gebhart/patrepeval huggingface dataset:
Influence of Late Side-Effects Upon Daily Life After Radiotherapy for Laryngeal and Pharyngeal Cancer (1994)

The influence on daily life from long-term side-effects was studied in patients treated more than 5 years ago with radiotherapy for laryngeal and pharyngeal cancer. Forty-six patients were asked to participate in telephone interviews and 44 participated. Only a minority (10%) stated serious problems related to the treatment. Problems related to the voice and severe xerostomia were especially mentioned. Half of the patients treated for pharyngeal cancer, complained of xerostomia and had occasionally a feeling of being handicapped. Social relations were impaired in 10% of the patients and 10% had retired due to their cancer or therapy related side-effects. It is concluded that radiotherapy seems to be a well tolerated treatment with relatively little impairment of the daily life in patients with laryngeal cancer. In patients with pharyngeal cancer, xerostomia is a major problem, which often persists more than 5 years after treatment.
Effective literacy pedagogy: amplified by technology? (2010)

The technical feasibility and favorable outcomes of several EVT strategies for ICAS-LVO were established in our study. First-line MT with a bailout angioplasty is a reasonable option for ICAS-LVO, and DA is an effective option for the cases when ICAS-LVO is strongly suspected before EVT procedure.
An Integrated Wafer-Scale Packaging Process for MEMS (2002)

Packaging is well known to impose significant cost, performance and fabrication constraints on MEMS devices. We have developed a wafer-scale, integrated packaging process which enables a released MEMS device to be sealed within a thick layer of epi-polysilicon. This encapsulation may be tailored to withstand conventional dicing saws, pick/place chip handling equipment, and even high-pressure injection molding for plastic DIP packages. This architecture can be adapted to a variety of MEMS devices, and is compatible with integrated electronics. This paper will describe this packaging technique and discuss applications.
A very low-power CMOS mixed-signal IC for implantable pacemaker applications (2004)

Low power consumption is crucial for medical implant devices. A single-chip, very-low-power interface IC used in implantable pacemaker systems is presented. It contains amplifiers, filters, ADCs, battery management system, voltage multipliers, high voltage pulse generators, programmable logic and timing control. A few circuit techniques are proposed to achieve nanopower circuit operations within submicron CMOS process. Subthreshold transistor designs and switched-capacitor circuits are widely used. The 200 k transistor IC occupies 49 mm/sup 2/, is fabricated in a 0.5-/spl mu/m two-poly three-metal multi-V/sub t/ process, and consumes 8 /spl mu/W.
Nucleotide sequence and transcriptional mapping of the yeastpet56-his3-dedlgene region (1985)

Genes of the baker's yeast Saccharomyces cerevisiae are densely clustered on 16 linear chromosomes. Here, I characterize a 1.8 kb region of chromosome XV containing the entire structural gene for the histidine biosynthetic enzyme imidazoleglycerolphosphate (IGP) dehydratase (his3) as well as the promoter sequences and 5'-proximal mRNA coding regions for the adjacent genes. The his3 gene encodes several mRNA species averaging 820 bases in length, all of which contain an open reading frame of 219 codons. The location of this open reading frame coincides with the his3 gene as defined by functional criteria, suggesting that the primary translation product of yeast IGP dehydratase has a molecular weight of 23,850. Phenotypic analysis of mutations constructed in vitro indicate that one of the adjacent genes (pet56) is required for mitochondrial function, whereas the other gene (ded1) is essential for cell viability. The pet56 and his3 genes are transcribed divergently from initiation sites that are separated by only 192 bp. Transcription of the ded1 gene is initiated only 130 bp beyond the 3'-end of the his3 mRNA coding region. These results suggest that these unrelated genes are located extremely close together and that the spacer regions between them consist largely of promoter and terminator sequences.
Effects in the use of a genetically engineered strain ofLactococcus lactisdelivering in situ IL-10 as a therapy to treat low-grade colon inflammation (2014)

International audience
Abstract 257: Apabetalone (RVX-208) Reduces Pathologic Cell-Cell Adhesion and Expression of Key Vascular Inflammation Markers in Monocytes, Endothelial Cells and Mouse Aorta (2018)

Apabetalone (RVX-208) is a bromodomain &amp; extraterminal (BET) protein inhibitor, an epigenetic modifier of gene expression, currently in a phase 3 major adverse cardiac events outcomes trial in post-acute coronary syndrome patients with type 2 diabetes mellitus (DM) (BETonMACE). CVD patients enrolled in phase 2b trials (ASSERT, SUSTAIN and ASSURE) demonstrated a 44% relative risk reduction in cardiovascular disease (CVD) events (Nicholls et al. 2017). In CVD and DM, elevated circulating cytokines potentiate vascular inflammation (VI) through recruitment of leukocytes to the vascular endothelium, which contributes to atherosclerosis and plaque rupture. Previous studies demonstrated that apabetalone has potent anti-inflammatory effects on human aortic endothelial cells (HAEC) and macrophage-like U937 cells. Here we show that TNFα stimulation induced significant adhesion of THP-1 monocytes to inflamed endothelial cells, an outcome reversed by apabetalone treatment under both static (human umbilical vein endothelial cells - HUVEC) and flow (HAEC) conditions. Mechanistically, apabetalone suppressed the TNFα and IL-1β-induced expression of mRNAs of multiple endothelial cell adhesion molecules (CD44, E-selectin, VCAM-1 and MCP-1) and inflammatory cytokines (IL-6, IL-8, IL-1β, and CSF2). Monocytes also respond to TNFα stimulation with an upregulation of inflammatory and adhesion marker expression. In THP-1 cells, apabetalone treatment significantly reduced mRNA expression of CCR1, CCR2, IL-1β, MCP-1, MYD88, TLR4, TNFα, and VLA-4. In the diet-induced obesity (DIO) mouse model that mimics metabolic syndrome, treatment with apabetalone, administered at 150 mg/kg BID for the last 16 weeks of a 22 week study, downregulated aortic adhesion markers (E-selectin and ICAM) and markers of infiltrating immune cells (CCR2 and CD11b). In summary, treatment with apabetalone causes transcriptional changes in monocytes and endothelial cells that translate into a reduction in adhesion under inflammatory conditions. We hypothesize that downregulation of VI by apabetalone may contribute to the reduction in CVD events observed in phase 2 studies. This hypothesis is currently being tested in the ongoing BETonMACE phase 3 trial.
Survey on NoSQL database (2011)

With the development of the Internet and cloud computing, there need databases to be able to store and process big data effectively, demand for high-performance when reading and writing, so the traditional relational database is facing many new challenges. Especially in large scale and high-concurrency applications, such as search engines and SNS, using the relational database to store and query dynamic user data has appeared to be inadequate. In this case, NoSQL database created. This paper describes the background, basic characteristics, data model of NoSQL. In addition, this paper classifies NoSQL databases according to the CAP theorem. Finally, the mainstream NoSQL databases are separately described in detail, and extract some properties to help enterprises to choose NoSQL.
A novel synthesis of the isoxazolo[5,4,3‐kl]acridine ring system (1990)

Abstract The Schmidt reaction of 6,7‐dihydro‐3‐phenyl‐1,2‐benzisoxazol‐4(5 H )‐one ( 1 ) is described. In addition to the expected isomeric lactams, 3‐phenyl‐5,6,7,8‐tetrahydro‐4 H ‐isoxazolo[4,5‐ c ]azepin‐4‐one ( 3 ) and 7,8‐dihydro‐3‐phenyl‐4 H ‐isoxazolo[4,5‐ b ]azepin‐5(6 H )‐one ( 4 ), 4‐amino‐3‐phenyl 1,2‐benzisoxazole (5) was isolated, along with 4,5‐dihydro‐3 H ‐isoxazolo[5,4,3‐ kl ]acridine ( 6 ). Possible mechanisms for the formation of these products are discussed and some chemistry of the little‐known ring system represented by 6 is also described.
Biochemical Distribution of Tau Protein in Synaptosomal Fraction of Transgenic Mice Expressing Human P301L Tau (2014)

Alzheimer's disease is a progressive dementia that is characterized by a loss of recent memory. Evidence has accumulated to support the hypothesis that synapses are critical storage sites for memory. However, it is still uncertain whether tau protein is involved in associative memory storage and whether tau is distributed in mature brain synapses. To address this question, we examined the synaptosomal distribution of tau protein in both JNPL3 transgenic mice expressing human P301L tau and non-transgenic littermates. The JNPL3 mouse line is known as one of the mouse models of human tauopathy that develop motor and behavioral deficits with intracellular tau aggregates in the spinal cord and brainstem. The phenotype of disease progression is highly dependent on strain background. In this study, we confirmed that male JNPL3 transgenic mice with C57BL/6J strain background showed neither any sign of motor deficits nor accumulation of hyperphosphorylated tau in the sarkosyl-insoluble fraction until 18 months of age. Subcellular fractionation analysis showed that both mouse tau and human P301L tau were present in the synaptosomal fraction. Those tau proteins were less-phosphorylated than tau in the cytosolic fraction. Human P301L tau was preferentially distributed in the synaptosomal fraction while mouse endogenous tau was more distributed in the cytosolic fraction. Interestingly, a human-specific tau band with phosphorylation at Ser199 and Ser396 was observed in the synaptosomal fraction of JNPL3 mice. This tau was not identical to either tau species in cytosolic fraction or a prominent hyperphosphorylated 64 kDa tau species that was altered to tau pathology. These results suggest that exogenous human P301L tau induces synaptosomal distribution of tau protein with a certain phosphorylation. Regulating the synaptosomal tau level might be a potential target for a therapeutic intervention directed at preventing neurodegeneration.
Genetic influence on disease course and cytokine response in relapsing experimental allergic encephalomyelitis (1998)

A protracted and relapsing form of experimental allergic encephalomyelitis (EAE) develops in the DA rat after immunization with rat spinal cord homogenate (SCH) emulsified in incomplete Freund's adjuvant (IFA). The genetic influence on this model has been analyzed by immunizing MHC congenic strains on both LEW and DA genetic backgrounds, and recombinant inbred strains between DA and E3 rats. An in situ hybridization assay was used to examine the expression of mRNA for IFN-gamma, IL-4, IL-10 and transforming growth factor (TGF)-beta both in sections of spinal cords and the antigen-induced expression for these cytokines by splenocytes after in vitro stimulation with encephalitogenic MBP peptides. The susceptibility of relapsing EAE after immunization with SCH in IFA in the DA strain, but not the E3 strain, was correlated with a lack of expression for TGF-beta in the spinal cord. The recombinant inbred DXEB rats developed a severe EAE while surprisingly no signs of disease were observed in the DXEA strain, which shares the MHC region with the DXEB strain, after immunization with the MBP 63-87 peptide. Resistance to relapsing EAE in the DXEA strain correlated with increased non-MHC controlled expression for TGF-beta and lack of IFN-gamma in the spinal cord. The same pattern of cytokine expression was seen in splenocytes after stimulation in vitro with the MBP 63-87 peptide. A spreading of the immune response to the MBP 87-110 peptide was seen. Non-MHC genes controlled the quality of this response: splenocytes from MBP 63-87 immunized DXEB rats responded in vitro towards the MBP 87-110 peptide by expressing mRNA for IFN-gamma, IL-10 and IL-4, whereas in the DXEA strain the corresponding response involved IL-4 and TGF-beta. Taken together these data show that non-MHC controlled expression of mRNA for TGF-beta is associated with resistance to EAE.
Inhibition of protein synthesis in frog (Xenopus laevis) egg extracts by an antibody against phosphatidylinositol 4,5-bisphosphate (1996)

The antibody kt10, which is directed against the phospholipid PtdIns(4,5)P2, inhibits protein synthesis when added to cytosolic extracts prepared from frog eggs. Addition of stable analogues of diacylglycerol and Ins(1,4,5)P3 failed to rescue the inhibition of translation, suggesting that the effect of the antibody was not to block hydrolysis of PtdIns(4,5)P2. Neomycin, which also binds PtdIns(4,5)P2, produced a similar reduction in protein-synthesis levels in the extract system, supporting the idea that it is the interaction of the antibody with PtdIns(4,5)P2 that is producing the effect.
Peripheral pharmacokinetics of apomorphine in humans (1989)

Apomorphine, a potent dopamine agonist, has been used in acute and chronic studies of parkinsonism and other neurological disorders. To define its peripheral pharmacokinetics, we administered apomorphine by subcutaneous injection, by subcutaneous infusion, and by intravenous infusion to 15 patients with parkinsonism and measured plasma apomorphine levels by high-performance liquid chromatography with electrochemical detection. The peak drug levels and area under the curve were closely correlated with the dose administered; time to peak was brief and was independent of dose. The variation in absorption was high between subjects but low within individual subjects. In 11 of 15 subjects, the disappearance of drug could be described by a two-compartment model, with a distribution half-life of 5 minutes and an elimination half-life of 33 minutes. The drug absorption, volume of distribution, plasma clearance, and half-lives were similar for subcutaneous injection, subcutaneous infusion, and intravenous infusion. We conclude that apomorphine is rapidly and completely absorbed from subcutaneous tissue, correlating with the rapid onset of clinical effects, and that the brief duration of clinical action of the drug is explained by its rapid clearance.
Antitumor properties of 2(1H)-pyrimidinone riboside (zebularine) and its fluorinated analogs (1991)

2(1H)-Pyrimidinone riboside (zebularine, 1b) and its 5-fluoro (6b) and 2'-ara-fluoro (7b) analogues have been synthesized and evaluated in vivo as antitumor agents. Zebularine provides increase in life span (ILS) values of ca. 70% against intraperitoneal (ip) murine B16 melanoma and 50% against P388 leukemia. This compound is active when administered either ip or orally against ip or subcutaneously implanted L1210 leukemia, producing ILS values of about 100% at an optimum dose of 400 mg/kg. 1b is also active (60% ILS) against ara-C-resistant L1210. The analogous unsubstituted purine riboside nebularine (2) has modest activity against P388 leukemia (60% ILS). While 2'-ara-fluorozebularine (7b) is only marginally active (40% ILS) at high doses against L1210 leukemia, 5-fluoro analogue 6b is more active than zebularine and is ca. 100 times more potent. Although the activity of 6b is about the same as that of 1b against P388 leukemia, greater potency also is realized in this model. Zebularine is a strong inhibitor of cytidine deaminase, but in contrast to tetrahydrouridine, 1b is acid-stable. In an attempt to use this property to advantage in oral administration, 1b and ara-C have been orally coadministered to mice with ip L1210 leukemia. When zebularine is given in divided doses, up to a 2-fold increase in activity is realized, relative to treatment with the same dose of ara-C alone.
Inhibition of the Renin-Angiotensin System for Prevention of Atrial Fibrillation (2010)

Atrial fibrillation (AF) is a source of considerable morbidity and mortality. There has been compelling evidence supporting the role of renin-angiotensin system (RAS) in the genesis and perpetuation of AF through atrial remodeling, and experimental studies have validated the utilization of RAS inhibition for AF prevention. This article reviews clinical trials on the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) for the prevention of AF. Results have been variable, depending on the clinical background of treated patients. ACEIs and ARBs appear beneficial for primary prevention of AF in patients with heart failure, whereas they are not equally effective in hypertensive patients with normal left ventricular function. Furthermore, the use of ACEIs or ARBs for secondary prevention of AF has been found beneficial only after electrical cardioversion. Additional data are needed to establish the potential clinical role of renin-angiotensin inhibition for prevention of AF.
Constitutive expression of catABC genes in the aniline-assimilating bacterium Rhodococcus species AN-22: production, purification, characterization and gene analysis of CatA, CatB and CatC (2005)

The aniline-assimilating bacterium Rhodococcus sp. AN-22 was found to constitutively synthesize CatB (cis,cis-muconate cycloisomerase) and CatC (muconolactone isomerase) in its cells growing on non-aromatic substrates, in addition to the previously reported CatA (catechol 1,2-dioxygenase). The bacterium maintained the specific activity of the three enzymes at an almost equal level during cultivation on succinate. CatB and CatC were purified to homogeneity and characterized. CatB was a monomer with a molecular mass of 44 kDa. The enzyme was activated by Mn2+, Co2+ and Mg2+. Native CatC was a homo-octamer with a molecular mass of 100 kDa. The enzyme was stable between pH 7.0 and 10.5 and was resistant to heating up to 90 degrees C. Genes coding for CatA, CatB and CatC were cloned and named catA, catB and catC respectively. The catABC genes were transcribed as one operon. The deduced amino acid sequences of CatA, CatB and CatC showed high identities with those from other Gram-positive micro-organisms. A regulator gene such as catR encoding a regulatory protein was not observed around the cat gene cluster of Rhodococcus sp. AN-22, but a possible relic of catR was found in the upstream region of catA. Reverse transcriptase-PCR and primer extension analyses showed that the transcriptional start site of the cat gene cluster was located 891 bp upstream of the catA initiation codon in the AN-22 strain growing on both aniline and succinate. Based on these data, we concluded that the bacterium constitutively transcribed the catABC genes and translated its mRNA into CatA, CatB and CatC.
Modulation of Osteoclast Differentiation and Function by the New Members of the Tumor Necrosis Factor Receptor and Ligand Families (1999)

Osteoblasts/stromal cells are essentially involved in osteoclast differentiation and function through cell-to-cell contact (Fig. 8). Although many attempts have been made to elucidate the mechanism of the so-called "microenvironment provided by osteoblasts/stromal cells," (5-8) it has remained an open question until OPG and its binding molecule were cloned. The serial discovery of the new members of the TNF receptor-ligand family members has confirmed the idea that osteoclast differentiation and function are regulated by osteoblasts/stromal cells. RANKL, which has also been called ODF, TRANCE, or OPGL, is a member of the TNF ligand family. Expression of RANKL mRNA in osteoblasts/stromal cells is up-regulated by osteotropic factors such as 1 alpha, 25(OH)2D3, PTH, and IL-11. Osteoclast precursors express RANK, a TNF receptor family member, recognize RANKL through cell-to-cell interaction with osteoblasts/stromal cells, and differentiate into pOCs in the presence of M-CSF. RANKL is also involved in the survival and fusion of pOCs and activation of mature osteoclasts. OPG, which has also been called OCIF or TR1, is a soluble receptor for RANKL and acts as a decoy receptor in the RANK-RANKL signaling system (Fig. 8). In conclusion, osteoblasts/stromal cells are involved in all of the processes of osteoclast development, such as differentiation, survival, fusion, and activation of osteoclasts (Fig. 8). Osteoblasts/stromal cells can now be replaced with RANKL and M-CSF in dealing with the whole life of osteoclasts. RANKL, RANK, and OPG are three key molecules that regulate osteoclast recruitment and function. Further studies on these key molecules will elucidate the molecular mechanism of the regulation of osteoclastic bone resorption. This line of studies will establish new ways to treat several metabolic bone diseases caused by abnormal osteoclast recruitment and functions such as osteopetrosis, osteoporosis, metastatic bone disease, Paget's disease, rheumatoid arthritis, and periodontal bone disease.
Particulate phase of cellulose cigarette smoke. (1980)

In order to obtain a general view of the particulate phase of cellulose cigarette smoke without losing some unstable components which are apt to degrade during fractionation procedures, particulate matter was collected on a aerosol filter and analysed either directly or after trimethylsilylation. Ninety nine compounds were either positively or tentatively identified. Of these 99 compounds, acetolformate, 2, 4-pentadien-4-olide, 2-hydroxy-3-ethyl-2-cyclopentenone, 1, 1, 2-trihydroxyethane and methyltrihydroxybenzene were identified for the first time in this study as the components of the cellulose pyrolysate. Semi-quantitative determination of some main components of the particulate phase revealed that levoglucosan was the most abundant followed by 1, 1, 2-trihydroxyethane, glycolic acid, acetol, 5-hydroxymethyl-2-furaldehyde, etc., in decreasing order.
The Molecular Control of Blood Cell Development (1987)

The establishment of a cell culture system for the clonal development of blood cells has made it possible to identify the proteins that regulate the growth and differentiation of different blood cell lineages and to discover the molecular basis of normal and abnormal cell development in blood forming tissues. A model system with myeloid blood cells has shown that (i) normal blood cells require different proteins to induce cell multiplication (growth inducers) and cell differentiation (differentiation inducers), (ii) there is a hierarchy of growth inducers as cells become more restricted in their developmental program, and (iii) a cascade of interactions between proteins determines the correct balance between immature and mature cells in normal blood cell development. Gene cloning has shown that there is a family of different genes for these proteins. Normal protein regulators of blood cell development can control the abnormal growth of certain types of leukemic cells and suppress malignancy by inducing differentiation to mature nondividing cells. Chromosome abnormalities that give rise to malignancy in these leukemic cells can be bypassed and their effects nullified by inducing differentiation, which stops cells from multiplying. These blood cell regulatory proteins are active in culture and in the body, and they can be used clinically to correct defects in blood cell development.
Motor Proficiency in Children With Neurofibromatosis Type 1 (2010)

Children with NF1 have significantly lower motor proficiency than the BOT 2 normative scores. The results indicate the BOT 2 is useful in identifying and characterizing delays in motor proficiency for children with NF1.