gebhart/patrepeval huggingface dataset:
Spontaneous recovery of rats from experimental allergic encephalomyelitis is dependent on regulation of the immune system by endogenous adrenal corticosteroids. (1989)

Lewis rats with experimental allergic encephalomyelitis (EAE), induced either by the subcutaneous injection of guinea pig myelin basic protein (MBP) or by the adoptive transfer of MBP-primed spleen cells, suffer from a single episode of paralysis from which they recover spontaneously. Animals developing EAE were found to have greatly elevated levels of corticosterone in the blood. This endogenous increase in steroid production was accompanied by lymphopenia and depressed delayed-type hypersensitivity responses to OVA, indicating that rats with EAE are immunosuppressed in an antigen-nonspecific fashion. Adrenalectomized rats given subcutaneous implants of corticosterone to maintain basal steroid levels invariably died when EAE was induced. However, if the steroid replacement therapy was adjusted to mimic the hormone levels that were observed in intact rats developing EAE, then the disease followed a nonfatal course closely resembling that seen in the nonadrenalectomized controls. Replacement therapy that achieved serum corticosterone levels slightly higher than those found in intact rats with EAE virtually suppressed the disease completely. It is concluded that endogenous corticosterone release in rats with EAE plays an essential role in the spontaneous recovery that is observed in this condition. However, the subsequent refractory phase that is characteristic of rats that have recovered from EAE induced by active immunization with MBP is not associated with chronically elevated corticosterone levels. This finding is discussed in the light of other data that suggest that unlike the spontaneous recovery, the refractory state has an immunological basis rather than an endocrinological basis.
Anti-inflammatory role and immunomodulation of mesenchymal stem cells in systemic joint diseases: potential for treatment (2013)

Clinical applications for MSCs have shown promise in a number of inflammatory and autoimmune disorders. Future work is likely to further reveal the immunosuppressive characteristics of MSCs, their role in the pathophysiology of joint diseases and provide the basis for new avenues for treatment.
Acquisition of Mn(II) in Addition to Fe(II) Is Required for Full Virulence of Salmonella enterica Serovar Typhimurium (2002)

The roles of the genes feoB (ABC ferrous iron transporter), mntH (proton-dependent manganese transporter), and sitABCD (putative ABC iron and/or manganese transporter) in Salmonella pathogenicity were investigated by using mutant strains deficient in one, two, or three transporters. Our results indicated that sitABCD encodes an important transporter of Mn(II) and Fe(II) which is required for full virulence in susceptible animals (Nramp1(-/-)) and for replication inside Nramp1(-/-) macrophages in vitro. The mntH sitABCD double mutant (mutant MS) showed minimal Mn(II) uptake and increased sensitivity to H(2)O(2) and to the divalent metal chelator 2,2'-dipyridyl (DP) and was defective for replication in macrophages. In vivo MS appeared to be as virulent as the sitABCD mutant in Nramp1(-/-) animals. The ferrous iron transporter Feo was required for full virulence in 129/Sv Nramp1(-/-) mice, and infection with multiple mutants lacking FeoB was not fatal. The sitABCD feoB mutant (mutant SF) and the mntH sitABCD feoB mutant (mutant MSF) showed minimal Fe(II) uptake and were slightly impaired for replication in susceptible macrophages. MSF showed reduced growth in minimal medium deficient in divalent cations. The role of the mntH gene, which is homologous to mammalian Nramp genes, was also investigated after overexpression in the double mutant MS. MntH preferred Mn(II) over Fe(II) and could suppress MS sensitivity to H(2)O(2) and to DP, and it also improved the intracellular survival in Nramp1(-/-) macrophages. This study indicates that acquisition of Mn(II), in addition to Fe(II), is required for intracellular survival and replication of Salmonella enterica serovar Typhimurium in macrophages in vitro and for virulence in vivo.
Iron‐free pyoverdin binds to its outer membrane receptor FpvA in Pseudomonas aeruginosa: a new mechanism for membrane iron transport (2001)

Under iron limitation, Pseudomonas aeruginosa secretes a fluorescent siderophore called pyoverdin, which, after complexing iron, is transported back into the cell via its outer membrane receptor FpvA. Previous studies demonstrated co-purification of FpvA with iron-free PaA and reported similar binding affinities of iron-free pyoverdin and ferric-pyoverdin to purified FpvA. The fluorescence resonance energy transfer between iron-free PaA and the FpvA receptor here reveals the existence of an FpvA-pyoverdin complex in P. aeruginosa in vivo, suggesting that the pyoverdin-loaded FpvA is the normal state of the receptor in the absence of iron. Using tritiated ferric-pyoverdin, it is shown that iron-free PaA binds to the outer membrane but is not taken up into the cell, and that in vitro and, presumably, in vivo ferric-pyoverdin displaces the bound iron-free pyoverdin on FpvA-PaA to form FpvA-PaA-Fe complexes. In vivo, the kinetics of formation of this FpvA-PaA-Fe complex are more than two orders of magnitude faster than in vitro and depend on the presence of TonB. In P. aeruginosa, two tonB genes have been identified (tonB1 and tonB2). TonB1 is directly involved in ferric-pyoverdin uptake, and TonB2 seems to be able partially to replace TonB1 in its role in iron acquisition. However, no effect of TonB1 or TonB2 on the apparent affinity of free pyoverdin to FpvA was observed, and a 17-fold difference was measured between the affinities of the two forms of pyoverdin (PaA and PaA-Fe) to FpvA in the absence of TonB1 or TonB2. The mechanism of iron uptake in P. aeruginosa via the pyoverdin pathway is discussed in view of these new findings.
Evolution of Genome Size in Brassicaceae (2004)

The tree roots at an ancestral genome size of approximately 1x = 0.2 pg. Arabidopsis thaliana (1C = 0.16 pg; approximately 157 Mbp) has the smallest genome size in Brassicaceae studied here and apparently represents an evolutionary decrease in genome size. Two other branches that represent probable evolutionary decreases in genome size terminate in Lepidium virginicum and Brassica rapa. Branches in the phylogenetic tree that represent probable evolutionary increases in genome size terminate in Arabidopsis halleri, A. lyrata, Arabis hirsuta, Capsella rubella, Caulanthus heterophyllus, Crucihimalaya, Lepidium sativum, Sisymbrium and Thlaspi arvense. Branches within one clade containing Brassica were identified that represent two ancient ploidy events (2x to 4x and 4x to 6x) that were predicted from published comparative mapping studies.
High‐ and low‐frequency transcutaneous electrical nerve stimulation delay sciatic nerve regeneration after crush lesion in the mouse (2008)

The stimulation of peripheral nerve regeneration has been studied in different ways, including the use of electrical fields. The capacity of this modality to enhance nerve regeneration is influenced by the parameters used, including current type, frequency, intensity, and means of administration. Transcutaneous electrical nerve stimulation (TENS) is a frequently used form of administering electrical current to the body, but its effects on peripheral nerve regeneration are not known. This study assessed the influence of TENS on sciatic nerve regeneration, using a model of crush lesion in the mouse. Mice were stimulated 30 min a day, 5 days a week, for 5 weeks with both high- (100 Hz) and low- (4 Hz) frequency TENS. Control animals had the sciatic nerve crushed but were not stimulated. Assessment was performed weekly by functional analysis using the Static Sciatic Index for the mouse and at the end of the experiment by light and electron microscopy. The results showed that although there were no differences between the groups regarding the Static Sciatic Index values, TENS led to nerves with morphological signs of impaired regeneration. At light microscopy level, TENS nerves presented more axons with dark axoplasm, signs of edema, and a less organized cytoarchitecture. Electronmicrographs showed fewer and thinner thick myelinated fibers and increased number of Schwann cell nuclei. Myelinated axon diameters and density and diameter of nonmyelinated fibers were not affected by TENS, leading to the conclusion that this regimen of electrical stimulation leads to a delayed regeneration after a crush lesion of the sciatic nerve in the mouse. All these effects were more pronounced on high-frequency TENS nerves.
HDAC6 Regulates Epidermal Growth Factor Receptor (EGFR) Endocytic Trafficking and Degradation in Renal Epithelial Cells (2012)

We present for the first time that histone deacetylase 6 (HDAC6) regulates EGFR degradation and trafficking along microtubules in Pkd1 mutant renal epithelial cells. HDAC6, the microtubule-associated α-tubulin deacetylase, demonstrates increased expression and activity in Pkd1 mutant mouse embryonic kidney cells. Targeting HDAC6 with a general HDAC inhibitor, trichostatin (TSA), or a specific HDAC6 inhibitor, tubacin, increased the acetylation of α-tubulin and downregulated the expression of EGFR in Pkd1 mutant renal epithelial cells. HDAC6 was co-localized with EGF induced endocytic EGFR and endosomes, respectively. Inhibition of the activity of HDAC6 accelerated the trafficking of EGFR from early endosomes to late endosomes along the microtubules. Without EGF stimulation EGFR was randomly distributed while after stimulation with EGF for 30 min, EGFR was accumulated around α-tubulin labeled microtubule bundles. These data suggested that the Pkd1 mutation induced upregulation of HDAC6 might act to slow the trafficking of EGFR from early endosomes to late endosomes along the microtubules for degradation through deacetylating α-tubulin. In addition, inhibition of HDAC activity decreased the phosphorylation of ERK1/2, the downstream target of EGFR axis, and normalized EGFR localization from apical to basolateral in Pkd1 knockout mouse kidneys. Thus, targeting HDAC6 to downregulate EGFR activity may provide a potential therapeutic approach to treat polycystic kidney disease.
Temporal Relationship Between Endothelin-1 Concentrations and Cerebral Vasospasm in Patients With Aneurysmal Subarachnoid Hemorrhage (2001)

CSF ET-1 levels were markedly elevated in patients with clinical manifestations of vasospasm (day 7) and with a poor neurological condition not related to vasospasm. However, ET-1 levels were low in clinical vasospasm patients before clinical symptoms were evident (day 4) and remained low in angiographic vasospasm patients throughout the study period. Thus, our data suggest that CSF ET-1 levels are increased in conditions of severe neuronal damage regardless whether this was due to vasospasm or to the primary hemorrhagic event. In addition, CSF ET-1 levels paralleled the neurological deterioration but were not predictive of vasospasm.
A Novel Two-Stage, Transdisciplinary Study Identifies Digoxin as a Possible Drug for Prostate Cancer Treatment (2011)

Our two-stage transdisciplinary approach for drug repositioning provides compelling justification for further mechanistic and possibly clinical testing of the leading nonchemotherapy candidate, digoxin, a cardiac glycoside, as a drug for prostate cancer treatment. Perhaps of equal importance, our study illustrates the power of the transdisciplinary approach in translational cancer research. By coupling laboratory and epidemiologic methods and thinking, we reduced the probability of identifying false-positive candidate drugs for the next steps in testing.
Performance evaluation of adaptive antenna base stations in a commercial GSM network (1999)

Base stations with adaptive antennas is a technology offering the opportunity to increase the capacity of a cellular mobile network by reducing transmitted interference. This paper presents a system description of the first GSM prototype base station with adaptive antenna technology and the results of the first commercial field trials of adaptive antennas for GSM using adaptation in uplink and downlink. The performance tests were conducted in the city center of Giessen, north of Frankfurt. The prototype base stations were connected to the commercial GSM infrastructure of Mannesmann Mobilfunk's D2 network. All measurement results are very positive and show the high potential of the adaptive antenna technology. A capacity increase of 120% has been achieved in the test scenario, which is in good agreement with expectations.
Adenosine A2A receptor agonists and PDE inhibitors: a synergistic multitarget mechanism discovered through systematic combination screening in B-cell malignancies (2010)

Using a combination high-throughput screening technology, multiple classes of drugs and targeted agents were identified that synergize with dexamethasone (Dex) in multiple myeloma (MM) cells. Performing combination screening with these enhancers, we discovered an unexpected synergistic interaction between adenosine receptor agonists and phosphodiesterase (PDE) inhibitors that displays substantial activity in a panel of MM and diffuse large B-cell lymphoma (DLBCL) cell lines and tumor cells from MM patients. We have used selective adenosine receptor agonists, antagonists, and PDE inhibitors as well as small interfering RNAs targeting specific molecular isoforms of these proteins to dissect the molecular mechanism of this synergy. The adenosine A2A receptor and PDE2, 3, 4, and 7 are important for activity. Drug combinations induce cyclic AMP (cAMP) accumulation and up-regulate PDE4B. We also observe rigorous mathematical synergy in 3-way combinations containing A2A agonists, PDE inhibitors, and Dex at multiple concentrations and ratios. Taken together, these data suggest that A2A agonist/PDE inhibitor combinations may be attractive as an adjunctive to clinical glucocorticoid containing regiments for patients with MM or DLBCL and confer benefit in both glucocorticoid-sensitive and -resistant populations.
70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer (2016)

Among women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence, the receipt of no chemotherapy on the basis of the 70-gene signature led to a 5-year rate of survival without distant metastasis that was 1.5 percentage points lower than the rate with chemotherapy. Given these findings, approximately 46% of women with breast cancer who are at high clinical risk might not require chemotherapy. (Funded by the European Commission Sixth Framework Program and others; ClinicalTrials.gov number, NCT00433589; EudraCT number, 2005-002625-31.).
mRNA Decay Mediated by Two Distinct AU-Rich Elements from c- fos and Granulocyte-Macrophage Colony-Stimulating Factor Transcripts: Different Deadenylation Kinetics and Uncoupling from Translation (1995)

Poly(A) tail removal is a critical first step in the decay pathway for many yeast and mammalian mRNAs. Poly(A) shortening rates can be regulated by cis-acting sequences within the transcribed portion of mRNA, which in turn control mRNA turnover rates. The AU-rich element (ARE), found in the 3' untranslated regions of many highly labile mammalian mRNAs, is a well-established example of this type of control. It represents the most widespread RNA stability determinant among those characterized in mammalian cells. Here, we report that two structurally different AREs, the c-fos ARE and the granulocyte-macrophage colony-stimulating factor (GM-CSF) ARE, both direct rapid deadenylation as the first step in mRNA degradation, but by different kinetics. For c-fos-ARE-mediated decay, the mRNA population undergoes synchronous poly(A) shortening and is deadenylated at the same rate, implying the action of distributive or nonprocessive ribonucleolytic digestion of poly(A) tails. In contrast, the population of granulocyte-macrophage colony-stimulating factor ARE-containing mRNAs is deadenylated asynchronously, with the formation of fully deadenylated intermediates, consistent with the action of processive ribonucleolytic digestion of poly(A) tails. An important general implication of this finding is that different RNA-destabilizing elements direct deadenylation either by modulating the processivity at which a single RNase functions or by recruiting kinetically distinct RNases. We have also employed targeted inhibition of translation initiation to demonstrate that the RNA-destabilizing function of both AREs can be uncoupled from translation by ribosomes. In addition, a blockade of ongoing transcription has been used to further probe the functional similarities and distinctions of these two AREs. Our data suggest that the two AREs are targets of two distinct mRNA decay pathways. A general model for ARE-mediated mRNA degradation involving a potential role for certain heterogeneous nuclear ribonucleoproteins and ARE-binding proteins is proposed.
Fast and Facile Preparation of Graphene Oxide and Reduced Graphene Oxide Nanoplatelets (2009)

In this study, we report an inexpensive, massively scalable, fast, and facile method for preparation of graphene oxide and reduced graphene oxide nanoplatelets. The basic strategy involved the preparation of graphite oxide (GO) from graphite through reaction with benzoyl peroxide (BPO), complete exfoliation of GO into graphene oxide sheets, followed by their in situ reduction to reduced graphene oxide nanoplatelets. The mechanism of graphene oxide producing is mainly the generation of oxygen-containing groups on graphene sheets. In addition, inserted BPO and expansion of CO2 evolved during reaction will expand the distance between graphite layers, which are also main factors for exfoliation. Thermogravimetric analysis, Raman spectroscopy, and Fourier transform infrared spectroscopy indicated the successful preparation of GO. X-ray diffraction proved the mechanism of intercalation and exfoliation of graphite. Transmission electron microscopy and atomic force microscopy were used to demonstrate the structure of produced graphene oxide and reduced graphene oxide nanoplatelets.
Fibroblast Growth Factor-1 and -2 Preserve Long-Term Repopulating Ability of Hematopoietic Stem Cells in Serum-Free Cultures (2006)

In this study, we demonstrate that extended culture of unfractionated mouse bone marrow (BM) cells, in serum-free medium, supplemented only with fibroblast growth factor (FGF)-1, FGF-2, or FGF-1 +2 preserves long-term repopulating hematopoietic stem cells (HSCs). Using competitive repopulation assays, high levels of stem cell activity were detectable at 1, 3, and 5 weeks after initiation of culture. FGFs as single growth factors failed to support cultures of highly purified Lin(-)Sca-1(+)c-Kit(+)(LSK) cells. However, cocultures of purified CD45.1 LSK cells with whole BM CD45.2 cells provided high levels of CD45.1 chimerism after transplant, showing that HSC activity originated from LSK cells. Subsequently, we tested the reconstituting potential of cells cultured in FGF-1 + 2 with the addition of early acting stimulatory molecules, stem cell factor +interleukin-11 + Flt3 ligand. The addition of these growth factors resulted in a strong mitogenic response, inducing rapid differentiation and thereby completely overriding FGF-dependent stem cell conservation. Importantly, although HSC activity is typically rapidly lost after short-term culture in vitro, our current protocol allows us to sustain stem cell repopulation potential for periods up to 5 weeks.
The Use of RP‐HPLC for measuring activation and cleavage of rFVIIa during purification (1995)

A reverse phase HPLC (RP-HPLC) method for analysis of recombinant factor VIIa (rFVIIa) has been developed. The method discriminates between different forms of recombinant FVII (rFVII). To obtain separation of these closely related molecules the method has been optimized with respect to gradient profile and temperature. The method has been used for optimization of purification processes and for kinetic studies. EVidence for autolytic cleavage was obtained. (c) 1995 John Wiley & Sons, Inc.
Cloning of the gene encoding Streptococcin A-FF22, a novel lantibiotic produced by Streptococcus pyogenes, and determination of its nucleotide sequence (1993)

Streptococcin A-FF22 (SA-FF22) is a lantibiotic produced by Streptococcus pyogenes FF22. The nucleotide sequence of the SA-FF22 structural gene (scnA) was determined and shown to encode a 51-amino-acid prepeptide. The proteolytic processing site of the SA-FF22 prepeptide differs from that which characterizes other type A lantibiotics.
The lipopolysaccharide biosynthesis locus of Campylobacter jejuni 81116 (1998)

Most Campylobacter jejuni strains express lipo-oligosaccharides. Some strains also express lipopolysaccharides (LPS), with O-antigen-like carbohydrate repeats. C. jejuni 81116 expresses an LPS containing both lipo-oligosaccharides and O-antigen-like repeats, but nothing is known about the structure or sugar composition of these LPS species. A cosmid library of the genome of C. jejuni 81116 was constructed and probed with Campylobacter hyoilei genes involved in LPS synthesis. Five cosmids hybridized with the probe and two of these expressed C. jejuni 81116 LPS in Escherichia coli. By subcloning, a 16 kb DNA region was identified which contains the genetic information required to express C. jejuni LPS. DNA sequence analysis revealed 11 ORFs homologous to genes involved in LPS synthesis of other bacteria. They consisted of three homologues of sugar biosynthesis genes, two homologues of transport genes and six homologues of sugar transferases.
A hardware logic simulation system (1990)

Multiple-delay logic simulation algorithms developed for the microprogrammable accelerator for rapid simulations (MARS) hardware simulator are discussed. In particular, timing-analysis algorithms for event cancellations, spike and race analyses, and oscillation detection are described. It is shown how a reconfigurable set of processors, called processing elements (PEs), can be arranged in a pipelined configuration to implement these algorithms. The algorithms operate within the partitioned-memory, message-passing architecture of MARS. Three logic simulators-two multiple delay and one unit delay-have been implemented using slightly different configuration of the available PEs. In these simulators, VLSI chips are modeled at the gate level with accurate rise/fall delays assigned to each logic primitive. On-chip memory blocks are modeled functionally and are integrated into the simulation framework. The MARS hardware simulator has been tested on many VLSI chip designs and has demonstrated a speed improvement of about 50 times that of an Amdahl 5870 system running a production-quality software simulator while retaining the accuracy of simulations.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Bacterial structure and functional relation to abscess formation. (1994)

The capsular polysaccharide complex (CPC) of Bacteroides fragilis exhibits unusual biologic properties. This polysaccharide complex promotes the formation of abscesses and prevents abscess induction in a rat model of intra-abdominal sepsis. Each of these biologic properties is mediated by a T cell-dependent immune mechanism. The CPC consists of two distinct polysaccharides, PS A and PS B, each with repeating units that have positively charged amino groups and negatively charged carboxyl or phosphate groups. Analysis of these polysaccharides as well as other charged carbohydrates before and after chemical modification revealed that these oppositely charged groups are required for promotion of intra-abdominal abscesses as well as for protection against abscess induction. These studies provide a structural rationale for the distinct properties associated with the B. fragilis CPC, and delineate one mechanism by which this host response occurs.