gebhart/patrepeval huggingface dataset:
Preclinical efficacy, safety, and ADME of GRN163L, a novel telomerase inhibitor developed for the treatment of cancer (2005)

3168 Background: Telomerase maintains telomeric DNA and plays a critical role in tumor cell immortality. Human telomerase is repressed or transiently active in normal somatic cells and telomeres gradually shorten over decades. In most cancers, telomeres are short, but maintained by telomerase. A correlation between tumor progression and telomerase activation makes the inhibition of telomerase a promising target for the treatment of cancer. GRN163L is a lipid-conjugated thio-phosphoramidate (N3’-P5’) oligonucleotide, developed as a potent and specific telomerase inhibitor for the treatment of cancer. Methods: GRN163L was administered systemically as a single agent or in combination with other chemotherapeutics in tumor models to assess activity of the molecule. IND-supporting preclinical toxicology, pharmacodynamic and ADME studies were carried out in multiple species to characterize the safety, pharmacokinetics and activity of GRN163L, and to determine the desired dose and schedule to be used in initial clinical trials for the treatment of cancer. Results: GRN163L administration in vivo inhibited telomerase activity and tumor growth in tumor xenografts. Models studied included melanoma, myeloma, hepatocellular, ovarian, and lung cancer. Combination studies of GRN63L with melphalan, Velcade, or taxol in various tumor models demonstrated increased efficacy of the combination regimens versus single agent treatment. ADME, pharmacodynamic and preclinical safety studies showed wide biodistribution and support an intermittent schedule and dose that should achieve efficacious levels of GRN163L in patients with an acceptable safety profile. Conclusions: Sufficient GRN163L has been manufactured under GLP and GMP conditions to support IND-enabling preclinical and Phase I clinical studies. The efficacy, PD, and ADME data have identified a target dose range and schedule for GRN163L, and preclinical safety studies have shown a robust safety margin that should allow attainment of this dose and schedule in the clinic. Additional studies to support the clinical development strategy are ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Geron Geron
Healthy Dwelling: Design of Biophilic Interior Environments Fostering Self-Care Practices for People Living with Migraines, Chronic Pain, and Depression (2022)

The benefits of biophilic interior design have been recognized by healthcare facilities, but residential environments receive relatively less attention with respect to improving the health of people living with chronic diseases. Recent "stay-at-home" restrictions due to the COVID-19 pandemic further emphasized the importance of creating interior spaces that directly and indirectly support physical and mental health. In this viewpoint article, we discuss opportunities for combining biophilic interventions with interior design, fostering disease-specific self-care. We provide examples of designing residential spaces integrating biophilic interventions, light therapy, relaxation opportunities, mindfulness meditation, listening to music, physical activities, aromatherapy, and quality sleep. These modalities can provide the clinical benefits of reducing migraine headaches and chronic pain, as well as improving depressive symptoms. The disease-specific interior environment can be incorporated into residential homes, workplaces, assisted-living residences, hospitals and hospital at home programs. This work aims to promote a cross-disciplinary dialogue towards combining biophilic design and advances in lifestyle medicine to create therapeutic interior environments and to improve healthcare outcomes.
Multi-band Characterization of Propagation in Industry Scenarios (2020)

Industry 4.0 is the scenario in which the 5G and beyond networks are expected to show all their potential. However, while propagation at sub-6 GHz has been widely investigated in industry environments, mm-waves propagation and channel modelling in those scenarios is still under early research. Therefore, we introduce novel simultaneous multiband ultra-wideband measurements at 6.75 GHz and 30 GHz in LOS and NLOS with RX below and above clutter level. This unique set-up allows a direct comparison between the sub-6 GHz and mm-wave channel. Results have shown larger specular to dense multi-path components power ratio and shorter large-scale parameters at mm-waves.
Migration and Homeostasis of Naive T Cells Depends on Coronin 1-Mediated Prosurvival Signals and Not on Coronin 1-Dependent Filamentous Actin Modulation (2011)

Abstract Coronins are WD repeat-containing proteins highly conserved in the eukaryotic kingdom implicated in the regulation of F-actin. Mammalian coronin 1, one of the most conserved isoforms expressed in leukocytes, regulates survival of T cells, which has been suggested to be due to its role in preventing F-actin–induced apoptosis. In this study, we come to a different conclusion. We show that coronin 1 does not modulate F-actin and that induction of F-actin failed to induce apoptosis. Instead, coronin 1 was required for providing prosurvival signals, in the absence of which T cells rapidly underwent apoptosis. These results argue against a role for coronin 1 in F-actin–mediated T cell apoptosis and establish coronin 1 as an essential regulator of the balance between prosurvival and proapoptotic signals in naive T cells.
Reaction of Soybean Cultivars to Isolates of Fusarium solani from the Red River Valley (1997)

Five isolates of Fusarium solani, originally isolated from diseased soybean roots in the Red River Valley (RRV) of Minnesota and North Dakota, were evaluated for their ability to cause symptoms on 10 genetically diverse soybean cultivars. Taproots of 2-week-old plants were inoculated with F. solani-infested oat kernels, and 3 and 10 weeks later, plants were evaluated for root rot and foliar symptoms. At 3 weeks after inoculation, taproots of all cultivars had extensive reddish brown to black lesions; root rot severity (1-6 scale) ranged from 4.8 to 5.1, and 3.5% of the plants had died. Foliar symptoms were not observed. At 10 weeks after inoculation, all cultivars showed extensive decay of taproots and >50% of lateral roots were necrotic; root rot severity (1-4 scale) ranged from 2.7 to 3.7, and 42.5% of the plants had died. Foliar symptoms were first observed between the R-1 to R-6 growth stages (about 5 weeks after inoculation) on the lower leaves and consisted of chlorosis at the margins that progressed inward. Veins initially were green, but leaves eventually became chlorotic, then necrotic, and fell with petioles still attached to the stem. In some cases, all of the foliage died. There was no significant (P = 0.05) isolate × cultivar interaction for root rot at 3 or 10 weeks after inoculation or for severity of foliar symptoms. Thirty-three cultivars commonly grown in southern Minnesota and the RRV were evaluated for reaction to one isolate of F. solani. Root rot severity ranged from 4.2 to 5.7 (1-6 scale) and 3.5 to 4.0 (1-4 scale), at 3 and 9 weeks after inoculation, respectively, and >50% of the plants died by 9 weeks after inoculation. Severity of foliar symptoms was low. These results indicate that isolates of F. solani from the RRV cause root rot and foliar symptoms on soybean and that cultivars grown in the region lack resistance to this pathogen. Foliar symptoms were not identical to those associated with sudden death syndrome.
Strengthening Causal Inference in Adolescent Drug Prevention Studies: Methods and Findings from a Controlled Study of the Urban Youth Connection Program (1998)

SUMMARY Introduction. The Urban Youth Connection represents a model substance abuse prevention program implemented in an urban public middle school and high school serving predominantly Hispanic and African American students. The program provided counseling, mentoring and academic support. Findings from the evaluation are presented in this paper. Methods. A pre-test, post-test comparison group design estimated the impact of the program on ultimate outcomes of 30-day use of alcohol, tobacco and other drugs, and intermediate outcomes of risk behaviors, psychosocial well-being, and school involvement, as measured by self-administered questionnaires given each fall and spring from 1993–1996. A non-equivalent comparison group was drawn from non-participants at each school. The data analysis strategy relied on a multivariate model comparing ultimate and intermediate outcomes at follow-up among treatment and comparison students after adjustment for demographic, baseline risk differences, and program exposures differences for treatment students. Results. The follow-up rate for treatment students at the middle school was 71% (n = 78), and 48% at the high school (n = 109). The comparison group students (n = 135 at the middle school and n = 308 at the high school) differed from the treatment group on selected demographic and behavioral measures at baseline. Unadjusted outcomes at follow-up were significantly worse in the treatment group than in the comparison group. Statistical adjustment eliminated significant differences between the treatment and comparison groups at follow-up, and higher program exposure was associated with better outcomes for some measures. Discussion. Adjustment for differences between treatment and comparison groups and correction for variation in program exposure within the treatment group are essential for accurate estimation of the benefits of drug prevention interventions.
Effect of core modification in star-shaped donor-acceptor oligomers on physical properties and photovoltaic performance (2017)

A series of star-shaped donor-acceptor oligomers having alkyldicyanovinyl fragments as electron-withdrawing groups, 2,2′-bithiophene as a conjugated π-bridge and either triphenylamine or its modified analogs (9-phenyl-9H-carbazole derivatives or tris(2-methoxyphenyl)amine as electron-donating cores was designed, synthesized and investigated. Variation of the chemical nature of the donor core allowed elucidating the structure-properties relationships for their solubility, absorption spectra, electrochemistry, phase behavior as well as photovoltaic performance in bulk heterojunction organic solar cells as donor materials in their mixtures with PC70BM. The star-shaped molecules based on triphenylamine and tris(2-methoxyphenyl)amine cores have reduced bandgaps, which leads to more efficient absorption of the sun light and better photovoltaic performance.
Studies of the reductive biotransformation of selected carbonyl compounds by whole cells and extracts of baker's yeast, Saccharomyces carevisiae (1991)

The progress of reductive biotransformations of a variety of earbonyl compounds by whole cells of baker's yeast was monitored with time. Biotransformations rates ranged from 0.11 to 112.12 mg product formed per g dry yeast per h. While rapid biotransformations of citronellal and ethyl benzoylformate were observed, complete conversion of substrate to product did not occur. Reductive conversions of ethyl- and methyl-acetoacetate went to completion in 6 and 12 h respectively. Ethyl mandelate was produced stereoselectively, favoring the (R)- stereoisomer and ethyl and methyl-3-hydroxybutyrate were produced with (S)-enantiospecificity. Yeast crude extract and resuspended presence of NAD(P)H. Ethyl benzoylformate and methyl-and ethyl-acetoacetate were preferentially reduced by yeast crude extract as compared to resuspended pellet and, in the case of the former two substrates, the reaction manifested a preference for NADPH over NADH.
Effect of machine shape on swimming properties of the spiral-type micro-machine (1999)

In this study, effect of machine shape on swimming properties of micro-machine were examined by means of two-dimensional finite volume method. The calculated data was compared with experimental results.
The Role of Transition Metal Oxides in Charge‐Generation Layers for Stacked Organic Light‐Emitting Diodes (2010)

Abstract The mechanism of charge generation in transition metal oxide (TMO)‐based charge‐generation layers (CGL) used in stacked organic light‐emitting diodes (OLEDs) is reported upon. An interconnecting unit between two vertically stacked OLEDs, consisting of an abrupt heterointerface between a Cs 2 CO 3 ‐doped 4,7‐diphenyl‐1,10‐phenanthroline layer and a WO 3 film is investigated. Minimum thicknesses are determined for these layers to allow for simultaneous operation of both sub‐OLEDs in the stacked device. Luminance–current density–voltage measurements, angular dependent spectral emission characteristics, and optical device simulations lead to minimum thicknesses of the n‐type doped layer and the TMO layer of 5 and 2.5 nm, respectively. Using data on interface energetic determined by ultraviolet photoelectron and inverse photoemission spectroscopy, it is shown that the actual charge generation occurs between the WO 3 layer and its neighboring hole‐transport material, 4,4',4”‐tris( N ‐carbazolyl)‐triphenyl amine. The role of the adjacent n‐type doped electron transport layer is only to facilitate electron injection from the TMO into the adjacent sub‐OLED.
Bioavailability, distribution and clearance of tracheally-instilled and gavaged uncoated or silica-coated zinc oxide nanoparticles (2014)

Although SiO2-coated ZnO NPs were more inflammogenic, the overall lung clearance rate was not affected. However, SiO2 coating altered the tissue distribution of 65Zn in some extrapulmonary tissues. For both IT instillation and gavage administration, SiO2 coating enhanced transport of 65Zn to thoracic lymph nodes and decreased transport to the skeletal muscle.
Polymer/Calcium Carbonate Layered Thin-Film Composites (2000)

Formation of the nacre of a shell is mimicked here to synthesize layered polymer/calcium carbonate composites such as that shown in the Figure. The combination of insoluble chitin or chitosan solid matrices with soluble acidic macromolecules such as poly(acrylic acid) is used to induce thin-film crystallization of CaCO3 on the solid matrices. The polymorph formed can also be controlled employing this method.
HLA class II gene polymorphism contributes little to Hashimoto's thyroiditis (1992)

DR antigens are unlikely to determine disease susceptibility directly. These findings indicate that any contribution of HLA genes to inherited susceptibility to Hashimoto's thyroiditis is small and requires confirmation in family studies.
First Principles Investigation of Cold Curves of Metals (2020)

Abstract The rapid development of better high pressure experimental techniques combined with efficient and accurate density functional calculations of the structural properties of materials provide a new avenue to promote the study of materials at high pressures, which is currently based mostly on simple phenomenological modelling. The progress of experimental results into higher‐pressure regimes represents a challenge to the phenomenological approaches, which can be addressed by carefully considered ab initio calculations. We present cold curves of several elements, calculated using different approximations of DFT and compare them with available experimental data. The comparison shows good agreement both in simple single phase and complex multi‐phase cases. It suggests that DFT may be used to extrapolate high pressure behaviour of materials beyond the currently possible pressure range, with a robust estimate of the accuracy of the extrapolation based on various DFT implementations.
Real-time replication garbage collection (1993)

We have implemented the first copying garbage collector that permits continuous unimpeded mutator access to the original objects during copying. The garbage collector incrementally replicates all accessible objects and uses a mutation log to bring the replicas up-to-date with changes made by the mutator. An experimental implementation demonstrates that the costs of using our algorithm are small and that bounded pause times of 50 milliseconds can be readily achieved.
MAP3K7 and CHD1 Are Novel Mediators of Resistance to Oncolytic Vesicular Stomatitis Virus in Prostate Cancer Cells (2020)

A key principle of oncolytic viral therapy is that many cancers develop defects in their antiviral responses, making them more susceptible to virus infection. However, some cancers display resistance to viral infection. Many of these resistant cancers constitutively express interferon-stimulated genes (ISGs). The goal of these experiments was to determine the role of two tumor suppressor genes, <i>MAP3K7</i> and <i>CHD1</i>, in viral resistance and ISG expression in PC3 prostate cancer cells resistant to oncolytic vesicular stomatitis virus (VSV). <i>MAP3K7</i> and <i>CHD1</i> are often co-deleted in aggressive prostate cancers. Silencing expression of <i>MAP3K7</i> and <i>CHD1</i> in PC3 cells increased susceptibility to the matrix (M) gene mutant M51R-VSV, as shown by increased expression of viral genes, increased yield of progeny virus, and reduction of tumor growth in nude mice. Silencing <i>MAP3K7</i> alone had a greater effect on virus susceptibility than did silencing <i>CHD1</i>. Silencing <i>MAP3K7</i> and <i>CHD1</i> decreased constitutive expression of ISG mRNAs and proteins, whereas silencing <i>MAP3K7</i> alone decreased expression of ISG proteins, but actually increased expression of ISG mRNAs. These results suggest a role for the protein product of <i>MAP3K7</i>, transforming growth factor β-activated kinase 1 (TAK1), in regulating translation of ISG mRNAs and a role of CHD1 in maintaining the transcription of ISGs.
Time since childbirth and prognosis in primary breast cancer: population based study (1997)

A diagnosis of breast cancer less than 2 years after having given birth is associated with a particularly poor survival irrespective of the stage of disease at debut. Therefore, a recent pregnancy should be regarded as a negative prognostic factor and should be considered in counselling these patients and in the decisions regarding adjuvant treatment.
Fed‐batch synthesis of galacto‐oligosaccharides with Aspergillus oryzae β‐galactosidase using optimal control strategy (2013)

Fed-batch synthesis of galacto-oligosaccharides (GOS) from lactose with β-galactosidase from Aspergillus oryzae was evaluated experimentally and reaction yield was maximized via optimal control technique. The optimal lactose and enzyme feed flow rate profiles were determined using a model for GOS synthesis previously reported by the authors. Experimentally it was found that fed-batch synthesis allowed an increase on the maximum total GOS concentration from 115 (batch synthesis) to 218 g L(-1) as consequence of the increase in total sugars concentration from 40 to 58% w/w. Such high concentration of total sugars was not attainable in batch operation because of the low solubility of lactose at the reaction temperature (40°C). Simulations predicted a GOS yield of 32.5 g g(-1) in fed-batch synthesis under optimal conditions, while experimentally the same yield as in batch synthesis was obtained (28 g g(-1) ). Besides, an enrichment of total oligosaccharides in GOS with a high polymerization degree (GOS-5 and GOS-6) was observed in the fed-batch synthesis. Experimental profiles for all sugars were similar to the ones predicted by simulation, which supports the use of this methodology for the optimization of GOS synthesis.
Androgen responsiveness of Renilla luciferase reporter vectors is promoter, transgene, and cell line dependent (2004)

Renilla based reporters are frequently used as transfection controls for luciferase transcriptional reporter assays. However, recent evidence suggests that a commonly used reporter (HSV-thymidine kinase driven Renilla) is responsive to androgen receptor (AR) and glucocorticoid receptors in the presence of the cognate ligands, dihydrotestosterone (DHT) and dexamethasone (DEX), respectively [1]. We further validate this important technical difficulty by illustrating that in LNCaP prostate cancer cells, spurious Renilla luciferase activity is a function of (a) the promoter driving Renilla expression, (b) the presence of co-transfected transgenes, and (c) the androgen responsiveness of the cell line used. Using inhibitors of transcription and translation we showed that transcript interference or translational modulation is not a major means by which androgens affect Renilla luciferase activity. As luciferase reporter assays are a frequent means of studying transcriptional co-regulation in the highly androgen dependent LNCaP cell line, our data serves as a cautionary note that alternative normalization techniques should be employed to avoid misinterpretation of data.
Preparation of manganese oxide–polyethylene oxide hybrid nanofibers through in situ electrospinning (2010)

Abstract Manganese oxide nanoparticles–polyethylene oxide nanofibers as organic–inorganic hybrid were prepared via in situ electrospinning. Thus, electrospinning of polyethylene oxide solution with different manganese chloride concentration was carried out in gaseous ammonia atmosphere containing oxygen. The reaction of manganese chloride with ammonia produces manganese hydroxide, and then oxygen in the reaction media reacts with manganese hydroxide to yield manganese oxide. These two reactions occur during fiber formation. Transmission electron microscopy and scanning electron microscopy showed that manganese oxide (MnO 2 ) nanoparticles were formed on the produced nanofibers of 100–600 nm in diameter. The existence of the formed MnO 2 was also proved by X‐ray diffraction analysis, and it showed that the λ‐MnO 2 nanoparticles were produced. Differential scanning calorimetry (DSC) analysis was used to determine the melting point and to calculate the crystallinity of the produced hybrid nanofibers. The DSC and thermogravimetric analysis results of the obtained nanofibers were compared with those of the nanofibers produced in electrospinning of pure polyethylene oxide solution. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Compact hybrid-integrated 100-Gbit/s TOSA for 40-km transmission (2015)

We developed a compact hybrid-integrated 100 Gbit/s TOSA using an EADFB laser array with a spot-size converter and a silica-based AWG multiplexer. Error-free operation for a 40-km transmission was demonstrated at an operating temperature of 55 °C.
Vronicle (2022)

Demonstrating veracity of videos is a longstanding problem that has recently become more urgent and acute. It is extremely hard to accurately detect manipulated videos using content analysis, especially in the face of subtle, yet effective, manipulations, such as frame rate changes or skin tone adjustments.