gebhart/patrepeval huggingface dataset:
Expression of four growth factors during fracture repair (1993)

Fracture repair offers an opportunity to study the physiology of bone formation at the fracture site. Isolation of growth factors from bone matrix has implicated growth factors as participants in bone physiology. We therefore examined the expression patterns of aFGF, IGF-I, PDGF, and TGF-beta during fracture repair. An animal model has been developed to study repair of tibial fractures. The model provides both reproducible and quantifiable results, allowing the fracture repair process to be divided into four stages (Bourque et al., Lab. Anim. Sci 42: 369-374, 1992). Fractured tibiae were examined immunohistochemically with polyclonal antibodies to four growth factors. PDGF was visualized in macrophages in close proximity to the periosteum during stage 1. aFGF was visualized in cells of the expanded cambial layer and was associated with a rapid increase in the population of fibroblast-like mesenchymal cells during stage 2. IGF-I was visualized in young chondroblasts at the edge of the cartilage mass replacing the fibrous callus during stage 3. TGF-beta was visualized in calcified matrix producing chondrocytes at the edge of ossification fronts penetrating the cartilage callus during stage 4. The immunohistochemical results suggest that these growth factors act as local simulators of the repair process.
Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease (1997)

To assess the relationship between dementia, neuronal loss, and neuropathological findings in Alzheimer's disease (AD), we counted the number of neurons, senile plaques, and neurofibrillary tangles in a high-order association cortex. We studied the superior temporal sulcus of 34 individuals with AD and 17 nondemented control subjects, using statistically unbiased, stereological counting techniques. The number of superior temporal sulcus neurons in nondemented control subjects was stable across the sixth to ninth decades. In AD, more than 50% of the neurons were lost. Both neuronal loss and neurofibrillary tangles increased in parallel with the duration and severity of illness, but the amount of neuronal loss exceeded by manyfold the amount of neurofibrillary tangles accumulated. In contrast to the correlation between neurofibrillary tangles and neuronal loss, the number of senile plaques and the percentage of the superior temporal sulcus that was covered by Abeta (amyloid burden) were not related to neuronal loss, number of neurofibrillary tangles, or duration of disease. Neither the amount nor the rate of neuronal loss in the superior temporal sulcus in AD correlated with apolipoprotein E genotype. These data suggest that neuronal loss in association areas such as the superior temporal sulcus contributes directly to cognitive impairment in AD.
LDL Immunization Induces T-Cell–Dependent Antibody Formation and Protection Against Atherosclerosis (2001)

Atherosclerosis is an inflammatory disease, and the involvement of immune mechanisms in disease progression is increasingly recognized. Immunization with oxidized low density lipoprotein (LDL) decreases atherosclerosis in several animal models. To explore humoral and cellular immune reactions involved in this protection, we immunized apolipoprotein E knockout mice with either homologous plaque homogenates or homologous malondialdehyde (MDA)-LDL. Immunization with both these antigen preparations reduced lesion development. The plaques contained immunogen(s) sharing epitopes on MDA-LDL, MDA-very low density lipoprotein, and oxidized cardiolipin. This shows that a T-cell-dependent antibody response was associated with protection against atherosclerosis. The protection was associated with specific T-cell-dependent elevation of IgG antibodies against MDA-LDL and oxidized phospholipids, and the increased titers of IgG antibodies were correlated with decreased lesion formation and lower serum cholesterol levels.
Particle transport onto human airway surfaces. (1982)

Three domains can be distinguished for particle transport onto human airway surfaces: 1. thermodynamic domain. Particles are transported by diffusion. Deposition decreases with particle diameter, is independent of particle density, increases with inspiration time and should be independent of flow rate. 2. intermediate domain. Particles are transported by diffusion and gravitational sedimentation. Deposition is slightly dependent on particle diameter, particle density and flow rate and increases with inspiration time. Since particles are effectively collected by inertial impaction in the nose this domain disappears for nose-breathing. 3. aerodynamic domain. Particles are transported by gravitational sedimentation and by inertial impaction. Deposition increases with particle diameter, particle density, inspiration time and flow rate. For normal breathing this domain consists of three subdomains. 3.1. sedimentation domain. Particles aerodynamically smaller than 2 micrometers are deposited by gravitational sedimentation in the alveolar region. 3.2. impaction-sedimentation domain. Particles aerodynamically between 2 and 12 micrometers are deposited by inertial impaction in the extrathoracic airways, by gravitational sedimentation and inertial impaction in the bronchial airways and by gravitational sedimentation in the alveolar region. 3.3 impaction domain. Particles aerodynamically larger than 12 micrometers are deposited by inertial impaction predominantly in the extrathoracic and less in the bronchial airways.
Characterization of a polyethylene glycol conjugate of recombinant human interferon-gamma. (1990)

Recombinant human interferon-gamma was conjugated with polyethylene glycol (PEG) using succinimidyl coupling of amino groups in the protein. The PEG conjugated material showed antiviral, growth inhibitory and macrophage activation activities indistinguishable from those of the unmodified protein. The PEG conjugation reduced the receptor binding affinity slightly, but increased the half-life of the protein when measured in rats. Almost no clearance was observed within 6 hr after injection for the PEG conjugated protein, whereas a rapid clearance was seen for the unmodified interferon-gamma. Two possible sites of PEG attachment were identified in the protein: the N-terminal amino group and either lysine 129 or 131.
DNMT3A Mutations in Acute Myeloid Leukemia (2010)

DNMT3A mutations are highly recurrent in patients with de novo AML with an intermediate-risk cytogenetic profile and are independently associated with a poor outcome. (Funded by the National Institutes of Health and others.).
In vivo obtained antigen presented by germinal center B cells to T cells in vitro. (1988)

Shortly after secondary immunization germinal center (GC) B cells obtain antigen from follicular dendritic cells (FDC) in the form of immune complexes. This antigen appears to be degraded by the GC B cells and may be processed for presentation to T cells. The present study was undertaken to determine whether GC B cells can process and present antigen obtained from FDC in vivo to appropriate T cells in vitro. GC B cells were isolated from immune mice with the use of Percoll density separation followed by a panning procedure which utilizes the ability of the plant lectin, peanut agglutinin (PNA), to selectively bind to GC B cells. The enriched GC B cells were approximately 80% highly positive for PNA, 97% positive for Ia and surface IgM, but less than 0.01% positive for Thy-1.2 or esterase. In some experiments, this population was further purified to near 100% highly PNA-positive cells with the use of fluoresceinated PNA and a fluorescence-activated cell sorter. Cell sorting analysis indicated that the antigen (125I-labeled ovalbumin (OVA)) was restricted to the highly PNA-positive cell fraction. The capacity of these highly PNA-positive B cells to present antigen was assessed by monitoring interleukin 2 (IL-2) production by the OVA-specific T cell hybridoma, 3DO-54.8. GC B cells obtained from mice 3 wk or more after secondary immunization did not elicit IL-2 production in the absence of added OVA. However, GC B cells isolated as early as 1 day and for over 1 wk after a challenge with OVA, were able to stimulate high levels of IL-2 production, in the absence of adding OVA to the cell cultures. This response was maximal on day 5 and corresponded precisely with the kinetics of the ultrastructural studies which document the uptake of antigen by GC B cells in vivo. The FDC-derived antigen was remarkably immunogenic when compared with exogenous antigen. These findings demonstrated that antigen obtained in vivo by GC B cells could be processed and presented to T cells. In vivo, GC B cells may induce the T cell help needed for the germinal center reaction, generate B memory cells, and help induce the high titers of antibody associated with the secondary antibody response.
An Immune Basis for Lung Parenchymal Destruction in Chronic Obstructive Pulmonary Disease and Emphysema (2004)

These data suggest that Th1 lymphoctytes in the lungs of people with smoking-related damage drive progression of emphysema through CXCR3 ligands, interferon-inducible protein 10, and monokine induced by interferon.
An Empirical Analysis of Unit Trust Performance in Singapore (2000)

The Singapore government’s recent strategic plan to develop the financial sector has placed much emphasis on the fund management industry. In this paper we examine the unit trust performance in Singapore in the 90s. Our results show that fund managers in general performed poorly in security analysis and market timing. However, they performed fairly well in risk-adjusted returns and generally maintained well-diversified portfolios. We find that there is little consistency in the performance ranking of the evaluated portfolios, although there is evidence of repeat performance of some top funds. Our analysis also shows that fund managers could indeed make excess returns above the risk-free rate in the medium- to long-term. Thus, unit trusts can be an ideal investment for small investors seeking sufficient diversification.
The Effect on Plant Growth of Saturating a Soil with Carbon Dioxide (1914)

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Molecular basis for discriminating between normal and damaged bases by the human alkyladenine glycosylase, AAG (2000)

The human 3-methyladenine DNA glycosylase [alkyladenine DNA glycosylase (AAG)] catalyzes the first step of base excision repair by cleaving damaged bases from DNA. Unlike other DNA glycosylases that are specific for a particular type of damaged base, AAG excises a chemically diverse selection of substrate bases damaged by alkylation or deamination. The 2.1-A crystal structure of AAG complexed to DNA containing 1,N(6)-ethenoadenine suggests how modified bases can be distinguished from normal DNA bases in the enzyme active site. Mutational analyses of residues contacting the alkylated base in the crystal structures suggest that the shape of the damaged base, its hydrogen-bonding characteristics, and its aromaticity all contribute to the selective recognition of damage by AAG.
Influence of Saturation Phenomena on Laser-Excited Atomic Fluorescence Flame Spectrometry (1973)

Using a simple rate equation model, the laser power density I c necessary to reach 50% of the saturation limited population of the excited atomic level under typical flame conditions is calculated. For Na atoms aspirated into the flame a saturating power density for irradiation with a narrow dye laser line (bandwidth 0.033 Å) of I c ~ 0.4 kW/cm 2 was determined. With the aid of a dye laser with an appropriate laser power density, analytical curves for Na were measured yielding a detection limit of 0.2 ng/ml. This sensitivity is comparable with the best results obtained by atomic emission flame spectrometry.
Defects in single-crystal silicon induced by hydrogenation (1987)

It is demonstrated that hydrogenation induces microdefects and electronic deep levels in single-crystal silicon, which are unrelated to either plasma or radiation damage. After hydrogenation of either n-type or p-type silicon, transmission electron microscopy reveals defects that can be described as hydrogen-stabilized platelets or microcracks which appear within 0.1 \ensuremath{\mu}m of the exposed surface and are predominantly oriented along {111} crystallographic planes. These defects correlate with high concentrations of hydrogen or deuterium as measured by secondary-ion mass spectrometry and with the appearance of Si---H bonds as revealed by Raman spectroscopy. The concomitant introduction of electrically active gap states is demonstrated with both photoluminescence spectroscopy (PL) and deep-level transient spectroscopy (DLTS). In PL several H-induced radiative transitions are observed, with the dominant peak at 0.98 eV, which had previously been ascribed to plasma damage. In n-type Schottky diodes, DLTS detects two H-induced levels with thermal activation energies for electron emission of approximately 0.06 and 0.51 eV. These defects are detected at depths greater than the surface layer, are in low concentrations (${&lt;10}^{13}$ ${\mathrm{cm}}^{\mathrm{\ensuremath{-}}3}$), are acceptorlike, and anneal with an activation energy of \ensuremath{\sim}0.3 eV.
Regulation of gene expression of branched-chain keto acid dehydrogenase complex in primary cultured hepatocytes by dexamethasone and a cAMP analog. (1994)

The present study demonstrates that dexamethasone and 8-(4-chlorophenylthio)adenosine 3',5'-monophosphate (CPT-cAMP), a cAMP analog, increase the substrate flux through branched-chain keto acid dehydrogenase (BCKDH) in primary rat hepatocytes cultured in defined medium. Maximum response (2.7-fold increase in flux) was observed when hepatocytes were cultured with 1 microM dexamethasone plus 50 microM CPT-cAMP for 24 h. This increase in the flux rate was accompanied by significant increases in both the basal and total activities of BCKDH (2.2- and 2.0-fold, respectively), without any significant change in the activity state of this enzyme. The increase in BCKDH activity was the result of increased protein mass of E1 alpha (3.2-fold), E1 beta (2.9-fold), and E2 (1.6-fold) subunits of BCKDH, indicating that E2 is the limiting subunit for the expression of BCKDH. The relative abundance of mRNAs encoding the E1 alpha, E1 beta, and E2 subunits of BCKDH increased by 7.4-, 21.7-, and 4.8-fold, respectively. We conclude that increased flux through BCKDH in hepatocytes cultured with dexamethasone and CPT-cAMP is due to increased expression of BCKDH subunit genes. However, nonstoichiometric expression of individual subunits and the corresponding mRNAs suggests regulation of BCKDH also at translational and post-translational steps.
Noxious thermal and chemical stimulation induce increases in 3H-phorbol 12,13-dibutyrate binding in spinal cord dorsal horn as well as persistent pain and hyperalgesia, which is reduced by inhibition of protein kinase C (1995)

We have previously suggested that protein kinase C (PKC) contributes to persistent pain in the formalin test. This study compared the effects of pharmacological inhibition of PKC with either GF 109203X or chelerythrine on persistent pain following noxious chemical stimulation with its effects on mechanical hyperalgesia, which develops in the hindpaw contralateral to an injury produced by noxious thermal stimulation. Furthermore, we have assessed changes in membrane-associated PKC in spinal cord in response to both noxious chemical and thermal stimulation. Nociceptive responses, to a hindpaw injection of 50 microliters of 2.5% formalin, and flexion reflex thresholds, to mechanical stimulation (Randall-Selitto test) in the hindpaw contralateral to a thermal injury (15 sec immersion in water at 55 degrees C), were assessed following intrathecal injection of PKC inhibitors (GF 109203X or chelerythrine). Changes in the levels of membrane-associated PKC, as assayed by quantitative autoradiography of the specific binding of 3H-phorbol-12,13-dibutyrate (3H-PDBu) in spinal cord sections, were assessed in rats after noxious chemical (50 microliters of 5.0% formalin) and noxious thermal (90 sec immersion in water at 55 degrees C) stimulation. Inhibitors of PKC (GF 109203X, chelerythrine), produced significant reductions of nociceptive responses to 2.5% formalin, as well as a significant reduction in the mechanical hyperalgesia in the hindpaw contralateral to a thermal injury. In addition, both noxious chemical and thermal stimulation produced significant increases in specific 3H-PDBu binding in the dorsal horn of the lumbar spinal cord, likely reflecting alterations in membrane-associated PKC. The results provide both pharmacological and anatomical evidence that persistent pain produced by chemical stimulation with formalin and mechanical hyperalgesia in the hindpaw contralateral to a thermal injury are influenced by the translocation and activation of PKC in spinal cord dorsal horn neurons.
Metal–Organic Frameworks in Adsorption-Driven Heat Pumps: The Potential of Alcohols as Working Fluids (2015)

A large fraction of global energy is consumed for heating and cooling. Adsorption-driven heat pumps and chillers could be employed to reduce this consumption. MOFs are often considered to be ideal adsorbents for heat pumps and chillers. While most published works to date on this topic have focused on the use of water as a working fluid, the instability of many MOFs to water and the fact that water cannot be used at subzero temperatures pose certain drawbacks. The potential of using alcohol-MOF pairs in adsorption-driven heat pumps and chillers is investigated. To this end, 18 different selected MOF structures in combination with either methanol or ethanol as a working fluid are considered, and their potential is assessed on the basis of adsorption measurements and thermodynamic efficiencies. If alcohols are used instead of water, then (1) adsorption occurs at lower relative pressures for methanol and even lower pressure for ethanol, (2) larger pores can be utilized efficiently, as hysteresis is absent for pores smaller than 3.4 nm (2 nm for water), (3) larger pore sizes need to be employed to ensure the desired stepwise adsorption, (4) the effect of (polar/apolar) functional groups in the MOF is far less pronounced, (5) the energy released or taken up per cycle is lower, but heat and mass transfer may be enhanced, (6) stability of MOFs seems to be less of an issue, and (7) cryogenic applications (e.g., ice making) become feasible. From a thermodynamic perspective, UiO-67, CAU-3, and ZIF-8 seem to be the most promising MOFs for both methanol and ethanol as working fluids. Although UiO-67 might not be completely stable, both CAU-3 and ZIF-8 have the potential to be applied, especially in subzero-temperature adsorption chillers (AC).
Examination of the Slow Unfolding of Pro-Nerve Growth Factor Argues against a Loop Threading Mechanism for Nerve Growth Factor (2006)

Nerve growth factor (NGF), a member of the neurotrophin family, is an all-beta-sheet protein with a characteristic structure motif, the cystine knot. Unfolding of NGF in 6 M GdnHCl has been described previously to involve an initial partial loss of structure and a subsequent very slow conversion to a second, completely unfolded state. This latter conversion was postulated to represent a back-threading of the disulfide bond that passes through the cystine knot (loop threading hypothesis). Here, this hypothesis was questioned with the pro form of the protein (proNGF). In proNGF, the mature part is preceded by the 103-amino acid pro-peptide. Consequently, loop threading of the N-terminally extended protein should be significantly delayed. However, unfolding kinetics of proNGF monitored by RP-HPLC, intrinsic fluorescence, and NMR spectroscopy were comparable to those of mature NGF. Time-resolved (1)H-(15)N HSQC spectra revealed a slow time-dependent loss of residual structure of which the kinetics correlated well with the transition observed by RP-HPLC. Refolding from the completely unfolded state led to a partial recovery of natively folded proNGF. In summary, the sequential unfolding of proNGF only marginally differed from that of mature NGF. Therefore, it is very unlikely that a loop threading mechanism is the cause of the slow unfolding step.
Abstract LB-090: Sequence-based discovery of fully human anti-CD3 and anti-PDL1 single domain antibodies using novel transgenic rats (2016)

Abstract We have created a new platform and method for discovering fully human single domain antibodies (UniDabs) by combining novel transgenic rats (UniRats), antibody repertoire sequencing, and high-throughput gene assembly, expression and screening. UniRats express a comprehensive human VH gene repertoire in a heavy chain only antibody format, and they mount robust immune responses to a variety of antigens. UniRats do not produce endogenous Ig as their heavy, kappa and lambda loci have been silenced, so the only Ig expression comes from the human heavy chain transgenes. Human VHs identified using high-throughput functional screening of heavy chain antibodies may also be converted to a single domain UniDab format. UniDabs are powerful and flexible modular binding domains that may be combined to form multivalent structures, nanoparticle conjugates, or antibody-drug conjugates. In our preclinical CD3 and PDL1 programs, we have identified hundreds of antigen-specific UniDabs. This large collection of UniDabs covers a diverse set of epitopes, a wide range of affinities, and is a valuable resource for creating next-generation multi-specific cancer therapeutics. Citation Format: Nathan Trinklein, Shelley Force Aldred, Ute Schellenberger, Kat Harris, Starlynn Clarke, Kevin Dang, Duy Pham, Marianne Bruggemann, Wim vanSchooten. Sequence-based discovery of fully human anti-CD3 and anti-PDL1 single domain antibodies using novel transgenic rats. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-090.
CHROMOSOMAL LOCATION OF PLEIOTROPIC NEGATIVE SPORULATION MUTATIONS IN BACILLUS SUBTILIS (1973)

Genetic analysis by PBS-1 transduction and transformation of a large group of pleiotropic negative sporulation mutants has shown that mutations of this phenotype may be located in five genetically distinct regions. The first group of mutant sites, spoA mutations, is located in the terminal region of the chromosome and linked to the lys-1 marker by PBS-1 transduction. The second group, spoB mutations, is located between phe-1 and the attachment site for the lysogenic bacteriophage varphi 105. Fine structure analysis of the mutant sites within the spoB locus has been accomplished. A third location for mutants of this phenotype, spoE mutants, was found between the metC3 and ura-1 markers. Two mutants were found at this site and both were capable of sporulation, in contrast to the rest of the pleiotropic sporulation mutants. A fourth chromosomal site, spoH mutations, was found near the ribosomal and RNA polymerase loci. A large group of mutant sites, spoF mutations, was found to be linked to each other by recombination index analysis in transformation but unlinked to any of the known auxotrophic mutations comprising the chromosomal map. All mutants analyzed showing a pleiotropic negative phenotype were found to map within one of these five regions. Interspecific transformation with Bacillus amyloliquefaciens as donor has shown that all of the pleiotropic negative sporulation mutations are conserved relative to a selected group of auxotrophic markers. The degree of conservation in decreasing order is: spoH > spoF = spoB > spoA.