gebhart/patrepeval huggingface dataset:
Rab7 is required for the normal progression of the autophagic pathway in mammalian cells (2004)

Autophagy is a normal degradative pathway that involves the sequestration of cytoplasmic components and organelles in a vacuole called an autophagosome that finally fuses with the lysosome. Rab7 is a member of the Rab family involved in transport to late endosomes and in the biogenesis of the perinuclear lysosome compartment. To assess the role of Rab7 in autophagy we stably transfected CHO cells with wild-type pEGFP-Rab7, and the mutants T22N (GDP form) and Q67L (GTP form). Autophagy was induced by amino acid starvation and the autophagic vacuoles were labeled with monodansylcadaverine. By fluorescence microscopy we observed that Rab7wt and the active mutant Rab7Q67L were associated with ring-shaped vesicles labeled with monodansylcadaverine indicating that these Rab proteins associate with the membrane of autophagic vesicles. As expected, in cells transfected with the negative mutant Rab7T22N the protein was diffusely distributed in the cytosol. However, upon induction of autophagy by amino acid starvation or by rapamycin treatment this mutant clearly decorated the monodansylcadaverine-labeled vesicles. Furthermore, a marked increase in the size of the monodansylcadaverine-labeled vacuoles induced by starvation was observed by overexpression of the inactive mutant T22N. Similarly, there was an increase in the size of vesicles labeled with LC3, a protein that specifically localizes on the autophagosomal membrane. Taken together the results indicate that a functional Rab7 is important for the normal progression of autophagy.
Relationship of pharmacokinetics (PK), toxicity, and initial evidence of clinical activity with IMGN853, a folate receptor alpha (FRa) targeting antibody drug conjugate in patients (Pts) with epithelial ovarian cancer (EOC) and other FRa-positive solid tumors. (2014)

5571 Background: IMGN853 is a FRα-targeting ADC that comprises a FRa-binding antibody conjugated with the potent maytansinoid tubulin inhibitor, DM4. FRa is highly expressed on many solid tumors, particularly EOC, endometrial, non-small cell lung cancer, and clear cell renal cancer Methods: The phase I primary objectives are to determine the maximum tolerated dose and recommended phase 2 dose. The secondary objectives include evaluation of safety, PK, pharmacodynamics and preliminary efficacy. Analysis of PK data and the relationship with ocular toxicity, the dose limiting toxicity at 7.0 mg/kg total body weight (TBW) and initial evidence of clinical activity from patients in this ongoing study is described. Results: Thirty pts have been enrolled across 7 dose levels 0.15 to 7.0 mg/kg TBW (IV) every 21 days (Q3W). The occurrence of ocular toxicity was associated with high Cmax (p=0.0004 Fisher exact test) and high early exposure levels, (area under the curve in the first 24 hours (AUC0-24) (p=0.0001)). Covariate analysis indicated a correlation between weight and Cmax (Pearson r=0.48, p=0.02). Preliminary evidence of clinical activity (CA125 CGIC response criteria, partial response (PR), SD > 6 cycles) was observed in 10/24 patients receiving doses > 3.3 mg/kg (TBW). There was evidence of a threshold exposure level for activity around AUC0- ∞>12,944 (hr ug/ml). In patients with these exposure levels, clinical activity was observed in 5/6 serous or transitional EOC pts and 2/4 endometrial pts. The final clinical activity threshold may vary slightly as additional pts are enrolled. Based on these results, and PK modeling, dosing by adjusted ideal body weight (ADJ) was identified as a means to decrease PK variability due to body weight dependence. The phase I trial has been amended to evaluate this hypothesis. Conclusions: Preliminary evidence of anti-tumor activity is encouraging, and results from the PK analysis suggest ADJ dosing should enable more pts to be treated within a clinically relevant therapeutic window. Clinical trial information: IMGN853-0401 NCT01609556.
Pollen grains as allergenic environmental factors – new approach to the forecasting of the pollen concentration during the season (2014)

The application of the recommended threshold values during the predictive models construction seems to be really useful to estimate the real threat of allergen exposure. It was indicated that the polynomial logistic regression models could be a practical tool for effective forecasting in biological monitoring of pollen exposure.
Search for deep slabs in the Northwest Pacific mantle (1989)

A residual sphere is formed by projecting seismic ray travel-time anomalies, relative to a reference Earth model, onto an imaginary sphere around an earthquake. Any dominant slab-like fast band can be determined with spherical harmonic expansion. The technique is useful in detecting trends associated with high-velocity slabs beneath deep earthquakes after deep-mantle and near-receiver effects are removed. Two types of corrections are used. The first uses a tomographic global mantle model; the second uses teleseismic station averages of residuals from many events over a large area centered on the events of interest. Under the Mariana, Izu-Bonin, and Japan trenches, the dominant fast bands are generally consistent with seismicity trends. The results are unstable and differ from the seismicity trend for Kurile events. The predominant fast band for most deep earthquakes under Japan is subhorizontal rather than near vertical. We find little support for the deep slab penetration hypothesis.
Anti‐inflammatory and immunomodulatory activities of polysaccharide from Chlorella stigmatophora and Phaeodactylum tricornutum (2003)

Crude polysaccharide extracts were obtained from aqueous extracts of the microalgae Chlorella stigmatophora and Phaeodactylum tricornutum. The crude extracts were fractionated by ion-exchange chromatography on DEAE-cellulose columns. The molecular weights of the polysaccharides in each fraction were estimated by gel filtration on Sephacryl columns. The crude polysaccharide extracts of both microalgae showed anti-inflammatory activity in the carrageenan-induced paw edema test. In assays of effects on the delayed hyper-sensitivity response, and on phagocytic activity assayed in vivo and in vitro, the C. stigmatophora extract showed immunosuppressant effects, while the P. tricornutum extract showed immunostimulatory effects.
Selective single-crystalline-silicon growth at the pre-defined active regions of TFTs on a glass by a scanning CW laser irradiation (2002)

We have developed a new Si crystallization method, which makes possible to form single-crystalline-silicon (Si) film in channel region of TFTs on non-alkali glass without introducing thermal damage into it, using a scanning solid-state CW laser (10 W). The peculiar characteristics of this crystallization method are introduction of pre-defined thick capping Si layer on the pre-patterned channel region and laser irradiation from back surface. We succeeded in formation of single-crystalline-Si with 1.5 /spl mu/m wide and 20 /spl mu/m long. High performance TFTs with mobility of 300 cm/sup 2//Vs, S-value 0.41 V/dec, Vth -0.5 V, and low off-current, were obtained by fabrication process below 450/spl deg/C. This crystallization uses stable solid-state laser and realizes the high-performance Si devices on non-alkali glass substrates, which are necessary to achieve System On Glass (SOG).
Television by Pulse Code Modulation* (1951)

Transmission by pulse code modulation presents inviting possibilities in the field of television in that information may be relayed by many repeater stations without deterioration. In a PCM system, the informal ion signal is periodically sampled and its instantaneous amplitude described by a group of pulses according to a pec-set code. These pulse groups occur at the sampling rate and constitute the transmitted signal. In this process an operation known as amplitude quantization is required.
Ordered Metal Nanohole Arrays Made by a Two-Step Replication of Honeycomb Structures of Anodic Alumina (1995)

A highly ordered metal nanohole array (platinum and gold) was fabricated by a two-step replication of the honeycomb structure of anodic porous alumina. Preparation of the negative porous structure of porous alumina followed by the formation of the positive structure with metal resulted in a honeycomb metallic structure. The metal hole array of the film has a uniform, closely packed honeycomb structure approximately 70 nanometers in diameter and from 1 to 3 micrometers thick. Because of its textured surface, the metal hole array of gold showed a notable color change compared with bulk gold.
Technique of the radical operation for cancer of the rectum (1914)

Journal Article Technique of the radical operation for cancer of the rectum Get access W Ernest Miles W Ernest Miles London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Surgery, Volume 2, Issue 6, January 1914, Pages 292–305, https://doi.org/10.1002/bjs.1800020609 Published: 02 March 2006
Development of multimedia E-mail system providing an integrated message view (2002)

E-mail is the most popular method for information exchange through communication networks. As multimedia technologies are developed rapidly, networks need to support multimedia data. In order to transmit multimedia messages, MIME (Multipurpose Internet Mail Extensions) was proposed, but a multimedia message consisting of different media is not viewed as an integrated form. In this paper, a multimedia E-mail system has been developed according to the MIME standard in order to solve the limitations of multimedia message transmission. A redefined HTML (Hypertext Markup Language) syntax is applied to the E-mail system for the purpose of viewing a multimedia message as an integrated form. It allows users to understand a message better. The proposed E-mail system also provides convenient functions of message authoring and display for users.
Too Much of a Good Thing? Tracing the History of the Propofol Infusion Syndrome (2007)

Rosen, Daniel J. MD; Nicoara, Alina MD; Koshy, Ninan MD; Wedderburn, Raymond V. MD Author Information
In vivo interaction of bacterial lipopolysaccharide (LPS) with rabbit platelets: modulation by C3 and high density lipoproteins. (1981)

Abstract We have examined the kinetics and specificity of binding of LPS to blood elements in rabbits after i.v. injection of 250 μg of the highly anticomplementary Salmonella minnesota R595 LPS (with tracer amounts of 125I-LPS). In blood samples obtained 0.5 to 2 min after injection of LPS, 35 ± 10 (S.D.) percent of the LPS was contained in the buffy coat, and autoradiography of blood smears revealed that 86% of the cell-associated grains were localized over platelets. The LPS remaining in blood at times &amp;gt; 5 min after injection (which we have previously shown to be in a form with a markedly reduced particle size and hydrated buoyant density, LD-LPS) was not bound to any formed blood elements. Likewise, injection of LD-LPS formed in vitro in serum did not result in detectable binding to platelets or other blood elements. In spite of the absence of detectable association with blood celts, i.v. injected LD-LPS (250 μg) produced slowly developing thrombocytopenia, hypotension, fibrin deposition in small vessels, and death of 8 of 8 rabbits within 8 to 20 hr. Binding of the parent R595 LPS to platelets also was not observed at any time between 0.5 min and 500 min post injection in rabbits depleted of C3 and terminal complement (C) components by prior injection of cobra venom factor. These results provide additional evidence that the initial C-dependent responses of platelets to LPS are not required for development of the subsequent pathophysiologic changes. Further, binding of LPS to platelets does not appear to play a major role in the initiation of hypotension and DIC after LPS injection.
[The effect of positive pressure ventilation combined with diaphragm pacing on respiratory mechanics in patients with respiratory failure]. (2011)

Compared with positive pressure ventilation , positive pressure ventilation combined with diaphragm pacing can decrease the Paw, increase intrathoracic negative pressure, transpulmonary pressure, and Cst, and decrease WOBv, while there is no effect on Raw and R(L).
Synthesis and Anti-HIV and Anti-HBV Activities of 2‘-Fluoro-2‘,3‘-unsaturated l-Nucleosides (1999)

The synthesis of L-nucleoside analogues containing 2'-vinylic fluoride was accomplished by direct condensation method, and their anti-HIV and anti-HBV activities were evaluated in vitro. The key intermediate 8, the sugar moiety of our target compounds, was prepared from 1,2-O-isopropylidene-L-glyceraldehyde via (R)-2-fluorobutenolide intermediate 5 in five steps. Coupling of the acetate 8 with the appropriate heterocycles (silylated uracil, thymine, N4-benzoylcytosine, N4-benzoyl-5-fluorocytosine, 6-chloropurine, and 6-chloro-2-fluoropurine) in the presence of Lewis acid afforded a series of 2'-fluorinated L-nucleoside analogues (15-18, 23-26, 36-45). The newly synthesized compounds were evaluated for their antiviral activities against HIV-1 in human peripheral blood mononuclear (PBM) cells and HBV in 2.2.15 cells. Cytosine 23, 5-fluorocytosine 25, and adenine 36 derivatives exhibited moderate to potent anti-HIV (EC50 0.51, 0.17, and 1.5 microM, respectively) and anti-HBV (EC50 0.18, 0.225, and 1.7 microM, respectively) activities without significant cytotoxicity up to 100 microM in human PBM, Vero, CEM, and HepG2 cells.
Adenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia B (2011)

Peripheral-vein infusion of scAAV2/8-LP1-hFIXco resulted in FIX transgene expression at levels sufficient to improve the bleeding phenotype, with few side effects. Although immune-mediated clearance of AAV-transduced hepatocytes remains a concern, this process may be controlled with a short course of glucocorticoids without loss of transgene expression. (Funded by the Medical Research Council and others; ClinicalTrials.gov number, NCT00979238.).
MIM, a Potential Metastasis Suppressor Gene in Bladder Cancer (2002)

Using a modified version of the mRNA differential display technique, five human bladder cancer cell lines from low grade to metastatic were analyzed to identify differences in gene expression. A 316-bp cDNA (C11-300) was isolated that was not expressed in the metastatic cell line TccSuP. Sequence analysis revealed that this gene was identical to KIAA 0429, has a 5.3-kb transcript that mapped to 8q24.1. The protein is predicted to be 356 amino acids in size and has an actin-binding WH2 domain. Northern blot revealed expression in multiple normal tissues, but none in a metastatic breast cancer cell line (SKBR3) or in metastatic prostatic cancer cell lines (LNCaP, PC3). We have named this gene Missing in Metastasis (MIM) and our data suggest that it may be involved in cytoskeletal organization.
CG island methylation changes near the GSTP1 gene in prostatic carcinoma cells detected using the polymerase chain reaction: a new prostate cancer biomarker. (1997)

Cancer-associated somatic genome alterations offer great promise as cancer biomarkers. Here we describe a new biomarker for human prostate cancer: extensive methylation of deoxycytidine nucleotides distributed throughout a 5' "CG island" region of the pi-class glutathione S-transferase gene (GSTP1). Using the PCR to amplify a GSTP1 promoter sequence fragment containing 12 recognition sites for HpaII and MspI, 52 of 57 (91%) prostatic carcinoma DNA specimens demonstrated extensive somatic increases in deoxycytidine methylation, detected as amplification of target GSTP1 promoter sequences following HpaII digestion, but not following MspI treatment. Using nested primer sets, a sensitive PCR assay for extensive GSTP1 CG island methylation changes was developed that was capable of detecting 200 pg of prostate cancer cell DNA among 1 microgram of normal leukocyte DNA. This GSTP1 CG island DNA methylation assay, which targets a somatic genome change present in most prostate cancer cells but not in normal cells, may serve as a new molecular diagnosis and staging tool to aid in prostate cancer detection and treatment.
ATTENUATION CHARACTERISTICS OF NATURAL CLAY MATERIALS IN SOUTH WALES AND THEIR USE AS LANDFILL LINERS (1997)

The paper reports the findings of a comprehensive, laboratory-based characterisation and attenuation study of clay materials from South Wales. Materials studied commonly underlie landfill sites and provide the only means of attenuating and/or retarding leachates, and include estuarine alluvium, weathered Coal Measures mudrocks and glacial till. The laboratory tests conducted include the physico-chemical and mineralogical properties of the soils, batch-equilibrium and leaching column tests, the latter two tests involving heavy metal species. Results to date indicate distinctly different characteristics and behaviours due to different geologic materials; higher compacted densities and permeabilities for the mudrocks and glacial till. (A) For the covering abstract see IRRD 898792.
The Efficacy of Acarbose in the Treatment of Patients with Non–Insulin-Dependent Diabetes Mellitus: A Multicenter, Controlled Clinical Trial (1994)

Acarbose improved long-term glycemic control in patients with non-insulin-dependent diabetes mellitus regardless of concomitant antidiabetic medication.
The Aging Heart, Myocardial Fibrosis, and its Relationship to Circulating C-Type Natriuretic Peptide (2010)

Myocardial aging is characterized by left ventricular (LV) fibrosis leading to diastolic and systolic dysfunction. Studies have established the potent antifibrotic and antiproliferative properties of C-type natriuretic peptide (CNP); however, the relationship between circulating CNP, LV fibrosis, and associated changes in LV function with natural aging are undefined. Accordingly, we characterized the relationship of plasma CNP with LV fibrosis and function in 2-, 11-, and 20-month-old male Fischer rats. Further in vitro, we established the antiproliferative actions of CNP and the participation of the clearance receptor using adult human cardiac fibroblasts. Here we establish for the first time that a progressive decline in circulating CNP characterizes natural aging and is strongly associated with a reciprocal increase in LV fibrosis that precedes impairment of diastolic and systolic function. Additionally, we demonstrate in cultured adult human cardiac fibroblasts that the direct antiproliferative actions of high-dose CNP may involve a non-cGMP pathway via the clearance receptor. Together, these studies provide new insights into myocardial aging and the relationship to the antifibrotic and antiproliferative peptide CNP.
A fragment of the HMGN2 protein homes to the nuclei of tumor cells and tumor endothelial cells in vivo (2002)

We used a screening procedure to identify protein domains from phage-displayed cDNA libraries that bind both to bone marrow endothelial progenitor cells and tumor vasculature. Screening phage for binding of progenitor cell-enriched bone marrow cells in vitro, and for homing to HL-60 human leukemia cell xenograft tumors in vivo, yielded a cDNA fragment that encodes an N-terminal fragment of human high mobility group protein 2 (HMGN2, formerly HMG-17). Upon i.v. injection, phage displaying this HMGN2 fragment homed to HL-60 and MDA-MB-435 tumors. Testing of subfragments localized the full binding activity to a 31-aa peptide (F3) in the HMGN2 sequence. Fluorescein-labeled F3 peptide bound to and was internalized by HL-60 cells and human MDA-MB-435 breast cancer cells, appearing initially in the cytoplasm and then in the nuclei of these cells. Fluorescent F3 accumulated in HL-60 and MDA-MB-435 tumors after an i.v. injection, appearing in the nuclei of tumor endothelial cells and tumor cells. Thus, F3 can carry a payload (phage, fluorescein) to a tumor and into the cell nuclei in the tumor. This peptide may be suitable for targeting cytotoxic drugs and gene therapy vectors into tumors.
Stability of the human dystrophin transcript in muscle (1996)

The human dystrophin gene has 79 exons spanning >2300 kb making it the largest known gene. In previous studies we showed that approximately 16 h are required to transcribe the gene in myogenic cultures [Tennyson, C.N., Klamut, H.J. and Worton, R.G. (1995) Nature Genet. 9, 184-190]. To estimate the half-life of the dystrophin mRNA, the decay of the transcript was monitored by quantitative RT-PCR in cultured human fetal myotubes following exposure to actinomycin D. Results from this analysis indicated that the half-life of the dystrophin mRNA is 15.6 +/- 2.8 h in these cultures. Transcript accumulation profiles were predicted using a mathematical model which incorporated the measured half-life. The modeled accumulation profiles were consistent with observed profiles supporting the half-life measured using actinomycin D. The kinetic model was then used to predict the relative amount of nascent and mature dystrophin transcript at steady state. Measurements by quantitative RT-PCR indicated that in adult skeletal muscle tissue the concentration of mature dystrophin mRNA is 5-10 molecules per nucleus, demonstrating, as expected, that it is a low abundance transcript. Furthermore the ratio of nascent to mature dystrophin transcript indicated that dystrophin synthesis may not be at steady state in the adult skeletal muscle we tested. Alternatively, the kinetics of transcript production in skeletal muscle tissue may be different from those observed in cultured fetal myogenic cells.
Overexpression of a dominant negative type II bone morphogenetic protein receptor inhibits the growth of human breast cancer cells. (2003)

Bone morphogenetic proteins (BMPs) exert cell type-specific effects on cell proliferation. To clarify the role of the BMP pathway in human breast cancer cells, we used a dominant negative strategy with a truncated human type II BMP receptor (DN-BMPRII; amino acid 1-172) fused to the NH2 terminus of enhanced green fluorescent protein. Transient overexpression of DN-BMPRII interfered with BMP-2-induced Smad1 transcriptional activity and caused cells to accumulate in G1. Stable cell lines that constitutively overexpressed DN-BMPRII were resistant to BMP-2-induced Smad1 phosphorylation and proliferated much more slowly than control stable cell lines. These results suggest that BMPs interacting with type II BMP receptors contribute to the proliferation and/or survival of human breast cancer cells.