gebhart/patrepeval huggingface dataset:
Cell signaling pathways in autosomal-dominant leukodystrophy (ADLD): the intriguing role of the astrocytes (2020)

Autosomal-dominant leukodystrophy (ADLD) is a rare fatal neurodegenerative disorder with overexpression of the nuclear lamina component, Lamin B1 due to LMNB1 gene duplication or deletions upstream of the gene. The molecular mechanisms responsible for driving the onset and development of this pathology are not clear yet. Vacuolar demyelination seems to be one of the most significant histopathological observations of ADLD. Considering the role of oligodendrocytes, astrocytes, and leukemia inhibitory factor (LIF)-activated signaling pathways in the myelination processes, this work aims to analyze the specific alterations in different cell populations from patients with LMNB1 duplications and engineered cellular models overexpressing Lamin B1 protein. Our results point out, for the first time, that astrocytes may be pivotal in the evolution of the disease. Indeed, cells from ADLD patients and astrocytes overexpressing LMNB1 show severe ultrastructural nuclear alterations, not present in oligodendrocytes overexpressing LMNB1. Moreover, the accumulation of Lamin B1 in astrocytes induces a reduction in LIF and in LIF-Receptor (LIF-R) levels with a consequential decrease in LIF secretion. Therefore, in both our cellular models, Jak/Stat3 and PI3K/Akt axes, downstream of LIF/LIF-R, are downregulated. Significantly, the administration of exogenous LIF can partially reverse the toxic effects induced by Lamin B1 accumulation with differences between astrocytes and oligodendrocytes, highlighting that LMNB1 overexpression drastically affects astrocytic function reducing their fundamental support to oligodendrocytes in the myelination process. In addition, inflammation has also been investigated, showing an increased activation in ADLD patients' cells.
Abstract P256: Development of an Automated High Throughput Screen for GRK4 as Potential Novel Therapeutics for Treatment of Hypertension and/or Salt Sensitivity (2018)

G protein coupled kinase type 4 (GRK4) reduces renal sodium excretion by deactivating the renal dopamine type 1 receptor (D 1 R) through serine phosphorylation. At least 3 polymorphisms in GRK4 have been shown to be associated with the expression of hypertension and/or salt sensitivity in humans and in mice. GRK4 is an ideal therapeutic target for treating hypertension since putting human GRK4 variants in mice results in hypertension which can be reversed by reducing the expression of GRK4. Inhibitors of GRK4 could serve as potent and selective agents to promote sodium excretion in salt sensitive and/or hypertensive individuals. Therefore, we developed an automated high throughput homogeneous time resolved fluorescent resonance energy transfer assay (TR-FRET) to identify small molecule inhibitors of GRK4 isoenzymes. The assay relies on the close proximity (90 A) transfer of 337 nm energy from a europium anti-phosphoserine antibody (Eu-pSer) to an allophycocyanin labeled streptavidin acceptor (streptavidin-APC), producing FRET at 665 nm. The assay was optimized through serial dilutions of streptavidin-APC, Eu-pSer, GRK4, and a peptide consisting of serine sites in the D 1 R, serving as a substrate. To validate the assay and determine its suitability for a large scale high throughput screen, three inhibitors, GRKA, GRKB, and GRKC were selected and concentration response assays were performed to determine IC50 values and variability analysis. The IC50 and (R 2 ) values of GRKA, GRKB, and GRKC were 4.99 μM (0.99), 26.52 μM (0.99), and 179.8 μM (0.82), respectively. GRKA is the most efficient GRK4 inhibitor, while GRKC is the least. This assay will be used to test congeners of compounds A, B, and C to identify more selective candidates, as well as for screening available small molecule compound libraries.
Figure S6 from A Four-Chemokine Signature Is Associated with a T-cell–Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer (2023)

&lt;p&gt;Supplementary Figure 6: Immune phenotypes were not impacted by cellularity in metastases&lt;/p&gt;
Control of Exocytosis in Yeast (1995)

In eukaryotic cells, the transport of material between organelles is most often mediated by vesicular carriers. Key questions concern the mechanisms by which vesicles are formed, transported to a specific region of the cell, and then targeted and fused to the membrane of the appropriate organelle. Recent advances in the field suggest that the interaction of an integral protein of the vesicle membrane, termed a v-SNARE, and an integral protein of the target membrane, termed a t-SNARE, defines the specificity of the vesicle-target interaction. However, additional levels of control are needed to determine when and where these proteins are allowed to interact with one another. We have focused on one specific transport event, the final stage of the secretory pathway in the budding yeast Saccharomyces cerevisiae. Our results indicate that vesicular traffic relies on the interaction of several different systems: a GTPase and its accessory proteins, the SNAREs, and a...
Heuristic techniques for synthesis of hard real-time DSP application specific systems (2002)

We introduce an approach for the design and optimization of ASIC implementations which realize multiple computational tasks under hard real-time constraints. The approach designs a multitask ASIC by combining techniques from hard real-time scheduling and behavioral synthesis. The key component of the methodology is the successive multiresolution synthesis technique. The technique starts from an incompletely specified preliminary solution and uses interchangeably operating systems and behavioral synthesis tools to derive increasingly more detailed and complete design solutions. The effectiveness of the optimization algorithms is demonstrated on several multiple task designs.
ChemInform Abstract: Nickel(II)‐Catalyzed Transformations of 5‐Azido‐5‐deoxy‐D‐glucofuranose and of 5‐Azido‐5‐deoxy‐L‐idofuranose. (1998)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
InGaN/GaN multiple-quantum-well light-emitting diodes grown on Si(111) substrates with ZrB2(0001) buffer layers (2012)

Multiple-quantum-well light-emitting diode (LED) structures of InGaN/GaN were grown by metalorganic chemical vapor deposition on Si(111) substrates via ZrB2(0001) buffer layers and a GaN template comprising composite AlxGa1-xN (where x lies in the range from 0 to 1) transition layers to minimize cracking due to thermal expansion mismatch between Si and GaN. Photoluminescence and electroluminescence results from the LED structures compared favorably with similar measurements obtained on identical LED structures grown on sapphire substrates. However, in spite of all the precautions taken, cracking was still present in the LED structures. Scanning electron microscopy and transmission electron microscopy in plan-view and cross-section geometries were conducted on the LED structures to examine the presence and the influence of various defects such as microvoids, micropipes, and threading dislocations on the mechanism of cracking. Our results suggest that the crack network propagates from microvoids on the surface of the LED structure. The formation of microvoids appears to originate from imperfections in the epitaxial ZrB2(0001) buffer layer.
Therapeutic antibody engineering (2013)

It is an important event in any knowledge area when an authority in the field decides that it is time to share all accumulated knowledge and learnings by writing a text book. This does not occur often in the biopharmaceutical industry, likely due to both the highly dynamic environment with tight timelines and policies and procedures at many pharmaceutical companies that hamper knowledge sharing. To take on a task like this successfully, a strong drive combined with a desire and talent to teach, but also an accommodating and stimulating environment is required. Luckily for those interested in therapeutic monoclonal antibodies, Dr. William R. Strohl decided about two years ago that the time was right to write a book about the past, present and future of these fascinating molecules. Dr. Strohl’s great expertise and passion for biotechnology is evident from his life story and his strong academic and industry track record. Dr. Strohl pioneered natural product biotechnology, first in academia as a full professor of microbiology and biochemistry at Ohio State University in Columbus, Ohio and later in industry while at Merck. Despite his notable advances in recombinant natural products, industry interest in this area waned and in 2001 Dr. Strohl sought new opportunities by entering the field of antibody therapeutics. He initiated antibody discovery through phage display at Merck, and then moved to Centocor Research and Development Inc. (now Janssen Biotech, Inc.) in 2008 to head Biologics Research, where he now directs the discovery of innovative therapeutic antibody candidates.
Local epidermal growth factor delivery using nanopillared chitosan–gelatin films for melanogenesis and wound healing (2022)

Epidermal growth factor (EGF) is required for various regulations of skin tissue including wound healing; however, it has limited stability due to the physicochemical conditions of the wound milieu. The lack of functional EGF within the wound can cause permanent tissue defects and therefore, current wound patch designs involve EGF-releasing components. Consequently, the focus of such systems is to improve the wound healing mechanism, with minimal attention on melanogenesis of the scar tissue. The present study investigates <i>in vitro</i>/<i>in vivo</i> wound healing and melanogenesis potential of the EGF-doped films comprised of arrays of chitosan:gelatin nanopillars (nano C:G films) prepared by using nanoporous anodic alumina molds. The potential of EGF-doped films in wound healing was examined with individual and coculture systems of fibroblasts and melanocytes to mimic the wound conditions. The outcomes demonstrated that compared to the control groups, the combination of EGF doping and nanotopography consistently provided the highest levels of melanogenic activity-related genes, melanin contents as well as EGFR expressions for both melanocyte-only and coculture setups. Proteomic, genomic and histological analysis of the excisional wound model further demonstrated that if EGF was present within the nanostructured films, the performance of these substrates in terms of wound closure, collagen thickness as well as melanin deposition was considerably improved. Furthermore, when compared with the control saline treatment and healthy mice groups, significant differences for such parameters were obtained for the nano C:G films, irrespective of their EGF contents. Overall, the results indicate that EGF-doped nano C:G films are good candidates as wound patches that not only provide desirable healing characteristics but also cause improved melanogenic outputs.
Molecular orientational properties of a high-tilt chiral smectic liquid crystal determined from its infrared dichroism (2007)

The orientational characterisitics and the temperature dependencies of the molecular apparent tilt angle of a partly fluorinated chiral smectic liquid crystal (/S/)-4-(1-methylheptyloxycarbonyl)phenyl ${4}^{\ensuremath{'}}$-[6-(3,4,4,4-tetrafluoro-3-trifluoromethylbutylcarbonyloxy)hexyloxy] biphenyl-4-carboxylate (acronym MHPHFHHOBC) are studied using the polarized Fourier transform infrared (FTIR) spectroscopy. The molecular orientational distributions and the orientational order parameters for a homogeneously aligned liquid crystalline sample at various temperatures and external electric fields are examined. The analysis uses the dichroic parameters of the phenyl and the carbonyl bands. For a temperature range of $65--80\phantom{\rule{0.2em}{0ex}}\ifmmode^\circ\else\textdegree\fi{}\mathrm{C}$ corresponding to the antiferroelectric $\mathrm{Sm}C_{A}{}^{*}$ phase, the molecular apparent tilt angle lies within the range 43\ifmmode^\circ\else\textdegree\fi{}--44\ifmmode^\circ\else\textdegree\fi{}; antiferroelectric smectic structure being rather close to the orthoconic $\mathrm{Sm}C_{A}{}^{*}$ phase. An application of sufficiently high dc field across the cell in its $\mathrm{Sm}{A}^{*}$ phase surprisingly shows that the dichroism first increases slowly and then rapidly in two stages and finally a saturated apparent tilt angle of $\ensuremath{\sim}30\ifmmode^\circ\else\textdegree\fi{}$ is reached. The IR dichroic data is used to estimate the polar angles and the degree of rotational biasing of the carbonyl groups with respect to the molecular long axis. In the $\mathrm{Sm}{A}^{*}$ phase, the sample appears to demonstrate some of the typical properties of a de Vries material.
Brazilian Jiu Jitsu Training for US Service Members and Veterans with Symptoms of PTSD (2019)

The results from this first-of-kind pilot study suggest that including BJJ as a complementary treatment to standard therapy for PTSD may be of value. It will be necessary to validate these promising results with a larger subject cohort and a more rigorous experimental design before routinely recommending this complementary therapy.
Dopaminergic modulation of glutamate-activated channels in the central nervous system. (1995)

Modulation of glutamate-activated currents by dopamine was studied in identified central neurons, alpha-motoneurons of the chick and horizontal cells of the perch. This modulation is mediated by a cAMP-dependent protein phosphorylation. The activation and desensitization time constants of glutamate currents were determined before and after incubation with dopamine. In the horizontal cells ultrafast glutamate (AMPA or quisqualate) application prior to the the dopamine incubation gives rise to fast transient current responses which desensitize within less than 100 ms. Kainate produced higher steady state currents. After incubation of the cells with dopamine (100 nM) for 30s the desensitization was dramatically reduced, but the amplitudes of the steady state currents were similar to the transient control currents. Kainate activated currents were not affected. In alpha-motoneurons the exposure to dopamine (100 nM) for 1 min was sufficient to increase the peak and steady state amplitudes but not the desensitization time constant of glutamate activated currents. Here enhancement was specific to the kainate component of glutamate activated currents; the decreased variance of currents reflects increased kainate channel activation. Measurements of motoneuronal cAMP concentrations showed an increase following addition of dopamine. mRNA encoding both D1 and D2 dopamine receptor subtypes was detected. We conclude that the dopamine dependent modulation which is mediated by a protein phosphorylation is due to an alteration of the desensitization of AMPA type receptors in horizontal cells and of the activation of kainate type receptors in motoneurons.
A Reactive Prodrug Ink Formulation Strategy for Inkjet 3D Printing of Controlled Release Dosage Forms and Implants (2020)

Abstract A strategy for creating tuneable 3D printed drug delivery devices is proposed. 3D printing offers the opportunity for improved compliance and patient treatment outcomes through personalization, but bottlenecks include finding formulations that provide a choice of drug loading and release rate, that are tuneable, and avoid the need for surgical removal. The suggested solution is to exploit 3D inkjet printing freedoms. A reactive prodrug is used that can polymerize into drug‐attached macromolecules during 3D printing and by tuning the hydrophilicity, hydrolysis can be facilitated or hindered, which in turn controls drug release. To demonstrate this approach, ibuprofen is attached to 2‐hydroxyethyl acrylate through a cleavable ester bond, formulated for inkjet 3D printing, and then printed to produce a solid dosage form. This allows a much higher loading than is usually achievable—in this case up to 58 wt%. Of equal importance, the 3D inkjet printing freedoms mean that the drug delivery device is highly tuneable: by selection of spacer monomers to adjust the hydrophilicity; through geometry; by spatially varying the components. Consequently, hierarchical release systems are created bespoke, from the molecular to macro. This approach represents a new paradigm for the formulation of printable inks for drug‐loaded medical devices.
Addressing Insider Threat using "Where You Are" as Fourth Factor Authentication. (2016)

Abstract not provided.
Constrained Optimization Applied to the Parameter Setting Problem for Analog Circuits (1991)

We use constrained optimization to select operating parameters for two circuits: a simple 3-transistor square root circuit, and an analog VLSI artificial cochlea. This automated method uses computer controlled measurement&#13;\nand test equipment to choose chip parameters which minimize&#13;\nthe difference between the actual circuit's behavior and a specified goal behavior. Choosing the proper circuit parameters is important to compensate for manufacturing deviations or adjust circuit performance within&#13;\na certain range. As biologically-motivated analog VLSI circuits become increasingly complex, implying more parameters, setting these parameters by hand will become more cumbersome. Thus an automated parameter&#13;\nsetting method can be of great value [Fleischer 90]. Automated parameter setting is an integral part of a goal-based engineering design methodology in which circuits are constructed with parameters enabling a wide range&#13;\nof behaviors, and are then "tuned" to the desired behaviors automatically.
Template sol–gel synthesis of mesostructured silica composites using metal complexes bearing amphiphilic side chains: immobilization of a polymeric Pt complex formed by a metallophilic interaction (2009)

A bipyridine-based ligand 1 bearing two amphiphilic side chains allowed for the formation of metal complexes Pt(1)Cl2 (2), [Pt(1)2](BF4)2 (3), and [Pt(1)2][Pt(CN)4] (4), which are capable of templating the sol-gel synthesis of mesostrucutred silica to give 2-MS, 3-MS and 4-MS, respectively, whose silicate channels are filled with the corresponding platinum complexes. In particular, silica composite 4-MS, upon spin-coating, gives a transparent film, which emits at 619 nm upon excitation at 495 nm, indicating that a weak Pt--Pt bond, formed between Pt(1)2(2+) and Pt(CN)4(2-) via a metallophilic interaction, is successfully incorporated into the silicate nanochannels.
Binuclear Palladium Macrocycles Synthesized via the Weak-Link Approach. (2002)

The “weak-link approach” to metallomacrocycle synthesis has been employed to synthesize\na series of Pd(II) macrocycles in high yield. Although this approach has been used to construct\nseveral Rh(I) complexes with a variety of ligands, the generality of this methodology with\nrespect to transition metals has not been demonstrated. When added to [Pd(NCCH&lt;sub&gt;3&lt;/sub&gt;)&lt;sub&gt;4&lt;/sub&gt;][BF&lt;sub&gt;4&lt;/sub&gt;]&lt;sub&gt;2&lt;/sub&gt;,\nthe phosphinoalkyl ether or thioether ligands produce “condensed intermediates”, [(μ-(1,4-(PPh&lt;sub&gt;2&lt;/sub&gt;CH&lt;sub&gt;2&lt;/sub&gt;CH&lt;sub&gt;2&lt;/sub&gt;X)&lt;sub&gt;2&lt;/sub&gt;−Y)&lt;sub&gt;2&lt;/sub&gt;Pd&lt;sub&gt;2&lt;/sub&gt;)][BF&lt;sub&gt;4&lt;/sub&gt;]&lt;sub&gt;4&lt;/sub&gt; (&lt;b&gt;4&lt;/b&gt;, X = O, Y = 2,3,5,6-((CH&lt;sub&gt;3&lt;/sub&gt;)&lt;sub&gt;4&lt;/sub&gt;C&lt;sub&gt;6&lt;/sub&gt;); &lt;b&gt;5&lt;/b&gt;, X = O, Y = C&lt;sub&gt;6&lt;/sub&gt;H&lt;sub&gt;4&lt;/sub&gt;; &lt;b&gt;6&lt;/b&gt;, X\n= S, Y = C&lt;sub&gt;6&lt;/sub&gt;H&lt;sub&gt;4&lt;/sub&gt;), containing strong P−Pd bonds and weaker O−Pd or S−Pd bonds. The weak\nbonds of these intermediates can be quantitatively broken through simple ligand substitution\nreactions to generate the macrocyclic structures [(μ-(1,4-(PPh&lt;sub&gt;2&lt;/sub&gt;CH&lt;sub&gt;2&lt;/sub&gt;CH&lt;sub&gt;2&lt;/sub&gt;X)&lt;sub&gt;2&lt;/sub&gt;−Y)&lt;sub&gt;2&lt;/sub&gt;(Z)&lt;sub&gt;4&lt;/sub&gt;Pd&lt;sub&gt;2&lt;/sub&gt;)][BF&lt;sub&gt;4&lt;/sub&gt;]&lt;i&gt;&lt;sub&gt;n&lt;/sub&gt;&lt;/i&gt;\n(&lt;b&gt;7&lt;/b&gt;, X = O, Y = 2,3,5,6-((CH&lt;sub&gt;3&lt;/sub&gt;)&lt;sub&gt;4&lt;/sub&gt;C&lt;sub&gt;6&lt;/sub&gt;), Z = CH&lt;sub&gt;3&lt;/sub&gt;CN, &lt;i&gt;n&lt;/i&gt; = 4; &lt;b&gt;8&lt;/b&gt;, X = O, Y = C&lt;sub&gt;6&lt;/sub&gt;H&lt;sub&gt;4&lt;/sub&gt;, Z = CH&lt;sub&gt;3&lt;/sub&gt;CN, &lt;i&gt;n&lt;/i&gt; =\n4; &lt;b&gt;9&lt;/b&gt;, X = O, Y = 2,3,5,6-((CH&lt;sub&gt;3&lt;/sub&gt;)&lt;sub&gt;4&lt;/sub&gt;C&lt;sub&gt;6&lt;/sub&gt;), Z = CN, &lt;i&gt;n&lt;/i&gt; = 0; &lt;b&gt;10&lt;/b&gt;, X = O, Y = C&lt;sub&gt;6&lt;/sub&gt;H&lt;sub&gt;4&lt;/sub&gt;, Z = CN, &lt;i&gt;n&lt;/i&gt; = 0; &lt;b&gt;11&lt;/b&gt;,\nX = S, Y = C&lt;sub&gt;6&lt;/sub&gt;H&lt;sub&gt;4&lt;/sub&gt;, Z = CN, &lt;i&gt;n&lt;/i&gt; = 0), in quantitative yields. The extension of this approach to\nPd(II) should provide new pathways for modifying the binding and catalytic capabilities of\nthese complexes. Solid-state structures as determined by single-crystal X-ray diffraction\nstudies are presented for compounds &lt;b&gt;6&lt;/b&gt;, &lt;b&gt;8&lt;/b&gt;, and &lt;b&gt;9&lt;/b&gt;.
Brain metabolism of children with profound deafness: a visual language activation study by 18F-fluorodeoxyglucose positron emission tomography (2008)

The widest bilaterally activated cortical area was detected in subject 1, who was the worst user of spoken language. By contrast, there was no significant difference between subject 6, who was the best user of spoken language with a hearing aid, and the normal hearing group.
A Comparison of Psoas Compartment Block and Spinal and General Anesthesia for Outpatient Knee Arthroscopy (2003)

Outpatient knee arthroscopy may be performed using a variety of anesthetic techniques. We report that spinal anesthesia and psoas compartment block are superior to general anesthesia when considering resource utilization, patient satisfaction, and postoperative analgesic management.
Next generation supply chains: making the right decisions about digitalisation (2017)

This white paper is based on research carried out by the IfM’s Centre for International Manufacturing and insights emerging from our work with industrial partners. In it we share our latest findings to help global companies consider their digital supply chain strategies.
Soft Lithography for Microfluidic Microelectromechanical Systems (MEMS) and Optical Devices (2008)

This chapter contains sections titled: Introduction Microfluidic Devices for Concentration Gradients Electrochemistry and Microfluidics PDMS and Electrochemistry Optics and Microfluidics Unconventional Soft Lithographic Fabrication of Optical Sensors Acknowledgments References
Resonant Raman scattering from single-wall nanotubes of diameters between 1.1 nm and 1.4 nm (1998)

Resonant Raman scattering has been measured on single-wall nanotubes of diameters from 1.1 nm to 1.4 nm. The spectra show groups of peaks near 180 cm−1, 360 cm−1, 440 cm−1, 600 cm−1, 720 cm−1, 880 cm−1, 1070 cm−1, 1320 cm−1 and 1580 cm−1. Observed resonant intensity enhancements show that peaks in each group belong to the same vibrational mode of different diameters, and hence different dependencies on the incident photon energy. These measurements, therefore, determine the diameter dependent vibrational modes and zone-folded electronic structures, yielding mode assignments that groups of peaks near 600 cm−1, 859 cm−1, 1070 cm−1 and 1580 cm−1 belong to optical modes and the rest to acoustic ones in graphite in the zone-folding scheme. Peaks near 360 cm−1, 720 cm−1 and 880 cm−1 are harmonics of 180 cm−1 or 440 cm−1.