary LTE4 after ASA ingestion in these patients using a placebo-controlled ASA challenge. Subjects were then randomized to a double-blind, crossover trial to examine the effects of zileuton versus placebo on the response to ASA. Zileuton treatment decreased baseline urinary LTE4 excretion from a mean of 469 +/- 141 pg/mg creatinine to 137 +/- 69 pg/mg creatinine (p < 0.02) and blunted the maximum increase in urinary LTE4 after ingestion of ASA (3,539 +/- 826 pg/mg creatinine versus 1,120 +/- 316 pg/mg creatinine [p < 0.01]). The pre-ASA challenge FEV1 was unchanged by zileuton (3.41 +/- 0.15 L versus 3.35 +/- 0.17 L, zileuton versus placebo). Zileuton prevented the fall in FEV1 in response to ingestion of ASA; post-ASA ingestion the mean of the minimal FEV1 fell to 2.72 +/- 0.18 L on the placebo day while there was no significant fall on the zileuton day (3.26 +/- 0.17 L; p < 0.014). Zileuton also prevented the development of the nasal, gastrointestinal (p < 0.006 and p < 0.025, respectively), and dermal symptoms which developed after ASA ingestion.(ABSTRACT TRUNCATED AT 250 WORDS)
The Salmonella typhimurium invasion genes invF and invG encode homologues of the AraC and PulD family of proteins (1994)

We have identified two novel Salmonella typhimurium genes, invF and invG, which are required for the efficient entry of these organisms into cultured epithelial cells. invF and invG are located immediately upstream of invE, a previously identified gene also required for Salmonella entry. Non-polar mutations in these genes rendered S. typhimurium severely deficient for entry into cultured epithelial cells. The nucleotide sequences of invF and invG indicated that these genes encode polypeptides with predicted molecular weights of 24,373 and 62,275, respectively. Proteins of similar sizes were observed when invF and invG were expressed in a bacteriophage T7 RNA polymerase-based expression system. Comparison of the predicted sequence of InvF with translated sequences in the existing databases indicated that this protein is homologous to members of the AraC family of prokaryotic transcription regulators. However, mutations in invF did not significantly affect the expression of other members of the inv locus. InvG was found to be homologous to members of the PulD family of specialized translocases. This homology suggests that InvG may be necessary for the export of invasion-related determinants or involved in the assembly of a supramolecular structure that promotes entry.
Infection Control in Gene Therapy (1999)

Abstract Gene therapy is now being studied for the treatment of a wide variety of acquired and inherited diseases. Viruses used as vectors for gene transfer include retroviruses, adenoviruses, vaccinia viruses, adeno-associated viruses, and herpesviruses. These vectors, developed in the laboratory and in animal studies, are now being introduced into the clinical arena. Infection control practitioners will be involved invariably in reviewing the use of these agents in their clinics and hospitals. This review summarizes key aspects of the more common vectors and makes recommendations for infection control.
Cyclodextrin and Polyethylenimine Functionalized Mesoporous Silica Nanoparticles for Delivery of siRNA Cancer Therapeutics (2014)

Effective delivery holds the key to successful in vivo application of therapeutic small interfering RNA (siRNA). In this work, we have developed a universal siRNA carrier consisting of a mesoporous silica nanoparticle (MSNP) functionalized with cyclodextrin-grafted polyethylenimine (CP). CP provides positive charge for loading of siRNA through electrostatic interaction and enables effective endosomal escape of siRNA. Using intravital microscopy we were able to monitor tumor enrichment of CP-MSNP/siRNA particles in live mice bearing orthotopic MDA-MB-231 xenograft tumors. CP-MSNP delivery of siRNA targeting the M2 isoform of the glycolytic enzyme pyruvate kinase (PKM2) resulted in effective knockdown of gene expression in vitro and in vivo. Suppression of PKM2 led to inhibition of tumor cell growth, invasion, and migration.
Low-Intensity Light Therapy: Exploring the Role of Redox Mechanisms (2008)

Low-intensity light therapy (LILT) appears to be working through newly recognized photoacceptor systems. The mitochondrial electron transport chain has been shown to be photosensitive to red and near-infrared (NIR) light. Although the underlying mechanisms have not yet been clearly elucidated, mitochondrial photostimulation has been shown to increase ATP production and cause transient increases in reactive oxygen species (ROS). In some cells, this process appears to participate in reduction/oxidation (redox) signaling. Redox mechanisms are known to be involved in cellular homeostasis and proliferative control. In plants, photostimulation of the analogous photosynthetic electron transport chain leads to redox signaling known to be integral to cellular function. In gene therapy research, ultraviolet lasers are being used to photostimulate cells through a process that also appears to involve redox signaling. It seems that visible and near visible low-intensity light can be used to modulate cellular physiology in some nonphotosynthetic cells, acting through existing redox mechanisms of cellular physiology. In this manner, LILT may act to promote proliferation and/or cellular homeostasis. Understanding the role of redox state and signaling in LILT may be useful in guiding future therapies, particularly in conditions associated with pro-oxidant conditions.
Pattern of cytokines and pharmacomodulation in sepsis induced by cecal ligation and puncture compared with that induced by endotoxin (1995)

The production of tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6 and their pharmacomodulation were evaluated in a model of polymicrobial sepsis induced in mice by cecal ligation and puncture (CLP) and were compared with the effects of endotoxin (lipopolysaccharide [LPS]) treatment. LPS levels rose as early as 1 h after CLP and increased further after 2 and 21 h. TNF-alpha was detectable in serum, spleen, liver, and lungs during the first 4 h, with a peak 2 h after CLP. IL-1 beta was measurable in serum after 24 h, and levels increased significantly in spleen and liver 4 and 8 h after CLP. IL-6 levels increased significantly in serum throughout the first 16 h after CLP. These cytokines were detectable after LPS injection, with kinetics similar to those after CLP but at a significantly higher level. To cast more light on the differences between these two animal models of septic shock, we studied the effects of different reference drugs. Pretreatment with dexamethasone (DEX); ibuprofen (IBU), an inhibitor of cyclooxygenase; and NG-nitro-L-arginine, an inhibitor of nitric oxide synthase, significantly reduced survival, while chlorpromazine (CPZ) and TNF did not affect it. Only the antibiotics and pentoxifylline significantly increased survival in mice with CLP. However, CPZ and DEX protected the mice from LPS mortality. On inhibiting TNF-alpha with DEX, CPZ, or pentoxifylline, survival was reduced, unchanged, and increased, respectively, and on increasing TNF-alpha with IBU and TNF, survival was decreased or unchanged, respectively, suggesting that the modulation of this cytokine does not play a significant role in sepsis induced by CLP, unlike treatment with LPS. The negative effects of IBU and N(G)-nitro-L-arginine suggest a protective role by prostaglandins and nitric oxide in sepsis induced by CLP.
A Catalytic Domain of Eukaryotic DNA Topoisomerase I (1998)

Eukaryotic type IB topoisomerases catalyze the cleavage and rejoining of DNA strands through a DNA-(3'-phosphotyrosyl)-enzyme intermediate. The 314-amino acid vaccinia topoisomerase is the smallest member of this family and is distinguished from its cellular counterparts by its specificity for cleavage at the target sequence 5'-CCCTT downward arrow. Here we show that Topo-(81-314), a truncated derivative that lacks the N-terminal domain, performs the same repertoire of reactions as the full-sized topoisomerase: relaxation of supercoiled DNA, site-specific DNA transesterification, and DNA strand transfer. Elimination of the N-terminal domain slows the rate of single-turnover DNA cleavage by 10(-3.6), but has little effect on the rate of single-turnover DNA religation. DNA relaxation and strand cleavage by Topo-(81-314) are inhibited by salt and magnesium; these effects are indicative of reduced affinity in noncovalent DNA binding. We report that identical properties are displayed by a full-length mutant protein, Topo(Y70A/Y72A), which lacks two tyrosine side chains within the N-terminal domain that contact the DNA target site in the major groove. We speculate that Topo-(81-314) is fully competent for transesterification chemistry, but is compromised with respect to a rate-limiting precleavage conformational step that is contingent on DNA contacts made by Tyr-70 and Tyr-72.
A conceptual model for vehicle navigation systems (2003)

The author shows how his conceptual model relates to the cognitive processes that go on during vehicle navigation and driving. Conceptually, the system may include human minds as well as various vehicle navigation aids. It must be able to perform five fundamental functions: geographic database, location of vehicle and destination, route planning, instruction generation, and vehicle control. It also must provide links or communication methods whereby information and commands may flow among these components. These functions may be grouped and assigned to various people and devices involved in the system. Adoption of this model allows researchers to focus more clearly on particular components of the system and on the associated research questions.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>