gebhart/patrepeval huggingface dataset:
Adhesion Force Measurements on Single Gecko Setae (2000)

Geckos are known for their exceptional ability to climb up vertical walls. The adhesion mechanism has been the subject of debate for nearly a century. It is commonly assumed in the biology community that this remarkable wall-climbing ability in geckos is attributed to van der Waals forces [l]. In this theory, the tiny hairlike structures on the bottom of gecko feet, known as setae, form van der Waals bonds with the surface to facilitate adhesion. These forces are on the order of pN per seta. Various attempts have been made to experimentally quantify the adhesive forces on whole animals, but none had been able to measure the forces on single setae. Recent development in MEMS technology has produced numerous highly sensitive devices for small force measurements, including a piezoresistive cantilever capable of simultaneous force detections in two directions [2]. We have successfully performed series of adhesion measurements on single setae using this device to support the van der Waals adhesion hypothesis. This paper describes the setup and procedures used to obtain adhesive force measurements on single gecko setae. Experimental results showed that adhesion increases with increasing contact preload and lateral pulling speed. Our data also revealed some interesting characteristics of setal adhesion. The magnitude of the adhesive forces measured supports the hypothesis that individual setae operate by van der Waals forces and sum to generate sufficient forces to explain macroscopic behavior such as clinging or vertical running.
OVERVIEW ON NATIVE CELLULOSE AND MICROCRYSTALLINE CELLULOSE I STRUCTURE STUDIED BY X-RAY DIFFRACTION (WAXD): COMPARISON BETWEEN MEASUREMENT TECHNIQUES (2011)

The crystalline structure of cellulose has been studied for a long time. It is well known that crystallinity of cellulose can be measured using quite a number of methods, X-ray diffraction, solid state 13 C CP-MAS NMR, Fourier transforminfrared (FT-IR) spectroscopy and Raman spectroscopy. The solid state 13 C CP-MAS NMR and FT-IR spectroscopy considers contributions from both crystalline and non-crystalline cellulose regions resulting in relative values, while the alternative X-ray diffraction approach gives more detailed data on features of crystalline and less on the non-crystalline fraction of cellulose. Raman spectroscopy is also used to study cellulose crystallinity. This paper gives an overview on the crystallinity of three cellulose samples, cotton linters, microcrystalline cellulose (cotton linters) and Avicel powder cellulose (Avicel PH101) determined by wide angle X-ray diffraction (WAXD). The study compares literature data with our data for the apparent crystallinity (%) of the mentioned samples from different sources to demonstrate the dissimilarities that can be obtained using different X-ray methods. For the crystallinity analysis, assumption had to be made that all cotton linters and Avicel PH-101 used in the literature were of the same quality, even though it has been reported that the quality of both samples can vary between batches and production locations. The reported crystallinity values of cotton linters were between 56-78 %, for microcrystalline cellulose (MCC), crystallinity varied within the range 65-83 % and Avicel PH-101 powder gave crystallinity values between 37-93 % dependent on the Xray methods and experimental mode used.
Enantioselective Synthesis of (−)-Terpestacin and (−)-Fusaproliferin:  Clarification of Optical Rotational Measurements and Absolute Configurational Assignments Establishes a Homochiral Structural Series (2002)

An enantioselective synthesis of the syncytium formation inhibitor (-)-terpestacin (1, 19 steps, 5.8% yield from the allylation product of (R,R)-pseudoephedrine propionamide, 3) and the fungal metabolite (-)-fusaproliferin (2, 21 steps, 5.3% yield from 3) in their natural configurations is described. The route employs a series of stereoselective enolate alkylation reactions to establish the initial stereogenic center, set the quaternary carbon configuration, close the 15-membered ring, and introduce the side-chain residue with proper stereocontrol. Careful analysis of our synthetic materials alongside natural samples has revealed that several errors were made in the earlier measurements of optical rotation or in the absolute stereochemical assignments of these natural products. Clarifying all discrepancies, we show here that natural terpestacin (1) is levorotatory, not dextrorotatory as originally described, but was correctly assigned as the (1S,11S,15R,23S)-enantiomer. Fusaproliferin (2) is levorotatory, as reported, but is in fact the (1S,11S,15R,23S)-enantiomer and not the antipodal configuration originally assigned.
Determination of procaine hydrochloride using flow injection inhibitory chemiluminescence (2003)

A new flow injection chemiluminescent method has been developed for the determination of procaine hydrochloride, based on the inhibition of the chemiluminescence reaction of luminol-hydrogen peroxide by procaine hydrochloride. The influence of several surfactants and beta-cyclodextrin on the chemiluminescence intensity were studied. It was found that beta-cyclodextrin enhanced the decrease in chemiluminescence intensity. The method is simple, convenient and sensitive, with a detection limit (3 sigma) of 0.08 micro g/mL. The decreased chemiluminescence intensity is linear, with the concentration of procaine hydrochloride in the range 0.2-100.0 micro g/mL and 100.0-400.0 micro g/mL. The relative standard deviation for 10 repeated measurements were 4.5% and 3.4% for 1.0 and 20.0 micro g/mL procaine hydrochloride, respectively. The method has been successfully applied to the determination of procaine hydrochloride in injection solutions of this drug.
Ion funnels for the masses: Experiments and simulations with a simplified ion funnel (2005)

A modified ion funnel is described. Counterintuitively, increased spacing between electrodes results in enhanced "focusing" of the ions through the funnel. Consequently, the internal diameter (i.d.) of the funnel need not decrease to the conductance limit (as in previous designs). A simple dc-only lens, which also serves as the conductance limit, combined with the natural flow of gas is used to extract the ions from the funnel. Ions with mass to charge ratios varying between 75 and 3000 m/z are passed through the funnel with no apparent discrimination. The funnel can be operated under mild conditions that preserve weakly bound noncovalent complexes. After testing several designs, a thin closely spaced dc lens was found to be the best solution for extracting ions. A simple method for simulating ion trajectories at nonzero pressures based on ion mobility and explicit diffusion is described. This theoretical approach was used to design and calculate ion trajectories for the modified funnel presented here. Finally, the increased spacing between electrodes in the current funnel significantly relaxes machining constraints, reduces cost, and enhances ease of use versus previous funnel designs.
Longitudinal Study of Painful Diabetic Neuropathy in the Zucker Diabetic Fatty Rat Model of Type 2 Diabetes: Impaired Basal G-Protein Activity Appears to Underpin Marked Morphine Hyposensitivity at 6 Months (2011)

Clinical management of diabetic neuropathic pain has been challenging. This study provides a mechanistic explanation regarding the effectiveness, or lack thereof, of opioid analgesia in the treatment of diabetic neuropathic pain.
Macrophages orchestrate the immune response to tumor cell death. (2001)

The mechanisms by which the immune system distinguishes normal developmental cell death from pathological immunogenic cell killing are central to effective cancer immunotherapy. Using HSVtk suicide gene therapy, we showed that macrophages can distinguish between tumor cells dying through classical apoptosis and tumor cells engineered to die through nonapoptotic mechanisms, resulting in secretion of either immunosuppressive cytokines (interleukin 10 and transforming growth factor beta) or inflammatory cytokines (tumor necrosis factor alpha or interleukin 1beta), respectively. Additionally heat shock protein 70 acts as one component of a bimodal alarm signal that activates macrophages in the presence of stressful, immunogenic tumor cell killing. These differential responses of macrophages can also be used to vaccinate mice against tumor challenge, using adoptive transfer, as well as to cure mice of established tumors.
On the peak-to-average power of ofdm signals based on oversampling (2003)

Orthogonal frequency-division multiplexing (OFDM) introduces large amplitude variations in time, which can result in significant signal distortion in the presence of nonlinear amplifiers. We introduce a new bound for the peak of the continuous envelope of an OFDM signal, based on the maximum of its corresponding oversampled sequence; it is shown to be very tight as the oversampling rate increases. The bound is then used to derive a closed-form probability upper bound for the complementary cumulative distribution function of the peak-to-mean envelope power ratio of uncoded OFDM signals for sufficiently large numbers of subcarriers. As another application of the bound for oversampled sequences, we propose tight relative error bounds for computation of the peak power using two main methods: the oversampled inverse fast Fourier transform and the method introduced for coded systems based on minimum distance decoding of the code.
Networked Windows NT system field failure data analysis (2003)

This paper presents a measurement-based dependability study of a Networked Windows NT system based on field data collected from NT System Logs from 503 servers running in a production environment over a four-month period. The event logs at hand contains only system reboot information. We study individual server failures and domain behavior in order to characterize failure behavior and explore error propagation between servers. The key observations from this study are: (1) system software and hardware failures are the two major contributors to the total system downtime (22% and 10%), (2) recovery from application software failures are usually quick, (3) in many cases, more than one reboots are required to recover from a failure, (4) the average availability of an individual server is over 99%, (5) there is a strong indication of error dependency or error propagation across the network, (6) most (58%) reboots are unclassified indicating the need for better logging techniques, (7) maintenance and configuration contribute to 24% of system downtime.
Glycogen synthase kinase 3β and the regulation of axon growth (2004)

One of the earliest hallmarks that distinguish growing axons from dendrites is their growth rate; axons grow faster than dendrites. In vertebrates, where axons are required to grow for considerable distances, particularly in the peripheral nervous system, a fast axon growth rate is a requisite property. In neurons that respond to the neurotrophin growth factor/nerve growth factor with increased axon growth rates, two distinct intracellular signalling pathways are recruited: the MAPK (mitogen-activated protein kinase) pathway and the phosphatidylinositol-3 kinase pathway. The activation of either pathway leads to changes in microtubule dynamics within growing axons and growth cones and these underlie fast axon growth rates. Microtubule dynamics is regulated by microtubule-associated proteins and in the MAPK pathway this function is subserved by microtubule-associated protein 1B, whereas in the phosphatidylinositol-3 kinase pathway, adenomatous polyposis coli is the regulating microtubule-associated protein.
Hyperexpression of CD40 ligand by B and T cells in human lupus and its role in pathogenic autoantibody production. (1996)

We investigated the role of the costimulatory molecules, CD40 and its ligand CD40L, in the pathogenesis of human SLE. In comparison to normal subjects or patients in remission, PBMC from active lupus patients had a 21-fold increase in the frequency of CD40L-expressing, CD4+T cells. However, the expression of CD40L induced in either lupus or normal T cells by mitogenic stimulation could be down-regulated equally well by CD40 molecules on autologous B cells. Active lupus patients also had a 22-fold increase in percentage of CD8+ T cells expressing CD40L, consistent with their unusual helper activity in SLE. Surprisingly, patients with active lupus had a 20.5-fold increase in B cells that spontaneously expressed high levels of CD40L, as strongly as their T cells. Although lupus patients in remission had low levels of CD40L+ cells in the range of normal subjects, mitogen-induced upregulation of CD40L expression in the T and B cells was markedly greater than normal, suggesting an intrinsic defect. A mAb to CD40L blocked significantly the ability of lymphocytes from lupus patients with active and established disease to produce the pathogenic variety of antinuclear autoantibodies in vitro, bolstering the possibility of anti-CD40L immunotherapy for lupus. Future studies on the hyperexpression of CD40L could elucidate a regulatory defect in the pathogenic T and B cells of lupus.
4. Treatment of Small Cell Lung Cancer (2014)

肺小細胞癌の増殖速度は速く，早期から容易に遠隔転移を来たすが，放射線治療や化学療法に対する反応性は良好である．そのため，特殊なI期症例を除いて初期手術は推奨されず，放射線治療や化学療法が治療の主体となる．治療は，限局型と進展型に分けて考え，全身状態（performance status：PS）と主要臓器機能が保たれた限局型症例には，加速多分割照射法による放射線治療と化学療法の早期同時併用，進展型症例には原疾患によるPS不良例を含めて化学療法が推奨される．高率に脳転移を起こすため，初回治療の完全奏効例には予防的全脳照射を行う．基礎研究も精力的に進められているが，肺非小細胞癌のような治療標的となる遺伝子異常は確立されておらず，今後の重要な課題である．
The Proprotein Convertase (PC) PCSK9 Is Inactivated by Furin and/or PC5/6A (2006)

PCSK9 is the ninth member of the proprotein convertase (PC) family. Some of its natural mutations have been genetically associated with the development of a dominant form of familial hyper- or hypocholesterolemia. The exact mechanism of action of PCSK9 is not clear, although it is known to enhance the intracellular degradation of the low density lipoprotein (LDL) receptor in acidic compartments, likely the endosomes/lysosomes. We analyzed the post-translational modifications of PCSK9 and show that it is sulfated within its prosegment at Tyr38. We also examined the susceptibility of PCSK9 to proteolytic cleavage by the other members of the PC family. The data show that the natural gain-of-function mutations R218S, F216L, and D374Y associated with hypercholesterolemia result in total or partial loss of furin/PC5/6A processing at the motif RFHR218 downward arrow. In contrast, the loss-of-function mutations A443T and C679X lead either to the lack of trans-Golgi network/recycling endosome localization and an enhanced susceptibility to furin cleavage (A443T) or to the inability of PCSK9 to exit the endoplasmic reticulum (C679X). Furthermore, we report the presence of both native and furin-like cleaved forms of PCSK9 in circulating human plasma. Thus, we propose that PCSK9 levels are finely regulated by the basic amino acid convertases furin and PC5/6A. The latter may reduce the lifetime of this proteinase and its ability to degrade the cell-surface LDL receptor, thereby regulating the levels of circulating LDL cholesterol.
Channel capacity and beamforming for multiple transmit and receive antennas with covariance feedback (2002)

We consider the capacity of a narrowband point to point communication system employing multiple-element antenna arrays at both the transmitter and the receiver with covariance feedback. Under covariance feedback the receiver is assumed to have perfect channel state information (CSI) while at the transmitter the channel matrix is modeled as consisting of zero mean complex jointly Gaussian random variables with known covariances. Specifically we assume a channel matrix with i.i.d. rows and correlated columns, a common model for downlink transmission. We determine the optimal transmit precoding strategy to maximize the Shannon capacity of such a system. We also derive closed form necessary and sufficient conditions on the spatial covariance for when the maximum capacity is achieved by beamforming. The conditions for optimality of beamforming agree with the notion of water-filling over multiple degrees of freedom.
CONDENSER: A Graph-Based Approachfor Detecting Botnets (2014)

Botnets represent a global problem and are responsible for causing large financial and operational damage to their victims. They are implemented with evasion in mind, and aim at hiding their architecture and authors, making them difficult to detect in general. These kinds of networks are mainly used for identity theft, virtual extortion, spam campaigns and malware dissemination. Botnets have a great potential in warfare and terrorist activities, making it of utmost importance to take action against. We present CONDENSER, a method for identifying data generated by botnet activity. We start by selecting appropriate the features from several data feeds, namely DNS non-existent domain responses and live communication packages directed to command and control servers that we previously sinkholed. By using machine learning algorithms and a graph based representation of data, then allows one to identify botnet activity, helps identifying anomalous traffic, quickly detect new botnets and improve activities of tracking known botnets. Our main contributions are threefold: first, the use of a machine learning classifier for classifying domain names as being generated by domain generation algorithms (DGA); second, a clustering algorithm using the set of selected features that groups network communication with similar patterns; third, a graph based knowledge representation framework where we store processed data, allowing us to perform queries.
Functional Annotation of ESR1 Gene Fusions in Estrogen Receptor-Positive Breast Cancer (2018)

RNA sequencing (RNA-seq) detects estrogen receptor alpha gene (ESR1) fusion transcripts in estrogen receptor-positive (ER<sup>+</sup>) breast cancer, but their role in disease pathogenesis remains unclear. We examined multiple ESR1 fusions and found that two, both identified in advanced endocrine treatment-resistant disease, encoded stable and functional fusion proteins. In both examples, ESR1-e6>YAP1 and ESR1-e6>PCDH11X, ESR1 exons 1-6 were fused in frame to C-terminal sequences from the partner gene. Functional properties include estrogen-independent growth, constitutive expression of ER target genes, and anti-estrogen resistance. Both fusions activate a metastasis-associated transcriptional program, induce cellular motility, and promote the development of lung metastasis. ESR1-e6>YAP1- and ESR1-e6>PCDH11X-induced growth remained sensitive to a CDK4/6 inhibitor, and a patient-derived xenograft (PDX) naturally expressing the ESR1-e6>YAP1 fusion was also responsive. Transcriptionally active ESR1 fusions therefore trigger both endocrine therapy resistance and metastatic progression, explaining the association with fatal disease progression, although CDK4/6 inhibitor treatment is predicted to be effective.
Interval simulation: Raising the level of abstraction in architectural simulation (2010)

Detailed architectural simulators suffer from a long development cycle and extremely long evaluation times. This longstanding problem is further exacerbated in the multi-core processor era. Existing solutions address the simulation problem by either sampling the simulated instruction stream or by mapping the simulation models on FPGAs; these approaches achieve substantial simulation speedups while simulating performance in a cycle-accurate manner. This paper proposes interval simulation which takes a completely different approach: interval simulation raises the level of abstraction and replaces the core-level cycle-accurate simulation model by a mechanistic analytical model. The analytical model estimates core-level performance by analyzing intervals, or the timing between two miss events (branch mispredictions and TLB/cache misses); the miss events are determined through simulation of the memory hierarchy, cache coherence protocol, interconnection network and branch predictor. By raising the level of abstraction, interval simulation reduces both development time and evaluation time. Our experimental results using the SPEC CPU2000 and PARSEC benchmark suites and the M5 multi-core simulator, show good accuracy up to eight cores (average error of 4.6% and max error of 11% for the multi-threaded full-system workloads), while achieving a one order of magnitude simulation speedup compared to cycle-accurate simulation. Moreover, interval simulation is easy to implement: our implementation of the mechanistic analytical model incurs only one thousand lines of code. Its high accuracy, fast simulation speed and ease-of-use make interval simulation a useful complement to the architect's toolbox for exploring system-level and high-level micro-architecture trade-offs.
Myeloma cells induce imbalance in the osteoprotegerin/osteoprotegerin ligand system in the human bone marrow environment (2001)

Although osteolysis is a common complication in patients with multiple myeloma (MM), the biologic mechanisms involved in the pathogenesis of MM-induced bone disease are poorly understood. Two factors produced by stromal-osteoblastic cells seem critical to the regulation of bone resorption: osteoprotegerin (OPG) and its ligand (OPGL). OPGL stimulates osteoclast differentiation and activity, whereas OPG inhibits these processes. The present study investigated whether myeloma cells affect physiologic OPG/OPGL balance in the bone marrow (BM) environment. Ten human myeloma cell lines and myeloma cells isolated from 26 consecutive patients with MM failed to express OPGL and only rarely produced a low amount of OPG. In a coculture system, human myeloma cells up-regulated OPGL expression but strongly down-regulated OPG production in preosteoblastic (preOB) or stromal cells (BMSCs) of primary human BM at the mRNA and protein levels. This effect, which was dependent on cell-to-cell contact between myeloma cells and BMSCs or preOB, partially involved the integrin VLA-4. In addition, overexpression of OPGL mRNA occurred in ex vivo BM cultures obtained from MM patients as compared with healthy donors, and immunohistochemical staining performed on BM biopsy specimens showed an increase of OPGL and a reduction of OPG expression in MM patients as compared with healthy subjects. In summary, these data indicate that myeloma cells affect the OPG/OPGL ratio in the BM environment and tend to confirm that the OPG/OPGL system is involved in the pathogenesis of MM-induced bone disease.