gebhart/patrepeval huggingface dataset:
APOBEC3G Inhibits Elongation of HIV-1 Reverse Transcripts (2008)

APOBEC3G (A3G) is a host cytidine deaminase that, in the absence of Vif, restricts HIV-1 replication and reduces the amount of viral DNA that accumulates in cells. Initial studies determined that A3G induces extensive mutation of nascent HIV-1 cDNA during reverse transcription. It has been proposed that this triggers the degradation of the viral DNA, but there is now mounting evidence that this mechanism may not be correct. Here, we use a natural endogenous reverse transcriptase assay to show that, in cell-free virus particles, A3G is able to inhibit HIV-1 cDNA accumulation not only in the absence of hypermutation but also without the apparent need for any target cell factors. We find that although reverse transcription initiates in the presence of A3G, elongation of the cDNA product is impeded. These data support the model that A3G reduces HIV-1 cDNA levels by inhibiting synthesis rather than by inducing degradation.
Finite-alphabet based channel estimation for OFDM and related multicarrier systems (2001)

Novel blind channel estimators based on the finite alphabet property of information symbols are derived in this paper for OFDM and related multicarrier code-division multiple access (MC-CDMA) systems. The resulting algorithms are applicable not only to standard OFDM transmitters with cyclic prefix, but also to the zero padded OFDM transmissions that improve symbol recovery at the expense of altering the transmitter and complicating the equalizer. Based on FFT-processed received data, channel identifiability is guaranteed regardless of channel zero locations and various channel estimation algorithms become available by trading on the complexity for performance. Unlike existing blind channel estimators, the proposed alternatives require short data records especially for PSK transmissions. The inherent scalar ambiguity is easily resolved because it has unit amplitude and phase values drawn from a finite set. Decoupling channel from symbol estimation enables a phase-directed operation that improves upon decision-directed schemes that are known to suffer from error propagation. Practical issues are also addressed including the presence of frequency guard intervals, constellation and power loading, various frame designs, coded transmissions as well as semi-blind and online implementations for systems with training sequences. The algorithms are tested with simulations and also compared with existing alternatives in a realistic HIPERLAN/2 setting.
Advanced gene delivery : from concepts to pharmaceutical products (1999)

1. Present and Future Status of Gene Therapy 2. DNA Packaging in Non Viral Systems 3. Biological Barriers to Gene Transfer 4. Therapeutic Applications of Lipid-Based Gene Delivery Systems 5. Polycation-based Delivery Systems for Receptor-Mediated Gene Delivery 6. DNA Delivery Systems Based on Synthetic Peptides 7. Expression Plasmids for Non-Viral Gene Therapy 8. Gene Therapy Clinical Trials for Cystic Fibrosis 9. Polymeric Gene Delivery Systems for In Vivo Gene Therapy 10. Intravascular Delivery of Naked Plasmid DNA 11. Cationic Lipid-Based Gene Delivery Systems 12. Gene-based Vaccines 13. Gene Therapy for Cancer: Strategies and Review of Clinical Trials
“System 48” High-Throughput Cloning and Protein Expression Analysis (2008)

We describe a plate-based cloning and expression strategy for efficient high-throughput generation of validated expression clones in Escherichia coli. The process incorporates 48- or 96-well plates at all stages including the cloning and colony selection phases which are often performed manually. A 48-grid agar growth plate has been integrated into the colony selection component to improve throughput at the cloning stage. The combinations of 48- and 96-well plate formats are compatible with automated liquid handlers and multichannel pipettes. This revised cloning and expression pipeline increases throughput significantly, and also results in a reduction in both time and material requirements. The system has been validated by the production and screening of several thousand clones at the Midwest Center for Structural Genomics.
Exposure to magnetic field (5 mT at 60 Hz) does not affect cell growth and c-myc gene expression. (1996)

We designed and manufactured equipment for long-term and low-density (0 to 9 mT) exposures of cultured cells to extremely low frequency magnetic fields (ELF-MF), and examined the effects of ELF-MF on cell growth and c-myc mRNA expression in Chinese hamster ovary (CHO) cells. The ELF-MF equipment consists of a CO2 incubator with a built-in magnet generator using Helmholtz coils being 250 mm in inner diameter, 160 mm in distance and 128 turns, a slide regulator and a thermocontroller. No significant difference in the growth rate and the c-myc expression of CHO cells was observed with 5 mT ELF-MF exposure, sham-exposure and incubation in a conventional incubator.
Oestriol and oestradiol increase cell to cell communication and connexin43 protein expression in human myometrium (2001)

Oestradiol increases the protein expression of connexin43 (Cx43) gap junctions in myometrium but the effect of oestriol on gap junction expression has not been described previously. Oestriol is the most abundant free oestrogen in pregnant women and there is a marked surge in oestriol concentrations before term and idiopathic preterm labour. In order to determine whether oestriol may have a physiological action on the myometrium, cultured human myometrial cells obtained from non-pregnant hysterectomy specimens were exposed to 10 nmol/l oestradiol or oestriol. Intercellular communication between myometrial cells was investigated by microinjection of confluent cultured cells with the gap junction-permeant tracer Cascade Blue. There was a progressive increase in coupling after exposure to oestradiol or oestriol (P < 0.0005). An increase in Cx43 protein expression was demonstrated by immunocytochemistry after 1 h (P < 0.01) and 3 days (P < 0.01) exposure, and by Western blotting after 1 h (P < 0.01) and 3 days (P < 0.05) exposure, to both oestradiol and to oestriol. We conclude that oestriol increases gap junction communication in human myometrium by increasing gap junction expression. Elevated oestriol concentrations may thus play a role in the initiation of labour in women, by increasing cell-cell communication in the myometrium.
Bruton’s tyrosine kinase (BTK) function is important to the development and expansion of chronic lymphocytic leukemia (CLL) (2013)

Chronic lymphocytic leukemia (CLL) is characterized by constitutive activation of the B-cell receptor (BCR) signaling pathway, but variable responsiveness of the BCR to antigen ligation. Bruton's tyrosine kinase (BTK) shows constitutive activity in CLL and is the target of irreversible inhibition by ibrutinib, an orally bioavailable kinase inhibitor that has shown outstanding activity in CLL. Early clinical results in CLL with other reversible and irreversible BTK inhibitors have been less promising, however, raising the question of whether BTK kinase activity is an important target of ibrutinib and also in CLL. To determine the role of BTK in CLL, we used patient samples and the Eμ-TCL1 (TCL1) transgenic mouse model of CLL, which results in spontaneous leukemia development. Inhibition of BTK in primary human CLL cells by small interfering RNA promotes apoptosis. Inhibition of BTK kinase activity through either targeted genetic inactivation or ibrutinib in the TCL1 mouse significantly delays the development of CLL, demonstrating that BTK is a critical kinase for CLL development and expansion and thus an important target of ibrutinib. Collectively, our data confirm the importance of kinase-functional BTK in CLL.
An electrochemical surface-enhanced Raman spectroscopy approach to anthrax detection (2003)

Metal film over nanosphere (MFON) electrodes are excellent substrates for surface-enhanced Raman scattering (SERS) spectroscopy. These surfaces are produced by vapor deposition of a metal film over nanospheres that are assembled in a hexagonally close packed arrangement. The efficiency and reproducibility of AgFON electrode as SERS substrates are confirmed by the repeatability of the electrochemical surface enhanced Raman scattering spectra of pyridine and the Ru(bpy)<sub>3</sub><sup>3+</sup>/Ru(bpy)<sub>3</sub><sup>2+</sup> complexes adsorbed on AgFON electrodes. The Raman signal for AgFON electrodes is observed to be extremely stable even at extremely negative potentials in both aqueous and nonaqueous electrolytes. Recent reports have indicated that SERS enhancement factors of up to 14 orders of magnitude can be achieved, providing the sensitivity requisite for ultra trace level detection of target analytes. For this reason, we are developing a method for bacterial endospore SERS detection based on the endospores marker -- dipicolinic acid (DPA). The SERS spectra of dipicolinic acid in aqueous solutions are reported. The dipicolinate vibrational features could be observed in the SERS spectra at the concentration as low as 8 × 10<sup>-5</sup> M in 5 minutes. These limits of detection are entirely controlled by the thermodynamics and kinetics of DPA binding to the AgFON surface.
DNA Double-stranded Breaks Induce Histone H2AX Phosphorylation on Serine 139 (1998)

When mammalian cell cultures or mice are exposed to ionizing radiation in survivable or lethal amounts, novel mass components are found in the histone H2A region of two-dimensional gels. Collectively referred to as gamma, these components are formed in vivo by several procedures that introduce double-stranded breaks into DNA. gamma-Components, which appeared to be the only major novel components detected by mass or 32PO4 incorporation on acetic acid-urea-Triton X-100-acetic acid-urea-cetyltrimethylammonium bromide or SDS-acetic acid-urea-cetyltrimethylammonium bromide gels after exposure of cells to ionizing radiation, are shown to be histone H2AX species that have been phosphorylated specifically at serine 139. gamma-H2AX appears rapidly after exposure of cell cultures to ionizing radiation; half-maximal amounts are reached by 1 min and maximal amounts by 10 min. At the maximum, approximately 1% of the H2AX becomes gamma-phosphorylated per gray of ionizing radiation, a finding that indicates that 35 DNA double-stranded breaks, the number introduced by each gray into the 6 x 10(9) base pairs of a mammalian G1 genome, leads to the gamma-phosphorylation of H2AX distributed over 1% of the chromatin. Thus, about 0.03% of the chromatin appears to be involved per DNA double-stranded break. This value, which corresponds to about 2 x 10(6) base pairs of DNA per double-stranded break, indicates that large amounts of chromatin are involved with each DNA double-stranded break. Thus, gamma-H2AX formation is a rapid and sensitive cellular response to the presence of DNA double-stranded breaks, a response that may provide insight into higher order chromatin structures.
Blood reservoir function of dog spleen, liver, and intestine (1977)

The reflex decrease in blood volume of the spleen, the liver, and the intestine of vagotomized dogs was measured by plethysmographic techniques during bilateral carotid occlusion and moderate and severe hemorrhage. The volume of blood mobilized from each organ during carotid occlusion and moderate hemorrhage was from 6 to 30% of their respective blood volumes and from 55 to 81% during severe hemorrhage. In each experimental situation the spleen exhibited the greatest ability to release blood and the intestine, the least. During moderate hemorrhage (9 ml/kg) the spleen yielded a volume equal to 35% of the blood lost, the liver 14% and the intestine 7%. Comparable figures for severe hemorrhage were 26, 13, and 5%, respectively. This order of ranking the component regions of the splanchnic circulation with regard to function as a blood reservoir may be specific for the dog.
Gene Replacement Therapy for Inborn Errors of Purine Metabolism (1986)

Effective retroviral vectors carrying the human HPRT and ADA genes have been described. Initial characterization of the retroviral gene transfer system using the HPRT vector allowed the delineation of several parameters important in viral titer, expression, and stability. Using the HPRT and ADA vectors, we have initiated experiments designed to insert these human genes into various tissues of the mouse and have demonstrated expression of both transduced genes in mouse bone marrow cells. Further work with these and other vector constructions is underway in the hope that this technique may allow safe and effective treatment of ADA and HPRT deficiencies, paving the way for treatments of other inborn errors of metabolism through somatic gene replacement therapy.
Transgenic mice as a model to study the role of TGF-beta-related molecules in hair follicles. (1993)

There is increasing evidence that members of the TGF-beta superfamily are important regulators of epithelial growth and differentiation in vivo. Here, transgenic mice have been used to study the role of the TGF-beta-related growth factors BMP-2 and BMP-4 in hair and whisker development. In the mature hair follicle, BMP-2 transcripts are normally seen only in precortex cells at the base of the hair shaft. In the transgenic mice reported here, BMP-4, a closely related molecule, has been ectopically expressed in the outer root sheath of hair and whisker follicles using an expression vector based on the bovine cytokeratin IV* promoter. In response to transgene expression, both outer root sheath cells below the stem cell compartment and hair matrix cells around the dermal papilla cease proliferation. In addition, the expression pattern of cytokeratin markers is disturbed in some transgenic hair follicles. These results support a model in which members of the TGF-beta superfamily play an active role in the inhibiton of cell proliferation and the onset of expression of trichocyte-specific genes that take place when cells leave the matrix of the follicle and differentiate into shaft cells.
Multi-weight enveloping (2002)

We present a process called multi-weight enveloping for deforming the skin geometry of the body of a digital creature around its skeleton. It is based on a deformation equation whose coefficients we compute using a statistical fit to an input training exercise. In this input, the skeleton and the skin move together, by arbitrary external means, through a range of motion representative of what the creature is expected to achieve in practice. The input can also come from existing pieces of handcrafted skin animation. Using a modified least-squares fitting technique, we compute the coefficients, or "weights", of the deformation equation. The result is that the equation generalizes the skin movement so that it applies well to other sequences of animation. The multi-weight deformation equation is computationally efficient to evaluate; once the training process is complete, even creatures with high levels of geometric detail can move at interactive frames rates with a look that approximates that of anatomical, physically-based models. We demonstrate the technique in a feature film production environment, on a human model whose input poses are sculpted by hand and an animal model whose input poses come from the output of an anatomically-based dynamic simulation.
Analysis of Dual-Mode Hydrocarbon Scramjet Operation at Mach 4-6.5 (2002)

Reynolds averaged Navier ‐Stokes calculations have been performed for a U.S. Air Force Research Laboratory/ Aerospace Propulsion Ofe ce scramjet combustor designed for Mach 4.0 ‐6.5 e ight. The combustor e owpath is unique in that it is entirely free of e ow obstructions with fuel injection from wall-mounted injection ports and e ameholding established by means of a recessed cavity. Calculations were performed at the minimum (Mach 4.0) andmaximum(Mach6.5)e ightdesign conditions.Thecombustoroperatedin dualmodeattheMach4.0condition. The precombustion shock train formed a region of low-momentum/separated e ow adjacent to the combustor side wall. This proved to be a primary source of e ameholding, with the recessed cavity adding additional e ameholding support. The e ow was notthermally choked at theMach 6.5 condition,resulting in very little upstream interaction. The mixing process at the Mach 4.0 e ight condition was considerably more efe cient than that seen at the Mach 6.5 condition, due primarily to the shock-induced e ow distortion and larger residence time. Even with the reduced mixing levels predicted at the Mach 6.5 condition, the combustion efe ciency was comparable to that achieved at the Mach 4.0 condition. The solutions obtained for dual-mode operation were particularly sensitive to choice of turbulence model and values specie ed for the turbulent Prandtl and Schmidt numbers. Overall, the solution sensitivity to grid resolution was small relative to the solution sensitivity to modeling uncertainties.
Epigenetic Regulator Smchd1 Functions as a Tumor Suppressor (2012)

SMCHD1 is an epigenetic modifier of gene expression that is critical to maintain X chromosome inactivation. Here, we show in mouse that genetic inactivation of Smchd1 accelerates tumorigenesis in male mice. Loss of Smchd1 in transformed mouse embryonic fibroblasts increased tumor growth upon transplantation into immunodeficient nude mice. In addition, loss of Smchd1 in Eμ-Myc transgenic mice that undergo lymphomagenesis reduced disease latency by 50% relative to control animals. In premalignant Eμ-Myc transgenic mice deficient in Smchd1, there was an increase in the number of pre-B cells in the periphery, likely accounting for the accelerated disease in these animals. Global gene expression profiling suggested that Smchd1 normally represses genes activated by MLL chimeric fusion proteins in leukemia, implying that Smchd1 loss may work through the same pathways as overexpressed MLL fusion proteins do in leukemia and lymphoma. Notably, we found that SMCHD1 is underexpressed in many types of human hematopoietic malignancy. Together, our observations collectively highlight a hitherto uncharacterized role for SMCHD1 as a candidate tumor suppressor gene in hematopoietic cancers.
Channel Estimation and Hybrid Precoding for Millimeter Wave Cellular Systems (2014)

Millimeter wave (mmWave) cellular systems will enable gigabit-per-second data rates thanks to the large bandwidth available at mmWave frequencies. To realize sufficient link margin, mmWave systems will employ directional beamforming with large antenna arrays at both the transmitter and receiver. Due to the high cost and power consumption of gigasample mixed-signal devices, mmWave precoding will likely be divided among the analog and digital domains. The large number of antennas and the presence of analog beamforming requires the development of mmWave-specific channel estimation and precoding algorithms. This paper develops an adaptive algorithm to estimate the mmWave channel parameters that exploits the poor scattering nature of the channel. To enable the efficient operation of this algorithm, a novel hierarchical multi-resolution codebook is designed to construct training beamforming vectors with different beamwidths. For single-path channels, an upper bound on the estimation error probability using the proposed algorithm is derived, and some insights into the efficient allocation of the training power among the adaptive stages of the algorithm are obtained. The adaptive channel estimation algorithm is then extended to the multi-path case relying on the sparse nature of the channel. Using the estimated channel, this paper proposes a new hybrid analog/digital precoding algorithm that overcomes the hardware constraints on the analog-only beamforming, and approaches the performance of digital solutions. Simulation results show that the proposed low-complexity channel estimation algorithm achieves comparable precoding gains compared to exhaustive channel training algorithms. The results illustrate that the proposed channel estimation and precoding algorithms can approach the coverage probability achieved by perfect channel knowledge even in the presence of interference.
CYP3A4*22 Genotype and Systemic Exposure Affect Paclitaxel-Induced Neurotoxicity (2013)

Paclitaxel exposure showed a relationship with the severity of paclitaxel-induced neurotoxicity. In this study, female CYP3A4*22 carriers had increased risk of developing severe neurotoxicity during paclitaxel therapy. These observations may guide future individualization of paclitaxel treatment.
Identification of molybdopterin as the organic component of the tungsten cofactor in four enzymes from hyperthermophilic Archaea. (1993)

The hyperthermophilic Archaea represent some of the most ancient organisms on earth. A study of enzymatic cofactors in these organisms could provide basic information on the origins of related cofactors in man and other more recently evolved organisms. To this end, the nature of the tungsten cofactor in aldehyde ferredoxin oxidoreductases from Pyrococcus furiosus and ES-4 and in formaldehyde ferredoxin oxidoreductases from P. furiosus and Thermococcus litoralis has been investigated. All four proteins contain molybdopterin, previously characterized as the organic component of the molybdenum cofactor in a large number of molybdoenzymes. Molybdopterin was identified by conversion to the dicarboxamidomethyl derivative by alkylation of the vicinal sulfhydryl groups on the pterin side chain and by conversion to the oxidized fluorescent derivative, Form A. The pterin of the tungsten cofactor in the four enzymes was examined for the presence of appended GMP, CMP, AMP, or IMP previously observed in molybdenum cofactors of some molybdoenzymes. No evidence for the presence of a molybdopterin dinucleotide or other modified form of molybdopterin was obtained. These results further document the essential nature of molybdopterin for the function of molybdenum and tungsten enzymes in diverse life forms.
A new hybrid active neutral point clamped flying capacitor multilevel inverter (2015)

This paper proposes a new five-level hybrid topology combining features of neutral point clamped and flying capacitor inverters. The proposed topology provides a tradeoff between different component counts to achieve a good loss distribution, avoid direct series connection of semiconductor devices, keep the balanced operation of dc-link capacitors while keeping the number of costly components such as capacitors and switches low. The required modulation strategy is developed and the operation of the proposed topology is studied. The features of the proposed topology are investigated and compared to other available topologies. Simulation results are provided to verify the performance of the converter for medium voltage applications.