gebhart/patrepeval huggingface dataset:
Human interleukin-9: genomic sequence, chromosomal location, and sequences essential for its expression in human T-cell leukemia virus (HTLV)-I-transformed human T cells (1991)

We have isolated the genomic sequence of human interleukin-9 (IL-9) based on its sequence homology with a human IL-9 cDNA isolated from human T-cell leukemia virus (HTLV)-I-transformed T cells by expression cloning. The entire genomic sequence has been determined and the gene consists of five exons and four introns. The human IL-9 gene is mapped to the long arm of human chromosome 5 at band 5q31–32, a region found to be deleted in a number of patients with acquired 5q- abnormalities and hematologic disorders. Several blocks of transcriptional control sequences have been identified at the 5′-flanking region of the human IL-9 gene that may play an important role in the control of IL-9 gene expression. The 5′-regulatory region of the human IL-9 gene also contains sequences identified in the 5′-flanking regions of other cytokine genes mapped to the long arm of human chromosome 5, including IL-3, IL-4, IL-5, and granulocyte-macrophage colony-stimulating factor and other T-cell growth factor genes including IL-2 and IL-6. The IL-9 gene is constitutively expressed in the HTLV-I-transformed human T cells and the expression of IL-9 in these cells can be further induced by 12-O-tetradecanoyl phorbol 13-acetate. Transient transfection analysis using the plasmid containing the 5′-flanking region of IL-9 gene upstream from the firefly luciferase ciferase report gene indicated that the 0.9-kb Smal-Sacl fragment of the IL-9 gene contains sequences required for the constitutive and activated expression of IL- 9 gene in HTLV-I-transformed cells. These results will now allow us to study the regulatory mechanism of IL-9 gene expression in normal and leukemic human T cells.
Isolation of Drosophila proteins that bind selectively to left-handed Z-DNA. (1982)

An affinity column for isolating Z-DNA binding proteins was made by attaching brominated poly(dG-dC) to Sephadex. Proteins from Drosophila nuclei were prepared and those that could bind to Escherichia coli B-DNA were removed from the solution. The remaining proteins were passed over the Z-DNA affinity column and then eluted with NaCl. Using both direct and competitive filter binding assays, we found that the eluted proteins bind to brominated poly(dG-dC) (Z-DNA) and poly(dG-m5dC) but not to poly(dG-dC) (B-DNA), native or denatured E. coli or calf thymus DNA, or brominated oligonucleotides. The proteins also bind to negatively supercoiled plasmids carrying Z-DNA sequences but not to relaxed or linearized plasmids in which the Z-DNA conformation is no longer present. Gel analysis reveals a mixture of several large proteins up to approximately 150,000 daltons.
Characterization of a recombinant antibody produced in the course of a high yield fed‐batch process (1994)

Abstract Many mammalian cell fed‐batch processes rely on maintaining the cells in a viable and productive state for extended periods of time in order to reach high final concentrations of secreted protein. In the work described herein, a nonamplified NSO cell line was transfected with a vector expressing a recombinant human anti‐HIV gp 120 monoclonal antibody (Mab) and a selectable marker, glutamine synthetase. A fed‐batch process was developed which improved product yields tenfold over the yields reached in batch culture. In this case, the clone was cultured for a period of 22 days and produced 0.85 g Mab/L. To gauge the effect of extended culture lifetime on product quality, biochemical characteristics of MAb isolated from different time points in the fed‐batch culture were determined. The apparent molecular weight of the MAb was constant throughout the course of the culture. Isoelectric focusing revealed four major charged species, with a fifth more acidic species appearing later in the culture. The antigen binding kinetics were constant for MAb isolated throughout the culture period. Glycosylation analysis, on the other hand, revealed that MAb produced later in the culture contained greater percentages of truncated N ‐acetylglucosamine and highmannose N ‐glycans. Possible contributions to this underglycosylated material from either cell lysis or synthesis from noviable cells were found to be negligible. Instead, the viable cells appeared to be secreting more truncated and high mannose MAb glycoforms as the culture progressed. © 1994 John Wiley &amp; Sons, Inc.
Biodistribution and vaccine efficiency of murine dendritic cells are dependent on the route of administration. (1999)

Dendritic cells (DCs) are professional antigen-presenting cells, well equipped to initiate an immune response. Currently, tumor antigen-derived peptide loaded DCs are used in clinical vaccination in cancer patients. However, the optimal dose and route of administration of a DC vaccine still remain to be determined. Using indium-111-labeled DCs, we investigated whether the route of administration does affect the biodistribution of DCs in lymphoid organs and whether it influences the outcome of DC vaccination in the B16 mouse melanoma tumor model. The results demonstrate that i.v. injected DCs mainly accumulate in the spleen, whereas s.c. injected DCs preferentially home to the T-cell areas of the draining lymph nodes. Using tyrosinase-related protein-2-derived peptide-loaded DC vaccination in a fully autologous B16 melanoma tumor model, we observed a delay in tumor growth, improved survival as well as increased antitumor cytotoxic T-cell reactivity after s.c. vaccination as compared to i.v. vaccination. These data demonstrate that optimal induction of antitumor reactivity against the autologous melanocyte differentiation antigen tyrosinase-related protein-2-derived peptide occurs after s.c. vaccination and correlates with the preferential accumulation of DCs in the T-cell areas of lymph nodes.
Blood Group Antigens as Tumor Markers, Parasitic/Bacterial/Viral Receptors, and Their Association with Immunologically Important Proteins (1995)

Blood group antigens (BGAs) are chemical moieties on the red blood cell (RBC) membrane. Some BGAs (e.g., A, B, H, Lewis, P, I) are widely distributed throughout the body and may not be primarily erythroid antigens. Statistical correlations with ABO blood groups and disease have been made for years and have been highly controversial. It is not known if BGAs have a biological function. There are increasing reports of BGAs [e.g., Le(x) (an isomer of Le(a)), Le(y) (an isomer of Le(b)), T, Tn, "A-like"] appearing as "new" antigens on malignant tissue. Their presence and membrane density appears to correlate with the metastatic potential of the tumor. This often parallels loss of normal BGAs (e.g., ABH) from the tissue. Some of these antigens have been shown to influence the humoral and cellular response and have been used in assays to determine preclinical cancer, and in tumor immunotherapy. Interactions of some parasites and bacteria with human cells have been shown to depend on the presence of certain BGAs. P. vivax malarial parasites only enter human RBCs when the Fy6 Duffy blood group protein is present on the RBCs. Certain E. coli will only attach to the epithelial cells of the urinary tract if P or Dr BGAs are present in the epithelial cells. The P antigen is also the RBC receptor for Parvovirus B19. Leb has recently been found to be the receptor for H. pylori in the gastric tissue. The high frequency BGA, AnWj, is the RBC receptor for H. influenzae. BGAs have been shown to be associated closely with some important complement proteins. Ch/Rg BGAs have been found not to be true BGAs but are RBC-bound C4 (C4d). Knops/McCoy/York BGAs have been located on the C3b/C4b receptor (CR1). The high frequency BGAs of the Cromer (Cr) system are located on decay accelerating factor (DAF or CD55). Cartwright (Yt) BGAs are located on RBC acetylcholinesterase molecules. DAF and acetylcholinesterase are on phosphatidylinositol-glycan (PIG) linked proteins. When the PIG anchor is missing from RBCs, as in paroxysmal nocturnal hemoglobinuria, the affected RBCs lack all Cr, Yt, JMH, Hy/Gy, Do and Emm BGAs. The most important ligand for P, E and L selectins is sialyl-Le(x). This interaction is the tethering stage that start the leukocytes' journey from the circulation into the tissue. It appears that malignant cells may move through tissue in a similar way and may explain the close association of Le(x) with metastasis. Thus, there are increasing data suggesting a biological role for BGAs unrelated to the RBC.
Induction of T-cell tolerance to an MHC class I alloantigen by gene therapy (2002)

Induction of immunologic tolerance to alloantigens is a major goal in the field of transplantation. Here, we demonstrate that efficient transduction and expression of a retrovirally transduced major histocompatibility complex (MHC) class I gene (H-2K(b)) in bone marrow (BM)-derived cells, resulting in a permanent state of hematopoietic molecular chimerism, induces stable tolerance to the transduced gene product. Reconstitution of lethally irradiated syngeneic recipients with BM transduced with virus encoding H-2K(b) resulted in life-long expression of the retroviral gene product on the surface of BM-derived hematopoietic lineages including Sca-1(+), lineage negative, hematopoietic progenitors. T cells from mice receiving MHC-transduced BM were unable to kill targets expressing H-2K(b) but were able to respond to third-party controls. Mice reconstituted with H-2K(b)-transduced BM exhibited long-term acceptance of H-2K(b) mismatched skin grafts but were able to rapidly reject third-party control grafts. Thus, gene therapy approaches may be used to induce T-cell tolerance.
Understanding the cancer stem cell (2010)

The last 15 years has seen an explosion of interest in the cancer stem cell (CSC). Although it was initially believed that only a rare population of stem cells are able to undergo self-renewing divisions and differentiate to form all populations within a malignancy, a recent work has shown that these cells may not be as rare as thought first, at least in some malignancies. Improved experimental models are beginning to uncover a less rigid structure to CSC biology, in which the concepts of functional plasticity and clonal evolution must be incorporated into the traditional models. Slowly the genetic programmes and biological processes underlying stem cell biology are being elucidated, opening the door to the development of drugs targeting the CSC. The aim of ongoing research to understand CSCs is to develop novel stem cell-directed treatments, which will reduce therapy resistance, relapse and the toxicity associated with current, non-selective agents.
AGiardia duodenalisgene encoding a protein with multiple repeats of a toxin homologue (1995)

A gene, CRP136, from the intestinal protozoan parasite Giardia duodenalis, expressed at a high level in a metronidazole-resistant line, encodes a 136 kDa protein with 23 copies of a 40 amino acid repeat. The protein is cysteine-rich and has the typical membrane-spanning region and CXXC amino acid motifs of a family of Giardia cysteine-rich surface proteins (CRSPs). The repeat unit in CRP136, shares 57% homology with the gene encoding the precursor of the sarafotoxins, a group of snake toxins from the burrowing adder known to cause symptoms similar to those of humans acutely infected with Giardia. The sarafotoxins are low molecular weight sulphydryl cross-linked peptides which are proteolytically cleaved from a precursor polyprotein. CRP136 has homology over the entire length of the sarafotoxin precursor, and the repeats are of the same length. Thus CRP136 represents the first evidence for a potential Giardia toxin. The genomic copy number of CRP136 appears to be the same in both the parent and drug-resistant lines and expression of this gene, and at least one other, is associated with a conserved partial duplication, but not amplification, of one chromosome.
Performance specifications for proton medical facility (1993)

Performance specifications of technical components of a modern proton radiotherapy facility are presented. The technical items specified include: the accelerator; the beam transport system including rotating gantry; the treatment beamline systems including beam scattering, beam scanning, and dosimetric instrumentation; and an integrated treatment and accelerator control system. Also included are treatment ancillary facilities such as diagnostic tools, patient positioning and alignment devices, and treatment planning systems. The facility specified will accommodate beam scanning enabling the three-dimensional conformal therapy deliver .
Prostacyclin agonist with thromboxane synthase inhibitory activity (ONO-1301) attenuates bleomycin-induced pulmonary fibrosis in mice (2005)

The balance between prostacyclin and thromboxane A2 (TXA2) plays an important role in pulmonary homeostasis. However, little information is available regarding the therapeutic potency of these prostanoids for pulmonary fibrosis. We have recently developed ONO-1301, a novel long-acting prostacyclin agonist with thromboxane synthase inhibitory activity. Thus we investigated whether repeated administration of ONO-1301 attenuates bleomycin-induced pulmonary fibrosis in mice. After intratracheal injection of bleomycin or saline, mice were randomized to receive repeated subcutaneous administration of ONO-1301 or vehicle. Bronchoalveolar lavage (BAL) and histological analyses were performed at 3, 7, and 14 days after bleomycin injection. In vitro studies using mouse lung fibroblasts were also performed. ONO-1301 significantly attenuated the development of bleomycin-induced pulmonary fibrosis, as indicated by significant decreases in Ashcroft score and lung hydroxyproline content. ONO-1301 significantly reduced total cell count, neutrophil count, and total protein level in BAL fluid in association with a marked reduction of TXB2. A single administration of ONO-1301 significantly increased plasma cAMP level for >2 h. In vitro, ONO-1301 and a cAMP analog dose-dependently reduced cell proliferation in mouse lung fibroblasts. The reduction in cell proliferation by ONO-1301 was attenuated by a protein kinase A (PKA) inhibitor. Furthermore, bleomycin mice treated with ONO-1301 had a significantly higher survival rate than those given vehicle. These results suggest that repeated administration of ONO-1301 attenuates the development of bleomycin-induced pulmonary fibrosis and improves survival in bleomycin mice, at least in part by inhibition of TXA2 synthesis and activation of the cAMP/PKA pathway.
Neuronal Intermediate Filaments (1996)

Neurofilaments (NFs) are the most abundant structural components in large-diameter myelinated axons. Assembled as obligate heteropolymers requiring NF-L and substoichiometric amounts of NF-M and/or NF-H, NF investment into axons is essential for establishment of axonal caliber, itself a key determinant of conduction velocity. Use of transgenic mice to increase axonal accumulation of NFs or to express mutant NFs subunits has proven that aberrant organization or assembly of NFs is sufficient to cause disease arising from selective dysfunction and degeneration of motor neurons. Because aberrant accumulation of NFs is a common pathology in a series of motor neuron diseases-including amyotrophic lateral sclerosis-NF misaccumulation, and the resultant disruption in axonal transport, is probably a key intermediate in the pathogenesis of these diseases.
[Sleep disturbances in Alzheimer's disease and other dementias]. (2010)

Sleep in dementias has been mainly studied in Alzheimer disease (AD). Sleep disturbances are found in 25 to 35% of subjects with AD. Subjective and objective disturbances are described. Long nocturnal awakenings disrupt sleep; total sleep time and sleep efficiency are reduced. Slow wave sleep is decreased and sometimes disappears. REM sleep percentage is also reduced and at a later stage of the disease, REM latency is increased. Sleep fragmentation can be associated with excessive daytime napping and sleepiness, and with other behavioral symptoms such as the sundowning syndrome and nocturnal agitation. Sleep abnormalities closely parallel the level of severity of dementia. The rest/activity ratio and the sleep-wake rhythms are more and more disturbed; the phase delay of the temperature rhythm is associated with the severity of the sundowning syndrome. Sleep disturbances and behavioral symptoms are the main reasons to institutionalize the patient. Sleep disturbances are related to multiple factors. Pathophysiological changes resulting of the disease itself, such as damage to the cholinergic pathways and to the circadian pacemaker in the suprachiasmatic nucleus, contribute to sleep changes in AD. Associated medical and psychiatric illness and their different treatments as well as environmental factors also induced sleep disturbances. Sleep-disordered breathing is a highly prevalent condition in AD patients and restless leg syndrome may account for nocturnal agitation. In Parkinson and in Lewy body dementias, sleep disturbances are more severe than in DA and REM sleep behavior disorder can precede by several years these diseases. Sleep attacks and sleepiness are very frequent in Parkinson disease. Specific etiologies should drive specific treatment. Several non pharmacologic treatments are usually associated to treat sleep disturbances in AD: information, increased daytime physical, social activities to minimize daytime naps and exposure to bright light. Some studies found advantages to associate melatonin in the evening.
In Re Dillon: Prima Facie Obviousness of Chemical Claims (1992)

After reviewing the facts of the Dillon case, this paper will illustrate, by analysis of prior caselaw, that Dillon has not revived the Hass-Henze doctrine of structural obviousness. Rather, Dillon will be revealed as having molded many years of sometimes inconsistent precedent into a coherent standard for prima facie obviousness. Subsequently, the legitimacy of the Dillon standard with respect to chemical compound, composition and process claims will be considered. Finally, the effect of Dillon on patent prosecution costs, and other policy considerations, will be discussed.
Synthesis and biological evaluation of structural variants of carbazoquinocin C (2003)

Abstract Some new structural variants of the alkaloid carbazoquinocin C were synthesized in a few steps with good to excellent yields. The key step comprises a cyclisation reaction of appropriate 2‐vinylindoles with oxalyl chloride. The carbazole‐3,4‐quinones are able to trap oxygen‐centred radicals. In some biological/biochemical assays some of these compounds exhibit extraordinary results including inhibition of cyclooxygenase‐1 and 5‐lipoxygenase in the μM‐range. Moreover some of the carbazoquinocin C‐variants inhibit significant oxidative damage of cellular DNA in nM‐range.
Trident: From High-Level Language to Hardware Circuitry (2007)

Unlocking the potential of field-programmable gate arrays requires compilers that translate algorithmic high-level language code into hardware circuits. The Trident open source compiler translates C code to a hardware circuit description, providing designers with extreme flexibility in prototyping reconfigurable supercomputers
Accelerated mRNA decay in conditional mutants of yeast mRNA capping enzyme (1998)

Current models of mRNA decay in yeast posit that 3' deadenylation precedes enzymatic removal of the 5' cap, which then exposes the naked end to 5' exonuclease action. Here, we analyzed gene expression in Saccharomyces cerevisiae cells bearing conditional mutations of Ceg1 (capping enzyme), a 52 kDa protein that transfers GMP from GTP to the 5' end of mRNA to form the GpppN cap structure. Shift of ceg1 mutants to restrictive temperature elicited a rapid decline in the rate of protein synthesis, which correlated with a sharp reduction in the steady-state levels of multiple individual mRNAs. ceg1 mutations prevented the accumulation of SSA1 and SSA4 mRNAs that were newly synthesized at the restrictive temperature. Uncapped poly(A)+ SSA4 mRNA accumulated in cells lacking the 5' exoribonuclease Xrn1. These findings provide genetic evidence for the long-held idea that the cap guanylate is critical for mRNA stability. The deadenylation-decapping-degradation pathway appears to be short-circuited when Ceg1 is inactivated.
Dominance of resistance to the cytocidal effect of tumor necrosis factor in heterokaryons formed by fusion of resistant and sensitive cells. (1988)

The mechanisms underlying differences in vulnerability to the cytocidal effect of TNF, among various cell lines and strains, were explored by examining the response to TNF of heterokaryons formed by fusing TNF-resistant and -sensitive cells. Several combination pairs of human and murine cells, differing significantly in response to TNF toxicity, yet expressing a similar level of TNF receptors, were examined. In all combinations tested, the heterokaryons exhibited resistance to TNF toxicity, comparable, in extent, to that of the more resistant of the two parental cell lines. This dominance of resistance suggests that differences in vulnerability to TNF toxicity reflect activities which are expressed by resistant cells and are deficient in vulnerable ones, activities which perhaps protect the cell against the cytocidal effect of TNF.
Candidate Markers Associated with the Probability of Future Pulmonary Exacerbations in Cystic Fibrosis Patients (2014)

Our results demonstrate that worse clinical and QOL assessments during stable disease are potential markers associated with a higher risk of future PEs, while higher levels of inflammatory markers at the end of antibiotic treatment may be associated with early re-exacerbation.
Modeling, Chemistry, and Biology of the Benzolactam Analogues of Indolactam V (ILV). 2. Identification of the Binding Site of the Benzolactams in the CRD2 Activator-Binding Domain of PKCδ and Discovery of an ILV Analogue of Improved Isozyme Selectivity (1997)

Protein kinase C (PKC) is a complex enzyme system comprised of at least 11 isozymes that serves to mediate numerous extracellular signals which generate lipid second messengers. The discovery of isozyme-selective activators and inhibitors (modulators) of PKC is crucial to ascertaining the role of the individual isozymes in physiological and pathophysiological processes and to manipulating their function. The discovery of such small molecule modulators of PKC is at present a largely unmet pharmacological need. Herein we detail our modeling studies which reveal how the natural product indolactam V (ILV) and its 8-membered ring analogue, the benzolactam 15, bind to the CRD2 activator domain of PKC. These modeling studies reveal that not all PKC ligands possess a common pharmacophore, and further suggest an important role of specific hydrophobic contacts in the PKC-ligand interaction. The modeling studies find strong experimental support from mutagenesis studies on PKC alpha that reveal the crucial role played by the residues proline 11, leucine 20, leucine 24, and glycine 27. Next, we describe the synthesis of two 8-substituted benzolactams starting from L-phenylalanine and characterize their isozyme selectivity; one of the two benzolactams exhibits improved isozyme selectivity relative to the n-octyl-ILV. Lastly, we report inhibition of cellular proliferation of two different breast carcinoma cell lines by the benzolactam 5 and show that the compound preferentially down-regulates PKCbeta in both cell lines.