gebhart/patrepeval huggingface dataset:
The amazing potential of fungi: 50 ways we can exploit fungi industrially (2019)

Fungi are an understudied, biotechnologically valuable group of organisms. Due to the immense range of habitats that fungi inhabit, and the consequent need to compete against a diverse array of other fungi, bacteria, and animals, fungi have developed numerous survival mechanisms. The unique attributes of fungi thus herald great promise for their application in biotechnology and industry. Moreover, fungi can be grown with relative ease, making production at scale viable. The search for fungal biodiversity, and the construction of a living fungi collection, both have incredible economic potential in locating organisms with novel industrial uses that will lead to novel products. This manuscript reviews fifty ways in which fungi can potentially be utilized as biotechnology. We provide notes and examples for each potential exploitation and give examples from our own work and the work of other notable researchers. We also provide a flow chart that can be used to convince funding bodies of the importance of fungi for biotechnological research and as potential products. Fungi have provided the world with penicillin, lovastatin, and other globally significant medicines, and they remain an untapped resource with enormous industrial potential.
Elimination of Latently HIV‐1‐Infected Cells by Lymphoblasts Armed with Bifunctional Antibody (2001)

The Fab' fragment of a monoclonal antibody (mAb) to CD3 and the F(ab')2 fragment of a mAb to human immunodeficiency virus 1 (HIV-1) gp41 were combined to generate a bifunctional antibody (BFA). The mAb to gp41 (IV1-4G6) has previously been shown to react with a number of HIV-1 strains and T-lymphoblastoid cells (TLBC) armed with the BFA (BFA-TLBC) effectively inhibited HIV-1 in primarily cultured lymphoblasts infected with the clinically isolated virus which was reactive to the mAb. Although BFA-TLBC could not cause cytolysis of 51Cr-labeled latently infected cells (OM-10.1) in 6 hr incubation, cocultivation of OM-10.1 cells with BFA-TLBC for 3 days or more eliminated the latently infected cells making the cells susceptible to BFA-TLBC. Therefore, BFA-TLBC may be beneficial for HIV-infected patients in eradicating latently infected cells which can not be eliminated even with highly active antiretroviral therapy (HAART).
Activation of the Erythropoietin (EPO) Receptor by Bivalent Anti-EPO Receptor Antibodies (1996)

Oligomerization of cytokine receptors including the erythropoietin (EPO) receptor has been advanced as a model for activation. If homodimerization of the EPO receptor activates it, then bivalent antibodies raised to the extracellular domain of the EPO receptor should also homodimerize and activate. Mouse monoclonal antibodies (IgG) raised to the soluble, extracellular domain of the human EPO receptor (EPOR) were found that would stimulate thymidine uptake of an human EPO-dependent cell line, UT-7/EPO. Dose response curves showed bell shapes where activity was low at low and high concentrations. Monovalent (Fab) fragments bound to the receptor but did not stimulate thymidine uptake, which indicates that two antibody binding sites are required for activation. The anti-EPOR antibodies stimulated the formation of burst forming unit erythroid colonies from human CD34+ cells purified from peripheral blood. This indicates that homodimerization of the EPO receptor by anti-EPOR antibodies is sufficient for both proliferation and differentiation of erythroid progenitor cells and that the constraints on dimerization necessary for activation are rather loose. Oligomerization of cytokine receptors including the erythropoietin (EPO) receptor has been advanced as a model for activation. If homodimerization of the EPO receptor activates it, then bivalent antibodies raised to the extracellular domain of the EPO receptor should also homodimerize and activate. Mouse monoclonal antibodies (IgG) raised to the soluble, extracellular domain of the human EPO receptor (EPOR) were found that would stimulate thymidine uptake of an human EPO-dependent cell line, UT-7/EPO. Dose response curves showed bell shapes where activity was low at low and high concentrations. Monovalent (Fab) fragments bound to the receptor but did not stimulate thymidine uptake, which indicates that two antibody binding sites are required for activation. The anti-EPOR antibodies stimulated the formation of burst forming unit erythroid colonies from human CD34+ cells purified from peripheral blood. This indicates that homodimerization of the EPO receptor by anti-EPOR antibodies is sufficient for both proliferation and differentiation of erythroid progenitor cells and that the constraints on dimerization necessary for activation are rather loose.
Technology evaluation: Matuzumab, Merck KGaA. (2004)

Merck KGaA is developing matuzumab, a fully humanized epidermal growth factor receptor (EGFR)-specific monoclonal antibody, as a potential treatment for EGFR-bearing tumors. Matuzumab is currently undergoing phase II clinical trials for gastric, cervical, pancreatic and ovarian cancers.
Expression of insulin-like growth factor-II mRNA-binding protein-3 as a marker for predicting clinical outcome in patients with esophageal squamous cell carcinoma (2014)

Insulin-like growth factor-II mRNA-binding protein-3 (IMP3) is an important factor in carcinogenesis, although its clinical significance in esophageal squamous cell carcinoma (ESCC) remains unknown. The present study investigated the associations between IMP3 expression and the clinicopathological parameters. IMP3 expression was assessed in 191 resected ESCC specimens, and the associations between IMP3 expression in ESCC, the clinicopathological parameters and patient prognosis were examined. Using immunohistochemistry, 113 (59.2%) tumors were identified as IMP3-positive. IMP3 positivity correlated significantly with high pathological (p)Stage, pT stage and pN stage. The IMP3-positive patients exhibited a poorer prognosis compared with the IMP3-negative patients. In univariate analyses, histology [hazard ratio (HR), 1.94; 95% confidence interval (CI), 1.18-3.49; P=0.0082], pT (HR, 2.34; 95% CI, 1.55-3.62; P<0.0001), pN (HR, 2.85; 95% CI, 1.81-4.69; P<0.0001), lymphatic invasion (HR, 2.08; 95% CI, 1.26-3.70; P=0.0036), venous invasion (HR, 1.79; 95% CI, 1.21-2.64; P=0.0039), neoadjuvant chemotherapy (NAC) (HR, 2.01; 95% CI, 1.35-3.00; P=0.0005) and IMP3 expression (HR, 2.12; 95% CI, 1.40-3.29; P=0.0003) were significantly associated with overall survival. Using multivariate analyses, histology (HR, 1.87; 95% CI, 1.13-3.29; P=0.014), pN (HR, 2.19; 95% CI, 1.36-3.66; P=0.0010), NAC (HR, 1.88; 95% CI, 1.24-2.86; P=0.0028) and IMP3 expression (HR, 1.84; 95% CI, 1.18-2.93; P=0.0064) were significant prognostic factors. IMP3 may therefore be a prognostic factor for patients with ESCC who have undergone a curative resection.
The rôle of proteases and antiproteases in bronchial secretions. (1987)

A number of proteolytic enzymes (proteases) and their inhibitors (anti-proteases) have been demonstrated in the bronchial secretions. The most important of these proteases is probably the potent elastase derived from polymorphonuclear leukocytes (PMN) which are recruited into the bronchial tree during inflammation. This enzyme can degrade elastin, collagen and proteoglycan and can damage the bronchial epithelium; it is inhibited by antileukoprotease and by alpha protease inhibitor (API). Pulmonary macrophages also secrete an elastase, but Pseudomonas aeruginosa is the only microorganism known to produce elastase. Antileukoprotease is probably the most important of the antiproteases to be found in bronchial secretions. Other antiproteases such as low molecular weight inhibitors, API and alpha 2 macroglobulin have been demonstrated in bronchial secretions but they are present in low concentration. A balance between proteolytic enzymes and their inhibitors is thought to be of great importance in the prevention of proteolytic damage to local tissues, not only in emphysema but also in chronic bronchitis, bronchiectasis and cystic fibrosis. Oxidants derived from PMN or from tobacco smoke can inactivate protease inhibitors and in both the bronchial tree and the lung parenchyma, a balance between oxidants and anti-oxidants must presumably also be maintained to prevent local tissue damage.
Genetic controls balancing excitatory and inhibitory synaptogenesis in neurodevelopmental disorder models (2010)

Proper brain function requires stringent balance of excitatory and inhibitory synapse formation during neural circuit assembly. Mutation of genes that normally sculpt and maintain this balance results in severe dysfunction, causing neurodevelopmental disorders including autism, epilepsy and Rett syndrome. Such mutations may result in defective architectural structuring of synaptic connections, molecular assembly of synapses and/or functional synaptogenesis. The affected genes often encode synaptic components directly, but also include regulators that secondarily mediate the synthesis or assembly of synaptic proteins. The prime example is Fragile X syndrome (FXS), the leading heritable cause of both intellectual disability and autism spectrum disorders. FXS results from loss of mRNA-binding FMRP, which regulates synaptic transcript trafficking, stability and translation in activity-dependent synaptogenesis and plasticity mechanisms. Genetic models of FXS exhibit striking excitatory and inhibitory synapse imbalance, associated with impaired cognitive and social interaction behaviors. Downstream of translation control, a number of specific synaptic proteins regulate excitatory versus inhibitory synaptogenesis, independently or combinatorially, and loss of these proteins is also linked to disrupted neurodevelopment. The current effort is to define the cascade of events linking transcription, translation and the role of specific synaptic proteins in the maintenance of excitatory versus inhibitory synapses during neural circuit formation. This focus includes mechanisms that fine-tune excitation and inhibition during the refinement of functional synaptic circuits, and later modulate this balance throughout life. The use of powerful new genetic models has begun to shed light on the mechanistic bases of excitation/inhibition imbalance for a range of neurodevelopmental disease states.
Comparative Study of Latent Carcinoma of the Prostate Among Japanese in Japan and Hawaii 2 (1973)

Journal Article Comparative Study of Latent Carcinoma of the Prostate Among Japanese in Japan and Hawaii Get access Kaneyoshi Akazaki, Kaneyoshi Akazaki Aichi Cancer Center Research Institute, Nagoya, Japan; and Kuakini Hospital, Honolulu, Hawaii 96817 Search for other works by this author on: Oxford Academic PubMed Google Scholar Grant N. Stemmermann Grant N. Stemmermann Aichi Cancer Center Research Institute, Nagoya, Japan; and Kuakini Hospital, Honolulu, Hawaii 96817 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 5, May 1973, Pages 1137–1144, https://doi.org/10.1093/jnci/50.5.1137 Published: 01 May 1973 Article history Received: 10 October 1972 Accepted: 12 January 1973 Published: 01 May 1973
Interaction of Quinolones with Metal Cations in Aqueous Solution. (1996)

Quinolones are a group of potent antibacterial agents. Many reports show that oral absorption of quinolones is reduced by coadministration of metallic preparations. For better understanding of this phenomenon, we investigated the complex formations of quinolones (DU-6859a, DV-7751a, DR-3862, levofloxacin) with various metal cations by pH titrations, NMR and spectrophotometry. Several metal complexes including hydroxo species were confirmed by pH titrations. The order of stability constants among trivalent metal cations was Fe3+>Al3+, and those among devalent metal cations was Cu2+>Fe2+>Zn2+>Mg2+>Ca2+. The differences in stability constants among quinolones were not as large. Complex structures and metal complex formation equilibria in aqueous solution were proposed. Quinolones were belived to bind metal cations through carboxyl group and carbonyl group of the quinolone ring, and these equilibria show that there are two types of deprotonation reactions from metal complex : the several Fe3+ complexes and Al3+ complexes liberate protons from coordinated water molecules under acidic to neutral conditions, while the other complexes liberate protons from amine groups under neutral to alkaline conditions. Moreover, quantitative behavior of metal complex in aqueous solution has been demonstrated by simulation for the first time. The simulation especially showed that quinolones interact with Al3+ in the stomach, but with Mg2+ in the intestines when coadministered with antacid containing Al3+ and Mg2+. These results suggest that the complex formation of quinolones with metal cations is an important factor affecting absorption of the former in the gastrointestinal tract.
Concerns regarding sacral neuromodulation as a treatment option for medical-refractory overactive bladder (2011)

acral neuromodulation (SNM) with Interstim therapy (Medtronic, Minneapolis, MN) has become one of the accepted treatment options for patients with medication-refractory overactive bladder (OAB) with or without incontinence. 1While this modality has shown some interesting results, many unanswered questions remain.With the current data available, we do not recommend SNM for OAB patients for the following reasons.
Celiac disease: how complicated can it get? (2010)

In the small intestine of celiac disease patients, dietary wheat gluten and similar proteins in barley and rye trigger an inflammatory response. While strict adherence to a gluten-free diet induces full recovery in most patients, a small percentage of patients fail to recover. In a subset of these refractory celiac disease patients, an (aberrant) oligoclonal intraepithelial lymphocyte population develops into overt lymphoma. Celiac disease is strongly associated with HLA-DQ2 and/or HLA-DQ8, as both genotypes predispose for disease development. This association can be explained by the fact that gluten peptides can be presented in HLA-DQ2 and HLA-DQ8 molecules on antigen presenting cells. Gluten-specific CD4(+) T cells in the lamina propria respond to these peptides, and this likely enhances cytotoxicity of intraepithelial lymphocytes against the intestinal epithelium. We propose a threshold model for the development of celiac disease, in which the efficiency of gluten presentation to CD4(+) T cells determines the likelihood of developing celiac disease and its complications. Key factors that influence the efficiency of gluten presentation include: (1) the level of gluten intake, (2) the enzyme tissue transglutaminase 2 which modifies gluten into high affinity binding peptides for HLA-DQ2 and HLA-DQ8, (3) the HLA-DQ type, as HLA-DQ2 binds a wider range of gluten peptides than HLA-DQ8, (4) the gene dose of HLA-DQ2 and HLA-DQ8, and finally,(5) additional genetic polymorphisms that may influence T cell reactivity. This threshold model might also help to understand the development of refractory celiac disease and lymphoma.
Genetic reductionist approach for studing the two-component signaling system in Staphylococcus aureus (2014)

Staphylococcus aureus es una bacteria ubicua capaz de colonizar una gran variedad de ambientes. En el hombre, S. aureus coloniza las fosas nasales, piel de las axilas, ingles, garganta o incluso el tracto intestinal. Se calcula que un 20% de las personas adultas son portadores nasales de S. aureus. En determinadas circunstancias. la bacteria es capaz de atravesar la barrera epitelial y alcanzar los organos internos. Cuando esto ocurre, S. aureus se convierte en un patogeno muy versatil capaz de causar enfermedades muy diversas que pueden ir desde infecciones leves como forunculos o abscesos hasta enfermedades graves como endocarditis, osteomielitis, neumonia osindrome del shock toxico. El desarrollo de S. aureus en distintos ambientes requiere que la bacteria sea capaz de sensar las condiciones ambientales, transmitir los estimulos al citoplasma y activar los cambios necesarios para adecuar la fisiologia a dicho ambiente. El principal mecanismo para sensar y responder a las senales ambientales en bacterias son los sistemas de dos-componentes (TCSs). Los TCSs estan formados por un sensor de membrana o histidina kinasa (HK) y un regulador de respuesta citoplasmico (RR). En el proceso de activacion, el sensor recibe su senal especifica y se autofosforila en un dominio histidina. A continuacion el fosfato es transferido al residuo aspartico del RR que se encuentra en el citoplasma. De esta forma, el RR se activa y desencadena una respuesta que sera acorde a la senal recibida. Normalmente, una bacteria posee varios TCSs, siendo su numero proporcional al tamano del genoma, al numero de ambientes distintos en las que es capaz de crecer y a la complejidad de su diferenciacion celular. Asi, bacterias que viven en ambientes muy constantes, como las bacterias intracelulares estrictas carecen de TCSs, mientras que bacterias que viven en ambientes diversos pueden poseer cientos de ellos. En relacion con el numero y la funcion de los TCSs existen varias preguntas que hasta ahora no han sido analizadas: ?Cuantos TCSs necesita una bacteria de vida libre? ?Son necesarios los TCSs cuando la bacteria crece en un ambiente constante? ?Existe activacion cruzada entre TCSs distintos in vivo?
Antibody‐induced degradation of acetylcholine receptor in myasthenia gravis (1981)

Sera of myasthenic patients containing anti-AChR antibodies increase the rate of degradation of mammalian AChR. This phenomenon, antigenic modulation (AMd), was tested on AChR of rat myotubes in serum from 48 myasthenic patients. Sixty-six percent of the sera increased AChR degradation. AMd activity was higher in more severely affected patients, paralleled clinical evolution in individual patients, and was related to AChR-antibody titer. Steroid treatment and thymectomy did not affect AMd activity. Patients who had a thymoma always had greater AMd activity.
Formulation Development and Evaluation of Gastroresistant Microparticles of Diosmin for the Treatment of Chronic Venous Insufficiency (CVI) (2015)

Diosmin exhibits antioxidant and anti-inflammatory activities, improves venous tone and is used for the treatment of chronic venous insufficiency. In this research, Gastroresistant microparticles of diosmin were prepared by a spray-drying process using cellulose acetate phthalate (CAP) as enteric polymer and a series of enhancers of dissolution rate, such as sodium carboxymethylcellulose (NaCMC), sodium lauryl sulphate and Tween 80. The raw materials were characterized by DSC. The prepared microparticles were analyzed by DSC and scanning electron microscopy. In-vitro dissolution tests were carried out using a pH-change method to find out the influence of formulative parameters on the drug release from microparticles. The presence of a combination of CAP and enhancers in the formulations produced microparticles with good resistance at low pH of the gastric fluid and complete flavanoid release in the simulated intestinal environment. The spraydrying technique and the process conditions selected for microparticles were able to give satisfactory encapsulation efficiency, production yield, microparticles morphology and a complete drug release in the intestine.
Regulation of cyclin D1, DNA topoisomerase I, and proliferating cell nuclear antigen promoters during the cell cycle. (1995)

Cyclin D1, DNA topoisomerase I, and proliferating cell nuclear antigen (PCNA) are three important cell cycle regulatory proteins. Recently, their promoters have been isolated, thus facilitating molecular analysis of transcriptional control mechanisms of these genes. Transcription of these three promoters in stable K562 transfectants during different cell cycle phases was analyzed after cell cycle synchronization. About 1 kb of 5' flanking region from either cyclin D1 or DNA topoisomerase I gene is sufficient to confer G1- or S-phase-specific transcription activity to chloramphenicol acetyltransferase (CAT) reporter genes, respectively. In contrast, 2.8 kb of 5' flanking sequences from the PCNA gene led to constitutive transcription, but the inclusion of a segment of the PCNA gene first intron, which contains evolutionarily conserved sequences, could enhance transcription in G1/S-enriched nuclei. This PCNA intron region contains a binding site recognized by the transcription factor E2F. To test whether this site is functional, we cotransfected PCNA-CAT genes with E2F-1 and DP-1 expression plasmids. Expression of the E2F-1/DP-1 heterodimer activated the CAT gene with the PCNA intron. Therefore, this intron region, involved in transcriptional activation at the cell cycle G1/S boundary, is also E2F inducible.
Integration Mechanisms in the FIELD Environment (1988)

Selective broadcasting is a mechanism that allows a wide variety of programming tools to be combined in an integrated environment. It follows the UNIX philosophy of allowing independent tools to cooperate easily though simple conventions while at the same time providing the functionality necessary to a complex programming environment. It is combined with an annotation editor that allows consistent, multi-function access to source files in the FIELD programming environment. FIELD demonstrates the power and capabilities of these mechanisms. It is currently being used for both instruction and research at Brown University.
Purification and characterization of a retinol-binding glycoprotein synthesized and secreted by bovine neural retina. (1984)

A retinol-binding glycoprotein ( IRBP ) was purified in milligram quantities from the extracellular matrix ( interphotoreceptor matrix) that occupies the subretinal space in bovine eyes. IRBP binds 2.2 molecules of all-trans retinol with a KD of approximately 10(-6) M. The holoprotein has lambda max at 280 nm (E1%1 cm = 10.99) and at 330 nm (E1%1 cm = 7.88). When freshly isolated from light-exposed eyes, IRBP contains up to 0.6 molecule of all-trans retinol, together with small amounts of the 11-cis and 13-cis isomers. IRBP also binds exogenous cholesterol, alpha-tocopherol, and all-trans retinoic acid, all of which are completely displaced by all trans retinol. The affinity of alpha-tocopherol for IRBP was at least several orders of magnitude less than that of all-trans retinol. IRBP contains 8.4% by weight of carbohydrate, which consists of sialic acid, neutral hexoses, and glucosamine in the molar ratio of approximately 1:3:2. No galactosamine was detected. Observations on the binding of 125I-labeled lectins to IRBP in sodium dodecyl sulfate-polyacrylamide gels before and after desialosylation suggest that at least one oligosaccharide chain is of the sialated biantennary complex type and contains fucose. The Mr of IRBP on calibrated size-exclusion columns averaged 249,000; on sodium dodecyl sulfate-polyacrylamide gels (with or without dithiothreitol) the apparent Mr was 144,000. IRBP exists in at least four isoelectric forms that bind concanavalin A and have pI values ranging from 4.4 to 4.8. Rabbit anti-bovine IRBP antiserum gave a single precipitin line against purified bovine IRBP , which showed a line of complete identity with crude bovine interphotoreceptor matrix and a line of partial identity with human interphotoreceptor matrix. The human material contains a prominent protein with lectin-binding properties similar to bovine IRBP but with a somewhat faster electrophoretic mobility. When isolated bovine neural retinas were incubated with 3H-labeled fucose, glucosamine, or leucine, a solitary labeled protein identified as IRBP was secreted into the medium. Labeled IRBP could not be detected in the medium when retinal pigment epithelium was incubated with these precursors under the same conditions. Neural retinas incubated with 3H-labeled leucine in the presence of tunicamycin secreted a form of IRBP that did not bind concanavalin A and had an Mr reduced by approximately 5,000.