gebhart/patrepeval huggingface dataset:
Rat NaV1.7 loss-of-function genetic model: Deficient nociceptive and neuropathic pain behavior with retained olfactory function and intra-epidermal nerve fibers (2019)

Recapitulating human disease pathophysiology using genetic animal models is a powerful approach to enable mechanistic understanding of genotype–phenotype relationships for drug development. Na V 1.7 is a sodium channel expressed in the peripheral nervous system with strong human genetic validation as a pain target. Efforts to identify novel analgesics that are nonaddictive resulted in industry exploration of a class of sulfonamide compounds that bind to the fourth voltage-sensor domain of Na V 1.7. Due to sequence differences in this region, sulfonamide blockers generally are potent on human but not rat Na V 1.7 channels. To test sulfonamide-based chemical matter in rat models of pain, we generated a humanized Na V 1.7 rat expressing a chimeric Na V 1.7 protein containing the sulfonamide-binding site of the human gene sequence as a replacement for the equivalent rat sequence. Unexpectedly, upon transcription, the human insert was spliced out, resulting in a premature stop codon. Using a validated antibody, Na V 1.7 protein was confirmed to be lost in the brainstem, dorsal root ganglia, sciatic nerve, and gastrointestinal tissue but not in nasal turbinates or olfactory bulb in rats homozygous for the knock-in allele (HOM-KI). HOM-KI rats exhibited normal intraepidermal nerve fiber density with reduced tetrodotoxin-sensitive current density and action potential firing in small diameter dorsal root ganglia neurons. HOM-KI rats did not exhibit nociceptive pain responses in hot plate or capsaicin-induced flinching assays and did not exhibit neuropathic pain responses following spinal nerve ligation. Consistent with expression of chimeric Na V 1.7 in olfactory tissue, HOM-KI rats retained olfactory function. This new genetic model highlights the necessity of Na V 1.7 for pain behavior in rats and indicates that sufficient inhibition of Na V 1.7 in humans may reduce pain in neuropathic conditions. Due to preserved olfactory function, this rat model represents an alternative to global Na V 1.7 knockout mice that require time-intensive hand feeding during early postnatal development.
ChemInform Abstract: C—H Activation A Surrogate for Selectivity (2014)

Abstract Review: use of a ombination of an alkene hydrosilylation, C‐H activation and C‐Si oxidtion to achieve a formal 1,4‐dioxygenation of alkenes; 10 refs.
Magnetism in Lithium–Oxygen Discharge Product (2013)

Nonaqueous lithium-oxygen batteries have a much superior theoretical gravimetric energy density compared to conventional lithium-ion batteries, and thus could render long-range electric vehicles a reality. A molecular-level understanding of the reversible formation of lithium peroxide in these batteries, the properties of major/minor discharge products, and the stability of the nonaqueous electrolytes is required to achieve successful lithium-oxygen batteries. We demonstrate that the major discharge product formed in the lithium-oxygen cell, lithium peroxide, exhibits a magnetic moment. These results are based on dc-magnetization measurements and a lithium-oxygen cell containing an ether-based electrolyte. The results are unexpected because bulk lithium peroxide has a significant band gap. Density functional calculations predict that superoxide-type surface oxygen groups with unpaired electrons exist on stoichiometric lithium peroxide crystalline surfaces and on nanoparticle surfaces; these computational results are consistent with the magnetic measurement of the discharged lithium peroxide product as well as EPR measurements on commercial lithium peroxide. The presence of superoxide-type surface oxygen groups with spin can play a role in the reversible formation and decomposition of lithium peroxide as well as the reversible formation and decomposition of electrolyte molecules.
Effect of Surface Wettability on the Adsorption of Proteins and Detergents (1998)

This report describes the use of surface plasmon spectroscopy to study the effect of surface wettability on the nonspecific adsorption of proteins and detergents to self-assembled monolayers (SAMs) of alkanethiolates on gold. The adsorption of both proteins and detergents to uncharged SAMs showed a general dependence on the wettability of the surface as determined by the contact angle of water on the SAM under cyclooctane (θco). The effect of the wettability of the SAMs on the adsorption of sodium dodecyl sulfate (SDS) was dependent on whether micelles were present. Above the critical micelle concentration (cmc), SDS adsorbed only on surfaces that gave contact angles with values of cos θco < 0 (i.e., the transfer of the surface from water to cyclooctane has a favorable free energy). Below the cmc, the requirement for adsorption was much more stringent: SDS adsorbed only on the surfaces that gave values of cos θco < −0.9. Similarly, the effect of the wettability of the SAMs on the adsorption of proteins showed a dependence on the size of the proteins. The smaller proteins tested (ribonuclease A and lysozyme) adsorbed only on the least wettable surfaces tested (cos θco < −0.83). The larger proteins tested (pyruvate kinase, fibrinogen, and γ-globulin) also adsorbed best to the least wettable surfaces, but adsorbed to some extent on almost all the surfaces; the single exception was a SAM presenting hexa(ethylene glycol) groups at the surface, to which no protein adsorbed. Films of adsorbed proteins were desorbed from the SAMs by treatment with detergent.
Effect of screw position on load transfer in lumbar pedicle screws: a non-idealized finite element analysis (2016)

Angled screw insertion has been advocated to enhance fixation strength during posterior spine fixation. Stresses on a pedicle screw and surrounding vertebral bone with different screw angles were studied by finite element analysis during simulated multidirectional loading. Correlations between screw-specific vertebral geometric parameters and stresses were studied. Angulations in both the sagittal and axial planes affected stresses on the cortical and cancellous bones and the screw. Pedicle screws pointing laterally (vs. straight or medially) in the axial plane during superior screw angulation may be advantageous in terms of reducing the risk of both screw loosening and screw breakage.
Speckle Tracking for the Recovery of Displacement and Velocity Information from Sequences of Ultrasound Images of the Tongue (2008)

This paper explores the use of deformable registration (speckle tracking) as a method for obtaining point correspondences on sequences of tongue images acquired via ultrasound in order to estimate tongue velocity and displacement. We model the velocity field as smooth Bspline functions and estimate it from adjacent frames. This model enables us to accumulate the motion and hence calculate the displacement from the first frame to any frame in the image sequence. Specifically, it provides the displacement estimates on the curve, enabling us to introduce “virtual flesh point markers ” on the tongue surface. We tested the algorithm on ultrasound image sequences that were taken during the production of domain initial vowels in two different prosodic domains – word initial and accentual phrase initial. The results demonstrate the utility of the algorithm in quantification of tongue motion in speech. 1
A low-overhead high-performance unified buffer management scheme that exploits sequential and looping references (2000)

In traditional file system implementations, the Least Recently Used (LRU) block replacement scheme is widely used to manage the buffer cache due to its simplicity and adaptability. However, the LRU scheme exhibits performance degradations because it does not make use of reference regularities such as sequential and looping references. In this paper, we present a Unified Buffer Management (UBM) scheme that exploits these regularities and yet, is simple to deploy. The UBM scheme automatically detects sequential and looping references and stores the detected blocks in separate partitions of the buffer cache. These partitions are managed by appropriate replacement schemes based on their detected patterns. The allocation problem among the divided partitions is also tackled with the use of the notion of marginal gains. In both trace-driven simulation experiments and experimental studies using an actual implementation in the FreeBSD operating system, the performance gains obtained through the use of this scheme are substantial. The results show that the hit ratios improve by as much as 57.7% (with an average of 29.2%) and the elapsed times are reduced by as much as 67.2% (with an average of 28.7%) compared to the LRU scheme for the workloads we used.
Extractive Summarization Method for Contact Center Dialogues based on Call Logs (2011)

This paper proposes a novel extractive summarization method for speech dialogues between agents and customers in contact centers. The proposed method does not require any extra cost for applying the method such as preparing rules or creating training data. Conventional methods such as the tf*idf method, which gives importance to characteristic words in an input text, can miss the essential points for contact center work. Our proposed method evaluates the importance of each utterance from the standpoint of call agents who report calls for managing or analyzing calls. Specifically, the proposed method includes information frequently reported by call agents in summaries using past call logs commonly recorded in the contact center. Evaluation using real data (call dialogues and call logs) shows that the proposed method can extract essential points in terms of contact center work and outperforms the conventional method.
Stability of a voice activity detector based on source separation (2002)

Source separation techniques been applied to the problem of voice activity detection (VAD) and a method has been developed which is able to perform well in very adverse. Environments (-5 to -10 dB). The optimisation procedure is totally iterative and therefore suitable for use in real-time, dynamically adapting situations. Stability considerations are addressed in this paper and simulation results are given. These show the new technique to be very robust to high levels of additive noise, with a relatively low complexity.
Effects of injection power and frequency detuning on noise characteristics of an injection-locked VCSEL (2012)

The noise characteristics of an injection-locked VCSEL are experimentally investigated. Effects of injection-ratio and detuning on the phase noise added by an injection-locked VCSEL are studied.
Scale up and industrial implementation: general discussion (2022)

Adam B. Braunschweig opened a general discussion of the paper by Matej Baláž: Although you noted that there were not any trends that you could see between the sulfur/copper ratio and ignition, I was wondering if there were any comments you could make about this relationship from your experiment
Promoter methylation of heat shock protein B2 in human esophageal squamous cell carcinoma (2011)

Hypermethylation of gene promoters and the corresponding loss of gene expression are recognized as a hallmark of human cancer, and DNA methylation has emerged as a promising biomarker for the detection of human esophageal squamous cell carcinoma (ESCC). To identify novel genes methylated in ESCC, we screened 35 candidate genes identified from an oligonucleotide microarray. Among them, the heat shock protein B2 (HSPB2) was methylated in 95.7% (67/70) of primary ESCCs, whereas no methylation was found in normal esophageal tissues from ESCC patients (0%, 0/20). RT-PCR analysis revealed that HSPB2 expression was silenced or weakly expressed in most ESCC cell lines, and re-activated by the demethylating agent 5-aza-2'-deoxy-cytidine. These results indicate that promoter methylation of HSPB2 is one of the causal factors for loss or down-regulation of HSPB2 expression. mRNA expression of HSPB2 in ESCC tissues was significantly down-regulated compared to normal tissues. Our data suggest that promoter methylation of HSPB2 deserves further attention as a novel molecular biomarker in human ESCC.
Impact of aging and gender on the lg‐containing cell profile of the lacrimal gland (1988)

The present study investigated the influence of age and gender on the number of IgA- and IgM-containing cells in the lacrimal gland. Tissues were obtained from male and female rats at 0.2 (infant), 0.6 (pre-pubertal), 1.3 (pubertal), 3 (adult), 8 (mid-life) and 17 (senescent) months of age, then processed for immunofluorescence microscopy. No IgA-containing cells could be detected in lacrimal glands from infant rats, but a significant accumulation had occurred by 0.6 months of age. The extent of this increase was gender-dependent: tissues from male rats had significantly higher IgA-positive cell densities than those of females. After 0.6 months of age, no further variations in the density of IgA-containing lymphocytes were observed in female gland. In contrast, male glands exhibited marked fluctuations in the density of IgA-containing lymphocytes during the time period spanning puberty (0.6----3 months). Of interest, the frequency distribution of IgA-containing cells in tissue sections was not uniform in rats older than 0.2 months. Correction of cell densities for age-related elevations in lacrimal gland weight demonstrated that the total accumulation of IgA-containing cells was both age- and gender-related. Highest cell numbers were attained at 3 months in females and 3 and 17 months in males. Moreover, at all assessed ages, the total IgA-containing cell number in glands of males was greater than, or equal to, that in tissues of females.(ABSTRACT TRUNCATED AT 250 WORDS)
Mice Deficient in the Respiratory Chain Gene Cox6a2 Are Protected against High-Fat Diet-Induced Obesity and Insulin Resistance (2013)

Oxidative phosphorylation in mitochondria is responsible for 90% of ATP synthesis in most cells. This essential housekeeping function is mediated by nuclear and mitochondrial genes encoding subunits of complex I to V of the respiratory chain. Although complex IV is the best studied of these complexes, the exact function of the striated muscle-specific subunit COX6A2 is still poorly understood. In this study, we show that Cox6a2-deficient mice are protected against high-fat diet-induced obesity, insulin resistance and glucose intolerance. This phenotype results from elevated energy expenditure and a skeletal muscle fiber type switch towards more oxidative fibers. At the molecular level we observe increased formation of reactive oxygen species, constitutive activation of AMP-activated protein kinase, and enhanced expression of uncoupling proteins. Our data indicate that COX6A2 is a regulator of respiratory uncoupling in muscle and we demonstrate that a novel and direct link exists between muscle respiratory chain activity and diet-induced obesity/insulin resistance.
S‐Nitrosohemoglobin Levels and Patient Outcome After Transfusion During Pediatric Bypass Surgery (2017)

Banked blood exhibits impairments in nitric oxide (NO)-based oxygen delivery capability, reflected in rapid depletion of S-nitrosohemoglobin (SNO-Hb). We hypothesized that transfusion of even freshly-stored blood used in pediatric heart surgery would reduce SNO-Hb levels and worsen outcome. In a retrospective review (n = 29), the percent of estimated blood volume (% eBV) replaced by transfusion directly correlated with ventilator time and inversely correlated with kidney function; similar results were obtained in a prospective arm (n = 20). In addition, an inverse association was identified between SNO-Hb and postoperative increase in Hb (∆Hb), reflecting the amount of blood retained by the patient. Both SNO-Hb and ∆Hb correlated with the probability of kidney dysfunction and oxygenation-related complications. Further, regression analysis identified SNO-Hb as an inverse predictor of outcome. The findings suggest that SNO-Hb and ∆Hb are prognostic biomarkers following pediatric cardiopulmonary bypass, and that maintenance of red blood cell-derived NO bioactivity might confer therapeutic benefit.
Cerebrospinal fluid proteomic study of two bipolar disorder cohorts (2022)

The pathophysiology of bipolar disorder remains to be elucidated and there are no diagnostic or prognostic biomarkers for the condition. In this explorative proteomic study, we analyzed 201 proteins in cerebrospinal fluid (CSF) from mood stable bipolar disorder patients and control subjects sampled from two independent cohorts, amounting to a total of 204 patients and 144 controls. We used three Olink Multiplex panels, whereof one specifically targets immune biomarkers, to assess a broad set of CSF protein concentrations. After quality control and removal of proteins with a low detection rate, 105 proteins remained for analyses in relation to case-control status and clinical variables. Only case-control differences that replicated across cohorts were considered. Results adjusted for potential confounders showed that CSF concentrations of growth hormone were lower in bipolar disorder compared with controls in both cohorts. The effect size was larger when the analysis was restricted to bipolar disorder type 1 and controls. We found no indications of immune activation or other aberrations. Growth hormone exerts many effects in the central nervous system and our findings suggest that growth hormone might be implicated in the pathophysiology of bipolar disorder.
High quality factor and high confinement silicon resonators using etchless process (2012)

We demonstrate high-Q factor and high confinement silicon ring resonators fabricated by a local oxidation of silicon (LOCOS) process. We achieve an intrinsic quality factor of 525,000 in 410 μm-circumference ring resonator.
Organic Materials: The Effect of Subtle Modifications on Device Performance (2014)

In the search of new high-mobility polymeric semiconductors with good processability and excellent environmental stability, diverse synthetic strategies have been approached. One of the most widely used consists in the alternation of donor and acceptor moieties in the conjugated skeleton, which allows fine tuning of the polymer frontier molecular orbitals. For organic field effect transistors (OFETs) applications, low-lying HOMOs are essential to resist air oxidation and thus increase device stability. However, if the HOMO energy is too low, the resulting barrier to hole injection may compromise the transistor performance. Thus, a delicate balance between these two effects is needed. Furthermore, high performance solution-processable materials require the correct selection and positioning of the specific solubilizing substituents in order to achieve proper HOMO and LUMO energy levels, planar molecular conformations, close intermolecular π-π stacking, and proper thin film crystallinity. Following these two combined strategies, diverse polymeric materials with great performances in both OFETs and solar cells, and having remarkable air stability, have been synthesized and characterized. , This contribution will analyze how small modifications in their molecular structures can have a great impact on the device performance.
Heterogeneous Integrated Microsystems With Nontraditional Through-Silicon Via Technologies (2017)

In this paper, the design, fabrication, and high-frequency characterization of three types of nontraditional through-silicon via (TSV) technologies are discussed. First, the integration of TSVs within a silicon microfluidic heat sink is presented; TSVs are fabricated within a pin-fin heat sink, and the frequency response of TSVs within a deionized-water-filled silicon pin-fin heat sink is experimentally analyzed. Second, to electrically shield the signal transmission of such TSVs, coaxially shielded TSVs consisting of multiple ground TSVs surrounding a single signal TSV are demonstrated. It is experimentally shown that as the number of ground TSVs increases, shielding is improved. Finally, a partial air-isolation technique is proposed to reduce TSV loss and capacitance at high frequencies.
Medical management of mild to moderate Crohn’s disease: evidence‐based treatment algorithms for induction and maintenance of remission (2007)

Selection of maintenance therapy is based on a combination of evidence from controlled trials and patient features including disease severity and location, co-morbidities, previous response to treatment, and previous surgical resection. The options for maintenance therapy include therapy cessation and patient observation following successful induction, budesonide, or immunosuppressive therapy.
Electrophoretic NMR studies of polymer and surfactant systems (2006)

The aim of this tutorial review is to introduce to a broader readership the emerging technique of electrophoretic NMR (eNMR). The "electrophoretic" element of the technique refers to the fact that charged particles are induced to flow by the application of an electric field. This flow is measured using pulsed-gradient spin-echo NMR (PGSE-NMR). The great potential of this experimental approach is the fact that NMR is chemically selective and non-invasive. eNMR, especially when combined with the more established PGSE-NMR experiment, may therefore be used to quantify the structure of multi-component systems via the dynamics and charge of each species within a complex mixture. Accordingly, eNMR is likely to be of great significance for colloid scientists, biologists, technologists and formulation scientists.
A novel 19F agent for detection and quantification of human dendritic cells using magnetic resonance imaging (2010)

Monitoring of cell therapeutics in vivo is of major importance to estimate its efficacy. Here, we present a novel intracellular label for (19)F magnetic resonance imaging (MRI)-based cell tracking, which allows for noninvasive, longitudinal cell tracking without the use of radioisotopes. A key advantage of (19)F MRI is that it allows for absolute quantification of cell numbers directly from the MRI data. The (19)F label was tested in primary human monocyte-derived dendritic cells. These cells took up label effectively, resulting in a labeling of 1.7 ± 0.1 × 10(13) (19)F atoms per cell, with a viability of 80 ± 6%, without the need for electroporation or transfection agents. This results in a minimum detection sensitivity of about 2,000 cells/voxel at 7 T, comparable with gadolinium-labeled cells. Comparison of the detection sensitivity of cells labeled with (19)F, iron oxide and gadolinium over typical tissue background showed that unambiguous detection of the (19)F-labeled cells was simpler than with the contrast agents. The effect of the (19)F agent on cell function was minimal in the context of cell-based vaccines. From these data, we calculate that detection of 30,000 cells in vivo at 3 T with a reasonable signal to noise ratio for (19)F images would require less than 30 min with a conventional fast spin echo sequence, given a coil similar to the one used in this study. This is well within acceptable limits for clinical studies, and thus, we conclude that (19)F MRI for quantitative cell tracking in a clinical setting has great potential.