gebhart/patrepeval huggingface dataset:
Phenotypic and functional characteristics of hematopoietic cell lineages in CD69-deficient mice (2000)

AIM/CD69 is the earliest leukocyte activation antigen and is expressed mainly by activated T, B, and natural killer (NK) cells. It is also constitutively expressed by platelets, by bone marrow myeloid precursors, and by small subsets of resident lymphocytes in the secondary lymphoid tissues. The engagement of CD69 by specific antibodies induces intracellular signals, including Ca(++) flux, cytokine synthesis, and cell proliferation. To investigate the physiological relevance of CD69, we generated mice deficient in CD69 (CD69-/-) by gene targeting in embryonic stem cells. CD69 (-/-) mice showed largely normal hematopoietic cell development and normal T-cell subpopulations in thymus and periphery. Furthermore, studies of negative- and positive-thymocyte selection using a T-cell receptor transgenic model demonstrated that these processes were not altered in CD69 (-/-) mice. In addition, natural killer and cytotoxic T lymphocyte cells from CD69-deficient mice displayed cytotoxic activity similar to that of wild-type mice. Interestingly, B-cell development was affected in the absence of CD69. The B220(hi)IgM(neg) bone marrow pre-B cell compartment was augmented in CD69 (-/-) mice. In addition, the absence of CD69 led to a slight increase in immunoglobulin (Ig) G2a and IgM responses to immunization with T-dependent and T-independent antigens. Nevertheless, CD69-deficient lymphocytes had a normal proliferative response to different T-cell and B-cell stimuli. Together, these observations indicate that CD69 plays a role in B-cell development and suggest that the putative stimulatory activity of this molecule on bone marrow-derived cells may be replaced in vivo by other signal transducing receptors.
Acne vulgaris treatment : The Current Scenario (2011)

Acne Vulgaris is one of the most common skin disorders which dermatologists have to treat. It mainly affect adolescent, though may present at any age. In recent years, due to better understanding of the pathogenesis of acne, new therapeutic modalities and various permutation and combinations have been designed. In topical agents; benzoyl peroxide, antibiotics, retinoids, etc are the mainstay of treatment; can be given in combinations. While systemic therapy includes oral antibiotics, hormonal therapy, and isotretinoin, depending upon the need of patients it has to be selected. Physical treatment in the form of lesion removal, photo-therapy is also helpful in few of them. Since various old and new topical and systemic agents are available to treat acne, it sometime confuse treating dermatologist. To overcome this, panel of physicians and researchers worked together as a global alliance and task force to improve outcomes in acne treatment. They have tried to give consensus recommendation for the treatment of acne. Successful management of acne needs careful selection of anti-acne agents according to clinical presentation and individual patient needs.
Isolation and characterization of the human interleukin-9 receptor gene (1994)

To better understand the regulation of interleukin-9 (IL-9) receptor expression, we have isolated the genomic clone of the human IL-9 receptor based on its sequence homology with a human IL-9 receptor cDNA isolated from the human megakaryocyte cell line UT-7. The entire genomic structure has been determined. The human IL-9 receptor gene consists of 10 exons spread over approximately 13.7 kb of DNA. The nucleotide sequence of the coding region from the genomic DNA is identical to our cDNA clone. Several blocks of transcriptional control sequence have been identified at the 5' noncoding region of the IL-9 receptor gene that may play an important role in the regulation of the IL-9 receptor gene. A fusion gene containing 659 bp of human IL-9 receptor 5' noncoding region linked to the firefly luciferase gene directed expression of luciferase activity in human embryonic kidney 293 cell line, but not in the mouse fibroblast cell line NIH3T3 cells.
The Peritoneal Cavity Provides a Protective Niche for B1 and Conventional B Lymphocytes during Anti-CD20 Immunotherapy in Mice (2005)

Although anti-CD20 immunotherapy effectively treats human lymphoma and autoimmune disease, the in vivo effect of immunotherapy on tissue B cells and their subsets is generally unknown. To address this, anti-mouse CD20 mAbs were used in a mouse model in which the extent and kinetics of tissue B cell depletion could be assessed in vivo. CD20 mAb treatment depleted most mature B cells within 2 days, with 95-98% of B cells in the bone marrow, blood, spleen, lymph nodes, and gut-associated lymphoid tissues depleted by day 7, including marginal zone and follicular B cells. The few spleen B cells remaining after CD20 mAb treatment included pre-B, immature, transitional, and some B1 B cells that expressed CD20 at low levels. By contrast, peritoneal cavity B cells expressed normal CD20 densities and were coated with CD20 mAb, but only 30-43% of B1 cells and 43-78% of B2 cells were depleted by day 7. Spleen B cells adoptively transferred into the peritoneal cavity were similarly resistant to mAb-induced depletion, while transferred B cells that had migrated to the spleen were depleted. However, peritoneal B1 and B2 cells were effectively depleted in mAb-treated wild-type and C3-deficient mice by thioglycolate-induced monocyte migration into this otherwise privileged niche. Inflammation-elicited effector cells did not promote peritoneal cavity B cell depletion in FcR-deficient mice treated with CD20 mAb. Thus, the majority of CD20(+) cells and B cell subsets within lymphoid tissues and the peritoneum could be depleted efficiently in vivo through Fc-dependent, but C-independent pathways during anti-CD20 immunotherapy.
Analysis and evaluation of neural network model for building artificial brain (2009)

At present,the artificial brain research is still at its initial period,and the methods to construct artificial brain are being explored.The key part determining the performance of artificial brain is the neural network evolved by genetic algorithm.This paper studied the performance of three models that had been proposed for building artificial brain,namely,CoDi model,TiPo model and DePo model.The models were compared by solving the curve following problems.Experiment results show that DePo model performs better than CoDi model and TiPo model.CoDi model is worst but simple.The further work in building artificial brain would be to develop models that are more consistent with biology mechanism,or to find more evolvable models in engineering respect.
Cross-parameterization and compatible remeshing of 3D models (2004)

Many geometry processing applications, such as morphing, shape blending, transfer of texture or material properties, and fitting template meshes to scan data, require a bijective mapping between two or more models. This mapping, or cross-parameterization , typically needs to preserve the shape and features of the parameterized models, mapping legs to legs, ears to ears, and so on. Most of the applications also require the models to be represented by compatible meshes, i.e. meshes with identical connectivity, based on the cross-parameterization. In this paper we introduce novel methods for shape preserving cross-parameterization and compatible remeshing. Our cross-parameterization method computes a low-distortion bijective mapping between models that satisfies user prescribed constraints. Using this mapping, the remeshing algorithm preserves the user-defined feature vertex correspondence and the shape correlation between the models. The remeshing algorithm generates output meshes with significantly fewer elements compared to previous techniques, while accurately approximating the input geometry. As demonstrated by the examples, the compatible meshes we construct are ideally suitable for morphing and other geometry processing applications.
Chicken interferon consensus sequence-binding protein (ICSBP) and interferon regulatory factor (IRF) 1 genes reveal evolutionary conservation in the IRF gene family. (1995)

Members of the IRF family mediate transcriptional responses to interferons (IFNs) and to virus infection. So far, proteins of this family have been studied only among mammalian species. Here we report the isolation of cDNA clones encoding two members of this family from chicken, interferon consensus sequence-binding protein (ICSBP) and IRF-1. The predicted chicken ICSBP and IRF-1 proteins show high levels of sequence similarity to their corresponding human and mouse counterparts. Sequence identities in the putative DNA-binding domains of chicken and human ICSBP and IRF-1 were 97% and 89%, respectively, whereas the C-terminal regions showed identities of 64% and 51%; sequence relationships with mouse ICSBP and IRF-1 are very similar. Chicken ICSBP was found to be expressed in several embryonic tissues, and both chicken IRF-1 and ICSBP were strongly induced in chicken fibroblasts by IFN treatment, supporting the involvement of these factors in IFN-regulated gene expression. The presence of proteins homologous to mammalian IRF family members, together with earlier observations on the occurrence of functionally homologous IFN-responsive elements in chicken and mammalian genes, highlights the conservation of transcriptional mechanisms in the IFN system, a finding that contrasts with the extensive sequence and functional divergence of the IFNs.
Tyrosine kinase inhibitors. 7. 7-amino-4-(phenylamino)- and 7-amino-4-[(phenylmethyl)amino]pyrido[4,3-d]pyrimidines: a new class of inhibitors of the tyrosine kinase activity of the epidermal growth factor receptor (1995)

The synthesis of 7-aminopyrido[4,3-d]pyrimidines bearing aromatic side chains at the 4-position is reported. These compounds are shown to be a new class of inhibitors of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR). Structure-activity relationships (SARs) for substitution in both 4-(phenylamino)- and 4-[(phenylmethyl)amino] side chains were determined, using a series of substituents (NO2, Br, CF3, OMe, NH2, and NMe2) selected primarily for their wide range of electronic properties. In the phenylamino series, 3-substituted derivatives were more potent than the corresponding 2- and 4-substituted analogues. For the 3-substituted compounds, activity was favored by electron withdrawal, in a relationship which could be quantified, with the 3-Br being the most potent compound (IC50 = 0.01 microM compared with IC50 = 0.34 microM for the unsubstituted side chain derivative). No such correlation was apparent for the 2- or 4-substituent, although Br was still the best substituent. In contrast, in the 4-[(phenylmethyl)amino] series, substitution of the side chain was not beneficial. For the 4-(phenylamino) series, the substituent SARs are broadly similar to that found previously for 4-(phenylamino)quinazolines. These results suggest that side chain SARs may be broadly invariant over a range of different chromophores, with the side chain of choice for optimization of EGFR inhibitory activity being 4-[(3-bromophenyl)amino].
In vivo base editing restores sensory transduction and transiently improves auditory function in a mouse model of recessive deafness (2020)

Most genetic diseases arise from recessive point mutations that require correction, rather than disruption, of the pathogenic allele to benefit patients. Base editing has the potential to directly repair point mutations and provide therapeutic restoration of gene function. Mutations of transmembrane channel-like 1 gene (<i>TMC1</i>) can cause dominant or recessive deafness. We developed a base editing strategy to treat Baringo mice, which carry a recessive, loss-of-function point mutation (<i>c.A545G</i>; resulting in the substitution p.Y182C) in Tmc1 that causes deafness. <i>Tmc1</i> encodes a protein that forms mechanosensitive ion channels in sensory hair cells of the inner ear and is required for normal auditory function. We found that sensory hair cells of Baringo mice have a complete loss of auditory sensory transduction. To repair the mutation, we tested several optimized cytosine base editors (CBEmax variants) and guide RNAs in Baringo mouse embryonic fibroblasts. We packaged the most promising CBE, derived from an activation-induced cytidine deaminase (AID), into dual adeno-associated viruses (AAVs) using a split-intein delivery system. The dual AID-CBEmax AAVs were injected into the inner ears of Baringo mice at postnatal day 1. Injected mice showed up to 51% reversion of the <i>Tmc1 c.A545G</i> point mutation to wild-type sequence (<i>c.A545A</i>) in <i>Tmc1</i> transcripts. Repair of <i>Tmc1</i> in vivo restored inner hair cell sensory transduction and hair cell morphology and transiently rescued low-frequency hearing 4 weeks after injection. These findings provide a foundation for a potential one-time treatment for recessive hearing loss and support further development of base editing to correct pathogenic point mutations.
Indústria e Engenheiros no Portugal de fins do século XIX: o caso de uma relação difícil (2000)

Os Alvitres, publicados na Revista de Obras Publicas e Minas,em 1899, constituem um documento extremamente interessante para a avaliacao do papel dos engenheiros portugueses no processo de implementacao da modernidade industrial em Portugal. Os Alvitres sao dirigidos simultaneamente ao governo e aos proprios engenheiros (estes na figura da Associacao dos Engenheiros Civis portugueses). As primeiras 10 sugestoes filiam-se, claramente, numa visao proteccionista, cobrindo tres areas fundamentais: competencias especificas e inovacao, industria e mercado de trabalho e sistema educativo. As restantes 8 sugestoes devem ser entendidas enquanto medidas de estrategia, permitindo-nos perceber a importância e o poder dos engenheiros portugueses em termos economicos e politicos. Na presente comunicacao pretendo analisar os Alvitres como um exemplo das dificeis relacoes entre a engenharia e a industria portuguesas em finais do seculo XIX.
Modulatory Effects of Regional Cortical Activation on the Onset Responses of the Cat Medial Geniculate Neurons (1997)

Corticofugal modulation on activity of the medial geniculate body (MGB) was examined by locally activating the primary auditory cortex (AI) and looking for effects on the onset responses of MGB neurons to acoustic stimuli. Of 103 MGB neurons recorded from 13 hemispheres of 11 animals, 91 neurons (88%) showed either a facilitatory or inhibitory effect or both; of these neurons, 72 showed facilitatory effects and 25 inhibitory effects. The average facilitatory effect was large, with a mean increase of 62.4%. Small inhibitory effects (mean: -16.2%) were obtained from a few neurons (6 of 103) when a pure tone stimulus was used, whereas the effect became larger and more frequent when a noise burst stimulus was used (mean: -27.3%, n = 22 of 27 neurons). Activation of an AI site having the same best frequency (BF) as the MGB neuron being recorded from produced mainly a facilitatory effect on MGB neuronal responses to pure tones. Activation of AI at a site neighboring the BF site produced inhibitory effects on the MGB response when noise burst stimuli were used. We found that the effective stimulation sites in AI that could modulate MGB activity formed patchlike maps with a diameter of 1.13 +/- 0.09 (SE) mm (range 0.6-1.9 mm, n = 15) being larger than the patches of thalamocortical terminal fields. Examining the effects of sound intensities, of 18 neurons tested 9 neurons showed a larger effect for low-sound-intensity stimuli and small or no effects for high-sound-intensity stimuli. These were named low-sound-intensity effective neurons. Five neurons showed high sound intensity effectiveness and four were non-intensity specific. Most low-sound-intensity effective neurons were monotonic rate-intensity function neurons. The AI cortical modulatory effect was frequency specific, because 15 of 27 neurons showed a larger facilitatory effect when a BF stimulus was used rather than a stimulus of any other frequency. The corticothalamic connection between the recording site in MGB and the most effective stimulation site in AI was confirmed by injecting wheat germ agglutinin-horseradish peroxidase tracer at the stimulation site and producing a small lesion in the recording site. The results suggest that 1) the large facilitation effects obtained by AI activation at the region that directly projected to the MGB could be the result mainly of the direct projection terminals to the MGB relay neurons; 2) the large size patches of the effective stimulation site in AI could be due to widely ramifying corticothalamic projections; and 3) the corticofugal projection selectively gates auditory information mainly by a facilitatory effect, although there is also an inhibitory effect that depends on the sound stimulus used.
AN EXPERIMENTAL STUDY OF SILICONE AS A SOFT TISSUE SUBSTITUTE (1959)

MARZONI, FRANCIS A. M.D.; UPCHURCH, SAMUEL E. M.D.; LAMBERT, C J M.D. Author Information
Production and Characterization of Monoclonal Antibodies Specific for Citrus Tristeza Virus and Their Use for Diagnosis (1986)

Summary Monoclonal antibodies (MAb) specific for citrus tristeza virus (CTV) were obtained from hybrid cells produced by fusion of a non-secreting myeloma cell line with spleen cells from BALB/c mice immunized with isolate T-308 of CTV. Three MAb were characterized for their immunoglobulin isotype and their titres in cell culture and ascites fluids. Each MAb was conjugated with alkaline phosphatase and used in a double-antibody sandwich enzyme-linked immunosorbent assay for CTV. When tested against 23 strains of CTV, each MAb recognized all the strains with uniform reactions and low background.
Expression of specific mRNAs during adipose differentiation: identification of an mRNA encoding a homologue of myelin P2 protein. (1984)

To identify and characterize specific mRNAs that increase in abundance during differentiation of mouse 3T3-L1 preadipocytes, a cDNA library was constructed from poly(A)+RNA isolated from differentiated 3T3-L1 adipocytes. Mixed probe isotope ratio selection and RNA blot analyses have identified several unique cDNA clones that represent mRNA species expressed either exclusively or at dramatically increased levels in differentiated cells. Further characterization of one such clone (pAL422) revealed that the corresponding mRNA, detectable only after differentiation, is approximately the same length (600 +/- 150 bases) as the cDNA insert (672 bases). The complete nucleotide sequence of the cDNA insert in pAL422 revealed a single long open reading frame that encodes a 132 amino acid polypeptide (the 422 protein) of 14.6 kDa. These and other results suggest that this cDNA may represent a nearly full-length copy of the mRNA. Computer-assisted analyses showed that the 422 protein shares 69% and 64% homology with myelin P2 proteins from rabbit and bovine peripheral nerves, respectively, as well as 23% and 30% homology with fatty-acid binding proteins from rat liver and intestine, respectively. Moreover, the mRNA hybrid selected by pAL422 DNA directs the in vitro translation of an approximately equal to 13 kDa polypeptide, and this protein is specifically immunoprecipitated by antiserum against bovine myelin P2. These observations strongly suggest that the 422 protein is a structural, and possibly functional, analog of myelin P2.
Characterization of the optimum transmitter correlation matrix for mimo with antenna subset selection (2003)

We give a simple and complete characterization of the optimum transmitter correlation matrix for multiple-input-multiple-output (MIMO) systems, when antenna subset selection is used. It is assumed that the receiver feeds back to the transmitter only the selected set of antennas without providing any kind of rank ordering of the selected antennas. It turns out that the optimal correlation matrix in this case must be a convex combination of an identity matrix and a matrix whose elements are all ones. This reduces the problem of finding the actual optimum to a one-dimensional search in any given scenario.
Regulation of the severity of neuroinflammation and demyelination by TLR‐ASK1‐p38 pathway (2010)

Apoptosis signal-regulating kinase 1 (ASK1) is an evolutionarily conserved mitogen-activated protein kinase (MAPK) kinase kinase which plays important roles in stress and immune responses. Here, we show that ASK1 deficiency attenuates neuroinflammation in experimental autoimmune encephalomyelitis (EAE), without affecting the proliferation capability of T cells. Moreover, we found that EAE upregulates expression of Toll-like receptors (TLRs) in activated astrocytes and microglia, and that TLRs can synergize with ASK1-p38 MAPK signalling in the release of key chemokines from astrocytes. Consequently, oral treatment with a specific small molecular weight inhibitor of ASK1 suppressed EAE-induced autoimmune inflammation in both spinal cords and optic nerves. These results suggest that the TLR-ASK1-p38 pathway in glial cells may serve as a valid therapeutic target for autoimmune demyelinating disorders including multiple sclerosis.
Regulation of fatty acid degradation in Escherichia coli: analysis by operon fusion (1981)

Fusion of the lacZ gene coding for beta-galactosidase to the fadA,B and fadE operons was accomplished by using the phage Mu d (Apr lac). In such fusion strains, beta-galactosidase was induced by long-chain fatty acids and repressed by glucose, as is the normal pattern of control for the enzymes of the fad regulon. The level of induction seen was approximately 10-fold for both the fadA and fadE operons. These results demonstrate that the previously observed regulation of both the fadA and fadE operons is at the transcriptional level. When an insertion mutation in the fadR (repressor) gene was introduced into the fusion strains, beta-galactosidase was produced constitutively. A series of fatty acids of different chain lengths were tested as inducers. Acids of chain lengths of 10 carbon atoms or less failed to induce, those of 12 carbon atoms induced partly, and those of 14 or more carbon atoms induced fully. Imidazole was found to counteract the glucose repression of the fadA operon as recently demonstrated for the ara operon.
Media design for user density of up to 3 bits per pulse width (1993)

It is noted that increasing the user density in digital recording by the use of linear equalization and sequence detection will provide new design opportunities and new constraints on the recording media. The authors have evaluated five head/media designs to determine how the media can benefit from systems operating at higher user density. They conclude that the limits to recording at high user density are nonlinearities in dibit amplitude and increases in the dibit amplitude jitter and correlation. The origins of the nonlinearities and noise are described by knockdown and recoil of the media magnetization. Head/media systems must be designed to avoid knockdown. The systems which will be the most successful in taking advantage of new channel techniques will be system using high-efficiency codes with multiple bits per flux change.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>