gebhart/patrepeval huggingface dataset:
Surface modification of aligned carbon nanotube arrays for electrochemical sensing applications (2003)

The excellent optoelectronic, mechanical, and thermal properties of carbon nanotubes have made them very attractive for a wide range of potential applications. However, many applications require the growth of aligned carbon nanotubes with surface modification. We have developed a simple pyrolytic method for large-scale production of aligned carbon nanotube arrays perpendicular to the substrate. These aligned carbon nanotube arrays can be transferred onto various substrates of particular interest (e.g., polymer films for organic optoelectronic devices) in either a patterned or non-patterned fashion. The well-aligned structure further allows us to prepare aligned coaxial nanowires by electrochemically depositing a concentric layer of an appropriate conducting polymer onto the individual aligned carbon nanotubes. This approach is particularly attractive, as it allows surface characteristics of the aligned carbon nanotubes to be tuned to meet specific requirements for particular applications while their alignment structure can be largely retained. These aligned carbon nanotubes with tunable surface characteristics are of great significance to various practical applications. In this paper, we demonstrate the use of the conducting-polymer-coated aligned carbon nanotubes for electrochemical sensing applications.
Modulation of the Effector Functions of a Human IgG1 through Engineering of Its Hinge Region (2006)

Abstract We report here the engineering of a humanized anti-human EphA2 mAb (mAb 12G3H11) in an effort to explore the relationship between the hinge of a human IgG1 and its effector functions. mAb 12G3H11, used here as a model, is directed against the human receptor tyrosine kinase EphA2, which is an actively investigated target for cancer therapy due to its up-regulation in many cancer cells. Various rational modifications were introduced into the hinge region of mAb 12G3H11. These mutations were predicted to modulate the hinge’s length, flexibility, and/or biochemical properties. We show that the upper and middle hinge both play important, although functionally distinct roles. In particular, middle hinge modifications predicted to decrease its rigidity or length as well as eliminating either one of its two cysteine residues had a strong negative impact on C1q binding and complement-dependent cytotoxicity. Disruption of covalent bonds between both H chains may account in part for these effects. We also describe middle hinge mutants with a significantly decreased ability to bind FcγRIIIA and trigger Ab-dependent cell-mediated cytotoxicity. Conversely, we also generated upper hinge mutants exhibiting an increase in C1q binding and complement-dependent cytotoxicity activity. Therefore, this approach represents a novel strategy to fine-tune the biological activity of a given human IgG1. We also define, for the first time in such a systematic fashion, the relationship between various characteristics of the middle and upper hinge and the corresponding effector functions.
Solubilization, Activation, and Insecticidal Activity ofBacillus thuringiensisSerovar thompsoni HD542 Crystal Proteins (2008)

Cry15Aa protein, produced by Bacillus thuringiensis serovar thompsoni HD542 in a crystal together with a 40-kDa accompanying protein, is one of a small group of nontypical, less well-studied members of the Cry family of insecticidal proteins and may provide an alternative for the more commonly used Cry proteins in insect pest management. In this paper, we describe the characterization of the Cry15Aa and 40-kDa protein's biochemical and insecticidal properties and the mode of action. Both proteins were solubilized above pH 10 in vitro. Incubation of solubilized crystal proteins with trypsin or insect midgut extracts rapidly processed the 40-kDa protein to fragments too small to be detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, whereas the Cry15 protein yielded a stable product of approximately 30 kDa. Protein N-terminal sequencing showed that Cry15 processing occurs exclusively at the C-terminal end. Cry15 protein showed in vitro hemolytic activity, which was greatly enhanced by preincubation with trypsin or insect gut extract. Larvae of the lepidopteran insects Manduca sexta, Cydia pomonella, and Pieris rapae were susceptible to crystals, and presolubilization of the crystals enhanced activity to P. rapae. Activity for all three species was enhanced by preincubation with trypsin. Larvae of Helicoverpa armigera and Spodoptera exigua were relatively insensitive to crystals, and activity against these insects was not enhanced by prior solubilization or trypsin treatment. The 40-kDa crystal protein showed no activity in the insects tested, nor did its addition or coexpression in Escherichia coli increase the activity of Cry15 in insecticidal and hemolytic assays.
Inhibition of Immune Complex Complement Activation and Neutrophil Extracellular Trap Formation by Peptide Inhibitor of Complement C1 (2018)

Two major aspects of systemic lupus erythematosus (SLE) pathogenesis that have yet to be targeted therapeutically are immune complex-initiated complement activation and neutrophil extracellular trap (NET) formation by neutrophils. Here, we report <i>in vitro</i> testing of peptide inhibitor of complement C1 (PIC1) in assays of immune complex-mediated complement activation in human sera and assays for NET formation by human neutrophils. The lead PIC1 derivative, PA-dPEG24, was able to dose-dependently inhibit complement activation initiated by multiple types of immune complexes (IC), including C1-anti-C1q IC, limiting the generation of pro-inflammatory complement effectors, including C5a and membrane attack complex (sC5b-9). In several instances, PA-dPEG24 achieved complete inhibition with complement effector levels equivalent to background. PA-dPEG24 was also able to dose-dependently inhibit NET formation by human neutrophils stimulated by PMA, MPO, or immune complex activated human sera. In several instances PA-dPEG24 achieved complete inhibition with NETosis with quantitation equivalent to background levels. These results suggest that PA-dPEG24 inhibition of NETs occurs by blocking the MPO pathway of NET formation. Together these results demonstrate that PA-dPEG24 can inhibit immune complex activation of the complement system and NET formation. This provides proof of concept that peptides can potentially be developed to inhibit these two important contributors to rheumatologic pathology that are currently untargeted by available therapies.
Temperature- and age-dependent seizures in a mouse model of severe myoclonic epilepsy in infancy (2009)

Heterozygous loss-of-function mutations in the alpha subunit of the type I voltage-gated sodium channel Na(V)1.1 cause severe myoclonic epilepsy in infancy (SMEI), an infantile-onset epileptic encephalopathy characterized by normal development followed by treatment-refractory febrile and afebrile seizures and psychomotor decline. Mice with SMEI (mSMEI), created by heterozygous deletion of Na(V)1.1 channels, develop seizures and ataxia. Here we investigated the temperature and age dependence of seizures and interictal epileptiform spike-and-wave activity in mSMEI. Combined video-EEG monitoring demonstrated that mSMEI had seizures induced by elevated body core temperature but wild-type mice were unaffected. In the 3 age groups tested, no postnatal day (P)17-18 mSMEI had temperature-induced seizures, but nearly all P20-22 and P30-46 mSMEI had myoclonic seizures followed by generalized seizures caused by elevated core body temperature. Spontaneous seizures were only observed in mice older than P32, suggesting that mSMEI become susceptible to temperature-induced seizures before spontaneous seizures. Interictal spike activity was seen at normal body temperature in most P30-46 mSMEI but not in P20-22 or P17-18 mSMEI, indicating that interictal epileptic activity correlates with seizure susceptibility. Most P20-22 mSMEI had interictal spike activity with elevated body temperature. Our results define a critical developmental transition for susceptibility to seizures in SMEI, demonstrate that body temperature elevation alone is sufficient to induce seizures, and reveal a close correspondence between human and mouse SMEI in the striking temperature and age dependence of seizure frequency and severity and in the temperature dependence and frequency of interictal epileptiform spike activity.
Using SAD data inPhaser (2011)

Phaser is a program that implements likelihood-based methods to solve macromolecular crystal structures, currently by molecular replacement or single-wavelength anomalous diffraction (SAD). SAD phasing is based on a likelihood target derived from the joint probability distribution of observed and calculated pairs of Friedel-related structure factors. This target combines information from the total structure factor (primarily non-anomalous scattering) and the difference between the Friedel mates (anomalous scattering). Phasing starts from a substructure, which is usually but not necessarily a set of anomalous scatterers. The substructure can also be a protein model, such as one obtained by molecular replacement. Additional atoms are found using a log-likelihood gradient map, which shows the sites where the addition of scattering from a particular atom type would improve the likelihood score. An automated completion algorithm adds new sites, choosing optionally among different atom types, adds anisotropic B-factor parameters if appropriate and deletes atoms that refine to low occupancy. Log-likelihood gradient maps can also identify which atoms in a refined protein structure are anomalous scatterers, such as metal or halide ions. These maps are more sensitive than conventional model-phased anomalous difference Fouriers and the iterative completion algorithm is able to find a significantly larger number of convincing sites.
ChemInform Abstract: Propane Oxidation Over Platinum Supported on Zirconia. (1993)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Lymphoid Neogenesis in Murine Cardiac Allografts Undergoing Chronic Rejection (2005)

Lymphoid neogenesis is the process by which ectopic lymphoid accumulations that resemble lymph nodes arise in nonlymphoid tissues. Such lymphoid accumulations, known as tertiary lymphoid organs (TLO), are observed in chronic autoimmunity and they propagate immune pathology by setting up local antigen presenting sites. Whether lymphoid neogenesis occurs in transplanted organs and contributes to rejection is not well understood. To begin to address this question, we retrospectively analyzed 319 murine cardiac allografts for microscopic evidence of lymph-node-like structures. We found 78 allografts that had either classical TLO, characterized by discrete T- and B-cell zones and high endothelial venules (HEV) expressing peripheral node addressin (PNAd) (n = 34), or PNAd(+) HEV without organized lymphoid accumulations (n = 44). These changes were present in both short- and long-lived allografts and were invariably associated with rejection. Importantly, they occurred in 78% of allografts undergoing chronic rejection (n = 85) but in only 7% of allografts undergoing primarily acute rejection (n = 184). These findings indicate that, like autoimmunity, alloimmunity is associated with lymphoid neogenesis in the target organ and suggest a role for local T-cell activation in chronic allograft rejection.
Physical location of the site for N-acetyl-L-glutamate, the allosteric activator of carbamoyl phosphate synthetase in the 20-kilodalton carboxy-terminal domain (1989)

Mammalian liver mitochondrial carbamoyl phosphate synthetase, a polypeptide of 160 kDa, is activated allosterically by N-acetyl-L-glutamate. The analogue of this activator N-(chloroacetyl)-L-[14C]glutamate has been found to serve as a photoaffinity label for this enzyme. The specificity was demonstrated by the drastic reduction in the radioactivity bound to the protein when (a) an excess of unlabeled acetylglutamate was present during the irradiation and (b) the enzyme was replaced by pyruvate kinase, an enzyme that is not affected by acetylglutamate. The labeling was due to the photoactivation of the chloroacetyl group since there was no labeling under equal conditions with acetyl[14C]glutamate. To localize the binding site, limited proteolysis was used. Trypsin cleaves carbamoyl phosphate synthetase into complementary NH2- and COOH-terminal fragments of about 140 and 20 kDa, respectively [Powers-Lee, S. G., & Corina, K. (1986) J. Biol. Chem. 261, 15349-15352], but only the latter was found to be labeled. Similarly, of the various fragments generated by elastase, only two, of 20 and 120 kDa, contain the COOH terminus [see Powers-Lee and Corina (1986) above] and were found to be labeled. Thus, the binding site for acetylglutamate is within 20 kDa from the COOH terminus. This excludes the possibility that the acetylglutamate binding site evolved from an ancestral substrate site for glutamine: this substrate binds to the small subunit of the Escherichia coli enzyme, which is homologous to the NH2-terminal domain of the rat liver enzyme. Exhaustive tryptic digestion of photolabeled carbamoyl phosphate synthetase yielded a single radioactive peak, suggesting that the labeling is restricted to a single minimal tryptic peptide.
Hypoxia-induced exocytosis of endothelial cell Weibel-Palade bodies. A mechanism for rapid neutrophil recruitment after cardiac preservation. (1996)

The period of hypoxia is an important priming event for the vascular dysfunction that accompanies reperfusion, with endothelial cells (ECs) and neutrophils (PMNs) playing a central role. We hypothesized that EC Weibel-Palade (WP) body exocytosis during the hypoxic/ischemic period during organ preservation permits brisk PMN recruitment into postischemic tissue, a process further amplified in an oxidant-rich milieu. Exposure of human umbilical vein ECs to a hypoxic environment (pO2 approximately 20 torr) stimulated release of von Willebrand factor (vWF), stored in EC WP bodies, as well as increased expression of the WP body-derived PMN adhesion molecule P-selectin at the EC surface. Increased binding of 111In-labeled PMNs to hypoxic EC monolayers (compared with normoxic controls) was blocked with a blocking antibody to P-selectin, but was not affected by a nonblocking control antibody. Although increased P-selectin expression and vWF release were also noted during reoxygenation, hypoxia alone (even in the presence of antioxidants) was sufficient to increase WP body exocytosis. To determine the relevance of these observations to hypothermic cardiac preservation, during which the pO2 within the cardiac vasculature declines to similarly low levels, experiments were performed in a rodent (rat and mouse) cardiac preservation/transplantation model. Immunodepletion of recipient PMNs or administration of a blocking anti-P-selectin antibody before transplantation resulted in reduced graft neutrophil infiltration and improved graft survival, compared with identically preserved hearts transplanted into control recipients. To establish the important role of endothelial P-selectin expression on the donor vasculature, murine cardiac transplants were performed using homozygous P-selectin deficient and wild-type control donor hearts flushed free of blood/platelets before preservation/transplantation. P-selectin-null hearts transplanted into wild-type recipients demonstrated a marked (13-fold) reduction in graft neutrophil infiltration and increased graft survival compared with wild-type hearts transplanted into wild-type recipients. To determine whether coronary endothelial WP exocytosis may occur during cardiac preservation in humans, the release of vWF into the coronary sinus (CS) was measured in 32 patients during open heart surgery. CS samples obtained at the start and conclusion of the ischemic period demonstrated an increase in CS vWF antigen (by ELISA) consisting of predominantly high molecular weight multimers (by immunoelectrophoresis). These data suggest that EC WP exocytosis occurs during hypothermic cardiac preservation, priming the vasculature to recruit PMNs rapidly during reperfusion.
Dual energy CT using slow kVp switching acquisition and prior image constrained compressed sensing (2010)

Dual energy computed tomography (DECT) is currently a subject of extensive investigation. DECT is currently implemented using either a dual source scanner with high and low kVp data acquired from separate sources or a single source scanner with both high and low kVp data acquired in an alternating manner. Both methods require dedicated hardware to enable data acquisition and image reconstruction for DECT. In this paper, we present a method to enable DECT using a single x-ray source with a slow kVp switching data acquisition. The enabling reconstruction technique allowing for the reduction in slew rate is the prior image constrained compressed sensing (PICCS) algorithm. When a slow kVp switching data acquisition method is used, the projection data with high and low kVp values are undersampled and the conventional filtered backprojection (FBP) image reconstruction does not enable streaking artifact-free images for material decomposition in DECT. In this paper, all of the acquired high and low kVp projection data were used to generate a prior image using the conventional FBP method. The PICCS algorithm was then used to reconstruct both high and low kVp images to enable material decomposition in the image domain. Both numerical simulations and physical phantom experimental studies were conducted to validate the proposed DECT scheme. The results demonstrate that a slew rate corresponding to 123 views at high and low kVp (high and low kVp values used for dual energy decomposition) is sufficient for the PICCS-based DECT method. In contrast, the slew rate should be high enough to obtain over 500 projections at each kVp for artifact-free reconstruction using an FBP-based DECT method.
A copper-deficient, zinc-supplemented diet produces emphysema in pigs. (1982)

A mild form of emphysema was produced in pigs raised on a copper-deficient, zinc-supplemented diet. The copper-requiring enzyme, lysyl oxidase, catalyzes the cross-linking of tropoelastin into mature elastin. Zinc further inhibits the activity of lysyl oxidase. Lungs from animals raised on copper-deficient, zinc-supplemented diets of demonstrate perforations in alveolar walls and diminished amounts of elastin bronchi and pulmonary arteries. Mean linear intercepts are greater and alveolar internal surface areas are less than those in control animals, fulfilling the generally accepted definition of emphysema. Physiologic confirmation is provided by a leftward shift of the saline volume-pressure curves when compared with those in control animals. Ultrastructurally, the alveolar walls are effaced and pores of Kohn are enlarged. There are areas in which elastin is absent leaving remnant microfibrils, and there are other changes consistent with active elastin synthesis. Biochemical data demonstrate no difference in elastin content as micrograms/ml of fat-free dry weight but do demonstrate increased collagen content in experimental animal lungs compared with that in control lungs. Ultrastructural similarities to enzyme-induced models of emphysema suggest the presence of elastin degradation in our model. We speculate that although the copper-deficient, zinc-supplemented state may stimulate protein synthesis in general, elastin is being degraded by endogenous means, but collagen is not.
Enzymatic Synthesis of Dehydro Cyclo(His–Phe)s, Analogs of the Potent Cell Cycle Inhibitor, Dehydrophenylahistin, and Their Inhibitory Activities toward Cell Division (2004)

Cyclo(His-Phe) was effectively converted to its dehydro derivatives by the enzyme of Streptomyces albulus KO-23, an albonoursin-producing actinomycete. Two types of dehydro derivatives were isolated from the reaction mixture and identified as cyclo(DeltaHis-DeltaPhe) and cyclo(His-DeltaPhe). This is the first report on cyclo(His-DeltaPhe) and the enzymatic preparation of both compounds. Cyclo(DeltaHis-DeltaPhe), a tetradehydro cyclic dipeptide, exhibited a minimum inhibitory concentration of 0.78 mumol/ml inhibitory activity toward the first cleavage of sea urchin embryos, in contrast to cyclo(His-DeltaPhe) that had no activity. The finding that the isoprenylated derivative of cyclo(DeltaHis-DeltaPhe), dehydrophyenylahistin, had 2,000 times higher activity than cyclo(DeltaHis-DeltaPhe) indicates that an isoprenyl group attached to an imidazole ring of the compound was essential for the inhibitory activity.
Emerging & re-emerging bacterial pathogens in India. (1996)

In spite of major successes against infectious diseases in the 20th century, new infectious diseases have emerged and old ones re-emerged in recent decades in different parts of the world. A brief survey of emerging and re-emerging bacterial diseases of public health importance in India is presented in this paper. Plague re-appeared in two outbreaks in Maharashtra and Gujarat in 1994, indicating a breakdown of the public health measures that had prevented its occurrence for several decades. Leptospirosis appears to be on the increase in Kerala, Tamilnadu and the Andamans during the last 2 decades, probably due to increased farming and inadequate rodent control. It is suggested that melioidosis due to the soil organism Burkholderia pseudomallei may be prevalent in many parts of India, but is under-diagnosed and under-reported. Since 1991, a completely new choleragenic Vibrio cholerae, designated 0139 has emerged in southern India and spread to other parts of India and to neighbouring countries, setting in motion the 8th cholera pandemic. Animal anthrax is very common in many parts of India, but human anthrax is recognised in only certain limited locations. In the Chittoor and North Arcot districts, its prevalence had increased in recent years. Since 1990, a multi-drug resistant variety of typhoid fever had been prevalent in many parts of India, caused by Salmonella typhi resistant to chloramphenicol, ampicillin and trimethoprim-sulphamethoxazole. Nosocomial methicillin-resistant Staphylococcus aureus infection seems to be widely prevalent in hospitals in many regions in India, and its prevalence seems to be on the rise. These pathogens pose new threats to public health, and call for appropriate responses. Microbiological expertise and epidemiological surveillance are deficient in the health care and public health systems in India; therefore even infections and diseases that have been under control elsewhere remain prevalent in the country, but are also under-diagnosed and under-reported. Without improving microbiological expertise and application as well as epidemiological skills and practices, emerging and re-emerging diseases may not be recognised, identified or intercepted in their early stages.