gebhart/patrepeval huggingface dataset:
Targeting DNA Double-Strand Breaks with TAL Effector Nucleases (2010)

Engineered nucleases that cleave specific DNA sequences in vivo are valuable reagents for targeted mutagenesis. Here we report a new class of sequence-specific nucleases created by fusing transcription activator-like effectors (TALEs) to the catalytic domain of the FokI endonuclease. Both native and custom TALE-nuclease fusions direct DNA double-strand breaks to specific, targeted sites.
<title>Video frame rate conversion for mobile devices</title> (2005)

These years the growing demand for innovative mobile devices has been a major driving force behind mobile multi-media applications. Essential for further growth is a wide range of multi-media content available through the networks either sent by mobile devices or network servers. Limitations on network bandwidth and storage capacity have a large impact on the quality of video. One important quality issue concerns the low video frame rate, typically between 5 and 15 frames per second. Such low frame rates lead to undesired artefacts like motion judder or blur. A typical refresh rate of a mobile display is 60Hz. Currently a frame memory is used as a buffer between the software application and the display to deal with the frequency mismatch, which can be considered as frame repetition. In this paper, frame rate conversion is considered to improve motion portrayal on mobile devices. Two motion estimators are discussed along with simplifications to comply with limited platform resources, and with refinements for acceptable quality. Two frame interpolators and their relationships with the motion estimators are treated. The proposed frame rate converter enhances the quality of portrayed motion significantly, while required platform resources are kept minimal by exploiting typical properties of mobile displays.
Modeling Alzheimer’s Disease in Mouse without Mutant Protein Overexpression: Cooperative and Independent Effects of Aβ and Tau (2013)

The APP/PS1/htau model represents a valuable and disease-relevant late-onset pre-clinical AD animal model because it incorporates human AD genetics without mutant protein overexpression. Analysis of the mice revealed both cooperative and independent effects of Aβ and p-tau.
Pilot study of the immunologic effects of recombinant human growth hormone and recombinant insulin-like growth factor in HIV-infected patients (1998)

These results suggest that treatment with rhGH/rhIGF-1 was reasonably well tolerated and that modest improvement in HIV-specific immune function was attained. Further studies will help clarify the therapeutic potential of rhGH/rhIGF-1 as an immunostimulator in the setting of HIV infection.
Preoperative Oral Rofecoxib Reduces Postoperative Pain and Tramadol Consumption in Patients After Abdominal Hysterectomy (2004)

This study was designed to determine whether the administration of a preoperative dose of rofecoxib to patients undergoing abdominal hysterectomy would decrease patient-controlled analgesia tramadol use or enhance analgesia. We conclude that the preoperative administration of oral rofecoxib provided a significant analgesic benefit and decreased the opioid requirements in patients undergoing abdominal hysterectomy.
IN VITRO STUDIES OF THE SUPPRESSION OF DELAYED HYPERSENSITIVITY BY THE INDUCTION OF PARTIAL TOLERANCE (1970)

Suppression of delayed hypersensitivity in vivo is correlated in vitro with the absence of macrophage migration inhibition in the presence of the antigen used to induce partial tolerance. The suppression of delayed hypersensitivity is antigen-specific in vivo as well as in vitro. The lymphocytes, and not the macrophages, are the cells involved in the induction of tolerance in terms of delayed hypersensitivity which is characterized by an absence of migratory factor activity.
Synthesis of oxaloacetate in Bacillus subtilis mutants lacking the 2-ketoglutarate dehydrogenase enzymatic complex (1984)

Bacillus subtilis mutants deficient in the 2-ketoglutarate dehydrogenase enzymatic complex required aspartate for growth at wild-type rates on carbon sources for which synthesis of the degradative enzymes is sensitive to catabolite repression (e.g., poor carbon sources), but did not require aspartate for growth on carbon sources which exert catabolite repression (e.g., good carbon sources). Measurement of metabolite pools in a mutant lacking the 2-ketoglutarate dehydrogenase active complex showed that the aspartate requirement for growth on poor carbon sources resulted from a deficiency in intracellular oxaloacetate pools even through pyruvate carboxylase was present at levels corresponding to those in wild-type cells. The oxaloacetate deficiency most likely resulted from the inability of the mutant to regenerate oxaloacetate from citrate due to the enzymatic block in the tricarboxylic acid cycle. Mutants in the enzymes of the dicarboxylic acid half of the citric acid cycle similarly required aspartate for wild-type growth in minimal medium. These results suggested that the complete turning of the tricarboxylic acid cycle is involved in the maintainance of oxaloacetate levels in B. subtilis. The ability of the mutants lacking the 2-ketoglutarate dehydrogenase enzymatic complex to grow at wild-type rates on media containing good carbon sources in the absence of exogenous aspartate is not understood.
Phosphorylation of eIF-4E on Serine 209 by Protein Kinase C Is Inhibited by the Translational Repressors, 4E-binding Proteins (1996)

Translation initiation in eukaryotes is facilitated by the mRNA 5' cap structure (m7GpppX, where X is any nucleotide) that binds the multisubunit initiation factor eIF4F through one of its subunits, eIF4E. eIF4E is a phosphoprotein whose phosphorylation state positively correlates with cell growth. Protein kinase C phosphorylates eIF4E in vitro, and possibly in vivo. Using recombinant eIF4E incubated in vitro with purified protein kinase C and analyzed by solid-phase phosphopeptide sequencing in combination with high performance liquid chromatography coupled to mass spectrometry, we demonstrated that the third amino acid of the peptide SGSTTK (Ser209) is the major site of phosphorylation. This finding is consistent with the newly assigned in vivo phosphorylation site of eIF4E (Joshi, B., Cai, A. L., Keiper, B. D., Minich, W. B., Mendez, R., Beach, C. M., Stepinski, J., Stolarski, R., Darzynkiewicz, E., and Rhoads, R. E. (1995) J. Biol. Chem. 270, 14597-14603). A S209A mutation resulted in dramatically reduced phosphorylation, both in vitro and in vivo. Furthermore, the mutant protein was phosphorylated on threonine (most probably threonine 210) in vivo. Here we show that in the presence of the recently characterized translational repressors 4E-BP1 or 4E-BP2, phosphorylation of eIF4E by protein kinase C is strongly reduced. This suggests a two-step model for the phosphorylation (and activation) of eIF4E by growth factors and hormones: first, dissociation of eIF4E from 4E-BPs, followed by eIF4E phosphorylation.
DNA Sensing Using Nanocrystalline Surface‐Enhanced Al2O3 Nanopore Sensors (2010)

A new solid-state, Al(2)O(3) nanopore sensor with enhanced surface properties for the real-time detection and analysis of individual DNA molecules is reported. Nanopore formation using electron beam based decomposition transformed the local nanostructure and morphology of the pore from an amorphous, stoichiometric structure (O to Al ratio of 1.5) to a hetero-phase crystalline network, deficient in O (O to Al ratio of ~0.6). Direct metallization of the pore region was observed during irradiation, thereby permitting the potential fabrication of nano-scale metallic contacts in the pore region with potential application to nanopore-based DNA sequencing. Dose dependent phase transformations to purely γ and/or α-phase nanocrystallites were also observed during pore formation allowing for surface charge engineering at the nanopore/fluid interface. DNA transport studies revealed an order of magnitude reduction in translocation velocities relative to alternate solid-state architectures, accredited to high surface charge density and the nucleation of charged nanocrystalline domains. The unique surface properties of Al(2)O(3) nanopore sensors makes them ideal for the detection and analysis of ssDNA, dsDNA, RNA secondary structures and small proteins. These nano-scale sensors may also serve as a useful tool in studying the mechanisms driving biological processes including DNA-protein interactions and enzyme activity at the single molecule level.
Fine tuning the immune response through B7‐H3 and B7‐H4 (2009)

B7-H3 and B7-H4 belong to a new class of immune regulatory molecules, which primarily execute their functions in peripheral tissues to fine tune immune responses in target organs. In normal circumstances, while the mRNA for both molecules is broadly distributed, tight control at the post-transcriptional level is imposed. Under a pathogenic environment, such as inflammation and cancer, the control is often aberrant. Upon engaging their receptors, these molecules regulate the immune response in positive or negative ways depending on the expression and type of cells bearing the receptors. Thus, manipulation of the expression of these molecules and/or their receptors may represent a realistic opportunity to fine tune immune responses and to design new immunotherapeutic approaches.
Prognostic significance of DAPK and RASSF1A promoter hypermethylation in non-small cell lung cancer (NSCLC). (2009)

The epigenetic inactivation of tumor suppressor genes may play an important role in the development and progression of many cancer types, including lung cancer. Therefore, we investigated the association between the aberrant promoter methylation of 2 genes: the Death-Associated Protein Kinase (DAPK) and the Ras Association Domain Family 1A (RASSF1A) by using methylation-specific PCR, and the clinicopathological features and prognosis in 70 radically resected non-small cell lung cancers (NSCLCs). Hypermethylation of the DAPK and RASSF1A promoters was found in 24 (34%), and in 18 (26%) tumor DNA samples, respectively. Regarding different clinicopathological features of NSCLCs, the DAPK promoter methylation was more frequently observed in squamous cell carcinoma (46%) than in adenocarcinoma (25%) and large cell carcinoma (22%), but there were no significant statistical differences (p=0.3). On the other hand, a statistically significant trend was observed between the RASSF1A methylation and a histological type of tumor (p=0.06). 45% of adenocarcinoma tumors showed RASSF1A promoter methylation in comparison to 17% of squamous cell carcinomas and 22% of large cell carcinomas. When both markers were analyzed according to the tumor-node-metastasis (TNM) staging system, no statistically significant differences were observed between stage I, II and IIIa, and the DAPK (p=0.2) and RASSF1A methylation (p=0.1). In comparison, when stage I and II were grouped together and considered vs. stage IIIa, a significant association between RASSF1A methylation and the TNM was found (p=0.03). The group of patients with tumors showing DAPK promoter methylation had significantly poorer overall survival rates (p=0.02) than the patients with tumors that did not show DAPK promoter methylation. However, the association between the RASSF1A promoter methylation status and the overall survival rates was not statistically significant (p=0.48). In conclusion, this paper supports the importance of epigenetic gene regulation in lung cancer progression and prognosis.
Mating-Type Genes andMATSwitching inSaccharomyces cerevisiae (2012)

Mating type in Saccharomyces cerevisiae is determined by two nonhomologous alleles, MATa and MATα. These sequences encode regulators of the two different haploid mating types and of the diploids formed by their conjugation. Analysis of the MATa1, MATα1, and MATα2 alleles provided one of the earliest models of cell-type specification by transcriptional activators and repressors. Remarkably, homothallic yeast cells can switch their mating type as often as every generation by a highly choreographed, site-specific homologous recombination event that replaces one MAT allele with different DNA sequences encoding the opposite MAT allele. This replacement process involves the participation of two intact but unexpressed copies of mating-type information at the heterochromatic loci, HMLα and HMRa, which are located at opposite ends of the same chromosome-encoding MAT. The study of MAT switching has yielded important insights into the control of cell lineage, the silencing of gene expression, the formation of heterochromatin, and the regulation of accessibility of the donor sequences. Real-time analysis of MAT switching has provided the most detailed description of the molecular events that occur during the homologous recombinational repair of a programmed double-strand chromosome break.
Antiplatelet agents for chronic kidney disease (2013)

Antiplatelet agents reduce myocardial infarction but increase major bleeding. Risks may outweigh harms among people with low annual risks of cardiovascular events, including those with early stages of CKD who do not have clinically-evident occlusive cardiovascular disease.
Invasive Pneumococcal Disease in Older Adults Residing in Long‐Term Care Facilities and in the Community (2003)

Older adults living in LTCFs are at a higher risk for invasive pneumococcal disease and death than are community-living older adults. Additionally, fluoroquinolone resistance is significantly higher in older adults living in LTCFs and may provide clues to emerging antimicrobial resistance in the general population.
NMR studies of Na atoms in silicon clathrate compounds (1996)

We observed the NMR spectrum of $^{23}\mathrm{Na}$ in the semimetallic clathrate (Na,Ba${)}_{\mathit{x}}$${\mathrm{Si}}_{46}$, which becomes superconducting at low temperatures (4 K). We also obtained spectra for isolated sodium atoms encapsulated in cages in the insulating clathrate ${\mathrm{Na}}_{\mathit{x}}$@${\mathrm{Si}}_{136}$. The observed NMR shifts in this phase are almost two times larger than the ordinary Knight shift in metallic sodium. We attribute this large paramagnetic shift to the fact that sodium atoms inside silicon clathrate cages are not ionized. Due to the interaction of unpaired sodium 3s electrons with silicon nuclei, we also observed very large shifts in the NMR spectrum of $^{29}\mathrm{Si}$. \textcopyright{} 1996 The American Physical Society.
Decreased percentages of regulatory T cells in peripheral blood of patients with Behcet’s disease before ocular attack: a possible predictive marker of ocular attack (2008)

The current study investigates the role of regulatory T (Treg) cells in the pathogenesis of ocular attack in patients with Behcet's disease (BD). Nineteen BD patients with ocular complications (BDo), including 11 BD patients with ocular attack (BDa) and eight BD patients with inactive ocular complications (BDi), were studied. Four BD patients without ocular complications (BDwo) were also evaluated as controls. All patients were prospectively followed by our outpatient clinic between autumn 2004 and spring 2005. CD4+ CD25+bright T cells (Treg cells) from peripheral blood were measured by flow cytometry. The percentages of Treg cells in CD4+ T cells from BDo were significantly decreased before ocular attack compared with those after ocular attack. Moreover, surprisingly, these levels before attack were significantly lower than normal level, whereas the percentages of Treg cells in both BDi and BDwo patients were normal. Treg cells were significantly decreased in BDa before active ocular attack. These findings suggest that Treg cells play an important role in ocular attack in BD patients. In addition, decreased percentages of Treg cells may be a predictive marker of ocular attack in BD patients allowing treatment of BD patients before an ocular attack.
Development of Th1 and Th2 Populations and the Nature of Immune Responses to Hepatitis B Virus DNA Vaccines Can Be Modulated by Codelivery of Various Cytokine Genes (1998)

In this study, we provide direct evidence that the magnitude and nature of the immune response to a DNA vaccine can be differentially regulated by codelivery of various mouse cytokine genes. Mice immunized with a hepatitis B virus (HBV) DNA vaccine and the IL-12 or IFN-gamma gene exhibited a significant enhancement of Th1 cells and increased production of anti-HBV surface IgG2a Ab, as well as a marked inhibition of Th2 cells and decreased production of IgG1 Ab. In contrast, coinjection of the IL-4 gene significantly enhanced the development of specific Th2 cells and increased production of IgG1 Ab, whereas Th1 differentiation and IgG2a production were suppressed. Coinjection of the IL-2 or the granulocyte-macrophage-CSF gene enhanced the development of Th1 cells, while the development of Th2 cells was not affected, and the production of IgG1 and IgG2a Ab were both increased. The CTL activity induced by HBV DNA vaccination was most significantly enhanced by codelivery of the IL-12 or IFN-gamma gene, followed by the IL-2 or granulocyte-macrophage-CSF gene, whereas codelivery of the IL-4 gene suppressed the activity. When challenged with HBV surface Ag (HBsAg)-expressing syngeneic tumors, significant reduction of tumor growth was observed in mice that were coadministered the IL-12 gene but not the IL-4 gene. Taken together, these results demonstrate that application of a cytokine gene in a DNA vaccine formulation can influence the differentiation of Th cells as well as the nature of an immune response and may thus provide a strategy to improve its prophylactic and therapeutic efficacy.
A method for combining radio link simulations and system simulations for a slow frequency hopped cellular system (2002)

To assess the performance of an advanced mobile radio access system, it is important to make use of suitable simulation tools in order to evaluate the impact on the system of the different control and adaptation mechanisms. In order to have accurate results from such system simulations, the radio link performance has to be modelled. Separate radio link simulations are used to give the performance results. A two step look-up table approach is presented for the combining of the radio link simulations with the system simulations. The look-up tables allow an accurate modelling of the transport chain in the system simulations.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Calibration of diffuse correlation spectroscopy blood flow index with venous-occlusion diffuse optical spectroscopy in skeletal muscle (2015)

We investigate and assess the utility of a simple scheme for continuous absolute blood flow monitoring based on diffuse correlation spectroscopy (DCS). The scheme calibrates DCS using venous-occlusion diffuse optical spectroscopy (VO-DOS) measurements of arm muscle tissue at a single time-point. A calibration coefficient (γ) for the arm is determined, permitting conversion of DCS blood flow indices to absolute blood flow units, and a study of healthy adults (N=10) is carried out to ascertain the variability of γ. The average DCS calibration coefficient for the right (i.e., dominant) arm was γ=(1.24±0.15)×10(8) (mL·100 mL(−1)·min(−1))/(cm(2)/s). However, variability can be significant and is apparent in our site-to-site and day-to-day repeated measurements. The peak hyperemic blood flow overshoot relative to baseline resting flow was also studied following arm-cuff ischemia; excellent agreement between VO-DOS and DCS was found (R(2)=0.95, slope=0.94±0.07, mean difference=−0.10±0.45). Finally, we show that incorporation of subject-specific absolute optical properties significantly improves blood flow calibration accuracy.
A TDC-Free Mostly-Digital FDC-PLL Frequency Synthesizer With a 2.8-3.5 GHz DCO (2014)

This paper presents the first published fully-integrated digital fractional- N PLL based on a second-order frequency-to-digital converter (FDC) instead of a time-to-digital converter (TDC). The PLL's quantization noise is nearly identical to that of a conventional analog delta-sigma modulator based PLL (ΔΣ-PLL). Hence, the quantization noise is highpass shaped and is suppressed by the PLL's loop filter to the point where it is not a dominant contributor to the PLL's output phase noise. However, in contrast to a ΔΣ-PLL, the new PLL has an entirely digital loop filter and its analog components are relatively insensitive to non-ideal analog circuit behavior. Therefore, it offers the performance benefits of a ΔΣ-PLL and the area and scalability benefits of a TDC-based digital PLL. Additionally, the PLL's digitally controlled oscillator (DCO) incorporates a new switched-capacitor frequency control element that is insensitive to supply noise and parasitic coupling. The PLL is implemented in 65 nm CMOS technology, has an active area of 0.56 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , dissipates 21 mW from 1.0 and 1.2 V supplies, and its measured phase noise at 3.5 GHz is -123, -135, and -150 dBc/Hz at offsets of 1, 3, and 20 MHz, respectively. The PLL's power consumption is lower than previously published digital PLLs with comparable phase noise performance.
The Granuloma in Tuberculosis: Dynamics of a Host–Pathogen Collusion (2013)

A granuloma is defined as an inflammatory mononuclear cell infiltrate that, while capable of limiting growth of Mycobacterium tuberculosis, also provides a survival niche from which the bacteria may disseminate. The tuberculosis lesion is highly dynamic and shaped by both, immune response elements and the pathogen. In the granuloma, M. tuberculosis switches to a non-replicating but energy-generating life style whose detailed molecular characterization can identify novel targets for chemotherapy. To secure transmission to a new host, M. tuberculosis has evolved to drive T cell immunity to the point that necrotizing granulomas leak into bronchial cavities to facilitate expectoration of bacilli. From an evolutionary perspective it is therefore questionable whether vaccination and immunity enhancing strategies that merely mimic the natural immune response directed against M. tuberculosis infection can overcome pulmonary tuberculosis in the adult population. Juxtaposition of molecular pathology and immunology with microbial physiology and the use of novel imaging approaches afford an integrative view of the granuloma's contribution to the life cycle of M. tuberculosis. This review revisits the different input of innate and adaptive immunity in granuloma biogenesis, with a focus on the co-evolutionary forces that redirect immune responses also to the benefit of the pathogen, i.e., its survival, propagation, and transmission.