gebhart/patrepeval huggingface dataset:
Phase 1 study of RG7155, a novel anti-CSF1R antibody, in patients with locally advanced pigmented villonodular synovitis (PVNS). (2014)

10504^ Background: PVNS, also known as tenosynovial giant cell tumor (TGCT), is a rare disease mainly affecting young adults. This neoplastic disease is driven in most cases by a t(1;2) translocation resulting in fusion of COL6A3 and M-CSF genes encoding for colony-stimulating factor 1 (CSF1). The bulk tumor mass consists of CSF1 receptor (CSF1R) positive cells. RG7155 is a monoclonal antibody that potently inhibits the dimerization of CSF1R. Methods: In this dose-escalation and –extension phase I study, we treated patients with locally advanced PVNS, who were not amenable to surgical treatment. Primary objectives were to assess safety, tolerability, pharmaco-kinetics and -dynamics. Clinical activity was evaluated using FDG-PET (at 4 weeks after treatment start; EORTC criteria) and MRI (at 6 weeks; RECIST 1.1). Pre- and on-treatment biopsies of tumor and surrogate skin tissue as well as peripheral blood PD markers were analyzed. Results: Between September 2012 and October 2013, 11 PVNS patients (median age 38 (range 18-64)) were treated at three French institutions at four different dose levels (q2w). Three patients had previously been treated with nilotinib and imatinib, respectively. Seven patients had undergone previous surgeries. RG7155 induced a sustained increase of CSF1 associated with a decrease of CD14+CD16+ monocytes in peripheral blood in all 10 evaluable patients. RG7155 led to striking reductions of CSF1R+ and CD163+ macrophages in tumor tissue associated with rapid onset of objective clinical responses in 7/9 patients (78%; partial metabolic response at 4 weeks; FDG-PET) and 7/10 patients (70%; PR at 6 weeks; MRI). All patients showed tumor shrinkage associated with symptomatic improvement. 9/10 patients remained clinically progression-free with a longest follow-up of 17 months. RG7155 was well tolerated with only two patients experiencing grade 3 adverse events (periorbital edema; mucositis). Conclusions: RG7155 treatment induced rapid clinical responses in the vast majority of PVNS patients associated with profound reduction of CSF1R+ and CD163+ macrophages in tumor tissue. Clinical trial information: NCT01494688. Clinical trial information: NCT01494688.
Investigation of the first step of biotin biosynthesis in Bacillus sphaericus. Purification and characterization of the pimeloyl-CoA synthase, and uptake of pimelate (1992)

The pimeloyl-CoA synthase from Bacillus sphaericus has been purified to homogeneity from an overproducing strain of Escherichia coli. The purification yielded milligram quantities of the synthase with a specific activity of 1 unit/mg of protein. Analysis of the products showed that this enzyme catalysed the transformation of pimelate into pimeloyl-CoA with concomitant hydrolysis of ATP to AMP. Using a continuous spectrophotometric assay, we have examined the catalytic properties of the pure enzyme. The pH profile under Vmax. conditions showed a maximum around 8.5. Apparent Km values for pimelate, CoASH, ATP.Mg2- and Mg2+ were respectively 145 microM, 33 microM, 170 microM and 2.3 mM. The enzyme was inhibited by Mg2+ above 10 mM. This acid-CoA ligase exhibited a very sharp substrate specificity, e.g. neither GTP nor pimelate analogues (di- or mono-carboxylic acids) were processed. The bivalent metal ion requirement was also investigated: Mn2+ (73%) and Co2+ (32%) but not Ca2+ could replace Mg2+. The enzyme was inhibited by metal chelators such as 1,10-phenanthroline and EDTA. The synthase was a homodimer with a 28,000-M(r) subunit. N-Terminal sequencing definitely proved that this enzyme was encoded by the bioW gene. A careful study of pimelate uptake by B. sphaericus, E. coli and Pseudomonas dentrificans showed that this metabolite crossed the membrane of these microorganisms by passive diffusion, ruling out the involvement of the bioX gene product as pimelate carrier.
Identification of Two Distinct Macrophage Subsets with Divergent Effects Causing either Neurotoxicity or Regeneration in the Injured Mouse Spinal Cord (2009)

Macrophages dominate sites of CNS injury in which they promote both injury and repair. These divergent effects may be caused by distinct macrophage subsets, i.e., "classically activated" proinflammatory (M1) or "alternatively activated" anti-inflammatory (M2) cells. Here, we show that an M1 macrophage response is rapidly induced and then maintained at sites of traumatic spinal cord injury and that this response overwhelms a comparatively smaller and transient M2 macrophage response. The high M1/M2 macrophage ratio has significant implications for CNS repair. Indeed, we present novel data showing that only M1 macrophages are neurotoxic and M2 macrophages promote a regenerative growth response in adult sensory axons, even in the context of inhibitory substrates that dominate sites of CNS injury (e.g., proteoglycans and myelin). Together, these data suggest that polarizing the differentiation of resident microglia and infiltrating blood monocytes toward an M2 or "alternatively" activated macrophage phenotype could promote CNS repair while limiting secondary inflammatory-mediated injury.
Induction of an endothelial cell growth factor by human cytomegalovirus infection of fibroblasts (1991)

Human cytomegalovirus (HCMV) induction of growth factors in fibroblasts was investigated after establishing serum-free culture conditions conducive to viral replication. HCMV infection induced a type II heparin-binding growth factor which stimulated human endothelial cell proliferation.
Metal-on-metal bearing in hip prosthesis generates 100-fold less wear debris than metal-on-polyethylene (1999)

Aseptic loosening due to osteolysis in total hip replacement has been related to wear debris released from prosthetic components. Retrospective longterm observations of patients with the metal-on-metal prosthesis has shown long-term survivorship and good mechanical performance. Thus, the new and modified metal-on-metal prosthesis has been introduced on the market. Historical clinical data from the 1st generation metal-on-metal hip prosthesis may not be relevant for the 2nd generation of metal-on-metal hip prosthesis. Therefore, preclinical testing of the prosthesis must be conducted before clinical evaluation. We assessed the tribological performance of the metal-on-metal prosthesis versus the metal-on-polyethylene prosthesis introduced on the market as Metasul and Protasul, respectively. In a 12-channel joint simulator, 6 metal-on-metal bearing and 3 metal on polyethylene prostheses were tested, with the same number of corresponding soak controls. The wear was assessed gravimetrically. The "steady-state" wear-rates from the metal-on-metal prosthesis were almost 100 times less than that from the metal-on-polyethylene prosthesis. The tribological wear performance of the metal-on-metal hip prosthetic system is promising.
Benzodiazepine mit psychotroper Wirkung, V1) 1.5‐Benzodiazepin‐trione und ihre Vorstufen (1972)

Abstract Die Oxidation der 3‐Aminomethylen‐1.5‐benzodiazepin‐2.4‐dione 1 zu den 1.5‐Benzodiazepin‐2.3.4‐trionen 5 führt über die entsprechenden 3‐Formyl‐3‐hydroxy‐ und 3‐Hydroxy‐1.5‐benzodiazepin‐2.4‐dione vom Typ 2 bzw. 3 . Verbindungen des Typs 3 liegen nicht wie Dialursäure in der Endiol‐Form vor. Die Benzodiazepin‐trionen 5 lassen sich in 6‐Ring‐Systeme umwandeln. Dazu wird ein möglicher Mechanismus diskutiert. Ihre Stabilität wird mit der analoger Mono‐ und Dioxo‐1.5‐benzodiazepine verglichen.
Permissive sites and topology of an outer membrane protein with a reporter epitope (1991)

We are developing a genetic approach to study with a single antibody the folding and topology of LamB, an integral outer membrane protein from Escherichia coli K-12. This approach consists of inserting the same reporter foreign antigenic determinant (the C3 epitope from poliovirus) at different sites of LamB so that the resulting hybrid proteins have essentially kept the in vivo biological properties of LamB and therefore its cellular location and structure; the corresponding sites are called permissive sites. A specific monoclonal antibody can then be used to examine the position of the reporter epitope with respect to the protein and the membrane. We present an improved and efficient procedure that led us to identify eight new permissive sites in LamB. These sites appear to be distributed on both sides of the membrane. At one of them (after residue 253), the C3 epitope was detected on intact bacteria, providing the first direct argument for exposure of the corresponding LamB region at the cell surface. At this site as well as at four others (after residues 183, 219, 236, and 352), the C3 epitope could be detected with the C3 monoclonal antibody at the surface of the extracted trimeric LamB-C3 hybrid proteins. We provide a number of convergent arguments showing that the hybrid proteins are not strongly distorted with respect to the wild-type protein so that the conclusions drawn are also valid for this protein. These conclusions are essentially in agreement with the proposed folding model for the LamB protein. They agree, in particular, with the idea that regions 183 and 352 are exposed to the periplasm. In addition, they suggest that region 236 is buried at the external face of the outer membrane and that region 219 is exposed to the periplasm. Including the 3 sites previously determined, 11 permissive sites are now available in LamB, including 3 at the cell surface and most probably at least 3 in the periplasm. We discuss the nature of such sites, the generalization of this approach to other proteins, and possible applications.
Probabilistic design verification (2002)

The authors present a novel method for verifying the equivalence of two Boolean functions. Each function is hashed to an integer code by assigning random integer values to the input variables and evaluating its integer-valued representation. The equivalence of two functions can be verified with a very low probability of error. The probability of error can be exponentially decreased by making multiple runs. Results indicate significant time and space advantages for this method over deterministic techniques. Some functions known to require space (and time) exponential in the number of input variables for deterministic verification require only polynomial resources using the proposed technique.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Low-Temperature Phase-Controlled Synthesis of Titanium Di- and Tri-sulfide by Atomic Layer Deposition (2019)

Phase-controlled synthesis of two-dimensional (2D) transition-metal chalcogenides (TMCs) at low temperatures with a precise thickness control has to date been rarely reported. Here, we report on a process for the phase-controlled synthesis of TiS<sub>2</sub> (metallic) and TiS<sub>3</sub> (semiconducting) nanolayers by atomic layer deposition (ALD) with precise thickness control. The phase control has been obtained by carefully tuning the deposition temperature and coreactant composition during ALD. In all cases, characteristic self-limiting ALD growth behavior with a growth per cycle (GPC) of ∼0.16 nm per cycle was observed. TiS<sub>2</sub> was prepared at 100 °C using H<sub>2</sub>S gas as coreactant and was also observed using H<sub>2</sub>S plasma as a coreactant at growth temperatures between 150 and 200 °C. TiS<sub>3</sub> was synthesized only at 100 °C using H<sub>2</sub>S plasma as the coreactant. The S<sub>2</sub> species in the H<sub>2</sub>S plasma, as observed by optical emission spectroscopy, has been speculated to lead to the formation of the TiS<sub>3</sub> phase at low temperatures. The control between the synthesis of TiS<sub>2</sub> and TiS<sub>3</sub> was elucidated by Raman spectroscopy, X-ray photoelectron spectroscopy, high-resolution electron microscopy, and Rutherford backscattering study. Electrical transport measurements showed the low resistive nature of ALD grown 2D-TiS<sub>2</sub> (1T-phase). Postdeposition annealing of the TiS<sub>3</sub> layers at 400 °C in a sulfur-rich atmosphere improved the crystallinity of the film and yielded photoluminescence at ∼0.9 eV, indicating the semiconducting (direct band gap) nature of TiS<sub>3</sub>. The current study opens up a new ALD-based synthesis route for controlled, scalable growth of transition-metal di- and tri-chalcogenides at low temperatures.
Differential expression of canonical and non‐canonical Wnt ligands in ameloblastoma (2011)

Differential expression of Wnt ligands in different ameloblastoma subtypes suggests that the canonical and non-canonical Wnt pathways are selectively activated or repressed depending on the tumor cell differentiation status. Canonical Wnt pathway is most likely the main transduction pathway while Wnt-1 might be the key signaling molecule involved in ameloblastoma tumorigenesis.
Long-Lasting Secretion of Transgene Product from Differentiated and Filter-Grown Retinal Pigment Epithelial Cells After Nonviral Gene Transfer (2005)

In contrast to most differentiated epithelial cells, the differentiated RPE cells can be transfected at high and prolonged levels with selected lipoplexes.
Sampling, synthesis, and input devices (1999)

article Free Access Share on Sampling, synthesis, and input devices Authors: George W. Fitzmaurice Alias/Wavefront, Inc. Alias/Wavefront, Inc.View Profile , Ravin Balakrisnan Alias/Wavefront, Inc. Alias/Wavefront, Inc.View Profile , Gordon Kurtenbach Alias/Wavefront, Inc. Alias/Wavefront, Inc.View Profile Authors Info & Claims Communications of the ACMVolume 42Issue 8Aug. 1999 pp 54–63https://doi.org/10.1145/310930.310973Published:01 August 1999Publication History 4citation993DownloadsMetricsTotal Citations4Total Downloads993Last 12 Months36Last 6 weeks5 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my Alerts New Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteView all FormatsPDF
Insecticidal and Genotoxic Activities of Mint Essential Oils (1997)

The essential oils (EOs) extracted from the mint species Mentha pulegium and Mentha spicata, together with their main constituents, pulegone, menthone, and carvone, were tested for insecticidal and genotoxic activities on Drosophila melanogaster. The EOs of both aromatic plants showed strong insecticidal activity, while only the oil of M. spicata exhibited a mutagenic one. Among the constituents studied, the most effective insecticide was found to be pulegone, while the most effective for genotoxic activity was menthone. Data show that both toxic and genotoxic activities of the EOs of the two studied mint plants are not in accordance with those of their main constituents, pulegone, menthone, and carvone. Pulegone is significantly more effective (9 times) as an insecticide, while menthone and carvone are less effective (6 and 2 times, respectively) insecticides when used in their authentic forms, and a mixture of authentic pulegone and menthone, in levels resembling their content in the oil of M. pulegium, showed that the strong toxicity of pulegone is suppressed in the presence of menthone. All the above suggest that synergistic/antagonistic phenomena may be involved that alter the toxicity of the whole EO. Keywords: Mint plants; pennyroyal oil; spearmint oil; essential oils; pulegone; menthone; carvone; insecticides; genotoxicity; Drosophila melanogaster
Spinal Cord Stimulation (2002)

Spinal cord stimulation is the most common mode of neuromodulation used in managing chronic low back pain. It is minimally invasive and reversible as opposed to nerve ablation. The basic scientific background of the initial spinal cord stimulation trials was based on the gate control theory of Melzack and Wall. It has been demonstrated in multiple studies that dorsal horn neuronal activity caused by peripheral noxious stimuli could be inhibited by concomitant stimulation of the dorsal columns. Various other mechanisms, which may play a significant role in the mechanism of action of spinal cord stimulation, include the suppressive effect of spinal cord stimulation on tactile allodynia, increased dorsal horn inhibitory action of gamma-aminobutyric acid (GABA), prevention or abolition of peripheral ischemia, and effects on human brain activity. Spinal cord stimulation is indicated in low back pain with radiculopathy, failed back surgery syndrome, complex regional pain syndrome, peripheral vascular disease, and ischemic heart disease. There is substantial scientific evidence on the efficacy of spinal cord stimulation for treatment of low back and lower extremity pain of neuropathic nature. Clinical studies revealed a success rate of from 50% to 70% with spinal cord stimulation, with decreased pain intensity scores, functional improvement and decreased medication usage. This review discusses multiple aspects of spinal cord stimulation, including pathophysiology and mechanism of action, rationale, indications, technique, clinical effectiveness, and controversial aspects.
Capacitor voltage balancing in multilevel flying capacitor inverters by rule-based switching pattern selection (2007)

A rule-based scheme is investigated for capacitor voltage balancing in a multilevel flying capacitor inverter (MFCI). Without using voltage feedback, the scheme determines the best switching pattern for maintaining nil mean current in all capacitors, hence minimising the capacitor voltage fluctuation. The method is developed to work with the selective harmonic elimination (SHE) technique for sinusoidal voltage generation applied to control static VAR compensators. The method has been designed using a four-cell five-level MFCI as an example. The selected pattern has been shown to give superior performance in load-voltage total-harmonies distortion level and mean capacitor voltage fluctuation. The method is validated experimentally for this form of MFCI.
Mycoplasma hominis and Ureaplasma urealyticum in neonates with suspected infection (1993)

The role of genital mycoplasmas in the pathogenesis of neonatal infection is incompletely understood. We performed nasopharyngeal, blood and cerebrospinal fluid (CSF) cultures for Mycoplasma hominis and Ureaplasma urealyticum in 69 neonates who underwent a diagnostic workup for suspected sepsis. The mean gestational age was 35.9 weeks (range, 25 to 42 weeks) with a mean birth weight of 2386 g (range, 652 to 4420 g). Twenty-seven infants (39.1%) had positive nasopharyngeal cultures; 6 were positive for M. hominis, 10 for U. urealyticum and 11 for both organisms. Seven (26%) of these 27 patients developed chronic lung disease compared with 2 (4.7%) infants in the non-colonized group. Nine infants had positive CSF cultures for M. hominis and one infant had a positive CSF culture for U. urealyticum. All blood cultures were sterile. One of the infants with a positive CSF culture for M. hominis had clinical evidence of systemic infection. All of the infants were treated with antibiotic agents that were not active against mycoplasmas. These data indicate that genital mycoplasmas can be found commonly in the CSF and nasopharynx of infants with suspected sepsis. Their etiologic role in the causation of infection and chronic lung disease, however, remains unclear.
Lipid modification of proteins : a practical approach (1992)

The diversity of lipid moodifications of proteins, Anthony J.Turner Labelling of cell proteins with radioactive fatty acids and methods for studying malmitoyl-acyl transferase, A.J,McIlhinney Methods for studying myristoyl-CoA - protein N-myriostoyltransferase, David A.Rudnick, Robert J.Durino, Jeffery I.Gordon structure determination of acylated proteins, Alastair Aitken identification of a glycosyl-phosphatidylinositol anchor on membrane proteins, Nigel M.Hooper phospholipases that degrade the glycosyl-phosphatidylinositol anchor of membrane proteins, Martin G.Low biosynthesis of glycosyl-phosphatidylinositol membrane protein anchors, Mark C.Field, Anant K.Menon chemical and enzymic analysis of glycosyl-phosphatidylinositol anchors, A.J.Ferguson structural analysis of prenylated proteins, Michael H.Gelb, Christopher C.Farnsworth, John A.Glomset identification and characterization of lipid-modified proteins in bacteria, Shigeru Hayashi, Henry C.Wu.
Bovine coronavirus spike glycoprotein: localization of an immunodominant region at the amino-terminal end of S2 (1992)

We have identified the binding site of monoclonal antibodies (MAbs) against the S2 subunit of the bovine coronavirus spike (S) glycoprotein. The location of this site was first investigated by using prokaryotic expression of DNA restriction fragments covering the entire S gene. The amino acid sequence containing the antibody binding site was shortened from 70 to 20 amino acids by digestion of plasmid DNA with exonuclease III, followed by sequencing of the smallest digestion product encoding an immunoreactive fusion protein. Finally we synthesized a set of nonapeptides covering the 20 amino acid sequence extending from the N-terminal residue of the S2 subunit (Ala 769 to Tyr 798). MAbs reacted mainly with six consecutive overlapping peptides with the sequence TTGYRFTNFEPFTV. Polyclonal antibodies from hyperimmunized or convalescent animals reacted only with the recombinant proteins identified by MAbs, and the hyperimmune serum bound to the same set of peptides. This suggests that this highly conserved linear antigenic determinant corresponds to an immunodominant region. This region resembles both in location and immunodominance the linear determinant defined on the infectious bronchitis virus S2 subunit. The presence of similar regions in the N-terminal region of the S2 subunit of other coronaviruses is discussed.
Erk1/2 MAPK and mTOR signaling sequentially regulates progression through distinct stages of oligodendrocyte differentiation (2011)

Myelination is the culmination of a complex process in which oligodendrocyte (OL) progenitors transition through defined stages in a well-coordinated differentiation program. The signaling mechanisms that regulate this progression are poorly understood. Here we investigate the role of extracellular signal-regulated-kinase-1,-2 (Erk1/2) and the mammalian target of rapamycin (mTOR), downstream effectors of the Ras/Raf/Mek/Erk and PI3K/Akt/mTOR pathways, at specific stages of OL development in vitro. Using a panel of developmental stage-specific antigenic markers and pharmacological inhibitors, we provide evidence that Erk1/2 signaling regulates transition of early progenitors to the late progenitor stage and, as a consequence, to the immature OL stage, but not the transition of immature OL to the mature OL stage. In contrast, mTOR signaling is not required for early progenitor transition to late progenitor stage. Surprisingly, it is also not required for the transition of late progenitors to terminally differentiated immature OLs, as has been reported previously, but is required for the next sequential transition of immature OLs to the mature OL stage. Furthermore, mTOR signaling regulates OL cytoskeletal organization and major myelin protein expression. These in vitro findings correlate with our in vivo data showing that inhibition of mTOR by rapamycin injection attenuated the onset of myelination in the early postnatal brain. Thus, these studies demonstrate that Erk1/2 and mTOR signaling sequentially regulates distinct stages of OL progenitor differentiation and suggest that cells in the OL-lineage require distinct signaling mechanisms to transition through specific stages of their development.