gebhart/patrepeval huggingface dataset:
Zinc: the neglected nutrient. (1989)

Zinc was first recognized as essential for animals at the University of Illinois School of Agriculture in 1916, when it was found that zinc-deficient baby pigs were runty, developed dermatitis on their legs, and were sterile. Zinc deficiency was first recognized in man by Dr. Ananda Prasad of Detroit 26 years ago when he measured serum and hair zinc levels in young male Egyptian dwarfs who had failed to mature and were small in stature. By simply adding zinc to their regular diet, they grew in height and became sexually mature. It is now recognized that dwarfism in males is frequent around the Mediterranean, where wheat is the staple of life and has been grown for 4,000 years on the same soil, thereby resulting in the depletion of zinc. Professor Robert Henkin first suggested that zinc deficiency might cause hearing-nerve impairment. Assay of the soft tissues of the cochlea and vestibule revealed a zinc level higher than that of any other part of the body. Previously, the eye was considered to have the highest level of zinc of any organ. To diagnose zinc deficiency clinically, we use serum zinc assays made at the Mayo Clinic Trace Element Laboratory. With zinc supplementation in patients who are marginally zinc deficient, there has been improvement in tinnitus and sensorineural hearing loss in about one-third of elderly adults. We believe zinc deficiency is one causation of presbycusis; by recognizing and correcting it, a progressive hearing loss can be arrested.
Introducing EzTaxon-e: a prokaryotic 16S rRNA gene sequence database with phylotypes that represent uncultured species (2011)

Despite recent advances in commercially optimized identification systems, bacterial identification remains a challenging task in many routine microbiological laboratories, especially in situations where taxonomically novel isolates are involved. The 16S rRNA gene has been used extensively for this task when coupled with a well-curated database, such as EzTaxon, containing sequences of type strains of prokaryotic species with validly published names. Although the EzTaxon database has been widely used for routine identification of prokaryotic isolates, sequences from uncultured prokaryotes have not been considered. Here, the next generation database, named EzTaxon-e, is formally introduced. This new database covers not only species within the formal nomenclatural system but also phylotypes that may represent species in nature. In addition to an identification function based on Basic Local Alignment Search Tool (blast) searches and pairwise global sequence alignments, a new objective method of assessing the degree of completeness in sequencing is proposed. All sequences that are held in the EzTaxon-e database have been subjected to phylogenetic analysis and this has resulted in a complete hierarchical classification system. It is concluded that the EzTaxon-e database provides a useful taxonomic backbone for the identification of cultured and uncultured prokaryotes and offers a valuable means of communication among microbiologists who routinely encounter taxonomically novel isolates. The database and its analytical functions can be found at http://eztaxon-e.ezbiocloud.net/.
Local Antibiotic Delivery Vehicles in the Treatment of Musculoskeletal Infection (2005)

The primary benefit achieved with local antibiotic delivery vehicles is the ability to obtain extremely high levels of local antibiotics without increasing systemic toxicity. Antibiotic-loaded bone cement represents the current standard as an antibiotic delivery vehicle in orthopaedic surgery. Biodegradable alternatives to antibiotic-loaded bone cement also are being used clinically and there are many new products in the active stages of development. These alternatives can be categorized as bone graft, bone graft substitutes or extenders, natural polymers (protein-based products), and synthetic polymers. Composite biomaterials that simultaneously provide the functions of variable antibiotic delivery patterns and also contribute to the process of bone regeneration represent the most ideal class of local antibiotic delivery vehicles. High concentrations of certain antibiotics have been shown to affect the process of normal bone regeneration adversely in a dose dependent response. Considerable investigation still is required to determine the proper use of locally administered antibiotics to negotiate the balance between eradicating infection without excessively inhibiting the processes of bone regeneration.
CD133+ and CD133− Glioblastoma-Derived Cancer Stem Cells Show Differential Growth Characteristics and Molecular Profiles (2007)

Although glioblastomas show the same histologic phenotype, biological hallmarks such as growth and differentiation properties vary considerably between individual cases. To investigate whether different subtypes of glioblastomas might originate from different cells of origin, we cultured tumor cells from 22 glioblastomas under medium conditions favoring the growth of neural and cancer stem cells (CSC). Secondary glioblastoma (n = 7)-derived cells did not show any growth in the medium used, suggesting the absence of neural stem cell-like tumor cells. In contrast, 11/15 primary glioblastomas contained a significant CD133(+) subpopulation that displayed neurosphere-like, nonadherent growth and asymmetrical cell divisions yielding cells expressing markers characteristic for all three neural lineages. Four of 15 cell lines derived from primary glioblastomas grew adherently in vitro and were driven by CD133(-) tumor cells that fulfilled stem cell criteria. Both subtypes were similarly tumorigenic in nude mice in vivo. Clinically, CD133(-) glioblastomas were characterized by a lower proliferation index, whereas glial fibrillary acidic protein staining was similar. GeneArray analysis revealed 117 genes to be differentially expressed by these two subtypes. Together, our data provide first evidence that CD133(+) CSC maintain only a subset of primary glioblastomas. The remainder stems from previously unknown CD133(-) tumor cells with apparent stem cell-like properties but distinct molecular profiles and growth characteristics in vitro and in vivo.
The Multifactorial Etiology of Inhibitor Development in Hemophilia: Genetics and Environment (2009)

The most important complication in the treatment of hemophilia A patients today is the development of inhibitory antibodies against infused factor VIII (FVIII). Inhibitor development is caused by a complex interplay between both genetic and environmental factors. The risk of developing inhibitors is greatest in previously untreated patients with severe hemophilia A. Several genetic factors, such as a positive family history of inhibitors, ethnicity, FVIII genotype, and certain polymorphisms in immune modulatory genes, are associated with the risk of inhibitor development. Treatment-related factors, such as intensive treatment with FVIII for bleeds or surgery, are associated with a higher inhibitor risk. However, regular prophylaxis seems to have a protective effect on inhibitor development. Knowledge about the risk factors of inhibitor development is a condition for predicting and in the future possibly even preventing the development of inhibitors in patients with severe hemophilia A. This review summarizes the current knowledge on the potential risk factors of inhibitor development. At present, many uncertainties still remain that will require collaborative investigation.
PARP Cleavage as a Means of Assessing Apoptosis (2003)

Although cell death is often seen as a pathological process, there are classically two types of cell death in biological systems, namely necrosis (accidental cell death) and apoptosis (programmed cell death). Although it was recognized from the early fifties that cell death was a natural process in normal tissue development and embryogenesis (,), the term apoptosis was first used by Wyllie et al. to describe a number of molecular and morphological processes in which individual cells actively undergo a programmed, genetically-regulated cell death (, , ). The term, derived from a Greek word meaning “the dropping off of leaves from trees,” was thus introduced to distinguish this mode of death from the more familiar process of necrosis and to emphasize its physiological role (programmed cell death and apoptosis are often used interchangeably).
Highly sensitive apurinic/apyrimidinic site assay can detect spontaneous and chemically induced depurination under physiological conditions. (1998)

One of the most prevalent lesions in DNA is the apurinic/apyrimidinic (AP) site, which is derived from the cleavage of the N-glycosyl bond by DNA glycosylase or by spontaneous depurination. AP sites are repaired by AP endonucleases during the process of base excision repair; however, an imbalance in this DNA repair system may cause mutations as well as cell death. We have established a sensitive and convenient slot-blot method to detect AP sites in genomic DNA using a novel aldehyde reactive probe (ARP), which reacts with the aldehydic group of ring-opened AP sites. The reaction of 1 mM of ARP with 15 microg of genomic DNA containing AP sites at 37 degrees C was completed within 1 min. The AP site-ARP complex was remarkably stable during incubation in TE buffer, even at 100 degrees C for 60 min. The sensitivity of this assay enables detection of 2.4 AP sites per 10(7) bases. By using this ARP-slot-blot assay, the rate of spontaneous depurination of calf thymus DNA was determined. Under physiological conditions, AP sites were increased at 1.54 AP sites/10(6) nucleotides/day (9000 AP sites/cell/day). This highly sensitive assay allows us to determine the endogenous level of AP sites in genomic DNA, as well as to investigate whether DNA-damaging agents cause imbalances of base excision/AP endonuclease repair in vivo and in vitro.
Model-based conifer-crown surface reconstruction from high-resolution aerial images (2001)

Knowledge of tree-crown parameters such as height, shape, and crown closure is desimble in forest and ecological studies, but those pammeters are difficult to measure on the ground. The stereoscopic capability of high-resolution aerial images provides a method for crown-surface reconstruction. However. 'existing digital photogrammet~packages, designed to map terrain surfaces. cannot accuratelv extmct tree-crown surfaces. particularb for-conifer-crowns dth steep vertical profilis. ' In this paper, we integrate crown features derived from images with stereo matching, and develop a model-based approach for reconstructing conifer-crown sqfaces. The model is based on the fact that most conifer crowns are a form of solid geometry. We model a conifer crown as a genemlized hemi-ellipsoid, establish the optimal tree model using a geometric equation, and apply the optimal tree model to guide a conventional pyramidal image matching in crown-surface reconstruction. The effectiveness of the approach is illustmted using an example of a redwood tree on 1:2,400-scale aerial photographs.
"Retreading" Ph.D.'s (1980)

Erratum In the report by K. L. Webb and C. F. D'Elia (29 Feb., p. 983),( )the title should read "Nutrient and oxygen redistribution during( )a spring neap tidal cycle in a temperate estuary." ( ).
Interleukin-1 beta gene polymorphism and its interactions with neuregulin-1 gene polymorphism are associated with (2008)

j Abstract Interleukin-1b (IL-1b) and neuregulin-1 (NRG-1) have an important role in development of the central nervous system. Several recent studies suggest that their genetic polymorphisms are associated with schizophrenia. We studied the effects of the IL-1b gene (IL-1B) -511 and NRG-1 SNP8NRG221533 polymorphisms and their interactions on the risk and age of onset of schizophrenia in 113 Finnish schizophrenic patients and 393 healthy controls. The allele and genotype frequencies of IL-1B and NRG-1 did not differ between schizophrenic patients and healthy controls, but the risk of schizophrenia was more than 10 times higher (odds ratio 10.20, 95% CI 2.53–41.09, p = 0.001) among subjects with the IL-1B 2.2, NRG-1 CC genotypes compared to subjects with the IL-1B 2.2, NRG-1 T-allele carriage. There was also a trend for an association between the interaction between IL1B and NRG-1 polymorphisms and the age at onset of schizophrenia (v 2 = 2.80; df = 1; p = 0.09, log rank test). IL-1B-511 allele 1 homozygotes had a significantly higher age of onset than allele 2 carriers (mean age of onset 25.9 ± 7.7 and 22.7 ± 5.4 years, t-test: t = 2.46; p = 0.032). Our results suggest that there is an interaction between the IL-1B and NRG-1 genes in schizophrenia. In addition, the IL-1B-511 polymorphism seems to be associated with the age at onset of schizophrenia.
Can oligonucleoside methylphosphonates form a stable triplet with a double DNA helix? (1990)

Molecular dynamics simulations of oligonucleoside methylphosphonates (MP) and naturally occurring oligodeoxynucleotides (ODN) as the third strand to double-stranded (ds) DNA targets predict that the third strand with MP backbone is more favorable to triple helix formation than the native phosphodiester ODN third strand. In contrast to experimental data, the calculated DNA conformations in both fully solvated triple helical system are found to be in hybrid A and B conformations. The calculations predict that a third strand with MP backbone is readily accommodated in the major groove of the ds DNA target, and adopts a different conformation from a helical triplet formed with native ODN as the third strand through the Hoogsteen base pairing scheme.
Evidence for protein-tyrosine-phosphatase catalysis proceeding via a cysteine-phosphate intermediate. (1991)

A recombinant protein-tyrosine-phosphatase has been expressed in Escherichia coli and purified to a single band by sodium dodecyl sulfate-polyacrylamide gel electrophoresis using affinity chromatography. When the phosphatase was allowed to react with 32P-labeled substrates and then rapidly denaturated, a 32P-labeled phosphoprotein could be visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Transient formation of a 32P-labeled phosphoprotein was observed, and the 32P-labeled protein disappeared as substrate was consumed. In the presence of 32P-labeled p-nitrophenyl phosphate, 0.27 mol of phosphate was incorporated per mol of protein-tyrosine-phosphatase. Site-directed mutagenesis of a catalytically essential cystine residue (position 215) in the recombinant protein resulted in an inactive enzyme, and no phosphoprotein was formed. The 32P-labeled phosphoprotein showed a maximum lability between pH 2.5 and 3.5 and was rapidly decomposed in the presence of iodine. These properties, along with additional site-directed mutations, suggest that the protein-tyrosine-phosphatase forms a covalent thiol phosphate linkage between Cys215 and phosphate.
Voltage emergency prediction: Using signatures to reduce operating margins (2009)

Inductive noise forces microprocessor designers to sacrifice performance in order to ensure correct and reliable operation of their designs. The possibility of wide fluctuations in supply voltage means that timing margins throughout the processor must be set pessimistically to protect against worst-case droops and surges. While sensor-based reactive schemes have been proposed to deal with voltage noise, inherent sensor delays limit their effectiveness. Instead, this paper describes a voltage emergency predictor that learns the signatures of voltage emergencies (the combinations of control flow and microarchitectural events leading up to them) and uses these signatures to prevent recurrence of the corresponding emergencies. In simulations of a representative superscalar microprocessor in which fluctuations beyond 4% of nominal voltage are treated as emergencies (an aggressive configuration), these signatures can pinpoint the likelihood of an emergency some 16 cycles ahead of time with 90% accuracy. This lead time allows machines to operate with much tighter voltage margins (4% instead of 13%) and up to 13.5% higher performance, which closely approaches the 14.2% performance improvement possible with an ideal oracle-based predictor.
The phosphodiesterase PDE4B limits cAMP-associated PI3K/AKT–dependent apoptosis in diffuse large B-cell lymphoma (2004)

Diffuse large B-cell lymphoma (DLBCL) is a common and often fatal malignancy. Advances in the treatment of this disease will require the identification of novel therapeutic targets. We previously defined an expression signature of outcome in DLBCL and found that the phosphodiesterase PDE4B was overexpressed in fatal/refractory tumors. Phosphodiesterase 4B (PDE4B) inactivates the second messenger cyclic adenosine 3',5' monophosphate (cAMP) and abrogates its inhibitory effects in B lymphocytes. Hence, DLBCLs that express high PDE4B levels may be resistant to cAMP-induced apoptosis, contributing to their less favorable outcome. Herein, we confirmed the risk-related expression of PDE4B in an independent series of primary DLBCLs and defined the enzyme's role in modulating cAMP-induced apoptosis in parental DLBCL cell lines or those reconstituted with wild-type or mutant PDE4B. The cAMP-mediated apoptosis of DLBCLs was largely independent of the previously described cAMP effectors, protein kinase A (PKA) and exchange protein directly activated by cAMP (EPAC), but associated with inhibition of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. The central role of AKT in this process was confirmed by expressing constitutively active mutants of this kinase in DLBCL cells. Our findings highlight the important role of cAMP signaling in DLBCL and suggest that clinically relevant PDE4 and PI3K/AKT inhibitors might be useful in the treatment of DLBCL and additional B-lymphoid malignancies with increased PDE4B expression.
Degradation and Reconstruction of Moenomycin A and Derivatives:  Dissecting the Function of the Isoprenoid Chain (2006)

Moenomycin A is the only known natural product that inhibits peptidoglycan biosynthesis by binding the bacterial transglycosylases. We describe a degradation/reconstruction route to manipulate the reducing end of moenomycin A. A comparison of the biological and enzyme inhibitory activity of moenomycin A and an analogue containing a nerol lipid in place of the natural C25 lipid chain provides insight into the role of the moenocinol unit. Our results show that a lipid chain having ten carbons in moenocinol is sufficient for enzyme inhibition, but a longer chain is required for biological acitivity, apparently because the molecule must partition into biological membranes to reach its target in bacterial cells.
Stacked What-Where Auto-encoders (2015)

We present a novel architecture, the "stacked what-where auto-encoders" (SWWAE), which integrates discriminative and generative pathways and provides a unified approach to supervised, semi-supervised and unsupervised learning without relying on sampling during training. An instantiation of SWWAE uses a convolutional net (Convnet) (LeCun et al. (1998)) to encode the input, and employs a deconvolutional net (Deconvnet) (Zeiler et al. (2010)) to produce the reconstruction. The objective function includes reconstruction terms that induce the hidden states in the Deconvnet to be similar to those of the Convnet. Each pooling layer produces two sets of variables: the "what" which are fed to the next layer, and its complementary variable "where" that are fed to the corresponding layer in the generative decoder.
Conformation-dependent Antibacterial Activity of the Naturally Occurring Human Peptide LL-37 (1998)

The influence of ion composition, pH, and peptide concentration on the conformation and activity of the 37-residue human antibacterial peptide LL-37 has been studied. At micromolar concentration in water, LL-37 exhibits a circular dichroism spectrum consistent with a disordered structure. The addition of 15 mM HCO3-, SO42-, or CF3CO2- causes the peptide to adopt a helical structure, with approximately equal efficiency, while 160 mM Cl- is less efficient. A cooperative transition from disordered to helical structure is observed as the peptide concentration is increased, consistent with formation of an oligomer. The extent of alpha-helicity correlates with the antibacterial activity of LL-37 against both Gram-positive and Gram-negative bacteria. Two homologous peptides, FF-33 and SK-29, containing 4 and 8 residue deletions at the N terminus, respectively, require higher concentrations of anions for helix formation and are less active than LL-37 against Escherichia coli D21. Below pH 5, the helical content of LL-37 gradually decreases, and at pH 2 it is entirely disordered. In contrast, the helical structure is retained at pH over 13. The minimal inhibitory concentration of LL-37 against E. coli is 5 microM, and at 13-25 microM the peptide is cytotoxic against several eukaryotic cells. In solutions containing the ion compositions of plasma, intracellular fluid, or interstitial fluid, LL-37 is helical, and hence it could pose a danger to human cells upon release. However, in the presence of human serum, the antibacterial and the cytotoxic activities of LL-37 are inhibited.
Regulation of the Erythropoietin Gene: Evidence That the Oxygen Sensor Is a Heme Protein (1988)

Erythropoietin (Epo), the hormone that stimulates red blood cell production, is synthesized in the kidney and liver in response to hypoxia. The human hepatoma cell line Hep3B regulates its production of Epo in a physiologic manner. Either hypoxia or cobalt chloride markedly increases expression of Epo mRNA as well as production of biologically active and immunologically distinct Epo protein. New protein synthesis is required before the induction of increased levels of hypoxia- or cobalt-induced Epo mRNA. Hypoxia, cobalt chloride, and nickel chloride appear to stimulate Epo production through a common pathway. The inhibition of Epo production at low partial pressures of oxygen by carbon monoxide provides evidence that a heme protein is integrally involved in the oxygen-sensing mechanism. This hypothesis is further supported by the finding that when heme synthesis is blocked, hypoxia-, cobalt-, and nickel-induced Epo production are all markedly inhibited. A model is proposed in which a ligand-dependent conformational change in a heme protein accounts for the mechanism by which hypoxia as well as cobalt and nickel stimulate the production of Epo.
Positive and Negative Regulation of Tetrahymena Telomerase Holoenzyme (2007)

Telomerase replenishes the telomeric repeats that cap eukaryotic chromosome ends. To perform DNA synthesis, the active site of telomerase reverse transcriptase (TERT) copies a template within the integral telomerase RNA (TER). In vivo, TERT and TER and additional subunits form a telomerase holoenzyme capable of telomere elongation. We previously purified epitope-tagged Tetrahymena thermophila TERT and characterized two of the associated proteins. Here we characterize the remaining two proteins that were enriched by TERT purification. The primary sequence of the p75 polypeptide lacks evident homology with other proteins, whereas the p20 polypeptide is the Tetrahymena ortholog of a conserved multifunctional protein, Skp1. Genetic depletion of p75 induced telomere shortening without affecting the accumulation of TER or TERT, suggesting that p75 promotes telomerase function at the telomere. Affinity purification of p75 coenriched telomerase activity and each other known telomerase holoenzyme protein. On the other hand, genetic depletion of Skp1p induced telomere elongation, suggesting that this protein plays a negative regulatory role in the maintenance of telomere length homeostasis. Affinity purification of Skp1p did not detectably enrich active telomerase but did copurify ubiquitin ligase machinery. These studies reveal additional complexity in the positive and negative regulation of Tetrahymena telomerase function.