gebhart/patrepeval huggingface dataset:
In Vivo Functional Analyses of the Type II Acyl Carrier Proteins of Fatty Acid Biosynthesis (2007)

Acyl carrier protein (ACP) is a key component of the fatty acid synthesis pathways of both type I and type II synthesis systems. A large number of structure-function studies of various type II ACPs have been reported, but all are in vitro studies that assayed function or interaction of mutant ACPs with various enzymes of fatty acid synthesis or transfer. Hence in these studies functional properties of various mutant ACPs were assayed with only a subset of the many ACP-interacting proteins, which may not give an accurate overall view of the function of these proteins in vivo. This is especially so because Escherichia coli ACP has been reported to interact with several proteins that have no known roles in lipid metabolism. We therefore tested a large number of mutant derivatives of E. coli ACP carrying single amino acid substitutions for their abilities to restore growth to an E. coli strain carrying a temperature-sensitive mutation in acpP, the gene that encodes ACP. Many of these mutant proteins had previously been tested in vitro thus providing data for comparison with our results. We found that several mutant ACPs containing substitutions of ACP residues reported previously to be required for ACP function in vitro support normal growth of the acpP mutant strain. However, several mutant proteins reported to be severely defective in vitro failed to support growth of the acpP strain in vivo (or supported only weak growth). A collection of ACPs from diverse bacteria and from three eukaryotic organelles was also tested. All of the bacterial ACPs tested restored growth to the E. coli acpP mutant strain except those from two related bacteria, Enterococcus faecalis and Lactococcus lactis. Only one of the three eukaryotic organellar ACPs allowed growth. Strikingly the ACP is that of the apicoplast of Plasmodium falciparum (the protozoan that causes malaria). The fact that an ACP from a such diverse organism can replace AcpP function in E. coli suggests that some of the protein-protein interactions detected for AcpP may be not be essential for growth of E. coli.
Obligatory Role for Cooperative Signaling by Pre-TCR and Notch during Thymocyte Differentiation (2004)

The first checkpoint during T cell development, known as beta selection, requires the successful rearrangement of the TCR-beta gene locus. Notch signaling has been implicated in various stages during T lymphopoiesis. However, it is unclear whether Notch receptor-ligand interactions are necessary during beta selection. Here, we show that pre-TCR signaling concurrent with Notch receptor and Delta-like-1 ligand interactions are required for the survival, proliferation, and differentiation of mouse CD4(-)CD8(-) thymocytes to the CD4(+)CD8(+) stage. Furthermore, we address the minimal signaling requirements underlying beta selection and show a hierarchical positioning of key proximal signaling molecules. Collectively, our results demonstrate an essential role for Notch receptor-ligand interactions in enabling the autonomous signaling capacity of the pre-TCR complex.
Structure and expression of the human cardiac troponin I gene. (1995)

Available from British Library Document Supply Centre- DSC:DXN002564 / BLDSC - British Library Document Supply Centre
Functional role of CCCTC binding factor in insulin‐stimulated cell proliferation (2007)

Our results indicate that CTCF is indeed a protein with multifunctional activity that plays a significant role in modulating signalling pathways to mediate insulin-induced ML-1 cell proliferation.
Forward body-bias MOS (FBMOS) dual rail logic usingan adiabaticcharging technique with sub –0.6 V operation (1997)

A novel logic family for low-voltage adiabatic logic, called forward body-bias MOS (FBMOS) dual rail logic, has been proposed. This technique uses forward body-bias effects to enable non-floating output levels during the entire data valid time without increased transistor count.
Alzheimer's beta‐amyloid precursor protein is expressed on the surface of immediately ex vivo brain cells: A flow cytometric study (1996)

Beta-amyloid precursor protein (βAPP) is ubiquitously expressed, but deposition of the βAPP proteolytic fragment Aβ is virtually restricted to the brain, suggesting cell-specific processing of this molecule. Our laboratory has investigated expression of βAPP in mechanically dissociated, unfixed, immediately ex vivo cells from various mouse and rat organs by flow cytometry. Epitopes of predicted extracellular domains of βAPP recognized by the N-terminal 22C11 monoclonal antibody (mAb) and the juxtamembrane 4G8 mAb were not detectable on the surface of lymphoid cells, hepatocytes, or kidney cells. In contrast, surface 22C11 and 4G8 βAPP immunoreactivity was abundant on intact (propidium iodide-excluding) dissociated brain cells. The predicted C-terminal intracellular βAPP determinant recognized by the mAb Jonas was not detectable on the surface of intact brain cells, but was present in ethanol-permeabilized cells, consistent with a transmembrane configuration of βAPP in brain cells. Trypsinization of intact brain cells abolished cell surface immunoreactivity for 22C11, which was then reestablished by short-term culture. Augmentation of 22C11 and 4G8 surface immunoreactivity occurred when brain cells were cultured short-term in phenylarsine oxide, a general endocytosis inhibitor. By double staining protocols of brain cells with mAbs directed against βAPP ecto-domain epitopes and the neuronal surface proteins Thy-1 or neural cell adhesion molecule (NCAM), we observed that all Thy-1+ and NCAM+ cells (∼50%) were immunoreactive for surface βAPP, but that some βAPP+ cells (∼20%) were negative for these neuronal markers. Our data suggest that neurons and a subpopulation of other brain cells, unlike peripheral cells, can support βAPP as a type I intrinsic membrane molecule with an intact ectodomain, and that βAPP surface abundance is regulated by an equilibrium between membrane vesicle insertion and endocytotic internalization. Transmembrane βAPP holoprotein may be a critical determinant of brain-predominant processing of βAPP to Aβ, and may participate in a receptor/transducer function unique to brain cells. © 1996 Wiley-Liss, Inc.
Immunotoxins for leukemia (2014)

Unconjugated monoclonal antibodies that target hematopoietic differentiation antigens have been developed to treat hematologic malignancies. Although some of these have activity against chronic lymphocytic leukemia and hairy cell leukemia, in general, monoclonal antibodies have limited efficacy as single agents in the treatment of leukemia. To increase their potency, the binding domains of monoclonal antibodies can be attached to protein toxins. Such compounds, termed immunotoxins, are delivered to the interior of leukemia cells based on antibody specificity for cell surface target antigens. Recombinant immunotoxins have been shown to be highly cytotoxic to leukemic blasts in vitro, in xenograft model systems, and in early-phase clinical trials in humans. These agents will likely play an increasing role in the treatment of leukemia.
A unified model for multi-objective evolutionary algorithms with elitism (2002)

Though it has been claimed that elitism could improve evolutionary multi-objective search significantly, a thorough and extensive evaluation of its effects is still missing. Guidelines on how elitism could successfully be incorporated have not yet been developed. This paper presents a unified model of multi-objective evolutionary algorithms, in which arbitrary variation and selection operators can be combined as building blocks, including archiving and re-insertion strategies. The presented model enables most specific multi-objective (evolutionary) algorithm to be formulated as an instance of it, which will be demonstrated by simple examples. We further show how elitism can be quantified by the model's parameters and how this allows an easy evaluation of the effect of elitism on different algorithms.
A nested electrostatically-actuated microvalve for an integrated microflow controller (2002)

Many semiconductor processes such as molecular beam epitaxy, low-pressure chemical vapor deposition, and reactive ion etching require precise control of ultraclean gas flows at very low flow rates. These applications are well suited to small electrostatically-actuated microvalves that can be merged with micromachined flow channels to form an integrated microflow controller (/spl mu/FC). This paper presents such a microvalve structure and its integration into a simple prototype /spl mu/FC. Produced using a nested bulk dissolved-wafer process, the microvalves utilize a three-electrode configuration which allows them to be actively pulled into both the on- and off-states. The valves actuate at 45-60 V, depending on dimensions. The /spl mu/FC reported here was designed for a maximum flow rate of ISCCM and a leak rate of less then O.1 SCCM at a differential pressure of 100 Torr and outlet pressures from vacuum to atmospheric. The paper illustrates the design process used to optimize the structure to prevent stiction and ensure operation with the desired performance.
Validation of an Immunoassay for Soluble Klotho Protein (2012)

The Klotho gene has been identified as an aging suppressor gene that encodes a transmembrane protein, which is expressed primarily in renal tubules. There are 2 forms of Klotho, membrane and secreted. However, there is a paucity of data on levels of soluble Klotho in diseases like diabetes and kidney disease. We validated an enzyme-linked immunosorbent assay for Klotho and quantitated Klotho levels separately in patients with diabetes and also in patients with chronic kidney disease (CKD). The Klotho assay showed good precision and was linear down to 19 ng/mL. There were no significant effects on Klotho levels with the addition of common interferents such as ascorbate, triglycerides, or hemolysis; only bilirubin (250 mg/L) significantly reduced Klotho levels (P < .05). There was a significant reduction in Klotho levels in samples with glycated hemoglobin (HbA(1c)) levels of 6.5% or more compared with control samples (HbA(1c) < 6.5%; P < .001). We also documented significantly higher levels of Klotho with CKD. Thus, we validated an assay for Klotho and made the novel observation that levels are decreased in diabetes and increased in CKD.
Genetic Changes in Ovarian Cancer (1995)

The development of cancer is a multistep process involving accumulation of genetic changes which progressively transform normal cells to neoplastic cells. During the last few years, our understanding and knowledge of the genetic changes involved in ovarian carcinogenesis have increased dramatically. In this review I will focus on karyotypic abnormalities in ovarian cancer and will also refer to molecular studies involving alterations in oncogenes and tumour suppressor genes in ovarian tumorigenesis. Cytogenetic analyses have identified two distinct subgroups. Simple karyotypic changes, trisomy 12 being the most common aberration in this group, are recurrently found in well differentiated ovarian carcinomas. Complex karyotypic abnormalities, including predominantly chromosome losses, deletions and unbalanced translocations, are found in moderately and poorly differentiated carcinomas. The bands and regions most commonly involved in structural rearrangements have been, in decreasing order of frequency, 19p13, 1p36, 1q21, 1q23-25, 3p11-13, 6q21, 19q13, 11p13-15, 11q13, 11q23, 12q24, 12p11-13, and 7p13-22. The finding of identical karyotypic and other genetic changes in tumour samples taken from different sites, such as tumours from both ovaries and omental metastases, indicate that ovarian cancer is of unicentric origin with subsequent metastatic spread giving rise to multiple implants. Molecular genetic changes important in ovarian cancer involve both classes of tumor-associated genes: RAS activation is generally not observed in ovarian cancer. Alterations of MYC1, ERBB2, AKT2, TP53 has been described in some ovarian carcinomas. The temporal relationship of these mutations, i.e. early or late events in ovarian carcinogenesis, remains to be determined.
Surface Modification for Enhancing Antibody Binding on Polymer-Based Microfluidic Device for Enzyme-Linked Immunosorbent Assay (2006)

A novel surface treatment method using poly(ethyleneimine) (PEI), an amine-bearing polymer, was developed to enhance antibody binding on the poly(methyl methacrylate) (PMMA) microfluidic immunoassay device. By treating the PMMA surface of the microchannel on the microfluidic device with PEI, 10 times more active antibodies can be bound to the microchannel surface as compared to those without treatment or treated with the small amine-bearing molecule, hexamethylenediamine (HMD). Consequently, PEI surface modification greatly improved the immunoassay performance of the microfluidic device, making it more sensitive and reliable in the detection of IgG. The improvement can be attributed to the spacer effect as well as the functional amine groups provided by the polymeric PEI molecules. Due to the smaller dimensions (140x125 microm) of the microchannel, the time required for antibody diffusion and adsorption onto the microchannel surface was reduced to only several minutes, which was 10 times faster than the similar process carried out in 96-well plates. The microchip also had a wider detection dynamic range, from 5 to 1000 ng/mL, as compared to that of the microtiter plate (from 2 to 100 ng/mL). With the PEI surface modification, PMMA-based microchips can be effectively used for enzyme linked immunosorbent assays (ELISA) with a similar detection limit, but much less reagent consumption and shorter assay time as compared to the conventional 96-well plate.
Image Analysis, Sediments and Paleoenvironments (2005)

1. An Introduction To Image Analysis, Sediments And Paleoenvironments Pierre Francus, Raymond S. Bradley and Jurgen W. Thurow 2. Image Acquisition Scott F. Lamoureux and Jorg Bollmann 3. Image Calibration, Filtering And Processing Alexandra J. Nederbragt, Pierre Francus, Jorg Bollmann and Michael J. Soreghan 4. Image Measurements Eric Pirard 5. Testing For Sources Of Errors In Quantitative Image Analysis Pierre Francus and Eric Pirard 6. Digital Sediment Colour Analysis As A Method To Obtain High Resolution Climate Proxy Records Alexandra J. Nederbragt and Jurgen W. Thurow 7. Toward A Non-Linear Grayscale Calibration Method For Legacy Photographic Collections Joseph D. Ortiz and Suzanne O'Connell 8. From Depth Scale To Time Scale: Transforming Sediment Image Color Data Into A High-Resolution Time Series Andreas Prokoph and R. Timothy Patterson 9. X-Ray Radiographs Of Sediment Cores: A Guide To Analyzing Diamicton Sarah M. Principato 10. Application Of X-Ray Radiography And Densitometry In Varve Analysis Antti E. K. Ojala 11. Processing Backscattered Electron Digital Images Of Thin Sections Michael J. Soreghan and Pierre Francus 12. Automated Particle Analysis: Calcareous Microfossils Jorg Bollmann, Patrick S. Quinn, Miguel Vela, Bernhard Brabec, Siegfried Brechner, Mara Y. Cortes, Heinz Hilbrecht, Daniela N. Schmidt, Ralpf Schiebel and Hans R. Thierstein 13. Software Aspects Of Automated Recognition Of Particles: The Example Of Pollen Ian France, A.W.G. Duller and G.A.T. Duller 14. Multiresolution Analysis Of Shell Growth Increments To Detect Natural Cycles Eric P. Verrecchia
A Role for CD40-CD40 Ligand Interactions in the Generation of Type 1 Cytokine Responses in Human Leprosy (2000)

The interaction of CD40 ligand (CD40L) expressed by activated T cells with CD40 on macrophages has been shown to be a potent stimulus for the production of IL-12, an obligate signal for generation of Th1 cytokine responses. The expression and interaction of CD40 and CD40L were investigated in human infectious disease using leprosy as a model. CD40 and CD40L mRNA and surface protein expression were predominant in skin lesions of resistant tuberculoid patients compared with the highly susceptible lepromatous group. IL-12 release from PBMC of tuberculoid patients stimulated with Mycobacterium leprae was partially inhibited by mAbs to CD40 or CD40L, correlating with Ag-induced up-regulation of CD40L on T cells. Cognate recognition of M. leprae Ag by a T cell clone derived from a tuberculoid lesion in the context of monocyte APC resulted in CD40L-CD40-dependent production of IL-12. In contrast, M. leprae-induced IL-12 production by PBMC from lepromatous patients was not dependent on CD40L-CD40 ligation, nor was CD40L up-regulated by M. leprae. Furthermore, IL-10, a cytokine predominant in lepromatous lesions, blocked the IFN-gamma up-regulation of CD40 on monocytes. These data suggest that T cell activation in situ by M. leprae in tuberculoid leprosy leads to local up-regulation of CD40L, which stimulates CD40-dependent induction of IL-12 in monocytes. The CD40-CD40L interaction, which is not evident in lepromatous leprosy, probably participates in the cell-mediated immune response to microbial pathogens.
Stem cell homing (2006)

Several components of the essential process of stem cell homing have now been characterized. Cell adhesion molecules and their ligands, extracellular matrix components, chemokines, and specialized bone marrow niches all participate in the precise regulation of this process.
Rapid Shape-Based Ligand Alignment and Virtual Screening Method Based on Atom/Feature-Pair Similarities and Volume Overlap Scoring (2011)

Shape-based methods for aligning and scoring ligands have proven to be valuable in the field of computer-aided drug design. Here, we describe a new shape-based flexible ligand superposition and virtual screening method, Phase Shape, which is shown to rapidly produce accurate 3D ligand alignments and efficiently enrich actives in virtual screening. We describe the methodology, which is based on the principle of atom distribution triplets to rapidly define trial alignments, followed by refinement of top alignments to maximize the volume overlap. The method can be run in a shape-only mode or it can include atom types or pharmacophore feature encoding, the latter consistently producing the best results for database screening. We apply Phase Shape to flexibly align molecules that bind to the same target and show that the method consistently produces correct alignments when compared with crystal structures. We then illustrate the effectiveness of the method for identifying active compounds in virtual screening of eleven diverse targets. Multiple parameters are explored, including atom typing, query structure conformation, and the database conformer generation protocol. We show that Phase Shape performs well in database screening calculations when compared with other shape-based methods using a common set of actives and decoys from the literature.
Signaling to p53: breaking the posttranslational modification code. (2000)

In unstressed cells, the tumor suppressor protein p53, a tetrameric transcription factor, is present in a latent state and is maintained at low levels through targeted degradation. A variety of cellular stresses including DNA damage, hypoxia, nucleotide depletion, viral infection, and cytokine-activated signaling pathways that transiently stabilize the p53 protein, cause it to accumulate in the nucleus, and activate it as a transcription factor. Activation leads either to growth arrest at the G1/S or G2/M transitions of the cell cycle or to apoptosis. The molecular mechanisms by which stabilization and activation occur are incompletely understood, but accumulating evidence points to roles for multiple posttranslational modifications in mediating these events through several potentially interacting but distinct pathways. Both the approximately 100 amino acid N-terminal and approximately 90 amino acid C-terminal domains are highly modified by phosphorylation and acetylation, whereas modifications to the central sequence-specific DNA binding domain have not been reported. Seven serines and one threonine in the first 46 residues of the transactivation domain and four to five serines in the carboxyl-terminal domain are now known to be phosphorylated, and Lys320 and Lys382 in the carboxyl-terminal domain (human p53) can be acetylated. Antibodies that recognize p53 only when it has been modified at specific sites have been developed by several laboratories, and studies with these have shown that most of the known posttranslational modifications are induced when cells are exposed to DNA-damaging agents. Exceptions are Ser378, which is reported to be constitutively phosphorylated, and Ser376, which is dephosphorylated in response to DNA damage. These recent results, coupled with biochemical and genetic studies, suggest that several amino-terminal phosphorylations can be important in stabilizing p53 in response to DNA damage and in directing acetylation at C-terminal sites. DNA damage-induced modifications to the C-terminus inhibit the ability of this domain to negatively regulate sequence-specific DNA binding either by inducing a conformational change in the protein or by inhibiting non-sequence-specific DNA binding by the C-terminus. C-terminal modifications also modulate the oligomerization state of p53, and may modulate nuclear import/export. Modifications in response to DNA damage to other components that interact with p53 may also be important. In most cases, clear roles for specific modifications, interactions among individual modifications, and the enzymes responsible for each modification remain to be defined. Nevertheless, the field appears poised for major advances in the understanding of the molecular mechanisms that regulate p53 function.
Identification of a human homologue of the murine tumor rejection antigen GP96. (1989)

A family of cell surface glycoproteins with a molecular weight of 96,000 (gp96) has recently been implicated in the individually distinct immunogenicity of chemically induced sarcomas of inbred mice. Rabbit antiserum to murine gp96 detects an antigenically related Mr 96,000 cell surface glycoprotein on two cultured human melanoma cell lines, SK-MEL-13 and SK-MEL-177. Molecular probes for 5' and 3' ends of the murine gp96 gene detect a 3.5-kilobase transcript in RNA preparations from melanoma cells, similar to the murine gp96 transcript. While 5' probes do not hybridize to Southern blots of genomic human DNA, the 3' probes identify several distinct bands under stringent hybridization and washing conditions. This suggests that the 3' end of the gp96 gene is more conserved than its 5' end. No gross alterations in gp96 gene organization were detected in melanoma cells. B-lymphoblastoid cell lines derived from four different individuals also showed no restriction fragment polymorphism in the gp96 gene.