gebhart/patrepeval huggingface dataset:
Cultivation of rat marrow‐derived mesenchymal stem cells in reduced oxygen tension: Effects on in vitro and in vivo osteochondrogenesis (2001)

Rat mesenchymal stem cells (rMSCs) represent a small portion of the cells in the stromal compartment of bone marrow and have the potential to differentiate into bone, cartilage, fat, and fibrous tissue. These mesenchymal progenitor cells were maintained as primary isolates and as subcultured cells in separate closed modular incubator chambers purged with either 95% air and 5% CO(2) (20% or control oxygen) or 5% oxygen, 5% CO(2), and 90% nitrogen (5% or low oxygen). At first passage, some cells from each oxygen condition were loaded into porous ceramic vehicles and implanted into syngeneic host animals in an in vivo assay for osteochondrogenesis. The remaining cells were continued in vitro in the same oxygen tension as for primary culture or were switched to the alternate condition. The first passage cells were examined for in vitro osteogenesis with assays involving the quantification of alkaline phosphatase activity and calcium and DNA content as well as by von Kossa staining to detect mineralization. Cultures maintained in low oxygen had a greater number of colonies as primary isolates and proliferated more rapidly throughout their time in vitro, as indicated by hemacytometer counts at the end of primary culture and increased DNA values for first passage cells. Moreover, rMSCs cultivated in 5% oxygen produced more bone than cells cultured in 20% oxygen when harvested and loaded into porous ceramic cubes and implanted into syngeneic host animals. Finally, markers for osteogenesis, including alkaline phosphatase activity, calcium content, and von Kossa staining, were elevated in cultures which had been in low oxygen throughout their cultivation time. Expression of these markers was usually increased above basal levels when cells were switched from control to low oxygen at first passage and decreased for cells switched from low to control oxygen. We conclude that rMSCs in culture function optimally in an atmosphere of reduced oxygen that more closely approximates documented in vivo oxygen tension.
Glucocorticoid-induced apoptosis in the thymus. (1992)

Destruction of thymus cells was one of the earliest observed properties of adrenal glucocorticoids. The cells affected are primarily immature, CD4/CD8 double-positive lymphocytes. This process has been clearly shown in vivo and in vitro to be apoptosis, as characterized by cell shrinkage, membrane alterations, nuclear collapse and chromatin fragmentation into oligonucleosomes. Glucocorticoid-induced thymocyte death requires new mRNA and protein synthesis. A beginning has been made in identifying the genes involved in thymocyte apoptosis. A case is made for the death of unselected thymocytes in vivo being regulated by endogenous glucocorticoids.
Controlled Release Technology, Agricultural (2004)

Abstract Controlled release formulations (CRFs) are intended to improve the delivery of pesticides and related biologically active substances. The consequent improvement in efficiency reduces losses in use and has many benefits, such as reduction in exposure to both workers and the environment, particularly in minimizing leaching and evaporation. This article introduces the advantages of CRFs and provides a theoretical rationale for their use based on pseudo‐first‐order loss kinetics, which are typical for pesticide dissipation in the environment. Thus, the greater the loss rate, especially for pesticides of short duration, the greater the potential for improvement in delivery to the target pest. As a consequence of this principle, reduced levels of pesticide delivered efficiently can be as efficacious as higher amounts of conventional formulations. The types of CRFs are introduced and are classified as physical, chemical, or biological. The kinetics of release from CRFs is central to their successful use, and the mathematical basics of this are described. The mechanisms of release vary according to the type of formulation, and these are covered for physical and chemical types. Common release characteristics include first order, diffusion (square root of time) based, and zero order (constant). Release kinetics are usually measured under controlled laboratory conditions, but field determination are preferable. Design of properties of CRFs then follow. The main groups of the physical‐type formulations, such as reservoirs with release‐rate controlling membranes and without membrane and the monolith or matrix structures, are those based on microencapsulated liquid cores in sprayable concentrate formulations, and polymeric matrix methods that are often fabricated as granules. The polymers used and the approaches employed for designing these types of CRFs are introduced with emphasis on encapsulation methods, such as phase separation and interfacial polymerization. In addition, other formulation types are included, such as laminates, coated granules, microparticles, matrix granules (swellable and nonswellable), matrix devices for animal and public health protection, plastic films, and mulches. The article closes with the recent biological approach to formulation based on living or dead genetically modified microorganisms containing proteinaceous toxins.
Improved base excision repair inhibition and bacteriophage Mu Gam protein yields C:G-to-T:A base editors with higher efficiency and product purity (2017)

We recently developed base editing, the programmable conversion of target C:G base pairs to T:A without inducing double-stranded DNA breaks (DSBs) or requiring homology-directed repair using engineered fusions of Cas9 variants and cytidine deaminases. Over the past year, the third-generation base editor (BE3) and related technologies have been successfully used by many researchers in a wide range of organisms. The product distribution of base editing-the frequency with which the target C:G is converted to mixtures of undesired by-products, along with the desired T:A product-varies in a target site-dependent manner. We characterize determinants of base editing outcomes in human cells and establish that the formation of undesired products is dependent on uracil N-glycosylase (UNG) and is more likely to occur at target sites containing only a single C within the base editing activity window. We engineered CDA1-BE3 and AID-BE3, which use cytidine deaminase homologs that increase base editing efficiency for some sequences. On the basis of these observations, we engineered fourth-generation base editors (BE4 and SaBE4) that increase the efficiency of C:G to T:A base editing by approximately 50%, while halving the frequency of undesired by-products compared to BE3. Fusing BE3, BE4, SaBE3, or SaBE4 to Gam, a bacteriophage Mu protein that binds DSBs greatly reduces indel formation during base editing, in most cases to below 1.5%, and further improves product purity. BE4, SaBE4, BE4-Gam, and SaBE4-Gam represent the state of the art in C:G-to-T:A base editing, and we recommend their use in future efforts.
Rare Types of Genetic Hemochromatosis (2009)

Most types of genetic hemochromatosis are due to mutations in the HFE gene, although similar iron overload and organ damage can also result from mutations in genes other than HFE in rare types of hemochromatosis. Non-HFE hemochromatoses have been divided into two subgroups with distinctive features. The first includes juvenile and TFR2-related hemochromatoses that, similar to HFE hemochromatosis, show recessive inheritance, increased transferrin saturation, iron storage in hepatocytes and responsiveness to phlebotomy. Disorders in this subgroup, although differing regarding the severity of iron overload and/or the age at presentation, are all either due to hepcidin deficiency or to the inability to increase hepcidin levels according to iron stores. The second subgroup of hemochromatosis is caused by autosomal dominant mutations in the SLC40A1 gene encoding the iron exporter ferroportin with distinctive features. Iron loading of Kupffer cells and normal transferrin saturation characterize the so-called 'ferroportin disease'. In contrast, few mutations in SLC40A1 that cause hepcidin resistance lead to a hemochromatosis-like phenotype with dominant inheritance. The precise diagnosis of the genetic type of hemochromatosis is relevant for the follow-up, treatment, and for family counseling.
Major human epididymis‐specific gene product, HE3, is the first representative of a novel gene family (1994)

Differential screening of a human epididymal cDNA library led to the isolation and characterization of a major epididymis-specific cDNA clone family, referred to as HE3. More detailed sequence and PCR analysis identified two different but homologous gene transcripts, HE3 alpha and HE3 beta. The former represents an mRNA of ca. 1 kb, encoding a putative small secretory polypeptide of 14903 MW. The HE3 beta transcript was only found as incomplete 3' fragments. Analysis of human genomic DNA by Southern blotting suggested the presence in the human genome of at least three independent HE3-related genes. Isolation of genomic clones for the HE3 alpha gene showed this to contain a single intron of 1.4 kb in the 5' noncoding region. Although genomic clones corresponding to HE3 beta could not be found, a third highly homologous gene, HE3 gamma, was identified as a potential pseudogene. Neither nucleotide nor encoded amino acid sequences of the HE3 gene family are related to any other known sequence in the central databases, and thus represents a novel human gene family, with at least three nonallelic members. Northern hybridization analysis showed that HE3 gene products are specifically expressed in the human epididymis, and not in any other tissue examined. Furthermore, except for the pig, no other nonprimate species has been identified to express homologous sequences in the epididymis. RNase protection assays showed that both the HE3 alpha and HE3 beta, but not the HE3 gamma genes, are expressed in the human epididymis.
Generating query substitutions (2006)

We introduce the notion of query substitution, that is, generating a new query to replace a user's original search query. Our technique uses modifications based on typical substitutions web searchers make to their queries. In this way the new query is strongly related to the original query, containing terms closely related to all of the original terms. This contrasts with query expansion through pseudo-relevance feedback, which is costly and can lead to query drift. This also contrasts with query relaxation through boolean or TFIDF retrieval, which reduces the specificity of the query. We define a scale for evaluating query substitution, and show that our method performs well at generating new queries related to the original queries. We build a model for selecting between candidates, by using a number of features relating the query-candidate pair, and by fitting the model to human judgments of relevance of query suggestions. This further improves the quality of the candidates generated. Experiments show that our techniques significantly increase coverage and effectiveness in the setting of sponsored search.
Viral expression of insulin-like growth factor-I isoforms promotes different responses in skeletal muscle (2006)

Insulin-like growth factor I (IGF-I) is a critical protein for skeletal muscle development and regeneration. Its ability to promote skeletal muscle hypertrophy has been demonstrated by several methods. Alternative splicing of the Igf-1 gene does not affect the mature IGF-I protein but does produce different E peptide extensions, which have been reported to modify the potency of IGF-I. Viral-mediated delivery of murine IGF-IA and IGF-IB into skeletal muscle of 2-wk-old and 6-mo-old mice was utilized to compare the effects of the isoforms on muscle mass. In young mice, tissue content of IGF-I protein was significantly higher in rAAV-treated muscles than control muscles at 1, 2, and 4 mo postinjection. Viral injection of IGF-IB produced two- to sevenfold more IGF-I than rAAVIGF-IA. Hypertrophy was observed 2 and 4 mo postinjection, where both rAAVIGF-IA and rAAVIGF-IB were equally effective in increasing muscle mass. These results suggest that there is a threshold of IGF-I production necessary to promote muscle hypertrophy in young growing animals regardless of isoform. In 6-mo-old animals, only rAAVIGF-IA produced significant increases in muscle size, even though increased IGF-I content was observed after injection of both isoforms. Therefore, the ability for IGF-IB to promote muscle hypertrophy is only effective in growing animals, suggesting that the bioavailability of this isoform or its receptor affinity diminishes with age.
Constitutive Proteolysis of the ErbB-4 Receptor Tyrosine Kinase by a Unique, Sequential Mechanism (1997)

The heregulin receptor tyrosine kinase ErbB-4 is constitutively cleaved, in the presence or absence of ligand, by an exofacial proteolytic activity producing a membrane-anchored cytoplasmic domain fragment of 80 kD. Based on selective sensitivity to inhibitors, the proteolytic activity is identified as that of a metalloprotease. The 80-kD product is tyrosine phosphorylated and retains tyrosine kinase activity. Importantly, the levels of this fragment are controlled by proteasome function. When proteasome activity is inhibited for 6 h, the kinase-active 80-kD ErbB-4 fragment accumulates to a level equivalent to 60% of the initial amount of native ErbB-4 (approximately 10(6) receptors per cell). Hence, proteasome activity is essential to prevent the accumulation of a significant level of ligand-independent, active ErbB-4 tyrosine kinase generated by metalloprotease activity. Proteasome activity, however, does not act on the native ErbB-4 receptor before the metalloprotease-mediated cleavage, as no ErbB-4 fragments accumulate when metalloprotease activity is blocked. Although no ubiquitination of the native ErbB-4 is detected, the 80-kD fragment is polyubiquitinated. The data, therefore, describe a unique pathway for the processing of growth factor receptors, which involves the sequential function of an exofacial metalloprotease and the cytoplasmic proteasome.
Inhibition of rat lipoprotein lipid peroxidation by the oral administration of D003, a mixture of very long-chain saturated fatty acids (2002)

Previous results have demonstrated that policosanol, a mixture of aliphatic primary alcohols isolated and purified from sugar cane wax, whose main component is octacosanol, inhibited lipid peroxidation in experimental models and human beings. D003 is a defined mixture of very long-chain saturated fatty acids, also isolated and purified from sugar cane wax, whose main component is octacosanoic acid followed by traicontanoic, dotriacontanoic, and tetracontanoic acids. Since very long-chain fatty acids are structurally related to their corresponding alcohols, we investigated the effect of oral treatment with D003 (0.5, 5, 50, and 100 mg/kg) over 4 weeks in reducing the susceptibility of rat lipoprotein to oxidative modification. The combined rat lipoprotein fraction VLDL + LDL was subjected to several oxidation systems, including those containing metal ions (CuSO4), those having the capacity to generate free radicals 2,2-azobis-2-amidinopropane hydrochloride (AAPH), and a more physiological system (resident macrophages). D003 (5, 50, and 100 mg/kg) significantly inhibited copper-mediated conjugated-diene generation in a concentration-dependent manner. D003 increased lag phase by 53.1, 115.3, and 119.3%, respectively, and decreased the rate of conjugate-diene generation by 16.6, 21.5, and 19.6%, respectively. D003 also inhibited azo-compound initiated and macrophage-mediated lipid peroxidation as judged by the significant decrease in thiobarbituric acid reactive substance (TBARS) generation. In all the systems the maximum effect was attained at 50 mg/kg. There was also a parallel attenuation in the reduction of lysine amino groups and a significant reduction of carbonyl content after oxidation of lipoprotein samples. Taken together, the present results indicate that oral administration of D003 protects lipoprotein fractions against lipid peroxidation in the lipid as well in the protein moiety.
Essentials of dynamic walking; analysis and design of two-legged robots (2004)

One of the main challenges in the design of human-like walking robots (useful for service or entertainment applications as well as the study of human locomotion) is to obtain dynamic locomotion, as opposed to the static form of locomotion demonstrated by most of the current prototypes. A promising concept is the idea of passive dynamic walking; even completely unactuated and uncontrolled mechanisms can perform a stable gait when walking down a shallow slope. This concept enables the construction of dynamically walking prototypes that are simpler yet more natural in their motions than the static bipeds. This paper presents three additions to the concept of passive dynamic walking. First, hip actuation is added to increase the fore-aft stability and to provide power to the system, removing the need for a downhill floor. Second, a bisecting hip mechanism is introduced to allow the addition of a passive upper body without compromising the simplicity, efficiency and naturalness of the concept of passive dynamic walking. Third, skateboard-like ankle joints are implemented to provide 3D stability. These ankles couple the unstable sideways lean motion to yaw (steering), a kinematic coupling which provides sideways stability when walking with sufficient forward velocity. The three additions are investigated both with elementary simulation models and with prototype experiments. All three prototypes demonstrate an uncannily natural and stable gait while requiring only two foot switches and three on/off actuators. This research was performed in the context of the STW project number DWT4551 "Development of a ballistic walking biped" at the Delft Biorobotics Laboratory of the Man Machine Systems Group in the department of Mechanical Engineering.
Insulin-like receptor and insulin-like peptide are localized at neuromuscular junctions in Drosophila (1993)

Insulin and insulin-like growth factor (IGF) receptors are members of the tyrosine kinase family of receptors, and are thought to play an important role in the development and differentiation of neurons. Here we report the presence of an insulin-like peptide and an insulin receptor (dInsR) at the body wall neuromuscular junction of developing Drosophila larvae. dInsR-like immunoreactivity was found in all body wall muscles at the motor nerve branching regions, where it surrounded synaptic boutons. The identity of this immunoreactivity as a dInsR was confirmed by two additional schemes, in vivo binding of labeled insulin and immunolocalization of phosphotyrosine. Both methods produced staining patterns markedly similar to dInsR-like immunoreactivity. The presence of a dInsR in whole larvae was also shown by receptor binding assays. This receptor was more specific for insulin (> 25-fold) than for IGF II, and did not appear to bind IGF I. Among the 30 muscle fibers per hemisegment, insulin-like immunoreactivity was found only on one fiber, and was localized to a subset of morphologically distinct synaptic boutons. Staining in the CNS was limited to several cell bodies in the brain lobes and in a segmental pattern throughout most of the abdominal ganglia, as well as in varicosities along the neuropil areas of the ventral ganglion and brain lobes. Insulin-like peptide and dInsR were first detected by early larval development, well after neuromuscular transmission begins. The developmental significance of an insulin-like peptide and its receptor at the neuromuscular junction is discussed.
Tolerability of memantine in combination with cholinesterase inhibitors in dementia therapy. (2003)

Memantine, a moderate-affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to be effective in dementia, including Alzheimer disease (AD). Therefore, its combination with acetylcholinesterase inhibitors (AChEIs) is anticipated. We report a postmarketing surveillance study conducted among German physicians who, during routine clinical practice, treated demented patients with memantine in combination with an AChEI. Most of the 158 surveyed patients (mean age, 74 years) were diagnosed with AD but other dementias were included. Memantine was prescribed at a wide range of daily doses (median, 20 mg/day) and was combined with donepezil for most patients (84%). Combination therapy was well tolerated for nearly all patients (98%) for an average observation period of 4 months at stable doses of both antidementia agents. No serious adverse drug reaction (ADR) was reported. No ADR or change in blood chemistry was experienced by most patients (96% and 81%, respectively); the six reported ADRs resolved without sequelae and without drug discontinuation. Global clinical status of most patients was judged as improved (54%) or stable (39%) over the observation period. These findings particularly suggest that memantine in combination with AChEIs is safe and well tolerated.
Evaluation of Anti-TGF-β2 Antibody as a New Postoperative Anti-scarring Agent in Glaucoma Surgery (2003)

Postoperative administration of CAT-152 significantly improved surgical outcome, reduced subconjunctival scarring, and minimized the risk of corneal side effects compared with the anti-scarring agent 5-FU. These findings suggest that CAT-152 may offer therapeutic benefit as a postoperative agent to prevent subconjunctival scarring after glaucoma filtration surgery.
Fiber-coupler fabrication with automatic fusion-elongation processes for low excess loss and high coupling-ratio accuracy (1987)

A novel fiber-coupler fabrication system which automatically processes fusion and elongation is presented. Not only conventional single-mode fiber couplers but also polarization-maintaining fiber couplers with excellent characteristics such as excess losses less than 0.11 dB and coupling-ratio accuracy better than 1.3 percent were obtained. In addition, it was confirmed that polarization crosstalk for polarization-maintaining fiber couplers in the present system was lower than that for the conventional manual method. The fabrication yield and reliability of the present system have been much higher than those of the conventional method and the processing time for fabrication could also be reduced.
Characterisation of Syncytiotrophoblast Vesicles in Normal Pregnancy and Pre-Eclampsia: Expression of Flt-1 and Endoglin (2013)

This study has found differences in physical and antigenic characteristics of normal and PE placenta STBM preparations produced by placental perfusion or mechanical disruption. We have also demonstrated that large quantities of biologically active STBM associated endoglin and Flt-1/sFlt-1 could contribute to the increased circulating levels measured in PE patients and add to the perturbation of the maternal vascular endothelium, normally attributed to non-membrane bound sFlt-1 and sEndoglin.
Restriction Fragment Length Polymorphisms Can Differentiate among U.S. Maize Hybrids (1991)

Previous methods to differentiate U.S. maize hybrids using biochemical data have been criticized on the basis that the genome has been inadequately sampled. The objective of this study was to utilize an additional set of highly polymorphic genetic markers (restriction fragment length polymorphisms; RFLPs) to establish the degree to which these data discriminate among 78 elite maize ( Zea mays L.) U.S. hybrids selected with a bias toward including hybrid pairs previously undifferentiated by biochemical data. Thirty‐eight probes revealed 288 RFLP variants across all hybrids. RFLP and biochemical data clustered most hybrids into similar groupings. For those hybrids of known pedigree, distances between hybrids on the basis of pedigree showed a correlation of r = 0.91 with RFLP distances. Where available, field performance data gave identical groupings of hybrids as were shown by RFLP data. These data show that RFLPs can provide a practical means of differentiating hybrids.