gebhart/patrepeval huggingface dataset:
The diversity of antigen‐specific monoclonal antibodies from transgenic mice bearing human immunoglobulin gene miniloci (1994)

An approach to the preparation of antigen-specific human monoclonal antibodies focuses on mice transgenic for human immunoglobulin gene miniloci; the V gene segments in these miniloci undergo productive rearrangement to yield mouse B cells expressing human immunoglobulin (Ig) chains. The general usefulness of this strategy hinges on whether it is feasible to obtain specific, high-affinity antibodies following immunization of such animals with a variety of antigens. To test this, we have investigated the antigen-specific responses in mice which carry human IgH miniloci (constaining just one or two VH segments) instead of a functional mouse IgH locus. Although serum responses were relatively weak, monoclonal antibodies were readily obtained to all immunogens tested (a hapten, foreign proteins and human lymphoma cells). The affinities of two of the hapten-specific (anti-2-phenyl-oxazol-5-one) antibodies were 60 and 160 nM, values intermediate between what is typically obtained in the primary and secondary response of normal mice. Sequence analysis of the rearranged V genes revealed that junctional events made a major contribution to diversity with a considerable amount of apparently non-templated sequence at the V-D and D-J borders. Somatic hypermutation was also evident within the expressed V gene segments of many of the antigen-specific hybridomas. These findings augur well for the general usefulness of the transgenic approach for the isolation of high-affinity human antibodies to a wide range of antigens and suggests that the miniloci need not be particularly large.
Testing of a Biomechanical Model of the Lumbar Muscle Force Distribution Using Quasi-Static Loading Exercises (1992)

The study of lumbar muscle force distribution in response to externally applied loads is based on the introduction of biomechanical models of the lumbar region. The evaluation of such models requires the execution of loading exercises while monitoring the EMG activity of certain lumbar muscles. This work uses muscle activity maps as the major design tool of such exercises, provided that the subject is constrained to an upright erect posture. The maps describe the predicted muscle force for a given combination of externally applied bending moments. A series of shoulder adduction exercises were designed and the EMG signals of eight lumbar muscles were measured while subjects performed the exercises. The results show good agreement between the model predictions and the EMG measurements, especially when the load and the muscle were contralateral to one another.
Purification of a glycoprotein vascular endothelial cell mitogen from a rat glioma-derived cell line. (1990)

A growth factor that is mitogenic for vascular endothelial cells, with an ED50 of approximately 1 ng/ml, has been purified 170,000-fold to apparent homogeneity from tissue culture medium conditioned by a rat glioma-derived cell line. The pure protein is a 46-kDa dimer composed of two subunits of equivalent mass as established by comparison of migration in SDS/polyacrylamide gels with and without prior reduction. This glioma-derived growth factor is a glycoprotein and is not mitogenic for BALB/c 3T3 fibroblasts, properties that further distinguish it from other well-characterized vascular endothelial cell mitogens. In contrast to acidic and basic fibroblast growth factors and to platelet-derived endothelial cell growth factor, which have no secretory leader sequences and might only be released by leakage from damaged cells, the glycoprotein nature of this mitogen implies that it is processed through the glycosylating secretory pathway. This secretable growth factor could, therefore, be readily available in the extracellular space under normal physiological conditions in vivo to promote vascular endothelial cell proliferation associated with blood-vessel growth and maintenance.
Matrix metalloproteinase (MMP) system in brain: identification and characterization of brain‐specific MMP highly expressed in cerebellum (2001)

The matrix metalloproteinase (MMP) family, comprising more than 20 isoforms, modulates the extracellular milieu by degrading extracellular matrix (ECM) proteins. Because MMP is one of the few groups of proteinases capable of hydrolysing insoluble fibrillar proteins, they are likely to play crucial roles in regulating both normal and pathophysiological processes in the brain. However, little is yet known about their possible neuronal functions due presumably to their unusual redundancy and to the absence of a complete catalogue of isoforms. As an initial step in understanding the MMP system in the brain, we analysed an expression spectrum of MMP in rat brain using RT-PCR and discovered a novel brain-specific MMP, MT5-MMP. MT5-MMP was the predominant species among the nongelatinase-type isoforms in brain. MT5-MMP, present in all brain tissues examined, was most strongly expressed in cerebellum and was localized in the membranous structures of expressing neurons, as assessed biochemically and immunohistochemically. In cerebellum, its expression was regulated developmentally and was closely associated with dendritic tree formation of Purkinje cells, suggesting that MT5-MMP may contribute to neuronal development. Furthermore, its stable postdevelopmental expression and colocalization with senile plaques in Alzheimer brain indicates possible roles in neuronal remodeling naturally occurring in adulthood and in regulating pathophysiological processes associated with advanced age.
In vivo effects of interferon beta-1a on immunosuppressive cytokines in multiple sclerosis (1998)

Recombinant interferon beta (IFNbeta) benefits patients with relapsing remitting multiple sclerosis (MS), but the mechanisms of action are unknown. We studied in vivo immunologic effects of IFNbeta treatment and their relationship to clinical efficacy. Cytokines were measured in blood and CSF from MS patients participating in a placebo-controlled phase III clinical trial and an open-label phase IV [corrected] tolerability study of IFNbeta-1a. Additionally, immunologic studies were conducted in animals with proteolipid protein (PLP)-induced chronic relapsing experimental autoimmune encephalomyelitis. Single intramuscular (IM) injections of IFNbeta-1a (6 MIU, 30 microg) were associated with significant in vivo upregulation of interleukin-10 (IL-10) and IL-4 but not IFNgamma mRNA in peripheral blood mononuclear cells. Forty-eight hours after each IFNbeta-1a injection, serum IL-10 levels increased and remained elevated for 1 week. IFNbeta-1a recipients in the placebo-controlled phase III clinical trial showed significantly increased concentrations of CSF IL-10 after 2 years of treatment. This response correlated with a favorable therapeutic response. Exposure of PLP-reactive murine T-cell lines to IFNbeta resulted in increased antigen-driven expression of IL-4 and IL-10 and reduced encephalitogenicity. IFNbeta-1a injections induce systemic and intrathecal immunosuppressive cytokines. Myelin-specific T cells treated with IFNbeta-1a demonstrate increased immunosuppressive cytokine expression and reduced encephalitogenicity. The relationship between increased CSF IL-10 and response to therapy suggests that induction of IL-10 is a mechanism underlying IFNbeta-1a effects in MS patients.
Rapid deprotection procedures for synthetic oligonucleotides. (1991)

Two new rapid procedures for the full deprotection of synthetic oligonucleotides has been developed. We have successfully used the mixture of ethanolamine and ethanol (1:1) or pure ethanolamine for deprotection of oligonucleotides, prepared by different methods. In the case of oligonucleotides prepared by commonly used beta-cyanoethyl phosphoramidite and H-phosphonates method deprotection takes half an hour at 70 degrees C. We have found also that mixture of hydrazine, ethanolamine and methanol (1:3:3, v/v/v) can serve as a very efficient reagent for deprotection of oligonucleotides, prepared by beta-cyanoethyl phosphoramidite method with isopropoxyacetyl protecting group for cytosine residues. In this case deprotection time is 12-17 min at room temperature.
Bulk and surface processes in low-energy-electron-induced decomposition ofCaF2 (1999)

The irradiation of ${\mathrm{CaF}}_{2}$ with low-energy (typically 1 keV) electrons results in a decomposition of the crystal and the formation of metallic clusters on its surface, and in a near-surface layer. In this paper we describe the formation of surface clusters and their typical shapes and transformations they undergo in an ultrahigh-vacuum environment. From the evidence found in a variety of experiments, we conclude that surface metallization is strongly related to diffusive transport of irradiation-induced defects. We can coherently explain experimental results presented here, and earlier observations, by assuming that both the conversion of primarily created F and H center defects into charged ${V}_{k}$ and I centers, as well as their electric-field-induced diffusion, are controlled by the electron irradiation. Fluorine diffusion into the bulk leads to the formation of subsurface fluorine gas bubbles appearing as micron-sized surface elevations in scanning force microscopy images. For the initial stages of metal cluster formation on the (111) surface, we observe ordering phenomena indicating an epitaxial growth. Due to oxidation the surface topography changes when metal clusters are subjected to a residual gas atmosphere of $1\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}9}\mathrm{mbar}$ for more than one day.
Infant Weight Gain and Childhood Overweight Status in a Multicenter, Cohort Study (2002)

A pattern of rapid weight gain during the first 4 months of life was associated with an increased risk of overweight status at age 7 years, independent of birth weight and weight attained at age 1 year. These findings may lead to new hypotheses regarding the cause of childhood obesity, which may contribute to our understanding of this increasing public health problem in the United States.
Layered organic–inorganic hybrid perovskites: structure, optical properties, film preparation, patterning and templating engineering (2010)

Organic–inorganic perovskites are a class of interesting compound in the perovskite family due to their unique structures of alternately stacking sheets of organic and inorganic components on the molecular scale. In this highlight, the basic knowledge and recent advances in organic–inorganic perovskites are reviewed with particular emphasis on the feature work including: the novel <110>- and <111>-oriented perovskite structures, synthesis, film preparation, patterning methods and optoelectronic properties of hybrid perovskites. Moreover, the small functional organic molecules can be templated into a regular arrangement by the inorganic perovskite framework. This unique material with nature-formed lamellar structure has the potential to be used as a template to create novel derivatives and bring about unique physical properties. Some interesting examples, such as intercalated polymer and silica network by topochemical polymerisation, fabrication of disk-like semiconductor nanocrystals and metal nanoparticles by hybrid perovskite templates are described.
Cutting Edge: Direct Action of Thymic Stromal Lymphopoietin on Activated Human CD4+ T Cells (2007)

Thymic stromal lymphopoietin (TSLP) is a cytokine that promotes CD4(+) T cell homeostasis and contributes to allergic and inflammatory responses. TSLP can act directly on mouse CD4(+) T cells, but in humans, the available data have indicated that TSLP receptors are not expressed on CD4(+) T cells and that TSLP instead activates dendritic cells, which in turn promote the proliferation and differentiation of CD4(+) T cells. We now unexpectedly demonstrate the presence of TSLP receptors on activated human CD4(+) T cells. Strikingly, whereas freshly isolated peripheral blood human T cells show little if any response to TSLP, TCR stimulation allows a potent response to this cytokine. Moreover, TSLP increases the sensitivity of human CD4(+) T cells to low doses of IL-2, augmenting responsiveness of these cells to TCR engagement. Our results establish that human CD4(+) T cells are direct targets for TSLP.
Design of sensitive fluorogenic substrates for human cathepsin D (1997)

Cathepsin D is a lysosomal aspartic proteinase that has been implicated in several pathological processes such as breast cancer and Alzheimer's disease. We designed and synthesized a number of quenched fluorogenic substrates with P2 variations in the series AcEE(EDANS)KPIXFFRLGK(DABCYL)E-NH2, where X=cysteine, methylcysteine, ethylcysteine, tert-butylcysteine, carboxymethylcysteine, methionine, valine or isoleucine. Most of the fluorogenic substrates exhibited greater k(cat)/Km ratios than the best cathepsin D substrates described so far. Differences in kinetic constants, which were rationalized using structure-based modeling, might make certain substrates useful for particular applications, such as active site titrations or initial velocity determination using a fluorescent plate reader.
Self-Assembly of Responsive Multilayered DNA Nanocages (2015)

Here we report the assembly of multilayered DNA nanocages. The layers can be separated in response to a chemical cue, ATP. This is an effort to increase the structural complexity of DNA nanocages. The structures have been characterized by native polyacrylamide gel electrophoresis, atomic force microscopy, and cryogenic electron microscopy. We envision that the layer-by-layer assembly strategy used in this study can be easily applied to other DNA nanocages to form Russian-doll-like semisolid structures, while the chemically activated layer separation makes a contribution to the development of "smart" DNA nanocages.
Immune landscape and biomarkers for immuno-oncology in colorectal cancers (2020)

Recent advances in immuno-oncology have increased understanding of the tumor immune microenvironment (TIME), and clinical trials for immune checkpoint inhibitor treatment have shown remission and/or durable response in certain proportions of patients stratified by predictive biomarkers. The TIME in colorectal cancer (CRC) was initially evaluated several decades ago. The prognostic value of the immune response to tumors, including tumor-infiltrating lymphocytes, peritumoral lymphoid reaction, and Crohn's-like lymphoid reaction, has been well demonstrated. In this review, we describe the chronology of TIME research and review the up-to-date high-dimensional TIME landscape of CRC. We also summarize the clinical relevance of several biomarkers associated with immunotherapy in CRC, such as microsatellite instability, tumor mutational burden, POLE/POLD mutation, consensus molecular subtype, and programmed death-ligand 1 expression.
Effects of two viral inactivation methods on platelets: laser-UV radiation and merocyanine 540-mediated photoinactivation. (1992)

Two viral inactivation methods suggested for use with cellular blood products have been evaluated as to their effects on platelets. In the first study, it was proposed that pulsed laser-ultraviolet radiation (UVB) at 308 nm could favor photodamage to UVB-sensitive viral nucleic acid with minimal effects on blood platelets. A "window of efficacy" was observed with UVB doses of 10.5-21.5 J/cm2 at which 4-6 log10 poliovirus were inactivated while platelets were relatively tolerant. However, this "window" occurred only with low-intensity UVB radiation (less than or equal to 0.25 MW/cm2). Damage to platelet proteins, evident at high laser intensities, was probably due to multiple photon excitation of amino acids. In the second study, platelets and viruses were treated with the photosensitizer, merocyanine 540 (MC 540) (less than or equal to 24 micrograms/ml), and visible light (450-600 nm) (less than or equal to J/cm2). Activation of washed platelets by dye/light treatment resulted in a spontaneous release of serotonin, spontaneous aggregation, and marked morphological changes. Increasing concentrations of albumin in the suspension medium protected against dye-mediated photodamage to platelets, but also significantly reduced the antiviral activity of MC 540 and light. These results illustrate the relative sensitivities of platelets and viruses to two inactivation methods and the difficulty in optimizing inactivation of viruses and preservation of platelet function in a protein-rich medium.
Factors affecting the long-term outcome of Buerger's disease (thromboangiitis obliterans). (1999)

The natural history of the limbs in patients with Buerger's disease is not completely discouraging, and in order to obtain a favourable outcome for patients with Buerger's disease we recommend complete smoking cessation with drug-therapy and surveillance for neoplasm, especially of the upper gastrointestinal tract and lung.
Housing Policy in the Soviet Union (1990)

The Soviet Union has faced a massive housing problem since its creation in 1917. A shortage of housing existed before the 1917 Revolution but the shortage in the cities has been exacerbated by rapid urbanisation of the population and by the destruction of 30 per cent of the housing stock during World War 2. Although significant improvements have been made in the sense that proportionately fewer households now share accommodation and the average space standard has risen, it nonetheless seems apposite to recognise that seventy-three years after the Revolution and forty-five years after World War 2 current housing problems are the result of policy choices or the failure of policy. That is, it does not seem appropriate to continue to locate the causes of current problems in the pre-revolutionary situation or the catastrophe of World War 2.
Ionotropic Nucleation of Calcium Carbonate by Molluscan Matrix (1984)

The hydrophilic, sulfated fraction of the organic matrix found in molluscan shells appears to be involved in crystal nucleation. It is located primarily at the sites of initial nucleation. The hydrophilic fraction favors in vitro formation of calcified deposits, when it is fixed in place on the hydrophobic fraction. Calcium is bound by the hydrophillic fraction with high affinity and selectivity. Enzymatic desulfation reduces the calcium binding. However, the binding stoichiometry of one calcium for every two ester sulfates is not altered. The calcium binding induces local anion binding, which induces secondary calcium binding. This coordinated ion binding is known as ionotropy. The resultant local high concentration of ions is thought to bring about nucleation.
A critique of multi-voxel pattern analysis (2010)

Multi-voxel pattern analysis (MVPA) is a popular analytical technique in neuroscience that involves identifying patterns in fMRI BOLD signal data that are predictive of task conditions.But the technique is also frequently used to make inferences about the regions of the brain that are most important to the tasks in question, and our analysis shows that this is a mistake.MVPA does not provide a reliable guide to what information is being used by the brain during cognitive tasks, nor where that information is.This is due in part to inherent run to run variability in the decision space generated by the classifier, but there are also several other issues, discussed here, that make inference from the characteristics of the learned models to relevant brain activity deeply problematic.These issues have significant implications both for many papers already published, and for how the field uses this technique in the future.
A Simple Model for Nitrogen-limited Plant Growth and Nitrogen Allocation (2005)

The agreement between model predictions and empirical findings suggests that the derived equation for nitrogen allocation and its relationship to plant nitrogen concentration might be generally applicable. The negative intercept in the linear relationship between relative growth rate and plant nitrogen concentration is interpreted as being equal to the degradation constant of photosynthetic nitrogen.
Cessation and reduction in alcohol consumption and misuse after psychedelic use (2019)

Although results cannot demonstrate causality, they suggest that naturalistic psychedelic use may lead to cessation or reduction in problematic alcohol use, supporting further investigation of psychedelic-assisted treatment for AUD.
Insulin-like growth factor I stimulates erythropoiesis in hypophysectomized rats. (1988)

Stimulation of erythropoiesis during growth is necessary to ensure proportionality between erythrocyte mass and body mass. However, the way by which erythrocyte formation is adapted to body growth is still unknown. Growth arrest in hypophysectomized rats is accompanied by decreased erythropoiesis. We have, therefore, examined whether insulin-like growth factor I (IGF-I), the mediator of growth hormone effects on body growth, is able to restore erythropoiesis in these animals. Subcutaneous infusions of 120 micrograms of recombinant human IGF-I per day in hypophysectomized rats led to increases in body weight, 59Fe incorporation into erythrocytes, and the number of reticulocytes that were similar to increases caused by infusions of 28 milliunits of human growth hormone per day. Body weight gain and 59Fe incorporation were linearly correlated. Like growth hormone, IGF-I also caused a significant rise in serum erythropoietin concentrations. However, the stimulatory effect on erythropoiesis occurred before serum erythropoietin levels had risen. These results demonstrate that IGF-I mediates the stimulatory effect of growth hormone on erythropoiesis in vivo and thus further support the somatomedin concept. They also show that IGF-I can stimulate erythropoiesis in an endocrine manner, and they suggest two possible routes of action: a direct one and an indirect one by means of enhanced erythropoietin production.
Efficient resource provisioning in compute clouds via VM multiplexing (2010)

Resource provisioning in compute clouds often require an estimate of the capacity needs of Virtual Machines (VMs). The estimated VM size is the basis for allocating resources commensurate with workload demand. In contrast to the traditional practice of estimating the VM sizes individually, we propose a joint-VM sizing approach in which multiple VMs are consolidated and provisioned, based on an estimate of their aggregate capacity needs. This new approach exploits statistical multiplexing among the workload patterns of multiple VMs, i.e., the peaks and valleys in one workload pattern do not necessarily coincide with the others. Thus, the unused resources of a low utilized VM can be directed to the other co-located VMs with high utilization. Compared to individual VM based provisioning, joint-VM sizing and provisioning may lead to much higher resource utilization. This paper presents three design modules to enable the concept in practice. Specifically, a performance constraint describing the capacity need of a VM for achieving a certain level of application performance; an algorithm for estimating the size of jointly provisioning VMs; a VM selection method that seeks to find good VM combinations for being provisioned together. We showcase that the proposed three modules can be seamlessly plugged into existing applications such as resource provisioning, and providing resource guarantees for VMs. The proposed algorithms and applications are evaluated by monitoring data collected from about 16 thousand VMs in commercial data centers. These evaluations reveal more than 45% improvements in terms of the overall resource utilization.
Antiinflammatory effects of apoptotic cells (2013)

Apoptotic cells are rapidly phagocytosed by macrophages, a process that represents a critical step in tissue remodeling, immune responses, and the resolution of inflammation. In 1998, Peter Henson, Donna Bratton, and colleagues at National Jewish Health demonstrated that phagocytosis of apoptotic cells actively suppresses inflammation by inhibiting the production of inflammatory cytokines and inducing production of antiinflammatory factors, including TGF-β and prostaglandin E2. Here they discuss the evolving relationship among apoptosis, phagocytosis, and inflammation.