gebhart/patrepeval huggingface dataset:
ICAM-1 Antisense Oligodeoxynucleotide Improves Islet Allograft Survival and Function (2000)

Expression of intercellular adhesion molecule-1 (ICAM-1) and its ligand, leukocyte function antigen-1 (LFA-1), after pancreatic islet transplantation may affect both nonspecific and alloantigen-specific phases of graft destruction. We examined the effects of ICAM-1/LFA-1 blockade on the survival of islet allografts. Fresh C57BL/10 (H2h) pancreatic islets were transplanted under the renal subcapsular space (KC) or embolized into the liver after portal vein (PV) injection to C3H (H2k) mice. Recipients remained untreated or were treated for 7 days by i.p. administration of: ICAM-1 antisense phosphorothioate oligodeoxynucleotide (oligo) alone; anti-1CAM-1 (alphaICAM-1) monoclonal antibody (mAb) alone: alphaLFA-1 mAb alone; ICAM-1 oligo/alphaLFA mAb combination; alphaICAM-1 mAb/alphaLFA-1 mAb combination; or control oligo IP-8997 or IP-1082. In some experiments, donors were pretreated with ICAM-1 oligo. Inhibition of single ligand with 5.0 mg/kg ICAM-1 oligo (25.1 +/- 10.3), 100 microg/daily alphaICAM-1 mAb (24.2 +/- 8.0 days), or 50 microg/daily alphaLFA-1 mAb (42.8 +/- 25.9 days) prolonged the survivals of KC islet allografts in comparison with untreated controls (11.9 +/- 1.0 days; all p < 0.01). However, dual ICAM-1/LFA-1 blockade with either ICAM-1 oligo/alphaLFA-1 mAb (78.3 +/- 16.5 days) or (alphaICAM-1 mAb/aLFA-1 mAb (65.2 +/- 31.3 days) was the most effective therapy. Although pretreatment of donors with ICAM-1 oligo alone was ineffective (12.2 +/- 0.8 days; NS), a combination of donor pretreatment and recipient treatment started 1 day prior to grafting with ICAM-1 oligo (39.2 +/- 14.0 days) was more effective than the recipient treatment alone (24.6 +/- 8.8 days). Furthermore, ICAM-1/LFA-1 blockade improved islet function as evaluated by glucose tolerance test, and decreased inflammation in comparison with untreated controls. Similar in vivo results were obtained following PV administration of islet allografts. Thus, ICAM-1/LFA-1 blockade prolongs the survival of pancreatic islet allografts and improves their early function.
High‐resolution capillary electrophoretic analysis of DNA in free solution (1992)

Capillary electrophoretic separations of double-stranded DNA fragments in the size range of 20-2200 base pairs were achieved in less than 20 min with the use of a Tris-borate buffer containing hydroxyethylcellulose. Analyses were carried out in both uncoated and phenylmethyl-coated capillaries of fused silica with internal diameters of 50 and 100 microns, respectively, and an effective column length of 50 cm. The addition of ethidium bromide resulted in an improved resolution of double-stranded DNA fragments, thereby permitting even the separation of fragments differing only 1-2 base pairs in length. Moreover, resolution was found to be linearly proportional to the size of the cation used to adjust ionic strength Cs+ greater than RB+ greater than K+ greater than Na+ greater than Li+. However, the analysis times also increased with increasing cation size due to a decrease in electroosmotic flow. Elution order was verified by spiking restriction digests with slab gel electrophoretically purified components. Subsequently, the described system was applied to the detection and quantitation of an mRNA transcript of the androgen receptor, which had been amplified by polymerase chain reaction and purified by size-exclusion chromatography to avoid peak broadening due to conductivity differences between sample and running buffer. Since the actual amount of DNA introduced into the capillary cannot be defined, molar ratio-peak area ratios of the polymerase chain reaction product to various restriction fragments of known concentration were used to determine the amount of amplified DNA. The coefficient of variation was as small as 3.4% and the results were in good agreement with a spectrophotometric assay.
Method to Correlate Tandem Mass Spectra of Modified Peptides to Amino Acid Sequences in the Protein Database (1995)

A method to correlate uninterpreted tandem mass spectra of modified peptides, produced under low-energy (10-50 eV) collision conditions, with amino acid sequences in a protein database has been developed. The fragmentation patterns observed in the tandem mass spectra of peptides containing covalent modifications is used to directly search and fit linear amino acid sequences in the database. Specific information relevant to sites of modification is not contained in the character-based sequence information of the databases. The search method considers each putative modification site as both modified and unmodified in one pass through the database and simultaneously considers up to three different sites of modification. The search method will identify the correct sequence if the tandem mass spectrum did not represent a modified peptide. This approach is demonstrated with peptides containing modifications such as S-carboxymethylated cysteine, oxidized methionine, phosphoserine, phosphothreonine, or phosphotyrosine. In addition, a scanning approach is used in which neutral loss scans are used to initiate the acquisition of product ion MS/MS spectra of doubly charged phosphorylated peptides during a single chromatographic run for data analysis with the database-searching algorithm. The approach described in this paper provides a convenient method to match the nascent tandem mass spectra of modified peptides to sequences in a protein database and thereby identify previously unknown sites of modification.
The Mechanism of Substrate Activation of Pyruvate Decarboxylase: A First Approach (1978)

The sigmoidal shape of the curve for v[S], characteristic of pyruvate decarboxylase, indicates that the catalytic activity of this enzyme is regulated by the substrate. The enzyme, which is inactive in the absence of its substrate, is activated not only by 2-oxo acids but also by 2-oxo acid amides, which cannot act as a substrate of the enzyme. Whilst the dissociation constant of the enzyme-activator complex depends on the electrophilic nature of the carbonyl group, the catalytic activity reached at saturation concentrations of the activator species is independent of the structure of the activator molecules. The mechanism of activation which proceeds via two reversible steps could be evaluated exactly by stopped-flow techniques. The kinetic parameters of the activation and deactivation reaction were estimated and the validity of the equations derived which describe the activation kinetics could be proved by comparing them with the measured data. Using glyoxylic acid as an irreversibly binding active-site marker, it could be shown that addition of the substrate to the enzyme-bound thiamin diphosphate is the step of the catalytic mechanism whose rate is controlled by the substrate (activator) molecule.
Action of a cationic surfactant on the activity and removal of bacterial biofilms formed under different flow regimes (2004)

The action of the cationic surfactant cetyltrimethylammonium bromide (CTAB) was investigated to control biofilms (aged 7d) formed by Pseudomonas fluorescens on stainless-steel slides, using flow cells reactors, under turbulent and laminar flow. The effect of CTAB was also investigated using planktonic cells in the presence and absence of BSA, by measuring the cellular respiratory activity and the ATP released. The action of CTAB on biofilms was assessed by means of cellular respiratory activity and variation of biofilm mass, immediately and 3, 7 and 12h after the application of CTAB. The physical stability of the biofilm was also assessed using a rotating device, where the effect of the surfactant on the biofilm stability was evaluated through the variation of the mass remaining on the surface. CTAB significantly reduced the activity of the planktonic cells probably due to the rupture of the cells. This effect was significantly reduced in the presence of BSA. Planktonic cells were more easily inactivated than bacteria in biofilms. Biofilms formed under laminar flow were more susceptible than those formed under turbulent flow, but in both cases total inactivation was not achieved. Biofilm recovery was observed, in terms of respiratory activity, in almost all the cases studied. CTAB application by itself did not promote the detachment of biofilms. The physical stability tests showed that the synergistic action of the surfactant and the application of high shear stress to the biofilm increase its detachment.
PCR fragmentation of DNA. (1999)

A method has been developed to prepare random DNA fragments using PCR. First, two cycles are carried out at 16 degrees C with the Klenow's fragment and oligonucleotides (random primers) with random 3'-sequences and the 5'-constant part containing the site for cloning with the site-specific endonuclease. The random primers can link to any DNA site, and random DNA fragments are formed during DNA synthesis. During the second cycle, after denaturation of the DNA and addition of the Klenow's fragment, the random primers can link to newly synthesized DNA strands, and after DNA synthesis single-stranded DNA fragments are produced which have a constant primer sequence at the 5'-end and a complementary to it sequence at the 3'-end. During the third cycle, the constant primer is added and double-stranded fragments with the constant primer sequences at both ends are formed during DNA synthesis. Incubation for 1 h at 37 degrees C degrades the oligonucleotides used at the first stage due to endonuclease activity of the Klenow's fragment. Then routine PCR amplification is carried out using the constant primer. This method is more advantageous than hydrodynamic methods of DNA fragmentation widely used for "shotgun" cloning.
Conductivity and pH dual detection of growth profile of healthy and stressed Listeria monocytogenes (2005)

In this study, growth of Listeria monocytogenes in a low conductivity growth medium (LCGM) was simultaneously monitored by conductivity and pH measurements. Detection times obtained from the conductivity and pH growth curves were inversely related to the initial concentration of L. monocytogenes in the medium. Linear responses were found by plotting detection times obtained from both conductivity and pH growth curves as a function of initial cell concentration in the range of 10(2) to 10(7) cfu/mL. The detection time was approximately 12 and 2 h for 10(2) and 10(7) cfu/mL of viable L. monocytogenes, respectively, using the conductivity growth curves, whereas it was approximately 1 h less using the pH growth curves. This dual detection system was used for evaluating the growth of acid-, temperature-, and salt-treated L. monocytogenes in the medium. Acid stress at pH 2 and 3 for 3 h caused approximately 12 and 4 h delay in the detection time on pH growth curves, while stress at pH 5 for 3 h did not cause a significant delay in detection time. Delay in detection times was also observed for L. monocytogenes cells exposed to 45 degrees C for more than 1 h (2 and 6 h). Exposure to 10% NaCl for 3 h did not cause visible delay in the detection time. These observations on detection times for stressed L. monocytogenes had a consistent trend with the cell number decrease determined by surface plating method.
Organization of Achlya mtDNA: a population with two orientations and a large inverted repeat containing the rRNA genes. (1983)

We have investigated mtDNA organization in the oömycetous water mold; Achlya, and report here that this primitive organism contains a circular mitochondrial genome of 49.8 kilobase pairs. Extensive restriction endonuclease analysis indicates that a significant portion of the genome is present as an inverted repeat. Of 52 restriction sites for 14 enzymes thus far mapped, 28 sites cluster in two 9.6-kilobase-pair regions; within these regions, the sequence of sites is inverted but the spacing between analogous sites is identical. The repeat arms have a maximum length of 12.1 kilobase pairs and are separated by 4.6-8.4 and 21.0-22.3 kilobase pairs of unique sequences. Transfer hybridization experiments show that genes for both the large and the small rRNAs are contained within each repeat. Restriction endonuclease analysis shows that the unique regions between the inverted repeats are present in both possible orientations with respect to each other and in approximately equal proportions. These orientational, or "flip-flop," isomers of the unique regions are postulated to occur by intramolecular homologous recombination between the repeated regions.
Towards an HIV cure based on targeted killing of infected cells (2015)

We present perspectives for complementing cART with targeted cytotoxic therapy, whereby HIV infection is either eradicated or fully controlled, thereby eliminating the need for lifelong cART.
A cell‐surface opsonic receptor on leucocytes from the phylogenetically primitive vertebrate, Eptatretus stouti (1994)

A humoral recognition molecule that is homologous to the mammalian complement components C3, C4 and C5 has recently been identified in the Pacific hagfish, Eptatretus stouti. One function of this complement-like protein (CLP) is to opsonize foreign material for phagocytosis by hagfish leucocytes. Here, we demonstrate that CLP's opsonic activity can be abrogated by pre-incubating phagocytes with an anti-hagfish leucocyte mAb (1B1). Moreover, antigen-activated CLP can block the binding of the 1B1 antibody to hagfish leucocytes. Flow cytometry and immunoprecipitation indicate that 1B1 recognizes a 105 kDa cell-surface, monomeric protein that is expressed exclusively on phagocytic hagfish leucocytes. It is concluded that this 105 kDa protein represents the cell surface receptor by which CLP mediates the phagocytosis of opsonized targets.
Antiviral and antitumor compounds from tunicates. (1983)

Tunicates provide a rich source of biologically active compounds with potentially useful medicinal properties. The most interesting compounds identified thus far are the didemnins, depsipeptides from a Caribbean Trididemnum species, which are potent inhibitors of L1210 leukemia cells in vitro and are also active in vivo against P388 leukemia and B16 melanoma. In addition the didemnins inhibit growth of a variety of RNA and DNA viruses in vitro and protect mice infected intravaginally with herpes simplex virus type 2. Didemnin B, a derivative of didemnin A, is far more active than A, which argues for the likelihood of further useful chemical modifications in the series.
Expression of the oncofetal ED-B–containing fibronectin isoform in hematologic tumors enables ED-B–targeted 131I-L19SIP radioimmunotherapy in Hodgkin lymphoma patients (2009)

Current treatment of hematologic malignancies involves rather unspecific chemotherapy, frequently resulting in severe adverse events. Thus, modern clinical research focuses on compounds able to discriminate malignant from normal tissues. Being expressed in newly formed blood vessels of solid cancers but not in normal mature tissues, the extradomain B of fibronectin (ED-B FN) is a promising target for selective cancer therapies. Using immunohistology with a new epitope retrieval technique for paraffin-embedded tissues, ED-B FN expression was found in biopsies from more than 200 Hodgkin and non-Hodgkin lymphoma patients of nearly all entities, and in patients with myeloproliferative diseases. ED-B FN expression was nearly absent in normal lymph nodes (n = 10) and bone marrow biopsies (n = 9). The extent of vascular ED-B FN expression in lymphoma tissues was positively correlated with grade of malignancy. ED-B FN expression was enhanced in lymph nodes with severe lymphadenopathy and in some hyperplastic tonsils. The in vivo accessibility of ED-B FN was confirmed in 3 lymphoma patients, in whom the lymphoma lesions were visualized on scintigraphy with (131)I-labeled L19 small immunoprotein ((131)I-L19SIP). In 2 relapsed Hodgkin lymphoma patients(131)I-L19SIP radioimmunotherapy induced a sustained partial response, qualifying ED-B FN as a promising target for antibody-based lymphoma therapies.
Silicon optical modulators (2004)

Ever since the earliest research on optical circuits, dating back to the 1970s, there have been visions of an optical superchip (see for example1, 2, containing a variety of integrated optical components to carry out light generation, modulation, manipulation, detection, and amplification (Fig. 1. The early work was associated with ferroelectric materials such as lithium niobate (LiNbO3), and III-V semiconductors such as gallium arsenide (GaAs) and indium phosphide (InP) based systems. LiNbO3 was interesting almost solely because of the fact that it possesses a large electro-optic coefficient3, enabling optical modulation via the Pockels effect. Alternatively, the III-V compounds were interesting because of the relative ease of laser fabrication and the prospect of optical and electronic integration.
Allelopathic Agents from Parthenium hysterophorus and Baccharis megapotamica (1985)

Parthenium hysterophorus is a weed with a history of being an agricultural pest. A water extraction of P. hysterophorous has yielded parthenin, coronopilin, and two new sesquiterpene lactones closely related in structure to the former compounds. These compounds are believed to be responsible, at least in part, for the allelopathic properties of this plant. An alcohol extract of the Brazilian shrub, Baccharis megapotamica has yielded a large number of closely related, highly toxic sesquiterpenes belonging to a class of mycotoxins known as the macrocyclic trichothecenes. Evidence has been gathered to show that these compounds are acquired by B. megapotamica from a fungal source and oxygenated by the plants to yield the baccharinoids which are potent in vivo active antileukemic agents. A large scale extraction (1800 Kg) has yielded over twenty different macrocyclic trichothecenes.
Evaluation of different doses of formoterol from a newly developed powder inhalation device in asthmatic patients (1995)

Administration of different doses of formoterol from a recently developed multiple dose dry powder device was tested in a placebo-controlled, single-centre, double-blind, within-patient trial. Eighteen patients of both sexes, aged 18-65 years, with a FEV1 of 50-80% and a reversibility of at least 15% were randomized. During four treatment periods of 8 days each, divided by approximately 6 days, patients received placebo or 6, 12 or 24 micrograms (PL, F6, F12 and F24, respectively) of formoterol from the powder device. Efficacy parameters (FEV1) and safety parameters (primarily pulse rate, electrocardiogram [ECG] and subjective experiences) were evaluated during 24 hours on the last day of each treatment period. Peak flow and the number of puffs of used rescue medication (100 micrograms of salbutamol) were registered during treatment periods. For efficacy analysis, 17 patients remained. For FEV1 0.5 hour before the last dose and 12 and 24 hours after the last dose all formoterol doses were statistically significant superior to placebo. Clinically relevant differences from placebo were found up to 8 hours (F6) and 12 hours (F12 and F24). The difference between doses was clinically relevant for the area under the FEV1 curve between F6 and F24. PEF on the treatment days corresponded to these findings. In three cases of 13 reported adverse effects, the relation to trial medication was probable (tremor) or possible (insomnia and hyperaesthesia). All other safety measurements showed no significant differences. We conclude that formoterol dry powder in the newly developed multiple dose inhalation device is an effective and safe beta 2-stimulant with a long duration of action in doses of 6, 12 and 24 micrograms. The 24 micrograms dose is superior to the 6 micrograms dose. Efficacy decreased considerably between the 12th and 24th hour after dosing.
A timing-constrained algorithm for simultaneous global routing of multiple nets (2000)

In this paper, we propose a new approach for VLSI interconnect global routing that can optimize both congestion and delay, which are often competing objectives. Our approach provides a general framework that may use any single-net routing algorithm and any delay model in global routing. It is based on the observation that there are several routing topology flexibilities under timing constraints. These flexibilities are exploited for congestion reduction through a network flow based hierarchical bisection and assignment process. Experimental results on benchmark circuits are quite promising.
PINK1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkin (2010)

Loss-of-function mutations in PINK1 and Parkin cause parkinsonism in humans and mitochondrial dysfunction in model organisms. Parkin is selectively recruited from the cytosol to damaged mitochondria to trigger their autophagy. How Parkin recognizes damaged mitochondria, however, is unknown. Here, we show that expression of PINK1 on individual mitochondria is regulated by voltage-dependent proteolysis to maintain low levels of PINK1 on healthy, polarized mitochondria, while facilitating the rapid accumulation of PINK1 on mitochondria that sustain damage. PINK1 accumulation on mitochondria is both necessary and sufficient for Parkin recruitment to mitochondria, and disease-causing mutations in PINK1 and Parkin disrupt Parkin recruitment and Parkin-induced mitophagy at distinct steps. These findings provide a biochemical explanation for the genetic epistasis between PINK1 and Parkin in Drosophila melanogaster. In addition, they support a novel model for the negative selection of damaged mitochondria, in which PINK1 signals mitochondrial dysfunction to Parkin, and Parkin promotes their elimination.
Vaccine adjuvants as potential cancer immunotherapeutics (2016)

Accumulated evidence obtained from various clinical trials and animal studies suggested that cancer vaccines need better adjuvants than those that are currently licensed, which include the most commonly used alum and incomplete Freund's adjuvant, because of either a lack of potent anti-tumor immunity or the induction of undesired immunity. Several clinical trials using immunostimulatory adjuvants, particularly agonistic as well as non-agonistic ligands for TLRs, C-type lectin receptors, retinoic acid-inducible gene I-like receptors and stimulator of interferon genes, have revealed their therapeutic potential not only as vaccine adjuvants but also as anti-tumor agents. Recently, combinations of such immunostimulatory or immunomodulatory adjuvants have shown superior efficacy over their singular use, suggesting that seeking optimal combinations of the currently available or well-characterized adjuvants may provide a better chance for the development of novel adjuvants for cancer immunotherapy.
Beamforming Degradation of a W-CDMA Smart Antenna Under FDD and MAI Channel Estimation Errors (2007)

A smart antenna adopts the beamforming technique to increase the signal-to-(interference plus noise) ratio (SINR) and system capacity. In this paper, the impact of two channel estimation errors - frequency-division duplex (FDD) estimation error and multiple-access interference (MAI) estimation error for the beamforming of a wide-band code-division multiple-access smart antenna - are analyzed by using the measured channel state information. Results show that for a complex conjugate beamforming, FDD estimation error will cause median degradation of less than 1 dB if the desired signal is in a line-of-sight (LOS) channel and 1-3 dB if in a non-LOS (NLOS) channel. In addition, the MAI estimation error will cause 0.3-0.5 dB degradation per interference in the LOS case and 0.5-1 dB degradation in the NLOS case
Total Synthesis of the Indolizidinium Alkaloid Ficuseptine (2002)

The first total synthesis of ficuseptine [4,6-bis(4-methoxyphenyl)-1,2,3-trihydroindolizidinium chloride] (1), an alkaloid from Ficus septica, is described. The crucial steps in this five-step synthesis are a palladium-catalyzed bis(arylation) of a dibromopyridine under Suzuki conditions and a palladium-catalyzed alkynylation of an iodopyridine under Sonogashira conditions, as well as a novel Sandmeyer-type iodination of a 2-aminopyridine derivative. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)