gebhart/patrepeval huggingface dataset:
Production and characterization of recombinant insulin-like growth factor-I (IGF-I) and potent analogues of IGF-I, with Gly or Arg substituted for Glu 3, following their expression in Escherichia coli as fusion proteins (1992)

The development of an efficient expression system for insulin-like growth factor-I (IGF-I) in Escherichia coli as a fusion protein is described. The fusion protein consists of an N-terminal extension made up of the first 46 amino acids of methionyl porcine GH ([Met1]-pGH) followed by the dipeptide Val-Asn. The latter two residues provide a unique hydroxylamine-sensitive link between [Met1]-pGH(1-46) and the N-terminal Gly of IGF-I. Downstream processing of the fusion proteins involved isolation of inclusion bodies, cleavage at the Asn-Gly bond, refolding of the reduced IGF-I peptide and purification to homogeneity. This expression system was also used to produce two variants of IGF-I in which Glu3 was substituted by either Gly or Arg to give [Gly3]-IGF-I and [Arg3]-IGF-I respectively. Production of milligram quantities of IGF-I peptide was readily achieved. The purity of the IGF-I, [Gly3]-IGF-I and [Arg3]-IGF-I was established by high-performance liquid chromatography and N-terminal sequence analysis. [Gly3]-IGF-I and [Arg3]-IGF-I were more potent than IGF-I in biological assays measuring stimulation of protein synthesis and DNA synthesis or inhibition of protein breakdown in rat L6 myoblasts. Both analogues bound very poorly to bovine IGF-binding protein-2 and slightly less well than IGF-I to the type-1 receptor on rat L6 myoblasts. We conclude that reduced binding to IGF-binding proteins rather than increased receptor binding is the likely explanation for the greater biological potency of the analogues compared with IGF-I.
Shape and Reflectance Estimation in the Wild (2015)

Our world is full of objects with complex reflectances situated in rich illumination environments. Though stunning, the diversity of appearance that arises from this complexity is also daunting. For this reason, past work on geometry recovery has tried to frame the problem into simplistic models of reflectance (such as Lambertian, mirrored, or dichromatic) or illumination (one or more distant point light sources). In this work, we directly tackle the problem of joint reflectance and geometry estimation under known but uncontrolled natural illumination by fully exploiting the surface orientation cues that become embedded in the appearance of the object. Intuitively, salient scene features (such as the sun or stained glass windows) act analogously to the point light sources of traditional geometry estimation frameworks by strongly constraining the possible orientations of the surface patches reflecting them. By jointly estimating the reflectance of the object, which modulates the illumination, the appearance of a surface patch can be used to derive a nonparametric distribution of its possible orientations. If only a single image exists, these strongly constrained surface patches may then be used to anchor the geometry estimation and give context to the less-descriptive regions. When multiple images exist, the distribution of possible surface orientations becomes tighter as additional context is given, though integrating the separate views poses additional challenges. In this paper we introduce two methods, one for the single image case, and another for the case of multiple images. The effectiveness of our methods is evaluated extensively on synthetic and real-world data sets that span the wide range of real-world environments and reflectances that lies between the extremes that have been the focus of past work.
Reflect on this, professor (1999)

I agree that reflective practice should be welcomed by patients, but this necessitates nurses having practice and experience to reflect on!
Association of latent membrane protein 1 and matrix metalloproteinase 9 with metastasis in nasopharyngeal carcinoma (2000)

The results suggest that the induction of MMP9 by LMP1 contributes to the metastatic potential of NPC.
Endoluminal exclusion of an iliac artery aneurysm by Wallstent endoprosthesis and PTFE vascular graft. (1997)

Aneurysms isolated in the iliac artery and measuring more than 3 cm in diameter are associated with an increased rate of rupture and a high mortality rate. The current therapy recommended for such aneurysms is surgical exclusion. Percutaneous exclusion of isolated iliac aneurysms with covered or uncovered stents, however, reduces the morbidity and mortality rates associated with surgery by obviating the need for general anesthesia, avoiding significant blood loss, and reducing in-hospital recuperation time. We report the case of a patient who had an isolated atherosclerotic iliac artery aneurysm that was successfully excluded percutaneously by use of an endovascular prosthesis (WALLSTENT Endoprosthesis) made by Schneider (USA), Inc; Minneapolis, Minn, in conjunction with the Thin-Walled GORE-TEX (polytetrafluoroethylene) Vascular Graft (W.L. Gore & Associates, Inc.; Flagstaff, Ariz). Although various stent devices have been used recently in conjunction with a polytetrafluoroethylene graft to exclude peripheral arterial aneurysms, the self-expandable WALLSTENT has not been used with polytetrafluoroethylene in this fashion and for this purpose until recently. We present herein the technical aspects of endoluminal exclusion of the isolated iliac artery aneurysm with this composite stent-graft.
Different ion channel mechanisms between low concentrations of capsaicin and high concentrations of capsaicin and nicotine regarding peptide release from pulmonary afferents (1992)

Vagal nerve stimulation (1 Hz for 1 min), capsaicin (10(-8) M and 10(-6) M), resiniferatoxin (3 x 10(-10) M) and nicotine (10(-4) M) evoked a non-cholinergic bronchoconstriction in the isolated perfused guinea-pig lung preparation. Simultaneously there was an increase in the perfusate levels of calcitonin gene-related peptide-like immunoreactivity, suggesting release from sensory nerves. Both the bronchoconstriction and peptide release evoked by a low concentration of capsaicin (10(-8) M) and that evoked by nerve stimulation were depressed by tetrodotoxin, suggesting involvement of Na+ channel dependent depolarization. Since the effects of capsaicin (10(-8) M) and vagal nerve stimulation were inhibited by omega-conotoxin but not influenced by nifedipine, the Ca(2+)-channel dependent is probably of N-type. Furthermore, the capsaicin analogue resiniferatoxin also evoked omega-conotoxin sensitive peptide release and bronchoconstriction. At the higher capsaicin concentration (10(-6) M), the functional response was only slightly inhibited by omega-conotoxin or tetrodotoxin indicating that capsaicin at this concentration evoked peptide release and functional effects through other mechanisms, probably involving Ca2+ fluxes in the non-selective cation channel associated with the proposed capsaicin receptor. The nicotine (10(-4) M) evoked peptide release and bronchoconstriction were only marginally influenced by omega-conotoxin or tetrodotoxin. It is concluded that the ion-channel mechanisms underlying the peptide releasing properties of antidromic nerve stimulation and low concentrations of capsaicin are similar and depend on action potential propagation, whereas capsaicin in high, toxic concentration and nicotine mainly act via receptor operated channels.
Direct Expression of a Synthetic Somatomedin C Gene in Escherichia coli by Use of a Two-Cistron System (1987)

Direct expression of a growth-promoting peptide hormone, somatomedin C/insulin-like growth factor I, which is quite difficult due to the instability of somatomedin C itself in Escherichia coli, has been achieved by the use of a two-cistron system. Assuming that basic somatomedin C might be stabilized by forming a complex with an acidic polypeptide, we constructed synthetic genes consisting of two cistrons; an acidic 93-amino-acid polypeptide was coded in the first cistron followed by a synthetic somatomedin C gene in the second cistron. The chain termination codon for the first polypeptide overlapped the initiation codon for the second polypeptide in the intercistronic region, as occurs in the polycistronic E. coli tryptophan operon, whose products are associated in multi-subunit enzyme complexes. In the expression of the resulting genetic system, recombinant somatomedin C associated with the acidic polypeptide was accumulated to high levels in the cells. After treatment of the product with acetic acid to dissociate the two components, the recombinant somatomedin C was isolated in a yield of 4.0 mg from a liter of culture broth at A600 = 1.6. It was determined to be Met-somatomedin C by chymotryptic mapping as well as amino-terminal analysis.
Low molecular weight heparin (dalteparin) for the treatment of venous thromboembolism in pregnancy (2003)

Our study suggests that dalteparin may be used for the treatment of acute venous thromboembolism in pregnancy. Approximately 10-20% higher doses of dalteparin may be needed as compared with non-pregnant individuals.
Endo[PA]R: An Open Evaluation System for Minimally Invasive Robotic Surgery (2004)

Abstract — EndoPAR (Endoscopic Partial-Autonomous Robot) is an open experimental platform for robot assisted minimally invasive heart surgery with haptic feedback. The manipulator set-up is composed of two low-payload robots equipped with sensorized surgical instruments and a third robot carrying a stereo camera system. Trocar kinematics, enabling surgical manipulation through small incisions, has been implemented for all robotic arms. In order to ensure operation close to reality, a thorax and heart phantom for surgical training was used in the experiments. Stereo vision is provided via a head-mounted display and force-reflective input devices are employed for user interaction. The system was evaluated by surgeons and it was capable of performing automated knot-tying. I.
Two‐color two‐photon excitation of indole (1997)

We observed two-color two-photon (2C2P) excitation of indole upon simultaneous illumination at 380 and 760 nm with picosecond pulses from a cavity-dumped dye laser. The emission spectrum of indole with 2C2P excitation was the same as observed for one-photon excitation with an equivalent energy of 250 nm. Observation of the 2C2P signal required temporal and spatial overlap of the 380- and 760-nm pulses. Illumination at 380 nm alone resulted in a background emission due to one-color two-photon excitation at 380 nm. This background was rendered insignificant compared to the 2C2P signal by attenuation of the 380-nm beam and amplification of the 760-nm beam. The ability to control the intensity of each beam is a unique advantage of 2C2P excitation. The amplitude of the 2C2P signal depended on the angle between the polarization of each beam in a manner which suggests participation of both the 1La and 1Lb states of indole to the 2C2P transitions. 2C2P excitation can provide a new tool to investigate the photophysical properties of indole, tryptophan, and proteins. © 1997 John Wiley & Sons, Inc. Biospect 3: 97–101, 1997
Implications of the Near-Planar Solution Structure of Human Myeloma Dimeric IgA1 for Mucosal Immunity and IgA Nephropathy (2008)

IgA is unique in being able to form a diverse range of polymeric structures. Increases in the levels of dimeric IgA1 (dIgA1) in serum have been implicated in diseases such as IgA nephropathy. We have determined the solution structure for dIgA1 by synchrotron x-ray and neutron scattering and analytical ultracentrifugation. The Guinier radius of gyration (RG) of 7.60-8.65 nm indicated that the two monomers within dIgA1 are arranged in an extended conformation. The distance distribution curve P(r) gave an overall length (L) of 22-26 nm. These results were confirmed by the sedimentation coefficient and frictional ratio of dIgA1. Constrained scattering modeling starting from the IgA1 monomer solution structure revealed a near-planar dimer structure for dIgA1. The two Fc regions form a slightly bent arrangement in which they form end-to-end contacts, and the J chain was located at this interface. This structure was refined by optimizing the position of the four Fab regions. From this, the best-fit solution structures show that the four Fab Ag-binding sites are independent of one another, and the two Fc regions are accessible to receptor binding. This arrangement allows dIgA1 to initiate specific immune responses by binding to FcalphaRI receptors, while still retaining Ag-binding ability, and to be selectively transported to mucosal surfaces by binding to the polymeric Ig receptor to form secretory IgA. A mechanism for the involvement of dIgA1 oligomers in the pathology of IgA nephropathy is discussed in the light of this near-planar structure.
Retinoblastoma growth suppressor and a 300-kDa protein appear to regulate cellular DNA synthesis. (1990)

Previous work has suggested that oncogenic transformation by the E1A gene products of adenovirus type 5 may be mediated through interactions with at least two cellular proteins, the 105-kDa product of the retinoblastoma growth suppressor gene (p105-Rb) and a 300-kDa protein (p300). By using viral mutants, we now show that the induction of cellular DNA synthesis in quiescent cells by E1A differs from transformation in that E1A products induce synthesis if they are able to bind to either p105-Rb or p300, and only mutant products that bind to neither are extremely defective. These results suggest that p105-Rb and p300 (or cellular proteins with similar E1A-binding properties) provide parallel means by which DNA synthesis can be regulated.
Overexpression of laminin gamma2 chain monomer in invading gastric carcinoma cells. (1999)

Laminin (LN)-5, a heterotrimer of alpha3, beta3, and gamma2 chains, has been suggested to be involved in tumor cell invasion. The present immunohistochemical study investigated the distribution of the LN gamma2 chain in 48 different human gastric adenocarcinomas. The immunohistochemical analysis showed two distinct patterns of LN gamma2 chain expression: (a) extracellular deposition; and (b) cytoplasmic accumulation. The extracellular deposition of the LN gamma2 chain was typically observed at neoplastic basement membranes of well-differentiated adenocarcinomas. The immunoreactivity was continuous along tumor basement membranes in these tumors but was irregular and diffuse in poorly differentiated carcinomas. These tumor cells coexpressed the LN alpha3 and beta3 chains, suggesting that the LN gamma2 chain was deposited as the LN-5 complex. In contrast, tumor cells at the invading fronts showed strong cytoplasmic staining for the LN gamma2 chain without any detectable signal for the LN alpha3 or beta3 chain in both well- and poorly differentiated carcinomas. On the other hand, in vitro analysis by two-dimensional SDS-PAGE demonstrated that human gastric carcinoma cells secrete a high level of LN gamma2 chain monomer in addition to the LN-5 complex into culture medium. These results indicate that the LN gamma2 chain can be secreted as a single subunit and might be involved in tumor cell invasion.
Rescue Screens with Secreted Proteins Reveal Compensatory Potential of Receptor Tyrosine Kinases in Driving Cancer Growth (2012)

The overall power of kinase inhibitors is substantially overshadowed by the acquisition of drug resistance. To address this issue, we systematically assessed the potential of secreted proteins to induce resistance to kinase inhibitors. To this end, we developed a high-throughput platform for screening a cDNA library encoding 3,432 secreted proteins in cellular assays. Using cancer cells originally dependent on either MET, FGFR2, or FGFR3, we observed a bypass of dependence through ligand-mediated activation of alternative receptor tyrosine kinases (RTK). Our findings indicate a broad and versatile potential for RTKs from the HER and FGFR families as well as MET to compensate for loss of each other. We further provide evidence that combined inhibition of simultaneously active RTKs can lead to an added anticancer effect.
Complete Genome Sequence of the Apicomplexan, Cryptosporidium parvum (2004)

The apicomplexan Cryptosporidium parvum is an intestinal parasite that affects healthy humans and animals, and causes an unrelenting infection in immunocompromised individuals such as AIDS patients. We report the complete genome sequence of C. parvum , type II isolate. Genome analysis identifies extremely streamlined metabolic pathways and a reliance on the host for nutrients. In contrast to Plasmodium and Toxoplasma , the parasite lacks an apicoplast and its genome, and possesses a degenerate mitochondrion that has lost its genome. Several novel classes of cell-surface and secreted proteins with a potential role in host interactions and pathogenesis were also detected. Elucidation of the core metabolism, including enzymes with high similarities to bacterial and plant counterparts, opens new avenues for drug development.
Role of viral infectivity in the induction of influenza virus-specific cytotoxic T cells. (1978)

This report examines the requirement for infectious virus in the induction of influenza virus-specific cytotoxic T cells. Infectious influenza virus was found to be highly efficient at generating both primary and secondary cytotoxic T-cell response in vivo. Inactivated influenza virus however, failed to stimulate a detectable cytotoxic T-cell response in vivo even at immunizing doses 10(5)-10(6)-fold higher than the minimum stimulatory dose of infectious virus. Likewise inactivated virus failed to sensitize target cells for T cell-mediated lysis in vitro but could stimulate a specific cytotoxic response from primed cells in vitro. Possible requirements for the induction of virus-specific cytotoxic T-cell responses are discussed in light of these observations and those of other investigators.
Sustained-release hydrogels of topotecan for retinoblastoma B Biointerfaces (2016)

Treatment of retinoblastoma, the most common primary ocular malignancy in children, has greatly improved over the last decade. Still, new devices for chemotherapy are needed to achieve better tumor control. The aim of this project was to develop an ocular drug delivery system for topotecan (TPT) loaded in biocompatible hydrogels of poly(e-caprolactone)-poly(ethyleneglycol)-poly(e-caprolactone) block copolymers (PCL-PEG-PCL) for sustained TPT release in the vitreous humor.Hydrogels were prepared from TPT and synthesized PCL-PEG-PCL copolymers. Rheological properties and in vitro and in vivo TPT release were studied. Hydrogel cytotoxicity was evaluated in retinoblastoma cells as a surrogate for efficacy and TPT vitreous pharmacokinetics and systemic as well as ocular toxicity were evaluated in rabbits. The pseudoplastic behavior of the hydrogels makes them suitable for intraocular administration. In vitro release profiles showed a sustained release of TPT from PCL-PEG-PCL up to 7days and drug loading did not affect the release pattern. Blank hydrogels did not affect retinoblastoma cell viability but 0.4% (w/w) TPT-loaded hydrogel was highly cytotoxic for at least 7days. After intravitreal injection, TPT vitreous concentrations were sustained above the pharmacologically active concentration. One month after injection, animals with blank or TPT-loaded hydrogels showed no systemic toxicity or retinal impairment on fundus examination, electroretinographic, and histopathological assessments. These novel TPT-hydrogels can deliver sustained concentrations of active drug into the vitreous with excellent biocompatibility in vivo and pronounced cytotoxic activity in retinoblastoma cells and may become an additional strategy for intraocular retinoblastoma treatment.
Miniature tri-axial force sensor for feedback in minimally invasive surgery (2012)

A miniature tri-axial force sensor has been developed that complies with the requirements of integration into biomedical and robotic devices due to its size and accuracy. The sensor is a machined Titanium alloy body of the overall dimensions 8.6 × Ø3.4 mm with semi-conductor strain gauges embedded on it. The sensing beam's size is 1 × 1 × 4.4 mm. We present here the design, calibration method and performance evaluation of our sensor. Properly calibrated, it can provide absolute resolution of 5 mN at 2 N full scale. The accuracy of the estimated angle of incidence is ±1°. The measured magnitude of the force is within the ±4% range of the actual one. At maximal load the accuracy of the shear angle is ±1°.
Molecular cloning and sequence analysis of the proBA operon from an extremely thermophilic eubacterium Thermus thermophilus (1994)

A 3.6 kb DNA fragment carrying the Thermus thermophilus proBA region, which encodes the first two steps in the proline biosynthetic pathway, was cloned from the Thermus thermophilus gene library, and its complete nucleotide sequence was determined. The deduced amino acid sequence of γ-glutamyl kinase (40,657 Da), the product of proB gene, and γ-glutamyl phosphate reductase (48, 747 Da), the product of proA gene, showed 44.1% and 44.4% identity to those of Escherichia coli, respectively. The termination codon of the proB gene and the initiation codon of the proA gene overlapped by 2 bp. A possible transcriptional termination structure was found downstream of the proA gene but not downstream of the proB gene. These results indicate that the proBA genes of T. thermophilus from a single operon as in E. coli.
Development of a central nervous system axonal myelination assay for high throughput screening (2016)

We have designed the first high capacity in vitro assay that assesses myelination of live axons. This assay will be ideal for screening large compound libraries to identify new drugs that stimulate myelination. Identification of agents capable of promoting the myelination of axons will likely lead to the development of new therapeutics for MS patients.
Treatment of intracranial dengue virus infections in mice with a lipophilic derivative of ribavirin (1983)

Rimantadine, ribavirin, and 6-mercapto-9-(tetrahydro-2-furyl)purine, administered intraperitoneally every 8 h for 7 days starting minutes after virus challenge, had no effect on survival and mean survival time of BALB/c mice inoculated intracranially with dengue virus type 2. In contrast, intraperitoneal treatment with ribavirin 2',3',5'-triacetate, a lipophilic analog of ribavirin, effected significant increases in both mean survival time and survival rate, suggesting that ribavirin 2',3',5'-triacetate may be superior to rabavirin for treatment of viral diseases of the brain.
Sterically Stabilized Cationic Liposomes Improve the Uptake and Immunostimulatory Activity of CpG Oligonucleotides (2001)

Immunostimulatory CpG oligonucleotides (ODN) show promise as immune adjuvants, anti-allergens, and immunoprotective agents. Increasing the bioavailability and duration of action of CpG ODN should improve their therapeutic utility. Encapsulating ODN in sterically stabilized cationic liposomes provides protection from serum nucleases while facilitating uptake by B cells, dendritic cells, and macrophages. In a pathogen challenge model, sterically stabilized cationic liposomes encapsulation doubled the duration of CpG ODN-induced immune protection. In an immunization model, coencapsulation of CpG ODN with protein Ag (OVA) magnified the resultant Ag-specific IFN-gamma and IgG responses by 15- to 40-fold compared with Ag plus CpG ODN alone. These findings support the use of sterically stabilized cationic liposomes to significantly enhance the therapeutic efficacy of CpG ODN.