gebhart/patrepeval huggingface dataset:
Cryo-electron tomography of vaccinia virus (2005)

The combination of cryo-microscopy and electron tomographic reconstruction has allowed us to determine the structure of one of the more complex viruses, intracellular mature vaccinia virus, at a resolution of 4-6 nm. The tomographic reconstruction allows us to dissect the different structural components of the viral particle, avoiding projection artifacts derived from previous microscopic observations. A surface-rendering representation revealed brick-shaped viral particles with slightly rounded edges and dimensions of approximately 360 x 270 x 250 nm. The outer layer was consistent with a lipid membrane (5-6 nm thick), below which usually two lateral bodies were found, built up by a heterogeneous material without apparent ordering or repetitive features. The internal core presented an inner cavity with electron dense coils of presumptive DNA-protein complexes, together with areas of very low density. The core was surrounded by two layers comprising an overall thickness of approximately 18-19 nm; the inner layer was consistent with a lipid membrane. The outer layer was discontinuous, formed by a periodic palisade built by the side interaction of T-shaped protein spikes that were anchored in the lower membrane and were arranged into small hexagonal crystallites. It was possible to detect a few pore-like structures that communicated the inner side of the core with the region outside the layer built by the T-shaped spike palisade.
Multiwavelength, densely-packed 2 x 2 vertical-cavity surface-emitting laser array fabricated using selective oxidation (1996)

Data are presented characterizing an individually addressable, multiwavelength 2×2 vertical-cavity surface-emitting laser array. The individual elements are fabricated on center-to-center spacings of 12 μm with the lasing wavelengths controlled through the selectively oxidized lateral device sizes. Devices sized 3.5, 3.0, 2.5, and 2.0 μm result in lasing wavelengths of 9608, 9598, 9587, and 9574 /spl Aring/, respectively. Continuous wave threshold currents of the four elements with decreasing device sizes are 240, 214, 187, and 169 μA, respectively.
Genome-wide quantitative assessment of variation in DNA methylation patterns (2011)

Genomic DNA methylation contributes substantively to transcriptional regulations that underlie mammalian development and cellular differentiation. Much effort has been made to decipher the molecular mechanisms governing the establishment and maintenance of DNA methylation patterns. However, little is known about genome-wide variation of DNA methylation patterns. In this study, we introduced the concept of methylation entropy, a measure of the randomness of DNA methylation patterns in a cell population, and exploited it to assess the variability in DNA methylation patterns of Alu repeats and promoters. A few interesting observations were made: (i) within a cell population, methylation entropy varies among genomic loci; (ii) among cell populations, the methylation entropies of most genomic loci remain constant; (iii) compared to normal tissue controls, some tumors exhibit greater methylation entropies; (iv) Alu elements with high methylation entropy are associated with high GC content but depletion of CpG dinucleotides and (v) Alu elements in the intronic regions or far from CpG islands are associated with low methylation entropy. We further identified 12 putative allelic-specific methylated genomic loci, including four Alu elements and eight promoters. Lastly, using subcloned normal fibroblast cells, we demonstrated the highly variable methylation patterns are resulted from low fidelity of DNA methylation inheritance.
Pyridazines. LXX. Reactions of azidoazolopyridazines with unsaturated compounds (1975)

Abstract Cycloaddition reactions of azidoazolopyridazines with unsaturated esters, cyclic enol ethers, styrene, 2‐vinyl‐pyridine, bicyclo[2.2.1]heptene, dicyclopentadiene and dehydrobenzene were investigated. The reaction proceed via the intermediate Δ 2 ‐1,2,3‐triazolines which were in most cases termolabile and decomposed further to give the final products which were enamines, imines of fused aziridines.
Production and Characterization of Novel Recombinant Adeno-Associated Virus Replicative-Form Genomes: A Eukaryotic Source of DNA for Gene Transfer (2013)

Conventional non-viral gene transfer uses bacterial plasmid DNA containing antibiotic resistance genes, cis-acting bacterial sequence elements, and prokaryotic methylation patterns that may adversely affect transgene expression and vector stability in vivo. Here, we describe novel replicative forms of a eukaryotic vector DNA that consist solely of an expression cassette flanked by adeno-associated virus (AAV) inverted terminal repeats. Extensive structural analyses revealed that this AAV-derived vector DNA consists of linear, duplex molecules with covalently closed ends (termed closed-ended, linear duplex, or "CELiD", DNA). CELiD vectors, produced in Sf9 insect cells, require AAV rep gene expression for amplification. Amounts of CELiD DNA produced from insect cell lines stably transfected with an ITR-flanked transgene exceeded 60 mg per 5 × 10(9) Sf9 cells, and 1-15 mg from a comparable number of parental Sf9 cells in which the transgene was introduced via recombinant baculovirus infection. In mice, systemically delivered CELiD DNA resulted in long-term, stable transgene expression in the liver. CELiD vectors represent a novel eukaryotic alternative to bacterial plasmid DNA.
Design and implementation of a lightweight dynamic optimization system (2004)

Many opportunities exist to improve micro-architectural performance due to performance events that are dicult to optimize at static compile time. Cache misses and branch mis-prediction patterns may vary for dierent micro-architectures using dierent inputs. Dynamic optimization provides an approach to address these and other performance events at runtime. This paper describes a software system of real implementation that detects performance problems of running applications and deploys optimizations to increase execution eciency. We discuss issues of detecting performance bottlenecks, generating optimized traces and redirecting execution from the original code to the dynamically optimized code. Our current system speeds up many of the CPU2000 benchmark programs having large numbers of D-Cache misses through dynamically deployed cache prefetching. For other applications that don’t benefit from our runtime optimization, the average cost is only 2% of execution time. We present this lightweight system as an example of using existing hardware and software to deploy speculative optimizations to improve a program’s runtime performance.
Modulation of translation by the 5' leader sequence of the mRNA encoding murine tissue inhibitor of metalloproteinases. (1990)

Murine tissue inhibitor of metalloproteinases (TIMP) is a Mr 28,000 secreted glycoprotein. The nucleotide sequence has been determined previously, and evidence for a multiplicity of TIMP transcripts presented. The longest TIMP transcript contains a small open reading frame (ORF) which is upstream of and overlaps the TIMP ORF, whereas the shorter inducible transcripts lack the AUG start codon of the upstream putative ORF. Serum stimulation of quiescent fibroblasts selectively enhances the abundance of the shorter transcripts (Edwards, D. R., Waterhouse, P., Holman, M. L., and Denhardt, D. T. (1986) Nucleic Acids Res. 14, 8863-8878). Here we have used an in vitro transcription/translation system to determine the effect of the upstream region on the efficiency of TIMP translation. TIMP transcripts either containing or lacking a segment including the AUG of the 5' ORF were generated by SP6 polymerase, and equal amounts of these transcripts were translated in reticulocyte lysates. TIMP synthesized in vitro was immunoprecipitable by an antiserum raised against a recombinant TIMP protein. TIMP was translated 3-fold more efficiently from the 5'-truncated transcript, consistent with the possibility that induction of shorter, more efficiently translated, TIMP transcripts are an important means of amplifying TIMP expression in response to serum.
Efficient Tandem Polymer Solar Cells Fabricated by All-Solution Processing (2007)

Tandem solar cells, in which two solar cells with different absorption characteristics are linked to use a wider range of the solar spectrum, were fabricated with each layer processed from solution with the use of bulk heterojunction materials comprising semiconducting polymers and fullerene derivatives. A transparent titanium oxide (TiO(x)) layer separates and connects the front cell and the back cell. The TiO(x) layer serves as an electron transport and collecting layer for the first cell and as a stable foundation that enables the fabrication of the second cell to complete the tandem cell architecture. We use an inverted structure with the low band-gap polymer-fullerene composite as the charge-separating layer in the front cell and the high band-gap polymer composite as that in the back cell. Power-conversion efficiencies of more than 6% were achieved at illuminations of 200 milliwatts per square centimeter.
Inhibition of tumor cell invasion and angiogenesis by motuporamines. (2001)

Tissue invasion is an important determinant of angiogenesis and metastasis and constitutes an attractive target for cancer therapy. We have developed an assay to identify agents that inhibit invasion by mechanisms other than inhibition of cell attachment or cytotoxicity. A screen of marine sponge extracts identified motuporamines as micromolar inhibitors of invasion of basement membrane gels by MDA-231 breast carcinoma, PC-3 prostate carcinoma, and U-87 and U-251 glioma cells. Motuporamine C inhibits cell migration in monolayer cultures and impairs actin-mediated membrane ruffling at the leading edge of lamellae. Motuporamine C also reduces beta1-integrin activation, raising the possibility that it interferes with "inside-out" signaling to integrins. In addition, motuporamine C inhibits angiogenesis in an in vitro sprouting assay with human endothelial cells and an in vivo chick chorioallantoic membrane assay. The motuporamines show little or no toxicity or inhibition of cell proliferation, and they are structurally simple and easy to synthesize, making them attractive drug candidates.
The hsc70 gene which is slightly induced by heat is the main virus inducible member of the hsp70 gene family (1994)

We have found that SV40 infection of CV1 cells induces the synthesis of a 72 kDa protein that upon molecular cloning was shown to be the product of the hsc70 gene. The above gene product was found to be mainly virus inducible, in contrast to the hsp70 gene product which was mainly heat inducible. The two genes were found to be cell cycle regulated in a distinctively different manner.
Perioperative Period: Immunological Modifications (2011)

Surgical stress induces complex modifications in the hemodynamic, metabolic, neuro-hormonal and immune response of the individual. The magnitude of these alterations depends on preoperative events leading to surgery, the severity of surgical trauma, and also on post-operative/post-traumatic complications (multiple hit hypothesis). As in other conditions of tissue damage, surgery trauma is followed by an immune-inflammatory response, initiated at the site of injury by the innate immune system, followed by a compensatory anti-inflammatory (or immunosuppressive) response (CARS), involving mainly cells of the adaptive immune system, which predispose the host to septic complications. The up-regulated inflammatory response, together with a profound impairment of macrophage and cell-mediated immunity, appear to be the cause for patients&#x0027; increased susceptibility in developing subsequent sepsis after major surgery.
Real-world dosing, management, and clinical outcomes of patients (pts) with metastatic pancreatic adenocarcinoma (mPDAC) treated with liposomal irinotecan. (2020)

e16780 Background: Pancreatic cancer remains one of the most lethal cancers in the United States (US) with a 5-year relative survival of 10%. Liposomal irinotecan is a topoisomerase inhibitor indicated, in combination with 5-fluorouracil and leucovorin, for pts with mPDAC following disease progression on gemcitabine-based therapy. This study examines the real-world use and therapeutic management of pts with mPDAC treated with liposomal irinotecan. Methods: This retrospective observational study utilized the Flatiron Health EHR-derived de-identified database from over 280 cancer clinics in the US. Data were analyzed for adult pts with mPDAC treated with liposomal irinotecan based regimens between Nov 2015 and Oct 2019. Pts were categorized into two starting dose groups: 70mg/m 2 and &lt; 65mg/m 2 . Pt characteristics, overall survival (OS), duration of treatment (DOT), and impact of dose reductions (DR, reduction ≥ 7mg/m 2 ) were assessed among pts who received ≥3 cycles of treatment (tx). Results: Of the 532 pts (median age: 69y, IQR: 62-75) included in the study, 95 (18%) had an ECOG score of 2+ at tx initiation. Of the 184 pts (69y, 42 – 84) that did not receive 3 cycles of tx, 47 (25%) had an ECOG score of 2+ and 83 (45%) had two or more prior lines of tx. 348 pts (69y, 43 – 85) received ≥3 cycles of tx. 116 (33%) pts had two or more prior lines of tx, 209 (60%) had an ECOG score of 0-1, 48 (14%) had an ECOG score of 2+, and 91 (26%) had missing scores. 220 (63%) initiated tx at 70mg/m 2 and 128 (37%) initiated at &lt; 65mg/m 2 . 83 (38%) 70mg/m 2 and 26 (20%) &lt; 65mg/m 2 pts experienced a DR during tx. 43 (52%) and 14 (54%) of the DRs occurred within the first 6 wks of tx in the 70mg/m 2 and &lt; 65mg/m 2 cohorts, respectively. Median DOT was 12.6 weeks for 70mg/mg 2 and 9.1 wks for &lt; 65mg/m 2 pts; DOT was longer among pts with a DR: 19.0 wks and 16.1 wks, respectively. Median OS (mOS) was 7.2 months (95% CI: 6.2 – 8.1) and 6.2 mos (5.0 – 7.4) for pts receiving 70mg/m 2 and &lt; 65mg/m 2 , respectively. mOS for pts with a DR was 8.9 mos (7.3 – 10.8) and 7.7 mos (5.0 – 14.9) for pts receiving 70mg/m 2 and &lt; 65mg/m 2 , respectively. mOS for pts with no DR was 6.0 mos (4.8 – 7.2) and 6.0 mos (4.7 - 7.2) for those receiving 70mg/m 2 and &lt; 65mg/m 2 , respectively. Conclusions: In this descriptive study among pts who were able to receive ≥3 cycles of liposomal irinotecan and remain on tx for ≥4 wks, DRs were effective in extending DOT and OS, independent of starting dose. The longest DOT and OS were observed in the pts who received 70mg/m 2 with DRs. Pts who received 70mg/m 2 and &lt; 65mg/m 2 had similar OS in the absence of DRs.
Advanced Drug Delivery (2003)

Advances in protein and peptide research have provided key information on distinctive disposition characteristics, molecular understanding of sequence determinants, details of the intricate barriers to protein absorption, and the mechanisms of distribution and elimination. The rapidly growing knowledge has allowed development of novel drug delivery strategies. By one estimate the annual sale of drug delivery products is over $40 billion and will reach $70 billion by 2006. Advanced drug delivery research has yielded products with improved therapeutic index and other improvements in safety and efficacy, such as reducing the frequency needed to provide similar or even better therapeutic responses. Drug delivery strategies have also benefited from the miniaturization of microprocessor-controlled programmable devices to fine-tune the therapeutic levels of biopharmaceuticals for chronic therapies, especially for drugs with short half-lives. Research to discover sites of drug action through proteomic modeling and high throughput screening has yielded targets that have been used to construct fusion proteins with added effector function to enhance pharmacologic activity. As the efficiency of identifying drug targets has improved and cloning technology has matured, pharmaceutical formulation and delivery have become the rate-limiting step in bringing new molecular entities to the market.
Methods for the synthesis of unnatural amino acids. (2001)

A wide variety of methods have been used to prepare unnatural amino acids. This review covers methods reported between 2000 and the early part of 2001. Some of the approaches discussed are applications of established methods, but emphasis has been given to new approaches that could be generally applicable to large-scale syntheses, including catalytic reactions such as the Strecker reaction and biological approaches.
Enhanced macrophage uptake of low density lipoprotein after self-aggregation. (1988)

Incubation of mouse peritoneal macrophages with native human low density lipoprotein (LDL) did not cause any significant storage of intracellular cholesteryl esters. However, when the LDL was subjected to brief (30-second) vortexing, it formed self-aggregates that were rapidly ingested and degraded by macrophages, converting them to cholesteryl ester-rich foam cells. Such aggregates were as potent as acetyl-LDL in stimulating cholesterol esterification in the macrophages. The degradation of LDL aggregates was strongly inhibited by cytochalasin B (85%), whereas degradation of native LDL was only weekly inhibited (23%), suggesting that uptake occurred by phagocytosis rather than pinocytosis. Several lines of evidence suggest that the phagocytic uptake depends, in part, upon the LDL receptor and not the acetyl-LDL receptor: 1) soluble, native LDL and beta-VLDL (but not acetyl-LDL) competed for uptake and degradation of LDL aggregates; 2) reductive methylation of LDL before vortexing reduced the effect of the aggregates on degradation and cholesterol esterification; 3) heparin, which inhibits binding of native LDL to its receptor, reduced the degradation of LDL aggregates. These studies show that self-aggregation of LDL markedly enhances its uptake by macrophages, probably by phagocytosis and at least, in part, via the LDL receptor. Aggregates of LDL in the artery wall--either self-aggregates or mixed aggregates including matrix components--may induce foam cell formation and favor the formation of the fatty streak.
Variations in abundances among main sequence stars in M71 (2000)

CH and CN variations are definitely present among the main sequence stars in a narrow range of luminosity just below the turnoff in the globular cluster stars. We show that the same set of C, N and O abundances that are used to fit the CN band in the CN-strong and CN-weak giants and subgiants in this cluster also successfully reproduce the behavior of the CH and CN molecular bands seen in the main sequence sample. This strongly suggests that the variations seen in M71 are primordial in origin. A hint of variation in the strength of the NaD lines is also seen in the main&#13;\nsequence sample. A range in Na abundance of about a factor of 3 is required to explain this. Strong Na among the main sequence stars appears to be correlated with strong CN, which is also characteristic&#13;\nof Na variations among red giants in globular clusters.
CXCR2: From Bench to Bedside (2012)

Leukocyte recruitment to sites of infection or tissue damage plays a crucial role for the innate immune response. Chemokine-dependent signaling in immune cells is a very important mechanism leading to integrin activation and leukocyte recruitment. CXC chemokine receptor 2 (CXCR2) is a prominent chemokine receptor on neutrophils. During the last years, several studies were performed investigating the role of CXCR2 in different diseases. Until now, many CXCR2 inhibitors are tested in animal models and clinical trials and promising results were obtained. This review gives an overview of the structure of CXCR2 and the signaling pathways that are activated following CXCR2 stimulation. We discuss in detail the role of this chemokine receptor in different disease models including acute lung injury, COPD, sepsis, and ischemia-reperfusion-injury. Furthermore, this review summarizes the results of clinical trials which used CXCR2 inhibitors.
Microfluidic Chip for Low-Flow Push-Pull Perfusion Sampling in Vivo with On-Line Analysis of Amino Acids (2005)

Multilayer soft lithography was used to prepare a poly(dimethylsiloxane) microfluidic chip that allows for in vivo sampling of amino acid neurotransmitters by low-flow push-pull perfusion. The chip incorporates a pneumatically actuated peristaltic pump to deliver artificial cerebrospinal fluid to a push-pull perfusion probe, pull sample from the probe, perform on-line derivatization with o-phthaldialdehyde, and push derivatized amino acids into the flow-gated injector of a high-speed capillary electrophoresis-laser-induced fluorescence instrument. Peristalsis was achieved by sequential actuation of six, 200 microm wide by 15 microm high control valves that drove fluid through three fluidic channels of equal dimensions. Electropherograms with 100,000 theoretical plates were acquired at approximately 20-s intervals. Relative standard deviations of peak heights were 4% in vitro, and detection limits for the excitatory amino acids were approximately 60 nM. For in vivo measurements, push-pull probes were implanted in the striatum of anesthetized rats and amino acid concentrations were monitored while sampling at 50 nL/min. o-Phosphorylethanolamine, glutamate, aspartate, taurine, glutamine, serine, and glycine were all detected with stable peak heights observed for over 4 h with relative standard deviations of 10% in vivo. Basal concentrations of glutamate were 1.9 +/- 0.6 microM (n = 4) in good agreement with similar methods. Monitoring of dynamic changes of neurotransmitters resulting from 10-min applications of 70 mM K(+) through the push channel of the pump was demonstrated. The combined system allows temporal resolution for multianalyte monitoring of approximately 45 s with spatial resolution 65-fold better than conventional microdialysis probe with 4-mm length. The system demonstrates the feasibility of sampling from a complex microenvironment with transfer to a microfluidic device for on-line analysis.
A modified Limulus amebocyte lysate test with increased sensitivity for detection of bacterial endotoxin. (1989)

We have developed a simple modification of the chromogenic Limulus amebocyte lysate test that increases the sensitivity for the detection of bacterial endotoxins. In this assay, free paranitroaniline, cleaved from synthetic chromogenic substrates by proteases that were generated by Limulus lysate after incubation with endotoxin, was then derived. Derivation was with p-dimethylaminocinnamaldehyde in the presence of strong acid, forming a stable Schiff base end product with much greater molar absorbancy than the parent chromogen. Conditions (times and temperatures of incubations, concentrations of reagents) for the augmented chromogenic procedure were optimized. A ten-fold or greater increase in sensitivity for bacterial endotoxin was obtained with the modified assay as compared with the standard chromogenic Limulus test, with unequivocal detection of endotoxin concentrations of less than 100 pg/ml. The greater sensitivity of this modified Limulus test increases its usefulness for a wide range of research applications and clinical investigations.