gebhart/patrepeval huggingface dataset:
The decapentaplegic gene: a TGF-β homologue controlling pattern formation in Drosophila (1989)

ABSTRACT The type β transforming growth factor (TGF-β) family of secreted factors encompasses a wide range of structurally related proteins that control the state of determination or differentiation in a wide variety of cell types. For all members of the family that have been studied at the protein level, the active moieties arise as dimers of the C-terminal ∼110 amino acid fragment derived from much longer precursor polypeptides. The hallmark of the family is a series of 7 completely conserved cysteine residues in the C-terminus; other conserved amino acid sequences generally cluster in the vicinity of 6 of these 7 cysteines. This report focuses on our current understanding of the genetic structure and developmental role of the decapentaplegic (dpp) gene in Drosophila, the only member of the TGF-β family thus far identified in invertebrates. The dpp polypeptide bears a sufficiently close relationship to two bone morphogenesis proteins (BMP-2A and BMP-2B) identified in mammals (Wozney et al. 1988, Science 242, 1528-1534) to warrant the suggestion that dpp and the BMP-2s are the descendants of a common ancestral gene. The protein-coding information for dpp is contained within a 6 kb DNA segment. An elaborate cis-regulatory apparatus, encompassing a &amp;gt;55 kb DNA segment, has evolved to control expression of the dpp gene, which is required for determination of dorsal ectoderm in the early embryo, for normal distal outgrowth of the adult appendages, and for sundry other developmental events, which are currently less well-defined. Studies of chimeric individuals and observations of transcript accumulation in situ have demonstrated that the dpp gene is expressed along the A/P boundary of the imaginai disks. A possible role of dpp in elaborating positional information in imaginai disk development is discussed.
RANTES-activated human T lymphocytes. A role for phosphoinositide 3-kinase (1995)

RANTES (regulated on activation, normal T cell expressed and secreted), a member of the chemokine family, is a potent chemoattractant for CD4+/CD45RO human T lymphocytes, but the signal-transduction mechanisms utilized by RANTES are poorly defined. In freshly isolated human T lymphocytes loaded with fura-2 acetoxymethyl, the CD3 mAb, UCHT-1, but not RANTES, elicited elevation of intracellular calcium levels. However, RANTES produced a bell-shaped chemotactic response and an increase in polarization of the T lymphocytes. Immunoprecipitates of phosphoinositide (PI) 3-kinase, derived from T lymphocytes stimulated with RANTES, contained increased in vitro PI 3-kinase activity compared with that present in immunoprecipitates derived from vehicle-treated cells. RANTES induction of PI 3-kinase activity was maximal at 10 to 100 ng/ml. Furthermore, the fungal metabolite, wortmannin, which is a potent PI 3-kinase inhibitor, inhibited RANTES-induced T lymphocyte migration, polarization, and increased PI 3-kinase activity. Our results show that RANTES activation of T lymphocytes seems to be independent of detectable elevation of cytosolic-free calcium, but the functional effects of chemotaxis and polarization, induced by RANTES, seem to involve the putative PI 3-kinase signal-transduction pathway.
Unraveling the potential of CRISPR-Cas9 for gene therapy (2014)

The molecular machinery from the prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)-Cas immune system has broadly been repurposed for genome editing in eukaryotes. In particular, the sequence-specific Cas9 endonuclease can be flexibly harnessed for the genesis of precise double-stranded DNA breaks, using single guide RNAs that are readily programmable. The endogenous DNA repair machinery subsequently generates genome modifications, either by random insertion or deletions using non-homologous end joining (NHEJ), or designed integration of mutations or genetic material using homology-directed repair (HDR) templates. This technology has opened new avenues for the investigation of genetic diseases in general, and for gene therapy applications in particular.
Correlation-Preserved Statistical Timing With a Quadratic Form of Gaussian Variables (2006)

A recent study shows that the existing first-order canonical timing model is not sufficient to represent the dependency of the gate/wire delay on the processing and operational variations when these variations become more and more significant. Due to nonlinear mapping from variation sources to the gate/wire delay, the distribution of the delay will no longer be Gaussian even if variation sources are normally distributed. A novel “quadratic timing model” is proposed to capture the nonlinearity of the dependency of gate/wire delays and arrival times on the variation sources. Systematic methodology is also developed to evaluate the correlation and distribution of the quadratic timing model. Based on these, a statistical static timing analysis algorithm that retains the complete correlation information during timing analysis and has linear computation complexity with respect to both the circuit size and the number of variation sources is proposed. Tested on the ISCAS circuits, the proposed algorithm shows significant accuracy improvement over the existing first-order algorithm with a small amount of computational cost.
Nanoscale Morphology of Polyanhydride Copolymers (2005)

The microphase separation in polyanhydride random copolymers composed of 1,6-bis(p-carboxyphenoxy)hexane and sebacic acid is described. Though the copolymers are random, the monomers are sufficiently long and the segment−segment interaction parameter is sufficiently high to promote microphase separation when the copolymer is rich in one component. Solid-state NMR spin diffusion experiments and synchrotron small-angle X-ray scattering are used to discern the length scales of the microphase separation. Both techniques reveal a nanostructure with domain sizes less than 25 Å. This nanostructure is compared to approximate calculations of chain dimensions based on a random coil model and discussed in the context of the rational design of these materials for drug delivery applications.
Effects of hindlimb contraction on pressor and muscle interstitial metabolite responses in the cat (1998)

We used the microdialysis technique to measure the interstitial concentration of several putative metabolic stimulants of the exercise pressor reflex during 3- and 5-Hz twitch contractions in the decerebrate cat. The peak increases in heart rate and mean arterial pressure during contraction were 20 +/- 5 beats/min and 21 +/- 8 mmHg and 27 +/- 9 beats/min and 37 +/- 12 mmHg for the 3- and 5-Hz stimulation protocols, respectively. All variables returned to baseline after 10 min of recovery. Interstitial lactate rose (P < 0. 05) by 0.41 +/- 0.15 and 0.56 +/- 0.16 mM for the 3- and 5-Hz stimulation protocols, respectively, and were not statistically different from one another. Interstitial lactate levels remained above (P < 0.05) baseline during recovery in the 5-Hz group. Dialysate phosphate concentrations (corrected for shifts in probe recovery) rose with stimulation (P < 0.05) by 0.19 +/- 0.08 and 0.11 +/- 0.03 mM for the 3- and 5-Hz protocols. There were no differences between groups. The resting dialysate K+ concentrations for the 3- and 5-Hz conditions were 4.0 +/- 0.1 and 3.9 +/- 0.1 meq/l, respectively. During stimulation the dialysate K+ concentrations rose steadily for both conditions, and the increase from rest to stimulation (P < 0.05) was 0.57 +/- 0.19 and 0.81 +/- 0.06 meq/l for the 3- and 5-Hz conditions, respectively, with no differences between groups. Resting dialysate pH was 6.915 +/- 0.055 and 6.981 +/- 0.032 and rose to 7.013 (P < 0.05) and 7.053 (P < 0.05) for the 3- and 5-Hz conditions, respectively, and then became acidotic (6. 905, P < 0.05) during recovery (5 Hz only). This study represents the first time simultaneous measurements of multiple skeletal muscle interstitial metabolites and pressor responses to twitch contractions have been made in the cat. These data suggest that interstitial K+ and phosphate, but not lactate and H+, may contribute to the stimulation of thin fiber muscle afferents during contraction.
Data for: 3487540 (2019)

A portfolio of commodity index-ETF pairs was constructed and its performance was compared against the Bloomberg commodity index. The portfolio was trained on data from 2011 to 2014 to determine the optimal parameters for trade-execution thresholds. Using these parameters and the optimal exposures found from optimizing the risk-adjusted expected returns, the trading strategy was tested from 2015 to 2018 with the portfolio rebalanced at the beginning of each year. Comparing the returns of the portfolio against the Bloomberg Barclays Commodities Index as a benchmark, it was found that the portfolio outperformed the benchmark in total returns and Sharpe ratio for 2015, 2017, and 2018, but it underperformed for both metrics in 2016. Performing a paired t-test on the portfolio and benchmark returns proved that the portfolio does not signiﬁcantly outperform the benchmark in any given year.
MafA Is a Key Regulator of Glucose-Stimulated Insulin Secretion (2005)

MafA is a transcription factor that binds to the promoter in the insulin gene and has been postulated to regulate insulin transcription in response to serum glucose levels, but there is no current in vivo evidence to support this hypothesis. To analyze the role of MafA in insulin transcription and glucose homeostasis in vivo, we generated MafA-deficient mice. Here we report that MafA mutant mice display intolerance to glucose and develop diabetes mellitus. Detailed analyses revealed that glucose-, arginine-, or KCl-stimulated insulin secretion from pancreatic beta cells is severely impaired, although insulin content per se is not significantly affected. MafA-deficient mice also display age-dependent pancreatic islet abnormalities. Further analysis revealed that insulin 1, insulin 2, Pdx1, Beta2, and Glut-2 transcripts are diminished in MafA-deficient mice. These results show that MafA is a key regulator of glucose-stimulated insulin secretion in vivo.
Energy conservation efforts in Indian ammonia plants (2005)

Modernization of old ammonia plants, reduction in specific energy consumption by using better technology and equipment in new plants, and better maintenance and operation practices are helping the Indian ammonia industry to achieve high on-stream and energy efficiencies comparable with international standards.
In vitrocorrection of cystic fibrosis epithelial cell lines by small fragment homologous replacement (SFHR) technique (2002)

These studies provide new insights into factors that underlie SFHR-mediated gene targeting efficacy and into the parameters that can be modulated for its optimization.
Butelase-mediated synthesis of protein thioesters and its application for tandem chemoenzymatic ligation (2015)

Using a recently discovered peptide ligase, butelase 1, we developed a novel method to access protein thioesters in good yield. We successfully combined it with native chemical ligation and sortase-mediated ligation in tandem for protein C-terminal labeling and dual-terminal labeling to exploit the orthogonality of these three ligation methods.
Unseasonable thoughts - a tale of two revolutions (1989)

This year is the bicentenary of the event traditionally regarded as the beginning of modern history - the French Revolution. To mark the occasion, I have recently been reading some of the classic accounts of its origins. There have been echoes of something familiar in what I have been reading. I finally realised what it was - the uncanny similarity between the problems facing the statesmen of pre-revolutionary France and those facing the Soviet leadership today.
Quantitative optical phase microscopy (1998)

We present a new method for the extraction of quantitative phase data from microscopic phase samples by use of partially coherent illumination and an ordinary transmission microscope. The technique produces quantitative images of the phase profile of the sample without phase unwrapping. The technique is able to recover phase even in the presence of amplitude modulation, making it significantly more powerful than existing methods of phase microscopy. We demonstrate the technique by providing quantitatively correct phase images of well-characterized test samples and show that the results obtained for more-complex samples correlate with structures observed with Nomarski differential interference contrast techniques.
Landsat Data Destriping Using Power Spectral Filtering (1988)

A new method is presented for destriping Landsat data and compen-sating for failed detectors. The basic spatial frequency composition of the degradation is determined from an easily computed one-dimensional power spectrum of the image. A convolutional restoration kernel is then created from a modified version of the power spectrum.
A new quasi-Yagi antenna for planar active antenna arrays (2000)

In this paper, a novel broadband planar antenna based on the classic Yagi-Uda dipole antenna is presented, and its usefulness as an array antenna is explored. This "quasi-Yagi" antenna is realized on a high dielectric-constant substrate, and is completely compatible with microstrip circuitry and solid-state devices. This antenna achieves a measured 48% frequency bandwidth for voltage standing-wave ratio <2, better than a 12-dB front-to-back ratio, smaller than -15 dB cross polarization, and 3-5-dBi absolute gain. Mutual coupling of the antenna in an array environment is investigated. Finally, three simple arrays are presented, demonstrating the usefulness of the antenna as an array element. This novel antenna should find wide application in wireless communication systems, power combining, phased arrays, and active arrays, as well as millimeter-wave imaging arrays.
Design and Synthesis of Bis-Biotin-Containing Reagents for Applications Utilizing Monoclonal Antibody-Based Pretargeting Systems with Streptavidin Mutants (2010)

Previous studies have shown that pretargeting protocols, using cancer-targeting fusion proteins, composed of 4 anti-CD20 single chain Fv (scFv) fragments and streptavidin (scFv(4)-SAv), followed by a biotinylated dendrimeric N-acetyl-galactosamine blood clearing agent (CA), 1, then a radiolabeled DOTA-biotin derivative (a monobiotin), 3a, can provide effective therapy for lymphoma xenografts in mouse models. A shortcoming in this pretargeting system is that endogenous biotin may affect its efficacy in patients. To circumvent this potential problem, we investigated a pretargeting system that employs anti-CD20 scFv(4)-SAv mutant fusion proteins with radioiodinated bis-biotin derivatives. With that combination of reagents, good localization of the radiolabel to lymphoma tumor xenografts was obtained in the presence of endogenous biotin. However, the blood clearance reagents employed in the studies were ineffective, resulting in abnormally high levels of radioactivity in other tissues. Thus, in the present investigation a bis-biotin-trigalactose blood clearance reagent, 2, was designed, synthesized, and evaluated in vivo. Additionally, another DOTA-biotin derivative (a bis-biotin), 4a, was designed and synthesized, such that radiometals (e.g., (111)In, (90)Y, (177)Lu) could be used in the pretargeting protocols employing scFv(4)-SAv mutant fusion proteins. Studies in mice demonstrated that the CA 2 was more effective than CA 1 at removing [(125)I]scFv(4)-SAv-S45A mutant fusion proteins from blood. Another in vivo study compared tumor targeting and normal tissue concentrations of the new reagents (2 and [(111)In]4b) with standard reagents (1 and [(111)In]3b) used in pretargeting protocols. The study showed that lymphoma xenografts could be targeted in the presence of endogenous biotin when anti-CD20 fusion proteins containing SAv mutants (scFv(4)-SAv-S45A or scFv(4)-SAv-Y43A) were employed in combination with CA 2 and [(111)In]4b. Importantly, normal tissue concentrations of [(111)In]4b were similar to those obtained using the standard reagents (1 and [(111)In]3b), except that the blood and liver concentrations were slightly higher with the new reagents. While the reasons for the higher blood and liver concentrations are unknown, the differences in the galactose structures of the clearance agents 1 and 2 may play a role.
Vaccine protection against simian immunodeficiency virus infection. (1989)

Rhesus monkeys were immunized by multiple inoculations with purified, disrupted, noninfectious simian immunodeficiency virus (SIV) in adjuvant. Immunized monkeys developed anti-SIV antibodies detectable by whole-virus ELISA and by immunoblot reactivity; these antibodies had weak neutralizing activity. One week after the last immunization, monkeys were challenged with 200-1000 animal infectious doses of uncloned, live SIV. The same strain of SIV that was used for vaccination was also used for challenge. Anamnestic antibody responses and SIV recovery from peripheral blood were used to evaluate infection following the live virus challenge; two of six vaccinated monkeys showed no evidence of infection following the live virus challenge. Transfusion of 10 ml of whole blood from these two into uninfected, naive rhesus monkeys did not result infection of the recipients, providing further support for the lack of infection in the two previously vaccinated animals. Four of four unvaccinated control monkeys inoculated with these doses of live SIV became infected and three of these died with AIDS 118-258 days after infection. Only one of the six vaccinated monkeys has died to date. In situ hybridization with lymph node biopsy specimens suggested that the virus load was much higher in control macaques than in vaccinated macaques. These results indicate that vaccination with inactivated whole virus can protect macaques against challenge with live SIV. Furthermore, they provide hope that vaccine protection against human AIDS virus infection may be possible.
Adherence to Colorectal Cancer Screening (2012)

The common practice of universally recommending colonoscopy may reduce adherence to CRC screening, especially among racial/ethnic minorities. Significant variation in overall and strategy-specific adherence exists between racial/ethnic groups; however, this may be a proxy for health beliefs and/or language. These results suggest that patient preferences should be considered when making CRC screening recommendations. Trial Registration clinicaltrials.gov Identifier: NCT00705731.
Archived Formalin-Fixed Paraffin-Embedded (FFPE) Blocks: A Valuable Underexploited Resource for Extraction of DNA, RNA, and Protein (2013)

Formalin-fixed paraffin-embedded (FFPE) material presents a readily available resource in the study of various biomarkers. There has been interest in whether the storage period has significant effect on the extracted macromolecules. Thus, in this study, we investigated if the storage period had an effect on the quantity/quality of the extracted nucleic acids and proteins. We systematically examined the quality/quantity of genomic DNA, total RNA, and total protein in the FFPE blocks of malignant tumors of lung, thyroid, and salivary gland that had been stored over several years. We show that there is no significant difference between macromolecules extracted from blocks stored over 11-12 years, 5-7 years, or 1-2 years in comparison to the current year blocks.
Growth, Nitrogen Fixation, and Spectral Attenuation in Cultivated Trichodesmium Species (1993)

Physiological studies of Trichodesmium species have been hindered by difficulties in maintaining actively growing, nitrogen-fixing cultures. Previous cultivation successes have not been widely duplicated. We present here a simple modified seawater medium and handling techniques which have been used to maintain actively growing Trichodesmium thiebautii in laboratory culture for over 1 year. The cultured population, isolated from coastal Atlantic waters, has a growth rate of 0.23 division day and exhibits light-dependent nitrogen fixation during exponential growth. Various morphologies, including solitary trichomes, and aggregates (spherical puffs and fusiform tufts) are present during growth. Spectral and scalar irradiance were measured within naturally occurring (coastal Atlantic) aggregates with small (diameter, 50 to 70 mum) spherical fiber-optic sensors. In contrast to naturally occurring puffs, cultivated Trichodesmium aggregates exhibited spectral properties consistent with low-light adaptation. Cultivated puff-type aggregates were also examined by using oxygen microelectrodes. The simple medium and approach used for cultivation should be easily reproducible and amenable to further manipulations and modifications useful for physiological studies of Trichodesmium spp. in culture.
Molecular Requirements for Human Immunodeficiency Virus Type 1 Plus-Strand Transfer: Analysis in Reconstituted and Endogenous Reverse Transcription Systems (1999)

We have developed a reconstituted system which models the events associated with human immunodeficiency virus type 1 (HIV-1) plus-strand transfer. These events include synthesis of plus-strand strong-stop DNA [(+) SSDNA] from a minus-strand DNA donor template covalently attached to human tRNA3Lys, tRNA primer removal, and annealing of (+) SSDNA to the minus-strand DNA acceptor template. Termination of (+) SSDNA synthesis at the methyl A (nucleotide 58) near the 3' end of tRNA3Lys reconstitutes the 18-nucleotide primer binding site (PBS). Analysis of (+) SSDNA synthesis in vitro and in HIV-1 endogenous reactions indicated another major termination site: the pseudouridine at nucleotide 55. In certain HIV-1 strains, complementarity between nucleotides 56 to 58 and the first three bases downstream of the PBS could allow all of the (+) SSDNA products to be productively transferred. Undermodification of the tRNA may be responsible for termination beyond the methyl A. In studies of tRNA removal, we find that initial cleavage of the 3' rA by RNase H is not sufficient to achieve successful strand transfer. The RNA-DNA hybrid formed by the penultimate 17 bases of tRNA still annealed to (+) SSDNA must also be destabilized. This can occur by removal of additional 3'-terminal bases by RNase H (added either in cis or trans). Alternatively, the nucleic acid chaperone activity of nucleocapsid protein (NC) can catalyze this destabilization. NC stimulates annealing of the complementary PBS sequences in (+) SSDNA and the acceptor DNA template. Reverse transcriptase also promotes annealing but to a lesser extent than NC.
Cellular and molecular mechanisms of liver tolerance (2006)

The liver exhibits a distinctive form of immune privilege, termed liver tolerance, in which orthotopic liver transplantation results in systemic donor-specific T-cell tolerance, while antigens introduced either into hepatocytes or via the portal vein also cause tolerance. Here we argue that the fundamental mechanism driving liver tolerance is likely to be the continuous exposure of diverse liver cell types to endotoxin, derived from the intestinal bacteria. This exposure promotes the expression of a set of cytokines, antigen-presenting molecules, and costimulatory signals that impose T-cell inactivation, partly via effects on liver antigen-presenting cells. The evidence favors clonal deletion mechanisms and is consistent with a role for regulatory T cells but does not support either anergy or immune deviation as important factors in liver tolerance.