gebhart/patrepeval huggingface dataset:
A 2-D numerical study of microscale phase change material thermal storage for GaN transistor thermal management (2011)

A novel thermal management technology was explored to lower the peak temperature associated with high power GaN transistors in pulse application. The technology involves the use of an embedded microscale PCM heat storage device within the chip (near the active channels of the GaN device), which effectively increases the heat capacity of the material by taking advantage of the latent heat of the PCM. In this study, 2-D transient thermal models were developed to characterize the thermal behavior of GaN transistors with micro-scale PCM heat storage device. The model is capable of computing the spatial-temporal temperature distribution of the GaN transistor as it is rapidly pulsed and captures the formation and evolution of hot spots that form within the device. The model also captures the PCM melting behavior and latent heat absorption during the transient. The use of a PCM can effectively control the hot spot temperature by absorbing a significant portion of the transient heat input. As shown in this modeling study, the use of PCM heat storage in GaN transistors reduces the GaN hot spot temperature for a given heat input. Alternatively, the maximum allowable GaN heat input can be increased with the use of PCM. At a given heat input flux of 5×10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sup> W/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , for example, the use of PCM heat storage can lower the peak temperature by 21~22°C, relative to transistors without PCM (baseline), regardless of the duty cycle ratio. In addition, a transistor with PCM heat storage can accommodate much higher joule heat generation without exceeding the maximum allowable temperature limit, 180°C. In this study, the modeling results show that by integrating a PCM that has a 140°C melting point in a 5μm×6μm groove configuration, the critical heat flux can be increased from 13.34×10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sup> W/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> (baseline) to 16.8×10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sup> W/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> (with PCM), a 26% improvement. Key PCM design parameters were identified in this modeling study: (1) PCM amount; (2) PCM melting point; and (3) PCM groove structure. Their coupling and the impact on design optimization require further investigation.
Cytogenetic investigations in employees from waste disposal sites (1998)

In connection with extensive health studies of employees from two big central waste disposal sites, cytogenetic investigations were performed. The subject of these special analyses was to examine whether the complex mixture of pollutants from waste disposal sites comprises a genotoxic hazardous potential. Cytogenetic analyses were performed on peripheral blood lymphocytes of 82 exposed and 71 control persons as a coded study. For chromosome analysis, 1000 cells and for sister chromatid exchange (SCE) analysis, 50 cells had been scored per person. Compared with the matched control group, a highly significant increase of the frequencies of chromosomal aberrations was detected, especially in dicentric chromosomes (4.1 +/- 0.2 vs 1.5 +/- 0.1 per 1000 cells) and acentric fragments (6.9 +/- 0.3 vs 2.8 +/- 0.2 per 1000 cells), whereas no difference was found in SCE analysis. The occurrence of multiaberrant cells with more than two dicentric chromosomes was a striking feature in waste disposal site workers (23 vs 1 in control group). Frequencies of chromosomal aberrations were similar in exposed non-smokers and smokers. Only in the control group, a significant difference was observed in the incidence of dicentric chromosomes and SCE between non-smokers and smokers. The results of the first cytogenetic investigations on employees of two waste disposal sites indicate a genotoxic hazardous potential. Further research is urgently required.
Oligodeoxynucleotides as Anti-Sense Inhibitors of Gene Expression: Therapeutic Implications (1989)

Etude du role therapeutique des oligodeoxynucleotides dans le traitement de cancers et d'infections virales
Role for HER2/neu and HER3 in fulvestrant-resistant breast cancer. (2007)

Tamoxifen resistance is common for estrogen receptor alpha (ERalpha) positive breast cancer. Second-line therapies include aromatase inhibitors or fulvestrant. We have shown previously that fulvestrant reversed 17beta-estradiol-induced tumor regression of tamoxifen-stimulated MCF-7 xenografts (MCF-7TAMLT) treated for >5 years with tamoxifen in athymic mice and paradoxically stimulated growth. We investigated mechanisms responsible for growth by fulvestrant in the presence of physiologic estradiol and therapeutic strategies in vivo. The results demonstrated that only estradiol increased expression of the estrogen-responsive genes, c-myc, igf-1, cathepsin D, and pS2 mRNAs, in MCF-7E2 and MCF-7TAMLT tumors. Tamoxifen or fulvestrant decreased the estradiol-induced increase of these mRNAs in both tumor models. However, tyrosine-phosphorylated HER2/ neu, HER3, phospho-extracellular-regulated kinase-1/2 (ERK-1/2), and phospho-glycogen synthetase kinase 3alpha (GSK3alpha) and beta proteins were increased in MCF-7TAMLT tumors treated with fulvestrant compared to estradiol, control, or tamoxifen. Phospho-HER2/neu interacted with HER3 protein in MCF-7TAMLT tumors. In order to determine whether the functional interaction of HER2/neu with HER3 is critical for growth of fulvestrant-stimulated MCF-7TAMLT tumors, pertuzumab (an antibody that blocks HER2/neu-HER3 interaction) was used in an in vivo xenograft growth assay. Only growth of fulvestrant-treated MCF-7TAMLT xenografts was decreased significantly by 37.2% in response to pertuzumab (P=0.004). Pertuzumab specifically decreased the interaction of HER2/neu protein with HER3 in fulvestrant-stimulated MCF-7TAMLT tumors. These results suggested growth of MCF-7TAMLT tumors by tamoxifen or fulvestrant is potentially independent of ERalpha transcriptional activity as evidenced by lack of induction of four estrogen-responsive genes. The results suggested that growth of MCF-7TAMLT tumors treated with fulvestrant in the presence of physiologic estradiol is in part mediated through enhanced signaling from the HER2/neu-HER3 pathway as pertuzumab partially inhibited growth and the interaction of HER2/neu with HER3 in vivo.
The effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin on estrogen metabolism in MCF-7 breast cancer cells: Evidence for induction of a novel 17β-estradiol 4-hydroxylase (1994)

Rates of microsomal 17 beta-estradiol (E2) hydroxylation at the C-2, -4, -6 alpha, and -15 alpha positions are each induced greater than 10-fold by treating MCF-7 breast cancer cells with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The TCDD-induced activities at the C-2, -6 alpha and -15 alpha positions have been attributed to cytochrome P450 1A1 (CYP1A1); however, the low Km 4-hydroxylase induced by TCDD appears to be a distinct enzyme. We report here that antibodies to cytochrome P450-EF (mouse CYP1B1) selectivity inhibited the C-4 hydroxylation of E2 catalyzed by microsomes from TCDD-treated MCF-7 cells. Western blots probed with anti-CYP1B antibodies showed the induction of a 52 kDa microsomal protein in response to treatment with TCDD in MCF-7 cells. Western blots of microsomes from HepG2 cells did not show the TCDD-induced 52 kDa protein, and microsomes from TCDD-treated HepG2 cells did not catalyze a low Km hydroxylation of E2 at C-4. Cellular metabolism experiments also showed induction of both the C-2 and -4 hydroxylation pathways in TCDD-treated MCF-7 cells as evidenced by elevated 2- and 4-methoxyestradiol (MeOE2) formation. In contrast, TCDD-treated HepG2 cells showed 2-MeOE2 formation predominantly over 4-MeOE2. Northern blots of RNA isolated from untreated and TCDD-treated cells, when probed with the human CYP1B1 cDNA, showed induction of a 5.2 kb RNA in MCF-7 cells but not in HepG2 cells in response to treatment with TCDD. These results provide additional evidence for the induction by TCDD of a novel E2 4-hydroxylase in MCF-7 cells but not in HepG2 cells and indicate possible endocrine regulatory roles for the newly discovered group of enzymes of the CYP1B subfamily.
Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study (2018)

Background CD37 is expressed on B-cell lymphoid malignancies, thus making it an attractive candidate for targeted therapy in non-Hodgkin lymphoma (NHL). IMGN529 is an antibody-drug conjugate comprising a CD37-binding antibody linked to the maytansinoid DM1, a potent anti-mitotic agent. Methods This first-in-human, phase 1 trial recruited adult patients with relapsed or refractory B-cell NHL. The primary objective was to determine the maximum tolerated dose (MTD) and recommended phase 2 dose. Secondary objectives were to evaluate safety, pharmacokinetics, and preliminary clinical activity. IMGN529 was administered intravenously once every 3 weeks, and dosed using a conventional 3 + 3 dose-escalation design. Results Forty-nine patients were treated at doses escalating from 0.1 to 1.8 mg/kg. Dose limiting toxicities occurred in eight patients and included peripheral neuropathy, febrile neutropenia, neutropenia, and thrombocytopenia. The most frequent treatment-emergent adverse events were fatigue (39%), neutropenia, pyrexia, and thrombocytopenia (each 37%). Adverse events led to treatment discontinuation in 10 patients (20%). Eight patients (16%) had treatment-related serious adverse events, the most common being grade 3 febrile neutropenia. The MTD (with growth factor support) was 1.4 mg/kg every 3 weeks. IMGN529 plasma exposure increased monotonically with dose and was consistent with target-mediated drug disposition. Five (13%) of 39 response-evaluable patients achieved an objective response (one complete response and four partial responses), four of which occurred in the subgroup of patients with diffuse large B-cell lymphoma. Conclusions The manageable safety profile of IMGN529 and preliminary evidence of activity, particularly in DLBCL patients, support the continued development of this novel CD37-targeting agent.
Effects of quinolone analog CI-960 in a monkey model of Chlamydia trachomatis salpingitis (1993)

Several quinolones have been shown to have antichlamydial activity in vitro and in vivo. We evaluated the effects of the quinolone CI-960 (Parke-Davis) on primary or repeated chlamydial infection in the monkey salpinx pocket model. The antichlamydial effect was evaluated in the tissues, and we tested for the presence of the organism by culture, immunocytochemical stains, in situ hybridization, and histopathology. An intravenous dosage of 5 mg/kg of body weight produced therapeutic concentrations in plasma (blood sera and pocket fluids) of at least 0.25 microgram/ml at 2 h posttreatment. In monkeys with primary infections, treatment was started 2 days after inoculation and was continued for 7 days. After CI-960 treatment, all animals became culture negative. One of two control animals was culture positive through day 10 postinoculation. In monkeys with repeated infections five inoculations were given within 2 weeks. A 7-day intravenous treatment was started on day 2 postinoculation following the last inoculation. Isolation of Chlamydia trachomatis prior to treatment was positive intermittently for all monkeys. After treatment, isolation of C. trachomatis was negative for all monkeys. In monkeys with both primary and repeated infections, no significant differences were noted in the inflammatory responses in the tissues of treated and untreated animals. All tissues tested were positive by immunoperoxidase staining and/or in situ hybridization. After CI-960 therapy, C. trachomatis organisms were no longer recoverable by cell culture. The persistent finding of chlamydial DNA throughout the observation periods following drug therapy may indicate the presence of dead organisms or viable organisms in an unculturable state.
High somatic mutation and neoantigen burden are correlated with decreased progression-free survival in multiple myeloma (2017)

Tumor-specific mutations can result in immunogenic neoantigens, both of which have been correlated with responsiveness to immune checkpoint inhibitors in highly mutagenic cancers. However, early results of single-agent checkpoint inhibitors in multiple myeloma (MM) have been underwhelming. Therefore, we sought to understand the relationship between mutation and neoantigen landscape of MM patients and responsiveness to therapies. Somatic mutation burden, neoantigen load, and response to therapy were determined using interim data from the MMRF CoMMpass study (NCT01454297) on 664 MM patients. In this population, the mean somatic and missense mutation loads were 405.84(s=608.55) and 63.90(s=95.88) mutations per patient, respectively. There was a positive linear relationship between mutation and neoantigen burdens (R<sup>2</sup>=0.862). The average predicted neoantigen load was 23.52(s=52.14) neoantigens with an average of 9.40(s=26.97) expressed neoantigens. Survival analysis revealed significantly shorter progression-free survival (PFS) in patients with greater than average somatic missense mutation load (N=163, 0.493 vs 0.726 2-year PFS, P=0.0023) and predicted expressed neoantigen load (N=214, 0.555 vs 0.729 2-year PFS, P=0.0028). This pattern is maintained when stratified by disease stage and cytogenetic abnormalities. Therefore, high mutation and neoantigen load are clinically relevant risk factors that negatively impact survival of MM patients under current standards of care.
Endothelin Receptor Type B Gene Promoter Hypermethylation in Salivary Rinses Is Independently Associated with Risk of Oral Cavity Cancer and Premalignancy (2010)

Endothelin receptor type B (EDNRB) and kinesin family member 1A (KIF1A) are candidate tumor suppressor genes that are inactivated in cancers. In this study, we evaluated the promoter hypermethylation of EDNRB and KIF1A and their potential use for risk classification in prospectively collected salivary rinses from patients with premalignant/malignant oral cavity lesions. Quantitative methylation-specific PCR was performed to analyze the methylation status of EDNRB and KIF1A in salivary rinses of 191 patients. We proceeded to determine the association of methylation status with histologic diagnosis and estimate classification accuracy. On univariate analysis, diagnosis of dysplasia/cancer was associated with age and KIF1A or EDNRB methylation. Methylation of EDNRB highly correlated with that of KIF1A (P < 0.0001). On multivariable modeling, histologic diagnosis was independently associated with EDNRB (P = 0.0003) or KIF1A (P = 0.027) methylation. A subset of patients analyzed (n = 161) without prior biopsy-proven malignancy received clinical risk classification based on examination. On univariate analysis, EDNRB and risk classification were associated with diagnosis of dysplasia/cancer and remained significant on multivariate analysis (EDNRB: P = 0.047, risk classification: P = 0.008). Clinical risk classification identified dysplasia/cancer with a sensitivity of 71% and a specificity of 58%. The sensitivity of clinical risk classification combined with EDNRB methylation improved to 75%. EDNRB methylation in salivary rinses was independently associated with histologic diagnosis of premalignancy and malignancy and may have potential in classifying patients at risk for oral premalignant and malignant lesions in settings without access to a skilled dental practitioner. This may also potentially identify patients with premalignant and malignant lesions that do not meet the criteria for high clinical risk based on skilled dental examination.
Thermoanaerobacter sp. CGTase: Its Properties and Application. (1992)

A novel CGTase (Cyclomaltodextrin glucanotransferase) has been isolated from a strain of Thermoanaerobacter, a thermophilic anaerobe. The enzyme is extremely heat stable and has a temperature optimum of 90-95°C at pH 6.0. It is active over a broad pH range, and exhibits more than 80% activity from pH 5.0-6.7. In the presence of starch, the enzyme is stable at temperatures in excess of 100°C. In addition to producing cyclodextrins from starch, Thermoanaerobacter sp. CGTase has excellent starch liquefying properties. It is possible to liquefy a 35% DS starch slurry at pH 4. 5, in the absence of calcium, using the "jet cooker" process developed for B. licheniformis α-amylase (105°C for 5 min, 90-95°C for 90 min). Saccharification of the liquefied starch with A. niger glucoamylase can therefore be carried out without further pH adjustment. Some of the properties of Thermoanaerobacter sp. CGTase are described, and examples of the use of the enzyme for cyclodextrin production, intermolecular transglycosylation and starch liquefaction are given. The gene coding for Thermoanaerobacter sp. CGTase has been transfered to a Bacillus host, making large-scale production of the enzyme in commercially acceptable yields possible.
Memory-specific temporal profiles of gene expression in the hippocampus (2002)

Many experiments in the past have demonstrated the requirement of de novo gene expression during the long-term retention of learning and memory. Although previous studies implicated individual genes or genetic pathways in learning and memory, they did not uncover the collective behaviors or patterns of the genes. We have used genome-scale screening to analyze gene expression during spatial learning of rats in the Morris water maze. Our results show distinct temporal gene expression profiles associated with learning and memory. Exogenous administration of one peptide whose sustained increase during memory retention was implicated by microarray analysis, fibroblast growth factor (FGF)-18, improved spatial learning behavior, suggesting that pharmacological modulation of pathways and targets identified may allow new therapeutic approaches for improving learning and memory. Results of this study also suggest that while learning and physical activity involve common groups of genes, the behavior of learning and memory emerges from unique patterns of gene expression across time.
Room-temperature operation of InGaAs-based hot-electron transistors (1993)

It is demonstrated that 300-K operation of an InGaAs-based HET (hot-electron transistor) can be achieved by further increasing the electron injection energy in combination with the use of a wide-bandgap base-collector isolation barrier. The characteristics of a device consisting of an InAlAs emitter, a 10-AA AlAs tunnel-barrier positioned at the emitter-base heterojunction, a 400-AA n+ InGaAs base region, and a 2500-AA InAlGaAs collector barrier are reported. The injected electrons are transported across the base region with over 80% efficiency, as measured in a common-base configuration. The maximum common-emitter current gain in this nonoptimized transistor is nearly four with an f/sub T/ of over 40 GHz and a base-collector breakdown voltage of 1.5 V. A systematic study of RHET (resonant tunneling HET) injector and collection properties indicates that the HET can operate at room temperature with a current gain on the order of 100. 300-K operation of a single-RHET, exclusive-NOR integrated circuit that is similar in design to the one demonstrated at 77 K by N. Yokoyama et al. (1985) is also shown.
Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. (1994)

The p53 tumor suppressor gene product can induce apoptotic cell death through an unknown mechanism. Here we demonstrate that a temperature-sensitive p53 induces temperature-dependent decreases in the expression of the apoptosis-suppressing gene bcl-2 in the murine leukemia cell M1, while simultaneously stimulating increases in the expression of bax, a gene which encodes a dominant-inhibitor of the Bcl-2 protein. Mice deficient in p53 exhibit increases in Bcl-2 and decreases in Bax protein levels in several tissues as determined by immunohistochemical and immunoblot methods. The findings suggest a potential mechanism by which p53 regulates apoptosis, as well as responses to radiation and chemotherapeutic drugs in cancer.
Process Meat Flavor Development and the Maillard Reaction (1989)

The flavor industry has introduced, over the years, methods of developing meat flavors by processing appropriate precursors under carefully controlled reaction conditions. As a result, meat flavors having a remarkably genuine meat character in the beef, chicken and pork tonalities are available for the food industry. It has repeatedly been stated that the Maillard reaction is particularly important for the formation of meat flavors. However, of the 600 volatile compounds isolated from natural beef aroma, only 12% of them find their origin in sugar/amino acid interactions and of these 70% are pyrazine derivatives. The precursors used for process meat flavors are reviewed and also discussed will be non-Maillard interactions of ribose-5-phosphate and lipid degradation products with sulfur giving a real meaty odor and meat specie specific odor compounds, respectively. More than 50 years were needed before the flavor industry started to use Maillard1s original work of heating together carbohydrates and
The fractional Fourier transform and time-frequency representations (1994)

The functional Fourier transform (FRFT), which is a generalization of the classical Fourier transform, was introduced a number of years ago in the mathematics literature but appears to have remained largely unknown to the signal processing community, to which it may, however, be potentially useful. The FRFT depends on a parameter /spl alpha/ and can be interpreted as a rotation by an angle /spl alpha/ in the time-frequency plane. An FRFT with /spl alpha/=/spl pi//2 corresponds to the classical Fourier transform, and an FRFT with /spl alpha/=0 corresponds to the identity operator. On the other hand, the angles of successively performed FRFTs simply add up, as do the angles of successive rotations. The FRFT of a signal can also be interpreted as a decomposition of the signal in terms of chirps. The authors briefly introduce the FRFT and a number of its properties and then present some new results: the interpretation as a rotation in the time-frequency plane, and the FRFT's relationships with time-frequency representations such as the Wigner distribution, the ambiguity function, the short-time Fourier transform and the spectrogram. These relationships have a very simple and natural form and support the FRFT's interpretation as a rotation operator. Examples of FRFTs of some simple signals are given. An example of the application of the FRFT is also given.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>