gebhart/patrepeval huggingface dataset:
STATISTICAL METHODS FOR IDENTIFYING DIFFERENTIALLY EXPRESSED GENES IN REPLICATED cDNA MICROARRAY EXPERIMENTS (2002)

DNA microarrays are a new and promising biotechnology whichallows the monitoring of expression levels in cells for thousands of genes simultaneously. The present paper describes statistical methods for the identification of differentially expressed genes in replicated cDNA microarray experiments. Although it is not the main focus of the paper, new methods for the important pre-processing steps of image analysis and normalization are proposed. Given suitably normalized data, the biological question of differential expression is restated as a problem in multiple hypothesis testing: the simultaneous test for each gene of the null hypothesis of no association between the expression levels and responses or covariates of interest. Di erentially expressed genes are identified based on adjusted p-values for a multiple testing procedure which strongly controls the family-wise Type I error rate and takes into account the dependence structure between the gene expression levels. No specific parametric form is assumed for the distribution of the test statistics and a permutation procedure is used to estimate adjusted p-values. Several data displays are suggested for the visual identification of differentially expressed genes and of important features of these genes. The above methods are applied to microarray data from a study of gene expression in the livers of mice with very low HDL cholesterol levels. The genes identified using data from multiple slides are compared to those identified by recently published single-slide methods.
Angelman syndrome: a review of the clinical and genetic aspects (2003)

Angelman syndrome (AS) is a neurodevelopmental disorder characterised by severe learning difficulties, ataxia, a seizure disorder with a characteristic EEG, subtle dysmorphic facial features, and a happy, sociable disposition. Most children present with delay in developmental milestones and slowing of head growth during the first year of life. In the majority of cases speech does not develop. Patients with AS have a characteristic behavioural phenotype with jerky movements, frequent and sometimes inappropriate laughter, a love of water, and sleep disorder. The facial features are subtle and include a wide, smiling mouth, prominent chin, and deep set eyes. It is caused by a variety of genetic abnormalities involving the chromosome 15q11-13 region, which is subject to genomic imprinting. These include maternal deletion, paternal uniparental disomy, imprinting defects, and point mutations or small deletions within the UBE3A gene, which lies within this region. UBE3A shows tissue specific imprinting, being expressed exclusively from the maternal allele in brain. The genetic mechanisms identified so far in AS are found in 85-90% of those with the clinical phenotype and all interfere with UBE3A expression.
Rate-constrained coder control and comparison of video coding standards (2003)

A unified approach to the coder control of video coding standards such as MPEG-2, H.263, MPEG-4, and the draft video coding standard H.264/AVC (advanced video coding) is presented. The performance of the various standards is compared by means of PSNR and subjective testing results. The results indicate that H.264/AVC compliant encoders typically achieve essentially the same reproduction quality as encoders that are compliant with the previous standards while typically requiring 60% or less of the bit rate.
El centro experimental Pestalozzi (2004)

El Pesta, en Ecuador, atiende a ninos y jovenes de 3 a 18 anos, en un entorno abierto, en contacto con la naturaleza y con amplias ofertas educativas. Los adultos no responsabilizan de grupos de edades sino de un area y los ninos eligen que hacer en cada momento en funcion de su propio ritmo vital. Un nuevo paradigma de la educacion disenado para madurar junto a los hijos.
BCL-2 gene family and the regulation of programmed cell death. (1999)

The BCL-2 gene was identified at the chromosomal breakpoint of t(14; 18)-bearing human follicular B cell lymphomas. BCL-2 proved to block programmed cell death rather than promote proliferation. Transgenic mice that overexpress Bcl-2 in the B cell lineage demonstrate extended cell survival and progress to high-grade lymphomas. Thus, BCL-2 initiated a new category of oncogenes, regulators of cell death. Bcl-2-deficient mice demonstrate fulminant apoptosis of lymphocytes, profound renal cell death and loss of melanocytes. BCL-2 protein duels with its counteracting twin, a partner known as BAX. When BAX is in excess, cells execute a death command; but, when BCL-2 dominates, the program is inhibited and cells survive. Bax-deficient mice display cellular hyperplasia, confirming its role as a proapoptotic molecule. An expanded family of BCL-2-related proteins shares homology clustered within four conserved regions termed BCL-2 homology 1 through 4 (BH1-4). These novel domains control the ability of these proteins to dimerize and function. An amphipathic alpha helix, BH3, is of particular importance for the proapoptotic family members. BID and BAD represent an evolving set of proapoptotic molecules, which bear sequence homology only at BH3. They appear to reside more proximal in the pathway serving as death ligands. BAD connects upstream signal transduction paths with the BCL-2 family, modulating this checkpoint for apoptosis. In the presence of survival factor interleukin-3, cells phosphorylate BAD on two serine residues. This inactivated BAD is held by the 14-3-3 protein, freeing BCL-XL and BCL-2 to promote survival. Activation of BAX results in the initiation of apoptosis. Downstream events in this program include mitochondrial dysfunction, as well as Caspase activation. The pro- and antiapoptotic BCL-2 family members represent central regulators in an evolutionarily conserved pathway of cell death. Aberrations in the BCL-2 family result in disordered homeostasis, a pathogenic event in diseases, including cancer.
Polyionic and cysteine-containing fusion peptides as versatile protein tags (2013)

In response to advances in proteomics research and the use of proteins in medical and biotechnological applications, recombinant protein production and the design of specific protein characteristics and functions has become a widely used technology. In this context, protein fusion tags have been developed as indispensable tools for protein expression, purification, and the design of functionalized surfaces or artificially bifunctional proteins. Here we summarize how positively or negatively charged polyionic fusion peptides with or without an additional cysteine can be used as protein tags for protein expression and purification, for matrix-assisted refolding of aggregated protein, and for coupling of proteins either to technologically relevant matrices or to other proteins. In this context we used cysteine-containing polyionic fusion peptides for the design of immunotoxins. In general, polyionic fusion tags can be considered as a multifunctional module in protein technology.
The NMDA Receptor NR2B Subunit: A Valid Therapeutic Target for Multiple CNS Pathologies (2004)

The NMDAR2B subunit is the focus of increasing interest as a therapeutic target in a wide range of CNS pathologies, including acute and chronic pain, stroke and head trauma, drug-induced dyskinesias, and dementias. Due to significant pharmaceutical endeavor, an impressive collection of chemical leads has been developed which target the NR2B subunit, some of which appear to discriminate between closely related subtypes. We now have the benefit of a structural template for the ifenprodil binding site which should further improve future structure activity relationships. A growing appreciation of the likely extrasynaptic localisation of the NR2B receptor subtype and importance of NR2B protein modification, notably tyrosine phosphorylation, may explain its therapeutic importance. The apparent superior preclinical and clinical data for the second and third generation NR2B compounds is likely to reflect subtype selectivity, a unique mode of action and cellular location of the NR2B receptors in the CNS.
Interactions among Serum Vitamin D Binding Protein, Monomeric Actin, Profilin, and Profilactin (1989)

Human serum vitamin D binding protein (hDBP), a 58-kDa inter-alpha-globulin, is known to bind, monomeric actin (G-actin) in equimolar quantities. Using monoclonal and polyclonal anti-hDBP antibodies, hDBP, and radioiodinated actin, we developed a reliable saturation assay for actin bound to hDBP. By utilizing this assay, kinetic analysis, and ultracentrifugal sedimentation in sucrose gradients, these proteins' binding affinities (Kd = 10(-9) M) were demonstrated to be 10- to 100-fold greater than earlier estimates. At 4 degrees C, hDBP has an association rate constant of 2.2 x 10(4) M-1 s-1 and a rate of dissociation displaying a t1/2 of 22 h. This high affinity binding was largely unaffected by conditions favoring actin filament formation (1 mM MgCl2 and/or 50 mM KCl), by the range of pH from 6.8 to 8.6 or by temperatures from 4 to 37 degrees C. Compared with ATP-alpha-actin, a 2-fold decrease of binding affinity was observed for the nonmuscle isoactins (beta,gamma), ADP-G-alpha-actin, and N'-ethylmaleimide-modified G-alpha-actin. The 25-hydroxyvitamin D3 and 1 alpha,25-dihydroxyvitamin D3 holo-sterol forms of hDBP bound actin in a manner indistinguishable from the apo-sterol hDBP. The common polymorphisms of hDBP (DBP1 slow, DBP1 fast, and DBP2) were shown to have an equal avidity for G-actin binding. Human platelet profilin competed with hDBP for binding to G-actin, but was 1000-fold less potent (Ki = 1.9 microM). When platelet profilactin was incubated with hDBP, profilin was liberated and hDBP-actin complexes formed. DNase I, which forms a triprotein complex with hDBP-G actin, did not alter the affinity of binding of actin by hDBP. The very high affinity binding observed, which was largely unaffected by the state of G-actin, pH, and ionic conditions, appears to support a constitutive role for plasma DBP in the sequestration of actin monomers, as well as actin from actin-profilin complexes, that are liberated during cell injury.
Paramagnetic Bis(amidinate) Iron(II) Complexes and their Diamagnetic Dicarbonyl Derivatives (2001)

Reactions of two equivalents of the lithium amidinate salts Li[tBuC(NR)2] (R = iPr, cyclohexyl) with FeCl2 have been found to yield paramagnetic bis(amidinate) iron(II) compounds of the type [tBuC(NR)2]2Fe. In the case of R = cyclohexyl, the product has been characterized by single-crystal X-ray diffraction analysis as having a distorted tetrahedral geometry. The derivative with R = iPr is an oil, but its 1H and 13C NMR spectra indicate a similar monomeric structure. Both species have been found to react readily with CO to give the new diamagnetic FeII dicarbonyls [tBuC(NR)2]2Fe(CO)2. The compound with R = iPr has been structurally characterized, which showed it to have a strongly distorted octahedral structure with the carbonyls in a cis arrangement.
ORTHOTOPIC CORNEAL TRANSPLANTATION IN MICE—EVIDENCE THAT THE IMMUNOGENETIC RULES OF REJECTION DO NOT APPLY (1992)

The fate of orthotopic corneal transplants has been studied in inbred strains of mice. Using a surgical technique that achieves > 95% success of syngeneic cornea grafts, it was determined that a high proportion of orthotopic cornea allografts were accepted indefinitely, irrespective of the degree of immunogenetic disparity between graft donor and recipient. Grafts that succumbed to irreversible rejection developed extensive corneal edema and intrastromal neovascularization as harbingers of corneal opacity and endothelial cell failure. The highest rate of rejection occurred among grafts that confronted their hosts with multiple minor histocompatibility antigens, with or without major histocompatibility antigens. Much lower rates of rejection (< 35%) were observed when the donors of the grafts differed from recipients at class I and/or class II major histocompatibility loci. Corneal grafts that confronted their hosts with class II MHC alloantigens alone experienced early, acute inflammation, and eventually developed stomal neovascularization, but only a small minority of these grafts were eventually destroyed. Allogeneic corneas that were transplanted orthotopically into eyes of presensitized mice were uniformly subjected to an acute rejection process that produced opacity within three weeks; however, in a minority of instances, the inflammation and opacity subside, and after eight weeks the grafts displayed a clear, nonvascularized appearance. The high rate of success of even grossly histoincompatible orthotopic corneal allografts in mice resembles the extraordinary success of unmatched allogeneic corneas transplanted into human eyes. The results are discussed in terms of the possible mechanisms that permit orthotopic corneal allografts to enjoy significantly better survival than orthotopic grafts of other types of solid tissues.
De Novo Prediction of Three-dimensional Structures for Major Protein Families (2002)

We use the Rosetta de novo structure prediction method to produce three-dimensional structure models for all Pfam-A sequence families with average length under 150 residues and no link to any protein of known structure. To estimate the reliability of the predictions, the method was calibrated on 131 proteins of known structure. For approximately 60% of the proteins one of the top five models was correctly predicted for 50 or more residues, and for approximately 35%, the correct SCOP superfamily was identified in a structure-based search of the Protein Data Bank using one of the models. This performance is consistent with results from the fourth critical assessment of structure prediction (CASP4). Correct and incorrect predictions could be partially distinguished using a confidence function based on a combination of simulation convergence, protein length and the similarity of a given structure prediction to known protein structures. While the limited accuracy and reliability of the method precludes definitive conclusions, the Pfam models provide the only tertiary structure information available for the 12% of publicly available sequences represented by these large protein families.
Adoptive T cell therapy: An overview of obstacles and opportunities (2017)

The therapeutic potential of adoptive cell therapy (ACT) in cancer patients was first acknowledged 3 decades ago, but it was an esoteric approach at the time. In recent years, technological advancements have transformed ACT into a viable therapeutic option that can be curative in some patients. In fact, current ACT response rates are 80% to 90% for hematological malignancies and 30% for metastatic melanoma refractory to multiple lines of therapy. Although these results are encouraging, there is still much to be done to fulfill ACT's potential, specifically with regard to improving clinical efficacy, expanding clinical indications, reducing toxicity, and increasing production and cost-effectiveness. This review addresses the current major obstacles to ACT and presents potential solutions. Cancer 2017;123:2154-62. © 2017 American Cancer Society.
Mutagenic and chemotherapeutic activity in L1210 leukemia of several monofunctional alkylating agents. (1985)

The mutagenic and chemotherapeutic activities of the following monofunctional alkylating agents were compared in vivo: beta-chloroethylamine, dimethyl- and diethylaminoethyl chloride; methyl- and ethylmethanesulfonate; methyl- and ethylnitrosourea; and procarbazine. The bifunctional alkylating agent diethylamine 2,2'-dichloro-N-methyl-hydrochloride was used as reference. The alkylating activity was assessed by reacting with 4-(p-nitrobenzyl)pyridine, and antitumor activity was determined against L1210 in vitro and in vivo. The L1210 response, which is consistent with useful alkylating reactivity, was very marked with the two nitrosoureas and procarbazine. The nitrosoureas and, to some extent, procarbazine decreased the tumorigenicity of L1210 leukemia as evidenced by the increase in survival times with increasing numbers of treatment generations. After treatment for about five transfers (10(6) cells i.p.) with methylnitrosourea (40 mg/kg i.p. on Days 1, 3, and 5), the untreated control mice consistently survived free of tumor, whereas the treated mice died before Day 30. After treatment with ethylnitrosourea (80 mg/kg), the survival times also increased but more in the treated than in the corresponding control groups. Methylnitrosourea was most efficient in increasing the survival times and abolishing tumor transplantability. Antigenic change and loss of growth potential presumably were the reason for this increase in survival time, as indicated by tests in X-irradiated and nude mice. The fact that nitrosoureas and triazenes, besides reducing tumorigenicity, have similarities in their chemistry in that they decompose or are metabolically converted into diazohydroxides and then to carbonium ions is possibly of significance.
Structural and Formulation Factors Influencing Pyridinium Lipid-Based Gene Transfer (2008)

A series of pyridinium lipids containing a heterocyclic ring and a nitrogen atom were synthesized to determine the structure-activity relationship for gene delivery. Pyrylium chloroaluminate was synthesized by monoacylation of mesityl oxide and converted into pyrylium hexafluorophosphate, which was used as the key intermediate for reaction with different primary amines, to yield hydroxyethylpyridinium hexafluorophosphate and aminoethylpyridinium hexafluorophosphate. Acylation of these pyridinium salts with different types of fatty acid chlorides afforded the final pyridinium lipids, which were mixed with a co-lipid, such as L-alpha-dioleoylphosphatidylethanolamine (DOPE) and cholesterol (Chol) to prepare cationic liposomes by sonication. These liposomes were mixed with plasmid DNA encoding enhanced green fluorescent protein (pCMS-EGFP) or luciferase (pcDNA3-Luc) and transfected into Chinese hamster ovary (CHO) cells. Several factors including hydrophobic anchor chain length, anchor chain type, configuration of double bond, linker type, co-lipid type, cationic lipid/co-lipid molar ratio, charge ratio (N/P), and cell type had significant influence on transfection efficiency and cytotoxicity. Pyridinium lipids with amide linker showed significantly higher transfection efficiency compared to their ester counterparts. Liposomes prepared at a 1:1 molar ratio of pyridinium lipid and co-lipid showed higher transfection efficiency when either DOPE or cholesterol was used as a co-lipid to prepare cationic liposomes for complex formation with plasmid DNA at 3:1(+/-) charge ratio. Pyridinium liposomes based on a hydrophobic anchor chain length of 16 showed higher transfection efficiency and lower cytotoxicity. The pyridinium lipid with a trans-configuration of the double bond in the fatty acid chain showed higher transfection efficiency than its counterpart with cis-configuration at the same fatty acid chain length. In the presence of serum, C16:0 and Lipofectamine significantly decreased their transfection efficiencies, which were completely lost at a serum concentration of 30% and higher, while C16:1 trans-isomer still had high transfection efficiency under these conditions. In conclusion, pyridinium lipids showed high transfection efficiency and have the potential to be used as transfection reagents in vitro and in vivo.
iPS and ES Cells: Do Both Roads Lead to Rome? (2010)

The seminal report from Takahashi and Yamanka in 2006 describing the reprogramming of somatic cells to induced pluripotent stem (iPS) cells [1] marked the beginning of a new field of research, resulting in hundreds of publications in a short 3 years. Among other things, the promise of iPS cells in cell therapy circumvents many of the ethical concerns associated with embryonic stem (ES) cell research, and autologous patient-specific cells can be generated. Nonetheless, the jury is still out on the extent to which iPS cells and ES cells are functionally equivalent. This review focuses on the genetic and functional comparisons between these two cells types.
Efficient geometric algorithms for parsing in two dimensions (2005)

Grammars are a powerful technique for modeling and extracting the structure of documents. One large challenge, however, is computational complexity. The computational cost of grammatical parsing is related to both the complexity of the input and the ambiguity of the grammar. For programming languages, where the terminals appear in a linear sequence and the grammar is unambiguous, parsing is O(N). For natural languages, which are linear yet have an ambiguous grammar, parsing is O(N/sup 3/). For documents, where the terminals are arranged in two dimensions and the grammar is ambiguous, parsing time can be exponential in the number of terminals. In this paper we introduce (and unify) several types of geometrical data structures which can be used to significantly accelerate parsing time. Each data structure embodies a different geometrical constraint on the set of possible valid parses. These data structures are very general, in that they can be used by any type of grammatical model, and a wide variety of document understanding tasks, to limit the set of hypotheses examined and tested. Assuming a clean design for the parsing software, the same parsing framework can be tested with various geometric constraints to determine the most effective combination.
Multi-scale image harmonization (2010)

Traditional image compositing techniques, such as alpha matting and gradient domain compositing, are used to create composites that have plausible boundaries. But when applied to images taken from different sources or shot under different conditions, these techniques can produce unrealistic results. In this work, we present a framework that explicitly matches the visual appearance of images through a process we call image harmonization , before blending them. At the heart of this framework is a multi-scale technique that allows us to transfer the appearance of one image to another. We show that by carefully manipulating the scales of a pyramid decomposition of an image, we can match contrast, texture, noise, and blur, while avoiding image artifacts. The output composite can then be reconstructed from the modified pyramid coefficients while enforcing both alpha-based and seamless boundary constraints. We show how the proposed framework can be used to produce realistic composites with minimal user interaction in a number of different scenarios.
Catechol releases iron(iii) from ferritin by direct chelation without iron(ii) production (2005)

It has been traditionally considered that catechols release iron from ferritin by reduction to iron(II), which diffuses through the ferritin channels into the intracellular milieu where it participates in the Fenton reaction, producing highly toxic hydroxyl radicals. However, in the present work we have proved that the mechanism of the release of iron from ferritin by catechol does not take place by iron(II) reduction but by direct iron(III) chelation and therefore without iron(II) production. A possible extension of these findings to other catechols is discussed on the basis of the stability with respect to the internal redox reaction of the iron(III)-catechol complexes.