gebhart/patrepeval huggingface dataset:
A Wnt/Calcium Signaling Cascade Regulates Neuronal Excitability and Trafficking of NMDARs (2017)

Wnt signaling controls multiple biological process, particularly the embryonic development of metazoans. Sustained expression of Wnt signaling components in the mature mammalian CNS and their apparent deregulation in certain neuropathologies suggest that it also plays a part beyond embryonic development to regulate normal brain function. We describe a noncanonical Wnt/Ca<sup>2+</sup> signaling cascade that regulates the electrophysiological intrinsic properties of rat neurons, resulting in sustained membrane depolarization and the mobilization of Ca<sup>2+</sup> from internal stores. These effects require tyrosine kinase-like orphan receptor 2 (RoR2), activation of PLC, and voltage-gated Ca<sup>2+</sup> channels. Activation of this signaling cascade then promotes surface expression of N-methyl-D-aspartate receptors (NMDARs) through a SNARE-dependent mechanism. This neuronal Wnt/Ca<sup>2+</sup> signaling pathway represents a mechanism for Wnt ligands to regulate normal brain processes in the mature animal and provides a framework for understanding how alterations in this pathway may contribute to the etiology of psychiatric disorders where NMDARs are compromised.
Molecular cloning of TvDAO1, a gene encoding a d-amino acid oxidase from Trigonopsis variabilis and its expression in Saccharomyces cerevisiae and Kluyveromyces lactis (1997)

The DAO1 gene of Trigonopsis variabilis encoding a D-amino acid oxidase (EC 1.4.3.3) was isolated from genomic clones selected for their specific hybridization to synthetic oligodeoxyribonucleotide probes based on regions of the enzyme that have been conserved through evolution. The nucleotide sequence of the gene predicts a protein with similarities to human, pig, rabbit, mouse and Fusarium solani D-amino acid oxidases. The open reading frame of the T. variabilis DAO1 gene was interrupted by an intron. The Dao1p sequence displays two regions, one in the N-terminal section—the FAD binding site—and the other near the C-terminal region that contains conserved signatures found in all the D-amino acid oxidases. The three C-terminal amino acids suggest that the enzyme may be located in peroxisomes. Northern blot experiments showed that no transcriptional activation occurred in the presence of D-methionine. The cDNA encoding Dao1p was expressed in Saccharomyces cerevisiae and Kluyveromyces lactis. Both yeast species are able to synthesize a functional enzyme under the control of the GAL1 promoter. In K. lactis, up to six times more enzyme units per gram of dry weight are produced with a multicopy plasmid in comparison with the wild-type strain of T. variabilis. The yeast expression system we describe may constitute an alternative source for the production of D-amino acid oxidases at industrial level. The sequence presented here has been submitted to the EMBL data library under Accession Number Z50019. © 1997 John Wiley & Sons, Ltd.
Transplantation of fresh allografts (homografts) of crushed and uncrushed cartilage and bone: A 1‐year analysis in rabbits (1980)

Fresh allografts (homografts) of cartilage and bone, crushed and uncrushed, were transplanted in 53 rabbits. Each material was implanted into the auricle and concomitantly into the subdermis of the face. Postoperative assessment was every 1 to 3 days; sacrifice was at 6 weeks, 6 months, and 1 year for microscopic evaluation. Uncrushed cartilage allografts remained viable, and no significant resorption occurred. Crushed cartilage was significantly resorbed by 6 weeks but changed little after that. Resorption of uncrushed bone was moderate and appeared to be ongoing. Total resorption by 1 year occurred in the absence of contact with perichondrium or periosteum. Crushed bone, like crushed cartilage, was largely resorbed. These data document the fact that uncrushed cartilage is superior to crushed cartilage, crushed bone, or uncrushed bone for fresh allograft transplantation in the rabbit and that uncrushed cartilage is probably superior to all other fresh allografts for use in the clinical setting.
Patterning of Thin‐Film Microstructures on Non‐Planar Substrate Surfaces Using Decal Transfer Lithography (2004)

Soft-lithographic patterning of thin-film material microstructures supported on spherically curved lenses (see Figure) using an extension of decal transfer lithography (DTL) is reported. These processes have been used to successfully create a pattern of amorphous silicon and gold thin-film microstructures with feature sizes ranging from 2 μm to 75 μm. This has been achieved without noticeable defects using wet and reactive-ion etching processes across large substrate areas.
Solving Ill-Conditioned and Singular Linear Systems: A Tutorial on Regularization (1998)

It is shown that the basic regularization procedures for finding meaningful approximate solutions of ill-conditioned or singular linear systems can be phrased and analyzed in terms of classical linear algebra that can be taught in any numerical analysis course. Apart from rewriting many known results in a more elementary form, we also derive a new two-parameter family of merit functions for the determination of the regularization parameter. The traditional merit functions from generalized cross validation (GCV) and generalized maximum likelihood (GML) are recovered as special cases.
In vivo imaging of proteolytic enzyme activity using a novel molecular reporter. (2000)

The single biggest challenge facing in vivo imaging techniques is to develop biocompatible molecular beacons that are capable of specifically and accurately measuring in vivo targets at the protein, RNA, or DNA level. Our efforts have focused on developing activatable imaging probes to measure specific enzyme activities in vivo. Using cathepsin D as a model target protease, we synthesized a long-circulating, synthetic graft copolymer bearing near-infrared (NIR) fluorochromes positioned on cleavable substrate sequences. In its native state, the reporter probe was essentially nonfluorescent at 700 nm due to energy resonance transfer among the bound fluorochromes (quenching) but became brightly fluorescent when the latter were released by cathepsin D. NIR fluorescence signal activation was linear over at least 4 orders of magnitude and specific when compared with scrambled nonsense substrates. Using matched rodent tumor models implanted into nude mice expressing or lacking the targeted protease, it could be shown that the former generated sufficient NIR signal to be directly detectable and that the signal was significantly different compared with negative control tumors. The developed probes should find widespread applications for real-time in vivo imaging of a variety of clinically relevant proteases, for example, to detect endogenous protease activity in disease, to monitor the efficacy of protease inhibitors, or to image transgene expression.
Isolation of a novel TP53 target gene from a colon cancer cell line carrying a highly regulated wild-type TP53 expression system (1998)

We established a colon cancer cell line SW480-LOWTP53-1 carrying a wild-type TP53 transgene that is inducible under control of the lactose operon. Induction of this transgene by isopropyl-beta-D-thiogalactoside (IPTG) arrests growth of the transfected cells. To investigate cellular responses related to the TP53 signaling pathway to induce growth arrest, we applied a differential display method to screen mRNAs isolated from this cell line and looked for genes whose expression was activated or suppressed after induction of wild-type TP53. Subsequent Northern blot analysis confirmed that expression of one novel gene was regulated by wild-type TP53. The cDNA, termed TP53TG1 (TP53 target gene 1), contained an open reading frame of 270 nucleotides encoding 90 amino acids. Under conditions of cellular stress (ultraviolet irradiation or exposure to bleomycin or cisplatin), expression of TP53TG1 was induced in a wild-type TP53-dependent manner, indicating that this gene is likely to play an important role in the signaling pathway of TP53 and may function in response to cellular damage.
Lithology Determination Using Downhole Bit Mechanics Data (1993)

Abstract A technique has been developed which uses downhole weight on bit (DWOB) and downhole torque (DTOR) measurements to determine the occurrence and thickness of cemented zones in the pay sands of the Kuparuk River oil field. The DWOB/DTOR measurements are made by the MWD tool which is located above the bit and is normally not affected by frictional losses along the drill string. The cemented zones, containing siderite in the upper sand and ankerite in the lower, are high density streaks that reduce production or in the case of Ankerite are non productive. Using these measurements the cemented zones can be detected, in real time, when the bit first contacts the zone. Because the downhole sensors respond immediately to the changes in lithology the vertical resolution is one ft. which is better than the open hole logs commonly obtained in the field. From comparisons with density-neutron log data it was demonstrated that the new technique reliably discriminated between cemented and non cemented zones while drilling. Because of the reliability and the high vertical resolution of the technique, the mapping of the cemented zones and the resulting oil in place estimates have improved. The lithology information obtained from the DWOB/DTOR measurements compliment the triple combo data. By comparing the drilling mechanics data with the density and neutron logs suspect data can be highlighted. In areas where washouts have occurred the wireline data may be adversely affected but the drilling mechanics arc not. The acquisition of downhole bit mechanics data is a useful addition to the logging program and can be effectively utilized in combination with a full log suite or as a replacement for the density-neutron tools as an ankerite or siderite locator.
Thrombospondin 1 and Its Specific Cysteine-Serine-Valine-Threonine-Cysteine-Glycine Receptor in Fetal Wounds (1999)

Thrombospondin 1 (TSP-1), an adhesive glycoprotein, plays an important role in platelet adhesion, inflammation, cell-cell interaction, and angiogenesis. TSP-1 is expressed by endothelial cells, fibroblasts, and macrophages. The unique cysteine-serinevaline-threonine-cysteine-glycine (CSVTCG) binding domain of TSP-1 also plays an important role in cell binding and modulation of cellular processes. The purpose of this study was to evaluate histologically and quantitatively TSP-1 and its CSVTCG receptor in fetal skin wounds over time. Pregnant ewes underwent laparotomy and hysterotomy. At 65 days gestation (term, 145 days), incisional and excisional wounds were created on the fetal back in a similar position on each animal. The uterus and laparotomy were closed. The wounds were harvested on days 1, 3, 7, 21, and 28. Expression of TSP-1 and its CSVTCG receptor was evaluated immunohistochemically and quantitated by computer image analysis in units of absorbance. Immunoglobulin G (negative) controls were performed and subtracted from the TSP-1 sample to eliminate background absorbance readings. Serum (negative) control was used for the CSVTCG receptor. Platelet concentrates were used as the positive control: TSP-1, 63.43; CSVTCG, 58.72. Results are expressed as absorbance+/-SEM. Results of TSP-1 are as follows: day 1, 33.02+/-0.26; day 3, 22.21+/-0.14; day 7, 20.56+/-1.07; day 21, 7.76+/-0.40; and day 28, 5.99+/-0.03. TSP-1 displays an early peak during fetal skin repair, followed by a steep decrease over the viewed time period. Results of CSVTCG receptor are as follows: day 1, 26.19+/-2.43; day 3, 30.20+/-0.64; day 7, 24.56+/-0.80; day 21, 24.70+/-0.40; and day 28, 21.65+/-1.39. Thus, CSVTCG receptor displays a slowed decrease in expression over time during fetal repair. No significant differences were noted between incisional and excisional samples. Temporal and histological differences exist in the localization and expression of TSP-1 and its CSVTCG receptor during fetal wound repair. TSP-1 is upregulated in tissues early. This corresponds with the known role of TSP-1 in cell-cell interaction, including potentiation of growth factor activity. TSP-1 also modulates matrix, allowing scar-free provisional matrix in the earlier stages of repair deposited by platelets. The potentiation of cell-associated protease activity by TSP-1 can support tissue and matrix turnover. This activity of TSP-1 may contribute to the formation of a scarless wound. TSP-1 destabilizes extracellular matrix contacts, and facilitates mitosis and migration. The action of TSP-1 as an adhesive protein allows numerous different cells to adhere to the extracellular membrane. CSVTCG receptor expression decreases during fetal repair as the cells migrate to the epithelial surface, suggesting a significant role of the CSVTCG receptor in keratinocytic maturation, differentiation, and epithelization.
Monoclonal antibody-mediated neutralization of infectious human papillomavirus type 11 (1990)

Monoclonal antibodies recognizing human papillomavirus type 11 (HPV-11) were prepared from BALB/c mice immunized with intact HPV-11 virions obtained from morphologically transformed human foreskin xenografts grown subrenally in athymic mice. Four of five monoclonal antibodies that were reactive by enzyme-linked immunosorbent assay only to intact virions neutralized HPV-11 infectivity in the athymic mouse xenograft system.
The ICEROSS concept (1993)

Prefabricated ICEROSS (Icelandic Roll On Silicone Socket) sockets have been in use in Iceland since early 1986. Use of custom-made silicone sockets began several years earlier, and a paper devoted to the subject was presented at the 1984 AOPA Assembly by the author of this article. The ICEROSS system is primarily used for suspension. At the same time the author believes it considerably improves the weight-bearing capability of the prosthesis and the interface between prosthesis and user. After being turned inside out and rolled over the stump, the silicone sleeve forces skin in a distal direction, stabilising soft tissue and minimising pistoning. Both prosthetist and user may experience some problems initially, although most can be overcome by careful socket design and skin care.
The Adrenal Androgen Androstenediol Is Present in Prostate Cancer Tissue after Androgen Deprivation Therapy and Activates Mutated Androgen Receptor (2004)

Despite an initial response to androgen deprivation therapy, prostate cancer (PCa) progresses eventually from an androgen-dependent to an androgen-independent phenotype. One of the mechanisms of relapse is antiandrogen withdrawal phenomenon caused by mutation of 877th amino acid of androgen receptor (AR). In the present study, we established a method to measure the concentration of androstenediol (adiol) in prostate tissue. We found that adiol maintains a high concentration in PCa tissue even after androgen deprivation therapy. Furthermore, adiol is a stronger activator of mutant AR in LNCaP PCa cells and induces more cell proliferation, prostate-specific antigen (PSA) mRNA expression, and PSA promoter than dihydrotestosterone (DHT). Because antiandrogen, bicalutamide, blocked adiol activity in LNCaP cells, it was suggested that adiol effect was mediated through AR. However, high concentration of bicalutamide was necessary to block completely adiol activity. These effects were specific to LNCaP cells because adiol had less effect in PC-3 PCa cells transfected with wild-type AR than DHT and had similar effect in PC-3 cells transfected with mutant AR. The mechanism that adiol activates mutant AR in LNCaP cells did not result from the increased affinity to mutant AR or from AR's association with coactivator ARA70. However, low concentration of adiol induced more AR nuclear translocation than DHT in LNCaP cells and not PC-3 cells transfected with AR. These results indicate that adiol may cause the progression of PCa even after hormone therapy.
Magnetically Induced Contraction of the Inspiratory Muscles in Dog (1990)

The inspiratory muscles in a dog were twitched to cause short-duration inspirations by discharging a capacitor bank into an excitation coil placed over the lower right chest.
Gamma Aminobutyric Acid (GABA) and Plant Responses to Stress (2000)

Abstract 4-aminobutyrate (GABA) is a non-protein amino acid that is widely distributed throughout the biological world. In animals, GABA functions as the predominant inhibitory neurotransmitter in the central nervous system by acting through the GABA receptors. The neuromuscular system enables animals to escape from environmental stresses. Being nonmotile, plants have evolved chemical responses to mitigate stress. Mechanisms by which GABA may facilitate these responses are discussed in this review. Environmental stresses increase GABA accumulation through two different mechanisms. Stresses causing metabolic and/or mechanical disruptions, resulting in cytosolic acidification, induce an acidic pH-dependent activation of glutamate decarboxylase and GABA synthesis. Extremely marked declines in cytosolic pH occur under oxygen deprivation, which is the primary stress factor in flooded soils, and this stress induces the greatest accumulation of GABA. Other stresses, including cold, heat, salt, and mild or transient environmental factors, such as touch, wind, rain, etc. rapidly increase cellular levels of Ca2+. Increased cytosolic Ca2+ stimulates calmodulin-dependent glutamate decarboxylase activity and GABA synthesis. A review of the kinetics of GABA accumulation in plants reveals a stress-specific pattern of accumulation that is consistent with a physiological role for GABA in stress mitigation. Recent physiological and genetic evidence indicates that plants may possess GAB A-like receptors that have features in common with the animal receptors. The mechanism of action of animal GABA receptors suggests a model for rapid amplification of ion-mediated signals and GABA accumulation in response to stress. Metabolic pathways that link GABA to stress-related metabolism and plant hormones are identified. The survival value of stress-related metabolism is dependent on metabolic changes occurring before stress causes irreversible damage to plant tissue. Rapid accumulation of GABA in stressed tissue may provide a critical link in the chain of events leading from perception of environmental stresses to timely physiological responses. Keywords: γ-aminobutyric acidcalciumGABA receptorGABA accumulationstress signalssignal transductionethylene.
RASAL2 activates RAC1 to promote triple-negative breast cancer progression (2014)

Patients with triple-negative breast cancer (TNBC) have a high incidence of early relapse and metastasis; however, the molecular basis for recurrence in these individuals remains poorly understood. Here, we demonstrate that RASAL2, which encodes a RAS-GTPase-activating protein (RAS-GAP), is a functional target of anti-invasive microRNA-203 and is overexpressed in a subset of triple-negative or estrogen receptor-negative (ER-negative) breast tumors. As opposed to luminal B ER-positive breast cancers, in which RASAL2 has been shown to act as a RAS-GAP tumor suppressor, we found that RASAL2 is oncogenic in TNBC and drives mesenchymal invasion and metastasis. Moreover, high RASAL2 expression was predictive of poor disease outcomes in patients with TNBC. RASAL2 acted independently of its RAS-GAP catalytic activity in TNBC; however, RASAL2 promoted small GTPase RAC1 signaling, which promotes mesenchymal invasion, through binding and antagonizing the RAC1-GAP protein ARHGAP24. Together, these results indicate that activation of a RASAL2/ARHGAP24/RAC1 module contributes to TNBC tumorigenesis and identify a context-dependent role of RASAL2 in breast cancer.
mRNA surveillance by the Caenorhabditis elegans smg genes. (1993)

mRNAs that contain premature stop codons are unstable in most eukaryotes, but the mechanism of their degradation is largely unknown. We demonstrate that functions of the six C. elegans smg genes are necessary for rapid turnover of nonsense mutant mRNAs of the unc-54 myosin heavy chain gene. Nonsense alleles of unc-54 express mRNAs that are unstable in smg(+) genetic backgrounds but have normal or near normal stability in smg(-) backgrounds. smg mutations also stabilize mRNA of unc-54(r293), a small deletion that removes the unc-54 polyadenylation site and expresses an aberrant mRNA. Most unc-54 nonsense mutations are recessive in both smg(+) and smg(-) genetic backgrounds. However, four specific alleles are recessive when smg(+) and dominant when smg(-). These smg-dependent dominant alleles express nonsense mutant polypeptides that disrupt thick filament and/or sarcomere assembly. All four alleles are predicted to express nonsense fragment polypeptides that contain most of the myosin globular head domain without an attached rod segment. By degrading messages that contain premature stop codons, the smg genes eliminate mRNAs that encode potentially toxic protein fragments. We propose that this system of mRNA turnover protects cells from their own errors of transcription, mRNA processing, or mRNA transport.
The prevalence of femoral osteolysis associated with components inserted with or without cement in total hip replacements. A retrospective matched-pair series. (1994)

The prevalence of femoral osteolysis in hips in which a femoral component had been inserted without cement was compared with that in hips with a cemented component, in a retrospective matched-pair study of the results of primary total hip arthroplasties; all patients had received the same type of acetabular component. Forty-one hips in thirty-nine patients who had a Harris-Galante porous-coated total hip prosthesis without cement were matched by age, sex, weight, duration of follow-up, and diagnosis with forty-one hips in thirty-eight patients who had a hybrid total hip reconstruction; the hybrid reconstruction consisted of the same acetabular component and a Precoat femoral component inserted with a so-called third-generation cementing technique. All of the operations were done by the same surgeon, who used the same operative approach and the same course of postoperative rehabilitation. All of the patients were followed for at least four years (mean, six years). Osteolysis developed in twelve (29 percent) of the hips that had a femoral component without cement compared with none of the hips that had a cemented component (p < 0.0002). At the latest follow-up examination, none of the femoral components that had been inserted with cement were loose and none had been revised, while eight (20 percent) of the femoral components that had been inserted without cement were loose and five (12 per cent) had been revised. This retrospective matched-pair study controlled for many of the variables associated with a comparison of the rates of femoral osteolysis in separate series of femoral components fixed with and without cement.(ABSTRACT TRUNCATED AT 250 WORDS)
Inside Cover: Catalytic Asymmetric Boration of Acyclic α,β‐Unsaturated Esters and Nitriles (Angew. Chem. Int. Ed. 1/2008) (2007)

Asymmetric conjugate addition of bis(pinacolato)diboron to α,β-unsaturated carbonyl compounds would provide easy access to enantioenriched functionalized organoboron compounds, which are useful intermediates in organic synthesis. In their Communication on page 145 ff., J.-E. Lee and J. Yun describe the enantioselective β-boration of α,β-unsaturated esters and nitriles using a copper catalyst and planar chiral diphosphine ligands.