gebhart/patrepeval huggingface dataset:
Cyclooxygenase-2 expression is induced during human megakaryopoiesis and characterizes newly formed platelets (2002)

Cyclooxygenase (COX)-1 or -2 and prostaglandin (PG) synthases catalyze the formation of various PGs and thromboxane (TX) A(2). We have investigated the expression and activity of COX-1 and -2 during human megakaryocytopoiesis. We analyzed megakaryocytes from bone marrow biopsies and derived from thrombopoietin-treated CD34(+) hemopoietic progenitor cells in culture. Platelets were obtained from healthy donors and patients with high platelet regeneration because of immune thrombocytopenia or peripheral blood stem cell transplantation. By immunocytochemistry, COX-1 was observed in CD34(+) cells and in megakaryocytes at each stage of maturation, whereas COX-2 was induced after 6 days of culture, and remained detectable in mature megakaryocytes. CD34(+) cells synthesized more PGE(2) than TXB(2) (214 +/- 50 vs. 30 +/- 10 pg/10(6) cells), whereas the reverse was true in mature megakaryocytes (TXB(2) 8,440 +/- 2,500 vs. PGE(2) 906 +/- 161 pg/10(6) cells). By immunostaining, COX-2 was observed in <10% of circulating platelets from healthy controls, whereas up to 60% of COX-2-positive platelets were found in patients. A selective COX-2 inhibitor reduced platelet production of both PGE(2) and TXB(2) to a significantly greater extent in patients than in healthy subjects. Finally, we found that COX-2 and the inducible PGE-synthase were coexpressed in mature megakaryocytes and in platelets. We conclude that both COX-isoforms contribute to prostanoid formation during human megakaryocytopoiesis and that COX-2-derived PGE(2) and TXA(2) may play an unrecognized role in inflammatory and hemostatic responses in clinical syndromes associated with high platelet turnover.
Original Research Paper FORMULATION DEVELOPMENT OF SELF NANOEMULSIFYING DRUG DELIVERY SYSTEM (SNEDDS) OF CELECOXIB FOR IMPROVEMENT OF ORAL BIOAVAILABILITY (2013)

Celecoxib is a hydrophobic and highly permeable drug which belongs to class II of biopharmaceutics classification system (BCS). Low aqueous solubility of celecoxib leads to high variability in absorption after oral administration. The present study was carried out for the formulation development of celecoxib loaded self nanoemulsifying drug delivery system (SNEDDS) with the aim of enhancement of oral bioavailability. The SNEDDS formulation was optimized using pseudo-ternary phase diagram composed of capryol 90, cremophor RH 40 and propylene glycol. Six formulations (F1, F2, F3, F4, F5 and F6) were developed with varying concentration of oil, surfactant and co-surfactant by sonication technique. The self nano-emulsifying drug delivery system of celecoxib was characterized for content uniformity, particle size, poly dispersity index, viscosity determination and robustness of dilution, drug loading efficiency and shape of globules, thermodynamic stability and self emulsification efficiency. In vitro dissolution and in vitro diffusion studies were also carried out to get final optimized formulation. The optimized celecoxib SNEDDS (F6) found to contain surfactant content less than 30% and yielded nanoemulsion of mean droplet size 169.4nm, which was not affected by the pH of dilution media. The zeta potential of the optimized SNEDDS (F6) found to be -32.9 mV. The drug loading efficiency of the formulation F6 was high at 98.98%. The developed celecoxib loaded SNEDDS formulation exhibited a complete in vitro drug release in 1hr as compared with the plain drug. Thus, the self nanoemulsifying drug delivery system (SNEDDS) using celecoxib as model drug found to achieve effective therapeutic concentration and intended to provide relief from pain associated with inflammation by single dose administration as compared to conventional tablets as well as prevent the cardiac risks due to lower dose size.
HEMODYNAMIC EFFECTS OF DOPAMINE AND/OR VOLUME EXPANSION IN ACUTE TENSE ABDOMINAL DISTENSION (1985)

Smith-Wright, Deborah L.; Einzig, Stanley; Howland, Donna F.; Schutjer, Robyn K.; Lorenz, Elizabeth A.; Fuhrman, Bradley P. Author Information
Utilization of Pipeline embolization device for treatment of ruptured intracranial aneurysms: US multicenter experience (2014)

Objective Utilization of the Pipeline embolization device (PED) in complex ruptured aneurysms has not been well studied. We evaluated the safety and effectiveness data from five participating US centers. Methods Records of patients with ruptured cerebral aneurysms who underwent PED treatment between 2011 and 2013 were retrospectively reviewed. Results 26 patients with ruptured aneurysms underwent PED treatment (mean age 51.4±13.2 years;16 women). At presentation, 8 patients (30.8%) had a Hunt–Hess grade of IV or above; 11 required extraventricular drain placement. Aneurysm morphologies were: 8 dissecting, 8 blister-like, 6 fusiform, and 4 saccular. There were 22 anterior circulation and 4 posterior circulation aneurysms. PED deployment was successful in all patients, with adjunctive coiling utilized in 12. Periprocedural complications occurred in 5 (19.2%), including 3 inhospital deaths. 23 patients (88.5%) had postoperative angiography at a mean of 5.9 months: 18 aneurysms (78.3%) were completely occluded, 3 (13.0%) had residual neck filling, and 2 (8.7%) had residual dome filling. All blister-type aneurysms were completely occluded at follow-up. Clinical follow-up was available for an average of 10.1 months (range 2–21 months), with one asymptomatic in-stent stenosis and one asymptomatic thromboembolic stroke noted. Good outcome (modified Rankin Scale (mRS) score of 0–2) was achieved in 20 patients (76.9%), fair (mRS 3–4) in 3 (11.5%), and 3 died (11.5%). Conclusions The PED can be utilized for ruptured aneurysms and is a good option for blister-type aneurysms. However, due to periprocedural complications, it should be reserved for lesions that are difficult to treat by conventional clipping or coiling.
Supercritical Fluid Technology in Materials Science and Engineering (2002)

Supercritical fluid technology in materials science and engineering , Supercritical fluid technology in materials science and engineering , کتابخانه مرکزی دانشگاه علوم پزشکی تهران
Promoters maintain their relative activity levels under different growth conditions (2013)

Most genes change expression levels across conditions, but it is unclear which of these changes represents specific regulation and what determines their quantitative degree. Here, we accurately measured activities of ~900 S. cerevisiae and ~1800 E. coli promoters using fluorescent reporters. We show that in both organisms 60-90% of promoters change their expression between conditions by a constant global scaling factor that depends only on the conditions and not on the promoter's identity. Quantifying such global effects allows precise characterization of specific regulation-promoters deviating from the global scale line. These are organized into few functionally related groups that also adhere to scale lines and preserve their relative activities across conditions. Thus, only several scaling factors suffice to accurately describe genome-wide expression profiles across conditions. We present a parameter-free passive resource allocation model that quantitatively accounts for the global scaling factors. It suggests that many changes in expression across conditions result from global effects and not specific regulation, and provides means for quantitative interpretation of expression profiles.
Innate immune responses to LPS in mouse lung are suppressed and reversed by neutralization of GM-CSF via repression of TLR-4 (2004)

The innate immune inflammatory response to lipopolysaccharide (LPS, an endotoxin) is essential for lung host defense against infection by gram-negative bacteria but is also implicated in the pathogenesis of some lung diseases. Studies on genetically altered mice implicate granulocyte-macrophage colony-stimulating factor (GM-CSF) in lung responses to LPS; however, the physiological effects of GM-CSF neutralization are poorly characterized. We performed detailed kinetic and dose-response analyses of the lung inflammation response to LPS in the presence of the specific GM-CSF-neutralizing antibody 22E9. LPS instilled into the lungs of BALB/c mice induced a dose-dependent inflammation comprised of intense neutrophilia, macrophage infiltration and proliferation, TNF-alpha and matrix metalloproteinase release, and macrophage inflammatory protein-2 induction. The neutralization of anti-GM-CSF in a dose-dependent fashion suppressed these inflammatory indexes by 85% when given before or after LPS or after repeat LPS challenges. Here we report for the first time that the physiological expression of Toll-like receptor-4 in lung is reduced by anti-GM-CSF. We observed that lower Toll-like receptor-4 expression correlated with a similar decline in peak TNF- levels in response to endotoxin. Consequently, sustained expression of key inflammatory mediators over 24 h was reduced. These data expand the understanding of the contribution of GM-CSF to innate immune responses in lung and suggest that blocking GM-CSF might benefit some lung diseases where LPS has been implicated in etiology.
Expression of a cloned bovine growth hormone gene in Escherichia coli minicells (1982)

The synthesis of polypeptides in Escherichia coli minicells, directed by a pBR322 plasmid and its derivative-carrying bovine growth hormone cDNA insert, was studied. Two polypeptides coded by the ampicillin-resistance (Apr) gene (32 000 and 28 000 daltons) and a tetracycline-resistance (Tcr) polypeptide (36 000 daltons) were identified by insertion inactivation. Two additional polypeptides of 37 000 and 34 000 daltons of as yet unknown function were detected in all extracts regardless of the presence of the Apr or Tcr genes in the plasmid. The pBR322-BGH recombinant plasmid coded for several novel polypeptides, among them one of 46 000 daltons, presumably a fused product of the BGH and beta-lactamase genes. This protein, however, was not secreted into the periplasmic space of the cells as was the beta-lactamase.
The "Reading the Mind in the Eyes" Test revised version: a study with normal adults, and adults with Asperger syndrome or high-functioning autism. (2001)

In 1997 in this Journal we published the "Reading the Mind in the Eyes" Test, as a measure of adult "mentalising". Whilst that test succeeded in discriminating a group of adults with Asperger syndrome (AS) or high-functioning autism (HFA) from controls, it suffered from several psychometric problems. In this paper these limitations are rectified by revising the test. The Revised Eyes Test was administered to a group of adults with AS or HFA (N = 15) and again discriminated these from a large number of normal controls (N = 239) drawn from different samples. In both the clinical and control groups the Eyes Test was inversely correlated with the Autism Spectrum Quotient (the AQ), a measure of autistic traits in adults of normal intelligence. The Revised Eyes Test has improved power to detect subtle individual differences in social sensitivity.
Integrated force arrays (2002)

Integrated force arrays (IFAs), which are flexible metallized membranes that can be patterned using the techniques of VLSI electronics and that undergo substantial deformation when voltage is applied, have been developed. They may be configured as macroscopic actuators or used in highly articulated systems of great complexity. The theory of operation, the methods of construction, and the observational results for IFA test structures are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A Divide-and-Conquer Articulated-Body Algorithm for Parallel O(log(n)) Calculation of Rigid-Body Dynamics. Part 2: Trees, Loops, and Accuracy (1999)

This paper is the second in a two part series describing a recursive, divide and conquer algorithm for calculating the forward dynamics of a robot mechanism, or a general rigid body system, on a parallel computer. This paper presents the general version of the algorithm. The derivation begins with an algorithm for kinematic trees, which is then extended to closed loop systems. The general algorithm achieves O(log(n)) time complexity on O(n) processors for all kinematic trees and a large subset of closed loop systems. This paper also presents a more accurate version of the algorithm and the results of some numerical accuracy tests that compare both versions with the standard articulated body algorithm. The tests use rigid body systems containing up to 1024 bodies, and they show that the divide and conquer algorithm is substantially less accurate than the best serial algorithm but still accurate enough to be useful.
Promoter interactions in retrovirus vectors introduced into fibroblasts and embryonic stem cells (1991)

The activity of the Moloney murine leukemia virus promoter is restricted in mouse embryonic stem cells. Gene expression with retrovirus vectors can be achieved in these cells if internal promoters are used. To address the possible influence of the viral enhancer sequences on expression from the internal promoter, we have constructed high-titer, self-inactivating retrovirus vectors which delete viral regulatory sequences upon integration in the host genome. We show that deleting most of the viral enhancer sequences has no significant effect on viral titer. This enhancer deletion leads to either an increase or a decrease in the amount of RNA transcribed from the internal promoter, but no consistent change can be found with any type of vector. The same changes in expression from the internal promoter observed in embryonic stem cells are also observed in 3T3 fibroblast cells, in which the viral promoter is active. These results indicate that viral regulatory elements influence expression from an internal promoter independently of expression from the virus promoter.
Otoferlin Couples to Clathrin-Mediated Endocytosis in Mature Cochlear Inner Hair Cells (2013)

The encoding of auditory information with indefatigable precision requires efficient resupply of vesicles at inner hair cell (IHC) ribbon synapses. Otoferlin, a transmembrane protein responsible for deafness in DFNB9 families, has been postulated to act as a calcium sensor for exocytosis as well as to be involved in rapid vesicle replenishment of IHCs. However, the molecular basis of vesicle recycling in IHCs is largely unknown. In the present study, we used high-resolution liquid chromatography coupled with mass spectrometry to copurify otoferlin interaction partners in the mammalian cochlea. We identified multiple subunits of the adaptor protein complex AP-2 (CLAP), an essential component of clathrin-mediated endocytosis, as binding partners of otoferlin in rats and mice. The interaction between otoferlin and AP-2 was confirmed by coimmunoprecipitation. We also found that AP-2 interacts with myosin VI, another otoferlin binding partner important for clathrin-mediated endocytosis (CME). The expression of AP-2 in IHCs was verified by reverse transcription PCR. Confocal microscopy experiments revealed that the expression of AP-2 and its colocalization with otoferlin is confined to mature IHCs. When CME was inhibited by blocking dynamin action, real-time changes in membrane capacitance showed impaired synaptic vesicle replenishment in mature but not immature IHCs. We suggest that an otoferlin-AP-2 interaction drives Ca(2+)- and stimulus-dependent compensating CME in mature IHCs.
Generation of RCAS Vectors Useful for Functional Genomic Analyses (2001)

Avian leukosis type A virus-derived retroviral vectors have been used to introduce genes into cells expressing the corresponding avian receptor tv-a. This includes the use of Replication-Competent Avian sarcoma-leukosis virus (ASLV) long terminal repeat (LTR) with Splice acceptor (RCAS) vectors in the analysis of avian development, human and murine cell cultures, murine cell lineage studies and cancer biology. Previously, cloning of genes into this virus was difficult due to the large size of the vector and sparse cloning sites. To overcome some of the disadvantages of traditional cloning using the RCASBP-Y vector, we have modified the RCASBP-Y to incorporate "Gateway" site-specific recombination cloning of genes into the construct, either with or without HA epitope tags. We have found the repetitive "att" sequences, which are the targets for site-specific recombination, do not impair the production of infectious viral particles or the expression of the gene of interest. This is the first instance of site-specific recombination being used to generate retroviral gene constructs. These viral constructs will allow for the efficient transfer and expression of cDNAs needed for functional genomic analyses.
Interleukin-8 receptor B immunoreactivity in brain and neuritic plaques of Alzheimer's disease. (1997)

Cytokines mediate inflammatory responses through their receptors in the hematopoietic system. In a search for potential mediators of inflammatory responses in Alzheimer's disease, we examined brain for cytokine receptors. Herein we describe interleukin-8 receptor B (IL-8RB, also termed CXCR2) immunoreactivity in the central nervous system. Strong IL-8RB immunoreactivity is present in both Alzheimer's disease and control brains. Neurons, dendrites, and axons are clearly immunoreactive. In Alzheimer's disease, IL-8RB immunoreactivity is also present in some swollen dystrophic neurites of neuritic plaques. Double staining and confocal microscopic analysis reveals that these IL-8RB-positive neurites in plaques are neurofilament positive and are distinct from astrocytic or microglial processes. In general, these IL-8RB-positive neurities do not co-localize with PHF-1 or AT8 (hyperphosphorylated tau) immunoreactive neurites but instead co-localize with beta PP-positive neurites. These results demonstrate for the first time IL-8RB immunoreactivity in the central nervous system and imply a new role for this receptor outside the hematopoietic system. The strong presence of IL-8RB on neurons and the potential of glial cells to produce IL-8 suggest that this system might mediate neuronal-glial interactions.
RAS and BRAF mutations in cell‐free DNA are predictive for outcome of cetuximab monotherapy in patients with tissue‐tested RAS wild‐type advanced colorectal cancer (2019)

In metastatic colorectal cancer, RAS and BRAF mutations cause resistance to anti-EGFR therapies, such as cetuximab. Heterogeneity in RAS and BRAF mutations might explain nonresponse in a subset of patients receiving cetuximab. Analyzing mutations in plasma-derived circulating tumor DNA (ctDNA) could provide a more comprehensive overview of the mutational landscape as compared to analyses of primary and/or metastatic tumor tissue. Therefore, this prospective multicenter study followed 34 patients with metastatic colorectal cancer who were tissue-tested as RAS wild-type (exons 2-4) during routine work-up and received third-line cetuximab monotherapy. BRAF mutation status was also tested but did not exclude patients from therapy. At baseline and upon disease progression, cell-free DNA (cfDNA) was isolated for targeted next-generation sequencing (NGS). At 8 weeks, we determined that patients had benefited from treatment. NGS of cfDNA identified three patients with RAS mutations not detected in tumor tissue during routine work-up. Another six patients had a BRAF or rare RAS mutation in ctDNA and/or tumor tissue. Relative to patients without mutations in RAS/BRAF, patients with mutations at baseline had shorter progression-free survival [1.8 versus 4.9 months (P < 0.001)] and overall survival [3.1 versus 9.4 months (P = 0.001)]. In patients with clinical benefit (progressive disease after 8 weeks), ctDNA testing revealed previously undetected mutations in RAS/BRAF (71%) and EGFR (47%), which often emerged polyclonally. Our results indicate that baseline NGS of ctDNA can identify additional RAS mutation carriers, which could improve patient selection for anti-EGFR therapies. Acquired resistance, in patients with initial treatment benefit, is mainly explained by polyclonal emergence of RAS, BRAF, and EGFR mutations in ctDNA.
Detection of Abnormal Texture in Chest X-rays with Reduction of Ribs. (2003)

This paper presents a method to apply the general image retrieval algorithm on chest radiographs using quasi-Gabor filter. The lung field is extracted to limit the region to be processed using knowledge based lung field extraction method and the rib shadow is reduced to emphasis the lung texture.
Released granulocytic elastase: an indicator of pathobiochemical alterations in septicemia after abdominal surgery. (1985)

To discover the role of lysosomal enzyme release from polymorphonuclear (PMN) leukocytes during septicemia, plasma levels of PMN elastase were measured with a newly developed enzyme-linked immunosorbent assay for detection of the PMN elastase-alpha 1-proteinase inhibitor complex (E-alpha 1PI). Plasma samples from 41 patients were assayed continuously before and after major abdominal surgery. The patients were divided into a group without infection (group A) and two septicemia groups (survivors in group B and nonsurvivors in group C). The E-alpha 1PI levels of the 11 patients in group A without any signs of pre- or postoperative infection were in the normal range (a normal value of 86.5 +/- 25.5 ng/ml has been reported in 153 healthy subjects), except for a small increase to 208.8 +/- 25.6 ng/ml 12 hours after surgery. When septicemia was confirmed clinically in patients in groups B and C, the E-alpha 1PI levels rose on average to six times the norm in group B (649.9 +/- 116.3 ng/ml) and to more than 10 times the norm in group C (985.0 +/- 154.6 ng/ml). Peak values greater than 2,200 ng/ml could be measured in both groups. In patients in group B, the E-alpha 1PI levels returned to normal during recovery, while in those in group C they remained significantly elevated (560.5 +/- 174.7 ng/ml) until death. Correlations were demonstrated between the amount of elastase released into the circulation and the decrease in the activities of antithrombin III, coagulation factor XIII, and alpha 2-macroglobulin, as well as the increased C-reactive protein in plasma. We conclude that release of elastase and other lysosomal factors from PMN cells plays a major role in the pathobiochemical alterations during septicemia. In addition, significantly elevated E-alpha 1PI levels in the postoperative course seem to be a suitable indicator for onset and persistance of sepsis as well as of the severity of this disorder in patients after major surgery.