gebhart/patrepeval huggingface dataset:
Photoaffinity Labeling of a Cell Surface Polyamine Binding Protein (1995)

Intracellular polyamine pools are partially maintained by an active transport apparatus that is specific for and regulated by polyamines. Although mammalian transport activity has been characterized by kinetic studies, the actual protein itself has yet to be identified, purified, or cloned. As one approach to this problem, we attempted photoaffinity labeling of plasma membrane proteins using two specifically designed and synthesized polyamine conjugates as photoprobes. The first is a spermidine conjugate bearing the photoreactive moiety 4-azidosalicylic acid at the N4 position via an alkyl linkage, and the second is a norspermine conjugate with 4-azidosalicylic acid at the N4 position via an acyl linkage. Labeling of murine L1210 lymphocytic leukemia cells was carried out at 4 degrees C to promote selective alkylation of cell surface proteins. Separation of plasma membrane proteins from cells cross-linked with the N4-spermidine conjugate by SDS-polyacrylamide gel electrophoresis revealed two heavily labeled proteins at approximately 118 and approximately 50 kDa (designated p118 and p50, respectively). Band p118 was more well defined and much more intensely labeled. Analogous proteins were also observed in human U937 lymphoma cells. Specificity of labeling was strongly suggested by competition with polyamines and analogs during labeling and further indicated by the nearly identical labeling of the same protein by the N1-norspermine photoprobe but not by the unconjugated photoreagent. Neuraminidase pretreatment of L1210 cells increased mobility of the p118, suggesting that it was glycosylated and, thus, of plasma membrane origin. In transport-deficient L1210 cells, p118 and p50 were found to have a slightly higher molecular mass and were accompanied by a less distinct protein band (approximately 100 kDa). These findings indicate the presence of a polyamine binding protein at the surface of murine and human leukemia cells, which could be directly or indirectly related to the polyamine transport apparatus.
Complete sequence of a gene encoding a human type I keratin: sequences homologous to enhancer elements in the regulatory region of the gene. (1985)

We report here the complete nucleotide sequence of a gene encoding the 50-kDa keratin expressed in abundance in human epidermal cells. According to its sequence, this gene has a single transcriptional initiation site and a single polyadenylylation signal. Nuclease S1 mapping of this gene with total human epidermal mRNA confirmed the presence of a single initiation site for the 50-kDa keratin gene. When the regulatory sequences 5' upstream from this gene were examined, three sequences that share significant homology with viral and immunoglobulin enhancer elements were found. In comparison, the sequence of the regulatory region of vimentin, a structurally similar intermediate filament gene, was highly divergent [Quax, W., Egberts, W. V., Hendriks, W., Quax-Jeuken, Y. & Bloemendal, H. (1983) Cell 35, 215-223]. This finding may provide a clue to understanding the molecular mechanisms underlying the widely varying levels of expression of different intermediate filament genes in different tissues.
Design of advanced porous graphene materials: from graphene nanomesh to 3D architectures (2013)

In order to make full utilization of the high intrinsic surface area of graphene, recently, porous graphene materials including graphene nanomesh, crumpled graphene and graphene foam, have attracted tremendous attention and research interest, owing to their exceptional porous structure (high surface area, and high pore volume) in combination with the inherent properties of graphene, such as high electronic conductivity, good thermal stability, and excellent mechanical strength. Interestingly, porous graphene materials and their derivatives have been explored in a wide range of applications in the fields of electronic and photonic devices, energy storage, gas separation/storage, oil absorption and sensors. This article reviews recent progress in the synthesis, characterization, properties, and applications of porous graphene materials. We aim to highlight the importance of designing different porous structures of graphene to meet future challenges, and the trend on future design of porous graphene materials is analyzed.
Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways (2000)

Somatic mutations of the receptor tyrosine kinase Flt3 consisting of internal tandem duplications (ITD) occur in 20% of patients with acute myeloid leukemia. They are associated with a poor prognosis of the disease. In this study, we characterized the oncogenic potential and signaling properties of Flt3 mutations. We constructed chimeric molecules that consisted of the murine Flt3 backbone and a 510-base pair human Flt3 fragment, which contained either 4 different ITD mutants or the wild-type coding sequence. Flt3 isoforms containing ITD mutations (Flt3-ITD) induced factor-independent growth and resistance to radiation-induced apoptosis in 32D cells. Cells containing Flt3-ITD, but not those containing wild-type Flt3 (Flt3-WT), formed colonies in methylcellulose. Injection of 32D/Flt3-ITD induced rapid development of a leukemia-type disease in syngeneic mice. Flt3-ITD mutations exhibited constitutive autophosphorylation of the immature form of the Flt3 receptor. Analysis of the involved signal transduction pathways revealed that Flt3-ITD only slightly activated the MAP kinases Erk1 and 2 and the protein kinase B (Akt) in the absence of ligand and retained ligand-induced activation of these enzymes. However, Flt3-ITD led to strong factor-independent activation of STAT5. The relative importance of the STAT5 and Ras pathways for ITD-induced colony formation was assessed by transfection of dominant negative (dn) forms of these proteins: transfection of dnSTAT5 inhibited colony formation by 50%. Despite its weak constitutive activation by Flt3-ITD, dnRas also strongly inhibited Flt3-ITD-mediated colony formation. Taken together, Flt3-ITD mutations induce factor-independent growth and leukemogenesis of 32D cells that are mediated by the Ras and STAT5 pathways. (Blood. 2000;96:3907-3914)
Specific Targeting of Tumor Angiogenesis by RGD-Conjugated Ultrasmall Superparamagnetic Iron Oxide Particles Using a Clinical 1.5-T Magnetic Resonance Scanner (2007)

Angiogenesis is essential for the development of malignant tumors and provides important targets for tumor diagnosis and therapy. To noninvasively assess the angiogenic profile of tumors, novel alpha(v)beta(3) integrin-targeted ultrasmall superparamagnetic iron oxide particles (USPIOs) were designed and their specific uptake by endothelial cells was evaluated in vitro and in vivo. USPIOs were coated with 3-aminopropyltrimethoxysilane (APTMS) and conjugated with Arg-Gly-Asp (RGD) peptides. Accumulation in human umbilical vein endothelial cells (HUVECs) was evaluated using Prussian blue staining, transmission electron microscopy, magnetic resonance (MR) imaging, and inductively coupled plasma mass spectrometry. Uptake of RGD-USPIO by HUVECs was significantly increased when compared with unlabeled USPIO and could be competitively inhibited by addition of unbound RGD. The ability of the RGD-USPIO to noninvasively distinguish tumors with high (HaCaT-ras-A-5RT3) and lower (A431) area fractions of alpha(v)beta(3) integrin-positive vessels was evaluated using a 1.5-T MR scanner. Indeed, after RGD-USPIO injection, there was a more pronounced decrease in T(2) relaxation times in HaCaT-ras-A-5RT3 tumors than in A431 tumors. Furthermore, T(2)*-weighted images clearly identified the heterogeneous arrangement of vessels with alpha(v)beta(3) integrins in HaCaT-ras-A-5RT3 tumors by an irregular signal intensity decrease. In contrast, in A431 tumors with predominantly small and uniformly distributed vessels, the signal intensity decreased more homogeneously. In summary, RGD-coupled, APTMS-coated USPIOs efficiently label alpha(v)beta(3) integrins expressed on endothelial cells. Furthermore, these molecular MR imaging probes are capable of distinguishing tumors differing in the degree of alpha(v)beta(3) integrin expression and in their angiogenesis profile even when using a clinical 1.5-T MR scanner.
Using Mice to Treat (Wo)men: Mining Genetic Changes in Patient Xenografts to Attack Breast Cancer (2013)

In this issue of Cell Reports, Li et al. show that the analysis of genetic changes in patient-derived xenografts can reveal crucial details of tumor evolution, such as the emergence of functional estrogen receptor mutations in endocrine-resistant breast cancer.
Nucleotide Sequences of 5S rRNAs from four jellyfishes (1982)

The nucleotide sequences of 5S rRNAs from four jellyfishes, Spirocodon saltatrix, Nemopsis dofleini, Aurelia aurita and Chrysaora quinquecirrha have been determined. The sequences are highly similar to each other. A fairly high similarity was also found between these jellyfishes and a sea anemone, Anthopleura japonica.
Superoxide dismutase is an abundant component in cell bodies, dendrites, and axons of motor neurons and in a subset of other neurons. (1995)

Mutation in superoxide dismutase 1 (SOD1), a Cu/Zn enzyme that removes oxygen radicals and protects against oxidative injury, has been implicated in some cases of familial amyotrophic lateral sclerosis (FALS). As a first approach to examining the mechanism(s) through which these mutations cause specific degeneration of motor neurons, we have used immunocytochemistry to identify the distribution of SOD1 in populations of cells in the peripheral and central nervous systems. In the spinal cord, intense SOD1 immunoreactivity was present in motor neurons, interneurons, and substantia gelatinosa. In motor neurons, SOD1 immunoreactivity was abundant in perikarya, dendrites, and axons; most of this activity appeared to be free in the cytoplasm, although a portion was associated with membranous vesicles, presumably peroxisomes. Since a variety of central nervous system neurons, including pyramidal cells in cerebral cortex and neurons of the CA3 and CA4 sectors of the hippocampus, showed high immunoreactivity but are unaffected in ALS, the apparent abundance of SOD1 does not predict vulnerability of neurons to mutations in SOD1. Rather, SOD1 accumulates in many neuronal populations but is particularly abundant in motor neurons. Consistent with recent studies of FALS-linked SOD1 mutations in vitro and in transgenic mice, our findings offer further support for the view that the mutations confer a gain of adverse function. In this view, high, rather than limiting, levels of SOD1 may place motor neurons selectively at risk in FALS.
Divergent functions of lectin‐like receptors on NK cells (1997)

NK cells express a superfamily of surface proteins that share a common structure: dimeric type II integral membrane proteins whose extracellular domains have structural features of C-type (calcium-dependent) lectins. These receptors are encoded in a single genetic region called the NK complex (NKC). The NKC encompasses several families of genes, including Ly-49 (in mice and rats), NKR-P1 (in mice, rats, and humans). NKG2 (in humans and rats), and CD94 (in humans). Different NKC receptors have been shown to activate or to inhibit NK function, and different receptors within the same family can have opposing functions. In this review, we discuss the molecular pathways by which NK cells are activated, and the mechanisms by which inhibitory receptors interrupt activation. By studying the inhibitory receptor Ly-49A, we have demonstrated that inhibition utilizes the cytoplasmic phosphatase, SHP-1, which binds to a motif in the receptor cytoplasmic domain, termed an immunoreceptor tyrosine-based inhibitory motif (ITIM). In this regard, the lectin-like receptors are functionally similar to the immunoglobulin-like killer inhibitory receptors (KIRs) on human NK cells. The presence of an ITIM generally correlates with inhibitory activity among NKC lectin-like receptors, as demonstrated by the human NKG2 receptor family. Lanier and his colleagues have recently shown that NKG2 receptors can form heterodimers with the invariant lectin-like receptor CD94. Selective association of CD94 with different NKG2 receptors may explain functional differences for CD94 in different NK clones.
Patterns of nucleotide substitution, insertion and deletion in the human genome inferred from pseudogenes (2003)

Nucleotide substitution, insertion and deletion (indel) events are the major driving forces that have shaped genomes. Using the recently identified human ribosomal protein (RP) pseudogene sequences, we have thoroughly studied DNA mutation patterns in the human genome. We analyzed a total of 1726 processed RP pseudogene sequences, comprising more than 700 000 bases. To be sure to differentiate the sequence changes occurring in the functional genes during evolution from those occurring in pseudogenes after they were fixed in the genome, we used only pseudogene sequences originating from parts of RP genes that are identical in human and mouse. Overall, we found that nucleotide transitions are more common than transversions, by roughly a factor of two. Moreover, the substitution rates amongst the 12 possible nucleotide pairs are not homogeneous as they are affected by the type of immediately neighboring nucleotides and the overall local G+C content. Finally, our dataset is large enough that it has many indels, thus allowing for the first time statistically robust analysis of these events. Overall, we found that deletions are about three times more common than insertions (3740 versus 1291). The frequencies of both these events follow characteristic power–law behavior associated with the size of the indel. However, unexpectedly, the frequency of 3 bp deletions (in contrast to 3 bp insertions) violates this trend, being considerably higher than that of 2 bp deletions. The possible biological implications of such a 3 bp bias are discussed.
Quasiparticle Relaxation of Superconducting Qubits in the Presence of Flux (2011)

Quasiparticle tunneling across a Josephson junction sets a limit for the lifetime of a superconducting qubit state. We develop a general theory of the corresponding decay rate in a qubit controlled by a magnetic flux. The flux affects quasiparticles tunneling amplitudes, thus making the decay rate flux-dependent. The theory is applicable for an arbitrary quasiparticle distribution. It provides estimates for the rates in practically important quantum circuits and also offers a new way of measuring the phase-dependent admittance of a Josephson junction.
Derivation of Human Embryonic Germ Cells: An Alternative Source of Pluripotent Stem Cells (2003)

Based on evidence suggesting similarities to human embryonic stem cells, human embryonic germ (hEG) cells have been advocated as an alternative pluripotent stem cell resource but have so far received limited attention. To redress this imbalance, human fetal gonads were collected for the isolation and culture of primordial germ cells at 7-9 weeks postconception. We provide evidence for the derivation, culture, and differentiation of hEG cells in vitro. This evidence includes the expression of markers characteristic of pluripotent cells, the retention of normal XX or XY karyotypes, and the demonstration of pluripotency, as suggested by the expression of markers indicative of differentiation along the three germ lineages (ectoderm, mesoderm, and endoderm) and an associated loss of pluripotent markers. In assessing this differentiation, however, we also demonstrate a hitherto unacknowledged overlap in gene expression profiles between undifferentiated and differentiated cell types, highlighting the difficulty in ascribing cell lineage by gene expression analyses. Furthermore, we draw attention to the problems inherent in the management of these cells in prolonged culture, chiefly the difficulty in preventing spontaneous differentiation, which hinders the isolation of pure, undifferentiated clonal lines. While these data advocate the pursuit of pluripotent hEG cell studies with relevance to early human embryonic development, culture limitations carry implications for their potential applicability to ambitious cell replacement therapies.
Neurotoxicity of Silica Nanoparticles: Brain Localization and Dopaminergic Neurons Damage Pathways (2011)

Silica nanoparticles (SiO(2)-NPs) are being used increasingly in diagnosis, imaging, and drug delivery for the central nervous system. However, to date, little is known concerning the potential adverse effects on the brain associated with exposure to SiO(2)-NPs. The present study was conducted to trace, locate, and quantify SiO(2)-NPs in the brain by a radiolabeling approach after intranasal instillation with SiO(2)-NPs. The oxidative stress, inflammatory response, and levels of neurochemicals in the brain were also analyzed. Furthermore, in vitro studies were carried out to elucidate the pathway and mechanism of in vivo damage with a co-incubation model of dopaminergic neuron PC12 and SiO(2)-NPs. The results indicated that SiO(2)-NPs via intranasal instillation entered into the brain and especially deposited in the striatum. Exposure to SiO(2)-NPs also induced oxidative damage and an increased inflammatory response in the striatum. Meanwhile, results of in vitro studies demonstrated that exposure to SiO(2)-NPs decreased cell viability, increased levels of lactate dehydrogenase, triggered oxidative stress, disturbed cell cycle, induced apoptosis, and activated the p53-mediated signaling pathway. In addition, the in vivo injury of neurochemicals occurred as the SiO(2)-NPs appeared to induce depleted dopamine in the striatum, and the down-regulation of tyrosine hydroxylase protein was the main contribution. These data demonstrate that SiO(2)-NPs possibly have a negative impact on the striatum and dopaminergic neurons as well as a potential risk for neurodegenerative diseases. There is potential concern with SiO(2)-NPs' neurotoxicity in biomedical applications and occupational exposure in large-scale production.
Mixed T cell receptor dimers harbor potentially harmful neoreactivity (2010)

Adoptive transfer of T cell receptor (TCR)-transduced T cells may be an attractive strategy to target both hematological malignancies and solid tumors. By introducing a TCR, large numbers of T cells with defined antigen (Ag) specificity can be obtained. However, by introduction of a TCR, mixed TCR dimers can be formed. Besides the decrease in TCR expression of the introduced and endogenous TCR, these mixed TCR dimers could harbor potentially harmful specificities. In this study, we demonstrate that introduction of TCRs resulted in formation of neoreactive mixed TCR dimers, composed of the introduced TCR chains pairing with either the endogenous TCR alpha or beta chain. Neoreactivities observed were HLA class I or class II restricted. Most neoreactive mixed TCR dimers were allo-HLA reactive; however, neoreactive mixed TCR dimers with autoreactive activity were also observed. We demonstrate that inclusion of an extra disulfide bond between the constant domains of the introduced TCR markedly reduced neoreactivity, whereas enhanced effectiveness of the introduced TCR was observed. In conclusion, TCR transfer results in the formation of neoreactive mixed TCR dimers with the potential to generate off-target effects, underlining the importance of searching for techniques to facilitate preferential pairing.
Collision‐induced dissociation mass spectra of glucosinolate anions (2009)

Collision-induced dissociation (CID) mass spectra of differently substituted glucosinolates were investigated under negative-ion mode. Data obtained from several glucosinolates and their isotopologues ((34)S and (2)H) revealed that many peaks observed are independent of the nature of the substituent group. For example, all investigated glucosinolate anions fragment to produce a product ion observed at m/z 195 for the thioglucose anion, which further dissociates via an ion/neutral complex to give two peaks at m/z 75 and 119. The other product ions observed at m/z 80, 96 and 97 are characteristic for the sulfate moiety. The peaks at m/z 259 and 275 have been attributed previously to glucose 1-sulfate anion and 1-thioglucose 2-sulfate anion, respectively. However, based on our tandem mass spectrometric experiments, we propose that the peak at m/z 275 represents the glucose 1-thiosulfate anion. In addition to the common peaks, the spectrum of phenyl glucosinolate (beta-D-Glucopyranose, 1-thio-, 1-[N-(sulfooxy)benzenecarboximidate] shows a substituent-group-specific peak at m/z 152 for C(6)H(5)-C(=NOH)S(-), the CID spectrum of which was indistinguishable from that of the anion of synthetic benzothiohydroxamic acid. Similarly, the m/z 201 peak in the spectrum of phenyl glucosinolate was attributed to C(6)H(5)-C(=S)OSO(2)(-).
Bacterial polysaccharide–protein conjugate vaccines (2004)

Following demonstration that chemical conjugation of polysaccharide antigens to proteins could enhance their immunogenicity in the 1920s, interest in this approach to primary prevention of bacterial infections waned with the development and widespread use of antibiotics. Emergence of resistant bacteria rekindled interest in the late 20th century, which saw extremely rapid development and implementation of several vaccines which are already rapidly changing the epidemiology of childhood infections with Haemophilus influenzae type b, Streptococcus pneumoniae and Neisseria meningitidis. Others such as Group B streptococcus and Salmonella typhi infections may soon follow. However, several important questions about the immunology of these antigens remain unanswered and the long-term implications of reducing or eliminating the circulation of organisms which are more commonly nasopharyngeal commensals than pathogenic invaders are uncertain.
Rooms: the use of multiple virtual workspaces to reduce space contention in a window-based graphical user interface (1986)

A key constraint on the effectiveness of window-based human-computer interfaces is that the display screen is too small for many applications. This results in “window thrashing,” in which the user must expend considerable effort to keep desired windows visible. Rooms is a window manager that overcomes small screen size by exploiting the statistics of window access, dividing the user's workspace into a suite of virtual workspaces with transitions among them. Mechanisms are described for solving the problems of navigation and simultaneous access to separated information that arise from multiple workspaces.
Reaction of L-Tryptophan with Alkyl Isocyanates (1987)

s 2 , 8 a n d 9 .
Sets of Aldolase Antibodies with Antipodal Reactivities. Formal Synthesis of Epothilone E by Large-Scale Antibody-Catalyzed Resolution of Thiazole Aldol (1999)

[formula: see text] Three monoclonal aldolase antibodies, generated against a beta-diketone hapten by reactive immunization, catalyzed rapid and highly enantioselective retro-aldol reactions of ent-8a-k, providing optically pure 8a-k by kinetic resolution. Compounds (+/-)-8a, (+/-)-8g, and (+/-)-8k have been resolved in multigram quantities using 0.003, 0.005, and 0.0004 mol% antibody catalysts, respectively. Resolved compounds 8a-k are useful synthons for the construction of epothilones A-E (2-6) and their analogues. Here, a formal synthesis of epothilone E, 6 has been achieved starting from compound 8g.