gebhart/patrepeval huggingface dataset:
Efforts to emulate human milk oligosaccharides (2007)

Research on human milk oligosaccharides (HMO) began with the characterisation of their chemical structures and is now focused on the elucidation of their biological roles. Previously, biological effects could only be investigated with fractions or structures isolated from breast milk; consequently, clinical observations were limited to comparisons between outcomes from breast-fed infants and their formula-fed counterparts. In some cases, it was inferred that the observed differences were caused by the presence of HMO in breast milk. Presently, analytical techniques allow for the fast analysis of milk samples, thus providing insights on the inherent variability of specimens. In addition, methods for the synthesis of HMO have provided single structures in sufficient quantities to perform clinical studies with oligosaccharide-supplemented formulae. Furthermore, studies have been conducted with non-mammalian oligosaccharides with the purpose of assessing the suitability of these structures to functionally emulate HMO. Taken together, these developments justify summarising current knowledge on HMO to further discussions on efforts to emulate human milk in regard to its oligosaccharide content. The present account summarises published data and intends to provide an historical context and to illustrate the state of the field.
RELATIONSHIPS BETWEEN LITTORAL DIATOMS AND THEIR CHEMICAL ENVIRONMENT IN NORTHEASTERN GERMAN LAKES AND RIVERS1 (2002)

We explored statistical relationships between the composition of littoral diatom assemblages and 21 chemical and physical environmental variables in 69 lakes and 15 river sites in the lowland of northeastern Germany. Canonical correspondence analysis with single treatment and with forward selection of environmental variables was used to detect 11 important ecological variables (dissolved inorganic carbon [DIC], Na + , total phosphorus [TP], dissolved organic carbon [DOC], total nitrogen [TN], pH, oxygen saturation, dissolved iron, SO 4 2 − , NH 4 + , soluble reactive silicium) and maximum water depth or Ca 2 + or soluble reactive phosphorus that most independently explain major proportions of the total diatom variance among the habitats. Monte Carlo permutation tests showed that each contributed a significant additional proportion ( P &lt; 0.05) of the variance in species composition. Together, these 11 most important environmental variables explained 34% of the total variance in species composition among the sites and captured 73% of the explained variance from the full 21 parameters model. Weighted‐averaging regression and calibration of 304 indicator taxa with tolerance down‐weighting and classic deshrinking was used to develop transfer functions between littoral diatoms and DIC, pH, TP, TN, and Cl − . The DOC:TP ratio was introduced and a weighted‐averaging model was developed to infer allochthonous DOC effects in freshwater ecosystems. This diatom‐DOC/TP model was significant ( P &lt; 0.001) and explained 7.6% of the total diatom variance among the sites, surpassing the inferential power of the diatom‐TP‐transfer function (7.3% explained variance). The root‐mean‐square errors of prediction of the models were estimated by jack‐knifing and were comparable with published data sets from surface sediment diatom samples. The data set of littoral diatoms and environmental variables allows use of the diatom‐environmental transfer functions in biomonitoring and paleolimnological approaches across a broad array of natural water resources (such as floodplains, flushed lakes, estuaries, shallow lakes) in the central European lowland ecoregion.
Marrow Transplantation for Acute Nonlymphoblastic Leukemia in First Remission (1979)

MARROW transplantation provides the opportunity for aggressive antileukemic therapy without regard to marrow toxicity.1 We have reported the application of this approach combined with intensive chemoradiotherapy in patients with several classes of leukemia; these patients had received the maximum benefit of combination chemotherapy and were considered to be in the end stages of the disease.2 Marrow donors were either identical twins or HLA-identical siblings. Six of 16 recipients of syngeneic marrow and 14 of 110 recipients of allogeneic marrow are still in remission after four to nine years.3 , 4 The allogeneic recipients included 54 patients with acute nonlymphoblastic leukemia, six of . . .
Relationship of aggressive monitoring and treatment to improved outcomes in severe traumatic brain injury (2009)

Aggressive ICP monitoring and treatment of patients with severe TBI is associated with a statistically significant improvement in outcome. This improvement occurs independently of temporal effects.
Inhibition of rotaviruses by selected antiviral substances: mechanisms of viral inhibition and in vivo activity (1982)

Several RNA virus inhibitors were evaluated against simian (SA11) rotavirus infections in vitro and murine rotavirus gastroenteritis in vivo. Test compounds included 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin), 3-deazaguanine (3-DG), 3-deazauridine, and 9-(S)-(2,3-dihydroxypropyl)adenine [(S)-DHPA]. All drugs inhibited total infectious SA11 virus yields in MA-104 cells. Ribavirin, 3-DG, and (S)-DHPA affected [3H]uridine uptake into uninfected MA-104 cells in both the acid-soluble and -insoluble fractions. All drugs reduced the levels of dense (precursor) and light (complete) SA11 particle yields compared with control but did not alter the relative amounts of dense compared with light particles, suggesting that the agents did not interfere with virus assembly. Ribavirin and 3-DG inhibited SA11 polypeptide synthesis, as determined by polyacrylamide gel electrophoresis studies. None of the agents or mono- and triphosphate derivatives of ribavirin inhibited SA11 RNA polymerase activity. In murine rotavirus studies, oral therapy with ribavirin-2',3',5'-triacetate and (S)-DHPA increased mean survival time, but no increase in survivor rate was observed. 3-DG- and (S)-DHPA-treated mice had a more rapid weight gain than controls, suggesting a probable lessening of the severity of the disease.
Genome Comparison of a Nonpathogenic Myxoma Virus Field Strain with Its Ancestor, the Virulent Lausanne Strain (2008)

One of the best-studied examples of host-virus coevolution is the release of myxoma virus (MV) for biological control of European rabbits in Australia and Europe. To investigate the genetic basis of MV adaptation to its new host, we sequenced the genome of 6918, an attenuated Spanish field strain, and compared it with that of Lausanne, the strain originally released in Europe in 1952. Although isolated 43 years apart, the genomes were highly conserved (99.95% identical). Only 32 of the 159 MV predicted proteins revealed amino acid changes. Four genes (M009L, M036L, M135R, and M148R) in 6918 were disrupted by frameshift mutations.
A combined clinical and biomarker approach to predict diuretic response in acute heart failure (2015)

Biomarkers indicate that diuretic unresponsiveness is associated with an atherosclerotic profile with abnormal renal function and electrolytes. However, predicting diuretic response is difficult and biomarkers have limited additive value. Patients at risk of poor diuretic response can be identified by measuring early diuretic response after 24 h.
VLDL-triglyceride production after alcohol ingestion, studied using [2-13C1] glycerol (1998)

We used [2-13C1]glycerol to characterize very low density lipoprotein (VLDL)-triglyceride kinetics and intrahepatic glycerol metabolism in normal men (n = 4) after alcohol (EtOH) ingestion. [2-13C1]glycerol was infused before and after the consumption of 48 g EtOH or a placebo. Three additional subjects also received [1-13C1]acetate in addition to the [2-13C1]glycerol with EtOH treatment. Incorporation of tracer into the glycerol or fatty acid moiety of VLDL-triglyceride was measured by gas chromatography-mass spectrometry and used to calculate VLDL-triglyceride production rates. Intrahepatic triose-phosphate enrichments were also calculated based on mass isotopomer distribution analysis of plasma glucose. There was no difference in VLDL-triglyceride production rates after 48 g EtOH (11.9 +/- 3.7 mg/kg/h) or placebo (14.7 +/- 3. 3 mg/kg/h). The VLDL-triglyceride rate constants calculated by kinetic modeling using the glycerol and acetate tracers in the combined isotope infusion subjects were very closely correlated (r 2 = 0.94). The peak VLDL-glycerol enrichments after EtOH were 22.5 +/- 3.3% versus 7.6 +/- 0.8% after placebo (P < 0.001), while intrahepatic triose-phosphate enrichments were 19.8 +/- 1.3% and 13. 1 +/- 1.2% (P < 0.001), respectively. Moreover, the calculated asymptotic VLDL-glycerol enrichments (representing the hepatic alpha-glycerol phosphate enrichment) were significantly higher after EtOH than placebo. The higher ratio of VLDL-glycerol to triose-phosphate labeling after EtOH suggests a metabolic block at glycerol 3-phosphate dehydrogenase. We conclude that consumption of 48 g EtOH does not increase VLDL-triglyceride production in normal men but does cause accumulation of tracer in hepatic alpha-glycerol phosphate.
Human thymus contains multipotent progenitors with T/B lymphoid, myeloid, and erythroid lineage potential (2005)

It is a longstanding question which bone marrow-derived cell seeds the thymus and to what level this cell is committed to the T-cell lineage. We sought to elucidate this issue by examining gene expression, lineage potential, and self-renewal capacity of the 2 most immature subsets in the human thymus, namely CD34+ CD1a- and CD34+ CD1a+ thymocytes. DNA microarrays revealed the presence of several myeloid and erythroid transcripts in CD34+ CD1a- thymocytes but not in CD34+ CD1a+ thymocytes. Lineage potential of both subpopulations was assessed using in vitro colony assays, bone marrow stroma cultures, and in vivo transplantation into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. The CD34+ CD1a- subset contained progenitors with lymphoid (both T and B), myeloid, and erythroid lineage potential. Remarkably, development of CD34+ CD1a- thymocytes toward the T-cell lineage, as shown by T-cell receptor delta gene rearrangements, could be reversed into a myeloid-cell fate. In contrast, the CD34+ CD1a+ cells yielded only T-cell progenitors, demonstrating their irreversible commitment to the T-cell lineage. Both CD34+ CD1a- and CD34+ CD1a+ thymocytes failed to repopulate NOD/SCID mice. We conclude that the human thymus is seeded by multipotent progenitors with a much broader lineage potential than previously assumed. These cells resemble hematopoietic stem cells but, by analogy with murine thymocytes, apparently lack sufficient self-renewal capacity.
The Role of Caspase Cleavage of Tau in Alzheimer Disease Neuropathology (2005)

Alzheimer disease (AD) is characterized by the accumulation of amyloid plaques and neurofibrillary tangles within selective brain regions. In addition, cell death pathways become active leading to neurodegeneration. Caspase activation, a key step in the programmed cell death pathway known as apoptosis, occurs in AD and leads to the proteolytic cleavage of several neuronal proteins. Previously, it was hypothesized that the development of the classical hallmarks of AD, amyloid plaques and neurofibrillary tangles, occur independently and do not involve the activation of caspases. However, recent studies suggest that plaques, tangles, and caspase activation share a common pathway. Beta-amyloid, the main component of amyloid plaques, activates caspases. Activated caspases can in turn cleave tau, the main component of neurofibrillary tangles. Caspase-cleaved tau (deltatau) may initiate or accelerate the development of tangle pathology. Tau, when cleaved by caspases at Asp421, "seeds" filamentous aggregates in vitro. Caspase-cleaved tau also adopts the MC1 conformation, one of the earliest pathologic events in tangle formation. Importantly, deltatau occurs early in the development of tangle pathology within AD brains and in a transgenic mouse model of AD. This review summarizes recent evidence suggesting that caspase cleavage of tau plays an important role in the development of neurofibrillary tangle pathology. In addition, a model is presented whereby caspase cleavage of tau provides a mechanistic link between the development of amyloid and tangle pathologies.
Isolation and Partial Structural Characterization of Macroglycolipid from Rabbit Erythrocyte Membranes1 (1981)

A macroglycolipid containing galactose and N-acetylglucosamine as predominant sugar constituents was prepared together with glycophorin from rabbit erythrocyte membranes by extraction with lithium diiodosalicylate and partition in aqueous phenol. The macroglycolipid was effectively separated from the glycophorin fraction by ion-exchange chromatography in the presence of a detergent, Ammonyx LO. Its yield (ca. 4 mg/100 ml erythrocytes) was significantly higher than that of the macroglycolipids from human erythrocytes. The structure of the carbohydrate moiety in the macroglycolipid was analyzed by methylation analysis, Smith degradation, nitrous acid deamination, and chromium trioxide oxidation. Assuming one ceramide residue per molecule, the average number of sugars in the macroglycolipid was about 30. The macroglycolipid had a highly branching structure: Gal(alpha 1 leads to 3)Gal(beta 1 leads to 4)GlcNAc sequences are present at nonreducing termini and leads to 3 Gal(beta 1-4)GlcNAc repeating units are present in the inner core of the sugar chain. Some of the inner galactose residues branch at the C-6 position. Constituents of the ceramide moiety were also characterized.
A nonerythroid GATA-binding protein is required for function of the human preproendothelin-1 promoter in endothelial cells. (1990)

Endothelin-1 (ET-1) is a 21-amino-acid peptide synthesized by endothelial cells that has potent vasoconstrictor activity. Human ET-1 is derived from a 212-amino-acid prepropeptide, termed preproendothelin-1 (PPET-1). To identify cis-acting sequences essential for PPET-1 gene transcription, bovine aortic endothelial (BAE) cells were transfected with plasmids containing 5'-flanking sequences of the human PPET-1 gene fused to the human growth hormone gene as a reporter. Deletional analysis of these fusion plasmids showed that the sequence spanning positions -141 to -127 of the human PPET-1 promoter is required for full transcription activity. Introduction of clustered point mutations into this region of the promoter reduced transcription activity. Gel shift analysis, methylation interference, protein-DNA cross-linking, and oligonucleotide competition studies revealed that BAE cell nuclear extract contains a 47-kilodalton DNA-binding protein recognizing the core motif TATC (GATA) located at positions -135 to -132 of the PPET-1 promoter. The size and specificity of this DNA-binding protein resemble GF-1, a previously described transcription factor of erythroid cells that binds to the same core motif. Gel shift analysis indicated that GF-1 and the DNA-binding protein interacting with the PPET-1 promoter have different tissue distributions; the former is restricted to a subset of hematopoietic cells, and the latter is found in various cell types, including BAE, NIH 3T3, and HeLa cells. By using an antiserum to the C-terminal region of GF-1, the two proteins were also found to be antigenically distinct. When a growth hormone fusion plasmid containing the proximal 141 nucleotides of the PPET-1 promoter was transfected into a variety of cell types, these was preferential expression in cells of endothelial origin. We conclude that a nuclear factor with binding specificity for a GATA motif similar to that of the transcriptional activator GF-1 is necessary for the efficient and cell-specific expression of the human PPET-1 gene.
The immunopathogenesis of HBV infection. (1998)

Clinical manifestations of hepatitis B virus (HBV) infection are a balance between viral and host factors. The immune response against any virus consists of a coordinated defence of innate immunity and acquired, virus-specific immunity. In acute HBV, immune responses associated with recovery include vigorous, polyclonal CD4 T cells directed against multiple epitopes within HBV; antibodies directed against surface envelope proteins (anti-HBs), the development of which requires the presence of a CD4 response; and HBV-specific cytotoxic T lymphocytes (CTLs). HBV-specific CTLs can induce death of infected hepatocytes as well as produce cytokines. Most individuals with acute HBV recover without evidence of massive liver destruction; this, plus evidence from transgenic animal models, suggests that these cytokines produced by T cells play an important role in controlling HBV replication. Individuals who fail to mount a vigorous response in acute HBV develop chronic infection. In these cases, the persisting ineffective immune response appears to be responsible for liver damage and is likely to initiate the process of hepatic fibrosis. Based on our current understanding of the immune response in acute and chronic HBV, several groups are investigating the prospect of manipulating the immune response in chronic HBV.
A Mutant Escherichia coli Tyrosyl-tRNA Synthetase Utilizes the Unnatural Amino Acid Azatyrosine More Efficiently than Tyrosine (2000)

Alloproteins, proteins that contain unnatural amino acids, have immense potential in biotechnology and medicine. Although various approaches for alloprotein production exist, there is no satisfactory method to produce large quantities of alloproteins containing unnatural amino acids in specific positions. The tyrosine analogue azatyrosine, l-beta-(5-hydroxy-2-pyridyl)-alanine, can convert the ras-transformed phenotype to normal phenotype, presumably by its incorporation into cellular proteins. This provided the stimulus for isolation of a mutant tyrosyl-tRNA synthetase (TyrRS) capable of charging azatyrosine to tRNA. A plasmid library of randomly mutated Escherichia coli tyrS (encoding TyrRS) was made by polymerase chain reaction techniques. The desired TyrRS mutants were selected by screening for in vivo azatyrosine incorporation of E. coli cells transformed with the mutant tyrS plasmids. One of the clones thus isolated, R-6-A-7, showed a 17-fold higher in vivo activity for azatyrosine incorporation than wild-type TyrRS. The mutant tyrS gene contained a single point mutation resulting in replacement of phenylalanine by serine at position 130 in the protein. Structural modeling revealed that position 130 is located close to Asp(182), which directly interacts with tyrosyladenylate. Kinetic analysis of aminoacyl-tRNA formation by the wild-type and mutated F130S TyrRS enzymes showed that the specificity for azatyrosine, measured by the ratios of k(cat)/K(m) for tyrosine and the analogue, increased from 17 to 36 as a result of the F130S mutation. Thus, the high discrimination against azatyrosine is significantly reduced in the mutant enzyme. These results suggest that utilization of F130S TyrRS for in vivo protein biosynthesis may lead to efficient production of azatyrosine-containing alloproteins.
Clinical Consequences of Delayed Addition of Adalimumab to Methotrexate Therapy Over 5 Years in Patients with Rheumatoid Arthritis (2011)

A 52-week delay in adding adalimumab to MTX led to worse radiographic, functional, and clinical outcomes at Year 5 for most patients who initially received placebo instead of adalimumab.
1,1,2,2-Tetrafluoroethyl-N,N-dimethylamine (2014)

(1,1,2,2-Tetrafluoroethyl-N,N-dimethylamine) [1550-50-1] C4H7F4N (MW 145.1) InChI = 1S/C4H7F4N/c1-9(2)4(7,8)3(5)6/h3H,1-2H3 InChIKey = VIRGYRZBWQFJGJ-UHFFFAOYSA-N (conversion of alcohols to alkyl fluorides,1 carboxylic acids to acyl fluorides,1 activated carbonyl groups to CF2,1, 2 formation of 2-difluoroacyl derivatives of cyclic 1,3-diketones,2 and 3-difluoromethyl pyrazoles3) Alternate Name: TFEDMA. Physical Data: bp 32 °C/127 mmHg, 77 °C/760 mmHg; flash point: 8–9 °C; vapor pressure: 1.48 psia at 21 °C; d 1.24 g cm−1. Solubility: soluble in carbon tetrachloride, chloroform, methylene chloride, acetonitrile, and diethyl ether. Reacts violently with water. Reacts with alcohols and THF. Form Supplied in: yellow liquid. Typical impurities: hydrolysis products: 2,2-difluoro-N,N-dimethylacetamide and HF. Analysis of Reagent Purity: 19F NMR.1 Preparative Method: prepared in >96% yield from tetrafluoroethylene (TFE) and dimethylamine.1 Purification: distillation–glass should be avoided, since TFEDMA reacts with glass at elevated temperatures. Handling, Storage, and Precautions: since TFEDMA reacts violently with water to produce HF (which can cause severe chemical burns) it has to be handled with caution, in a fume hood, by trained personnel. Due to the high reactivity of TFEDMA toward water, it is important that all substrates and solvents are dry. This material is best stored in fluoropolymer (Teflon® PTFE/Teflon® PFA) or polyethylene bottles. Glass should be avoided for storage as well as for reactions of this reagent.
Platelet receptor interplay regulates collagen-induced thrombus formation in flowing human blood (2003)

The platelet glycoproteins (GPs) Ib, integrin alpha(2)beta(1), and GPVI are considered central to thrombus formation. Recently, their relative importance has been re-evaluated based on data from murine knockout models. To examine their relationship during human thrombus formation on collagen type I fibers at high shear (1000 s(-1)), we tested a novel antibody against GPVI, an immunoglobulin single-chain variable fragment, 10B12, together with specific antagonists for GPIb alpha (12G1 Fab(2)) and alpha(2)beta(1) (6F1 mAb or GFOGER-GPP peptide). GPVI was found to be crucial for aggregate formation, Ca(2+) signaling, and phosphatidylserine (PS) exposure, but not for primary adhesion, even with more than 97% receptor blockade. Inhibiting alpha(2)beta(1) revealed its involvement in regulating Ca(2+) signaling, PS exposure, and aggregate size. Both GPIb alpha and alpha(2)beta(1) contributed to primary adhesion, showing overlapping function. The coinhibition of receptors revealed synergism in thrombus formation: the coinhibition of adenosine diphosphate (ADP) receptors with collagen receptors further decreased adhesion and aggregation, and, crucially, the complete eradication of thrombus formation required the coinhibition of GPVI with either GPIb alpha or alpha(2)beta(1). In summary, human platelet deposition on collagen depends on the concerted interplay of several receptors: GPIb in synergy with alpha(2)beta(1) mediating primary adhesion, reinforced by activation through GPVI, which further regulates the thrombus formation.
Profilometry without phase unwrapping using multi-frequency and four-step phase-shift sinusoidal fringe projection (2009)

A three-dimensional (3D) profilometry method without phase unwrapping is proposed. The key factors of the proposed profilometry are the use of composite projection of multi-frequency and four-step phase-shift sinusoidal fringes and its geometric analysis, which enable the proposed method to extract the depth information of even largely separated discontinuous objects as well as lumped continuous objects. In particular, the geometric analysis of the multi-frequency sinusoidal fringe projection identifies the shape and position of target objects in absolute coordinate system. In the paper, the depth extraction resolution of the proposed method is analyzed and experimental results are presented.