gebhart/patrepeval huggingface dataset:
Design of Potent Mannose 6‐Phosphate Analogues for the Functionalization of Lysosomal Enzymes To Improve the Treatment of Pompe Disease (2016)

Improving therapeutics delivery in enzyme replacement therapy (ERT) for lysosomal storage disorders is a challenge. Herein, we present the synthesis of novel analogues of mannose 6-phosphate (M6P), known as AMFAs and functionalized at the anomeric position for enzyme grafting. AMFAs are non-phosphate serum-resistant derivatives that efficiently bind the cation-independent mannose 6-phosphate receptor (CI-M6PR), which is the main pathway to address enzymes to lysosomes. One of the AMFAs was used to improve the treatment of the lysosomal myopathy Pompe disease, in which acid α-glucosidase (GAA) is defective. AMFA grafting on a M6P-free recombinant GAA led to a higher uptake of the GAA in adult Pompe fibroblasts in culture as compared to Myozyme, the M6P recombinant GAA. Moreover, the treatment of Pompe adult mice with the AMFA-grafted recombinant enzyme led to a remarkable improvement, even at low doses, in muscle functionality and regeneration, whereas Myozyme had limited efficacy.
3D Printing: 3D Printing of Highly Stretchable and Tough Hydrogels into Complex, Cellularized Structures (Adv. Mater. 27/2015) (2015)

X. Zhao and co-workers develop on page 4035 a new biocompatible hydrogel system that is extremely tough and stretchable and can be 3D printed into complex structures, such as the multilayer mesh shown. Cells encapsulated in the tough and printable hydrogel maintain high viability. 3D-printed structures of the tough hydrogel can sustain high mechanical loads and deformations.
Late-breaking abstract: Inhibition of RC kinase is a novel therapeutic approach for the treatment of COPD and IPF (2014)

RC kinase is a novel serine/threonine kinase, expressed predominantly by pulmonary macrophage and type II bronchial epithelial cells. Examination of BAL macrophage mRNA isolated from COPD and IPF patients showed increased expression of RC kinase compared to normal smokers and non-smoking patients. In vitro studies showed an upregulation of RC kinase upon cell stress, including oxidative stress. This correlated with an increase of NF-kb activity and IL-8 production that could be inhibited by RC kinase siRNA or small molecule antagonists. Biochemical analysis revealed that RC kinase is predominantly a nuclear protein and interacts with p27, a CDK inhibitor protein, and the NF-kb pathway. We have developed specific, extremely potent and orally administered small molecule antagonists of RC kinase with a favorable ADME profile. Mice treated with these compounds in an acute model of COPD showed significant reductions in the number of BAL neutrophils and the chemokine KC. Similar results were seen in mice treated with RC kinase siRNA. In a chronic (5 month) cigarette smoke exposure model, the small molecule antagonists were effective in both reducing inflammation and significantly limiting alveoli destruction. Inhibition of RC kinase in an acute cigarette smoke and viral exacerbation model reduced BAL neutrophils, inhibited cytokines such as IL-6 and significantly reduced viral titers. In a murine xenograft model of IPF, inhibition of RC kinase by small molecules or siRNA caused significant reductions in the inflammatory infiltrate, hydroxyproline production and collagen deposition in the lungs. Additionally, mRNA levels of collagens 1 &amp; 3, smooth muscle actin and fibronectin were also reduced.
Structure of the Nucleotide Radical Formed during Reaction of CDP/TTP with the E441Q-α2β2 ofE. coliRibonucleotide Reductase (2008)

The Escherichia coli ribonucleotide reductase (RNR) catalyzes the conversion of nucleoside diphosphates to deoxynucleotides and requires a diferric-tyrosyl radical cofactor for catalysis. RNR is composed of a 1:1 complex of two homodimeric subunits: alpha and beta. Incubation of the E441Q-alpha mutant RNR with substrate CDP and allosteric effector TTP results in loss of the tyrosyl radical and formation of two new radicals on the 200 ms to min time scale. The first radical was previously established by stopped flow UV/vis spectroscopy and pulsed high field EPR spectroscopy to be a disulfide radical anion. The second radical was proposed to be a 4'-radical of a 3'-keto-2'-deoxycytidine 5'-diphosphate. To identify the structure of the nucleotide radical [1'-(2)H], [2'-(2)H], [4'-(2)H], [5'-(2)H], [U-(13)C, (15)N], [U-(15)N], and [5,6 -(2)H] CDP and [beta-(2)H] cysteine-alpha were synthesized and incubated with E441Q-alpha2beta2 and TTP. The nucleotide radical was examined by 9 GHz and 140 GHz pulsed EPR spectroscopy and 35 GHz ENDOR spectroscopy. Substitution of (2)H at C4' and C1' altered the observed hyperfine interactions of the nucleotide radical and established that the observed structure was not that predicted. DFT calculations (B3LYP/IGLO-III/B3LYP/TZVP) were carried out in an effort to recapitulate the spectroscopic observations and lead to a new structure consistent with all of the experimental data. The results indicate, unexpectedly, that the radical is a semidione nucleotide radical of cytidine 5'-diphosphate. The relationship of this radical to the disulfide radical anion is discussed.
PGP in constrained wireless devices (2000)

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Photoelectrochemical cells for solar hydrogen production: Challenges and opportunities (2019)

As the Holy Grail to a carbon-free hydrogen economy, photoelectrochemical (PEC) water splitting offers a promising path for sustainable production of hydrogen fuel from solar energy. Even though much progress has been made over the past decade, the effectiveness and robustness of PEC cells are still far from a mature phase that would allow for widespread deployment. This perspective discusses the key challenges facing the current level of PEC development and proposes experimental approaches and strategies that can be adopted to address the issues. Focuses are mainly placed on the employment of in situ and operando spectroscopic measurements, the introduction of alternative, high value-added oxidation reactions, and the creation of near infrared-responsive photoelectrodes. A brief outlook that may assist the future advancement of PEC technology is also presented.
Implementation of a miniaturized lumped-distributed balun in balanced filtering for wireless applications (2005)

This paper reports on miniaturized lumped-distributed balun for balanced filtering applications. Detailed analysis of suppression performance of the lumped-distributed balun is introduced. Different types of baluns and their interconnection in series with filter were considered. Baluns have been implemented using LTCC technology and experimentally validated.
Monobit receiver (2002)

This paper presents a very simple digital receiver design which can cover approximately 1 GHz bandwidth and process two simultaneous signals. The design has the potential to be fabricated on a single chip.
Microarray-based detection of extended virulence and antimicrobial resistance gene profiles in phylogroup B2 Escherichia coli of human, meat and animal origin (2011)

Extra-intestinal pathogenic Escherichia coli (ExPEC) causing urinary tract infections (UTIs) most often belong to phylogenetic group B2 and stem from the patient's own faecal flora. It has been hypothesized that the external reservoir for these uropathogenic E. coli in the human intestine may be meat and food-production animals. To investigate such a connection, this study analysed an E. coli phylogroup B2 strain collection (n = 161) of geographical and temporally matched isolates, published previously, from UTI patients (n = 52), community-dwelling humans (n = 36), imported (n = 5) and Danish (n = 13) broiler chicken meat, Danish broiler chickens (n = 17), imported (n = 3) and Danish (n = 27) pork, and healthy Danish pigs (n = 8). The isolates were subjected to microarray analysis for 315 virulence genes and variants and 82 antimicrobial resistance genes and variants. In total, 133 different virulence and antimicrobial resistance genes were detected in at least one UTI isolate. Between 66 and 87 of these genes were also detected in meat and animal isolates. Cluster analyses of virulence and resistance gene profiles, respectively, showed that UTI and community-dwelling human isolates most often grouped with meat and animal isolates, indicating genotypic similarity among such isolates. Furthermore, B2 isolates were detected from UTI patients and meat, with indistinguishable gene profiles. A considerable proportion of the animal and meat isolates belonged to the ExPEC pathotype. In conclusion, these findings suggest that B2 E. coli from meat and animal origin can be the source of most of the virulence and antimicrobial resistance genes detected in uropathogenic E. coli isolates and that there is a general resemblance of animal, meat and UTI E. coli based on extended gene profiling. These findings support the hypothesis of a zoonotic link between E. coli causing UTIs and E. coli from meat and animals.
Postpolypectomy Lower Gastrointestinal Bleeding: Potential Role of Aspirin (2004)

Postpolypectomy bleeding is an uncommon but important complication of endoscopic polypectomy. There was no statistically relevant difference in prior aspirin use before polypectomy in the bleeding group and the matched controls.
A semi-supervised deep learning algorithm for abnormal EEG identification (2019)

Systems that can automatically analyze EEG signals can aid neurologists by reducing heavy workload and delays. However, such systems need to be first trained using a labeled dataset. While large corpuses of EEG data exist, a fraction of them are labeled. Hand-labeling data increases workload for the very neurologists we try to aid. This paper proposes a semi-supervised learning workflow that can not only extract meaningful information from large unlabeled EEG datasets but also make predictions with minimal supervision, using labeled datasets as small as 5 examples.
Asymptotic Theory of Information-Theoretic Experimental Design (2005)

We discuss an idea for collecting data in a relatively efficient manner. Our point of view is Bayesian and information-theoretic: on any given trial, we want to adaptively choose the input in such a way that the mutual information between the (unknown) state of the system and the (stochastic) output is maximal, given any prior information (including data collected on any previous trials). We prove a theorem that quantifies the effectiveness of this strategy and give a few illustrative examples comparing the performance of this adaptive technique to that of the more usual nonadaptive experimental design. In particular, we calculate the asymptotic efficiency of the information-maximization strategy and demonstrate that this method is in a well-defined sense never less efficient--and is generically more efficient--than the nonadaptive strategy. For example, we are able to explicitly calculate the asymptotic relative efficiency of the staircase method widely employed in psychophysics research and to demonstrate the dependence of this efficiency on the form of the psychometric function underlying the output responses.
Effect of a Middle Ear Immune Response on Inner Ear Antibody Levels (1985)

The effect of a middle ear immune response upon antibody levels in the perilymphatic compartment of the inner ear was investigated in the guinea pig. Animals were systemically sensitized with keyhole limpet hemocyanin (KLH) and bovine serum albumin (BSA) until high circulating levels were achieved. The middle ear cavity was then challenged with KLH, resulting in a vigorous immune response with effusion and mucosal inflammation. Antibody levels against KLH and BSA were then compared in serum, middle ear effusions, and perilymph. Anti-KLH levels in perilymph were found to increase substantially during middle ear response to challenge, while the anti-BSA levels did not, indicating a local origin for the anti-KLH antibody. The most likely explanations for these findings are inner ear antibody originated in the middle ear and diffused across the round window membrane, or antigen diffused across the round window membrane and evoked local production of antibody within the inner ear.
Search for anomalous production of prompt like-sign muon pairs and constraints on physics beyond the standard model with the ATLAS detector (2012)

Search for anomalous production of prompt like-sign muon pairs and constraints on physics beyond the standard model with the ATLAS detector
The Use of Functional Analysis in Evaluating Knee Kinematics (2003)

The importance of understanding the six-degrees-of-freedom kinematics of the knee during ambulatory activities was examined in the context of the function of total knee arthroplasty. Studies of knee kinematics during walking, stair climbing, and a deep flexion squat indicate that knee kinematics is activity-dependent. A comparative study of patients and healthy subjects during stair climbing indicates the importance of maintaining the function of the posterior cruciate ligament. A second study used walking kinematics derived from patient testing as input to a wear simulator. There was increased wear relative to standard simulator input that was related to the slip velocity at the contact surface. Finally, results from a study of deep flexion indicate that substantial femoral rotation is required during deep flexion activities. The current study shows the importance of studying in vivo knee kinematics for future enhancement in the treatment of the arthritic knee.
Ultrashort‐TE stimulated echo acquisition mode (STEAM) improves the quantification of lipids and fatty acid chain unsaturation in the human liver at 7 T (2015)

Ultrahigh-field, whole-body MR systems increase the signal-to-noise ratio (SNR) and improve the spectral resolution. Sequences with a short TE allow fast signal acquisition with low signal loss as a result of spin-spin relaxation. This is of particular importance in the liver for the precise quantification of the hepatocellular content of lipids (HCL). In this study, we introduce a spoiler Gradient-switching Ultrashort STimulated Echo AcqUisition (GUSTEAU) sequence, which is a modified version of a stimulated echo acquisition mode (STEAM) sequence, with a minimum TE of 6 ms. With the high spectral resolution at 7 T, the efficient elimination of water sidebands and the post-processing suppression of the water signal, we estimated the composition of fatty acids (FAs) via the detection of the olefinic lipid resonance and calculated the unsaturation index (UI) of hepatic FAs. The performance of the GUSTEAU sequence for the assessment of UI was validated against oil samples and provided excellent results in agreement with the data reported in the literature. When measuring HCL with GUSTEAU in 10 healthy volunteers, there was a high correlation between the results obtained at 7 and 3 T (R(2) = 0.961). The test-retest measurements yielded low coefficients of variation for HCL (4 ± 3%) and UI (11 ± 8%) when measured with the GUSTEAU sequence at 7 T. A negative correlation was found between UI and HCL (n = 10; p < 0.033). The ultrashort TE MRS sequence (GUSTEAU; TE = 6 ms) provided high repeatability for the assessment of HCL. The improved spectral resolution at 7 T with the elimination of water sidebands and the offline water subtraction also enabled an assessment of the unsaturation of FAs. This all highlights the potential use of this MRS acquisition scheme for studies of hepatic lipid composition in vivo.
Low-Temperature, Solution-Processed Zinc Tin Oxide Thin-Film Transistors Fabricated by Thermal Annealing and Microwave Irradiation (2012)

In this study, we fabricated zinc tin oxide (ZTO) thin-film transistors (TFTs) using a sol–gel solution at a low annealing temperature of 350 °C. We found that the combination of conventional hot plate annealing and microwave irradiation was effective for achieving high performance of ZTO-TFTs. Solution-processed ZTO-TFTs prepared at 350 °C by microwave irradiation showed enhanced device characteristics of 1.84 cm 2 V -1 s -1 mobility and a 10 6 on/off current ratio. X-ray photoelectron spectroscopy analyses confirmed that residual hydroxyls in solution-processed ZTO films can be decomposed at low temperatures by microwave irradiation. Low-temperature microwave-assisted processing makes ZTO TFTs promising for use in flexible, transparent electronics.
Correlation of sperms' swimming force to their swimming speed assessed by optical tweezers (2005)

The purpose of this study is to seek a correlation between the swimming forces of sperm, their swimming speed and the speed of progression score (SOP), which is given to them by the generally applied subjective 1 - 5 system. This study also examines the effects of length of exposure to the laser trap and laser power on sperm motility. Sperm with SOPs of 2-4 were trapped by a continuous wave 1064 nm single point gradient laser trap. To study trap duration effects, sperm were trapped for fifteen, ten and five seconds at 420mW laser power. To study laser power effects within the trap, powers of 420mW, 350mW, 300mW, and 250mW were applied for a constant duration (5 seconds). The correlations between sperm swimming force, swimming speed and speed of progression were examined at a trap duration and trapping power that were statistically shown to not significantly affect sperm motility. Swimming forces were measured by trapping sperm and subsequently decreasing laser power until the sperm were capable of escaping the trap (escape laser power is directly proportional to swimming force). Swimming speeds were calculated by custom built software, and speed of progression scores were assigned in a blind study by fertility experts examining offline video of the experiments. Sperm swimming force measurements by optical trapping may be a method to quantitatively measure sperm vitality that augments currently used methods.
Anomalous Pressure-Induced Enhancement of GMR in Fe/Cr Magnetic Multilayers (2007)

We report the first observation of a large pressure-induced enhancement of the giant magnetoresistance (GMR) in magnetic multilayers (MMLs). In Fe/Cr MMLs with a Cr layer thickness ( t Cr ) of ∼30 Å, a crossover from biquadratic to bilinear interlayer exchange coupling (IEC) was clearly observed by applying pressure and simultaneously the GMR under high pressure (>2 GPa) was enhanced to be twice as large as that at ambient pressure. The enhanced GMR is attributed to the suppression of the biquadratic IEC due to the application of pressure.
Pathogenic E. coli Exploits SslE Mucinase Activity to Translocate through the Mucosal Barrier and Get Access to Host Cells (2015)

SslE is a zinc-metalloprotease involved in the degradation of mucin substrates and recently proposed as a potential vaccine candidate against pathogenic E. coli. In this paper, by exploiting a human in vitro model of mucus-secreting cells, we demonstrated that bacteria expressing SslE have a metabolic benefit which results in an increased growth rate postulating the importance of this antigen in enhancing E. coli fitness. We also observed that SslE expression facilitates E. coli penetration of the mucus favouring bacteria adhesion to host cells. Moreover, we found that SslE-mediated opening of the mucosae contributed to the activation of pro-inflammatory events. Indeed, intestinal cells infected with SslE-secreting bacteria showed an increased production of IL-8 contributing to neutrophil recruitment. The results presented in this paper conclusively designate SslE as an important colonization factor favouring E. coli access to both metabolic substrates and target cells.
Mid-IR heterogeneous silicon photonics (2013)

In this paper we discuss silicon-based photonic integrated circuit technology for applications beyond the telecommunication wavelength range. Silicon-on-insulator and germanium-on-silicon passive waveguide circuits are described, as well as the integration of III-V semiconductors, IV-VI colloidal nanoparticle films and GeSn alloys on these circuits for increasing the functionality. The strong nonlinearity of silicon combined with the low nonlinear absorption in the mid-infrared is exploited to generate picosecond pulse based supercontinuum sources and optical parametric oscillators that can be used as spectroscopic sensor sources.
BLAST training : Estimating Channel Characteristics for High-Capacity Space-Time Wireless (1999)

BLAST (Bell Labs Layered Space-Time) is a multiple-antenna communication scheme whose outage capacity in a Rayleigh flat fading environment grows linearly with the minimum of the number of transmit and receive antennas, with no increase in bandwidth or transmitted power. Based on its knowledge of the matrix of propagation coefficients, the receiver performs two critical operations: nulling and cancellation, that in effect create independent virtual subchannels. Assume that the receiver estimates the propagation matrix from a known set of transmitted training signals, and then uses the estimate as though it were correct for nulling and cancellation. How much training is needed for satisfactory operation? The optimal training signals are orthogonal with respect to time among the transmit antennas, and each transmit antenna is fed equal energy. Errors in estimating the propagation matrix manifest themselves as crosstalk among the virtual subchannels. If its magnitude is too large, the cro...
Big Data Transforms Discovery–Utilization Therapeutics Continuum (2016)

Enabling omic technologies adopt a holistic view to produce unprecedented insights into the molecular underpinnings of health and disease, in part, by generating massive high-dimensional biological data. Leveraging these systems-level insights as an engine driving the healthcare evolution is maximized through integration with medical, demographic, and environmental datasets from individuals to populations. Big data analytics has accordingly emerged to add value to the technical aspects of storage, transfer, and analysis required for merging vast arrays of omic-, clinical-, and eco-datasets. In turn, this new field at the interface of biology, medicine, and information science is systematically transforming modern therapeutics across discovery, development, regulation, and utilization.