gebhart/patrepeval huggingface dataset:
Partial correction of the α‐galactosidase A deficiency and reduction of glycolipid storage in Fabry mice using synthetic vectors (2003)

Systemic delivery of a cationic lipid-pDNA complex partially corrected the enzyme deficiency and reduced glycolipid storage in a mouse model of Fabry disease. The results are one of the few demonstrations of long-term efficacy in a genetic disease model using nonviral vectors. However, substantial improvements in expression, especially in critical organs such as the kidney, are required before these vectors can become a viable approach to treat Fabry disease and other lysosomal storage disorders.
Pre-stack deghosting for variable-depth streamer data (2012)

Variable-depth streamer acquisition is an acquisition technique aiming at achieving the best possible signal-to-noise ratio at low frequencies by towing the streamer very deeply, but by using a depth profile varying with offset in order not to limit the high frequency bandwidth. Previous papers have shown how a joint deconvolution allows the post-stack deghosting of such variable-depth streamer acquisitions, and the purpose of this paper is to show how this can be generalized to a multi-channel joint deconvolution that allows pre-stack though post imaging deghosting of such acquisitions. After computing migrated gathers as well as mirror migrated gathers, a deghosted gather is computed through joint deconvolution by assuming a parametrical form in offset for the events. This method preserves the AVO behaviour. Synthetic and real data examples are shown.
Longitudinal comparison of preterm pain responses to repeated heelsticks. (2005)

Nurses' use of developmental care and the QuickHeel device may result in lower pain scores. Higher severity of illness and number of prior heelsticks may lower pain scores.
Improved local delivery of TGF-?2 by binding to injectable fibrillar collagen via difunctional polyethylene glycol (1998)

To overcome rapid diffusion and clearance from the implant site and to increase stability, recombinant transforming growth factor beta2 (TGF-beta2) was covalently bound to injectable bovine dermal fibrillar collagen (FC) and its activity compared to admixed TGF-beta2. Covalent binding was achieved in a two-step procedure: First, TGF-beta2 was reacted with the difunctional polyethylene glycol (PEG) linker, and then the PEG-attached TGF-beta2 (PEG-TGF-beta2) was bound to the fibrillar collagen (FC-PEG-TGF-beta2). Initial binding of TGF-beta2 to difunctional succinimidyl glutarate (D-SG-PEG) or succinimidyl propionate polyethylene glycol (D-SE-PEG) linkers was completed after reacting for 8 or 10 min as monitored by reverse-phase high-performance liquid chromatography. After reaction with injectable fibrillar collagen, extraction of unbound PEG-TGF-beta2 and Western blot analysis, using a TGF-beta specific antibody, demonstrated that at least 85% of the TGF-beta2 was bound to the fibrillar collagen. The activity of PEG-TGF-beta2 was fully stable in phosphate-buffered saline at 4 degrees C and 37 degrees C for at least up to 4 weeks. Unmodified TGF-beta2 mixed with fibrillar collagen was completely inactivated after 1 week of incubation, as measured by the mink lung epithelial cell (Mv1Lu) growth inhibition assay. Formulations of FC-PEG-TGF-beta2 containing 40 microg/ mL TGF-beta2 were implanted subcutaneously into rats and analyzed after days 7, 21, and 42. All TGF-beta2-containing formulations showed the TGF-beta typical fibroblastic response at the day 7 time point. Covalent binding of TGF-beta2 to collagen with both difunctional PEG crosslinkers resulted in a significantly stronger and longer-lasting TGF-beta2 response than that observed with admixed formulations of collagen and TGF-beta. The TGF-beta response with FC-PEG-TGF-beta2 lasted up to day 42 but was not seen after day 7 for TGF-beta2 admixed to FC. These findings clearly demonstrate that TGF-beta2 remains fully active after being covalently bound to collagen via difunctional PEG. In addition, covalent binding potentiates and prolongs in vivo TGF-beta responses and stabilizes the TGF-beta in vitro. Results suggest that this method of formulation could be useful to stabilize and deliver similar peptide growth factors or biologically active agents.
pH‐dependent formation of ethylenediaminetetraacetic acid supramolecular aggregates (1994)

Pure ethylenediaminetetraacetic acid tetrasodium salt (EDTA.Na4) in water showed a pH-dependent change of optical density detected in the ultraviolet region. The most important change was found between pH 4 and 8, corresponding to the deprotonation of the third ionizable group having a pK of 6.2. The absorbance change was reversible and depended on the addition/removal of only 1 proton equivalent. The presence of supramolecular aggregates was suggested by size-exclusion chromatography, dialysis and cryo-electronmicroscopy. The molecular weight of EDTA supramolecular aggregates was 10-15,000 and 8-14,000, as determined by gel chromatography and dialysis, respectively. Cryo-electronmicroscopy revealed structures of 2-4 nm in diameter.
Biological Regulation of Factor VIII Activity (1992)

Factor VIII, the plasma protein deficient in hemophilia A, is a crucial cofactor for regulation of hemostasis. Our understanding of factor VIII increased tremendously once it became possible to isolate homogeneous preparations of this protein from plasma. In addition, the isolation of the factor VIII gene has provided new means of exploring the structure and function of factor VIII. This increasing knowledge also sheds light on the genetic alterations resulting in hemophilia as well as in thrombophilia. This chapter summarizes our current understanding of the regulation of factor VIII function and raises questions to be answered in the years to come.
An interaction between replication protein A and SV40 T antigen appears essential for primosome assembly during SV40 DNA replication. (1993)

Replication protein A from human cells (hRPA) is a multisubunit single-stranded DNA-binding protein (ssb) and is essential for SV40 DNA replication in vitro. The related RPA from Saccharomyces cerevisiae (scRPA) is unable to substitute for hRPA in SV40 DNA replication. To understand this species specificity, we evaluated human and yeast RPA in enzymatic assays with SV40 T antigen (TAg) and human DNA polymerase alpha/primase, the factors essential for initiation of SV40 DNA replication. Both human and yeast RPA stimulated the polymerase and (at subsaturating levels of RPA) the primase activities of human DNA polymerase alpha/primase on homopolymer DNA templates. In contrast, both human and yeast RPA inhibited synthesis by DNA polymerase alpha/primase on natural single-stranded DNA (ssDNA) templates. T antigen reversed the inhibition of DNA polymerase alpha/primase activity on hRPA-coated natural ssDNA, as previously described, but was unable to reverse the inhibition on scRPA or Escherichia coli ssb-coated templates. Therefore, the ability of an ssb to reconstitute SV40 DNA replication correlated with its ability to allow the TAg stimulation of polymerase alpha/primase in this assay. Enzyme-linked immunoassays demonstrated that hRPA interacts with TAg, as previously described; however, scRPA does not bind to TAg in this assay. These and other recent results suggest that T antigen contains a function analogous to some prokaryotic DNA replication proteins that facilitate primosome assembly on ssb-coated template DNAs.
Tcf3 is an integral component of the core regulatory circuitry of embryonic stem cells (2008)

Embryonic stem (ES) cells have a unique regulatory circuitry, largely controlled by the transcription factors Oct4, Sox2, and Nanog, which generates a gene expression program necessary for pluripotency and self-renewal. How external signals connect to this regulatory circuitry to influence ES cell fate is not known. We report here that a terminal component of the canonical Wnt pathway in ES cells, the transcription factor T-cell factor-3 (Tcf3), co-occupies promoters throughout the genome in association with the pluripotency regulators Oct4 and Nanog. Thus, Tcf3 is an integral component of the core regulatory circuitry of ES cells, which includes an autoregulatory loop involving the pluripotency regulators. Both Tcf3 depletion and Wnt pathway activation cause increased expression of Oct4, Nanog, and other pluripotency factors and produce ES cells that are refractory to differentiation. Our results suggest that the Wnt pathway, through Tcf3, brings developmental signals directly to the core regulatory circuitry of ES cells to influence the balance between pluripotency and differentiation.
Proliferation of distinct human T cell subsets in response to live, killed or soluble extracts of Mycobacterium tuberculosis and Myco. avium (1996)

The proliferative responses of distinct cell subsets from healthy, bacille Calmette-Guérin (BCG)-vaccinated blood donors were assessed after in vitro stimulation with live or UV-killed Mycobacterium tuberculosis and Myco. avium or with soluble extracts obtained from either mycobacterial species. Proliferation of cell subsets was evaluated by flow cytometric determination of 5-bromo-2'-deoxy-uridine incorporation into DNA and simultaneous identification of surface phenotypic markers. In the presence of monocytes, the response to whole (live or killed) bacteria was characterized by a predominant proliferation of CD4+ alphabeta+ T cells and, to a lesser extent, of CD8+ alphabeta+ T cells. Proliferation of CD8+ alphabeta+ T cells was primarily elicited by live rather than killed bacilli (P < 0.05). Conversely, when soluble bacterial extracts were used as stimulators, a preferential proliferation of gammadelta+ T cells, expressing predominantly Vgamma9+ and Vdelta2+ T cell receptor chains, was recorded. Moreover, when monocyte-depleted cell populations were directly cultured with live bacteria, a marked proportion of CD3- CD16+ (natural killer (NK)) cells was detected among the responding cells. Although both alphabeta, gammadelta and NK cells have been previously shown to react with mycobacteria in vitro, their relative contributions to the response have been difficult to assess. Using a flow cytometric technique which allows direct identification of proliferating cells within complex cell populations, our study demonstrates significant differences in the ability of various mycobacterial antigen preparations to elicit proliferation of distinct cell subsets.
Vitamin C as an Antioxidant: Evaluation of Its Role in Disease Prevention (2003)

Vitamin C in humans must be ingested for survival. Vitamin C is an electron donor, and this property accounts for all its known functions. As an electron donor, vitamin C is a potent water-soluble antioxidant in humans. Antioxidant effects of vitamin C have been demonstrated in many experiments in vitro. Human diseases such as atherosclerosis and cancer might occur in part from oxidant damage to tissues. Oxidation of lipids, proteins and DNA results in specific oxidation products that can be measured in the laboratory. While these biomarkers of oxidation have been measured in humans, such assays have not yet been validated or standardized, and the relationship of oxidant markers to human disease conditions is not clear. Epidemiological studies show that diets high in fruits and vegetables are associated with lower risk of cardiovascular disease, stroke and cancer, and with increased longevity. Whether these protective effects are directly attributable to vitamin C is not known. Intervention studies with vitamin C have shown no change in markers of oxidation or clinical benefit. Dose concentration studies of vitamin C in healthy people showed a sigmoidal relationship between oral dose and plasma and tissue vitamin C concentrations. Hence, optimal dosing is critical to intervention studies using vitamin C. Ideally, future studies of antioxidant actions of vitamin C should target selected patient groups. These groups should be known to have increased oxidative damage as assessed by a reliable biomarker or should have high morbidity and mortality due to diseases thought to be caused or exacerbated by oxidant damage.
Systematic Analysis of Large Screening Sets in Drug Discovery (2004)

Each year large pharmaceutical companies produce massive amounts of primary screening data for lead discovery. To make better use of the vast amount of information in pharmaceutical databases, companies have begun to scrutinize the lead generation stage to ensure that more and better qualified lead series enter the downstream optimization and development stages. This article describes computational techniques for end to end analysis of large drug discovery screening sets. The analysis proceeds in three stages: In stage 1 the initial screening set is filtered to remove compounds that are unsuitable as lead compounds. In stage 2 local structural neighborhoods around active compound classes are identified, including similar but inactive compounds. In stage 3 the structure-activity relationships within local structural neighborhoods are analyzed. These processes are illustrated by analyzing two large, publicly available databases.
Structure-Based Design, Synthesis, and Evaluation of Conformationally Constrained Mimetics of the Second Mitochondria-Derived Activator of Caspase That Target the X-Linked Inhibitor of Apoptosis Protein/Caspase-9 Interaction Site (2004)

A successful structure-based design of conformationally constrained second mitochondria-derived activator of caspase (Smac) mimetics that target the XIAP/caspase-9 interaction site is described. The most potent Smac mimetic 12d has a Ki of 350 nM for binding to the XIAP BIR3 domain protein. 12d is found to be effective in enhancing apoptosis induced by cisplatin in PC-3 human prostate cancer cells.
A dual role of extracellular DNA during biofilm formation of Neisseria meningitidis (2010)

Major pathogenic clonal complexes (cc) of Neisseria meningitidis differ substantially in their point prevalence among healthy carriers. We show that frequently carried pathogenic cc (e.g. sequence type ST-41/44 cc and ST-32 cc) depend on extracellular DNA (eDNA) to initiate in vitro biofilm formation, whereas biofilm formation of cc with low point prevalence (ST-8 cc and ST-11 cc) was eDNA-independent. For initial biofilm formation, a ST-32 cc type strain, but not a ST-11 type strain, utilized eDNA. The release of eDNA was mediated by lytic transglycosylase and cytoplasmic N-acetylmuramyl-L-alanine amidase genes. In late biofilms, outer membrane phospholipase A-dependent autolysis, which was observed in most cc, but not in ST-8 and ST-11 strains, was required for shear force resistance of microcolonies. Taken together, N. meningitidis evolved two different biofilm formation strategies, an eDNA-dependent one yielding shear force resistant microcolonies, and an eDNA-independent one. Based on the experimental findings and previous epidemiological observations, we hypothesize that most meningococcal cc display a settler phenotype, which is eDNA-dependent and results in a stable interaction with the host. On the contrary, spreaders (ST-11 and ST-8 cc) are unable to use eDNA for biofilm formation and might compensate for poor colonization properties by high transmission rates.
Effects of human stem cell factor (c-kit ligand) on proliferation of myeloid leukemia cells: heterogeneity in response and synergy with other hematopoietic growth factors (1992)

A novel hematopoietic growth factor, the stem cell factor (SCF), for primitive hematopoietic progenitor cells has recently been purified and its gene has been cloned. In this study we tested the mitogenic activity of recombinant human SCF on myeloid leukemia cells as well as the expression of its receptor. We have investigated the proliferation of 31 myeloid leukemia cell lines as well as fresh myeloid leukemic blasts from 17 patients in a 72-hour 3H-thymidine uptake assay in the presence of various concentrations of recombinant human (rh) SCF alone or in combination with saturating concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, M-CSF, interleukin-3 (IL-3), or erythropoietin (EPO). Only five of 31 lines, but fresh leukemic blasts from 12 of 17 patients with acute myeloid leukemia (AML), significantly responded to SCF. The responding cell lines were of the acute promyelocytic, chronic myeloid, megakaryoblastic, and erythroleukemia origin, the responding blast preparations of all French-American-British subtypes. Synergistic activities of SCF were found with G-CSF, GM-CSF, EPO, and IL-3. To determine the SCF binding sites on leukemic cells, we used 125I-radiolabeled SCF in Scatchard analysis and cross-linking studies. The leukemic cell lines responding to SCF expressed from 2,300 up to 29,000 binding sites per cell. The SCF receptor expression was downregulated in vitro by the presence of its ligand. Cross-linking studies demonstrated a 150-Kd SCF receptor on the surface of all responding myeloid leukemias. This study suggests that SCF may be an important factor for the growth of myeloid leukemia cells, either as a direct stimulus or as a synergistic factor for other cytokines. Furthermore, using polymerase chain reaction analysis of total RNA from the myeloid leukemia lines, we found expression of SCF-mRNA in 17 of 30 lines, suggesting autocrine mechanisms in the growth of a subgroup of leukemic cells by coexpression of SCF and its receptor.
Regulatory elements in vivo in the promoter of the abscisic acid responsive gene rab17 from maize (1997)

The rab17 gene from maize is transcribed in late embryonic development and is responsive to abscisic acid and water stress in embryo and vegetative tissues. In vivo footprinting and transient transformation of rab17 were performed in embryos and vegetative tissues to characterize the cis-elements involved in regulation of the gene. By in vivo footprinting, protein binding was observed to nine elements in the promoter, which correspond to five putative ABREs (abscisic acid responsive elements) and four other sequences. The footprints indicated that distinct proteins interact with these elements in the two developmental stages. In transient transformation, six of the elements were important for high level expression of the rab17 promoter in embryos, whereas only three elements were important in leaves. The cis-acting sequences can be divided in embryo-specific, ABA-specific and leaf-specific elements on the basis of protein binding and the ability to confer expression of rab17. We found one positive, new element, called GRA, with the sequence CACTGGCCGCCC. This element was important for transcription in leaves but not in embryos. Two other non-ABRE elements that stimulated transcription from the rab17 promoter resemble previously described abscisic acid and drought-inducible elements. There were differences in protein binding and function of the five ABREs in the rab17 promoter. The possible reasons for these differences are discussed. The in vivo data obtained suggest that an embryo-specific pathway regulates transcription of the rab genes during development, whereas another pathway is responsible for induction in response to ABA and drought in vegetative tissues.
Heterodimers of the neurotrophic factors: Formation, isolation, and differential stability (1993)

We have determined that all four known members of the neurotrophin family, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4 (NT-4), are capable of forming noncovalent heterodimers. The formation of these heterodimers was accomplished by homodimer subunit exchange promoted by treatment with guanidine hydrochloride, urea, low pH, or acetonitrile. In some cases (BDNF and mouse NGF; BDNF and NT-4), generation of the heterodimers was achieved by incubating homodimer mixtures in a neutral buffer at ambient temperature. The formation of heterodimers was in each case detected by nondenaturing gel electrophoresis at pH 7.4. High-performance cation-exchange chromatography was used to separate neurotrophin heterodimers from their parental homodimers. Heterodimers between BDNF and NT-3, BDNF and NT-4, and NT-3 and NT-4 are stable and show only a very small increase in homodimer content after 24 h of incubation at 37 degrees C. In contrast, heterodimers containing NGF subunits undergo gradual rearrangement to the homodimers. Our studies indicate that low pH, acetonitrile, and urea merely increase the neurotrophin subunit exchange rate and decrease the time needed to reach an equilibrium between a heterodimer and its two parental homodimers.
Correlation Transfer and Diffusion of Ultrasound-Modulated Multiply Scattered Light (2006)

We develop a temporal correlation transfer equation (CTE) and a temporal correlation diffusion equation (CDE) for ultrasound-modulated multiply scattered light. These equations can be applied to an optically scattering medium with embedded optically scattering and absorbing objects to calculate the power spectrum of light modulated by a nonuniform ultrasound field. We present an analytical solution based on the CDE and Monte Carlo simulation results for light modulated by a cylinder of ultrasound in an optically scattering slab. We further validate with experimental measurements the numerical calculations for an actual ultrasound field. The CTE and CDE are valid for moderate ultrasound pressures and on a length scale comparable with the optical transport mean-free path. These equations should be applicable to a wide spectrum of conditions for ultrasound-modulated optical tomography of soft biological tissues.
Expression of a nonpolymorphic MHC class I-like molecule, CD1D, by human intestinal epithelial cells (1991)

The human CD1 locus encodes three nonpolymorphic MHC class I-like cell surface glycoproteins, CD1a-c, which are expressed primarily by immature thymocytes. A mAb and antipeptide antiserum were utilized to determine the tissue distribution of a fourth CD1 molecule, CD1d. Within the lymphoid lineage, CD1d was expressed on B cells but not on thymocytes. Immunoperoxidase staining of fresh frozen intestinal tissues demonstrated that the majority of intestinal epithelial cells, with the exception of cells at the base of some crypts, expressed CD1d. The CD1d staining was observed in the cytoplasm and along the basolateral membranes of the epithelial cells. The intestinal epithelial cell expression of CD1d was confirmed by immunoblotting with a CD1d antipeptide antiserum. Further immunoperoxidase studies indicated that CD1d, unlike murine CD1, was also expressed by nonlymphoid tissues outside of the gastrointestinal tract. The expression of CD1d outside the lymphoid and myeloid lineages clearly distinguishes this molecule from CD1a-c and suggests that it may serve a distinct function. The prominent expression of CD1d by intestinal epithelial cells suggests that this molecule may be an important ligand for T lymphocytes within the gut-associated lymphoid tissue.
미래에 성립될 자연과 인간의 새로운 관계 (1991)

미래의 우리와 자연과의 관계는 과거로부터 출발한다. 그러나 이 관계가 반드시 오늘날의 서구 문명의 위기를 야기시킨 주요 발전들에 국한해 성립할 필요는 없다. 이 발전들은 (1) 고대 그리스의 과학의 이념，(2) 기독교 유일신론에 의한 자연의 세속화와 함께 출발해서 (3) 근대 초기 유럽의 지구 탐험에 이어 과학기술적 자연 탐사에까지 이르렀다. 이 발 전들을 뿌리로 삼아 성장해 온 산업 사회는 전세계적으로 확산되고 있으며, 현재에도 그럴 것처럼 미래의 모습도 결정지을 것이다. 산업 경제는 세계의 일부 지역에 이제까지는 알려지지 않았던 부를 가져다 주었다. 그러나 이 부가 인류 전체에게로 일반화될 수는 없다. 만약 50억 또는 그 이상의 인구가 오늘날의 서유럽인이나 북미인처럼 생활한다면, 자연은 더 이상 인류를 지탱해 낼 수도 먹여살릴 수도 없다. 이런 의미에서 인구 문제는 잘사는 나라들의 문제이며, 인구 증가의 문제가 아니다. 특히 지구환경 파괴의 75%는 산업 국가들에 의해서 저질러지는 데 반해, 제3세계가 당하는 고통은, 또는 이산화탄소량을 기준으로 해서 볼 때, 그 자신의 몫인 25%가 아닌 무려 75~85%에 육박하고 있다. 이는 산업화한 국가들의 생존이 세계의 나머지를 대가로 하고 있음을 뜻하는 것이다.