gebhart/patrepeval huggingface dataset:
Selective Inactivation of p53 Facilitates Mouse Epithelial Tumor Progression without Chromosomal Instability (2001)

We examined the selective pressure for, and the impact of, p53 inactivation during epithelial tumor evolution in a transgenic brain tumor model. In TgT(121) mice, cell-specific inactivation of the pRb pathway in brain choroid plexus epithelium initiates tumorigenesis and induces p53-dependent apoptosis. We previously showed that p53 deficiency accelerates tumor growth due to diminished apoptosis. Here we show that in a p53(+/-) background, slow-growing dysplastic tissue undergoes clonal progression to solid angiogenic tumors in all animals. p53 is inactivated in all progressed tumors, with loss of the wild-type allele occurring in 90% of tumors. Moreover, similar progression occurs in 38% of TgT(121)p53(+/+) mice, also with loss of at least one p53 allele and inactivation of p53. Thus, the selective pressure for p53 inactivation, likely based on its apoptotic function, is high. Yet, in all cases, p53 inactivation correlates with progression beyond apoptosis reduction, from dysplasia to solid vascularized tumors. Hence, p53 suppresses tumor progression in this tissue by multiple mechanisms. Previous studies of fibroblasts and hematopoietic cells show that p53 deficiency can be associated with chromosomal instability, a mechanism that may drive tumor progression. To determine whether genomic gains or losses are present in tumors that progress in the absence of p53, we performed comparative genomic hybridization analysis. Surprisingly, the only detectable chromosomal imbalance was partial or complete loss of chromosome 11, which harbors the p53 gene and is thus the selected event. Flow cytometry confirmed that the majority of tumor cells were diploid. These studies indicate that loss of p53 function is frequent under natural selective pressures and furthermore that p53 loss can facilitate epithelial tumor progression by a mechanism in addition to apoptosis reduction and distinct from chromosomal instability.
Sensorless adaptive optics with a laser free spinning disk confocal microscope (2020)

Specimen induced aberrations can have detrimental effects in all types of high-resolution microscope. In this study, we present a sensorless technique that uses a deformable mirror (DM) to correct aberrations of both the system and sample. Using a laser-free confocal microscope, with patterned disk illumination and detection. The system is based on a commercial confocal module (Clarity, Aurox Ltd., UK) that uses Light Emitting Diode (LED) illumination to obtain optically sectioned 3D images. The results obtained show that the setup was able to correct aberrations of biological samples used in the study. These systems will help researchers working on various biological systems to obtain improved quality images when focussing deep into thick specimens.
Assessment of bio-activities of the crude extract and components of Withania somnifera leaves by bioinformatics (2011)

Traditional herbal medicines are now increasingly being appreciated with Western models of integrative health sciences and evidence-based approach both in the basic research and clinic scenario. Ashwagandha is a commonly used plant in Ayurvedic, Indian traditional medicine. Medicinal value of Ashwagandha (WithaniasomniferaDunal) extends from anti-inflammatory, anti-arthritic, anti-rheumatic, rejuvenation and anti-cancer. Based on the belief that holistic multi-site mechanism of action offers greater chance of success, the traditional Ayurvedicmedicine practices the use of whole herb or its crude extract. It opposes with the mainstream of pharmaceutical industry that uses single and purified molecules. In the present study, we used bioinformatics approach to reveal the mechanism of action of (i) crude extract of Ashwagandha leaf extract and its purified components, (ii) Withanone and (iii) Withaferin A. Whereas p53-p21 was identified as a common signaling pathway for the three kinds of reagents, specific signaling pathways for Withaferin-A and Withanone were identified. Whereas the crude extract and Withanone were selectively toxic to human cancer cells, WithaferinA showed cytotoxicity to the normal cells too. The study suggested that the crude extract or a combinational formulamay be a superior and safenatural reagent for cancer treatment.
Ribosylation by mycobacterial strains as a new mechanism of rifampin inactivation (1995)

Several fast-growing Mycobacterium strains were found to inactivate rifampin. Two inactivated compounds (RIP-Ma and RIP-Mb) produced by these organisms were different from previously reported derivatives, i.e., phosphorylated or glucosylated derivatives, of the antibiotic. The structures of RIP-Ma and RIP-Mb were determined to be those of 3-formyl-23-[O-(alpha-D-ribofuranosyl)]rifamycin SV and 23-[O-(alpha-D-ribofuranosyl)]rifampin, respectively. To our knowledge, this is the first known example of ribosylation as a mechanism of antibiotic inactivation.
Tracking Tetrahymena Pyriformis Cells using Decision Trees (2016)

Matching cells over time has long been the most dif-ficult step in cell tracking. In this paper, we approach this problem by recasting it as a classification problem. We construct a feature set for each cell, and compute a feature difference vector between a cell in the current frame and a cell in a previous frame. Then we deter-mine whether the two cells represent the same cell over time by training decision trees as our binary classifiers. With the output of decision trees, we are able to formu-late an assignment problem for our cell association task and solve it using a modified version of the Hungarian algorithm. 1
Real-time path planning for a robotic arm (2011)

With robotics technology, services can be provided to care for individuals with disabilities. This paper describes an effort to improve path planning performance for a robotic arm, resulting in faster user response in real-time. For a robotic arm, particularly with multiple degrees of freedom, path planning is computationally expensive. We propose that it is possible to achieve rapid response times with an assistive robotic arm by caching frequent arm trajectories and creating a "roadmap" of arm movements. By calculating trajectories to possible target goals in advance, we anticipate an improvement in user response times.
CHAT: a conversational helper for automotive tasks (2006)

Spoken dialogue interfaces, mostly command-and-control, become more visible in applications where attention needs to be shared with other tasks, such as driving a car. The deployment of the simple dialog systems, instead of more sophisticated ones, is partly because the computing platforms used for such tasks have been less powerful and partly because certain issues from these cognitively challenging tasks have not been well addressed even in the most advanced dialog systems. This paper reports the progress of our research effort in developing a robust, wide-coverage, and cognitive load-sensitive spoken dialog interface called CHAT: Conversational Helper for Automotive Tasks. Our research in the past few years has led to promising results, including high task completion rate, dialog efficiency, and improved user experience. Index Terms: dialog systems, cognitive load, robustness
Insights on film growth conditions on a floating substrate during reactive Ar/O2 bipolar high power impulse magnetron sputter deposition (2023)

Abstract We report several effects found in reactive bipolar high-power impulse magnetron sputtering (abbreviated as bipolar HiPIMS or BPH) discharges at the substrate level. The role of the negative peak current and the positive pulse voltage, U <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:msub> <mml:mi> </mml:mi> <mml:mo>+</mml:mo> </mml:msub> </mml:math> , on the deposition flux at the electrically insulating substrate is discussed and the results are compared to conventional DC discharges. In particular, the normalized energy flux, ϕ n , delivered to the substrate is found higher under BPH conditions at U <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:msub> <mml:mi/> <mml:mo>+</mml:mo> </mml:msub> </mml:math> = +300 V ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:msub> <mml:mi>φ</mml:mi> <mml:mi>n</mml:mi> </mml:msub> <mml:mo>=</mml:mo> <mml:mn>3.43</mml:mn> <mml:mo>×</mml:mo> <mml:msup> <mml:mn>10</mml:mn> <mml:mrow> <mml:mn>15</mml:mn> </mml:mrow> </mml:msup> </mml:math> eV·nm −3 ) as compared to the HiPIMS ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:msub> <mml:mi>φ</mml:mi> <mml:mi>n</mml:mi> </mml:msub> <mml:mo>=</mml:mo> <mml:mn>0.78</mml:mn> <mml:mo>×</mml:mo> <mml:msup> <mml:mn>10</mml:mn> <mml:mrow> <mml:mn>15</mml:mn> </mml:mrow> </mml:msup> </mml:math> eV·nm −3 ) and DCMS ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:msub> <mml:mi>φ</mml:mi> <mml:mi>n</mml:mi> </mml:msub> <mml:mo>=</mml:mo> <mml:mn>1.23</mml:mn> <mml:mo>×</mml:mo> <mml:msup> <mml:mn>10</mml:mn> <mml:mrow> <mml:mn>15</mml:mn> </mml:mrow> </mml:msup> </mml:math> eV·nm −3 ) regimes which is assumed to be provoked by an intensification of the positive ion bombardment. Accordingly, the mean energy and the count of positively charged metal and gaseous ions increase in line with U <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:msub> <mml:mi/> <mml:mo>+</mml:mo> </mml:msub> </mml:math> as measured by energy-resolved mass spectrometry. Contrariwise, our analysis has shown a significant decrease (≈20 %) of negative oxygen ion count under BPH conditions.
Toward an experimental methodology for studying persuasion-based online security (2009)

In this paper we highlight a controlled experimental design in development to investigate how the intersection of a brand's familiarity and persuasive appeal impact user willingness to engage in increased web security procedures. We offer the results of a 2 (Source: familiar vs. unfamiliar brand) x 2 (Persuasive Strategy: benefit to user vs. benefit to site) web experiment (N=48) using this approach to demonstrate its viability and generate ideas for future directions. Lessons learned and opportunities to improve this experimental methodology to further psychological research in the web security domain are discussed.
Ultrasonic hearing: transient evoked otoacoustic emissions elicited by bone-conducted ultrasonic stimuli (1997)

The existence of Transient Evoked Otoacoustic Emissions (TEOAEs) due to bone-conducted near-ultrasonic stimulation is assumed and a suitable investigation method is developed. Ultrasonic bone-elicited TEOAEs are recorded and their main features examined. Results show similarities of the ultrasonic bone-elicited TEOAEs to conventionally-elicited TEOAEs regarding stimulus and response amplitude dependency, duration of the stimulus artifact and of the active response of the ear. The frequency spectrum of TEOAEs show high frequency components, suggesting the method's potential as a fast screening method for the whole audiometric frequency range.
Loop Optimizations for Acyclic Object-Oriented Queries (1996)

Nested loop execution of object-oriented queries retains the promise of maintaining the full generality of the object paradigm, independent of the specifics of any single object model. Thus, from this starting point we have developed an object-oriented query optimizer and execution engine. The methods, developed to date for only acyclic queries, augment nested loops structures with a simple marking mechanism such that unnecessary loop iterations are not repeated. In the case of acyclic queries, the executions are asymptotically optimal. In contrast to optimal query methods based on semijoin reductions our method involves no preprocessing step and thus avoids the extra I/O associated with semijoins and prevents the formal benefits of semijoin reduction from appearing as a practical improvement. Empirical results comparing our query environment with a commercially available product demonstrate significant performance improvement. 1 Introduction We develop a technique for the optimizatio...
An efficient gene transfer method mediated by ultrasound and microbubbles into the kidney (2004)

Overall, an ultrasound-mediated gene transfer method with Optison enhanced the efficiency of gene transfer and expression in the rat kidney. This novel non-viral method may be useful for gene therapy for renal disease.
Preparation and properties of pure, full‐length Ic1R protein of escherichia coli. Use of time‐of‐flight mass spectrometry to investigate the problems encountered (1996)

IclR protein, the repressor of the aceBAK operon of Escherichia coli, has been examined by time-of-flight mass spectrometry, with ionization by matrix assisted laser desorption or by electrospray. The purified protein was found to have a smaller mass than that predicted from the base sequence of the cloned iclR gene. Additional measurements were made on mixtures of peptides derived from IclR by treatment with trypsin and cyanogen bromide. They showed that the amino acid sequence is that predicted from the gene sequence, except that the protein has suffered truncation by removal of the N-terminal eight or, in some cases, nine amino acid residues. The peptide bond whose hydrolysis would remove eight residues is a typical target for the E. coli protease OmpT. We find that, by taking precautions to minimize Omp T proteolysis, or by eliminating it through mutation of the host strain, we can isolate full-length IclR protein (lacking only the N-terminal methionine residue). Full-length IclR is a much better DNA-binding protein than the truncated versions: it binds the aceBAK operator sequence 44-fold more tightly, presumably because of additional contacts that the N-terminal residues make with the DNA. Our experience thus demonstrates the advantages of using mass spectrometry to characterize newly purified proteins produced from cloned genes, especially where proteolysis or other covalent modification is a concern. This technique gives mass spectra from complex peptide mixtures that can be analyzed completely, without any fractionation of the mixtures, by reference to the amino acid sequence inferred from the base sequence of the cloned gene.
Periostin Expression in Non-Small Cell Lung Cancer: Clinical Significance (2017)

Periostin is an extracellular matrix N-glycoprotein that is a major constituent of the desmoplastic stroma around solid tumors. Periostin promotes tumor invasion and metastasis via epithelial-mesenchymal transition. The aims of this study were to evaluate periostin expression immunohistochemically and quantitatively in patients with non-small cell lung cancer (NSCLC) and to assess any associations with clinical features and prognosis. A total of 184 specimens of NSCLC tissue were investigated, including 134 adenocarcinomas, 39 squamous cell carcinomas, and 11 other histologic subtypes. The intra-tumoral periostin expression area in each captured field was calculated using the image processing integration software WinROOF. The mean periostin expression score was classified as high or low by the median value of its expression area. Univariate analysis demonstrated that gender, tumor size, T status, N status, stage, histologic type, smoking habits, percent vital capacity, 1% forced expiratory volume, and pleural invasion were each significantly associated with periostin scores. Multivariate analysis revealed that high periostin expression score was an independent prognostic factor significantly associated with decreased cancer-specific survival (HR, 3.65; 95% CI, 1.04-12.84; P=0.0439). We concluded that intratumoral periostin expression was an independent prognostic factor for NSCLC.
Amyloid Fibril-Forming Hexapeptides Modulate The Immune Response And Reduce Symptoms In An Animal Model Of Multiple Sclerosis (S14.002) (2014)

OBJECTIVE: To determine the immune pathways modulated by amyloid fibril-forming peptides composed of six amino acids that have been found to be anti-inflammatory and therapeutic in an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). BACKGROUND: Our earlier work showed that amyloid fibril formation of a small peptide corresponding to residues 73-92 from the small heat shock protein alpha B crystallin (HspB5) correlated with chaperone activity and amelioration of EAE. However, exchange of one hydrophobic amino acid at position 77, 79, or 81 with a lysine disrupted amyloid formation, chaperone function, and therapeutic efficacy of the peptide. To eliminate the toxicity of amyloid fibrils formed by larger peptides and proteins, we used the minimum number of amino acids capable of forming amyloid fibrils. Peptides composed of six amino acids that form amyloid fibrils were shown to have chaperone activity and were therapeutic in EAE. RESULTS: The levels of IL-6, IL-2, TNF alpha, and IFN gamma were all decreased following treatment with the hexapeptide tau 623-628. We also show that tau 623-628 induces type I interferon (IFN), which is a treatment in MS and indicates a distinct effect not seen in HspB5 treatment. Tau 623-628 was therapeutic in Th1 adoptively transferred EAE, but ineffective in Th17 adoptively transferred EAE, which corresponds with the observation that type I IFN is beneficial in Th1 EAE, but not in Th17 EAE (Axtell et al., Nat Med 2010; 16: 406-412). Amylin 28-33, a polar, non-ionizable peptide, induces very low levels of type I IFN and is therapeutic in Th17 EAE, indicating other immune pathways play a role in amelioration of EAE. CONCLUSIONS: The mode of action of the amyloid-forming hexapeptides is similar to HspB5 in its capacity to bind pro-inflammatory proteins in the plasma, which could have pleiotropic effects including the reduction of pro-inflammatory cytokines. However, the amyloidogenic peptides also modulate diverse immunological pathways, which can differ based upon the composition of the hexapeptides.
A 20 V, 8 MHz resonant DCDC converter with predictive control for 1 ns resolution soft-switching (2015)

Fast switching power supplies allow to reduce the size and cost of external passive components. However, the capacitive switching losses of the power stage will increase and become the dominant part of the total losses. Therefore, resonant topologies are the known key to reduce the losses of the power stage. A power switch with an additional resonant circuit can be turned on under soft-switching conditions, ideally with zero-voltage-switching (ZVS). As conventional resonant converts are only efficient for a constant load, this paper presents a predictive regulation loop to approach soft-switching conditions under varying load and component tolerances. A sample and hold based detection circuit is utilized to control the turn-on of the power switch by a digital regulation. The proposed design was fabricated in a 180 nm high-voltage BiCMOS technology. The efficiency of the converter was measured to be increased by up to 16 % vs. worst case timing and by 13 % compared to a conventional hard-switching buck converter at 20 V input voltage and at approximately 8 MHz switching frequency.
Distributed Gradient Descent: Nonconvergence to Saddle Points and the Stable-Manifold Theorem (2019)

The paper studies continuous-time distributed gradient descent (DGD) and considers the problem of showing that in nonconvex optimization problems, DGD typically converges to local minima rather than saddle points. In centralized settings, the problem of demonstrating nonconvergence to saddle points is typically handled by way of the stable-manifold theorem from classical dynamical systems theory. However, the classical stable-manifold theorem is not applicable in the distributed setting. The paper develops an appropriate stable-manifold theorem for DGD. This shows that convergence to saddle points may only occur from a low-dimensional stable manifold. Under appropriate assumptions (e.g., coercivity), the result implies that DGD almost always converges to local minima.
Electron Transfer between RE3+ Ions in Oxide Hosts: Experiments and Initial Quantitative Analysis (2009)

We discuss the electron transfer (ET) reactions between the excited Ce3+(5d1) level and Yb3+/Eu3+ in oxide hosts. The exothermic free energy of this ET reaction is estimated using spectroscopic parameters, while the re-organizational energy is estimated using the Marcus theory for ET in molecular systems and solvents. Using these parameters and a semi-classical model for the ET rate, we quantitatively analyze these ET processes.
Flux Chamber Design and Operation for the Measurement of Municipal Solid Waste Landfill Gas Emission Rates (1992)

This paper describes a hybrid Flux Chamber-Soil Gas Probe methodology for measuring municipal solid waste (MSW) gas emission rates. Following the design of the flux chamber, the chamber was laboratory tested to define its mixing characteristics and optimum operating parameter values. Flux chamber operating parameters included: chamber pressure, sweep air flow rate, landfill surface insertion depth, and sweep air velocity. Optimum operating parameter values were determined by operating the flux chamber on a simulated subsurface emission source and varying the operating parameters. The laboratory tests indicated that the flux chamber could be operated to provide zero biasing of gas emission rates, resulting in accurate measurement of gas emission rates.
Laboratory Evolution of Escherichia coli Thioredoxin for Enhanced Catalysis of Protein Oxidation in the Periplasm Reveals a Phylogenetically Conserved Substrate (2008)

Thioredoxin exported into the Escherichia coli periplasm catalyzes the oxidation of protein thiols in a DsbB-dependent function. However, the oxidative activity of periplasmic thioredoxin is insufficient to render dsbA cells susceptible to infection by M13, a phenotype that is critically dependent on disulfide bond formation in the cell envelope. We sought to examine the molecular determinants that are required in order to convert thioredoxin from a reductant into an efficient periplasmic oxidant. A genetic screen for mutations in thioredoxin that render dsbA cells sensitive to infection by M13 led to the isolation of a single amino acid substitution, G74S. In vivo the TrxA(G74S) mutant exhibited enhanced catalytic activity in the oxidation of alkaline phosphatase but was unable to oxidize FlgI and restore cell motility. In vitro studies revealed that the G74S substitution does not affect the redox potential of the thioredoxin-active site or its kinetics of oxidation by DsbB. Thus, the gain of function afforded by G74S stems in part from its altered substrate specificity, which also rendered the protein more resistant to reduction by DsbD/DsbC in the periplasm.
Influence of Impact Velocity and Chest Compression on Experimental Pulmonary Injury Severity in Rabbits (1981)

The effect of impact velocity and displacement on pulmonary injury in rabbits was investigated by producing a series of nonpenetrating anteroposterior sternal impacts involving velocities of 5 to 18 m/s and displacements of 2 to 45 mm. Contusion of the bronchial region was dominant at impact velocities below 6 m/s and displacements above 20 mm; contusion of the alveolar region was dominant at impact velocities above 15 m/s and displacements above 2 mm. When impact velocity and displacement were high, both bronchial and alveolar regions were injured. Pulmonary injury severity, expressed as a severity index adopted from the Abbreviated Injury Scale 1976 (AIS), correlated well with impact displacement at a given velocity but poorly with the peak reactive force, impulse transfer, peak esophageal pressure, or the amount of of available energy.