gebhart/patrepeval huggingface dataset:
Nutrition and lysosomal activity. The influence of vitamin E deficiency and its duration on the stability of lysosomes in the kidneys of rats (1967)

1. Experiments on rats were made to find whether the increased liability of the kidney-cortex tubules to autolysis post mortem, which is a well-established abnormality in vitamin E deficiency, can be correlated with changes in lysosomal activity. Parallel observations were made on the development of certain other abnormalities characteristic of avitaminosis E. 2. In rats killed after long periods (8-10 months) of subsistence on a standard vitamin E-deficient diet, containing lard, both the rate of kidney autolysis post mortem and the enzyme activity of lysosome preparations from the fresh tissues were much greater than in controls. A greater percentage difference was usually found in the ;free' enzyme fraction than in ;bound' or ;total' activity. 3. In rats killed after graded periods (3-8 months) of deficiency, two abnormalities (decreased resistance of the erythrocytes to haemolysis, and brown discoloration of the uterus) were already evident at a stage (3-4 months) when the liability to rapid kidney autolysis had not begun. At this point the enzymic activity of kidney extracts differed little between deficient animals and controls given alpha-tocopherol. As the duration of deficiency advanced, parallel increases occurred in the rate of kidney autolysis and in lysosomal instability. 4. When cod-liver oil, rich in polyunsaturated fatty acids but freed from vitamin A, was substituted for lard in the diet, the time (1(1/2) months) required for the inducement of both rapid kidney autolysis and decreased lysosomal stability was greatly shortened. The time for the inducement of brown discoloration of the uterus was not shortened and the kidney abnormalities appeared while the uterus was still normal. 5. Confirmation was thus obtained for the view that the various tissues of the rat respond differently to the relationship between the adequacy of the vitamin E status and the intake of polyunsaturated fatty acids. The kidney-cortex tubules, as evidenced by autolysis post mortem and the corresponding decrease in lysosomal stability, may be classed among those tissues that are most sensitive to the effect of high intakes of polyunsaturated acids.
Gene Targeting in Aspergillus fumigatus by Homologous Recombination Is Facilitated in a Nonhomologous End- Joining-Deficient Genetic Background (2006)

The akuA gene encoding the Ku70 component of the nonhomologous end-joining machinery was deleted in the opportunistic pathogen Aspergillus fumigatus. No obvious phenotype could be assessed for the corresponding mutant strain but relative frequencies of homologous recombination were increased as deduced from targeting the laccase-encoding abr2 gene.
Ultrashort echo time imaging using pointwise encoding time reduction with radial acquisition (PETRA) (2011)

Sequences with ultrashort echo times enable new applications of MRI, including bone, tendon, ligament, and dental imaging. In this article, a sequence is presented that achieves the shortest possible encoding time for each k-space point, limited by pulse length, hardware switching times, and gradient performance of the scanner. In pointwise encoding time reduction with radial acquisition (PETRA), outer k-space is filled with radial half-projections, whereas the centre is measured single pointwise on a Cartesian trajectory. This hybrid sequence combines the features of single point imaging with radial projection imaging. No hardware changes are required. Using this method, 3D images with an isotropic resolution of 1 mm can be obtained in less than 3 minutes. The differences between PETRA and the ultrashort echo time (UTE) sequence are evaluated by simulation and phantom measurements. Advantages of pointwise encoding time reduction with radial acquisition are shown for tissue with a T(2) below 1 ms. The signal to noise ratio and Contrast-to-noise ratio (CNR) performance, as well as possible limitations of the approach, are investigated. In-vivo head, knee, ankle, and wrist examples are presented to prove the feasibility of the sequence. In summary, fast imaging with ultrashort echo time is enabled by PETRA and may help to establish new routine clinical applications of ultrashort echo time sequences.
Release of Intact and Fragmented Osteocalcin Molecules from Bone Matrix during Bone Resorption in Vitro (2004)

Osteocalcin detected from serum samples is considered a specific marker of osteoblast activity and bone formation rate. However, osteocalcin embedded in bone matrix must also be released during bone resorption. To understand the contribution of each type of bone cell in circulating osteocalcin levels, we used immunoassays detecting different molecular forms of osteocalcin to monitor bone resorption in vitro. Osteoclasts were obtained from rat long bones and cultured on bovine bone slices using osteocalcin-depleted fetal bovine serum. In addition, human osteoclasts differentiated from peripheral blood mononuclear cells were used. Both rat and human osteoclasts released osteocalcin from bovine bone into medium. The amount of osteocalcin increased in the presence of parathyroid hormone, a stimulator of resorption, and decreased in the presence of bafilomycin A1, an inhibitor of resorption. The amount of osteocalcin in the medium correlated with a well characterized marker of bone resorption, the C-terminal telopeptide of type I collagen (r > 0.9, p < 0.0001). The heterogeneity of released osteocalcin was determined using reverse phase high performance liquid chromatography, and several molecular forms of osteocalcin, including intact molecule, were identified in the culture medium. In conclusion, osteocalcin is released from the bone matrix during bone resorption as intact molecules and fragments. In addition to the conventional use as a marker of bone formation, osteocalcin can be used as a marker of bone resorption in vitro. Furthermore, bone matrix-derived osteocalcin may contribute to circulating osteocalcin levels, suggesting that serum osteocalcin should be considered as a marker of bone turnover rather than bone formation.
Misfit strain relaxation in GexSi1−x/Si heterostructures: The structural stability of buried strained layers and strained-layer superlattices (1990)

The critical thickness-strain relationships for buried strained layers and strained-layer superlattices (SLSs) are derived using an energy balance model. Relaxation of the entire heterostructure and individual strained layers by both 60° type a/2〈011〉 and pure edge dislocations is considered. GexSi1−x/Si heterostructures designed to investigate the stability regimes predicted by the model were grown by molecular-beam epitaxy. The extent of relaxation and the detailed dislocation structure were assessed in annealed structures by x-ray rocking curve analysis, transmission electron microscopy, and Nomarski microscopy of etched samples. Comparison of metastable as-grown and post-growth annealed microstructures revealed the evolution of misfit dislocation structure as equilibrium was approached on annealing in the temperature range 600–900 °C. The predominant relaxation mechanism for most GexSi1−x/Si heterostructures was by 60° a/2 〈011〉 misfit dislocations at the first strained-layer/substrate interface. However, for SLSs with strained layers exceeding their individual critical thickness, pairs of dislocations and prismatic loops on (011) planes were observed entrained within the GexSi1−x layers. The agreement between experimentally observed relaxation behavior and the critical thickness versus strain predictions of the energy balance model is remarkable. Superlattices and buried strained layers were found to be only slightly more stable than an uncapped strained layer of the equivalent strained-layer thickness. Interdiffusion was observed at annealing temperatures above 800 °C; annealing at 900 °C for 30 min was sufficient to eliminate the strain and composition modulation in a superlattice with a 55-nm period and x=0.25. The relative influence of the various strain relaxation mechanisms is discussed for the alloy range 0&amp;lt;x&amp;lt;1 and for geometries with strained-layer dimensions varying from 0.8 to ∼500 nm.
Acute Renal Failure in Natural Disasters (1992)

Sudden-impact natural disasters such as earthquakes present a serious challenge to medical personnel in both developed and less developed countries. Crush syndrome with acute renal failure has been identified as a major medical complication that occurs among people whose limbs are trapped by heavy objects during natural disasters such as earthquakes or volcanic eruptions. Rescue and field medical teams should be trained to recognize and promptly treat the problems associated with prolonged limb compression and should carry the appropriate fluids and medications to treat the complications of traumatic rhabdomyolysis. Early, aggressive volume replacement followed by forced solute-alkaline diuresis therapy may protect the kidney against acute renal failure. Better epidemiologic knowledge of the specific disaster conditions that predispose traumatic rhabdomyolysis to develop is clearly essential for those who must determine when emergency dialysis services are required in response to injuries sustained during natural disasters. Disaster health care personnel involved with providing emergency acute renal care should have a basic familiarity with disaster epidemiology in order to determine whether a given event requires their intervention. This paper includes recommendations for improving medical planning, preparedness, and response to natural disasters that cause acute renal failure.
Relationship between Histone H3 Lysine 9 Methylation, Transcription Repression, and Heterochromatin Protein 1 Recruitment (2005)

Histone H3 lysine 9 (H3-K9) methylation has been shown to correlate with transcriptional repression and serve as a specific binding site for heterochromatin protein 1 (HP1). In this study, we investigated the relationship between H3-K9 methylation, transcriptional repression, and HP1 recruitment by comparing the effects of tethering two H3-K9-specific histone methyltransferases, SUV39H1 and G9a, to chromatin on transcription and HP1 recruitment. Although both SUV39H1 and G9a induced H3-K9 methylation and repressed transcription, only SUV39H1 was able to recruit HP1 to chromatin. Targeting HP1 to chromatin required not only K9 methylation but also a direct protein-protein interaction between SUV39H1 and HP1. Targeting methyl-K9 or a HP1-interacting region of SUV39H1 alone to chromatin was not sufficient to recruit HP1. We also demonstrate that methyl-K9 can suppress transcription independently of HP1 through a mechanism involving histone deacetylation. In an effort to understand how H3-K9 methylation led to histone deacetylation in both H3 and H4, we found that H3-K9 methylation inhibited histone acetylation by p300 but not its association with chromatin. Collectively, these data indicate that H3-K9 methylation alone can suppress transcription but is insufficient for HP1 recruitment in the context of chromatin exemplifying the importance of chromatin-associated factors in reading the histone code.
Molecular Mechanism of Neuronal Plasticity: Induction and Maintenance of Long-Term Potentiation in the Hippocampus (2006)

Recent studies have demonstrated that activation of enzymes can be observed in living cells in response to stimulation with neurotransmitters, hormones, growth factors, and so forth. Thus, the activation of enzymes was shown to be closely related to the dynamic states of various cell functions. The development of new experimental methodologies has enabled researchers to study the molecular basis of neuronal plasticity in living cells. In 1973, Bliss and his associates identified the phenomena of long-term potentiation (LTP). Since it was thought to be a model for neuronal plasticity such as learning and memory, its molecular mechanism has been extensively investigated. The mechanism was found to involve a signal transduction cascade that includes release of glutamate, activation of the NMDA glutamate receptors, Ca(2+) entry, and activations of Ca(2+)/calmodulin-dependent protein kinases (CaM kinases) II and IV and mitogen-activated protein kinase (MAPK). Consequently, AMPA glutamate receptors were activated by phosphorylation by CaM kinase II, resulting in an increase of Ca(2+) entry into postsynaptic neurons. Furthermore, activation of CaM kinase IV and MAPK increased phosphorylation of CREB (cyclic AMP response element binding protein) and expression of c-Fos by stimulation of gene expression. These results suggest that LTP induction and maintenance would be models of short- and long-term memory, respectively.
Primary structure of the catalytic subunit of calf thymus DNA polymerase .delta.: sequence similarities with other DNA polymerases (1991)

The 125- and 48-kDa subunits of bovine DNA polymerase delta have been isolated by SDS-polyacrylamide gel electrophoresis and demonstrated to be unrelated by partial peptide mapping with N-chlorosuccinimide. A 116-kDa polypeptide, usually present in DNA polymerase delta preparations, was shown to be a degraded form of the 125-kDa catalytic subunit. Amino acid sequence data from Staphylococcus aureus V8 protease, cyanogen bromide, and trypsin digestion of the 125- and 116-kDa polypeptides were used to design primers for the polymerase chain reaction to determine the nucleotide sequence of a full-length cDNA encoding the catalytic subunit of bovine DNA polymerase delta. The predicted polypeptide is 1106 amino acids in length with a calculated molecular weight of 123,707. This is in agreement with the molecular weight of 125,000 estimated from SDS-polyacrylamide gel electrophoresis. Comparison of the deduced amino acid sequence of the catalytic subunit of bovine DNA polymerase delta with that of its counterpart from Saccharomyces cerevisiae showed that the proteins are 44% identical. The catalytic subunit of bovine DNA polymerase delta contains the seven conserved regions found in a number of bacterial, viral, and eukaryotic DNA polymerases. It also contains five additional regions that are highly conserved between bovine and yeast DNA polymerase delta, but these regions share little or no homology with the alpha polymerases. Four of these additional regions are also highly homologous to the herpes virus family of DNA polymerases, whereas one region is not homologous to any other DNA polymerase that has been sequenced thus far.(ABSTRACT TRUNCATED AT 250 WORDS)
Cytotoxic analogs of luteinizing hormone-releasing hormone containing doxorubicin or 2-pyrrolinodoxorubicin, a derivative 500-1000 times more potent. (1996)

Doxorubicin (DOX) and its daunosamine-modified derivative, 2-pyrrolino-DOX, which is 500-1000 times more active than DOX, were incorporated into agonistic and antagonistic analogs of luteinizing hormone-releasing hormone (LH-RH). The conjugation of DOX with LH-RH analogs was performed by using N-(9-fluorenylmethoxycarbonyl)-DOX-14-O-hemiglutarate, a dicarboxylic acid ester derivative of DOX. Coupling this derivative covalently to the epsilon-amino group of the D-Lys side chain of agonist [D-Lys6]LH-RH or antagonistic analog AC-D-Nal(2)-D-Phe(4Cl)-D-Pal(3)-Ser-Tyr-D-Lys-Leu-Arg-Pro-D-Ala-NH 2 [where Nal(2) = 3-(2-naphthyl)alanine, Pal(3) = 3-(3-pyridyl)alanine, and Phe(4CI) = 4-chlorophenylalanine] was followed by the removal of the 9-fluorenylmethoxycarbonyl protective group to yield cytotoxic derivatives of LH-RH analogs containing DOX. From these DOX containing LH-RH hybrids, intensely potent analogs with daunosamine-modified derivatives of DOX can be readily formed. Thus, cytotoxic LH-RH agonist containing DOX (AN-152) can be converted in a 66% yield by a reaction with a 30-fold excess of 4-iodobutyraldehyde in N,N-dimethylformamide into a derivative having 2-pyrrolino-DOX (AN-207). Hybrid molecules AN-152 and AN-207 fully preserve the cytotoxic activity of their radicals, DOX or 2-pyrrolino-DOX, respectively, in vitro, and also retain the high binding affinity of the peptide hormone portion of the conjugates to rat pituitary receptors for LH-RH. These highly potent cytotoxic analogs of LH-RH were designed as targeted anti-cancer agents for the treatment of various tumors that possess receptors for the carrier peptide. Initial in vivo studies show that the hybrid molecules are much less toxic than the respective cytotoxic radicals incorporated and significantly more active in inhibiting tumor growth.
Analyzing Fair Use Claims: A Quantitative and Paradigmatic Approach (1994)

supra note 2, at 1161.Professor Weinreb suggests that the fluid definition of fair use is an advantage:The reference to fairness in the doctrine of fair use imparts to the copyright scheme a bounded normative element that is desirable in itself.It gives effect to the community's established practices and understandings and allows the location of copyright within the framework of property generally.Adjudication according to a standard of fairness calls for the exercise of great judicial skill, or art.See also Sony, 464 U.S. at 448 n.31.5. One observer attempted to define a fair use as one "technically forbidden by the law, but allowed as reasonable and customary on the theory that the author must have foreseen it and tacitly consented to it."
The Path to Cancer — Three Strikes and You're Out (2015)

Focusing on driver-gene mutations and the pathways they control has rendered complex cancer-genome landscapes intelligible. In solid tumors of adults, alterations in as few as three driver genes appear to suffice for a cell to evolve into an advanced cancer.
B cell response to T helper cell subsets. II. Both the stage of T cell differentiation and the cytokines secreted determine the extent and nature of helper activity (1991)

Helper activity of several murine CD4+ T cell subsets was examined. Effector Th, derived from naive cells after 4 days of in vitro stimulation with alloantigen, when generated in the presence of IL-4, secreted high levels of IL-4, IL-5, and IL-6, and low levels of IL-2 and IFN-gamma, and induced the secretion of all Ig isotypes particularly IgM, IgG1, IgA, and IgE from resting allogeneic B cells. Effectors generated with IL-6 secreted IL-2, IL-4, IL-5, IL-6, and IFN-gamma, and induced similar levels of total Ig, 25 to 35 micrograms/ml, but with IgM, IgG3, IgG1, and IgG2a isotypes predominating. Helper activity of these Th was significantly greater than that of effectors generated with IL-2 (10-15 micrograms/ml Ig) and of 24-h-activated naive and memory cells (2-4 micrograms/ml), both of which induced mainly IgM. Unlike other isotypes, IgE was induced only by effector Th generated with IL-4. Blocking studies showed that secretion of all isotypes in response to IL-6-primed effectors was dependent on IL-2, IL-5, and IL-6. IL-4 was required for optimal IgM, IgG1, and IgA secretion, but limited secretion of IgG2a, whereas IFN-gamma was required for optimal IgG2a secretion, and limited IgM, IgG1, and IgA. In contrast, secretion of all isotypes in response to IL-4-primed effectors was dependent on IL-5, although IL-4 and IFN-gamma were also essential for IgE and IgG2a, respectively. Addition of exogenous IL-5 to B cell cultures driven by IL-6-primed effectors did not obviate the requirement for IL-2, IL-4, and IL-6, suggesting that interaction of IL-4-primed effectors with B cells was qualitatively different from that of IL-6-primed effectors, driving B cells to a stage requiring only IL-5 for differentiation. Addition of exogenous factors to IL-2-primed effector Th, particularly IL-4 in the presence of anti-IFN-gamma, resulted in levels of Ig, including IgE, comparable to those induced with other effectors. These results show that functionally distinct Th cell subsets can be generated rapidly in vitro, under the influence of distinct cytokines, which vary dramatically in their levels of help for resting B cells. The cytokines involved in responses to distinct Th cells differ depending on the quality of interaction with the B cell, and the extent of help is strongly determined by the quantity and nature of cytokines secreted by the T cells.
Functional and Clinical Consequences of Novel α-Galactosidase A Mutations in Fabry Disease (2015)

Fabry disease (FD) is a rare metabolic disorder of glycosphingolipid storage caused by mutations in the GLA gene encoding lysosomal hydrolase α-galactosidase A (α-gal A). Recently, the diagnostic procedure for FD has advanced in several ways, through the development of a specific biomarker (lyso-Gb3) and the implementation of newborn screenings, which acted as a catalyst to augment general awareness of the disease. Heterologous over-expression of α-gal A variants and subsequent in vitro measurement of enzyme activity provided molecular data to elucidate the relationship between mutation, enzyme damage, lyso-Gb3 biomarker levels, and clinical phenotype. This knowledge is the foundation for improved counseling with regard to prognosis and therapeutic decisions. Herein, we resume the approach of in vitro characterization, with a further 73 mainly novel GLA gene mutations. Patient lyso-Gb3 data were available for most of the mutations. All mutations were tested for responsiveness to pharmacological chaperone treatment and phenotypic data for 61 hemizygous male and 116 heterozygous female patients carrying a mutation associated with ≥ 20% residual activity, formerly classified as "mild" variant, were collected in order to evaluate the pathogenicity. We conclude that a mild GLA variant is typically characterized by high residual enzyme activity and normal biomarker levels. We found evidence that these variants can still be classified as a distinctive, but milder, sub-type of FD.
Large-Scale Proteomic Characterization of Melanoma Expressed Proteins Reveals Nestin and Vimentin as Biomarkers That Can Potentially Distinguish Melanoma Subtypes (2014)

Melanoma is an aggressive type of skin cancer, which accounts for only 4% of skin cancer cases but causes around 75% of skin cancer deaths. Currently, there is a limited set of protein biomarkers that can distinguish melanoma subtypes and provide an accurate prognosis of melanoma. Thus, we have selected and profiled the proteomes of five different melanoma cell lines from different stages of progression in comparison with a normal melanocytes using tandem mass spectrometry. We also profiled the proteome of a solid metastatic melanoma tumor. This resulted in the identification of 4758 unique proteins, among which ∼200-300 differentially expressed proteins from each set were found by quantitative proteomics. Correlating protein expression with aggressiveness of each melanoma cell line and literature mining resulted in the final selection of six proteins: vimentin, nestin, fibronectin, annexin A1, dipeptidyl peptidase IV, and histone H2A1B. Validation of nestin and vimentin using 40 melanoma samples revealed pattern of protein expression can help predict melanoma aggressiveness in different subgroups of melanoma. These results, together with the combined list of 4758 expressed proteins, provide a valuable resource for selecting melanoma biomarkers in the future for the clinical and research community.