gebhart/patrepeval huggingface dataset:
Ribozyme-targeted destruction of RNA associated with autosomal-dominant retinitis pigmentosa. (1998)

Ribozymes can discriminate between the mutant and wild-type sequences of mRNA associated with autosomal dominant retinitis pigmentosa. The kinetics and specificity of ribozyme cleavage indicate that they should reduce the amount of aberrant rhodopsin in the rod cells and may have potential as therapeutic agents against genetic disease.
Development of Biisoquinoline-Based Chiral Diaminocarbene Ligands:  Enantioselective SN2‘ Allylic Alkylation Catalyzed by Copper−Carbene Complexes (2008)

Chiral biisoquinoline-based diaminocarbene ligands (BIQ) were designed to create a chiral environment extended toward the metal center, which was confirmed by an X-ray structure. The concise ligand synthesis is highlighted by a modified Bischler-Napieralski cyclization of bisamides prepared from readily available chiral phenethylamines, and allows easy variation of the stereodifferentiating groups. The cyclohexyl-BIQ-copper complex is an efficient catalyst for enantioselective SN2' allylic alkylation with Grignard reagents showing SN2' regioselectivity higher than 5:1 and enantioselectivity in the range of 68-77% ee.
Phosphotyrosyl-specific protein phosphatase activity of a bovine skeletal acid phosphatase isoenzyme. Comparison with the phosphotyrosyl protein phosphatase activity of skeletal alkaline phosphatase. (1985)

A partially purified bovine cortical bone acid phosphatase, which shared similar characteristics with a class of acid phosphatase known as tartrate-resistant acid phosphatase, was found to dephosphorylate phosphotyrosine and phosphotyrosyl proteins, with little activity toward other phosphoamino acids or phosphoseryl histones. The pH optimum was about 5.5 with p-nitrophenyl phosphate as substrate but was about 6.0 with phosphotyrosine and about 7.0 with phosphotyrosyl histones. The apparent Km values for phosphotyrosyl histones (at pH 7.0) and phosphotyrosine (at pH 5.5) were about 300 nM phosphate group and 0.6 mM, respectively, The p-nitrophenyl phosphatase, phosphotyrosine phosphatase, and phosphotyrosyl protein phosphatase activities appear to be a single protein since these activities could not be separated by Sephacryl S-200, CM-Sepharose, or cellulose phosphate chromatographies, he ratio of these activities remained relatively constant throughout the purification procedure, each of these activities exhibited similar thermal stabilities and similar sensitivities to various effectors, and phosphotyrosine and p-nitrophenyl phosphate appeared to be alternative substrates for the acid phosphatase. Skeletal alkaline phosphatase was also capable of dephosphorylating phosphotyrosyl histones at pH 7.0, but the activity of that enzyme was about 20 times greater at pH 9.0 than at pH 7.0. Furthermore, the affinity of skeletal alkaline phosphatase for phosphotyrosyl proteins was low (estimated to be 0.2-0.4 mM), and its protein phosphatase activity was not specific for phosphotyrosyl proteins, since it also dephosphorylated phosphoseryl histones. In summary, these data suggested that skeletal acid phosphatase, rather than skeletal alkaline phosphatase, may act as phosphotyrosyl protein phosphatase under physiologically relevant conditions.
Predicting and estimating the accuracy of a subpixel registration algorithm (1990)

It is shown that an efficient practical registration algorithm previously described by H.G. Barrow et al. (1977) can provide high-accuracy registration. Experiments with a quantized video image of a solid triangle yielded registration that was accurate to 3% of the interpixel spacing (i.e. accurate to 0.5 mils) in the x and y directions and 0.015 degrees in rotation. It may also be important to predict the accuracy in advance, to see whether specifications can be met and to estimate accuracy during registration, in order to control quality. The authors provide practical formulas for both purposes for two kinds of image point data: edge detection (ED) data and direct measurement (DM) data. In two experiments using ED data, the predicted, estimated, and observed accuracies are all in agreement. The prediction theory developed suggests five precautions to avoid loss of registration accuracy. Perhaps most important is Precaution c, the necessity of the ED case not to have a large fraction of the total segment length of the model aligned with the horizontal or vertical directions of the pixel grid. When the model consists largely of horizontal and vertical segments, a good way to observe this precaution is to tilt the pixel grid a few degrees away from perfect alignment, e.g. by tilting the video camera. A third experiment verifies that violating Precaution c can seriously degrade accuracy.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A Novel Rabbit Model of Mild, Reproducible Disc Degeneration by an Anulus Needle Puncture: Correlation Between the Degree of Disc Injury and Radiological and Histological Appearances of Disc Degeneration (2005)

The needle puncture approach, using 16G to 21G needles, resulted in a reproducible decrease of disc height and magnetic resonance imaging grade. The ease of the procedure and transfer of the methodology will benefit researchers studying disc degeneration.
Cetuximab alleviates neuropathic pain despite tumour progression (2012)

The authors present the case of a 68-year-old male patient with metastatic rectal cancer. A pelvic recurrence resulted in neuropathic pain, radiating down his left leg. The pain was resistant to standard treatments. However, after nearly 3 years of debilitating pain, the patient experienced dramatic relief just hours after an infusion of the antiepidermal growth factor receptor antibody cetuximab. The analgesic effect lasted for 10–12 days and was repeated roughly every 12 days for three and a half years. To test for placebo effect, the patient received (unknown to him) 20% of his usual cetuximab dose and experienced no pain relief. The dramatic analgesic effect was documented in clinical notes, medication lists and in numeric rating scales even while his cancer was in radiological progression. Mitogen-activated protein kinase (MAPK)-signalling is believed to be an important driver of neuropathic pain and therefore, the authors hypothesise a direct inhibition of MAPK-signalling by cetuximab in neuronal or glial cells.
Precise Sequential DNA Ligation on A Solid Substrate: Solid-Based Rapid Sequential Ligation of Multiple DNA Molecules (2013)

Ligation, the joining of DNA fragments, is a fundamental procedure in molecular cloning and is indispensable to the production of genetically modified organisms that can be used for basic research, the applied biosciences, or both. Given that many genes cooperate in various pathways, incorporating multiple gene cassettes in tandem in a transgenic DNA construct for the purpose of genetic modification is often necessary when generating organisms that produce multiple foreign gene products. Here, we describe a novel method, designated PRESSO (precise sequential DNA ligation on a solid substrate), for the tandem ligation of multiple DNA fragments. We amplified donor DNA fragments with non-palindromic ends, and ligated the fragment to acceptor DNA fragments on solid beads. After the final donor DNA fragments, which included vector sequences, were joined to the construct that contained the array of fragments, the ligation product (the construct) was thereby released from the beads via digestion with a rare-cut meganuclease; the freed linear construct was circularized via an intra-molecular ligation. PRESSO allowed us to rapidly and efficiently join multiple genes in an optimized order and orientation. This method can overcome many technical challenges in functional genomics during the post-sequencing generation.
Protein Interactions within the N-end Rule Ubiquitin Ligation Pathway (2003)

Rate studies have been employed as a reporter function to probe protein-protein interactions within a biochemically defined reconstituted N-end rule ubiquitin ligation pathway. The concentration dependence for E1-catalyzed HsUbc2b/E2(14kb) transthiolation is hyperbolic and yields K(m) values of 102 +/- 13 nm and 123 +/- 19 nm for high affinity binding to rabbit and human E1/Uba1 orthologs. Competitive inhibition by the inactive substrate and product analogs HsUbc2bC88A (K(i) = 104 +/- 15 nm) and HsUbc2bC88S-ubiquitin oxyester (K(i) = 169 +/- 17 nm), respectively, indicates that the ubiquitin moiety contributes little to E1 binding. Under conditions of rate-limiting E3alpha-catalyzed conjugation to human alpha-lactalbumin, HsUbc2b-ubiquitin thiolester exhibits a K(i) of 54 +/- 18 nm and is competitively inhibited by the substrate analog HsUbc2bC88S-ubiquitin oxyester (K(i) = 66 +/- 29 nm). In contrast, the ligase product analog HsUbc2bC88A exhibits a K(i) of 440 +/- 55 nm with respect to the wild type HsUbc2b-ubiquitin thiolester, demonstrating that ubiquitin binding contributes to the ability of E3alpha to discriminate between substrate and product E2. A survey of E1 and E2 isoform distribution in selected cell lines demonstrates that Ubc2 isoforms are the predominant intracellular ubiquitin carrier protein. Intracellular levels of E1 and Ubc2 are micromolar and approximately equal based on in vitro quantitation by stoichiometric (125)I-ubiquitin thiolester formation. Comparison of intracellular E1 and Ubc2 pools with the corresponding ubiquitin pools reveals that most of the free ubiquitin in cells is present as thiolesters to the components of the conjugation pathways. The present data represent the first comprehensive analysis of protein interactions within a ubiquitin ligation pathway.
An interinstitutional and interspecialty comparison of treatment outcome data for patients with prostate carcinoma based on predefined prognostic categories and minimum follow‐up (2002)

The current data suggest that interinstitutional and interspecialty comparisons of treatment outcome for patients with prostate carcinoma are possible but that results must be based on all major prognostic variables to be meaningful. Analyzed in this fashion, 5-year PSA results were similar for patients in low-risk and intermediate-risk groups, regardless of the form of therapy. Findings from prospective, randomized trials using survival (cause specific and overall) as the end point for judging treatment efficacy and longer follow-up will be needed to validate these findings and to identify the most appropriate management option for patients with all stages of disease.
Sphingosine and its methylated derivative N,N-dimethylsphingosine (DMS) induce apoptosis in a variety of human cancer cell lines (1996)

In the study of apoptosis initiated by various signals including ligands binding to cell membrane receptors such as Fas and TNFRI, the sphingomyelin pathway and its resulting metabolites, the sphingolipids, have been suggested to be involved in the signaling pathway. In earlier studies we presented data which indicated that sphingosine (Sph) itself was increased during apoptosis induced by phorbol myristate acetate (PMA) in HL60 cells and tumor necrosis factor (TNF) in neutrophils, and when added exogenously was able to induce apoptosis. We report here that Sph and its methylated derivative N,N,-dimethylsphingosine (DMS) are able to induce apoptosis in cancer cells of both hematopoietic and carcinoma origin. In human leukemic cell lines CMK-7, HL60 and U937, treatment with 20 microM Sph for 6 hr caused apoptosis in up to 90% of cells. Human colonic carcinoma cells HT29, HRT18, MKN74 and COLO205 were shown to be more susceptible to apoptosis upon addition of DMS (>50%) than of Sph (<50%), yet were weakly or not sensitive to N,N,N-trimethylsphingosine (TMS). Under the same conditions, in the presence of serum, neither Sph-1-phosphate nor ceramide analogues C2-, C6- or C8-ceramide were able to induce apoptosis in any cell lines. However, in the absence of serum, ceramide analogues induced apoptosis in leukemia cell lines after 18 hr, yet much less so than Sph or DMS. Furthermore, apoptosis induced by Sph or DMS could not be inhibited by the ceramide synthase inhibitor fumonisin B1. Apoptosis was not induced by sphingolipids in primary culture cells, such as HUVEC or rat mesangial cells, but was apparent in transformed rat mesangial cells. Additionally, apoptosis induced by Sph, DMS or C2Cer was inhibited by protease inhibitors. Our data further support the evidence that the catabolic pathway of sphingomyelin involving Sph and other metabolites is an integral part of the apoptosis pathway.
Oncolytic Immunotherapy for Bladder Cancer Using Coxsackie A21 Virus (2018)

As a clinical setting in which local live biological therapy is already well established, non-muscle invasive bladder cancer (NMIBC) presents intriguing opportunities for oncolytic virotherapy. Coxsackievirus A21 (CVA21) is a novel intercellular adhesion molecule-1 (ICAM-1)-targeted immunotherapeutic virus. This study investigated CVA21-induced cytotoxicity in a panel of human bladder cancer cell lines, revealing a range of sensitivities largely correlating with expression of the viral receptor ICAM-1. CVA21 in combination with low doses of mitomycin-C enhanced CVA21 viral replication and oncolysis by increasing surface expression levels of ICAM-1. This was further confirmed using 300-μm precision slices of NMIBC where levels of virus protein expression and induction of apoptosis were enhanced with prior exposure to mitomycin-C. Given the importance of the immunogenicity of dying cancer cells for triggering tumor-specific responses and long-term therapeutic success, the ability of CVA21 to induce immunogenic cell death was investigated. CVA21 induced immunogenic apoptosis in bladder cancer cell lines, as evidenced by expression of the immunogenic cell death (ICD) determinant calreticulin, and HMGB-1 release and the ability to reject MB49 tumors in syngeneic mice after vaccination with MB49 cells undergoing CVA21 induced ICD. Such CVA21 immunotherapy could offer a potentially less toxic, more effective option for the treatment of bladder cancer.
[Seminal plasma levocarnitine significantly correlated with semen quality]. (2008)

The level of seminal plasma levocarnitine is positively correlated with sperm motility and vitality, and more significantly with sperm concentration.
DESIGN OF DOUBLE DIPOLE ANTENNA WITH ENHANCED USABLE BANDWIDTH FOR WIDEBAND PHASED ARRAY APPLICATIONS (2006)

In this paper, the regular microstrip-fed dipole antenna with simplified balun is modified to improve the usable bandwidth by increasing the stability of the radiation patterns. The presented antenna consists of two parallel dipoles of different lengths to obtain two main resonances. The distance between the two dipoles is adjusted to reduce the return loss between the two main resonances. A wide usable bandwidth of more than 84% is obtained with high radiation pattern stability. The proposed antenna is simple and small in size. The results of a modified two-element array configuration from this antenna show that it is very good candidate for wideband phased array applications.
Blood-Brain Barrier Disruption with Focused Ultrasound Enhances Delivery of Chemotherapeutic Drugs for Glioblastoma Treatment (2010)

This study demonstrates a means of increasing localized chemotherapeutic drug delivery for brain tumor treatment and strongly supports the feasibility of this treatment in a clinical setting.
CONFORMATIONAL CHANGES IN ENZYME CATALYSIS (1962)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Ana Heva lava tube (Easter Island, Chile): Preliminary characterization of the internal layers of coralloid-type speleothems (2015)

Journal Article Ana Heva lava tube (Easter Island, Chile): Preliminary characterization of the internal layers of coralloid-type speleothems Get access AZ Miller, AZ Miller CERENA/CEPGIST, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001, Lisbon, PORTUGAL Email: ana.miller@tecnico.ulisboa.pt Search for other works by this author on: Oxford Academic Google Scholar MFC Pereira, MFC Pereira CERENA/CEPGIST, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001, Lisbon, PORTUGAL Search for other works by this author on: Oxford Academic Google Scholar JM Calaforra, JM Calaforra Department of Biology and Geology, University of Almeria, Ctra. Sacramento s/n, La Cañada de San Urbano 04120, Almería, SPAIN Search for other works by this author on: Oxford Academic Google Scholar P Forti, P Forti Department of Earth Sciences and Environmental Geology, University of Bologna, Via Zamboni 33, 40126, Bologna, ITALY Search for other works by this author on: Oxford Academic Google Scholar A Dionísio, A Dionísio CERENA/CEPGIST, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001, Lisbon, PORTUGAL Search for other works by this author on: Oxford Academic Google Scholar C Saiz-Jimenez C Saiz-Jimenez Instituto de Recursos Naturales y Agrobiologia, IRNAS-CSIC, Av. Reina Mercedes 10, 41012, Seville, SPAIN Search for other works by this author on: Oxford Academic Google Scholar Microscopy and Microanalysis, Volume 21, Issue S6, 1 August 2015, Pages 68–69, https://doi.org/10.1017/S1431927614014044 Published: 10 September 2015
Multilevel signaling for increasing the reach of 10 Gb/s lightwave systems (1999)

Polybinary, optical amplitude modulated phase shift keying (AM-PSK) polybinary, M-ary amplitude shift keying (ASK), and polyquaternary signaling schemes operating at 10 Gb/s are investigated in 1550-nm lightwave systems operating over standard, single-mode fiber. The premise for exploring these signal types is that they concentrate power at frequencies closer to the optical carrier where phase distortion of the optical field from chromatic dispersion is less severe. Issues such as modulator chirp, optimal level spacing in a 4-ary ASK signal, and phase modulated to amplitude modulated (PM-AM) noise conversion from a nonzero laser linewidth are studied. It is found that higher order polybinary signals do not offer an improvement in dispersion tolerance over a duobinary signal. 4-ary ASK is demonstrated to increase the dispersion-limited distance to 225 km experimentally and 350 km through simulation, but at the expense of a /spl sim/8 dB degradation in receiver sensitivity due to the increased number of levels and the signal dependence of signal-spontaneous beat noise. Furthermore, the linewidth requirement for a 4-ary ASK signal is less than 1 MHz in order to minimize the impact of PM-AM relative intensity noise (RIN) when transmitting over 200-300 km.
Comparative Enzymatic Study of HIV-1 Reverse Transcriptase Resistant to 2‘,3‘-Dideoxynucleotide Analogs Using the Single-Nucleotide Incorporation Assay (1997)

Employing the single-nucleotide incorporation assay using a heteropolymeric RNA template and DNA primers, we defined enzymatic profiles of recombinant human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) containing a set of five mutations [A62V, V75I, F77L, F116Y, and Q151M] which confers resistance to multiple 2',3'-dideoxynucleosides (ddNs) on HIV-1. RTs containing other drug-resistance-associated mutations were also examined. The K(m) for dNTPs, the kcat, and the kcat/ K(m) ratios of mutant RTs were all comparable to those of wild-type RT (RTwt). The processive primer extension activity of mutant RTs was also comparable to that of RTwt as examined in the presence of saturating concentrations of dNTPs and heparin. Determination of the Ki values toward 5'-triphosphates (TP) of various ddNs [3'-azido-2',3'-dideoxythymidine (AZT), 2',3'-didehydro-2',3'-dideoxythymidine (D4T), 2',3'-dideoxycytidine (ddC), (-)-beta-L-2',3'-dideoxy-3'-thiacytidine (3TC), (-)-beta-L-2',3'-dideoxy-5-fluorocytidine (FddC), 2',3'-dideoxyadenosine (ddA), and 2'-beta-fluoro-2',3'-dideoxyadenosine (FddA)] and 9-(2-phosphonylmethoxyethyl)adenine diphosphate (PMEApp) revealed that RTA62V/V75I/F77L/F116Y/Q151M was insensitive to ddATP, AZTTP, D4TTP, FddATP, and ddCTP, but was sensitive to PMEApp, 3TCTP, and FddCTP. RTK65R was less sensitive to ddATP, FddATP, PMEApp, ddCTP, and 3TCTP, while RTM184V was less sensitive only to 3TCTP and ddCTP. The determination of Ki(ddNTP)/K(m)(dNTP) ratios showed that AZTTP, D4TTP, and ddCTP are, as substrates, as efficient for RTwt as their corresponding dNTPs, that ddATP, PMEApp, and 3TCTP are moderately efficient substrates for RTwt, and that FddATP is the least efficient substrate among ddNTPs examined. The observed cross-resistance of HIV-1 RT to various ddNTPs should reflect the alteration of RT's substrate recognition and should provide insights into the molecular mechanism of RT discrimination of ddNTPs from natural substrates.
FcγRIIB1/SHIP-mediated Inhibitory Signaling in B Cells Involves Lipid Rafts (2001)

One type of membrane microdomain, enriched in glycosphingolipids and cholesterol and referred to as lipid rafts, has been implicated in the generation of activating signals triggered by a variety of stimuli. Several laboratories, including ours, have recently demonstrated that the B cell receptor (BCR) inducibly localizes to the rafts upon activation and that functional lipid rafts are important for BCR-mediated "positive" signaling. In the later phases of the immune response, coligation of the BCR and the inhibitory receptor Fc gamma RIIB1 leads to potent inhibition of BCR-induced positive signaling through the recruitment of the inositol phosphatase SHIP to Fc gamma RIIB1. One potential model is that the Fc gamma RIIB1 itself might be excluded from the rafts basally and that destabilization of raft-dependent BCR signaling might be part of the mechanism for the Fc gamma RIIB1-mediated negative regulation. We tested this hypothesis and observed that preventing BCR raft localization is not the mechanism for this inhibition. Surprisingly, a fraction of Fc gamma RIIB1 is constitutively localized in the rafts and increases further after BCR + FcR coligation. SHIP is actively recruited to lipid rafts under negative stimulation conditions, and the majority of Fc gamma RIIB1-SHIP complexes localize to lipid rafts compared with non-raft regions of the plasma membrane. This suggested that this negative feedback loop is also initiated in the lipid rafts. Despite its basal localization to the rafts, Fc gamma RIIB1 did not become phosphorylated after BCR alone cross-linking and did not colocalize with the BCR that moves to rafts upon BCR engagement alone (positive signaling conditions), perhaps suggesting the existence of different subsets of rafts. Taken together, these data suggest that lipid rafts play a role in both the positive signaling via the BCR as well as the inhibitory signaling through Fc gamma RIIB1/SHIP.