gebhart/patrepeval huggingface dataset:
Expression of growth/differentiation factor 1 in the nervous system: conservation of a bicistronic structure. (1991)

Growth/differentiation factor 1 (GDF-1) is a recently described member of the transforming growth factor beta superfamily isolated from a day-8.5 mouse embryo cDNA library. Northern (RNA) analysis of embryonic mRNA detected two GDF-1 transcripts [1.4 kilobases (kb) and 3.0 kb in length] displaying distinct temporal patterns of expression. Only the 3.0-kb transcript was detected in adult tissues, where its expression was restricted almost exclusively to the central nervous system. Comparison of murine and human brain cDNA sequences corresponding to the 3.0-kb transcript revealed high conservation of two nonoverlapping open reading frames with poor conservation of the intervening spacer region and the putative 5' and 3' untranslated sequences. By immunohistochemical analysis, the protein encoded by the downstream open reading frame (GDF-1) was detected exclusively in the brain, spinal cord, and peripheral nerves in day-14.5 mouse embryos. The upstream open reading frame encodes a protein of unknown function containing multiple putative membrane-spanning domains. These findings raise the possibility that this mRNA may give rise to two different proteins.
Concerted evolution of class I genes in the major histocompatibility complex of murine rodents. (1990)

Full-length cDNA sequences of two class I major histocompatibility complex molecules from the DA strain of Rattus norvegicus are reported. One codes for the classical class I restriction element RT1.Aa, which maps to the locus in the rat major histocompatibility complex homologous to H-2K in the mouse. The other probably codes for a soluble nonclassical class I molecule present in DA rat serum; a short deletion in the fifth exon implies that the translated product will terminate in the membrane-spanning region. These sequences have been compared with mouse classical class I sequences as well as with three published rat class I cDNA partial sequences. The results show, first, that "locus-specific" substitutions from the H-2K, H-2D, and H-2L data set are scrambled in the RT1.Aa molecule; a majority of these substitutions have H-2D/L-specific features. Second, the data show that the four rat sequences are strikingly similar to one another regardless of locus or haplotype of origin; they share a number of apparently species-specific features that distinguish them all from mouse classical class I sequences, which likewise share distinctive features of their own. The results suggest that segmental sequence exchange plays a major role in determining the evolution of sequence in class I major histocompatibility complex molecules.
Using bioinformatics and genome analysis for new therapeutic interventions (2005)

The genome era provides two sources of knowledge to investigators whose goal is to discover new cancer therapies: first, information on the 20,000 to 40,000 genes that comprise the human genome, the proteins they encode, and the variation in these genes and proteins in human populations that place individuals at risk or that occur in disease; second, genome-wide analysis of cancer cells and tissues leads to the identification of new drug targets and the design of new therapeutic interventions. Using genome resources requires the storage and analysis of large amounts of diverse information on genetic variation, gene and protein functions, and interactions in regulatory processes and biochemical pathways. Cancer bioinformatics deals with organizing and analyzing the data so that important trends and patterns can be identified. Specific gene and protein targets on which cancer cells depend can be identified. Therapeutic agents directed against these targets can then be developed and evaluated. Finally, molecular and genetic variation within a population may become the basis of individualized treatment.
Serial Assessment of Lymphocytes and Apoptosis in the Prostate During Coordinated Intraprostatic Dendritic Cell Injection and Radiotherapy (2012)

Local radiotherapy plus intratumoral syngeneic dendritic cell injection can mediate apoptosis/cell death and immunological tumor eradication in murine models. A novel method of coordinated intraprostatic, autologous dendritic cell injection together with radiation therapy was prospectively evaluated in five HLA-A2(+) subjects with high-risk, localized prostate cancer, using androgen suppression, 45 Gy external beam radiation therapy in 25 fractions over 5 weeks, dendritic cell injections after fractions 5, 15 and 25 and then interstitial radioactive seed placement. Serial prostate biopsies before and during treatment showed increased apoptotic cells and parenchymal distribution of CD8(+) cells. CD8(+) T-cell responses to test peptides were assessed using an enzyme-linked immunosorbent spot IFN-γ production assay, demonstrating some prostate cancer-specific protein-derived peptides associated with increased titer. In conclusion, the technique was feasible and well-tolerated and specific immune responses were observable. Future trials could further test the utility of this approach and improve on temporal coordination of intratumoral dendritic cell introduction with particular timelines of therapy-induced apoptosis.
Lessons Learned from Radiation Oncology Clinical Trials (2013)

A workshop entitled "Lessons Learned from Radiation Oncology Trials" was held on December 7-8, 2011, in Bethesda, MD, to present and discuss some of the recently conducted radiation oncology clinical trials with a focus on those that failed to refute the null hypothesis. The objectives of this workshop were to summarize and examine the questions that these trials provoked, to assess the quality and limitations of the preclinical data that supported the hypotheses underlying these trials, and to consider possible solutions to these challenges for the design of future clinical trials. Several themes emerged from the discussions: (i) opportunities to learn from null-hypothesis trials through tissue and imaging studies; (ii) value of preclinical data supporting the design of combinatorial therapies; (iii) significance of validated biomarkers; (iv) necessity of quality assurance in radiotherapy delivery; (v) conduct of sufficiently powered studies to address the central hypotheses; and (vi) importance of publishing results of the trials regardless of the outcome. The fact that well-designed hypothesis-driven clinical trials produce null or negative results is expected given the limitations of trial design and complexities of cancer biology. It is important to understand the reasons underlying such null results, however, to effectively merge the technologic innovations with the rapidly evolving biology for maximal patient benefit through the design of future clinical trials.
A Comparison Study on Experimental Design and Response Surface Methodologies (2005)

Abstract Experimental design method is an alternative to traditional sensitivity analysis. The basic idea behind this methodology is to vary multiple parameters at the same time so that maximum inference can be attained with minimum cost. Once the appropriate design is established and the corresponding experiments (simulations) are performed, the results can be investigated by fitting them to a response surface. This surface is usually an analytical or a simple numerical function which is cheap to sample. Therefore it can be used as a proxy to reservoir simulation to quantify the uncertainties. Designing an efficient sensitivity study poses two main issues: Designing a parameter space sampling strategy and carrying out experiments.Analyzing the results of the experiments. (Response surface generation) In this paper we investigate these steps by testing various experimental designs and response surface methodologies on synthetic and real reservoir models. We compared conventional designs such as Plackett-Burman, central composite and D-optimal designs and a space filling design technique that aim at optimizing the coverage of the parameter space. We analyzed these experiments using linear, second order polynomials and more complex response surfaces such as kriging, splines and neural networks. We compared these response surfaces in terms of their capability to estimate the statistics of the uncertainty (i.e., P10, P50 and P90 values), their estimation accuracy and their capability to estimate the influential parameters (heavy-hitters). Comparison with our exhaustive simulations showed that experiments generated by the space filling design and analyzed with kriging, splines and quadratic polynomials gave the greatest accuracy while traditional designs and the associated response surfaces performed poorly for some of the cases we studied. We also found good agreement between polynomials and complex response surfaces in terms of estimating the effect of each parameter on the response surface.
Patterning of a nanoporous membrane for multi-sample DNA extraction (2005)

A novel method for patterning a nanoporous aluminum oxide membrane was developed using SU-8 to allow for extraction of DNA from multiple samples simultaneously. To facilitate the patterning process, the spin curve for SU-8 2015 on the membrane was determined. The correlation profile of the SU-8 spin curve was similar in form to curves of SU-8 spun on silicon wafers, but with a uniform decrease in thickness across the curve. Characterization of the patterned SU-8 regarding step height and surface roughness was determined using pin-based surface profilometry. The patterned aluminum oxide membrane displayed acceptable flatness and precise pattern replication. Thickness uniformity was also observed to be approximately ±2.8% for a 29.3 µm thick pattern. SEM imaging was used to examine the exposed membrane surface for any visible changes or damage to the membrane caused by the patterning process, with none observed. DNA extraction was performed on the patterned membrane using multiple wells to show the ability of collecting multiple DNA samples simultaneously. DNA, marked with a fluorescent dye, was collected on the membrane and successfully observed using a fluorescence microscope. The techniques developed in this work have application to lab-on-a-chip type systems that include DNA extraction steps.
Encapsulation of food ingredients (1993)

Microencapsulation is a relatively new technology that is used for protection, stabilization, and slow release of food ingredients. The encapsulating or wall materials used generally consist of starch, starch derivatives, proteins, gums, lipids, or any combination of them. Methods of encapsulation of food ingredients include spray-drying, freeze-drying, fluidized bed-coating, extrusion, cocrystallization, molecular inclusion, and coacervation. This paper reviews techniques for preparation of microencapsulated food ingredients and choices of coating material. Characterization of microcapsules, mechanisms of controlled release, and efficiency of protection/stabilization of encapsulated food ingredients are also presented.
Multilayer Optical Learning Networks (1987)

In this paper we present a new approach to learning in a multilayer optical neural network which is based on holographically interconnected nonlinear Fabry-Perot etalons. The network can learn the interconnections that form a distributed representation of a desired pattern transformation operation. The interconnections are formed in an adaptive and self aligning fashion, as volume holographic gratings in photorefractive crystals. Parallel arrays of globally space integrated inner products diffracted by the interconnecting hologram illuminate arrays of nonlinear Fabry-Perot etalons for fast thresholding of the transformed patterns. A phase conjugated reference wave interferes with a backwards propagating error signal to form holographic interference patterns which are time integrated in the volume of the photorefractive crystal in order to slowly modify and learn the appropriate self aligning interconnections. A holographic implementation of a single layer perceptron learning procedure is presented that can be extendept ,to a multilayer learning network through an optical implementation of the backward error propagation (BEP) algorithm.
Overcoming the blood-brain barrier with high-dose enzyme replacement therapy in murine mucopolysaccharidosis VII (2005)

Enzyme replacement therapy (ERT) effectively reverses storage in several lysosomal storage diseases. However, improvement in brain is limited by the blood-brain barrier except in the newborn period. In this study, we asked whether this barrier could be overcome by higher doses of enzyme than are used in conventional trials. We measured the distribution of recombinant human beta-glucuronidase (hGUS) and reduction in storage by weekly doses of 0.3-40 mg/kg administered i.v. over 1-13 weeks to mucopolysaccharidosis type VII mice immunotolerant to recombinant hGUS. Mice given up to 5 mg/kg enzyme weekly over 3 weeks had moderate reduction in meningeal storage but no change in neo-cortical neurons. Mice given 20-40 mg/kg three times over 1 week showed no reduction in storage in any area of the CNS except the meninges. In contrast, mice receiving 4 mg/kg per week for 13 weeks showed clearance not only in meninges but also in parietal neocortical and hippocampal neurons and glia. Mice given 20 mg/kg once weekly for 4 weeks also had decreased neuronal, glial, and meningeal storage and averaged 2.5% of wild-type hGUS activity in brain. These results indicate that therapeutic enzyme can be delivered across the blood-brain barrier in the adult mucopolysaccharidosis type VII mouse if administered at higher doses than are used in conventional ERT trials and if the larger dose of enzyme is administered over a sufficient period. These results may have important implications for ERT for lysosomal storage diseases with CNS involvement.
Biologically active, alternatively processed interleukin‐1β in psoriatic scales (1997)

The aims of the present work were to elucidate the biochemical properties of interleukin-1 beta (IL-1 beta) in psoriatic scales to get information on the processing of epidermal IL-1 beta in psoriasis, and to elucidate whether the IL-1 beta in psoriatic scales possesses biological activity. By means of ion exchange chromatography, IL-1 beta in extracts of psoriatic scales was purified to a stage where it could be analyzed with electrophoretic methods and immunoblotting. Compared to mature recombinant human IL-1 beta (Ala 117 IL-1 beta), IL-1 beta in psoriatic scales had a slightly higher apparent molecular mass and a more acidic isoelectric point, as revealed by two-dimensional electrophoresis under denaturing conditions. Isoelectric focusing under non-denaturing conditions of IL-1 beta partially purified from psoriatic scales, or from non-inflamed plantar stratum corneum (Nylander Lundqvist, E., Bäck, O. and Egelrud, T., J. Immunol. 1996. 157: 1699), and of mature IL-1 beta, followed by immunoblotting with IL-1 beta-specific antibodies, showed that psoriatic scales contained two components with IL-1 beta-like immunoreactivity which were isoelectric at pH 6.1 and 6.3, respectively. These components could also be detected in extracts of plantar stratum corneum, which also contained small amounts of an IL-1 beta-like component isoelectric at pH 6.9. Mature IL-1 beta was isoelectric at pH 6.9. No IL-1 beta-like biological activity could be detected in crude extracts of psoriatic scales. These extracts also contained high amounts of IL-1 receptor antagonist. Partially purified preparations of IL-1 beta from psoriatic scales, in which an apparently total separation of IL-1 beta and IL-1 receptor antagonist had been achieved, could induce expression of E-selectin in human umbilical vein endothelial cells. This activity was inhibited by antibodies specific for IL-1 beta, but not by antibodies specific for IL-1 alpha. It is concluded that psoriatic scales contain biologically active IL-1 beta, which has been processed by a mechanism which may be similar to that present in non-inflamed plantar stratum corneum, and which does not involve IL-1 beta converting enzyme.
The Malmö polymorphism of coagulation factor IX, an immunologic polymorphism due to dimorphism of residue 148 that is in linkage disequilibrium with two other F.IX polymorphisms. (1988)

A mouse monoclonal antibody (MAB 9.9) to coagulation factor IX (F.IX) detects a polymorphism in the plasma of normal people. Its epitope has been narrowed down to less than 6 amino acids in the activation peptide of the X-linked F.IX protein. The activation peptide contains a dimorphism--Thr:Ala--at position 148 of the protein. Using synthetic oligonucleotides, we have demonstrated that (1) the F.IX which reacts with 9.9 has Thr at position 148 and (2) that which does not has Ala. Positive reactors (148thr) are designated Malmö A, and negative reactors (148ala) are designated Malmö B. The plasma levels of AA women are indistinguishable from those of A men, and both B men and BB women are null against MAB 9.9. The plasma level of Malmö A in AB women is approximately half that of AA women, and "lyonization" is clearly operating in the heterozygotes. The dimorphism is in strong linkage disequilibrium with two other intragenic RFLPs, TaqI and XmnI. Furthermore, intragenic crossing-over--including double crossing-over--appears to have occurred between the three sites. Seven of the eight possible haplotypes have been identified, five in men and two others in women. The immunoassay that identifies approximately 50% of the AB women in the pool of Malmö A females with 95% confidence identifies men unambiguously as A or B. The assay would be very useful for population-genetic studies of the Malmö epitope if the studies were limited to men.
Gene transfer and kidney disease. (1998)

There is little doubt that molecular biological intervention therapy has come of age and its potential is arousing tremendous excitement. A gene transfer technique, the HVJ-liposome method, is now applicable as a tool for the dissection of molecular aspects in the pathophysiology of renal diseases, and for gene therapy in experimental glomerulonephritis. Overexpressed transforming growth factor (TGF)-beta in the normal rat glomeruli, by gene transfer of TGF-beta cDNA, leads to glomerulosclerosis. However, inhibition of the TGF-beta action by antisense oligonucleotides can suppress the development of the experimental glomerulonephritis. We investigated whether in vivo gene transfer of chimeric proteins, composed of the extracellular domain of TGF-beta type II receptor fused with IgC-Fc, suppresses experimental glomerulonephritis. The expression of TGF-beta in glomeruli was suppressed and so was the extracellular matrix expansion. Taken together with clinical observation of up-regulation of TGF-beta in various glomerulopathies, the dys-regulation of the TGF-beta is important in the development of glomerulosclerosis, and manipulation of this overexpression may prove a novel therapeutic approach for slowing the progression of the disease.
The C-terminus of factor H: monoclonal antibodies inhibit heparin binding and identify epitopes common to factor H and factor H-related proteins (1998)

We have generated monoclonal antibodies (mAbs) specific for the C-terminus of factor H that can be used as inhibitory antibodies for heparin binding and for the specific detection of factor H and factor H-related proteins (FHRs) in plasma and triacylglycerol-rich lipoproteins. Four distinct mAbs were established: IXF9 (IgG1), VD3 (IgG2a), VIG8 (IgG1) and IIC5 (IgG1). Each reacts specifically with FHR-1 and factor H (and also with FHR-2 in the case of VIG8), but none binds to the related FHR-3 and FHR-4 proteins nor to factor H-like protein 1. By the use of deletion mutants of factor H and by comparing the reactivity with FHR-1 and FHR-2, the binding epitopes of the mAbs were identified and localized to different short consensus repeats (SCRs): mAbs IXF9 and VD3 bind to related or even identical sites within SCR18 (factor H) and SCR3 (FHR-1) respectively. mAbs VIG8 and IIC5 bind to different epitopes located within SCRs 19 to 20 of factor H and SCRs 4 to 5 of FHR-1 respectively. Only mAb VIG8 reacts with the corresponding SCRs 3 to 4 of FHR-2. These antibodies are useful for the detection of the corresponding proteins in biological specimens such as fractions of lipoproteins. In addition, mAb VIG8 has the unique feature of inhibiting binding of factor H to heparin. Given the recent identification of a heparin- and a C3b-binding domain within the C-terminus of factor H, these mAbs should provide useful tools for functional analysis and for the precise localization of the domain(s) required for this interaction.
A Diverse Group of Previously Unrecognized Human Rhinoviruses Are Common Causes of Respiratory Illnesses in Infants (2007)

By molecular analysis, over 50% of HRV detected in sick infants were previously unrecognized strains, including 9 strains that may represent a new HRV group. These findings indicate that the number of HRV strains is considerably larger than the 101 serotypes identified with traditional diagnostic techniques, and provide evidence of a new HRV group.
Incidence of open-angle glaucoma: the Barbados Eye Studies. The Barbados Eye Studies Group. (2001)

This longitudinal study provides new information on OAG risk, as well as the first incidence measurement in a black population. Although intraocular pressure increased risk, about half of the new cases had baseline pressures of 21 mm Hg or less. Results substantiate the high OAG risk in the population of African origin, especially in older adults; the relative role of intraocular pressure; and the considerable underdetection of new disease after 4 years of follow-up.
Oriented and covalent immobilization of target molecules to solid supports: Synthesis and application of a light-activatable and thiol-reactive cross-linking reagent (1993)

Light-dependent oriented and covalent immobilization of target molecules has been achieved by combining two modification procedures: light-dependent coupling of target molecules to inert surfaces and thiol-selective reactions occurring at macromolecule or substrate surfaces. For immobilization purposes the heterobifunctional reagent N-[m-[3-(trifluoromethyl)diazirin-3-yl]phenyl]-4-maleimidobutyr amide was synthesized and chemically characterized. The photosensitivity of the carbene-generating reagent and its reactivity toward thiols were ascertained. Light-induced cross-linking properties of the reagent were documented (i) by reacting first the maleimide function with a thiolated surface, followed by carbene insertion into applied target molecules, (ii) by photochemical coupling of the reagent to an inert support followed by thermochemical reactions with thiol functions, and (iii) by thermochemical modification of target molecules prior to carbene-mediated insertion into surface materials. Procedures mentioned led to light-dependent covalent immobilization of target molecules including amino acids, a synthetic peptide, and antibody-derived F(ab') fragments. Topically selective, light-dependent immobilization was attained with the bifunctional reagent by irradiation of coated surfaces through patterned masks. Glass and polystyrene served as substrates. Molecular orientation is asserted by inherently available or selectively introduced terminal thiol functions in F(ab') fragments and synthetic polypeptides, respectively.