gebhart/patrepeval huggingface dataset:
Advantages and limitations of quantitative PCR (Q-PCR)-based approaches in microbial ecology (2008)

Quantitative PCR (Q-PCR or real-time PCR) approaches are now widely applied in microbial ecology to quantify the abundance and expression of taxonomic and functional gene markers within the environment. Q-PCR-based analyses combine 'traditional' end-point detection PCR with fluorescent detection technologies to record the accumulation of amplicons in 'real time' during each cycle of the PCR amplification. By detection of amplicons during the early exponential phase of the PCR, this enables the quantification of gene (or transcript) numbers when these are proportional to the starting template concentration. When Q-PCR is coupled with a preceding reverse transcription reaction, it can be used to quantify gene expression (RT-Q-PCR). This review firstly addresses the theoretical and practical implementation of Q-PCR and RT-Q-PCR protocols in microbial ecology, highlighting key experimental considerations. Secondly, we review the applications of (RT)-Q-PCR analyses in environmental microbiology and evaluate the contribution and advances gained from such approaches. Finally, we conclude by offering future perspectives on the application of (RT)-Q-PCR in furthering understanding in microbial ecology, in particular, when coupled with other molecular approaches and more traditional investigations of environmental systems.
Smoothing of discontinuous signals: the competitive approach (1995)

Discontinuous signals buried in noise cannot be recovered by linear filtering methods. This paper presents a new class of nonlinear filters in which sets of forward and backward linear predictors and smoothers compete with each other at each timestep. The winner of each competition is granted the right to produce the smoothed estimate at that timestep. This conceptually simple approach to nonlinear filtering, called the competitive smoothing approach, is justified by considering sets of Kalman filters (corresponding to the hypotheses used in the Bayesian framework) which are used to derive model credibility coefficients. These are shown to essentially "switch" between the various models. We argue that the concept of competitive smoothing is considerably more general than just the Kalman setting, and can be used with almost any predictors and/or smoothers. Several examples are presented which demonstrate the efficacy of the approach at both smoothing and preserving jump discontinuities. Comparisons are made with the other main nonlinear filtering approach, the median filter.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Notch2 governs the rate of generation of mouse long- and short-term repopulating stem cells (2011)

HSCs either self-renew or differentiate to give rise to multipotent cells whose progeny provide blood cell precursors. However, surprisingly little is known about the factors that regulate this choice of self-renewal versus differentiation. One candidate is the Notch signaling pathway, with ex vivo studies suggesting that Notch regulates HSC differentiation, although a functional role for Notch in HSC self-renewal in vivo remains controversial. Here, we have shown that Notch2, and not Notch1, inhibits myeloid differentiation and enhances generation of primitive Sca-1(+)c-kit(+) progenitors following in vitro culture of enriched HSCs with purified Notch ligands. In mice, Notch2 enhanced the rate of formation of short-term repopulating multipotential progenitor cells (MPPs) as well as long-term repopulating HSCs, while delaying myeloid differentiation in BM following injury. However, consistent with previous reports, once homeostasis was achieved, neither Notch1 nor Notch2 affected repopulating cell self-renewal. These data indicate a Notch2-dependent role in assuring orderly repopulation by HSCs, MPPs, myeloid cells, and lymphoid cells during BM regeneration.
Ruxolitinib for the treatment of myelofibrosis (2011)

Ruxolitinib is an orally available, ATP-competitive inhibitor, selective for tyrosine-protein kinases JAK1 and JAK2 and is the most advanced JAK1/JAK2 inhibitor in development for the treatment of myeloproliferative neoplasms. The suggested mechanism of action of ruxolitinib is attenuation of cytokine signaling via the inhibition of JAK1 and JAK2 (wild-type or mutated forms), resulting in antiproliferative and proapoptotic effects. In the phase III COMFORT-I trial conducted in patients with myelofibrosis, ruxolitinib demonstrated durable reductions in splenomegaly. The proportion of patients that achieved spleen volume reduction ≥ 35% from baseline to 24 weeks was 41.9 % with ruxolitinib versus 0.7% with placebo (P < 0.0001), as evaluated by magnetic resonance imaging or computed tomography. In the phase III COMFORT-II trial, reductions in spleen volume ≥ 35% were observed in 31.9% of patients treated with ruxolitinib versus 0% with best available therapy at week 24, and 28.5% versus 0% at week 48 (both P < 0.0001). Low toxicity, alleviation of constitutional symptoms, weight gain and improvement in general physical condition were observed with ruxolitinib treatment which may substantially improve quality of life in patients with myelofibrosis.
Functional Expression of Miraculin, a Taste-Modifying Protein in Escherichia Coli (2009)

Miraculin isolated from red berries of Richadella dulcifica, a native shrub of West Africa, has the unusual property of modifying a sour taste into a sweet one. This homodimer protein consists of two glycosylated polypeptides that are cross-linked by a disulfide bond. Recently, functional expression of miraculin was reported in host cells with the ability to glycosylate proteins, such as lettuce, tomato and the microbe Aspergillus oryzae, but not Escherichia coli. Thus, a question remains as to whether glycosylation of miraculin is essential for its taste-modifying properties. Here we show that recombinant miraculin expressed in E. coli has taste-modifying properties as a homodimer, not as a monomer, indicating that glycosylation is not essential for the taste-modifying property.
Optimizing cooperative cognitive search and rescue UAVs (2018)

A need exists for a self-forming, self-organizing, cognitive, cooperative, automated unmanned aerial vehicle (UAV) network system to more efficiently perform UAV-based maritime search and rescue (SAR) operations. Although current search patterns (e.g., traditional “lawn mower” methods) are thorough, they result in too much time spent searching lowprobability areas. This decreases the chances of a successful rescue and increases the risk of lost recovery opportunities (e.g., death due to hypothermia in the case of human search targets). Our goal is to optimize UAV-based SAR operations. As directed by an onboard computer, UAVs would fly coordinated search patterns based on the target’s last known position and the direction and speed of winds and currents. By enabling the UAVs to act collectively and cooperatively, we can enhance the efficiency and effectiveness of a multi-UAV network’s SAR mission. To achieve this, we applied cooperative game theory as an enabling function in the development of a cognitive system encompassing multiple vehicles. Based on simulations, we showed that an optimal dynamic search pattern and vehicle positioning strategy can be realized using decision algorithms based on elements of game theory.
The major protein from lipid bodies of maize. Characterization and structure based on cDNA cloning. (1987)

In plant seeds, the storage triacylglycerol is packed in discrete particles called lipid bodies which consist of a lipid core surrounded by a phospholipid monolayer with embedded proteins. We have cloned and sequenced a nearly full-length cDNA for the major protein (L3) associated with the lipid bodies of maize. The L3-cDNA clone was identified by hybrid-selected translation analysis and contains the complete 3' noncoding region and an open reading frame of 432 nucleotides. This open reading frame encodes a polypeptide with amino acid composition, hydrophobicity, and predicted protease digestion pattern which correlate well with those of the authentic L3 protein. Analyses of predicted secondary structure and local hydropathy of the deduced amino acid sequence suggest three structural domains in the protein. An internal domain of 72 contiguous hydrophobic or neutral amino acids is bounded at the amino-terminal side by a hydrophilic alpha-helix and on the carboxyl-terminal side by an amphipathic alpha-helix. The data suggest that L3 is uniquely suited to interact with both lipid and phospholipid moieties of the lipid body. A simple model for the topology of L3 on the lipid body is proposed. The unusual structure of the lipid body protein is discussed and compared to those of the two well-studied classes of lipid-associated proteins, apolipoproteins and intrinsic membrane proteins.
Comparison of defect size distributions based on electrical and optical measurement procedures (2002)

Defect size distributions play an important role in process characterization and yield prediction. To determine efficient procedures to extract defect size distributions, a database was set up that consists of hundreds of defect images to provide defect size distributions also reflecting irregular outlines of defects. Further investigation shows that even a single extension value per defect may provide a precise size distribution. Furthermore, the proposed Harp Test Structure (HTS) containing hundreds of parallel lines will also provide a defect size distribution, but it is based on electrical measurements only. The comparison of defect size distributions using both measurement procedures shows that not only optical measurements, but also electrical measurements at a Harp Test Structure are sufficient to obtain a precise defect size distribution that also enables size distribution modeling for yield prediction.
The Structural Unit of the Thiazide-sensitive NaCl Cotransporter Is a Homodimer (2003)

The thiazide-sensitive NaCl cotransporter (NCC) is responsible for the reabsorption of 5% of the filtered load of NaCl in the kidney. Mutations in NCC cause Gitelman syndrome. To gain insight into its regulation, detailed information on the structural composition of its functional unit is essential. Western blot analysis of total membranes of Xenopus laevis oocytes heterologously expressing FLAG-tagged NCC revealed the presence of both complex-(140-kDa) and core (100-kDa)-glycosylated monomers and a broad band of high molecular mass (250-350-kDa) complexes. Chemical cross-linking with dithiobispropionimidate eliminated the low molecular weight bands and increased the intensity of the high molecular weight bands, indicating that NCC is present in multimeric complexes. Co-expression of HA- and FLAG-tagged NCC followed by co-immunoprecipitation demonstrated that these multimers contained at least two complex-glycosylated NCC proteins. The dimeric nature of the multimers was further substantiated by sucrose gradient centrifugation yielding a peak of approximately 310 kDa. A concatameric construct of two NCC polyproteins exhibited significant 22Na+ uptake, indicating that the transporter is functional as a homodimer. A concatamer of partially retarded G980R- and wild type (wt)-NCC displayed normal Na+ transport. This demonstrates that G980R-NCC, provided that it reaches the surface, is fully active and that wt-NCC is dominant in its association with this mutant. Conversely a concatamer of fully retarded G741R- and wt-NCC did not reach the cell surface, showing that wt-NCC is recessive in its association with this mutant. Oocytes co-expressing G741R- and wt-NCC did not show G741R staining at the plasma membrane, whereas Na+ transport was normal, indicating that wt-NCC dimerizes preferentially with itself. The results are discussed in relation to the recessive nature of NCC mutants in Gitelman syndrome.
Pseudotyped retroviral vectors reveal restrictions to reticuloendotheliosis virus replication in rat cells (1986)

Reticuloendotheliosis viruses (Rev) replicate in chicken and dog cells, but not in rat cells. Amphotropic murine leukemia viruses (Am-MLV) replicate in chicken, dog, and rat cells. Transcription from the Rev long terminal repeat, determined by the chloramphenicol acetyltransferase assay, was not significantly different from transcription from the MLV long terminal repeat in rat cells. To determine further the step(s) in the retroviral life cycle that is blocked for Rev replication in rat cells, we took advantage of the wide host range of Am-MLV (S. Rasheed, M. B. Gardner, and E. Chan, J. Virol. 19:13-18, 1976) and the ability to form Rev-Am-MLV pseudotypes. Data from these pseudotypes indicate that the block to Rev replication in rat cells is posttranscriptional.
study of incremental step pulse programming (ISPP) and STI edge effect of BE-SONOS NAND Flash (2008)

Incremental-step-pulse programming (ISPP) is a key enabler for achieving tight V <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</inf> distribution for MLC NAND Flash. The ISPP characteristics for BE-SONOS NAND Flash are studied extensively in this work. Experimentally we find that the ISPP slope is very close to 1 for BE-SONOS capacitors for a wide range of EOT and O1 variations. A theoretical model is developed to prove that ISPP slope∼1 is a universal property for any charge-trapping devices, assuming charges are fully captured. However, when the device is integrated in various STI geometries, the ISPP slope is often degraded. This is due to the STI edge effect. Non-uniform injection happens along the channel width and degrades the programming efficiency at higher VT levels. The degradation of trans-conductance (g <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m</inf> ) and subthreshold slope (S.S) during programming validates the STI edge effect. We find that through process modifications for the STI edge, the ISPP slope can be improved.
Cyclization of Certain Heterocyclic Azides (1959)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCyclization of Certain Heterocyclic AzidesGEORGE A. REYNOLDS, JAMES A. VanALLAN, and JOHN F. TINKERCite this: J. Org. Chem. 1959, 24, 9, 1205–1209Publication Date (Print):September 1, 1959Publication History Published online1 May 2002Published inissue 1 September 1959https://pubs.acs.org/doi/10.1021/jo01091a010https://doi.org/10.1021/jo01091a010research-articleACS PublicationsRequest reuse permissionsArticle Views476Altmetric-Citations60LEARN 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
Agents for treating human immunodeficiency virus infection (1994)

The replicative cycle of the human immunodeficiency virus (HIV) is reviewed, and currently used and investigational agents directed against the virus are discussed. The first step in the replication of HIV is selective binding of the envelope glycoprotein to CD4 receptors located on T lymphocytes. The virion is then uncoated within the cytoplasm, yielding viral genomic RNA. Reverse transcriptase uses the viral RNA as a template to form single-stranded DNA, which is duplicated to form proviral DNA through the activity of ribonuclease H. Host RNA polymerases transcribe the integrated proviral DNA into messenger RNA, and there is subsequent translation to viral proteins. After translation, further modification of precursor polyproteins is necessary to produce functional peptides. The assembled virus then buds from the cell surface and invades other cells. Targets of drug intervention in the replicative cycle include (1) binding and entry, (2) reverse transcriptase, (3) transcription and translation, and (4) viral maturation and budding. Inhibitors of binding and entry include recombinant soluble CD4, immunoadhesins, peptide T, and hypericin. Nucleoside reverse-transcriptase inhibitors include zidovudine, didanosine, zalcitabine, and stavudine. Foscarnet, tetrahydroimidazobenzo-diazepinthione compounds, and nevirapine are some nonnucleoside reverse-transcriptase inhibitors. Inhibitors of transcription and translation include antagonists of the tat gene and GLQ223. Castanospermine, N-butyldeoxynojirimycin, and protease inhibitors interfere with viral maturation and budding. Drug combinations that have been or are being investigated include zidovudine plus interferon alfa, zidovudine plus zalcitabine, and zidovudine plus didanosine. Four agents currently have approved labeling for use against HIV infection: zidovudine, didanosine, zalcitabine, and stavudine. Monotherapy with zidovudine remains the treatment of first choice. Although progress has been made in developing drug therapies for HIV infection, more selective and more potent drugs are urgently needed. The best approach at present is to optimize the use of available agents, continue to investigate new therapies, and educate the public about prevention.
Lack of promiscuity in autoantigen-specific H and L chain combinations as revealed by human H and L chain “roulette” (1993)

Individual H or L chains from a human autoantibody were used to search for other L or H chains that could form antigen-binding fragments, Fab, with the same specificity. The parent Fab (SP1.2) exhibits high affinity binding for thyroid peroxidase (TPO), a 107-kDa protein that is the major autoantigen in human autoimmune thyroiditis. This autoantibody "roulette," performed by using Ig H and L chain gene libraries expressed in bacteria, increased the frequency of TPO-binding clones in the new libraries. However, the frequency was still much lower than would be the case if promiscuous combinations with a variety of H or L chains were compatible with specific Ag binding. Nucleotide sequence analysis of the H and L chains of the new TPO-binding clones revealed even more restriction. Thus, with the SP1.2 H chain, all 11 new Fab utilized L chains from the same V kappa 1 family germline gene as SP1.2 itself. Similarly, five of six H chains "captured" by the SP1.2 L chain were very closely related to the SP1.2 H chain. However, one totally different H chain was isolated: SP4.6 has a VH region that differs substantially from that of SP1.2. SP4.6 also has a distinct D region, uses a different JH, and, unlike SP1.2, which is an IgG1, belongs to subclass IgG4. The affinities for TPO of SP4.6 (with the different H chain) and SP1.20 (which had the least mutated L chain germline gene) were similar to that of SP1.2 (approximately 10(-10) M). As expected, the SP1.2 and SP1.20 Fab, which have the same H chain and closely related L chains, bound to the same domain on TPO. However, a similar domain on TPO was recognized by both SP4.6 and SP1.2, despite the fact that their V, D, and J regions are quite different. This observation raises the possibility that the L chain is critical in defining epitope specificity, even in the presence of completely different D regions and nonidentical VH regions.
Pancreas Transplantation (2008)

In summary, solitary pancreas transplants (alone in non-uremics—PTA; or after a kidney—PAK) should be done, as well as simultaneous pancreas-kidney (SPK) transplants in uremic diabetics who cannot get a kidney transplant first (to preempt or shorten the time on dialysis). The approach depends on the recipient candidate characteristics and on living or deceased donor availability and suitability. It is regressive to restrict pancreas transplants to just the uremic population, and in this restricted population to just those who cannot get an early kidney transplant to preempt the dialysis that would otherwise be necessary while waiting for both organs from a deceased donor. For the uremic diabetic in centers where there is a long wait time for a deceased donor SPK transplants (because of kidney allocation policies), the best option is a living donor kidney followed by a pancreas transplant; a living donor eliminates waiting for a kidney, and the waiting time for a solitary pancreas at present is relatively short. The patient survival rates are high after either PTA, PAK or SPK transplants, at 3 years 93%;, 90% and 91% respectively, with corresponding graft survival (insulin-independence) rates of 60%, 66% and 78%, respectively. Even though pancreas graft survival rates are higher after SPK transplants, the gain in patient survival rates by doing a preemptive kidney transplant more than offsets the lower insulin-independence rates after a PAK. The outcomes justify the continuance of pancreas transplants in all three categories of recipients, with nearly all nephropathic diabetics being PAK or SPK candidates (since immunosuppression will be obligatory for a kidney transplant), and selected non-uremic diabetics, particularly those with hypoglycemic unawareness, being candidates for a PTA.
A phase I study including pharmacokinetics of polyethylene glycol conjugated interleukin-2 (1991)

A more soluble formulation of recombinant interleukin-2 with a prolonged half-life would allow alternate routes or schedules of administration and enhance patient comfort. The covalent attachment of polyethylene glycol to recombinant interleukin-2 provides an analog with preclinical data suggesting those desired characteristics while maintaining biologic activity. This is the report of a phase I study in which we sought to determine the maximum tolerated dose of polyethylene glycol interleukin-2, observe biologic activity, and confirm the prolonged half-life in vivo. Sixty-six patients were entered into the study during 19 months. Polyethylene glycol interleukin-2 was administered intravenously once a week over 15 minutes. The maximum tolerated dose was 20 x 10(6) U/M2. The pattern of toxicity was quite similar to that of the parent compound. Four patients had evidence of tumor regression (three partial remission; one minor response). The pharmacokinetic data confirmed a 10- to 20-fold prolongation in half-life compared with recombinant interleukin-2. No neutralizing antibodies were detected. This study provides sufficient impetus for the ongoing phase II studies of polyethylene glycol interleukin-2.