gebhart/patrepeval huggingface dataset:
DPP-4 Inhibitors and Combined Treatment in Type 2 Diabetes: Re-evaluation of Clinical Success and Safety (2007)

The incretin system has proven to be a new source of glucose-lowering drugs. Glucon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are the incretins which are degraded by dipeptidyl peptidase-4 (DPP-4). GLP-1 is the major relevant incretin in type 2 diabetes, GIP has little stimulatory capacity. Oral inhibitors of DPP-4 increase GLP-1 levels and this leads to lower glucose levels caused by increased insulin secretion and decreased glucagon levels. There are currently two oral drugs registered with the European Medicinal Evaluation Agency: sitagliptin and vidagliptin. Both compounds have shown similar effects to date. A main issue is to establish the value of this new class of drugs in the treatment of patients with type 2 diabetes. In this article, results from randomized studies on the efficacy of the new drugs are discussed: 1. comparison with placebo to establish long-term efficacy, 2. comparison with placebo when added to the regimen in patients failing on another oral glucose-lowering drug and 3. comparison in a head-to-head trial with other conventional drugs. Also, the combination with insulin is a promising new avenue. Both efficacy and safety (regarding hypoglycemia, body weight changes and changes in lipid levels) are major components in the decision of the optimal pharmacological treatment, which is discussed in this article. Finally, the advantages, disadvantages and risks of the new anti-diabetic compounds are highlighted, which are applicable to other classes of diabetes drugs.
Tetrachloroethylene as electron acceptor for the anaerobic degradation of benzoate (1990)

Teltrachloroethylene (PCE) was biotransformed by reductive dehalgenation under anoxic conditions with benzoate as the electron donor. The experiments were carried out under batch culture conditions with biomass from an anoxic fixed bed reactor fed with benzoate and PCE. Inhibition of methanogenesis by bromoethane-sulfonic acid (BES) resulted in a complete inhibition of benzoate degradation. Benzoate, however, was decomposed in the presence of BES if PCE was added to the cultures. With 2.8 mmol/1 PCE, that was transformed to 1.4 mmol/1 cis-1,2-dichloroethylene (DCE) and 3.8 mmol/1 chloride, 2 mmol/1 benzoate were degraded to about 3.2 mmol/1 acetate. The elimination of benzoate was directly proportional to DCE accumulation, ranging between 1:0.5 and 1:1.
Raman enhancement of graphene oxide via reduced Ag nanoparticles on the suface (2012)

Graphene oxide sheets adsorbed with Ag nanoparticles were synthesized in a facile way. Raman spectra measured at different excitation wavelength were carried out. Efficient in vivo Raman detection experiments using GO-Ag nanoparticles were demonstrated.
The Reimer-Tiemann Reaction. (1960)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Reimer-Tiemann Reaction.Hans WynbergCite this: Chem. Rev. 1960, 60, 2, 169–184Publication Date (Print):April 1, 1960Publication History Published online1 May 2002Published inissue 1 April 1960https://pubs.acs.org/doi/10.1021/cr60204a003https://doi.org/10.1021/cr60204a003research-articleACS PublicationsRequest reuse permissionsArticle Views6756Altmetric-Citations182LEARN 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
Use of 33P for Sanger DNA sequencing. (1991)

The use of [alpha-33P]deoxyadenosine 5'-triphosphate ([alpha-33P]dATP) in DNA sequencing has been described. 33P has a maximum beta-emission energy that is 50% stronger than 35S, but fivefold weaker than 32P. As a result, sequences generated using [alpha-33P]dATP have short exposure times like 32P, yet they maintain band resolution similar to 35S. Handling of [alpha-33P]dATP is straightforward because no special lead or Plexiglas shielding is necessary.
Development of a set of multiplex PCR assays for the detection of genes encoding important β-lactamases in Enterobacteriaceae (2010)

We report here the development of a useful method composed of a set of six multiplex PCRs and one simplex PCR for the rapid screening of the most frequently encountered beta-lactamases. This method allowed direct sequencing from the PCR products.
Towards collisions: An enhanced successive interference cancellation with asynchronism (2012)

In this paper, we consider a hidden terminal scenario where two transmitters A and B, hidden to each other, wish to communicate to a common access point, AP. When a collision occurs at AP, due to the inherent asynchrony between the colliding packets, the mutual interference between them is effectively decreased. This achieves a higher signal-to-interference-plus-noise (SINR) ratio which improves the probability of successfully decoding both colliding packets through conventional successive interference cancellation (SIC). When neither colliding packet can be decoded first through SIC, we propose an enhanced SIC (ESIC) scheme. The proposed decoding scheme does not require synchronization, coordination or power control between the transmitters or a sophisticated coding design. By exploiting the inherent asynchrony between the two colliding packets, there exists, with high probability, an interference-free chunk together with an interfered chunk in a packet ready for decoding. Thus it is still possible for both colliding packets to be recovered eventually from a single collision. Our results demonstrate that through the proposed ESIC scheme, both colliding packets can be recovered with a higher probability thus improving the system throughput.
Coding and modulation under power constraints (1998)

An issue arising at the physical layer in digital wireless transmission is the choice of the coding/modulation scheme taking into account the availability of a limited energy source. This article is devoted to a description of the rationales behind this choice. As the latter depends on the channel model, we examine four of these, namely, the Gaussian channel, the independent-fading channel, the block-fading channel, and a channel where the transmission quality is limited by interference rather than by noise. Code selection and power-allocation strategies are discussed.
Effect of Inhibiting Nitric Oxide Production on Mouse Preimplantation Embryo Development and Metabolism1 (2004)

Nitric oxide (NO) is a free radical that functions as a cell signaling molecule but at high concentrations can be toxic. It is formed from arginine, which is consumed by the mouse blastocyst, but its effect on early embryo development has been little studied. In this study, the role of NO in mouse preimplantation development has been examined in terms of developmental rate and oxidative metabolism. Zygotes were cultured in one of four media; potassium simplex optimization medium (KSOM), KSOM with amino acids (KSOMaa), KSOM without glutamine (KSOM-glut), or KSOM with 0.5 mM arginine (KSOMarg) +/- l-NAME (a specific inhibitor of NO production). End points were Day 4 blastocyst rates, cell counts determined using bisbenzimide and oxygen consumption. In KSOM and KSOM-glut, the blastocyst rate was decreased by 1 mM l-NAME from 50.2% +/- 3.1% and 37.4% +/- 4.5% to 6% +/- 3% and 0%, respectively. In KSOMaa, cavitation rates were unaltered but the blastocysts contained fewer cells (P < 0.001). Blastocysts cultured in KSOM and KSOM-glut consumed significantly more oxygen than those cultured in KSOMaa (P < 0.001 and P < 0.05, respectively). However, the addition of 0.1 mM or 1 mM l-NAME to KSOMaa significantly increased the amount of oxygen consumed (P < 0.05 and P < 0.001, respectively). The data suggest a physiological role for NO in mouse preimplantation metabolism and development. One possibility is that NO may limit oxygen consumption at the blastocyst stage at the level of mitochondrial cytochrome c oxidase.
The Dyeing of Direct Dyes on Cotton* (1946)

Summary Rate‐of‐dyeing measurements have been carried out on over fifty direct cotton dyes dyed on cotton in two liquor lengths and with three salt concentrations. The results are expressed in terms of the time of half‐dyeing and the equilibrium exhaustion. The value of the results in predicting the dyeing behaviour of binary combinations of dyes has been critically examined. It is shown that in approximately one in three cases, the course of dyeing is not that which would be predicted from the rate‐of‐dyeing measurements on the individual components, whilst the prediction of truly compatible mixtures is even less successful. From this is is concluded that rate‐of‐dyeing data on direct dyes are of little practical value. It is suggested that the rate of migration of direct dyes is of more importance than the rate of dyeing, and measurements of the migration rate and its variation with salt and dye concentrations have been made. The controllability of the dyes by salt is also highly important in practice, and the dyebath exhaustion produced by the addition of salt has been measured over a wide range of salt concentrations for all the dyes. A method of defining salt controllability is developed. On the basis of the rate of migration and salt controllability, a system of classification of the direct dyes is derived which provides some indication of the best practical method of application.
미호종개 metallothionein 유전자의 구조 및 중금속 노출과 고온 자극에 대한 MT mRNA의 발현 특징 분석 (2011)

멸종위기 어류 미호종개(Cobitis choii)로부터 중금속해독 단백질(metallothionein) 유전자를 분리, 클로닝하고 중금속 및 고온 스트레스에 대한 전사 발현 특징을 분석하였다. 미호종개 metallothionein는 gDNA, mRNA 및 아미노산 서열 모두에서 경골 어류 MT들의 구조적 특징을 잘 보전하고 있었으며, 생물정보분석을 통해 미호종개 MT 유전자 5`-upstream 영역은 중금속 조절, 면역 반응 및 온도 반응에 관여하는 다양한 전사 조절인자들의 부착 위치들을 포함하는 것으로 관찰되었다. 카드뮴(Cd), 구리(Cu), 니켈(Ni), 망간(Mn) 및 아연(Zn)을 이용한 침지 노출 실험(0.5 및 1.0 μM; 24시간)에서 미호종개 MT mRNA 발현은 구리 및 카드뮴 처리군에서 가장 많이 유도되었고(1.0 μM Cu 처리군에서 최대 10배), 망간 처리군에서는 비교적 적은 양의 MT 발현이 유도된 반면(2배), 아연 및 니켈 노출 군에서는 유의적인 MT 발현의 증감이 관찰되지 않았다. 또한 미호종개 MT 전사 발현은 고온 자극(25°C로부터 31°C까지 증가)에도 민감하게 반응하는 것으로 나타나, 31°C 도달시점에서 25°C 초기 MT mRNA 발현 수준보다 9배 높은 mRNA 발현이 관찰되었다. 본 연구 결과는 MT 기반의 유전자 발현 분석을 이용함으로써, 향후 멸종위기 어류 미호종개의 스트레스 반응 연구에 유용한 기초 자료를 제공할 수 있다고 기대된다.
The Cell Cycle Checkpoint Gene <i>Rad9</i> Is a Novel Oncogene Activated by 11q13 Amplification and DNA Methylation in Breast Cancer (2005)

Human Rad9 (hRad9), a structural homologue of yeast Schizosaccharomyces pombe rad9, is involved in cell cycle checkpoints and apoptosis. hRad9 can serve as a corepressor of androgen receptor in prostate cancer cells, but little is known about its role in the development of breast or other cancers. In the present study, semiquantitative reverse transcription-PCR showed that Rad9 mRNA levels were up-regulated in 52.1% (25 of 48) of breast tumors, and this up-regulation correlated with tumor size (P = 0.037) and local recurrence (P = 0.033). Overexpression of Rad9 mRNA was partly due to an increase in Rad9 gene number as measured by quantitative PCR. In other breast tumors with Rad9 mRNA overexpression but without increase in gene number, there was differential methylation of two putative Sp1/3 binding sites within the first and second introns of the Rad9 gene, which was similarly found in MCF-7 breast cancer cell line with increased Rad9 mRNA. Silencing Rad9 expression by RNA interference in MCF-7 cell line inhibited its proliferation in vitro. Promoter assays indicated that the Sp1/3 site in intron 2 may act as a silencer. In vivo binding of Sp3 to intron 2 was shown by chromatin immunoprecipitation assays. Treatment of MCF-7 cell line with 5'-aza-2'-deoxycytidine reduced Rad9 mRNA expression and also increased binding of Sp3 to the demethylated intron 2 region. Collectively, these findings suggest that Rad9 is a novel oncogene candidate activated by 11q13 amplification and DNA hypermethylation in breast cancer and may play a role in tumor proliferation and local invasion.
Peptide Mass Fingerprinting after Less Specific In-Gel Proteolysis Using MALDI-LTQ-Orbitrap and 4-Chloro-α-cyanocinnamic Acid (2010)

Peptide Mass Fingerprinting (PMF) of tryptically in-gel digested samples is a well-established protein identification technique for MALDI mass spectrometry but an in-depth PMF evaluation for in-gel digestions of less specific enzymes is still missing. This study demonstrates that the MALDI-LTQ-Orbitrap provides the mass accuracy to gain significant database search results via PMF for the less specific enzymes chymotrypsin and elastase. Additionally, the highly sensitive MALDI matrix ClCCA was compared to the most widely used matrix CHCA by means of the detected peptide number, peptide composition, pI and S/N distribution, sequence coverage, and Mascot score. Therefore, several proteins were in-gel digested by chymotrypsin and elastase. Trypsin and proteinase K were included as references for specific and nonspecific proteases, respectively. Compared to CHCA, ClCCA resulted in a better mapping in all cases of the more complex peptide mixtures generated by less specific enzymes. In summary, the MALDI-LTQ-Orbitrap combined with the matrix ClCCA makes PMF of less specific digests possible in an easy and fast way. Moreover, it opens more possibilities for PMF in the analysis of difficult tasks such as membrane proteins.
Discrete-time adaptive control of systems with unknown deadzones (1995)

An adaptive deadzone inverse approach is developed for control of discrete-time systems with unknown deadzones at the input of linear dynamics. The proposed controller consists of an adaptive deadzone inverse, whose parameters are updated to cancel the effect of the deadzone, and a linear part, which is designed to achieve tracking of a reference signal by the system output. When the linear part of the system is known, its parameters are used to specify the parameters of the linear part of the controller. When the linear part of the plant is unknown, the linear control parameters are adaptively estimated. The control error caused by the adaptive deadzone inverse is expressed as a linearly parametrizable part plus a bounded disturbance. Adaptive laws which employ parameter projection are used to update the controller parameters. They are robust with respect to the bounded disturbance, and they result in parameter estimates needed to implement an adaptive deadzone inverse. We prove the closed-loop signal boundedness, and illustrate by simulations that the system tracking performance is significantly improved.
Analysis of protein A encoded by a mutated gene of <i>Staphylococcus aureus</i> Cowan I (1985)

The protein A (spa) genes from Staphylococcus aureus Cowan I and a mutant strain of Cowan I called V-1 earlier suggested to produce a monovalent IgG-binding protein A have been cloned in Escherichia coli. The DNA sequences coding for the IgG-binding part of the spa genes from both strains have been determined and compared with each other and with a partial amino acid sequence of purified protein A from strain V-1. The nucleotide sequence of the spa gene from strain V-1 reveals an NH2-terminally located IgG-binding region homologous to region E first reported for strain 8325-4, region D and the major portion of region A. The amino acid sequence analysis of the purified protein A from this strain also shows the presence of regions E and D but only a minor part of region A. Reversed-phase high-performance liquid chromatography fractionation of purified protein A from strain V-1 revealed that the preparation was heterogeneous, containing mainly two peptides with different abilities to bind IgG molecules. A shuttle vector containing the cloned protein A gene from V-1 was constructed and transformed into different strains of S. aureus and the produced protein A was purified and analysed using sodium dodecyl sulfate/polyacrylamide gel electrophoresis.
Automated pose estimation in 3D point clouds applying annealing particle filters and inverse kinematics on a GPU (2010)

Current experiments with HCIs have shown a high demand for more natural interaction paradigms. Gestures are thereby considered the most important cue besides speech. In order to recognize gestures it is necessary to extract meaningful motion features from the body. Up to now mostly marker based tracking systems are used in virtual reality environments, since these were traditionally more reliable than purely image based detection methods. However, markers tend to be distracting and cumbersome. Following recent advances in processing power, it becomes possible to use a camera system in order to obtain a depth image of the test subject, match it to a pre-defined body model, and thus track the body parts over time. We will present a full-body system based on APF which enables full body tracking utilizing point clouds recorded with a 3D sensor. Further refinement is provided by a specially adapted inverse kinematics system. A GPU based implementation speeds up processing significantly and allows near real time performance.
Characterization of hydrophobic interaction and antioxidant properties of the phenothiazine nucleus in mitochondrial and model membranes (2010)

The antioxidant properties of the phenothiazine nucleus (PHT) associated with mitochondrial membranes and liposomes were investigated. PHT exhibited hydrophobic interaction with lipid bilayers, as shown by the quenching of excited states of 1-palmitoyl-2[10-pyran-1-yl)]-decanoyl-sn-glycero-3-phophocholine (PPDPC) incorporated in phosphatidylcholine/phosphatidylethanolamine/cardiolipin liposomes, observed even in high ionic strength; and by the spectral changes of PHT following the addition of mitochondrial membranes. Inserted into bilayers, 5 microM PHT was able to protect lipids and cytochrome c against pro-oxidant agents and exhibited spectral changes suggestive of oxidative modifications promoted by the trapping of the reactive species. In this regard, PHT exhibited the ability to scavenge DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) free radical. PHT was also able to protect rat liver mitochondria against peroxide- and iron-induced oxidative damage and consequent swelling. At the concentration range in which the antioxidant properties were observed, PHT did not cause alterations in the membrane structure and function. This study contributes to the comprehension of the correlation structure and function of phenothiazines and antioxidant properties.
Development Of RNAi Therapeutics Targeting The Complement Pathway (2013)

Abstract The complement system is a pivotal player in multiple hematological conditions. Antibody blockade of the C5 component of complement has been approved as a treatment for both paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic-uremic syndrome (aHUS), validating C5 as an important therapeutic target. Recently, we developed a robust RNAi therapeutics platform for the delivery of siRNAs to the liver using trivalent GalNAc conjugates, enabling silencing of hepatocyte-expressed genes following subcutaneous (SC) injection. The liver is a major source of C5 and other complement pathway components. The GalNAc conjugate technology allows rapid development of siRNAs targeting multiple members of the complement cascade and evaluation of their silencing in pre-clinical models. To examine the utility of the siRNA approach for targeting complement pathway components we designed and synthesized GalNAc conjugated siRNAs targeting rodent, primate and human C5. Potent siRNA duplexes, showing greater than 95% silencing of C5 mRNA were selected using in vitro screening in human cell lines and mouse primary hepatocytes. C5 silencing and serum hemolytic activity inhibition were evaluated in rodents using single and multi-dose SC treatment regimens. A C5-targeting siRNA conjugate demonstrated a single dose ED50 of 0.625 mg/kg in the mouse with greater than 90% silencing of serum C5 achievable at higher doses. Serum C5 silencing was durable, with recovery starting two weeks after a single SC injection We went on to examine the efficacy of C5 silencing in the rat and observed robust lowering of serum C5 with 2.5 and 5 mg/kg multi-dose regimens, resulting in up to ∼90% inhibition of complement classical pathway hemolytic activity. Evaluation of the translation of this approach to higher species is in progress. Since PNH erythrocyte lysis is thought to be mediated by the activation of the alternative pathway of complement we initiated work on the development of siRNA conjugates targeting Factor B, an essential component of the alternative pathway C3 convertase. siRNAs targeting rodent, primate and human Factor B were identified by in vitro screening and demonstrate >90% silencing of Factor B mRNA in human cell lines and primary mouse hepatocytes. Evaluation of Factor B silencing in rodent models is ongoing. siRNA-mediated silencing of liver-derived complement components is a promising novel therapeutic approach for inhibiting the activity of C5 and other complement pathway targets, with the potential to enable subcutaneous treatment for patients with PNH and related disorders. Disclosures: Borodovsky: Alnylam: Employment. Yucius:Alnylam: Employment. Sprague:Alnylam: Employment. Butler:Alnylam: Employment. Fishman:Alnylam: Employment. Nguyen:Alnylam: Employment. Vaishnaw:Alnylam: Employment. Maier:Alnylam: Employment. Kallanthottathil:Alnylam: Employment. Kuchimanchi:Alnylam: Employment. Manoharan:Alnylam: Employment. Meyers:Alnylam: Employment. Fitzgerald:Alnylam: Employment.
RGD-independent Cell Adhesion via a Tissue Transglutaminase-Fibronectin Matrix Promotes Fibronectin Fibril Deposition and Requires Syndecan-4/2 and α5β1 Integrin Co-signaling (2010)

Fibronectin (FN) deposition mediated by fibroblasts is an important process in matrix remodeling and wound healing. By monitoring the deposition of soluble biotinylated FN, we show that the stress-induced TG-FN matrix, a matrix complex of tissue transglutaminase (TG2) with its high affinity binding partner FN, can increase both exogenous and cellular FN deposition and also restore it when cell adhesion is interrupted via the presence of RGD-containing peptides. This mechanism does not require the transamidase activity of TG2 but is activated through an RGD-independent adhesion process requiring a heterocomplex of TG2 and FN and is mediated by a syndecan-4 and β1 integrin co-signaling pathway. By using α5 null cells, β1 integrin functional blocking antibody, and a α5β1 integrin targeting peptide A5-1, we demonstrate that the α5 and β1 integrins are essential for TG-FN to compensate RGD-induced loss of cell adhesion and FN deposition. The importance of syndecan-2 in this process was shown using targeting siRNAs, which abolished the compensation effect of TG-FN on the RGD-induced loss of cell adhesion, resulting in disruption of actin skeleton formation and FN deposition. Unlike syndecan-4, syndecan-2 does not interact directly with TG2 but acts as a downstream effector in regulating actin cytoskeleton organization through the ROCK pathway. We demonstrate that PKCα is likely to be the important link between syndecan-4 and syndecan-2 signaling and that TG2 is the functional component of the TG-FN heterocomplex in mediating cell adhesion via its direct interaction with heparan sulfate chains.