gebhart/patrepeval huggingface dataset:
A geminivirus-based guide RNA delivery system for CRISPR/Cas9 mediated plant genome editing (2015)

CRISPR/Cas has emerged as potent genome editing technology and has successfully been applied in many organisms, including several plant species. However, delivery of genome editing reagents remains a challenge in plants. Here, we report a virus-based guide RNA (gRNA) delivery system for CRISPR/Cas9 mediated plant genome editing (VIGE) that can be used to precisely target genome locations and cause mutations. VIGE is performed by using a modified Cabbage Leaf Curl virus (CaLCuV) vector to express gRNAs in stable transgenic plants expressing Cas9. DNA sequencing confirmed VIGE of endogenous NbPDS3 and NbIspH genes in non-inoculated leaves because CaLCuV can infect plants systemically. Moreover, VIGE of NbPDS3 and NbIspH in newly developed leaves caused photo-bleached phenotype. These results demonstrate that geminivirus-based VIGE could be a powerful tool in plant genome editing.
Interferon-induced human protein MxA is a GTPase which binds transiently to cellular proteins (1992)

MxA is an abundant and ubiquitous cytoplasmic protein induced by alpha/beta interferon in human cells. Upon full induction, it can constitute 0.5 to 1% of cytosolic proteins. MxA can bind elements of the cytoskeleton, such as actin and tubulins, and several larger cellular proteins. However, these protein-protein interactions seem to be transitory. The human MxA protein contains a tripartite GTP-binding domain consisting of GxxxxGKS, DxxG, and TKxD, where x is any amino acid. It is shown here that the native MxA protein has GTPase activity (GTP----GDP) when purified by immunoprecipitation with affinity-purified polyclonal antibodies directed against the C-terminal domain of MxA. The GTPase activity is greatly diminished by polyclonal antibodies directed against the N-terminal domain of MxA (the domain which contains the GTP-binding consensus elements). Amino acid substitution within the GTP-binding domain abolished the GTPase activity of the mutated MxA protein expressed in transfected CHO cells. The reaction is specific for GTP, and the approximate Km is 0.1 mM. The reaction has an absolute requirement for Mg2+. The turnover number is approximately 70 molecules of GTP hydrolyzed per min per MxA molecule. It is suggested that the human MxA protein has certain characteristics of the stress proteins.
Circulating Adhesion Molecules in Cystic Fibrosis (1998)

A marked influx of inflammatory cells occurs into the airways of patients with cystic fibrosis (CF), which may contribute to the development of lung injury. Leukocyte-endothelial adhesion molecules play a crucial role in the recruitment of inflammatory cells, and soluble forms of these molecules have been shown to increase in several inflammatory diseases. By using a capture ELISA, we determined serum levels of soluble ICAM-1 (sICAM-1), E-selectin (sE-selectin), and VCAM-1 (sVCAM-1) in patients with CF, in stable clinical conditions (n = 29, mean age: 25.8+/-1.5 yr), and healthy control subjects (n = 12, mean age: 27.6+/-1.5 yr). Clinical, spirometric, microbiological, and hematological assessments were made in all subjects. sICAM-1 and sE-selectin concentrations, but not sVCAM-1 levels were significantly increased in CF patients as compared with normal subjects (both p < 0.001). sICAM-1 levels were inversely related to FEV1 values (r = -0.519, p = 0.004) and Schwachman score (r = -0.405, p = 0.03) in CF patients. In 7 of 29 CF patients, soluble adhesion molecule levels were determined not only at the time of stable clinical conditions, but also before and after antibiotic treatment for a pulmonary exacerbation. sICAM-1 and sE-selectin levels increased in all patients at the time of the exacerbation, compared with levels at the time of stable conditions (p < 0.02 for both comparisons); antibiotic treatment induced a significant decrease of both circulating adhesion molecules (p < 0.02). The elevated serum levels of sICAM-1 and sE-selectin in CF patients, even when they are clinically stable, may reflect the marked and persistent inflammatory process in the disease.
Clinical indicators of progression in psoriatic arthritis: multivariate relative risk model. (1995)

Evidence of significant inflammation at first visit predicts progression of damage in the future, suggesting that patients with PsA should be offered more aggressive treatment early in the course of their disease.
Yeast Phenylalanine Ammonia-lyase (1971)

Abstract Phenylalanine ammonia-lyase from the yeast Rhodotorula glutinis was purified by salt fractionations and Sephadex chromatography. Density gradient centrifugation and Sephadex chromatography indicated its molecular weight to be about 275,000. Enzymatic deamination of several ring-substituted phenylalanine analogues and d-phenylalanine was studied. While cinnamic acid, a product of deamination, acted as a competitive inhibitor, phenylpropiolic acid, its acetylenic analogue, was a noncompetitive inhibitor. This latter finding is consistent with the presence of more than one form of enzyme during the reaction sequence. The enzyme was inactivated by borohydride or cyanide. In addition, 0.7 to 1.2 atoms of tritium (incorporated from NaB3H4) or about 1.4 moles of cyanide completely inactivated 1 mole of enzyme. After acid hydrolysis of the enzyme labeled with Na14CN, the radioactivity was recovered primarily as 14C-aspartic acid. The 4-carboxyl group of this aspartate was radioactive. Hydrolysis of 3H-NaBH4-inactivated enzyme yielded radioactive alanine. This evidence indicates that bound dehydroalanine is at the active site of the enzyme.
Enantio- and Diastereoselective Synthesis of (Protected) 2-Formyl- and 2-(Hydroxymethyl)-1-phenylalkane-1,3-diols from Chiral 2-Methoxy-3-tosyl-1,3-oxazolidines by Subsequent Asymmetric Formylation and Aldolization (2000)

Trimethylsilyl enol ethers are successively converted into chirally protected α-formyl ketones by asymmetric formylation with the 2-methoxy-1,3-oxazolidine 2, transformed into the corresponding, thermodynamically determined (Z)-TMS enol ethers, and then are allowed to condense with aldehydes. All steps proceed with high stereoselectivity. Some synthetic options, arising from the three differentiated oxygen functionalities in the intermediates 8 are illustrated for the title target compounds.
Deletion analysis of the proteinase gene of Streptococcus cremoris Wg2 (1988)

The Streptococcus cremoris Wg2 proteinase gene, cloned in S. lactis, specified a proteinase which exhibited the same specificity toward casein as did the proteinase isolated from the original host. Although the cloned gene lacked the last 130 codons, the proteinase still specifically degraded beta-casein. Deletion of the C-terminal 343 amino acids from the proteinase did not influence this specificity. Cell-free transcription-translation studies of plasmids carrying deletion derivatives of the proteinase gene showed that the 100-kilodalton C-terminally truncated proteinase still exhibited proteolytic activity. Crossed immunoelectrophoresis revealed that proteins A and B identified in the proteolytic system of S. cremoris Wg2 are both encoded by the proteinase gene. A working model based on integration of available genetic, immunological, and biochemical data is presented to explain this result.
Introduction of a human X-6 translocation chromosome into a mouse teratocarcinoma: investigation of control of HLA-A, B, C expression. (1982)

We have developed an approach to human developmental biology which exploits somatic cell genetics. With this system we have examined the production of the HLA-A,B,C antigens, A human-mouse somatic cell hybrid was constructed which contained a human X-7 chromosome translocation carrying the HLA region; this hybrid was used as a donor of the X-6 translocation in the technique of microcell transfer. The X-6 chromosome recipient was the mouse embryonal carcinoma cell line PCC4. The microcell hybrid MCP-6 retained the embryonal carcinoma phenotype as judged by shape and absence of H-2 expression. Nonetheless, the expression of the HLA-A,B,C genes was not extinguished. HLA-A,B,C antigen production of the cell surface, however, was not detected because this hybrid apparently could not make beta 2-microglobulin.
Two-dimensional NMR and photo-CIDNP studies of the insulin monomer: assignment of aromatic resonances with application to protein folding, structure, and dynamics (1989)

The aromatic 1H NMR resonances of the insulin monomer are assigned at 500 MHz by comparative studies of chemically modified and genetically altered variants, including a mutant insulin (PheB25----Leu) associated with diabetes mellitus. The two histidines, three phenylalanines, and four tyrosines are observed to be in distinct local environments; their assignment provides sensitive markers for studies of tertiary structure, protein dynamics, and protein folding. The environments of the tyrosine residues have also been investigated by photochemically induced dynamic nuclear polarization (photo-CIDNP) and analyzed in relation to packing constraints in the crystal structures of insulin. Dimerization involving specific B-chain interactions is observed with increasing protein concentration and is shown to depend on temperature, pH, and solvent composition. In the monomer large variations are observed in the line widths of amide resonances, suggesting intermediate exchange among conformational substates; such substates may relate to conformational changes observed in different crystal states and proposed to occur in the hormone-receptor complex. Additional evidence for multiple conformations in solution is provided by comparative studies of an insulin analogue containing a peptide bond between residues B29 and A1 (mini-proinsulin). This analogue forms dimers and higher-order oligomers under conditions in which native insulin is monomeric, suggesting that the B29-A1 peptide bond stabilizes a conformational substate favorable for dimerization. Such stabilization is not observed in corresponding studies of native proinsulin, in which a 35-residue connecting peptide joins residues B30 and A1; this extended tether is presumably too flexible to constrain the conformation of the B-chain. The differences between proinsulin and mini-proinsulin suggest a structural mechanism for the observation that the fully reduced B29-A1 analogue folds more efficiently than proinsulin to form the correct pattern of disulfide bonds. These results are discussed in relation to molecular mechanics calculations of insulin based on the available crystal structures.
Blockade of TREM‐2 exacerbates experimental autoimmune encephalomyelitis (2007)

Triggering receptor expressed on myeloid cells (TREM-2) is a membrane receptor associated with DAP12 that is expressed primarily in myeloid cells, including dendritic cells and microglia, and promotes fusion of osteoclast precursors into multinucleated cells. A rare autosomal recessive condition, Nasu-Hakola disease (NHD) is associated with loss-of-function mutations in DAP12 and TREM-2. The brain pathology observed in NHD patients suggests that disruption of the TREM-2/DAP12 pathway leads to neurodegeneration with demyelination and axonal loss. In this study, we have characterized TREM-2 protein expression on microglia using a newly produced monoclonal antibody directed against the mouse TREM-2 receptor. We report that TREM-2 expression is up-regulated in the spinal cord during both the early inflammatory and chronic phases of myelin oligodendrocyte glycoprotein (MOG)(35-55)peptide-induced experimental autoimmune encaphalomyelitis (EAE). We also demonstrate that TREM-2 is highly expressed on microglial cells in the central nervous system (CNS) during EAE and that blockade of TREM-2 during the effector phase of EAE results in disease exacerbation with more diffuse CNS inflammatory infiltrates and demyelination in the brain parenchyma. These results demonstrate a critical role for TREM-2 during inflammatory responses in the CNS.
Modification of the Intestinal Microflora Using Probiotics and Prebiotics (1997)

Probiotics and prebiotics modulate the composition of the human gut microbiota. The beneficial effects may result from suppression of harmful microorganisms or stimulation of organisms which contribute in a positive way to the nutrition and health of the host. Both types of supplement represent an attempt to reconstitute the gut flora to its normal composition which has been adversely affected by dietary and environmental stresses.
Phage-Display Selection of a Human Single-Chain Fv Antibody Highly Specific for Melanoma and Breast Cancer Cells Using a Chemoenzymatically Synthesized GM3−Carbohydrate Antigen (2002)

Overexpression of the cell-surface glycosphingolipid G(M3) is associated with a number of different cancers, including those of the skin, colon, breast, and lung. Antibodies against the G(M3) epitope have potential application as therapeutic agents in the treatment of these cancers. We describe the chemoenzymatic synthesis of two G(M3)-derived reagents and their use in the panning of a phage-displayed human single-chain Fv (scFv) antibody library derived from the blood of cancer patients. Three scFv-phage clones, GM3A6, GM3A8, and GM3A15, were selected for recombinant expression and were characterized using BIAcore and flow cytometry. BIAcore measurements using the purified, soluble scFvs yielded dissociation constants (K(d)) ranging from 4.2 x 10(-7) to 2.1 x 10(-5) M. Flow cytometry was used to evaluate the ability of each scFv to discriminate between normal human cells (human dermal fibroblast, HDFa), melanoma cells (HMV-1, M21, and C-8161), and breast cancer cells (BCM-1, BCM-2, and BMS). GM3A6 displayed cross-reactivity with normal cells, as well as tumor cells, and GM3A15 possessed little or no binding activity toward any of the cell lines tested. However, GM3A8 bound to five of the six tumor cell lines and showed no measurable reactivity against the HDFa cells. Hence, we have demonstrated that a synthetic G(M3) panning reagent can be used to isolate a fully human scFv that is highly specific for native G(M3) on the surface of tumor cells. The result is a significant step toward effective immunotherapies for the treatment of cancer.
Ultrafast nonlinear gain dynamics in semiconductor nanocrystals (1999)

Abstract II - VI semiconductor (CdS, CdSe) nanocrystals with an average size of approximately one bulk exciton Bohr radius are embedded in a glass matrix. Due to the quantum confinement effect, they act as a quasi zero-dimensional system (quantum dots). Under strong nanosecond and femtosecond optical excitation, these quantum dots exhibit optical amplification (gain). We investigate the ultrashort gain dynamics of the strongly confined CdSe quantum dots by femtosecond pump-probe spectroscopy. From multiple-beam pump-probe measurements, we conclude that the gain mechanism is governed by biexciton to exciton transitions. Femtosecond dephasing measurements reveal a constant scattering rate across the gain region and confirm the two-electron-hole pair gain model. Nanosecond pump-probe measurements on CdS quantum dots in sol-gel glasses show optical gain up to room temperature. In all cases, the gain region is broad and stretches below the fundamental absorption of the nanocrystals. The reason is the multitude of transitions involved in the gain formation. No phonon bottleneck did prevent any quick relaxation or any fast scattering that would replenish the spectral holes in the gain region. The relaxation rates are on the order of 10ps. The luminescence decay time is nonexponentiai with a 40–100 ps component for the stimulated emission.
Drug-induced Modulation of Heat Shock Protein HSPB1 in an Ovarian Cancer Cell Model. (2016)

Despite its current lack of analysis in patient samples, serum soluble HSPB1 may function as a specific biomarker for monitoring response to chemotherapy in patients with OC.
Stemless wine-glass-mode disk micromechanical resonators (2003)

Polysilicon wine-glass mode micromechanical disk resonators using a stemless, non-intrusive suspension structure have been demonstrated in both vacuum and atmospheric pressure at frequencies around 73.4 MHz with Q's as high as 98,000 in vacuum, and 8,600 in atmosphere-the highest ever reported Q's at this frequency range and in these environments for any on-chip micro-scale resonator. The Q of 98,000 in vacuum for this wine-glass mode resonator is more than 10X higher than measured on radial contour mode counterparts, and more than 8X higher than exhibited by published free-free beams at 70 MHz.
Dysregulation of Monocytic Nuclear Factor-κB by Oxidized Low-Density Lipoprotein (1997)

Nuclear factor-kappa B (NF-kappa B)/Rel transcription factors may be involved in atherosclerosis, as is suggested by the presence of activated NF-kappa B in human atherosclerotic lesions. The aim of the present study was to investigate the effects of oxidized LDL (oxLDL) on the NF-kappa B system in human THP-1 monocytic cells as well as adherent monocytes. Our results demonstrate that short-term incubation of these cells with oxLDL activated p50/p65 containing NF-kappa B dimers and induced the expression of the target gene IL-8. This activation of NF-kappa B was inhibited by the antioxidant and H2O2 scavenger pyrrolidine dithiocarbamate and the proteasome inhibitor PSI. The oxLDL-induced NF-kappa B activation was accompanied by an initial depletion of I kappa B-alpha followed by a slight transient increase in the level of this inhibitor protein. In contrast, long-term treatment with oxLDL prevented the lipopolysaccharide-induced depletion of I kappa B-alpha, accompanied by an inhibition of both NF-kappa B activation and the expression of tumor necrosis factor-alpha and interleukin-1 beta genes. These observations provide additional evidence that oxLDL is a potent modulator of gene expression and suggest that (dys)regulation of NF-kappa B/Rel is likely to play an important role in atherogenesis.
Bioterrorism-Related Inhalational Anthrax: The First 10 Cases Reported in the United States (2001)

From October 4 to November 2, 2001, the first 10 confirmed cases of inhalational anthrax caused by intentional release of Bacillus anthracis were identified in the United States. Epidemiologic investigation indicated that the outbreak, in the District of Columbia, Florida, New Jersey, and New York, resulted from intentional delivery of B. anthracis spores through mailed letters or packages. We describe the clinical presentation and course of these cases of bioterrorism-related inhalational anthrax. The median age of patients was 56 years (range 43 to 73 years), 70% were male, and except for one, all were known or believed to have processed, handled, or received letters containing B. anthracis spores. The median incubation period from the time of exposure to onset of symptoms, when known (n=6), was 4 days (range 4 to 6 days). Symptoms at initial presentation included fever or chills (n=10), sweats (n=7), fatigue or malaise (n=10), minimal or nonproductive cough (n=9), dyspnea (n=8), and nausea or vomiting (n=9). The median white blood cell count was 9.8 X 10(3)/mm(3) (range 7.5 to 13.3), often with increased neutrophils and band forms. Nine patients had elevated serum transaminase levels, and six were hypoxic. All 10 patients had abnormal chest X-rays; abnormalities included infiltrates (n=7), pleural effusion (n=8), and mediastinal widening (seven patients). Computed tomography of the chest was performed on eight patients, and mediastinal lymphadenopathy was present in seven. With multidrug antibiotic regimens and supportive care, survival of patients (60%) was markedly higher (<15%) than previously reported.
The nature of the ligand-binding pocket of estrogen receptor alpha and beta: The search for subtype-selective ligands and implications for the prediction of estrogenic activity (2003)

The ligand-binding pockets of estrogen receptor alpha and beta (ERα and ERβ) appear to have subpockets of different size and flexibility. To find ligands that will discriminate between the two ER subtypes on the basis of affinity or efficacy, we have prepared compounds of varying size, shape and structure. We have evaluated the binding affinity of these compounds and their potency and efficacy as transcriptional activators through ERα and ERβ. In this manner, we have identified a number of ligands that show pronounced ER subtype selectivity. These studies also highlight the eclectic structure–activity relationships of estrogens and the challenges inherent in developing computational methods for the prediction of estrogenic activity.
An adenoviral vector deleted for all viral coding sequences results in enhanced safety and extended expression of a leptin transgene (1998)

Adenoviral (Ad)-mediated in vivo gene transfer and expression are limited in part by cellular immune responses to viral-encoded proteins and/or transgene immunogenicity. In an attempt to diminish the former responses, we have previously developed and described helper-dependent (HD) Ad vectors in which the viral protein coding sequences are completely eliminated. These HD vectors have up to 37 kb insert capacity, are easily propagated in a Cre recombinase-based system, and can be produced to high concentration and purity (>99.9% helper-free vector). In this study, we compared safety and efficacy of leptin gene delivery mediated by an HD vector (HD-leptin) and a first-generation E1-deleted Ad vector (Ad-leptin) in normal lean and ob/ob (leptin-deficient) mice. In contrast to evidence of liver toxicity, inflammation, and cellular infiltration observed with Ad-leptin delivery in mice, HD-leptin delivery was associated with a significant improvement in associated safety/toxicity and resulted in efficient gene delivery, prolonged elevation of serum leptin levels, and associated weight loss. The greater safety, efficient gene delivery, and increased insert capacity of HD vectors are significant improvements over current Ad vectors and represent favorable features especially for clinical gene therapy applications.
Combining local and remote visualization techniques for interactive volume rendering in medical applications (2000)

For a comprehensive understanding of tomographic image data in medicine, interactive and high-quality direct volume rendering is an essential prerequisite. This is provided by visualization using 3D texture mapping which is still limited to high-end graphics hardware. In order to make it available in a clinical environment, we present a system which uniquely combines local desktop computers and remote high-end graphics hardware. In this context, we exploit the standard visualization capabilities to a maximum which are available in the clinical environment. For 3D representations of high resolution and quality we access the remote specialized hardware. Various tools for 2D and 3D visualization are provided which meet the requirements of a medical diagnosis. This is demonstrated with examples from the field of neuroradiology which show the value of our strategy in practice.
Biological Effects of Electromagnetic Fields (1999)

Abstract The sections in this article are Exposure and Dose Sources of Exposure and Typical Exposure Levels Coupling Between External and Internal Fields Mechanisms of Interaction Biological Effects of Electromagnetic Fields in Humans Exposure Standards Summary
True CW 1934-nm light generation based on frequency conversion of fiber amplifiers (2011)

We present a source of line-narrowed continuous-wave (CW) radiation at 193.4 nm with over 10 mW of output power for the first time, to our knowledge. The system configures four successive frequency conversions of outputs from three single-frequency fiber amplifiers at 1064, 1107, and 1963 nm. The 266-nm beam produced by frequency quadrupling of 1064-nm light is sum-frequency mixed with the 1963-nm light to generate 234.3-nm radiation, which is consequently mixed with the 1107-nm light to generate 193.4-nm radiation. Both mixings are achieved in temperature-tuned non-critically phase-matched (NCPM) crystals.