gebhart/patrepeval huggingface dataset:
TRANSLATIONAL CONTROL IN MAMMALIAN CELLS (1991)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Patient adherence and persistence with oral anticancer treatment (2009)

Given the recent significant increase in the use of oral therapies in cancer management, an understanding of patients' adherence to and persistence with oral therapy is crucial. Nonadherence and early cessation may be substantial barriers to the delivery of valuable therapies, and may impair health. Potential obstacles to adherence and persistence include personal characteristics, treatment features, and system factors. Techniques for measuring adherence and persistence include self-report, pill counts, microelectronic monitoring systems (MEMS), prescription database analysis, and the assessment of serum or urine drug levels. This review article describes available data regarding adherence and persistence among patients with cancer, as well as studies of interventions to improve adherence. All reports of studies of adherence with oral cancer therapy that the authors could find on PubMed or in the reference sections of these PubMed-located articles were included. Adherence and persistence rates ranged from 16% to 100% with different therapies and different methods of measurement. Studies that included educational, behavioral, and multidimensional interventions to improve adherence were also described.
Abstract 53: Krebs cycle substrate-level phosphorylation drives metastatic cancer cells (2010)

Abstract Many metastatic cancers are derived from compromised respiration in tissue cells of myeloid origin (e.g., macrophages), which use glutamine as a major energy substrate. Although impaired respiration can render tumor cells dependent on glycolysis for energy in the presence of oxygen (Warburg effect), it has not been determined if glutamine alone could provide enough energy (ATP) through substrate level phosphorylation in the TCA (Krebs) cycle to maintain tumor cell viability. Using a bioluminescent-based ATP assay, we determined the viability of metastatic mouse VM-M3 tumor cells grown in serum free medium in the presence of glucose alone (25 mM), glutamine alone (4 mM), or in glucose + glutamine. The VM-M3 cells could not survive on glucose alone, but could survive in glutamine alone indicating an absolute requirement for glutamine in these metastatic tumor cells. Glucose + glutamine acted synergistically in providing growth and viability. Lactic acid production was 10-fold lower in the cells grown in glutamine alone than in glucose alone. Glutamine could also maintain viability in the absence of glucose and in the presence of the F1 ATPase inhibitor oligomycin. Glutamine could not maintain viability in the presence of the TCA cycle enzyme inhibitor, 3-Nitropropionic acid. NMR analysis indicated that glutamine metabolism via the TCA cycle was active resulting in accumulation of both succinate and aspartate. The data indicate that glutamine can provide ATP for viability in the metastatic VM-M3 cells through Krebs cycle phosphorylation in the absence of energy from either glycolysis or oxidative phosphorylation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 53.
Statistics of duration and intensity of path loss in a microwave transhorizon sea-path (1990)

A preliminary analysis of basic transmission loss and duration of events is presented from one and a half years of data obtained in a 152 km transhorizon path over a sea environment at 11.65 GHz. The distributions for troposcatter and anomalous propagation conditions indicate a path loss well modelled by two distinct normal distributions. The statistics of event durations D conditioned to a decrease in a given path loss L, P(D/L), are accurately modelled by the log-normal distribution. Illustrative values are presented in graphical and tabular form.
Multicenter phase II trial of interleukin-2, interferon-alpha, and 13-cis-retinoic acid in patients with metastatic renal-cell carcinoma. (1998)

Outpatient CRA plus IL2 and IFNA is feasible and modestly effective in metastatic RCC. The prolonged median survival is encouraging, but randomized trials are required to show that the combination represents an improvement over single-agent immunotherapy.
Charge generation layers comprising transition metal-oxide/organic interfaces: Electronic structure and charge generation mechanism (2010)

The energetics of an archetype charge generation layer (CGL) architecture comprising of 4,4′,4″-tris(N-carbazolyl)triphenylamine (TCTA), tungsten oxide (WO3), and bathophenanthroline (BPhen) n-doped with cesium carbonate (Cs2CO3) are determined by ultraviolet and inverse photoemission spectroscopy. We show that the charge generation process occurs at the interface between the hole-transport material (TCTA) and WO3 and not, as commonly assumed, at the interface between WO3 and the n-doped electron-transport material (BPhen:Cs2CO3). However, the n-doped layer is also essential to the realization of an efficient CGL structure. The charge generation mechanism occurs via electron transfer from the TCTA highest occupied molecular orbital level to the transition metal-oxide conduction band.
Studies on Cerebral Protective Agents. VII. Synthesis of Novel 4-Arylazole Derivatives with Anti-anoxic Activity. (1995)

Novel 4-arylazole (i.e. thiazole, oxazole, and imidazole) derivatives, possessing an amino moiety at the C-5 position of the azole ring, were prepared and tested for anti-anoxic (AA) activity in mice. Among them, 5-(4-methylpiperazin-1-yl)methyl-4-(3-nitrophenyl)-2-phenylthia zole (3b, FR75094) possessed significant AA activity (10 mg/kg, i.p. and 100 mg/kg, p.o., respectively), and was also effective on anti-lipid peroxidation (ALP) assay and inhibited arachidonate-induced cerebral edema in rats. Structure-activity relationships in regard to AA activity of this series of compounds are discussed.
Advanced cooling system using miniature heat pipes in mobile PC (2000)

This paper describes various cooling solutions using heat pipes for cooling a notebook PC. These are: 1) heat pipe with heat spreader plate; 2) hybrid system-i.e., heat pipe with heat sink and fan; and 3) hinged heat pipe system. For heat input of less than 12 W, the thermal resistance measured between the surface of the CPU to ambient was obtained as follows: greater than 8/spl deg/C/W for system 1) and 4-6/spl deg/C/W for systems 2) and 3). For the CPU having specification of surface temperature of 95/spl deg/C and 40/spl deg/C ambient, then system 1) can be dissipated by about 6 W, whereas systems 2) and 3) can handle 13 W. Experimental results of these three systems are included and discussed in this paper.
Isolation and characterization of a new human breast cancer cell line, KPL-4, expressing the Erb B family receptors and interleukin-6 (1999)

A new human breast cancer cell line, KPL-4, was recently isolated from the malignant pleural effusion of a breast cancer patient with an inflammatory skin metastasis. This cell line can be cultured under serum-free conditions and is tumorigenic in female athymic nude mice. Flow cytometric analysis revealed the expression of Erb B-1, -2 and -3. Dot blot hybridization showed a 15-fold amplification of the erb B-2. Reverse transcription-polymerase chain reaction analysis showed a detectable level of mRNA expression of all the Erb B family receptors. In addition, all the receptors were autophosphorylated under a serum-supplemented condition. Unexpectedly, transplanted KPL-4 tumours induced cachexia of recipient mice. A high concentration of interleukin-6 (IL-6) was detected in both the culture medium and the serum of mice. The weight of tumours significantly correlated with the serum IL-6 level. The antiproliferative effect of a humanized anti-Erb B-2 monoclonal antibody, rhuMAbHER2, was investigated. This antibody significantly inhibited the growth of KPL-4 cells in vitro but modestly in vivo. Loss of mouse body weight was partly reversed by rhuMAbHER2. These findings suggest that KPL-4 cells may be useful in the development of new strategies against breast cancer overexpressing the Erb B family receptors and against IL-6-induced cachexia.
Structure-Based Development of Small Molecule PFKFB3 Inhibitors: A Framework for Potential Cancer Therapeutic Agents Targeting the Warburg Effect (2011)

Cancer cells adopt glycolysis as the major source of metabolic energy production for fast cell growth. The HIF-1-induced PFKFB3 plays a key role in this adaptation by elevating the concentration of Fru-2,6-BP, the most potent glycolysis stimulator. As this metabolic conversion has been suggested to be a hallmark of cancer, PFKFB3 has emerged as a novel target for cancer chemotherapy. Here, we report that a small molecular inhibitor, N4A, was identified as an initial lead compound for PFKFB3 inhibitor with therapeutic potential. In an attempt to improve its potency, we determined the crystal structure of the PFKFB3•N4A complex to 2.4 Å resolution and, exploiting the resulting molecular information, attained the more potent YN1. When tested on cultured cancer cells, both N4A and YN1 inhibited PFKFB3, suppressing the Fru-2,6-BP level, which in turn suppressed glycolysis and, ultimately, led to cell death. This study validates PFKFB3 as a target for new cancer therapies and provides a framework for future development efforts.
What Is the Goal of Sensory Coding? (1994)

A number of recent attempts have been made to describe early sensory coding in terms of a general information processing strategy. In this paper, two strategies are contrasted. Both strategies take advantage of the redundancy in the environment to produce more effective representations. The first is described as a “compact” coding scheme. A compact code performs a transform that allows the input to be represented with a reduced number of vectors (cells) with minimal RMS error. This approach has recently become popular in the neural network literature and is related to a process called Principal Components Analysis (PCA). A number of recent papers have suggested that the optimal “compact” code for representing natural scenes will have units with receptive field profiles much like those found in the retina and primary visual cortex. However, in this paper, it is proposed that compact coding schemes are insufficient to account for the receptive field properties of cells in the mammalian visual pathway. In contrast, it is proposed that the visual system is near to optimal in representing natural scenes only if optimality is defined in terms of “sparse distributed” coding. In a sparse distributed code, all cells in the code have an equal response probability across the class of images but have a low response probability for any single image. In such a code, the dimensionality is not reduced. Rather, the redundancy of the input is transformed into the redundancy of the firing pattern of cells. It is proposed that the signature for a sparse code is found in the fourth moment of the response distribution (i.e., the kurtosis). In measurements with 55 calibrated natural scenes, the kurtosis was found to peak when the bandwidths of the visual code matched those of cells in the mammalian visual cortex. Codes resembling “wavelet transforms” are proposed to be effective because the response histograms of such codes are sparse (i.e., show high kurtosis) when presented with natural scenes. It is proposed that the structure of the image that allows sparse coding is found in the phase spectrum of the image. It is suggested that natural scenes, to a first approximation, can be considered as a sum of self-similar local functions (the inverse of a wavelet). Possible reasons for why sensory systems would evolve toward sparse coding are presented.
The engagement of β1 integrins on promonocytic cells promotes phosphorylation of Syk and formation of a protein complex containing Lyn and β1 integrin (1999)

The protein-tyrosine kinase Syk participates in signal transduction pathways downstream from multiple immune recognition receptors. Recent evidence indicates that Syk is also functionally coupled to cell surface integrins, which mediate interactions between the actin cytoskeleton and extracellular matrix proteins. The interactions of undifferentiated, promonocytic HL60 or U937 cells with fibronectin or anti-beta1 integrin antibodies leads to an apparent activation and tyrosine phosphorylation of Syk that is independent of tight cellular adhesion and spreading. In response to fibronectin or anti-beta1 integrin antibodies, beta1 integrins become associated with a complex of proteins that include the Lyn protein tyrosine kinase and endogenous kinase substrates of 29 and 75-80 kDa. Lyn becomes transiently activated following integrin engagement and co-localizes with the actin cytoskeleton. These studies suggest a major role for Lyn in coupling beta1 integrins to the activation of Syk.
Vaccination with a bivalent G(M2) and G(D2) ganglioside conjugate vaccine: a trial comparing doses of G(D2)-keyhole limpet hemocyanin. (2000)

Immunization with GMK vaccine (G(M2) ganglioside conjugated to keyhole limpet hemocyanin mixed with QS-21 adjuvant) induces anti-G(M2) antibodies in close to 100% of patients. We found previously that anti-G(D2) antibodies could be induced in some patients using G(D2)-keyhole limpet hemocyanin + QS-21 (GDK). In this trial, we wished: (a) to determine whether immunization with both GMK and GDK vaccines could induce antibodies against both G(M2) and G(D2); and (b) to determine the optimal dose of GDK. Thirty-one patients with melanoma or sarcoma who had no evidence of disease after complete surgical resection were immunized with both GMK (30 microg of G(M2)) and GDK on weeks 1, 2, 3, 4, 12, 24, and 36. Patients were assigned to one of five GDK dose levels (3, 10, 30, 70, or 130 microg of G(D2)). Anti-G(M2) IgM or IgG were induced in 97% of patients. The dose of GDK did not affect the anti-G(M2) response, although at the highest GDK dose level, 3 of 7 patients did not make anti-G(M2) IgG. GDK was less immunogenic; overall 45% of patients developed either IgM or IgG against G(D2). At GDK doses of 30 or 70 microg, 8 of 11 patients (73%) made either IgM or IgG anti-G(D2) antibodies. We conclude that both GMK and GDK vaccines can induce antibodies against G(M2) and G(D2) in a majority of patients and are safe. The optimal dose of GDK appears to be either 30 or 70 microg when administered with GMK vaccine.
Gene Expression Commons: An Open Platform for Absolute Gene Expression Profiling (2012)

Gene expression profiling using microarrays has been limited to comparisons of gene expression between small numbers of samples within individual experiments. However, the unknown and variable sensitivities of each probeset have rendered the absolute expression of any given gene nearly impossible to estimate. We have overcome this limitation by using a very large number (>10,000) of varied microarray data as a common reference, so that statistical attributes of each probeset, such as the dynamic range and threshold between low and high expression, can be reliably discovered through meta-analysis. This strategy is implemented in a web-based platform named "Gene Expression Commons" (https://gexc.stanford.edu/) which contains data of 39 distinct highly purified mouse hematopoietic stem/progenitor/differentiated cell populations covering almost the entire hematopoietic system. Since the Gene Expression Commons is designed as an open platform, investigators can explore the expression level of any gene, search by expression patterns of interest, submit their own microarray data, and design their own working models representing biological relationship among samples.
Genome-Wide CRISPR-Cas9 Screen Reveals Selective Vulnerability of ATRX -Mutant Cancers to WEE1 Inhibition (2019)

The tumor suppressor gene <i>ATRX</i> is frequently mutated in a variety of tumors including gliomas and liver cancers, which are highly unresponsive to current therapies. Here, we performed a genome-wide synthetic lethal screen, using CRISPR-Cas9 genome editing, to identify potential therapeutic targets specific for <i>ATRX</i>-mutated cancers. In isogenic hepatocellular carcinoma (HCC) cell lines engineered for ATRX loss, we identified 58 genes, including the checkpoint kinase <i>WEE1</i>, uniquely required for the cell growth of ATRX null cells. Treatment with the WEE1 inhibitor AZD1775 robustly inhibited the growth of several ATRX-deficient HCC cell lines <i>in vitro</i>, as well as xenografts <i>in vivo</i>. The increased sensitivity to the WEE1 inhibitor was caused by accumulated DNA damage-induced apoptosis. AZD1775 also selectively inhibited the proliferation of patient-derived primary cell lines from gliomas with naturally occurring <i>ATRX</i> mutations, indicating that the synthetic lethal relationship between <i>WEE1</i> and <i>ATRX</i> could be exploited in a broader spectrum of human tumors. As WEE1 inhibitors have been investigated in several phase II clinical trials, our discovery provides the basis for an easily clinically testable therapeutic strategy specific for cancers deficient in <i>ATRX</i>. SIGNIFICANCE: <i>ATRX</i>-mutant cancer cells depend on WEE1, which provides a basis for therapeutically targeting WEE1 in <i>ATRX</i>-deficient cancers.<i>See related commentary by Cole, p. 375</i>.
Block-LDPC: a practical LDPC coding system design approach (2005)

This paper presents a joint low-density parity-check (LDPC) code-encoder-decoder design approach, called Block-LDPC, for practical LDPC coding system implementations. The key idea is to construct LDPC codes subject to certain hardware-oriented constraints that ensure the effective encoder and decoder hardware implementations. We develop a set of hardware-oriented constraints, subject to which a semi-random approach is used to construct Block-LDPC codes with good error-correcting performance. Correspondingly, we develop an efficient encoding strategy and a pipelined partially parallel Block-LDPC encoder architecture, and a partially parallel Block-LDPC decoder architecture. We present the estimation of Block-LDPC coding system implementation key metrics including the throughput and hardware complexity for both encoder and decoder. The good error-correcting performance of Block-LDPC codes has been demonstrated through computer simulations. With the effective encoder/decoder design and good error-correcting performance, Block-LDPC provides a promising vehicle for real-life LDPC coding system implementations.
Clara cell secretory protein gene expression in bronchiolar epithelium (1992)

To determine the mechanisms of Clara cell secretory protein (CCSP) gene expression, a cDNA clone was isolated and used in RNA blot analysis. A single 600 bp CCSP specific transcript was detected in the developing rat lung on fetal day 18. This transcript increased in abundance during late fetal life such that adult levels were attained within 2 wk postpartum. CCSP gene expression was tissue specific, being confined to lung and trachea at all developmental stages. The abundance of CCSP mRNA in lung tissue was unchanged after the induction of lung injury in adult rats either with lipopolysaccharide or prolonged exposure to hyperoxia. In situ hybridization of lung tissue revealed that CCSP gene expression is localized to the nonciliated epithelial (Clara) cells of the bronchiolar epithelium throughout fetal and postnatal development. Taken together the results indicate that the gene for CCSP is abundantly expressed in a cell-specific fashion in the lung and suggest that analysis of such expression will be useful in elucidating the role of Clara cells in the growth and development of the bronchiolar epithelium.
DNA Vaccines Expressing Different Forms of Simian Immunodeficiency Virus Antigens Decrease Viremia upon SIVmac251 Challenge (2005)

We have tested the efficacy of DNA immunization as a single vaccination modality for rhesus macaques followed by highly pathogenic SIVmac251 challenge. To further improve immunogenicity of the native proteins, we generated expression vectors producing fusion of the proteins Gag and Env to the secreted chemokine MCP3, targeting the viral proteins to the secretory pathway and to a beta-catenin (CATE) peptide, targeting the viral proteins to the intracellular degradation pathway. Macaques immunized with vectors expressing the MCP3-tagged fusion proteins developed stronger antibody responses. Following mucosal challenge with pathogenic SIVmac251, the vaccinated animals showed a statistically significant decrease in viral load (P = 0.010). Interestingly, macaques immunized with a combination of vectors expressing three forms of antigens (native protein and MCP3 and CATE fusion proteins) showed the strongest decrease in viral load (P = 0.0059). Postchallenge enzyme-linked immunospot values for Gag and Env as well as gag-specific T-helper responses correlated with control of viremia. Our data show that the combinations of DNA vaccines producing native and modified forms of antigens elicit more balanced immune responses able to significantly reduce viremia for a long period (8 months) following pathogenic challenge with SIVmac251.
Statistical potential for assessment and prediction of protein structures (2006)

Protein structures in the Protein Data Bank provide a wealth of data about the interactions that determine the native states of proteins. Using the probability theory, we derive an atomic distance-dependent statistical potential from a sample of native structures that does not depend on any adjustable parameters (Discrete Optimized Protein Energy, or DOPE). DOPE is based on an improved reference state that corresponds to noninteracting atoms in a homogeneous sphere with the radius dependent on a sample native structure; it thus accounts for the finite and spherical shape of the native structures. The DOPE potential was extracted from a nonredundant set of 1472 crystallographic structures. We tested DOPE and five other scoring functions by the detection of the native state among six multiple target decoy sets, the correlation between the score and model error, and the identification of the most accurate non-native structure in the decoy set. For all decoy sets, DOPE is the best performing function in terms of all criteria, except for a tie in one criterion for one decoy set. To facilitate its use in various applications, such as model assessment, loop modeling, and fitting into cryo-electron microscopy mass density maps combined with comparative protein structure modeling, DOPE was incorporated into the modeling package MODELLER-8.