gebhart/patrepeval huggingface dataset:
Urotensin II: a somatostatin-like peptide in the caudal neurosecretory system of fishes. (1980)

Urotensin II, a peptide hormone from the caudal neurosecretory system of the teleost, Gillichthys mirabilis, was isolated by using classical chromatographic techniques and high-performance liquid chromatography (HPLC). Direct microtechniques for sequence determination were used to establish its structure. Urotensin II from Gillichthys is a 1363-dalton dodecapeptide with the amino acid sequence Ala-Gly-Thr-Ala-Asp-Cys-Phe-Trp-Lys-Tyr-Cys-Val. This sequence is homologous with somatostatin in positions 1 and 2 and 7-9. The sequence has been verified by the production of a bioactive synthetic urotensin II. The possible chemical and physiological significance of its homology to somatostatin is discussed.
Scalable link-state Internet routing (2002)

We present and verify the adaptive link-state protocol (ALP), a new link-state routing protocol that does not require the state of each link to be flooded to the entire internetwork, or to entire areas if hierarchical routing is used. A router in ALP disseminates link-state updates incrementally to its neighbors for only those links along paths used to reach destinations. Link-state updates are validated using time stamps and contain the same information used in other link-state protocols. For the case of neighbor routers connected through a broadcast medium, a designated router is distributedly elected for each link state reported over the medium, rather than requiring a designated router to report every topology change over the broadcast medium, like OSPF does. Simulation experiments illustrate that ALP is as efficient as the distributed-Bellman Ford algorithm when distances to destinations do not increase and resources do not fail, and more efficient than traditional link-state protocols based on flooding after distances increase or resources fail. ALP also outperforms the link-vector algorithm (LVA), which is the only prior routing algorithm based on selective dissemination of link states.
Two distinct destabilizing elements in the c-fos message trigger deadenylation as a first step in rapid mRNA decay. (1991)

The mechanisms by which c-fos mRNA is targeted for decay have been examined. Rapid removal of the poly(A) tail occurs before the transcribed portion of the c-fos message is degraded. Identification of the determinants that mediate c-fos message deadenylation reveals that they coincide directly with previously characterized determinants of c-fos mRNA instability, one in the protein-coding region and the other an AU-rich element (ARE) in the 3'-untranslated region. Insertion of either of these c-fos instability elements into the stable beta-globin message confers the property of rapid deadenylation. Mutation of the ARE indicates that this sequence controls two steps in the process of c-fos mRNA degradation: removal of the poly(A) tail, which does not require intact AUUUA pentanucleotides within the ARE, and subsequent degradation of the transcribed portion of the message, which appears to be dependent on the AUUUA pentanucleotides. These results indicate that structurally distinct instability determinants within the transcribed portion of labile messages can function by promoting rapid removal of the poly(A) tail as a first step in the decay process.
Enantiospecific Formal Total Synthesis of the Tumor and GSK-3β Inhibiting Alkaloid, (−)-Agelastatin A (2003)

[reaction: see text] An enantiospecific total synthesis of Weinreb's advanced intermediate 2 for (-)-agelastatin A has been achieved from the Hough-Richardson aziridine 8. Noteworthy reactions in our sequence include the highly regioselective trans-diaxial ring-opening of 8 with azide ion to set up the vicinal diamido functionality present within (-)-2 and the Grubbs-Hoveyda ring-closing metathesis (RCM) reaction that was used to construct its cyclopentene core.
3-(4-Phenoxyphenyl)pyrazoles:  A Novel Class of Sodium Channel Blockers (2004)

A series of 3-(4-phenoxyphenyl)-1H-pyrazoles were synthesized and characterized as potent state-dependent sodium channel blockers. A limited SAR study was carried out to delineate the chemical requirements for potency. The results indicate that the distal phenyl group is critical for activity but will tolerate lipophilic (+pi) electronegative (+sigma) substituents at the ortho and/or para position. Substitution at the pyrazole nitrogen with a H-bond donor improves potency. Compound 18 showed robust activity in the rat Chung neuropathy paradigm.
CVS‐3983, a selective matriptase inhibitor, suppresses the growth of androgen independent prostate tumor xenografts (2004)

These results identify CVS-3983 as a potent inhibitor of AI prostate cancer cell invasion in vitro and established xenograft tumor growth in vivo.
Comparative Assessment of Substrates and Activity Based Probes as Tools for Non-Invasive Optical Imaging of Cysteine Protease Activity (2009)

Recent advances in the field of non-invasive optical imaging have included the development of contrast agents that report on the activity of enzymatic targets associated with disease pathology. In particular, proteases have proven to be ideal targets for development of optical sensors for cancer. Recently developed contrast agents for protease activity include both small peptides and large polymer-based quenched fluorescent substrates as well as fluorescently labeled activity based probes (ABPs). While substrates produce a fluorescent signal as a result of processing by a protease, ABPs are retained at the site of proteolysis due to formation of a permanent covalent bond with the active site catalytic residue. Both methods have potential advantages and disadvantages yet a careful comparison of substrates and ABPs has not been performed. Here we present the results of a direct comparison of commercially available protease substrates with several recently described fluorescent ABPs in a mouse model of cancer. The results demonstrate that fluorescent ABPs show more rapid and selective uptake into tumors as well as overall brighter signals compared to substrate probes. These data suggest that the lack of signal amplification for an ABP is offset by the increased kinetics of tissue uptake and prolonged retention of the probes once bound to a protease target. Furthermore, fluorescent ABPs can be used as imaging reagents with similar or better results as the commercially available protease substrates.
Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in head and neck cancers. (2008)

The expanding and established literature that correlates tumor infiltrating lymphocytes (TILs) with outcomes of patients with solid tumors has contributed greatly to the appreciation of the interaction between the host immune system with neoplastic growth. This analysis has been limited to specific tumors, such as melanoma and ovarian cancer, and our understanding of TILs in relation to many other malignancies has yet to be explored. We review one less well studied malignancy, head and neck squamous cell carcinoma (HNSCC), and the initial attempts to examine the impact of TILs on outcomes of these patients. To provide a context for the discussion of TILs and HNSCC, we first review the epidemiology, relevant head and neck anatomy, immune responses and discuss the historical data regarding the unique immunobiology of these tumors. Finally, with this perspective, we describe our current understanding of tumor infiltrating lymphocyte data for head and neck cancers.
Activation of Type I Interferon Pathway in Systemic Lupus Erythematosus: Association with Distinct Clinical Phenotypes (2011)

Growing evidence over the last few years suggests a central role of type I IFN pathway in the pathogenesis of systemic autoimmune disorders. Data from clinical and genetic studies in patients with systemic lupus erythematosus (SLE) and lupus-prone mouse models, indicates that the type I interferon system may play a pivotal role in the pathogenesis of several lupus and associated clinical features, such as nephritis, neuropsychiatric and cutaneous lupus, premature atherosclerosis as well as lupus-specific autoantibodies particularly against ribonucleoproteins. In the current paper, our aim is to summarize the latest findings supporting the association of type I IFN pathway with specific clinical manifestations in the setting of SLE providing insights on the potential use of type I IFN as a therapeutic target.
A real-time garbage collector based on the lifetimes of objects (1983)

In previous heap storage systems, the cost of creating objects and garbage collection is independent of the lifetime of the object. Since objects with short lifetimes account for a large portion of storage use, it is worth optimizing a garbage collector to reclaim storage for these objects more quickly. The garbage collector should spend proportionately less effort reclaiming objects with longer lifetimes. We present a garbage collection algorithm that (1) makes storage for short-lived objects cheaper than storage for long-lived objects, (2) that operates in real time—object creation and access times are bounded, (3) increases locality of reference, for better virtual memory performance, (4) works well with multiple processors and a large address space.
The role of I-Ag7 beta chain in peptide binding and antigen recognition by T cells (1997)

We examine here how the beta chain of the class II MHC molecule I-Ag7 influences T cell recognition. Three sets of T cell clones were identified. The first set recognizes peptides bound to I-Ag7, I-Ad and I-Ag7 mutant in which the allele-specific residues His and Ser at position 56 and 57 were changed to the Pro at residue 56 and to non-polymorphic Asp at residue 57. The second set responds to the antigen presented only by I-Ag7 and does not recognize the peptides bound to the other class II molecules. The third set is also specific for I-Ag7 as a result of the poor binding of the peptide to I-Ad and the mutant I-Ag7. These results indicate that positions 56 and 57 of the I-Ag7 class II MHC beta chain play a role in both T cell recognition of the MHC-peptide complex and peptide binding to MHC. These two different functions may be involved in I-Ag7-restricted beta cell antigen recognition by diabetogenic T cell clones.
Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (2014)

This EAS Consensus Panel highlights the need for early identification of HoFH patients, prompt referral to specialized centres, and early initiation of appropriate treatment. These recommendations offer guidance for a wide spectrum of clinicians who are often the first to identify patients with suspected HoFH.
Activin/Nodal signalling maintains pluripotency by controlling Nanog expression (2009)

The pluripotent status of embryonic stem cells (ESCs) confers upon them the capacity to differentiate into the three primary germ layers, ectoderm, mesoderm and endoderm, from which all the cells of the adult body are derived. An understanding of the mechanisms controlling pluripotency is thus essential for driving the differentiation of human pluripotent cells into cell types useful for clinical applications. The Activin/Nodal signalling pathway is necessary to maintain pluripotency in human ESCs and in mouse epiblast stem cells (EpiSCs), but the molecular mechanisms by which it achieves this effect remain obscure. Here, we demonstrate that Activin/Nodal signalling controls expression of the key pluripotency factor Nanog in human ESCs and in mouse EpiSCs. Nanog in turn prevents neuroectoderm differentiation induced by FGF signalling and limits the transcriptional activity of the Smad2/3 cascade, blocking progression along the endoderm lineage. This negative-feedback loop imposes stasis in neuroectoderm and mesendoderm differentiation, thereby maintaining the pluripotent status of human ESCs and mouse EpiSCs.
Expressed swine VH genes belong to a small VH gene family homologous to human VHIII. (1994)

The sequences of 34 swine H chain V-regions expressed with either IgG, IgA, or IgM C regions in adult swine and newborn piglets are described and compared. Sixteen of these V-regions were cloned by using a specific leader primer whereas 18 were cloned by anchored PCR. According to the operational criterion of VH family classification, i.e., > 80% DNA sequence similarity, all sequences belong to a homogeneous VH gene family. A total of 31 additional VH-bearing C mu clones obtained by anchored PCR from colostrum-deprived newborn piglets hybridized equally with a probe for C mu and a pan-VH probe. When the consensus sequence of the expressed swine VH genes were compared with those of VH gene for humans (VHI, II, III), mouse (VHI, II, III), rabbit, and chicken, swine VH genes seem to have common ancestry with the human VHIII family, rabbit VH genes, and the single functional VH gene of the chicken. The leader peptides of all clones obtained by anchored PCR showed < 1% variability, and the deduced amino acid sequences from aa4 to aa25 in all 34 clones are identical. Framework (FR)1 and FR2 are conserved whereas FR3 shows greater variability. A total of 23 of 30 JH sequences were identical, suggesting preferential use of one JH. This frequent, putative JH sequence is not similar to any JH gene in humans. Identical genomic Southern hybridization patterns, each with 13 bands of differing intensity and regardless of stringency, were obtained when either a leader or a pan-specific VH probe was used. Analyses of individual genomic bands by single strand conformational polymorphism and sequence analysis suggest that the number of VHIII-related genes in the swine genome is < 20.
On the Challenges of Physical Implementations of RBMs (2014)

Restricted Boltzmann machines (RBMs) are powerful machine learning models, but learning and some kinds of inference in the model require sampling-based approximations, which, in classical digital computers, are implemented using expensive MCMC. Physical computation offers the opportunity to reduce the costof sampling by building physical systems whose natural dynamics correspond to drawing samples from the desired RBM distribution. Such a system avoids the burn-in and mixing cost of a Markov chain. However, hardware implementations of this variety usually entail limitations such as low-precision and limited range of the parameters and restrictions on the size and topology of the RBM. We conduct software simulations to determine how harmful each of these restrictions is. Our simulations are based on the D-Wave Two computer, but the issues we investigate arise in most forms of physical computation.Our findings suggest that designers of new physical computing hardware and algorithms for physical computers should focus their efforts on overcoming the limitations imposed by the topology restrictions of currently existing physical computers.
Transiently lowering tumor necrosis factor-α synthesis ameliorates neuronal cell loss and cognitive impairments induced by minimal traumatic brain injury in mice (2015)

These results implicate that TNF-α in mTBI induced secondary brain damage and indicate that pharmacologically limiting the generation of TNF-α post mTBI may mitigate such damage, defining a time-dependent window of up to 12 h to achieve this reversal.
Determination of the Gram Type Using the Reaction Between Polymyxin B and Lipopolysaccharides of the Outer Cell Wall of Whole Bacteria (1982)

The polymyxin B-dependent formation of protrusions (blebs) of lipopolysaccharides on the cell wall of whole bacteria is suggested as a specific reaction for the determination of the Gram type of newly isolated bacteria. A total of 35 different bacterial species from 27 genera were studied as well as the influence of various test parameters. The reaction was specific: all 13 species of the positive Gram type gave a negative reaction, but all bacteria of the negative Gram type gave a distinct positive reaction.
In vitro Plant Formation from Stem Explants of Rape (Brassica napus cv. Zephyr) (1974)

Abstract Internodal segments from 6‐weeks‐old rape plants ( Brassica napus L. cv. Zephyr) were induced to differentiate in vitro producing shoots or shoots and roots on synthetic nutrient medium under controlled conditions. Benzyladenine (BA) alone (5 × 10 −6 M) induced multiple shoot formation on all stem explants. Roots were induced on shoots when recultured on nutrient medium supplemented with auxins such as naphthalene‐acetic acid (NAA) or indoleacetic acid (1AA) or when planted in vermiculite. Complete plant formation was obtained when NAA (2 × 1 −6 , 5 × 10 −6 and 10 −5 M) was employed in conjunction with BA at 5 × 10 −6 M. At higher concentrations (10 −5 M ) NAA retards the shoot development while 1AA suppresses it totally. Lower levels of auxins along with the cytokinin did not retard or inhibit shoot differentiation.
A back-illuminated megapixel CMOS image sensor (2005)

In this paper, we present the test and characterization results for a back-illuminated megapixel CMOS imager. The imager pixel consists of a standard junction photodiode coupled to a three transistor-per-pixel switched source-follower readout [1]. The imager also consists of integrated timing and control and bias generation circuits, and provides analog output. The analog column-scan circuits were implemented in such a way that the imager could be configured to run in off-chip correlated double-sampling (CDS) mode. The imager was originally designed for normal front-illuminated operation, and was fabricated in a commercially available 0.5 pn triple-metal CMOS-imager compatible process. For backside illumination, the imager was thinned by etching away the substrate was etched away in a post-fabrication processing step.
TNF receptor 1-dependent beta cell toxicity as an effector pathway in autoimmune diabetes. (1999)

Autoimmune diabetes is characterized by a chronic progressive inflammatory autoimmune reaction that ultimately causes the selective elimination of pancreatic beta cells. To address the question of whether the cell death-inducing cytokines TNF and lymphotoxin alpha are involved in this process, we generated nonobese diabetic (NOD) mice that are deficient for TNF receptor 1 (TNFR1 or TNFRp55). Insulitis developed in these mice similarly to that in normal control NOD mice, but progression to diabetes was completely abrogated. Since this was probably due to the complex immunomodulatory effects of TNF and lymphotoxin alpha signaled via TNFR1 on lymphohemopoietic cells, adoptive transfer experiments with spleen cells from diabetic NOD mice were conducted. It was found that the absence of TNFR1 in recipients delayed diabetes induced by normal control and precluded diabetes induced by perforin-deficient spleen cells. In a CD8+ T cell-mediated model of diabetes, however, diabetes induced by adoptive transfer of TCR transgenic lymphocytic choriomeningitis virus glycoprotein-specific CD8+ T cells was not delayed by the absence of TNFR1 in recipient mice. Together with the described expression patterns of perforin and TNF in the mononuclear islet infiltrates of NOD mice, these results indicate that two diabetogenic effector mechanisms are delivered by distinct cell populations: CD8+ T cells lyse beta cells via perforin-dependent cytotoxicity, whereas CD4+ T cells, macrophages, and dendritic cells contribute to diabetes development via TNFR1-dependent beta cell toxicity.
Conditional linkage disequilibrium analysis of a complex disease superlocus, IDDM1 in the HLA region, reveals the presence of independent modifying gene effects influencing the type 1 diabetes risk encoded by the major HLA-DQB1, -DRB1 disease loci (2001)

Type 1 diabetes mellitus is a common disease with a complex mode of inheritance. Its aetiology is underpinned by a major locus, insulin-dependent diabetes mellitus 1 (IDDM1) in the human leukocyte antigen (HLA) region of chromosome 6p21, and an unknown number of loci of lesser individual effect. In linkage analyses IDDM1 is a single peak, but it is evident that the linkage is caused by allelic variation of three adjacent genes in a 75 kb region, namely the class II genes, HLA-DRB1, -DQA1 and -DQB1. However, even these three genes may not explain all of the HLA association. We investigated, in the founder population of Sardinia, whether non-DQ/DR polymorphic markers within a 9.452 Mb region encompassing the whole HLA complex further influence the disease risk, after taking into account linkage disequilibrium with the disease loci HLA-DQB1, -DQA1 and -DRB1. We generalized the conditional association test, the haplotype method, to detect marker associations that are independent of the main DR/DQ disease associations. Three regions were identified as risk modifiers. These associations were not only independent of the polymorphic exon 2 sequences of HLA-DQB1, -DQA1 and -DRB1, but also independent of each other. The individual contributions of these risk modifiers were relatively modest but their combined impact was highly significant. Together, alleles of single nucleotide polymorphisms at the DMB and DOB genes, and the microsatellite locus TNFc, identified approximately 40% of Sardinian DR3 haplotypes as non-predisposing. This conditional analysis approach can be applied to any chromosome region involved in the predisposition to complex traits.
Transforming Thymidine into a Magnetic Resonance Imaging Probe for Monitoring Gene Expression (2013)

Synthetic chemistry has revolutionized the understanding of many biological systems. Small compounds that act as agonists and antagonists of proteins, and occasionally as imaging probes, have contributed tremendously to the elucidation of many biological pathways. Nevertheless, the function of thousands of proteins is still elusive, and designing new imaging probes remains a challenge. Through screening and characterization, we identified a thymidine analogue as a probe for imaging the expression of herpes simplex virus type-1 thymidine kinase (HSV1-TK). To detect the probe, we used chemical exchange saturation transfer magnetic resonance imaging (CEST-MRI), in which a dynamic exchange process between an exchangeable proton and the surrounding water protons is used to amplify the desired contrast. Initially, five pyrimidine-based molecules were recognized as putative imaging agents, since their exchangeable imino protons resonate at 5-6 ppm from the water proton frequency and their detection is therefore less affected by endogenous CEST contrast or confounded by direct water saturation. Increasing the pK(a) value of the imino proton by reduction of its 5,6-double bond results in a significant reduction of the exchange rate (k(ex)) between this proton and the water protons. This reduced k(ex) of the dihydropyrimidine nucleosides fulfills the "slow to intermediate regime" condition for generating high CEST-MRI contrast. Consequently, we identified 5-methyl-5,6-dihydrothymidine as the optimal probe and demonstrated its feasibility for in vivo imaging of HSV1-TK. In light of these findings, this new approach can be generalized for designing specific probes for the in vivo imaging of a variety of proteins and enzymes.