gebhart/patrepeval huggingface dataset:
Intracellular pathway of Onconase that enables its delivery to the cytosol (2007)

Onconase is an RNase with a very specific property because it is selectively toxic to transformed cells. This toxin is thought to recognize cell surface receptors, and the protection conferred by metabolic poisons against Onconase toxicity indicated that this RNase relies on endocytic uptake to kill cells. Nevertheless, its internalization pathway has yet to be unraveled. We show here that Onconase enters cells using AP-2/clathrin-mediated endocytosis. It is then routed, together with transferrin, to the receptor recycling compartment. Increasing the Onconase concentration in this structure using tetanus toxin light chain expression enhanced Onconase toxicity, indicating that recycling endosomes are a key compartment for Onconase cytosolic delivery. This intracellular destination is specific to Onconase because other (and much less toxic) RNases follow the default pathway to late endosomes/lysosomes. Drugs neutralizing endosomal pH increased Onconase translocation efficiency from purified endosomes during cell-free translocation assays by preventing Onconase dissociation from its receptor at endosomal pH. Consistently, endosome neutralization enhanced Onconase toxicity up to 100-fold. Onconase translocation also required cytosolic ATP hydrolysis. This toxin therefore shows an unusual entry process that relies on clathrin-dependent endocytic uptake and then neutralization of low endosomal pH for efficient translocation from the endosomal lumen to the cytosol.
Coverage of Postprandial Blood Glucose Excursions With Inhaled Technosphere Insulin in Comparison to Subcutaneously Injected Regular Human Insulin in Subjects With Type 2 Diabetes (2007)

Technosphere Insulin (TI) is a formulation of regular human insulin (RHI) that provides efficient pulmonary administration (1) and demonstrates unique pharmacokinetic and pharmacodynamic properties compared with subcutaneous RHI, rapid-acting insulin analogs, and other inhaled insulins (2). Administration of TI results in a time to maximum insulin concentration of ∼15 min, with almost complete absorption within 3 h (3,4). With an onset of action comparable to intravenous insulin, TI represents the first formulation that approaches the physiological early insulin release. In this study, we evaluated the efficacy and safety of TI compared with subcutaneous RHI in covering prandial insulin needs. We measured blood glucose excursions after a meal challenge after individual titration of either insulin formulation during a 7-day treatment period in subjects with type 2 diabetes.

This prospective, open-label, randomized, two-period, cross-over study was conducted at one center (Profil Institute for Metabolic Research, Neuss, Germany). The study included a screening visit, 24-h in-house exposure to TI to establish initial dosing, two 7-day ambulant periods of daily mealtime TI or subcutaneous RHI separated by a 2- to 7-day washout, and a final visit. In-house meal challenges, using a standardized mixed meal with 496 kcal, were conducted at the end of each ambulant period. During treatment periods, each subject inhaled TI via a MedTone Model C Inhaler (MannKind Corporation, Valencia, CA) …
Tyrosines 559 and 807 in the Cytoplasmic Tail of the Macrophage Colony-Stimulating Factor Receptor Play Distinct Roles in Osteoclast Differentiation and Function (2002)

Osteoclast (OC) differentiation requires that precursors, such as macrophage colony-stimulating factor (M-CSF)-dependent bone marrow macrophages, receive signals transduced by receptor activator of nuclear factor kappaB (RANK) and c-Fms, receptors for RANK ligand (RANKL) and M-CSF, respectively. Activated c-Fms autophosphorylates cytoplasmic tail tyrosine residues, which, by recruiting adaptor molecules, initiate specific signaling pathways. To identify which tyrosine residues are involved in c-Fms signaling in primary cells, we retrovirally transduced M-CSF-dependent bone marrow macrophages with a chimera comprising the external domain of the erythropoietin (Epo) receptor linked to the transmembrane and cytoplasmic domains of c-Fms. Transduced cells differentiate into bone-resorbing osteoclasts when treated with RANKL and either M-CSF or Epo, confirming that both endogenous and chimeric receptors transmit osteoclastogenic signals. Cells expressing chimeric receptors with Y(697)F, Y(706)F, Y(721)F, and Y(921)F single point mutations generate normal numbers of bone-resorbing OCs, with normal bone-resorbing activity when treated with RANKL and Epo. In contrast, those expressing Y(559)F generate fewer OCs, whereas theY807F mutant is incapable of osteoclastogenesis. Finally, although mature OCs expressing Y(559)F exhibit impaired bone resorption, those bearing Y807F do not. Thus, we have identified specific tyrosine residues in the cytoplasmic tail of c-Fms that are critical for transmitting M-CSF-initiated signals individually required for OC formation or function, respectively.
High-Efficiency Gene Targeting in Drosophila with Zinc Finger Nucleases (2010)

We describe a method for making targeted double-strand breaks in Drosophila melanogaster using zinc finger nucleases (ZFNs). After design and construction of the appropriate coding sequences, synthetic mRNAs for the ZFNs are injected directly into fly embryos. Frequencies of target cleavage and mutagenesis in the range of 1-10% have been achieved at several different loci. A donor DNA carrying desired sequence changes can be incorporated in the injection mix and leads to targeted gene replacement, with particularly good efficiency when the recipient embryos are defective for nonhomologous end joining.
Experimental Results for a Heat-Sink Mechanical Seal (2005)

This work presents experimental results for a heat-sink mechanical seal installed in a 1 × 1.5 × 6 in. ANSI centrifugal water pump. The heat-sink seal is constructed of a stainless steel substrate with an electrodeposited pin fin micro-heat sink located within 3 mm of the end face. Each pin has a ten-sided polygon cross section with a flat-to-flat diameter of 675 μm, a height of 856 μm, and a 300-μm edge-to-edge spacing. The end face is coated with a WC thin film that forms the wear surface for the rotating ring. The heat-sink seal's effectiveness is demonstrated in a significant reduction of both the seal interface and seal chamber temperature when compared to a similar industry standard seal. The heat-sink seal removes 750 W of heat and reduces the stationary ring temperature by 80°C under dead-head conditions using only 1.6 W of coolant pumping power.
SIMULTANEOUS OPTICAL PARAMETRIC OSCILLATION, SECOND HARMONIC GENERATION, AND DIFFERENCE-FREQUENCY GENERATION (1971)

We report the observation of simultaneous phase matching of three separate nonlinear optical processes. The second harmonic of the signal wavelength of a parametric oscillator was generated and then mixed with the idler wavelength of the oscillator to produce a difference frequency, all in the same nonlinear crystal. We have observed 34% average power conversion from the signal to its second harmonic, which is at a shorter wavelength than the pump.
Central Role of Peroxisome Proliferator–Activated Receptors in the Actions of Peroxisome Proliferators (2000)

Peroxisome proliferators (PPs) are a large class of structurally dissimilar chemicals that have diverse effects in rodents and humans. Most, if not all, of the diverse effects of PPs are mediated by three members of the nuclear receptor superfamily called peroxisome proliferator-activated receptors (PPARs). In this review, we define the molecular mechanisms of PPs, including PPAR binding specificity, alteration of gene expression through binding to DNA response elements, and cross talk with other signaling pathways. We discuss the roles of PPARs in growth promotion in rodent hepatocarcinogenesis and potential therapeutic effects, including suppression of cancer growth and inflammation.
Direct electrical communication between chemically modified enzymes and metal electrodes. 2. Methods for bonding electron-transfer relays to glucose oxidase and D-amino-acid oxidase (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDirect electrical communication between chemically modified enzymes and metal electrodes. 2. Methods for bonding electron-transfer relays to glucose oxidase and D-amino-acid oxidaseYinon. Degani and Adam. HellerCite this: J. Am. Chem. Soc. 1988, 110, 8, 2615–2620Publication Date (Print):April 1, 1988Publication History Published online1 May 2002Published inissue 1 April 1988https://pubs.acs.org/doi/10.1021/ja00216a040https://doi.org/10.1021/ja00216a040research-articleACS PublicationsRequest reuse permissionsArticle Views1502Altmetric-Citations347LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Study of Potential Integrated Management of Water Resources in Las Vegas Valley (2017)

Water resource management under short term system perturbations such as storms and longer-term systemic changes caused by climate change such as droughts is a challenge when multiple agencies are involved. To address this challenge this research focuses on water management under changing climate conditions and population growth through understanding the agency water jurisdictions, management strategies, and modes of operation in Las Vegas Valley. A framework for integrated management through sharing data and models is presented that combines drinking water supply, flood control, and waste water treatment. This framework can be adopted to improve coordination among different water management agencies.
Bone-Conduction Sensitivity along with Static Force, Location, and Stimulus (2012)

This study sought to estimate bone-conducted hearing sensitivity as static force levels of the oscillator as well as identify the most sensitive bone-conducted location on the human head when stimulated by tone and speech stimuli. In Experiment I, 24 young normal hearing listeners responded to bone-conducted thresholds ranging from 250 to 8,000 Hz in three placement locations: the forehead and the left and right mastoids. At each location and across all participants, the static force applied to various forces related to the individual's head size (i.e., Hooke's raw). The results of this experiment indicated that increased static force would not significantly cause more sensitive (or lower) thresholds. Thresholds of the forehead placement were less sensitive than both mastoids. Experiment II involved 24 young normal hearing listeners to determine the bone-conducted hearing thresholds at five placements (i.e., condyle, jaw angle, mastoid, temple, vertex) of the head, using tones ranging from 500 to 6,000 Hz and spondee words. The results indicated that the condyle and vertex are the most and least sensitive placements, respectively, regardless of tone and speech stimuli. Such information may be extended to future series of studies related to develop effective bone-conduction communication devices under harmful noisy conditions as well as contribute to the development of a computational model of bone-conducted sound transmission pathways in the human skull.
Quantum well photoconductors in infrared detector technology (2003)

The paper compares the achievements of quantum well infrared photodetector (QWIP) technology with those of competitive technologies, with the emphasis on the material properties, device structure, and their impact on focal plane array (FPA) performance. Special attention is paid to two competitive technologies, QWIP and HgCdTe, in the long-wavelength IR (LWIR) and very-long-wavelength IR (VLWIR) spectral ranges. Because so far, the dialogue between the QWIP and HgCdTe communities is limited, the paper attempts to settle the main issues of both technologies. Such an approach, however, requires the presentation of fundamental limits to the different types of detectors, which is made at the beginning. To write the paper more clearly for readers, many details are included in the Appendix. In comparative studies both photon and thermal detectors are considered. Emphasis is placed on photon detectors. In this group one may distinguish HgCdTe photodiodes, InSb photodiodes, and doped silicon detectors. The potential performance of different materials as infrared detectors is examined utilizing the α/G ratio, where α is the absorption coefficient and G is the thermal generation rate. It is demonstrated that LWIR QWIP’s cannot compete with HgCdTe photodiodes as single devices, especially at higher operating temperatures (&amp;gt;70 K). This is due to the fundamental limitations associated with intersubband transitions. The advantage of HgCdTe is, however, less distinct at temperatures lower than 50 K due to problems inherent in the HgCdTe material (p-type doping, Shockley–Read recombination, trap-assisted tunneling, surface and interface instabilities). Even though QWIP is a photoconductor, several of its properties, such as high impedance, fast response time, long integration time, and low power consumption, comply well with the requirements imposed on the fabrication of large FPA’s. Due to a high material quality at low temperatures, QWIP has potential advantages over HgCdTe in the area of VLWIR FPA applications in terms of array size, uniformity, yield, and cost of the systems. The performance figures of merit of state-of-the-art QWIP and HgCdTe FPA’s are similar because the main limitations come from the readout circuits. Performance is, however, achieved with very different integration times. The choice of the best technology is therefore driven by the specific needs of a system. In the case of readout-limited detectors a low photoconductive gain increases the signal-to-noise ratio and a QWIP FPA can have a better noise equivalent difference temperature than an HgCdTe FPA with a charge well of similar size. Both HgCdTe photodiodes and QWIP’s offer multicolor capability in the MWIR and LWIR range. Powerful possibilities offered by QWIP technology are associated with VLWIR FPA applications and with multicolor detection. The intrinsic advantage of QWIP’s in this niche is due to the relative ease of growing multicolor structures with a very low defect density.
Recombination pattern of the TCR γ locus in human peripheral T‐cell lymphomas (1994)

The recombination events of the gamma and beta T-cell receptor (TCR) loci were analysed in a series of 39 peripheral T-cell lymphomas (PTCLs) in association with the expression of TCR chains. In TCR alpha beta PTCLs, 22/23 cases showed a gamma-gene rearrangement while only 18/23 showed a concomitant beta-gene rearrangement. The germline configuration of the beta locus was found in angiommunoblastic lymphadenopathy and lymphoepithelioid lymphomas. Three gamma delta PTCLs rearranged both gamma and beta genes. TCR silent PTCLs showed three different patterns of gamma- and beta-gene rearrangements. Three cases were in germline configuration for both loci; five cases had a rearranged gamma and a germline beta locus; and five cases had the two loci rearranged. Regarding the variable genes in the gamma-rearranged alleles, members of the V gamma I subgroup were the most frequently presented (39/50), followed by V gamma II, V gamma III, and V gamma IV (9/50, 1/50, and 1/50, respectively). Joining segment usage was as follows: J1 or J2 (32/50), JP1 or JP2 (17/50), and JP (1/50). Taken together, these data demonstrate that the gamma locus is more frequently rearranged whatever the TCR expression. The gamma-locus analysis provides a better diagnostic yield than the beta locus in the study of PTCL clonality.
Growth of carbon nanotubes by gas source molecular beam epitaxy (2001)

Multiwall carbon nanotubes have been grown by gas source molecular beam epitaxy in the presence of Ni catalyst. Some nanotubes show thinner bases compared with their heads. First- and second-order Raman scattering spectra are used to study the structure of samples with different initial thicknesses of Ni layers. The second-order 2D Raman mode of carbon nanotubes shows a downshift compared with the graphite-like structure. The growth of carbon nanotubes is found to depend on the size of the metal droplets. When the initial Ni layer is either too thick or too thin, few carbon nanotubes are observed. The Raman spectra show graphite and glassy carbon structures for too thick and too thin initial Ni layer films, respectively. Only when a proper range of Ni catalyst film is used, carbon nanotubes could be found.
An Integrated Nanoliter DNA Analysis Device (1998)

A device was developed that uses microfabricated fluidic channels, heaters, temperature sensors, and fluorescence detectors to analyze nanoliter-size DNA samples. The device is capable of measuring aqueous reagent and DNA-containing solutions, mixing the solutions together, amplifying or digesting the DNA to form discrete products, and separating and detecting those products. No external lenses, heaters, or mechanical pumps are necessary for complete sample processing and analysis. Because all of the components are made using conventional photolithographic production techniques, they operate as a single closed system. The components have the potential for assembly into complex, low-power, integrated analysis systems at low unit cost. The availability of portable, reliable instruments may facilitate the use of DNA analysis in applications such as rapid medical diagnostics and point-of-use agricultural testing.
A putative new growth factor in ascitic fluid from ovarian cancer patients: identification, characterization, and mechanism of action. (1988)

Ascitic fluid form ovarian cancer patients (n = 16), but not from patients with other cancers or with benign diseases, contains a growth-promoting activity which induces the proliferation of both fresh ovarian cancer cells (n = 5) and the ovarian cancer cell line HEY. The ascitic fluid growth factor(s) appears to signal cells through binding and activation of specific, saturable, high-affinity cell surface receptors. Incubation of fresh or cultured ovarian cancer cells with a partially purified preparation of ascitic fluid stimulates phosphatidylinositol turnover and increases cytosolic-free calcium. Each of these biochemical events has been implicated in the action of growth factors. Purified preparations of previously identified growth factors including epidermal growth factor, transforming growth factor-beta, tumor necrosis factor, platelet-derived growth factor, thrombin, insulin, interleukin-1, interleukin-2, vasopressin, angiotensin, alpha- and gamma-interferons, and fibroblast growth factor did not increase cytosolic-free calcium in either fresh ovarian cancer cells or HEY cells. Therefore, ascitic fluid appears to contain one or more previously unidentified growth factors which activate ovarian cancer cells through phosphatidylinositol hydrolysis and resultant changes in cytosolic-free calcium.
Polarization dependence of light emitted from GaAs p-n junctions in quantum wire crystals (1994)

Micro p-n junctions are formed in GaAs nanowhiskers having diameters of about 100 nm by metalorganic vapor phase epitaxy. The result of photoluminescence measurement shows that nanowhiskers with p-n junctions have the same confinement effect as one-dimensional quantum wires, the average effective width of which is about 30 nm. Infrared light emitted from the whisker as a result of carrier injection is observed at 4.2 and 77 K. The most important feature of this emitted light is the dependence of its intensity on the polarization. The intensity of the emitted light whose polarization is perpendicular to the whisker axis is about 20% less than the intensity of light with parallel polarization when the influence of the electrode structure is eliminated. This value is in agreement with the theoretically predicted value of 25%, confirming that a nanowhisker is a kind of quantum wire.
Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263 (navitoclax) (2015)

The anti-apoptotic protein MCL-1 is a key regulator of cancer cell survival and a known resistance factor for small-molecule BCL-2 family inhibitors such as ABT-263 (navitoclax), making it an attractive therapeutic target. However, directly inhibiting this target requires the disruption of high-affinity protein-protein interactions, and therefore designing small molecules potent enough to inhibit MCL-1 in cells has proven extremely challenging. Here, we describe a series of indole-2-carboxylic acids, exemplified by the compound A-1210477, that bind to MCL-1 selectively and with sufficient affinity to disrupt MCL-1-BIM complexes in living cells. A-1210477 induces the hallmarks of intrinsic apoptosis and demonstrates single agent killing of multiple myeloma and non-small cell lung cancer cell lines demonstrated to be MCL-1 dependent by BH3 profiling or siRNA rescue experiments. As predicted, A-1210477 synergizes with the BCL-2/BCL-XL inhibitor navitoclax to kill a variety of cancer cell lines. This work represents the first description of small-molecule MCL-1 inhibitors with sufficient potency to induce clear on-target cellular activity. It also demonstrates the utility of these molecules as chemical tools for dissecting the basic biology of MCL-1 and the promise of small-molecule MCL-1 inhibitors as potential therapeutics for the treatment of cancer.
Biomimetic Tactile Sensor Array (2008)

The performance of robotic and prosthetic hands in unstructured environments is severely limited by their having little or no tactile information compared to the rich tactile feedback of the human hand. We are developing a novel, robust tactile sensor array that mimics the mechanical properties and distributed touch receptors of the human fingertip. It consists of a rigid core surrounded by a weakly conductive fluid contained within an elastomeric skin. The sensor uses the deformable properties of the finger pad as part of the transduction process. Multiple electrodes are mounted on the surface of the rigid core and connected to impedance-measuring circuitry safely embedded within the core. External forces deform the fluid path around the electrodes, resulting in a distributed pattern of impedance changes containing information about those forces and the objects that applied them. Here we describe means to optimize the dynamic range of individual electrode sensors by texturing the inner surface of the silicone skin. Forces ranging from 0.1 to 30 N produced impedances ranging from 5 to 1000 kΩ. Spatial resolution (below 2 mm) and frequency response (above 50 Hz) appeared to be limited only by the viscoelastic properties of the silicone elastomeric skin.