gebhart/patrepeval huggingface dataset:
Expression of the mRNA of Seven Metabotropic Glutamate Receptors (mGluR1 to 7) in the Rat Retina. An In Situ Hybridization Study on Tissue Sections and Isolated Cells (1995)

We have studied the expression of mRNAs for seven metabotropic glutamate receptors (mGluR1-7) in the retina of the adult rat by in situ hybridization with tissue sections and isolated cells using [alpha 35S]dATP-labelled oligonucleotide probes. Hybridization revealed the expression of six of the metabotropic receptor mRNAs, mGluR1, 2 and 4-7, in the retina, while mGluR3 was not detected. Each of the expressed receptor mRNAs showed a distinct pattern of expression. In the outer nuclear layer, corresponding to photoreceptor somata, no labelling was detected. In the outer part of the inner nuclear layer, putative horizontal cells were labelled for mGluR5. More proximal in this layer, corresponding to the position of bipolar cell somata, there was strong labelling for mGluR6. A small number of bipolar cells were also labelled for mGluR5 and mGluR7. In situ hybridization with isolated cells showed that mGluR6 was expressed by rod bipolar cells. Subsets of amacrine cells, with cell bodies along the border between the inner nuclear layer and the inner plexiform layer, were positive for mGluR1, 2, 4 and 7, suggesting considerable heterogeneity of these receptors among amacrine cells. None of the seven metabotropic receptor mRNAs was expressed in isolated Müller glial cells. In the ganglion cell layer, virtually every ganglion cell and displaced amacrine cell was labelled for mGluR1 and mGluR4. Some cells in this layer (approximately 20% of the total), most likely both ganglion cells and displaced amacrine cells, were also labelled for mGluR2 and mGluR7. These findings suggest that metabotropic glutamate receptors are considerably more widespread among neurons in the retina than indicated by previous physiological and pharmacological investigations.
Antitumor therapy with bacterial DNA and toxin: complete regression of established tumor induced by liposomal CpG oligodeoxynucleotides plus interleukin-13 cytotoxin. (2003)

Despite urgent need, no single strategy has been widely effective at controlling the growth of rapidly progressive solid tumors. We demonstrate here a potent antitumor therapy using modified bacterial DNA and toxin. Treatment of human head and neck cancer established as xenografts in athymic mice with immunostimulatory CpG oligodeoxynucleotides encapsulated in sterically stabilized cationic liposome [(CpG ODN)(SSCL)] and recombinant interleukin-13 Pseudomonas exotoxin (IL13-PE) significantly reduced the tumor growth followed by complete regression in most animals. The antitumor activity of (CpG ODN)(SSCL) was dependent on natural killer cells that infiltrated within tumors. Interestingly, IL13-PE enhanced (CpG ODN)(SSCL)-induced natural killer cell activity and cytokine production in vivo and in vitro. These data strongly suggest that a combination of innate immune activation by (CpG ODN)(SSCL) and tumor-directed targeting by IL13-PE is a novel approach for human cancer immunotherapy.
Evolutionarily Conserved Paired Immunoglobulin-like Receptor α (PILRα) Domain Mediates Its Interaction with Diverse Sialylated Ligands (2012)

Paired immunoglobulin-like receptor (PILR) α is an inhibitory receptor that recognizes several ligands, including mouse CD99, PILR-associating neural protein, and Herpes simplex virus-1 glycoprotein B. The physiological function(s) of interactions between PILRα and its cellular ligands are not well understood, as are the molecular determinants of PILRα/ligand interactions. To address these uncertainties, we sought to identify additional PILRα ligands and further define the molecular basis for PILRα/ligand interactions. Here, we identify two novel PILRα binding partners, neuronal differentiation and proliferation factor-1 (NPDC1), and collectin-12 (COLEC12). We find that sialylated O-glycans on these novel PILRα ligands, and on known PILRα ligands, are compulsory for PILRα binding. Sialylation-dependent ligand recognition is also a property of SIGLEC1, a member of the sialic acid-binding Ig-like lectins. SIGLEC1 Ig domain shares ∼22% sequence identity with PILRα, an identity that includes a conserved arginine localized to position 97 in mouse and human SIGLEC1, position 133 in mouse PILRα and position 126 in human PILRα. We observe that PILRα/ligand interactions require conserved PILRα Arg-133 (mouse) and Arg-126 (human), in correspondence with a previously reported requirement for SIGLEC1 Arg-197 in SIGLEC1/ligand interactions. Homology modeling identifies striking similarities between PILRα and SIGLEC1 ligand binding pockets as well as at least one set of distinctive interactions in the galactoxyl-binding site. Binding studies suggest that PILRα recognizes a complex ligand domain involving both sialic acid and protein motif(s). Thus, PILRα is evolved to engage multiple ligands with common molecular determinants to modulate myeloid cell functions in anatomical settings where PILRα ligands are expressed.
Static and Dynamic Weaving in System Software with AspectC++ (2006)

System software strongly relies on the availability of static as well as dynamic adaptation techniques. With Aspect-Oriented Programming (AOP) it is now possible to adapt even policy-like crosscutting concerns in the implementation of system software. While this is straightforward in the static case, dynamic adaptation of crosscutting concerns requires an expensive dynamic aspect weaving infrastructure. Furthermore, the relation between static and dynamic aspects is widely unexplored. In this paper we present our experiences with static and dynamic adaptation of crosscutting concerns in the embedded operating system eCos. The work is based on the novel "single language approach", which allows us to configure the binding time of aspects, and a "family-based dynamic weaver infrastructure", which reduces the resource consumption needed for dynamic AOP by tailoring the run time system. In our prototype implementation all this has been integrated into an environment, which allows us to "play" with the binding time of aspects and supported dynamic weaver features. Thus, we can now answer questions about the resource consumption of these adaptation techniques and the relationship of static and dynamic aspects in general.
Genetic variations and treatments that affect the lifespan of the NPC1 mouse (2007)

Niemann-Pick type C (NPC) disease is a multisystem disorder caused primarily by a mutation in the npc1 gene. These studies evaluated the effect of genetic background, deletion of additional genes, and administration of several agents on the age at death in a murine model of this disorder. Such factors as differing strain background or genetic drift within a given background in the npc1(-/-) mouse significantly altered the age at death and the degree of organ disease. Genetic deletion of Siat9 (GM3 synthetase) or Nr1h2 [liver X receptor (LXR)beta] shortened the life of the npc1(-/-) animals. Daily treatment of the npc1(-/-) mice with an LXR agonist or administration of a single dose of cyclodextrin, with or without the neurosteroid allopregnanolone, significantly slowed neurodegeneration and increased the lifespan of these animals. These data illustrate that the age at death of the npc1(-/-) mouse can be significantly influenced by many factors, including differences in strain background, other inactivating gene mutations (Siat9 and lxrbeta), and administration of agents such as LXR agonists and, particularly, cyclodextrin. It is currently not clear which of these effects is nonspecific or which might relate directly to the molecular defect present in the NPC1 syndrome.
Autonomous DNA Replication in Human Cells Is Affected by the Size and the Source of the DNA (1991)

We previously developed short-term and long-term assays for autonomous replication of DNA in human cells. This study addresses the requirements for replication in these assays. Sixty-two random human genomic fragments ranging in size from 1 to 21 kb were cloned in a prokaryotic vector and tested for their replication ability in the short-term assay. We found a positive correlation between replication strength and fragment length, indicating that large size is favored for efficient autonomous replication in human cells. All large fragments replicated efficiently, suggesting that signals which can direct the initiation of DNA replication in human cells are either very abundant or have a low degree of sequence specificity. Similar results were obtained in the long-term assay. We also used the same assays to test in human cells a random series of fragments derived from Escherichia coli chromosomal DNA. The bacterial fragments supported replication less efficiently than the human fragments in the short-term and long-term assays. This result suggests that while the sequence signals involved in replication in human cells are found frequently in human DNA, they are uncommon in bacterial DNA.
Amino acid substitutions in HIV-1 reverse transcriptase with corresponding residues from HIV-2. Effect on kinetic constants and inhibition by non-nucleoside analogs (1993)

Nevirapine is a highly potent and specific inhibitor of human immunodeficiency virus type 1 (HIV-1) polymerase, but is inactive against HIV-2 and other polymerase. Previous studies demonstrated that residues 176-190 of HIV-1 reverse transcriptase (RT) can confer nevirapine sensitivity to HIV-2 RT. To better characterize the role of this sequence in HIV-1 RT, we have progressively substituted residues 176-190 of HIV-2 RT for those of HIV-1 RT and monitored the impact on the kinetic properties; inhibitory activity of nevirapine (11-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido[2,3-b:2',3'-e] [1,4]diazepin-6-one), E-BPU (5-ethyl-1-benzyloxymethyl-6-(phenylthio)-uracil), and TIBO-R82150 ((+)-S-4,5,6,7-tetrahydro-5-methyl-6-(3-methyl-2-butenyl)imidazo[4,5,1-j k] [1,4]benzodiazepin-2(1H)-thione); and inhibitor-induced fluorescence changes of the mutant enzymes. The study revealed that in addition to Try-181 and Tyr-188, a new amino acid residue (Gly-190) plays an important role in determining susceptibility to nevirapine and E-BPU, but not to TIBO-R82150. These data argue that these non-nucleoside inhibitors fit differently, even though they share a common binding pocket. Nevirapine was seen to exert inhibitory activity by altering the interaction of the enzyme with the template-primer. Kinetic parameters were modulated by the template (DNA versus RNA) as well as by some of the mutations.
Modern oxygen carriers: state of art 1990. (1991)

Three major components of blood with clearly defined functions are: 1) red cells 2) plasma volume 3) coagulation factors At the present time artificial or synthetic coagulation factors are not available. Plasma volume expanders are well known in clinical practice. The main subject of this paper is the complex area of red cell substitutes with particular reference to the oxygen carrying capacity. The history of blood oxygen carrying capacity is briefly presented with particular reference to contributions by G. S. Adair, C. Bohr, M. Perutz and R. R. Benesch. 3 oxygen carrying developments are discussed in detail: 1) perfluorocarbons 2) artificial red cells 3) stroma-free haemoglobin solution Perfluorocarbons were used as carriers of oxygen in experiments and clinical practice. Before their wide clinical application a number of potential problems must be solved. In selected patients (coronary angioplasty, cerebral thrombosis, cardiopulmonary by-pass) perfluorocarbons (Fluosol D-A) could be considered as beneficial. Artificial red cells (neohaemocytes) are available in some centres in which progress of micro-technology appears to lead to encapsulation of purified human haemoglobin. These preparations should receive more attention. Finally stroma-free haemoglobin solution was the subject of our own research for several years. Our preparation met the requirements of the blood substitute, but had the short half-life in the circulation. Recent advances in chemistry in some centres resulted in the modification of hb molecule and linking with P-5-P. The modified poly hb solution is an ideal oxygen delivering fluid.
Late-Stage Fluorination: From Fundamentals to Application (2014)

In this brief account, we review work from our lab with a focus on late-stage introduction of fluorine and fluorinated functional groups into small molecules. We attempt to highlight practical developments, which we believe may have potential for industrial applications, and critically reflect on developments that may not yet meet the bar for practical use.
Pluripotential hematopoietic stem cells in post-5-fluorouracil murine bone marrow express the Thy-1 antigen. (1985)

Expression of the Thy-1 alloantigen by hematopoietic stem and progenitor cells in post-5-fluorouracil (5-FU) murine bone marrow was investigated. FACS analysis of BDF1 bone marrow stained for Thy-1.2 with a triple-layer amplified labeling technique demonstrated that 35% of the total bone marrow population expressed Thy-1.2 (Thy-1.2+). Two distinct size subpopulations were observed in post-5-FU BDF1 marrow. Thy-1.2+ cells were present in both the large and the small subpopulations. FACS-separated bone marrow cells were also plated in methylcellulose cultures. Ninety percent of all colony-forming cells surviving in vivo administration of 5-FU were Thy-1.2+. Replating of primary hemopoietic colonies and morphologic examination of primary and secondary colonies demonstrated that the most primitive stem cells including "stem" (S) cells were Thy-1.2+. These cells (Thy-1.2+) were capable of self-renewal in vitro and exhibited multiple differentiation potentials in comparison to Thy-1.2-cells, which lacked significant self-renewal capability and were mono- or bipotent progenitor cells. Separation of Thy-1.2+ cells into large or small Thy-1.2+ subpopulations showed that only the large Thy-1.2+ colony-forming cells possessed significant self-renewal capacity. Treatment of BDF1 bone marrow with anti-Thy-1.2 plus complement reduced primary colony formation by 67% and eliminated those colony-forming cells which had extensive self-renewal properties. In the presence of PWMSCM, depletion and reconstitution of T lymphocytes had no effect on primary or secondary colony formation. These data demonstrate that Thy-1 is present on primitive hematopoietic stem cells in post-5-FU bone marrow. In addition, they show that the murine S cell is Thy-1+.
A new electrocatalyst consisting of a molecularly homogeneous platinum–aerogel nanocomposite (1997)

Aerogels offer interesting opportunities for (electro)catalysis due to their high porosity and specific surface area. A new electrocatalytic material consisting of a molecularly homogeneous platinum–aerogel nanocomposite was prepared. The mixed components represent, at the microscopic level, very homogeneous combinations originating from chemical interactions at the molecular scale in the liquid phase that can be viewed as "frozen in" in the solid state via supercritical drying. Transmission electron microscopy (TEM) images of this material clearly show that nanometer-size platinum particles are homogeneously distributed and are a part of the molecular architecture of the composite. An X-ray photoelectronic spectroscopy (XPS) study indicates that there exists a special interaction between platinum and the support within a polyacrylonitrile–Pt (PAN-Pt) electrocatalyst. This material is a promising electrocatalyst for oxygen reduction, and its electrocatalytic activity arises from the nanodispersed platinum particles present in the nanocomposite. Keywords: electrocatalyst, aerogel, nanocomposite, oxygen reduction, metal–support interaction.
Recent Advances in the Neuropathology of Schizophrenia (1993)

This article reviews some 50 neuroanatomical postmortem studies published in the last 20 years. The majority of these studies demonstrated various types of subtle anomalies in limbic structures, that is, the hippocampus, parahippocampal gyrus, entorhinal cortex, amygdala, cingulate gyrus, and septum of schizophrenia patients. A number of schizophrenic symptoms might be related to structural and functional disturbances of these brain regions. But these studies also reported subtle changes in parts of the basal ganglia, thalamus, cortex, corpus callosum, and brainstem neurotransmitter systems. Many of the studies, however, are based on small sample sizes and, therefore, must be regarded as preliminary. Cytoarchitectonic abnormalities and lack of gliosis in limbic structures as well as the absence of normal structural cerebral asymmetry in a substantial proportion of patients indicate that these structural anomalies may reflect a disorder of prenatal brain development and argue against the notion that schizophrenia is a progressive degenerative brain disorder.
Concanavalin A induces perforin-mediated but not Fas-mediated hepatic injury (1996)

Concanavalin A (Con A) induces T-cell-mediated hepatic injury in vivo, although Con A-stimulated lymphocytes are not cytotoxic to normal hepatocytes in vitro. This contradiction makes the mechanism of Con A-induced hepatitis elusive. In this study, we demonstrate that Con A but not tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), or actinomycin D (ActD) induced the susceptibility of hepatocytes to activated autologous lymphocyte cytotoxicity. Con A sensitized hepatocytes within 30 minutes after the stimulation in a dose-dependent fashion. The cytotoxicity was dose-dependently inhibited by either a Con A ligand, alpha-methyl mannoside, or a perforin inhibitor, concanamycin A (CMA), but not by anti-Fas ligand antiserum. In addition, Con A-treated hepatocytes were not sensitive to autologous activated lymphocytes from a perforin-deficient mouse, while hepatocytes from lpr mice were sensitized by Con A. In fact, Con A did not induce liver injury in perforin-deficient mice within the concentration employed in this study. Therefore, we conclude that the cytotoxicity was mediated through perforin/granzymes but not through the Fas/Fas ligand pathway. The cytotoxicity was inhibited by anti-intercellular adhesion molecule-1 (ICAM-1)/LFA-1 antibodies, but not by anti-VCAM-1/VLA-4 antibodies, both in vitro and in vivo. The cytotoxicity appears to be caused by CD8+ T cells; however, the cytokines from activated CD4+ T cells play a critical role in the pathogenesis of the hepatitis in vivo, because administration of anti-IFN-gamma antibodies inhibited the occurrence of the hepatitis. In conclusion, Con A-induced hepatitis is thought to be dominantly mediated by a perforin-dependent pathway through ICAM-1/LFA-1 interaction.
Doxil (D), Vincristine (V), Reduced Frequency Dexamethasone (d) and Revlimid(R) (DVd-R) Results in a High Response Rate in Patients with Refractory Multiple Myeloma (RMM). (2005)

Abstract Background: The combination of DVd with Thalidomide (T) results in a high response rate (greater than 80% with about 50% of patients achieving a CR or NCR) in multiple myeloma. Revlimid, an immunomodulatory drug (IMiD) is active in patients with MM. We previously reported on a phase I trial of DVd-R in patients with MM, in which the maximum tolerated dose of R was 10mg daily. Methods: The DVd-R regimen was given as follows: on day 1 D was given at 40 mg/m2 IVPB; V at 2 mg IVP; d at 40 mg PO daily for 4 days, R was started at 10mg daily. R was given for 21 days consecutively. For the first cycle R was started 7 days prior to chemotherapy, while it was started on day 1 on subsequent cycles (cycle 1 was 35 days). DVd was planned every 28 days for 2 cycles after best response or a minimum of 4 cycles. Maintenance therapy consisted of R +/− Prednisone 50 mg Qod. All patients received amoxicillin, acyclovir and aspirin 81mg prophylactically. Responses were assessed based on the criteria set forth by SWOG. Patients: The study accrued 58 patients to date (36 refractory and 22 relapsed patients), 45 are evaluable for response. The median patient age at the start of the study is 62 years and 74% are males. The median number of prior chemotherapeutic regimen is 3 (range 1–7), 67% of patients had progressed after a Thalidomide containing regimen, 70% had received a VAD like regimen and 17% had received a prior autologous stem cell transplant. The median time from diagnosis to study entry is 39 month (range 5–182). Eighty six percent had Durie Salomon stage III. The mean serum B2microglobin was 6.6mg/dL (s.d.4.2). Results: The median number of cycles of DVd-R delivered was 4. Of evaluable patients, 6 patients had a CR (13%), 5 had a NCR (11%), 16 had a PR (35%), 11 had stable disease (24%), and 7 had progressive disease (15%) as their best response. The median time to best response was 38 days. After a median follow up of 7.3 month (range 0–24 months), 23 patients had progressive disease and 16 patients had died. Fifty two percent of refractory patients (19/36) had a response on DVd-R. Grade 3 and 4 leukopenia occurred in 24% and 15% respectively, however febrile neutropenia occurred in only 1 patient. Grade 3 and 4 infections occurred in 26% and 3% respectively (all but one were pneumonia). Grade 3 thrombocytopenia occurred in 20%. Venous thromboembolic events occurred in 5 patients (9%) (2 patients with pulmonary embolus and 4 with deep venous thrombosis). Grade 3 neuropathy occurred in 3 patients (no patients had grade 4 neuropathy). Two patients developed grade 3 tumor lysis syndrome. Conclusion: DVd-R is an effective chemotherapeutic regimen in patients with RMM who progressed or did not respond to VAD like regimens or to Thalidomide containing regimens, produces a high response rate among chemotherapy resistant patients, and has a manageable toxicity profile. The results will be updated at the time of the meeting.
Acyl CoA:Cholesterol Acyltransferase (ACAT) Inhibitors: Synthesis and Structure-Activity Relationship Studies of a New Series of Trisubstituted Imidazoles (1994)

A series of 4,5-diaryl-2-(substituted thio)-1H-imidazoles has been synthesized and demonstrated to be potent inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). The design, synthesis, and structure-activity relationships for this series are reported herein. One of the compounds from this series, N'-(2,4-difluorophenyl)-N-[5-[(4,5-diaryl-1H-imidazol-2- yl)thio]pentyl]-N-heptylurea (DuP 128), was selected for development as an intestinally active ACAT inhibitor. DuP 128 is a potent ACAT inhibitor in vitro and in vivo, inhibiting ACAT in rat hepatic microsomes with an IC50 = 10 nM and possessing potent antihypercholesterolemic activity in vivo.
Arteriovenous malformations of the brain: choosing embolic materials to enhance safety and ease of excision (1992)

The authors report their experience with surgical resection of 108 previously embolized arteriovenous malformations (AVM's). Embolization was performed via only transfemoral catheterization in 70 lesions and via the surgical exposure of feeding vessels in 32. The remaining six patients were referred for resection following silicone sphere embolization elsewhere. Materials used included polyvinyl alcohol (PVA) foam, platinum microcoils, detachable silicone balloons, surgical silk, a mixture of 33% ethanol and microfibrillar collagen, and isobutyl cyanoacrylate (IBCA). It is believed that proximal arterial occlusion with balloons is an inferior choice for preresection embolization, because the technical difficulty of placement is high and the nidus of the AVM is unaffected. Vascular coagulation and section and AVM retraction are more difficult with IBCA; therefore, this is also considered an inferior choice. Among the materials studied, the combination of PVA for distal occlusion and microcoils for proximal occlusion appears to be the superior choice. Fewer complications (stroke or hemorrhage) are seen when intraarterial Amytal (amobarbital) testing is used to guide the embolization. Data regarding toxicity, oncogenicity, and vascular metabolism or recanalization associated with PVA, IBCA, and n-butyl cyanoacrylate are reviewed.