gebhart/patrepeval huggingface dataset:
Vaporization of perfluorocarbon droplets using optical irradiation (2011)

Micron-sized liquid perfluorocarbon (PFC) droplets are currently being investigated as activatable agents for medical imaging and cancer therapy. After injection into the bloodstream, superheated PFC droplets can be vaporized to a gas phase for ultrasound imaging, or for cancer therapy via targeted drug delivery and vessel occlusion. Droplet vaporization has been previously demonstrated using acoustic methods. We propose using laser irradiation as a means to induce PFC droplet vaporization using a method we term optical droplet vaporization (ODV). In order to facilitate ODV of PFC droplets which have negligible absorption in the infrared spectrum, optical absorbing nanoparticles were incorporated into the droplet. In this study, micron-sized PFC droplets loaded with silica-coated lead sulfide (PbS) nanoparticles were evaluated using a 1064 nm laser and ultra-high frequency photoacoustic ultrasound (at 200 and 375 MHz). The photoacoustic response was proportional to nanoparticle loading and successful optical droplet vaporization of individual PFC droplets was confirmed using photoacoustic, acoustic, and optical measurements. A minimum laser fluence of 1.4 J/cm(2) was required to vaporize the droplets. The vaporization of PFC droplets via laser irradiation can lead to the activation of PFC agents in tissues previously not accessible using standard ultrasound-based techniques.
Elotuzumab in Combination With Lenalidomide and Low-Dose Dexamethasone in Relapsed or Refractory Multiple Myeloma (2012)

The combination of elotuzumab, lenalidomide, and low-dose dexamethasone was generally well tolerated and showed encouraging response rates in patients with relapsed or refractory MM.
Anticancer Drug Discovery Targeting DNA Hypermethylation (2008)

DNA methyltransferases (DNMTs) are important regulators of gene transcription and their roles in carcinogenesis have been a topic of considerable interest in the last few years. Diverse classes of chemical compounds including nucleotide analogues, adenosine analogues, aminobenzoic derivatives, polyphenols, hydrazines, phthalides, disulfides and antisenses are being discovered and evaluated as DNMT inhibitors targeting DNA hypermethylation. Among them, 5-Azacytidine 5 and Decitabine 6 were launched recently. Several other compounds are under clinical trials. Some of these compounds were discovered from structure-based drug design. These compounds exert their DNA methylation inhibitory by different mechanisms. This review will present a brief account of various DNA methyltransferases and their biological functions, with focus on actuality of design and synthesis of various inhibitors of DNA hypermethylation as anticancer drugs.
Integrated circuits for particle physics experiments (2000)

High energy particle physics experiments investigate the nature of matter through the identification of subatomic particles produced in collisions of protons, electrons, or heavy ions which have been accelerated to very high energies. Future experiments will have hundreds of millions of detector channels to observe the interaction region where collisions take place at a 40 MHz rate. This paper gives an overview of the electronics requirements for such experiments and explains how data reduction, timing distribution, and radiation tolerance in commercial CMOS circuits are achieved for these big systems. As a detailed example, the electronics for the innermost layers of the future tracking detector, the pixel vertex detector, is discussed with special attention to system aspects. A small-scale prototype (130 channels) implemented in standard 0.25 /spl mu/m CMOS remains fully functional after a 30 Mrad(SiO/sub 2/) irradiation. A full-scale pixel readout chip containing 8000 readout channels in a 14 by 16 mm/sup 2/ area has been designed.
Role of endothelium-derived relaxing factor during transition of pulmonary circulation at birth (1990)

To examine the potential role of endothelium-derived relaxing factor (EDRF) in regulation of the perinatal pulmonary circulation, we studied the hemodynamic effects of a selective inhibitor of EDRF production, nitro-L-arginine (L-NA), on pulmonary vascular tone and dilator reactivity in the late-gestation ovine fetus and on the pulmonary vasodilation that normally occurs at birth. L-NA infusion decreased pulmonary blood flow from 78 +/- 8 to 65 +/- 6 ml/min (P less than 0.01) and increased pulmonary artery pressure from 48 +/- 2 to 54 +/- 3 mmHg (P less than 0.002, n = 8 animals). To study the selectivity of L-NA on vasodilator responses to endothelium-dependent (acetylcholine) and -independent (atrial natriuretic factor) stimuli, we measured responses to brief infusions of each dilator before and after L-NA treatment. Acetylcholine increased pulmonary blood flow during the control period but not after L-NA treatment. In contrast, L-NA had little effect on the vasodilator response to atrial natriuretic factor. To study the role of EDRF in the transition of the pulmonary circulation from fetal to neonatal conditions, we infused L-NA into the left pulmonary artery immediately before cesarean-section delivery. In comparison with control animals, the rise in pulmonary blood flow at 1 h after delivery was reduced in the L-NA-treated animals (331 +/- 28 in control vs. 185 +/- 16 ml/min in treated, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Remodeling of mouse thymocyte nuclei depends on the time of their transfer into activated, homologous oocytes (1988)

The potential of parthenogenetically activated mouse oocytes to remodel somatic cell nuclei was studied by ultrastructural means using oocyte-thymocyte hybrids. Complete nuclear remodeling, initiated by nuclear envelope breakdown and chromosome condensation (which is followed by formation of pronucleus-like nucleus) is possible only during a short time gap between metaphase II and telophase of meiotic division. Maturation-promoting factor activity is high during this period. The thymocyte nucleus can follow the sequence of morphological changes only in concert with the development of the native nucleus and only after exposure of the chromatin to the ooplasm. If hybridization is effected with pronucleate oocytes, the thymocyte nucleus retains its interphase character but shows particular modifications in nucleolar morphology (identical to changes observed during reactivation of the nucleolus in stimulated lymphocyte) and in the activity of the nuclear envelope (blebbing). Thus the nucleus not exposed to maturation-promoting factor activity may be influenced by a 'programme' specific for oocyte (blebbing) and by a programme inherent in the introduced somatic cell nucleus.
Redundancy of Mammalian Proteasome β Subunit Function during Endoplasmic Reticulum Associated Degradation (2001)

Misfolded proteins in the endoplasmic reticulum (ER) are degraded by N-terminal threonine proteases within the 26S proteasome. Each protease is formed by an activated beta subunit, beta5/X, beta1/Y, or beta2/Z, that exhibits chymotrypsin-like, peptidylglutamyl-peptide hydrolyzing, or trypsin-like activity, respectively. Little is known about the relative contribution of specific beta subunits in the degradation of endogenous protein substrates. Using active site proteasome inhibitors and a reconstituted degradation system, we now show that all three active beta subunits can independently contribute to ER-associated degradation of the cystic fibrosis transmembrane conductance regulator (CFTR). Complete inactivation (>99.5%) of the beta5/X subunit decreased the rate of ATP-dependent conversion of CFTR to trichloroacetic acid soluble fragments by only 40%. Similarly, proteasomes containing only active beta1/Y or beta2/Z subunits degraded CFTR at approximately 50% of the rate observed for fully functional proteasomes. Simultaneous inhibition (>93%) of all three beta subunits blocked CFTR degradation by approximately 90%, and inhibition of both protease and ATPase activities was required to completely prevent generation of small peptide fragments. Our results demonstrate both a conserved hierarchy (ChT-L > PGPH > or = T-L) as well as a redundancy of beta subunit function and provide insight into the mechanism by which active site proteasome inhibitors influence degradation of endogenous protein substrates at the ER membrane.
Folding quality control in the export of proteins by the bacterial twin-arginine translocation pathway (2003)

To examine the relationship between folding and export competence by the twin-arginine translocation (Tat) pathway we analyzed the subcellular localization of fusions between a set of eight putative Tat leader peptides and alkaline phosphatase in isogenic Escherichia coli strains that either allow or disfavor the formation of protein disulfide bonds in the cytoplasm. We show that export by the Tat translocator is observed only in strains that enable oxidative protein folding in the cytoplasm. Further, we show that other disulfide-containing proteins, namely single-chain Fv and heterodimeric F(AB) antibody fragments, are export-competent only in strains having an oxidizing cytoplasm. Functional, heterodimeric F(AB) protein was exported from the cytoplasm by means of a Tat leader peptide fused to the heavy chain alone, indicating that the formation of a disulfide-bonded dimer preceeds export. These results demonstrate that in vivo only proteins that have attained the native conformation are exported by the Tat translocator, indicating that a folding quality-control mechanism is intrinsic to the export process. The ability to export proteins with disulfide bonds and the folding proofing feature of the Tat pathway are of interest for biotechnology applications.
Multiple apoptotic death types triggered through activation of separate pathways by cAMP and inhibitors of protein phosphatases in one (IPC leukemia) cell line (1994)

The protein phosphatase inhibitors okadaic acid and calyculin A at moderate concentrations induced three types of apoptotic promyelocytic leukemia cell death, distinct with respect to ultrastructure and polynucleotide fragmentation. Calyculin A at higher concentrations (> 50 nM) induced a non-apoptotic death type with high ATP and pronounced micromitochondriosis. This suggests that protein phosphorylation pathways are involved in the triggering of several death pathways. Activation of the cAMP kinase induced yet another apoptotic death type, preferentially affecting cells in S-phase. In fact, cAMP acted in two ways to stop IPC promyelocyte proliferation: (1) block in late G1 (preventing new cells from entering DNA replication); and (2) induction of apoptosis in S-phase. cAMP and phosphatase inhibitors acted via distinct pathways. The inhibitors suppressed cAMP-induced death, but only at concentrations high enough to commit the cells to alternative, less conspicuous death types. The tumor-promoting activity of okadaic acid and calyculin A may therefore not be by protection against apoptosis. DNA fragmentation correlated with the novel feature of limited 28 S rRNA cleavage, suggesting co-ordinated polynucleotide cleavage, possibly directed against illegitimate polynucleotides, in some apoptotic death types.
Asymmetric Inheritance of Oxidatively Damaged Proteins During Cytokinesis (2003)

Carbonylated proteins were visualized in single cells of the budding yeast Saccharomyces cerevisiae, revealing that they accumulate with replicative age. Furthermore, carbonylated proteins were not inherited by daughter cells during cytokinesis. Mother cells of a yeast strain lacking the sir2 gene, a life-span determinant, failed to retain oxidatively damaged proteins during cytokinesis. These findings suggest that a genetically determined, Sir2p-dependent asymmetric inheritance of oxidatively damaged proteins may contribute to free-radical defense and the fitness of newborn cells.
Combining structural analysis of DNA with search routines for the detection of transcription regulatory elements (1996)

Using molecular modelling techniques, we have created a complete database for the conversion of base sequences into profiles of structural parameters of DNA. On this basis, search routines can be developed that scan for profile matches. They may be used instead of or, probably most appropriate in most cases, in combination with conventional sequence pattern searches.
SpliceRover: interpretable convolutional neural networks for improved splice site prediction (2018)

Supplementary data are available at Bioinformatics online.
Interaction as a basis for empirical computer science (1995)

Computer scientists are blessed with a universal device which can be instructed to perform any computation and simulate any physical process (as described by our current laws of physics), but which is therefore chaotic and must be controlled with unprecedented precision. This is achieved by the successive layers of implemented abstraction wrapped around the chaotic universal machines that help to bridge the many orders of magnitude in the scale of things, JURIS HARTMANIS, Communications
Film Characteristics of APCVD Oxide Using Organic Silicon and Ozone (1991)

Film characteristics of APCVD oxide using octamethylcyclo tetrasiloxane (OMCTS) and O 3 (AP-OMCTS oxide) have been investigated minutely for applications to advanced VLSI devices. Deposition characteristics of AP-OMCTS oxide strongly depend on deposition temperature and high quality films can be formed by increasing the deposition temperature. The step coverage shows a most smooth “flowing profile” around at 425°C. The dependence of the deposition characteristics on O 3 concentration can not be observed in contrast with the deposition characteristics of AP-TEOS oxide which evidently depend on the O 3 concentration. From these results, it is supposed that CVD reactions based on OMCTS-O 3 chemistry consist of the precursor production correspond to CH 3 elimination reaction with O radicals and the subsequent polymerization (dehydration) caused by thermal energy provided from hot substrate.
Immunologic versus toxicologic mechanisms in airway responses. (2000)

There is now considerable evidence that T lymphocytes play an important role in generating the IgE-mediated immune response of classical allergic asthma. An immune response can be generated by other routes, including IgG- and cell-mediated mechanisms, as well. Regardless of the mechanism, it is clear that allergic asthma is an inflammatory disease, with activated T lymphocytes, eosinophils, mast cells, and other leucocytes all playing a role. Recently, an irritant asthma called reactive airway dysfunction syndrome also has emerged. It appears to be due to direct irritant or toxic effects, but shares many features of allergic asthma. Thus, several different pathways lead to the inflammatory changes and nonspecific airway responsiveness underlying asthma.
Neurologizing the Psychology of Affects: How Appraisal-Based Constructivism and Basic Emotion Theory Can Coexist (2007)

Abundant neurobehavioral data, not discussed by Lisa Feldman Barrett (2006), support the existence of a variety of core emotional operating systems in ancient subneocortical regions of the brain (Panksepp, 1998a, 2005a). Such brain systems are the primary-process ancestral birthrights of all mammals. There may be as many genetically and neurochemically coded subcortical affect systems in emotionally rich medial regions of the brain as there are "natural" emotional action systems in the brain. When emotional primes are aroused directly, as with local electrical or chemical stimulation, the affective changes sustain conditioned place preferences and place aversions, which are the premier secondary-process indices of affective states in animals. Humans are not immune to such brain manipulations; they typically exhibit strong emotional feelings. Human emotion researchers should not ignore these systems and simply look at the complex and highly variable culturally molded manifestations of emotions in humans if they wish to determine what kinds of "natural" emotional processes exist within all mammalian brain. Basic emotion science has generated workable epistemological strategies for under-standing the primal sources of human emotional feelings by detailed study of emotional circuits in our fellow animals.
Elevated expression of SLC34A2 inhibits the viability and invasion of A549 cells (2014)

Abnormal expression of solute carrier family 34 (sodium phosphate), member 2 (SLC34A2) in the lung may induce abnormal alveolar type II (AT II) cells to transform into lung adenocarcinoma cells, and may also be important in biological process of lung adenocarcinoma. However, at present, the effects and molecular mechanisms of SLC34A2 in the initiation and progression of lung cancer remain to be elucidated. To the best of our knowledge, the present study revealed for the first time that the expression levels of SLC34A2 were downregulated in the A549 and H1299 lung adenocarcinoma cell lines. Further investigation demonstrated that the elevated expression of SLC34A2 in A549 cells was able to significantly inhibit cell viability and invasion in vitro. In addition, 10 upregulated genes between the A549‑P‑S cell line stably expressing SLC34A2 and the control cell line A549‑P were identified by microarray analysis and quantitative polymerase chain reaction, including seven tumor suppressor genes and three complement genes. Furthermore, the upregulation of complement gene C3 and complement 4B preproprotein (C4b) in A549‑P‑S cells was confirmed by ELISA analysis and was identified to be correlated with recovering Pi absorption in A549 cells by the phosphomolybdic acid method by enhancing the expression of SLC34A2. Therefore, it was hypothesized that the mechanisms underlying the effect of SLC34A2 on A549 cells might be associated with the activation of the complement alternative pathway (C3 and C4b) and upregulation of the expression of selenium binding protein 1, thioredoxin‑interacting protein, PDZK1‑interacting protein 1 and dual specificity protein phosphatase 6. Downregulation of SLC34A2 may primarily cause abnormal AT II cells to escape from complement‑associated immunosurveillance and abnormally express certain tumor‑suppressor genes inducing AT II cells to develop into lung adenocarcinoma. The present study further elucidated the effects and mechanisms of SLC34A2 in the generation and development of lung cancer.
Current Tumor Ablation Technologies: Basic Science and Device Review (2010)

Image-guided tumor ablation is an increasingly utilized tool to treat focal malignancy. Tumor ablation can be divided into two large categories, thermal and chemical ablation. The authors provide an overview of the current methods used to achieve thermal and chemical ablation of tumors, specifically addressing the basic science behind the ablation methods as well as providing a brief synopsis of the commercial devices currently available for use in the United States.
Effect of the 5-lipoxygenase inhibitor ZD2138 on allergen-induced early and late asthmatic responses. (1994)

In asthmatic subjects the 5-lipoxygenase inhibitor ZD2138 did not protect against allergen-induced asthmatic responses, despite substantial inhibition of 5-lipoxygenase.
Cancer Genome Landscapes (2013)

Over the past decade, comprehensive sequencing efforts have revealed the genomic landscapes of common forms of human cancer. For most cancer types, this landscape consists of a small number of "mountains" (genes altered in a high percentage of tumors) and a much larger number of "hills" (genes altered infrequently). To date, these studies have revealed ~140 genes that, when altered by intragenic mutations, can promote or "drive" tumorigenesis. A typical tumor contains two to eight of these "driver gene" mutations; the remaining mutations are passengers that confer no selective growth advantage. Driver genes can be classified into 12 signaling pathways that regulate three core cellular processes: cell fate, cell survival, and genome maintenance. A better understanding of these pathways is one of the most pressing needs in basic cancer research. Even now, however, our knowledge of cancer genomes is sufficient to guide the development of more effective approaches for reducing cancer morbidity and mortality.
Endothelial Cell Gene Expression of a Neutrophil Chemotactic Factor by TNF-α, LPS, and IL-1β (1989)

Human endothelial cells produced a neutrophil chemotactic factor (NCF) upon stimulation with tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), or lipopolysaccharide (LPS). The expression of endothelial cell-derived NCF messenger RNA and biological activity was both time- and concentration-dependent. Maximal NCF mRNA expression occurred at 10 and at 2 nanograms per milliliter for TNF and IL-1 beta, respectively; mRNA expression was first observed 1 hour after stimulation and was maintained for at least 24 hours. In situ hybridization analysis showed that NCF mRNA peaked in treated cells by 24 hours, whereas unstimulated cells were negative. These studies demonstrated that endothelial cells may participate in neutrophil-mediated inflammation by synthesizing a chemotactic factor in response to specific monokines and LPS.
Use of Dinitrophenol in Nutritional Disorders (1934)

Use of Dinitrophenol in Nutritional Disorders A Critical Survey of Clinical Results † Maurice L. Tainter, Windsor C. Cutting, and A. B. Stockton CopyRight*Read before the Food and Nutrition Section of the American Public Health Association at the Sixty-third Annual Meeting in Pasadena, Calif., September 3, 1934.†Supported in part by grants from the Rockefeller Fluid Research Fund of the School of Medicine, Stanford University, and by Grant 320 from the Committee on Scientific Research of the American Medical Association. https://doi.org/10.2105/AJPH.24.10.1045 Published Online: August 29, 2011
Eicosapentaenoic acid but not docosahexaenoic acid restores skeletal muscle mitochondrial oxidative capacity in old mice (2015)

Mitochondrial dysfunction is often observed in aging skeletal muscle and is implicated in age-related declines in physical function. Early evidence suggests that dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) improve mitochondrial function. Here, we show that 10 weeks of dietary eicosapentaenoic acid (EPA) supplementation partially attenuated the age-related decline in mitochondrial function in mice, but this effect was not observed with docosahexaenoic acid (DHA). The improvement in mitochondrial function with EPA occurred in the absence of any changes in mitochondrial abundance or biogenesis, which was evaluated from RNA sequencing, large-scale proteomics, and direct measurements of muscle mitochondrial protein synthesis rates. We find that EPA improves muscle protein quality, specifically by decreasing mitochondrial protein carbamylation, a post-translational modification that is driven by inflammation. These results demonstrate that EPA attenuated the age-related loss of mitochondrial function and improved mitochondrial protein quality through a mechanism that is likely linked with anti-inflammatory properties of n-3 PUFAs. Furthermore, we demonstrate that EPA and DHA exert some common biological effects (anticoagulation, anti-inflammatory, reduced FXR/RXR activation), but also exhibit many distinct biological effects, a finding that underscores the importance of evaluating the therapeutic potential of individual n-3 PUFAs.