gebhart/patrepeval huggingface dataset:
Six Amino Acid Changes Confined to the Leucine-Rich Repeat β-Strand/β-Turn Motif Determine the Difference between the P and P2 Rust Resistance Specificities in Flax (2001)

At least six rust resistance specificities (P and P1 to P5) map to the complex P locus in flax. The P2 resistance gene was identified by transposon tagging and transgenic expression. P2 is a member of a small multigene family and encodes a protein with nucleotide binding site (NBS) and leucine-rich repeat (LRR) domains and an N-terminal Toll/interleukin-1 receptor (TIR) homology domain, as well as a C-terminal non-LRR (CNL) domain of approximately 150 amino acids. A related CNL domain was detected in almost half of the predicted Arabidopsis TIR-NBS-LRR sequences, including the RPS4 and RPP1 resistance proteins, and in the tobacco N protein, but not in the flax L and M proteins. Presence or absence of this domain defines two subclasses of TIR-NBS-LRR resistance genes. Truncations of the P2 CNL domain cause loss of function, and evidence for diversifying selection was detected in this domain, suggesting a possible role in specificity determination. A spontaneous rust-susceptible mutant of P2 contained a G-->E amino acid substitution in the GLPL motif, which is conserved in the NBS domains of plant resistance proteins and the animal cell death control proteins APAF-1 and CED4, providing direct evidence for the importance of this motif in resistance gene function. A P2 homologous gene isolated from a flax line expressing the P resistance specificity encodes a protein with only 10 amino acid differences from the P2 protein. Chimeric gene constructs indicate that just six of these amino acid changes, all located within the predicted beta-strand/beta-turn motif of four LRR units, are sufficient to alter P2 to the P specificity.
Reaction of a Biscationic Distamycin-Ellipticine Hybrid Ligand with DNA. Mode and Sequence Specificity of Binding (1994)

Molecular modeling of complexes between the octanucleotide d(CGATATCG)2 and either a monocationic or biscationic distamycin-ellipticine hybrid molecule predicted that the extra positive charge on the latter conjugate ligand should ensure tight fitting into the minor groove of the duplex without affecting intercalation of the ellipticine chromophore. To test this prediction, we have synthesized a biscationic compound Distel (2+) and investigated its interaction with DNA using various optical and gel electrophoresis techniques. Viscosity, fluorescence lifetime, and circular and linear dichroism measurements bear out the validity of the calculations and show that Distel (2+) does indeed come to lie with its distamycin moiety in the minor groove of DNA and its ellipticine ring intercalated nearby. Linear dichroism experiments with a range of polynucleotides indicate that, unlike its monocationic homologue, the biscationic ligand engages in bidentate binding to AT sequences but not to GC sequences. Footprinting studies employing DNase I and methidiumpropyl-EDTA.FeII as DNA cleaving agents reveal that the biscationic hybrid is notably selective for AT-rich sequences in DNA. The concentrations required to detect a clear footprint at AT sites with Distel (2+) are 4- to 10-fold lower than those required to produce comparable DNase I footprints with distamycin alone. Also, in accord with the energy-minimized model of the hybrid-oligonucleotide complex, chemical probing experiments using diethyl pyrocarbonate and osmium tetroxide reveal that the hybrid causes significant distortion of the DNA helix, explicable in terms of bending of the duplex toward the minor groove, which greatly enhances the reactivity toward probes in the major groove of the DNA. The experimental results help to identify the determinant factors, predominantly steric and electrostatic interactions, which shape the DNA-binding reaction. Thus, molecular modeling has correctly predicted the DNA-binding properties of a doubly charged ligand and shown that appending an auxiliary basic group onto the distamycin moiety was the right way to proceed in order to convert a nonspecific conjugate into a highly specific DNA reader.
Gabapentin in patients with the pruritus of cholestasis: A double-blind, randomized, placebo-controlled trial (2006)

Pruritus is defined as the second order of nociception, the first being pain; thus, there is a rationale to study gabapentin, a drug that increases the threshold to experience nociception. The aim of this double-blind, randomized, placebo-controlled trial was to study the effect of gabapentin on the perception of pruritus and its behavioral manifestation, scratching, in cholestasis. The participants were 16 women with chronic liver disease and chronic pruritus. Hourly scratching activity (HSA) was continuously recorded for up to 48 hours at baseline and on treatment for at least 4 weeks in an inpatient setting. The perception of pruritus was assessed by interviews and by a visual analog score (VAS) of pruritus recorded every hour while patients were awake. Patients were randomized to the study drug (gabapentin or placebo) at a starting dose of 300 mg orally per day in divided doses to a maximum of 2,400 mg or until relief from pruritus. Gabapentin was associated with an increase in mean HSA, in contrast to the placebo, which was associated with a decrease. The mean VAS decreased significantly among those taking the placebo and in some patients on gabapentin. In conclusion, gabapentin did not provide a significant therapeutic advantage over the placebo; in fact, it was associated with an increase in the perception of pruritus and in HSA in some patients.
Structure, Expression, and Antisense Inhibition of the Systemin Precursor Gene (1992)

A gene that encodes systemin, a mobile 18-amino acid polypeptide inducer of proteinase inhibitor synthesis in tomato and potato leaves, has been isolated from tomato, Lycopersicon esculentum. Induction of proteinase inhibitors in plants is a response to insect or pathogen attacks. The gene has 10 introns and 11 exons, ten of which are organized as five homologous pairs with an unrelated sequence in the eleventh, encoding systemin. Systemin is proteolytically processed from a 200-amino acid precursor protein, prosystemin. Prosystemin messenger RNA was found in all organs of the plant except the roots and was systemically wound-inducible in leaves. Tomato plants transformed with an antisense prosystemin complementary DNA exhibited greatly suppressed systemic wound induction of proteinase Inhibitor I and II synthesis in leaves.
A small cassette enables conditional gene inactivation by CRISPR/Cas9 (2017)

The availability of CRISPR/Cas9 technology has enabled the rapid establishment of gene knockouts in many cell types and even whole organisms. However, conditional inactivation of essential genes remains a challenge. We devised an approach named DECAI (DEgradation based on Cre-regulated- Artificial Intron). It utilizes a small cassette of just 201 nucleotides that is inserted into the coding exon of a target gene using CRISPR/Cas9 technology and homology-directed repair. As its sequence is derived from an artificial intron, the cassette is removed by the splicing machinery and thus leaves no trace in the "off-state". Upon activation with Cre recombinase ("on-state"), the intron is crippled and the target gene is disrupted by a series of stop codons. We exemplify the utility of this approach on several non-essential and essential human genes. Clones bearing the conditional knockout cassette are recovered at frequencies above 5% and cassette function can be traced at the genomic DNA and the mRNA level. Importantly, cassette activation leads to loss of gene expression as judged by flow cytometry, Western blot or immunofluorescence. Altogether, this highlights the broad utility of the approach for conditional gene inactivation and suggests that this tool could be used to study the loss-of-function phenotypes of essential genes.
Generation of an adenoviral vaccine vector based on simian adenovirus 21 (2006)

Adenoviral vectors can be used to generate potent humoral and cellular immune responses to transgene products. Use of adenoviral vectors based on non-human isolates may allow for their utilization in populations harbouring neutralizing antibodies to common human serotypes. A vector chimera was constructed using simian adenovirus 22 (a serotype belonging to the species Human adenovirus E) and simian adenovirus 21 (a serotype belonging to the species Human adenovirus B) expressing the Ebola (Zaire) virus glycoprotein (Ad C5/C1-ZGP). This chimeric adenovirus vector was used as a model to test its efficacy as a genetic vaccine and comparisons were made to a vector based on the commonly used human adenovirus C serotype 5 (Adhu5-ZGP). Ebola glycoprotein-specific T- and B-cell responses were measured in B10BR mice vaccinated with either Adhu5-ZGP or Ad C5/C1-ZGP vectors. Both vectors resulted in Ebola glycoprotein-specific gamma interferon-expressing T cells, although the Ad C5/C1-ZGP vector appeared to induce lower frequencies with kinetics slower than those elicited by the Adhu5-ZGP vector. The total immunoglobulin G response to Ebola glycoprotein was similar in sera from mice vaccinated with either vector. Two rhesus macaques vaccinated with the Ad C5/C1-ZGP vector were found to mount T-cell and antibody responses to the Ebola glycoprotein. It was found that a single administration of the chimeric Ad C5/C1-ZGP vector protected mice against a lethal challenge with a mouse-adapted strain of the Ebola (Zaire) virus.
Detection of glutamic acid decarboxylase-activated T cells with I-Ag7tetramers (2000)

CD4(+) T cells selected by the type 1 diabetes associated class II MHC I-A(g7) molecules play a critical role in the disease process. Multivalent MHC/peptide tetramers have been used to directly detect antigen-specific T cells. Detection of autoantigen-activated CD4(+) T cells with tetramers should be very helpful in the study of the roles of these cells in diabetes. We report here the generation of tetramers of I-A(g7) covalently linked to two glutamic acid decarboxylase (GAD) peptides and the detection of GAD peptide-activated T cells from nonobese diabetic (NOD) mice. The I-A(g7) heterodimers can form stable complexes with a covalently bound GAD peptide and can stimulate antigen specific T cells. Furthermore, I-A(g7)/GAD peptide tetramer can detect most if not all of the antigen-specific CD4(+) T cells from immunized NOD mice. Antigen-specific T cells detected by the tetramers can up-regulate their CD4 expression on the cell surface after being restimulated with the GAD peptides in vitro. In contrast, the tetramers can detect a percentage of T cells in lymph nodes and spleens and T cells infiltrating islets from nonimmunized mice that is not significantly above the background. Therefore, T cells specific for the GAD peptides are present in NOD mice at a frequency too low to be detected, but immunization of NOD mice can facilitate their detection by tetramers.
Atomic layer deposition of photoactive CoO/SrTiO3 and CoO/TiO2 on Si(001) for visible light driven photoelectrochemical water oxidation (2013)

Cobalt oxide (CoO) films are grown epitaxially on Si(001) by atomic layer deposition (ALD) using a thin (1.6 nm) buffer layer of strontium titanate (STO) grown by molecular beam epitaxy. The ALD growth of CoO films is done at low temperature (170–180 °C), using cobalt bis(diisopropylacetamidinate) and water as co-reactants. Reflection high-energy electron diffraction, X-ray diffraction, and cross-sectional scanning transmission electron microscopy are performed to characterize the crystalline structure of the films. The CoO films are found to be crystalline as-deposited even at the low growth temperature with no evidence of Co diffusion into Si. The STO-buffered Si (001) is used as a template for ALD growth of relatively thicker epitaxial STO and TiO2 films. Epitaxial and polycrystalline CoO films are then grown by ALD on the STO and TiO2 layers, respectively, creating thin-film heterostructures for photoelectrochemical testing. Both types of heterostructures, CoO/STO/Si and CoO/TiO2/STO/Si, demonstrate water photooxidation activity under visible light illumination. In-situ X-ray photoelectron spectroscopy is used to measure the band alignment of the two heterojunctions, CoO/STO and CoO/TiO2. The experimental band alignment is compared to electronic structure calculations using density functional theory.
A Series of Halogenated Heterodimeric Inhibitors of Prostate Specific Membrane Antigen (PSMA) as Radiolabeled Probes for Targeting Prostate Cancer (2008)

Prostate specific membrane antigen (PSMA) is a validated molecular marker for prostate cancer. A series of glutamate-urea (Glu-urea-X) heterodimeric inhibitors of PSMA were designed and synthesized where X = epsilon-N-(o-I, m-I, p-I, p-Br, o-Cl, m-Cl, p-Cl, p-F, H)-benzyl-Lys and epsilon-(p-I, p-Br, p-Cl, p-F, H)-phenylureido-Lys. The affinities for PSMA were determined by screening in a competitive binding assay. PSMA binding of the benzyllysine series was significantly affected by the nature of the halogen substituent (IC(50) values, Cl < I = Br << F = H) and the ring position of the halogen atom (IC(50) values, p-I < o-I << m-I). The halogen atom had little affect on the binding affinity in the para substituted phenylureido-Lys series. Two lead iodine compounds were radiolabeled with (123)I and (131)I and demonstrated specific PSMA binding on human prostate cancer cells, warranting evaluation as radioligands for the detection, staging, and monitoring of prostate cancer.
Incidence of Insulin-dependent Diabetes Mellitus in Young Adults: Experience of 1,587,630 US Navy Enlisted Personnel (1993)

First hospitalizations (n = 1,293) for diabetes mellitus between 1974 and 1988 were used as a surrogate for insulin-dependent diabetes mellitus incidence among 17-34-year-old US Navy enlisted personnel followed for 6,077,856 person-years. In the 15-year period, the overall incidence of insulin-dependent diabetes mellitus was 21.3 per 100,000 person-years. Incidence did not differ significantly by sex, but was higher for blacks than whites (28.4 vs. 20.2 per 100,000 person-years, respectively; p < 0.05). Incidence increased with age threefold for white men and fivefold for black men (p < 0.05) between the ages of 17-19 and 30-34 years.
Heat-Induced Gelation of Globular Proteins. 2. Effect of Environmental Factors on Single-Component and Mixed-Protein Gels (1997)

In the first paper in this series, we investigated heat-induced gelation of single component systems of the globular protein, bovine serum albumin. A series of rheological experiments revealed that we can describe gelation time in terms of two physical parameters, concentration and temperature. In this paper we examine more complex systems, including the effect of pH and ionic strength, on heat-induced gelation of bovine serum albumin (BSA), and another globular protein, β-lactoglobulin (β-Lg). These factors significantly influenced protein gelation, a result which has not been reported in detail before. However, no detailed analysis was possible, because the behavior is very complex. We also consider the extension of both model and experiments to (quasi-) binary mixed systems, viz. the gelation of binary systems chosen from three globular proteins: BSA, β-Lg, and α-lactalbumin (α-La). We have obtained reliable results only for the BSA and β-Lg system because of experimental difficulties. From the data of the BSA/β-Lg system, it was found that gelation behavior changed significantly with the ratio of the two proteins. The change in the gelation time and temperatures was not expressed as a linear equation but required a cross-term. This strongly suggests that current models for the concentration dependence of modulus for mixed biopolymer gels will need to be modified.
Voiding dysfunction in women: How to manage it correctly (2013)

Female VD might be related to DU or/and BOO. Voiding and storage symptoms can coexist, making the diagnosis challenging, with the need for a targeted clinical investigation, and further evaluation by imaging and urodynamics. To date there is no universally accepted precise diagnostic criterion to diagnose and quantify DU and BOO in women. For therapy, a complete cure might not be possible for patients with VD, therefore relieving the symptoms and minimising the long-term complications associated with it should be the goal. Treatment options are numerous and must be applied primarily according to the underlying pathophysiology, but also considering disease-specific considerations and the abilities and needs of the individual patient. The treatment options range from behavioural therapy, intermittent (self-)catheterisation, and electrical neuromodulation and neurostimulation, and up to urinary diversion in rare cases.
The tricho‐rhino‐phalangeal syndrome with exostoses (or Langer‐Giedion syndrome): Four additional patients without mental retardation and review of the literature (1984)

We report on four patients with tricho-rhino-phalangeal syndrome with exostoses (TRPSE) who were not mentally retarded and review 32 previously published cases. These data enable more complete delineation of the phenotype and document the variability of the clinical and radiographic manifestations. Information on the genetics and the association with del(8q) is discussed, as are management and avenues for further investigation. The apparent variability of intelligence in TRPSE patients together with the high incidence of other problems, including significant delay in speech development and hearing loss, make systematic multidisciplinary evaluation and long-term treatment necessary to achieve the best outcome.
Fusion of yeast spheroplasts (1977)

Spheroplasts of two different auxotrophic strains of Saccharomyces cerevisiae, both of mating type a, were fused with the aid of polyethylene glycol and calcium ions. After reversion to vegetative cells in solid media, the resulting zygotes were shown to be diploid cells of mating type aa.
Chemotherapy responsiveness of human tumors as first transplant generation xenografts in the normal mouse: Six-day subrenal capsule assay (1981)

Feasibility of utilizing human tumors as first transplant generation xenografts in the normal immunocompetent mouse for determining tumor sensitivity to chemotherapeutic agents was demonstrated by applying subrenal capsule (SRC) assay methodology to fresh surgical explants in a six-day time frame. A total of 37 human breast tumors were tested in assays in which 254 xenografts were implanted into control animals. Fifty (20%) of the controls showed some degree of partial regression in the six-day assay period. Using a mean control growth having a positive change in tumor size as the criterion for evaluability, first transplant generation human breast tumors provided an evaluable assay rate of 86%. A tumor response profile was obtained as a result of testing seven clinically active drugs against 32 previously untreated breast cancers. The pattern of responses obtained indicated that no single agent was active against all tumors, nor were tumors which were responsive to one agent necessarily responsive to another, suggesting the feasibility of predicting individual tumor response to specific chemotherapeutic agents. Had these seven drugs been developmental agents of unknown activity which were being tested for the first time against such a panel of human tumors the result would have not only predicted their clinical activity, but the tumor response rates would have also provided an indication of the relative potential of each drug for the specific treatment of breast cancer.
Clustered multithreaded architectures -pursuing both IPC and cycle time (2004)

Summary form only given. Clustering is an architectural technique that allows the design of wide superscalar processors without sacrificing cycle time, but at the cost of longer communication latencies. Simultaneous multithreading architectures effectively tolerate instruction latency, but put even more pressure on timing-critical processor resources. We show that the synergistic combination of the two techniques minimizes the IPC impact of the clustered architecture, and even permits more aggressive clustering of the processor than is possible with a single-threaded processor. Additionally, we show that multithreading enables effective instruction steering policies unavailable to a single-threaded clustered architecture. We explore the impact of aggressively clustering four complex processor structures, (1) instruction window wakeup and functional unit bypass logic, (2) register renaming logic, (3) the fetch unit, and (4) the integer register file, on a simultaneous multithreading processor.
Catumaxomab, a rat/murine hybrid trifunctional bispecific monoclonal antibody for the treatment of cancer. (2008)

Fresenius Biotech GmbH (licensed from TRION Pharma GmbH) is developing catumaxomab, a rat/murine hybrid, trifunctional, bispecific (anti-epithelial cell adhesion molecule and anti-CD3) mAb for the potential intravenous and intraperitoneal treatment of ovarian cancer, gastric cancer, malignant pleural effusion and other cancers, and also for malignant ascites associated with various cancers. In 2007, following the successful completion of a phase II/III clinical trial in patients with malignant ascites from various cancers, Fresenius filed for European approval. Catumaxomab is currently undergoing phase II clinical trials in patients with malignant ascites, ovarian and stomach cancer.
Intracellular trafficking of lysosomal membrane proteins (1996)

Lysosomes are the site of degradation of obsolete intracellular material during autophagy and of extracellular macromolecules following endocytosis and phagocytosis. The membrane of lysosomes and late endosomes is enriched in highly glycosylated transmembrane proteins of largely unknown function. Significant progress has been made in recent years towards elucidating the pathways by which these lysosomal membrane proteins are delivered to late endosomes and lysosomes. While some lysosomal membrane proteins follow the constitutive secretory pathway and reach lysosomes indirectly via the cell surface and endocytosis, others exit the trans-Golgi network in clathrin-coated vesicles for direct delivery to endosomes and lysosomes. Sorting from the Golgi or the plasma membrane into the endosomal system is mediated by signals encoded by the short cytosolic domain of these proteins. This review will discuss the role of lysosomal membrane proteins in the biogenesis of the late endosomal and lysosomal membranes, with particular emphasis on the structural features and molecular mechanisms underlying the intracellular trafficking of these proteins.