gebhart/patrepeval huggingface dataset:
Stressing the Ubiquitin-Proteasome System without 20S Proteolytic Inhibition Selectively Kills Cervical Cancer Cells (2011)

Cervical cancer cells exhibit an increased requirement for ubiquitin-dependent protein degradation associated with an elevated metabolic turnover rate, and for specific signaling pathways, notably HPV E6-targeted degradation of p53 and PDZ proteins. Natural compounds with antioxidant properties including flavonoids and triterpenoids hold promise as anticancer agents by interfering with ubiquitin-dependent protein degradation. An increasing body of evidence indicates that their α-β unsaturated carbonyl system is the molecular determinant for inhibition of ubiquitin-mediated protein degradation up-stream of the catalytic sites of the 20S proteasome. Herein we report the identification and characterization of a new class of chalcone-based, potent and cell permeable chemical inhibitors of ubiquitin-dependent protein degradation, and a lead compound RAMB1. RAMB1 inhibits ubiquitin-dependent protein degradation without compromising the catalytic activities of the 20S proteasome, a mechanism distinct from that of Bortezomib. Treatment of cervical cancer cells with RAMB1 triggers unfolded protein responses, including aggresome formation and Hsp90 stabilization, and increases p53 steady state levels. RAMB1 treatment results in activation of lysosomal-dependent degradation pathways as a mechanism to compensate for increasing levels of poly-ubiquitin enriched toxic aggregates. Importantly, RAMB1 synergistically triggers cell death of cervical cancer cells when combined with the lysosome inhibitor Chloroquine.
A Realization of Multilateral Force Feedback Control for Cooperative Motion (2006)

The paper proposes a novel control design for multilateral system considering different degrees of freedom (DOF) and structure. The conventional coordinate transformation with respect to the Cartesian coordinate system is not always suitable for bilateral and/or multilateral control for dexterous tasks including grasping motion. The paper introduces spatial mode transformation, which is corresponding to human's tasks. The spatial modes are abstracted by using mode quarry matrices. The order of the mode quarry matrices means the task DOF, and the decoupled modes correspond to "translational task", "yawing task", "grasping task", and so on. Thus the problems for motion integration of different DOF and structure are solved to design multilateral controller in the spatial mode coordinate systems. Furthermore, the proposed multilateral control is designed based on acceleration control to realize both the force servoing and the position regulator for action-reaction law in remote environment simultaneously. The proposed multilateral control is applied for a multimaster/single-slave system, where the DOF is different from each other. As a result, a complicated task for slave system is easily realized by two master system with vivid force feedback based on modal control design of the multilateral system. The experimental results show viability of the proposed method.
How much is a patent worth? (2014)

‘A book may be good for nothing; or there may be only one thing in it worth knowing; are we to read it all through?’ (Samuel Johnson) This section is dedicated to the review of ideas, articles, books, films and other media. It will include replies (and rejoinders) to articles, the evaluation of new ideas or proposals, and reviews of books and articles both directly and indirectly related to intellectual property law. The book fills a gap between the ‘how to’ guides, aimed towards patent attorneys, and the guides to complex valuation and economics of intellectual property. Goldstein's book is thus of interest to the directors of companies, to investors and non-practising entities. It can also help the heads of research and development (R&D) by showing how a patent application fits into a bigger picture. The book is of interest to patent attorneys as well. In fact, there are several...
Abstract 857: Notch Regulates Cardiac Progenitor Cell Commitment and Myocyte Formation in the Embryonic Mouse Heart (2007)

The effect of GABAA receptor activation varies from inhibition to excitation depending on the state of the transmembrane anionic concentration gradient (delta anion). delta anion was genetically altered in cultured dorsal root ganglion neurons via adenoviral vector-mediated expression of ClC-2, a Cl- channel postulated to regulate the Cl- concentration in neurons in which GABAA receptor activation is predominantly inhibitory. ClC-2 expression was verified by the presence of the appropriate mRNA, protein, and membrane conductance. CIC-2 expression resulted in a large negative shift in the Cl- equilibrium potential (ECl) that attenuated the GABA-mediated membrane depolarization and prevented GABAA receptor-mediated action potentials. These results establish that gene transfer of transmembrane ion channels to neurons can be used to demonstrate their physiological function, and that delta anion can be genetically manipulated to alter the function of neuronal GABAA receptors in situ.
EPA Overestimates the Benefit of Biennial Inspection and Maintenance (1996)

The United States Environmental Protection Agency (EPA) computer model of mobile source emissions is used to estimate the benefits of future emissions control programs. Four input assumptions are discussed, each of which tends to overestimate the benefits of biennial testing programs. The assumptions are: each model year drives the same number of miles; high/superemitters, absent initially, increase linearly with mileage; inspection and maintenance (I/M) readings are invariant, and I/M repairs last forever. States opting for these programs should be aware that the predicted benefits may not materialize.
Reducing substrate noise coupling in a 3D-PICS Integrated Passive Device by localized P+ guard rings (2013)

This paper presents an original concept of a P+ guard ring realized in a 300μm depth High Resistivity Silicon Substrate (HRS) in order to reduce the substrate noise coupling in a 3D-PICS Integrated Passive Device technology. Guard rings have been designed to be a reliable and efficient protection against noise signals propagation. Case study presented in this work illustrates its significant role. In this paper, a 3D-PICS IPD test chip was studied as a first passive part prototype of a System-In-Package chip in combination with RF transceiver operating in the ISM band (863-870 MHz). Various configurations of the passive chip layout (including implementation of guard rings) have been characterized by Direct Power Injection. 3D-PICS electrical performances deduced from two-ports S-parameters are reported, as well as the guard rings efficiency measurements extracted from these S-parameters. Coupling isolation performances of the new integrated PICS components are found satisfactory.
Platelet‐derived growth factor receptor‐α promotes lymphatic metastases in papillary thyroid cancer (2012)

Lymph node metastases are common in papillary thyroid cancer (PTC) and can be resistant to surgical extirpation or radioiodine ablation. We examined the role of platelet-derived growth factor receptor (PDGFR) in mediating lymph node metastases in PTC. Clinical specimens of PTC (n = 137) were surveyed in a tissue array and by western blots to examine the relationship between expression of the α and β subunits of PDGFR and lymph node metastases. PDGFR-α was found at high levels in primary tumours with known lymphatic metastases but not in those tumours lacking nodal involvement (p < 0.0001). However, PDGFR-β expression was not linked to metastatic disease (p = 0.78) as it was found in virtually all PTC specimens. A matching analysis in fresh PTC specimens (n = 13) confirmed that PDGFR-α expression was strongly linked to metastatic spread (p = 0.0047). PDGFR-α and -β were not found in normal thyroid tissue (p < 0.0001). PTC cell lines selectively expressing PDGFR-α or -β were assessed for invasive potential and activation of downstream signal transduction pathways. PTC cell lines expressing PDGFR-α responded to PDGF-BB stimulation with increased invasive potential and this process can be blocked by the tyrosine kinase receptor inhibitor sunitinib (p < 0.009). Cell lines with only PDGFR-β, or no PDGFR, did not show significant changes in invasive potential. Activation of PDGFR-α led to downstream up-regulation of both the MAPK/ERK and PI3K/Akt pathways and disruption of either pathway is sufficient to block PDGFR-mediated increases in invasive potential. Thus, PDGFR-α is associated with lymph node metastases in papillary thyroid carcinoma and PDGFR-α promotes increased invasive potential in PTC cell lines. PDGFR-α is a strong candidate for a diagnostic biomarker to identify patients at risk of nodal metastases. Our results also strengthen the rationale for selection of tyrosine kinase receptor inhibitors that target PDGFR in the treatment of progressive, metastatic PTC.
Mapping of a Region of the PA-X Protein of Influenza A Virus That Is Important for Its Shutoff Activity (2015)

Influenza A virus PA-X comprises an N-terminal PA endonuclease domain and a C-terminal PA-X-specific domain. PA-X reduces host and viral mRNA accumulation via its endonuclease function. Here, we found that the N-terminal 15 amino acids, particularly six basic amino acids, in the C-terminal PA-X-specific region are important for PA-X shutoff activity. These six basic amino acids enabled a PA deletion mutant to suppress protein expression at a level comparable to that of wild-type PA-X.
A new tumor promoter from the seed oil of Jatropha curcas L., an intramolecular diester of 12-deoxy-16-hydroxyphorbol. (1988)

A new type of phorbol ester, which has a macrocyclic dicarboxylic acid diester structure, was isolated from the seed oil of Jatropha curcas L. (Euphorbiaceae). Based on the results of spectroscopic analyses of the compound and its chemical degradation products, its structure is proposed to be an intramolecular 13,16-diester of 12-deoxy-16-hydroxyphorbol, 12-deoxy-16-hydroxyphorbol-4'-[12',14'-butadienyl]-6'-[16',18',20' - nonatrienyl]-bicyclo[3.1.0]hexane-(13-O)-2'-[carboxylate]-(16-O)-3 '- [8'-butenoic-10']ate (DHPB). DHPB showed slightly weaker biological and biochemical activities than 12-O-tetradecanoylphorbol-13-acetate (TPA). DHPB induced ornithine decarboxylase in mouse skin (2.8 nmol CO2/30 min/mg protein/34 nmol application), inhibited the specific binding of [3H]-12-O-tetradecanoylphorbol-13-acetate to phorbol ester receptors (50% effective dose, 17.0 nM), and activated protein kinase C in vitro (50% effective dose, 36.0 nM). Also, a weak tumor-promoting activity of DHPB was found in a two-stage carcinogenesis experiment on mouse skin. One week after initiation of mice with 100 micrograms of 7,12-dimethyl-benz(a)anthracene, topical application, twice a week, of 2 micrograms of DHPB until week 17, followed by application of 5 microgram of DHPB until week 30 at the same rate, resulted in 46.7% incidence of tumors by week 30. The groups treated with 7,12-dimethylbenz(a)anthracene alone or DHPB alone did not produce significant numbers of tumors. These results indicate that the new phorbol ester, DHPB, is a tumor promoter with weaker activity than 12-O-tetradecanoylphorbol-13-acetate.
Resonator Embedded Photonic Crystal Surface Emitting Lasers (2022)

Resonator embedded photonic crystal surface emitting lasers are reported. Reduced threshold current and enhanced slope efficiencies are demonstrated in InP-based 1310nm PCSELs. Band-structure analysis of 1550nm devices demonstrates that frequency selective cavity enhancement of band-edges (and hence lasing mode selection) may be obtained.
Cilkmem: Algorithms for Analyzing the Memory High-Water Mark of Fork-Join Parallel Programs (2019)

Software engineers designing recursive fork-join programs destined to run on massively parallel computing systems must be cognizant of how their program's memory requirements scale in a many-processor execution. Although tools exist for measuring memory usage during one particular execution of a parallel program, such tools cannot bound the worst-case memory usage over all possible parallel executions. This paper introduces Cilkmem, a tool that analyzes the execution of a deterministic Cilk program to determine its p-processor memory high-water mark (MHWM), which is the worst-case memory usage of the program over all possible p-processor executions. Cilkmem employs two new algorithms for computing the p-processor MHWM. The first algorithm calculates the exact p-processor MHWM in O(T1 ·p) time, where T1 is the total work of the program. The second algorithm solves, in O(T1) time, the approximate threshold problem, which asks, for a given memory threshold M, whether the p-processor MHWM exceeds M/2 or whether it is guaranteed to be less than M. Both algorithms are memory efficient, requiring O(p·D) and O(D) space, respectively, where D is the maximum call-stack depth of the program's execution on a single thread. Our empirical studies show that Cilkmem generally exhibits low overheads. Across ten application benchmarks from the Cilk-bench suite, the exact algorithm incurs a geometric-mean multiplicative overhead of 1.54 for p=128, whereas the approximation-threshold algorithm incurs an overhead of 1.36 independent of p. In addition, we use Cilkmem to reveal and diagnose a previously unknown issue in a large image-alignment program contributing to unexpectedly high memory usage under parallel executions.
Assessing the effect of vibrotactile feedback during continuous multidirectional platform motion: A frequency domain approach (2009)

This study uses frequency domain techniques to demonstrate the effect of vibrotactile feedback during continuous multidirectional perturbations of a support platform. Eight subjects with bilateral or unilateral vestibular loss were subjected to two-axis pseudo random surface platform motion while donning a multi-axis feedback balance aid that mapped body tilt estimates onto their trunks via a 3-row by 16-column array of tactile vibrators (tactors). Four tactor display configurations with spatial resolutions ranging between 22.5 degrees and 90 degrees , in addition to the tactors off configuration, were evaluated. Power spectral density (PSD) functions of body sway in the anterior-posterior (A/P) and medial-lateral (M/L) directions were computed at frequencies ranging from 0.0178 Hz to 3.56 Hz. Transfer functions between the platform motion and body sway were also computed. Vibrotactile feedback produced significant decreases in A/P and M/L spectral power, decreased transfer function gains up to a frequency of 1.8 Hz and 0.6 Hz in the A/P and M/L directions, respectively, and increased phase leads above 0.3 Hz. The lack of a consistent difference among tactor configurations argue in favor of the simplest 4-column configuration during multidirectional continuous surface perturbations.
Abstract 5743: Positron emission tomography (PET) imaging analogs of glutamine: Development and evaluation as probes for cancer imaging (2012)

Abstract Emerging evidence suggests that nutrient uptake in cancer cells is controlled by oncogenic signaling pathways. The natural amino acid glutamine is an essential nutrient for cell growth and proliferation. Glutamine also participates in protein synthesis and is a nitrogen source for the production of select nucleotides and amino acids. Consequently, quantitative measures of glutamine uptake may reflect critical processes in oncology. Recently, a fluorinated glutamine analog for positron emission tomography (PET) was shown to possess both highly specific cellular uptake in glioma cell lines and in vivo tumor localization (J Am Chem Soc 2011;133:1122-1133). Synthetic methodology leading to this agent, an optically pure 4-fluoro-glutamine derivative, was also reported. Though effective, this convergent synthesis requires multiple steps, extensive chromatographic separation, and nearly a week of reaction time. Employing a chiral auxiliary Schiff base and microwave-assisted organic synthesis, we have significantly improved the synthesis of this and similar agents, drastically reducing the number of synthetic steps (from ten to four) and the overall reaction time (from seven days to two hours). While the radiochemistry relies upon traditional box methods, we are also currently employing high-throughput microfluidic radiolabeling strategies to expedite probe production and labeling efficiency. Finally, using optically pure [18F]4-FGln (2S,4R) synthesized by our improved synthesis, we report preclinical PET images of models of human colorectal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5743. doi:1538-7445.AM2012-5743
A scalable, timing-safe, network-on-chip architecture with an integrated clock distribution method (2007)

Growing system sizes together with increasing performance variability are making globally synchronous operation hard to realize. Mesochronous clocking constitutes a possible solution to the problems faced. The most fundamental of problems faced when communicating between mesochronously clocked regions concerns the possibility of data corruption caused by metastability. This paper presents an integrated communication and mesochronous clocking strategy, which avoids timing related errors while maintaining a globally synchronous system perspective. The architecture is scalable as timing integrity is based purely on local observations. It is demonstrated with a 90 nm CMOS standard cell network-on-chip design which implements completely timing-safe, global communication in a modular system.
Thermal Isolation and Cooling Technologies for Heterogeneous 3D‐ and 2.5D‐ICs (2019)

Heat removal and thermal isolation are two distinct challenges facing heterogeneous 3D- and 2.5D-ICs. This chapter summarizes the thermal challenges in heterogeneous three-dimensional (3D) and 2.5D die integration architectures. To solve these challenges, interposer- and tier-embedded microfluidic cooling technologies are proposed in conjunction with thermal isolation technologies. Two novel architectures for 3D and 2.5D integration are proposed and thermally evaluated through modeling and experimental demonstrations. To ease the thermal challenges, microfluidic cooling and isolation technologies were proposed. Moreover, fine-pitch electrical and fluidic IOs were introduced to address the signaling and fluidic interconnection requirements. To to address off-chip signaling bandwidth and fluidic interconnection requirements, fine-pitch electrical and fluidic IOs are designed, fabricated, and tested. To reduce the capacitance of TSVs, the chapter also presents the fabrication of high aspect ratio (23:1) TSVs within a microfluidic heat sink (MFHS).
Signal Peptide Efficiency: from High-throughput Data to Prediction and Explanation (2022)

ABSTRACT The passage of proteins across biological membranes via the general secretory (Sec) pathway is a universally conserved process with critical functions in cell physiology and important industrial applications. Proteins are directed into the Sec pathway by a signal peptide at their N-terminus. Estimating the impact of physicochemical signal peptide features on protein secretion levels has not been achieved so far, partially due to the extreme sequence variability of signal peptides. To elucidate relevant features of the signal peptide sequence that influence secretion efficiency, an evaluation of ~12,000 different designed signal peptides was performed using a novel miniaturized high-throughput assay. The results were used to train a machine learning model, and a post-hoc explanation of the model is provided. By describing each signal peptide with a selection of 156 physicochemical features, it is now possible to both quantify feature importance and predict the protein secretion levels directed by each signal peptide. Our analyses allow the detection and explanation of the relevant signal peptide features influencing the efficiency of protein secretion, generating a versatile tool for the in silico evaluation of signal peptides.
Dynamics of thin filopodia during sea urchin gastrulation (1995)

At gastrulation in the sea urchin embryo, a dramatic rearrangement of cells establishes the three germ layers of the organism. Experiments have revealed a number of cell interactions at this stage that transfer patterning information from cell to cell. Of particular significance, primary mesenchyme cells, which are responsible for production of the embryonic skeleton, have been shown to obtain extensive positional information from the embryonic ectoderm. In the present study, high resolution Nomarski imaging reveals the presence of very thin filopodia (02-0.4 micron in diameter) extending from primary mesenchyme cells as well as from ectodermal and secondary mesenchyme cells. These thin filopodia sometimes extend to more than 80 microns in length and show average growth and retraction rates of nearly 10 microns/minute. The filopodia are highly dynamic, rapidly changing from extension to resorption; frequently, the resorption changes to resumption of assembly. The behavior, location and timing of active thin filopodial movements does not correlate with cell locomotion; instead, there is a strong correlation suggesting their involvement in cell-cell interactions associated with signaling and patterning at gastrulation. Nickel-treatment, which is known to create a patterning defect in skeletogenesis due to alterations in the ectoderm, alters the normal position-dependent differences in the thin filopodia. The effect is present in recombinant embryos in which the ectoderm alone was treated with nickel, and is absent in recombinant embryos in which only the primary mesenchyme cells were treated, suggesting that the filopodial length is substratum dependent rather than being primary mesenchyme cell autonomous. The thin filopodia provide a means by which cells can contact others several cell diameters away, suggesting that some of the signaling previously thought to be mediated by diffusible signals may instead by the result of direct receptor-ligand interactions between cell membranes.
The contribution of microbial biotechnology to economic growth and employment creation (2017)

Our communication discusses the profound impact of bio-based economies – in particular microbial biotechnologies – on SDG 8: Promote sustained, inclusive and sustainable economic growth, full and productive employment and decent work for all. A bio-based economy provides significant potential for improving labour supply, education and investment, and thereby for substantially increasing the demographic dividend. This, in turn, improves the sustainable development of economies.
1-(Alkyl/Arylthiocarbamoyl)benzotriazoles as Stable Isothiocyanate Equivalents:  Synthesis of Di- and Trisubstituted Thioureas (2004)

1-(Alkyl/arylthiocarbamoyl)benzotriazoles 4a-i were synthesized in yields of 91-99% from bis(benzotriazolyl)methanethione (3). Reagents 4a-g were then used as isothiocyanate equivalents for the efficient synthesis of 10 secondary and 14 tertiary thioureas in high-yielding, convenient processes.