gebhart/patrepeval huggingface dataset:
Refined x-ray structure of papain.E-64-c complex at 2.1-A resolution. (1991)

E-64-c, a synthetic cysteine protease inhibitor designed from E-64, binds to papain through a thioether covalent bond. The x-ray diffraction data for 2.1-A resolution were used to determine the three-dimensional structure of this complex and refined it to R = 0.159. 0.159. In the complex structure, the configurational conversion from S to R took place on the epoxy carbon of E-64-c, implying that the nucleophilic attack of the Cys-25 thiol group occurs at the opposite side of the epoxy oxygen atom. The leucyl and isoamylamide groups of E-64-c were strongly fixed to papain S subsites by specific interactions, including hydrogen bonding to the Gly-66 residue. The carboxyl-terminal anion of E-64-c formed an electrostatic interaction with the protonated His-159 imidazole ring (O-...HN+ = 3.76 A) and consequently prevented the participation of this residue in the hydrolytic charge-relay system. No significant distortion caused by the binding of E-64-c was shown in the secondary structure of papain. It is important to note that inhibitor and substrate have opposite binding modes for the peptide groups. The possible relationship between the binding mode and inhibitory activity is discussed on the basis of the crystal structure of this complex.
Recent Advances in the Search for the μ-Opioidergic System: Differential Antinociceptive Effects Induced by Intrathecally-Administered Endomorphin-1 and Endomorphin-2 in Mice (2002)

Two highly selective μ-opioid receptor (MOP-R) agonists, endomorphin-1 (EM-1) and endomorphin-2 (EM-2), have been identified and postulated to be endogenous ligands for MOP-R. Experiments were designed to determine the involvement of subtypes of MOP-R on the antinociceptive effects of EM-1 or EM-2 using the paw withdrawal test. The intrathecal (i.t.) injection of EM-1 and EM-2 produced dose-dependent antinociception in mice 1 min after the injection. Subcutaneous (s.c.) pretreatment with naloxon-azine (NLZ), a selective MOP1-R antagonist, dose-dependently antagonized the antinociceptive effect of EMs. The antinociceptive effect of EM-2 was more sensitive to NLZ than that of EM-1. The selective heroin/morphine-6β-glucuronide antagonist 3-methoxynaltrexone (3-MNT) blocked EM-2-induced anti-nociception, but not EM-1-induced antinociception. The dose-response curve of EM-2 was shifted threefold to the right by pretreatment with s.c. 3-MNT at a dosage of 0.25 mg /kg. EM-2-induced antinociception was attenuated by pretreatment with s.c. nor-binaltorphimine and naltrindole, whereas the effect of EM-1 was not affected. Moreover, the antinociceptive effect of EM-2 was attenuated by i.t. pretreatment with antisera against dynorphin A(1 - 17) or methionine-enkephalin. These results suggest that EM-2-induced antinociception may be mediated by the subtype of MOP-R, which is sensitive to NLZ and 3-MNT, and by subsequent release of dynorphin A(1 - 17) and methionine-enkephalin in the spinal cord.
Mutation of R555 in CFTR-delta F508 enhances function and partially corrects defective processing. (1996)

The most common cystic fibrosis mutation deletes phenylalanine 508 in CFTR (CFTR-F508). This mutation causes the loss of CFTR Cl- channel activity by disrupting biosynthetic processing so that mutant protein does not reach the plasma membrane. It also decreases the rate at which mutant channels open. To identify second-site mutations that could reverse the effects of delta F508, we used a chimeric yeast STE6/CFTR system bearing the delta F508 mutation. This chimera manifests defective mating. After mutagenesis of the first nucleotide-binding domain, we found that mutation R555K partially restored mating. However, it also increased mating in the chimera lacking the delta F508 mutation. When we introduced the R555K mutation into human CFTR-delta F508, we found that the loss of apical Cl- current caused by delta F508 was partially restored, predominantly due to a partial correction of the delta F508 processing defect. Analysis of single CFTR Cl- channels showed that the R555K mutation did not correct the prolonged closed time associated with delta F508, rather it increased activity of both wild-type and delta F508 channels by prolonging the duration of bursts of activity. These data suggest that the region around residue R555 in the first nucleotide-binding domain is important both in determining the ability of the delta F508 protein to be properly processed and in determining channel function.
Biological behavior of human breast carcinoma-associated antigens expressed during cellular proliferation. (1983)

The cell surface-binding properties of two murine monoclonal antibodies reactive with human mammary tumor cells are described. Fluorescence-activated cell sorter analyses demonstrate that both monoclonal antibodies, B6.2 and B38.1, are reactive with the surface of the majority of human breast tumor cell lines tested but are unreactive with a variety of normal human cell lines, melanomas, sarcomas, and lymphoid tumors. Antibody B6.2 was also reactive with selective carcinomas, while antibody B38.1 showed even broader reactivity. The two monoclonal antibodies were unreactive with the surface of a variety of normal human tissues obtained at biopsy, including lymph nodes, bone marrow, and spleen, but were reactive with mammary tumor cells obtained from four of six pleural effusions. Surface binding to mammary tumor cells by both monoclonal antibodies was shown to decrease during density-dependent arrest; further cell cycle analysis demonstrated differential antibody surface binding during S phase. Prolonged exposure of mammary tumor cells to antibody showed no evidence of antigen capping or internalization. Both monoclonal antibodies were shown to lyse mammary tumor cells in antibody-dependent cell-mediated cytotoxicity.
S-Nitrosothiol-Modified Dendrimers as Nitric Oxide Delivery Vehicles (2008)

The synthesis and characterization of two generation-4 polyamidoamine (PAMAM) dendrimers with S-nitrosothiol exteriors are reported. The hyperbranched macromolecules were modified with either N-acetyl-D, L-penicillamine (NAP) or N-acetyl-L-cysteine (NACys) and analyzed via 1H and 13C NMR, UV absorption spectroscopy, MALDI-TOF mass spectrometry, and size exclusion chromatography. Treatment of the dendritic thiols with nitrite solutions yielded the corresponding S-nitrosothiol nitric oxide (NO) donors (G4-SNAP, G4-NACysNO). Chemiluminescent NO detection demonstrated that the dendrimers were capable of storing approximately 2 micromol NO x mg (-1) when exposed to triggers of S-nitrosothiol decomposition (e.g., light and copper). The kinetics of NO release were found to be highly dependent on the structure of the nitrosothiol (i.e., tertiary vs primary) and exhibited similar NO release characteristics to classical small molecule nitrosothiols reported in the literature. As a demonstration of utility, the ability of G4-SNAP to inhibit thrombin-mediated platelet aggregation was assayed. At equivalent nitrosothiol concentrations (25 microM), the G4-SNAP dendrimer resulted in a 62% inhibition of platelet aggregation, compared to only 17% for the small molecule NO donor. The multivalent NO storage, the dendritic effects exerted on nitrosothiol stability and reactivity, and the utility of dendrimers as drug delivery vehicles highlight the potential of these constructs as clinically useful S-nitrosothiol-based therapeutics.
Blind separation of multiple co-channel BPSK signals arriving at an antenna array (1995)

In this letter, we propose a method for blind separation of d co-channel BPSK signals arriving at an antenna array. Our method involves two steps. In the first step, the received data vectors at the output of the array is grouped into 2/sup d/ clusters. In the second step, we assign the 2/sup d/ d-tuples with /spl plusmn/1 elements to these clusters in a consistent fashion. From the knowledge of the cluster to which a data vector belongs, we estimate the bits transmitted at that instant. Computer simulations are used to study the performance of our method.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Hybrid DCF Supporting Hybrid Antennas in a WLAN (2006)

Hybrid distributed coordination function (H-DCF), a modified medium access control protocol of IEEE 802.11, is proposed in this paper to support hybrid antennas, i.e., smart adaptive array antennas and normal omni-directional antennas in one WLAN. Nodes equipped with smart antennas follow directional DCF (D-DCF) and nodes equipped with omnidirectional antennas follow DCF. In D-DCF, before sending any data-frames, the sender and receiver node transmit its pilot sequence respectively by means of omni-directional RTS/omni-directional CTS (ORTS/OCTS) handshake mechanism. Based on the pilot, the directional beam can be formed by the smart antenna. Then the sender can transmit its data-frame in the directional mode. Based on virtual carrier sense mechanism, the omni-directional transmission between the sender and receiver cannot interfere with the other nodes. When the sender and receiver communicate in the directional mode, the other nodes can contend the channel to send their data-frames. Hence, D-DCF supports space division multiplexing. D-DCF is compatibility with DCF by means of ORTS/CTS or RTS/OCTS mechanism. Moreover, D-DCF supports service differentiation. Smart antennas have a higher priority to access channel than normal antennas by differentiating the contention parameters, such as initial contention window size, the maximum backoff stage and retry limit. A simple analytical model is presented to compute saturation throughput and bandwidth. Simulation results show that H-DCF can support hybrid antenna system effectively and provide much higher network throughput, lower delay and jitter than DCF does, and that the analytical model is valid
A Simple and Convenient Method for the Selective N-Acylations of Cytosine Nucleosides (1989)

Abstract A simple procedure for the selective N-acylation of cytosine nucleosides has been developed by reacting the appropriate nucleoside with acid anhydrides at room temperature employing N,N-dimethylformamide as the solvent.
Biodegradable hydrophobic–hydrophilic hybrid hydrogels: swelling behavior and controlled drug release (2008)

The objective of this work was to investigate a new family of hydrophobic-hydrophilic biodegradable hybrid hydrogels as drug carriers. A series of hydrophobic-hydrophilic biodegradable hybrid hydrogels was formulated via photo means from hydrophobic three-arm poly (epsilon-caprolactone) maleic acid (PGCL-Ma) and hydrophilic dextran maleic acid (Dex-Ma) precursors over a wide range of the two precursors' feed ratio (PGCL-Ma/Dex-Ma at 100:0, 70:30, 50:50, 30:70 and 0:100). A low-molecular-weight and hydrophilic drug, the alpha-7 agonist cocaine methiodide, was used as the model drug for the release study from the hybrid hydrogels in pH 7.4 phosphate buffer solution at 37 degrees C. The swelling data of these hybrid hydrogels depended on the hydrophobic to hydrophilic precursors' feed ratio, and there were several-fold differences in swelling ratios between a pure hydrophilic Dex-Ma and a pure hydrophobic PGCL-Ma hydrogels. The presence of the hydrophobic PGCL-Ma component significantly reduced the initial burst swelling of the hybrid hydrogels. Depending on the two precursors' feed ratios, the swelling data during the early period obeyed either Fickian diffusion (for 50:50 PGCL-Ma/Dex-Ma hydrogel), non-Fickian or anomalous transport (for 70:30 and 100:0 PGCL-Ma/Dex-Ma), or relaxation-controlled (for 30:70 and 0:100 PGCL-Ma/Dex-Ma). A wide range of cocaine methiodide release profiles was achieved by controlling hydrophobic to hydrophilic precursors' feed ratios. Initial drug burst release was significantly reduced as the concentration of the hydrophobic PGCL-Ma component increased in the hybrid hydrogels. The bulk of cocaine methiodide released during the 160-h period was via diffusion-controlled mechanism, while degradation-controlled mechanism dominated thereafter.
Emission color control from blue to red with nanocolumn diameter of InGaN/GaN nanocolumn arrays grown on same substrate (2010)

A novel technology for controlling the In composition of InGaN quantum wells on the same wafer was developed, which paved the way for the monolithic integration of three-primary-color nano-light-emitting diodes. In the experiment, InGaN/GaN multiple quantum well nanocolumn arrays with nanocolumn diameters from 137 to 270 nm were prepared on the same substrate with the Ti-mask selective area growth by rf-plasma-assisted molecular beam epitaxy. The emission color changed from blue to red (from 479 to 632 nm in wavelength) with increasing nanocolumn diameter. The emission color change mechanism was clearly explained by the beam shadow effect of the neighboring nanocolumns.
Structural organization of the human kininogen gene and a model for its evolution. (1985)

The entire human kininogen gene has been isolated as a set of overlapping genomic DNA fragments, and the 11 exons encompassing approximately 27 kilobase pairs have been mapped by restriction enzyme analysis and nucleotide sequence determination. The nine 5'-terminal exons encode the 5'-untranslated region and the protein-coding region for the signal peptide and the heavy chain, which are common for high molecular weight (HMW) and low molecular weight (LMW) prekininogen mRNAs. Exon 10 consists of the common sequence for bradykinin and the immediately following unique sequence for HMW prekininogen mRNA. Exon 11 is then located following a 90-nucleotide sequence downstream from exon 10 and precisely specifies the sequence unique to LMW prekininogen mRNA. This, together with the hybridization analysis of total human cellular DNA, leads us to conclude that human HMW and LMW prekininogen mRNAs are produced from a single gene as a consequence of alternative RNA processing events. The structural analysis of the kininogen gene also shows that each of the nine 5'-terminal exons discretely specifies the nine protein domains observed in the amino-terminal portion of the kininogens. Furthermore, these nine genetic domains can be characterized by a thrice repeated pattern of three genetic segments, and two sets of these three domains, encompassing exons 3-5 and exons 6-8, are most closely related to each other. Therefore, we have proposed two successive duplication mechanisms as a model for the generation of the structure of the kininogen gene.
Markerless lung tumor tracking and trajectory reconstruction using rotational cone-beam projections: a feasibility study (2010)

Algorithms for direct tumor tracking in rotational cone-beam projections and for reconstruction of phase-binned 3D tumor trajectories were developed. The feasibility of the algorithm was demonstrated on a digital phantom, a physical phantom and two patients. Tracking results were obtained by comparing reference templates generated from 4DCT to rotational cone-beam projections. The 95th percentile absolute errors (e(95)) in phantom tracking results did not exceed 1.7 mm in either imager dimension, while e(95) in the patients was 3.3 mm or less. Accurate phase-binned trajectories were reconstructed in each case, with 3D maximum errors of no more than 1.0 mm in the phantoms and 2.0 mm in the patients. This work shows the feasibility of a direct tumor tracking technique for rotational images, and demonstrates that an accurate 3D tumor trajectory can be reconstructed from relatively less accurate tracking results. The ability to reconstruct the tumor's average trajectory from a 3D cone-beam CT scan on the day of treatment could allow for better patient setup and quality assurance, while direct tumor tracking in rotational projections could be clinically useful for rotational therapy such as volumetric modulated arc therapy (VMAT).
Diels‐alder cycloadditions of diene‐substituted N‐ethoxycarbonyl‐2‐methyl‐1,2‐dihydropyridines with N‐phenylmaleimide (1985)

Abstract The ten possible substitution patterns for N ‐Ethoxycarbonyl‐2‐methyl‐1,2‐dihydropyridines 5 in which one or two olefinic sites are alkyl substituted were synthesized and reacted with N ‐phenylmaleimide 2 to provide cycloadducts 6. N ‐Ethoxycarbonyl‐5,6‐cyclohexyl‐2‐methyl‐1,2‐dihydropyridine 51 provided the novel spirocycle 61.
Identification and characterization of enamel proteinases isolated from developing enamel. Amelogeninolytic serine proteinases are associated with enamel maturation in pig (1988)

During tooth formation nearly all of the protein matrix of enamel is removed before final mineralization. To study this process, enamel proteins and proteinases were extracted from pig enamel at different stages of tooth development. In the enamel maturation zones, the major enamel matrix proteins, the amelogenins, were rapidly processed and removed. Possibly associated with this process in vivo are two groups of proteinases which were identified in the enamel extracts by enzymography using amelogenin-substrate and gelatin-substrate polyacrylamide gels and by the degradation in vitro of guanidinium chloride-extracted amelogenins. One group of proteinases with gelatinolytic activity consisted of several neutral metalloendoproteinases having Mr values from 62,000 to 130,000. These proteinases were inactive against amelogenins, casein and albumin, and were present in approximately equal proportions in enamel at all developmental stages. In the other group, two serine proteinases, with apparent non-reduced Mr of 31,000 and 36,000 exhibited amelogeninolytic activity. The substrate preference of the enamel serine proteinases was indicated by their limited degradation of casein and their inability to degrade gelatin and albumin. Contrasting with the distribution of the metalloendoproteinase enzymes, the serine proteinases were found only in the enamel scrapings taken from late-maturing enamel. The amelogenin degradation patterns in vivo, observed in the enamel scrapings, were similar to those produced in assays in vitro using partially purified fractions of enamel proteinases and amelogenin substrate. Together, these data strongly indicate an important role for the serine proteinases, and possibly the gelatinolytic proteinases, in the organized processing of the enamel protein matrix during enamel formation.
Mapping the confined optical field in a microcavity via the emission from a conjugated polymer (1997)

The distribution of a confined optical field within a microcavity was determined using a thin layer of the fluorescent polymer PPV as a probe of the local-field amplitude. It is shown that the photoluminescence emission intensity from the cavity is a function of the axial position of the polymer, and confirms that a microcavity can be used to control spontaneous emission.
Phase I Clinical Trial of the Immunocytokine EMD 273063 in Melanoma Patients (2004)

Treatment with the immunocytokine EMD 273063 induced immune activation and was associated with reversible clinical toxicities at the MTD of 7.5 mg/m2/d in melanoma patients.
Effects of profession and facility type on research utilization by rehabilitation professionals. (2004)

Information about the use of research by rehabilitation professionals to make clinical decisions in everyday practice is limited. This study compared perceived research use and knowledge sources across professions, practice situations, and work environments. Participants were 165 randomly selected Canadian occupational therapists, physical therapists, and speech-language pathologists. Self-report ratings during an interview, an interviewer rating, and questionnaire scores (Edmonton Research Orientation Survey, General Use of Research, Knowledge Acquisition Survey) were compared. Speech-language pathologists had the most education and the highest research use ratings. Research use was highest during program planning. Programs to encourage research use must consider the research available to guide practice and therapists' education level. Facility size and location (rural, urban) do not affect perceived research use.
Neutrophils in the tumor microenvironment: trying to heal the wound that cannot heal (2016)

Neutrophils are the first responders to infection and injury and are critical for antimicrobial host defense. Through the generation of reactive oxidants, activation of granular constituents and neutrophil extracellular traps, neutrophils target microbes and prevent their dissemination. While these pathways are beneficial in the context of trauma and infection, their off-target effects in the context of tumor are variable. Tumor-derived factors have been shown to reprogram the marrow, skewing toward the expansion of myelopoiesis. This can result in stimulation of both neutrophilic leukocytosis and the release of immature granulocytic populations that accumulate in circulation and in the tumor microenvironment. While activated neutrophils have been shown to kill tumor cells, there is growing evidence for neutrophil activation driving tumor progression and metastasis through a number of pathways, including stimulation of thrombosis and angiogenesis, stromal remodeling, and impairment of T cell-dependent anti-tumor immunity. There is also growing appreciation of neutrophil heterogeneity in cancer, with distinct neutrophil populations promoting cancer control or progression. In addition to the effects of tumor on neutrophil responses, anti-neoplastic treatment, including surgery, chemotherapy, and growth factors, can influence neutrophil responses. Future directions for research are expected to result in more mechanistic knowledge of neutrophil biology in the tumor microenvironment that may be exploited as prognostic biomarkers and therapeutic targets.
Amplified detection of viral nucleic acid at subattomole levels using Q beta replicase. (1990)

A sensitive, amplified assay for HIV-1 pol region RNA was developed using RNA probes which are replicated by the RNA-dependent RNA polymerase, Q beta replicase. A synthetic target RNA was hybridized in cell lysates prepared with guanidine thiocyanate with an RNA reporter probe and four deoxyoligonucleotide "capture" probes. The RNA reporter probe was a recombinant MDV RNA molecule generated by transcription from a cloned cDNA template. Capture probes are synthetic oligonucleotides that are complementary to the target nucleic acid and that bear 3' poly d(A) tails. The ternary hybrids (of target RNA with capture probe and reporter probe) were captured on oligo d(T)-derivatized paramagnetic particles by hybridization with the d(A) tails of the capture probes. Non-hybridized reporter probes were removed by washing and successively eluting and recapturing the ternary hybrids on fresh particles. After three cycles of elution and capture, the hybrids were eluted in a low ionic strength buffer and the MDV RNA reporter probes were amplified directly by Q beta replicase. Amplified product RNA was detected by fluorescence using propidium iodide. The assay detects one femtogram (600 molecules) of a synthetic target RNA containing the pol region of HIV-1. The complete assay takes about 2.5 hours.