gebhart/patrepeval huggingface dataset:
Force-Free Motion in Asymmetric Structures: A Mechanism without Diffusive Steps (1994)

A particle experiencing alternatively in time at least two potential landscapes macroscopically flat but locally asymmetric can be set into directed macroscopic motion. We show here that if the potentials have the same spatial period but extrema shifted with respect to each other in a suitable way, no diffusive step is involved in the motion generation. This model of "force-free" motion suggests the possibility of new separation techniques and completes existing paradigms for motor protein behaviour.
Clockwork PCR Including Sample Preparation (2008)

For whom the bell tolls: Surface-functionalized superparamagnetic particles emulsified in mineral oil turn a free-standing droplet into a flexible virtual laboratory with (sub)microliter volumes. By using magnetic forces, rare acute monocytic leukaemia cells are extracted from blood, preconcentrated, purified, lysed, and subjected to a real-time PCR in minutes. The PCR works like a clockwork by rotating the droplet over different temperature zones. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2008/z705016_s.html or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Synthesis and Antiviral Activity of Phosphonylmethoxyethyl Derivatives of Purine and Pyrimidine Bases (1989)

Acyclic nucleotide analogues having a common (2-phosphonylmethoxy) ethyl (PME) side chain attached to a purine or pyrimidine base were prepared and selected for in vivo studies based on in vitro antiviral activity against retroviruses and herpesviruses. The adenine derivative PMEA (2) showed good in vitro activity against human immunodeficiency virus (HIV) and Rauscher murine leukemia virus (R-MuLV), and was more potent in vivo than 3'-azido-3'-deoxythymidine (AZT) in the treatment of R-MuLV infection in mice. PMEA also had a significant antiviral effect in vivo against murine cytomegalovirus. The guanine derivative PMEG (10) was exceptionally potent in vitro against herpesviruses. In vivo, PMEG was >50-fold more potent than acyclovir against HSV 1 infection in mice. A number of analogues of PMEG were also prepared, but these derivatives were less potent than PMEG or devoid of antiviral activity.
[A study of trientine therapy in Wilson's disease with neurological symptoms]. (1993)

D-penicillamine, an orally-administered chelating agent, is effective for Wilson's disease (WD). However 25% of WD patients showed serious adverse reactions to D-penicillamine cause this drug to be discontinued after months or years of treatment. For these cases, trientine-2HCl and trientine-4HCl, less toxic agents, are investigated. Three patients with WD, associated with neurological symptoms, were given either trientine-2HCl or trientine-4HCl. These patients had been on therapy with D-penicillamine. Severe adverse reactions had developed during the course of therapy, and D-penicillamine was discontinued, pancytopenia in case 1, nephrotic syndrome in case 2, and myasthenia gravis in case 3. Trientine-2HCl for case 1, and trientine-4HCl for cases 2 and 3 were instituted and continued. The neurological findings in all patients were extremely improved without side effects by trientine therapy. Though the chelating action on copper is weaker than that of D-penicillamine, it is efficient in improvement of the clinical neurological symptoms.
Survey of Stochastic Computing (2013)

Stochastic computing (SC) was proposed in the 1960s as a low-cost alternative to conventional binary computing. It is unique in that it represents and processes information in the form of digitized probabilities. SC employs very low-complexity arithmetic units which was a primary design concern in the past. Despite this advantage and also its inherent error tolerance, SC was seen as impractical because of very long computation times and relatively low accuracy. However, current technology trends tend to increase uncertainty in circuit behavior and imply a need to better understand, and perhaps exploit, probability in computation. This article surveys SC from a modern perspective where the small size, error resilience, and probabilistic features of SC may compete successfully with conventional methodologies in certain applications. First, we survey the literature and review the key concepts of stochastic number representation and circuit structure. We then describe the design of SC-based circuits and evaluate their advantages and disadvantages. Finally, we give examples of the potential applications of SC and discuss some practical problems that are yet to be solved.
A new mast cell degranulating peptide "mastoparan" in the venom of Vespula lewisii. (1979)

The new mast cell degranulating peptide "mastoparan" was isolated from the venom of Vespula lewisii (Vespid wasp) and the peptide was synthesized chemically. Mastoparan is tetradecapeptide amide constituted of the restricted amino acid and the repeated sequence.
Biochemical Characterization of Human Collagenase-3 (1996)

The cDNA of a novel matrix metalloproteinase, collagenase-3 (MMP-13) has been isolated from a breast tumor library (Freije, J. M. P., Dicz-Itza, I., Balbin, M., Sanchez, L. M., Blasco, R., Tolivia, J., and López-Otin, C. (1994) J. Biol. Chem. 269, 16766-16773), and a potential role in tumor progression has been proposed for this enzyme. In order to establish the possible role of collagenase-3 in connective tissue turnover, we have expressed and purified recombinant human procollagenase-3 and characterized the enzyme biochemically. The purified procollagenase-3 was shown to be glycosylated and displayed a M(r) of 60,000, the N-terminal sequence being LPLPSGGD, which is consistent with the cDNA-predicted sequence. The proenzyme was activated by p-aminophenylmercuric acetate or stromelysin, yielding an intermediate form of M(r) 50,000, which displayed the N-terminal sequence L58EVTGK. Further processing resulted in cleavage of the Glu84-Tyr85 peptide bond to the final active enzyme (M(r) 48,000). Trypsin activation of procollagenase-3 also generated a Tyr85 N terminus, but it was evident that the C-terminal domain was rapidly lost, and hence the collagenolytic activity diminished. Analysis of the substrate specificity of collagenase-3 revealed that soluble type II collagen was preferentially hydrolyzed, while the enzyme was 5 or 6 times less efficient at cleaving type I or III collagen. Fibrillar type I collagen was cleaved with comparable efficiency to the fibroblast and neutrophil collagenases (MMP-1 and MMP-8), respectively. Unlike these collagenases, gelatin and the peptide substrates Mea-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 and Mca-Pro-Cha-Gly-Nva-His-Ala-Dpa-NH2 were efficiently hydrolyzed as well, as would be predicted from the similarities between the active site sequence of collagenase-3 (MMP-13) and the gelatinases A and B. Active collagenase-3 was inhibited in a 1:1 stoichiometric fashion by the tissue inhibitors of metalloproteinases, TIMP-1, TIMP-2, and TIMP-3. These results suggest that in vivo collagenase-3 could play a significant role in the turnover of connective tissue matrix constituents.
Targeted inhibition of Stat3 with a decoy oligonucleotide abrogates head and neck cancer cell growth (2003)

The transcription factor signal transducer and activator of transcription 3 (Stat3) is constitutively activated in a variety of cancers including squamous cell carcinoma of the head and neck (SCCHN). Previous investigations have demonstrated that activated Stat3 contributes to a loss of growth control and transformation. To investigate the therapeutic potential of blocking Stat3 in cancer cells, we developed a transcription factor decoy to selectively abrogate activated Stat3. The Stat3 decoy was composed of a 15-mer double-stranded oligonucleotide, which corresponded closely to the Stat3 response element within the c-fos promoter. The Stat3 decoy bound specifically to activated Stat3 and blocked binding of Stat3 to a radiolabeled Stat3 binding element. By contrast, a mutated version of the decoy that differed by only a single base pair did not bind the activated Stat3 protein. Treatment of head and neck cancer cells with the Stat3 decoy inhibited proliferation and Stat3-mediated gene expression, but did not decrease the proliferation of normal oral keratinocytes. Thus, disruption of activated Stat3 by using a transcription factor decoy approach may serve as a novel therapeutic strategy for cancers characterized by constitutive Stat3 activation.
von Willebrand factor and von Willebrand disease [published erratum appears in Blood 1988 Mar;71(3):830] (1987)

Progress has occurred in the past several years in the understanding of the structure and function of von Willebrand factor (vWF). This multimeric glycoprotein exhibits a dual role, that of mediating platelet adhesion and aggregation onto thrombogenic surfaces, and that of functioning as carrier in plasma for the factor VIII procoagulant protein. New insights into the nature of the several functional domains of vWF have led to the identification of the regions of the molecule that interact with factor VIII, heparin, the glycoprotein lb of platelets, and collagen. Alterations of vWF are the cause of von Willebrand disease (vWD), a congenital bleeding disorder. In the majority of patients, the plasma levels of vWF are decreased, but there is no demonstrable structural or functional alteration of the protein. In other patients, however, the structure of vWF is abnormal. This review summarizes the current knowledge on vWF and vWD.
Interaction of Ganglioside with Specific Peptide Sequences as a Mechanism for the Modulation of Calmodulin-Dependent Enzymes (1996)

We examined the interaction between gangliosides and synthetic peptides of calmodulin (CaM)-dependent enzymes to confirm the hypothesis that interaction between gangliosides and the CaM-like site (CLS) of the enzyme is a mechanism for the modulation of the enzyme activity by gangliosides. Gangliosides, GD1b, GT1b, and GD1a, inhibited the activity of CaM-independently activated cAMP-phosphodiesterase and their inhibition was cancelled by a peptide consisting of 17 amino acid residues of a plasma membrane Ca(2+)-pump CLS, suggesting the involvement of the interaction between the peptide and the gangliosides. The peptide of an assumed CLS of phosphodiesterase also cancelled the inhibition. On the other hand, the gangliosides interacted with synthetic CaM-binding site (CBS) peptides of phosphodiesterase, calcineurin, Ca(2+)-pump, and Ca2+/calmodulin-dependent protein kinase II. Moreover, gangliosides GM3 and LM1, that activate but do not inhibit phosphodiesterase, interacted with the CBS peptides, whereas they did not bind to CLS peptides. On the basis of these new findings, we propose a revised model for the ganglioside-mediated modulation of CaM-dependent enzymes, i.e. without CaM, gangliosides bind to CBS and thus stimulate the enzyme activity, acting like CaM. At higher concentrations, they bind to CLS of the enzymes as well and inhibit the activity, acting like the CBS of the enzyme.
Chronic Cough 2 Management of chronic cough (2008)

Cough that remains unexplained after basic clinical assessment is a common reason for referral to secondary care. Much of the evidence about management of isolated chronic cough is derived from case series; this evidence suggests that isolated chronic cough is usually due to asthma, gastro-oesophageal refl ux disease, and upper airway conditions, and that it can be cured in most people by treatment of these conditions. However, there is increasing recognition that satisfactory control of chronic cough is not achieved in a substantial number of patients seen in secondary care. Moreover, there is a concern that perpetuation of the belief that chronic cough is solely due to the eff ects of comorbid conditions is inhibiting research into the pathophysiology of an abnormally heightened cough refl ex, and jeopardising development of improved treatments. We advocate a change in emphasis, which makes a clear distinction between cough due to corticosteroid-responsive eosinophilic airway diseases and corticosteroid-resistant non-eosinophilic cough. We recommend that some factors with weak evidence of an association with cough are best viewed as potential aggravating factors of an intrinsic abnormality of the cough refl ex, rather than the cause. We call for more research into the basic mechanisms and pharmacological control of an abnormally heightened cough refl ex, and recommend ways to assess the eff ects of potentially antitussive treatments.
Tiratricol Neutralizes Bacterial Endotoxins and Reduces Lipopolysaccharide‐Induced TNF‐α Production in the Cell (2008)

The screening of a commercially available library of compounds has proved a successful strategy for the identification of a lead compound in a drug discovery programme. Here, we analysed 880 off-patent drugs, which initially comprised the Prestwick Chemical library, as sources of bacterial endotoxin neutralizers. We identified 3,3',5-triiodo-thyroacetic acid (tiratricol) as a non-antibacterial compound that neutralizes the toxic lipopolysaccharide.
Evidence for a human-specific mechanism for diet and antibody-mediated inflammation in carcinoma progression (2008)

Patients with cancer have circulating heterophile antibodies that agglutinate animal red cells via recognition of the mammalian cell surface sialic acid N-glycolylneuraminic acid (Neu5Gc), which was long considered an oncofetal antigen in humans. However, humans are genetically deficient in Neu5Gc production and instead metabolically accumulate Neu5Gc from dietary sources, particularly red meats and milk products. Moreover, mice with a human-like defect showed no alternate pathway for Neu5Gc synthesis and even normal humans express anti-Neu5Gc antibodies. We show here that human tumors accumulate Neu5Gc that is covalently attached to multiple classes of glycans. The paradox of human tumor Neu5Gc accumulation in the face of circulating anti-Neu5Gc antibodies was hypothesized to be due to facilitation of tumor progression by the resulting low-grade chronic inflammation. Indeed, murine tumors expressing human-like levels of Neu5Gc show accelerated growth in syngeneic mice with a human-like Neu5Gc deficiency, coincident with the induction of anti-Neu5Gc antibodies and increased infiltration of inflammatory cells. Transfer of polyclonal monospecific syngeneic mouse anti-Neu5Gc serum also enhanced growth of transplanted syngeneic tumors bearing human-like levels of Neu5Gc, with tumors showing evidence for antibody deposition, enhanced angiogenesis and chronic inflammation. These effects were suppressed by a cyclooxygenase-2 inhibitor, a drug type known to reduce human carcinoma risk. Finally, affinity-purified human anti-Neu5Gc antibodies also accelerate growth of Neu5Gc-containing tumors in Neu5Gc-deficient mice. Taken together, the data suggest that the human propensity to develop diet-related carcinomas is contributed to by local chronic inflammation, resulting from interaction of metabolically-accumulated dietary Neu5Gc with circulating anti-Neu5Gc antibodies.
CIRCULATORY AND RESPIRATORY EFFECTS OF GUANETHIDIN (1962)

Guanethidin has been shown by Maxwell et al. (1959) to be a potent antihypertensive agent in dogs, and by Page and Dustan (1959) and Leishman et al. (1959) to be hypotensive in human patients. It selectively inhibits sympathetic activity, probably by blocking postganglionic adrenergic neurones.
IL-15 Links TLR2/1-Induced Macrophage Differentiation to the Vitamin D-Dependent Antimicrobial Pathway (2008)

An essential function of the innate immune system is to directly trigger antimicrobial mechanisms to defend against invading pathogens. In humans, one such pathway involves activation by TLR2/1L leading to the vitamin D-dependent induction of antimicrobial peptides. In this study, we found that TLR2/1-induced IL-15 was required for induction of CYP27b1, the VDR and the downstream antimicrobial peptide cathelicidin. Although both IL-15 and IL-4 triggered macrophage differentiation, only IL-15 was sufficient by itself to induce CYP27b1 and subsequent bioconversion of 25-hydroxyvitamin D3 (25D3) into bioactive 1,25D3, leading to VDR activation and induction of cathelicidin. Finally, IL-15-differentiated macrophages could be triggered by 25D3 to induce an antimicrobial activity against intracellular Mycobacterium tuberculosis. Therefore, IL-15 links TLR2/1-induced macrophage differentiation to the vitamin D-dependent antimicrobial pathway.
Gene mapping and expression of two immunodominant Epstein-Barr virus capsid proteins (1993)

The genomic localization of two immunodominant genes encoding two proteins of the Epstein-Barr virus capsid antigen (VCA) complex, VCA-p18 and VCA-p40, has been identified. For that purpose, lambda gt11-based cDNA libraries were constructed from HH514.c16 cells induced for virus production. The libraries were screened with a monoclonal antibody, EBV.OT41A, directed against VCA-p40 or with affinity-purified human antibodies against VCA-p18. Sequencing of the inserts of positive plaques showed that VCA-p18 and VCA-p40 are encoded within open reading frames (ORFs) BFRF3 and BdRF1, respectively. Peptide scanning analysis of the predicted protein of ORF BdRF1 resulted in defining the epitope of monoclonal antibody EBV.OT41A at the C-terminal region. The dominant VCA-p18 reactivity of human sera can be completely inhibited by preadsorption with Escherichia coli-expressed BFRF3-beta-galactosidase. Serum of a rabbit immunized with BFRF3-beta galactosidase reacts with a VCA-specific protein of 18 kDa. In addition, BFRF3-beta-galactosidase affinity-purified antibodies react with VCA-p18 of virus-producing cells (HH514.c16). Complete inhibition of viral DNA polymerase activity by phosphonoacetic acid is associated with the absence of RNAs and protein products of both ORFs, indicating that VCA-p18 and VCA-p40 are true late antigens.
The neural basis of decision-making during sensemaking: Implications for human-system interaction (2015)

We have created a high-fidelity model of 9 regions of the brain involved in making sense of complex and uncertain situations. Sense making is a proactive form of situation awareness requiring sifting through information of various types to form hypotheses about evolving situations. The MINDS model (Mirroring Intelligence in a Neural Description of Sensemaking) reveals the neural principles and cognitive tradeoffs that explain weaknesses in human reasoning and decision-making.
Scaling learning algorithms towards AI (2007)

One long-term goal of machine learning research is to produce methods that are applicable to highly complex tasks, such as perception (vision, audition), rea-soning, intelligent control, and other artificially intelligent behaviors. We argue that in order to progress toward this goal, the Machine Learning community must endeavor to discover algorithms that can learn highly complex functions, with min-imal need for prior knowledge, and with minimal human intervention. We present mathematical and empirical evidence suggesting that many popular approaches to non-parametric learning, particularly kernel methods, are fundamentally lim-ited in their ability to learn complex high-dimensional functions. Our analysis focuses on two problems. First, kernel machines are shallow architectures, in which one large layer of simple template matchers is followed by a single layer of trainable coefficients. We argue that shallow architectures can be very ineffi-cient in terms of required number of computational elements and examples. Sec-ond, we analyze a limitation of kernel machines with a local kernel, linked to the curse of dimensionality, that applies to supervised, unsupervised (manifold learn-ing) and semi-supervised kernel machines. Using empirical results on invariant image recognition tasks, kernel methods are compared with deep architectures, in which lower-level features or concepts are progressively combined into more ab-stract and higher-level representations. We argue that deep architectures have the potential to generalize in non-local ways, i.e., beyond immediate neighbors, and that this is crucial in order to make progress on the kind of complex tasks required for artificial intelligence. 1 1
The T cell receptor V alpha 11 gene family. Analysis of allelic sequence polymorphism and demonstration of J alpha region-dependent recognition by allele-specific antibodies (1991)

Allelic polymorphism in TCR loci may play an important role in shaping the T cell repertoire and in disease susceptibility. We have used a combination of antibody and sequence analysis to investigate polymorphism in the murine V alpha 11 family. Two different antibodies have been analyzed that recognize particular V alpha 11 family members of the V alpha b and V alpha d haplotypes. One antibody shows J alpha dependency, suggesting a conformational element to the epitope. Investigation of the anti-V alpha 11 staining pattern on different mouse strains indicates that there is a marked influence of MHC haplotype on V alpha 11 selection and that V alpha 11 is preferentially expressed on CD4+ cells. Sequence analysis of V alpha 11 genes from the V alpha a, V alpha b, and V alpha d haplotypes shows two potential regions for the haplotype-specific epitopes. The relatedness of the different V alpha 11 family members from different haplotypes suggests that the V alpha 11.1/11.2 gene duplication is relatively recent, but that V alpha 11.3 separated much earlier. Differences between V alpha 11.3 and V alpha 11.1/11.2 are concentrated in the putative complementarity determining regions (CDR), whereas differences between alleles are not clearly clustered. However, the V alpha 11.1a and V alpha 11.1d alleles differ from V alpha 11.1b and V alpha 11.2b in CDR1. A V alpha 11.2-expressing anti-cytochrome c T cell has the same V-J junction as a V alpha 11.1-bearing cell with a similar fine specificity, indicating that V alpha 11.1b and V alpha 11.2b do not contribute different Ag specificities.