gebhart/patrepeval huggingface dataset:
Prevention of graft-versus-host disease with T cell depletion or cyclosporin and methotrexate. A randomized trial in adult leukemic marrow recipients. (1991)

In adult leukemic marrow recipients of HLA identical sibling marrow, 23 patients were randomized to T cell depletion and 25 received cyclosporin (CSA) and four doses of methotrexate (MTX) to prevent graft-versus-host disease (GVHD). Anti-CD8 and anti-CD6 antibodies plus complement depleted 95.3 +/- 5.8% (mean +/- SE) CD3 cells. All patients engrafted except one who died early. Patients receiving T cell-depleted marrow had a faster time to 0.2 x 10(9) WBC/l (p less than 0.001), but required more erythrocyte units (p = 0.03). Platelet transfusions, infections and time in hospital did not differ. The incidence of grade II-III acute GVHD was 23% following T cell depletion and 12% for those receiving CSA + MTX. Chronic GVHD occurred in 51% and 23% in the two groups, respectively (p = 0.06). Recipients of T cell-depleted marrow who developed grade I-III acute GVHD received more T cells compared to those without acute GVHD (p = 0.02). The major cause of death in both groups was relapse, the cumulative incidence of which, at 4 years, was 39% in the recipients of T cell-depleted marrow and 54% in the CSA + MTX group. The 3-year actuarial leukemia-free survival was 42% and 44% in the two respective groups.
Immune response to porins isolated from Salmonella typhi in different mouse strains. (1995)

Outer membrane proteins (OMPs) are able to induce protection against the challenge with S. typhi in a murine model. Both humoral and cellular immunity are involved in the protective mechanisms. In order to determine whether the responsiveness to S. typhi porins is genetically controlled in mice, different strains were immunized i.p. with 30 micrograms of OMPs isolated from S. typhi 9,12,Vi:d at days 0 and 7. On day 21, spleen cells were recovered and the lymphoproliferative response to porins was assessed. The highest responses were found in mice with H-2k and H-2a haplotypes (C3H/HeJ and A/J), intermediate responses were found in mice with H-2b haplotype (C57Bl/6) and the lowest responses in H-2d mice (Balb/c). These results demonstrate that the responsiveness to S. typhi porins is in part controlled by the major histocompatibility complex class II molecules and will help to further study the mechanisms of the immune response to these proteins.
TEACHER'S CORNER: Structural Equation Modeling With the sem Package in R (2006)

R is free, open-source, cooperatively developed software that implements the S statistical programming language and computing environment. The current capabilities of R are extensive, and it is in wide use, especially among statisticians. The sem package provides basic structural equation modeling facilities in R, including the ability to fit structural equations in observed variable models by two-stage least squares, and to fit latent variable models by full information maximum likelihood assuming multinormality. This article briefly describes R, and then proceeds to illustrate the use of the tsls and sem functions in the sem package. The article also demonstrates the integration of the sem package with other facilities available in R, for example for computing polychoric correlations and for bootstrapping.
Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects (2003)

Previously we described a reliable method based on immunodepletion for isolating mesenchymal stem cells (MSCs) from murine bone marrow and showed that, after intracranial transplantation, the cells migrated throughout forebrain and cerebellum and adopted neural cell fates. Here we systemically administered MSCs purified by immunodepletion from male bleomycin (BLM)-resistant BALB/c mice into female BLM-sensitive C57BL/6 recipients and quantified engraftment levels in lung by real-time PCR. Male DNA accounted for 2.21 x 10(-5)% of the total lung DNA in control-treated mice but was increased 23-fold (P = 0.05) in animals exposed to BLM before MSC transplantation. Fluorescence in situ hybridization revealed that engrafted male cells were localized to areas of BLM-induced injury and exhibited an epithelium-like morphology. Moreover, purification of type II epithelial cells from the lungs of transplant recipients resulted in a 3-fold enrichment of male, donor-derived cells as compared with whole lung tissue. MSC administration immediately after exposure to BLM also significantly reduced the degree of BLM-induced inflammation and collagen deposition within lung tissue. Collectively, these studies demonstrate that murine MSCs home to lung in response to injury, adopt an epithelium-like phenotype, and reduce inflammation and collagen deposition in lung tissue of mice challenged with BLM.
Bioresponsive, Cell-Penetrating, and Multimeric MR Contrast Agents (2009)

Magnetic resonance imaging (MRI) has become increasingly popular in experimental molecular imaging and clinical radiology because it is non-invasive and capable of producing three-dimensional representations of opaque organisms with high spatial and temporal resolution. Approximately 35% of all clinical MR scans utilize contrast media, however a primary limitation of MR imaging is the sensitivity of contrast agents that require high concentrations (0.1-0.6 mM). A number of strategies have been employed to amplify the observed in vivo signal of MR contrast agents. Approaches include attachment of Gd(III) chelates to polymers, proteins and particles, encapsulation into micelles and caged structures, and targeting to receptors. While each of these approaches has yielded significant increases in the relaxivity of MR contrast agents (and therefore sensitivity), all of these classes of complexes possess intrinsic background signal and function solely as anatomical reporters. In order to reduce the background signal and simultaneously create probes that are modulated by biochemical processes, caged complexes were designed to coordinatively saturate the paramagnetic ion. Coupled with amplification strategies, these agents represent a means to selectively modulate the observed MR signal and function as in vivo biochemical reporters. For example, to create an in vivo MR assay of enzymatic activities and secondary messengers, agents have been designed and synthesized with removable protection groups that largely prevent access of water to a paramagnetic center. By limiting the access of bulk water (q-modulation) the unprocessed agent is designed to be an ineffective contrast agent, and hence serves as a reliable marker for regions of enzyme activity or the presence of secondary messengers. Further, we have focused on designing multimodal contrast agents that are simultaneously detectable by more than one imaging technique. For example, attaching an optical probe to a MR contrast agent provides the means to detect the probe in a whole animal and subsequently validate the results by histological methods. Finally, we describe strategies for signal amplification, and cell delivery vehicles attached to imaging probes for in vivo long-term fate mapping experiments.
Assay of factor VIII antigen (VIII:CAg) in 294 Haemophilia A patients by a new commercial ELISA using monoclonal antibodies (1998)

Monoclonal antibodies (MoAbs 833 and D4H1) directed against human factor VIII (FVIII) have been produced on a large scale to measure VIII:CAg by two-site ELISA (Asserachrom VIII:CAg, Diagnostica Stago). F(ab')2 from MoAb 833 were used for coating and bound VIII:CAg was revealed with MoAb D4H1 coupled to peroxidase. Control plasma (100 VIII:CAg U dL-1 by comparing with the International Standard) was used as reference. The assay sensitivity was 0.1 U dL-1 VIII:CAg. No apparent effect of the plasma proteins was observed provided plasma dilution was > or = 5. Thus this ELISA allowed us to estimate VIII:CAg levels of 0.5 U dL-1 in plasma. Levels of VIII:CAg were similar to those of VIII:C (correlation coefficient r = 0.87) in plasma from normal individuals (32 cases) and in patients with von Willebrand disease of various types (30 cases). Among 294 patients with haemophilia A (HA), 161 had severe HA (VIII:C < 1 U dL-1). Among those patients, 124 were cross-reacting material (CRM) negative with undetectable VIII:CAg and 37 were CRM+ (VIII:CAg 1-31 U dL-1). In 42 patients with moderate HA (VIII:C 1-5 U dL-1), 33 were CRM reduced (VIII:CAg 0.5-8 U dL-1) and nine were CRM+ with a VIII:CAg/VIII:C ratio of 6-91 (mean 34.3). In mild HA (91 cases with VIII:C > or = 6 U dL-1), 29 patients were classified as CRM+ (VIII:C 6-57 U dL-1, VIII:CAg 17-130 U dL-1 and VIII:CAg/VIII:C ratio 1.8-13.7 (mean 4.51)). In 62 CRM reduced patients there was a linear correlation between VIII:C (6-39 U dL-1) and VIII:CAg (2-36 U dL-1) levels (r = 0.88). In conclusion, this sensitive assay allows us to distinguish the quantitative CRM reduced and negative from the qualitative (CRM+) abnormalities in haemophilia A.
Identification of candidate genes for drug discovery by differential display (1997)

Regulation of gene expression can specify cellular fate, define responses to stimuli, and contribute to complex microenvironments present in tissues. Identification of differentially expressed genes in experimental paradigms can help elucidate underlying biochemical pathways and thus reveal potential therapeutic targets. The technique of differential display uses arbitrarily primed PCR to sample complex cDNA populations of interest; amplified portions of messenger RNAs are analyzed by denaturing gel electrophoresis and those which are differentially represented can be directly visualized and cloned. PCR-based techniques for analysis of gene expression are reliable and extremely sensitive. In comparison to traditional methods, such as subtractive hybridization, differential display allows for many samples to be compared in parallel, and the requirement for starting material is low. There are a plethora of examples in the literature of how differentially expressed genes can be rapidly identified in experimental paradigms ranging from cells treated in culture to whole organs of treated animals. The challenge for the researcher is then defining candidate genes for drug discovery from an initial screen based only on differential expression patterns. Careful experimental design and execution are critical for optimal use of such methodologies to fill a gene discovery pipeline. In this article, the merits and potential pitfalls of differential display and related PCR-based techniques are discussed. Current protocols are reviewed and innovations pertaining to high- throughput applications are noted. Drug Dev. Res. 41:142–159, 1997. © 1997 Wiley-Liss, Inc.
Digital signal processing: theory, applications, and hardware (1991)

Designed for graduate students and signal processing practitioners with an introductory background in DSP, this new text gives representative coverage of advanced topics (orthogonal expansions, optimal filters, and two-dimensional DSP), and advanced aspects of familiar topics (fast transforms beyond the FFT, non-uniform sampling and quantization). Providing a self-contained blending of DSP theory, applications to speech and image processing, and state-of-the-art DSP hardware, Digital Signal Processing includes: introductory DSP concepts summarized in five appendixes; DSP filter algorithms - e.g.subband and median filters; least squares, optimal, and adaptive filters spectral estimation and deconvolution; speech and image processing applications; and DSP hardware realizations.
Imaging Mass Spectrometry—A New and Promising Method to Differentiate Spitz Nevi From Spitzoid Malignant Melanomas (2011)

Imaging Mass Spectrometry analysis can reliably differentiate SN from SMM in formalin-fixed, paraffin-embedded tissue based on proteomic differences.
The Gastrointestinal Tract The “Undrained Abscess” of Multiple Organ Failure (1993)

The upper GI tract is an important reservoir of the organisms causing ICU-acquired infection. Pathologic GI colonization is associated with the development of MOF in the critically ill surgical patient.
PREPL: a putative novel oligopeptidase propelled into the limelight (2006)

The prolyl endopeptidase-like protein PREPL has recently attracted attention because its gene is located within two contiguous gene-deletion syndromes, the 2p21 deletion syndrome and the hypotonia-cystinuria syndrome. Deletion of the gene results in hypotonia at birth, failure to thrive and growth hormone deficiency. PREPL is highly reactive against an activity-based probe, which indicates the presence of an intact catalytic machinery. However, no substrate has been found yet. The unique carboxy-terminus of the catalytic domain might contain the key to the as yet elusive specificity.
Adaptive Subgradient Methods for Online Learning and Stochastic Optimization (2010)

Stochastic subgradient methods are widely used, well analyzed, and constitute effective tools for optimization and online learning. Stochastic gradient methods ’ popularity and appeal are largely due to their simplicity, as they largely follow predetermined procedural schemes. However, most common subgradient approaches are oblivious to the characteristics of the data being observed. We present a new family of subgradient methods that dynamically incorporate knowledge of the geometry of the data observed in earlier iterations to perform more informative gradient-based learning. The adaptation, in essence, allows us to find needles in haystacks in the form of very predictive but rarely seenfeatures. Ourparadigmstemsfromrecentadvancesinstochasticoptimizationandonlinelearning which employ proximal functions to control the gradient steps of the algorithm. We describe and analyze an apparatus for adaptively modifying the proximal function, which significantly simplifies setting a learning rate and results in regret guarantees that are provably as good as the best proximal function that can be chosen in hindsight. In a companion paper, we validate experimentally our theoretical analysis and show that the adaptive subgradient approach outperforms state-of-the-art, but non-adaptive, subgradient algorithms. 1
Prevention of Drug Access to Bacterial Targets: Permeability Barriers and Active Efflux (1994)

Some species of bacteria have low-permeability membrane barriers and are thereby "intrinsically" resistant to many antibiotics; they are selected out in the multitude of antibiotics present in the hospital environment and thus cause many hospital-acquired infections. Some strains of originally antibiotic-susceptible species may also acquire resistance through decreases in the permeability of membrane barriers. Another mechanism for preventing access of drugs to targets is the membrane-associated energy-driven efflux, which plays a major role in drug resistance, especially in combination with the permeation barrier. Recent results indicate the existence of bacterial efflux systems of extremely broad substrate specificity, in many ways reminiscent of the multidrug resistance pump of mammalian cells. One such system seems to play a major role in the intrinsic resistance of Pseudomonas aeruginosa, a common opportunistic pathogen. As the pharmaceutical industry succeeds in producing agents that can overcome specific mechanisms of bacterial resistance, less specific resistance mechanisms such as permeability barriers and multidrug active efflux may become increasingly significant in the clinical setting.
Regulated Cell Surface Pro-EGF Ectodomain Shedding Is a Zinc Metalloprotease-dependent Process (2003)

Epidermal growth factor receptor (EGFR) ligands are synthesized as type I membrane protein precursors exposed at the cell surface. Shedding of the ectodomain of these proteins is the way cells regulate the equilibrium between cell-associated and diffusible forms of these growth factors. Whereas the regulated shedding of transforming growth factor-alpha, HB-EGF, and amphiregulin precursors have been clearly established, regulation of full-length pro-EGF shedding has not been clearly demonstrated. Here, using both wild-type and M2 mutant CHO-K1 as well as HeLa cell lines transiently transfected with epitope-tagged rat pro-EGF expression plasmid, we demonstrate that these cells synthesize EGF as a high molecular weight membrane-associated precursor glycoprotein expressed at the cell surface. All cell lines are able to release the entire ectodomain of pro-EGF in the extracellular medium following juxtamembrane cleavage of the precursor once it is present at the cell surface. More significantly we clearly established that CHO-M2 and HeLa cells only constitutively release low levels of pro-EGF. This shedding is a regulated phenomenon in wild-type CHO cells where it can be induced by different agents such as phorbol 12-myristate 13-acetate (PMA), pervanadate, and serum but not by calcium ionophores. Using specific inhibitors as well as protein kinase C (PKC) depletion, PMA stimulation was shown to be completely dependent on PKC activation whereas pervanadate and serum stimulation were not. Regulated ectodomain shedding involves the activity of a zinc metalloprotease as determined by inhibition with phenantrolin and TAPI-2 and by the results obtained with the CHO-M2 shedding defective mutant cell line. Comparison of the ability of CHO and HeLa cell lines to shed pro-EGF and pro-TNF-alpha upon stimulation greatly suggests that TACE (ADAM 17) may not be the ectoprotease involved in the secretion of pro-EGF ectodomain and that this protease, which remains to be identified, shows a restricted cellular expression pattern.
SALT AND DROUGHT STRESS SIGNAL TRANSDUCTION IN PLANTS (2002)

Salt and drought stress signal transduction consists of ionic and osmotic homeostasis signaling pathways, detoxification (i.e., damage control and repair) response pathways, and pathways for growth regulation. The ionic aspect of salt stress is signaled via the SOS pathway where a calcium-responsive SOS3-SOS2 protein kinase complex controls the expression and activity of ion transporters such as SOS1. Osmotic stress activates several protein kinases including mitogen-activated kinases, which may mediate osmotic homeostasis and/or detoxification responses. A number of phospholipid systems are activated by osmotic stress, generating a diverse array of messenger molecules, some of which may function upstream of the osmotic stress-activated protein kinases. Abscisic acid biosynthesis is regulated by osmotic stress at multiple steps. Both ABA-dependent and -independent osmotic stress signaling first modify constitutively expressed transcription factors, leading to the expression of early response transcriptional activators, which then activate downstream stress tolerance effector genes.
Transepithelial potential difference in cystic fibrosis. (1985)

In cystic fibrosis the potential difference between interstitial fluid and the surface of respiratory and sweat duct epithelia is abnormally large. This study attempted to confirm this finding and investigate its value for a diagnostic test. With a subcutaneous reference electrode the mean potential difference of the inferior turbinate was -25 mv in 19 patients with cystic fibrosis, which was significantly greater than the difference of -13 mv in 22 normal subjects (p less than 0.02). Of the observations in the patients with cystic fibrosis, 67% were greater than the largest potential difference observed in normal individuals. Potential differences from the lip and forearm were also significantly greater in cystic fibrosis than in normal subjects, but there was considerable overlap. Changes in the electrical properties of nasal epithelium and skin have been confirmed in cystic fibrosis, but these have limited use for diagnosis.
Inhibition of murine AIDS by a heterodinucleotide of azidothymidine and 9-(R)-2-(phosphonomethoxypropyl)adenine (2002)

Tenofovir [9-(R)-2-(phosphonomethoxypropyl)adenine (PMPA)] and zidovudine [azidothymidine (AZT)] are potent anti-HIV agents that have shown a strong synergy in in vitro studies. In this paper we have investigated both the potentiality of this synergy in vivo and the possibility to administer AZT and PMPA simultaneously as a single drug AZTpPMPA. The pharmacokinetic studies reported here have shown that AZTpPMPA administered intraperitoneally in mice performs as a prodrug, providing a slow delivery of AZT and PMPA in circulation. C57BL/6 mice infected with the retroviral complex LP-BM5 were used to evaluate the efficacy of AZTpPMPA in inhibiting disease progression. Furthermore, the effectiveness of the heterodinucleotide was compared with that of AZT and PMPA, administered as single drugs, or as a combination (AZT plus PMPA). The results obtained showed that AZTpPMPA is able to reduce lymphoadenopathy (88%), splenomegaly (64%), lymph node BM5 proviral DNA content (49%) and hypergammaglobulinaemia (40%). However, upon AZT plus PMPA administration, similar (splenomegaly and lymphoadenopathy reduction) or better results (64% hypergammaglobulinaemia reduction and 75% lymph node BM5 proviral DNA content inhibition) were obtained. Furthermore, these results overlapped those obtained upon PMPA administration. Thus, no synergy between PMPA and AZT was observed in murine AIDS and administration of AZT does not improve the antiviral results obtained by PMPA administration.
UV-light imprinted Bragg grating in sol-gel ridgeglass waveguide with almost 100% reflectivity (1997)

The authors report the fabrication of sol-gel ridge waveguides with a grating. The singlemode ridge waveguide for 1.55 µm applications is made by ultraviolet light imprinting. The grating is written by the phase mask technique. 97 and 95% reflection is achieved for TE and TM polarisations, respectively, in a waveguide with a 1.5 mm long grating.
Rheumatoid factor isotype switch and somatic mutation variants within rheumatoid arthritis synovium (1999)

The presence of clonally-related B-lymphocyte aggregates within synovial lining tisue of rheumatoid arthritis (RA) patients suggests a germinal centre-like reaction, which may hold implications for disease pathogenesis and the causes of chronic inflammation. We studied 250 rheumatoid factor (RF) heavy-chain sequences cloned from the synovium of three patients with RA, to determine whether they undergo both somatic mutation and isotype switching consistent with this hypothesis. Size analysis of immunoglobulin heavy-chain cDNAs from synovial RF+ B cells revealed oligoclonal RF+ populations and identically-sized VH-D-JH transcripts of different immunoglobulin isotypes. Sequencing of individual inserts selected from cloned immunoglobulin heavy-chain cDNAs demonstrated a clonal relationship between immunoglobulin M (IgM) RF and IgA RF, suggesting that this isotype switch occurred in synovium. Furthermore, most somatic mutations were found to have occurred after this isotype switch. This finding suggests that the RA synovial microenvironment sustains somatic mutation and isotype switching in RF-specific B lymphocytes akin to secondary lymphoid organs.
PASADO, PRESENTE Y FUTURO DE LAS INVESTIGACIONES SOBRE EL MUNDO PÚNICO: UNA REVISIÓN ANTE EL NUEVO MILENIO (2001)

Ahora que iniciamos un nuevo siglo, la arqueología púnica cuenta con más de cien años de historia. En el presente artículo se va a tratar de realizar un recorrido a lo largo de la historia de las investigaciones sobre el mundo púnico así como de establecer un estado de la cuestión del desarrollo de esta disciplina y su posición de cara al futuro.ResuméL’archéologie punique a déjà plus d’un siecle d’histoire. Dans cet étude, on va faire un bilan sur l’histoire des recherches scientiphiques sur le monde punique et sur certaines perspectives generaux et l’avenir de cette discipline archéologique.