gebhart/patrepeval huggingface dataset:
Transgene‐mediated suppression of chalcone synthase expression in Petunia hybrida results from an increase in RNA turnover (1994)

Summary Co‐suppression of the pigmentation gene chalcone synthase ( chs ) in Petunia hybrida by chs transgenes leads to white or variegated flowers and is characterized by a reduction in steady‐state mRNA levels. To determine the level at which suppression occurs different petunia transformants were analysed containing CaMV‐35S RNA promoter‐driven hybrid genes consisting of the β‐glucuronidase gene ( uidA ) linked to the full‐length chsA cDNA, the 5′ half or to the 3′ half. With these transgenes one out of 12–15 primary transformants showed suppression of the transgenes and of the resident chs genes throughout the flower or in sectors. The reduction in steady‐state chs mRNA was not the result of a transcriptional inactivation event. As determined by nuclear run‐on experiments, transcription of suppressed chs genes was similar to that of non‐suppressed genes. This indicates that co‐suppression occurs post‐transcriptionally. Among individual transformants the transgenes were transcribed at different levels but neither a high nor a low level correlated with a particular degree or pattern of suppression. Surprisingly, even a promoterless chs transgene construct was found to suppress the endogenous chs genes in three out of 15 transformants. It remains, however, unknown whether or not transcription of the transgene locus is required to induce co‐suppression. The data suggest that properties of the chs transgene locus other than the expression level are important for inducing co‐suppression. The possible role of antisense RNA, which was detected in all transformants, ectopic pairing and the structure of the integrated T‐DNAs in the mechanism of the selective increase in chs RNA turnover are discussed.
Interaction of Deoxyinosine 3′-Endonuclease from Escherichia coli with DNA Containing Deoxyinosine (1995)

By using a band mobility shift assay, deoxyinosine 3'-endonuclease, an Escherichia coli enzyme which recognizes deoxyinosine, AP site, urea residue, and base mismatches in DNA, was shown to bind tightly to deoxyinosine-containing oligonucleotide duplexes. Two distinct protein-DNA complexes were observed, the faster migrating complex (complex I, Kd = 4 x 10(-9) M) contained one molecule of deoxyinosine 3'-endonuclease, while the slower migrating complex (complex II, Kd = 4 x 10(-7) M) contained two molecules of the protein bound to every molecule of duplex DNA. The endonucleolytic activity of deoxyinosine 3'-endonuclease paralleled the formation of the complex I. Interestingly, deoxyinosine 3'-endonuclease exhibited similar affinities for both the substrate and the nicked duplex product and thus remained bound to the DNA after the cleavage reaction. The formation of a stable complex required the presence of a duplex structure 5' to the deoxyinosine residue. DNase I footprinting revealed that deoxyinosine 3'-endonuclease protected 4-5 nucleotides 5' to the deoxyinosine, and when complex II was formed, at least 13 nucleotides 3' to deoxyinosine were protected. Based on these results, a model is proposed for the interaction of deoxyinosine 3'-endonuclease with DNA containing deoxyinosine.
A point mutation in an invariant splice donor site leads to exon skipping in two unrelated Dutch patients with dihydropyrimidine dehydrogenase deficiency (1996)

Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disease characterized by thymine-uraciluria and associated with a variable clinical phenotype. In order to identify the molecular defect underlying complete DPD deficiency in a Dutch patient previously shown to have a 165 base pair deletion in the mature DPD mRNA, we cloned the genomic region encompassing the skipped exon and its flanking intron sequences. Sequence analysis revealed that the patient was homozygous for a single G-->A point mutation in the invariant GT dinucleotide splice donor site downstream of the skipped exon. The same mutation was identified in another, unrelated, Dutch patient. Because this mutation destroys a unique MaeII restriction site, rapid screening using restriction enzyme cleavage of the amplified genomic region encompassing this mutation is possible. Analysis of 50 controls revealed no individuals heterozygous for this mutation.
Deletion of the putative effector region of Era, an essential GTP-binding protein in Escherichia coli, causes a dominant-negative phenotype (1996)

era is an essential gene in E. coli, encoding a GTP-binding protein of unknown function. In the present work, a mutant designated Era-dE, for deletion of effector region is described. This is the first and only known era allele that confers a dominant-negative phenotype. Phenotypic analysis of the mutant showed that overproduction of Era-dE caused a dominant inhibition of growth when TCA cycle intermediates such as succinate, pyruvate, malate, α-ketoglutarate, and fumarate were provided as the sole carbon source. Examination of the macromolecular composition of cells overexpressing the mutant showed protein, DNA, and ATP levels expected for cells growing at slow rates. The response of cells expressing Era-dE to different stress conditions was studied by examining the rates of synthesis of stress-inducible proteins. Interestingly, when subjected to succinate starvation, cells expressing Era-dE showed a defective carbon starvation response, whereas response to glucose starvation was similar to that seen in control cells. Taken together with previous results, these studies indicate that Era is perhaps involved in multiple cellular processes and Era-dE disrupts more than one of these functions. Furthermore, it appears that some possible functions of Era include regulation of the TCA cycle and response to carbon starvation.
Molecular mechanisms of inflammasome activation during microbial infections (2011)

The innate immune system plays a crucial role in the rapid recognition and elimination of invading microbes. Detection of microbes relies on germ-line encoded pattern recognition receptors (PRRs) that recognize essential bacterial molecules, so-called pathogen-associated molecular patterns (PAMPs). A subset of PRRs, belonging to the NOD-like receptor (NLR) and the PYHIN protein families, detects viral and bacterial pathogens in the cytosol of host cells and induces the assembly of a multi-protein signaling platform called the inflammasome. The inflammasome serves as an activation platform for the mammalian cysteine protease caspase-1, a central mediator of innate immunity. Active caspase-1 promotes the maturation and release of interleukin-1β (IL-1β) and IL-18 as well as protein involved in cytoprotection and tissue repair. In addition, caspase-1 initiates a novel form of cell death called pyroptosis. Here, we discuss latest advances and our insights on inflammasome stimulation by two model intracellular pathogens, Francisella tularensis and Salmonella typhimurium. Recent studies on these pathogens have significantly shaped our understanding of the molecular mechanisms of inflammasome activation and how microbes can evade or manipulate inflammasome activity. In addition, we review the role of the inflammasome adapter ASC in caspase-1 autoproteolysis and new insights into the structure of the inflammasome complex.
Gangliosides and membrane receptors for cholera toxin (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTGangliosides and membrane receptors for cholera toxinPedro CuatrecasasCite this: Biochemistry 1973, 12, 18, 3558–3566Publication Date (Print):August 1, 1973Publication History Published online1 May 2002Published inissue 1 August 1973https://pubs.acs.org/doi/10.1021/bi00742a032https://doi.org/10.1021/bi00742a032research-articleACS PublicationsRequest reuse permissionsArticle Views513Altmetric-Citations406LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Optimizing extended-release carbidopa/levodopa in Parkinson disease (2017)

Because the pharmacokinetics of ER CD/LD differ from those of IR CD/LD, modification of dosage and dosing frequency are to be expected. Initial regimens may be based on doubling the patient's preconversion levodopa daily dosage and choosing a division of doses to address the patient's motor complications, e.g., wearing-off (warranting a relatively high ER CD/LD dose, possibly at a lower frequency than for IR CD/LD) or dyskinesia (warranting a relatively low dose, perhaps at an unchanged frequency). Patients should know that the main goal of conversion is a steadier levodopa clinical response, even if dosing frequency is unchanged.
Particle Characterization and Separation by a Coupled Acoustic−Gravity Field (2001)

A coupled acoustic-gravity field is proposed as a novel external field for particle separation and characterization. When a standing plane ultrasound wave is generated, particles move to the node of the wave along the ultrasound force gradient. If the particles also undergo a sedimentation force, they aggregate at the equilibrium position, where these two forces are balanced. The equilibrium position, which is determined by the density and compressibility of a medium and particles, characterizes the particles. The local ultrasound energy, which is necessary for quantitative discussions, is evaluated by using a standard particle, the physical parameters of which are unambiguously determined; aluminum particles are used in the present study. The local ultrasound energy makes possible the determination of the compressibility of unknown materials. Nonporous particles of inorganic and polymeric materials, the particle sizes of which range from 3 to 100 microm, follow a derived model, suggesting that the local ultrasound energy and a derived model be valid. The proposed external field can be used for separation of particles having different acoustic natures.
Identification of MicroRNA Markers of Sensitivity to the Novel Bruton’s Tyrosine Kinase (BTK) Inhibitor PCI-32765 in Non-Hodgkin’s Lymphoma. (2008)

Abstract PCI-32765 is a novel, first-in-class small molecule inhibitor of Bruton’s tyrosine kinase (BTK), currently in preclinical development and shortly entering Phase I clinical trials for the treatment of hematological malignancies. BTK is essential in B-cells for signalling via the B-cell receptor (BCR), and mutations in BTK have been shown to cause x-linked agammaglobulinemia in humans and x-linked immunodeficiency (xid) in mice. We have found that PCI-32765 has demostrated significant growth inhibitory activity in vitro in a number of non-Hodgkin’s lymphoma (NHL) cell lines as well as primary human NHL tumors cultivated ex-vivo. However, certain subsets of NHL cell lines were found to respond better to the inhibitor, and in keeping with this, a wide variance was also observed in the response among primary human tumors. PCI-32765 had GI50 &lt;3uM in 7/15 cell lines (46%), including 3 follicular lymphoma (FL) and 3 diffuse large B-cell lymphoma (DLBCL) lines. Based on these results, we tested primary tumors including 15 FL and 7 DLBCL, utilizing a modified version of Oncotech’s EDR Assay. We found that while only 1 of the DLBCL tumors showed a similar response, PCI-32765 had a response rate of 40% in the primary FL samples. The reasons for this variation are still under investigation but one reason may be that that not all tumors are equally dependent on BTK activation for their survival. In order to obtain a predictive marker for response to PCI-32765 in human tumors, we utilized a microRNA (miRNA) profiling approach in the primary FL tumors using a commercially available miRNA array platform. We hypothesized that miRNA might be a better diagnostic tool than mRNA because miRNA function is more conserved and it is more stable than mRNA (thus easier to harvest successfully from paraffin embedded blocks). Further, it has been shown that miRNA signatures can predict responsive and resistant phenotypes based on basal miRNA levels, and have been found to have essential functions in lymphomas. When the miRNA profiles from the FL tumors were analyzed, we found that a signature consisting of 4 miRNAs could predict the sensitive tumors with a p-value &lt;0.01. Of these, 2 were upregulated and 2 were downregulated in the sensitive samples compared to the resistant ones. It is likely therefore that these are implicated in the mechansisms of sensitivity and resistance to PCI-32765 in the FL tumors, and the connections between genes regulated by these miRNAs to pathways controlled by BTK are being explored.
An ultrasonic approach to localization of fiducial markers for interactive, image-guided neurosurgery. II. Implementation and automation (1998)

Registration of image space and physical space lies at the heart of any interactive, image-guided neurosurgery system. This paper, in conjunction with the previous companion paper [1], describes a localization technique that enables bone-implanted fiducial markers to be used for the registration of these spaces. The nature of these subcutaneous markers allows for their long-term use for registration which is desirable for surgical follow-up, monitoring of therapy efficacy, and performing fractionated stereotactic radiosurgery. The major challenge to using implanted markers is determining the location of the markers in physical space after implantation. The A-mode ultrasonic technique described here is capable of determining the three-dimensional (3-D) location of small implanted cylindrical markers. Accuracy tests were conducted on a phantom representing a human head. The accuracy of the system was characterized by comparing the location of a marker analogue as determined with an optically tracked pointer and the location as determined with the ultrasonic localization. Analyzing the phantom in several orientations revealed a mean system accuracy of 0.5 mm with a +/- 0.1-mm 95% confidence interval. These tests indicate that transcutaneous localization of implanted fiducial markers is possible with a high degree of accuracy.
Skewed Rotation Symmetry Group Detection (2009)

We present a novel and effective algorithm for affinely skewed rotation symmetry group detection from real-world images. We define a complete skewed rotation symmetry detection problem as discovering five independent properties of a skewed rotation symmetry group: 1) the center of rotation, 2) the affine deformation, 3) the type of the symmetry group, 4) the cardinality of the symmetry group, and 5) the supporting region of the symmetry group in the image. We propose a frieze-expansion (FE) method that transforms rotation symmetry group detection into a simple, 1D translation symmetry detection problem. We define and construct a pair of rotational symmetry saliency maps, complemented by a local feature method. Frequency analysis, using Discrete Fourier Transform (DFT), is applied to the frieze-expansion patterns (FEPs) to uncover the types (cyclic, dihedral, and O2), the cardinalities, and the corresponding supporting regions, concentric or otherwise, of multiple rotation symmetry groups in an image. The phase information of the FEP is used to rectify affinely skewed rotation symmetry groups. Our result advances the state of the art in symmetry detection by offering a unique combination of region-based, feature-based, and frequency-based approaches. Experimental results on 170 synthetic and natural images demonstrate superior performance of our rotation symmetry detection algorithm over existing methods.
Experimental therapeutics in Huntington's disease (2003)

Our understanding of the molecular basis of Huntington's disease is increasing at an exponential rate. Over the next few years an increasing number of potential therapeutic compounds will have been identified. It will only be possible to take a small number of these through to phase III clinical trials. The challenge will be to use the in-vivo models of Huntington's disease to best predict which of these compounds should be pursued in the clinic, to avoid depleting the patient population willing to enter into trials, and demoralizing them by conducting repeated unsuccessful trials.
Sanctum: Minimal Hardware Extensions for Strong Software Isolation (2016)

Sanctum offers the same promise as SGX, namely strong provable isolation of software modules running concur-rently and sharing resources, but protects against an im-portant class of additional software attacks that infer private information from a program’s memory access patterns. We follow a principled approach to eliminat-ing entire attack surfaces through isolation, rather than plugging attack-specific privacy leaks. Sanctum demonstrates that strong software isolation is achievable with a surprisingly small set of minimally invasive hardware changes, and a very reasonable over-head. Sanctum does not change any major CPU building block. Instead, we add hardware at the interfaces be-tween building blocks, without impacting cycle time. Our prototype shows a 2 % area increase in a Rocket RISC-V core. Over a set of benchmarks, Sanctum’s worst observed overhead for isolated execution is 15.1% over an idealized insecure baseline, and 2.7 % average overhead over a representative insecure baseline. 1
Lab-in-a-tube: on-chip integration of glass optofluidic ring resonators for label-free sensing applications (2012)

The fabrication of tubular rolled-up optofluidic ring resonators (RU-OFRRs) based on glass (SiO(2)) material with high quality factors is reported. A novel methodology combining lab-on-a-chip fabrication methods and rolled-up nanotech is presented for the fabrication of fully integrated tubular optofluidic sensors. The microfluidic integration of several RU-OFRRs on one chip is solved by enclosing the microtubes with a patterned robust SU-8 polymeric matrix. A viewport on each microtube enables exact excitation and monitoring of whispering gallery modes with a photoluminescence spectroscopy system under constant ambient conditions, while exchanging the content of the RU-OFRR with liquids of different refractive indices. The refractrometric sensor capabilities are investigated regarding signal stability, sensitivity and reliability. The sensitivity of the integrated RU-OFRR, which is the response of the modes to the change in refractive index of the liquid, is up to 880 nm/refractive index units (RIU).
Treatment selections of 239 patients with blepharospasm and Meige syndrome over 11 years. (1996)

While botulinum toxin is the most highly effective treatment for benign essential blepharospasm and Meige syndrome over a long period of time, adjunctive oral drug therapy, including minor tranquillisers as well as eyelid surgery, may augment its effectiveness.
Effect of Electrical Myostimulation on the Function of Lower Leg Muscles (2016)

Electrical myostimulation (EMS) method is applied to improve skeletal muscle function. The aim of this study was to evaluate the efficacy of EMS applied to the sole and calf muscles on their strength and on maximal sprint performance. Each of 10 training sessions involved 10 seconds of stimulation and 50 seconds of rest for a total of 10 minutes. After the 10 training sessions, the maximal voluntary contraction (MVC) of right calf muscles increased by 6.0% from 830.0 ± 47.0 N to 878.0 ± 45.3 N (p ≤ 0.05). When EMS was applied to trained athletes, their 10-m sprint performance improved by 2.1% (p ≤ 0.05). In the second part of the study, a 3-week training program with EMS was applied to athletes, which significantly improved their 10-m sprint performance from a standing start by 5.3% and from a running start by 4.7% (p ≤ 0.05). Thus, 10 EMS cycles up to the maximal tolerated intensity applied every other day improved the MVC of foot flexion muscles and 10-m sprint performance from both standing and running starts. Three weeks of EMS training did not affect the intensity of calf muscle blood flow and oxygen saturation at rest. The training program supplemented with 10 EMS sessions produced significantly greater effects on the 10-m sprint performance from both a standing and a running start.
Alirocumab for Hyperlipidemia: Physiology of PCSK9 inhibition, Pharmacodynamics and Phase I and Ii Clinical Trial Results of a PCSK9 Monoclonal Antibody (2014)

Statins have been the cornerstone of lipid therapy for the last two decades, but despite significant clinical efficacy in the majority of patients, a large residual risk remains for the development of initial or recurrent atherosclerotic cardiovascular disease. In addition, owing to side effects, a significant percentage of patients cannot tolerate any statin dose or a high enough statin dose to reach their recommended LDL cholesterol goals. Monoclonal antibodies (mAbs) to PCSK9 have recently been shown to be highly efficacious in lowering LDL cholesterol, while demonstrating a favorable adverse event profile in early clinical trials. This review of alirocumab (formerly REGN727/SAR236553) explains the physiology and pharmacodynamics of PCSK9 inhibition with a mAb, as well as the Phase I and II clinical trial results of alirocumab and the ongoing Phase III trial designs. Several mAbs to PCSK9 are currently in development and approval may be 1-3 years away. We will focus this review on alirocumab, but mAbs to PCSK9 are the most promising cholesterol-lowering medication since statins and have the potential to significantly reduce further the occurrence of atherosclerotic cardiovascular disease.
Myocardial ischemia-reperfusion injury in CD18- and ICAM-1-deficient mice (1998)

Previous studies have demonstrated that circulating neutrophils (PMNs) contribute to the pathophysiology of myocardial ischemia-reperfusion (MI/R) injury. PMN-endothelial cell interactions are highly regulated by adhesive interactions between PMN CD11/CD18 and coronary endothelial cell intercellular adhesion molecule-1 (ICAM-1). We investigated the effects of MI/R in wild-type, CD18-, and ICAM-1-deficient (-/-) mice. Wild-type (n = 6), CD18 -/- (n = 6), and ICAM-1 -/- (n = 6) mice were subjected to 30 min of myocardial ischemia and 120 min of reperfusion to determine the extent of PMN infiltration and myocardial cell necrosis. Myocardial infarction (% of the area at risk) was 45.1 +/- 5.9 in wild-type mouse hearts. In contrast, the extent of myocardial infarction was significantly (P < 0.05) reduced in the CD18 (19.3 +/- 5.1%)- and ICAM-1 (17.9 +/- 3.2%)-deficient mice. Similarly, PMN infiltration into the ischemic-reperfused myocardium was attenuated by 54% in the CD18 -/- mice and by 32% in ICAM-1 -/- mice compared with wild-type hearts. Deficiency in either CD18 or ICAM-1 expression results in a marked reduction in PMN accumulation and myocardial necrosis after acute MI/R.