gebhart/patrepeval huggingface dataset:
CD4-Chemokine Receptor Hybrids in Human Immunodeficiency Virus Type 1 Infection (1999)

ABSTRACT Most human immunodeficiency virus (HIV) strains require both CD4 and a chemokine receptor for entry into a host cell. In order to analyze how the HIV-1 envelope glycoprotein interacts with these cellular molecules, we constructed single-molecule hybrids of CD4 and chemokine receptors and expressed these constructs in the mink cell line Mv-1-lu. The two N-terminal (2D) or all four (4D) extracellular domains of CD4 were linked to the N terminus of the chemokine receptor CXCR4. The CD4(2D)CXCR4 hybrid mediated infection by HIV-1 LAI to nearly the same extent as the wild-type molecules, whereas CD4(4D)CXCR4 was less efficient. Recombinant SU LAI protein competed more efficiently with the CXCR4-specific monoclonal antibody 12G5 for binding to CD4(2D)CXCR4 than for binding to CD4(4D)CXCR4. Stromal cell-derived factor 1 (SDF-1) blocked HIV-1 LAI infection of cells expressing CD4(2D)CXCR4 less efficiently than for cells expressing wild-type CXCR4 and CD4, whereas down-modulation of CXCR4 by SDF-1 was similar for hybrids and wild-type CXCR4. In contrast, the bicyclam AMD3100, a nonpeptide CXCR4 ligand that did not down-modulate the hybrids, blocked hybrid-mediated infection at least as potently as for wild-type CXCR4. Thus SDF-1, but not the smaller molecule AMD3100, may interfere at multiple points with the binding of the surface unit (SU)-CD4 complex to CXCR4, a mechanism that the covalent linkage of CD4 to CXCR4 impedes. Although the CD4-CXCR4 hybrids yielded enhanced SU interactions with the chemokine receptor moiety, this did not overcome the specific coreceptor requirement of different HIV-1 strains: the X4 virus HIV-1 LAI and the X4R5 virus HIV-1 89.6 , unlike the R5 strain HIV-1 SF162 , infected Mv-1-lu cells expressing the CD4(2D)CXCR4 hybrid, but none could use hybrids of CD4 and the chemokine receptor CCR2b, CCR5, or CXCR2. Thus single-molecule hybrid constructs that mimic receptor-coreceptor complexes can be used to dissect coreceptor function and its inhibition.
Mutagenesis of the conserved 51-nucleotide region of Sindbis virus (1990)

We have constructed 25 site-specific mutations in a domain of 51 nucleotides in Sindbis virus that is highly conserved among all alphaviruses sequenced to date. These 51 nucleotides are capable of forming two hairpin structures and are found from nucleotides 155 to 205 in Sindbis virus within the region encoding nsP1. Of the mutations, 21 were silent and did not lead to a change in the amino acid sequence encoded. These silent mutations changed not only the linear sequence but also the stability of the hairpins in most cases. Two double mutants that were constructed led to the replacement of one base pair by another so that the linear sequence was altered but the nature of the hairpins was not. All of the mutants with silent mutations were viable, but 19 of the 21 mutants were severely impaired for growth in both chicken and mosquito cells. Compared with the parental virus, they grew slowly and produced virus at rates of 10(-1) to 10(-4) times the parental rate. Surprisingly, however, the plaques produced by these mutants were indistinguishable from those produced by the parental virus. Two of the silent mutations, found within the first hairpin structure, produced virus at a faster rate than the parental virus. It is clear that the exact sequence of this region is important for some aspect of virus replication. We suggest that one or more proteins, either virus encoded or cellular, bind to the hairpin structures in a sequence-specific fashion in a step that promotes replication of the viral RNA. Of the mutations that resulted in a change of coding, only one of four was viable, suggesting that the amino acid sequence encoded in this domain is essential for virus replication.
Microstrip resonators and filters using high-T/sub c/ superconducting thin films on LaAlO/sub 3/ (1991)

Very low microwave losses have been measured in YBa/sub 2/Cu/sub 3/O/sub 7/ linear resonators, ring resonators, and bandpass filters. The stoichiometric 1-2-3 compound was deposited on LaAlO/sub 3/ substrates, patterned microwave circuits, and overcoated with a passivating LaAlO/sub 3/ layer. HTS (high T/sub c/ superconductor) linear microstrip resonators demonstrated Q values greater than 1200 at 10 GHz, corresponding to surface resistances less than 300 mu Omega . Identical silver resonators showed Q values of 60 and surface resistance of 15 m Omega . The high-frequency transition temperature for these HTS films was greater than 83 K. Q values of 240 were measured in ring resonators at 15 GHz. Finally, the authors designed, fabricated, and tested a two-pole, Chebyshev narrow-bandwidth bandpass filter. The HTS filter was designed to be a 1% bandwidth with 0.2-dB ripple. Insertion loss was 2 dB at 4 K, rising to 3 dB at 77 K. The authors observed a temperature dependence in the filter center frequency which they attribute to kinetic inductance effects. The proposed HTS filters outperform similar cryogenic silver filters, indicating that practical levels of HTS performance have been achieved.
Control of Memory Formation Through Regulated Expression of a CaMKII Transgene (1996)

One of the major limitations in the use of genetically modified mice for studying cognitive functions is the lack of regional and temporal control of gene function. To overcome these limitations, a forebrain-specific promoter was combined with the tetracycline transactivator system to achieve both regional and temporal control of transgene expression. Expression of an activated calcium-independent form of calcium-calmodulin-dependent kinase II (CaMKII) resulted in a loss of hippocampal long-term potentiation in response to 10-hertz stimulation and a deficit in spatial memory, a form of explicit memory. Suppression of transgene expression reversed both the physiological and the memory deficit. When the transgene was expressed at high levels in the lateral amygdala and the striatum but not other forebrain structures, there was a deficit in fear conditioning, an implicit memory task, that also was reversible. Thus, the CaMKII signaling pathway is critical for both explicit and implicit memory storage, in a manner that is independent of its potential role in development.
Improvement in Outflow Facility by Two Novel Microinvasive Glaucoma Surgery Implants (2014)

Both implants effectively increased C in human eyes ex vivo. The scaffold increased C by a greater percentage (73% vs. 34%) and at a greater range of perfusion pressures (20 to 50 mm Hg vs. 40 mm Hg) than the two micro-bypasses, suggesting that the 8-mm dilation of Schlemm's canal by the scaffold may have additional benefits in lowering the outflow resistance. The Hydrus Microstent scaffold may be an effective therapy for increasing outflow facility and thus reducing the IOP in patients with glaucoma.
Senescence and cell density of human diploid fibroblasts influence metabolism of insulin‐like growth factor binding proteins (1994)

In order to analyze changes in metabolism of insulin-like growth factor binding proteins (IGFBPs) related to cell senescence and cell density, we compared human diploid fibroblasts (HDF) in the proliferatively vigorous first half (young cells) and senescent HDF in the last 10% (old cells) of the replicative lifespan after seeding cells over an eightfold range and proliferation to high density. Increasing the seeding cell density of both young and old HDF led to elevated rates of IGFBP-3 secretion, an increasing ratio of the 42/38 kDa species of IGFBP-3, and degradation of all species of IGFBPs derived from both the fetal bovine serum component of the culture medium and from HDF. At a given seeding density old HDF produced more IGFBP-3 and degraded more IGFBPs than young HDF. IGFBP-4 was degraded by a protease that appeared to be different from the protease(s) involved in degradation of the other IGFBPs. Young HDF at all seeding densities contained a cell-associated 29 kDa IGFBP, whereas this protein could not be detected in old cells. Thus, although certain changes in IGFBP metabolism are similar in young HDF seeded at high densities and in old HDF, young and old phenotypes can be distinguished by characteristic qualitative and quantitative changes in IGFBPs derived from fetal bovine serum and from HDF.
Palladium‐Catalyzed Selective Anti‐Markovnikov Oxidation of Allylic Esters (2013)

Eine Alternative zu gekreuzten Aldolreaktionen bietet die Palladium(II)-katalysierte Anti-Markownikow-Oxidation von Allylestern zu Aldehyden bei Raumtemperatur. Durch den Einsatz der Ester-Schutzgruppe für den Allylalkohol wird das Aldehydprodukt hoch regioselektiv erhalten. Die zügige Isomerisierung und die viel schnellere Oxidation des verzweigten Isomers sorgen dafür, dass lineare wie verzweigte Allylester dasselbe Produkt ergeben. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Adhesion molecules in iris biopsy specimens from patients with uveitis (1998)

An increased expression of adhesion molecules was found in the iris of patients with uveitis, indicating an immunoregulatory function for adhesion molecules in the pathogenesis of uveitis.
The subunits of succinyl-coenzyme A synthetase--function and assembly. (1987)

Succinyl-CoA synthetase is made up of two kinds of subunits, designated alpha and beta. The enzyme from Escherichia coli is an alpha 2 beta 2 tetramer (mol. mass. 142 kDa), whereas the mammalian mitochondrial species is an alpha beta dimer. By means of active enzyme centrifugation, we have shown that the active form of the bacterial enzyme is the tetramer even at very low assay concentrations, while the pig heart enzyme is a non-associating dimer over a wide concentration range. The E. coli enzyme shows distinct half-of-the-sites reactivity with respect to the phosphorylation of a histidine residue in the alpha-subunit that represents a step in catalysis. Many lines of evidence (hybrid enzyme formation, oxygen exchange kinetics, 31P-n.m.r. studies) suggest that co-operative interactions between alternatingly functional active sites on the two halves of the E. coli enzyme contribute to its catalytic efficacy. In further refining this model for catalysis, we have shown that the monothiophosphorylated E. coli enzyme does not catalyse exchange of 18O from the beta, gamma-bridge to the beta-non-bridge position of ATP, indicating that the enzyme does not undergo even transient bis-phosphorylation. As a first step in studying the in vivo synthesis and assembly of the enzyme in the mammalian mitochondrial matrix, we have cloned and sequenced a 900 bp cDNA fragment that encodes most of the alpha subunit of rat liver succinyl-CoA synthetase. The derived amino acid sequence shows an impressive degree of homology to that of the alpha subunit of the enzyme from E. coli. We have shown that the alpha subunit in rat liver is a discrete nuclear gene product, complete with cleavable signal sequence to specify mitochondrial targetting.
STAT3: A critical transcription activator in angiogenesis (2007)

Angiogenesis, the formation of new blood vessels from the pre-existing vasculature, is a complex multistage process regulated by a number of signal transduction pathways. Accumulating evidence suggests that signal transducer and activator of transcription (STATs), mainly STAT3, play an important role in angiogenesis under both physiological and pathological conditions in addition to cell survival, proliferation, differentiation, and oncogenesis. STAT3, as a critical multifunctional mediator, regulates many aspects of angiogenesis at the transcriptional level. This review will highlight the pivotal role of STAT3 in well-studied tumorous angiogenesis and cardiac angiogenesis, and summarize various potential mechanisms utilized by STAT3 to regulate the transcriptional activation of VEGF.
Enhancement of DNA uptake in FUT8‐deleted CHO cells for transient production of afucosylated antibodies (2010)

Removal of the core alpha1,6 fucose from the glycans in the Fc region of IgG1 antibodies has been demonstrated to improve antibody-dependent cellular cytotoxicity (ADCC) activity. In order to produce afucosylated antibodies using transient transfection, a FUT8 knockout (FUT8KO) cell line was generated in a CHO host cell line using the zinc finger nuclease technology. Transient transfection of DNA into mammalian cells using the cationic polymer, polyethylenimine (PEI), is commonly used for rapid generation of recombinant proteins. FUT8KO cells evaluated in PEI transfections yielded lower titers than parental CHO WT cells. FACS and HPLC analyses revealed that the FUT8KO cells had lower cell surface heparan sulfate (HS) levels than CHO WT. Removal of cell surface HS resulted in reduced uptake of PEI-transfected DNA (PEI:DNA) and lower transfection titers suggesting that PEI:DNA relies on HS for binding and cellular entry. The absence of cell surface HS did not severely impact transfections performed with cationic liposomes. We undertook two approaches to improve transient production of afucosylated antibodies. First, we evaluated transfection of FUT8KO cells with cationic liposomes, which were observed to be less dependent on HS levels for uptake. Transfection of FUT8KO cells using the cationic liposome, DMRIE-C, produced similar titers to CHO WT in both shake flask and large-scale 10 L bioreactors. The second approach was to engineer a cell line overexpressing exostosin-1 (EXT1), an enzyme responsible for HS chain elongation, to increase HS content. EXT1-FUT8KO and CHO WT cells produced comparable levels of antibody from PEI transfections.
Optical spectra of Cu2+ ions in LiF crystals (1995)

Abstract Optical absorption and luminescence of Cu2+ ions in LF are measured in the UV and VUV spectral regions. Absorption peaks are identified at 133 and 145 nm, in good agreement with predictions of a model valid for LiCl:Cu2+ and LiBr:Cu2+. Three emission bands, excited with different efficiencies in the two absorptions, are revealed at 270, 320 and 360 nm.
EFFECTS OF FASTING AND FEEDING ON SERUM UREA AND SERUM CREATININE LEVELS IN POLAR BEARS (1990)

A bstract Polar bears were held in captivity and fasted for an average of 38 d prior to being fed for three days. Blood samples were collected prior to feeding and then at one and three days post‐feeding in 1984 and at one, four, and seven days post‐feeding in 1985. The ratio of serum urea to serum creatinine varied significantly in 1984, rising from a pre‐feeding mean of 11.0 (SE = 2.6) to 32.0 (SE = 3.2) on the first day post‐feeding and then dropped to 22.8 (SE =3.2) in the last sample. In 1985, the ratio of serum urea to serum creatinine increased from a pre‐feeding mean of 15.8 (SE = 2.3) to 61.2 (SE = 10.6) after three days of feeding and dropped to a mean of 29.2 (SE = 5.1) seven days after feeding ended. Serum urea levels varied over the study period in both years. No significant variation in serum creatinine levels was found in 1984, but in 1985, serum creatinine levels demonstrated significant variation, declining from the pre‐feeding mean of 1.83 mg/dl (SE = 0.29) to 0.96 mg/dl (SE = 0.12) in the last sample. The findings suggest that polar bears can have a low serum urea to serum creatinine ratio, similar to that found in hibernating black bears, or higher ratios after feeding. Polar bears can rapidly return to a fasting serum urea to creatinine ratio after food is withheld. Polar bears may demonstrate urea conservation, similar to that found in black bears, and may be able to move between a fasting and a feeding metabolism based on food availability throughout the year, an adaptation to life on the labile sea ice.
Efficient Target-Selected Mutagenesis in Zebrafish (2003)

One of the most powerful methods available to assign function to a gene is to inactivate or knockout the gene. Recently,we described the first target-selected knockout in zebrafish. Here,we report on the further improvements of this procedure,resulting in a highly efficient and easy method to do target-selected mutagenesis in zebrafish. A library of 4608 ENU-mutagenized F1 animals was generated and kept as a living stock. The DNA of these animals was screened for mutations in 16 genes by use of CEL-I-mediated heteroduplex cleavage (TILLING) and subsequent resequencing. In total,255 mutations were identified,of which 14 resulted in a premature stop codon,7 in a splice donor/acceptor site mutation,and 119 in an amino acid change. By this method,we potentially knocked out 13 different genes in a few months time. Furthermore,we show that TILLING can be used to detect the full spectrum of ENU-induced mutations in a vertebrate genome with the presence of many naturally occurring polymorphisms.
Two Photon Absorption and Coherent Control with Broadband Down-Converted Light (2004)

We experimentally demonstrate two-photon absorption with broadband down-converted light (squeezed vacuum). Although incoherent and exhibiting the statistics of a thermal noise, broadband down-converted light can induce two-photon absorption with the same sharp temporal behavior as femtosecond pulses, while exhibiting the high spectral resolution of the narrow band pump laser. Using pulse-shaping methods, we coherently control two-photon absorption in rubidium, demonstrating spectral and temporal resolutions that are 3-5 orders of magnitude below the actual bandwidth and temporal duration of the light itself. Such properties can be exploited in various applications such as spread-spectrum optical communications, tomography, and nonlinear microscopy.
Doose syndrome (myoclonic–astatic epilepsy): 40 years of progress (2010)

Doose syndrome, otherwise traditionally known as myoclonic-astatic epilepsy, was first described as a unique epilepsy syndrome by Dr Hermann Doose in 1970. In 1989, the International League Against Epilepsy classified it formally as a symptomatic generalized epilepsy, and 20 years later it was renamed 'epilepsy with myoclonic-atonic seizures'. In this review, we discuss the components of this unique disorder including its incidence, clinical features, and electroencephalographic findings. Recent evidence has suggested possible genetic links to the GEFS+ (generalized epilepsy with febrile seizures plus) family, and, additionally, some children with structural brain lesions can mimic the Doose syndrome phenotype. Treatment strategies such as corticosteroids, ethosuximide, and valproate have been described as only partially effective, but newer anticonvulsants, such as levetiracetam and zonisamide, may provide additional seizure control. The most effective treatment reported to date appears to be the ketogenic diet. Prognosis is quite varied in this disorder; however, many children can have a remarkably normal neurodevelopmental outcome.
Persistence of sleep-temperature coupling after suprachiasmatic nuclei lesions in rats (2005)

The suprachiasmatic nucleus (SCN) regulates the circadian rhythms of body temperature (T(b)) and vigilance states in mammals. We studied rats in which circadian rhythmicity was abolished after SCN lesions (SCNx rats) to investigate the association between the ultradian rhythms of sleep-wake states and brain temperature (T(br)), which are exposed after lesions. Ultradian rhythms of T(br) (mean period: 3.6 h) and sleep were closely associated in SCNx rats. Within each ultradian cycle, nonrapid eye movement (NREM) sleep was initiated 5 +/- 1 min after T(br) peaks, after which temperature continued a slow decline (0.02 +/- 0.006 degrees C/min) until it reached a minimum. Sleep and slow wave activity (SWA), an index of sleep intensity, were associated with declining temperature. Cross-correlation analysis revealed that the rhythm of T(br) preceded that of SWA by 2-10 min. We also investigated the thermoregulatory and sleep-wake responses of SCNx rats and controls to mild ambient cooling (18 degrees C) and warming (30 degrees C) over 24-h periods. SCNx rats and controls responded similarly to changes in ambient temperature. Cooling decreased REM sleep and increased wake. Warming increased T(br), blunted the amplitude of ultradian T(br) rhythms, and increased the number of transitions into NREM sleep. SCNx rats and controls had similar percentages of NREM sleep, REM sleep, and wake, as well as the same average T(b) within each 24-h period. Our results suggest that, in rats, the SCN modulates the timing but not the amount of sleep or the homeostatic control of sleep-wake states or T(b) during deviations in ambient temperature.
Glycemic penalty index for adequately assessing and comparing different blood glucose control algorithms (2008)

The GPI is an alternative method for evaluating the performance of BG control algorithms. The blood glucose sampling frequency and the duration of algorithm application should be similar when comparing algorithms.
Noninvasive measurement of androgen receptor signaling with a positron-emitting radiopharmaceutical that targets prostate-specific membrane antigen (2011)

Despite encouraging clinical results with next generation drugs (MDV3100 and abiraterone) that inhibit androgen receptor (AR) signaling in patients with castration-resistant prostate cancer (CRPC), responses are variable and short-lived. There is an urgent need to understand the basis of resistance to optimize their future use. We reasoned that a radiopharmaceutical that measures intratumoral changes in AR signaling could substantially improve our understanding of AR pathway directed therapies. Expanding on previous observations, we first show that prostate-specific membrane antigen (PSMA) is repressed by androgen treatment in multiple models of AR-positive prostate cancer in an AR-dependent manner. Conversely, antiandrogens up-regulate PSMA expression. These expression changes, including increased PSMA expression in response to treatment with the antiandrogen MDV3100, can be quantitatively measured in vivo in human prostate cancer xenograft models through PET imaging with a fully humanized, radiolabeled antibody to PSMA, (64)Cu-J591. Collectively, these results establish that relative changes in PSMA expression levels can be quantitatively measured using a human-ready imaging reagent and could serve as a biomarker of AR signaling to noninvasively evaluate AR activity in patients with CRPC.
Research progress of cladribine in chronic lymphocytic leukemia (2015)

Cladribine is a purine analogue, which is used in treatment of multiple sclerosis and hairy cell leukemia. Recently, more and more studies have shown that cladribine is a good anti-tumor choice for chronic lymphocytic leukemia (CLL). Clinical trials results show that either use alone or in combination with other drugs in patients with CLL, cladribine has shown good effect. This article focuses on the research progress of cladribine in CLL, in order to provide references for clinical medication in CLL treatment.


Key words: 
Cladribine; Leukemia, lymphocytic, chronic, B-cell; Purine analog
Low-complexity block-based motion estimation via one-bit transforms (1997)

We present an algorithm and a hardware architecture for block-based motion estimation that involves transforming video sequences from a multibit to a one-bit/pixel representation and then applying conventional motion estimation search strategies. This results in substantial reductions in arithmetic and hardware complexity and reduced power consumption, while maintaining good compression performance. Experimental results and a custom hardware design using a linear array of processing elements are also presented.