gebhart/patrepeval huggingface dataset:
The Earliest Thymic T Cell Progenitors Sustain B Cell and Myeloid Lineage Potentials (2011)

Abstract Abstract 2335 The stepwise lineage-commitment from hematopoietic stem cells (HSCs) in the bone marrow (BM) to T-lymphocyte-restricted progenitors in the thymus represents a paradigm for how distinct stages of lineage restriction from a multipotent to a lineage-restricted progenitor require different extrinsic cues. However, the commitment stage at which progenitors migrate from the BM to the thymus remains unclear. Previous studies demonstrated the existence of adult early thymic progenitors (ETPs) restricted to T lymphocyte and granulocyte-monocyte (GM) fates (Bell and Bhandoola, Nature 2008; Wada et al., Nature 2008). The challenge remains to couple this thymic T–GM restricted progenitor to candidate thymus seeding progenitors (TSPs) identified in the BM, such as common lymphoid progenitors, lymphoid-primed multipotent progenitors (LMPPs) and HSCs, which all also possess B cell potential. Using high resolution FACS and sensitive clonal assays, we have identified the most primitive ETPs in the neonatal thymus and demonstrate at the single cell level that rare Lin−CD4−CD8a−CD25−KIThiFLT3hi ETPs possess combined granulocyte-monocyte (GM), T and B lymphocyte but not megakaryocyte-erythroid (MkE) lineage potentials, identical to closely molecularly related thymus-seeding progenitors in the BM. Moreover, global molecular profiling demonstrates that neonatal Lin−CD4−CD8a−CD25−KIThiFLT3hi ETPs cluster closest to multipotent progenitors in the BM, rather than subsequent (DN1 and DN2) progenitor stages in the thymus. Finally, in support of Lin−CD4−CD8a−CD25−KIThiFLT3hi ETPs with combined T, B and GM lineage potentials, being the most multipotent progenitors in the thymus, phenotypic and functional studies demonstrate that the neonatal thymus is not seeded by HSCs or MPPs with MkE potential. These findings establish for the first time a distinct lineage commitment stage for the transition of T-lineage commitment from the BM to the remote thymus. Disclosures: No relevant conflicts of interest to declare.
Synthesis of poly(3-hydroxyalkanoates) in Escherichia coli expressing the PHA synthase gene phaC2 from Pseudomonas aeruginosa: comparison of PhaC1 and PhaC2 (2006)

In order to obtain functional expression of PHA synthase gene phaC2 from Pseudomonas aeruginosa in Escherichia coli, the coding region of phaC2 was subcloned, including the ribosomal binding site, into pBluescript SK- collinear to the lac promoter. This plasmid pBHR71-C2 enabled functional expression of phaC2 in E. coli LS1298 (fadB) under lac promoter control, leading to PHA accumulation, when grown in LB medium containing 0.5% (w/v) of various fatty acids (C8-C14). The strongest accumulation of PHA was observed, when dodecanoate was provided as carbon source, and PHA contributed to 15% of cell dry weight, which was composed of 35 mol% 3-hydroxydodecanoate, 60 mol% 3-hydroxydecanoate and 5 mol% 3-hydroxyoctanoate. Plasmid pBHR78, which contained both genes phaC1 and phaC2 from P. aeruginosa under lac promoter control in pBluescript SK- led in E. coli LS1298 to PHA accumulation, which contributed to 13% of cell dry weight, when cells were grown on decanoate. Only slight differences in PHA composition compared with either PhaC1 or PhaC2 were obtained. The weight average molecular masses of PHA purified from decanoate-grown cells of E. coli LS1298 expressing PhaC1 or PhaC2 alone or both PHA synthases, were 106 x 10(3), 70 x 10(3) or 67 x 10(3), respectively. This study clearly demonstrated that both PHA synthases from P. aeruginosa exhibit very similar properties resulting in similar extent of PHA accumulation, similar composition and molecular mass, when expressed in E. coli and that fatty acid beta-oxidation provides substrates for both PHA synthases.
Current understanding of dystrophin-related muscular dystrophy and therapeutic challenges ahead (2006)

Further understanding of pathophysiological mechanisms at molecular levels and regenerative properties of myogenic precursor/stem cells will promote the development of multiple therapeutic strategies. The combined use of multiple strategies may represent the major challenge as well as the greatest hope for the therapy of these diseases in coming years.
Polymers from Renewable Resources: A Challenge for the Future of Macromolecular Materials (2008)

This perspective article examines the state of the art regarding the field of polymers from renewable resources and attempts to give a critical appraisal of the situation related to a representative number of specific materials, in terms of their interest, present degree of advancement, and prospective development within short- and medium-term projections. The selected examples include polysaccharides and their derivatives, lignin, suberin, vegetable oils, tannins, natural monomers like terpenes, and monomers derived from sugars, with particular emphasis on furan derivatives and lactic acid, bacterial cellulose, and poly(hydroxyalkanoates), ending with a brief assessment of the potential role of glycerol and ethanol as future precursors to monomers.
The vacuum assisted closure of complex wounds: report of 3 cases (2003)

Treatment of wounds using conventional methods is frequently limited by inadequate local wound conditions, or by a poor systemic clinical situation. Vacuum system may promote faster granulation tissue formation, remove excessive exudate, increase blood flow in the wound, and attract the borders of the wound to the center, reducing its dimension. We present 3 cases of patients with difficult wounds, due to bad local conditions, or poor clinical situation, in whom we used a vacuum system to prepare the wound for the surgical closure. One patient had a pressure ulcer, another had a diabetic foot ulcer, and the third one had an open foot stump. In the 3 cases a significant improvement of the wound conditions was achieved after 7 to 8 days, allowing successful surgical treatment with flap or skin grafts.
Synthesis of Enantiopure Pyrrolidine-Derived Peptidomimetics and Oligo-β-peptides via Nucleophilic Ring-Opening of β-Lactams (2006)

The synthesis of the two enantiomers of pyrrolidine-derived spiro beta-lactams by resolution with D- and L-Boc phenylalanine is described. The potential of these optically active spiro beta-lactams on the synthesis of peptidomimetics as analogues of melanostatin is evaluated. Theoretical studies of several models, at the Becke3LYP/6-31+G* level of theory, together with previous experimental evidences from our group, gathered by NMR, allow us to design structures that can efficiently mimic some biologically active peptide-type molecules. On the other hand, the spiro beta-lactams have shown their utility in the preparation of beta-peptides. As an example, a homo-tetra-beta-peptide was synthesized. This research will continue in the future in order to obtain higher peptides with potential biological activity.
Overview of digital UNIX cluster system architecture (2002)

Digital UNIX clusters allow highly available high performance computing systems to be built from a multicomputer cluster. A single system image is presented to applications through a single file name space and clusterwide access to storage devices. Support for a cluster alias presents the same single system view to networking clients and peers. Interfaces are provided for application synchronization and enhanced application availability.
Questionable Relevance of γδ T Lymphocytes in Renal Cell Carcinoma (2008)

Adoptive gammadelta T cell immunotherapy has moved briskly into clinical trials prompted by several small studies suggesting abundant accumulation of gammadelta T cells within renal cell carcinoma (RCC). In this study, we re-examined levels of gammadelta T cells within RCC tumors and correlated levels of these cells with pathologic features and outcome associated with this form of cancer. Tissues from 248 consecutive clear cell RCC tumors obtained from 2000 to 2003 were stained and quantified for total CD3+ and gammadelta T cells per mm2. Wilcoxon rank sum and Kruskal-Wallis tests were used to evaluate associations between T cell amounts and prognostic factors (age, gender, tumor size, stage, grade, tumor necrosis). Cox models were used to assess associations with RCC-specific death. Median numbers of total CD3+ and gammadelta T cells were 281/mm2 (interquartile range (IQR): 149-536) and 2.6/mm2 (IQR: 1.3-4.6), respectively. The median percentage of CD3+ T cells that were gammadelta T cells was 1.0% (IQR: 0.4-1.9). This low percentage of intratumoral gammadelta T cells was diluted even further with rising CD3+ T cell infiltration. Percentages of gammadelta T cells were not associated with even one single clinicopathologic feature examined. Median follow-up for this study was 3.1 years (48 patients died of RCC) and Cox analysis failed to demonstrate that gammadelta T cells (hazard ratio=1.02, p=0.25) were predictive of RCC-specific death. gammadelta T cells are rare and not recruited nor expanded within RCC tumors. Percentages of gammadelta T cells fail to correlate with any prognostic features of RCC nor specific death. As such, the role of gammadelta T cells in RCC immunobiology remains questionable.
Data throughput of CDMA-HDR a high efficiency-high data rate personal communication wireless system (2002)

Forward link data throughput performance of a high data rate wireless access system is presented. On the forward link of the proposed system data is transmitted to different access terminals (AT) in a TDM fashion. The rate transmitted to each AT is variable and depends on each AT's measured SINR. ATs send to the access points (AP) the index of the highest data rate which can be received reliably. A scheduler at the AP determines the next terminal to be served based on the reported data rate requests from the terminals and the amount of data that has already been transmitted to each terminal. A cell layout of 19 3-sector and 6-sector hexagonal cells is considered. The throughput of the forward link of the embedded sector is simulated for stationary terminals.
FAK Activation and the Role of Epithelial Membrane Protein 2 (EMP2) in Collagen Gel Contraction (2009)

ARPE-19-mediated collagen gel contraction is a multistep process that requires integrin ligation and activation of the FAK/Src complex. EMP2 positively modulates collagen gel contraction by ARPE-19 cells through increased FAK activation.
Nicotine reduces Aβ in the brain and cerebral vessels of APPsw mice (2004)

Ten days treatment with nicotine reduced insoluble amyloid A beta 1-40 and Alpha beta 1-42 peptides by 80% in the cortex of 9-month-old APPsw mice, which is more than that observed in 14.5-month-old mice following nicotine treatment for 5.5 months. A reduction in A beta associated with cerebral vessels was observed in addition to that deposited as parenchymal plaques after 5.5 months treatment. The diminution in A beta peptides observed was not accompanied by changes in brain alpha, beta or gamma secretase-like activities, NGF or BDNF protein expression measured in brain homogenates. A significant increase in sAPP was observed after nicotine treatment of SH-SY5Yneuroblastoma cells that could be blocked by the nicotinic antagonist mecamylamine. Attenuation of elevated [(125)I]-alpha bungarotoxin binding (alpha 7) in APPsw mice was observed after 5.5 months nicotine treatment. Both these observations suggest that the reduction in insoluble A beta by nicotine might be in part mediated via the alpha 7 nicotinic receptor. Further studies are required to identify potential mechanisms of the nicotine's amyloid-reducing effect.
Multiband planar inverted-F car antenna for mobile phone and GPS (2003)

With the rapid growth of new cellular communication systems on different frequency ranges and the introduction of satellite navigation systems (i.e. GPS) in modern cars a multitude of car antennas is required, which all have to be mounted on the car body. In the paper a multiband car antenna is presented, designed as a dual band planar inverted-F antenna (PIFA) with integrated additional GPS antenna.
Oxygen-derived radicals: a link between reperfusion injury and inflammation. (1987)

Oxygen-derived free radicals (superoxide and hydroxyl) and related species (hydrogen peroxide and hypohalous acids) have well-defined roles in the inflammatory process. Their actions include the killing of microorganisms as well as participation in cell-to-cell communication among phagocytes via the activation of a superoxide-dependent chemoattractant. The active oxygen species also have roles in postischemic injury brought about by the conversion during ischemia of the enzyme xanthine dehydrogenase (EC 1.1.1.204) to the radical-producing xanthine oxidase (EC 1.1.3.22). Although the enzymes responsible for producing superoxide in inflammation and ischemia are quite distinct, and are triggered by very different events, there are points of interplay in the two mechanisms whereby an ischemia/reperfusion-induced injury would lead to inflammation, and conversely whereby inflammation could lead to impairment of the circulation and hence to ischemic injury.
Syntheses of a series of linear pentaamines with three and four methylene chain intervals. (1986)

The kinds of linear pentaamines with various combinations of 3 or 4 methylene chain intervals were synthesized. The methods were tentatively classified into two, leading to symmetrical and unsymmetrical pentaamines, all of which were prepared by successive alkylation of secondary amino derivatives of benzylamine with N-(3-bromopropyl or 4-bromobutyl)phthalimide in the presence of KF-Celite, coupled with the purification of the phthaloyl compounds by silica gel column chromatography. Protecting benzyl and phthaloyl groups were removed by usual methods. The carbon-13 unclear magnetic resonance (13C-NMR) spectra of the ten pentaamines were recorded in D2O as fully protonated forms, and a comparative analysis of their spectra allowed the complete assignment of all 13C chemical shifts.
Cytochemical localization of peroxidase activity in the developing erythrocyte. (1972)

Peroxidase activity, demonstrated with diaminobenzidine as the electron donor according to the method of Graham and Karnovsky, was used as a cytochemical marker in a study of developing erythrocytes in guinea pig and rabbit bone marrow. Peroxidase activity was deposited diffusely in the cytoplasm and nuclear matrix of developing cells and was thought to represent hemoglobin, which others have shown by independent criteria to have a similar distribution. Diffuse localization was first observed in erythroblasts and at all subsequent stages of development. Another finding was the significant particulate localization of peroxidase activity apparently associated with cytoplasmic ribosomes and nuclear particles of immature erythrocytes. This activity differentiated the most primitive erythroid precursors from hemocytoblasts of other marrow cell lines, a distinction impossible by strictly morphologic criteria. Particulate peroxidase localization was identified in erythroid hemocytoblasts, erythroblasts, normoblasts and reticulocytes but not in mature erythrocytes. The nature of the particle-associated peroxidase activity was not determined with certainty. However, it could not be differentiated from the diffuse activity, thought to reflect hemoglobin, by several inhibitors and could not be attributed to erythrocyte catalase. The possibility is therefore raised that this activity represents hemoglobin, newly assembled either on or immediately adjacent to nuclear particles and cytoplasmic ribosomes.
Ligand-independent activation of the estrogen receptors alpha and beta by mutations of a conserved tyrosine can be abolished by antiestrogens. (1998)

It has recently been suggested that mutation of a conserved tyrosine to asparagine within the ligand-binding domain of the estrogen receptor (ER) alpha confers hormone-independent activation and insensitivity to antiestrogens (Q. X. Zhang et al., Cancer Res., 57: 1244-1249, 1997). In view of the recent discovery of ERbeta and the development of the novel nonsteroidal antiestrogen EM-800 and its active metabolite EM-652, we decided to reexamine this issue by introducing a series of mutations at the conserved tyrosine 537 in ERalpha and 443 in ERbeta and measuring their transcriptional activity in the absence and presence of estradiol and the antiestrogens EM-652, ICI 182,780, and 4-hydroxytamoxifen. As demonstrated previously for ERalpha, we observed that substituting a serine or asparagine but not a phenylalanine for the conserved tyrosine 443 in ERbeta confers constitutive transcriptional activity to the receptor. This activity was apparent on both the vitA2-ERE and the pS2 promoters in Cos-1 and HeLa cell lines as well as the human breast cancer cell line MDA-MB-231. However, the ligand-independent transcriptional activity of all ERalpha and ERbeta mutants examined, including the tyrosine to asparagine substitutions, was completely abolished by the three antiestrogens tested in this system. Furthermore, hormone-independent interaction of ERalpha and ERbeta mutant receptors with the steroid receptor coactivator-1 was abrogated by these antiestrogens. Our report, therefore, indicates that antiestrogens would be effective agents against constitutively active tyrosine ERalpha and ERbeta mutants and suggests that this particular type of modified receptors are unlikely to contribute to resistance toward antiestrogens in breast cancer therapy.
Intraductal carcinoma. Long-term follow-up after treatment by biopsy alone (1978)

A follow-up period averaging 21.6 years was obtained for patients with low-grade papillary intraductal carcinoma initially treated only by biopsy between 1940 and 1950. Subsequent carcinoma was diagnosed in the same breast in seven of the ten patients after an average interval of 9.7 years. Six of the seven subsequent carcinomas were invasive. Two of the patients died of metastatic carcinoma and two were known to be alive with metastases when last contacted. Three patients were without carcinoma following mastectomy. When these results were combined with the few reports available in the literature, it appeared that at least 39% of patients with intraductal carcinoma treated by biopsy alone subsequently had clinically evident carcinoma, invariably in the same breat, with an average latent period of about ten years. This was undoubtedly a result of the multicentric nature of the disease in many patients.
A Multidimensional Tool to Quantify Treatment Resistance in Depression (2009)

This staging model has reasonable face and predictive validity and may have better utility in staging treatment resistance than currently available methods.
Overview and Epidemiologic Assessment of the Current Global Tuberculosis Situation with an Emphasis on Control in Developing Countries (1989)

The global epidemiologic situation of tuberculosis is reviewed, with emphasis on the disappointing achievements in its control in developing countries over the last three decades. In developed countries where prevalence of tuberculosis is low, it will take at least 30-50 years to eliminate the disease because of exacerbation by individuals who acquire infection abroad. In developing countries, 2-3 million deaths will occur among the estimated 4 million new smear-positive and 4 million new smear-negative and extrapulmonary cases of tuberculosis. The low cure rate with standard chemotherapy is the chief reason for failure of tuberculosis control in developing countries. The basic chemotherapeutic regimen (streptomycin for 2 months then a combination of isoniazid and thiacetazone for 12 months) does not achieve a high cure rate in developing countries. Under routine conditions the cure rate is high (90%) with an inexpensive 8-month regimen consisting of 2 months of strictly supervised daily administration of isoniazid, rifampin, pyrazinamide, and streptomycin and then 6 months of self-administration of a tablet containing both isoniazid and thiacetazone. A substantial decrease in the risk of tuberculous infection in developing countries is essential because of the increase in number of AIDS patients with tuberculosis. Vaccination alone, at least with the present vaccine, cannot substantially influence the epidemiologic situation but should be continued for children when its use is justified for prevention.
Synthesis and Degradation of pH-Sensitive Linear Poly(amidoamine)s (2007)

The design and synthesis of a family of cationic, pH-sensitive poly(amidoamine)s are reported. Acetal or ketal linkages were incorporated into the backbone of the polymers to provide for degradation into low molecular weight hydrophilic compounds upon lowering of the pH. All of the polymers demonstrated a pH-dependent degradation profile with a very significant increase in hydrolysis rate as the pH was lowered from 7.4 to the pH value of 5.0 commonly found in lysosomes. The hydrolysis half-life of the poly(amidoamine)s varied from 0.03 to 81.5 days at pH 5.0 and from 6.0 to 161 days at pH 7.4, depending upon the structure of the components used to prepare each of the acid-degradable polymers. This data suggests that these new pH-sensitive hydrophilic poly(amidoamine)s and analogous structures may prove useful in the field of polymer therapeutics and drug delivery.
Covalent Inhibition of Ubc13 Affects Ubiquitin Signaling and Reveals Active Site Elements Important for Targeting (2015)

Ubc13 is an E2 ubiquitin conjugating enzyme that functions in nuclear DNA damage signaling and cytoplasmic NF-κB signaling. Here, we present the structures of complexes of Ubc13 with two inhibitors, NSC697923 and BAY 11-7082, which inhibit DNA damage and NF-κB signaling in human cells. NSC697923 and BAY 11-7082 both inhibit Ubc13 by covalent adduct formation through a Michael addition at the Ubc13 active site cysteine. The resulting adducts of both compounds exploit a binding groove unique to Ubc13. We developed a Ubc13 mutant which resists NSC697923 inhibition and, using this mutant, we show that the inhibition of cellular DNA damage and NF-κB signaling by NSC697923 is largely due to specific Ubc13 inhibition. We propose that unique structural features near the Ubc13 active site could provide a basis for the rational development and design of specific Ubc13 inhibitors.
Constitutive and enhanced expression from the CMV major IE promoter in a defective adenovirus vector (1992)

A defective adenovirus (Ad) type 5 E1- vector has been combined with the powerful constitutive cytomegalovirus (CMV) major immediate early (IE) promoter to produce a novel eukaryotic expression system. The Ad vector can replicate to high titres in 293 cells and then be used to infect a wide variety of non-permissive cell types. The Escherichia coli lacZ and CMV IE1 genes have been cloned to generate the Ad recombinants RAd35 and RAd31 respectively. In human fibroblasts infected with RAd35 beta-galactosidase (beta-gal) expression could be detected in virtually 100% of target cells, there was no detectable transcription from the Ad genome and extremely high levels of expression could be achieved with beta-gal representing the predominant cytoplasmic cellular protein. Additionally, a number of agents, including the CMV IE1 gene product (in RAd31) and forskolin, significantly enhanced expression from RAd35-infected human fibroblasts. Lower levels of constitutive beta-gal expression were obtained in RAd35-infected HeLa cells but again expression could be enhanced (up to 60 fold) by chemical inducing agents. Expression from the IE promoter in the Ad vector could be repressed by coinfection with CMV.
Novel drug delivery systems for inner ear protection and regeneration after hearing loss (2008)

Drug delivery systems with the potential for immediate clinical translation, as well as those that will contribute to the future of hearing preservation or cochlear cellular regeneration, are identified.