gebhart/patrepeval huggingface dataset:
Minds, brains, and programs (1980)

Abstract This article can be viewed as an attempt to explore the consequences of two propositions. (1) Intentionality in human beings (and animals) is a product of causal features of the brain. I assume this is an empirical fact about the actual causal relations between mental processes and brains. It says simply that certain brain processes are sufficient for intentionality. (2) Instantiating a computer program is never by itself a sufficient condition of intentionality. The main argument of this paper is directed at establishing this claim. The form of the argument is to show how a human agent could instantiate the program and still not have the relevant intentionality. These two propositions have the following consequences: (3) The explanation of how the brain produces intentionality cannot be that it does it by instantiating a computer program. This is a strict logical consequence of 1 and 2. (4) Any mechanism capable of producing intentionality must have causal powers equal to those of the brain. This is meant to be a trivial consequence of 1. (5) Any attempt literally to create intentionality artificially (strong AI) could not succeed just by designing programs but would have to duplicate the causal powers of the human brain. This follows from 2 and 4. “Could a machine think?” On the argument advanced here only a machine could think, and only very special kinds of machines, namely brains and machines with internal causal powers equivalent to those of brains. And that is why strong AI has little to tell us about thinking, since it is not about machines but about programs, and no program by itself is sufficient for thinking.
Antibiotic production by the marine photosynthetic bacterium Chromatium purpuratum NKPB 031704: localization of activity to the chromatophores (1991)

Over 200 strains of marine purple photosynthetic bacteria were isolated. Two strains showed antibiotic activity towards Saccharomyces cerevisiae and were tentatively identified as Chromatium purpuratum. Crude antibiotic, prepared by solvent extraction, showed a broad antimicrobial spectrum. The highest activity was found in the chromatophore fraction. Chromatographic separation of purified light harvesting complex from one strain, NKPB 031704, showed the presence of two separate pigmented compounds which were responsible for antimicrobial activity. Our findings reveal the unexpected ability of photosynthetic bacteria to produce broad spectrum antibiotics. In addition, this is the first example of intracellular localization of antibiotic activity in a marine bacterium.
Double cervices in a Gypsy Vanner mare (2023)

A 7-year, purebred Gypsy Vanner, maiden mare was presented with abnormal cervical tissue that was detected during prebreeding examination. External vulvar examination, transrectal and ultrasonographic examination of uterus, and internal vaginal vault and cervical examination (via speculum and endoscopy) were conducted. Karyotype analysis included sex chromosome study with dual-color fluorescence in situ hybridization and polymerase chain reaction for SRY gene. Mare had normal 64,XX karyotype with no evidence of mosaicism. Two distinct, patent, cervical ora separated by a frenulum, leading to a single uterine body, were observed. It was recommended to avoid breeding because of dystocia risk. To the authors’ knowledge, this is the first reported case of this nature in a mare.
Histone hypoacetylation is required to maintain late replication timing of constitutive heterochromatin (2011)

The replication of the genome is a spatio-temporally highly organized process. Yet, its flexibility throughout development suggests that this process is not genetically regulated. However, the mechanisms and chromatin modifications controlling replication timing are still unclear. We made use of the prominent structure and defined heterochromatic landscape of pericentric regions as an example of late replicating constitutive heterochromatin. We manipulated the major chromatin markers of these regions, namely histone acetylation, DNA and histone methylation, as well as chromatin condensation and determined the effects of these altered chromatin states on replication timing. Here, we show that manipulation of DNA and histone methylation as well as acetylation levels caused large-scale heterochromatin decondensation. Histone demethylation and the concomitant decondensation, however, did not affect replication timing. In contrast, immuno-FISH and time-lapse analyses showed that lowering DNA methylation, as well as increasing histone acetylation, advanced the onset of heterochromatin replication. While dnmt1(-)(/)(-) cells showed increased histone acetylation at chromocenters, histone hyperacetylation did not induce DNA demethylation. Hence, we propose that histone hypoacetylation is required to maintain normal heterochromatin duplication dynamics. We speculate that a high histone acetylation level might increase the firing efficiency of origins and, concomitantly, advances the replication timing of distinct genomic regions.
Effect of pore size on the performance of immobilised enzymes (2013)

Porous materials are widely employed as supports in the immobilisation of enzymes. Traditionally macroporous materials with pore diameters >50 nm were believed to be the most suitable support material, ensuring no spatial restrictions upon enzyme molecules entering such large pores. In recent years however, there has been growing emphasis in the use of mesoporous supports with pore diameters ranging between 2 and 50 nm. It is thought this smaller pore range may offer enhanced conformational stability to immobilised enzymes while not being so small as to restrict enzyme access. Despite their increasing popularity, many argue that mesoporous materials have not yet proven superior to traditional macroporous supports for enzyme immobilisation. Through the design and application of a unique confidence rating system we were able to accurately compare data and establish trends between pore characteristics and protein loading. By analysing published data (182 experiments in total) and extracting pore characteristics and protein loading values, we have described three categories of pore diameters in which correlations between pore characteristics and protein loading are noted. With pore diameters less than 10 nm we see a general decrease in protein loading as the enzymes find physical restrictions in accessing the high surface offered in this pore diameter range. At pore sizes greater than 100 nm, protein loading generally decreases due to a concomitant reduction in available surface area. In the pore range of 10-100 nm there it is expected to see a decrease in protein loading level with increasing pore diameter. In fact protein loading in this range remains largely constant, suggesting some degree of protein-protein interaction blocking pores and restricting access to the increasing surface area available at decreasing pore diameters. No trends were established between pore characteristics and retention of activity.
Ensemble Forecasting at NMC: The Generation of Perturbations (1993)

Abstract On 7 December 1992, The National Meteorological Center (NMC) started operational ensemble forecasting. The ensemble forecast configuration implemented provides 14 independent forecasts every day verifying on days 1–10. In this paper we briefly review existing methods for creating perturbations for ensemble forecasting. We point out that a regular analysis cycle is a “breeding ground” for fast-growing modes. Based on this observation, we devise a simple and inexpensive method to generate growing modes of the atmosphere. The new method, “breeding of growing modes”, or BGM, consists of one additional, perturbed short-range forecast, introduced on top of the regular analysis in an analysis cycle. The difference between the control and perturbed six-hour (first guess) forecast is scaled back to the size of the initial perturbation and then reintroduced onto the new atmospheric analysis. Thus, the perturbation evolves along with the time dependent analysis fields, ensuring that after a few days of cycl...
Motor Neuron Involvement in a Patient with Long-term Corticosteroid Administration (2003)

An asthmatic patient with corticosteroid treatment for 45 years presented with slowly progressive limb muscle atrophy. His muscle symptoms were involved in four limbs and tongue, and deep tendon reflexes were exaggerated. Biopsied muscle pathology indicated the presence of neurogenic muscular atrophy in combination with corticosteroid myopathy. Furthermore, 8-hydroxy-deoxyguanosine (8-OH-dG) was prominently increased in mitochondrial and nuclear DNA. An aerobic exercise test demonstrated remarkable serum lactate elevation, which was attenuated by the administration of coenzyme Q10. These findings are consistent with the assumption that long-term corticosteroid administration potentially induces not only myopathy but also motor neuron involvement as in mitochondrial diseases.
Costs and Cost-Effectiveness in Hip and Knee Replacements:A Prospective Study (1997)

The extensive benefits of the total hip (THA) and knee (TKA) replacements are well documented, but surprisingly little is known about their economics. We assessed costs, cost-effectiveness (C/E), and patient-related C/E variances in THA and TKA from data on 276 THA and 176 TKA patients. Patients with primary arthrosis, primary operation, and total joint replacement were recruited from seven hospitals between March 1991 and June 1992. Their use of health and other welfare services together with health-related quality of life (HRQoL) were measured before the surgery and at 6, 12, and 24 months postoperatively. HRQoL was assessed by the 15D, a 15-dimensional HRQoL instrument, and the Nottingham Health Profile. Costs were assessed from questionnaire responses, the Finnish Hospital Discharge Register, and Finnish Arthroplasty Register. Total hospital costs per patient were 45,000 FIM (US $10,500) for THA and 49,600 FIM (US $11,500) for TKA. Prosthesis costs comprised 21% of these costs in THA and 24% in TKA. On average, hip patients gained more in terms of HRQoL, and the operations were more cost-effective. The C/E ratio for younger (< or = 60 years) knee patients did not differ from those in all age groups of hip patients, whereas TKAs in those over 60 years had a worse C/E ratio compared with all other patient subgroups. It was concluded that allocation efficiency can be improved by considering not only the intervention but also patient characteristics such as age. Indeed, the C/E ratio varied more across age groups of knee patients than between average THA and TKA patients.
Surface Treatments Solutions to Green Tribology (2020)

The objective of this paper is to highlight the need to combine lifecycle environmental assessment with durability evaluation (tribology and engine tests) to evaluate the potential of surface technologies to contribute to the green deal, in order to make Europe the first climate-neutral continent. Tribology is a scientific discipline that allows one to understand the system reaction to friction and wear. Tribological testing machines are prepared to measure friction at the laboratory level to minimize the wear and heat dissipation of two bodies in relative movement, thus improving the energy efficiency and minimizing CO2 emissions. In this paper, different surface technologies, such as high-velocity oxyfuel (HVOF), physical vapor deposition (PVD), and clean Cr electrolytic processes, are analyzed as promising surface technology solutions from both performance and environmental impact perspectives to replace harmful Cr(VI) coatings. The tribology simulates the working conditions of the real system at the laboratory level, reproducing the failure mechanism and facilitating the laboratory screening of the energy efficiency and durability of materials solutions for certain tribological systems—in this case, engine components. The tribological test results give information about the behavior of materials, while the engine tests gives information about the behavior of components. In this paper, the environmental impact of the production process of the coatings is also analyzed. Two hard chrome processes are compared, demonstrating that by controlling the production process it is possible to significantly reduce the environmental impact of the chrome-plated process, minimizing the environmental impact to that of PVD coatings. The environmental impact of the tested HVOF process is lower than traditional Cr(VI)-plated coatings but higher than PVD coatings. Combining the information from the lifecycle assessment (LCA) and tribological studies, it is possible to assess both the performance and the environmental impact of the surface treatments. This methodology is a tool to that can be used minimize CO2 emissions at the design phase to improve the energy efficiency of products and processes.
The Proline-rich Domain of Dynamin-2 Is Responsible for Dynamin-dependent in Vitro Potentiation of Endothelial Nitric-oxide Synthase Activity via Selective Effects on Reductase Domain Function (2003)

The GTPase dynamin-2 (dyn-2) binds and positively regulates the nitric oxide-generating enzyme, endothelial nitric-oxide synthase (eNOS) (Cao, S., Yao, Y., McCabe, T., Yao, Q., Katusic, Z., Sessa, W., and Shah, V. (2001) J. Biol. Chem. 276, 14249-14256). Here we demonstrate, using purified proteins, that this occurs through a selective influence of the dyn-2 proline-rich domain (dyn-2 PRD) on the eNOS reductase domain. In vitro studies demonstrate that dyn-2 PRD fused with glutathione S-transferase (GST) binds recombinant eNOS protein specifically and with binding kinetics comparable with that observed between dyn-2 full-length and eNOS. Additionally, GST-dyn-2 PRD binds the in vitro transcribed (35)S-eNOS reductase domain but not the (35)S-eNOS oxygenase domain. Furthermore GST-dyn-2 PRD binds a (35)S-labeled eNOS reductase domain fragment (amino acids 645-850) that partially overlaps with the FAD binding domain of eNOS. A recombinant form of the SH3-containing protein Fyn competes the binding of recombinant eNOS protein with dyn-2 PRD, thereby implicating the SH3-like region contained within this reductase domain fragment as the dyn-2 binding region. Mammalian two-hybrid screen corroborates these interactions in cells as well. Functional studies demonstrate that dyn-2 PRD selectively potentiates eNOS activity in a concentration-dependent manner in an order of magnitude similar to that observed with dyn-2 full-length and in a manner that requires calmodulin. Although dyn-2 PRD does not influence eNOS oxygenase domain function or ferricyanide reduction, it does potentiate the ability of recombinant eNOS to reduce cytochrome c, supporting an influence of dyn-2 PRD on electron transfer between FAD and FMN. (These data indicate that the binding domains of dyn-2 and eNOS reside within the dyn-2 PRD domain and the FAD binding region of the eNOS reductase domains, respectively, and that dyn-2 PRD is sufficient to mediate dyn-2-dependent potentiation of eNOS activity, at least in part, by potentiating electron transfer.)
Outer Membrane Protein A (OmpA) of Shigella flexneri 2a, Induces Protective Immune Response in a Mouse Model (2011)

These results suggest that the OmpA of S. flexneri 2a can be an efficacious mucosal immunogen inducing protective immune responses. Our findings also demonstrate that antibodies and Th1 immune response may be associated with the marked protective efficacy of immunized mice after intranasal shigellae infection.
Intragastric Distribution of Ion-exchange Resins: a Drug Delivery System for the Topical Treatment of the Gastric Mucosa (1995)

Previous studies by this group on freeze-dried oral dosage forms containing finely-divided ion-exchange resins revealed prolonged gastric residence and uniform distribution within the stomach. The present study was carried out to ascertain whether this was due to freeze-drying, properties of the radiolabelled ionic exchange resin, or the small dosing volume used. 99mTc-labelled cholestyramine resin was administered in two dosage forms, a freeze-dried tablet which dissolved in the oral cavity (orally dissolving tablet; ODT) and a 1.5 mL aqueous suspension. Two resin particle sizes (20-40 and 90-125 microns) were studied. Oesophageal transit and intragastric distribution and residence were followed by gamma scintigraphy. In a second study, in six subjects, gastric emptying of the water-soluble fraction of the ODT and 1.5 mL of water, was measured using 99mTc diethylenetriaminepentaacetic acid. Oesophageal transit of a water-soluble marker and resin in suspension was rapid, but the transit of the resin in the ODTs was significantly prolonged. Regardless of particle size or dosage form, the resin was evenly distributed throughout the stomach with 20-25% remaining for 5.5 h. In contrast, the water-soluble marker cleared from the stomach rapidly from both dosage forms. We suggest that oral dose forms containing finely-divided ion-exchange resins may form a useful system for topical treatment of the gastric mucosa, for example in targeting to Helicobacter pylori infection.
Deletion of AA9 Lytic Polysaccharide Monooxygenases Impacts A. nidulans Secretome and Growth on Lignocellulose (2022)

Lytic polysaccharide monooxygenases (LPMOs) are oxidative enzymes found in viruses, archaea, and bacteria as well as eukaryotes, such as fungi, algae and insects, actively contributing to the degradation of different polysaccharides. In Aspergillus nidulans, LPMOs from family AA9 (<i>An</i>LPMO9s), along with an AA3 cellobiose dehydrogenase (<i>An</i>CDH1), are cosecreted upon growth on crystalline cellulose and lignocellulosic substrates, indicating their role in the degradation of plant cell wall components. Functional analysis revealed that three target LPMO9s (<i>An</i>LPMO9C, <i>An</i>LPMO9F and <i>An</i>LPMO9G) correspond to cellulose-active enzymes with distinct regioselectivity and activity on cellulose with different proportions of crystalline and amorphous regions. <i>An</i>LPMO9s deletion and overexpression studies corroborate functional data. The abundantly secreted <i>An</i>LPMO9F is a major component of the extracellular cellulolytic system, while <i>An</i>LPMO9G was less abundant and constantly secreted, and acts preferentially on crystalline regions of cellulose, uniquely displaying activity on highly crystalline algae cellulose. Single or double deletion of <i>An</i>LPMO9s resulted in about 25% reduction in fungal growth on sugarcane straw but not on Avicel, demonstrating the contribution of LPMO9s for the saprophytic fungal lifestyle relies on the degradation of complex lignocellulosic substrates. Although the deletion of <i>An</i>CDH1 slightly reduced the cellulolytic activity, it did not affect fungal growth indicating the existence of alternative electron donors to LPMOs. Additionally, double or triple knockouts of these enzymes had no accumulative deleterious effect on the cellulolytic activity nor on fungal growth, regardless of the deleted gene. Overexpression of <i>An</i>LPMO9s in a cellulose-induced secretome background confirmed the importance and applicability of <i>An</i>LPMO9G to improve lignocellulose saccharification. <b>IMPORTANCE</b> Fungal lytic polysaccharide monooxygenases (LPMOs) are copper-dependent enzymes that boost plant biomass degradation in combination with glycoside hydrolases. Secretion of LPMO9s arsenal by Aspergillus nidulans is influenced by the substrate and time of induction. These findings along with the biochemical characterization of novel fungal LPMO9s have implications on our understanding of their concerted action, allowing rational engineering of fungal strains for biotechnological applications such as plant biomass degradation. Additionally, the role of oxidative players in fungal growth on plant biomass was evaluated by deletion and overexpression experiments using a model fungal system.
Formation of a stable ascorbic acid 2-glucoside by specific transglucosylation with rice seed .ALPHA.-glucosidase. (1990)

The enzymatic transglucosylation to synthesize a chemically stable form of I -ascorbic acid (AA) was further investigated by using commercially available enzymes. Among various glycosidases examined, only rice seed α-glucosidase could produce a nonreducing and stable glucoside of AA, which was identified as 2-O-α-D-glucopyranosyl-L-ascorbic acid (AA-2G). The enzyme showed the same regioselective transglucosylase activity as rat intestinal α-glucosidase that had been demonstrated by us to be effective in this reaction, although these two enzymes had different pH optima for maltose hydrolysis. The substrate specificity of rice α-glucosidase for AA-2G formation was considerably different from that of rat α-glucosidase. However, both α-glucosidases had high specificity for the α-1, 4-glucosidic linkage but not α-1, 6, suggesting that they can catalyze a preferential transglucosylation to the 2-position but not to the 6-position of AA. Thus, these results allows us to produce a sufficient amount of AA-2G with rice seed α-glucosidase for its application to medicinal and other uses.
Review of Hemoglobin‐Vesicles as Artificial Oxygen Carriers (2009)

Blood transfusion systems have greatly benefited human health and welfare. Nevertheless, some problems remain: infection, blood type mismatching, immunological response, short shelf life, and screening test costs. Blood substitutes have been under development for decades to overcome such problems. Plasma component substitutes have already been established: plasma expanders, electrolytes, and recombinant coagulant factors. Herein, we focus on the development of red blood cell (RBC) substitutes. Side effects hindered early development of cell-free hemoglobin (Hb)-based oxygen carriers (HBOCs) and underscored the physiological importance of the cellular structure of RBCs. Well-designed artificial oxygen carriers that meet requisite criteria are expected to be realized eventually. Encapsulation of Hb is one idea to shield the toxicities of molecular Hbs. However, intrinsic issues of encapsulated Hbs must be resolved: difficulties related to regulating the molecular assembly, and management of its physicochemical and biochemical properties. Hb-vesicles (HbV) are a cellular type of HBOC that overcome these issues. The in vivo safety and efficacy of HbV have been studied extensively. The results illustrate the potential of HbV as a transfusion alternative and promise its use for other clinical applications that remain unattainable using RBC transfusion.