gebhart/patrepeval huggingface dataset:
Effective Genetic Therapy of Established Medullary Thyroid Carcinomas with Murine Interleukin-2: Dissemination and Cytotoxicity Studies in a Rat Tumor Model (1999)

Replication-defective adenovirus (AdCMVmIL2) expressing murine interleukin-2 was directly injected into rat medullary thyroid carcinomas to examine antitumor activity. AdCMVmIL2 cured 42.9% of all treated tumor bearing animals. Most cured rats were protected against tumor growth after subsequent rechallenge with wild-type tumor cells, reflecting the immunity obtained from the original treatment. Studies of viral dissemination showed that the intratumoral inoculated viruses can enter the circulation, infect peripheral tissues, and express genes driven by the CMV promoter. Liver is the main target organ. In a toxicity study, AdCMVmIL2 was administered iv at a dose five times higher than that given directly into tumor. No detectable side effect was found. Histological studies showed variable degrees of lymphocyte infiltration in the livers of studied animals, and no functional change indicated by the normal serum level of glutamic oxalacetic transaminase and glutamic pyruvic transaminase was found in all animals studied. These data demonstrate that AdCMVmIL2 is an effective antitumor agent in this animal model, and that virus treatment can be given without significant toxicity to other organs.
Regulators of G Protein Signaling Exhibit Distinct Patterns of Gene Expression and Target G Protein Specificity in Human Lymphocytes (1999)

The newly recognized regulators of G protein signaling (RGS) attenuate heterotrimeric G protein signaling pathways. We have cloned an IL-2-induced gene from human T cells, cytokine-responsive gene 1, which encodes a member of the RGS family, RGS16. The RGS16 protein binds Gialpha and Gqalpha proteins present in T cells, and inhibits Gi- and Gq-mediated signaling pathways. By comparison, the mitogen-induced RGS2 inhibits Gq but not Gi signaling. Moreover, the two RGS genes exhibit marked differences in expression patterns. The IL-2-induced expression of the RGS16 gene in T cells is suppressed by elevated cAMP, whereas the RGS2 gene shows a reciprocal pattern of regulation by these stimuli. Because the mitogen and cytokine receptors that trigger expression of RGS2 and RGS16 in T cells do not activate heterotrimeric G proteins, these RGS proteins and the G proteins that they regulate may play a heretofore unrecognized role in T cell functional responses to Ag and cytokine activation.
Reversible Hydration of CH3NH3PbI3 in Films, Single Crystals, and Solar Cells (2015)

Solar cells composed of methylammonium lead iodide perovskite (MAPI) are notorious for their sensitivity to moisture. We show that (i) hydrated crystal phases are formed when MAPI is exposed to water vapor at room temperature and (ii) these phase changes are fully reversed when the material is subsequently dried. The reversible formation of CH3NH3PbI3·H2O followed by (CH3NH3)4PbI6·2H2O (upon long exposure times) was observed using time-resolved XRD and ellipsometry of thin films prepared using “solvent engineering”, single crystals, and state-of-the-art solar cells. In contrast to water vapor, the presence of liquid water results in the irreversible decomposition of MAPI to form PbI2. MAPI changes from dark brown to transparent on hydration; the precise optical constants of CH3NH3PbI3·H2O formed on single crystals were determined, with a bandgap at 3.1 eV. Using the single-crystal optical constants and thin-film ellipsometry measurements, the time-dependent changes to MAPI films exposed to moisture were modeled. The results suggest that the monohydrate phase forms independent of the depth in the film, suggesting rapid transport of water molecules along grain boundaries. Vapor-phase hydration of an unencapsulated solar cell (initially Jsc ≈ 19 mA cm–2 and Voc ≈ 1.05 V at 1 sun) resulted in more than a 90% drop in short-circuit photocurrent and ∼200 mV loss in open-circuit potential; however, these losses were fully reversed after the device was exposed to dry nitrogen for 6 h. Hysteresis in the current–voltage characteristics was significantly increased after this dehydration, which may be related to changes in the defect density and morphology of MAPI following recrystallization from the hydrate. Based on our observations, we suggest that irreversible decomposition of MAPI in the presence of water vapor only occurs significantly once a grain has been fully converted to the monohydrate phase.
Burkholderia mallei expresses a unique lipopolysaccharide mixture that is a potent activator of human Toll‐like receptor 4 complexes (2006)

Burkholderia mallei, the aetiologic agent of glanders, causes a variety of illnesses in animals and humans ranging from occult infections to acute fulminating septicaemias. To better understand the role of lipopolysaccharide (LPS) in the pathogenesis of these diseases, studies were initiated to characterize the structural and biological properties of lipid A moieties expressed by this organism. Using a combination of chemical analyses and MALDI-TOF mass spectrometry, B. mallei was shown to express a heterogeneous mixture of tetra- and penta-acylated lipid A species that were non-stoichiometrically substituted with 4-amino-4-deoxy-arabinose residues. The major penta-acylated species consisted of bisphosphorylated d-glucosamine disaccharide backbones possessing two amide linked 3-hydroxyhexadecanoic acids, two ester linked 3-hydroxytetradecanoic acids [C14:0(3-OH)] and an acyloxyacyl linked tetradecanoic acid, whereas, the major tetra-acylated species possessed all but the 3'-linked C14:0(3-OH) residues. In addition, although devoid of hexa-acylated species, B. mallei LPS was shown to be a potent activator of human Toll-like receptor 4 complexes and stimulated human macrophage-like cells (THP-1 and U-937), monocyte-derived macrophages and dendritic cells to produce high levels of TNF-alpha, IL-6 and RANTES. Based upon these results, it appears that B. mallei LPS is likely to play a significant role in the pathogenesis of human disease.
Synthesis of a Glycolipidic Amphiphilic Nitrone as a New Spin Trap (1999)

The synthesis of a new amphiphilic nitrone, A, derived from a digalactosyl tris(hydroxymethyl)aminomethane bearing a perfluorocarbon chain is described. A exhibited a surfactant behavior (cmc = 1.6 x 10(-)(5) mol/L), and the specific recognition of the galactosyl moiety grafted on A by the KbCWL1 membrane lectin was established. Preliminary experiments showed that A was able to trap free radicals in aqueous media, the shape of the observed ESR spectra being strongly dependent upon the nature of the trapped free radical.
Expression of foreign genes and selection of promoter sequences in Acholeplasma laidlawii (1995)

The stable maintenance and expression of foreign genes in mollicutes (mycoplasmas) have been difficult to achieve due to the lack of suitable vectors. In this paper we show for the first time that a replicating vector can been used to express foreign genes other than antibiotic resistance genes in Acholeplasma laidlawii. Plasmids derived from the lactococcal vector pNZ18 could introduce and maintain four different genes for many generations in A. laidlawii. One of these, encoding the dominant membrane lipoprotein spiralin from the mollicute Spiroplasma citri, was expressed; however, expression was weak, the signal peptide of spiralin was not cleaved and the protein was not covalently modified by fatty acids. This resulted in a hydrophilic character of spiralin and its cytoplasmic localization in A. laidlawii. To increase the expression of foreign genes, random A. laidlawii DNA fragments were cloned into a pNZ18-related plasmid and expression signals were selected using the Bacillus licheniformis alpha-amylase gene as a probe. Selection was done in Escherichia coli as well as directly in A. laidlawii. Active recombinants from E. coli were also able to express alpha-amylase activities and an enzyme of native size in A. laidlawii. The highest activity was obtained from a recombinant selected directly in A. laidlawii. This is the first example of a promoter sequence selected in a mollicute. Analysis of the putative promoters in seven clones revealed similar -10 and -35 regions, and similar spacer distances in A. laidlawii, Acholeplasma oculi, Lactococcus and E. coli. Vectors related to pNZ18 should be useful for the genetic analysis of specific A. laidlawii proteins and functions.
Detection of Proteins in Normal and Alzheimer's Disease Cerebrospinal Fluid with a Sensitive Sandwich Enzyme‐Linked Immunosorbent Assay (1993)

Alzheimer's disease is a progressive degenerative dementia characterized by the abundant presence of neurofibrillary tangles in neurons. This study was designed to test whether the microtubule-associated protein tau, a major component of neurofibrillary tangles, could be detected in CSF. Additionally, we investigated whether CSF tau levels were abnormal in Alzheimer's disease as compared with a large group of control patients. We developed a sensitive sandwich enzyme-linked immunosorbent assay using AT120, a monoclonal antibody directed to human tau, as a capturing antibody. With this technique, the detection limit for tau was less than 5 pg/ml of CSF. Using AT8, which recognizes abnormally phosphorylated serines 199-202 in tau, the detection limit was below 20 pg/ml of CSF. However, with AT8, we found no immunoreactivity in CSF, suggesting that only a small fraction of CSF tau contains the abnormally phosphorylated AT8 epitope. Our results indicate that CSF tau levels are significantly increased in Alzheimer's disease. Also, CSF tau levels in a large group of patients with a diversity of neurological diseases showed overlap with CSF tau levels in Alzheimer's disease.
Corticosteroid-Sparing Effect of Azelastine in the Management of Bronchial Asthma (1996)

The objective of this double-blind trial was to evaluate the corticosteroid-sparing effect of azelastine in patients with chronic bronchial asthma. A total of 193 subjects received either 6 mg of azelastine twice per day or placebo (in a 2:1 ratio) in combination with beclomethasone dipropionate (6 to 16 inhalations per day). The number of daily inhalations of the corticosteroid was reduced until maximum reduction or elimination was achieved. Patients then entered a 12-wk maintenance period, during which patients were maintained on their lowest possible dose of inhaled corticosteroid. Compared with placebo, the azelastine group had a statistically significantly greater overall median reduction in inhaled corticosteroids (4.9 puffs/day for azelastine versus 3.1 puffs/day for placebo; p < or = 0.010) during the maintenance period. The azelastine group also had a statistically significantly higher percentage of patients with reductions of > or = 50% and > or = 75% from the baseline level (53 and 31%, respectively, for azelastine versus 34 and 14%, respectively, for placebo; p < or = 0.028). The results demonstrated that azelastine, 6 mg twice per day, can reduce the need for inhaled corticosteroids in patients with chronic bronchial asthma and not lead to a deterioration in pulmonary function.
Protective Effect of a Recombinant Amino-Terminal Fragment of Bactericidal/Permeability-Increasing Protein in Experimental Endotoxemia (1993)

Bactericidal/permeability-increasing protein (BPI), a cationic protein found in neutrophil granules, binds with high affinity to gram-negative bacterial lipopolysaccharide (LPS) and can inhibit its actions in vitro. The in vivo efficacy of a recombinant 23-kDa amino-terminal LPS-binding fragment of BPI (rBPI23) was assessed in a mouse model of lethal endotoxemia. Systemic administration of rBPI23 protected actinomycin D-sensitized mice from lethal LPS (Escherichia coli O111:B4) challenge in a dose-dependent manner, with almost complete protection at the highest dose (10 mg/kg; 93% survival vs. 13% in vehicle-treated controls). Surviving rBPI23-treated animals did not show histopathologic signs of tissue damage evident in control animals that had died after LPS challenge. rBPI23 also attenuated the LPS-induced elevation in serum levels of tumor necrosis factor-alpha and interleukin-1 alpha, mediators believed to be involved in the pathogenesis of endotoxemia and sepsis. Thus, rBPI23 may be a potential new therapeutic agent for the treatment of gram-negative bacterial infection and sepsis.
ChemInform Abstract: TOTAL SYNTHESIS OF THIENAMYCIN ANALOGS ‐ III. SYNTHESES OF 2‐ARYL AND 2‐HETEROARYL ANALOGS OF THIENAMYCIN (1983)

Abstract Die aus der Vorstufe (I) erhältlichen Thioester (IIIa) bzw. (IIIb) werden in die Ketone (V) bzw. (VII) übergeführt; weitere Ketone (IX) werden ausgehend vom Aldehyd (VIII) in mehreren Schritten dargestellt.
Direct interaction of the Wiskott-Aldrich syndrome protein with the GTPase Cdc42. (1996)

Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency disorder with the most severe pathology in the T lymphocytes and platelets. The disease arises from mutations in the gene encoding the WAS protein. T lymphocytes of affected males with WAS exhibit a severe disturbance of the actin cytoskeleton, suggesting that the WAS protein could regulate its organization. We show here that WAS protein interacts with a member of the Rho family of GTPases, Cdc42. This interaction, which is guanosine 5'-triphosphate (GTP)-dependent, was detected in cell lysates, in transient transfections and with purified recombinant proteins. A weaker interaction was also detected with Rac1 using WAS protein from cell lysates. It was also found that different mutant WAS proteins from three affected males retained their ability to interact with Cdc42 and that the level of expression of the WAS protein in these mutants was only 2-5% of normal. Taken together these data suggest that the WAS protein might function as a signal transduction adaptor downstream of Cdc42, and in affected males, the cytoskeletal abnormalities may result from a defect in Cdc42 signaling.
ChemInform Abstract: A Highly Efficient Synthesis of Civetone. (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Temporally resolved growth of InP in the openings off-oriented from [110] direction (2002)

Temporally resolved growth of InP on patterned substrates with opening off-oriented from [110] direction was studied by low pressure hydride vapour phase epitaxy system. Lateral overgrowth and vertical growth were analysed. The lateral growth rate was observed to be strongly dependent on the orientation of the openings. The maximum lateral growth rate was achieved at 30/spl deg/ and 60/spl deg/ off [110] direction. The vertical growth rate was relatively constant, independent of the opening orientation. The optimum lateral overgrowth condition of InP was explored, which may be used for heteroepitaxy of InP on Si.
Placebo‐Controlled Phase 3 Trial of a Recombinant Glycoprotein 120 Vaccine to Prevent HIV‐1 Infection (2005)

There was no overall protective effect. The efficacy trends in subgroups may provide clues for the development of effective immunization approaches.
Rapid Selection of Oseltamivir‐ and Peramivir‐Resistant Pandemic H1N1 Virus during Therapy in 2 Immunocompromised Hosts (2010)

Pandemic 2009 H1N1 virus isolates containing the neuraminidase inhibitor resistance mutation H275Y have been reported. We describe rapid selection for the H275Y resistance mutation during therapy in 2 immunocompromised individuals at 9 and 14 days of therapy, as well as the first described case of clinically significant resistance to peramivir.
Five-base codons for incorporation of nonnatural amino acids into proteins (2001)

Extension of the genetic code for the introduction of nonnatural amino acids into proteins was examined by using five-base codon-anticodon pairs. A streptavidin mRNA containing a CGGUA codon at the Tyr54 position and a tRNA(UACCG) chemically aminoacylated with a nonnatural amino acid were added to an Escherichia coli in vitro translation system. Western blot analysis indicated that the CGGUA codon is decoded by the aminoacyl-tRNA containing the UACCG anticodon. HPLC analysis of the tryptic fragment of the translation product revealed that the nonnatural amino acid was incorporated corresponding to the CGGUA codon without affecting the reading frame adjacent to the CGGUA codon. Another 15 five-base codons CGGN(1)N(2), where N(1) and N(2) indicate one of four nucleotides, were also successfully decoded by aminoacyl-tRNAs containing the complementary five-base anticodons. These results provide a novel strategy for nonnatural mutagenesis as well as a novel insight into the mechanism of frameshift suppression.
Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer (2018)

We conducted a pilot clinical trial testing a personalized vaccine generated by autologous dendritic cells (DCs) pulsed with oxidized autologous whole-tumor cell lysate (OCDC), which was injected intranodally in platinum-treated, immunotherapy-naïve, recurrent ovarian cancer patients. OCDC was administered alone (cohort 1, <i>n</i> = 5), in combination with bevacizumab (cohort 2, <i>n</i> = 10), or bevacizumab plus low-dose intravenous cyclophosphamide (cohort 3, <i>n</i> = 10) until disease progression or vaccine exhaustion. A total of 392 vaccine doses were administered without serious adverse events. Vaccination induced T cell responses to autologous tumor antigen, which were associated with significantly prolonged survival. Vaccination also amplified T cell responses against mutated neoepitopes derived from nonsynonymous somatic tumor mutations, and this included priming of T cells against previously unrecognized neoepitopes, as well as novel T cell clones of markedly higher avidity against previously recognized neoepitopes. We conclude that the use of oxidized whole-tumor lysate DC vaccine is safe and effective in eliciting a broad antitumor immunity, including private neoantigens, and warrants further clinical testing.
The Effect of Serial Passaging on the Proliferation and Differentiation of Bovine Adipose-Derived Stem Cells (2011)

Adipose-derived stem cells (ASCs) represent an excellent cell source for the development of regenerative therapies for a broad variety of tissue disorders. Commonly, in vitro expansion is necessary to obtain sufficient cell populations for research purposes and clinical applications. Although it has been demonstrated that human ASCs can maintain their adipogenic, chondrogenic and osteogenic potential in long-term culture (up to 15 passages), it is not guaranteed that a satisfactory level of differentiation is achievable in later passages. In this study, we investigated the self-renewal and multilineage differentiation capacity of bovine ASCs, isolated from the interdigital fat pad, and explored how serial passaging influences the cells. A proliferation study examined the changes in growth kinetics from passage 1 to 5, and multilineage (adipogenesis, chondrogenesis and osteogenesis) differentiation studies were conducted to compare the potential between passage 2 (P2) and passage 5 (P5). From the proliferation study, a statistically significant change in the doubling time did not appear until P5. In the differentiation study, both P2 and P5 ASCs could be stimulated to undergo multilineage differentiation under specific culturing conditions. However, adipogenic and chondrogenic cultures showed significantly lower levels of differentiation in the P5-induced cultures. In contrast, P5-induced osteogenic cultures had higher alkaline phosphatase enzyme activity than P2-induced cultures, suggesting an increase in the osteogenic response with serial passaging. Overall, bovine ASCs are capable of self-renewal and multilineage differentiation; however, long-term in vitro expansion has a negative effect on adipogenic and chondrogenic differentiation, while potentially favoring osteogenesis.
Blind Detection, Separation, and Location of Dense Co-Channel Emitters using Multiplatform Spatial-Coherence Restoral (2006)

The multiplatform spatial-coherence restoral (MP-SCORE) algorithm, introduced in 1988 to blindly separate spatially-coherent, temporally featureless signals based on their differing TDOA and FDOA at spatially separated antenna arrays, is extended to blind detection, separation, and location of dense co-channel emitters using wide-baseline collection networks. The original MP-SCORE algorithm is reviewed and related to the ML estimator of the location of a Gaussian-distributed source (or of the location and content of an unknown source) received in the presence of independent Gaussian-distributed interference with arbitrary spatial covariance at each array in the network. False-alarm and miss-rates for the corresponding MP-SCORE detector are also derived, and are shown to be a function of only the time-bandwidth product of the detector and the maximum source SENR attainable at each array in the network. Practical methods for detecting, separating, and locating multiple co-channel sources using MP-SCORE are then presented, and the end-to-end algorithm is demonstrated for a GPS C/A code jamming scenario in which two 8-sensor airborne receivers attempt to detect and locate 100 narrowband (2 MHz) noise-loaded emitters continuously transmitting over a wide (150times150 nmi) geographical region at the center of the GPS L1 frequency band. The simulated algorithm detects and geolocates 27 emitters to within 1/2 nmi over a single 26 ms snapshot, and detects and geolocates 38 emitters to within 445 feet over eleven 26 ms snapshots collected at 15 nmi intervals along the edge of the emission region
Synthesis of 8‐[18O]hydroxy‐2′‐deoxyguanosine (1994)

Abstract 8‐[ 18 O]Hydroxy‐2′‐deoxyguanosine was synthesized starting from 8‐bromo‐2′‐deoxyguanosine and the sodium salt of [ 18 O]benzyl alcohol, resulting in the intermediate 8‐[ 18 O]benzyloxy‐2′‐deoxyguanosine. Subsequent reduction by catalytic transfer hydrogenation, yielded the desired product 8‐[ 18 O]hydroxy‐2′‐deoxyguanosine. 8‐Bromo‐2′‐deoxyguanosine was synthesized from 2′‐deoxyguanosine by treatment with Br 2 . The sodium salt of [ 18 O]benzyl alcohol was prepared by treatment of ethyl benzimidate hydrochloride with H 2 18 O (95%), LiAlH 4 and sodium hydride. Starting from H 2 18 O the overall yield of 8‐[ 18 O]hydroxy‐2′‐deoxyguanosine was approximately 4%. The isotopic purity was calculated to be 93.4 atom% based on GC‐MS measurements. The chemical purity and the isotopic purity comply with the planned application, namely as internal standard for the determination of 8‐hydroxy‐2′‐deoxyguanosine by GC‐MS.
An interface for virtual 3D sculpting via physical proxy (2006)

We explore the design space of using direct finger input in conjunction with a deformable physical prop for the creation and manipulation of conceptual 3D geometric models. The user sculpts virtual models by manipulating the space on, into, and around the physical prop, in an extension of the types of manipulations one would perform on traditional modeling media such as clay or foam. The prop acts as a proxy to the virtual model and hence as a frame of reference to the user's fingers. A prototype implementation uses camera-based motion tracking technology to track passive markers on the fingers and prop. The interface supports a variety of clay-like sculpting operations including deforming, smoothing, pasting, and extruding. All operations are performed using the unconstrained fingers, with command input enabled by a small set of finger gestures coupled with on-screen widgets.