gebhart/patrepeval huggingface dataset:
Discovery of Itraconazole with Broad-Spectrum In Vitro Antienterovirus Activity That Targets Nonstructural Protein 3A (2015)

There is currently no approved antiviral therapy for the prophylaxis or treatment of enterovirus infections, which remain a substantial threat to public health. To discover inhibitors that can be immediately repurposed for treatment of enterovirus infections, we developed a high-throughput screening assay that measures the cytopathic effect induced by enterovirus 71 (EV71) to screen an FDA-approved drug library. Itraconazole (ITZ), a triazole antifungal agent, was identified as an effective inhibitor of EV71 replication in the low-micromolar range (50% effective concentrations [EC50s], 1.15 μM). Besides EV71, the compound also inhibited other enteroviruses, including coxsackievirus A16, coxsackievirus B3, poliovirus 1, and enterovirus 68. Study of the mechanism of action by time-of-addition assay and transient-replicon assay revealed that ITZ targeted a step involved in RNA replication or polyprotein processing. We found that the mutations (G5213U and U5286C) conferring the resistance to the compound were in nonstructural protein 3A, and we confirmed the target amino acid substitutions (3A V51L and 3A V75A) using a reverse genetic approach. Interestingly, posaconazole, a new oral azole with a molecular structure similar to that of ITZ, also exhibited anti-EV71 activity. Moreover, ITZ-resistant viruses do not exhibit cross-resistance to posaconazole or the enviroxime-like compound GW5074, which also targets the 3A region, indicating that they may target a specific site(s) in viral genome. Although the protective activity of ITZ or posaconazole (alone or in combination with other antivirals) remains to be assessed in animal models, our findings may represent an opportunity to develop therapeutic interventions for enterovirus infection.
Convex corner undercutting of {100} silicon in anisotropic KOH etching: the new step-flow model of 3-D structuring and first simulation results (2001)

In this paper, the mechanism of convex corner (CC) undercutting of Si/sub {100}/ in pure aqueous KOH solutions is revisited by proposing the step-flow model of 3-D structuring as a proper description of the observed phenomena. The basic idea is to conceive the Si/sub {100}/ anisotropic etching process, on the atomic scale, as a "peeling" process of terraced {111} planes at [110] oriented steps to understand also the arising shape in Si/sub [100]/ etching. On the basis of our new model, we are able to predict the microscopic three-dimensional (3-D) structure of the characteristic CC undercutting without any compensation etchmask structures. Furthermore, the theoretical description has been implemented in a new 3-D simulation tool. Its ability to calculate the shape of simple beam structures of different orientation is experimentally shown.
Optical and Electrical Characteristics of Silicon Nanowires Prepared by Electroless Etching (2017)

Silicon nanowires (SiNWs) were fabricated by the electroless etching of an n-type Si (100) wafer in HF/AgNO<sub>3</sub>. Vertically aligned and high-density SiNWs are formed on the Si substrates. Various shapes of SiNWs are observed, including round, rectangular, and triangular. The recorded maximum reflectance of the SiNWs is approximately 19.2%, which is much lower than that of the Si substrate (65.1%). The minimum reflectance of the SiNWs is approximately 3.5% in the near UV region and 9.8% in the visible to near IR regions. The calculated band gap energy of the SiNWs is found to be slightly higher than that of the Si substrate. The I-V characteristics of a freestanding SiNW show a linear ohmic behavior for a forward bias up to 2.0 V. The average resistivity of a SiNW is approximately 33.94 Ω cm.
Mechanisms of Pathogen-Derived Resistance to Viruses in Transgenic Plants. (1996)

lhe Sainsbury Laboratory, John lnnes Centre, Colney, Norwich NR4 7UH, United Kingdom INTRODUCTION In 1985, Sanford and Johnston developed the simple and ele- gant concept of parasite- or pathogen-derived resistance (Sanford and Johnston, 1985). Subsequently, there have been numerous attempts to generate virus resistance in transgenic plants based on this concept through the expression of virus- derived genes or genome fragments (Beachy, 1993; Wilson, 1993; Baulcombe, 1994b; Lomonossoff, 1995). Many of these attempts have been successful, and some have led to the de- velopment of virus-resistant potato and squash cultivars for commercial application. In this article, the major emphasis is on the mechanisms of pathogen-derived resistance rather than on the practicali- ties of using this technology for crop improvement. These mechanisms have proven difficult to unravel largely because a resistance mechanism related to transgene silencing can override the direct phenotype of virus-derived transgenes. lhe examples discussed first are those in which it is clear whether the mechanism involves gene silencing. In later sections, some less well understood examples are reviewed. The final sec- tion anticipates likely future developments in pathogen-derived resistance.
Insulin-Like Growth Factors in Vitreous: Studies in Control and Diabetic Subjects with Neovascularization (1986)

Vitreous and serum were obtained at the time of vitrectomy from 23 diabetic subjects with proliferative retinopathy and from 8 nondiabetic subjects. The mean concentration of IGF-I in vitreous from diabetic patients with neovascularization was 6.3 +/- 0.93 versus 2.7 +/- 0.96 ng/ml. Chi-square and rank analysis indicated that higher concentrations of IGF-I occurred in diabetic vitreous (P less than 0.01 by both analyses). IGF-II concentrations in vitreous of control and diabetic subjects were not significantly different. A positive correlation existed between the concentrations of IGF-I and IGF-II in vitreous and their concentrations in serum in diabetic subjects, but not in control subjects. When vitreous concentrations of IGF-I were calculated for diabetic subjects studied previously with rapid acceleration of retinal disease, these concentrations varied from 20 to 30 ng/ml. The concentrations of IGF-I in the vitreous of most diabetic subjects with severe neovascularization are thus in the range known to stimulate cellular differentiation and growth in several systems. Whether they do so in the eye, and thus contribute to the development of retinopathy, remains to be determined.
Diverse Structure−Activity Trends in Amine Bis(phenolate) Titanium Polymerization Catalysts (2004)

The activity of amine bis(phenolate) Ti dibenzyl complexes in 1-hexene polymerization catalysis as a function of the phenolate substituents was investigated. Two series of Ti complexes carrying either a dimethylamino or a methoxy sidearm donor were prepared and characterized. In each series, the substituents on the phenolate rings were either alkyl groups of varying bulk or electron-withdrawing chloro groups. When activated with a suitable Lewis acid, all precatalysts have shown reactivity toward 1-hexene. Different structure−activity trends were observed in the two series: The activity of the catalysts of the “OMe” series was low to moderate and was almost independent of the phenolate substituents. In contrast, the activity of the “NMe2” catalysts had a strong dependence on both the steric and electronic character of the phenolate substituents, ranging from mild to highly active. The difference in polymerization activity trends between the two series may be traced back to their different tendency toward misinsertions. A “NMe2”-Ti complex having Cl groups in the ortho, para positions of the phenolate rings led to the most active catalyst and to a remarkably high-Mw polymer (>4 000 000) obtained within 1 h of polymerization at RT. The characterization of this ultrahigh-Mw atactic poly(1-hexene) by means of oscillatory rheometry and stress relaxation experiments indicated typical elastomeric behavior at RT.
The Specific Genes for Lantibiotic Mutacin II Biosynthesis in Streptococcus mutans T8 Are Clustered and Can Be Transferred En Bloc (1999)

Mutacin II is a ribosomally synthesized peptide lantibiotic produced by group II Streptococcus mutans. DNA sequencing has revealed that the mutacin II biosynthetic gene cluster consists of seven specific open reading frames: a regulator (mutR), the prepromutacin structural gene (mutA), a modifying protein (mutM), an ABC transporter (mutT), and an immunity cluster (mutFEG). Transformations of a non-mutacin-producing strain, S. mutans UA159, and a mutacin I-producing strain, S. mutans UA140, with chromosomal DNA from S. mutans T8 with an aphIII marker inserted upstream of the mutacin II structural gene yielded transformants producing mutacin II and mutacins I and II, respectively.
Patent Update: Biologicals & Immunologicals: Advances in vector systems for gene therapy (1995)

Innovation in gene therapy has become an area of intense interest to biomedical researchers, due to the failure of conventional methods to provide safe, prolonged expression of genes in vivo. Transfection methods provide safe, efficient delivery, but only transient expression. Although viral transduction methods provide permanent insertion of genes into the genome (via retroviruses), they are subject to safety problems, complement inactivation, size limitations and transcriptional inactivation of the viral promoter. This void between the two methods is being fulfilled by new materials and procedures aimed at utilising the best of both transduction and transfection manoeuvres. Synthetic vectors and delivery systems are also being devised to permit more selective targeting on three levels: transductional targeting (entry into desired cells); transcriptional targeting (selective expression); and positional targeting (entry into precise genomic loci). The tools for these advanced molecular conjugate vectors include combinations of polycations, peptide signals, liposomes, viral enzymes, and the appropriate nucleic acid substrates.
Lambda-Interacting Protein, A Novel Protein That Specifically Interacts with the Zinc Finger Domain of the Atypical Protein Kinase C Isotype λ/ι and Stimulates Its Kinase Activity In Vitro and In Vivo (1996)

The members of the atypical subfamily of protein kinase C (PKC) show dramatic structural and functional differences from other PKC isotypes. Thus, in contrast to the classical or novel PKCs, they are not activated by diacylglycerol or phorbol esters. However, the atypical PKCs are the target of important lipid second messengers such as ceramide, phosphatidic acid, and 3'-phosphoinositides. The catalytic and pseudosubstrate sequences in the two atypical PKCs (lambda/iota PKC and zeta PKC) are identical but are significantly different from those of conventional or novel PKCs. It has been shown that microinjection of a peptide with the sequence of the pseudosubstrate of the atypical PKC isotypes but not of alpha PKC or epsilon PKC dramatically inhibited maturation and NF-kappa B activation in Xenopus oocytes, as well as reinitiation of DNA synthesis in quiescent mouse fibroblasts. This indicates that either or both atypical isoforms are important in cell signalling. Besides the pseudosubstrate, the major differences in the sequence between lambda/iota PKC and zeta PKC are located in the regulatory domain. Therefore, any functional divergence between the two types of atypical PKCs will presumably reside in that region. We report here the molecular characterization of lambda-interacting protein (LIP), a novel protein that specifically interacts with the zinc finger of lambda/iota PKC but not zeta PKC. We show in this paper that this interaction is detected not only in vitro but also in vivo, that LIP activates lambda/iota PKC but not zeta PKC in vitro and in vivo, and that this interaction is functionally relevant. Thus, expression of LIP leads to the transactivation of a kappa B-dependent promoter in a manner that is dependent on lambda/iota PKC. To our knowledge, this is the first report on the cloning and characterization of a protein activator of a PKC that binds to the zinc finger domain, which has so far been considered a site for binding of lipid modulators. The fact that LIP binds to lambda/iota PKC but not to the highly related zeta PKC isoform suggests that the specificity of the activation of the members of the different PKC subfamilies will most probably be accounted for by proteins like LIP rather than by lipid activators.
Hetero-oligomeric MspA pores inMycobacterium smegmatis (2016)

The porin MspA of Mycobacterium smegmatis is a biological nanopore used for DNA sequencing. The octameric MspA pore can be isolated from M. smegmatis in milligram quantities, is extremely stable against denaturation and rapidly inserts into lipid membranes. Here, we show that MspA pores composed of different Msp subunits are formed in M. smegmatis and that hetero-oligomers of different Msp monomers increase the heterogeneity of MspA pores designed for DNA sequencing. To improve the quality of preparations of mutant MspA proteins, all four msp genes were deleted from the M. smegmatis genome after insertion of an inducible porin gene from M. tuberculosis. In the msp quadruple mutant M. smegmatis ML712 no Msp porins were detected and mutant MspA proteins were produced at wild-type levels. Lipid bilayer experiments demonstrated that MspA pores isolated from ML712 formed functional channels and had a narrower conductance distribution than pores purified from M. smegmatis with background msp expression. Thus, the M. smegmatis msp quadruple mutant improves the homogeneity of MspA pores designed for DNA sequencing and might also facilitate the identification and functional characterization of other mycobacterial pore proteins.
Small bowel bacterial overgrowth and type 1 diabetes. (2010)

Pts with autonomic neuropathy have a significantly higher prevalence of SIBO, that is also associated with a higher daily insulin requirements.
Iodo-cyclization of N-Homoallyl Thioamides Leading to 2,4-Diaryl-5,6-dihydro-4H-1,3-thiazines (2004)

Abstract Iodo-cyclization of N-homoallyl thioamides was carried out in the presence of Et3N to form 2,4-diaryl-5,6-dihydro-4H-1,3-thiazines in good to high yields. The reaction of thioamides bearing 1-naphthyl or 2-methoxyphenyl group at the carbon atom adjacent to the nitrogen atom showed high diastereoselectivity. The relative stereochemistry was confirmed by X-ray molecular structure analyses. The obtained thiazines were converted to 6-alkylidene-1,3-thiazines by treating with pyrrolidine.
Reverse Engineering of Biological Complexity (2002)

Advanced technologies and biology have extremely different physical implementations, but they are far more alike in systems-level organization than is widely appreciated. Convergent evolution in both domains produces modular architectures that are composed of elaborate hierarchies of protocols and layers of feedback regulation, are driven by demand for robustness to uncertain environments, and use often imprecise components. This complexity may be largely hidden in idealized laboratory settings and in normal operation, becoming conspicuous only when contributing to rare cascading failures. These puzzling and paradoxical features are neither accidental nor artificial, but derive from a deep and necessary interplay between complexity and robustness, modularity, feedback, and fragility. This review describes insights from engineering theory and practice that can shed some light on biological complexity.
A Convenient Preparation of a New C-5 Biotinylated dUTP Derivative (1986)

Abstract An improved method for the C-5 biotinylation of dUTP is herein described. Palladium-catalyzed condensation of conjugated olefin 3 with mercurated dUTP 4 gave C-5 biotinylated dUTP derivative 5 in 50–70% yield. Enzymatic characterization of 5 demonstrated versatile substrate activity for incorporation into DNA.
Epidemiology of lower limb fractures in general practice in the United Kingdom (2004)

Many risk factors for lower limb fracture have been identified, but population attributable risk estimates for various risk factors are small. These findings suggest that multifactorial prevention programs are needed to decrease the incidence of lower limb fractures in the general population.
Anti-CD25 Antibody-Mediated Depletion of Effector T Cell Populations Enhances Susceptibility of Mice to Acute but Not Chronic Toxoplasma gondii Infection (2009)

Natural regulatory T cells (Tregs) constitutively express the IL-2R alpha-chain (CD25) on their surface. Consequently, administration of anti-CD25 Abs is a commonly used technique to deplete Treg populations in vivo. However, activated effector T cells may also transiently express CD25, and are thus also potential targets for anti-CD25 Abs. In this study using Toxoplasma gondii as a model proinflammatory infection, we have examined the capacity of anti-CD25 Abs to target effector T cell populations during an inflammatory episode, to determine to what extent that this action may modulate the outcome of disease. Anti-CD25 Ab-treated C57BL/6 mice displayed significantly reduced CD4(+) T cell IFN-gamma production during acute T. gondii infection and exhibited reduced weight loss and liver pathology during early acute infection; aspects of infection previously associated with effector CD4(+) T cell responses. In agreement, anti-CD25 Ab administration impaired parasite control and caused mice to succumb to infection during late acute/early chronic stages of infection with elevated tissue parasite burdens. In contrast, anti-CD25 Ab treatment of mice with established chronic infections did not markedly affect brain parasite burdens, suggesting that protective T cell populations do not express CD25 during chronic stages of T. gondii infection. In summary, we have demonstrated that anti-CD25 Abs may directly abrogate effector T cell responses during an inflammatory episode, highlighting important limitations of the use of anti-CD25 Ab administration to examine Treg function during inflammatory settings.
Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of β-cell formation in the pancreas (2000)

Most insulin-producing beta-cells in the fetal mouse pancreas arise during the secondary transition, a wave of differentiation starting at embryonic day 13. Here, we show that disruption of homeobox gene Nkx6.1 in mice leads to loss of beta-cell precursors and blocks beta-cell neogenesis specifically during the secondary transition. In contrast, islet development in Nkx6. 1/Nkx2.2 double mutant embryos is identical to Nkx2.2 single mutant islet development: beta-cell precursors survive but fail to differentiate into beta-cells throughout development. Together, these experiments reveal two independently controlled pathways for beta-cell differentiation, and place Nkx6.1 downstream of Nkx2.2 in the major pathway of beta-cell differentiation.
A tunable microwave frequency alternating current scanning tunneling microscope (1994)

By modulating the scanning tunneling microscope junction bias voltage at microwave frequencies, imaging and spectroscopy of insulating surfaces have become possible. In order to explore the spectroscopic capabilities of this instrument, we have developed a tunable microwave frequency alternating current scanning tunneling microscope. We combine the reliable beetle-style sample approach with coaxial sample and tip contacts. This provides us with a stable microwave-frequency-compatible scanning tunneling microscope. This alternating current scanning tunneling microscope design is compatible with ultrahigh vacuum and low-temperature operation.
Mechanisms and Measurement of Dyspnea in Chronic Obstructive Pulmonary Disease (2006)

Patients with chronic obstructive pulmonary disease (COPD) describe their breathlessness as related to the work and effort associated with breathing. Current evidence suggests that the perception of dyspnea is due to a "mismatch" between the outgoing motor command from the central nervous system and the corresponding afferent information from chemoreceptors and/or mechanoreceptors. To measure the severity of dyspnea the principles of psychophysics (stimulus --> response relationship) can be applied. One approach is to consider activities of daily living as a putative stimulus. Although this method relies on patient recall and description of daily tasks, ability to function, as well as time and effort to complete an activity, select clinical instruments have demonstrated appropriate measurement criteria in randomized clinical trials involving patients with COPD. Another approach is for a patient to report the intensity of dyspnea during exercise, and current practice is to provide ratings each minute "on cue" during the exercise test. A computerized system has been developed whereby the person can report ratings spontaneously and continuously by moving a computer mouse that adjusts a vertical bar adjacent to 0-10 category-ratio scale positioned on a monitor. With this continuous method the patient reports twice the number of dyspnea ratings during exercise compared with discrete ratings each minute. Patient-reported dyspnea based on activities of daily living and exercise testing provides distinct but complimentary information.
The Human Immunodeficiency Virus: Infectivity and Mechanisms of Pathogenesis (1988)

Infection with the human immunodeficiency virus (HIV) results in a profound immunosuppression due predominantly to a selective depletion of helper/inducer T lymphocytes that express the receptor for the virus (the CD4 molecule). HIV also has tropism for the brain leading to neuropsychiatric abnormalities. Besides inducing cell death, HIV can interfere with T4 cell function by various mechanisms. The monocyte serves as a reservoir for HIV and is relatively refractory to its cytopathic effects. HIV can exist in a latent or chronic form which can be converted to a productive infection by a variety of inductive signals.
Chemistry for biologists : instant notes (2004)

A. The elements. B. Chemical bonds and molecular shape. C. Water - the biological solvent. D. Carbon, the basis for life on Earth. E. 3D-molecular structure of organic compounds. F. Small inorganic molecules of biological importance. G. Some metals in biology. H. Molecular interactions. I. Common reaction types of carbon based compounds. J. Organic compounds by chemical class. K. Important biological macromolecules by class. L. Aromatic compounds. M. Chemical synthesis of biological molecules. N. Aqueous behavior. O. Elementary thermodynamics. P. Kinetics. Q. Spectroscopy. Further Reading. Index.