gebhart/patrepeval huggingface dataset:
How the <i>Bfi</i> I restriction enzyme uses one active site to cut two DNA strands (2003)

Unlike other restriction enzymes, BfiI functions without metal ions. It recognizes an asymmetric DNA sequence, 5'-ACTGGG-3', and cuts top and bottom strands at fixed positions downstream of this sequence. Many restriction enzymes are dimers of identical subunits, with one active site for each DNA strand. Others, like FokI, dimerize transiently during catalysis. BfiI is also a dimer but it has only one active site, at the dimer interface. We show here that BfiI remains a dimer as it makes double-strand breaks in DNA and that its single active site acts sequentially, first on the bottom and then the top strand. Hence, after cutting the bottom strand, a rearrangement of either the protein and/or the DNA in the BfiI-DNA complex must switch the active site to the top strand. Low pH values selectively block top-strand cleavage, converting BfiI into a nicking enzyme that cleaves only the bottom strand. The switch to the top strand may depend on the ionization of the cleaved 5' phosphate in the bottom strand. BfiI thus uses a mechanism for making double-strand breaks that is novel among restriction enzymes.
An adult patient with severe hypercalcaemia and hypocalciuria due to a novel homozygous inactivating mutation of calcium‐sensing receptor (1999)

Inactivating mutations in the calcium-sensing receptor (CaSR) cause familial hypocalciuric hypercalcaemia (FHH) and neonatal severe hyperparathyroidism (NSHPT). Earlier investigations showed patients with FHH are heterozygous, and NSHPT are homozygous for inactivating mutations. However, one adult patient with severe hypercalcaemia and hypocalciuria has been reported to have a homozygous inactivating mutation in CaSR (Pro39Ala). This suggested that mutant CaSR in this patient had some residual activity and hypercalcaemia was not so severe as to be fatal. However, the function of this mutant CaSR was not evaluated. In the present study, we describe a novel homozygous mutation in an adult patient with severe hypercalcaemia and hypocalciuria, and evaluate the function of the mutant CaSRs. The DNA sequence of CaSR gene was determined by direct sequencing of the polymerase chain reaction product. The function of mutant CaSR was analysed by creating mutant cDNAs by in vitro mutagenesis, transfection of mutant cDNAs into HEK293 cells and measuring intracellular ionized Ca in response to changes in extracellular Ca. A 26-year-old Japanese woman showed marked hypercalcaemia with an elevated parathyroid hormone (PTH) level. Her consanguineous parents had asymptomatic hypercalcaemia with relative hypocalciuria. The proband had a homozygous mutation at codon 27 of CaSR gene (CAA-->CGA, Gln27Arg). Her parents were heterozygous for this mutation. EC50 for Ca of this mutant CaSR (GIn27Arg) was 4.9 mM. EC50 of another mutant CaSR (Pro39Ala) whose homozygous mutation was discovered in an adult patient was 4.4 mM. These EC50s were significantly higher than that of wild-type CaSR (3.7} 0.1 mM), but were the lowest among the reported EC50s for inactivating mutations of CaSR. These results indicate that serum Ca and PTH levels are determined by residual function of mutant CaSR in patients with homozygous mutation in CaSR, and that patients having homozygous mutant CaSRs with mild dysfunction do not suffer from fatal hypercalcaemia in infancy and can survive into adulthood.
Acetyldinaline: a new oral cytostatic drug with impressive differential activity against leukemic cells and normal stem cells--preclinical studies in a relevant rat model for human acute myelocytic leukemia. (1993)

Acetyldinaline [CI-994; GOE 5549; PD 123 654; 4-acetylamino-N-(2'-aminophenyl)-benzamide] is the acetylated derivative form of the original compound Dinaline (GOE 1734; PD 104 208). The efficacy and toxicity of Acetyldinaline for remission-induction treatment of leukemia were evaluated and compared with those observed in previous studies of Dinaline in the Brown Norway acute myelocytic leukemia, as a preclinical model for human acute myelocytic leukemia. There were three treatment groups. Leukemic animals received either 1 or 2 courses of 5 daily p.o. administrations of Acetyldinaline with a "full dose" of 23.7 mg/kg once daily (first group), a twice daily "half dose" of 11.85 mg/kg with an interval of 8 h (second group), or a "half dose" of 11.85 mg/kg once daily (third group). The drug-free interval between the 2 courses was 2 or 9 days. With repeated daily p.o. administrations of 23.7 mg/kg either in a single daily dose or a split daily dose of 2 x 11.85 mg/kg for 1 course, at least an 8-log leukemic cell kill was achieved. In contrast, with these treatment schedules, less than a 1-log cell kill of normal pluripotent hemopoietic stem cells (CFU-S) in the femoral bone marrow was found. Split daily dose treatment was more effective resulting in 37.5% cures, while no cures were observed with the single daily treatment for one course. Treatment with single daily dose of 23.7 mg/kg or a split daily dose of 2 x 11.85 mg/kg for 2 courses, with either a 2- or 9-day interval in between, resulted in lethal toxicity in most of rats. This result was comparable with that previously observed after equimolar doses of Dinaline (20 mg/kg). The half-dose once daily treatment with Acetyldinaline (11.85 mg/kg) for 1 or 2 cycles resulted in about a 4.5 or > 8-log leukemic cell kill, respectively. Toxic side effects, i.e., damage to the gastro-intestinal tract and hemorrhages in the lungs, were more pronounced with full dose either in the single or the split daily dose regimen. No significant toxicity was observed at the half-dose treatment once daily. In conclusion, the impressive differential activity against leukemic cells and normal stem cells observed in this relevant rat model for human acute myelocytic leukemia warrants the introduction of this compound in clinical phase I/II studies.
<title>Very low rate compression of speckled SAR imagery</title> (1998)

Synthetic aperture radars produce coherent, and speckled, high resolution images of the ground. Because modern systems can generate large amounts of imagery, there is substantial interest in applying image compression techniques to these products. In this paper, the authors examine the properties of speckled imagery relevant to the task of data compression. In particular, they demonstrate the advisability of compressing the speckle mean function rather than the literal image. The theory, methodology, and an example are presented.
The Overexpression of the<i>Insl3</i>in Female Mice Causes Descent of the Ovaries (2002)

Testicular descent in mice is dependent upon proper outgrowth of the gubernaculum primordia under the influence of the insulin-like 3 gene product (Insl3). Deletion of this gene prevents gubernaculum growth and causes bilateral cryptorchidism. In vitro experiments have led to the suggestion that Insl3 and androgens together induce outgrowth of the gubernacular primordia. The experiments reported here were designed specifically to determine whether in vivo the Insl3-mediated gubernaculum development is independent of androgens. To that effect transgenic male and female mice were generated that overexpressed Insl3 in the pancreas during fetal and postnatal life. Expression of the transgenic allele in the Insl3-deficient mice rescued the cryptorchidism in male mutant, indicating that the islet beta-cells efficiently processed the Insl3 gene product to the functional hormone. All transgenic females displayed bilateral inguinal hernia. The processus vaginalis developed containing intestinal loops. The Müllerian derivatives gave rise to oviduct, uterus, and upper vagina, and Wolffian duct derivatives were missing, indicating the absence of the androgen- and anti-Müllerian hormone-mediated activities in transgenic females. The ovaries descended into a position over the bladder and attached to the abdominal wall via the well developed cranial suspensory ligament and the gubernaculum. Administration of dihydrotestosterone during prenatal development suppressed formation of the cranial suspensory ligament and thereby allowed the descent of the ovaries into the processus vaginalis. These results suggest that Insl3-mediated activity induces gubernaculum development and precludes a role of androgen in this process. Furthermore, the transgenic females exhibit reduced fertility, which is due to fetal mortality during midgestation.
Bench- and pilot-scale evaluation of mercury speciation measurement methods (1996)

The 1990 Clean Air Act Amendments require the US Environmental Protection Agency (EPA) to assess the health risks associated with mercury. Since the rate of mercury deposition and the type of control strategies used may depend on the type of mercury species emitted, a proven sampling method that can reliably and accurately speciate mercury at the very low concentrations found in coal combustion flue gas is necessary. A number of mercury speciation methods have been proposed, including wet-chemistry methods, such as EPA Method 29, the Ontario Hydro method, and the tris-buffer method, as well as dry methods such as the Mercury Speciation Absorption method (MESA). In addition, a number of companies are developing continuous emissions monitors to speciate mercury by difference. Bench- and pilot-scale tests, sponsored by the Electric Power Research Institute (EPRI) and the US Department of Energy (DOE), are currently under way at the Energy and Environmental Research Center (EERC) to determine the most accurate and precise mercury speciation method available. The overall objective of the test program is to determine whether EPA Method 29 or other sampling methods can reliably quantify and speciate mercury in flue gas from coal-fired boilers at both the inlet and outlet of a particulate control device such as a pulse-jet baghouse. A specific goal of the project is to determine the precision and bias of the various mercury speciation methods as a function of process variables.
Olfactory Dysfunction Predicts 5-Year Mortality in Older Adults (2014)

Prediction of mortality has focused on disease and frailty, although antecedent biomarkers may herald broad physiological decline. Olfaction, an ancestral chemical system, is a strong candidate biomarker because it is linked to diverse physiological processes. We sought to determine if olfactory dysfunction is a harbinger of 5-year mortality in the National Social Life, Health and Aging Project [NSHAP], a nationally representative sample of older U.S. adults. 3,005 community-dwelling adults aged 57-85 were studied in 2005-6 (Wave 1) and their mortality determined in 2010-11 (Wave 2). Olfactory dysfunction, determined objectively at Wave 1, was used to estimate the odds of 5-year, all cause mortality via logistic regression, controlling for demographics and health factors. Mortality for anosmic older adults was four times that of normosmic individuals while hyposmic individuals had intermediate mortality (p,0.001), a ''dose-dependent'' effect present across the age range. In a comprehensive model that included potential confounding factors, anosmic older adults had over three times the odds of death compared to normosmic individuals (OR, 3.37 [95%CI 2.04, 5.57]), higher than and independent of known leading causes of death, and did not result from the following mechanisms: nutrition, cognitive function, mental health, smoking and alcohol abuse or frailty. Olfactory function is thus one of the strongest predictors of 5-year mortality and may serve as a bellwether for slowed cellular regeneration or as a marker of cumulative toxic environmental exposures. This finding provides clues for pinpointing an underlying mechanism related to a fundamental component of the aging process.
Optical Propulsion of Individual and Clustered Microspheres along Sub-Micron Optical Wires (2008)

The evanescent field of sub-micron optical wires has been found to extend for longer distances when compared with planar waveguides. The large evanescent field associated with sub-micron optical wires has been exploited to propel 10 mm polystyrene spheres and sphere clusters at the velocity of 12 and 8 mm/s, respectively in water with about 0.4W of laser light at 1047 nm.
Low Vision and Brain Plasticity (2011)

Evidence for the functional reorganization of visual brain areas in blind people provides compelling examples of brain plasticity associated with visual impairment. But what sorts of plasticity are present in cases of low vision? “Low vision” refers to any long-term visual deficit, not correctable by lenses, affecting everyday visual function while preserving some level of useful vision. In cases of low vision, visual cortex still participates in visual processing, but with abnormal input, characterized clinically as reduced acuity, reduced contrast sensitivity, and/or visual-field loss. What sorts of plastic changes in the visual pathway accompany these three types of vision loss? What are the behavioral consequences of these changes? What is the impact of the age of onset of low vision on plasticity? I will discuss these unresolved questions, using examples of psychophysical and fMRI studies from my research. An important example is macular degeneration. This common eye disease often results in central-field loss, requiring the use of peripheral vision for reading and other tasks usually mediated by central vision. I will also address the relevance of research on low-vision plasticity for rehabilitation.
Design of chimeric expression elements that confer high‐level gene activity in chromoplasts (2012)

Non-green plastids, such as chromoplasts, generally have much lower activity of gene expression than chloroplasts in photosynthetically active tissues. Suppression of plastid genes in non-green tissues occurs through a complex interplay of transcriptional and translational control, with the contribution of regulation of transcript abundance versus translational activity being highly variable between genes. Here, we have investigated whether the low expression of the plastid genome in chromoplasts results from inherent limitations in gene expression capacity, or can be overcome by designing appropriate combinations of promoters and translation initiation signals in the 5' untranslated region (5'-UTR). We constructed chimeric expression elements that combine promoters and 5'-UTRs from plastid genes, which are suppressed during chloroplast-to-chromoplast conversion in Solanum lycopersicum (tomato) fruit ripening, either just at the translational level or just at the level of mRNA accumulation. These chimeric expression elements were introduced into the tomato plastid genome by stable chloroplast transformation. We report the identification of promoter-UTR combinations that confer high-level gene expression in chromoplasts of ripe tomato fruits, resulting in the accumulation of reporter protein GFP to up to 1% of total cellular protein. Our work demonstrates that non-green plastids are capable of expressing genes to high levels. Moreover, the chimeric cis-elements for chromoplasts developed here are widely applicable in basic and applied research using transplastomic methods.
Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer’s disease-relevant murine model (2015)

This is the first study to directly examine amelioration of NAD(+) catabolism and changes in mitochondrial morphological dynamics in brain utilizing the immediate precursor NMN as a potential therapeutic compound. This might lead to well-defined physiologic abnormalities that can serve an important role in the validation of promising agents such as NMN that target NAD(+) catabolism preserving mitochondrial function.
T Cell Chemokine Receptor Expression in Aging (2003)

Changes in chemokine receptor expression are important in determining T cell migration and the subsequent immune response. To better understand the contribution of the chemokine system in immune senescence we determined the effect of aging on CD4(+) T cell chemokine receptor function using microarray, RNase protection assays, Western blot, and in vitro chemokine transmigration assays. Freshly isolated CD4(+) cells from aged (20-22 mo) mice were found to express a higher level of CCR1, 2, 4, 5, 6, and 8 and CXCR2-5, and a lower level of CCR7 and 9 than those from young (3-4 mo) animals. Caloric restriction partially or completely restored the aging effects on CCR1, 7, and 8 and CXCR2, 4, and 5. The aging-associated differences in chemokine receptor expression cannot be adequately explained by the age-associated shift in the naive/memory or Th1/Th2 profile. CD4(+) cells from aged animals have increased chemotactic response to stromal cell-derived factor-1 and macrophage-inflammatory protein-1alpha, suggesting that the observed chemokine receptor changes have important functional consequences. We propose that the aging-associated changes in T cell chemokine receptor expression may contribute to the different clinical outcome in T cell chemokine receptor-dependent diseases in the elderly.
Ferredoxins from the Photosynthetic Purple Non-Sulfur Bacterium Rhodopseudomonas palustris. Isolation and Amino Acid Sequence of Ferredoxin I1 (1984)

Two ferredoxins, ferredoxins I and II, were prepared from Rhodopseudomonas palustris . They were separated on a Sephadex column after carboxymethylation and ferredoxin I, the major component, was subjected to an amino acid sequence study. The protein was composed of 63 amino acid residues and the sequence was as follows: Ala-Tyr-Lys-Ile-Ile-Thr-Ser-Gln-Cys-Thr-Val-Cys-Gly-Ala-Cys-Glu-Phe-Glu-Cys-Pro-Asn-Ala-Ala-Ile-Ala-Met-Lys-Arg-Gly-Thr-Tyr-Val-Ile-Asp-Ala-Val-Lys-Cys-Thr-Glu-Cys-Glu-Gly-His-Phe-Asp-Lys-Pro-Gln-Cys-Val-Ala-Cys-Pro-Val-Asp-Asn-Thr-Cys-Val-Pro-Ala. The molecular weight was calculated to be 6,718, excluding iron and sulfur atoms. The distribution of the nine cysteine residues was similar to but clearly distinct from those of ferredoxins of other photosynthetic bacteria. Comparison of this ferredoxin with those of other bacteria suggests that the photosynthetic bacteria evolved on separate lines. Ferredoxin II was also subjected to analyses of amino acid composition and terminal sequences, but no further study was possible due to the limited material. Although the composition was different from that of ferredoxin I, the terminal sequences were exactly the same as those of ferredoxin I.
Broad-Band Coaxial Choked Coupling Design (1960)

Equations and curves are presented to predict the frequency bandwidth of coaxial choke couplings in terms of the choke parameters. Choke couplings discussed are those applicable to rotary joints and dc isolation units.
Clustering of null mutations in the <i>Eco</i>RI endonuclease (1987)

EcoRI endonuclease mutants were isolated in a methylase-deficient background following in vitro hydroxylamine mutagenesis of plasmid pKG2 (Kuhn et al.: Gene 44:253-263, 1986). Mutants which survived high-level endonuclease expression (IPTG induction) were termed null mutants. Sixty-two of 121 null mutants tested by Western blot contained normal levels of endonuclease cross-reacting protein. The complete endonuclease gene was sequenced for 27 null mutants. This group was found to consist of 20 single base-change missense mutations, 6 double mutations, and 1 triple mutation. Ten of the 20 single mutations were clustered between residues 139 and 144. When examined with respect to the structure of the EcoRI-DNA complex (McClarin et al.: Science 234:1526-1541, 1986), these alterations were found to fall predominantly into two classes: substitutions at the protein-DNA interface or substitutions at the protein-protein (dimer) interface. Protein from several of the mutants was purified and sized by using HPLC. Wild-type EcoRI endonuclease and protein from three of the DNA interface mutations (Ala139----Thr, Gly140----Ser, Arg203----Gln) appeared to be dimeric, while protein from subunit interface mutations (Glu144----Lys, Glu152----Lys, Gly210----Arg) migrated as monomers.
Blind bandwidth extension of audio signals based on harmonic mapping in phase space (2013)

Audio bandwidth extension can artificially restore the truncated high frequencies at the decoder from the transmitted low-frequency signal. This paper presents a new method for blind bandwidth extension of wideband audio based on harmonic mapping in phase space. First, the spectral series of audio signal is represented by using phase space reconstruction. Then, the harmonics of high frequencies are mapped out from the evolutionary trajectories of low-frequency components in phase space by using nonlinear prediction. Combining with spectral envelope estimation of high frequencies based on Gaussian mixture model, the bandwidth of wideband audio signals can be effectively extended to super wideband, without any side information. Subjective and objective testing results indicate that the proposed method improves the harmonic characteristics of the extended super-wideband audio and achieves a better quality than conventional blind bandwidth extension methods.
Estimation of frequency offset in TDMA-based satellite systems (2006)

It is required for correct signal detection to accurately maintain the synchronization of frequency and timing in a TDMA system. In this paper, we consider nondecision-aided estimation of frequency offset for the\ntransmission of QPSK signal in a TDMA-based satellite system. The proposed scheme estimates the phases of two parts in the burst and then estimates the frequency offset based on the difference between the two estimated phases. Thus, it can provides performance comparable to that of conventional schemes, while significantly\nreducing the implementation complexity. The performance of the proposed scheme is analyzed and verified by computer simulation, when applied to a GSM based geostationary earth orbit mobile radio(GMR) system. ; TDMA 시스템에서 신호를 수신하기 위해서는 정확한 주파수 및 시간 동기가 필요하다. 본 논문에서는 QPSK 신호를 전송하는 TDMA 방식의 위성통신 시스템에서 훈련 신호 없이 주파수 편이를 추정하는 방법을 제안한다. 제안된 방법은 수신 신호의 두 부분에서 정확도가 높게 위상을 추정하고, 이 위상 차이로부터 주파수 편이를 추정함으로써 기존의 주파수 편이 추정 방법과 비슷한 성능을 보이면서 적은 연산량이 요구된다. 제안된 방법을 GSM을 기반으로 확장된 GMR 위성통신 시스템에 적용하고 시뮬레이션을 통해 성능을 검증한다.
Tissue site-specific enhancer function of the upstream regulatory region of human papillomavirus type 11 in cultured keratinocytes (1989)

The human papillomavirus type 11 regulatory region was cloned upstream of a reporter complex and microinjected into nuclei of individual primary human keratinocytes. Genital and laryngeal keratinocytes, normal host cells for this virus, exhibited higher levels of expression than cutaneous keratinocytes. We conclude that a papillomavirus enhancer(s) shows preferences among epithelial cells from different tissue sites.
Soft Two-Degree-of-Freedom Dielectric Elastomer Position Sensor Exhibiting Linear Behavior (2014)

Soft robots could bring robotic systems to new horizons, by enabling safe human-machine interaction. For precise control, these soft structures require high-level position feedback that is not easily achieved through conventional one-degree-of-freedom (DOF) sensing apparatus. In this paper, a soft two-DOF dielectric elastomer (DE) sensor is specifically designed to provide accurate position feedback for a soft polymer robotic manipulator. The technology is exemplified on a soft robot intended for MRI-guided prostate interventions. DEs are chosen for their major advantages of softness, high strains, low cost, and embedded multiple-DOF sensing capability, providing excellent system integration. A geometrical model of the proposed DE sensor is developed and compared to experimental results in order to understand sensor mechanics. Using a differential measurement approach, a handmade prototype provided linear sensory behavior and 0.2 mm accuracy on two-DOF. This correlates to a 0.7% error over the sensor's 30 mm × 30 mm planar range, demonstrating the outstanding potential of DE technology for accurate multiDOF position sensing.