gebhart/patrepeval huggingface dataset:
Studies on the Mechanism of Hypoxic Selectivity in Copper Bis(Thiosemicarbazone) Radiopharmaceuticals (2002)

Copper diacetyl-bis(N4-methylthiosemicarbazone), Cu(II)ATSM, is a promising agent for imaging hypoxic tissue. Here we present results that provide insight into the chemical and electronic properties underlying previously observed structure-activity relationships. Density functional theory (DFT) calculations on the electronic structures and molecular orbitals of a series of 13 Cu(II)bis(thiosemicarbazone) analogues with different alkylation patterns and with fixed geometries based on the known structure of Cu(II)PTSM showed that the LUMO and the next lowest orbital were very close in energy, and their energy order was strikingly dependent on the ligand alkylation pattern in a way that correlated with hypoxia-selectivity and redox potentials. The LUMOs of Cu(II)ATSM and other hypoxia-selective analogues were predominantly metal-based (leading to a singlet reduced species) while the LUMOs of Cu(II)PTSM and other nonselective analogues were predominantly ligand-based (leading to a triplet reduced species). Upon relaxation of the geometric constraint and full optimization in both Cu(II)ATSM and Cu(II)GTS, the metal-based orbital became the LUMO, and the singlet was the thermodynamically preferred form of the reduced species. Chemical and electrochemical investigation showed that all Cu(II) complexes were reducible, but Cu(I)PTSM and other nonselective analogues dissociated immediately upon reduction with release of ligand (detected by UV-vis) while Cu(I)ATSM and other hypoxia-selective analogues did not. Instead they were rapidly re-oxidized to the Cu(II) complex by molecular oxygen. The reversible electrochemical reduction of nonselective complexes Cu(II)PTSM and Cu(II)GTS became irreversible in the presence of weak acid, whereas that of Cu(II)ATSM was unaffected. In light of these results we present a model to explain the structure-activity relationships on the basis of electronic structure and molecular vibrations.
Starting the protein synthesis machine: eukaryotic translation initiation (2003)

The final assembly of the protein synthesis machinery occurs during translation initiation. This delicate process involves both ends of eukaryotic messenger RNAs as well as multiple sequential protein-RNA and protein-protein interactions. As is expected from its critical position in the gene expression pathway between the transcriptome and the proteome, translation initiation is a selective and highly regulated process. This synopsis summarises the current status of the field and identifies intriguing open questions.
Human Follicle-Stimulating Hormone β-Subunit Gene Encodes Multiple Messenger Ribonucleic Acids (1988)

FSH is a pituitary gonadotropin that is encoded by separate alpha- and beta-subunit genes. We isolated a 12 kilobase (kb) DNA fragment containing the entire human FSH beta gene from a lambda phage genomic DNA library. The nucleotide sequence of the FSH beta gene predicts a 19 amino acid signal sequence and a 111 amino acid apoprotein that differs from the reported protein sequence at three residues and lacks the carboxyterminal eight amino acids, thereby bringing the human FSH beta sequence into register with those described for other mammalian species. Southern blot analyses of human genomic DNA are consistent with a single copy of the FSH beta gene per haploid genome. The FSH beta transcriptional unit spans 3.9 kb and contains two introns. The second intron (1.4 kb) is located between amino acids 35 and 36, a position that is strictly conserved among all of the glycoprotein hormone beta-subunit genes. The first intron occurs 6 base pairs upstream from the start of translation in a location analogous to that of the TSH beta gene. The first exon contains an alternate splicing donor site resulting in 5'-untranslated sequences of 63 (Exon IA) and 33 (Exon IB) bases in length. Approximately 65% of transcripts contain exon IA and 35% contain exon IB. Two different polyadenylation sites are also used. One polyadenylation site coincides with the stop codon, while the other site, which is used in greater than 80% of FSH beta mRNA transcripts, is located approximately 1 kb downstream, resulting in an unusually long 3'-untranslated sequence. The distribution of polyadenylation sites is similar for FSH beta mRNAs containing either Exons IA or IB suggesting that intron processing and polyadenylation are regulated independently. Thus, at least four distinct species of FSH beta mRNA transcripts, all encoding identical peptides, are processed from a single FSH beta gene. The distribution of different FSH beta mRNAs is similar in normal human pituitary tissue and several different FSH producing pituitary adenomas.
Final analysis of the phase III non-inferiority COLUMBA study of subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (2022)

In the primary analysis of the phase III COLUMBA study, daratumumab by subcutaneous administration (DARA SC) demonstrated non-inferiority to intravenous administration (DARA IV) for relapsed or refractory multiple myeloma (RRMM). Here, we report the final analysis of efficacy and safety from COLUMBA after a median of 29.3 months follow-up (additional 21.8 months after the primary analysis). In total, 522 patients were randomized (DARA SC, n=263; DARA IV, n=259). With longer follow-up, DARA SC and DARA IV continued to show consistent efficacy and maximum trough daratumumab concentration as compared with the primary analysis. The overall response rate was 43.7% for DARA SC and 39.8% for DARA IV. The maximum mean (standard deviation [SD]) trough concentration (cycle 3, day 1 pre-dose) of serum DARA was 581 (SD, 315) μg/mL for DARA SC and 496 (SD, 231) μg/mL for DARA IV. Median progression-free survival was 5.6 months for DARA SC and 6.1 months for DARA IV; median overall survival was 28.2 months and 25.6 months, respectively. Grade 3/4 treatment-emergent adverse events occurred in 50.8% of patients in the DARA SC group and 52.7% in the DARA IV group; the most common (≥10%) were thrombocytopenia (DARA SC, 14.2%; DARA IV, 13.6%), anemia (13.8%; 15.1%), and neutropenia (13.1%; 7.8%). The safety profile remained consistent with the primary analysis after longer follow-up. In summary, DARA SC and DARA IV continue to demonstrate similar efficacy and safety, with a low rate of infusion-related reactions (12.7% vs. 34.5%, respectively) and shorter administration time (3-5 minutes vs. 3-7 hours) supporting DARA SC as a preferable therapeutic choice. (Clinicaltrials gov. Identifier: NCT03277105.
Tissue Engineers Build New Bone (2000)

Bone repair may be one of the first major applications of tissue engineering; efforts to encourage the growth of new bone using novel matrices, bone morphogenic proteins, gene therapy, and stem cells are all showing promise. But the commercial stakes are so high that some researchers are worried that patent claims, and a reluctance to test competing technologies in combination, could delay progress in the field.
Intravenous immunoglobulins containing antibodies against -amyloid for the treatment of Alzheimer's disease (2004)

Although the sample size of this pilot study is too small to draw a clear conclusion, the results of this pilot study provide evidence for a more detailed investigation of IVIgG for the treatment of AD.
Isolation, Characterization, Molecular Gene Cloning, and Sequencing of a Novel Phytase from Bacillus subtilis (1998)

The Bacillus subtilis strain VTT E-68013 was chosen for purification and characterization of its excreted phytase. Purified enzyme had maximal phytase activity at pH 7 and 55 degrees C. Isolated enzyme required calcium for its activity and/or stability and was readily inhibited by EDTA. The enzyme proved to be highly specific since, of the substrates tested, only phytate, ADP, and ATP were hydrolyzed (100, 75, and 50% of the relative activity, respectively). The phytase gene (phyC) was cloned from the B. subtilis VTT E-68013 genomic library. The deduced amino acid sequence (383 residues) showed no homology to the sequences of other phytases nor to those of any known phosphatases. PhyC did not have the conserved RHGXRXP sequence found in the active site of known phytases, and therefore PhyC appears not to be a member of the phytase subfamily of histidine acid phosphatases but a novel enzyme having phytase activity. Due to its pH profile and optimum, it could be an interesting candidate for feed applications.
Prospects for the Use of ATR Inhibitors to Treat Cancer (2010)

ATR is an apical kinase in one of the DNA-damage induced checkpoint pathways. Despite the development of inhibitors of kinases structurally related to ATR, as well as inhibitors of the ATR substrate Chk1, no ATR inhibitors have yet been developed. Here we review the effects of ATR downregulation in cancer cells and discuss the potential for development of ATR inhibitors for clinical use.
Synthesis of 3‘-C- and 4‘-C-Branched Oligodeoxynucleotides and the Development of Locked Nucleic Acid (LNA) (1998)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of 3'-C- and 4'-C-Branched Oligodeoxynucleotides and the Development of Locked Nucleic Acid (LNA)Jesper WengelView Author Information Center for Synthetic Bioorganic Chemistry, Department of Chemistry, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen, Denmark Cite this: Acc. Chem. Res. 1999, 32, 4, 301–310Publication Date (Web):December 4, 1998Publication History Received30 June 1998Published online4 December 1998Published inissue 20 April 1999https://pubs.acs.org/doi/10.1021/ar980051phttps://doi.org/10.1021/ar980051presearch-articleACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views1584Altmetric-Citations288LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Conformation,Cytosine,Genetics,Monomers,Nucleic acids Get e-Alerts
Bright high efficiency blue organic light-emitting diodes with Al2O3/Al cathodes (1997)

The behavior of bright, efficient, low-driving-voltage blue organic light-emitting diodes based on amino-oxadiazole-fluorenes (AODFs) with Al2O3/Al cathodes is described. It is shown that the thin Al2O3 buffer layer sharply enhances current injection, increases the device efficiency, and reduces the driving voltage; the performance of devices with the optimal oxide buffer layer thickness approaches those with Mg0.9Ag0.1 cathodes. The effects of the Al2O3 buffer layer are believed to result from the removal of interface gap states induced by defects and chemical bonds between the AODF and Al, which trap carriers and quench singlet excitons nonradiatively.
I. Development of suspension media (1980)

Abstract A number of aqueous solutions were evaluated as possible pollen carriers for the spray pollination of fruit trees. The viability of apple, kiwifruit, oil palm, and plum pollen was markedly reduced after pollen was suspended in water. This loss of viability could be partly overcome by slow hydration of the pollen in moist air before its suspension. The viability of hydrated oil palm and kiwifruit pollen after suspension in calcium nitrate solution of low concentration with or without boric acid, was similar to that of hydrated pollen germinated directly. Similar results were obtained with apple and plum pollens, provided that pentaerythritol was added to the suspension medium. However, the viability of apple, kiwifruit, and plum pollen that had been suspended in these media was substantially reduced during drying on a simulated stigma surface. For kiwifruit, the loss of pollen viability after drying could be partially overcome by the further addition of sodium carboxymethyl cellulose, with or without sodium alginate, to the suspension medium.
Preclinical Studies of Pf-04849285, An Interferon-α8 Fusion Protein for the Treatment of HCV (2012)

The biomarker and toxicological findings were consistent with a potent IFN molecule. The potency and pharmacokinetic properties of the molecule are consistent with dosing at least every two weeks with the potential for monthly dosing' and not 'at least twice daily' as presented in the original [corrected].
PPFNet: Global Context Aware Local Features for Robust 3D Point Matching (2018)

We present PPFNet - Point Pair Feature NETwork for deeply learning a globally informed 3D local feature descriptor to find correspondences in unorganized point clouds. PPFNet learns local descriptors on pure geometry and is highly aware of the global context, an important cue in deep learning. Our 3D representation is computed as a collection of point-pair-features combined with the points and normals within a local vicinity. Our permutation invariant network design is inspired by PointNet and sets PPFNet to be ordering-free. As opposed to voxelization, our method is able to consume raw point clouds to exploit the full sparsity. PPFNet uses a novel $\textit{N-tuple}$ loss and architecture injecting the global information naturally into the local descriptor. It shows that context awareness also boosts the local feature representation. Qualitative and quantitative evaluations of our network suggest increased recall, improved robustness and invariance as well as a vital step in the 3D descriptor extraction performance.
An MCMC algorithm for haplotype assembly from whole-genome sequence data (2008)

In comparison to genotypes, knowledge about haplotypes (the combination of alleles present on a single chromosome) is much more useful for whole-genome association studies and for making inferences about human evolutionary history. Haplotypes are typically inferred from population genotype data using computational methods. Whole-genome sequence data represent a promising resource for constructing haplotypes spanning hundreds of kilobases for an individual. In this article, we propose a Markov chain Monte Carlo (MCMC) algorithm, HASH (haplotype assembly for single human), for assembling haplotypes from sequenced DNA fragments that have been mapped to a reference genome assembly. The transitions of the Markov chain are generated using min-cut computations on graphs derived from the sequenced fragments. We have applied our method to infer haplotypes using whole-genome shotgun sequence data from a recently sequenced human individual. The high sequence coverage and presence of mate pairs result in fairly long haplotypes (N50 length ~ 350 kb). Based on comparison of the sequenced fragments against the individual haplotypes, we demonstrate that the haplotypes for this individual inferred using HASH are significantly more accurate than the haplotypes estimated using a previously proposed greedy heuristic and a simple MCMC method. Using haplotypes from the HapMap project, we estimate the switch error rate of the haplotypes inferred using HASH to be quite low, ~1.1%. Our Markov chain Monte Carlo algorithm represents a general framework for haplotype assembly that can be applied to sequence data generated by other sequencing technologies. The code implementing the methods and the phased individual haplotypes can be downloaded from (http://www.cse.ucsd.edu/users/vibansal/HASH/).
Marked Attenuation of Ultradian and Circadian Rhythms of Dehydroepiandrosterone in Postmenopausal Women: Evidence for a Reduced 17,20-Desmolase Enzymatic Activity* (1990)

Circulating levels of adrenal delta 5-androgens [dehydroepiandrosterone (DHEA), and its sulfate (DS)] selectively decrease with age in both sexes, while cortisol secretion remains unchanged. The mechanism(s) to account for this dissociation is unclear. We tested the hypothesis that a reduced enzymatic activity for delta 5-androgen biosynthesis may be responsible for this phenomenon by examining the ultradian and circadian rhythmicity (15-min sampling frequency for 24 h) of DHEA and cortisol and the responsiveness of DHEA, DS, and cortisol to human CRF stimulation and by the analysis of relative enzymatic activities in the biosynthesis of adrenal steroids in older postmenopausal women (PMW) and younger cycling women (NCW). Our data show that the timing of the circadian rhythm of DHEA secretion was not altered, but the acrophase amplitude was decreased (P less than 0.01) in aged PMW compared to NCW. While the pulse frequency of DHEA remained unchanged, the pulse amplitude was markedly attenuated in PMW compared with NCW (3.5 +/- 0.6 vs. 8.1 +/- 1.1 nmol/L; P less than 0.01). Correspondingly, the 24-h mean of DHEA was markedly reduced (P less than 0.001) in PMW (5.5 +/- 0.8 nmol/L) from that in NCW (12.1 +/- 1.4 nmol/L). For cortisol, all parameters were similar between the two groups. Thus, compared to NCW, the decline of circulating DHEA level in PMW was expressed by attenuations of pulse amplitude and circadian amplitude, without changes in the timing of the circadian rhythm or pulse frequency. Further, DHEA and DS, but not cortisol, responses to 8-h hCRF infusion were significantly (P less than 0.01) diminished in PMW. These findings together with decreased product/precursor ratios for DHEA/17-hydroxypregnenolone (P less than 0.01) and androstenedione/17-hydroxyprogesterone (P less than 0.05) suggest a reduction of 17,20-desmolase enzymatic activity in PMW compared to that in NCW. Steroid ratios for 3 beta-hydroxysteroid dehydrogenase and 17 alpha-hydroxylase were unaltered. We conclude from these preliminary data that the disparity of DHEA and cortisol secretion in aged PMW is probably related to an intraadrenal event, resulting from a decrease in 17,20-desmolase expression, which governs the biosynthesis of delta 5-adrenal androgen.
Integration of Postprandial Function in the Proximal Gastrointestinal Tract (1994)

Cholecystokinin (CCK) stimulates vagal afferent fiber discharge, both gastric and intestinal, which seems to result in reflex decrease in gastric motility, gastric acid secretion, and stimulation of pancreatic protein secretion. Endogenous release of CCK by fat or soybean trypsin inhibitor also alters function by way of a capsaicin-sensitive pathway. We suggest that CCK is released locally from the intestine and acts locally or systemically to stimulate vagal afferent fiber discharge to alter proximal gastrointestinal function (Fig. 14). In this way, in addition to its effect on food intake, CCK and the neural pathway integrate function in the proximal gastrointestinal tract, regulating the entry of food into the duodenum to ensure effective digestion and absorption.
Chronic experimental hyperuricemic nephropathy. (1975)

Sustained, moderately severe hyperuricemia and severe uricosuria were produced in male Wistar rats by feeding dietary supplements of oxonic acid (0.4 gm. per day) and uric acid (0.6 gm per day). After 1 month, the kidneys showed the previously described histologic features of urate-blockade nephropathy characterized by intratubular deposits, tubular injury, and an exudative response consisting of neutrophilic granulocytes with early tophus formation. After 36 and 52 weeks of hyperuricemia, and with no gross evidence of renal failure, the kidneys showed a predominantly interstitial mononuclear cell infiltrate around regenerated tubules, an increase in interstitial fibrous tissue, infrequent renal tophi, and renal stones. The glomeruli and blood vessels appeared completely normal. There was no evidence of arthritis and no other target organ damage was detected. The chronic renal changes present in this animal model of induced hyperuricemia resemble those seen in human gouty nephropathy. The evolution of the experimental urate nephropathy observed during 1 year suggests that a primary acute inflammatory tubular injury is followed by a diffuse chronic interstitial nephritis and that the glomeruli and blood vessels are not primarily involved in the renal disease. This animal model may provide the opportunity to study factors influencing the renal sequelae of sustained hyperuricemia.
Detection of Serum Antibodies to Borna Disease Virus in Patients with Psychiatric Disorders (1985)

Borna disease virus causes a rare meningoencephalitis in horses and sheep and has been shown to produce behavioral effects in some species. The possibility that the Borna virus is associated with mental disorders in humans was evaluated by examining serum samples from 979 psychiatric patients and 200 normal volunteers for the presence of Borna virus-specific antibodies. Antibodies were detected by the indirect immunofluorescence focus assay. Antibodies to the virus were demonstrated in 16 of the patients but none of the normal volunteers. The patients with the positive serum samples were characterized by having histories of affective disorders, particularly of a cyclic nature. Further studies are needed to define the possible involvement of Borna virus in human psychiatric disturbances.
Eager Aggregation and Lazy Aggregation (1995)

Efficient processing of aggregation queries is essential for decision support applications. This paper describes a class of query transformations, called eager aggregation and lazy aggregation, that allows a query optimizer to move group-by operations up and down the query tree. Eager aggregation partially pushes a group-by past a join. After a group-by is partially pushed down, we still need to perform the original group-by in the upper query block. Eager aggregation reduces the number of input rows to the join and thus may result in a better overall plan. The reverse transformation, lazy aggregation, pulls a group-by above a join and combines two group-by operations into one. This transformation is typically of interest when an aggregation query references a grouped view (a view containing a group-by). Experimental results show that the technique is very beneficial for queries in the TPC-D benchmark. 1 Introduction Aggregation is widely used in decision support systems. All queries...
Severe respiratory syncytial virus pneumonia after autologous bone marrow transplantation: a report of three cases and review. (1992)

Three patients with acute leukemia who underwent autologous bone marrow transplantation (BMT) in complete remission, developed a severe respiratory syncytial virus (RSV) pneumonia, which was fatal in two. Identification of RSV was made on the products of bronchoalveolar lavage by direct immunofluorescence. As already described by others, the initial course of RSV infection varies, depending on whether it occurs sooner or later after BMT with a better prognosis in the latter situation. Treatment consists of aerosolized ribavirin. Infection by RSV is caused by manual contact with infected persons and contaminated surfaces. The severity of lung RSV infection in the course of BMT suggests the need for prophylactic measures in addition to standard isolation precautions.