gebhart/patrepeval huggingface dataset:
A Robust Procedure for Comparing Multiple Means under Heteroscedasticity in Unbalanced Designs (2010)

Investigating differences between means of more than two groups or experimental conditions is a routine research question addressed in biology. In order to assess differences statistically, multiple comparison procedures are applied. The most prominent procedures of this type, the Dunnett and Tukey-Kramer test, control the probability of reporting at least one false positive result when the data are normally distributed and when the sample sizes and variances do not differ between groups. All three assumptions are non-realistic in biological research and any violation leads to an increased number of reported false positive results. Based on a general statistical framework for simultaneous inference and robust covariance estimators we propose a new statistical multiple comparison procedure for assessing multiple means. In contrast to the Dunnett or Tukey-Kramer tests, no assumptions regarding the distribution, sample sizes or variance homogeneity are necessary. The performance of the new procedure is assessed by means of its familywise error rate and power under different distributions. The practical merits are demonstrated by a reanalysis of fatty acid phenotypes of the bacterium Bacillus simplex from the "Evolution Canyons" I and II in Israel. The simulation results show that even under severely varying variances, the procedure controls the number of false positive findings very well. Thus, the here presented procedure works well under biologically realistic scenarios of unbalanced group sizes, non-normality and heteroscedasticity.
D614G Substitution of SARS-CoV-2 Spike Protein Increases Syncytium Formation and Virus Titer via Enhanced Furin-Mediated Spike Cleavage (2021)

Since the D614G substitution in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, the variant strain has undergone a rapid expansion to become the most abundant strain worldwide. Therefore, this substitution may provide an advantage for viral spreading. To explore the mechanism, we analyzed 18 viral isolates containing S proteins with either G614 or D614 (S-G614 and S-D614, respectively). The plaque assay showed a significantly higher virus titer in S-G614 than in S-D614 isolates. We further found increased cleavage of the S protein at the furin substrate site, a key event that promotes syncytium formation, in S-G614 isolates. The enhancement of the D614G substitution in the cleavage of the S protein and in syncytium formation has been validated in cells expressing S protein. The effect on the syncytium was abolished by furin inhibitor treatment and mutation of the furin cleavage site, suggesting its dependence on cleavage by furin. Our study pointed to the impact of the D614G substitution on syncytium formation through enhanced furin-mediated S cleavage, which might increase the transmissibility and infectivity of SARS-CoV-2 strains containing S-G614. <b>IMPORTANCE</b> Analysis of viral genomes and monitoring of the evolutionary trajectory of SARS-CoV-2 over time has identified the D614G substitution in spike (S) as the most prevalent expanding variant worldwide, which might confer a selective advantage in transmission. Several studies showed that the D614G variant replicates and transmits more efficiently than the wild-type virus, but the mechanism is unclear. By comparing 18 virus isolates containing S with either D614 or G614, we found significantly higher virus titers in association with higher furin protease-mediated cleavage of S, an event that promotes syncytium formation and virus infectivity, in the S-G614 viruses. The effect of the D614G substitution on furin-mediated S cleavage and the resulting enhancement of the syncytium phenotype has been validated in S-expressing cells. This study suggests a possible effect of the D614G substitution on S of SARS-CoV-2; the antiviral effect through targeting furin protease is worthy of being investigated in proper animal models.
Intra-articular injection of an autologous preparation rich in growth factors for the treatment of knee OA: a retrospective cohort study. (2009)

Although these preliminary results need to be evaluated in a randomized clinical trial, they provide useful infomration about the safety of PRGF and open new perspectives on autologous treatments for joint diseases.
Novel Inhibitors of Cytokine-induced IκBα Phosphorylation and Endothelial Cell Adhesion Molecule Expression Show Anti-inflammatory Effects in Vivo (1997)

We have identified two compounds that inhibit the expression of endothelial-leukocyte adhesion molecules intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin. These compounds act by inhibiting tumor necrosis factor-alpha-induced phosphorylation of IkappaB-alpha, resulting in decreased nuclear factor-kappaB and decreased expression of adhesion molecules. The effects on both IkappaB-alpha phosphorylation and surface expression of E-selectin were irreversible and occurred at an IC50 of approximately 10 microM. These agents selectively and irreversibly inhibited the tumor necrosis factor-alpha-inducible phosphorylation of IkappaB-alpha without affecting the constitutive IkappaB-alpha phosphorylation. Although these compounds exhibited other activities, including stimulation of the stress-activated protein kinases, p38 and JNK-1, and activation of tyrosine phosphorylation of a 130-140-kDa protein, these effects are probably distinct from the effects on adhesion molecule expression since they were reversible. One compound was evaluated in vivo and shown to be a potent anti-inflammatory drug in two animal models of inflammation. The compound reduced edema formation in a dose-dependent manner in the rat carrageenan paw edema assay and reduced paw swelling in a rat adjuvant arthritis model. These studies suggest that inhibitors of cytokine-inducible IkappaBalpha phosphorylation exert anti-inflammatory activity in vivo.
Antimicrobial Resistance (2016)

Antimicrobial resistance poses significant challenges for current clinical care. Modified use of antimicrobial agents and public health interventions, coupled with novel antimicrobial strategies, may help mitigate the effect of multidrug-resistant organisms in the future.
Whole-home gesture recognition using wireless signals (2013)

This paper presents WiSee, a novel gesture recognition system that leverages wireless signals (e.g., Wi-Fi) to enable whole-home sensing and recognition of human gestures. Since wireless signals do not require line-of-sight and can traverse through walls, WiSee can enable whole-home gesture recognition using few wireless sources. Further, it achieves this goal without requiring instrumentation of the human body with sensing devices. We implement a proof-of-concept prototype of WiSee using USRP-N210s and evaluate it in both an office environment and a two- bedroom apartment. Our results show that WiSee can identify and classify a set of nine gestures with an average accuracy of 94%.
Inhibition of human tumor xenograft growth by treatment with the farnesyl transferase inhibitor B956. (1995)

ras oncogenes are present in several types of cancers but are most frequently described in colon and pancreatic carcinomas. Consequently, ras is being targeted for drug development as a means to develop therapies for these types of cancer. The ras protein is posttranslationally modified by the addition of a farnesyl group, followed by cleavage of the COOH-terminal 3 amino acids and methylation of the prenylated cysteine. Because the posttranslational addition of farnesyl is obligatory not only for the remaining modifications to take place but also for ras control of cell growth, inhibitors of farnesylation are being developed as potential antitumor agents. In this report, a new peptidomimetic inhibitor of farnesyl transferase is described. This compound, B956, and its methyl ester B1086, inhibit the formation of colonies in soft agar of 14 human tumor cell lines expressing different ras oncogenes at concentrations between 0.2 and 60 microM. Higher concentrations of B956 (10-80 microM) were required to inhibit colony formation by 5 tumor cell lines without ras mutations. B956/B1086 at 100 mg/kg also inhibited tumor growth by EJ-1 human bladder carcinoma, HT1080 human fibrosarcoma, and to a lesser extent by HCT116 human colon carcinoma xenografts in nude mice. Furthermore, inhibition of tumor growth by B956 is shown to be correlated with inhibition of ras posttranslational processing in the tumor. Thus, peptidomimetic inhibitors of ras farnesylation have the potential to be developed as therapy for ras-dependent tumors.
Treatment of congenital coronary arteriovenous malformations with micro‐particle embolization (1991)

The successful treatment of a symptomatic coronary arteriovenous malformation (CAVM) by a percutaneous embolization technique with micro-particles is described. Objective evidence of ischemia and its subsequent disappearance after embolization is presented. The embolization technique and possible indications and contraindications are discussed.
Improving energy efficiency of location sensing on smartphones (2010)

Location-based applications have become increasingly popular on smartphones over the past years. The active use of these applications can however cause device battery drain owing to their power-intensive location-sensing operations. This paper presents an adaptive location sensing framework that significantly improves the energy efficiency of smartphones running location-based applications. The underlying design principles of the proposed framework involve substitution, suppression, piggybacking, and adaptation of applications' location-sensing requests to conserve energy. We implement these design principles on Android-based smartphones as a middleware. Our evaluation results show that the design principles reduce the usage of the power-intensive GPS (Global Positioning System) by up to 98% and improve battery life by up to 75%.
North Carolina Banking in 1997: The Year in Review (1998)

The banking industry is in the midst of radical change.The distinctions between banks, thrifts, and other financial institutions are diminishing rapidly.'In addition, the geographic restraints on banking are disintegrating, leading to nationwide and worldwide banking.'Finally, the number of banks is decreasing due to mergers, acquisitions, and consolidation through interstate branching, while the largest banks are steadily increasing in size. 3 North Carolina banks are at the forefront of this radical change.Charlotte, North Carolina, is second only to New York in terms of banking assets and houses two of the nation's largest bank holding companies-NationsBank Corporation which is ranked third in terms of asset size and First Union Corporation which is ranked sixth. 4 In addition, North Carolina serves as home to Wachovia Corporation, the seventeenth-largest bank holding company in the country, as measured by assets at year-end 1997This review of North Carolina banking surveys some of the major developments in the North Carolina banking industry in 1997.
Peptoids that mimic the structure, function, and mechanism of helical antimicrobial peptides (2008)

Antimicrobial peptides (AMPs) and their mimics are emerging as promising antibiotic agents. We present a library of "ampetoids" (antimicrobial peptoid oligomers) with helical structures and biomimetic sequences, several members of which have low-micromolar antimicrobial activities, similar to cationic AMPs like pexiganan. Broad-spectrum activity against six clinically relevant BSL2 pathogens is also shown. This comprehensive structure-activity relationship study, including circular dichroism spectroscopy, minimum inhibitory concentration assays, hemolysis and mammalian cell toxicity studies, and specular x-ray reflectivity measurements shows that the in vitro activities of ampetoids are strikingly similar to those of AMPs themselves, suggesting a strong mechanistic analogy. The ampetoids' antibacterial activity, coupled with their low cytotoxicity against mammalian cells, make them a promising class of antimicrobials for biomedical applications. Peptoids are biostable, with a protease-resistant N-substituted glycine backbone, and their sequences are highly tunable, because an extensive diversity of side chains can be incorporated via facile solid-phase synthesis. Our findings add to the growing evidence that nonnatural foldamers will emerge as an important class of therapeutics.
Fifteen Years of Work on Thin-Disk Lasers: Results and Scaling Laws (2007)

The principal ideas of the thin-disk laser design will be illustrated and the advantages for operating different laser materials will be explained. The results for continuous-wave (CW) and Q-switched operation as well as for amplification of short (nanosecond) and ultrashort (picosecond, femtosecond) pulses demonstrate the potential of the thin-disk laser design. The scaling laws for this laser design show that the power limit for CW operation is far beyond 40 kW for one single disk and the energy limit is higher than 3 J from one disk in pulsed operation. Also, the applicability of the thin-disk laser concept to optically pumped semiconductor structures will be discussed. When pumping directly into the quantum wells, the energy defect between the pump photon and the laser photon can be smaller than 5%, thus reducing the waste heat generated inside the semiconductor structure. First results demonstrate the potential of this new concept. Finally, a short overview of the industrial realization of the thin-disk laser technology will be given.
In situX-ray analysis of protein crystals in low-birefringent and X-ray transmissive plastic microchannels (2008)

Plastic microchannel crystallization template designs made from inexpensive cyclic olefin copolymers have been shown to be low-birefringent, X-ray transmissive and compatible with microfluidic fabrication in restricted geometry. The model proteins thaumatin, lysozyme and bacteriorhodopsin demonstrated the feasibility of conducting counter-diffusion equilibration within the new plastic configuration. Crystals of each of these proteins were directly evaluated in situ using synchrotron radiation and their diffraction quality was evaluated without invasive manipulation or cryofreezing. Protein crystals able to produce complete X-ray data sets were used to calculate electron-density maps for structure determination. Fluidic crystallization in the plastic platform was also coupled with a commercialized automated imager and an in situ X-ray scanner that allowed optical and X-ray inspection of crystallization hits. The results demonstrate the feasibility of rapid nanovolume counter-diffusion crystallization experiments without the need for additional instrumentation.
Synthesis of Novel Cationic Lipids with a Guanidine Group. Cationic Lipids 31 (1996)

Potentially cell biodegradable cationic lipids having a strongly basic guanidine group have been prepared by the reaction of lipophilic derivatives of diethanolamine with cyanamide.
Executive health: Building strength, managing risks (2000)

Executive Overview CEOs and senior executives can have a positive impact on their firms, creating value and thus contributing to the wealth of their nations. Therefore, safeguarding executives' health is of concern to all stakeholders in the organization. We present an executive health model and define executive health as physical, psychological, spiritual, and ethical well-being. There is a collective interest in enhancing and maintaining the health of executives as key organizational leaders. This special issue on Executive Health includes articles, book reviews, research briefs, a Country Close-Up, and an Executive Voice interview addressing strength factors that enhance executive health and health risk factors that concern executives' vulnerabilities. The four health risk factors for executives examined in this article are the Achilles Heel, loneliness of command, work demands and overload, and crises and failures. By building on strengths and managing health risks, executives may enhance their own health and the health of their organizations.
Imaging with Fresnel zone pupil masks: extended depth of field (1984)

Fresnel zone plates are used as pupil apertures to extend the depth of field of an incoherent imaging system. The defocused optical transfer function is evaluated approximately, and the results are confirmed by experiments and by subjective evaluations of the images of a test chart. With a pupil having four zones, for example, the resolution limit at four depths of field out of focus is improved by a factor of 10.
Effects of MgO‐CaO‐P2O5‐Na2O‐based additives on mechanical and biological properties of hydroxyapatite (2004)

In this research, we improved densification, hardness, and compression strength of synthetic hydroxyapatite (HAp) ceramics by introducing small quantities of MgO-CaO-P(2)O(5)-Na(2)O-based sintering additives. Biological properties of HAp were not altered by this procedure. Phase analyses were performed by using a Philips Xpert fully automated diffractometer with Co K-alpha radiation to understand the influence of additives on phase purity in the final products. All compositions were characterized at green and sintered densities to understand the influence of additives on densification. Some of the compositions showed >40% increase in Vickers microhardness compared with pure HAp processed under the same conditions. Improvement in compression strength was also detected in some compositions. In vitro biological testing used a modified human osteoblast cell line to test biocompatibility, cell attachment, and cell proliferation. All these compositions were nontoxic and biocompatible. Our results indicate that MgO-CaO-P(2)O(5)-Na(2)O-based sintering additives can be used to improve both mechanical and biological properties of HAp ceramics.
Subgroup analysis by prior lines of metastatic therapy (mtx) in NAPOLI-1: A global, randomized phase 3 study of liposomal irinotecan (nal-IRI) ± 5-fluorouracil and leucovorin (5-FU/LV), vs. 5-FU/LV in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) who have progressed following gemcitabine-based therapy. (2017)

4127 Background: In the NAPOLI-1 study, nal-IRI+5-FU/LV significantly increased median OS vs. 5-FU/LV control (6.1 vs. 4.2 mo; unstratified HR = 0.67 [0.49–0.92]; p = .012). This is a subgroup analysis by prior lines of mtx. Methods: Study methodology has been published (Wang-Gillam; Lancet 2016). This exploratory subgroup analysis compares outcomes in pts with 0–1 vs. ≥2 prior mtx lines, based on primary survival analysis data (cut-off February 2014) of the ITT population. Results: OS, PFS and CA19-9 response rates in pts with 0–1 (65.8% of pts) or ≥2 (34.2%) prior mtx lines are shown (see Table). Median OS for nal-IRI+5-FU/LV improved vs. 5-FU/LV by 2.1 mo to 6.2 mo (HR = 0.66; p = .03) in pts with 0–1 prior mtx lines and by 1.1 mo to 5.4 mo (HR = 0.68; p = .18) in pts with ≥2 prior mtx lines. The safety profile was similar between subgroups with nal-IRI+5-FU/LV (≥grade 3 drug-related AEs: 43 [55%] with 0–1 and 20 [51%] with ≥2 prior mtx lines). Conclusions: This post-hoc subgroup analysis shows significant increases for nal-IRI+5-FU/LV over 5-FU/LV in OS, PFS and CA19-9 response in pts with 0–1 prior mtx lines. Median OS benefit was less prominent in later lines, but conclusions are restricted by limited pt numbers. Clinical trial information: NCT01494506. [Table: see text]
Advanced Engineering of Lipid Metabolism in Nicotiana benthamiana Using a Draft Genome and the V2 Viral Silencing-Suppressor Protein (2012)

The transient leaf assay in Nicotiana benthamiana is widely used in plant sciences, with one application being the rapid assembly of complex multigene pathways that produce new fatty acid profiles. This rapid and facile assay would be further improved if it were possible to simultaneously overexpress transgenes while accurately silencing endogenes. Here, we report a draft genome resource for N. benthamiana spanning over 75% of the 3.1 Gb haploid genome. This resource revealed a two-member NbFAD2 family, NbFAD2.1 and NbFAD2.2, and quantitative RT-PCR (qRT-PCR) confirmed their expression in leaves. FAD2 activities were silenced using hairpin RNAi as monitored by qRT-PCR and biochemical assays. Silencing of endogenous FAD2 activities was combined with overexpression of transgenes via the use of the alternative viral silencing-suppressor protein, V2, from Tomato yellow leaf curl virus. We show that V2 permits maximal overexpression of transgenes but, crucially, also allows hairpin RNAi to operate unimpeded. To illustrate the efficacy of the V2-based leaf assay system, endogenous lipids were shunted from the desaturation of 18∶1 to elongation reactions beginning with 18∶1 as substrate. These V2-based leaf assays produced ∼50% more elongated fatty acid products than p19-based assays. Analyses of small RNA populations generated from hairpin RNAi against NbFAD2 confirm that the siRNA population is dominated by 21 and 22 nt species derived from the hairpin. Collectively, these new tools expand the range of uses and possibilities for metabolic engineering in transient leaf assays.
Structural Basis for the Substrate Specificity of Tobacco Etch Virus Protease (2002)

Because of its stringent sequence specificity, the 3C-type protease from tobacco etch virus (TEV) is frequently used to remove affinity tags from recombinant proteins. It is unclear, however, exactly how TEV protease recognizes its substrates with such high selectivity. The crystal structures of two TEV protease mutants, inactive C151A and autolysis-resistant S219D, have now been solved at 2.2- and 1.8-A resolution as complexes with a substrate and product peptide, respectively. The enzyme does not appear to have been perturbed by the mutations in either structure, and the modes of binding of the product and substrate are virtually identical. Analysis of the protein-ligand interactions helps to delineate the structural determinants of substrate specificity and provides guidance for reengineering the enzyme to further improve its utility for biotechnological applications.
Alzheimer's soluble amyloid β is a normal component of human urine (1997)

Soluble A beta (Sa beta) is normally present at a low concentration in human plasma and cerebrospinal fluid. Although the factors involved in the regulation of Sa beta plasma levels are still unknown, we have explored its excretion in the urine as one of the possible homeostatic mechanisms. The presence of Sa beta in the urine was investigated via immunoprecipitation experiments with anti-A beta antibodies followed by detection and identification by immunoblot, MALDI mass spectrometry and sequence analysis. Soluble A beta (4.3 kDa) immunoreactivity was present in the urine of normal donors, Down's syndrome individuals as well as in patients with renal disorders exhibiting glomerular or mixed proteinuria. Edman degradation of the immunoprecipitated material yielded the intact A beta N-terminus and mass spectra analysis indicated the existence of a major component at mlz 4327, corresponding to the molecular mass of A beta1-40. Semiquantitative data obtained from the immunoprecipitation experiments indicate that under normal conditions the daily excretion of intact Sa beta in the urine represents less than 1% of the circulating pool.