gebhart/patrepeval huggingface dataset:
Testing that a Local Optimum of the Likelihood is Globally Optimum using\n Reparameterized Embeddings (2019)

Many mathematical imaging problems are posed as non-convex optimization\nproblems. When numerically tractable global optimization procedures are not\navailable, one is often interested in testing ex post facto whether or not a\nlocally convergent algorithm has found the globally optimal solution. When the\nproblem is formulated in terms of maximizing the likelihood function under a\nstatistical model for the measurements, one can construct a statistical test\nthat a local maximum is in fact the global maximum. A one-sided test is\nproposed for the case that the statistical model is a member of the generalized\nlocation family of probability distributions, a condition often satisfied in\nimaging and other inverse problems. We propose a general method for improving\nthe accuracy of the test by reparameterizing the likelihood function to embed\nits domain into a higher dimensional parameter space. We show that the proposed\nglobal maximum testing method results in improved accuracy and reduced\ncomputation for a physically-motivated joint-inverse problem arising in\ncamera-blur estimation.\n
Effects of long-term low-level charge injection on insulating oil (1984)

Low-level charge injection into insulating oils was maintained for six months. The permittivity of the oil was unaffected, and the conductivity-fell in response to this treatment. After the injection was stopped, the conductivity slowly rose. We conclude that, at the levels used here, charge injection will not affect dielectric constant, and will increase resistivity.
A Network Integration Approach to Predict Conserved Regulators Related to Pathogenicity of Influenza and SARS-CoV Respiratory Viruses (2020)

Respiratory infections stemming from influenza viruses and the Severe Acute Respiratory Syndrome corona virus (SARS-CoV) represent a serious public health threat as emerging pandemics. Despite efforts to identify the critical interactions of these viruses with host machinery, the key regulatory events that lead to disease pathology remain poorly targeted with therapeutics. Here we implement an integrated network interrogation approach, in which proteome and transcriptome datasets from infection of both viruses in human lung epithelial cells are utilized to predict regulatory genes involved in the host response. We take advantage of a novel "crowd-based" approach to identify and combine ranking metrics that isolate genes/proteins likely related to the pathogenicity of SARS-CoV and influenza virus. Subsequently, a multivariate regression model is used to compare predicted lung epithelial regulatory influences with data derived from other respiratory virus infection models. We predicted a small set of regulatory factors with conserved behavior for consideration as important components of viral pathogenesis that might also serve as therapeutic targets for intervention. Our results demonstrate the utility of integrating diverse 'omic datasets to predict and prioritize regulatory features conserved across multiple pathogen infection models.
Appendix E: MATLAB Basics (2004)

MATLAB BasicsIn this appendix we provide a brief introduction to the features and use of MATLAB.Parts of this tutorial are borrowed with permission from [47].Recent versions of MATLAB have excellent online tutorials and documentation-please refer to those for more details.At the end of the appendix we list some MATLAB tutorials that are available on the Web.Readers are encouraged to follow along by typing the examples into a MATLAB interpreter as they are presented.In the following, user input to MATLAB follows the MATLAB prompt (">>").The system response is given in this font.
Data from <i>De Novo</i> Lipogenesis Alters the Phospholipidome of Esophageal Adenocarcinoma (2023)

&lt;div&gt;Abstract&lt;p&gt;The incidence of esophageal adenocarcinoma is rising, survival remains poor, and new tools to improve early diagnosis and precise treatment are needed. Cancer phospholipidomes quantified with mass spectrometry imaging (MSI) can support objective diagnosis in minutes using a routine frozen tissue section. However, whether MSI can objectively identify primary esophageal adenocarcinoma is currently unknown and represents a significant challenge, as this microenvironment is complex with phenotypically similar tissue-types. Here, we used desorption electrospray ionization-MSI (DESI-MSI) and bespoke chemometrics to assess the phospholipidomes of esophageal adenocarcinoma and relevant control tissues. Multivariate models derived from phospholipid profiles of 117 patients were highly discriminant for esophageal adenocarcinoma both in discovery (AUC = 0.97) and validation cohorts (AUC = 1). Among many other changes, esophageal adenocarcinoma samples were markedly enriched for polyunsaturated phosphatidylglycerols with longer acyl chains, with stepwise enrichment in premalignant tissues. Expression of fatty acid and glycerophospholipid synthesis genes was significantly upregulated, and characteristics of fatty acid acyls matched glycerophospholipid acyls. Mechanistically, silencing the carbon switch &lt;i&gt;ACLY&lt;/i&gt; in esophageal adenocarcinoma cells shortened glycerophospholipid chains, linking &lt;i&gt;de novo&lt;/i&gt; lipogenesis to the phospholipidome. Thus, DESI-MSI can objectively identify invasive esophageal adenocarcinoma from a number of premalignant tissues and unveils mechanisms of phospholipidomic reprogramming.&lt;/p&gt;Significance:&lt;p&gt;These results call for accelerated diagnosis studies using DESI-MSI in the upper gastrointestinal endoscopy suite, as well as functional studies to determine how polyunsaturated phosphatidylglycerols contribute to esophageal carcinogenesis.&lt;/p&gt;&lt;/div&gt;
P601 Upadacitinib improves steroid-free clinical and endoscopic endpoints in patients with Crohn’s disease: Data from the CELEST study (2018)

The efficacy and safety of upadacitinib (UPA), an oral selective JAK1 inhibitor, were assessed in patients with moderate-to-severe Crohn’s disease (CD) and with inadequate response/intolerance to an immunomodulator or tumour necrosis factor inhibitor (TNFi).1 We report the steroid-free endpoints in the 16-week induction phase of CELEST in patients receiving corticosteroid (CS) at baseline (BL). Patients with CD Activity Index (CDAI) 220–450, average daily very soft/liquid stool frequency (SF) ≥2.5 or abdominal pain score (AP) ≥2.0 and Simplified Endoscopic Score for CD (SES-CD) ≥6 (or ≥4 for those with isolated ileal disease) were randomised equally to receive either placebo (PBO) or UPA 3, 6, 12, 24 mg twice daily (BID) or 24 mg once daily (QD) for 16 weeks. Patients were also randomised 1: 1 at BL for follow-up ileocolonoscopy at either 12 or 16 weeks. Beginning at Week 2, CS was tapered in patients on CS at BL. The proportion of patients who discontinued CS and achieved endoscopic remission, endoscopic response, clinical remission, modified clinical remission (all defined in Figure), and CDAI <150 were assessed at Week 16 in patients on CS at BL. Patients with missing data or who prematurely discontinued or received CS dose higher than BL were considered non-responders. Comparisons of each dose of UPA vs. PBO were performed using Chi-square test. Treatment-emergent adverse events (AEs) collected throughout the study in patients with at least one UPA dose up to 30 days of the last dose were stratified by CS use at BL. Among 220 randomised patients, 96 (43.6%) received CS at BL: median (min–max) age 38.5 (19.0–69.0) years, CDAI 291.0 (162–599), CD duration 9.4 (0.1–44.7) years and 95 (99.0%) had failed one or more TNFi. More patients taking UPA were able to discontinue CS and achieve endoscopic endpoints at 12 of 16 weeks and clinical endpoints at 16 weeks than patients on PBO (Figure). Patients on 24 mg BID achieved a statistically significant difference from PBO in all clinical remission endpoints. The rates of any AEs were similar between patients with or without CS use in the UPA (85.2% and 80.4%, in all UPA arms, respectively) and PBO groups (73.3% and 72.7%). Proportion of subjects who discontinued corticosteroid and achieved clinical and endoscopic endpoints at 16 weeks. Patients with long-standing CD refractory to conventional/TNFi therapy who received CS at BL achieved statistically significant steroid-free endoscopic and clinical improvements at 16 weeks of treatment with UPA. The safety profile of UPA in patients taking CS at BL was consistent with the overall study population. 1. Sandborn WJ et al. Gastroenterology 2017;152(Suppl. 1):S1308–9.
High throughput high intensity focused ultrasound (HIFU) treatment for tissue necrosis (2005)

To increase HIFU throughput, a HIFU transducer (diameter of 7 cm, focal length of 6 cm, operating frequency of 3.4 MHz), coupled to an imaging probe (ICT 7-4, Sonosite), was driven by 100 W driving unit with 500 W amplifier. A water pillow connected to a circulation pump with degassed water provided transducer coupling and cooling. Input electrical power was 400 W, corresponding to focal intensity of 51&amp;lt;th&amp;gt;300 W/cm2 (in water). HIFU was applied transcutaneously in porcine thigh muscle in vivo, and intraoperatively in liver hilum, for 30–60 s. After 30 s of treatment, muscle lesions had diameter of 2.1±0.4 cm and length of 2.0±0.4 cm. After 60 s of treatment, muscle lesions had diameter of 3.1±0.9 cm and length of 3.1±1.0 cm. In few cases of severe skin burns, the lesions were formed immediately under the skin and were shallow (∼1 cm). Liver lesions had diameter of 2.1±0.3 cm and length of 2.3±0.6 cm. In comparison, after the 30 s treatment with our standard HIFU device (focal intensity of 27&amp;lt;th&amp;gt;000 W/cm2, in water) the muscle lesions had diameter of 1.3±0.6 cm and length of 1.1±0.6 cm. High power HIFU device can quickly coagulate large tissue volumes.
Development of a new direct liquid injection system for nanoparticle deposition by chemical vapor deposition using nanoparticle solutions (2016)

Nanoparticles of different materials are already in use for many applications. In some applications, these nanoparticles need to be deposited on a substrate in a fast and reproducible way. We have developed a new direct liquid injection system for nanoparticle deposition by chemical vapor deposition using a liquid nanoparticle precursor. The system was designed to deposit nanoparticles in a controlled and reproducible way by using two direct liquid injectors to deliver nanoparticles to the system. The nanoparticle solution is first evaporated and then the nanoparticles flow onto a substrate inside the vacuum chamber. To allow injection and evaporation of the liquid, a direct liquid injection and vaporization system are mounted on top of the process chamber. The deposition of the nanoparticles is controlled by parameters such as deposition temperature, partial pressure of the gases, and flow rate of the nanoparticle suspension. The concentration of the deposited nanoparticles can be varied simply by changing the flow rate and deposition time. We demonstrate the capabilities of this system using gold nanoparticles. The selected suspension flow rates were varied between 0.25 and 1 g/min. AFM analysis of the deposited samples showed that the aggregation of gold nanoparticles is well controlled by the flow and deposition parameters.
Cln3‐mutations underlying juvenile neuronal ceroid lipofuscinosis cause significantly reduced levels of Palmitoyl‐protein thioesterases‐1 (Ppt1)‐protein and Ppt1‐enzyme activity in the lysosome (2019)

Mutations in at least 13 different genes (called CLNs) underlie various forms of neuronal ceroid lipofuscinoses (NCLs), a group of the most common neurodegenerative lysosomal storage diseases. While inactivating mutations in the CLN1 gene, encoding palmitoyl-protein thioesterases-1 (PPT1), cause infantile NCL (INCL), those in the CLN3 gene, encoding a protein of unknown function, underlie juvenile NCL (JNCL). PPT1 depalmitoylates S-palmitoylated proteins (constituents of ceroid) required for their degradation by lysosomal hydrolases and PPT1-deficiency causes lysosomal accumulation of autofluorescent ceroid leading to INCL. Because intracellular accumulation of ceroid is a characteristic of all NCLs, a common pathogenic link for these diseases has been suggested. It has been reported that CLN3-mutations suppress the exit of cation-independent mannose 6-phosphate receptor (CI-M6PR) from the trans Golgi network (TGN). Because CI-M6PR transports soluble proteins such as PPT1 from the TGN to the lysosome, we hypothesized that CLN3-mutations may cause lysosomal PPT1-insufficiency contributing to JNCL pathogenesis. Here, we report that the lysosomes in Cln3-mutant mice, which mimic JNCL, and those in cultured cells from JNCL patients, contain significantly reduced levels of Ppt1-protein and Ppt1-enzyme activity and progressively accumulate autofluorescent ceroid. Furthermore, in JNCL fibroblasts the V0a1 subunit of v-ATPase, which regulates lysosomal acidification, is mislocalized to the plasma membrane instead of its normal location on lysosomal membrane. This defect dysregulates lysosomal acidification, as we previously reported in Cln1 <sup>-/-</sup> mice, which mimic INCL. Our findings uncover a previously unrecognized role of CLN3 in lysosomal homeostasis and suggest that CLN3-mutations causing lysosomal Ppt1-insuffiiciency may at least in part contribute to JNCL pathogenesis.
Attentional modulation of cortical plasticity (2006)

This chapter develops a possible model for the role of attention in cortical plasticity. It presents the definition of attention, its behavioral implications, and its neural and pharmacological basis. Attention is most frequently studied in the visual domain, where attention is known to improve the processing of certain visual information at the expense of other information that is presented simultaneously. The chapter also presents evidence that attention or behavioral interaction is required. It outlines some examples of plasticity that appears to occur in the absence of behavioral engagement. The chapter considers studies where attentional modulation or awareness of stimuli was required for learning to occur. The concept of a common pathway for attention and learning is supported by psychophysical studies that show that attentional enhancement of perception and learning enhancement of perception operate on the same substrates.
PERFORMANCE BASED STABILIZATION OF SEISMICALLY UNSTABLE SLOPES BY LARGE DIAMETER PILES (2014)

This paper aims at summarizing the methodology, proposed by Ozcebe (2014) to estimate the amount of reduction in residual displacements demand of pile-reinforced slopes through normalized mean stabilization curves. Ozcebe (2014) carried out numerous advanced numerical analyses using FLAC 2D and FLAC 3D commercial computer programs (Itasca, 2011 and Itasca, 2009) which were functional for setting up an innovative performance-based design method. Relatively simple elastic-plastic constitutive law with hysteretic unloading-reloading associated with Mohr-Coulomb yield criterion has been chosen to idealize soil response which had been tested and calibrated on the basis of two seismic centrifuge tests carried out in the ISMGEO laboratory at Seriate in Northern Italy, which stands out of scope of the current paper.
Miniaturised artificial magnetic conductors with wide split ring resonators and interdigital structures (2012)

Miniaturised artificial magnetic conductors (AMCs) using wide split ring resonator (SRR) loadings and interdigital structures are proposed. Compared to an AMC with normal SRR loadings, an AMC with wide SRR loadings shows lower resonance frequency because of the increased capacitance. The insertion of interdigital structures at top patches and wide SRR loadings further decreases the resonance frequency.
Failure of Bone Marrow to Reconstitute Lung Epithelium (2005)

A new paradigm of epithelial tissue reconstitution has been suggested whereby circulating cells derived from bone marrow contribute to a variety of epithelial cell types. With regard to the lung, several recent reports have used immunofluorescence microscopy to demonstrate engraftment of bone marrow-derived cells as type II pneumocytes, the endogenous progenitors of the lung alveolus. We show here that immunofluorescence microscopy, as has been used in previous reports, cannot reliably identify rare engrafted cells in lung tissue sections after transplantation of bone marrow cells or purified hematopoietic stem cells tracked with ubiquitous labels. We have employed a lineage-specific reporter system based on transgenic mice that express the GFP reporter gene only in lung epithelial cells (surfactant protein C-GFP) to assay for engrafted cells by flow cytometry, histology, and molecular methods. Using this approach to evaluate transplant recipients, including those subjected to bleomycin-induced lung injury, we demonstrate that when autofluorescence, dead cells, and contaminating blood cells are excluded from analysis, there is no detectable reconstitution of lung alveolar epithelial cells by unfractionated bone marrow cells or purified hematopoietic stem cells.
Identification of PD sources in solids (1992)

It is of great importance not only to detect but also to localise and identify the source of partial discharges (PD). If the PD source type can be identified, it is possible to give a more reliable estimate of the potential damage. The authors present some general arguments for the acoustic mode density in cavities of different dimensionality: flat, hole or spherical. This knowledge may be utilised to identify the shape and size of a discharging cavity in solid insulators using the acoustic technique. >
The 2019 IEEE International Conference on Microwaves, Communications, Antennas, and Electronic Systems [Conference Report] (2020)

Presents information on the 2019 IEEE International Conference on Microwaves, Communications, Antennas, and Electronic Systems.
Technical Note: Retrospective reduction in systematic differences across scanner changes by accounting for noise floor effects in diffusion tensor imaging (2018)

Accounting for noise floor effects can boost the robustness of DTI measurements in the presence of scanner changes, potentially improving the reliability of DTI for studies of neurological disease.
Molecular Analysis of the SCARECROW Gene in Maize Reveals a Common Basis for Radial Patterning in Diverse Meristems (2000)

Jun Lim, Yrjo Helariutta, Chelsea D. Specht, Jee Jung, Lynne Sims, Wesley B. Bruce, Scott Diehn, Philip N. Benfey, Molecular Analysis of the SCARECROW Gene in Maize Reveals a Common Basis for Radial Patterning in Diverse Meristems, The Plant Cell, Vol. 12, No. 8 (Aug., 2000), pp. 1307-1318
Disruption of NMDAR–CRMP-2 signaling protects against focal cerebral ischemic damage in the rat middle cerebral artery occlusion model (2012)

Collapsin response mediator protein 2 (CRMP-2), traditionally viewed as an axon/dendrite specification and axonal growth protein, has emerged as nidus in regulation of both pre- and post-synaptic Ca ( 2+) channels. Building on our discovery of the interaction and regulation of Ca ( 2+) channels by CRMP-2, we recently identified a short sequence in CRMP-2 which, when appended to the transduction domain of HIV TAT protein, suppressed acute, inflammatory and neuropathic pain in vivo by functionally uncoupling CRMP-2 from the Ca ( 2+) channel. Remarkably, we also found that this region attenuated Ca ( 2+) influx via N-methylD-Aspartate receptors (NMDARs) and reduced neuronal death in a moderate controlled cortical impact model of traumatic brain injury (TBI). Here, we sought to extend these findings by examining additional neuroprotective effects of this peptide (TAT-CBD3) and exploring the biochemical mechanisms by which TAT-CBD3 targets NMDARs. We observed that an intraperitoneal injection of TAT-CBD3 peptide significantly reduced infarct volume in an animal model of focal cerebral ischemia. Neuroprotection was observed when TAT-CBD3 peptide was given either prior to or after occlusion but just prior to reperfusion. Surprisingly, a direct biochemical complex was not resolvable between the NMDAR subunit NR2B and CRMP-2. Intracellular application of TAT-CBD3 failed to inhibit NMDAR current. NR2B interactions with the post synaptic density protein 95 (PSD-95) remained intact and were not disrupted by TAT-CBD3. Peptide tiling of intracellular regions of NR2B revealed two 15-mer sequences, in the carboxyl-terminus of NR2B, that may confer binding between NR2B and CRMP-2 which supports CRMP-2's role in excitotoxicity and neuroprotection.
Data from Fc Optimization of Therapeutic Antibodies Enhances Their Ability to Kill Tumor Cells <i>In vitro</i> and Controls Tumor Expansion <i>In vivo</i> via Low-Affinity Activating Fcγ Receptors (2023)

&lt;div&gt;Abstract&lt;p&gt;Monoclonal antibodies (mAb) are widely used in the treatment of non-Hodgkin's lymphoma and autoimmune diseases. Although the mechanism of action &lt;i&gt;in vivo&lt;/i&gt; is not always known, the therapeutic activity of several approved mAbs depends on the binding of the Fcγ regions to low-affinity Fcγ receptors (FcγR) expressed on effector cells. We did functional genetic screens to identify IgG1 Fc domains with improved binding to the low-affinity activating Fc receptor CD16A (FcγRIIIA) and reduced binding to the low-affinity inhibitory Fc receptor, CD32B (FcγRIIB). Identification of new amino acid residues important for FcγR binding guided the construction of an Fc domain that showed a dramatically enhanced CD16A binding and greater than a 100-fold improvement in antibody-dependent cell-mediated cytotoxicity. In a xenograft murine model of B-cell malignancy, the greatest enhancement of an Fc-optimized anti-human B-cell mAb was accounted for by improved binding to FcγRIV, a unique mouse activating FcγR that is expressed by monocytes and macrophages but not natural killer (NK) cells, consistent with experimental and clinical data suggesting that mononuclear phagocytes, effector cells expressing both activating and inhibitory FcγR, are critical mediators of B-cell depletion &lt;i&gt;in vivo&lt;/i&gt;. By using mice transgenic for human &lt;i&gt;CD16A&lt;/i&gt;, enhanced survival was observed due to expression of &lt;i&gt;CD16A-158&lt;/i&gt;&lt;sup&gt;phe&lt;/sup&gt; on monocytes and macrophages as well as on NK cells in these mice. The design of new generations of improved antibodies for immunotherapy should aim at Fc optimization to increase the engagement of activating FcγR present on the surface of tumor-infiltrating effector cell populations. [Cancer Res 2007;67(18):8882–90]&lt;/p&gt;&lt;/div&gt;
The Anion Exchanger Pendrin (SLC26A4) and Renal Acid-base Homeostasis (2011)

The anion exchanger pendrin (Pds, SLC26A4) transports various anions including bicarbonate, chloride and iodide. In the kidney, pendrin is exclusively expressed on the luminal pole of bicarbonate-secretory type B intercalated cells. Genetic ablation of pendrin in mice abolishes luminal chloride-bicarbonate exchanger activity from type B intercalated cells suggesting that pendrin is the apical bicarbonate extruding pathway. The renal expression of pendrin is developmentally adapted and pendrin positive cells originate from both the uretric bud and mesenchyme. In adult kidney, pendrin expression and activity is regulated by systemic acid-base status, dietary electrolyte intake (mostly chloride), and hormones such as angiotensin II and aldosterone which can affect subcellular localization, the relative number of pendrin expressing cells, and the overall abundance consistent with a role of pendrin in maintaining normal acid-base homeostasis. This review summarizes recent findings on the role and regulation of pendrin in the context of the kidneys role in acid-base homeostasis in health and disease.