gebhart/patrepeval huggingface dataset:
Interface mechanics of porous titanium implants (1981)

The interfacial shear properties of bone tissue growth into porous coated Ti-6-A1-4V femoral implants have been examined as a function of the pore size of the porous surface. Three particle size range powders (297 microns, 420-500 microns, 595-707 microns) were used to fabricate cylindrical implants which were inserted into the femoral medullary canal of dogs for 6 months. Push-out tests on the removed femurs are reported and reveal: (i) that those implants residing in cortical bone exhibited significantly higher shear properties than the equivalent implants in cancellous bone and (ii) that the interfacial shear strength and stiffness decreased with increasing pore diameter within the range 175-325 microns. The extent of bone ingrowth into the surface of the implants was measured using quantitative optical microscopic techniques. This indicated that the percentage of bone which had grown into the surface was inversely proportional to the square root of the pore size and that further the shear properties of the interface were proportional to the extent of bone ingrowth.
STING Signaling in Cancer Cells: Important or Not? (2017)

Stimulator of interferon genes (STING) is an adaptor protein that plays an important role in the activation of type I interferons in response to cytosolic nucleic acid ligands. Recent evidence indicates involvement of the STING pathway in the induction of antitumor immune response. Therefore, STING agonists are now being extensively developed as a new class of cancer therapeutics. However, little is known about the consequences of activated STING-mediated signaling in cancer cells on the efficacy of the antitumor treatment. It has been shown that activation of the STING-dependent pathway in cancer cells can result in tumor infiltration with immune cells and modulation of the anticancer immune response. Understanding the function of STING pathway in cancer cells might provide important insights into the development of effective therapeutic strategies. This review focuses on the role of STING pathway in cancer cells, the largely unknown topic that has recently emerged to be important in the context of STING-mediated antitumor responses.
Analytical Ultracentrifugation as an Approach to Characterize Recombinant Adeno-Associated Viral Vectors (2015)

Recombinant adeno-associated viral (rAAV) vectors represent a novel class of biopharmaceutical drugs. The production of clinical-grade rAAV vectors for gene therapy would benefit from analytical methods that are able to monitor drug product quality with regard to homogeneity, purity, and manufacturing consistency. Here, we demonstrate the novel application of analytical ultracentrifugation (AUC) to characterize the homogeneity of preparations of rAAV vectors. We show that a single sedimentation velocity run of rAAV vectors detected and quantified a number of different viral species, such as vectors harboring an intact genome, lacking a vector genome (empty particles), and containing fragmented or incomplete vector genomes. This information is obtained by direct boundary modeling of the AUC data generated from refractometric or UV detection systems using the computer program SEDFIT. Using AUC, we show that multiple parameters contributed to vector quality, including the AAV genome form (i.e., self-complementary vs. single-stranded), vector genome size, and the production and purification methods. Hence, AUC is a critical tool for identifying optimal production and purification processes and for monitoring the physical attributes of rAAV vectors to ensure their quality.
Gene Therapy for Amyotrophic Lateral Sclerosis (ALS) Using a Polymer Encapsulated Xenogenic Cell Line Engineered to Secrete hCNTF. Lausanne University Medical School, Lausanne, Switzerland (1996)

The gene therapy approach presented in this protocol employs a polymer encapsulated, xenogenic, transfected cell line to release human ciliary neurotrophic factor (hCNTF) for the treatment of Amyotrophic Lateral Sclerosis (ALS). A tethered device, containing around 10(6) genetically modified cells surrounded by a semipermeable membrane, is implanted intrathecally; it provides for slow continuous release of hCNTF at a rate of 0.25 to 1.0 micrograms/24 hours. The semipermeable membrane prevents immunologic rejection of the cells and interposes a physical, virally impermeable barrier between cells and host. Moreover, the device and the cells it contains may be retrieved in the event of side effects. A vector containing the human CNTF gene was transfected into a line of baby hamster kidney cells (BHK) with calcium phosphate using a dihydrofolate reductase-based selection vector with a SV40 promoter and contains a HSV-tk killer gene. hCNTF is a potent neurotrophic factor which may have utility for the treatment of ALS. Systemic delivery of hCNTF in humans has been frustrated by peripheral side effects, the molecule's short half life, and its inability to cross the blood-brain barrier. The gene therapy approach described in this protocol is expected to mitigate such difficulties by local intrathecal delivery of a known quantity of continuously-synthesized hCNTF from a retrievable implant.
Guide: Towards Understanding Daily Life via Auto- Identification and Statistical Analysis (2003)

Many recent studies have underscored the applicability to healthcare of a system able to observe and understand day-to-day human activities. The Guide project is aimed at building just such a system. The project combines novel sensing technology, expressive but scalable learners and unsupervised mining of activity models from the web to address the problem. An early prototype, Carnac, has shown considerable promise. This paper provides a high-level overview of the Guide approach, briefly discusses Carnac, and details our expectations of the workshop.
Image Processing Equipment (1999)

Abstract The sections in this article are Image Sensing Equipment Image Computing Equipment Video and Image Compression Equipment Image Database Equipment Image Display Equipment Image Printing Equipment
Origin of endothelial progenitors in human postnatal bone marrow (2002)

MethodsMAPC cultures.BM was obtained from 55 healthy volunteer donors (2-45 years of age) after obtaining informed consent per the guidelines of the University of Minnesota Committee on the Use of Human Subjects in Research.MAPCs were generated as previously described (3).Briefly, BM mononuclear cells were depleted of CD45 + and glycophorin A + cells using micromagnetic beads (Miltenyi Biotec, Sunnyvale, California, USA).Cells (5 10 3 ) that were negative for CD45 and glycophorin A were diluted in 200 l expansion medium consisting of 58% low-glucose DMEM (Invitrogen Corp., Grand Island, New York, USA) and 40% MCDB-201 (Sigma Chemical Co., St. Louis, Missouri, USA), supplemented with 1 insulin-transferrinselenium, 1 linoleic acid-BSA, 10 -8 M dexamethasone, 10 -4 M ascorbic acid 2-phosphate (all from Sigma Chemical Co.), 100 U penicillin, and 1,000 U streptomycin (Invitrogen Corp.); along with 0-10% FCS (HyClone Laboratories, Logan, Utah, USA), 10 ng/ml EGF (Sigma Chemical Co.), and 10 ng/ml PDGF-BB
Registered report: Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs (2015)

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of 50 papers in the field of cancer biology published between 2010 and 2012. This Registered report describes the proposed replication plan of key experiments from 'Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs' by Sugahara and colleagues, published in <i>Science</i> in 2010 (Sugahara et al., 2010). The key experiments being replicated include Figure 2 and Supplemental Figure 9A. In Figure 2, Sugahara and colleagues presented data on the tumor penetrance of doxorubicin (DOX) when co-administered with the peptide iRGD, as well as the effect of co-treatment of DOX and iRGD on tumor weight and cell death. In Supplemental Figure 9A, they tracked body weight of mice treated with DOX and iRGD to provide evidence that iRGD does not increase known DOX toxicity. The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published by <i>eLife</i>.
Synthesis and activity of 6-aryl-3-(hydroxypolymethyleneamino)pyridazines in animal models of epilepsy (1986)

A series of 6-aryl-3-(hydroxypolymethyleneamino)pyridazines derivatives was synthesized and evaluated for anticonvulsant activity. The compounds were screened in mice for their ability to antagonize maximal electroshock- and bicuculline-induced seizures; neurotoxicity was evaluated in the rotorod test. The anticonvulsant activity of the most potent compounds in this series was also examined in kindled amygdaloid rats and in photoepileptic Papio papio baboons. Phenobarbital, diphenylhydantoin, carbamazepine, and sodium valproate were used as standard antiepileptic drugs. The structure-activity relationships in this series were examined by either varying the aryl ring in the 6-position of the pyridazine ring or by modifying the 3-amino side chain. Only the compounds with a phenyl ring in the 6-position of the pyridazine ring exhibited appreciable anticonvulsant activity. Furthermore, a 4-hydroxypiperidine side chain in the 3-position of the pyridazine ring appeared essential for anticonvulsant activity. Substituting the phenyl ring with a Cl in the 2-position led to a substantial increase of activity; disubstituting the phenyl ring with a Cl in the 2- and 4-positions yielded the most potent compounds in this series, some of which were as potent or more potent than phenobarbital. Two compounds, 6-(2-chlorophenyl)-3-(4-hydroxypiperidino)pyridazine (2) and 6-(2,4-dichlorophenyl)-3-(4-hydroxypiperidino)pyridazine (3), were selected for further studies. Clinical evaluation of these compounds is in progress.
Birth of lambs of a pre-determined sex after in vitro production of embryos using frozen–thawed sex-sorted and re-frozen–thawed ram spermatozoa (2004)

36 +/- 3.3%, FSF: 28 +/- 3.1%, FCF: 20 +/- 2.0%). In a sperm migration test greater numbers of FS spermatozoa penetrated 5 mm into the artificial cervical mucus compared with spermatozoa from all other treatments (152 +/- 39.4 vs 31 +/- 9.2 spermatozoa respectively; P < 0.05). Fertilisation and cleavage rates were higher (P < 0.05) for in vitro matured oocytes inseminated with CONTROL compared with FSF spermatozoa. However, the Day 7 blastocyst development rate was higher for oocytes inseminated with FSF (62.2%) than FS and CONTROL spermatozoa (52.7 and 50.0%; P < 0.05). The number of ewes pregnant (Day 60), lambing and the in vivo embryo survival rate was greater (P < 0.01) after the transfer of fresh embryos rather than vitrified embryos derived from X- and Y-spermatozoa (67.6, 64.7 and 41.2% vs 29.6, 25.9 and 14.8% respectively). Twenty-six of the 30 (86.7%) lambs derived from sex-sorted spermatozoa were of the correct sex. These results demonstrate that frozen-thawed ram spermatozoa can be sex-sorted for immediate or future use after re-cryopreservation and, in conjunction with IVF and embryo transfer, can be used to efficiently produce offspring of pre-determined sex.
miR‐206 regulates brain‐derived neurotrophic factor in Alzheimer disease model (2012)

Our findings demonstrate a novel miRNA-dependent regulation of BDNF in AD and suggest possible therapeutic approaches, such as noninvasive intranasal delivery of AM206.
Incidence of chronic immune-mediated inflammatory diseases after diagnosis with Kawasaki disease: a population-based cohort study (2021)

Children diagnosed with KD were at increased risk of arthritis following the acute KD event, but not other IMIDs. Health-care providers should monitor for arthritis in children following a diagnosis of KD.
A Novel Matrix Attachment Region DNA Binding Motif Identified Using a Random Phage Peptide Library (1995)

SATB1 is a nuclear matrix attachment DNA (MAR)-binding protein which is predominantly expressed in thymocytes. This protein binds to the minor groove specifically recognizing an unusual DNA context exhibited by a specific MAR region with strong base-unpairing propensity. A phage library displaying nonamer random peptides without any built-in structure was used to identify a MAR binding motif of SATB1. One predominant cyclic peptide C1 of CRQNWGLEGC selected by a MAR-affinity column showed 50% identity with a segment in SATB1 (amino acids 355-363). Replacement of the C1 similarity segment in SATB1 by a random amino acid sequence or its truncation resulted in more than 80% reduction in MAR binding. In contrast, replacement of the same SATB1 segment with the C1 peptide restored full MAR binding activity and specificity as the wild-type protein. Single amino acid mutation of the conserved Arg or Glu residue to Ala greatly reduced MAR binding. Taken together our data show that a nine amino acid sequence in SATB1 represents a key MAR binding motif. Phage display may provide a general tool for rapid identification of DNA binding peptide motifs.
Uptake by mouse liver and intracellular fate of plasmid DNA after a rapid tail vein injection of a small or a large volume (2002)

The fact that after an hydrodynamic injection (35)S-DNA remains bound to the outside face of the plasma membrane for at least 1 h indicates that it is not, or very slowly, internalised during that period. The relatively small difference in the amount of DNA picked up by hepatocytes depending on the type of injection could not explain the absence of expression after a conventional injection and the strong expression after a hydrodynamic injection. If DNA enters the cells by endocytosis, even after an hydrodynamic injection, its persistence at the outside face of the plasma membrane could favour transfection by allowing hepatocytes to dispose for a relatively long time of a reservoir of intact DNA.
Acoustic nonlinearity parameter B/A of aqueous solutions of some amino acids and proteins (1990)

A precision ultrasonic velocimeter and a new differential method of calculation of specific concentration increments were employed to study the nonlinear acoustic properties of aqueous solutions of ten amino acids and six proteins. The greater precision of the velocity measurements allows much more dilute solutions to be treated, providing for a wider range of amino acids and proteins to be studied. The specific increment of B/A of amino acids was found to exhibit a significant sensitivity to change of position or replacement of a single atomic group of the solute molecule. A strong influence of the character of the solute–solvent interaction on the B/A value is revealed. It is shown that the specific increment of B/A of a solute could be much more sensitive to the molecular structural features than other parameters such as the specific increments of sound velocity and density.
A Kinetic and ESR Investigation of Iron(II) Oxalate Oxidation by Hydrogen Peroxide and Dioxygen as a Source of Hydroxyl Radicals (1997)

The reaction of Fe(II) oxalate with hydrogen peroxide and dioxygen was studied for oxalate concentrations up to 20 mM and pH 2-5, under which conditions mono- and bis-oxalate complexes (Fe[II](ox) and Fe[II](ox)2[2-]) and uncomplexed Fe2+ must be considered. The reaction of Fe(II) oxalate with hydrogen peroxide (Fe2+ + H2O2 --> Fe3+ + .OH + OH-) was monitored in continuous flow by ESR with t-butanol as a radical trap. The reaction is much faster than for uncomplexed Fe2+ and a rate constant, k = 1 x 10(4) M(-1) s(-1) is deduced for Fe(II)(ox). The reaction of Fe(II) oxalate with dioxygen is strongly pH dependent in a manner which indicates that the reactive species is Fe(II)(ox)2(2-), for which an apparent second order rate constant, k = 3.6 M(-1) s(-1), is deduced. Taken together, these results provide a mechanism for hydroxyl radical production in aqueous systems containing Fe(II) complexed by oxalate. Further ESR studies with DMPO as spin trap reveal that reaction of Fe(II) oxalate with hydrogen peroxide can also lead to formation of the carboxylate radical anion (CO2-), an assignment confirmed by photolysis of Fe(II) oxalate in the presence of DMPO.
Detection of Porcine reproductive and respiratory syndrome virus infection in porcine oral fluid samples: a longitudinal study under experimental conditions (2008)

Isolation of Porcine reproductive and respiratory syndrome virus (PRRSV) from oral fluids was first reported in 1997. The objective of the present study was to determine whether PRRSV and/or anti-PRRSV antibodies were present in oral fluids at diagnostic levels. The level and duration of PRRSV and anti-PRRSV antibodies in serum and oral fluids was evaluated in 3 age groups of pigs (4, 8, or 12 weeks of age) inoculated with a type 2 (North American) PRRSV isolate. Serum, buccal swabs, and pen-based oral fluid samples were collected for 63 days following inoculation. Specimens were assayed for PRRSV by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), and for anti-PRRSV antibodies by enzyme-linked immunosorbent assay (ELISA) and indirect fluorescent antibody test (IFAT). Porcine reproductive and respiratory syndrome virus was detected by real-time qRT-PCR in serum for approximately 5 weeks and in oral fluids for approximately 4 weeks postinoculation. Pig age at the time of inoculation had no effect on the quantity or duration of virus in oral fluid samples. Low levels of anti-PRRSV antibody were detected in oral fluid samples by ELISA and IFAT. Although the approach remains to be validated in the field, the results of this experiment suggest that pen-based oral fluid sampling could be an efficient, cost-effective approach to PRRSV surveillance in swine populations.
Energy conservation techniques for disk array-based servers (2004)

In this paper, we study energy conservation techniques for disk array-based network servers. First, we introduce a new conservation technique, called Popular Data Concentration (PDC), that migrates frequently accessed data to a subset of the disks. The goal is to skew the load towards a few of the disks, so that others can be transitioned to low-power modes. Next, we introduce a user-level file server that takes advantage of PDC. In the context of this server, we compare PDC to the Massive Array of Idle Disks (MAID). Using a validated simulator, we evaluate these techniques for conventional and two-speed disks and a wide range of parameters. Our results for conventional disks show that PDC and MAID can only conserve energy when the load on the server is extremely low. When two-speed disks are used, both PDC and MAID can conserve significant energy with only a small fraction of delayed requests. Overall, we find that PDC achieves more consistent and robust energy savings than MAID.
The defined attenuated Listeria monocytogenes Δmpl2 mutant is an effective oral vaccine carrier to trigger a long‐lasting immune response against a mouse fibrosarcoma (1997)

Listeria monocytogenes has been proposed as a carrier to elicit major histocompatibility complex class-I restricted immune responses able to protect against tumor challenge. In this study the properties of the attenuated L. monocytogenes delta mp12 mutant has been evaluated in vivo against a highly aggressive mouse fibrosarcoma which expresses beta-galactosidase (beta-gal) as a tumor-associated antigen (TAA). Immunization with the vaccine prototypes resulted in both elicitation of specific antibodies and generation of cytotoxic lymphocytes (CTL). Oral vaccination protected 55-64% of the immunized animals from tumor take (p < 0.01) and strongly reduced the average size of the tumor in the other 34-45% (p < 0.01). Vaccinated mice developed a long-lasting response, which resulted in 100% protection from a subsequent tumor challenge. Substitution of the whole TAA by its CTL-defined immunodominant epitope resulted in 43% protection, suggesting a contribution of the humoral response to the observed antitumor effect. No statistically significant differences were observed in the antitumor response when mice were immunized with strains expressing the immunodominant TAA epitope in the context of carrier proteins which were either exported or restricted to the bacterial cytoplasm. This suggests that the topology of the recombinant antigen does not play a major role in the outcome of the protective response.
Biosynthesis and metabolism of brassinosteroids (1997)

Natural brassinosteroids so far identified from various plant species include biosynthetic congeners of brassinolide, such as cathasterone, teasterone, 3‐dehydroteasterone, typhasterol and castasterone as well as another series of 6‐deoxoteasterone, 3‐dehydro‐6‐deoxoteasterone, 6‐deoxotyphasterol and 6‐deoxocastasterone. Using cell culture system of Catharanthus roseus , the outlines of biosynthetic pathways of brassinolide, via plant sterol of campesterol, have now been demonstrated. There are two pathways, named early C6‐oxidation pathway and late C6‐oxidation pathway, both of which would be operating in wide varieties of plants. Metabolic studies with various plant systems revealed multiple paths of metabolism such as hydroxylation, epimerization, side chain cleavage, reduction and conjugation with glucose and fatty acids. Recent progress of biosynthesis and metabolism of brassinosteroids is described.
Distinct Early Folding and Aggregation Properties of Alzheimer Amyloid-β Peptides Aβ40 and Aβ42 (2006)

The amyloid beta peptide (Abeta), composed of 40 or 42 amino acids, is a critical component in the etiology of the neurodegenerative Alzheimer disease. Abeta is prone to aggregate and forms amyloid fibrils progressively both in vitro and in vivo. To understand the process of amyloidogenesis, it is pivotal to examine the initial stages of the folding process. We examined the equilibrium folding properties, assembly states, and stabilities of the early folding stages of Abeta40 and Abeta42 prior to fibril formation. We found that Abeta40 and Abeta42 have different conformations and assembly states upon refolding from their unfolded ensembles. Abeta40 is predominantly an unstable and collapsed monomeric species, whereas Abeta42 populates a stable structured trimeric or tetrameric species at concentrations above approximately 12.5 microm. Thermodynamic analysis showed that the free energies of Abeta40 monomer and Abeta42 trimer/tetramer are approximately 1.1 and approximately 15/ approximately 22 kcal/mol, respectively. The early aggregation stages of Abeta40 and Abeta42 contain different solvent-exposed hydrophobic surfaces that are located at the sequences flanking its protease-resistant segment. The amyloidogenic folded structure of Abeta is important for the formation of spherical beta oligomeric species. However, beta oligomers are not an obligatory intermediate in the process of fibril formation because oligomerization is inhibited at concentrations of urea that have no effect on fibril formation. The distinct initial folding properties of Abeta40 and Abeta42 may play an important role in the higher aggregation potential and pathological significance of Abeta42.