gebhart/patrepeval huggingface dataset:
The extracellular matrix coordinately modulates liver transcription factors and hepatocyte morphology. (1991)

The extracellular matrix (ECM) promotes tissue morphogenesis, cell migration, and the differentiation of a variety of cell types. However, the mechanisms by which ECM causes differentiated gene expression have been unknown. In this report, we show that culturing the hepatocyte-derived cell line H2.35 on an ECM gel changes cell morphology and selectively stimulates the transcription of a subset of liver-specific genes, including serum albumin. Transcriptional activation by ECM also occurs with transfected plasmids bearing the transcriptional enhancer of the albumin gene. ECM substrates of different composition activated the albumin enhancer only when the ECM promoted a cuboidal, differentiated cell morphology. Enhancer activation by the ECM was mediated by two liver transcription factors, HNF3 alpha and eH-TF, which appear to be regulated differently by matrix. Specifically, we found that a collagen gel substratum caused a selective increase in the factor HNF3 alpha at the levels of mRNA accumulation and DNA-binding activity in nuclear extracts, both in H2.35 cells and in the hepatoma cell line HepG2. We conclude that the ECM can stimulate cell differentiation by selectively activating transcriptional regulatory factors and that such regulation occurs coordinately with ECM-promoted changes in cell shape.
Yeast KEX2 protease and mannosyltransferase I are localized to distinct compartments of the secretory pathway (1989)

The KEX2 protease (product of the KEX2 gene) functions late in the secretory pathway of Saccharomyces cerevisiae by cleaving the polypeptide chains of prepro-killer toxin and prepro-alpha-factor at paired basic amino acid residues. The intracellular vesicles containing KEX2 protease sedimented in density gradients to a position distinct from those containing mannosyltransferase I (product of the MNN1 gene), a marker enzyme for the Golgi complex. The recovery of intact compartments containing these enzymes approached 80% after sedimentation. We propose that the KEX2 protease and mannosyltransferase I reside within distinct compartments.
Death by neglect as a deletional mechanism of peripheral tolerance (1999)

In contrast to most organs, the anatomy of the liver may allow naive CD8(+) T cells to make direct contact with liver parenchymal cells. We have previously shown, using a combination of TCR transgenic T cells specific for H-2 K(b) and hepatocytes expressing a transgenic H-2 K(b) molecule, that hepatocytes can induce antigen-specific activation and proliferation of naive CD8(+) T cells independently of CD28 co-stimulation. However, T cell activation by hepatocytes leads to premature T cell death and tolerance, both in vivo and in vitro. In this study, we investigated the mechanisms of T cell death induced by hepatocytes in vitro using primary hepatocytes to activate purified CD8(+) T cells. Neither Fas nor tumor necrosis factor receptor were involved, indicating that hepatocyte- induced death was distinct from activation-induced cell death. Before they started to divide, T cells activated by hepatocytes expressed lower levels of the bcl-x(L) survival gene and 30 times less IL-2 mRNA than CD8(+) cells activated by splenic antigen-presenting cells. Since CD28 co-stimulation increases both IL-2 and bcl-x(L) expression, this suggests that hepatocyte-activated T cells die by neglect because they fail to receive effective co-stimulatory signals. In agreement with this model, premature death promoted by hepatocytes could be prevented by cross-linking CD28. Survival after CD28 cross-linking correlated with increased IL-2 and bcl-x(L) expression, and sustained T cell proliferation, while cytotoxic T lymphocyte activity was prolonged as compared with cells stimulated without CD28 co-stimulation. This study confirms that high- affinity TCR transgenic antigen-specific CD8(+) T cells can be activated to proliferate and differentiate into cytotoxic effector cells. However, prolonged T cell survival and cytotoxicity required CD28 co-stimulation as well. To our knowledge, this is the first report suggesting that tolerance in the context of lack of CD28 co-stimulation can result from Fas-independent peripheral deletion rather than from anergy.
RST-style Discourse Parsing and Its Applications in Discourse Analysis (2015)

Discourse parsing is the task of identifying the relatedness and the particular discourse relations among various discourse units in a text. In particular, among various theoretical frameworks of discourse parsing, I am interested in Rhetorical Structure Theory (RST). I hypothesize that, given its ultimate success, discourse parsing can provide a general solution for use in many downstream applications.This thesis is composed of two major parts. First, I overview my work on discourse segmentation and discourse tree-building, which are the two primary components of RST-style discourse parsing. Evaluated on the RST Discourse Treebank (RST-DT), both of my discourse segmenter and tree-builder achieve the state-of-the-art performance.Later, I discuss the application of discourse relations to some specific tasks in the analysis of discourse, including the evaluation of coherence, the identification of authorship, and the detection of deception. In particular, I propose to use a set of application-neutral features, which are derived from the discourse relations extracted by my discourse parser, and compare the performance of these application-neutral features against the classic application-specific approaches to each of these tasks. On the first two tasks, experimental results show that discourse relation features by themselves often perform as well as those classic application-specific features, and the combination of these two kinds of features usually yields further improvement. These results provide strong evidence for my hypothesis that discourse parsing is able to provide a general solution for the analysis of discourse. However, we failed to observe a similar effectiveness of discourse parsing on the third task, the detection of deception. I postulate that this might be due to several confounding factors of the task itself.
Microdosing psychedelics: More questions than answers? An overview and suggestions for future research (2019)

Background: In the past few years, the issue of ‘microdosing’ psychedelics has been openly discussed in the public arena where claims have been made about their positive effect on mood state and cognitive processes such as concentration. However, there are very few scientific studies that have specifically addressed this issue, and there is no agreed scientific consensus on what microdosing is. Aim: This critique paper is designed to address questions that need to be answered by future scientific studies and to offer guidelines for these studies. Approach: Owing to its proximity for a possible approval in clinical use and short-lasting pharmacokinetics, our focus is predominantly on psilocybin. Psilocybin is allegedly, next to lysergic acid diethylamide (LSD), one of the two most frequently used psychedelics to microdose. Where relevant and available, data for other psychedelic drugs are also mentioned. Conclusion: It is concluded that while most anecdotal reports focus on the positive experiences with microdosing, future research should also focus on potential risks of (multiple) administrations of a psychedelic in low doses. To that end, (pre)clinical studies including biological (e.g. heart rate, receptor turnover and occupancy) as well as cognitive (e.g. memory, attention) parameters have to be conducted and will shed light on the potential negative consequences microdosing could have.
Phase I Studies of Anti–Epidermal Growth Factor Receptor Chimeric Antibody C225 Alone and in Combination With Cisplatin (2000)

C225 has dose-dependent pharmacokinetics, and doses that achieve saturation of systemic clearance are well tolerated. C225 given in combination with cisplatin has biologic activity at pharmacologically relevant doses.
CARD Proteins as Therapeutic Targets in Cancer (2004)

Proteins containing a caspase-associated recruitment domain (CARD) have been established as key regulators of cell death and, more recently, cytokine production. During the last several years, the number of proteins identified within this family has grown immensely and many aspects of their function point to their potential utility as novel drug targets in the treatment of cancer. Several CARD family proteins are critical components of the conserved cell death machinery which, when dysregulated, promotes oncogenesis and contributes prominently to tumor resistance to chemotherapy. The pro-apoptotic protein Apaf1, which is inactivated in some cancers, is a CARD protein that is indispensable for mitochondria-induced apoptosis. Other anti-apoptotic CARD proteins, such as TUCAN/CARDINAL/CARD8, have been shown to protect tumors from cell death stimuli and to be over-expressed in certain forms of cancer. Therapeutics that activate or inhibit CARD proteins may therefore be potentially utilized as novel chemo-sensitizing agents when used in conjunction with conventional chemotherapy. Other CARD proteins influence cellular processes through the regulation of NF-kappaB or caspase-1, which governs the levels of interleukin-1beta (IL-1beta). In addition to its pro-inflammatory properties, this cytokine also contributes to neoplastic progression by promoting angiogenesis, proliferation, and the metastasis of many tumors. Many of the IL-1beta-regulating CARD proteins also contain a nucleotide binding/oligomerization domain known as a NACHT and may therefore be amenable to targeting by small molecule compounds. This review examines the role of CARD proteins in cytoprotection and cytokine processing in the context of neoplasia and presents strategies for using this information in devising potential novel anticancer agents.
Survival of Macroencapsulated Allogeneic Parathyroid Tissue One Year after Transplantation in Nonimmunosuppressed Humans (2001)

The use of immunoisolation devices may allow transplantation without need for immunosuppression and could widen the indications for cell transplantation. In this study, we evaluated the survival of encapsulated parathyroid tissue in nonimmunosuppressed humans. Autologous parathyroid implants: Seven patients undergoing parathyroidectomy had devices containing small pieces of their own parathyroid tissue implanted SC. These devices were explanted after 2-4 weeks for histological evaluation. Allogeneic parathyroid implants: Four patients with chronic hypoparathyroidism were transplanted with one to three large (40 microl) and one small (4.5 microl) device filled with meshed parathyroid tissue and implanted SC. The small devices were explanted at 4 weeks, while the large ones were explanted 8.5 to 14 months after implantation. In both studies, control implants were placed in nude mice. Autologous study results: At explantation, the grafts consisted of 22 +/- 6% endocrine tissue and 63 +/- 7% fibrosis, while 15 +/- 5% of the grafts were necrotic. Allogeneic study results: In devices explanted from the patients at 4 weeks, fibrosis dominated and only 1%, 5%, and 23% of the grafts consisted of endocrine tissue. A similar histological appearance was found in grafts from nude mice. In devices explanted at 8.5-14 months, histologically intact endocrine tissue was found in all patients. However, nearly all the tissue consisted of fibrosis. There was no detectable increase in the parathormone (PTH) level in all patients. Macroencapsulated human allogeneic parathyroid tissue can survive up to 1 year after transplantation into nonimmunosuppressed patients. However, marked fibroblast overgrowth occurred, especially in the allogeneic implant study, using meshed parathyroid tissue. This was probably not related to the allo-response, because similar findings were observed in the nude mouse implants. In future studies, better tissue preparation and improvements in the physiological milieu inside the device may help to reduce fibroblast overgrowth and increase survival of the parathyroid cells.
Synthesis of supported metal nanoparticle catalysts using ligand assisted methods (2012)

The synthesis and characterization methods of metal nanoparticles (NPs) have advanced greatly in the last few decades, allowing an increasing understanding of structure-property-performance relationships. However, the role played by the ligands used as stabilizers for metal NPs synthesis or for NPs immobilization on solid supports has been underestimated. Here, we highlight some recent progress in the preparation of supported metal NPs with the assistance of ligands in solution or grafted on solid supports, a modified deposition-reduction method, with special attention to the effects on NPs size, metal-support interactions and, more importantly, catalytic activities. After presenting the general strategies in metal NP synthesis assisted by ligands grafted on solid supports, we highlight some recent progress in the deposition of pre-formed colloidal NPs on functionalized solids. Another important aspect that will be reviewed is related to the separation and recovery of NPs. Finally, we will outline our personal understanding and perspectives on the use of supported metal NPs prepared through ligand-assisted methods.
Heterocyclic Carbenes: A High‐Yielding Synthesis of Novel, Functionalized N‐Heterocyclic Carbenes in Liquid Ammonia (1996)

Abstract To date the only free carbenes of the imidazoline‐2‐ylidene type to have been described in the literature are those bearing simple hydrocarbon or haloalkyl and ‐aryl substituents. We report here a novel, versatile and high‐yielding method for the synthesis of N‐heterocyclic carbenes in a mixture of liquid ammonia and aprotic organic solvents. Deprotonation of the imidazolium precursor salts proceeds under mild conditions within a few minutes at temperatures below –30°C, and side reactions are thus avoided. The imidazolium salts are much more soluble in organic solvents if liquid ammonia is added. Furthermore, the acidity of the C‐2 protons appears to be enhanced by hydrogen bonding. Not only are the known free ylidenes conveniently and quantitatively accessible by this procedure, but also novel functionalized derivatives that are not accessible by known procedures. Imidazoline‐2‐ylidenes with linear, branched, cyclic, heteroatom‐substituted (O, N, P) and chiral hydrocarbon residues are accessible through the novel route. Stable carbene‐metal “adducts” are conveniently obtained by treating the free carbenes with chloro‐ or acetato‐bridged dinuclear metal complexes, or by displacement of coordinated ligands such as carbon monoxide, THF or acetonitrile by the free carbenes. The syntheses of novel imidazolium salts. N‐heterocyclic carbenes and carbene adducts of Ru II , RH I , W 0 and sulfur are reported, and the structures of five products analysed by single‐crystal X‐ray diffraction. N‐Heterocyclic carbenes bearing functionalized side chains are important because a number of these complexes show excellent activity in catalytic reactions. They do not show the typical reactivity of metal‐carbon “double bonds” and are remarkably stable both thermally and chemically. For a number of reasons, they are best viewed as donor adducts of the highly Lewis basic imidazoline‐2‐ylidene ligands and the Lewis acidic organometallic fragments. The new synthetic procedure reported here makes N‐heterocylic carbenes a generally accessible class of useful ligands in coordination chemistry and catalysis.
Localized scleroderma: response to occlusive treatment with tacrolimus ointment (2005)

Journal Article Localized scleroderma: response to occlusive treatment with tacrolimus ointment Get access G. Mancuso, G. Mancuso Department of Dermatology, Municipal Hospital of Lugo, Ravenna, Italy E‐mail: mavelabs@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar R.M. Berdondini R.M. Berdondini Department of Dermatology, Municipal Hospital of Lugo, Ravenna, Italy E‐mail: mavelabs@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 152, Issue 1, 1 January 2005, Pages 180–182, https://doi.org/10.1111/j.1365-2133.2004.06318.x Published: 01 January 2005
Automated Control of an Adaptive Bihormonal, Dual-Sensor Artificial Pancreas and Evaluation During Inpatient Studies (2014)

Automated control of blood glucose in patients with type-1 diabetes has not yet been fully implemented. The aim of this study was to design and clinically evaluate a system that integrates a control algorithm with off-the-shelf subcutaneous sensors and pumps to automate the delivery of the hormones glucagon and insulin in response to continuous glucose sensor measurements. The automated component of the system runs an adaptive proportional derivative control algorithm which determines hormone delivery rates based on the sensed glucose measurements and the meal announcements by the patient. We provide details about the system design and the control algorithm, which incorporates both a fading memory proportional derivative controller (FMPD) and an adaptive system for estimating changing sensitivity to insulin based on a glucoregulatory model of insulin action. For an inpatient study carried out in eight subjects using Dexcom SEVEN PLUS sensors, prestudy HbA1c averaged 7.6, which translates to an estimated average glucose of 171 mg/dL. In contrast, during use of the automated system, after initial stabilization, glucose averaged 145 mg/dL and subjects were kept within the euglycemic range (between 70 and 180 mg/dL) for 73.1% of the time, indicating improved glycemic control. A further study on five additional subjects in which we used a newer and more reliable glucose sensor (Dexcom G4 PLATINUM) and made improvements to the insulin and glucagon pump communication system resulted in elimination of hypoglycemic events. For this G4 study, the system was able to maintain subjects' glucose levels within the near-euglycemic range for 71.6% of the study duration and the mean venous glucose level was 151 mg/dL.
A 150 MeV FFAG synchrotron with "Return-Yoke Free" magnet (2002)

The 150 MeV proton FFAG (Fixed Field Alternating Gradient) synchrotron is under construction at KEK to investigate the possibilities of various applications such as proton beam therapy after the success of the POP FFAG synchrotron. One of distinguished features of this machine compared with the PoP FFAG is to use a new type of magnet, "Return-Yoke Free" magnet. Because there is no return-yoke in the median plane in this magnet, the beam injection and extraction become easier.
Corneoscleral Melt After Pterygium Surgery Using a Single Intraoperative Application of Mitomycin-C (1996)

A 59-year-old man underwent pterygium excision with intraoperative application of 0.2 mg/ml (0.02%) mitomycin-C placed on the scleral bed for 3 min. A sliding conjunctival flap was used to cover the exposed limbus and sclera. Five weeks after the original surgery, the patient had mild trauma and noted decreased vision. At that time, it was noted that he had a corneoscleral melt with perforation. The patient was managed with a lamellar transplant in this area. Intraoperative single-dose application of topical mitomycin-C can be associated with serious complications. This case occurred despite the fact that this patient received the lowest dose used in a series of 25 eyes using the same technique without any other complications. Although topical mitomycin-C is effective as an adjunct to pterygium surgery and may reduce recurrence, the safety and efficacy of various concentrations and dosing schedules need further definition.
Expression profiling identifies a novel alpha-methylacyl-CoA racemase exon with fumarate hydratase homology. (2003)

Human alpha-methylacyl-CoA racemase (AMACR) was overexpressed in prostate cancer compared with nonmalignant tissues. The Gene Logic Inc. BioExpress database containing Affymetrix U133 GeneChip expression profiles of 4400 human normal, benign, diseased, and tumor samples from >60 tissue types was examined to determine the specificity of AMACR mRNA expression. One particular AMACR probeset was derived from an alternatively spliced exon with 88% identity to a 521-bp sequence that spans four exons of the fumarate hydratase. The predicted protein sequence revealed a novel GLGELIL peptide shared by both proteins. Whether the mitochondrial and peroxisomal AMACR described previously are distinct products from alternatively spliced transcripts remains to be determined. The determination of the cellular location and function of the altered AMACR will be critical in the elucidation of the role of AMACR in prostate cancer diagnosis and pathogenesis.
Upstream sequences confer atrial-specific expression on the human atrial natriuretic factor gene. (1988)

5'-Flanking sequences from the human atrial natriuretic factor (hANF) gene were subcloned into a reporter plasmid (pSVOCAT) and transfected into primary cultures of neonatal rat atrial cardiocytes. Hybrid hANFCAT genes containing either 2500 or 409 base pairs of 5'-flanking sequence DNA were expressed at similar levels. When sequences between -409 and -332 were deleted, reporter gene (CAT) activity decreased significantly. Expression of the hANFCAT constructs was specific for atrial cells, as no expression was detected in primary cultures of ventricular cardiocytes or nonmyocardial cells derived from the neonatal hearts. Correct transcription start sites for the transfected hANF genes were confirmed by S1 nuclease mapping and RNase protection analysis. A "gel shift" assay was used to identify a specific cardiac nuclear protein which bound to the 5'-flanking sequence of the hANF gene. A 192-base pair PvuII fragment (-400 to -208) associated with a protein in these extracts in a tissue- and sequence-specific fashion. These findings indicate that the DNA sequence between -409 and -332 in the hANF gene harbors a tissue-specific element whose activity may involve association with a cardiac-specific nuclear protein.
Maximum likelihood frequency detectors for orthogonal multicarrier systems (2002)

A frequency estimation algorithm for a multicarrier system based on the maximum likelihood principle is derived. A frequency detector structure directly based on this algorithm is proposed, together with a reduced complexity structure having the same performance. Such a detector shows a very small acquisition range due to the particular form of the likelihood functions for a multicarrier sytem. To overcome this limitation, a modified version of the frequency detector is proposed. It has a considerably increased acquisition range together with low augmentation in complexity.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Novel Window-Structure AlGaInP Visible-Light Laser Diodes with Non-Absorbing Facets Fabricated by Utilizing GaInP Natural Superlattice Disordering (1990)

Window-structure AlGaInP visible-light ( λ L =680 nm) laser diodes (LDs) have been fabricated, for the first time, by utilizing GaInP natural superlattice (NSL) disordering with selective Zn diffusion. The bandgap energy for the active layer near the mirror facets is increased by 70 meV by the NSL disordering. An 80 mW output power in a fundamental transverse-mode has been achieved for the uncoated window LDs under 1 µsec long pulsed operations. The maximum output power density for the window LDs is estimated to be 10 MW/cm 2 , which is five times higher than that for conventional LDs.