gebhart/patrepeval huggingface dataset:
A NEW FLUOROMETRIC ASSAY FOR CYTOTOXICITY MEASUREMENTS IN-VITRO (1993)

Cytotoxicity testing of anticancer drugs requires techniques which are sensitive, reproducible and applicable to large scale testing using automated instruments. These assays are presently performed with end point staining of cell proteins with dyes, viability stains or energy dependent of substrates such as MTT or XTT. Although reliable. these assays are not sensitive enough, too expensive for large scale screening or they use reagents that may be harmful for personnel or equipment. We describe, the use of Alamar Blue, a new non fluorescent substrate, which after reduction in living cells, yields a very strong fluorescent product. Using the automated fluorescence plate reader Cytofluor, we have evaluated the various parameters such as substrate concentration, time and volume of incubation with respect to linearity and lower limit of detection. We found that for a two hour assay, this new non toxic substrate could detect as low as 200 cells per well with a useful measurement range up to 20,000 cells per well. The fluorescent assay is more than ten times as sensitive as the colorimetric assay. When the cytotoxicity of daunorubicin was measured with this assay and compared to the XTT formazan assay we found comparable IC50 values but this new assay was more economical and results are obtained in two hours as compared to four hours for the formazan assay. This new economical and versatile assay could be used with advantage for large scale in vitro screening of anticancer drugs and other cytotoxic agents.
The action of structural analogues of γ‐aminobutyric acid on binding sites in mouse brain (1984)

Abstract Nineteen structural analogues of γ‐aminobutyric acid (GABA) and the anxiolytics buspirone and diazepam were tested for their ability to modify GABA function in vitro. Each compound was added to the GABA receptor binding assay, the flunitrazepam receptor binding assay, the sodium‐dependent GABA binding assay, and the assay for GABA aminotransferase. It was anticipated that some of these analogues would substantially affect several of these assays. The most interesting compound to emerge was phenylthiohydantoic acid. This not only inhibited GABA receptor binding (K i = 121 μM) but also stimulated flunitrazepam binding and inhibited the activity of GABA aminotransferase. In light of the evidence that a reduced GABA function can be a factor in anxiety, phenylthiohydantoic acid has the potential to be a GABA‐mimetic and thus be useful in the treatment of anxiety.
ALTERATION OF NUCLEOSOME STRUCTURE AS A MECHANISM OF TRANSCRIPTIONAL REGULATION (1998)

The nucleosome, which is the primary building block of chromatin, is not a static structure: It can adopt alternative conformations. Changes in solution conditions or changes in histone acetylation state cause nucleosomes and nucleosomal arrays to behave with altered biophysical properties. Distinct subpopulations of nucleosomes isolated from cells have chromatographic properties and nuclease sensitivity different from those of bulk nucleosomes. Recently, proteins that were initially identified as necessary for transcriptional regulation have been shown to alter nucleosomal structure. These proteins are found in three types of multiprotein complexes that can acetylate nucleosomes, deacetylate nucleosomes, or alter nucleosome structure in an ATP-dependent manner. The direct modification of nucleosome structure by these complexes is likely to play a central role in appropriate regulation of eukaryotic genes.
Synthesis of Mono‐ and Bis(fluoroalkyl)pyrimidines from FARs, Fluorinated Acetoacetates, and Malononitrile Provides Easy Access to Novel High‐Value Pyrimidine Scaffolds (2017)

A new strategy was developed using fluorinated acetoacetates, malononitrile, and fluoroalkyl amino reagents (FARs) to access unprecedented 4,6-bis(fluoroalkyl)pyrimidine-5-carboxylates, their carboxylic acid analogues, and 4-amino-6-(fluoroalkyl)pyrimidine-5-carbonitriles. An efficient cyclization step using suitable amidines was developed under microwave irradiation, providing the desired pyrimidines rapidly and efficiently. Standard saponification conditions were applied from carboxylate derivatives to access to the corresponding carboxylic acids. These new valuable building blocks, bearing either a single or two emergent fluorinated substituents, hold strong potential for medicinal and agrochemical research.
Production of Anti-Müllerian Hormone: Another Homology between Sertoli and Granulosa Cells (1984)

Anti-Müllerian hormone (AMH) has been detected by RIA in the follicular fluid of mature bovine ovaries and in incubation medium of bovine granulosa cells. Purification of AMH from two independent batches of follicular fluid was achieved with a yield of 11% and 15% respectively. Both ovarian and control testicular AMH produced near-complete regression of fetal rat Müllerian ducts exposed to it in culture at a final concentration of 200-300 mU/ml and were recognized by the same monoclonal and polyclonal antibodies. These findings indicate that adult mammalian granulosa cells are capable of producing immunoreactive and bioactive AMH at a rate apparently similar to that already demonstrated for mature Sertoli cells and add yet another item to the homologies reported between male and female somatic gonadal cells.
Surface thiols of human lymphocytes and their changes after in vitro and in vivo activation (1996)

Cellular thiols have long been known to play a role in cell activation and proliferation; however, the differential expression of surface thiols on the lymphoid subsets had not been described. Neither was it known whether alteration of surface thiols occurs after exposure to mitogens or infectious agents. Herein, an impermeant thiol-specific fluorescent probe was employed for flow cytometric analysis of surface thiols. Quantification of surface thiols on resting lymphocytes revealed that some subsets expressed different concentrations of surface thiols (CD19+ > CD8+ > CD4+). Furthermore, surface thiols increased on all subsets by 8 h after mitogenic activation. This increase was blocked by cycloheximide or monensin but not by actinomycin D or inhibition of glutathione synthesis by buthionine sulfoximine. In addition, bacitracin, an inhibitor of protein disulfide isomerase, inhibited the increase in surface thiols and DNA synthesis. Lymphocytes from HIV-infected individuals displayed increased surface thiols on CD19+ and CD4+ cells but not CD8+ cells. Although cellular thiols in general have been believed to play a role in protection against oxidants, signaling associated with cell growth, and apoptosis, there is now evidence that changes in exofacial thiols appear to be involved in some of these critical cell reactivities. Thus, quantitative and possibly qualitative differences in surface thiols correlate with membrane differences between lymphoid subsets and with their differential sensitivities to oxidative stress, which suggests that the mechanisms by which surface thiols are maintained and modified after activation are important cellular functions that need to be further evaluated.
Anti-CD3 Monoclonal Antibody in New-Onset Type 1 Diabetes Mellitus (2002)

Treatment with hOKT3gamma1(Ala-Ala) mitigates the deterioration in insulin production and improves metabolic control during the first year of type 1 diabetes mellitus in the majority of patients. The mechanism of action of the anti-CD3 monoclonal antibody may involve direct effects on pathogenic T cells, the induction of populations of regulatory cells, or both.
Spontaneous and IL-2-induced anti-leukemic and anti-host effects against tumor- and host-specific alloantigens. (1993)

The graft-vs-leukemia (GVL) effect and its connection to graft-vs-host disease (GVHD) were studied in F1 hybrid mice after parental bone marrow transplantation. (BALB/c x C57BL/6) F1 mice (F1) were sublethally and lethally irradiated and inoculated with 10(4) BCL1 cells, a murine leukemia of BALB/c (BALB) origin. Subsequently mice were transplanted with F1 (syngeneic), BALB (allogeneic to the host but syngeneic to the tumor), C57BL/6 (B6) (allogeneic to both host and tumor) spleen cells, or spleen cells mixed with syngeneic (F1) bone marrow cells, respectively. Fresh BALB (H-2d) and B6 (H-2b) spleen cells, which induce equally strong GVHD in the F1 recipient against H-2b and H-2d alloantigens, respectively, were assayed for their ability to induce GVL effects on BCL1 (H-2d) cells with and without in vivo administration of human rIL-2. In order to increase the GVL effects, spleen cells were incubated for 4 days with rIL-2 to generate IL-2-activated killer cells. The results of adoptive transfer experiments showed that only immunocompetent B6 cells led to consistent eradication of leukemia. Neither BALB nor syngeneic F1 cells induced curative GVL effects regardless of whether spleen cells were further stimulated with rIL-2 in vitro, in vivo, or both. Our data support the theory that GVL effects are caused by T cell-dependent immune responses of allogeneic T cells and not by MHC-nonrestricted NK or rIL-2-activated NK cells, independently of the GVHD process itself. Hence, recognition and killing of tumor cells is most probably a MHC-restricted T cell-dependent process.
Online Learning of Region Confidences for Object Tracking (2006)

This paper presents an online learning method for object tracking. Motivated by the attention shifting among local regions of a human vision system during tracking, we propose to allow different regions of an object to have different confidences. The confidence of each region is learned online to reflect the discriminative power of the region in feature space and the probability of occlusion. The distribution of region confidences is employed to guide a tracking algorithm to find correspondences in adjacent frames of video images. Only high confidence regions are tracked instead of the entire object. We demonstrate feasibility of the proposed method in video surveillance applications. The method can be combined with many other existing tracking systems to enhance robustness of these systems.
Activation of the Alternative Pathway of Complement in Psoriatic Lesional Skin (1990)

The complement system may play an important role in the inflammatory reaction of psoriasis. While the classical pathway of the complement has been shown to be activated in psoriasis, there have been few reports on the involvement of the alternative pathway in the inflammatory reactions in psoriasis. Complement fragments, C4d and Bb, are released at the time of the classical and alternative pathway activation, respectively. The presence of the C4d or Bb fragment, therefore, denotes a preceding complement activation through the classical and/or alternative pathway. In the present study, we have measured the levels of C4d and Bb in psoriatic scale extracts using enzyme immunoassay techniques. The scales of these dermatoses contained higher levels of C4d and Bb detectable by enzyme immunoassay than those in the stratum corneum of noninflammatory skin. These results suggest that the alternative as well as the classical pathway of complement are activated in psoriatic lesional skin.
Gene therapy using genetically modified lymphocytes targeting VEGFR-2 inhibits the growth of vascularized syngenic tumors in mice (2010)

Immunotherapies based on adoptive cell transfer are highly effective in the treatment of metastatic melanoma, but the use of this approach in other cancer histologies has been hampered by the identification of appropriate target molecules. Immunologic approaches targeting tumor vasculature provide a means for the therapy of multiple solid tumor types. We developed a method to target tumor vasculature, using genetically redirected syngeneic or autologous T cells. Mouse and human T cells were engineered to express a chimeric antigen receptor (CAR) targeted against VEGFR-2, which is overexpressed in tumor vasculature and is responsible for VEGF-mediated tumor progression and metastasis. Mouse and human T cells expressing the relevant VEGFR-2 CARs mediated specific immune responses against VEGFR-2 protein as well as VEGFR-2-expressing cells in vitro. A single dose of VEGFR-2 CAR-engineered mouse T cells plus exogenous IL-2 significantly inhibited the growth of 5 different types of established, vascularized syngeneic tumors in 2 different strains of mice and prolonged the survival of mice. T cells transduced with VEGFR-2 CAR showed durable and increased tumor infiltration, correlating with their antitumor effect. This approach provides a potential method for the gene therapy of a variety of human cancers.
Flickr tag recommendation based on collective knowledge (2008)

Online photo services such as Flickr and Zooomr allow users to share their photos with family, friends, and the online community at large. An important facet of these services is that users manually annotate their photos using so called tags, which describe the contents of the photo or provide additional contextual and semantical information. In this paper we investigate how we can assist users in the tagging phase. The contribution of our research is twofold. We analyse a representative snapshot of Flickr and present the results by means of a tag characterisation focussing on how users tags photos and what information is contained in the tagging. Based on this analysis, we present and evaluate tag recommendation strategies to support the user in the photo annotation task by recommending a set of tags that can be added to the photo. The results of the empirical evaluation show that we can effectively recommend relevant tags for a variety of photos with different levels of exhaustiveness of original tagging.
Cap-Independent Translation Conferred by the 5′ Leader of Tobacco Etch Virus Is Eukaryotic Initiation Factor 4G Dependent (2001)

ABSTRACT The 5′ leader of tobacco etch virus (TEV) genomic RNA directs efficient translation from the naturally uncapped viral mRNA. Two distinct regions within the TEV 143-nucleotide leader confer cap-independent translation in vivo even when present in the intercistronic region of a discistronic mRNA, indicating that the TEV leader contains an internal ribosome entry site (IRES). In this study, the requirements for TEV IRES activity were investigated. The TEV IRES enhanced translation of monocistronic or dicistronic mRNAs in vitro under competitive conditions, i.e., at high RNA concentration or in lysate partially depleted of eukaryotic initiation factor 4F (eIF4F) and eIFiso4F, the two cap binding complexes in plants. The translational advantage conferred by the TEV IRES under these conditions was lost when the lysate reduced in eIF4F and eIFiso4F was supplemented with eIF4F (or, to a lesser extent, eIFiso4F) but not when supplemented with eIF4E, eIFiso4E, eIF4A, or eIF4B. eIF4G, the large subunit of eIF4F, was responsible for the competitive advantage conferred by the TEV IRES. TEV IRES activity was enhanced moderately by the poly(A)-binding protein. These observations suggest that the TEV IRES directs cap-independent translation through a mechanism that involves eIF4G specifically.
Identification of Tyrosyl Residue Present in the High-affinity Saccharide-binding Site of Ricin D (1986)

We analyzed [125I]iodotyrosyl residues in the B-chain of ricin D iodinated at pH 7.0 and 0°C for 60 min in the presence and absence of lactose. Peptides containing such [125I]iodotyrosyl residues were isolated from the subtilisin digest of iodinated B-chains by gel filtration on Sephadex G-25 followed by paper chromatography and paper electrophoresis. Their locations in the primary structure were assigned based on their amino acid composition. In the absence of lactose, five tyrosyl residues were susceptible to iodonation, but their reactivities varied; Tyr-248 seemed to be the most reactive, followed by Tyr-148, Tyr-78 (or Tyr-125), and Tyr-67; Tyr-176 was the least reactive. In the presence of lactose, however, Tyr-248 was completely protected from iodination, and the reactivity of Tyr-67 increased more than two-fold; that of Tyr-78 (or Tyr-125) decreased by about half. From these and earlier results, we concluded that Tyr-248 exists in the high-affinity saccharide-binding site of the B-chain. Tyr-67 and Tyr-78 (or Tyr-125) may exist next to each other near the low-affinity saccharide-binding site of the B-chain, and their iodination may cause a loss of lactose-binding ability.
Small Interfering RNA–Mediated Polo-Like Kinase 1 Depletion Preferentially Reduces the Survival of p53-Defective, Oncogenic Transformed Cells and Inhibits Tumor Growth in Animals (2005)

Polo-like kinase 1 (Plk1) is required for multiple stages of mitosis and is up-regulated in many human malignancies. We depleted Plk1 expression using small interfering RNA (siRNA) and showed defects in bipolar spindle formation and cytokinesis, growth inhibition, and apoptosis induction in human cancer cell lines. To our surprise, depletion of Plk1 in normal human cells did not result in obvious cell cycle defects, and did not induce significant inhibition of cell growth for at least two cell cycles. In addition, Plk1 siRNA inhibited colony formation in soft agar and tumorigenesis in a HT1080 xenograft model in a dose-dependent manner. Analysis with isogenic pairs of cell lines, differing in p53 status, revealed that Plk1 depletion preferentially induced mitotic arrest, aneuploidy, and reduced cell survival in the p53-defective cell lines. No obvious defects were observed in most p53 wild-type cells during the first few cell cycles. In addition, long-term survival studies revealed that p53 facilitates survival upon Plk1 depletion. Therefore, short-term inhibition of Plk1 can kill tumor cells while allowing normal cells to survive. These data validate the episodic inhibition of Plk1 as a very useful approach for cancer treatment.
Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut (2014)

Alterations in the gastrointestinal microbiota have been implicated in obesity in mice and humans, but the key microbial functions influencing host energy metabolism and adiposity remain to be determined. Despite an increased understanding of the genetic content of the gastrointestinal microbiome, functional analyses of common microbial gene sets are required. We established a controlled expression system for the parallel functional analysis of microbial alleles in the murine gut. Using this approach we show that bacterial bile salt hydrolase (BSH) mediates a microbe-host dialogue that functionally regulates host lipid metabolism and plays a profound role in cholesterol metabolism and weight gain in the host. Expression of cloned BSH enzymes in the gastrointestinal tract of gnotobiotic or conventionally raised mice significantly altered plasma bile acid signatures and regulated transcription of key genes involved in lipid metabolism (Pparγ, Angptl4), cholesterol metabolism (Abcg5/8), gastrointestinal homeostasis (RegIIIγ), and circadian rhythm (Dbp, Per1/2) in the liver or small intestine. High-level expression of BSH in conventionally raised mice resulted in a significant reduction in host weight gain, plasma cholesterol, and liver triglycerides, demonstrating the overall impact of elevated BSH activity on host physiology. In addition, BSH activity in vivo varied according to BSH allele group, indicating that subtle differences in activity can have significant effects on the host. In summary, we demonstrate that bacterial BSH activity significantly impacts the systemic metabolic processes and adiposity in the host and represents a key mechanistic target for the control of obesity and hypercholesterolemia.
To exploit uncertainty masking for adaptive image rendering (2013)

For high-quality image rendering using Monte Carlo methods, a large number of samples are required to be computed for each pixel. Adaptive sampling aims to decrease the total number of samples by concentrating samples on difficult regions. However, existing adaptive sampling schemes haven't fully exploited the potential of image regions with complex structures to the reduction of sample numbers. To solve this problem, we propose to exploit uncertainty masking in adaptive sampling. Experimental results show that incorporation of uncertainty information leads to significant sample reduction and therefore time-savings.
An absorbable pinned‐ring device for microvascular anastomosis of vein grafts: Experimental studies (1999)

In the rabbit, posterior facial vein segments were grafted to the femoral arteries using either conventional suture technique or a mechanical absorbable pinned-ring device. The purpose of this study was to compare patency rates and anastomotic times for the two different methods. The anastomoses were evaluated macroscopically and using light and scanning electron microscopy. The grafts anastomosed with the absorbable rings exhibited 100% patency, while only 83% of the sutured grafts were patent. The mean anastomotic time using the mechanical pinned-ring device was 18.1 min (range 9.8–30 min). The conventionally sutured anastomoses were completed in a mean time of 60 min (range 50–75 min). The experiment has confirmed that the absorbable pinned-ring device provides a safe and fast way to perform microvascular anastomosis. © 1999 Wiley-Liss, Inc. MICROSURGERY 19:128–134 1999
Conditional knockdown of hMRS2 results in loss of mitochondrial Mg + uptake and cell death (2008)

The human gene MRS2L encodes a mitochondrial protein distantly related to CorA Mg(2+) transport proteins. Constitutive shRNA-mediated knockdown of hMRS2 in human HEK-293 cell line was found here to cause death. To further study its role in Mg(2+) transport, we have established stable cell lines with conditionally expressing shRNAs directed against hMRS2L. The cells expressing shRNA for several generations exhibited lower steady-state levels of free mitochondrial Mg(2+) ([Mg(2+)](m)) and reduced capacity of mitochondrial Mg(2+) uptake than control cells. Long-term expression of shRNAs resulted in loss of mitochondrial respiratory complex I, decreased mitochondrial membrane potential and cell death. We conclude that hMrs2 is the major transport protein for Mg (+) uptake into mitochondria and that expression of hMrs2 is essential for the maintenance of respiratory complex I and cell viability.
Endocannabinoids Acting at Cannabinoid-1 Receptors Regulate Cardiovascular Function in Hypertension (2004)

We conclude that endocannabinoids tonically suppress cardiac contractility in hypertension and that enhancing the CB1-mediated cardiodepressor and vasodilator effects of endogenous anandamide by blocking its hydrolysis can normalize blood pressure. Targeting the endocannabinoid system offers novel therapeutic strategies in the treatment of hypertension.
Human cytomegalovirus harbors its own unique IL-10 homolog (cmvIL-10) (2000)

We identified a viral IL-10 homolog encoded by an ORF (UL111a) within the human cytomegalovirus (CMV) genome, which we designated cmvIL-10. cmvIL-10 can bind to the human IL-10 receptor and can compete with human IL-10 for binding sites, despite the fact that these two proteins are only 27% identical. cmvIL-10 requires both subunits of the IL-10 receptor complex to induce signal transduction events and biological activities. The structure of the cmvIL-10 gene is unique by itself. The gene retained two of four introns of the IL-10 gene, but the length of the introns was reduced. We demonstrated that cmvIL-10 is expressed in CMV-infected cells. Thus, expression of cmvIL-10 extends the range of counter measures developed by CMV to circumvent detection and destruction by the host immune system.