gebhart/patrepeval huggingface dataset:
Interferon α/β and Interleukin 12 Responses to Viral Infections (2002)

Interferon (IFN)-alpha/beta and interleukin (IL)-12 are cytokines critical in defense against viruses, but their cellular sources and mechanisms of regulation for in vivo expression remain poorly characterized. The studies presented here identified a novel subset of dendritic cells (DCs) as major producers of the cytokines during murine cytomegalovirus (MCMV) but not lymphocytic choriomeningitis virus (LCMV) infections. These DCs differed from those activated by Toxoplasma antigen but were related to plasmacytoid cells, as assessed by their CD8alpha(+)Ly6G/C(+)CD11b(-) phenotype. Another DC subset (CD8alpha(2)Ly6G/C(-)CD11b(+)) also contributed to IL-12 production in MCMV-infected immunocompetent mice, modestly. However, it dramatically increased IL-12 expression in the absence of IFN-alpha/beta functions. Conversely, IFN-alpha/beta production was greatly reduced under these conditions. Thus, a cross-regulation of DC subset cytokine responses was defined, whereby secretion of type I IFNs by CD8alpha(+) DCs resulted in responses limiting IL-12 expression by CD11b(+) DCs but enhancing overall IFN-alpha/beta production. Taken together, these data indicate that CD8alpha(+)Ly6G/C(+)CD11b(-) DCs play important roles in limiting viral replication and regulating immune responses, through cytokine production, in some but not all viral infections. They also illustrate the plasticity of cellular sources for innate cytokines in vivo and provide new insights into the roles of IFNs in shaping immune responses to viruses.
Disulfide-Based Multifunctional Conjugates for Targeted Theranostic Drug Delivery (2015)

Theranostics, chemical entities designed to combine therapeutic effects and imaging capability within one molecular system, have received considerable attention in recent years. Much of this interest reflects the promise inherent in personalized medicine, including disease-targeted treatments for cancer patients. One important approach to realizing this latter promise involves the development of so-called theranostic conjugates, multicomponent constructs that selectively target cancer cells and deliver cytotoxic agents while producing a readily detectable signal that can be monitored both in vitro and in vivo. This requires the synthesis of relatively complex systems comprising imaging reporters, masked chemotherapeutic drugs, cleavable linkers, and cancer targeting ligands. Ideally, the cleavage process should take place within or near cancer cells and be activated by cellular components that are associated with cancer states or specifically expressed at a higher level in cancer cells. Among the cleavable linkers currently being explored for the construction of such localizing conjugates, disulfide bonds are particularly attractive. This is because disulfide bonds are stable in most blood pools but are efficiently cleaved by cellular thiols, including glutathione (GSH) and thioredoxin (Trx), which are generally found at elevated levels in tumors. When disulfide bonds are linked to fluorophores, changes in emission intensity or shifts in the emission maxima are typically seen upon cleavage as the result of perturbations to internal charge transfer (ICT) processes. In well-designed systems, this allows for facile imaging. In this Account, we summarize our recent studies involving disulfide-based fluorescent drug delivery conjugates, including preliminary tests of their biological utility in vitro and in vivo. To date, a variety of chemotherapeutic agents, such as doxorubicin, gemcitabine, and camptothecin, have been used to create disulfide-based conjugates, as have a number of fluorophores, including naphthalimide, coumarin, BODIPY, rhodol, and Cy7. The resulting theranostic core (drug-disulfide-fluorophore) can be further linked to any of several site-localizing entities, including galactose, folate, biotin, and the RGD (Arg-Gly-Asp) peptide sequence, to create systems with an intrinsic selectivity for cancer cells over normal cells. Site-specific cleavage by endogenous thiols serves to release the cytotoxic drug and produce an easy-to-monitor change in the fluorescence signature of the cell. On the basis of the results summarized in this Account, we propose that disulfide-based cancer-targeting theranostics may have a role to play in advancing drug discovery efforts, as well as improving our understanding of cellular uptake and drug release mechanisms.
Guidewire Stiffness: What's in a Name? (2011)

The Instructions for Use of some endovascular devices specify a wire type selected from a range of undefined "stiffness" descriptors. These descriptors have little correlation with the measured flexural modulus. Two guidewires with the description "extra stiff" can have a 5-fold difference in flexural modulus. We recommend that guidewire catalogues and packaging include the flexural modulus and that device manufacturers amend their Instructions for Use accordingly.
Computer‐aided design of a catalyst for Edman degradation utilizing substrate‐assisted catalysis (2014)

Abstract Molecular biology has been revolutionized by the miniaturization and parallelization of DNA sequencing assays previously performed on bulk samples. Many of these technologies rely on biomolecular reagents to facilitate detection, synthesis, or labeling of samples. To aid in the construction of analogous experimental approaches for proteins and peptides, we have used computer‐aided design to engineer an enzyme capable of catalyzing the cleavage step of the Edman degradation. We exploit the similarity between the sulfur nucleophile on the Edman reagent and the catalytic cysteine in a naturally occurring protease to adopt a substrate‐assisted mechanism for achieving controlled, step‐wise removal of N‐terminal amino acids. The ability to expose amino acids iteratively at the N‐terminus of peptides is a central requirement for protein sequencing techniques that utilize processive degradation of the peptide chain. While this can be easily accomplished using the chemical Edman degradation, achieving this activity enzymatically in aqueous solution removes the requirement for harsh acid catalysis, improving compatibility with low adsorption detection surfaces, such as those used in single molecule assays.
<title>Use of 8-methoxypsoralen and long-wavelength ultraviolet radiation for decontamination of platelet concentrates</title> (1992)

Transmission of viral diseases through blood products remains a problem in transfusion medicine. We have developed a photochemical decontamination system (PCD) for platelet concentrates (PC) utilizing treatment with long wavelength ultraviolet radiation (UVA, 320-400 nm) and 8-methoxypsorlan (8-MOP). This system is capable of inactivating 25-30 logs/hour of bacteria E. coli or S. aureus, 6 logs/hour of bacteriophage fd, 0.9 log/hour of bacteriophage R17, and 1.1 logs/hour of feline leukemia virus (FeLV) in PC. Immediately following 6 hours of PCD treatment, platelet integrity and function of PCD-treated and control PC were equivalent. After overnight storage, PCD-treated and control PC platelet properties were equal, but there was a slight reduction in TXB-2 production of PCD-treated PC compared to controls. Following PCD treatment, PC were stored for 48 to 96 hours. Platelet counts, morphology scores, extracellular LDH levels, aggregation response, dense body (db) content, and alpha granule (alpha g) content of PCD-treated and control PC were comparable. We assessed the ability of the PCD technique to inactivate intracellular and extracellular virus, quantified the degree of DNA adduct formation in contaminating lymphocytes, and measured the inhibition of polymerase chain reaction (PCR) mediated amplification of intracellular DNA. High titers of cell-free murine cytomegalovirus added to human platelet concentrates (final concentration 10(6)) were inactivated by PCD within 30 minutes. Cat renal fibroblasts infected at high levels with feline rhinotracheitis virus (FeRTV) were seeded into PC followed by PCD treatment with inactivation of 4.8 logs of FeRTV within 10 minutes. Purified human lymphocytes were seeded into PC and treated with PCD in the presence of 3H 8-MOP. Six hours of PCD treatment resulted in the formation of 9.3 to 12.8 8-MOP adducts per 1000 base pairs (bp) of DNA. PCR amplification of a 242 bp segment at the HLA-DQ alpha locus was examined. Inhibition of PCR DNA amplification was dependent on the numbers of 8-MOP adducts formed, and no amplification was present when greater than 12 adducts per 1000 bp were formed. These studies indicate that PCD can effectively inactivate high titers of cell-associated and cell-free virus seeded into standard human PC. The efficiency of DNA adduct formation can be quantitated, and the level of 8-MOP adduct formation in lymphocytes contaminating PC is comparable to the level of adduct formation in cellular DNA reported in the absence of platelets.
Direct studies of 1,1-diazenes. Syntheses, infrared and electronic spectra, and kinetics of the thermal decomposition of N-(2,2,6,6-tetramethylpiperidyl)nitrene and N-(2,2,5,5-tetramethylpyrrolidyl)nitrene (1982)

The syntheses, direct spectroscopic observation, and kinetics of thermal decomposition of the persistent 1,1-diazenes, N-(2,2,6,6-tetramethylpiperidyl)nitrene (4) and N-(2,2,5,5-tetramethylpyrrolidyl)nitrene (5) are reported. The electronic absorption spectrum of 4 at -78 °C reveals a structured absorption for the n,π* transition: λmax= 543 nm, λ_(0,0) = 620 nm, and εmax = 18 ± 3 in Et_2O; λmax= 541 nm and λ_(0,0) = 610 nm in CH_2Cl_2; λmax= 526 nm and λ_(0,0) = 592 nm in i-PrOH. The infrared spectrum of 4 shows a strong absorption at 1595 cm^(-1)(R_2^(14) = ^(14)N stretch) and provides evidence that 1,1-diazene 4 has considerable N=N double-bond character in the ground state. The infrared spectrum of 5 shows a strong absorption at 1638 cm^(-1)(R_2^(14) = ^(14)N stretch). The unimolecular rate of thermal decomposition of 4 is sensitive to solvent, the rate increasing with decreasing solvent polarity (k_(re1) = 1.0, 1.7, 4.8 in THF, Et_2O, and hexane, respectively). The activation parameters for the unimolecular fragmentation of 1,1-diazene 4 are as follows: log A = 11.6 • 0.5 and E_a= 16.9 ± 0.7 kcal mo1^(-1) in hexane; log A = 13.7 ± 0.3 and E_a = 20.0 ± 0.4 kcal mo1^(-1) in Et_2O; log A = 13.6 ± 0.3 and E_a = 20.l ± 0.4 kcal mol^(-1) in THF. The activation parameters for the bimolecular dimerization of 4 are log A = 3.8 ± 0.7 and E_a = 6.4 ± 0.9 kcal mol^(-1) in CDC1_3. The unimolecular rate of thermal decomposition of 5 is sensitive to solvent, the rate increasing with decreasing solvent polarity, k_(rel) = 1.0, 2.4, and 5.1 for THF, Et_2O, and hexane, respectively. The activation parameters for the unimolecular fragmentation of 1,1-diazene 5 are as follows: log A = 10.9 ± 0.3 and E_a = 16.8 ± 0.5 kcal mo1^(-1) in hexane; log A = 12.4 ± 0.4 and E_a = 19.0 ± 0.6 kcal mo1^(-1) in Et_2O; log A= 12.1 ± 0.3 and E_a = 19.l ± 0.4 kcal mo1^(-1) in THF. At -41.1 °C the bimolecular rate constant for the dimerization of 5 is 8.5 X 10^(-5) L/(mol s), 90 times slower than that found for 4. The change from a six-membered to a five-membered ring 1,1-diazene causes a shift to higher energy for the n,π'* transition and a shift to increased wavenumber (cm^(-1)) for the N=N stretching frequency, not unlike that of the isoelectronic ketones, tetramethylcyclohexanone and tetramethylcyclopentanone. Similar E_a values for the unimolecular thermal fragmentation of 4 and 5 may indicate the strain energy difference between 4 and 5 is also small. An approximate value of 30.5 kcal mo1^(-1) for the heat of formation of the 1,1-diazene 5 is estimated, indicating the 1,1-diazene 5 has a higher heat of formation than the cis-1,2-diazene isomer by 20 kcal mo1^(-1).
Synthetic analogues of polynucleotides. Part V. Analogues of trinucleoside diphosphates containing carboxymethylthymidine (1971)

Analogues of trinucleoside diphosphates in which the nucleoside units are linked by acetate ester linkages (·O·CH2·-CO2·), instead of the phosphodiester linkages of the natural compounds, have been synthesised. 3′-O-Carboxy-methyl-5′-O-tritylthymidine was condensed with the 2-cyanoethyl ester of 3′-O-carboxymethylthymidine to give a compound in which two thymidine residues were linked by an acetate ester linkage (II; R1= trityl, R2= CH2·-CH2·CN). The cyanoethyl group was selectively removed with potassium t-butoxide in dimethylformamide and the resulting carboxylic acid was condensed with 2′,3′-O-isopropylidene- or 2′,3′-O-anisylidene-ribonucleosides to give, after removal of the acid-labile protecting groups, thymidinylacetyl-(3′→ 5′)-thymidinylacetyl-(3′→ 5′)-ribonucleosides (III; R1= R2= R3= H), where the ribonucleosides were adenosine, uridine, guanosine, inosine, and cytidine. Evidence for base stacking in these analogues was obtained by u.v. and n.m.r. spectroscopy.
Semliki Forest virus E2 envelope epitopes induce a nonneutralizing humoral response which protects mice against lethal challenge (1989)

Along the 422 amino acids of the Semliki Forest virus (SFV) E2 envelope glycoprotein, we identified 13 peptide cassettes (ranging in size from 15 to 25 amino acids and designated A through N) that contain hydrophilic sequences flanked by amino acid sequences conserved in the E2 envelopes of the alphavirus family. Six peptide blocks containing either a single cassette or two to three contiguous cassettes (A, BC, DE, FG, HIK, and LMN) were produced in Escherichia coli as recombinant proteins fused to the N terminus of beta-galactosidase. All of the SFV E2 recombinant polypeptides except A-beta-galactosidase were recognized on Western blots (immunoblots) by anti-SFV polyclonal antisera. In addition, these five recombinant proteins induced in mice antibodies that interacted specifically with SFV E2 protein on Western blots as well as with the intact virions in an enzyme-linked immunosorbent assay. The six hybrid proteins were used to vaccinate mice and were tested for the ability to confer resistance against lethal doses of SFV. Peptides BC and HIK, located at amino acid positions 114 to 149 and 216 to 288, respectively, of E2, protected partially (40 to 60%) against SFV challenge. A third peptide, LMN, located between amino acid positions 289 and 352, rendered mice totally resistant to an SFV challenge of 250 50% lethal doses. The partially protective effects of the BC and HIK cassettes and the high efficacy of the LMN cassette were consistently demonstrated, independent of the adjuvant (complete Freund or alum), immunization protocol, and strain of mice used. None of the antisera raised against any given cassette could neutralize the virus in an in vitro tissue culture assay or in a plaque reduction neutralization test. Nevertheless, passive transfer experiments demonstrated that in the case of LMN, the protective effect was mainly of a humoral nature.
Highly Selective Decarbonylation of 5‐(Hydroxymethyl)furfural in the Presence of Compressed Carbon Dioxide (2011)

Less is more: The integrated development and optimization of catalysts and reaction media led to a highly selective decarbonylation of 5-(hydroxymethyl)furfural (HMF) to furfuryl alcohol (FFA) with an iridium/phosphine catalyst in the presence of compressed carbon dioxide. Subsequent hydrogenation over ruthenium nanoparticles (RuNPs) led to tetrahydrofurfuryl alcohol (THFA), a possible solvent for the decarbonylation reaction (see scheme). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Coronary artery disease regression. Convincing evidence for the benefit of aggressive lipoprotein management. (1994)

These trials present convincing evidence that aggressive lipoprotein manipulation can result in improved arteriographic measurements and fewer cardiovascular events in a relatively short period of time of 2 to 4 years. Extrapolation of this information to the larger population with known coronary artery disease suggests that directed lipoprotein manipulation can reduce clinical events in a cost-effective manner.
Mutation Detection in Colorectal Cancers: Direct Sequencing of DNA Mismatch Repair Genes (2003)

The detection of unknown mutations has proved complex and time consuming, and this is certainly the case for HNPCC. Germline mutations have been detected in five of the six human DNA mismatch repair genes (in hMLH1, hMSH2, hMSH6, hPMS1, hPMS2, but not hMSH3) in HNPCC patients (1-7) with hMLH1 and hMSH2 being the most frequently affected (8-9). Point mutations resulting in missense, nonsense and frameshift alterations are found in HNPCC, as well as mutations leading to splicing alterations (9). The detection of mutations in these genes has relied upon direct sequencing of genomic DNA. Scanning or prescreening methods have been investigated (12-15), but at this stage direct sequencing is the gold standard by which these methods are generally judged. One caveat however, is that this method does not detect deletions that span exons or entire genes, the frequency of which may be up to 6.5% of HNPCC cases (16). To be rigorous, it would be prudent to include direct sequencing along with Southern analysis. This chapter will focus on the direct sequencing of hMLH1 and hMSH2, although the overall strategy may also be used for the analysis of the other mismatch repair genes.
Effects of Glial Transplantation on Functional Recovery following Acute Spinal Cord Injury (2005)

Numerous efforts have been made to maximize the efficacy of treatment for spinal cord injury (SCI). Recently, oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells have been reported to remyelinate focal areas of demyelinated spinal cord in adult rats. We conducted a study to investigate the therapeutic potential of transplantation of O-2A cells in a rat model of acute SCI. SCI was induced with an NYU Impactor at T9 of rats. O-2A cells labeled with bromodeoxyuridine (BrdU) were transplanted into sites of SCI at 1 week after the induction of SCI. At 6 weeks after cell transplantation, a behavioral test showed significant functional improvement in animals that had received O-2A-cell transplants as compared to animals given cell-culture medium alone. An electrophysiological study revealed that the transplants did not improve the amplitude or latency of somatosensory evoked potentials, but a recording of motor evoked potentials showed that the latency of these potentials in the O-2A-cell-transplant group was significantly shorter than that in the group treated with cell-culture medium. Following transplantation of BrdU-labeled O-2A cells, cells positive for BrdU were detected at and near sites of SCI. Cells labeled for both BrdU and 2',3' -cyclic nucleotide-3-phosphodiesterase were also detected, showing that the transplanted O-2A cells differentiated into oligodendrocytes. By contrast, cells labeled for BrdU and glial fibrillary acidic protein, or for neuronal nuclei antigen, were not detected. Furthermore, a tract-tracing study showed that numbers of retrogradely labeled neurons increased in areas of the brain stem after O-2A-cell transplantation. The study data showed that after being transplanted into an animal with SCI, O-2A cells migrated to the area adjacent to the site of injury and differentiated into oligodendrocytes. The behavioral test and the electrophysiological and morphological studies showed that transplantation of O-2A cells may play an important role in functional recovery and the regeneration of axons after SCI.
Time-to-Digital Converter (TDC) for WiMAX ADPLL in State-of-The-Art 40-nm CMOS (2011)

WiMAX (Worldwide Interoperability for Microwave Access) is the emerging wireless technology standard of the near future, which enables high speed packet data access. To anticipate the future demands on WiMAX technology, we proposed an ADPLL (all-digital phase locked loop) solution for the WiMAX system. The developed ADPLL system has targeted frequencies from 2.3 GHz to 2.7 GHz and from 3.3 GHz to 3.8 GHz for low band and high band, respectively. In this approach, an ADPLL replaces the conventional RF synthesizer based on charge-pump architecture. There are three main components of the ADPLL system. One of them is the time-to-digital converter (TDC) system. A TDC in state-of-the-art 40 nm CMOS technology for WiMAX ADPLL system is chosen and presented in this thesis. The TDC architecture is based on a pseudo-differential structure. This architecture utilizes an inverter as a delay element and a sense amplifier flip-flop as a time comparator. In comparison, the two other TDC architectures evaluated in this thesis (two-dimensional Vernier algorithm TDC and time-windowed TDC) have very complex architectures and complex calibration methods, while the chosen TDC architecture has a simple calibration method. Moreover, this pseudo-differential TDC can meet the time resolution required by the WiMAX ADPLL system. The TDC system has been tested on a 1.2 V power supply, 33.868 MHz frequency reference clock FREF and with 4.25 GHz frequency of CKV. It is found that the power consumption is about 2.99 mW without a clock gating scheme. Moreover, it is expected that the power consumption can be reduced to 0.78 mW with a clock gating scheme. The INL and DNL of the TDC are lower than 0.4 LSB. The measured TDC resolution is around 10.84 ps - 12.55 ps. In the worst case condition, the TDC resolution of 12.55 ps will give an in-band phase noise better than the limit , which is -95 dBc/Hz as required by the WiMAX ADPLL System. The TDC core layout has an area of only 125 x 11 ?m2.
The Role of the Inherited Disorders of Hemoglobin, the First “Molecular Diseases,” in the Future of Human Genetics (2013)

Although the inherited hemoglobin disorders were the first genetic diseases to be explored at the molecular level, they still have important messages for the future of medical genetics. In particular, they can offer a better understanding of the evolutionary and population biology of genetic disease, the mechanisms that underlie the phenotypic diversity of monogenic disease, and how, by developing appropriate partnerships, richer countries can help low-income countries to evolve programs for the control and management of these diseases where, in many cases, they are particularly common.
The Pathology of the Joint Tissues and its Clinical Relevance in Prosthesis Failure (1976)

Thirty-four hip and knee total arthroplasty failures due to infection, loosening, intractable pain and dislocation were examined for synovial and capsular tissue debris. Simiquantitative assessments were made for metal polyethylene, acrylic and cellular debris and inflammation. The most important finding was that in the amounts normally shed into joints, debris particles do not appear to stimulate a polymorphonuclear response. The magnitude of this response correlates best with clinical and/or bacteriological evidence of infection. The quantity of acrylic particles could be correlated with clinical evidence of loosening. Since the correlation between infection and polymorphonuclear leukocytes, debris particles, and the reasons for failure is high, frozen section may aid the surgeon in determining the methods and timing of revision operations.