gebhart/patrepeval huggingface dataset:
Molecular cloning and functional expression of codeinone reductase: the penultimate enzyme in morphine biosynthesis in the opium poppy Papaver somniferum (1999)

Summary The narcotic analgesic morphine is the major alkaloid of the opium poppy Papaver somniferum . Its biosynthetic precursor codeine is currently the most widely used and effective antitussive agent. Along the morphine biosynthetic pathway in opium poppy, codeinone reductase catalyzes the NADPH‐dependent reduction of codeinone to codeine. In this study, we have isolated and characterized four cDNAs encoding codeinone reductase isoforms and have functionally expressed them in Escherichia coli . Heterologously expressed codeinone reductase‐calmodulin‐binding peptide fusion protein was purified from E. coli using calmodulin affinity column chromatography in a yield of 10 mg enzyme l ‐1 . These four isoforms demonstrated very similar physical properties and substrate specificity. As least six alleles appear to be present in the poppy genome. A comparison of the translations of the nucleotide sequences indicate that the codeinone reductase isoforms are 53% identical to 6′‐deoxychalcone synthase from soybean suggesting an evolutionary although not a functional link between enzymes of phenylpropanoid and alkaloid biosynthesis. By sequence comparison, both codeinone reductase and 6′‐deoxy‐ chalcone synthase belong to the aldo/keto reductase family, a group of structurally and functionally related NADPH‐dependent oxidoreductases, and thereby possibly arise from primary metabolism.
MYD88 L265P Somatic Mutation in Waldenström's Macroglobulinemia (2012)

MYD88 L265P is a commonly recurring mutation in patients with Waldenström's macroglobulinemia that can be useful in differentiating Waldenström's macroglobulinemia and non-IgM LPL from B-cell disorders that have some of the same features. (Funded by the Peter and Helen Bing Foundation and others.).
Investigation of novel circulating proteins, germ line single-nucleotide polymorphisms, and molecular tumor markers as potential efficacy biomarkers of first-line sunitinib therapy for advanced renal cell carcinoma (2014)

Serum Ang-2 and MMP-2 and tumor HIF-1α were identified as relevant baseline biomarkers of sunitinib activity in advanced RCC, warranting further research into their prognostic versus predictive value.
Association of Variation in the Chromosome 9p21 Locus With Myocardial Infarction Versus Chronic Coronary Artery Disease (2008)

The chromosome 9p21 locus was not associated with incident events or prevalent MI, although it did predict CAD diagnosis. This contradicts reports of a 9p21 association with MI, likely because of differences in phenotype assignment. This suggests that high-quality phenotyping for CAD and MI is required to dissect the specific contributions of genetic variation to each stage of coronary heart disease pathophysiology.
Inhibition of malaria parasite invasion of human erythrocytes by a lymphocyte membrane polypeptide (1987)

Extraction by boiling of the buffy coat of human blood yields a protein solution which inhibits the propagation of the human malaria parasite Plasmodium falciparum in culture with a 50% inhibitory dose of 105 micrograms of protein per ml. The inhibitory activity is associated exclusively with the lymphocytes and affects solely the invasion of erythrocytes by free merozoites. Boiled extracts of isolated lymphocytes had a 50% inhibitory dose of 22 micrograms/ml. Fractionation of surface-labeled or pronase-treated lymphocytes revealed that the antimalarial lymphocyte factor is associated with the intracellular aspect of the membrane fraction and is probably not involved in the host defense system against malaria. Further purification by salt extraction, ion-exchange chromatography, molecular gel filtration, and electroelution from lithium dodecyl sulfate-polyacrylamide gels resulted in 300- to 550-fold purification, i.e., a 50% inhibitory dose of 40 to 70 ng/ml. All inhibitory fractions contained a 48-kilodalton polypeptide which eluted from a gel filtration column as a 400-kilodalton species, implying multimeric association. Some 6,000 molecules of the 48-kilodalton polypeptide bind with high affinity to one merozoite, the free form of the parasite. The Kd of 0.1 to 0.5 nM for the binding of the 48-kilodalton polypeptide correlated well with the 50% inhibitory dose of 0.3 to 0.4 nM obtained with purified active antimalarial lymphocyte factor. We therefore suggest that the 48-kilodalton polypeptide partially purified from lymphocyte membranes is the antimalarial lymphocyte factor and that it exerts its inhibitory activity by binding to merozoites, thereby preventing their invasion into erythrocytes. The antimalarial lymphocyte factor or a polypeptide sequence thereof could serve for further probing of invasion at the molecular level.
Applications of MALDI‐TOF MS to large‐scale human mtDNA population‐based studies (2009)

Analysis of the mitochondrial DNA variation in populations is commonly carried out in many fields of biomedical research. We propose the analysis of mitochondrial DNA coding region SNP (mtSNP) variation to a high level of phylogenetic resolution based on MALDI-TOF MS. The African phylogeny has been chosen to test the applicability of the technique but any other part of the worldwide phylogeny (or any other mtSNP panel) could be equally suitable for MALDI-TOF MS genotyping. SNP selection thus aimed to fully cover all the mtSNPs defining major and minor branches of the known African tree, including, macro-haplogroup L, and haplogroups M1, and U6. A total of 230 mtSNPs were finally selected. We used tests samples collected from two different African locations, namely, Mozambique and Chad Basin. Different internal genotyping controls and other indirect approaches (e.g. phylogenetic checking coupled with automatic sequencing) were used in order to evaluate the reproducibility of the technique, which resulted to be 100% using samples previously subjected to whole genome amplification. The advantages of the MALDI-TOF MS are also discussed in comparison with other popular methods such as minisequencing, highlighting its high-throughput nature, which is particularly suitable for case-control medical studies, forensic databasing or population and anthropological studies.
3D Culture of Adipose-Tissue-Derived Stem Cells Mainly Leads to Chondrogenesis in Poly(ethylene glycol)-Poly(l-alanine) Diblock Copolymer Thermogel (2013)

Poly(ethylene glycol)-b-poly(L-alanine) (PEG-L-PA)s with L-PA molecular weights of 620, 1100, and 2480 Da and a fixed molecular weight of PEG at 5000 Da were synthesized to compare the thermosensitive behavior, and to investigate their potential as a three-dimensional (3D) culture matrix of adipose-tissue-derived stem cells (ADSCs). The sol-to-gel transition temperature and the concentration ranges where the transition was observed decreased as the L-PA molecular weight increased. ADSCs were cultured in the 3D matrixes of in situ formed PEG-L-PA hydrogels, which were produced by increasing the temperature of cell-suspended PEG-L-PA aqueous solutions. The spherical morphology was maintained in the PEG-L-PA hydrogel, while the cells underwent fibroblastic morphological changes in the Matrigel over 14 days of incubation. ADSCs exhibited high expression of type II collagen in the PEG-L-PA thermogel. In addition, they also moderately expressed the biomarker of myogenic differentiation factor 1 as the same mesodermal lineages, as well as the type III β-tubulin as a cross-differentiation biomarker. Similar to the in vitro study, the ADSCs predominantly exhibited chondrogenic biomarkers in the in vivo study. The study demonstrates that the polypeptide thermogel of PEG-L-PA is promising as a 3D culture matrix of ADSCs and as an injectable tissue engineering biomaterial.
What Makes for Effective Detection Proposals? (2015)

Current top performing object detectors employ detection proposals to guide the search for objects, thereby avoiding exhaustive sliding window search across images. Despite the popularity and widespread use of detection proposals, it is unclear which trade-offs are made when using them during object detection. We provide an in-depth analysis of twelve proposal methods along with four baselines regarding proposal repeatability, ground truth annotation recall on PASCAL, ImageNet, and MS COCO, and their impact on DPM, R-CNN, and Fast R-CNN detection performance. Our analysis shows that for object detection improving proposal localisation accuracy is as important as improving recall. We introduce a novel metric, the average recall (AR), which rewards both high recall and good localisation and correlates surprisingly well with detection performance. Our findings show common strengths and weaknesses of existing methods, and provide insights and metrics for selecting and tuning proposal methods.
Sugar Response Sequence in the Promoter of a Rice α-Amylase Gene Serves as a Transcriptional Enhancer (1998)

Expression of alpha-amylase genes in both rice suspension cells and germinating embryos is repressed by sugars and the mechanism involves transcriptional regulation. The promoter of a rice alpha-amylase gene alphaAmy3 was analyzed by both loss- and gain-of-function studies and the major sugar response sequence (SRS) was located between 186 and 82 base pairs upstream of the transcription start site. The SRS conferred sugar responsiveness to a minimal promoter in an orientation-independent manner. It also converted a sugar-insensitive rice actin gene promoter into a sugar-sensitive promoter in a dose-dependent manner. Linker-scan mutation studies identified three essential motifs: the GC box, the G box, and the TATCCA element, within the SRS. Sequences containing either the GC box plus G box or the TATCCA element each mediated sugar response, however, they acted synergistically to give a high level glucose starvation-induced expression. Nuclear proteins from rice suspension cells binding to the TATCCA element in a sequence-specific and sugar-dependent manner were identified. The TATCCA element is also an important component of the gibberellin response complex of the alpha-amylase genes in germinating cereal grains, suggesting that the regulation of alpha-amylase gene expression by sugar and hormone signals may share common regulatory machinery.
Validation of spermidine synthase as a drug target in African trypanosomes (2007)

The trypanocidal activity of the ODC (ornithine decarboxylase) inhibitor DFMO (difluoromethylornithine) has validated polyamine biosynthesis as a target for chemotherapy. As DFMO is one of only two drugs used to treat patients with late-stage African trypanosomiasis, the requirement for additional drug targets is paramount. Here, we report the biochemical properties of TbSpSyn (Trypanosoma brucei spermidine synthase), the enzyme immediately downstream of ODC in this pathway. Recombinant TbSpSyn was purified and shown to catalyse the formation of spermidine from putrescine and dcSAM (decarboxylated S-adenosylmethionine). To determine the functional importance of TbSpSyn in BSF (bloodstream form) parasites, we used a tetracycline-inducible RNAi (RNA interference) system. Down-regulation of the corresponding mRNA correlated with a decrease in intracellular spermidine and cessation of growth. This phenotype could be complemented by expressing the SpSyn (spermidine synthase) gene from Leishmania major in cells undergoing RNAi, but could not be rescued by addition of spermidine to the medium due to the lack of a spermidine uptake capacity. These results therefore genetically validate TbSpSyn as a target for drug development and indicate that in the absence of a functional biosynthetic pathway, BSF T. brucei cannot scavenge sufficient spermidine from their environment to meet growth requirements.
HMM-Based Segmentation and Recognition of Human Activities from Video Sequences (2005)

Recognizing human activities from image sequences is an active area of research in computer vision. Most of the previous work on activity recognition focuses on recognition from video clips that show only single activities. There are few published algorithms for segmenting and recognizing complex activities that are composed of more than one single activity. In this paper, we present a novel HMM-based approach that uses threshold and voting to automatically and effectively segment and recognize complex activities. Experiments on a database of video clips of different activities show that our method is effective
Detection of minimal residual disease identifies differences in treatment response between T-ALL and precursor B-ALL (2002)

We performed sensitive polymerase chain reaction-based minimal residual disease (MRD) analyses on bone marrow samples at 9 follow-up time points in 71 children with T-lineage acute lymphoblastic leukemia (T-ALL) and compared the results with the precursor B-lineage ALL (B-ALL) results (n = 210) of our previous study. At the first 5 follow-up time points, the frequency of MRD-positive patients and the MRD levels were higher in T-ALL than in precursor-B-ALL, reflecting the more frequent occurrence of resistant disease in T-ALL. Subsequently, patients were classified according to their MRD level at time point 1 (TP1), taken at the end of induction treatment (5 weeks), and at TP2 just before the start of consolidation treatment (3 months). Patients were considered at low risk if TP1 and TP2 were MRD negative and at high risk if MRD levels at TP1 and TP2 were 10(-3) or higher; remaining patients were considered at intermediate risk. The relative distribution of patients with T-ALL (n = 43) over the MRD-based risk groups differed significantly from that of precursor B-ALL (n = 109). Twenty-three percent of patients with T-ALL and 46% of patients with precursor B-ALL were classified in the low-risk group (P =.01) and had a 5-year relapse-free survival (RFS) rate of 98% or greater. In contrast, 28% of patients with T-ALL were classified in the MRD-based high-risk group compared to only 11% of patients with precursor B-ALL (P =.02), and the RFS rates were 0% and 25%, respectively (P =.03). Not only was the distribution of patients with T-ALL different over the MRD-based risk groups, the prognostic value of MRD levels at TP1 and TP2 was higher in T-ALL (larger RFS gradient), and consistently higher RFS rates were found for MRD-negative T-ALL patients at the first 5 follow-up time points.
Adjusting the Structure of 2′-Modified Nucleosides and Oligonucleotides via C4′-α-F or C4′-α-OMe Substitution: Synthesis and Conformational Analysis (2018)

We report the first syntheses of three nucleoside analogues, namely, 2',4'-diOMe-rU, 2'-OMe,4'-F-rU, and 2'-F,4'-OMe-araU, via stereoselective introduction of fluorine or methoxy functionalities at the C4'-α-position of a 4',5'-olefinic intermediate. Conformational analyses of these nucleosides and comparison to other previously reported 2',4'-disubstituted nucleoside analogues make it possible to evaluate the effect of fluorine and methoxy substitution on the sugar pucker, as assessed by NMR, X-ray diffraction, and computational methods. We found that C4'-α-F/OMe substituents reinforce the C3'-endo ( north) conformation of 2'-OMe-rU. Furthermore, the predominant C2'-endo ( south/ east) conformation of 2'-F-araU switches to C3'-endo upon introduction of these substituents at C4'. The nucleoside analogues were incorporated into DNA and RNA oligonucleotides via standard phosphoramidite chemistry, and their effects on the thermal stability of homo- and heteroduplexes were assessed via UV thermal melting experiments. We found that 4'-substituents can modulate the binding affinity of the parent 2'-modified oligomers, inducing a mildly destabilizing or stabilizing effect depending on the duplex type. This study expands the spectrum of oligonucleotide modifications available for rational design of oligonucleotide therapeutics.
Molecular Mapping of Disease Resistance Genes for Halo Blight, Common Bacterial Blight, and Bean Common Mosaic Virus in a Segregating Population of Common Bean (1999)

Diseases of beans ( Phaseolus vulgaris L.) are primary constraints affecting bean production. Information on tagging and mapping of genes for disease resistance is expected to be useful to breeders. The objectives of this study were to develop a random amplified polymorphic DNA (RAPD) marker linkage map using 78 F9 recombinant inbred (RI) lines derived from a Middle-American common bean cross Great Northern Belneb RR-1 [resistant to common bacterial blight (CBB) and halo blight (HB)] × black A 55 [dominant I gene resistance to bean common mosaic potyvirus] and to map genes or QTL (quantitative trait loci) for resistance to CBB, HB, BCMV (bean common mosaic virus), and BCMNV (bean common mosaic necrosis virus) diseases. The RI lines were evaluated for resistance to leaf and pod reactions to Xanthomonas campestris pv. phaseoli ( Xcp ) (Smith Dye) strain EK-11, leaf reactions to two Pseudomonas syringae pv. phaseolicola ( Psp ) (Burkholder) Young et al. (1978) strains HB16 and 83-Sc2A, and BCMV strain US-5 and BCMNV strain NL-3. The linkage map spanned 755 cM, including 90 markers consisting of 87 RAPD markers, one sequence characterized amplified region (SCAR), the I gene , and a gene for hypersensitive resistance to HB 83-Sc2A. These were grouped into 11 linkage groups (LG) corresponding to the 11 linkage groups in the common bean integrated genetic map. A major gene and QTL for leaf resistance to HB were mapped for the first time. Three QTL for leaf reactions to HB16 were found on linkage groups 3, 5, and 10. Four regions on linkage groups 2, 4, 5, and 9, were significantly associated with leaf reactions to HB strain 83-Sc2A. The gene controlling the hypersensitive reaction to HB 83-Sc2A mapped to the same region as the QTL on LG 4. The I locus for resistance to BCMV and BCMNV was mapped to LG 2 at about 1.4 cM from RAPD marker A10.1750. Five and four markers were significantly associated with QTL for resistance to CBB in leaves and pods, respectively, with four of them associated with resistance in both plant organs. A marker locus was discovered on LG 10, W10.550, which could account for 44% and 41% of the phenotypic variation for CBB resistance in leaves and pods, respectively. QTL for resistance in pod to CBB, leaf resistance to HB, and the I gene were linked on LG 2.
Computing Architectural Vulnerability Factors for Address-Based Structures (2005)

Processor designers require estimates of the architectural vulnerability factor (AVF) of on-chip structures to make accurate soft error rate estimates. AVF is the fraction of faults from alpha particle and neutron strikes that result in user-visible errors. This paper shows how to use a performance model to calculate the AVF of address-based structures, using a data cache, a data translation buffer, and a store buffer as examples. We describe how to perform a detailed breakdown of lifetime components (e.g., fill-to-read, read-to-evict) of bits in these structures into ACE (required for architecturally correct execution), un-ACE (unnecessary for ACE), and unknown components. This lifetime analysis produces best estimate AVFs for these three structuresý data arrays of 6%, 36%, and 4%, respectively. We then present a new technique,hamming-distance-one analysis, and show that it predicts surprisingly low best estimate AVFs of 0.41%, 3%, and 7.7% for the structuresý tag arrays. Finally, using our lifetime analysis framework, we show how two AVF reduction techniques - periodic flushing and incremental scrubbing - can reduce the AVF by converting ACE lifetime components into un-ACE without affecting performance significantly.
Chromosome fragility and predisposition to childhood malignancies. (1998)

In order to clarify the possible connection between autosomal folate sensitive Fragile Sites (FS) and genetic susceptibility to haemopoetic disease in children we investigated the frequency and distribution of FS in the Peripheral Blood Lymphocytes (PBL) of 56 children with newly diagnosed and untreated haematologic malignancies and their parents. The incidence was compared with that of 146 normal controls (children and adults). In all patients the Bone Marrow (BM) karyotype was also determined. Heritable FS were detected in 49 patients (87.5%). 20 children had more than one FS and in all cases it was inherited from one of their parents, although there was a significant excess of transmitting mothers. 19 different FS were identified: 14 common, 4 rare and one, 22q11, which has not been previously reported, but it is considered as important as it coincides with the cancer breakpoint resulting in the formation of the Philadelphia (Ph) chromosome. The frequency of FS in the PBL of the patients was significantly higher than in the controls and this increase was independent of any abnormality detected in the malignant cells of the BM. However, patients with an abnormal BM karyotype displayed increased frequency of FS induction as compared to patients with a normal karyotype. In three cases the heritable FS was found to be at or near the breakpoints of the chromosomal rearrangements detected in the malignant cells. The findings are discussed with regard to cancer specific breakpoints, oncogene loci and sites where viral DNA can be inserted to the genome. The results of this study suggest that autosomal folate sensitive FS may increase the risk for haematologic malignancies through a complex mechanism which remains to be clarified.
Calcitonin Gene-Related Peptide as a Biomarker in Migraine (2017)

Background: Migraine is a prevalent disease with much economic burden and relatively inadequate available treatment. Calcitonin gene-related peptide (CGRP) is the most abundant neuropeptide in the trigeminal nerve and it may be involved in the pathogenesis of migraine. The aim of the study was to determine the plasma level of CGRP in patients with primary headache, and if it could be a potential biomarker for migraine. Methods: The study involved four groups with 20 patients in each one: chronic migraine, episodic migraine, cluster headache and tension type headache subjects, as well as healthy volunteers of matched age and sex as controls. Their venous blood was drawn, plasma was separated, and CGRP was analyzed with commercially available ELISA kit. Results: Plasma CGRP levels were significantly increased in chronic migraine (165.0 ± 17.9 ng/L, range 131.8 - 194.6) as compared with control group (70.5 ± 8.36 ng/L, range 51.7 - 83.65), patients with episodic migraine (94.1 ± 17.83 ng/L, range 69.6 - 121.9), and patients with cluster headache and tension type headache (87.2 ± 13.8 ng/L, range 62.8 - 110.8). Plasma CGRP levels in chronic migraine were significantly higher in patients with aura (191.32 ± 5.09, range 185.45 - 194.60) than without aura (160.30 ± 14.93, range 131.80 - 186.0), and in episodic migraine were significantly higher in patients with aura (109.88 ± 7.54, range 100.70 - 116.30) than without aura (90.16 ± 17.56, range 69.60 - 121.90). Conclusion: The plasma CGRP levels were elevated in patients with chronic migraine and may be considered a potential biomarker for it. This opens the door for a therapeutic role of it for migraine. J Neurol Res. 2017;7(6):103-107 doi: https://doi.org/10.14740/jnr460w
Extracting Opinion Expressions and Their Polarities -- Exploration of Pipelines and Joint Models (2011)

We investigate systems that identify opinion expressions and assigns polarities to the ex-tracted expressions. In particular, we demon-strate the benefit of integrating opinion ex-traction and polarity classification into a joint model using features reflecting the global po-larity structure. The model is trained using large-margin structured prediction methods. The system is evaluated on the MPQA opinion corpus, where we compare it to the only previ-ously published end-to-end system for opinion expression extraction and polarity classifica-tion. The results show an improvement of be-tween 10 and 15 absolute points in F-measure. 1