gebhart/patrepeval huggingface dataset:
Comparative analysis and application of fluorescent protein-tagged connexins (2001)

In order to examine connexin transport, assembly, and turnover in living cells, we tagged green fluorescent protein or its color variants to several members of the connexin family of proteins. When green fluorescent protein was tagged to the carboxyl terminal end of connexin43 (Cx43-GFP), the resulting fusion protein was transported and assembled into functional gap junctions. However, when GFP was tagged to the amino terminal end of Cx43 (GFP-Cx43), this chimera was biosynthesized, transported to the plasma membrane, but failed to form gap junction channels that could transfer Lucifer yellow. Single cells that expressed Cx43-GFP were capable of transporting this fusion protein to the cell surface in the absence of cell-cell contact. Imaging of Cx43-yellow (Y)FP (Cx43-YFP) was quite efficient; however, the low quantum yield Cx43-BFP and the requirement for ultraviolet excitation made this chimera less suitable for time-lapse imaging. Cx43-cyan C(FP) (Cx43-CFP) was more suitable for imaging than Cx43-blue (B)FP and could be effectively separated from Cx43-YFP. The versatility of tagging GFP to the carboxyl terminal end of other members of the connexin family was established when Cx32-GFP and Cx26-YFP were found to assemble into gap junctions capable of transferring Lucifer yellow. Finally, we are examining the effectiveness of using a new red fluorescent protein (DsRed) fused to connexins in combination with Cx-GFP to simultaneously examine the kinetics, transport and turnover of two connexins. Together, our studies suggest that tagging fluorescent proteins to the carboxyl terminal end of connexins is an effective and valuable approach for studying the life cycle and dynamics of connexins in living cells.
A practical approach to wound care in patients with complex enterocutaneous fistulas. (1985)

A practical, low cost method for controlling high output enterocutaneous fistulas is presented herein. The technique is advantageous because it provides for excellent protection of the skin, is low in cost and is constructed from readily available materials. It is applicable to all fistulas which do not readily accept prefabricated base plate appliances. Its components are so simple that minimal time for wound care on the part of the surgeon, nursing staff or stomal therapist is required.
Eradication of bacterial persisters with antibiotic-generated hydroxyl radicals (2012)

During Mycobacterium tuberculosis infection, a population of bacteria likely becomes refractory to antibiotic killing in the absence of genotypic resistance, making treatment challenging. We describe an in vitro model capable of yielding a phenotypically antibiotic-tolerant subpopulation of cells, often called persisters, within populations of Mycobacterium smegmatis and M. tuberculosis. We find that persisters are distinct from the larger antibiotic-susceptible population, as a small drop in dissolved oxygen (DO) saturation (20%) allows for their survival in the face of bactericidal antibiotics. In contrast, if high levels of DO are maintained, all cells succumb, sterilizing the culture. With increasing evidence that bactericidal antibiotics induce cell death through the production of reactive oxygen species (ROS), we hypothesized that the drop in DO decreases the concentration of ROS, thereby facilitating persister survival, and maintenance of high DO yields sufficient ROS to kill persisters. Consistent with this hypothesis, the hydroxyl-radical scavenger thiourea, when added to M. smegmatis cultures maintained at high DO levels, rescues the persister population. Conversely, the antibiotic clofazimine, which increases ROS via an NADH-dependent redox cycling pathway, successfully eradicates the persister population. Recent work suggests that environmentally induced antibiotic tolerance of bulk populations may result from enhanced antioxidant capabilities. We now show that the small persister subpopulation within a larger antibiotic-susceptible population also shows differential susceptibility to antibiotic-induced hydroxyl radicals. Furthermore, we show that stimulating ROS production can eradicate persisters, thus providing a potential strategy to managing persistent infections.
Action potential conduction block of nerves in vitro by potassium citrate, potassium tartrate and potassium oxalate (1999)

Potassium citrate and potassium tartrate were more effective than other potassium salts in blocking nerve conduction and may be more effective dentinal desensitising agents.
Both the ADP receptors P2Y 1 and P2Y 12 , play a role in controlling shape change in human platelets (2003)

Two types of ADP receptors, P2Y 1 and P2Y 12 are involved in platelet aggregation. The P2X 1 receptor is also present but its role, in terms of platelet function, is not yet defined. The aim of this study was to establish if the ADP receptors, P2Y 1, P2Y 12 and P2X 1 play a role in controlling platelet shape change (PSC) in human platelets. PSC is an early phase of platelet activation that precedes aggregation. Using a high-resolution channelyzer, PSC was assessed by measuring the median platelet volume (MPV). The P2Y 1 receptor antagonist MRS 2179 (1.06 m 10.25 µmol/l) blocked ADP-induced PSC (by 100%). The median IC 50 was 3.16 µmol/l. MRS 2179 also significantly ( P = 0.01) inhibited PSC induced by the combination of ADP + serotonin (5HT). The P2Y 12 receptor antagonist AR-C69931MX significantly inhibited (at 10s, P = 0.009; 15 s, P = 0.001 and 30 s, P = 0.015) ADP-induced PSC. The P2X 1 receptor antagonist TNP-ATP had no significant effect on ADP- or ADP + 5HT-induced PSC. We conclude that the IC 50 of a P2Y 1 -blocker can be derived because of the high-resolution and reproducibility of the channelyzer technique. In addition to the P2Y 1 purinoceptor, the P2Y 12 receptor appears to be involved in ADP-induced PSC since this process was significantly inhibited by AR-C69931MX. The channelyzer technique may be more reliable than optical aggregometry to assess PSC.
Synthesen mit substituierten Malondialdehyden, VII1) Darstellung von Fluor‐ und Jodmalondialdehyd (1970)

Abstract Es wird über die Darstellung und Eigenschaften des Fluor‐ ( 5 ) und des Jodmalondialdehyds ( 12 ) berichtet. 5 entsteht durch alkalische Hydrolyse des 2‐Fluor‐3‐dimethylamino‐acroleins ( 3 ), das durch Vilsmeier‐Formylierung von Fluoressigsäure nach Arnold erhalten wird. Die Darstellung von 3 wird verbessert. ‐ 12 wird aus Malondialdehyd durch direkte elektrophile Substitution mit Jod(I)‐chlorid gewonnen.
Importance of intermolecular interactions in the nonlinear optical properties of poled polymers (2000)

A series of phenylbithiophene stilbenes and phenyltetraenes were synthesized and their first-order molecular hyperpolarizabilities determined. Optical nonlinearities up to μβo=9300×10−69 C m5/V were measured at 1907 nm. We show that intermolecular interactions have a large influence on the optical nonlinearity of the molecules in solution and in guest-host polymers with polymethylmethacrylate and polyquinoline as the host. We propose the use of a bulky donor group and a side chain perpendicular to the molecule’s conjugate bridge to reduce aggregation. Electro-optic coefficients as high as r33=30 pm/V at 1.55 μm in polymethylmethacrylate with 25 wt % chromophore loading were measured.
New Transition‐Metal‐Dependent DNAzymes as Efficient Endonucleases and as Selective Metal Biosensors. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Characterization of Glycoprotein PAS‐6/7 from Membranes of Bovine Milk Fat Globules (1996)

Glycoprotein components PAS-6 and PAS-7 were purified from bovine milk-fat-globule membranes and the amino acid sequence of their common polypeptide core, PAS-6/7, was determined by peptide and cDNA sequencing. The cDNA encoded a signal peptide of 18 amino acid residues and a mature PAS-6/ 7 protein of 409 amino acid residues. A cDNA splice variant was identified by reverse transcription/ PCR. Results obtained by amino acid analyses, amino-acid-sequence analyses, carbohydrate-composition determinations, and MS analyses of glycopeptides revealed that both proteins were glycosylated with a carbohydrate structure that contained galactose, N-acetylgalactosamine and fucose, and which was O-linked to Ser9 in PAS-6 and to Thr16 in PAS-7. In addition, PAS-6 and PAS-7 were N-glycosylated at Asn41 with a hybrid-type-carbohydrate structure. A high-mannose glycan was N-linked to Asn209 of PAS-6. The sequence of PAS-6/7 contained two epidermal growth factor (EGF)-like domains in the N-terminal region, the second of which contained an RGD cell-adhesion sequence in an extended loop. The EGF-like domains were followed by a C-terminal tandem repeat, which showed 60-63% similarity to the C1-C2 domain of blood-clotting factors V and VIII. The disulfide bonds within the C1-C2 domain were identified.
Study of the Biological Activities of Toxic Shock Syndrome Toxin‐1 (1986)

The mitogenic and interleukin 2 (IL 2) production-inducing effects of toxic shock syndrome toxin-1 (TSST-1) on murine lymphocytes were investigated. TSST-1, an exotoxin produced by Staphylococcus aureus recovered from patients with toxic shock syndrome (TSS), is thought to be a causative agent of the syndrome. TSST-1 was mitogenic for splenic T cells and peanut agglutinin (PNA)-negative thymocytes, but not for T cell-depleted spleen cells, PNA-positive thymocytes or IL 2-dependent CTLL 2-cells. A factor mitogenic for CTCC-2 cells with a molecular weight of 30-35 kdaltons was obtained by stimulating spleen cells with TSST-1 and it was absorbed by CTLL-2 cells, indicating that the factor is IL 2. For substantial amounts of IL 2 to be produced, 10 ng or more of TSST-1 per ml and 48 hr or more of incubation were required. Removal of T cells abrogated the IL 2 production by spleen cells. T cells obtained by the nylon wool column method alone produced IL 2 on TSST-1 stimulation in the presence of either macrophages or a macrophage lysate containing interleukin 1. However, T cells obtained by a combination of the nylon wool column method and anti-Ia antibody treatment produced IL 2 in the presence of macrophages but not of the macrophage lysate, indicating that IL 2 production by TSST-1-stimulated T cells is absolutely dependent on the presence of accessory cells.
Genome editing in maize directed by CRISPR–Cas9 ribonucleoprotein complexes (2016)

Targeted DNA double-strand breaks have been shown to significantly increase the frequency and precision of genome editing. In the past two decades, several double-strand break technologies have been developed. CRISPR-Cas9 has quickly become the technology of choice for genome editing due to its simplicity, efficiency and versatility. Currently, genome editing in plants primarily relies on delivering double-strand break reagents in the form of DNA vectors. Here we report biolistic delivery of pre-assembled Cas9-gRNA ribonucleoproteins into maize embryo cells and regeneration of plants with both mutated and edited alleles. Using this method of delivery, we also demonstrate DNA- and selectable marker-free gene mutagenesis in maize and recovery of plants with mutated alleles at high frequencies. These results open new opportunities to accelerate breeding practices in a wide variety of crop species.
Pathophysiology of hypophosphatasia and the potential role of asfotase alfa (2016)

Hypophosphatasia (HPP) is an inherited systemic bone disease that is characterized by bone hypomineralization. HPP is classified into six forms according to the age of onset and severity as perinatal (lethal), perinatal benign, infantile, childhood, adult, and odontohypophosphatasia. The causative gene of the disease is the ALPL gene that encodes tissue-nonspecific alkaline phosphatase (TNAP). TNAP is expressed ubiquitously, and its physiological role is apparent in bone mineralization. A defect in bone mineralization can manifest in several ways, including rickets or osteomalacia in HPP patients. Patients with severe forms suffer from respiratory failure because of hypoplastic chest, which is the main cause of death. They sometimes present with seizures due to a defect in vitamin B6 metabolism resulting from the lack of alkaline phosphatase activity in neuronal cells, which is also lethal. Patients with a mild form of the disease exhibit rickets or osteomalacia and a functional defect of exercise. Odontohypophosphatasia shows only dental manifestations. To date, 302 mutations in the ALPL gene have been reported, mainly single-nucleotide substitutions, and the relationships between phenotype and genotype have been partially elucidated. An established treatment for HPP was not available until the recent development of enzyme replacement therapy. The first successful enzyme replacement therapy in model mice using a modified human TNAP protein (asfotase alfa) was reported in 2008, and subsequently success in patients with severe form of the disease was reported in 2012. In 2015, asfotase alfa was approved in Japan in July, followed by in the EU and Canada in August, and then by the US Food and Drug Administration in the USA in October. It is expected that therapy with asfotase alfa will drastically change treatments and prognosis of HPP.
A Construction of Systematic MDS Codes With Minimum Repair Bandwidth (2011)

In a distributed storage system based on erasure coding, an important problem is the repair problem: If a node storing a coded piece fails, in order to maintain the same level of reliability, we need to create a new encoded piece and store it at a new node. This paper presents a construction of systematic (n,k)-MDS codes for 2k ≤ n that achieves the minimum repair bandwidth when repairing from k+1 nodes.
Analysis of a Symmetric Rank-One Trust Region Method (1996)

Several recent computational studies have shown that the symmetric rank-one (SR1) update is a very competitive quasi-Newton update in optimization algorithms. This paper gives a new analysis of a trust region SR1 method for unconstrained optimization and shows that the method has an $n + 1$ step q-superlinear rate of convergence. The analysis makes neither of the assumptions of uniform linear independence of the iterates nor positive definiteness of the Hessian approximations that have been made in other recent analyses of SR1 methods. The trust region method that is analyzed is fairly standard, except that it includes the feature that the Hessian approximation is updated after all steps, including rejected steps. We also present computational results that show that this feature, safeguarded in a way that is consistent with the convergence analysis, does not harm the efficiency of the SR1 trust region method.
Adaptive behavior with fixed weights in RNN: an overview (2003)

In this paper we review recent results on the adaptive behavior attained with fixed-weight recurrent neural networks (meta-learning). We argue that such behavior is a natural consequence of prior training.
A framework for targeting banner advertising on the Internet (2002)

Constraints that limit accurate targeting of advertising in traditional media may not hold in cyberspace. This paper presents a model for effectively and efficiently targeting hypermedia-based banner advertisements in an online information service. The model takes advantage of information technology to micro-target banner advertisements based on individual characteristics of users. A simple version of the model, which has the virtue of ease of development, is presented. Enhancements are also proposed. These require more effort to develop, but may lead to even more precise targeting of advertisements. Implementation of this framework may benefit both online advertisers and online consumers.
THE PATHOPHYSIOLOGICAL ROLE OF PEROXYNITRITE IN SHOCK, INFLAMMATION, AND ISCHEMIA-REPERFUSION INJURY (1996)

Peroxynitrite is a reactive oxidant produced from nitric oxide (NO) and superoxide, which reacts with proteins, lipids, and DNA under conditions of inflammation and shock. Here we overview the role of peroxynitrite in circulatory shock and inflammation. Immunohistochemical and biochemical evidence demonstrate production of peroxynitrite in endotoxic and hemorrhagic shock, chronic bowel inflammation, and in various forms of ischemia-reperfusion injury. The reactivity and decomposition of peroxynitrite is determined by the chemical environment, and the ratio of superoxide versus NO. Peroxynitrite can initiate toxic oxidative reactions in vitro and in vivo. Initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3-phosphate dehydrogenase, inhibition of membrane Na+/K+ ATP-ase activity, inactivation of membrane sodium channels, and other oxidative protein modifications contribute to the cytotoxic effect of peroxynitrite. In addition, peroxynitrite is a potent trigger of DNA strand breakage, with subsequent activation of the nuclear enzyme poly-ADP ribosyl synthetase, with eventual severe energy depletion of the cells. Pharmacological evidence suggests that the peroxynitrite-poly-ADP ribosyl synthetase pathway importantly contributes to the cellular injury in endotoxic shock, inflammatory pancreatic islet cell destruction, and central nervous system ischemia. The proposal that peroxynitrite is a major cytotoxic mediator would change the interpretation of previous data on the effects of NO donors, NO synthase inhibitors, and superoxide neutralizing strategies in shock and inflammation.
Treatment of Lennox-Gastaut syndrome: overview and recent findings (2008)

Lennox-Gastaut syndrome (LGS) is a rare, age-related syndrome, characterized by multiple seizure types, a specific electro-encephalographic pattern, and mental regression. However, published data on the etiology, evolution, and therapeutic approach of LGS are contradictory, partly because the precise definition of LGS used in the literature varies. In the most recent classification, LGS belongs to the epileptic encephalopathies and is highly refractory to all antiepileptic drugs. Numerous treatments, medical and non-medical, have been proposed and results mostly from open studies or case series have been published. Sometimes, patients with LGS are included in a more global group of patients with refractory epilepsy. Only 6 randomized double-blind controlled trials of medical treatments, which included patients with LGS, have been published. Overall, treatment is rarely effective and the final prognosis remains poor in spite of new therapeutic strategies. Co-morbidities need specific treatment. This paper summarizes the definition, diagnosis and therapeutic approach to LGS, including not only recognized antiepileptic drugs, but also "off label" medications, immune therapy, diet, surgery and some perspectives for the future.
Fast and high conversion phase-transfer synthesis exploiting the liquid–liquid interface formed in a microchannel chip (2001)

The large specific interfacial areas and short molecular diffusion distances provided by glass microchips play important roles not only for effective phase-transfer synthetic reaction, but also for avoiding an undesirable side reaction.
Mutational analysis of the major heparan sulfate-binding domain of herpes simplex virus type 1 glycoprotein C (2001)

Heparan sulfate (HS) has been identified as a receptor molecule for numerous microbial pathogens, including herpes simplex virus type 1 (HSV-1). To further define the major HS-binding domain of the HSV-1 attachment protein, i.e. glycoprotein C (gC), virus mutants carrying alterations of either two neighbouring basic amino acid residues or a single hydrophobic amino acid residue within the N-terminal domain of the protein (residues 26-227) were constructed. In addition, a mutant lacking the Asn148 glycosylation site was included in the study. Binding of purified mutated gC proteins to isolated HS chains showed that viruses with mutations at residues Arg(129,130), Ile142, Arg(143,145), Arg(145,147), Arg(151,155) and Arg(155,160) had significantly impaired HS binding, in contrast to the other mutations, including Asn148. Impairment of the HS-binding activity of gC by these mutations had profound consequences for virus attachment and infection of cells in which amounts of HS exposed on the cell surface had been reduced. It is suggested that basic and hydrophobic residues localized at the Cys127-Cys144 loop of HSV-1 gC constitute a major HS-binding domain, with the most active amino acids situated near the C-terminal region of the two cysteines.
SMA CARNI-VAL Trial Part I: Double-Blind, Randomized, Placebo-Controlled Trial of L-Carnitine and Valproic Acid in Spinal Muscular Atrophy (2010)

Clinicaltrials.gov NCT00227266.
Long‐Term Drug Treatment of Obesity in a Private Practice Setting (1997)

This study evaluated the long-term efficacy and safety of the combination of phentermine and fenfluramine for the treatment of obesity in a private practice setting. A total of 1388 consecutive, qualified patients presenting to a private general internal medicine practice in Charlotte, NC, were enrolled with eligibility criteria including: age 18 years to 60 years, 20% over "desirable" bodyweight or body mass index > 27, no serious medical or psychiatric disease, and no contraindications to drug therapy. Patients were instructed in diet, exercise, and behavior modification techniques and received phentermine (15 mg/day to 30 mg/day) and fenfluramine (20 mg/day to 60 mg/day) continuously for over 3 years. Average duration of treatment was 15.9 months, and average weight loss at the last visit was 11.6 kg, or 11.7% of initial bodyweight. For patients completing 1 year of drug treatment, mean weight loss was 16.5 kg, or 16% of initial weight. Weight loss persisted for 2 years, but partial regain was seen at 3 years. The dropout rates were 18% at 6 months, 39% at 1 year, 68% at 2 years, and 78% at 3 years. At 1 year, blood pressure of hypertensive patients fell from 151/95 mm Hg to 127/78 mm Hg, and serum cholesterol and triglycerides of hyperlipidemic patient fell by 0.750 mmol/L (29 mg/dL) and 0.937 mmol/L (83 mg/dL), respectively. Adverse events were modest. We conclude that, in a private practice setting, long-term treatment of obesity with the combination of phentermine, fenfluramine, and a weight maintenance program is generally safe and effective. More research is needed to determine efficacy and safety for longer than 3 years.