gebhart/patrepeval huggingface dataset:
Coherent Power Combination of Semiconductor Lasers Using Optical Phase-Lock Loops (2009)

Heterodyne optical phase-lock loops (OPLLs) enable the precise electronic control over the frequency and phase of a semiconductor laser (SCL) locked to a ldquomasterrdquo reference laser. One of the more interesting applications of OPLLs is the creation of coherent arrays by locking a number of ldquoslaverdquo SCLs to a common master laser. In this paper, we demonstrate the coherent power combination of various high-power semiconductor lasers using OPLLs in both the filled-aperture and tiled-aperture configurations. We further demonstrate the electronic control over the phase of each individual SCL using a voltage-controlled oscillator. It is feasible to combine a large number of SCLs using this approach, leading to compact, efficient, and cost-effective high-power and high-radiance optical sources.
Different Adaptations of IgG Effector Function in Human and Nonhuman Primates and Implications for Therapeutic Antibody Treatment (2012)

Safety of human therapeutic Abs is generally assessed in nonhuman primates. Whereas IgG1 shows identical FcγR interaction and effector function profile in both species, fundamental differences in the IgG2 and IgG4 Ab subclasses were found between the two species. Granulocytes, the main effector cells against IgG2- and IgG4-opsonized bacteria and parasites, do not express FcγRIIIb, but show higher levels of FcγRII in cynomolgus monkey. In humans, IgG2 and IgG4 adapted a silent Fc region with weak binding to FcγR and effector functions, whereas, in contrast, cynomolgus monkey IgG2 and IgG4 display strong effector function as well as differences in IgG4 Fab arm exchange. To balance this shift toward activation, the cynomolgus inhibitory FcγRIIb shows strongly increased affinity for IgG2. In view of these findings, in vitro and in vivo results for human IgG2 and IgG4 obtained in the cynomolgus monkey have to be cautiously interpreted, whereas effector function-related effects of human IgG1 Abs are expected to be predictable for humans.
DPP‐IV‐resistant, long‐acting oxyntomodulin derivatives (2011)

Obesity is one of the major risk factors for type 2 diabetes, and the development of agents, that can simultaneously achieve glucose control and weight loss, is being actively pursued. Therapies based on peptide mimetics of the gut hormone glucagon-like peptide 1 (GLP-1) are rapidly gaining favor, due to their ability to increase insulin secretion in a strictly glucose-dependent manner, with little or no risk of hypoglycemia, and to their additional benefit of causing a modest, but durable weight loss. Oxyntomodulin (OXM), a 37-amino acid peptide hormone of the glucagon (GCG) family with dual agonistic activity on both the GLP-1 (GLP1R) and the GCG (GCGR) receptors, has been shown to reduce food intake and body weight in humans, with a lower incidence of treatment-associated nausea than GLP-1 mimetics. As for other peptide hormones, its clinical application is limited by the short circulatory half-life, a major component of which is cleavage by the enzyme dipeptidyl peptidase IV (DPP-IV). SAR studies on OXM, described herein, led to the identification of molecules resistant to DPP-IV degradation, with increased potency as compared to the natural hormone. Analogs derivatized with a cholesterol moiety display increased duration of action in vivo. Moreover, we identified a single substitution which can change the OXM pharmacological profile from a dual GLP1R/GCGR agonist to a selective GLP1R agonist. The latter finding enabled studies, described in detail in a separate study (Pocai A, Carrington PE, Adams JR, Wright M, Eiermann G, Zhu L, Du X, Petrov A, Lassman ME, Jiang G, Liu F, Miller C, Tota LM, Zhou G, Zhang X, Sountis MM, Santoprete A, Capitò E, Chicchi GG, Thornberry N, Bianchi E, Pessi A, Marsh DJ, SinhaRoy R. Glucagon-like peptide 1/glucagon receptor dual agonism reverses obesity in mice. Diabetes 2009; 58: 2258-2266), which highlight the potential of GLP1R/GCGR dual agonists as a potentially superior class of therapeutics over the pure GLP1R agonists currently in clinical use.
Efficient bypass of mutations in dysferlin deficient patient cells by antisense-induced exon skipping (2009)

Mutations in DYSF encoding dysferlin cause primary dysferlinopathies, autosomal recessive diseases that mainly present clinically as Limb Girdle Muscular Dystrophy type 2B and Miyoshi myopathy. More than 350 different sequence variants have been reported in DYSF. Like dystrophin, the size of the dysferlin mRNA is above the limited packaging size of AAV vectors. Alternative strategies to AAV gene transfer in muscle cells must then be addressed for patients. A gene therapy approach for Duchenne muscular dystrophy was recently developed, based on exon-skipping strategy. Numerous sequences are recognized by splicing protein complexes and, when specifically blocked by antisense oligoucleotides (AON), the corresponding exon is skipped. We hypothesized that this approach could be useful for patients affected with dysferlinopathies. To confirm this assumption, exon 32 was selected as a prioritary target for exon skipping strategy. This option was initially driven by the report from Sinnreich and colleagues of a patient with a very mild and late-onset phenotype associated to a natural skipping of exon 32. Three different antisense oligonucleotides were tested in myoblasts generated from control and patient MyoD transduced fibroblasts, either as oligonucleotides or after incorporation into lentiviral vectors. These approaches led to a high efficiency of exon 32 skipping. Therefore, these results seem promising, and could be applied to several other exons in the DYSF gene. Patients carrying mutations in exons whose the in-frame suppression has been proven to have no major consequences on the protein function, might benefit of exon-skipping based gene correction.
Lipoproteins alter the catalytic behavior of the platelet-activating factor acetylhydrolase in human plasma. (1989)

Platelet-activating factor (PAF) has been implicated as a mediator of inflammation, allergy, shock, and thrombosis. A specific degradative enzyme, PAF acetylhydrolase (EC 3.1.1.47), is found in plasma and could regulate the concentration of PAF in blood. In plasma, 70% of the PAF acetylhydrolase is found with low density lipoprotein (LDL), and the remainder is in high density lipoprotein (HDL). In previous studies we found that with subsaturating concentrations of PAF the activity in LDL seemed to be the relevant one; e.g., depletion of LDL slowed degradation of PAF, while removal of HDL accelerated the degradation slightly. We have pursued this observation by using plasma from humans with lipoprotein mutations. In abetalipoproteinemia, all of the PAF acetylhydrolase activity was in HDL, whereas in Tangier disease all of the activity was in LDL. In both conditions the total activity measured in an optimized assay was normal or increased. However, when we measured the t1/2 of PAF in plasma, we found that it was prolonged in subjects with abetalipoproteinemia compared to normal controls. Conversely, the t1/2 in Tangier plasma was shortened. We next demonstrated that the PAF acetylhydrolase in HDL was recognized by an antibody to the enzyme purified from LDL, establishing that the enzyme in the two particles is the same protein. Finally, we inactivated the PAF acetylhydrolase in isolated lipoprotein particles and then reconstituted them with enzyme from the opposite particle. The reconstituted particles were used to measure the t1/2 of PAF, and we again found that the LDL particle was more efficient. We conclude that the lipoprotein environment of the PAF acetylhydrolase markedly influences its catalytic behavior. This may be important in pathophysiology and will complicate attempts to assess the role of this enzyme in such circumstances.
Stable and functional lymphoid reconstitution of common cytokine receptor γ chain deficient mice by retroviral-mediated gene transfer (2000)

Mutations in the gene encoding the common cytokine receptor gamma chain (γc) are responsible for human X-linked severe combined immunodeficiency disease (SCIDX1). We have used a γc-deficient mouse model to test the feasibility and potential toxicity of γc gene transfer as a therapy for SCIDX1. A retrovirus harboring the murine γc chain was introduced into γc-deficient bone marrow cells, which were then transplanted into alymphoid RAG2/γcdouble-deficient recipient mice. Circulating lymphocytes appeared 4 weeks postgraft and achieved steady-state levels by 8 weeks. The mature lymphocytes present in the grafted mice had integrated the γc transgene, expressed γc transcripts, and were able to proliferate in response to γc-dependent cytokines. The γc-transduced animals demonstrated (1) normal levels of immunoglobulin subclasses, including immunoglobulin G1 (IgG1) and IgG2a (which are severely decreased in γc- mice); (2) the ability to mount an antigen-specific, T-dependent antibody response showing effective in vivo T-B cell cooperation, and (3) the presence of gut-associated cryptopatches and intraepithelial lymphocytes. Importantly, peripheral B and T cells were still present 47 weeks after a primary graft, and animals receiving a secondary graft of γc-transduced bone marrow cells demonstrated peripheral lymphoid reconstitution. That γc gene transfer to hematopoietic precursor cells can correct the immune system abnormalities in γc- mice supports the feasibility of in vivo retroviral gene transfer as a treatment for human SCIDX1.
Cell surface sulfhydryls are required for the cytotoxicity of diphtheria toxin but not of ricin in Chinese hamster ovary cells. (1991)

A previous study on cleavage of disulfide bonds in endocytosed model compounds had shown that an initial phase of cleavage was totally inhibited by membrane-impermeant sulfhydryl inhibitors and thus was mediated by cell surface sulfhydryls (Feener, E. P., Shen, W.-C., and Ryser, H. J.-P. (1990) J. Biol. Chem. 265, 18780-18785). This paper uses the same inhibitors (5,5'-dithiobis(2-nitrobenzoic acid) and p-chloromercuriphenylsulfonic acid) to examine the role of surface sulfhydryls in the cytotoxicity of diphtheria toxin (DT). Since the interchain disulfide of endocytosed DT must be cleaved prior to translocation of chain A from endosomes to cytoplasm, it was postulated that surface sulfhydryls might mediate the cleavage of that disulfide bond as well. Both sulfhydryl blockers did indeed markedly inhibit DT cytotoxicity. This effect was not due to inactivation of unbound DT, inhibition of receptor-mediated endocytosis, or impairment of acidification of endosomes. We conclude that cell surface sulfhydryls susceptible to blockage by 5,5'-dithiobis(2-nitro-benzoic acid) and p-chloromercuriphenylsulfonic acid are required for the cytotoxicity of DT and, most likely, for the reductive cleavage of DT's interchain disulfides. Ricin cytotoxicity was not decreased; this is consistent with the view that ricin reaches the cytoplasm from a late endocytic structure and with the finding that endocytosed disulfides are also cleaved in a cell fraction containing elements of the Golgi apparatus (Feener, E. P., Shen, W.-C., and Ryser, H. J.-P. (1990) J. Biol. Chem. 265, 18780-18785).
Epidemiology of depression. (1989)

Recent advances in the methodology of epidemiology in psychiatry are briefly reviewed, along with remaining problems, such as the defining of a "case" of depression. Findings from recent studies of the epidemiology of depression are outlined.
The PROSITE database, its status in 1999 (1999)

The PROSITE database (http://www.expasy.ch/sprot/prosite.htm l) consists of biologically significant patterns and profiles formulated in such a way that with appropriate computational tools it can help to determine to which known family of protein (if any) a new sequence belongs, or which known domain(s) it contains.
Targeting of the creating kinase M gene in embryonic stem cells using isogenic and nonisogenic vectors (1992)

Replacement vectors with genomic DNA originating from different mouse strains were used to introduce site-specific mutations into the creatine kinase M (CKM) gene of mouse embryonic stem (ES) cells. Here we demonstrate that in mouse strain 129-derived ES cells, the gene is at least 25-fold more efficiently targeted with an isogenic, 129-derived vector (129-pRV8.3) than with a nonisogenic, BALB/c-specific vector (BALB/c-pRV8.3). The two targeting constructs were identical except for allelic differences which were typed by partial sequencing. These included base pair mismatches (2%) and a polymorphic [GTC]-repeat length variation. Both in separate transfections as well as in cotransfections with mixed vectors, homologous disruption of the CKM gene resulted uniquely from the 129-isogenic DNA. Our data confirm earlier observations on requirements for homologous recombination in pro- and eukaryotic systems and indicate that targeting of the CKM locus is highly sensitive to small sequence differences between cognate segments in the endogenous and incoming DNA.
Screening for Galectin-3 Inhibitors from Synthetic Lacto-N-biose Libraries Using Microscale Affinity Chromatography Coupled to Mass Spectrometry (2006)

The synthesis and screening of two beta-D-Galp-(1-3)-beta-d-GlcpN (lacto-N-biose) disaccharide libraries are reported. Solution-phase synthetic modifications at the HO-2' and NH positions were performed in an effort to enhance the affinity toward galectin-3, a galactose-binding protein involved in tumor metastasis, apoptosis, and inflammation. The libraries were screened for galectin-3 binding by microscale frontal affinity chromatography coupled to mass spectrometry (FAC/MS) allowing for rapid ranking of the different inhibitors and the determination of the galectin-3 binding Kd's. Compounds bearing a hydrophobic substituent on the NH group showed the highest affinity for the lectin. The N-naphthoyl derivative (Kd = 10.6 microM) was the best inhibitor with a 7 times increased affinity as compared to the N-acetyl parent compound (Kd = 73.3 microM).
体系的时代终止了——与A．赖夫的谈话 (2007)

存在哲学的某种衰弱，对于那些拙劣的模仿者来说，哲学确实“终结了”。但是，作为对世界之谜的描述、对“为何”的追问，哲学本身从未终结，也不会终结。全部哲学依靠持续不断的惊异而生活，哲学思维的根本问题仍然是希望。希望既不同于确信，更不同于绝望，希望不是处在中间，而是不停地处在运动之中，并且不断地碰撞、寻找和发现新的角落和出口。哲学载有神话，而幻想能够保存幻想，在印度或其他第三世界的国家存在另一种哲学思维。辩证法使马克思主义成为可能，社会变革的理论属于马克思主义。为了变革世界，需要传播现实的看法，陈词滥调是反革命的行为。
Synthesis and preclinical evaluation of a new C-6 alkylated pyrimidine derivative as a PET imaging agent for HSV1-tk gene expression. (2013)

[(18)F]FHOMP (6-((1-[(18)F]-fluoro-3-hydroxypropan-2-yloxy)methyl)-5-methylpyrimidine-2,4(1H,3H)-dione), a C-6 substituted pyrimidine derivative, has been synthesized and evaluated as a potential PET agent for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene expression. [(18)F]FHOMP was prepared by the reaction of the tosylated precursor with tetrabutylammonium [(18)F]-fluoride followed by acidic cleavage of the protecting groups. In vitro cell accumulation of [(18)F]FHOMP and [(18)F]FHBG (reference) was studied with HSV1-tk transfected HEK293 (HEK293TK+) cells. Small animal PET and biodistribution studies were performed with HEK293TK+ xenograft-bearing nude mice. The role of equilibrative nucleoside transporter 1 (ENT1) in the transport and uptake of [(18)F] FHOMP was also examined in nude mice after treatment with ENT1 inhibitor nitrobenzylmercaptopurine ribonucleoside phosphate (NBMPR-P). [(18)F]FHOMP was obtained in a radiochemical yield of ~25% (decay corrected) and the radiochemical purity was greater than 95%. The uptake of [(18)F]FHOMP in HSV1-TK containing HEK293TK+ cells was 52 times (at 30 min) and 244 times (at 180 min) higher than in control HEK293 cells. The uptake ratios between HEK293TK+ and HEK293 control cells for [(18)F]FHBG were significantly lower i.e. 5 (at 30 min) and 81 (240 min). In vivo, [(18)F]FHOMP accumulated to a similar extend in HEK293TK+ xenografts as [(18)F]FHBG but with a higher general background. Blocking of ENT1 reduced [(18)F]FHOMP uptake into brain from a standardized uptake value (SUV) of 0.10±0.01 to 0.06±0.02, but did not reduce the general background signal in PET. Although [(18)F]FHOMP does not outperform [(18)F]FHBG in its in vivo performance, this novel C-6 pyrimidine derivative may be a useful probe for monitoring HSV1-tk gene expression in vivo.
Palette mode &#x2014; A new coding tool in screen content coding extensions of HEVC (2015)

Palette mode, as a new coding tool, is adopted in the Screen Content Coding Extensions of High Efficiency Video Coding (HEVC SCC) that is being defined by the Joint Collaborative Team on Video Coding (JCT-VC). In the palette mode, pixels in a coding unit (CU) are represented by selected representative colours according to the characteristics of screen contents in which pixel values usually concentrate on few colour values. This paper introduces the palette mode in HEVC SCC, and our contributions to the palette mode are also presented. Experimental results show that disabling the palette mode suffers 20.3%, 13.0%, and 7.5% BD-rate increases for “YUV, text & graphics with motion, 1080p & 720p sequences” under all intra (AI), random access (RA), and low-delay B (LB) common test conditions, respectively.
The Correlation Analysis on the Soil Total Nitrogen Content of Lateritic Red Soil and Terrain Characteristics in Guangdong Province Based on DEM (2010)

DEM of lateritic red soil in Guangdong Province was set up by using ArcGIS 9.2 based on soil type map,topographic map,and total nitrogen map data.Altitude,slope,aspect and undulating terrain were extracted to explore the correlation in large-scale between topographic factors and total nitrogen content of lateritic red soil in Guangdong Province.The results show that total nitrogen content of lateritic red soil had high correlation with the distribution area of the indices of height,slope and relief amplitude.The distribution area of total nitrogen content in soil was decreased as those terrain indices increased.As for aspect,the distribution area of soil total nitrogen content was mainly in flat region and south-east slope.
Hepatitis C Virus Core and E2 Protein Expression in Transgenic Mice (1997)

Transgenic mice have been produced that express the hepatitis C virus (HCV) core protein in the liver under the transcriptional control of the mouse major urinary protein promoter. These animals express the full length core protein in cytoplasm of their hepatocytes at levels comparable to those detected in naturally infected patients, without histological or biochemical evidence of liver disease or hepatocellular carcinoma. This contrasts with recent reports that HCV core protein can transform NIH 3T3 cells and cooperates with H-ras to transform primary rat fibroblasts in vitro. Coexpression of HCV core protein in double transgenic mice that replicate the hepatitis B virus (HBV) does not inhibit hepatocellular HBV gene expression or replication, contrary to reports that it inhibits HBV replication in HuH-7 cells after transient transfection in vitro. We have also produced transgenic mice in which a C-terminally truncated (aa384-715) glycosylated HCV E2 protein is expressed in the liver under the transcriptional control of the mouse albumin promoter. Despite the high level expression of HCV E2 protein, no evidence of liver disease was detected in these animals. These results suggest that the HCV core and E2 proteins are not cytopathic for the hepatocyte in vivo, and they represent an initial step in the development of a small animal model of HCV immunopathology.
Omega 3 fatty acid inhibition of inflammatory cytokine-mediated Connexin43 regulation in the heart (2012)

Background: The proinflammatory cytokine Interleukin-1β (IL-1β), which increases in the heart post myocardial infarction (MI), has been shown to cause loss of Connexin43 (Cx43) function, an event known to underlie formation of the arrhythmogenic substrate. Omega 3 Fatty acids exhibit antiarrhythmic properties and impact IL-1β signaling. We hypothesize that Omega-3 fatty acids prevent arrhythmias in part, by inhibiting IL-1β signaling thus maintaining functional Cx43 channels. Methods: Rat neonatal myocytes or Madin-Darby Canine Kidney Epithelial (MDCK) cells grown in media in the absence (Ctr) or presence of 30μM docosahexaenoic acid (DHA, an Omega-3 Fatty acid) were treated with 0.1μM activated IL-1β. We determined Cx43 channel function using a dye spread assay. Western blot and immunostaining were used to examine Cx43 levels/localization and downstream effectors of IL-1 β. In addition we used a murine model of myocardial infarction (MI) for 24 hours to determine the impact of an Omega-3 fatty acid enriched diet on Cx43 levels/localization post myocardial infarction. Results: IL-1β significantly inhibited Cx43 function in Ctr cells (200.9 +/- 17.7 μm [Ctr] vs. 112.8 +/- 14.9 μm [0.1uM IL-1β], p&lt;0.05). However, DHA-treated cells remained highly coupled in the presence of IL-1β [167.9 +/- 21.9 μm [DHA] vs. 164.4 +/- 22.3 μm [DHA+0.1uM IL-1β], p&lt;0.05, n=4). Additionally, western blot showed that IL-1β treatment caused a 38.5% downregulation of Cx43 [1.00au [Ctr] vs 0.615au (0.1μM IL-1β) which was completely abolished in DHA treated cells (0.935au [DHA] vs. 1.02au [DHA+0.1μM IL-1β), p&lt;0.05, n=3]. Examination of the downstream modulator of IL-1β, NFκβ showed that while hypoxia caused translocation of NFκβ to the nucleus, this was inhibited by DHA. Additionally we found that a diet enriched in Omega-3 Fatty acids inhibited lateralization of Cx43 in the post-myocardial infarction murine heart as well as limited activation of fibroblasts which would lead to decreased fibr