gebhart/patrepeval huggingface dataset:
Evidence Based Selection of Housekeeping Genes (2007)

For accurate and reliable gene expression analysis, normalization of gene expression data against housekeeping genes (reference or internal control genes) is required. It is known that commonly used housekeeping genes (e.g. ACTB, GAPDH, HPRT1, and B2M) vary considerably under different experimental conditions and therefore their use for normalization is limited. We performed a meta-analysis of 13,629 human gene array samples in order to identify the most stable expressed genes. Here we show novel candidate housekeeping genes (e.g. RPS13, RPL27, RPS20 and OAZ1) with enhanced stability among a multitude of different cell types and varying experimental conditions. None of the commonly used housekeeping genes were present in the top 50 of the most stable expressed genes. In addition, using 2,543 diverse mouse gene array samples we were able to confirm the enhanced stability of the candidate novel housekeeping genes in another mammalian species. Therefore, the identified novel candidate housekeeping genes seem to be the most appropriate choice for normalizing gene expression data.
Neuronal Expression of Truncated Tau Efficiently Promotes Neurodegeneration in Animal Models: Pitfalls of Toxic Oligomer Analysis (2017)

Animal models of neurodegeneration induced by neuronal expression of truncated tau protein emerge as an important tool for understanding the pathogenesis of human tauopathies and for therapy development. Here we highlight common features of truncated tau models and make a critical assessment of possible pitfalls in their analysis. Particularly, the amount of soluble tau oligomers, which are suspected to be neurotoxic agents participating on the spreading of pathology inside the brain, may be overestimated due to a post-lysis oxidative tau oligomerization. Using a mouse brain lysate spiked with recombinant truncated and full length tau forms, we show that tau oligomers might inadvertently be produced during the isolation procedure. This finding is further corroborated by the analysis of brain lysates originated from a mouse model expressing truncated tau variant. Our results underline the necessity of thiol-protecting conditions during the analysis of tau oligomers involved in the etiopathogenesis of various tauopathies including Alzheimer's disease.
Phase II Study of Amrubicin As Second-Line Therapy in Patients With Platinum-Refractory Small-Cell Lung Cancer (2010)

Single-agent amrubicin showed promising activity with a 21.3% ORR and an acceptable safety profile when used as second-line therapy patients with platinum-refractory SCLC. Amrubicin did not induce early cardiotoxicity, but its long-term effects are unknown.
The SIR1 gene of Saccharomyces cerevisiae and its role as an extragenic suppressor of several mating-defective mutants. (1991)

The SIR1 gene product of Saccharomyces cerevisiae is one of several proteins involved in repressing transcription of the silent mating-type genes. Strains with mutations in the genes coding for these proteins are defective in mating due to derepression of the silent loci. We have found that overexpression of the SIR1 gene suppresses the mating defects of several of these mutants, including nat1 and ard1 mutants (the products of these two genes are responsible for N-terminal acetylation of a subset of yeast proteins), certain sir3 mutants, and a histone H4 mutant. The SIR1 gene has been sequenced and found to contain an open reading frame coding for a 678-amino-acid protein.
Prospects for the Use of Next-Generation Sequencing Methods in Ornithology (2010)

Nearly all aspects of avian biology, from behavior to conservation to systematics, have benefited from the application of molecular methods over the past two decades. New technologies of high-throughput DNA sequencing are sparking a revolution in the life sciences that is sure to further transform our understanding of avian systems. Next-generation (also called "massively parallel") sequencing methods were first introduced commercially just years ago (Roche GS FLX; Margulies et al. ), yet their capacity to process millions of sequences in parallel, in contrast to the conventional -capillary capacity of Sanger sequencing, has rapidly placed them at the forefront of genetic research (Fig. Although individual read lengths are currently limited ( base pairs [bp] for most platforms), the depth of coverage per base pair and advanced sequenceassembly software allow sequencing of .- giga base pairs (Gbp). Thus, in a single run, depending on the platform (Table These methods extend far beyond simply genome sequencing and have already greatly benefited the field of biology, leading to advances in evolution (
Formation of sulphmyoglobin during expression of horse heart myoglobin in Escherichia coli (1994)

Expression of recombinant horse heart myoglobin in Escherichia coli has been found to result in the production of both native and variable amounts (approximately 16-17% total) of two sulphmyoglobin isomers. The recombinant sulphmyoglobin produced consists primarily of the A and B isomers as identified by 1H NMR spectroscopy with no evidence for production of the C isomer. Conversion of recombinant sulphmyoglobin to the native protein can be achieved by reconstitution with protohaem IX. The possible relationship of this observation to recombinant expression of other heme proteins is discussed.
Improved Therapeutic Responses in a Xenograft Model of Human B Lymphoma (Namalwa) for Liposomal VincristineversusLiposomal Doxorubicin Targeted via Anti-CD19 IgG2a or Fab′ Fragments (2004)

Treatment of a B lymphoma model with single injections of anti-CD19-targeted liposomal formulations of VCR resulted in high levels of response and long-term survivors. Responses to anti-CD19-targeted liposomal DXR were more modest, although the longer circulation times of SIL[Fab'] versus SIL[alphaCD19] led to superior therapeutics for DXR-loaded immunoliposomes.
Education problems and Web-based teaching: how it impacts dental educators? (2001)

This article looks at six problems that vex educators and how web-based teaching might help solve them. These problems include: (1) limited access to educational content, (2) need for asynchronous access to educational content, (3) depth and diversity of educational content, (4) training in complex problem solving, (5) promotion of lifelong learning behaviors and (6) achieving excellence in education. The advantages and disadvantage of web-based educational content for each problem are discussed. The article suggests that when a poorly organized course with inaccurate and irrelevant content is placed online, it solves no problems. However some of the above issues can be partially or fully solved by hosting well-constructed teaching modules on the web. This article also reviews the literature investigating the efficacy of off-site education as compared to that provided on-site. The conclusion of this review is that teleconference-based and web-based delivery of educational content can be as effective as traditional classroom-based teaching assuming the technologic problems sometimes associated with delivering teaching content to off-site locations do not interfere in the learning process. A suggested hierarchy for rating and comparing e-learning concepts and methods is presented for consideration.
Assessment of Etiologic Agents in Acne Pathogenesis (2003)

Acne is a chronic inflammatory disease of the pilosebaceous units. Traditional etiologic factors include increased sebum production, ductal hyperkeratosis, abnormality of the microbial flora within the pilosebaceous unit, and mediators of inflammation. Recent developments do not refute these familial elements, but rather refine particular aspects. Interleukin-1a influences hypercornification of the infundibulum as well as the inflammatory response by inducing the production of vascular endothelial growth factor in dermal papilla cells and follicular keratinocytes of the pilosebaceous unit. New retinoids have been developed based on controlling cellular proliferation and differentiation in the pilosebaceous unit by their action on nuclear receptors of cells. Dermal inflammation is not due to presence of bacteria, but from biologically active mediators produced by Propionibacterium acnes. The environment within the pilosebaceous unit is probably more important than the absolute number of P. acnes organisms. Indeed, the major role of the sebaceous gland appears to be supplying P. acnes needed nutrients. Moreover, the microbiologic principle of biofilms appears to be applicable to P. acnes in acne.
Derivation of pluripotent, embryonic cell lines from the pig and sheep. (1991)

As previously described for the establishment of stable, pluripotent cell lines from pig blastocysts, an analogous cell line was isolated from a sheep blastocyst. There are common features in the morphologies and growth characteristics of the pig and sheep cells in culture; in particular, pig and sheep cells display large nuclei and relatively sparse cytoplasm, as is observed in mouse embryonic stem cells. Furthermore, the morphology of the sheep cells closely resembles that of cells in primary cultures of inner cell masses isolated immunosurgically from sheep blastocysts. This suggests that the sheep cell line represents a primary ectodermal lineage.
Irreversible opiate agonists and antagonists: the 14-hydroxydihydromorphinone azines. (1982)

Further investigations into the molecular actions of the 14-hydroxydihydromorphinone hydrazones (naloxazone, oxymorphazone, and naltrexazone) have suggested that their irreversible actions can be explained by the formation of their azines. These azines, naloxonazine, naltrexonazine, and oxymorphonazine, irreversibly block opiate binding in vitro 20- to 40-fold more potently than their corresponding hydrozones, naloxazone, naltrexazone, and oxymorphazone. The blockade of binding by naloxonazine shows the same selectivity for high affinity, or mu1, sites as naloxazone.
FAS Engagement Induces the Maturation of Dendritic Cells (Dcs), the Release of Interleukin (Il)-1β, and the Production of Interferon γ in the Absence of IL-12 during Dc–T Cell Cognate Interaction (2000)

Ligation of the Fas (CD95) receptor leads to an apoptotic death signal in T cells, B cells, and macrophages. However, human CD34(+)-derived dendritic cells (DCs) and mouse DCs, regardless of their maturation state, are not susceptible to Fas-induced cell death. This resistance correlates with the constitutive expression of the Fas-associated death domain-like IL-1beta-converting enzyme (FLICE)-inhibitory protein (FLIP) ligand. We demonstrate a new role of Fas in DC physiology. Engagement of Fas on immature DCs by Fas ligand (FasL) or by anti-Fas antibodies induces the phenotypical and functional maturation of primary DCs. Fas-activated DCs upregulate the expression of the major histocompatibility complex class II, B7, and DC-lysosome-associated membrane protein (DC-LAMP) molecules and secrete proinflammatory cytokines, in particular interleukin (IL)-1beta and tumor necrosis factor alpha. Mature DCs, if exposed to FasL, produce even higher amounts of IL-1beta. Importantly, it is possible to reduce the production of IL-1beta and interferon (IFN)-gamma during DC-T cell interaction by blocking the coupling of Fas-FasL with a Fas competitor. Finally, during cognate DC-T cell recognition, IL-12 (p70) could not be detected at early or late time points, indicating that Fas-induced, IFN-gamma secretion is independent of IL-12.
Enhanced CRISPR/Cas9-mediated precise genome editing by improved design and delivery of gRNA, Cas9 nuclease, and donor DNA (2016)

While CRISPR-based gene knock out in mammalian cells has proven to be very efficient, precise insertion of genetic elements via the cellular homology directed repair (HDR) pathway remains a rate-limiting step to seamless genome editing. Under the conditions described here, we achieved up to 56% targeted integration efficiency with up to a six-nucleotide insertion in HEK293 cells. In induced pluripotent stem cells (iPSCs), we achieved precise genome editing rates of up to 45% by co-delivering the Cas9 RNP and donor DNA. In addition, the use of a short double stranded DNA oligonucleotide with 3' overhangs allowed integration of a longer FLAG epitope tag along with a restriction site at rates of up to 50%. We propose a model that favors the design of donor DNAs with the change as close to the cleavage site as possible. For small changes such as SNPs or short insertions, asymmetric single stranded donor molecules with 30 base homology arms 3' to the insertion/repair cassette and greater than 40 bases of homology on the 5' end seems to be favored. For larger insertions such as an epitope tag, a dsDNA donor with protruding 3' homology arms of 30 bases is favored. In both cases, protecting the ends of the donor DNA with phosphorothioate modifications improves the editing efficiency.
Sacituzumab govitecan: an antibody–drug conjugate (2017)

Despite advances in the diagnosis and treatment of patients with cancer, patients with metastatic cancer have limited therapeutic options after initial lines of therapy. Understanding tumor biology has translated into the identification of actionable targets that resulted in therapeutics. Antibody-drug conjugates (ADC) are capitalizing on this explosion of scientific information. ADCs allow an antibody to a unique target to be conjugated via an innovative linker, to a highly toxic drug which is delivered to its target. Sacituzumab govitecan is an ADC that combines the active molecule in irinotecan, SN-38, to an antibody targeting trop2. Areas covered: In this review, the authors introduce the reader to the ADC sacituzumab govitecan providing the reader with details about its pharmacokinetics, pharmacodynamics, efficacy and safety. The authors also give their expert analysis about its potential future use. Expert opinion: Sacituzumab govitecan is a novel and well-tolerated therapeutic showing promising results in difficult to treat cancers. Further studies are underway to optimize the group of patients that would benefit from it. Given its excellent performance, we are cautiously optimistic it will be approved by the FDA.
Comparison of the Suppressive Effects of Antisense Oligonucleotides and siRNAs Directed Against the Same Targets in Mammalian Cells (2003)

RNA interference appears to be a potentially powerful tool for studies of genes of unknown function. However, differences in efficacy at different target sites remain problematic when small interfering RNA (siRNA) is used as an effector. Similar problems are associated with attempts at gene inactivation using antisense oligonucleotides (ODNs) and ribozymes. We performed a comparative analysis of the suppressive effects of three knockdown methods, namely, methods based on RNA interference (RNAi), antisense ODNs, and ribozymes, using a luciferase reporter system. Dose-response experiments revealed that the IC50 value for the siRNA was about 100-fold lower than that of the antisense ODN. Our results provide useful information about the positional effects in RNAi, which might help to improve the design of effective siRNAs.
Mannose 6-Phosphate Receptor–mediated Transport of Sulfamidase Across the Blood–brain Barrier in the Newborn Mouse (2008)

Mucopolysaccharidosis type IIIA (MPS IIIA), which is a lysosomal storage disorder (LSD) caused by inherited deficiency of sulfamidase, is characterized by severe, progressive central nervous system (CNS) dysfunction. Enzyme replacement therapy (ERT) to treat CNS storage is challenging, because the access of enzymes to the brain is restricted by the blood-brain barrier (BBB). In a prior study, we found that phosphorylated beta-glucuronidase (P-GUS) could be transcytosed across the BBB in newborn mice by the mannose 6-phosphate (M6P) receptor. In order to determine whether sulfamidase can utilize this pathway, we examined brain influx and the specificity of uptake of sulfamidase after intravenous (i.v.) injection in 2-day-old and 8-week-old mice. [(131)I]Sulfamidase was transported across the BBB in neonates at rates higher than that of simultaneously injected [(125)I]albumin. In contrast, the transport of [(131)I]sulfamidase was negligible in 8-week-old mice, thereby showing that the BBB transport mechanism is developmentally downregulated. Capillary depletion revealed that 83.7% of the [(131)I]sulfamidase taken up by the brain was in the parenchyma, demonstrating transfer across the capillary wall. The uptake of [(131)I]sulfamidase into the brain was significantly reduced by co-injections of M6P and P-GUS. That is, the transport of sulfamidase into the brain parenchyma in early postnatal life is mediated by the M6P receptor, which is shared with P-GUS and is likely accessible to other M6P-containing lysosomal enzymes.
The effect of network topology on the spread of epidemics (2005)

Many network phenomena are well modeled as spreads of epidemics through a network. Prominent examples include the spread of worms and email viruses, and, more generally, faults. Many types of information dissemination can also be modeled as spreads of epidemics. In this paper we address the question of what makes an epidemic either weak or potent. More precisely, we identify topological properties of the graph that determine the persistence of epidemics. In particular, we show that if the ratio of cure to infection rates is larger than the spectral radius of the graph, then the mean epidemic lifetime is of order log n, where n is the number of nodes. Conversely, if this ratio is smaller than a generalization of the isoperimetric constant of the graph, then the mean epidemic lifetime is of order e/sup na/, for a positive constant a. We apply these results to several network topologies including the hypercube, which is a representative connectivity graph for a distributed hash table, the complete graph, which is an important connectivity graph for BGP, and the power law graph, of which the AS-level Internet graph is a prime example. We also study the star topology and the Erdos-Renyi graph as their epidemic spreading behaviors determine the spreading behavior of power law graphs.
Effect of High Salt Treatment on Influenza B Viral Protein Synthesis in MDCK Cells (1983)

Based on the information that high salt inhibits the initiation of cellular mRNA translation which depends on the function of the 5'-terminal structure of mRNA, we compared the effect of high salt on translation of host cellular mRNAs and influenza viral mRNAs, both of which are of 5'-terminal structure. Brief exposure of influenza B virus-infected MDCK cells to high salt medium resulted in a dose-dependent inhibition of viral polypeptide synthesis as well as of cellular polypeptide synthesis, but it had less effect on synthesis of viral polypeptides, particularly nonstructural protein (NS). Under these conditions the Na+ content of the infected cells was significantly increased. A similar salt effect on in vitro translation of viral and cellular mRNAs extracted from infected cells was also observed. There was no significant difference in sensitivity to hypertonic block of in vivo translation of influenza viral mRNAs and vesicular stomatitis virus mRNAs, the latter of which possess a virus-directed structure at the 5'-terminus.
The IL-2 Receptor Complex: Its Structure, Function, and Target Genes (1993)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Direct C(1) hydroxylation of vitamin D3 and related compounds (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDirect C(1) hydroxylation of vitamin D3 and related compoundsHerbert E. Paaren, Hector F. DeLuca, and Heinrich K. SchnoesCite this: J. Org. Chem. 1980, 45, 16, 3253–3258Publication Date (Print):August 1, 1980Publication History Published online1 May 2002Published inissue 1 August 1980https://pubs.acs.org/doi/10.1021/jo01304a022https://doi.org/10.1021/jo01304a022research-articleACS PublicationsRequest reuse permissionsArticle Views655Altmetric-Citations52LEARN 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 Get e-Alerts
Time Geography for Ad-Hoc Shared-Ride Trip Planning (2006)

Ad-hoc shared-ride trip planning is a planning task on a non-deterministic transportation network. We propose to solve this task in a mobile geosensor network, which consists of transportation clients and hosts. In a mobile geosensor network the communication costs are a critical factor. Trip planning agents need communication to collect knowledge about the current network, and any way to limit this need reduces the costs of a solution. This paper introduces a theoretical model based on time geography, where clients, as trip planning agents, can actively identify relevant transportation hosts before communication starts, and hosts can identify whether their route is relevant for a specific planning task before responding to any request. This model reduces the communication costs significantly, which is at first derived theoretically, and then confirmed by an example.
Effect of Dietary Nucleotides on Response to Bacterial Infections (1986)

A nucleotide-free diet (NFD) suppresses cellular immunity including suppression of both murine allograft rejection and murine graft-vs-host disease in H2 mismatched marrow recipients. To explore the effect of this diet upon response to a bacterial challenge, BALB/c mice were placed upon one of four diets: NFD, NFD supplemented with 0.25% RNA (NFR) and NFD reconstituted with either 0.06% adenine (NFA) or 0.06% uracil (NFU). After 8 weeks on the diets, which supported normal growth in all groups, each dietary group of 10 mice was challenged with an intravenous injection of 1 X 10(7) live Staphylococcus aureus (Strain ATCC 25923). By 120 hr postinoculation all mice in the NFD group had died; mortality was only 56% in the NFR group (p less than 0.05). Addition of uracil resulted in mortality similar to that of the NFR group. Addition of adenine resulted in mortality close to that of the NFD group. Thus, dietary nucleotide restriction increases the mortality from staphylococcal sepsis. Addition of certain dietary nucleotides appears to decrease this susceptibility to bacterial challenge.