gebhart/patrepeval huggingface dataset:
Chimeric aptamers in cancer cell-targeted drug delivery (2011)

Aptamers are single-stranded structured oligonucleotides (DNA or RNA) that can bind to a wide range of targets ("apatopes") with high affinity and specificity. These nucleic acid ligands, generated from pools of random-sequence by an in vitro selection process referred to as systematic evolution of ligands by exponential enrichment (SELEX), have now been identified as excellent tools for chemical biology, therapeutic delivery, diagnosis, research, and monitoring therapy in real-time imaging. Today, aptamers represent an interesting class of modern pharmaceuticals which with their low immunogenic potential mimic extend many of the properties of monoclonal antibodies in diagnostics, research, and therapeutics. More recently, chimeric aptamer approach employing many different possible types of chimerization strategies has generated more stable and efficient chimeric aptamers with aptamer-aptamer, aptamer-nonaptamer biomacromolecules (siRNAs, proteins) and aptamer-nanoparticle chimeras. These chimeric aptamers when conjugated with various biomacromolecules like locked nucleic acid (LNA) to potentiate their stability, biodistribution, and targeting efficiency, have facilitated the accurate targeting in preclinical trials. We developed LNA-aptamer (anti-nucleolin and EpCAM) complexes which were loaded in iron-saturated bovine lactofeerin (Fe-blf)-coated dopamine modified surface of superparamagnetic iron oxide (Fe(3)O(4)) nanoparticles (SPIONs). This complex was used to deliver the specific aptamers in tumor cells in a co-culture model of normal and cancer cells. This review focuses on the chimeric aptamers, currently in development that are likely to find future practical applications in concert with other therapeutic molecules and modalities.
Anti‐tumor effects of interleukin‐2 and interleukin‐1 in mice transplanted with different syngeneic tumors (1989)

We have studied the anti-tumor effects of human recombinant IL-2, alone or in association with LAK cells, in mice transplanted subcutaneously (s.c.) with the following syngeneic tumors: highly metastatic Friend leukemia cells (FLC), nonmetastatic FLC, lymphoma RBL-5 cells and HeJ16 fibrosarcoma cells. In these tumor models, peri-tumoral injections of IL-2 were more effective in inhibiting tumor growth than a systemic treatment. Although s.c. IL-2 treatment resulted in marked inhibition of tumor growth in mice injected s.c. with highly metastatic FLC, it was not effective in inhibiting growth of FLC in the liver and spleen. IL-2 therapy was more effective at increasing survival time in mice transplanted with non-metastatic FLC or with RBL-5 cells. In mice transplanted with HeJ16 fibrosarcomas, s.c. IL-2 treatment resulted in highly significant anti-tumor effect and survival of 70% of tumor-injected mice. No general correlation was found between in vitro sensitivity or resistance to the cytolytic activity of LAK cells and the anti-tumor effects observed in vivo. Subcutaneous injection of IL-1 beta in mice transplanted with highly metastatic FLC resulted in a marked increase in survival time and inhibition of metastatic tumor growth in liver and spleen. Combined treatment of IL-1 beta and IL-2 produced a synergistic anti-tumor effect: 60% of mice injected with highly metastatic FLC survived. Combined IL-1/IL-2 treatments exerted no anti-tumor activity either in DBA/2 mice injected with antibody to Thy 1.2 antigen or in nude mice, indicating that T cells play important roles during IL-1/IL-2 therapy. In vitro treatment of FLC with IL-1 beta resulted in a slight inhibition of cell multiplication, whereas even high doses of IL-2 did not affect FLC multiplication. Our results indicate that local combined treatments with IL-1 and IL-2 can induce potent, host-dependent (T cell-mediated) anti-tumor effects against highly malignant tumors.
Response of Forage Fiber Degradation by Ruminal Microorganisms to Branched-Chain Volatile Fatty Acids, Amino Acids, and Dipeptides (2002)

This study evaluated the effect of branched-chain volatile fatty acids (VFA; isobutyric acid, isovaleric acid), amino acids (valine, leucine), and dipeptides (valine-valine, leucine-leucine) on neutral detergent fiber (NDF) degradation by rumen microorganisms in vitro. The CP (%) and in situ NDF degradation rate (%/h) for alfalfa, bermudagrass, and pangolagrass hays, and napiergrass silage were 17.2 and 7.5, 4.7 and 3.1, 8.3 and 5.3, and 9.6 and 3.4, respectively. In vitro NDF digestibility was the lowest for bermudagrass; alfalfa and napiergrass were the highest. When the incubation contained more ammonia initially, digestibilities increased, but relative differences among forages were unchanged. Adding branched-chain VFA (2 mM) to incubations increased digestibilities more than controls on 15 out of 16 occasions. The effectiveness varied with isoacids and forages used. Amino acid (2 mM) or dipeptide (1 mM) addition consistently increased digestibility over controls. Amino acids further increased digestibility over corresponding isoacids on 14 occasions. Improvement in digestibility over control by leucine appeared to be greater than that by valine. Digestibilities with dipeptides were always greater than those with isoacids, except for one case. Dipeptide addition further increased digestibility significantly over corresponding amino acids on only six occasions, while percent improvement in digestibility numerically by dipeptides occurred in 10 cases. Valine-valine seemed to exert different effect than leucine-leucine, depending on initial ammonia availability. The results indicate that dipeptides could be more effective than isoacids and amino acids in improving NDF digestion. Forages with high CP content or rapid NDF degradation rate appeared to respond to additives to smaller degrees.
Flash-Lamp-Induced Crystal Growth of Silicon on Amorphous Substrates Using Artificial Surface-Relief Structures (1982)

Crystallization of amorphous silicon films deposited over surface-relief structures etched into SiO2 layers is achieved by large area processing with incoherent light pulses of 10 ms duration. The structures are either gratings with a constant top width of 3 μm and bottoms with a width between 3 and 20 μm or otherwise shaped artificial surface-relief micropatterns. The crystalline films are found to consist of very large crystallites, which are either separated from each other by grain boundaries or twinned to one another. Amorphe Siliziumfilme werden auf eine reliefartig strukturierte SiO2-Schicht aufgebracht und mit inkohärentem Licht einer Impulsdauer von 10 ms bestrahlt. Die Strukturen sind entweder Gitter mit rechteckigem Profil einer constanten Stegbreite von 3 μm und variablen Grabenbreiten zwischen 3 und 20 μm oder andersartig geformten Mikrostrukturen. Es wird gefunden, daß die kristallinen Filme aus großen Kristallitblöcken, die entweder durch Korngrenzen getrennt oder untereinandr verzwillingt sind, bestehen.
Pathways for Potentiation of Immunogenicity during Adjuvant-Assisted Immunizations withPlasmodium falciparumMajor Merozoite Surface Protein 1 (1998)

Vaccine adjuvants exert critical and unique influences on the quality of immune responses induced during active immunizations. We investigated the mechanisms of action of immunological adjuvants in terms of their requirements for cytokine-mediated pathways for adjuvanticity. Antibody responses potentiated by several adjuvants to a Plasmodium falciparum MSP1-19 (C-terminal 19-kDa processing fragment of MSP1) vaccine were studied in gamma interferon (IFN-gamma) or interleukin (IL-4) knockout mice. The levels of anti-MSP1-19 antibodies and the induction of Th1- and Th2-type antibodies were analyzed. Results revealed a spectrum of requirements for cytokine-mediated pathways in the potentiation of immunogenicity, and such requirements were influenced by interactions among individual components of the adjuvant formulations. One adjuvant strictly depended on IFN-gamma to induce appreciable levels of anti-MSP1-19 antibodies, while some formulations required IFN-gamma only for the induction of Th1-type antibodies. Other formulations induced exclusively Th2-type antibodies and were not affected by IFN-gamma knockout. There were three patterns of requirements for IL-4 by various adjuvants in the induction of Th2-type anti-MSP1-19 antibodies. Moreover, the induction of Th1-type anti-MSP1-19 antibodies by adjuvants showed two distinct patterns of regulation by IL-4. The utilization of an IL-4 regulated pathway(s) for the induction of Th2-type antibodies by the same adjuvant differed between mouse strains, suggesting that animal species variability in responses to vaccine adjuvants may be due, at least in part, to differences in the utilization of immune system pathways by an adjuvant among animal hosts.
Mitogenic Activity of Purified Capsular Polysaccharide A from Bacteroides fragilis : Differential Stimulatory Effect on Mouse and Rat Lymphocytes In Vitro (1999)

Bacteroides fragilis, a Gram-negative colonic bacterium, induces the formation of abscesses associated with intra-abdominal sepsis in humans. The singular ability of this organism to modulate abscess formation in experimental rodent models resides in the structurally distinct and ionically charged capsular polysaccharides A (PS A) and B (PS B). The regulation of abscess formation in animals is dependent on T lymphocytes. However, the manner in which PS A interacts with T cells remains unknown. We therefore tested the T cell stimulatory capacity of purified PS A on mouse and rat lymphocytes in cellular proliferation assays and found that the PS A molecule possesses mitogenic characteristics distinguishable from those of the polyclonal B cell activator LPS, the T cell mitogen Con A, and staphylococcal enterotoxin A superantigen. Further, PS A stimulated proliferation of normal mouse and rat lymphocytes differentially. Mouse B cells responded to PS A in a fashion that did not require exogenous APC function, while rat T lymphocyte responses to PS A required APC function derived from autologous or xenogenic feeder cells. Cellular depletion experiments showed that the CD4+ subset of rat spleen cells was the primary responder cell type to PS A in vitro. The differential stimulatory effects of PS A on mouse and rat lymphocytes may reflect its ability to stimulate different lymphocyte subsets in vivo through the activities of receptor/counter-receptor pairs present on responder lymphocytes and cognate APC.
Role of Matrix Metalloproteinases 2 and 9 in Lacrimal Gland Disease in Animal Models of Sjögren's Syndrome (2015)

We conclude that MMP2/9 expression and activity are elevated in lacrimal glands of two murine models of Sjögren's syndrome, suggesting that manipulation of MMP2/9 activity might be a potential therapeutic target in chronically inflamed lacrimal glands.
Molecular characterization of epididymal proteins (1998)

By using various methods, ranging from conventional protein separation and purification to monoclonal antibody and cDNA cloning strategies, a considerable body of information has been obtained on mammalian epididymal proteins. Molecular characterization of proteins specifically produced in the human epididymis has been achieved by cDNA cloning, followed by raising antibodies against synthetic peptide epitopes. The predicted proteins have been localized in the human epididymal epithelium, within the lumen of the epididymal duct and vas deferens, and also on the surface of ejaculated spermatozoa. Sperm association has been reported for at least four human epididymal proteins, ARP, HE2, HE4, and HE5/CD52. However, as is largely the case in other species, a link to a specific function for any luminal component of the human epididymis, including the cloned secretory glycoproteins, to either sperm maturation or storage has not yet been demonstrated convincingly. Indirect evidence for a function for epididymal proteins comes from their relatively high frequency and tissue-specific expression as well as from their distinct spatial expression patterns along the human epididymal duct. However, it remains to be established (for example, by using the proteins and their antibodies in functional tests) whether, besides being essential markers of sperm maturation, they are also functionally important.
A Variant in the Promoter of MUC5B and Idiopathic Pulmonary Fibrosis (2011)

In this study, a single-nucleotide polymorphism in the mucus-forming gene MUC5B was strongly associated with the presence of idiopathic pulmonary fibrosis (IPF). These results replicate the findings of other investigators, also published in this issue.
In vitro characterization and inhibition of the CXCR4/CXCL12 chemokine axis in human uveal melanoma cell lines (2007)

Interfering with the CXCR4/CXCL12 axis, using TN14003 was shown to effectively down regulate UM cell migration in vitro. Knowing that UM expresses the CXCR4 receptor, these CXCR4+ cells may be less likely to colonize distant organs that secrete the CXCL12 ligand, if treated with an inhibitor that binds CXCR4. Further studies should be pursued in order to test TN14003 efficacy in vivo.
Cloning and characterization of the human ribosomal protein S21 gene [. (2000)

A full-size functional gene encoding the human ribosomal protein S21 was cloned and characterized. Its nucleotide sequence, exon-intron organization, and transcription initiation site were determined. The gene comprises 1417 bp and is composed of six exons and five introns. Like most known genes of mammalian ribosomal proteins, it lacks the canonical TATA- and CAAT sequences in the promoter region and harbors potential binding sites for transcription factors both upstream and downstream the transcription initiation site. The first intron of the rpS21 gene is located in the 5'-untranslated region. The transcription initiation site is at a 53-bp distance from the ATG codon, and the initiation cytidine is surrounded by polypyrimidine tracts. The 5'-flanking region contains two repeats belonging to the Alu-S and Alu-J families.
Cloning, Expression and Purification of Human Heart Type Fatty Acid Binding Protein in E.coli (2005)

Objective To obtain recombinant human heart type fatty acid binding protein(H-FABP) by prokaryotic expression for clinical use in diagnosis. Methods The encoding sequence for mature peptide of human H-FABP was amplified with RT-PCR and inserted into pQE30 vector to establish the prokaryotic expressing system coupled with 6His. The competent cells of host strain of M15 were transformed by the recombinant plasmid(pQE-H-FABP). Expression of the target protein was induced with IPTG and assayed by SDS-PAGE and immunoblot after sequencing. The recombinant products were purified by Ni~+-NTA agarose column. Results The cloned fragment of human H-FABP was 99.9% consistent with that in genbank(NM004012), which was deduced to express 132 Aa mature peptide of human H-FABP correctly. The Expressed fusion-protein was 15 kD in SDS-PAGE as expected, was recognized by a commercial McAb(Clone 6B6) and was 27% in the total quatiy of germ proteins. Conclusion The homologous recombinant human H-FABP is obtained after Ni~+-affinity chromatograph, which may benefit for preparation of specific antibodies and diagnosis for some related diseases.
Pyrimidine Homoribonucleosides: Synthesis, Solution Conformation, and Some Biological Properties (1987)

Conversion of uridine and cytidine to their 5'-O-tosyl derivatives, followed by cyanation with tetraethylammonium cyanide, reduction and deamination, led to isolation of the hitherto unknown homouridine (1-(5'-deoxy-beta-D-allofuranosyl)uracil) and homocytidine (1-(5'-deoxy-beta-D-allofuranosyl)cytosine), analogues of uridine and cytidine in which the exocyclic 5'-CH2OH chain is extended by one carbon to CH2CH2OH. Homocytidine was also phosphorylated to its 6'-phosphate and 6'-pyrophosphate analogues. In addition, it was converted, via its 2,2'-anhydro derivative, to arahomocytidine, an analogue of the chemotherapeutically active araC. The structures of all the foregoing were established by various criteria, including 1H and 13C NMR spectroscopy, both of which were also applied to analyses of the solution conformations of the various compounds, particularly as regards the conformations of the exocyclic chains. The behaviour of the homo analogues was examined in several enzymatic systems. Homocytidine was a feeble substrate, without inhibitory properties, of E. coli cytidine deaminase. Homocytidine was an excellent substrate for wheat shoot nucleoside phosphotransferase; while homouridine was a good substrate for E. coli uridine phosphorylase. Although homoCMP was neither a substrate, nor an inhibitor, of snake venom 5'-nucleotidase, homoCDP was a potent inhibitor of this enzyme (Ki approximately 6 microM). HomoCDP was not a substrate for M. luteus polynucleotide phosphorylase. None of the compounds exhibited significant activity vs herpes simplex virus type 1, or cytotoxic activity in several mammalian cell lines.
Epidural Morphine for Postoperative Pain: Experience with 1085 Patients (1985)

A prospective study of the effect and side-effects of epidural morphine for pain relief in 1085 patients after thoracic, abdominal, urologic, or orthopaedic surgery was performed. Morphine chloride was diluted in saline or bupivacaine and administered through an epidural catheter placed at a segmental level appropriate for the type of surgery. The initial dose was 4 or 6 mg morphine and supplementary doses were given when needed to obtain complete freedom from pain during deep breathing or nursing care. The total dose of epidural morphine from end of surgery until the next morning varied from 4 to 18 mg. 97% of hip arthroplasty patients, 91% of prostatectomy patients and thoracotomy patients, 90% of patients after major lower extremity surgery and 88% of patients after laparotomy were completely satisfied with the postoperative course. For hip arthroplasty and major extremity surgery, an initial dose of 4 mg of epidural morphine was as effective as 6 mg. After prostatectomy, laparotomy, and thoracotomy, an initial dose of 6 mg gave significantly better effect than 4 mg. Pruritus occurred in 11%, nausea or vomiting in 34%, and respiratory depression in 0.9% of the total patient population. Urinary retention occurred in 42% of patients not having urinary catheters in place. Postoperative nausea or vomiting was more frequent in women than in men (P less than 0.001). There was a higher incidence of nausea or vomiting in men experiencing pain than in men who were completely pain-free after abdominal surgery (P less than 0.001). Respiratory depression was rare and occurred as a gradually decreasing respiratory rate.(ABSTRACT TRUNCATED AT 250 WORDS)
A Scalable Three-Step Approach for Demand Side Management of Plug-in Hybrid Vehicles (2012)

In this paper, we present a scalable approach for DSM (demand side management) of PHEVs (plug-in hybrid electric vehicles). Essentially, our approach consists of three steps: aggregation, optimization, and control. In the aggregation step, individual PHEV charging constraints are aggregated upwards in a tree structure. In the optimization step, the aggregated constraints are used for scalable computation of a collective charging plan, which minimizes costs for electricity supply. In the real-time control step, this charging plan is used to create an incentive signal for all PHEVs, determined by a market-based priority scheme. These three steps are executed iteratively to cope with uncertainty and dynamism. In simulation experiments, the proposed three-step approach is benchmarked against classic, fully centralized approaches. Results show that our approach is able to charge PHEVs with comparable quality to optimal, centrally computed charging plans, while significantly improving scalability.
Use of a Hybrid Grid in Reservoir Simulation (1986)

Summary A technique is presented to improve the treatment of wells in reservoir simulators by the use of an orthogonal curvilinear grid (cylindrical or elliptical) in well regions and a rectangular grid elsewhere in the reservoir. Special methods are developed to handle irregular blocks connecting the two types of regions. The nonlinear equations for the two Regions are solved with different levels of implicitness; the simultaneous solution (implicit) method is applied to the well regions, while an implicit pressure, explicit saturation (IMPES) technique is used for the reservoir region. An efficient approach, requiring no outer iterations, between well and reservoir regions is used to couple different regions. The scheme is validated by the simulation of the flow of a slightly compressible fluid in a square domain with one boundary open to flow. For this case, the numerical solution with the hybrid grid approach matches the analytical solution exactly. A computer model based on the approach was developed for simulating two-phase flow in multiwell horizontal reservoirs. We show that* the proposed technique provides much better prediction of the phase split in the producers than the conventional approach.
LEF-1, a gene encoding a lymphoid-specific protein with an HMG domain, regulates T-cell receptor alpha enhancer function [corrected] (1991)

Lymphoid-specific cDNA clones were isolated that encode a nuclear protein with homology to the chromosomal nonhistone protein HMG-1 and to putative regulators of cell specialization, including the mammalian testis-determining factor SRY and fungal mating-type proteins. The gene represented by the isolated cDNA clones, termed LEF-1 (lymphoid enhancer-binding factor 1), is developmentally regulated and expressed in pre-B and T lymphocytes but not in later-stage B cells or nonlymphoid tissues. Both endogenous and recombinant LEF-1 were shown to bind to a functionally important site in the T-cell antigen receptor (TCR) alpha enhancer. Maximal TCR alpha enhancer activity was found to parallel the cell type-specific expression pattern of LEF-1. Moreover, forced expression of recombinant LEF-1 in late stage B cells increases TCR alpha enhancer function. Taken together, these data suggest that LEF-1 is a regulatory participant in lymphocyte gene expression and differentiation.
Polymerase θ is a robust terminal transferase that oscillates between three different mechanisms during end-joining (2016)

DNA polymerase θ (Polθ) promotes insertion mutations during alternative end-joining (alt-EJ) by an unknown mechanism. Here, we discover that mammalian Polθ transfers nucleotides to the 3' terminus of DNA during alt-EJ in vitro and in vivo by oscillating between three different modes of terminal transferase activity: non-templated extension, templated extension in cis, and templated extension in trans. This switching mechanism requires manganese as a co-factor for Polθ template-independent activity and allows for random combinations of templated and non-templated nucleotide insertions. We further find that Polθ terminal transferase activity is most efficient on DNA containing 3' overhangs, is facilitated by an insertion loop and conserved residues that hold the 3' primer terminus, and is surprisingly more proficient than terminal deoxynucleotidyl transferase. In summary, this report identifies an unprecedented switching mechanism used by Polθ to generate genetic diversity during alt-EJ and characterizes Polθ as among the most proficient terminal transferases known.