gebhart/patrepeval huggingface dataset:
A clinical study of long-term administration of dextran sulfate (MDS Kowa) in patients with retinopathy. (1983)

We administered MDS at a daily dose of 1,800 mg to 25 patients with diabetic retinopathy for periods ranging from 12 to 48 months (mean: 28 months) and achieved the following results: 1) During the administration period total cholesterol, triglyceride and fibrinogen levels were all maintained at significantly lower levels. 2) Eye fundus findings showed an improvement in 38.9% no change in 47. 2% and a deterioration in 13.9% of the cases. 3) No side-effects or abnormalities in clinical findings were observed in any of the cases even though clinical tests of hepatic function, renal function, blood chemistry, and urinalysis were conducted. The above results demonstrate that MDS has a marked effect on diabetic retinopathy, especially in cases with moderate to severe symptoms during the non-proliferative stage.
T cell receptor V alpha-V beta repertoire and cytokine gene expression in active multiple sclerosis lesions. (1992)

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with presumed autoimmune etiology. A recent study has suggested the presence of a restricted T cell receptor (TCR) V alpha repertoire in MS lesions. The presence of such a restricted TCR repertoire at the site of inflammation would have important consequences for the pathogenesis and the ultimate treatment of MS. To further characterize the TCR V alpha and V beta repertoire in MS plaque tissue, we examined a series of 26 histologically well-characterized central nervous system (CNS) tissue specimens from six MS patients as well as samples from five normal postmortem cases and a case of subacute sclerosing panencephalitis. RNA was extracted from frozen sections and cDNAs were amplified by polymerase chain reaction using primers for TCR V alpha (V alpha 1-18) and V beta (V beta 1-19) gene families. This analysis demonstrated a broad TCR V alpha-V beta repertoire in active lesions, while fewer TCR V genes were detected in chronic plaques and control samples. Even though a large number of TCR V alpha and V beta gene segments were present in the majority of active lesions, there were clear differences in the TCR repertoire between plaques from the same case, suggesting that local events influence the TCR repertoire at the level of T cell recruitment or T cell expansion. Examination of cytokine mRNAs demonstrated that IL-1 mRNA was present in the majority of acute and subacute plaques, while IL-2 and IL-4 mRNA were detected in only a few acute lesions. These data demonstrate that the TCR repertoire in MS plaques is polyclonal. However, autoreactive alpha/beta T cells thought to be critical in the initiation of the inflammatory process probably represent a minor fraction of T cells in active MS plaques and may use a limited number of TCR V gene segments for recognition of the autoantigen.
Sequence Analysis Using Logic Regression (2001)

Logic Regression is a new adaptive regression methodology that attempts to construct predictors as Boolean combinations of (binary) covariates. In this paper we use this algorithm to deal with single-nucleotide polymorphism (SNP) sequence data. The predictors that are found are interpretable as risk factors of the disease. Significance of these risk factors is assessed using techniques like cross-validation, permutation tests, and independent test sets. These model selection techniques remain valid when data is dependent, as is the case for the family data used here. In our analysis of the Genetic Analysis Workshop 12 data we identify the exact locations of mutations on gene 1 and gene 6 and a number of mutations on gene 2 that are associated with the affected status, without selecting any false positives.
Controlled Release of Paclitaxel from Heparinized Metal Stent Fabricated by Layer-by-Layer Assembly of Polylysine and Hyaluronic Acid-g-Poly(lactic-co-glycolic acid) Micelles Encapsulating Paclitaxel (2009)

Drug-eluting stent (DES) has been widely used for effective treatment of obstructive coronary artery disease, preventing the occurrence of restenosis that is mainly caused by hyper-proliferation of smooth muscle cells. Here, we demonstrate the immobilization of heparin on the metal surface via a bioinspired manner and subsequent build-up of a therapeutic layer-by-layer multilayer composed of paclitaxel (PTX) encapsulated poly(lactic-co-glycolic acid) grafted hyaluronic acid (HA-g-PLGA) micelles, heparin, and poly-L-lysine (PLL). It was hypothesized that the heparinized metallic surface would create a nonthrombogenic environment, while controlled release of PTX from the surface could induce antiproliferation of smooth muscle cells. For the surface immobilization of heparin on the surface of cobalt-chromium alloy (L605), dopamine-derivatized heparin was synthesized and anchored on the surface by a mussel-inspired adhesion mechanism. An amphiphilic graft copolymer of HA-g-PLGA was synthesized and utilized for the formation of anionic PTX loaded micelles. A PTX eluting multilayer composed of anionic HA-g-PLGA micelles, heparin, and PLL was self-assembled on the metal surface by a layer-by-layer fashion. The loading amount of PTX on the metal surface could be readily controlled with concomitantly achieving sustained release profiles of PTX over an extended period. The proliferation of human coronary artery smooth muscle cells was successfully arrested by controlled released PTX from the therapeutic multilayer coated on the metallic substrate.
Signalling specificity of Ser/Thr protein kinases through docking-site-mediated interactions (2003)

Signal transduction pathways use protein kinases for the modification of protein function by phosphorylation. A major question in the field is how protein kinases achieve the specificity required to regulate multiple cellular functions. Here we review recent studies that illuminate the mechanisms used by three families of Ser/Thr protein kinases to achieve substrate specificity. These kinases rely on direct docking interactions with substrates, using sites distinct from the phospho-acceptor sequences. Docking interactions also contribute to the specificity and regulation of protein kinase activities. Mitogen-activated protein kinase (MAPK) family members can associate with and phosphorylate specific substrates by virtue of minor variations in their docking sequences. Interestingly, the same MAPK docking pocket that binds substrates also binds docking sequences of positive and negative MAPK regulators. In the case of glycogen synthase kinase 3 (GSK3), the presence of a phosphate-binding site allows docking of previously phosphorylated (primed) substrates; this docking site is also required for the mechanism of GSK3 inhibition by phosphorylation. In contrast, non-primed substrates interact with a different region of GSK3. Phosphoinositide-dependent protein kinase-1 (PDK1) contains a hydrophobic pocket that interacts with a hydrophobic motif present in all known substrates, enabling their efficient phosphorylation. Binding of the substrate hydrophobic motifs to the pocket in the kinase domain activates PDK1 and other members of the AGC family of protein kinases. Finally, the analysis of protein kinase structures indicates that the sites used for docking substrates can also bind N- and C-terminal extensions to the kinase catalytic core and participate in the regulation of its activity.
Hematopoietic stem cells express multiple myeloid markers: implications for the origin and targeted therapy of acute myeloid leukemia (2005)

Human hematopoietic stem cells (HSCs) are generally regarded as being devoid of the markers expressed by differentiated blood cells, the lineage-specific antigens. However, recent work suggests that genes associated with the myeloid lineage are transcribed in mouse HSCs. Here, we explore whether myeloid genes are actually translated in human HSCs. We show that CD33, CD13, and CD123, well-established myeloid markers, are expressed on human long-term repopulating cells from cord blood and bone marrow. In addition, we demonstrate that nonobese diabetic/severe combined immunodeficiency (NOD/SCID) leukemia-initiating cells (SL-ICs) are restricted to the CD33+ fraction in 11 of 12 acute myeloid leukemia (AML) samples studied, indicating that leukemic stem cells (LSCs) express this antigen. This study changes our view of HSCs and the process of differentiation. Furthermore, based on the phenotypic similarity of HSCs and LSCs, our data provide support for the hypothesis that AML derives from an HSC. Our findings also provide a challenge to contemporary attempts to improve the outcome of AML using myeloid antigen-targeted therapies, given the potential for HSC killing.
A chip set for lossless image compression (1991)

The authors describe two chips which form the basis of a high-speed lossless image compression/decompression system. They present the transform and coding algorithms and the main architectural features of the chips and outline some performance specifications. Lossless compression can be achieved by a transformation process followed by entropy coding. The two application-specific integrated circuits (ASICs) perform S-transform image decomposition and the Lempel-Ziv (L-Z) type of entropy coding. The S-transform, besides decorrelating the image, provides a convenient method of hierarchical image decomposition. The data compressor/decompressor IC is a fast and efficient implementation of the L-Z algorithm. The chips can be used independently or together for image compression.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Recent Developments in Topical Wound Therapy: Impact of Antimicrobiological Changes and Rebalancing the Wound Milieu (2014)

Wound therapy improves every year by developing new wound treatment options or by advancing already existing wound materials, for example, adding self-releasing analgesic drugs or growth factors to wound dressings, or by binding and inactivating excessive proteases. Also new dressing materials based on silk fibers and enhanced methods to reduce bacterial burden, for example, cold argon plasma, might help to fasten wound healing.
The DNA‐Binding Efficiency of Sp1 is Affected by Redox Changes (1994)

We have previously demonstrated that the DNA-binding efficiency of Sp1 is greatly decreased in nuclear extracts from 30-month-old rat tissues compared to those from young ones, although its gene appears to be normally expressed. As reactive oxygen intermediates are known to accumulate in aged animals, we investigated the effect of oxidation on the Sp1 DNA-binding activity. Electrophoretic mobility shift assays and DNase I footprintings showed that high concentrations of dithiothreitol, added to the aged tissue extracts, fully restore the Sp1 DNA-binding efficiency. However, in young nuclear extracts hydrogen peroxide treatment strongly decreases the Sp1 DNA-binding activity that is restored by the treatment with high dithiothreitol concentrations. To ascertain whether the oxidative stress is directed toward the Sp1 molecule alone, or whether it acts on unknown Sp1 cofactor(s) necessary for DNA binding, we purified Sp1 from young rat liver and demonstrated that when the purified protein is added to aged nuclear extracts, it efficiently binds to its DNA cis-element. Moreover, purified Sp1 treated with hydrogen peroxide lost its ability to bind its cis-element and the DNA-binding efficiency was fully restored after incubation with dithiothreitol.
Developing a universal T cell for use in adoptive immunotherapy (2015)

Adoptive immunotherapy with genetically-engineered T-cells is showing promise in a clinical setting. However, this approach is limited by the requirement to generate autologous, patient-derived, T-cells, which is both costly and time-consuming. To address this, a methodology which would allow the generation of allogeneic universal T-cells would be highly beneficial. In this project, I have attempted to develop a protocol by which the following T-cell modifications will be introduced: (1) a chimeric antigen receptor (CAR), (2) a sort-suicide gene, (3) human leukocyte antigen (HLA) knock-down, (4) T cell receptor (TCR) knock-down (5) natural killer (NK) cell inhibition. Various strategies have been tested to attempt these modifications. Firstly, I knocked down HLA Class I by using two viral proteins, US11 and infected cell protein (ICP)-47, which give knock-down of 88% and 91% of HLA Class I expression respectively when tested in donor peripheral blood mononuclear cells (PBMCs). In a mixed lymphocyte reaction (MLR) with HLA mis-matched donors, US11 has clearly been shown to reduce the proliferation of effector PBMCs. To address rejection of HLA negative cells by NK cells, HLA-G has been cloned and expressed in cell lines and donor PBMCs to mimic the expression of HLA-G by trophoblast cells in the uterus and by certain cancers. TCR knock-down has been demonstrated in PBMCs, and CD52 knock-down has been achieved in a cell line by using DNA-editing transcription activator-like effector nucleases (TALENs). A CAR can be introduced to redirect the T-cells and a sort-suicide gene can be used to select modified cells and also provide a mechanism to deplete therapeutic cells in case of an adverse event. Some of these strategies have been combined with each other, with limited success.
Synthetic analogs of the carboxyl-terminus of .beta.-thyrotropin: the importance of basic amino acids in receptor binding activity (1992)

Previously, using a synthetic peptide strategy, we determined that four distinct regions of human beta-thyrotropin (beta TSH) were responsible for interaction of TSH with the TSH receptor. The most potent of these four regions was the carboxyl-terminus of the subunit, represented by the peptide sequence beta 101-112, which inhibited binding of radiolabeled beta TSH to receptor in radioreceptor assay with an IC50 of approximately 100 microM. In the current studies, we systematically substituted the native amino acids in region beta 101-112 with alanine, and we have determined which residues within this span are important to the binding activity of TSH to its receptor. Substitution of Lys101, Asn103, Tyr104, Cys105, Lys107, and Lys110 with alanine each caused a significant fall in activity as compared to the native sequence, whereas substitution at the remaining positions had little or no effect. Because three of these residues are positively charged at physiologic pH, we hypothesized that this charge may be important to the binding activity of the sequence. We modified the charge characteristics of the region by synthesizing two series of analogs in which the residues identified in the alanine substitution studies were substituted with Arg, D-Lys, and D-Arg at each position. In addition, a series of analogs containing basic residues, either added to or substituted for nonbasic residues in the sequence beta 101-112, was synthesized. Substitution of Arg, D-Lys, and D-Arg for Lys101, Lys107, and Lys110 had little effect on activity; however, inclusion of additional basic residues in the beta 101-112 sequence significantly enhanced the inhibitory activity of the region.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparative analysis of the Corynebacterium glutamicum group and complete genome sequence of strain R (2007)

The complete genome sequence of Corynebacterium glutamicum strain R was determined to allow its comparative analysis with other corynebacteria. The biology of corynebacteria was explored by refining the definition of the subset of genes that constitutes the corynebacterial core as well as those characteristic of saprophytic and pathogenic ecological niches. In addition, the relative scarcity of corynebacterial sigma factors and the plasticity of their two-component system machinery reflect their relatively exacting nutritional requirements and reduced membrane-associated and secreted proteins. The conservation of key genes and pathways between corynebacteria, mycobacteria and Nocardia validates the use of C. glutamicum to study fundamental processes that are conserved in slow-growing mycobacteria, including pathogenesis-associated mechanisms. The discovery of 39 novel genes in C. glutamicum R that have not been previously reported in other corynebacteria supports the rationale for sequencing additional corynebacterial genomes to better define the corynebacterial pan-genome and identify previously undetected metabolic pathways in these organisms.
Detection of bacteria in platelet concentrates: comparison of broad‐range real‐time 16S rDNA polymerase chain reaction and automated culturing (2005)

Compared to culture in the BacT/ALERT system, the PCR assay had a sensitivity of 100 percent and a specificity of 100 percent. This real-time PCR assay has a much shorter turnaround time of 4 hours, which offers the possibility to test and obtain results on PCs before release or the day they are transfused. This would permit the withdrawal of contaminated PCs before transfusion.
Sulbactam-cefoperazone polyhydroxybutyrate-co- hydroxyvalerate (PHBV) local antibiotic delivery system:In vivo effectiveness and biocompatibility in the treatment of implant-related experimental osteomyelitis (1999)

In this study, a novel antibiotic carrier system for use in the treatment of implant-related and chronic osteomyelitis was developed. Sulbactam-cefoperazone was introduced to rods of polyhydroxybutyrate-co-hydroxyvalerate (22 mol % HV, w/w), a member of a family of microbial-origin polymer that is biodegradable, biocompatible, and osteoconductive due to its piezoelectric property. The antibiotic-loaded carrier was implanted into the infection site that was induced by Staphylococcus aureus inoculation into the rabbit tibia. The effectiveness of this was assessed macroscopically, radiographically, bacteriologically, and histopathologically. Findings of infection subsided on day 15 and almost complete remission was observed on day 30. The control side that contained antibiotic-free rods, however, worsened. These findings prompted us to conclude that the novel biodegradable antibiotic carrier developed in the present study seems to be a promising candidate for use in the treatment of severe bone infection.
Glycosylation sites and site-specific glycosylation in human Tamm-Horsfall glycoprotein (1999)

The N-glycosylation sites of human Tamm-Horsfall glycoprotein from one healthy male donor have been characterized, based on an approach using endoproteinase Glu-C (V-8 protease, Staphylococcus aureus ) digestion and a combination of chromatographic techniques, automated Edman sequencing, and fast atom bombardment mass spectrometry. Seven out of the eight potential N-glycosylation sites, namely, Asn52, Asn56, Asn208, Asn251, Asn298, Asn372, and Asn489, turned out to be glycosylated, and the potential glycosylation site at Asn14, being close to the N-terminus, is not used. The carbohydrate microheterogeneity on three of the glycosylation sites was studied in more detail by high-pH anion-exchange chromatographic profiling and 500 MHz1H-NMR spectroscopy. Glycosylation site Asn489 contains mainly di- and tri-charged oligosaccharides which comprise, among others, the GalNAc4 S (beta1-4)GlcNAc terminal sequence. Only glycosylation site Asn251 bears oligomannose-type carbohydrate chains ranging from Man5GlcNAc2to Man8GlcNAc2, in addition to a small amount of complex-type structures. Profiling of the carbohydrate moieties of Asn208 indicates a large heterogeneity, similar to that established for native human Tamm-Horsfall glycoprotein, namely, multiply charged complex-type carbohydrate structures, terminated by sulfate groups, sialic acid residues, and/or the Sda-determinant.
Community detection algorithms: A comparative analysis (2009)

Uncovering the community structure exhibited by real networks is a crucial step toward an understanding of complex systems that goes beyond the local organization of their constituents. Many algorithms have been proposed so far, but none of them has been subjected to strict tests to evaluate their performance. Most of the sporadic tests performed so far involved small networks with known community structure and/or artificial graphs with a simplified structure, which is very uncommon in real systems. Here we test several methods against a recently introduced class of benchmark graphs, with heterogeneous distributions of degree and community size. The methods are also tested against the benchmark by Girvan and Newman [Proc. Natl. Acad. Sci. U.S.A. 99, 7821 (2002)] and on random graphs. As a result of our analysis, three recent algorithms introduced by Rosvall and Bergstrom [Proc. Natl. Acad. Sci. U.S.A. 104, 7327 (2007); Proc. Natl. Acad. Sci. U.S.A. 105, 1118 (2008)], Blondel [J. Stat. Mech.: Theory Exp. (2008), P10008], and Ronhovde and Nussinov [Phys. Rev. E 80, 016109 (2009)] have an excellent performance, with the additional advantage of low computational complexity, which enables one to analyze large systems.
Projections from the central cervical nucleus to the cerebellar nuclei in the rat, studied by anterograde axonal tracing (1995)

Projections from the central cervical nucleus (CCN) to the cerebellar nuclei were examined following injections of Phaseolus vulgaris-leucoagglutinin or cholera toxin subunit B into the C1-C3 segments in the rat. Labeled axons and terminals were immunohistochemically demonstrated. Labeled spinocerebellar fibers arising from the CCN entered the cerebellum through the inferior and the superior cerebellar peduncles. Labeled mossy fiber terminals were seen in lobules I-VI, sublobule VIIb, lobules VIII and IX, and the copula pyramidis of the cerebellar cortex. Labeled axons ran toward the cerebellar cortex, through and between the medial and the interpositus nuclei, and gave off collateral axons and terminal axons to the cerebellar nuclei. The projections to the cerebellar nuclei were predominantly contralateral to the cells of origin. Labeled terminals were distributed from the medial to the ventrolateral part of the middle subdivision of the medial nucleus throughout its rostrocaudal extent. Labeled terminals were also seen in the lateral part of the medial nucleus and in the border region between the medial nucleus and the interpositus nuclei, which corresponds to the rostromedial extension of the posterior interpositus nucleus. In the anterior interpositus nucleus, labeled terminals were distributed dorsoventrally in the middle third of the mediolateral extent. They were more numerous in the rostrodorsal part of this area. Labeled terminals were distributed dorsally and caudally in the medial third of the posterior interpositus nucleus. No labeled terminals were seen in the caudomedial subdivision and the dorsolateral protuberance of the medial nucleus, the dorsolateral hump region and the lateral nucleus. The present study demonstrates that the CCN projects to specific areas of the cerebellar cortex and the medial and the interpositus nuclei.