gebhart/patrepeval huggingface dataset:
Indenylidene Ruthenium Complex Bearing a Sterically Demanding NHC Ligand: An Efficient Catalyst for Olefin Metathesis at Room Temperature (2009)

The synthesis and characterization of a novel indenylidene-containing ruthenium catalyst bearing the N-heterocyclic carbene (NHC) ligand 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene (SIPr) are reported. Comparative reactivity studies with other indenylidene complexes using various substrates show the importance of the sterically demanding SIPr ligand on catalyst reaction profile. The investigation of the reaction scope for ring-closing metathesis transformations establishes the influence of the NHC on catalyst activity especially as a function of substrate steric bulk. The novel catalyst was found very efficient at room temperature for nonsterically hindered substrates. Since the new catalyst was found to be soluble in a variety of solvents, a number of these were examined to gauge the importance of solvent effects.
Combretastatin A-4 Phosphate Suppresses Development and Induces Regression of Choroidal Neovascularization (2003)

These data indicate that CA-4-P suppresses the development of VEGF-induced neovascularization in the retina and both blocks development and promotes regression of CNV. Therefore, CA-4-P shows potential for both prevention and treatment of ocular neovascularization.
Characterization of switched direct current gas sampling glow discharge ionization source for the time-of-flight mass spectrometer (2000)

A variable frequency, switched, direct-current gas sampling glow discharge ionization source was interfaced to an orthogonally extracted time-of-flight mass spectrometer for the purpose of dynamically generating atomic and molecular mass spectra of halogenated hydrocarbons. The plasma duty cycle is 50% in each mode of operation. The operating mode is selected simply by switching the polarity of voltage applied to the sample-introduction plate. The self-igniting helium discharge is contained within the first vacuum stage of the differentially pumped spectrometric interface. Both atomic and molecular mass spectra could be obtained with similar ion-optical lens settings, with the exception of the steering plate potential, which had to be alternated between two values (at the plasma switching frequency). A range of discharge switching rates can be used, although a non-linear drop in the modulated signal occurs with frequency. Switching rates above 100 Hz appears to be impractical with current experimental apparatus. Long-term temporal stability of the atomic (79Br+) and molecular (172CHBr2+) signals was measured over a period greater than 1 h, with an overall precision of 13.3 and 6.1% RSD, respectively. The 79Br+/81Br+ isotope ratio precision was 1.1% RSD over this period, while the 172CHBr2+/173CHBr2+ molecular ratio was determined to be 1.6% RSD. The precision of the isotope and ionic ratios are counting statistics limited. The atomic detection limit is in the range 3–110 pg s−1 (as the halogen) and 15–250 pg s−1 (molecular) for analytes manually introduced into an exponential-dilution sample-introduction device, with boxcar averagers being employed for data collection. A variety of chlorinated hydrocarbons were introduced into the discharge via the flow cell, and it was possible to differentiate (or speciate) the compounds based on their 35Cl+/12C+ elemental ratios with a correlation coefficient (R) of 0.995.
High-frequency irreversible electroporation is an effective tumor ablation strategy that induces immunologic cell death and promotes systemic anti-tumor immunity (2019)

Cell death and tumor ablation following H-FIRE treatment activates the local innate immune system, which shifts the tumor microenvironment from an anti-inflammatory state to a pro-inflammatory state. The non-thermal damage to the cancer cells and increased innate immune system stimulation improves antigen presentation, resulting in the engagement of the adaptive immune system and improved systemic anti-tumor immunity.
Defective CD95/APO-1/Fas signal complex formation in the human autoimmune lymphoproliferative syndrome, type Ia (1999)

Heterozygous mutations in the CD95 (APO-1/Fas) receptor occur in most individuals with autoimmune lymphoproliferative syndrome (ALPS) and dominantly interfere with apoptosis by an unknown mechanism. We show that local or global alterations in the structure of the cytoplasmic death domain from nine independent ALPS CD95 death-domain mutations result in a failure to bind the FADD/MORT1 signaling protein. Despite heterozygosity for the abnormal allele, lymphocytes from ALPS patients showed markedly decreased FADD association and a loss of caspase recruitment and activation after CD95 crosslinking. These data suggest that intracytoplasmic CD95 mutations in ALPS impair apoptosis chiefly by disrupting death-domain interactions with the signaling protein FADD/MORT1.
Protection of Skeletal Muscles from Ischemic Injury: Low-Level Laser Therapy Increases Antioxidant Activity (2005)

The present study describes for the first time the ability of LLLT to significantly prevent degeneration following ischemia/reperfusion injury in skeletal muscles, probably by induction of synthesis of antioxidants and other cytoprotective proteins, such as hsp-70i. The elevation of antioxidants was also evident in intact muscle following LLLT. The above phenomenon may also be of clinical relevance in scheduled surgery or microsurgery requiring extended tourniquet applications to skeletal muscle followed by reperfusion.
A low cost point-of-care viscous sample preparation device for molecular diagnosis in the developing world; an example of microfluidic origami (2011)

The lab-on-a-chip concept has led to several point-of-care (POC) diagnostic microfluidic platforms. However, few of these can process raw samples for molecular diagnosis and fewer yet are suited for use in a resource-limited setting without permanent electrical infrastructure. We present here a very low cost paper microfluidic device for POC extraction of bacterial DNA from raw viscous samples--a challenge for conventional microfluidic platforms. This is an example of "microfluidic origami" in that the system is activated by folding; demonstrated here is room temperature cell lysis and DNA extraction from pig mucin (simulating sputum) spiked with E. coli without the use of external power. The microfluidic origami device features dry reagent storage and rehydration of the lysis buffer. We demonstrate DNA extraction from samples with a bacterial load as low as 33 CFU ml(-1). Extraction times, starting from the raw sample, have been optimized to about 1.5 h without the use of external power, or to within 1 h using an oven or a heater block. The fabrication of this paper microfluidic device can be translated into high volume production in the developing world without the need for a semiconductor clean room or a microfabrication facility. The sample preparation can be performed with the addition of just the sample, water, ethanol and elute buffer to the device, thus reducing chemical hazards during transport and handling.
Tissue engineering of cultured skin substitutes (2005)

Skin replacement has been a challenging task for surgeons ever since the introduction of skin grafts by Reverdin in 1871. Recently, skin grafting has evolved from the initial autograft and allograft preparations to biosynthetic and tissue-engineered living skin replacements. This has been fostered by the dramatically improved survival rates of major burns where the availability of autologous normal skin for grafting has become one of the limiting factors. The ideal properties of a temporary and a permanent skin substitute have been well defined. Tissue-engineered skin replacements: cultured autologous keratinocyte grafts, cultured allogeneic keratinocyte grafts, autologous/allogeneic composites, acellular biological matrices, and cellular matrices including such biological substances as fibrin sealant and various types of collagen, hyaluronic acid etc. have opened new horizons to deal with such massive skin loss. In extensive burns it has been shown that skin substitution with cultured grafts can be a life-saving measure where few alternatives exist. Future research will aim to create skin substitutes with cultured epidermis that under appropriate circumstances may provide a wound cover that could be just as durable and esthetically acceptable as conventional split-thickness skin grafts. Genetic manipulation may in addition enhance the performance of such cultured skin substitutes. If cell science, molecular biology, genetic engineering, material science and clinical expertise join their efforts to develop optimized cell culture techniques and synthetic or biological matrices then further technical advances might well lead to the production of almost skin like new tissue-engineered human skin products resembling natural human skin.
Adult Stromal Cells Derived from Human Adipose Tissue Provoke Pancreatic Cancer Cell Death both In Vitro and In Vivo (2009)

These data indicate that ADSC strongly inhibit PDAC proliferation, both in vitro and in vivo and induce tumor cell death by altering cell cycle progression. Therefore, ADSC may constitute a potential cell-based therapeutic alternative for the treatment of PDAC for which no effective cure is available.
The single-cell chemostat: an agarose-based, microfluidic device for high-throughput, single-cell studies of bacteria and bacterial communities (2012)

Optical microscopy of single bacteria growing on solid agarose support is a powerful method for studying the natural heterogeneity in growth and gene expression. While the material properties of agarose make it an excellent substrate for such studies, the sheer number of exponentially growing cells eventually overwhelms the agarose pad, which fundamentally limits the duration and the throughput of measurements. Here we overcome the limitations of exponential growth by patterning agarose pads on the sub-micron-scale. Linear tracks constrain the growth of bacteria into a high density array of linear micro-colonies. Buffer flow through microfluidic lines washes away excess cells and delivers fresh nutrient buffer. Densely patterned tracks allow us to cultivate and image hundreds of thousands of cells on a single agarose pad over 30-40 generations, which drastically increases single-cell measurement throughput. In addition, we show that patterned agarose can facilitate single-cell measurements within bacterial communities. As a proof-of-principle, we study a community of E. coli auxotrophs that can complement the amino acid deficiencies of one another. We find that the growth rate of colonies of one strain decreases sharply with the distance to colonies of the complementary strain over distances of only a few cell lengths. Because patterned agarose pads maintain cells in a chemostatic environment in which every cell can be imaged, we term our device the single-cell chemostat. High-throughput measurements of single cells growing chemostatically should greatly facilitate the study of a variety of microbial behaviours.
Role of Macrophage Migration Inhibitory Factor in Conjunctival Pathology in Ocular Cicatricial Pemphigoid (2004)

This study demonstrated an increased conjunctival expression of MIF in patients with OCP. MIF may be actively involved in the pathogenesis of OCP, possibly regulating the inflammatory events of the disease process.
Feasibility study of beam orientation class‐solutions for prostate IMRT (2004)

IMRT is being increasingly used for treatment of prostate cancer. In practice, however, the beam orientations used for the treatments are still selected empirically, without any guideline. The purpose of this work was to investigate interpatient variation of the optimal beam configuration and to facilitate intensity modulated radiation therapy (IMRT) prostate treatment planning by proposing a set of beam orientation class-solutions for a range of numbers of incident beams. We used fifteen prostate cases to generate the beam orientation class-solutions. For each patient and a given number of incident beams, a multiobjective optimization engine was employed to provide optimal beam directions. For the fifteen cases considered, the gantry angle of any of the optimized plans were all distributed within a certain range The angular distributions of the optimal beams were analyzed and the most selected directions are identified as optimal directions. The optimal directions for all patients are averaged to obtain the class-solution. The class-solution gantry angles for prostate IMRT were found to be: three beams (0 degrees, 120 degrees, 240 degrees), five beams (35 degrees, 110 degrees, 180 degrees, 250 degrees, 325 degrees), six beams (0 degrees, 60 degrees, 120 degrees, 180 degrees, 240 degrees, 300 degrees), seven beams (25 degrees, 75 degrees, 130 degrees, 180 degrees, 230 degrees, 285 degrees, 335 degrees), eight beams (20 degrees, 70 degrees, 110 degrees, 150 degrees, 200 degrees, 250 degrees, 290 degrees, 340 degrees), and nine beams (20 degrees, 60 degrees, 100 degrees, 140 degrees, 180 degrees, 220 degrees, 260 degrees, 300 degrees, 340 degrees). The level of validity of the class-solutions was tested using an additional clinical prostate case by comparing with the individually optimized beam configurations. The difference between the plans obtained with class-solutions and patient-specific optimizations was found to be clinically insignificant.
Analysis of the Soluble Human Tooth Proteome and Its Ability to Induce Dentin/Tooth Regeneration (2010)

While the soluble proteins of human teeth consist of various extracellular matrix and bioactive proteins, they have not yet been characterized fully. Moreover, the role they play in tooth regeneration is not clear. Analysis of the soluble proteins in human teeth by liquid chromatography-mass spectrometry revealed 147 different ethylenediaminetetraacetic acid-soluble tooth proteins (ESTPs). Of these, 29 had not been shown previously to be present in human teeth. To determine their effect on the in vitro responses of dental pulp stem cells (DPSCs), DPSCs were cultured in ESTP-coated culture plates and three-dimensional scaffolds. The ESTPs significantly enhanced DPSC odontoblast differentiation and mineralization in vitro, but had only partial effect on bone marrow stem cells or adipose tissue stem cells. To test the effect of ESTPs on in vivo dentin and tooth formation, mouse embryonic tooth-forming primordia and xenogenic murine apical bud epithelium/human DPSC composites were treated with ESTPs before implantation under the renal capsule of ICR mice. ESTP treatment promoted the formation of morphologically normal teeth by the tooth-forming primordium regions and enhanced the development of a regular and large dentin structure by the composites. These observations suggest that human ESTPs contain dentinogenic proteins and can promote dentin and tooth formation.
Dimethyl fumarate inhibits osteoclasts via attenuation of reactive oxygen species signalling by augmented antioxidation (2017)

Bone destructive diseases are common worldwide and are caused by dysregulation of osteoclast formation and activation. During osteoclastogenesis, reactive oxygen species (ROS) play a role in the intracellular signalling triggered by receptor activator of nuclear factor-κB ligand (RANKL) stimulation. Previously, we demonstrated that induction of antioxidant enzymes by Nrf2 activation using Nrf2-gene transfer, an ETGE-peptide or polyphenols, successfully ameliorated RANKL-dependent osteoclastogenesis. Dimethyl fumarate (DMF) has been shown to activate Nrf2 signalling and has been lately used in clinical trials for neurodegenerative diseases. In this study, we hypothesized that Nrf2 activation by DMF would inhibit osteoclastogenesis and bone destruction via attenuation of intracellular ROS signalling through antioxidant mechanisms. RAW 264.7 cells were used as osteoclast progenitor cells. We found that DMF induced Nrf2 translocation to the nucleus, augmented Nrf2 promoter-luciferase reporter activity and increased antioxidant enzyme expression. Using flow cytometry, we found that DMF attenuated RANKL-mediated intracellular ROS generation, which resulted in the inhibition of RANKL-mediated osteoclastogenesis. Local DMF injection into the calvaria of male BALB/c mice resulted in attenuated bone destruction in lipopolysaccharide-treated mice. In conclusion, we demonstrated in a preclinical setting that DMF inhibited RANKL-mediated osteoclastogenesis and bone destruction via induction of Nrf2-mediated transcription of antioxidant genes and consequent decrease in intracellular ROS levels. Our results suggest that DMF may be a promising inhibitor of bone destruction in diseases like periodontitis, rheumatoid arthritis and osteoporosis.
Delayed emergence of effects of memory-enhancing drugs: implications for the dynamics of long-term memory. (1994)

Many theories of memory postulate that processing of information outlasts the learning situation and involves several different physiological substrates. If such physiologically distinct mechanisms or stages of memory do in fact exist, they should be differentially affected by particular experimental manipulations. Accordingly, a selective improvement of the processes underlying short-term memory should be detectable only while the information is encoded in the short-term mode, and a selective influence on long-term memory should be detectable only from the moment when memory is based on the long-term trace. Our comparative study of the time course of the effects of the cholinergic agonist arecoline, the gamma-aminobutyric acid type B receptor antagonist CGP 36742, the angiotensin-converting enzyme inhibitor captopril, and the nootropic oxiracetam, four substances with completely different primary sites of action, show that the memory-enhancing effects consistently come into evidence no sooner than 16-24 h after the learning trial. On the one hand, this finding suggests that all these substances act by way of the same type of mechanism; on the other hand, it demonstrates that the substrate modulated by the compounds forms the basis of memory only after 16-24 h. From the observation that animals also show clear signs of retention during the first 16 h--i.e., before the effects of the substances are measurable--it can be inferred that retention during this time is mediated by other mechanisms that are not influenced by any of the substances.
The Properties of Cenospheres and the Mechanism of Their Formation During High-Temperature Coal Combustion at Thermal Power Plans (2010)

A systematic analysis of the probable scenario of the supramolecular structure (texture) formation of mineral products, formed during the high-temperature combustion of pulverized bituminous coals at thermal power plants (TPP) is provided. The general physico-chemical consideration of the processes that occur at different stages (heating, burning, viscoplastic state in the hot zone, and cooling) during the combustion of bituminous coal makes it possible to allocate the following systematic transformations: coal → char → network structures (including plerospheres)→cenospheres→fly ash..
Morbidity associated with asthma and audit of asthma treatment in out-patient clinics. (1992)

A study was undertaken to determine the extent of morbidity associated with asthma and to audit the management of asthma in two out-patient clinics of two district hospitals. Patients were recruited for the study during a 3-month period from December 1990 to February 1991. Seventy asthmatic patients were studied. Eighty-six percent of the patients had their sleep disturbed by asthma, 77% took daily medication regularly, 63% felt that their activities were restricted by asthma, 60% had at least one acute exacerbation in the preceding six months. Of those who had their peak expiratory flow rate (PEFR) measured, 40% had a PEFR below 50% predicted, and only 11% had normal PEFR (greater than 80% predicted). The morbidity of asthma was thus considerable. On the other hand, the drug treatment of these asthmatics was grossly inadequate. They were prescribed on average 2.1 item of drugs, which for most patients comprised an oral beta agonist and a theophylline. Only 43% of the patients received inhaler therapy, but no patients were given steroids, inhaled or oral. The drug treatment was unrelated to the severity of patients' asthma. Further, objective measurement of severity was under-used in the assessment of asthma, only 8.5% of patients ever had their PEFR recorded. This study has found that asthma is poorly managed in out-patient clinics. We need to improve the training of doctors in the optimal management of asthma.
Characterization of Sfp, a Bacillus subtilis Phosphopantetheinyl Transferase for Peptidyl Carrier Protein Domains in Peptide Synthetases (1998)

The Bacillus subtilis enzyme Sfp, required for production of the lipoheptapeptide antibiotic surfactin, posttranslationally phosphopantetheinylates a serine residue in each of the seven peptidyl carrier protein domains of the first three subunits (SrfABC) of surfactin synthetase to yield docking sites for amino acid loading and peptide bond formation. With recombinant Sfp and 16-17-kDa peptidyl carrier protein (PCP) domains excised from the SrfB1 and SrfB2 modules as apo substrates, kcat values of 56-104 min-1 and K(m) values of 1.3-1.8 microM were determined, indicating equivalent recognition of the adjacent PCP domains by Sfp. In contrast to other phosphopantetheinyl transferases (PPTases) previously examined, Sfp will modify the apo forms of heterologous recombinant proteins, including the PCP domain of Saccharomyces cerevisiae Lys2 (involved in lysine biosynthesis), the aryl carrier protein (ArCP) domain of Escherichia coli EntB (involved in enterobactin biosynthesis), and the E. coli acyl carrier protein (ACP) subunit, suggesting Sfp as a good candidate for heterologous coexpression with peptide and polyketide synthase genes to overproduce holo-synthase enzymes. Cosubstrate coenzyme A (CoA), the phosphopantetheinyl group donor, has a K(m) of 0.7 microM. Desulfo-CoA and homocysteamine-CoA are also substrates of Sfp, and benzoyl-CoA and phenylacetyl-CoA are also utilized by Sfp, resulting in direct transfer of acyl phosphopantetheinyl moieties into the carrier protein substrate. Mutagenesis in Sfp of five residues conserved across the PPTase family was assessed for in vivo effects on surfactin production and in vitro effects on PPTase activity.
IL-5-mediated eosinophil survival requires inhibition of GSK-3 and correlates with β-catenin relocalization (2006)

Interleukin (IL)-5 is a hematopoietic cytokine able to regulate differentiation, survival, and effector functions of eosinophils. It binds specifically to its receptor, which is composed of a cytokine-specific alpha-chain and a beta-chain shared with the receptors for IL-3 and the granulocyte macrophage-colony stimulating factor. The molecular mechanisms by which IL-5 modulates eosinophil survival remain unclear. In this study, we demonstrate that IL-5 withdrawal induces eosinophil apoptosis through a mitochondria-dependent pathway, independently of Fas receptor activation. The lipid kinase phosphatidylinositol-3 kinase plays a crucial role in the maintenance of eosinophil survival, as inhibition of its activity results in apoptosis. IL-5 induces phosphorylation and thus, inhibition of the Forkhead transcription factor FOXO3a and glycogen synthase kinase 3 (GSK-3). We analyzed expression of FOXO3a-dependent transcriptional targets: Fas ligand or Bim (a proapoptotic Bcl-2 family member), but neither was detected in apoptotic eosinophils. We further show that GSK-3 is activated after IL-5 withdrawal, and inhibition of its activity rescues eosinophils from apoptosis. beta-catenin, a direct GSK-3 substrate, is present in the nucleus of IL-5-stimulated eosinophils, but it is translocated to the plasma membrane in the absence of cytokine in a GSK-3-dependent manner. This is the first report describing a potential role for GSK-3 and beta-catenin in regulating eosinophil survival and suggests a novel mechanism by which IL-5 inhibits the constitutive apoptotic program in these cells.