gebhart/patrepeval huggingface dataset:
Persistence of rare Salmonella Typhi genotypes susceptible to first-line antibiotics in the remote islands of Samoa (2022)

ABSTRACT For decades, the remote island nation of Samoa (pop. ~200,000) has faced endemic typhoid fever despite improvements in water quality, sanitation, and economic development. We recently described the epidemiology of typhoid fever in Samoa from 2008-2019 by person, place, and time; however, the local Salmonella enterica serovar Typhi ( S. Typhi) population structure, evolutionary origins, and genomic features remained unknown. Herein, we report whole genome sequence analyses of 306 S. Typhi isolates from Samoa collected between 1983 and 2020. Phylogenetics revealed a dominant population of rare genotypes 3.5.4 and 3.5.3, together comprising 292/306 (95.4%) of Samoan versus 2/4934 (0.04%) global S. Typhi isolates. Three distinct 3.5.4 genomic sub-lineages were identified and their defining polymorphisms were determined. These dominant Samoan genotypes, which likely emerged in the 1970s, share ancestry with other clade 3.5 isolates from South America, Southeast Asia, and Oceania. Additionally, a 106-kb pHCM2 phenotypically-cryptic plasmid, detected earliest in a 1992 Samoan S. Typhi isolate, was identified in 106/306 (34.6%) of Samoan isolates; this is more than double the observed proportion of pHCM2-containing isolates in the global collection. In stark contrast with global S. Typhi trends, resistance-conferring polymorphisms were detected in only 15/306 (4.9%) of Samoan S. Typhi, indicating overwhelming susceptibility to antibiotics that are no longer effective in most of South and Southeast Asia. This country-level genomic framework can help local health authorities in their ongoing typhoid surveillance and control efforts, as well as to fill a critical knowledge gap in S. Typhi genomic data from Oceania. IMPORTANCE In this study we used whole genome sequencing and comparative genomics analyses to characterize the population structure, evolutionary origins, and genomic features of S. Typhi associated with decades of endemic typhoid fever in Samoa. Our analyses of Samoan isolates from 1983 to 2020 identified a rare S. Typhi population in Samoa that likely emerged around the early 1970s and evolved into sub-lineages that presently dominate. The dominance and persistence of these endemic genotypes in Samoa are not readily explained by any apparent genomic competitive advantage or widespread acquisition of antimicrobial resistance. These data establish the necessary framework for future genomic surveillance of S. Typhi in Samoa for public health benefit.
The mitophagy effector FUNDC1 controls mitochondrial reprogramming and cellular plasticity in cancer cells (2020)

Mitochondria are signaling hubs in eukaryotic cells. Here, we showed that the mitochondrial FUN14 domain-containing protein-1 (FUNDC1), an effector of Parkin-independent mitophagy, also participates in cellular plasticity by sustaining oxidative bioenergetics, buffering ROS production, and supporting cell proliferation. Targeting this pathway in cancer cells suppressed tumor growth but rendered transformed cells more motile and invasive in a manner dependent on ROS-mediated mitochondrial dynamics and mitochondrial repositioning to the cortical cytoskeleton. Global metabolomics and proteomics profiling identified a FUNDC1 interactome at the mitochondrial inner membrane, comprising the AAA+ protease, LonP1, and subunits of oxidative phosphorylation, complex V (ATP synthase). Independently of its previously identified role in mitophagy, FUNDC1 enabled LonP1 proteostasis, which in turn preserved complex V function and decreased ROS generation. Therefore, mitochondrial reprogramming by a FUNDC1-LonP1 axis controls tumor cell plasticity by switching between proliferative and invasive states in cancer.
Spectrum sharing and scheduling in D2D-enabled dense cellular networks (2015)

We study device-to-device (D2D) enabled hierarchical cellular networks consisting of a macro base station (BS), a dense network of access nodes (ANs) and mobile users, where spectrum is shared between cellular traffic and D2D traffic. Further, (the receivers of) mobile users dynamically time-share between the cellular and D2D networks. We develop algorithms for channel allocation and mobile-user receiver mode selection (choosing which network to participate in) with the objectives of minimizing delay for cellular traffic, and capacity maximization for D2D traffic. Our proposed solution takes advantage of the unique features offered by large and densified cellular networks such as multi-point connectivity, channel diversity, spatial reuse and load distribution. Given a BS-to-mobile delay requirement of d + 1 time-slots, we show that by appropriately scheduling channels and receiver modes, we can (with exponentially high probability) guarantee that cellular traffic reaches its intended destination within d timeslots. By leveraging spatial channel reuse, we show that this is achieved by utilizing a vanishingly small fraction of the available spatial capacity. Further, in the presence of delay-constrained cellular traffic, our scheduling algorithm guarantees D2D traffic can achieve rates within a (1-1/d) factor of the corresponding achievable rates without cellular traffic.
Systematic design of slow-light photonic waveguides (2011)

A pulse-delaying optimization scheme based on topology optimization for transient response of photonic crystal structures (PhCs) is formulated to obtain slow-light devices. The optimization process is started from a qualified W1 PhC waveguide design with group index ng≈40 obtained from a simple Edisonian parameter search. Based on this, the proposed pulse delaying and subsequent pulse restoring strategies yield a design that increases the group index by 75% to ng≈70±10% for an operational full-width at half-maximum (FWHM) bandwidth BFWHM=6 nm, and simultaneously minimizes interface penalty losses between the access ridge and the W1 PhC waveguide. To retain periodicity and symmetry, the active design set is limited to the in-/outlet region and a distributed supercell, and manufacturability is further enhanced by density filtering techniques combined with material phase projections.
Correction for Romano et al., MiR-494 is regulated by ERK1/2 and modulates TRAIL-induced apoptosis in non–small-cell lung cancer through BIM down-regulation (2014)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Fabrication of 2-D Glass Lens Arrays by a Photolithographic Technique (1990)

The method of preparing glass microlenses by a photo-thermal process has been described in prior publications. (1-4). In brief, it involves the photonucleation of a phase within the glass. The physical density of the photonucleated phase is larger than that of the unexposed virgin glass. Thus an exposure through an appropriate exposure mask,(opaque dots on an otherwise clear background), followed by heating to 600°C, forms cylindrical regions of soft unexposed glass which are squeezed beyond the surface during the thermal treatment, forming the spherical shaped protrusions.
Microfluidics in Nanomedicine (2015)

Nanomedicine is the medical application of nanotechnology for the treatment and prevention of major ailments, including cancer and cardiovascular diseases. Despite the progress and potential of nanomedicines, many such materials fail to reach clinical trials due to critical challenges that include poor reproducibility in high-volume production that have led to failure in animal studies and clinical trials. Recent approaches using microfluidic technology have provided emerging platforms with great potential to accelerate the clinical translation of nanomedicine. Microfluidic technologies for nanomedicine development are reviewed in this chapter, together with a detailed discussion of microfluidic assembly, characterization and evaluation of nanomedicine, and a description of current challenges and future prospects.


Keywords:

microfluidics;
nanotechnology;
nanomedicine;
biomimetic microsystem;
clinical translation
Core−Shell Nanorods of SnS−C and SnSe−C:  Synthesis and Characterization (2008)

The straightforward, efficient, solventless, RAPET (reactions under autogenic pressure at elevated temperature) approach was explored for the fabrication of core-shell nanomaterials. Carbon-encapsulated SnS and SnSe nanorods were synthesized by a one-step thermal decomposition of tetramethyltin in the presence of either S or Se powder in a closed reactor at 700 degrees C for 40 min, under their autogenic pressure in an inert atmosphere. The powder X-ray diffraction measurements provided structural evidence for the formation of pure orthorhombic phases of SnS or SnSe particles. The Raman spectroscopy measurements ensured that the nature of the coated carbon was semigraphitic. The scanning electron micrographs verified the 1D morphology of the formed SnS and SnSe chalcogenides, and their stoichiometry was confirmed by EDAX measurements. The HR-TEM micrographs distinguished between core and shell morphologies. The nitrogen gas adsorption on the surface of core-shell nanostructures was determined by BET surface area analysis. The plausible mechanism for the creation of chalcogenide cores (SnS or SnSe) with a carbon shell was elucidated.
2-Chloro-4-(1H-pyrazol-1-yl)-5-(trifluoromethyl)pyrimidine (2010)

The reaction of 2,4-dichloro-5-(trifluoro-meth-yl)pyrimidine with 1H-pyrazole gave two structural isomers in a 1:1 ratio that were separable by chromatography. The title compound, C(8)H(4)ClF(3)N(4), was the first product to elute and was characterized in the present study to confirm that substitution by the pyrazolyl group had occurred at position 4. The mol-ecule (with the exception of the F atoms) is essentially planar, with a mean deviation of 0.034 Å from the least-squares plane through all non-H and non-F atoms. The bond angles in the pyrimidine ring show a pronounced alternating pattern with three angles, including those at the two N atoms being narrower, and the remaining three wider than 120°.
The Two-Component System CprRS Senses Cationic Peptides and Triggers Adaptive Resistance in Pseudomonas aeruginosa Independently of ParRS (2012)

Cationic antimicrobial peptides pass across the outer membrane by interacting with negatively charged lipopolysaccharide (LPS), leading to outer membrane permeabilization in a process termed self-promoted uptake. Resistance can be mediated by the addition of positively charged arabinosamine through the action of the arnBCADTEF operon. We recently described a series of two-component regulators that lead to the activation of the arn operon after recognizing environmental signals, including low-Mg(2+) (PhoPQ, PmrAB) or cationic (ParRS) peptides. However, some peptides did not activate the arn operon through ParRS. Here, we report the identification of a new two-component system, CprRS, which, upon exposure to a wide range of antimicrobial peptides, triggered the expression of the LPS modification operon. Thus, mutations in the cprRS operon blocked the induction of the arn operon in response to several antimicrobial peptides independently of ParRS but did not affect the response to low Mg(2+). Distinct patterns of arn induction were identified. Thus, the responses to polymyxins were abrogated by either parR or cprR mutations, while responses to other peptides, including indolicidin, showed differential dependency on the CprRS and ParRS systems in a concentration-dependent manner. It was further demonstrated that, following exposure to inducing antimicrobial peptides, cprRS mutants did not become adaptively resistant to polymyxins as was observed for wild-type cells. Our microarray studies demonstrated that the CprRS system controlled a quite modest regulon, indicating that it was quite specific to adaptive peptide resistance. These findings provide greater insight into the complex regulation of LPS modification in Pseudomonas aeruginosa, which involves the participation of at least 4 two-component systems.
Evaluating White Matter Lesion Segmentations with Refined Sørensen-Dice Analysis (2020)

The Sørensen-Dice index (SDI) is a widely used measure for evaluating medical image segmentation algorithms. It offers a standardized measure of segmentation accuracy which has proven useful. However, it offers diminishing insight when the number of objects is unknown, such as in white matter lesion segmentation of multiple sclerosis (MS) patients. We present a refinement for finer grained parsing of SDI results in situations where the number of objects is unknown. We explore these ideas with two case studies showing what can be learned from our two presented studies. Our first study explores an inter-rater comparison, showing that smaller lesions cannot be reliably identified. In our second case study, we demonstrate fusing multiple MS lesion segmentation algorithms based on the insights into the algorithms provided by our analysis to generate a segmentation that exhibits improved performance. This work demonstrates the wealth of information that can be learned from refined analysis of medical image segmentations.
An Injectable Nano-Enabled Thermogel to Attain Controlled Delivery of p11 Peptide for the Potential Treatment of Ocular Angiogenic Disorders of the Posterior Segment (2021)

This investigation focused on the design of an injectable nano-enabled thermogel (nano-thermogel) system to attain controlled delivery of p11 anti-angiogenic peptide for proposed effective prevention of neovascularisation and to overcome the drawbacks of the existing treatment approaches for ocular disorders characterised by angiogenesis, which employ multiple intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) antibodies. Synthesis of a polyethylene glycol-polycaprolactone-polyethylene glycol (PEG-PCL-PEG) triblock co-polymer was undertaken, followed by characterisation employing Fourier-transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy and differential scanning calorimetry (DSC) to ascertain the chemical stability and integrity of the co-polymer instituted for nano-thermogel formulation. The p11 anti-angiogenic peptide underwent encapsulation within poly(lactic-<i>co</i>-glycolic acid) (PLGA) nanoparticles via a double emulsion solvent evaporation method and was incorporated into the thermogel following characterisation by scanning electron microscopy (SEM), zeta size and zeta-potential analysis. The tube inversion approach and rheological analysis were employed to ascertain the thermo-sensitive sol-gel conversion of the nano-thermogel system. Chromatographic assessment of the in vitro release of the peptide was performed, with stability confirmation via Tris-Tricine PAGE (Polyacrylamide Gel Electrophoresis). In vitro biocompatibility of the nano-thermogel system was investigated employing a retinal cell line (ARP-19). A nanoparticle size range of 100-200 nm and peptide loading efficiency of 67% was achieved. Sol-gel conversion of the nano-thermogel was observed between 32-45 °C. Release of the peptide in vitro was sustained, with maintenance of stability, for 60 days. Biocompatibility assessment highlighted 97-99% cell viability with non-haemolytic ability, which supports the potential applicability of the nano-thermogel system for extended delivery of peptide for ocular disorder treatment.
Plasma transforming growth factor-beta1 levels in patients with erectile dysfunction. (2004)

Vascular risk factors are associated with an elevated plasma TGF-beta1 level, which may contribute to cavernous fibrosis and ED.
Abstract 3352: Intracoronary Administration Of Bone Marrow-derived Progenitor Cells Abrogates Progressive Left Ventricular Enlargement After AMI: Insights from the REPAIR-AMI Trial (2007)

Left ventricular (LV) enlargement is the most important independent determinant of adverse outcome in patients (pts) after AMI. Depressed LV ejection fraction (LVEF) despite successful reperfusion therapy is the single most powerful predictor of progressive LV enlargement after AMI. Therefore, we investigated whether the intracoronary (i.c.) administration of bone marrow-derived progenitor cells (BMC) alters the association between LVEF within 7 days after successful reperfusion therapy for AMI and enddiastolic (EDV) and endsystolic (ESV) volume expansion at 4 months. In the REPAIR-AMI trial paired quantitative LV angiographic data at baseline (4.3 ± 1 days after AMI reperfusion) and at 4 months follow-up were available in 187 pts. 95 pts received i.c. BMC (4.4±1 days post AMI reperfusion therapy), whereas 92 pts received placebo at 4.3 ± 1 days after reperfusion. Baseline LVEF were similar in the BMC (47±10%) and in the placebo group (48±9 %, p = n.s.). At 4 months, ESV increased in the placebo (+6±22ml), but not in the BMC group (−0.6±19ml, p = 0.04 vs. placebo). Baseline LVEF was inversely correlated with ESV expansion at 4 months in the placebo, but not in the BMC group (figure ). Likewise, EDV expansion was closely correlated with baseline LVEF in the placebo (r=−0.36, p&lt;0.001), but not in the BMC group (r=−0.17, p=1.0). Finally, ESV expansion determined changes in NT-proBNP serum levels in the placebo (r=−0.38, p=0.006), but not in the BMC group(r=0.05, p=0.68). Conclusion: I.c. administration of BMC eliminates the correlation between depressed LVEF after reperfusion therapy and LV expansion during follow-up and thereby abrogates progressive LV enlargement after AMI. Change in endsystolic volume (baseline to 4 months , ml)
Reducing Leakage Currents in n-Channel Organic Field-Effect Transistors Using Molecular Dipole Monolayers on Nanoscale Oxides (2013)

Leakage currents through the gate dielectric of thin film transistors remain a roadblock to the fabrication of organic field-effect transistors (OFETs) on ultrathin dielectrics. We report the first investigation of a self-assembled monolayer (SAM) dipole as an electrostatic barrier to reduce leakage currents in n-channel OFETs fabricated on a minimal, leaky ∼10 nm SiO2 dielectric on highly doped Si. The electric field associated with 1H,1H,2H,2H-perfluoro-octyltriethoxysilane (FOTS) and octyltriethoxysilane (OTS) dipolar chains affixed to the oxide surface of n-Si gave an order of magnitude decrease in gate leakage current and subthreshold leakage and a two order-of-magnitude increase in ON/OFF ratio for a naphthalenetetracarboxylic diimide (NTCDI) transistor. Identically fabricated devices on p-Si showed similarly reduced leakage and improved performance for oxides treated with the larger dipole FOTS monolayer, while OTS devices showed poorer transfer characteristics than those on bare oxide. Comparison of OFETs on both substrates revealed that relative device performance from OTS and FOTS treatments was dictated primarily by the organosilane chain and not the underlying siloxane-substrate bond. This conclusion is supported by the similar threshold voltages (VT) extrapolated for SAM-treated devices, which display positive relative VT shifts for FOTS on either substrate but opposite VT shifts for OTS treatment on n-Si and p-Si. Our results highlight the potential of dipolar SAMs as performance-enhancing layers for marginal quality dielectrics, broadening the material spectrum for low power, ultrathin organic electronics.
Influence of different magnetites on properties of magnetic Pseudomonas aeruginosa immobilizates used for biosurfactant production (2009)

During the last decades, whole-cell immobilization has been used successfully in many bioprocesses. In particular, it is aimed at implementing continuous production processes, reaching higher production rates, and reusing the biocatalyst. In some cases, effective retention of immobilizates in the bioprocess is not feasible by membranes or sieves due to pore plugging or undesired losses of immobilizates. In the present publication, it is reported about the investigation of magnetic immobilizates of Pseudomonas aeruginosa for application in continuous biosurfactant production of rhamnolipids by foam fractionation and retention of entrained immobilizates by high-gradient magnetic separation from foam. Different materials and methods were tested with respect to important parameters, such as stability, diffusion properties or magnetic separation. Good magnetic separation of immobilizates was achieved at 5% (w/w) magnetite loading. Best results in terms of homogeneous embedding, good diffusion properties, and stability enhancement vis-à-vis pure alginate beads was achieved with alginate beads with embedded Bayoxide magnetite or MagPrep silica particles. Although polyurethane immobilizates showed higher stabilities compared with alginate beads, rhamnolipid diffusion in immobilizates was superior in magnetic alginate beads. Regarding bead production, smaller immobilizates were achieved with suspension polymerization compared to droplet extrusion by the JetCutting technology. In total, magnetic immobilizates are a promising tool for an easier handling of biocatalysts in a continuous biological production process, but they have to be adapted to the current production task.
Dynamics of sympathetic baroreflex control of arterial pressure in rats (2003)

By a white noise approach, we characterized the dynamics of the sympathetic baroreflex system in 11 halothane-anesthetized rats. We measured sympathetic nerve activity (SNA) and systemic arterial pressure (SAP), while carotid sinus baroreceptor pressure (BRP) was altered randomly. We estimated the transfer functions from BRP to SNA (mechanoneural arc), from SNA to SAP (neuromechanical arc), and from BRP to SAP (total arc). The gain of the mechanoneural arc gradually increased about threefold as the frequency of BRP change increased from 0.01 to 0.8 Hz. In contrast, the gain of the neuromechanical arc rapidly decreased to 0.4% of the steady-state gain as the frequency increased from 0.01 to 1 Hz. Although the total arc also had low-pass characteristics, the rate of attenuation in its gain was significantly slower than that of the neuromechanical arc, reflecting the compensatory effect of the mechanoneural arc for the sluggish response of the neuromechanical arc. We conclude that the quantitative estimation of the baroreflex dynamics is vital for an integrative understanding of baroreflex function in rats.