gebhart/patrepeval huggingface dataset:
Transcriptional regulation of the virA and virG genes of Agrobacterium tumefaciens (1988)

We have used transcriptional and translational fusions between various vir gene promoters and the lacZ gene to study the regulation of vir genes. Like other vir promoters, the virA promoter was induced by acetosyringone in a virA virG-dependent fashion. In addition to being induced by acetosyringone, the virG promoter was partially induced by acidic growth conditions and by starvation for inorganic phosphate. These two conditions appeared to act synergistically. The response to low pH and to phosphate starvation occurred in the absence of the Ti plasmid and must therefore have been mediated by chromosomal genes. Two transposon-generated mutations were obtained which attenuated induction by low pH. One of these transposons was cloned along with flanking DNA; the flanking DNA was sequenced (858 base pairs total), and the predicted amino acid sequence showed homology with a family of proteins including the Rhizobium leguminosarum nodI gene, many of whose members bind ATP and have been implicated in active transport systems. These results are discussed as possible explanations for previous observations that the induction of the octopine vir regulon (i) occurs only in acidic media and (ii) shows hyperbolic kinetics after a long lag phase.
Solid Phase Synthesis (1986)

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Immunochemical analysis of myosin heavy chain during avian myogenesis in vivo and in vitro. (1982)

Monoclonal antibodies (McAbs) against the myosin heavy chain (MHC) of adult chicken pectoralis muscle have been tested for reactivity with pectoralis myosin at selected stages of chick development in vivo and in vitro. Three such McAbs, MF 20 and MF 14, which bind to light meromyosin, and MF 30, which binds to myosin subfragment two (S2), were used to assay the appearance and accumulation of specific MHC epitopes with: (a) indirect, solid phase radioimmune assay (RIA), (b) immunoautoradiography, (c) immunofluorescence microscopy. McAb MF 20 bound strongly and equivalently to MHC at all stages of embryonic development in vivo. In contrast, the MF 30 epitope was barely detectable at 12 d of incubation but its concentration rose rapidly just before hatching. No detectable binding of MF 14 to pectoralis myosin could be measured during myogenesis in vivo until 1 wk after hatching. Immunofluorescence studies revealed that all three epitopes accumulate in the same myocytes of the developing pectoralis muscle. Since all three McAbs bound with high activity to native and denatured forms of myosin, it is unlikely that differential antibody reactivity can be explained by conformational changes in myosin during development in vivo. When myogenesis in vitro was monitored using the same McAbs, MF 20 bound to the MHC at all stages tested while reactivity of MF 30 and MF 14 with myosin from cultured muscle was never observed. Thus, this study demonstrates three different immunochemical states of the MHC during development in vivo of chick pectoralis muscle and the absence of later occurring immunochemical transitions in the MHC of cultured embryonic muscle.
Glutamate Receptors in Plants (2002)

Ionotropic glutamate receptors function in animals as glutamate-gated non-selective cation channels. Numerous glutamate receptor-like (GLR) genes have been identified in plant genomes, and plant GLRs are predicted, on the basis of sequence homology, to retain ligand-binding and ion channel activity. Non-selective cation channels are ubiquitous in plant membranes and may function in nutrient uptake, signalling and intra-plant transport. However, there is little evidence for amino acid gating of plant ion channels. Recent evidence suggests that plant GLRs do encode non-selective cation channels, but that these channels are not gated by amino acids. The functional properties of these proteins and their roles in plant physiology remain a mystery. The problems surrounding characterization and assignation of function to plant GLRs are discussed in this Botanical Briefing, and potential roles for GLR proteins as non-selective cation channels involved in metabolic signalling are described.
High throughput analysis of gene expression in the human brain (2000)

The human brain is thought to have the greatest complexity of gene expression of any region of the body, reflecting the diverse functions of neurons and glia. Studies of gene expression in the human brain may yield fundamental information about the phenotype of brain cells in different stages of development, in different brain regions, and in different physiological and pathological states. As the human genome project nears completion, several technological advances allow the analysis of thousands of expressed genes in a small brain sample. This review describes available sources of human brain material, and several high throughput techniques used to measure the expression of thousands of genes. These techniques include expressed sequence tag (EST) sequencing of cDNA libraries; differential display; subtractive hybridization; serial analysis of gene expression (SAGE); and the emerging technology of high density DNA microarrays. Measurement of gene expression with microarrays and other technologies has potential applications in the study of human brain diseases, including cognitive disorders for which animal models are typically not available. Gene expression measurements may be used to identify genes that are abnormally regulated as a secondary consequence of a disease state, or to identify the response of brain cells to pharmacological treatments.
Protection of Calves Against Rhinovirus Infection by Nasal Secretion Interferon Induced by Infectious Bovine Rhinotracheitis Virus (1980)

SUMMARY Six calves were inoculated intranasally with a vaccinal strain of infectious bovine rhinotracheitis ( ibr ) virus, and six calves were given a placebo. All calves were challenge exposed (aerosol) with a bovine rhinovirus 4 days later. Nasal excretion of ibr virus and rhinovirus, interferon concentrations in the nasal secretions ( ns ), and serum antibody were measured before, and at times after, calves were inoculated. All calves given ibr virus had detectable interferon in their ns . Four of the calves had interferon in their ns at 24 hours after ibr viral inoculation. All six calves had interferon at 2, 4, and 5 days, and 5 calves continued to have interferon in their ns at 7 days after ibr viral inoculation. Nasal excretion of ibr virus usually persisted longer than did secretion of interferon. Interferon was not detected in the ns of control calves after challenge exposure with rhinovirus. Serum interferon was not detected in any calf. After rhinovirus challenge, nasal excretion of rhinovirus was detected only one time in one calf given ibr virus. In contrast, rhinovirus excretion was detected in five control calves on at least two consecutive days. Excretion of rhinovirus was detected in 3 control calves at 6 days, in 2 calves at 10 days, and 1 calf at 14 days after rhinovirus inoculation. Clinical signs of respiratory tract disease were not observed in control calves excreting rhinovirus. All of the 12 calves in the experiment had serum antibody against rhinovirus at the time of challenge exposure, but this antibody did not protect against infection of the controls as evidenced by rhinovirus excretion in the ns .
Development of monoclonal antibody imaging of metastatic prostatic carcinoma (1989)

Indium-111-labeled monoclonal antibody directed against prostate-specific antigen was injected into ten patients with known prostatic carcinoma, nine with metastatic disease. The monoclonal antibody scan was compared to the standard technetium bone scan, and both were correlated to clinical status and to 2-year follow-up. The ratio of target-to-nontarget activity and pharmacokinetics of the radiolabeled antibody were determined. Based on these findings we are hopeful that modifications of this radiolabeled antibody approach may be used for staging and may be developed as a therapeutic adjuvant.
Real-Time PCR Technology for Cancer Diagnostics (2002)

There is a need to translate recent discoveries in oncology research into clinical practice. This requires objective, robust, and cost-effective molecular techniques for clinical trials and, eventually, routine use. Real-time PCR has attractive features for tumor profiling in the clinical laboratory.
Radiofrequency Neurotomy for Low Back Pain: Evidence-Based Procedural Guidelines (2005)

The evidence-based procedural guidelines provide consistent criteria for multisite studies that could enroll a sufficiently large homogenous study cohort.
Some novel windows and a concise tutorial comparison of window families (1978)

Some novel windows are introduced. A comparison of these and the well-known windows in terms of their frequency domain properties is given. It is concluded that Kaiser, modified Kaiser, Tukey, and three-coefficient window families appear to be the best of the known windows of 6, 12, and 18 dB/oct decay rates.
Spatial management of information (1978)

Methods of spatially managing data are currently under study at the Architecture Machine Group. Management concepts are drawn from everyday examples of paper and document handling. However, the work elaborates data types to include: animation, movies, and sound-sync computer graphics.
Toe temperature change: a measure of sleep onset? (1980)

In an attempt to provide a more "physiological" measure of sleep onset, temperature of the great toe was monitored for 166 sleeper-nights in both insomniac and control groups. All subjects were women between 21 and 45 years of age. Earlier published reports had suggested that toe temperature elevation was the result of lowered sympathetic tone and marked a "vegetative preparedness for sleep." More recently, elevation of the toe temperature has been used to denote a level of chemical anesthesia sufficient for major surgery. In this study, however, the mean latency of the time course of the temperature elevation of the toe was uncorrelated with sleep onset determined by EEG criteria. Temperature elevations were frequently of large magnitude but were not uniformly observed across all subjects and all nights. It is suggested that the toe temperature elevation is reflective of metabolic adjustments which coincide with the onset of the night's first period of slow wave sleep.
The therapy of constipation (2001)

Constipation is a common symptom that may be idiopathic or due to various identifiable disease processes. Laxatives are agents that add bulk to intestinal contents, that retain water within the bowel lumen by virtue of osmotic effects, or that stimulate intestinal secretion or motility, thereby increasing the frequency and ease of defecation. Drugs which improve constipation by stimulating gastrointestinal motility by direct actions on the enteric nervous system are under development. Other modalities used to treat constipation include biofeedback and surgery. Laxatives and lavage solutions are also used for colon preparation and evacuation of the bowels after toxic ingestions.
High-resolution structure of a mutagenic lesion in DNA. (1990)

The self-complementary dodecanucleotide d[CGC(m6G)AATTTGCG]2 (where m6G is O6-methylguanine), which contains two m6G.T base pairs, has been analyzed by x-ray diffraction methods and the structure has been refined to a residual error of R = 0.185 at 2.0-A resolution. The m6G.T mispair closely resembles a Watson-Crick base pair and there are very few structural differences between the m6G.T duplex and the native analogue. The similarity between the m6G.T base pair and a normal G.C base pair explains the failure of mismatch repair enzymes to recognize and remove this mutagenic lesion. A series of ultraviolet melting studies over a wide pH range on a related dodecamer indicate that the m6G.C mispair can exist in two conformations; one is a wobble pair and the other is a protonated Watson-Crick pair. The former, which predominates at physiological pH, will be removed by normal proofreading and repair enzymes, whereas the latter is likely to escape detection. Hence, the occasional occurrence of the protonated m6G.C base pair may explain why the presence of m6G in genomic DNA does not always give rise to a mutation.
Alternate Splicing of the p53 Inhibitor HDMX Offers a Superior Prognostic Biomarker than p53 Mutation in Human Cancer (2012)

Conventional high-grade osteosarcoma is the most common primary bone malignancy. Although altered expression of the p53 inhibitor HDMX (Mdmx/Mdm4) is associated with cancer risk, progression, and outcome in other tumor types, little is known about its role in osteosarcoma. High expression of the Hdmx splice variant HDMX-S relative to the full-length transcript (the HDMX-S/HDMX-FL ratio) correlates with reduced HDMX protein expression, faster progression, and poorer survival in several cancers. Here, we show that the HDMX-S/HDMX-FL ratio positively correlates with less HDMX protein expression, faster metastatic progression, and a trend to worse overall survival in osteosarcomas. We found that the HDMX-S/HDMX-FL ratio associated with common somatic genetic lesions connected with p53 inhibition, such as p53 mutation and HDM2 overexpression in osteosarcoma cell lines. Interestingly, this finding was not limited to osteosarcomas as we observed similar associations in breast cancer and a variety of other cancer cell lines, as well as in tumors from patients with soft tissue sarcoma. The HDMX-S/HDMX-FL ratio better defined patients with sarcoma with worse survival rates than p53 mutational status. We propose a novel role for alternative splicing of HDMX, whereby it serves as a mechanism by which HDMX protein levels are reduced in cancer cells that have already inhibited p53 activity. Alternative splicing of HDMX could, therefore, serve as a more effective biomarker for p53 pathway attenuation in cancers than p53 gene mutation.
Nanodisks: hydrophobic drug delivery vehicles (2008)

Members of the class of exchangeable apolipoproteins possess the unique capacity to transform phospholipid vesicle substrates into nanoscale disk-shaped bilayers. This reaction can proceed in the presence of exogenous hydrophobic biomolecules, resulting in the formation of novel transport vehicles termed nanodisks (NDs). The objective of this study is to describe the structural organization of NDs and evaluate the utility of these complexes as hydrophobic biomolecule transport vehicles. The topics presented focus on two distinct water insoluble drugs, amphotericin B (AMB) and all trans retinoic acid (ATRA). In vitro and in vivo studies reveal that AMB-ND display potent anti-fungal and anti-protozoal activity, while ATRA-ND show promise in the treatment of cancer. The versatility conferred by the presence of a polypeptide component provides opportunities for targeted delivery of ND to cells.
Induction of Highly Embryogenic Calli and Plant Regeneration in Upland (Gossypium hirsutum L.) and Pima (Gossypium barbadense L.) Cottons (2001)

To accomplish our objective of broadening the number of regenerable cotton lines, we developed a protocol capable of producing plants through somatic embryogenesis of diverse cotton species. Callus was initiated from hypocotyl and cotyledon explants on a callus initiation medium [CIM; modified MS with 1 mg L −1 kinetin and 2 mg L −1 naphthaleneacetic acid (NAA)]. Friable embryogenic callus was periodically selected and transferred onto callus selection/maintenance medium (CS/MM) [modified MS with 0.1 mg L −1 kinetin and 0.5 mg L −1 NAA]. The selected callus was then transferred into a liquid embryo initiation medium (EIM) (modified MS medium in which NH 4 NO 3 was removed and KNO 3 amount doubled) followed by transfer to solid embryo maturation media EMMS 2 (0.5 mg L −1 NAA + 0.05 mg L −1 kinetin). The liquid step not only decreased the culturing time but also increased the number of embryos per gram of cultured tissue. Germinating somatic embryos were placed on MS medium with no hormones and plantlets were acclimatized before transfer to the greenhouse. Significant numbers of somatic embryos and their derived plantlets were obtained from a commercial cultivar of G. hirsutum , Deltapine 90 and G. barbadense accession GB‐35B126 (PI‐528306). The mean embryos per gram for Deltapine 90 on EMMS 2 were higher than those previously reported for Coker 312. Highly significant differences were found between the two genotypes for both embryo and plant production. To our knowledge, this is the first report of regeneration of G. barbadense through somatic embryogenesis.
Protein-Protein Interactions as Therapeutic Targets for Cancer (1994)

Abstract: The recent elucidation of many of the pathways involved in the regulation of cellular proliferation provides new opportunities for therapeutic intervention in the treatment of cancer. The inherent specificity of many of these protein-protein interactions should provide great selectivity, and emerging models of cell cycle control suggest that disrupting growth factor signalling pathways might selective_ly induce programmed cell death in cancer cells. However, many of these protein-protein interactions appear to occur over fairly large surfaces, suggesting that the identification of small molecules with the necessary affinity and specificity to disrupt these interactions in vivo represents a challenging undertaking. In the current review, we highlight three particular targets in the growth factor signalling pathways : growth factor - receptor binding, using Gastrin Releasing Peptide as a specific example; SH2 I SH3 domain interactions; and viral oncoprotein interaction with cellular proteins in the nucleus, focusing on the binding of Human Papillomavirus proteins with cellular growth suppressor gene products. These studies highlight both the promise and the pitfalls of selectively targeting protein-protein interactions for the treatment of cancer.
Identification of a Selective Nonpeptide Antagonist of the Anaphylatoxin C3a Receptor That Demonstrates Antiinflammatory Activity in Animal Models (2001)

The anaphylatoxin C3a is a potent chemotactic peptide and inflammatory mediator released during complement activation which binds to and activates a G-protein-coupled receptor. Molecular cloning of the C3aR has facilitated studies to identify nonpeptide antagonists of the C3aR. A chemical lead that selectively inhibited the C3aR in a high throughput screen was identified and chemically optimized. The resulting antagonist, N(2)-[(2,2-diphenylethoxy)acetyl]-L-arginine (SB 290157), functioned as a competitive antagonist of (125)I-C3a radioligand binding to rat basophilic leukemia (RBL)-2H3 cells expressing the human C3aR (RBL-C3aR), with an IC(50) of 200 nM. SB 290157 was a functional antagonist, blocking C3a-induced C3aR internalization in a concentration-dependent manner and C3a-induced Ca(2+) mobilization in RBL-C3aR cells and human neutrophils with IC(50)s of 27.7 and 28 nM, respectively. SB 290157 was selective for the C3aR in that it did not antagonize the C5aR or six other chemotactic G protein-coupled receptors. Functional antagonism was not solely limited to the human C3aR; SB 290157 also inhibited C3a-induced Ca(2+) mobilization of RBL-2H3 cells expressing the mouse and guinea pig C3aRS: It potently inhibited C3a-mediated ATP release from guinea pig platelets and inhibited C3a-induced potentiation of the contractile response to field stimulation of perfused rat caudal artery. Furthermore, in animal models, SB 290157, inhibited neutrophil recruitment in a guinea pig LPS-induced airway neutrophilia model and decreased paw edema in a rat adjuvant-induced arthritis model. This selective antagonist may be useful to define the physiological and pathophysiological roles of the C3aR.
Design, Synthesis, and Biological Evaluation of Indole Biphenylcarboxylic Acids as PPARγ Antagonists (2015)

The thiazolidinediones (TZD) typified by rosiglitazone are the only approved therapeutics targeting PPARγ for the treatment of type-2 diabetes (T2DM). Unfortunately, despite robust insulin sensitizing properties, they are accompanied by a number of severe side effects including congestive heart failure, edema, weight gain, and osteoporosis. We recently identified PPARγ antagonists that bind reversibly with high affinity but do not induce transactivation of the receptor, yet they act as insulin sensitizers in mouse models of diabetes (SR1664).1 This Letter details our synthetic exploration around this novel series of PPARγ antagonists based on an N-biphenylmethylindole scaffold. Structure-activity relationship studies led to the identification of compound 46 as a high affinity PPARγ antagonist that exhibits antidiabetic properties following oral administration in diet-induced obese mice.
Adenovirus VA1 Noncoding RNA Can Inhibit Small Interfering RNA and MicroRNA Biogenesis (2004)

Although inhibition of RNA interference (RNAi) by plant virus proteins has been shown to enhance viral replication and pathogenesis in plants, no viral gene product has as yet been shown to inhibit RNAi in vertebrate cells. Here, we present evidence demonstrating that the highly structured approximately 160-nucleotide adenoviral VA1 noncoding RNA can inhibit RNAi at physiological levels of expression. VA1, which is expressed at very high levels in adenovirus-infected cells, potently inhibited RNAi induced by short hairpin RNAs (shRNAs) or human microRNA precursors but did not affect RNAi induced by artificial short interfering RNA duplexes. Inhibition appeared to be due both to inhibition of nuclear export of shRNA or premicro-RNA precursors, competition for the Exportin 5 nuclear export factor, and inhibition of Dicer function by direct binding of Dicer. Together, these data argue that adenovirus infection can result in inhibition of RNAi and identify VA1 RNA as the first viral gene product able to inhibit RNAi in human cells.
Cellular Origin of Human B-Cell Lymphomas (1999)

The origin of human lymphomas has been studied by various approaches, including histology and immunophenotyping. In some types of lymphoma these studies suggested the cellular origin, but in many instances the origin could not be identified. When somatic mutations of the genes for the variable region of the B-lymphocyte antigen receptor proved to be a hallmark of germinal-center B cells and their descendants, sequence analysis of the variable-region genes of B-cell lymphomas offered a molecular approach to studying the origin of the tumors. Before discussing the results of these studies, we outline the human peripheral B-cell repertoire and its generation. . . .
Impact of Ergocalciferol Treatment of Vitamin D Deficiency on Serum Parathyroid Hormone Concentrations in Chronic Kidney Disease (2007)

Ergocalciferol therapy is a reasonable initial therapy for vitamin D deficiency associated with elevated PTH levels in stage 3 CKD. It does not appear to have equivalent benefits in stage 4 CKD.
Increased synthesis of α-tocopherol, paramylon and tyrosine by Euglena gracilis under conditions of high biomass production (2010)

By combining different carbon and nitrogen sources and inducing a tolerable stress to the cell by adding ethanol, it was possible to increase the production of biomass, paramylon, α-tocopherol and some amino acids. The concentrations of α-tocopherol achieved in this study are higher than others reported previously for Euglena, plant and algal systems. This work helps to understand the effect of different carbon sources on the synthesis of bio-molecules by E. gracilis and can be used as a basis for future works to improve the production of different metabolites of biotechnological importance by this organism.
Target to apoptosis: A hopeful weapon for prostate cancer (1997)

Modulation of apoptotic response represents a novel mechanism-based approach which may help identify novel drugs and/or develop new therapeutic regimens for the treatment of prostate cancers.