gebhart/patrepeval huggingface dataset:
Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy (2004)

Restrictive dermopathy (RD), also called tight skin contracture syndrome (OMIM 275210), is a rare disorder mainly characterized by intrauterine growth retardation, tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, facial features (small mouth, small pinched nose and micrognathia), sparse/absent eyelashes and eyebrows, mineralization defects of the skull, thin dysplastic clavicles, pulmonary hypoplasia, multiple joint contractures and an early neonatal lethal course. Liveborn children usually die within the first week of life. The overall prevalence of consanguineous cases suggested an autosomal recessive inheritance. We explored nine fetuses/newborns children with RD. Two were found to have an heterozygous splicing mutation in the LMNA gene, leading to the complete or partial loss of exon 11 in mRNAs encoding Lamin A and resulting in a truncated Prelamin A protein. Lamins are major constituents of the nuclear lamina, a filamentous meshwork underlying the inner nuclear envelope. In the other seven patients, a unique heterozygous insertion leading to the creation of a premature termination codon was identified in the gene ZMPSTE24, also known as FACE-1 in human. This gene encodes a metalloproteinase specifically involved in the post-translational processing of Lamin A precursor. In all patients carrying a ZMPSTE24 mutation, loss of expression of Lamin A as well as abnormal patterns of nuclear sizes and shapes and mislocalization of Lamin-associated proteins was evidenced. Our results indicate that a common pathogenetic pathway, involving defects of the nuclear lamina and matrix, is involved in all RD cases. RD is thus one of the most deleterious laminopathies identified so far in humans caused by (primary or secondary) A-type Lamin defects and nuclear structural and functional alterations.
The derivation problem of summary data (1988)

Given a statistical database consisting of two summary tables based on a common but not identical classification criterion (e.g., two geographical partitionings of a country) there are additional summary tables that are derivable in the sense that they are uniquely (i.e., with no uncertainty) determined by the tables given. Derivable tables encompass not only, of course, “less detailed” tables (that is, aggregated data) but also “more detailed” tables (that is, disaggregated data). Tables of the second type can be explicitly constructed by using a “procedure of data refinement” based on the graph representation of the correspondences between the categories of the two classification systems given in some cases, that is, when such a graph representation meets the acyclicity condition, the underlying database is “equivalent” to a single table (called representative table ) and then a necessary and sufficient condition for a table to be derivable can be stated.
Clinical validation of an in-house EPID dosimetry system for IMRT QA at the Prince of Wales Hospital (2013)

In this study a simple method using standard flood-field corrected Electronic Portal Imaging Device (EPID) images for routine Intensity Modulated Radiation Therapy (IMRT) Quality Assurance (QA) was investigated. The EPID QA system was designed and tested on a Siemens Oncor Impression linear accelerator with an OptiVue 1000ST EPID panel (Siemens Medical Solutions USA, Inc, USA) and an Elekta Axesse linear accelerator with an iViewGT EPID (Elekta AB, Sweden) for 6 and 10 MV IMRT fields with Step-and-Shoot and dynamic-MLC delivery. Two different planning systems were used for patient IMRT field generation for comparison with the measured EPID fluences. All measured IMRT plans had >95% agreement to the planning fluences (using 3 cGy / 3 mm Gamma Criteria) and were comparable to the pass-rates calculated using a 2-D diode array dosimeter.
Photoluminescence Studies on Eu2+-Activated Li2SrSiO4a Potential Orange-Yellow Phosphor for Solid-State Lighting (2006)

A series of Eu2+-activated Li2SrSiO4 orange-yellow phosphor compositions exhibiting intense emission under 400−470 nm excitation are synthesized by solid-state reaction, and their luminescence properties are investigated as a function of activator concentration (Eu2+). The critical concentration is found to be 0.005 mol of Eu2+ (Rc = 34 Å) per formula unit. The composition containing 0.005 mol of Eu2+ is also synthesized by a combustion technique followed by postannealing at different temperatures. The luminescence emission intensity of a combustion-synthesized sample increases with increasing annealing temperature. This is attributed to increased crystallinity and improved distribution of activator in the lattice in the combustion-synthesized sample. Attempts are made to develop white light-emitting diodes by combining an InGaN blue LED chip (420 nm) and a Li2SrSiO4: Eu2+ phosphor. Two distinct emission bands from the InGaN and Li2SrSiO4:Eu2+ (562 nm) are observed that combine to give a spectrum that appears white to the naked eye. The values of the CIE coordinates indicate that the Li2SrSiO4:Eu2+-coated LED has improved red emission compared to the commercial YAG:Ce phosphor.
Expression of the mucosal lymphocyte integrin alpha E beta 7 and its ligand E-cadherin in the synovium of patients with rheumatoid arthritis. (1996)

The synovial expression of the mucosal lymphocyte integrin alpha E beta 7 and its ligand E-cadherin was analysed in order to study the relationship between T lymphocytes of the gastrointestinal tract and the synovium in patients with rheumatoid arthritis (RA). Immunohistochemical evaluation of synovium revealed that the alpha E beta 7-expression was detectable in 16 of the 38 samples examined. A concomitant examination on circulating lymphocytes by flow cytometry showed that alpha E beta 7-expressing lymphocytes occur less frequently in peripheral blood (PB). In vitro culture of lymphocytes increased the alpha E beta 7-expression on synovial lymphocytes six-fold, whereas PB lymphocytes expressed a two-fold increase. The addition of PHA to the culture medium did not dramatically increase the alpha E beta 7-expression on synovial lymphocytes, in contrast to PB lymphocytes where a 24-fold increase was detected. The addition of TGF-beta 1 to the culture of PB lymphocytes increased the alpha E beta 7-expression three-fold. E-cadherin expression was found in all synovial tissues analysed by immunohistochemistry. These results demonstrate that synovial T lymphocytes have the capacity to express the 'mucosal-type' integrin alpha E beta 7, possibly due to high levels of intra-articular TGF-beta 1. This expression might be of physiological importance since E-cadherin, the ligand for alpha E beta 7, is richly expressed by synoviocytes. In addition, the results indicate that a high in vivo expression of alpha E beta 7 is suppressed in the synovial tissue by a hitherto unknown mechanism.
Site‐directed mutagenesis studies of the metal‐binding center of the iron‐dependent propanediol oxidoreductase from Escherichia coli (1998)

The amino acid residues involved in the metal-binding site in the iron-containing dehydrogenase family were characterized by the site-directed mutagenesis of selected candidate residues of propanediol oxidoreductase from Escherichia coli. Based on the findings that mutations H263R, H267A and H277A resulted in iron-deficient propanediol oxidoreductases without catalytic activity, we identified three conserved His residues as iron ligands, which also bind zinc. The Cys362, a residue highly conserved among these dehydrogenases, was considered another possible ligand by comparison with the sequences of the medium-chain dehydrogenases. Mutation of Cys362 to Ile, resulted in an active enzyme that was still able to bind iron, with minor changes in the Km values and decreased thermal stability. Furthermore, in an attempt to produce an enzyme specific only for the zinc ion, three mutations were designed to mimic the catalytic zinc-binding site of the medium-chain dehydrogenases: (1) V262C produced an enzyme with altered kinetic parameters which nevertheless retained a significant ability to bind both metals, (2) the double mutant V262C-M265D was inactive and too unstable to allow purification, and (3) the insertion of a cysteine at position 263 resulted in a catalytically inactive enzyme without iron-binding capacity, while retaining the ability to bind zinc. This mutation could represent a conceivable model of one of the steps in the evolution from iron to zinc-dependent dehydrogenases.
Modelling and optimization of the (R)-(+)-3, 4-dihydroxyphenyllactic acid production catalyzed with D-lactate dehydrogenase from Lactobacillus leishmannii using genetic algorithm (2005)

A mathematical model for the enzymatic kinetics of the synthesis of (R)-(+)-3,4-dihydroxyphenyllactic acid (DHPL) was developed. The synthesis was catalyzed by D-lactate dehydrogenase from Lactobacillus leishmannii. Sincethis enzyme requires NADH as a coenzyme, formate dehydrogenase system was used for NADH regeneration. Kinetic constants of both enzymes were estimated independently from initial reaction rate experiments. The developed mathematical model was verified by the batch reactor experiment (volumetric productivity in this experiment was 4.76 g dm - 3 d - 1 ). Optimization of initial reaction conditions for DHPL synthesis was performed using the genetic algorithm (GA). The genetic algorithm as a flexible optimization tool had been used to obtain the experimental conditions where maximal volumetric productivity could be achieved. The optimal initial conditions were found in the investigated parameter area: c 3 , 4 - d i h y d r o x p h e n y l p y r u v i c a c i d = 4.69 mmol dm - 3 , c N A D + = 4.95 mmol dm - 3 , c f o r m a t e = 36.85 mmol dm - 3 , γ D - l a c t a t e d e h y d r o g e n a s e = 3 mg cm - 3 , γ f o r m a t e d e h y d r o g e n a s e = 2.94 mg cm - 3 and the reaction time 8.5 min. At these conditions volumetric productivity of 93.06 g dm - 3 d - 1 can be achieved.
Dynamic Infinite Relational Model for Time-varying Relational Data Analysis (2010)

We propose a new probabilistic model for analyzing dynamic evolutions of relational data, such as additions, deletions and split &amp;amp; merge, of relation clusters like communities in social networks. Our proposed model abstracts observed timevarying object-object relationships into relationships between object clusters. We extend the infinite Hidden Markov model to follow dynamic and time-sensitive changes in the structure of the relational data and to estimate a number of clusters simultaneously. We show the usefulness of the model through experiments with synthetic and real-world data sets. 1
Improved Procedure for the Reduction of N - 1 Content in Synthetic Oligonucleotides (1995)

Abstract By incorporating a “capping step” at the start of an oligonucleotide synthesis (“pre-cap”) and following a “SUP” work-up protocol with ammonium hydroxide, an overall improvement is observed in the quality of oligonucleotides synthesized on a large scale on controlled pore glass support (CPG). Rationalization of these results is provided.
Studies on a novel series of acyl ester prodrugs of prostaglandin F2 alpha. (1994)

A novel series of prostaglandin F2 alpha (PGF2 alpha) prodrugs, with acyl ester groups at the 9, 11, and 15 positions, was prepared in order to design clinically acceptable prostaglandins for treating glaucoma. Studies involving isolated esterases and ocular tissue homogenates indicated that 9-acyl esters cannot provide a prodrug since PGF2 alpha would not be formed as a product. In contrast, 11-mono, 15-mono, and 11, 15-diesters were converted to PGF2 alpha in ocular tissues and could, therefore, be considered as prodrugs of PGF2 alpha. Carboxylesterase (CE) appeared critically important for the hydrolytic conversion of those PGF2 alpha prodrugs where the 11 or 15-OH group was esterified and such prodrugs were not substrates for acetylcholinesterase (ACHE) or butyrylcholinesterase (BuCHE). The enzymatic hydrolysis of PGF2 alpha-1-isopropyl ester was also investigated for comparative purposes. This PGF2 alpha prodrug was a good substrate for CE, but was also hydrolysed by BuCHE, albeit at a much slower rate. The most striking feature of the enzymatic hydrolysis of PGF2 alpha-1-isopropyl ester in ocular tissue homogenates was that it was much faster than for prodrugs esterified at the 11 and/or 15 positions. In terms of ocular hypotensive activity, all prodrugs which showed detectable conversion to nascent PGF2 alpha were potent ocular hypotensives. Although no separation of ocular hypotensive and ocular surface hyperaemic effects was apparent for PGF2 alpha-1-isopropyl ester, a temporal separation of these effects was apparent for the novel PGF2 alpha ester series. This difference may reflect an unfavourably rapid conversion of PGF2 alpha-1-isopropyl ester in ocular surface tissues compared with anterior segment tissues.
Comparison of instruments for geoelectrical soil mapping at the field scale (2009)

In precision agriculture geoelectrical methods have shown their capability to detect spatial variation of important physico‐chemical soil parameters in an efficient way. Nevertheless, relationships between the electrical parameters (electrical conductivity or resistivity) and other soil properties are not always consistent over different fields. This can, to some extent, be due to the characteristics of instruments used for soil mapping. However, a limited amount of research has addressed this issue. In this study, seven instruments for mobile mapping (continuous geoelectrical measurements) available on the market were tested (ARP 03, CM‐138, EM38, EM38‐DD, EM38‐MK2, OhmMapper and Veris 3100). Instruments were employed on a sandy site in north‐east Germany. Measurements were compared to a profile, which has been investigated with a high accuracy reference. Additional investigations were conducted concerning the influences of temperature drift, seasonal variations and soil properties on soil EC. Marked differences between the instruments were found with respect to depth of investigation, accuracy and handling that have to be taken into account when geoelectrical surveys are planned or interpreted. Regarding depth of investigation and robustness of the measurements, ARP 03 and Veris 3100 seem to be the most suitable instruments for precision agriculture.
Esterases and putative lipases from tropical isolates of Aureobasidium pullulans (2007)

Esterases and lipases have been studied in a number of fungi, though very little is known about esterases from Aureobasidium pullulans especially from the African tropics. In this study, forty-two Zimbabwean isolates were screened for lipase activity on tributyrin agar. Extracellular esterase activities of seven selected isolates were studied under varying conditions using para-nitrophenol acetate as substrate. Twenty isolates (48%) showed lipolytic activity; sixteen showed negative results for lipase activity while the rest showed weak activities. Esterase activities in broth cultures ranged from 0.011-0.223 mmol/microg protein/min while activities ranged from 1.5-12.8 U/ml under solid state fermentation. The esterases were optimally active at pH 7.6-8.0, showed a temperature optimum of 35 degrees C and retained more than 50% activity at temperatures up to 60 degrees C and at pH 4.0-7.0 after 150 min. Enzyme production was optimal after 5-6 days with diammonium hydrogen phosphate as nitrogen source. Isolates showed variations in preference for carbon source for esterase production. The A. pullulans esterases differed from most fungal esterases in that they are optimally active in alkaline conditions and are active over a broad pH range.
Activity of N6-substituted 2-chloroadenosines at A1 and A2 adenosine receptors (1991)

Radioligand binding studies of N6-substituted adenosines at the A1 and A2 adenosine receptors of rat brain cortex and rat brain striatum, respectively, show that a 2-chloro substituent does not consistently change the affinity or the selectivity of these analogues for the A1 receptor. A 2-chloro substituent lowers the characteristic stereoselectivity of the A1 receptor toward the R diastereomer of N6-(1-phenyl-2-propyl)adenosine. A 2-chloro substituent consistently increases potency of N6-substituted adenosines as agonists at an adenosine A2 receptor stimulatory to adenylate cyclase in PC12 cell membranes.
Vibration Reduction Using Multi-Hump Extra-Insensitive Input Shapers (1995)

Input shaping is a method for reducing residual vibrations in computer controlled machines. Vibration is eliminated by convolving an input shaper, which is a sequence of impulses, with a desired system command to produce a shaped input. The shaped input then becomes the command to the system. Requiring the vibration reduction to be insensitive to modeling errors and system nonlinearities is critical to the success of the shaping process on any real system. Input shapers can be made very insensitive to parameter uncertainty; however, increasing insensitivity usually increases system delays. A design process is presented that generates input shapers with insensitivity-to-time-delay ratios that are much larger than traditionally designed input shapers. The advantages of the new shapers are demonstrated with simulations of a simple linear system and simulations of the MACE experimental apparatus.
Meis1 is specifically upregulated in kidney myofibroblasts during aging and injury but is not required for kidney homeostasis or fibrotic response (2018)

The homeobox transcription factor Meis1 is required for mammalian development, and its overexpression plays a role in tumorigenesis, especially leukemia. Meis1 is known to be expressed in kidney stroma, but its function in kidney is undefined. We hypothesized that Meis1 may regulate stromal cell proliferation in kidney development and disease and tested the hypothesis using cell lineage tracing and cell-specific Meis1 deletion in development, aging, and fibrotic disease. We observed strong expression of Meis1 in platelet-derived growth factor receptor-β-positive pericytes and perivascular fibroblasts, both in adult mouse kidney and to a lesser degree in human kidney. Either bilateral ischemia-reperfusion injury or aging itself led to strong upregulation of Meis1 protein and mRNA in kidney myofibroblasts, and genetic lineage analysis confirmed that Meis1-positive cells proliferate as they differentiate into myofibroblasts after injury. Conditional deletion of Meis1 in all kidney stroma with two separate tamoxifen-inducible Cre recombinase drivers had no phenotype with the exception of consistent induction of the tubular injury marker kidney injury molecule-1 (Kim-1) only in Meis1 mutants. Further examination of Kim-1 expression revealed linkage disequilibrium of Kim-1 and Meis1, such that Meis1 mutants carried the longer BALB/c Kim-1 allele. Unexpectedly, we report that this Kim-1 allele is expressed at baseline in wild-type BALB/c mice, without any associated abnormalities, including long-term fibrosis, as predicted from the literature. We conclude that Meis1 is specifically expressed in stroma and myofibroblasts of mouse and human kidney, that it is not required for kidney development, disease, or aging, and that BALB/c mice unexpectedly express Kim-1 protein at baseline without other kidney abnormality.
Serum insulin‐like growth factor‐I and insulin‐like growth factor binding protein‐3 in premature rupture of membranes (2002)

IGF-I and IGFBP-3 do not appear to play any significant role in the maintenance of pregnancy in PROM patients with preterm delivery, whether or not associated with emerging intrauterine infection.
A mouse model for beta 0-thalassemia. (1995)

We have used a "plug and socket" targeting technique to generate a mouse model of beta 0-thalassemia in which both the b1 and b2 adult globin genes have been deleted. Mice homozygous for this deletion (Hbbth-3/Hbbth-3) die perinatally, similar to the most severe form of Cooley anemia in humans. Mice heterozygous for the deletion appear normal, but their hematologic indices show characteristics typical of severe thalassemia, including dramatically decreased hematocrit, hemoglobin, red blood cell counts, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration, as well as dramatically increased reticulocyte counts, serum bilirubin concentrations, and red cell distribution widths. Tissue and organ damage typical of beta-thalassemia, such as bone deformities and splenic enlargement due to increased hematopoiesis, are also seen in the heterozygous animals, as is spontaneous iron overload in the spleen, liver, and kidneys. The mice homozygous for the b1 and b2 deletions should be of great value in developing therapies for the treatment of thalassemias in utero. The heterozygous animals will be useful for studying the pathophysiology of thalassemias and have the potential of generating a model of sickle cell anemia when mated with appropriate transgenic animals.
Leukotriene receptor antagonists for the treatment of asthma. (2000)

Leukotriene receptor antagonists (LTRAs) are novel medications that provide symptom control in patients with persistent asthma. Current guidelines recommend the use of LTRAs as a treatment option for patients with mild-persistent asthma of at least 12 years of age. As illustrated by the results of controlled, multicenter clinical trials with zafirlukast and montelukast, as well as studies with pranlukast in Japan, LTRAs reduce daytime and night time asthma symptoms, improve pulmonary function, lower beta-adrenergic agonist use, and reduce asthma morbidity in patients with mild-intermittent to moderate-persistent asthma. Moreover, several recent clinical studies demonstrate that these agents are effective in preventing exercise-induced bronchoconstriction in children, and in improving disease control in symptomatic patients taking inhaled steroids. Based on clinical results to date, LTRAs appear to be safe and well tolerated in patients with mildto- moderate asthma. These agents represent an important addition to the drug armamentarium against asthma.
Zinc Finger Tools: custom DNA-binding domains for transcription factors and nucleases (2006)

Individual zinc finger (ZF) domains that recognize DNA triplets with high specificity and affinity can be used to create designer transcription factors and nucleases that are specific for nearly any site in the genome. These domains can be treated as modular units and assembled to create a polydactyl protein that recognizes extended DNA sequences. Deter-mination of valid target sites and the subsequent design of ZF proteins (ZFPs) is error-prone and not trivial, however. As a result, the use of ZFPs have been restricted primarily to those labs with the appropriate expertise. To address these limitations, we have created a user-friendly utility called Zinc Finger Tools (ZF Tools) that can be accessed at the URL http://www.zincfingertools.org. User-supplied DNA sequences can be searched for target sites appropriate for either gene regulation or nuclease targeting. Using a database of experimentally characterized zinc finger domains, the amino acid sequence for a ZFP expected to bind to any chosen target site can be generated. A reverse engineering utility is provided to predict the binding site for a ZFP of known sequence.