gebhart/patrepeval huggingface dataset:
The functional human dihydrofolate reductase gene. (1984)

Molecular cloning, mapping, and DNA sequencing techniques have been used to characterize the functional human dihydrofolate reductase (DHFR) gene. The gene is about 30 kilobases in length. Its coding portions are separated into 6 exons, the intron-exon boundaries of which are identical to those of the previously characterized mouse DHFR gene. The 5 introns vary in length from 362 to 12,000 base pairs. The position of the DHFR gene promoter was identified as being shortly upstream from the initiation codon in an in vitro transcription reaction by polymerase II. A DHFR minigene was constructed in a plasmid expression vector by combining a DNA fragment containing exon 1, intron I, and a small part of exon 2 from the functional gene, with a second DNA fragment containing exons 2-6 from a processed intronless gene, the coding sequences of which are identical to those of the normal locus. Transcription initiation from the DHFR promoter was localized to a position 71 +/- 2 base pairs upstream from the initiation codon, both in monkey kidney cells transfected with vectors containing the DHFR minigene, and in human HeLa cells. This single transcription start and the three previously identified polyadenylation sites account for the 800-, 1,000-, and 3,800-nucleotide DHFR mRNA species found in human cells. On comparison of the mouse and human DHFR genes, sequence homology was shown to be limited to the coding regions and 100 base pairs of the 3' untranslated region up to the first polyadenylation site of both genes. In addition, there is fairly extensive homology in the 5' flanking region, although the quadruply repeated 48-base pair sequence found in the mouse genome is represented only once in human DNA.
Expression of Transforming Growth Factor-alphaand Epidermal Growth Factor in Patientswith Malignant Tumors (2001)

ve: To evaluate the clinical significance of the expression of transforming growth factor-alpha (TGF-α) and epidermal growth factor (EGF) in patients with malignant tumors. Methods: Radiation immunoassay was used to determine the levels of TGF-α and EGF in 206 cases of malignant tumors, and the results were compared with those on healthy people. Results: The serum levels of TGF-a and EGF were sighificantly increased in patients with malignant tumors, compared to those of the control group (P0.01). In the liver cancer group and breast cancer group,the serum levels of TGF-a were higher than that in the other groups (P 0.05). The serum level of EGF was not significant different among different tumor groups. The serum level of TGF-α was significantly higher in metastatic tumor group than that in non-metastatic group, indicating the correlation of tumor stage with the expression of TGF-α. Conclusion: The results suggest that the serum levels of TGF-α and EGF are highly expressed in malignant tumors. TGF-α and EGF could be used as markers of tumor and the malignancy of tumor. TGF-α may also serve as an important indicator of clinical stage of tumor.
Topological routing path search algorithm with incremental routability test (1999)

This paper describes a topological routing path search algorithm embedded in our rubber-band-based autorouter for single-layer printed circuit boards. The algorithm searches for a topological path that is guaranteed to be transformable into a physical wire satisfying design rules. Topological path search algorithms used in existing autorouters verify design rules only locally and approximately. However, it is preferable to satisfy design rules exactly in the global routing phase, especially for routing a densely wired printed circuit board. We propose a method for incrementally verifying design rules during the topological routing path search and describe several improvements to the algorithm that reduce the overhead of the routability test and suppress combinatorial explosion. We also discuss the practical feasibility of the proposed algorithm on the basis of the results of experiments using several printed circuit boards.
The performance of rate-compatible punctured convolutional codes for digital mobile radio (1990)

The unequal error protection capabilities of convolutional codes belonging to the family of rate-compatible punctured convolutional codes (RCPC codes) are studied. The performance of these codes is analyzed and simulated for the first fading Rice and Rayleigh channels with differentially coherent four-phase modulation (4-DPSK). To mitigate the effect of fading, interleavers are designed for these unequal error protection codes, with the interleaving performed over one or two blocks of 256 channel bits. These codes are decoded by means of the Viterbi algorithm using both soft symbol decisions and channel state information. For reference, the performance of these codes on a Gaussian channel with coherent binary phase-shift keying (2-CPSK) is presented. A number of examples are provided to show that it is possible to accommodate widely different error protection levels within short information blocks. Unequal error protection codes for a subband speech coder are studied in detail. A detailed study of the effect of the code and channel parameters such as the encoder memory, the code rate, interleaver depth, fading bandwidth, and the contrasting performance of hard and soft decisions on the received symbols is provided.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Generation and Large-Scale Expansion of Human Inducible Regulatory T Cells That Suppress Graft-Versus-Host Disease (2011)

Adoptive transfer of thymus-derived natural regulatory T cells (nTregs) effectively suppresses disease in murine models of autoimmunity and graft-versus-host disease (GVHD). TGFß induces Foxp3 expression and suppressive function in stimulated murine CD4+25- T cells, and these induced Treg (iTregs), like nTreg, suppress auto- and allo-reactivity in vivo. However, while TGFß induces Foxp3 expression in stimulated human T cells, the expanded cells lack suppressor cell function. Here we show that Rapamycin (Rapa) enhances TGFß-dependent Foxp3 expression and induces a potent suppressor function in naive (CD4+ 25-45RA+) T cells. Rapa/TGFß iTregs are anergic, express CD25 at levels higher than expanded nTregs and few cells secrete IL-2, IFNγ or IL-17 even after PMA and Ionomycin stimulation in vitro. Unlike other published methods of inducing Treg function, Rapa/TGFß induces suppressive function even in the presence of memory CD4+ T cells. A single apheresis unit of blood yields an average ~240 × 10⁹ (range ~ 70-560 × 10⁹) iTregs from CD4+25- T cells in ≤ 2 weeks of culture. Most importantly, Rapa/TGFß iTregs suppress disease in a xenogeneic model of GVHD. This study opens the door for iTreg cellular therapy for human diseases.
Concepts in sperm heterogeneity, sperm selection and sperm competition as biological foundations for laboratory tests of semen quality (2004)

Stringent selection mechanisms, in both internal and external fertilisation systems, reject all but a significant minority of the spermatozoa released at ejaculation. Sperm competition theory provides circumstantial evidence that the selection process involves mechanisms by which the quality of the fertilising spermatozoon is controlled, thereby ensuring that females and their offspring receive high quality genetic material. In this review we examine some of these selection processes to see whether they could be exploited for the improvement of laboratory tests of sperm quality. Such tests are not only required for clinical and agricultural purposes, but are increasingly needed in fields such as reproductive and environmental toxicology where the species requirement is much broader. Despite many years of research, sperm quality assessment methods continue to provide imprecise data about fertility; here we suggest that this may be a consequence of using tests that focus on the spermatozoa that would normally be unable to fertilise under natural conditions. To achieve fertilisation a spermatozoon must be capable of responding appropriately to external signalling stimuli; those involving protein kinase-regulated flagellar function seem especially influential in governing effects ranging from non-Mendelian inheritance in mammals to sperm chemotaxis in sea urchins. Examination of the elicited responses reveals considerable heterogeneity in all species. Here we propose that this level of heterogeneity is meaningful both in terms of understanding how spermatozoa from some individuals possess fertility advantages over spermatozoa from their rivals in sperm competition, and in that the heterogeneity should be exploitable in the development of more accurate laboratory tests.
Assignment of the human protein tyrosine phosphatase, receptor-type, zeta (PTPRZ) gene to chromosome band 7q31.3 (1995)

Human protein tyrosine phosphatase, receptor-type, zeta (PTPRZ; also denoted HPTP zeta or RPTP beta) has a large extracellular region with the N-terminal carbonic anhydrase-like domain and a cytoplasmic region with two tandemly located protein tyrosine phosphatase domains. One of the characteristics of PTPRZ is its preferential expression in the central nervous system. We localized the human PTPRZ gene to chromosome band 7q31.3 by somatic cell hybrid mapping and fluorescence in situ hybridization.
A cyclic tetra-nuclear dinitrosyl iron complex [Fe(NO)2(imidazolate)]4: synthesis, structure and stability (2004)

A novel cyclic tetra-nuclear dinitrosyl iron complex [Fe(NO)2(Im-H)]4 was isolated and characterized by X-ray crystallography, and in donor solvents this fragments into 17 e- monomeric units that give EPR spectra analogous to the g= 2.03 species seen in mammalian biology.
c-Ha-ras down regulates the alpha-fetoprotein gene but not the albumin gene in human hepatoma cells. (1990)

We studied the effects of transfection of the normal c-Ha-ras gene, rasGly-12, and its oncogenic mutant, rasVal-12, on expression of the alpha-fetoprotein (AFP) and albumin genes in a human hepatoma cell line, HuH-7. The mutant and, to a lesser extent, the normal ras gene caused reduction of the AFP mRNA but not the albumin mRNA level in transfected HuH-7 cells. Cotransfection experiments with a rasVal-12 expression plasmid and a chloramphenicol acetyltransferase reporter gene fused to AFP regulatory sequences showed that rasVal-12 suppressed the activity of enhancer and promoter regions containing A + T-rich sequences (AT motif). In contrast, rasVal-12 did not affect the promoter activity of the albumin and human hepatitis B virus pre-S1 genes even though these promoters contain homologous A + T-rich elements. ras transfection appeared to induce phosphorylation of nuclear proteins that interact with the AFP AT motif, since gel mobility analysis revealed the formation of slow-moving complexes which was reversed by phosphatase treatment. However, similar changes in complex formation were observed with the albumin and hepatitis B surface antigen pre-S1 promoters. Therefore, this effect alone cannot explain the specific down regulation of the AFP promoter and enhancer activity. ras-mediated suppression of the AFP gene may reflect the process of developmental gene regulation in which AFP gene transcription is controlled by a G-protein-linked signal transduction cascade triggered by external growth stimuli.
Cross Correlation of Intra-day Stock Prices in Comparison to Random Matrix Theory (2011)

We propose and apply a new algorithm of principal component analysis which is suitable for a large sized, highly random time series data, such as a set of stock prices in a stock market. This algorithm utilizes the fact that the major part of the time series is random, and compare the eigenvalue spectrum of cross correlation matrix of a large set of random time series, to the spectrum derived by the random matrix theory (RMT) at the limit of large dimension (the number of independent time series) and long enough length of time series. We test this algorithm on the real tick data of American stocks at different years between 1994 and 2002 and show that the extracted principal components indeed reflects the change of leading stock sectors during this period.
Photoimmobilization of biomolecules within a 3-dimensional hydrogel matrix (2002)

It has been recognized that a three-dimensional cell invasive scaffold that provides both topographical and chemical cues is desirable in regenerative tissue engineering to encourage cell attachment, migration, regrowth and ultimately tissue repair. Carbohydrate hydrogels are attractive for such applications because they are generally biocompatible and able to match the mechanical properties of most soft tissues. Although carbohydrate hydrogels have been previously modified with cell adhesive peptides and proteins, complicated hydrogel matrix activation was required prior to biomolecule coupling and, perhaps more importantly, the overall immobilization yield was low at approximately 1%. In this study, we report the photo-immobilization of a model biomolecule, ovalbumin (OVA), to agarose gel. We describe two methods of modification where the photoactive moiety is coupled to either the protein (i.e. OVA) or the matrix (i.e. agarose) prior to immobilization. We found that the photo-immobilization yield depends on the location of the photoactive moiety. Using photoactive OVA, 1.8% of the OVA initially incorporated into the agarose gel is immobilized; using photoactive agarose, 9.3% of the OVA initially mixed with the agarose is immobilized. The latter is a significant improvement over previous yields and may be useful in attaining our goal of immobilizing a biomolecule gradient for guided tissue regeneration.
Identification by Electron Microscopy of the Maturation Steps in Vaccinia Virus Morphogenesis Inhibited by the Interferon-Induced Enzymes, Protein Kinase (PKR), 2-5A Synthetase, and Nitric Oxide Synthase (iNOS) (2000)

Interferons (IFN) play a major role as a first-line host defense mechanism against viral infections. As treatment of animal cells with IFN induces a large number of genes, it has been difficult to assign the role of these genes in the antiviral action of IFN. Vaccinia virus (VV) is an ideally suited system to study IFN action because all steps in viral morphogenesis can be followed easily by electron microscopy (EM) of ultrathin sections from infected cells. To define the role of IFN-induced genes in viral morphogenesis, we have independently expressed from VV recombinants in primary chicken embryo fibroblast (CEF) cells each of the three IFN-induced genes encoding protein kinase (PKR), 2-5A synthetase, and inducible nitric oxide synthase (iNOS). By EM analysis, we have identified the steps in VV morphogenesis that are affected by each of the IFN-induced enzymes in comparison with untreated and IFN-treated cells. We found that in cells pretreated with IFN and infected with VV, immature virus (IV) is formed, but further stages of maturation are blocked. In cells infected with a VV recombinant expressing PKR (VV-PKR), there is severe inhibition on virus factories, and only few IV are formed. In cells infected with a VV recombinant expressing 2-5A synthetase (VV-2-5A), VV assembly is inhibited at or after IV formation. In cells infected with a VV recombinant expressing iNOS (VV-iNOS), all stages in VV morphogenesis are observed but with aberrant forms. In addition to the effects on viral assembly, in cells infected with either VV-PKR, VV-2-5AS, or VV-iNOS, there is nucleus condensation characteristic of apoptosis. Our findings have identified the steps in VV morphogenesis inhibited by PKR, 2-5A, and iNOS, provided a distinction between these effects, and highlighted a functional redundancy of the IFN system to block viral infection and to induce apoptosis.
The Perth HLB bifurcated endoluminal graft: A review of the experience and intermediate results (1998)

Endoluminal grafting for abdominal aortic aneurysm based upon Dacron-coated Z stents was commenced in March 1993. A modular system for treatment of infrarenal aorto-iliac aneurysmal disease was developed in 1994. The experimental model, method of delivery, graft construction and initial results were reported. Since 1994, 108 bifurcated HLB (Perth) endografts for infrarenal aorto-iliac aneurysmal disease have been implemented. Initial technical success in deployment and exclusion of the aneurysm was achieved in 94 (87%) cases. Secondary endovascular procedures were performed in six cases and were successful in excluding the aneurysm. Ninety patients are alive currently. Twelve have died of co-morbid conditions. Six have died of aneurysmal disease, either from rupture or the result of treatment attempts. Fifteen early endoleaks (within 30 days) have been detected with three persisting. Four have sealed without further intervention, six after the secondary procedure and two patients have died. Conversion to open aneurysmal repair has been performed in five cases: three early and two late. Two of the early group but none of the late intervention group died. No graft infections have been detected to date. With increasing experience criteria for patient selection for endoluminal grafting and the type of graft to be inserted, have been developed. These criteria, lessons learnt and technical points of importance are discussed.
Characterization of the signal for rapid internalization of the bovine mannose 6-phosphate/insulin-like growth factor-II receptor. (1992)

The signal for rapid internalization of the mannose 6-phosphate/insulin-like growth factor II receptor has been localized to the sequence Tyr-Lys-Tyr-Ser-Lys-Val in positions 24-29 of its 163-residue cytoplasmic tail. Most of the activity of this signal is mediated by the carboxyl 4 amino acids, especially Tyr26 and Val29 (Canfield, W. M., Johnson, K. F., Ye, R. D., Gregory, W. and Kornfeld, S. (1991) J. Biol. Chem. 266, 5682-5688). In this study, we have tested the effect of a series of mutations on the internalization rate of a mutant receptor that contains a 29-amino acid cytoplasmic tail terminating with the 4-amino acid internalization sequence Tyr-Ser-Lys-Val. Replacement of Tyr26 with Phe or Trp gave rise to mutant receptors that were internalized at 10% the wild-type rate, while receptors with Ala, Leu, Ile, Val, or Asn at this position were totally inactive. Val29 could be replaced by other large hydrophobic residues (Phe, Leu, Ile, or Met) with no loss of activity, but the presence of Ala, Gly, Arg, Gln, or Tyr in this position inactivated the signal. Ser27 could be effectively replaced by many different amino acids, but not by Pro or Gly. However, Gly27 could be tolerated if the residues at positions 28 and 29 were also changed. A change in the 2-residue spacing between Tyr26 and Val29 destroyed the signal. These data show that the essential elements of this signal are an aromatic residue, especially a Tyr in the first position, separated from a large hydrophobic residue in the last position by 2 amino acids. The residues in positions 2 and 3 of the signal may have a modulating effect on its activity. The Tyr-Ser-Lys-Val signal could be moved to a more proximal region of the cytoplasmic tail with only a modest loss of activity. In addition, the signal could be effectively replaced by the putative 4-residue signals of seven other receptors and membrane proteins known to undergo rapid endocytosis, including the Tyr-Thr-Arg-Phe sequence of the transferrin receptor, a Type II membrane protein. These results are compatible with the 4-residue signals of this type being interchangeable, even among Type I and Type II membrane proteins.
DNA-mediated gene transfer: recombination between cotransferred DNA sequences and recovery of recombinants in a plasmid. (1982)

Ltk- aprt- mouse L cells were transformed to the tk+ phenotype with 10 ng of the herpes simplex virus-1 thymidine kinase (tk) gene and 20 micrograms of pBR322 or simian virus 40 (SV40) DNA. DNAs from five cloned cell lines show restriction endonuclease fragments that hybridize to both tk and pBR322 or SV40 DNA. In all of the cell lines some of these fragments also contain cellular DNA sequences. The use of carrier DNAs with defined sequences has enabled us to demonstrate that the joining of carrier and selectable gene sequences occurs in mouse cells. In one case we have been able to use the ampicillin resistance marker of pBR322 to "rescue" a recombinant plasmid. An analysis of the junction between pBR322 and tk in this plasmid suggests that a small area of homology (16 of 19 base pairs) might be involved in the recombination process.
Carbon–carbon bond cleavage by cytochrome P450BioI(CYP107H1) (2003)

Cytochrome p450(BioI)(CYP107H1) is believed to supply pimelic acid equivalents for biotin biosynthesis in Bacillus subtilis: we report here that the mechanistic pathway adopted by this multifunctional p450 for the in-chain cleavage of fatty acids is via consecutive formation of alcohol and threo-diol intermediates, with the likely absolute configuration of the intermediates also reported.
No compromises (2015)

Transactions with strong consistency and high availability simplify building and reasoning about distributed systems. However, previous implementations performed poorly. This forced system designers to avoid transactions completely, to weaken consistency guarantees, or to provide single-machine transactions that require programmers to partition their data. In this paper, we show that there is no need to compromise in modern data centers. We show that a main memory distributed computing platform called FaRM can provide distributed transactions with strict serializability, high performance, durability, and high availability. FaRM achieves a peak throughput of 140 million TATP transactions per second on 90 machines with a 4.9 TB database, and it recovers from a failure in less than 50 ms. Key to achieving these results was the design of new transaction, replication, and recovery protocols from first principles to leverage commodity networks with RDMA and a new, inexpensive approach to providing non-volatile DRAM.
A Vicious Circle of Alveolar Macrophages and Fibroblasts Perpetuates Pulmonary Fibrosis via CCL18 (2006)

Our findings suggest that AMs from patients with pulmonary fibrosis disclose a phenotype of alternative activation and might be a part of a positive feedback loop with lung fibroblasts perpetuating fibrotic processes.
Four Classes of HERV-K LongTerminal Repeats and TheirRelative Promoter Strengths forTranscription (1997)

The human genome contains abundant copies of HERV-K endogenous retrovirus sequences. These remnants of ancient infection have the potential to reshape the genome by retrotransposition or infection since they are highly expressed in cells of germ line origin. When conserved nucleotide sequence variations in the U3 region of the HERV-K 3' LTR were used to distinguish between individual HERV-K proviruses, 4 major classes of HERV-K LTRs were identified. HERV-K U3 regions from the different classes were compared in an in vitro transcription assay and were found to vary significantly in their promoter activities.
Bicyclic Peptides as Next‐Generation Therapeutics (2017)

Bicyclic peptides have greater conformational rigidity and metabolic stability than linear and monocyclic peptides and are capable of binding to challenging drug targets with antibody-like affinity and specificity. Powerful combinatorial library technologies have recently been developed to rapidly synthesize and screen large bicyclic peptide libraries for ligands against enzymes, receptors, and protein-protein interaction targets. Bicyclic peptides have been developed as potential therapeutics against a wide range of diseases, drug targeting agents, imaging/diagnostic probes, and research tools. In this Minireview, we provide a summary of the recent progresses on the synthesis and applications of bicyclic peptides.