gebhart/patrepeval huggingface dataset:
Rb−129Xe spin-exchange rates due to binary and three-body collisions at high Xe pressures (1992)

We have studied the spin relaxation of $^{129}\mathrm{Xe}$ nuclei due to collisions with Rb atoms at Xe pressures of 245--1817 Torr. Our results can be characterized by two parameters, the Rb${\mathrm{\ensuremath{-}}}^{129}$Xe velocity-averaged binary spin-exchange cross section 〈\ensuremath{\sigma}v〉 and a rate ${\ensuremath{\gamma}}_{\mathit{M}}$ that characterizes spin relaxation due to van der Waals molecules. Our results complement earlier studies performed at Xe pressures of about 1 Torr and ${\mathrm{N}}_{2}$ pressures of 10--100 Torr. This work is useful for predicting spin-exchange rates between polarized Rb atoms and $^{129}\mathrm{Xe}$ nuclei.
Abnormal development of secondary lymphoid tissues in lymphotoxin β-deficient mice (1997)

The tumor necrosis factor (TNF) family cytokines lymphotoxin (LT) alpha and LTbeta form heterotrimers that are expressed on the surface of activated lymphocytes and natural killer cells; LTalpha homotrimers can be secreted as well. Mice with a disrupted LTalpha gene lack lymph nodes (LN), Peyer's patches (PP), and follicular dendritic cell (FDC) networks and reveal profound defects of the splenic architecture. However, it is unclear which of these abnormalities is the result of the absence in LTalpha homotrimers or LTalphabeta heterotrimers. To distinguish between these two possibilities, a mouse strain deficient in LTbeta was created employing Cre/loxP-mediated gene targeting. Mice deficient in LTbeta reveal severe defects in organogenesis of the lymphoid system similar to those of LTalpha-/- mice, except that mesenteric and cervical LN are present in most LTbeta-deficient mice. Both LTbeta- and LTalpha-deficient mice show significant lymphocytosis in the circulation and peritoneal cavity and lymphocytic infiltrations in lungs and liver. After immunization, PNA-positive B cell clusters were detected in the splenic white pulp of LTbeta-deficient mice, but FDC networks were severely underdeveloped. Collectively, these results indicate that LTalpha can signal independently from LTbeta in the formation of PNA-positive foci in the spleen, and especially in the development of mesenteric and cervical LN.
Patient-reported outcomes of parenteral somatostatin analogue injections in 195 patients with acromegaly (2015)

Lifelong injections of long-acting somatostatin analogues have significant burden on the functioning, well-being and daily lives of patients with acromegaly.
Multi-media information services: a laboratory study (1988)

An overview is given of the work of a research group studying advanced information services. The general form of today's information services is discussed as a baseline for considering the future, and some key technological advances (including a broadband public-switched network) that are expected to greatly influence the continuing evolution of such services are listed. A description is given of a multimedia information services laboratory, consisting of a services testbed and application prototypes, which was constructed to illustrate and study important aspects of future services. The end-to-end performance requirements for these services are examined. Two examples are given to illustrate universal communications.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Mycophenolic Acid Inhibits IL-2-Dependent T Cell Proliferation, But Not IL-2-Dependent Survival and Sensitization to Apoptosis (2002)

Mycophenolic acid (MPA), the active metabolite of the immunosuppressive drug mycophenolate mofetil, is a selective inhibitor of inosine 5'-monophosphate dehydrogenase type II, a de novo purine nucleotide synthesis enzyme expressed in T and B lymphocytes and up-regulated upon cell activation. In this study, we report that the blockade of guanosine nucleotide synthesis by MPA inhibits mitogen-induced proliferation of PBL, an effect fully reversed by addition of guanosine and shared with mizoribine, another inhibitor of inosine 5'-monophosphate dehydrogenase. Because MPA does not inhibit early TCR-mediated activation events, such as CD25 expression and IL-2 synthesis, we investigated how it interferes with cytokine-dependent proliferation and survival. In activated lymphoblasts that are dependent on IL-2 or IL-15 for their proliferation, MPA does not impair signaling events such as of the extracellular signal-regulated kinase 2 and Stat5 phosphorylation, but inhibits down-regulation of the cyclin-dependent kinase inhibitor p27(Kip1). Therefore, in activated lymphoblasts, MPA specifically interferes with cytokine-dependent signals that control cell cycle and blocks activated T cells in the mid-G(1) phase of the cell cycle. Although it blocks IL-2-mediated proliferation, MPA does not inhibit cell survival and Bcl-x(L) up-regulation by IL-2 or other cytokines whose receptors share the common gamma-chain (CD132). Finally, MPA does not interfere with IL-2-dependent acquisition of susceptibility to CD95-mediated apoptosis and degradation of cellular FLIP. Therefore, MPA has unique functional properties not shared by other immunosuppressive drugs interfering with IL-2R signaling events such as rapamycin and CD25 mAbs.
Categorization and characterization of transcript-confirmed constitutively and alternatively spliced introns and exons from human (2002)

By spliced alignment of human DNA and transcript sequence data we constructed a data set of transcript-confirmed exons and introns from 2793 genes, 796 of which (28%) were seen to have multiple isoforms. We find that over one-third of human exons can translate in more than one frame, and that this is highly correlated with G+C content. Introns containing adenosine at donor site position +3 (A3), rather than guanosine (G3), are more common in low G+C regions, while the converse is true in high G+C regions. These two classes of introns are shown to have distinct lengths, consensus sequences and correlations among splice signals, leading to the hypothesis that A3 donor sites are associated with exon definition, and G3 donor sites with intron definition. Minor classes of introns, including GC-AG, U12-type GT-AG, weak, and putative AG-dependant introns are identified and characterized. Cassette exons are more prevalent in low G+C regions, while exon isoforms are more prevalent in high G+C regions. Cassette exon events outnumber other alternative events, while exon isoform events involve truncation twice as often as extension, and occur at acceptor sites twice as often as at donor sites. Alternative splicing is usually associated with weak splice signals, and in a majority of cases, preserves the coding frame. The reported characteristics of constitutive and alternative splice signals, and the hypotheses offered regarding alternative splicing and genome organization, have important implications for experimental research into RNA processing. The 'AltExtron' data sets are available at http://www.bit.uq.edu.au/altExtron/ and http://www.ebi.ac.uk/~thanaraj/altExtron/.
In Vitro Phosphorylation of the Epidermal Growth Factor Receptor Autophosphorylation Domain by c-src: Identification of Phosphorylation Sites and c-src SH2 Domain Binding Sites (1995)

During epidermal growth factor mediated signal transduction, intracellular receptor autophosphorylation on tyrosine residues results in the localization of several SH2 domain bearing proteins, including c-src, to the plasma membrane. This process is part of a complex pathway of specific protein associations that culminates in the regulation of cell growth and mitogenesis. The SH2 domain-mediated interaction of c-src with the EGF receptor has been demonstrated, yet the precise function of c-src in EGF receptor signaling remains unclear. The phosphorylation of EGFR by c-src was studied in order to evaluate the molecular basis for this interaction. The C-terminal autophosphorylation domain of EGFR was extensively phosphorylated by c-src and EGFR kinase activities in vitro as determined by electrospay ionization mass spectrometry. The sites of phosphorylation within the autophosphorylation domain (residues 976-1186) were identified by LC/MS, LC/MS/MS, and Edman sequencing. The majority of the sites identified corresponded to the known autophosphorylation sites of EGFR. Kinetic analyses of site-specific phosphorylation were made combining very fast enzyme digests (< = or 2 min) and high-speed, perfusion chromatography. These studies revealed that Y1086 was phosphorylated to a significantly higher extent by c-src than by EGFR. Additionally, Y1101 was identified as a unique c-src phosphorylation site. The function of these phosphorylation sites with respect SH2 domain interactions was investigated by affinity chromatography/mass spectrometry. A subset of peptides corresponding to the eight possible tyrosine phosphorylation sites within the EGFR autophosphorylation domain was demonstrated to bind to the SH2 domain of c-src. Those which bound to the SH2 domain included peptides derived from EGFR sequences flanking Y992, Y1086, Y1101, and Y1148. These data indicate that specific EGF receptor c-src phosphorylation sites are also ligands for the SH2 domain of c-src. Finally, extensive c-src phosphorylation of EGFR promoted its conversion to a form that exhibits high-affinity (KD = 380 nM) and cooperative (Hill coefficient; n = 2) binding to the SH2 domain of c-src as measured by surface plasmon resonance. The identification of c-src phosphorylation sequences on EGFR as c-src SH2 binding sites supports the notion that this interaction plays a significant role in the regulation of growth factor receptor function and signal transduction.
Separation of viable T and B lymphocytes using a cytochemical stain, Hoechst 33342. (1980)

Data are presented that show that a histochemical stain, Hoeschst 33342, can be used to discriminate between viable B and T lymphocytes in the mouse. Quantitative analysis of the staining of cells from various lymphoid tissues with Hoechst 33342 using a Fluorescence-Activated Cell Sorter (FACS) indicates that two populations of cells can be identified. In the spleen approximately 60% of the lymphocytes can be classified as brightly stained with 1 microgram/ml of Hoechst 33342, while in the lymph node only 40% of the cells stain brightly. Thymocytes exhibit only the dull staining profile. Separation of these two populations from the spleen using the FACS and reanalyzing them for cell surface antigenic markers shows that the lymphocytes stained brightly with Hoechst 33342 are predominantly immunoglobulin positive, while the cells that stain less brightly express Thy 1.2. This indicates that a histochemical stain correlates directly with classical immunological markers on cell surfaces.
Velocity-Modulation Transistor (VMT) –A New Field-Effect Transistor Concept (1982)

Field-effect transistors of a completely new category are proposed and analysed, in which the conductivity modulation Δ G by the gate voltage V g is brought forth mainly through the V g -dependence of electron mobility. Since the sheet concentration of electrons in such FETs need not be modulated, the switching speed of the device is expected to be free from the transit time limitation, reaching the range of subpicosecond. As a specific example, an FET with a dual-channel configuration is discussed.
Preliminary report of a phase I study of combination chemotherapy and humanized A33 antibody immunotherapy in patients with advanced colorectal cancer. (2003)

huA33 can be safely combined with BOF-Strep chemotherapy. The present report provides compelling evidence supporting our previous observations of major antitumor activity with the combination of huA33 and BOF-Strep chemotherapy. huA33 is still immunogenic when administered with chemotherapy. Future studies to evaluate the immunogenicity of new huA33 antibodies and identify which drugs in the BOF-Strep regimen are critical for enhanced antitumor efficacy are planned.
Recombinant Leech-Derived Tryptase Inhibitor: Construction, Production, Protein Chemical Characterization and Inhibition of HIV-1 Replication (1994)

A synthetic gene coding for leech-derived tryptase inhibitor, form C (LDTI-C), was designed, cloned and expressed. The gene assembled via 6 oligonucleotides contains linker sequences, stop codons and internal restriction recognition sites for cloning, expression and cassette mutagenesis. Periplasmatic expression products could not be detected in Escherichia coli (E. coli), but strong expression was found using Saccharomyces cerevisiae (S. cerevisiae) ( > 10 mg/l culture broth) if a variant of pVT102U/alpha was used as vector. The secreted material was isolated after cross-flow filtration and purified by cation exchange chromatography. The recombinant material proved to be pure and homogeneous by electrophoretic and chromatographic analyses. Amino acid sequencing and molecular mass determination (4737.6 +/- 0.77 Da) by electrospray ionization mass spectrometry confirmed that rLDTI-C was processed correctly and that it is indistinguishable from LDTI-C. The far UV-CD (circular dichroism) spectrum of the recombinant inhibitor is typical for a small folded protein. rLDTI-C is inhibitorily fully active, its complexes with bovine trypsin and human mast cell tryptase display equilibrium dissociation constants which are nearly identical to those with the natural inhibitor. Remarkably, the inhibitor blocked replication of HIV-1 in HUT-78 cells at a concentration of 20 microM.
Cytokine Modulatable Signalling Through Macrophage HLA Class II. 1. IFN-γ Upregulates the Efficiency of Ca2+ Mobilization in Response to Ligation of Macrophage HLA-DP (1997)

The human macrophage line 2MAC, established recently from peripheral blood, expresses a number of lineage-specific markers as well as a broad array of intercellular adhesion molecules, including high levels of HLA class I and class II. We have presented evidence elsewhere that 2MAC can be productively applied to the study of signal transduction through macrophage HLA class II. Namely, we showed that ligation of 2MAC HLA class II, but not HLA class I, by monoclonal antibody (mAb) elicits an increase in free cytoplasmic Ca2+ concentration [Ca2+]i. Moreover, this Ca2+ flux appears to be functionally relevant: ligation of HLA-DR, but not HLA class I, by mAb results in the Ca2+ mobilization-dependent induction of tissue factor, the high-affinity cellular receptor for factor VII/VIIa. Here we show that 2MAC is uniquely valuable for addressing the efficiency of signal transduction through HLA class II. Namely, we show here that prior culture of 2MAC cells with interferon-gamma (IFN-gamma) profoundly upregulates subsequent Ca2+ mobilization in response to ligation of HLA-DP in the absence of increased cell surface HLA-DP expression. Because IFN-gamma has no effect on 2MAC HLA-DP expression, IFN-gamma must upregulate Ca2+ mobilization by increasing the efficiency of signal transduction through HLA class II (HLA-DP), by targeting some other component of the macrophage HLA class II signalling pathway.
A cross-section of the fitness landscape of dihydrofolate reductase (2001)

In vitro molecular evolution is regarded as a hill-climbing on a fitness landscape in sequence space, where the 'fitness' is a quantitative measure of a certain physicochemical property of a biopolymer. We analyzed a 'cross-section' of the enzymatic activity landscape of dihydrofolate reductase (DHFR) by using a method of analysis of a fitness landscape. We limited the sequence space of interest to the five-dimensional sequence space, where the coordinate corresponds to the 1st, 16th, 20th, 42nd and 92nd site in the DHFR sequence. Thirty six mutants mapped into the limited sequence space were taken in the analysis. As a result, the cross-section is of the rough Mt Fuji type based on the mutational additivity. The ratio of the mean slope to the roughness is 2.8 and the Z-score of the original ratio against a distribution of random references is 7.0, which indicates a large statistical significance. The existence of such a cross-section was discussed in terms of the occurrence probability of sets of five sites distantly separated from each other on the DHFR 3D structure. Our results support the effectiveness of the evolution strategy which exploits the accumulation of advantageous single point mutations in such a cross-section.
Protecting low-to-medium-rise buildings by scrap tyre-soil mixtures (2009)

The stockpiling of scrap tyres is a significant threat to our environment and has been a hot topic amongst the engineering community which has been looking for long term viable solutions to the recycling and reuse of rubber. This paper proposes a new method of utilizing scrap tyres for applications in infrastructure protection forming part of the solution strategy. The method involves mixing scrap tyres with soil materials and placing the mixtures around building foundations, for vibration absorption. The potential of the proposed method will be demonstrated by numerical modelling to show its effectiveness and robustness as a means of protecting low-to-medium-rise buildings in an earthquake.
Simultaneous all-optical packet-header replacement and wavelength shifting for a dynamically-reconfigurable WDM network (1995)

We experimentally demonstrate a method of simultaneous all-optical header replacement and wavelength shifting. These functions, important in a dynamically-reconfigurable WDM network, are realized by using cross-gain compression in a semiconductor optical amplifier, and by using three-level modulation of a probe laser only when the header bits require changing. We simultaneously replace the 8-bit header of a 1-Gb/s packet and wavelength-shift the entire packet by 19 nm. A receiver sensitivity of -27 dBm at 10/sup -9/ BER is measured when using a 416-bit NRZ data packet. Our approach requires no guard bits and allows both the header and data to be at the same bit rate and wavelength.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Cryosurgery of breast cancer. (2012)

With recent improvements in breast imaging, the ability to identify small breast tumors is markedly improved, prompting significant interest in the use of cryoablation without surgical excision to treat early-stage breast cancer. The cryoablation is often performed using ultrasound-guided tabletop argon-gas-based cryoablation system with a double freeze/thaw cycle. Recent studies have demonstrated that, as a primary therapy for small breast cancer, cryoablation is safe and effective with durable results, and can successfully destroy all cancers <1.0 cm and tumors between 1.0 and 1.5 cm without a significant ductal carcinoma-in-situ (DCIS) component. Presence of noncalcified DCIS is the cause of most cryoablation failures. At this time, cryoablation should be limited to patients with invasive ductal carcinoma <1.5 cm and with <25% DCIS in the core biopsy. For unresectable advanced breast cancer, cryoablation is a palliation modality and may be used as complementary for subsequent resection or other therapies.
Amyloidogenic nature of spider silk (2002)

In spiders soluble proteins are converted to form insoluble silk fibres, stronger than steel. The final fibre product has long been the subject of study; however, little is known about the conversion process in the silk-producing gland of the spider. Here we describe a study of the conversion of the soluble form of the major spider-silk protein, spidroin, directly extracted from the silk gland, to a beta-sheet enriched state using circular dichroism (CD) spectroscopy. Combined with electron microscopy (EM) data showing fibril formation in the beta-sheet rich region of the gland and amino-acid sequence analyses linking spidroin and amyloids, these results lead us to suggest that the refolding conversion is amyloid like. We also propose that spider silk could be a valuable model system for testing hypotheses concerning beta-sheet formation in other fibrilogenic systems, including amyloids.
Plasma Luteinizing Hormone (LH) and Progesterone Levels in Heifers on Restricted Energy Intakes (1973)

A Reversal type experiment was conducted in which measurements were made of plasma levels of luteinizing hormone (LH) and progesterone in six Holstein heifers during three estrous cycles when they were maintained on either 100% or 62% of Morrison's TDN allowances. A progressive increase in plasma LH was noted from the first to third estrous cycle in heifers on the low energy intake. This increase was first seen in the estrous peaks, but by the third cycle the basal mean for the low TDN group (2.7 ng/ml) was also significantly higher than that of the control heifers (1.9 ng/ml, P<0.005). During the first cycle, plasma progesterone was slightly higher in the low calorie group, but became progressively lower in the subsequent cycles (P<0.05 and P<0.01). Both total progesterone and progesterone concentration in corpora lutea taken on the 10th day of the third cycle were lower in the low-TDN heifers than in their normal counterparts, P<0.01 and <0.05, respectivley. The results show that ovarian hypofunction under conditions of restricted energy intake is not due to reduced circulating levels of LH, as was previously hypothesized, and further suggest that the first effect is a reduced ability of the ovarian tissue to respond to LH.
In Vitro Expansion of Human Gastric Epithelial Stem Cells and Their Responses to Bacterial Infection (2014)

We developed a system to culture human gastric organoids. This system can be used to study H pylori infection and other gastric pathologies.
High-content affinity-based proteomics: unlocking protein biomarker discovery (2010)

Single protein biomarkers measured with antibody-based affinity assays are the basis of molecular diagnostics in clinical practice today. There is great hope in discovering new protein biomarkers and combinations of protein biomarkers for advancing medicine through monitoring health, diagnosing disease, guiding treatment, and developing new therapeutics. The goal of high-content proteomics is to unlock protein biomarker discovery by measuring many (thousands) or all (∼23,000) proteins in the human proteome in an unbiased, data-driven approach. High-content proteomics has proven technically difficult due to the diversity of proteins, the complexity of relevant biological samples, such as blood and tissue, and large concentration ranges (in the order of 10(12) in blood). Mass spectrometry and affinity methods based on antibodies have dominated approaches to high-content proteomics. For technical reasons, neither has achieved adequate simultaneous performance and high-content. Here we review antibody-based protein measurement, multiplexed antibody-based protein measurement, and limitations of antibodies for high-content proteomics due to their inherent cross-reactivity. Finally, we review a new affinity-based proteomic technology developed from the ground up to solve the problem of high content with high sensitivity and specificity. Based on a new generation of slow off-rate modified aptamers (SOMAmers), this technology is unlocking biomarker discovery.