gebhart/patrepeval huggingface dataset:
RapidCaP, a Novel GEM Model for Metastatic Prostate Cancer Analysis and Therapy, Reveals Myc as a Driver of Pten -Mutant Metastasis (2014)

Genetically engineered mouse (GEM) models are a pillar of functional cancer research. Here, we developed RapidCaP, a GEM modeling system that uses surgical injection for viral gene delivery to the prostate. We show that in Pten deficiency, loss of p53 suffices to trigger metastasis to distant sites at greater than 50% penetrance by four months, consistent with results from human prostate cancer genome analysis. Live bioluminescence tracking showed that endogenous primary and metastatic disease responds to castration before developing lethal castration resistance. To our surprise, the resulting lesions showed no activation of Akt but activation of the Myc oncogene. Using RapidCaP, we find that Myc drives local prostate metastasis and is critical for maintenance of metastasis, as shown by using the Brd4 inhibitor JQ1. Taken together, our data suggest that a "MYC-switch" away from AKT forms a critical and druggable event in PTEN-mutant prostate cancer metastasis and castration resistance.
Isatoribine, an Agonist of TLR7, Reduces Plasma Virus Concentration in Chronic Hepatitis C Infection * (2005)

Immune-based therapy is the mainstay treatment for chronic hepatitis C virus (HCV) infection but causes multiple side effects and achieves durable viral clearance in only approximately 50% of patients. Most new investigational anti-HCV compounds are direct-acting antivirals for which durability of response and risk of viral mutations and resistance are not yet known. Therefore, continuing discovery and development of new immune-based treatments is desirable. Toll-like receptors (TLRs) are pathogen recognition receptors that initiate the innate immune response. The responsiveness of HCV or other ongoing chronic systemic infections to treatment with a selective TLR agonist has not been reported. Isatoribine is a selective agonist of TLR7. In a proof-of-concept study, we found that once-daily 7-day treatment with intravenous isatoribine 800 mg caused a significant (P = .001) reduction of plasma HCV RNA (mean, -0.76; range, -2.85 to +0.21 log(10) units) in otherwise untreated patients (n = 12) who were chronically infected with HCV. Viral load reduction occurred in patients infected with genotype 1 as well as non-genotype 1 HCV. The reduction of viral load was correlated with induction of markers of a heightened immune antiviral state, including 2'-, 5'- oligoadenylate synthetase levels in whole blood. This treatment was well tolerated, with a low frequency of mild to moderate adverse events. In conclusion, systemic administration of the selective TLR7 agonist isatoribine resulted in dose-dependent changes in immunologic biomarkers and a statistically significant antiviral effect with relatively few and mild side effects.
Current and Emerging Treatment Options for Castration-Resistant Prostate Cancer: A Focus on Immunotherapy (2011)

It is hypothesized that the combination of immunotherapeutic agents with traditional and novel chemotherapeutics will potentiate the efficacy of the chemotherapeutics while maintaining manageable toxicity.
Direct preparation of diacetals from 1,2-diketones and their use as 1,2-diol protecting groups (1997)

A range of 1,2-diketones have been evaluated as potential protecting groups for trans-1,2-diols via 1,2-diacetal formation. The procedure is especially useful in oligosaccharide and natural product synthesis.
Pro-inflammatory Cytokines and Environmental Stress Cause p38 Mitogen-activated Protein Kinase Activation by Dual Phosphorylation on Tyrosine and Threonine (1995)

Protein kinases activated by dual phosphorylation on Tyr and Thr (MAP kinases) can be grouped into two major classes: ERK and JNK. The ERK group regulates multiple targets in response to growth factors via a Ras-dependent mechanism. In contrast, JNK activates the transcription factor c-Jun in response to pro-inflammatory cytokines and exposure of cells to several forms of environmental stress. Recently, a novel mammalian protein kinase (p38) that shares sequence similarity with mitogen-activated protein (MAP) kinases was identified. Here, we demonstrate that p38, like JNK, is activated by treatment of cells with pro-inflammatory cytokines and environmental stress. The mechanism of p38 activation is mediated by dual phosphorylation on Thr-180 and Tyr-182. Immunofluorescence microscopy demonstrated that p38 MAP kinase is present in both the nucleus and cytoplasm of activated cells. Together, these data establish that p38 is a member of the mammalian MAP kinase group.
NBI suppression UWB system based on novel nonlinear chirp pulses (2009)

In this paper, we employ two novel non-linear chirp functions, arc trigonometric function and arc hyperbolic function, to construct ultra wideband (UWB) pulses and alleviate narrowband interference (NBI). The UWB systems composed of the new pulses have significant performance in suppressing the NBI. Both of them require only time domain processing for the inherent characteristics of these chirp waveforms. Simulation results show that the NBI suppression ability of the direct sequence pulse amplitude modulation (DS-PAM) UWB system with the proposed chirp waveforms can be enhanced greatly and are superior to the conventional linear chirp pulses.
Geometrical cross-sectional imaging by a heterodyne wavelength-scanning interference confocal microscope (2000)

We developed a heterodyne interference confocal microscope, using wavelength modulation of a laser diode to realize quick separate measurement of the refractive indices and geometrical thicknesses of multiple layers. This microscope requires only a single axial movement of the specimen. We can display the geometrical cross sections of the interfaces and the refractive indices of a three-layered object.
Characterization of the antibody response specific for the human endogenous retrovirus HTDV/HERV-K (1997)

Differentiated human teratocarcinoma cell lines produce the human teratocarcinoma-derived virus (HTDV) particles encoded by the human endogenous retrovirus sequence HERV-K. We screened almost 2,000 human sera for antibodies against this endogenous human retrovirus, HTDV/HERV-K. Specificity of the immunofluorescence reactions using particle producing teratocarcinoma cells was confirmed by immunoelectron microscopy of ultrathin frozen sections. Immunoblot analyses using lysates of HTDV-producing cells revealed a 80-kDa HERV-K Gag precursor and a 90-kDa putative viral Env protein after incubation with positive sera. No processed Gag protein could be observed. Virus-specific bands were not detected in lysates of nonproducing cells. High antibody titers were found in about 60% of male patients with germ cell tumors. Antibody reactivity declined after tumor removal. In healthy blood donors, anti-HTDV reactivity was found only at low titers in a small percentage (3.9%) of individuals. A slightly elevated but statistically significant percentage of HTDV positivity was also observed for sera of pregnant women, whereas human immunodeficiency virus-positive individuals exhibited no peculiarity compared to normal blood donors. Our results provide evidence that HTDV particles are expressed in vivo and that the immune reaction against HTDV/HERV-K is specific for defined viral proteins.
The effect of oxygen on formation of syngas contaminants during the thermochemical conversion of biomass (2015)

The effect of oxygen on the formation of syngas contaminants during the thermochemical conversion of carbonaceous feedstocks has been quantified using an integrated biorefinery plant operated at a biomass input of about 4.5 metric tons/day. This plant combines solids steam reforming and gases steam reforming processes for the conversion of biomass to syngas. It was found that the presence of low concentrations of oxygen (in air) during the thermochemical conversion process had a significant effect on the formation of contaminants in the syngas. For example, particulate organic carbon compounds (organic particulate contaminants) increased from 3.3 to 122 mg/m3 when the oxygen input was increased from 225 ppm to 4.1 vol.% during the thermochemical conversion of wood to syngas. It is proposed that the primary free radical ( $$^{*}$$ ) species H $$^{*}$$ , OH $$^{*}$$ , O $$^{*}$$ , CH3 $$^{*}$$ and $${\rm OOH}^{*}$$ , formed from the presence of O2 in this high-temperature process, react with the myriad of organic compounds in the syngas at varying rates, depending upon their structure and reactivity. These processes represent the primary chemical mechanisms for the formation of high molecular weight hydrocarbons, polynuclear aromatic hydrocarbons, oxygenated hydrocarbons and polymeric materials, commonly referred to as organic particulate contaminants. The potential importance of these free-radical oxidation processes was supported by measuring the concentrations of selected oxygenated hydrocarbons in the syngas over a range of 225 ppm to 4.1 vol.% of O2 in the thermochemical process. The concentrations of oxygenated polycyclic aromatic hydrocarbons (hydroxy-naphthalene, dihydroxy-naphthalene, dihydro-indene-2-one, and benzo-pyranone) increased by 732, 244, 83 and 195 times, respectively, when the oxygen concentration was increased from 225 ppm to 2.5 vol.%. These increases were due to the free-radical oxidation of the highly reactive PAHs during the thermochemical processes. The importance of these oxidation processes was further confirmed by studying the decrease of easily oxidized olefins. For example, the concentrations of 1,3-butadiene, acetylene, propene and ethene decreased by 9.3, 5.2, 4.5 and 3.4 times, respectively, when oxygen in the plant was increased from 1.6 to 2.5 vol.%. It is concluded that the formation of organic particulate contaminants during the thermochemical conversion of carbonaceous feedstocks can be minimized by maintaining the concentration of oxygen below 500 ppm.
Homogentisate Phytyltransferase Activity Is Limiting for Tocopherol Biosynthesis in Arabidopsis (2003)

Tocopherols are essential components of the human diet and are synthesized exclusively by photosynthetic organisms. These lipophilic antioxidants consist of a chromanol ring and a 15-carbon tail derived from homogentisate (HGA) and phytyl diphosphate, respectively. Condensation of HGA and phytyl diphosphate, the committed step in tocopherol biosynthesis, is catalyzed by HGA phytyltransferase (HPT). To investigate whether HPT activity is limiting for tocopherol synthesis in plants, the gene encoding Arabidopsis HPT, HPT1, was constitutively overexpressed in Arabidopsis. In leaves, HPT1 overexpression resulted in a 10-fold increase in HPT specific activity and a 4.4-fold increase in total tocopherol content relative to wild type. In seeds, HPT1 overexpression resulted in a 4-fold increase in HPT specific activity and a total seed tocopherol content that was 40% higher than wild type, primarily because of an increase in gamma-tocopherol content. This enlarged pool of gamma-tocopherol was almost entirely converted to alpha-tocopherol by crossing HPT1 overexpressing plants with lines constitutively overexpressing gamma-tocopherol methyltransferase. Seed of the resulting double overexpressing lines had a 12-fold increase in vitamin E activity relative to wild type. These results indicate that HPT activity is limiting in various Arabidopsis tissues and that total tocopherol levels and vitamin E activity can be elevated in leaves and seeds by combined overexpression of the HPT1 and gamma-tocopherol methyltransferase genes.
Classification of Daily and Near‐Daily Headaches: Proposed Revisions to the IHS Criteria (1994)

The International Headache Society (IHS) headache classification, while a major advance, does not adequately classify the daily and near-daily headache disorders known as chronic daily headache (CDH). We believe that chronic daily headache is a group of disorders which includes chronic tension-type headache (CTTH), transformed migraine (TM), new daily persistent headache (NDPH), and hemicrania continua (HC). We propose specific criteria for transformed migraine, new daily persistent headache, and hemicrania continua, and have modified the criteria for chronic tension-type headache.
Identification of novel driver tumor suppressors through functional interrogation of putative passenger mutations in colorectal cancer (2012)

Cancer genome sequencing efforts are leading to the identification of genetic mutations in many types of malignancy. However, the majority of these genetic alterations have been considered random passengers that do not directly contribute to tumorigenesis. We have previously conducted a soft agar-based short hairpin RNA (shRNA) screen within colorectal cancer (CRC) candidate driver genes (CAN-genes) using a karyotypically diploid hTERT- and CDK4-immortalized human colonic epithelial cell (HCEC) model and discovered that depletion of 65 of the 151 CAN-genes enhanced anchorage-independent growth in HCECs with ectopic expression of K-Ras(V12) and/or TP53 knockdown. We now constructed an interaction map of the confirmed CAN-genes with CRC non-CAN-genes and screened for functional tumor suppressors. Remarkably, depletion of 15 out of 25 presumed passenger genes that interact with confirmed CAN-genes (60%) promoted soft agar growth in HCECs with TP53 knockdown compared to only 7 out of 55 (12.5%) of presumed passenger genes that do not interact. We have thus demonstrated a pool of driver mutations among the putative CRC passenger/incidental mutations, establishing the importance of employing biological filters, in addition to bioinformatics, to identify driver mutations.
Preclinical evaluation of light-activatable, bispecific anti-human CD3 antibody conjugates as anti-ovarian cancer therapeutics (2009)

The administration of anti-CD3 antibodies, either unmodified or in bispecific formats, has been shown to kill tumors. However, their activity needs to be carefully controlled. We have approached this problem by inhibiting their anti-CD3 activity until it is required. Folated anti-human CD3 antibody bispecific conjugates were therefore synthesised in which the folate portion of the conjugates remained free to bind to folate receptor (FR) expressing cancer cells, whilst their anti-CD3 activity was reversibly inhibited. On irradiation with UV-A light, the T-cell binding activity of the anti-CD3 antibody can be restored only when and where it is required, i.e., adjacent to a tumor. Conjugate bound to FR expressed on normal tissues in other parts of the body remains inactive. This report describes the preclinical in vivo testing of these conjugates in transgenic mice whose T-cells express human CD3 molecules. When the 'cloaked' conjugates were reactivated in the region of the primary tumor, both primary tumor growth and liver metastasis were markedly reduced. That the deliberate targeting of T-cell activity locally to the primary tumor also resulted in reduced distant metastatic growth was a key finding. Light-activatable bispecific antibody conjugates similar to those described here offer a means to control T-cell targeting with a much higher degree of specificity to tumors because they minimize potentially dangerous and unwanted side effects in non-illuminated areas. The addition of light-specific targeting to the inherent tumor specific targeting of therapeutic antibody conjugates could result in the development of safer treatments for patients.
Differential scanning calorimetry of the irreversible thermal denaturation of thermolysin (1988)

A differential scanning calorimetry study of the thermal denaturation of Bacillus thermoproteolyticus rokko thermolysin was carried out. The calorimetric traces were found to be irreversible and highly scan-rate dependent. The shape of the thermograms, as well as their scan-rate dependence, can be explained by assuming that the thermal denaturation takes place according to the kinetic scheme N k----D, where k is a first-order kinetic constant that changes with temperature, as given by the Arrhenius equation, N the native state, and D the unfolded state or, more probably, a final state, irreversibly arrived at from the unfolded one. On the basis of this model, the value of the rate constant as a function of temperature and the activation energy have been calculated. It is shown that the proposed model may be considered as being one particular case of that proposed by Lumry and Eyring [Lumry, R., & Eyring, H. (1954) J. Phys. Chem. 58, 110] N in equilibrium D----I, where N is the native state, D the unfolded one, and I a final state, irreversibly arrived at from D. Lastly, some comments are made on the use of the scan-rate effect on the calorimetric traces as an equilibrium criterion in differential scanning calorimetry.
A Peripheral Mechanism for CB1 Cannabinoid Receptor-Dependent Modulation of Feeding (2002)

Recent studies suggest that the endocannabinoid system modulates feeding. Despite the existence of central mechanisms for the regulation of food intake by endocannabinoids, evidence indicates that peripheral mechanisms may also exist. To test this hypothesis, we investigated (1) the effects of feeding on intestinal anandamide accumulation; (2) the effects of central (intracerebroventricular) and peripheral (intraperitoneal) administration of the endocannabinoid agonist anandamide, the synthetic cannabinoid agonist R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrol[1,2,3-de]-1,4-benzoxazin-6-yl)(1-naphthalenyl) methanone monomethanesulfonate (WIN55,212-2), and the CB1-selective antagonist N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (SR141716A) on food intake in rats; and (3) the effects of sensory deafferentation on the modulation of feeding by cannabinoids. Food deprivation produced a sevenfold increase in anandamide content in the small intestine but not in the brain or stomach. Refeeding normalized intestinal anandamide levels. Peripheral but not central administration of anandamide or WIN55,212-2 promoted hyperphagia in partially satiated rats. Similarly, peripheral but not central administration of SR141716A reduced food intake. Capsaicin deafferentation abolished the peripheral effects of both cannabinoid agonists and antagonists, suggesting that these agents modulate food intake by acting on CB1 receptors located on capsaicin-sensitive sensory terminals. Oleoylethanolamide, a noncannabinoid fatty ethanolamide that acts peripherally, prevented hyperphagia induced by the endogenous cannabinoid anandamide. Pretreatment with SR141716A enhanced the inhibition of feeding induced by intraperitoneal administration of oleoylethanolamide. The results reveal an unexpected role for peripheral CB1 receptors in the regulation of feeding.
Some implications of zero sheets for blind deconvolution and phase retrieval (1990)

The insight into deconvolution and phase retrieval afforded by the concept of the zero sheet (of the spectrum of a compact image) is summarized. Difficulties associated with practical implementation of the zero-sheet concept are outlined. Possible means for overcoming these difficulties are suggested and are illustrated with selected examples for several types of deconvolution, i.e., standard, ensemble blind (i.e., blind deconvolution in Stockham’s sense), and pure blind (i.e., deconvolution of a single blurred image without prior knowledge of the point-spread function). A specialized procedure is described for blindly deconvolving a blurred image when the spectrum of the point-spread function is an unknown pure phase function. It is indicated how this procedure may facilitate phase retrieval for spectra of complex-valued images. Possible effects on Wiener filtering and on astronomical speckle imaging are discussed.
Quantification of human immunodeficiency virus type 1 RNA from dried plasma spots collected on filter paper (1997)

To assess dried plasma spots (DPSs) as a source of material for virus quantification, human immunodeficiency virus type 1 (HIV-1) RNA levels were quantified in matched DPS and liquid plasma samples from 73 infected patients, including 5 neonates and 4 adult patients with acute HIV-1 infection. Quantifications were performed by commercially available assays (NASBA [nucleic acid sequence-based amplification] or Amplicor, or both). There was a strong correlation between HIV-1 RNA levels in plasma and DPSs. More importantly, there was no decline in HIV-1 RNA levels in DPSs stored for as long as 2 weeks at 20 degrees C. Similarly, storage of DPSs for 3 days at 37 degrees C resulted in no decrease in viral RNA levels. For patients with primary infection, the DPS method allowed for the measurement of RNA levels in plasma during the initial spike in the level of viremia and in the subsequent period of suppressed viral replication. DPS quantification was equally informative in the neonatal setting, with all five newborns showing HIV-1 RNA loads of greater than 4.991 log10 copies/ml. We conclude that the viral RNA levels in DPSs are equivalent to those measured in fresh-frozen plasma. The ease and economy of DPS sampling, the minute volumes required, and the unexpected stability of dried RNA suggest that the use of DPSs will be particularly valuable for small-volume neonatal samples and large, population-based studies in which cold storage and transportation present special problems, as is often the case in developing countries. The ability to measure viral changes during primary infection suggests that the method will be useful for assessing vaccine efficacy in large field trials.
Drainage Systems (1987)

In recent years, studies have demonstrated that the risk of wound infection can be reduced by careful wound management and adequate wound drainage. Evidence indicates that if a wound is not allowed to drain freely, blood, body fluids, pus, and necrotic material will collect in the wound, providing a growth medium for microorganisms. Surgical wound drainage is recognized as a key element in facilitating the healing process. Wound drainage systems are designed to allow enough moisture to remain in tissues to promote regeneration and lessen inflammation, while removing excess exudate or material that may hamper the healing process. Regardless of the system selected, it must be able to apply enough negative pressure to maintain surface apposition in the healing wound. This requires careful nursing assessment to ensure constancy of vacuum pressure. As the cost of treating preventable infections increases, infection control is becoming a high priority. Health care workers have therefore become increasingly interested in any product or system that contributes to the prevention of costly surgical wound infections.