gebhart/patrepeval huggingface dataset:
Spectrum of Bmp5 Mutations From Germline Mutagenesis Experiments in Mice (1997)

Over 40 years of mutagenesis experiments using the mouse specific-locus test have produced a large number of induced germline mutations at seven loci, among them the short ear locus. We have previously shown that the short ear locus encodes bone morphogenetic protein 5 (BMP5), a member of a large family of secreted signaling molecules that play key roles in axis formation, tissue differentiation, mesenchymalepithelial interactions, and skeletal development. Here we examine 24 chemical- and radiation-induced mutations at the short ear locus. Sequence changes in the Bmp5 open reading frame confirm the importance of cysteine residues in the function of TGF beta superfamily members. The spectrum of N-ethyl-N-nitrosourea-induced mutations also provides new information about the basepair, sequence context, and strand specificity of germline mutations in mammals.
Optical halide sensing using fluorescence quenching: theory, simulations and applications - a review (2001)

In the last century the production and application of halides assumed an ever greater importance. In the fields of medicine, dentistry, plastics, pesticides, food, photography etc many new halogen containing compounds have come into everyday use. In an analogous manner many techniques for the detection and determination of halogen compounds and ions have been developed with scientific journals reporting ever more sensitive methods.
In Vitro Evaluation of Functional Interaction of Integrin αvβ3 and Matrix Metalloprotease-2 (2009)

Integrin alphavbeta3 and matrix metalloprotease-2 (MMP-2) are two established molecular targets of angiogenesis. Basic understanding of various forms of functional interaction of integrin alphavbeta3 and active MMP-2 may be used to develop therapeutic approaches. Based upon the idea that integrins are present on the surface of invasive cells and MMP-2 may be localized to this and other cell-surface receptors, we investigated the hypothesis that integrin binding will alter cleavage of MMP-2 substrates. To investigate this hypothesis, integrin-binding and MMP-2 cleavable motifs were combined in a single peptide, MMP-RGD, designed with fluorescent probes for monitoring peptide cleavage. MMP-RGD was bound to integrin alphavbeta3 with equal affinity compared to the integrin-binding motif and was cleaved with equal specificity by active MMP-2. MMP-RGD bound to human umbilical vein endothelial cells (HUVECs). MMP-2 from HUVECs cleaved MMP-RGD, but the cleavage was not altered due to integrin binding. Our results indicate that integrin alphavbeta3 and active MMP-2 may not be as functionally collaborative for substrate cleavage as expected based on the current knowledge of their cell surface colocalization.
Overexpression of human aspartyl(asparaginyl)beta-hydroxylase in hepatocellular carcinoma and cholangiocarcinoma. (1996)

To characterize genes that become upregulated with malignant transformation of human hepatocytes, a library of monoclonal antibodies was produced against the FOCUS hepatocellular carcinoma cell line. Antibody FB-50 reacted with an antigen that was highly expressed in 4 of 10 primary hepatocellular carcinomas, in all 20 cholangiocarcinomas we studied, and in a variety of transformed cell lines. This antigen was also highly expressed in neoplastic epithelial cells of breast and colon carcinomas in contrast to its low level of expression in normal hepatocytes and in non-neoplastic epithelial cells. Among the normal adult tissues studied, high levels were observed only in proliferating trophoblastic cells of the placenta and in adrenal glands. A 636-bp partial cDNA, isolated from a gamma GT11 expression library generated with HepG2 human hepatoblastoma cells, and a complete cDNA, generated by reverse transcriptase-PCR, identified the antigen as the human form of aspartyl(asparaginyl)beta-hydroxylase. This enzyme catalyzes posttranslational hydroxylation of beta carbons of specific aspartyl and asparaginyl residues in EGF-like domains of certain proteins. Analyses of extracts prepared from several human tumor cell lines compared to their normal tissue counterparts indicate that the increase in hydroxylase, approximately 10-fold, is controlled at the level of transcription and the protein is expressed in an enzymatically active form. In similar analyses, comparing hepatocellular carcinomas to adjacent uninvolved liver from five patients, enzymatic activity was much higher in the tumor tissue from the four patients whose immunoblots revealed increased hydroxylase protein in the malignant tissue. EGF repeats in the extracellular domain of Notch or its homologs contain the consensus sequence for hydroxylation. Deletion mutants lacking this domain are gain-of-function mutants, suggesting that the domain modulates signal transduction by the cytoplasmic domain. While the function imparted by beta hydroxylation is unknown, our studies raise the possibility that beta hydroxylation is regulated in proteins like the mammalian Notch homologs, whose cytoplasmic domains have been shown to be oncogenic.
Bit-serial pipeline synthesis for multi-FPGA systems with C++ design capture (1996)

Developing applications for a large-scale configurable system composed of state-of-the-art FPGA technology is a grand challenge. FPGAs are inherently resource limited devices in terms of logic, routing, and IO. Without a careful circuit implementation strategy, one would waste a large portion of the potential capacity of the configurable hardware. Also, high-level design entry support is essential for such large-scale hardware. A C++ design tool has been implemented which maps the computational algorithms onto bit-serial pipeline networks which exhibit high performance and maximize the device utilization of each FPGA. With this tool, the designer is able to develop applications in a very short time, and also is able to try out different algorithm implementations easily to see the trade-offs in terms of performance and hardware size instantaneously. Based on this C++ design tool, a number of DSP applications such as 1D and 2D filters, adaptive filters, Inverse Discrete Cosine Transform, and digital neural networks were designed.
On the use of windows for harmonic analysis with the discrete Fourier transform (1978)

This paper makes available a concise review of data windows and their affect on the detection of harmonic signals in the presence of broad-band noise, and in the presence of nearby strong harmonic interference. We also call attention to a number of common errors in the application of windows when used with the fast Fourier transform. This paper includes a comprehensive catalog of data windows along with their significant performance parameters from which the different windows can be compared. Finally, an example demonstrates the use and value of windows to resolve closely spaced harmonic signals characterized by large differences in amplitude.
RegulonDB (version 6.0): gene regulation model of Escherichia coli K-12 beyond transcription, active (experimental) annotated promoters and Textpresso navigation (2007)

RegulonDB (http://regulondb.ccg.unam.mx/) is the primary reference database offering curated knowledge of the transcriptional regulatory network of Escherichia coli K12, currently the best-known electronically encoded database of the genetic regulatory network of any free-living organism. This paper summarizes the improvements, new biology and new features available in version 6.0. Curation of original literature is, from now on, up to date for every new release. All the objects are supported by their corresponding evidences, now classified as strong or weak. Transcription factors are classified by origin of their effectors and by gene ontology class. We have now computational predictions for sigma(54) and five different promoter types of the sigma(70) family, as well as their corresponding -10 and -35 boxes. In addition to those curated from the literature, we added about 300 experimentally mapped promoters coming from our own high-throughput mapping efforts. RegulonDB v.6.0 now expands beyond transcription initiation, including RNA regulatory elements, specifically riboswitches, attenuators and small RNAs, with their known associated targets. The data can be accessed through overviews of correlations about gene regulation. RegulonDB associated original literature, together with more than 4000 curation notes, can now be searched with the Textpresso text mining engine.
Molecular cloning of partial cDNA copies of two distinct mouse IFN-β mRNAs (1982)

Two cDNA libraries were constructed, using respectively the 12S and the 16S sucrose gradient fractions of polysomal poly (A)+ RNA from mouse C243 cells induced with Newcastle disease virus. Screening of a part of both libraries by mRNA selection hybridization assays revealed the presence of two plasmids hybridizing to an mRNA, whose translation product was characterized as mouse IFN-beta. Blot analysis of RNA indicated that mRNA hybridizing to the DNA from both plasmids could be detected in induced but not in uninduced C243 cells. The two cDNA inserts did not cross hybridize and had distinct restriction maps. Sequencing revealed that both inserts represented the end of the coding region and the entire 3' non coding region of two district mRNAs. Although different, the putative 39 AA and 65 AA carboxy termini of both Mu IFN-beta s display some homology to human IFN-beta 1. Thus there are at least two different murine IFN-beta genes.
Humoral immune responses of Solomon Islanders to the merozoite surface antigen 2 of Plasmodium falciparum show pronounced skewing towards antibodies of the immunoglobulin G3 subclass (1997)

The immunoglobulin G (IgG) subclass distribution of antibodies to merozoite surface antigen 2 of Plasmodium falciparum in Solomon Islanders showed marked skewing towards the IgG3 subclass. This was not observed with crude P. falciparum schizont antigen. IgG3 responses may be short-lived and require repeated restimulation for their maintenance. This may be provided by persistent infection (premunition) or new infections.
CCAAT/Enhancer-Binding Protein Homologous (CHOP) Protein Promotes Carcinogenesis in the DEN-Induced Hepatocellular Carcinoma Model (2013)

Background and Aims: C/EBP homologous protein (CHOP) plays pro-apoptotic roles in the integrated stress response. Recently, a tumor suppressive role for CHOP was demonstrated in lung cancer via regulation of tumor metabolism. To explore the role of CHOP in hepatocarcinogenesis, we induced hepatocellular carcinoma (HCC) in wild type (wt) and CHOP knockout (KO) mice using the carcinogen N-diethylnitrosamine (DEN).
Chemical stability of insulin. 3. Influence of excipients, formulation, and pH. (1992)

The influence of auxiliary substances and pH on the chemical transformations of insulin in pharmaceutical formulation, including various hydrolytic and intermolecular cross-linking reactions, was studied. Bacteriostatic agents had a profound stabilizing effect--phenol > m-cresol > methylparaben--on deamidation as well as on insulin intermolecular cross-linking reactions. Of the isotonicity substances, NaCl generally had a stabilizing effect whereas glycerol and glucose led to increased chemical deterioration. Phenol and sodium chloride exerted their stabilizing effect through independent mechanisms. Zinc ions, in concentrations that promote association of insulin into hexamers, increase the stability, whereas higher zinc content had no further influence. Protamine gave rise to additional formation of covalent protamine-insulin products which increased with increasing protamine concentration. The impact of excipients on the chemical processes seems to be dictated mainly via an influence on the three-dimensional insulin structure. The effect of the physical state of the insulin on the chemical stability was also complex, suggesting an intricate dependence of intermolecular proximity of involved functional groups. At pH values below five and above eight, insulin degrades relatively fast. At acid pH, deamidation at residue A21 and covalent insulin dimerization dominates, whereas disulfide reactions leading to covalent polymerization and formation of A- and B-chains prevailed in alkaline medium. Structure-reactivity relationship is proposed to be a main determinant for the chemical transformation of insulin.
The molecular biology of Oct-4 in the early mouse embryo (1998)

Preimplantation development in the mouse is characterized by the occurrence of several critical genetic and epigenetic events. Until recently, very little was known about the regulation of these events. The search for genes which are involved in the control of the earliest stages of mouse development has so far resulted in only a few candidates. Oct-4, a member of the POU transcription factor family, is encoded by a gene belonging to this group. Initially present as a maternal factor in the oocyte, Oct-4 is expressed by the embryo throughout the preimplantation period, as well as in germ cell precursors of adult mice. Oct-4 expression is correlated with an undifferentiated phenotype, both in the embryo and in cell lines derived from it. Regulation of the Oct-4 gene is dependent on the activity of two separate enhancers, one of which is specifically active in pluri- and totipotent cells. Its function as a transcriptional regulator is supported by the identification of an increasing number of potential target genes, including some known to be essential for early embryonic development.
CONTENTION RESOLUTION ALGORITHMS (2000)

Bidirectional Cable TV networks using hybrid fiber coaxial (HFC) systems are good examples of broadcast environments where a contention resolution algorithm is needed in order to allocate the multiaccess medium (in this case the upstream link) among the various nodes. Recent activities of the IEEE 802.14 Working Group aimed at defining the physical and medium access control (MAC) layer protocols for HFC cable networks have focused on the study and evaluation of several contention resolution solutions for inclusion in the MAC protocol specifications. In this article several contention resolution algorithms considered by the IEEE 802.14 group are reviewed. Different implementations for several well known contention resolution algorithms such as tree-based and p-persistence are presented. Their performance is evaluated in the HFC context with respect to upstream channel allocation, roundtrip delay, various traffic types, and number of stations in the network. Simulation results for configurations and scenarios of interest are also presented.
A gene for non-syndromic autosomal dominant progressive postlingual sensorineural hearing loss maps to chromosome 14q12-13 (1996)

We report a novel locus responsible for postlingual progressive sensorineural hearing loss (designated DFNA9) that maps to chromosome 14q12-13. A large kindred with autosomal dominant transmission of non-syndromic hearing loss was clinically studied. Hearing in affected individuals deteriorated at approximately 20 years of age and progressed to anacusis in the fifth decade. A random genome-wide search using polymorphic short tandem repeats demonstrated linkage with D14S121 (maximum two point LOD score = 6.19, theta = 0). Haplotype analysis of recombination events defined a 9 cM disease interval, between D14S252 and D14S49.
MDA-7/IL-24 plus radiation enhance survival in animals with intracranial primary human GBM tumors (2008)

Melanoma differentiation associated gene-7/interleukin 24 (mda-7/IL-24) is a cytokine displaying selective apoptosis-inducing activity in tumors, including glioblastoma (GBM), without damaging normal cells. The present studies focused on defining whether an adenovirus expressing MDA-7/IL-24, Ad.mda-7, infused into pre-formed invasive primary human GBM tumors growing in athymic mouse brains altered tumor cell growth and animal survival, and whether Ad.mda-7 radiosensitized GBM cells and enhanced the survival benefit of irradiation. Ad.mda-7 directly radiosensitized glioma cells in vitro in a JNK1-3- and caspase 9-dependent fashion and demonstrated bystander-effect killing and radiosensitization of GBM cells when primary human astrocytes were infected with Ad.mda-7. Infusion of Ad.mda-7 into pre-formed glioma tumors caused a rapid decrease in proliferation and blood vessel density and an increase in cell killing. Irradiation of Ad.mda-7 infected tumors enhanced cell death. Cell killing correlated with pro-caspase 3 cleavage, enhanced phosphorylation of JNK1-3 and reduced phosphorylation of ERK1/2. Ad.mda-7 enhanced the survival of animals implanted with GBM6 and GBM12 tumors, and significantly increased the survival benefit of irradiation in animals bearing GBM12 tumors. Ad.mda-7 toxicity was evident against CD133+ and CD133- GBM cells; upon tumor re-growth approximately 70-100 days after virus infusion, the relative CD133+ level within the tumor was profoundly reduced with lower Ki67 reactivity and increased beta-galactosidase staining. Infusion of Ad.mda-7 into an immune competent rat brain did not cause normal tissue toxicity 1-4 weeks after infusion using T1 and T2 weighted MRI and H&E staining. Our data demonstrate that Ad.mda-7 prolongs the survival of animals bearing GBM tumors and does so through multiple mechanisms including direct tumor cell killing and selection for surviving cells that are more differentiated and potentially displaying a putatively senescent phenotype.
Mining Pure, Strict Epistatic Interactions from High-Dimensional Datasets: Ameliorating the Curse of Dimensionality (2012)

We conclude that the bound appears to ameliorate the curse of dimensionality in high-dimensional datasets. This is a very consequential result and could be pivotal in our efforts to reveal the dark matter of genetic disease risk from high-dimensional datasets.
CD147 subunit of lactate/H + symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors (2011)

Malignant tumors exhibit increased dependence on glycolysis, resulting in abundant export of lactic acid, a hypothesized key step in tumorigenesis. Lactic acid is mainly transported by two H(+)/lactate symporters, MCT1/MCT4, that require the ancillary protein CD147/Basigin for their functionality. First, we showed that blocking MCT1/2 in Ras-transformed fibroblasts with AR-C155858 suppressed lactate export, glycolysis, and tumor growth, whereas ectopic expression of MCT4 in these cells conferred resistance to MCT1/2 inhibition and reestablished tumorigenicty. A mutant-derivative, deficient in respiration (res(-)) and exclusively relying on glycolysis for energy, displayed low tumorigenicity. These res(-) cells could develop resistance to MCT1/2 inhibition and became highly tumorigenic by reactivating their endogenous mct4 gene, highlighting that MCT4, the hypoxia-inducible and tumor-associated lactate/H(+) symporter, drives tumorigenicity. Second, in the human colon adenocarcinoma cell line (LS174T), we showed that combined silencing of MCT1/MCT4 via inducible shRNA, or silencing of CD147/Basigin alone, significantly reduced glycolytic flux and tumor growth. However, both silencing approaches, which reduced tumor growth, displayed a low level of CD147/Basigin, a multifunctional protumoral protein. To gain insight into CD147/Basigin function, we designed experiments, via zinc finger nuclease-mediated mct4 and basigin knockouts, to uncouple MCTs from Basigin expression. Inhibition of MCT1 in MCT4-null, Basigin(high) cells suppressed tumor growth. Conversely, in Basigin-null cells, in which MCT activity had been maintained, tumorigenicity was not affected. Collectively, these findings highlight that the major protumoral action of CD147/Basigin is to control the energetics of glycolytic tumors via MCT1/MCT4 activity and that blocking lactic acid export provides an efficient anticancer strategy.
Topologically complex molecules obtained by transition metal templation: it is the presentation that determines the synthesis strategy (2012)

Topological constructions made from closed curves range from simple links to intricate knots and started to capture the chemists' attention in the early sixties. These mathematical objects result from particular embeddings of a single or a set of closed curves in the three-dimensional space that show an infinite variety of presentations. Simple catenanes, higher order interlocked macrocycles, and molecular knots can be synthesized via the metal template approach, just as simple macrocycles. However, this requires that rigid presentations with appropriate geometrical characteristics be identified prior to molecular design, and those selected for the metal-templated synthesis of some of these fascinating molecules are reviewed here.
Aluminium coordination complexes in copolymerization reactions of carbon dioxide and epoxides (2013)

Al complexes are widely used in a range of polymerization reactions (ROP of cyclic esters and cationic polymerization of alkenes). Since the discovery in 1978 that an Al porphyrin complex could copolymerize propylene oxide with carbon dioxide, Al coordination compounds have been studied extensively as catalysts for epoxide-carbon dioxide copolymerizations. The most widely studied catalysts are Al porphyrin and Al salen derivatives. This is partially due to their ability to act as mechanistic models for more reactive, paramagnetic Cr catalysts. However, this in depth mechanistic understanding could be employed to design more active Al catalysts themselves, which would be beneficial given the wide availability of this metal. Polymerization data (% CO3 linkages, M(n), M(w)/M(n) and TON) for these complexes are presented and mechanisms discussed. In most cases, especially those employing square-based pyramidal Al complexes, co-catalysts are required to obtain high levels of carbon dioxide incorporation. However, in some cases, the use of co-catalysts inhibits the copolymerization reaction. Lewis acidic Al phenolate complexes have been used as activators in CHO-carbon dioxide copolymerizations to increase TOF and this has recently led to the development of asymmetric copolymerization reactions. Given the ready availability of Al, the robustness of many complexes (e.g. use in immortal polymerizations) and opportunity to prepare block copolymers and other designer materials, Al complexes for copolymerization of carbon dioxide are surely worth a second look.
A microresonator frequency comb optical clock (2013)

Optical-frequency combs enable measurement precision at the 20th digit, and accuracy entirely commensurate with their reference oscillator. A new direction in experiments is the creation of ultracompact frequency combs by way of nonlinear parametric optics in microresonators. We refer to these as microcombs, and here we report a silicon-chip-based microcomb optical clock that phase-coherently converts an optical-frequency reference to a microwave signal. A low-noise comb spectrum with 25 THz span is generated with a 2 mm diameter silica disk and broadening in nonlinear fiber. This spectrum is stabilized to rubidium frequency references separated by 3.5 THz by controlling two teeth 108 modes apart. The optical clocks output is the electronically countable 33 GHz microcomb line spacing, which features an absolute stability better than the rubidium transitions by the expected factor of 108. Our work demonstrates the comprehensive set of tools needed for interfacing microcombs to state-of-the-art optical clocks.
Design space exploration of instruction schedulers for out-of-order soft processors (2010)

This work explores instruction scheduler designs for single-issue, out-of-order soft processors targeting irregular workloads. It shows the effect of scheduler size, scheduling policy and back-to-back scheduling on performance, area, and frequency. It is shown that for a modern, high-end FPGA (Altera Stratix III) the best performance is achieved by a small, 4-entry instruction scheduler with an age-based instruction selection policy and back-to-back scheduling. A combined scheduler and register renamer is shown to operate at 303 MHz.