gebhart/patrepeval huggingface dataset:
Phase I/II study exploring ImMucin, a pan‐major histocompatibility complex, anti‐MUC1 signal peptide vaccine, in multiple myeloma patients (2014)

ImMucin, a 21-mer cancer vaccine encoding the signal peptide domain of the MUC1 tumour-associated antigen, possesses a high density of T- and B-cell epitopes but preserves MUC1 specificity. This phase I/II study assessed the safety, immunity and clinical response to 6 or 12 bi-weekly intradermal ImMucin vaccines, co-administered with human granulocyte-macrophage colony-stimulating factor to 15 MUC1-positive multiple myeloma (MM) patients, with residual or biochemically progressive disease following autologous stem cell transplantation. Vaccination was well tolerated; all adverse events were temporal grade 1 2 and spontaneously resolved. ImMucin vaccination induced a robust increase in γ-interferon (IFN-γ-producing CD4+ and CD8+ T-cells (≤80-fold), a pronounced population of ImMucin multimer CD8+ T-cells (>2%), a 9·4-fold increase in peripheral blood mononuclear cells proliferation and 6·8-fold increase in anti-ImMucin antibodies, accompanied with T-cell and antibody-dependent cell-mediated cytotoxicity. A significant decrease in soluble MUC1 levels was observed in 9/10 patients. Stable disease or improvement, persisting for 17·5-41·3 months (ongoing) was achieved in 11/15 patients and appeared to be associated with low-intermediate PDL1 (CD274) bone marrow levels pre- and post-vaccination. In summary, ImMucin, a highly tolerable cancerous vaccine, induces robust, diversified T- and B-cell ImMucin-specific immunity in MM patients, across major histocompatibility complex-barrier, resulting in at least disease stabilization in most patients.
Investigation of partially gated Si tunnel FETs for low power integrated optical sensing (2014)

This paper presents experimental results regarding optical and electrical characteristics of a partially gated p-i-n structure that has an extension in the channel region coated with transparent material. The correlation between band to band tunneling and photo current is discussed. Four main phenomena are observed under illumination: (1) negative transconductance can be obtained under reverse bias conditions (2) the off current is governed by the photocurrent and subthreshold slope is degraded (3) a kink in the saturation current appears in the output characteristics (4) the light sensitivity of the transconductance in P mode operation can be tuned with the back gate bias.
SPECIFIC UNRESPONSIVENESS IN RATS WITH PROLONGED CARDIAC ALLOGRAFT SURVIVAL AFTER TREATMENT WITH CYCLOSPORINE (1993)

CD4+ cells from CsA-treated DA rats with long-surviving PVG heart allografts specifically suppress the capacity of naive CD4+ cells to restore allograft rejection in irradiated DA rats, but have normal donor-specific alloreactivity in MLC. CD4+ suppressor cells from CsA-treated DA rats cultured for 3 days against either PVG or DA spleen cells lost the capacity to transfer suppression into irradiated DA rats grafted with PVG hearts and regained the ability to mediate rejection. However, these cells retained suppressor function when stimulated with donor-specific alloantigen in media supplemented with 20% Con A supernatant. CD4+ cells from CsA-treated rats cultured against either third-party stimulator cells or syngeneic cells expressing anti-PVG idiotype in media supplemented with Con A supernatant failed to maintain suppressor cell function. CD4+ cells from CsA-treated rats cultured in media supplemented with Con A supernatant alone also failed to maintain suppressor function. Suppressor cell function in culture was not maintained by rIL-2. mAb to the IL-2 receptor alpha chain (CD25) prevented the maintenance of suppressor cell function in media supplemented with Con A supernatant. Con A supernatant is rich in IFN-gamma, but addition of an anti-IFN-gamma mAb to the culture did not affect the maintenance of suppressor cells. These studies demonstrate that the CD4+ suppressor cell from CsA-treated rats with long-surviving grafts is short-lived; its survival is dependent upon contact with specific alloantigens and cytokines, one of which is IL-2. In the absence of cytokines and/or specific alloantigen, the CD4+ cells regain the capacity to initiate graft rejection in irradiated rats, suggesting that within the CD4+ subpopulation there is a fragile balance between cells with the capacity to suppress and effect rejection.
Cornified Cell Envelope (1990)

The cornified cell envelope (CE) is a highly insoluble structure on the inside of the plasma membrane of terminally differentiated keratinocytes. The cellular and molecular biology of the CE is outlined and new areas of research involving the CE are reviewed focussing on morphological and biochemical connections, the sequential gene expression during terminal differentiation, the interaction of lipids and proteins forming the epidermal barrier, the cysteine-rich pool of proteins in the epidermis as well as the molecular cloning and/or characterization of major components of the CE.
Mutations, epimutations, and the developmental programming of the maize Suppressor‐mutator transposable element (1989)

Information about the structure, function and regulation of the maize Suppressor-mutator (Spm) transposable element has emerged from the genetic and molecular characterization of both deletion mutations and an unconventional type of reversible genetic change (epimutation). The element is subject to an epigenetic mechanism that can either stably inactivate it or specify one of a variety of heritable programs of differential element expression in development. The essay explores the relationship between the Spm element's epigenetic developmental programming mechanism and the determinative events central to plant development and differentiation.
Understanding the control of metabolism (1997)

Introduction - regulation and control methods for studying metabolism and its regulation traditional approaches to metabolic regulation enzyme activity - the molecular basis for its regulation metabolic control analysis control structures in metabolism. (Part contents)
La atribución judicial de la vivienda familiar y su temporalización existiendo hijos menores de edad: actuales líneas jurisprudenciales y doctrinales (2012)

Uno de los problemas a resolver en los casos de crisis matrimonial es el de determinar cual de los progenitores ha de continuar en el uso de la misma cuando, existiendo hijos menores de edad en el matrimonio, los progenitores no han llegado a un acuerdo al respecto o este no ha sido aprobado por el Juez. En tales casos, es la autoridad judicial la que ha de decidir sobre esta cuestion conforme a los criterios que le brinda el Art. 96.1 CC. Sin embargo, resultan de gran transcendencia los problemas que plantea en relacion al posible caracter automatico o no de la atribucion de manera temporal.
ON ELEMENTARY FLUX MODES IN BIOCHEMICAL REACTION SYSTEMS AT STEADY STATE (1994)

A mathematical definition of the concept of elementary mode is given so as to apply to biochemical reaction systems subsisting at steady state. This definition relates to existing concepts of null-space vectors and includes a condition of simplicity. It is shown that for systems in which all fluxes have fixed signs, all elementary modes are given by the generating vectors of a convex cone and can, thus, be computed by an existing algorithm. The present analysis allows for the more general case that some reactions can proceed in either direction. Basic ideas on how to compute the complete set of elementary modes in this situation are outlined and verified by way of several examples, with one of them representing glycolysis and gluconeogenesis. These examples show that the elementary modes can be interpreted in terms of the particular biochemical functions of the network. The relationships to (futile) substrate cycles are elucidated.
Deep traps in quartz and their use for optical dating (1996)

We describe a number of optical properties of a natural quartz that are related to the presence of electron traps having an optical depth of about 3 eV below the conduction band. Such traps are populated as a consequence of a radiation dose, and can be depopulated by optical excitation. An understanding of these processes is necessary in order to make use of these phenomena to determine the ages of sediments by optical dating. The recombination emission spectrum is found to consist mainly of a 0.65 eV wide band at 3.35 eV (370 nm). This and other information are used to deduce that the traps are electron traps. The excitation efficiency is found to increase with photon energy, and with temperature. The data are roughly in accordance with Urbach's rule, and an optical trap depth of about 2.9 eV is deduced. Above 100 °C thermal quenching causes a reduction in the observed luminescence. Isothermal decay studies show that there are actually several traps, possibly including a distribution of traps, with most of the luminescence arising from traps with thermal depths of about 1.6 eV and lifetimes deduced from extrapolation to be &gt;2 × 10 6 years at 20 °C. The ratio of optical to thermal trap depths is in accordance with the Mott and Gurney prediction. A laboratory dose, besides filling traps, also has an effect that we attribute to population of competing recombination centres; this can be reversed with appropriate heating. Our understanding of the dose response and kinetics was tested on two samples of known age, and correct ages of ~ 120 000 years were obtained.
Patient autoantibodies deplete postsynaptic muscle-specific kinase leading to disassembly of the ACh receptor scaffold and myasthenia gravis in mice (2010)

The postsynaptic muscle-specific kinase (MuSK) coordinates formation of the neuromuscular junction (NMJ) during embryonic development. Here we have studied the effects of MuSK autoantibodies upon the NMJ in adult mice. Daily injections of IgG from four MuSK autoantibody-positive myasthenia gravis patients (MuSK IgG; 45 mg day(1)i.p. for 14 days) caused reductions in postsynaptic ACh receptor (AChR) packing as assessed by fluorescence resonance energy transfer (FRET). IgG from the patients with the highest titres of MuSK autoantibodies caused large (51-73%) reductions in postsynaptic MuSK staining (cf. control mice; P < 0.01) and muscle weakness. Among mice injected for 14 days with control and MuSK patient IgGs, the residual level of MuSK correlated with the degree of impairment of postsynaptic AChR packing. However, the loss of postsynaptic MuSK preceded this impairment of postsynaptic AChR. When added to cultured C2 muscle cells the MuSK autoantibodies caused tyrosine phosphorylation of MuSK and the AChR beta-subunit, and internalization of MuSK from the plasma membrane. The results suggest a pathogenic mechanism in which MuSK autoantibodies rapidly deplete MuSK from the postsynaptic membrane leading to progressive dispersal of postsynaptic AChRs. Moreover, maintenance of postsynaptic AChR packing at the adult NMJ would appear to depend upon physical engagement of MuSK with the AChR scaffold, notwithstanding activation of the MuSK-rapsyn system of AChR clustering.
Induction of Multidrug Resistance in Human Cells by Transient Exposure to Different Chemotherapeutic Drugs (1993)

Induction of MDR1 expression in response to cellular damage may account for increased MDR1 expression in treated human tumors. Protein kinase inhibitors may be useful in preventing the emergence of multidrug resistance during cancer chemotherapy.
Microdermabrasion as a Novel Tool to Enhance Drug Delivery via the Skin (2006)

BACKGROUND Microdermabrasion is a widely performed skin rejuvenation procedure. It can partly ablate and homogenize the stratum corneum (SC) layers. OBJECTIVE The effect of microdermabrasion treatment on the skin permeation of hydrophilic and lipophilic drugs was examined in this study. METHODS 5-Fluorouracil (5-FU) and clobetasol 17-propionate were used as the hydrophilic and lipophilic permeants, respectively. In vitro skin delivery using porcine skin and in vivo topical application employing nude mouse as the animal model were both used to examine the effect of microdermabrasion. The vacuum pressures used in this study (15–25 cmHg) were much lower than those used for therapeutic purposes. RESULTS The 5-FU permeation across microdermabrasion-treated skin was 8- to 24-fold higher than that across intact skin and depended on differences in treatment pressure and duration. An intensity of 15 cmHg for 10 seconds showed the greatest enhancement of 5-FU delivery via the skin. In contrast to the results for 5-FU, microdermabrasion reduced the skin permeation and deposition of topically applied clobetasol. The partitioning effect of clobetasol from the vehicle to the SC may have predominated this result. Microdermabrasion also enhanced the skin delivery of the hydrophilic 5-aminolevulinic acid (ALA). Confocal laser scanning microscopy (CLSM) of microdermabrasion-treated skin revealed intense red fluorescence of ALA-transformed protoporphyrin (PpIX) within the epidermis and upper dermis. CONCLUSIONS Microdermabrasion can improve the skin permeation of hydrophilic molecules.
Multivalency: the hallmark of antibodies used for optimization of tumor targeting by design (2008)

High-precision tumor targeting with conventional therapeutics is based on the concept of the ideal drug as a "magic bullet"; this became possible after techniques were developed for production of monoclonal antibodies (mAbs). Innovative DNA technologies have revolutionized this area and enhanced clinical efficiency of mAbs. The experience of applying small-size recombinant antibodies (monovalent binding fragments and their derivatives) to cancer targeting showed that even high-affinity monovalent interactions provide fast blood clearance but only modest retention time on the target antigen. Conversion of recombinant antibodies into multivalent format increases their functional affinity, decreases dissociation rates for cell-surface and optimizes biodistribution. In addition, it allows the creation of bispecific antibody molecules that can target two different antigens simultaneously and do not exist in nature. Different multimerization strategies used now in antibody engineering make it possible to optimize biodistribution and tumor targeting of recombinant antibody constructs for cancer diagnostics and therapy.
Acquisition of Suppressive Function by Activated Human CD4+CD25− T Cells Is Associated with the Expression of CTLA-4 Not FoxP3 (2008)

The role of CTLA-4 in regulatory T cell (Treg) function is not well understood. We have examined the role of CTLA-4 and its relationship with the transcription factor FoxP3 using a model of Treg induction in human peripheral blood. Activation of human CD4(+)CD25(-) T cells resulted in the appearance of a de novo population of FoxP3-expressing cells within 48 h. These cells expressed high levels of CTLA-4 and cell sorting on expression of CTLA-4 strongly enriched for FoxP3(+)-expressing cells with suppressive function. Culture in IL-2 alone also generated cells with suppressive capacity that also correlated with the appearance of CTLA-4. To directly test the role of CTLA-4, we transfected resting human T cells with CTLA-4 and found that this method conferred suppression, similar to that of natural Tregs, even though these cells did not express FoxP3. Furthermore, transfection of FoxP3 did not induce CTLA-4 and these cells were not suppressive. By separating the expression of CTLA-4 and FoxP3, our data show that FoxP3 expression alone is insufficient to up-regulate CTLA-4; however, activation of CD4(+)CD25(-) T cells can induce both FoxP3 and CTLA-4 in a subpopulation of T cells that are capable of suppression. These data suggest that the acquisition of suppressive behavior by activated CD4(+)CD25(-) T cells requires the expression of CTLA-4, a feature that appears to be facilitated by, but is not dependent on, expression of FoxP3.
Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. (1995)

The eukaryotic protein kinases make up a large superfamily of homologous proteins. They are related by virtue of their kinase domains (also known as catalytic domains), which consist of approximately 250-300 amino acid residues. The kinase domains that define this group of enzymes contain 12 conserved subdomains that fold into a common catalytic core structure, as revealed by the 3-dimensional structures of several protein-serine kinases. There are two main subdivisions within the superfamily: the protein-serine/threonine kinases and the protein-tyrosine kinases. A classification scheme can be founded on a kinase domain phylogeny, which reveals families of enzymes that have related substrate specificities and modes of regulation.
Contrast-enhanced microwave imaging of breast tumors: a computational study using 3D realistic numerical phantoms (2010)

The detection of early-stage tumors in the breast by microwave imaging is challenged by both the moderate endogenous dielectric contrast between healthy and malignant glandular tissues and the spatial resolution available from illumination at microwave frequencies. The high endogenous dielectric contrast between adipose and fibroglandular tissue structures increases the difficulty of tumor detection due to the high dynamic range of the contrast function to be imaged and the low level of signal scattered from a tumor relative to the clutter scattered by normal tissue structures. Microwave inverse scattering techniques, used to estimate the complete spatial profile of the dielectric properties within the breast, have the potential to reconstruct both normal and cancerous tissue structures. However, the ill-posedness of the associated inverse problem often limits the frequency of microwave illumination to the UHF band within which early-stage cancers have sub-wavelength dimensions. In this computational study, we examine the reconstruction of small, compact tumors in three-dimensional numerical breast phantoms by a multiple-frequency inverse scattering solution. Computer models are also employed to investigate the use of exogenous contrast agents for enhancing tumor detection. Simulated array measurements are acquired before and after the introduction of the assumed contrast effects for two specific agents currently under consideration for breast imaging: microbubbles and carbon nanotubes. Differential images of the applied contrast demonstrate the potential of the approach for detecting the preferential uptake of contrast agents by malignant tissues.
Trace gases in breath of healthy volunteers when fasting and after a protein-calorie meal: a preliminary study (1999)

The selected ion flow tube technique was used to quantify in breath the trace gases acetone, ammonia, ethanol, isoprene, and methanol during single exhalations while fasting and in response to feeding. Six normal volunteers were fasted for 12 h, and, after baseline breath samples were obtained, were fed a liquid protein-calorie meal to provide 0.47 g/kg of protein (Fortisip). Further breath samples were obtained at 20, 40, and 60 min, and then hourly for a further 5 h. Breath acetone concentrations fell from a maximum during fasting, reaching their nadir between 4 and 5 h. Breath ammonia concentrations fell immediately to one-half their fasting levels before a steady increase to two or three times baseline values at 5 h. There was a brief increase in breath ethanol concentrations after feeding, reflecting detectable ethanol contamination of the food. Subsequently, breath ethanol levels remained low throughout the experimental protocol. Isoprene concentrations did not change significantly, whereas changes in methanol concentrations reflected those in the ambient air. This preliminary study indicates that the selected ion flow tube technique may be used to detect changes in the trace gases present in breath and define their concentrations in the fasting and replete state. Of particular interest is the biphasic response of the breath ammonia concentration after feeding.
Simulation of high-energy proton production by fast magnetosonic shock waves in pinched plasma discharges (2007)

High-energy particles of a few hundred keV for electrons and up to MeV for ions were observed in a plasma focus device. Haruki et al. [Phys. Plasmas 13, 082106–1 (2006)] studied the mechanism of high-energy particle production in pinched plasma discharges by use of a 3D relativistic and fully electromagnetic particle-in-cell code. It was found that the pinched current is unstable against a sausage instability, and then becomes unstable against a kink instability. As a result high-energy electrons were observed, but protons with MeV energies were not observed. In this paper the same pinch dynamics as Haruki and co-workers is investigated, focusing on the shock formation and the shock acceleration during the pinched current. It is found that a fast magnetosonic shock wave is produced during the pinching phase which, after the maximum pinch occurs, is strongly enhanced and propagates outwards. Some protons trapped in the electrostatic potential produced near the shock front can be accelerated to a few MeV by the surfatron acceleration mechanism. It is also found that the protons accelerated along the pinched axis have a ring-shaped angular distribution that is observed from numerous experiments.
Evaluation of Different Ventricular Pacing Sites in Patients With Severe Heart Failure (1997)

In patients with severe congestive heart failure, both LV pacing alone and BIV pacing resulted in a similar and significant acute improvement in SBP, PCWP, and V-wave amplitude compared with baseline measurements and RV pacing alone. These results provide a strong basis for initiating long-term studies examining the chronic effects of LV-based pacing in patients with medically refractory congestive heart failure.
Short Hairpin Activated Gene Silencing in Mammalian Cells (2004)

RNA interference (RNAi) is now a popular method for silencing gene expression in a variety of systems. RNAi methods use double-stranded RNAs (dsRNAs) to target complementary RNAs for destruction. In mammalian systems, very short dsRNAs (22-25 bp) such as short interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs) are used to avoid endogenous nonspecific antiviral responses that target longer dsRNAs. siRNAs elicit a transient silencing response, while shRNAs can be expressed continuously to establish stable gene silencing. shRNAs can be introduced into cells and animals using a variety of standard vectors as well as retroviral or lentiviral expression systems. This chapter describes the design, construction, validation, and use of shRNAs for silencing genes. We report our results from testing a variety of shRNA design features and shRNA expression vectors. We also provide methods that use shRNAs to permit different levels of gene expression. Additionally, we discuss some aspects important for constructing an information pipeline to support development of a large shRNA library.