gebhart/patrepeval huggingface dataset:
Identification of a de novo keratin 1 mutation in epidermolytic hyperkeratosis with palmoplantar involvement. (2007)

Epidermolytic hyperkeratosis (EHK) (OMIM 113800) is a generalized skin disease with mostly autosomal dominant inheritance, caused by mutations in keratin 1 or keratin 10. These genes are expressed in suprabasal epidermal layers, resulting in abnormal keratin-intermediate filament cytoskeleton. We present a male patient with generalized hyperkeratosis involving palms and soles. In lesional skin massive hyperkeratosis and cytolysis in the suprabasal layers of the epidermis were observed. Immunohistochemistry staining for keratin 1 (and keratin 10) showed abnormal clumping in suprabasal keratinocytes. By electron microscopy perinuclear intermediate filament clumps were detected in the keratinocytes. A heterozygous missense mutation, designated L187F, was identified in exon 1 of the keratin 1 gene by direct sequencing. This mutation was not detected in his unaffected parents, indicative of a de novo mutational event. The homologous mutation (L187F, also designated L7F) in basal keratin genes keratin 5 or -14 causes epidermolysis bullosa simplex. The amount of keratin 1-mRNA in the patient's skin was not altered compared to controls. We propose that the severe EHK phenotype observed in our patient results from a dominant negative effect of the L187F mutant Keratin 1 allele exerted on keratin 10, the associated partner-keratin. These findings should be helpful for genetic counseling, prenatal diagnosis and studying molecular structure-function relationship in EHK.
ChemInform Abstract: New Generation Dopaminergic Agents. Part 5. Heterocyclic Bioisosteres That Exploit the 3‐OH‐N1‐Phenylpiperazine Dopaminergic Template. (1999)

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.
Measurement of Interface Propertes from Fiber Push-Out Tests (2008)

The fiber debonding and pullout behavior in a model ceramic composite system has been investigated using a novel singlel-fiber pullout technique. Stable, progressive debonding was observed prior to fiber fracture and frictional fiber pullout. Interfacial parameters were calculated from single load-displacement curves using a recent analysis of the fiber debonding and pullout process. The interfacial parameters extracted from these experiments are consistent with independent measurements reported in the literature. The morphology of the fiber surface appears to play a significant role in determining the fiber debonding and sliding behavior.
Modulation of Diastolic Filling Using an Epicardial Diastolic Recoil Device (2013)

Diastolic dysfunction likely contributes to all cases of congestive heart failure and is solely responsible for many. Existing cardiac support devices largely ignore diastolic dysfunction and may exacerbate it. Current diastolic devices in development rely on either extensive extraventricular fixation or intraventricular implantation with complications associated with blood contact. A diastolic recoil device is proposed that pneumatically locks to the outside of the heart wall. The end-diastolic total biventricular pressure-volume relationship (EDTBPVR) was used to evaluate, in vitro, the ability of a recoil device to modulate filling mechanics through pneumatic locking as the method of fixation. The pressure in a model heart was incremented and the corresponding volume changes were measured. The heart model and device were pneumatically locked together using a vacuum sac to model the pericardium. The diastolic recoil component shifted the EDTBPVR towards lower pressures at low volumes, providing up to 0.9 kPa (9 cm H2O) of suction, demonstrating enhanced diastolic recoil at beginning diastole. We conclude that pneumatic locking appears to be a viable method for a recoil device to engage the heart.
Study ofB−→DK−π+π−andB−→Dπ−π+π−decays and determination of the CKM angleγ (2015)

We report a study of the suppressed ${B}^{\ensuremath{-}}\ensuremath{\rightarrow}D{K}^{\ensuremath{-}}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}$ and favored ${B}^{\ensuremath{-}}\ensuremath{\rightarrow}D{\ensuremath{\pi}}^{\ensuremath{-}}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}$ decays, where the neutral $D$ meson is detected through its decays to the ${K}^{\ensuremath{\mp}}{\ensuremath{\pi}}^{\ifmmode\pm\else\textpm\fi{}}$ and $CP$ -even ${K}^{+}{K}^{\ensuremath{-}}$ and ${\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}$ final states. The measurement is carried out using a proton-proton collision data sample collected by the LHCb experiment, corresponding to an integrated luminosity of $3.0\text{ }\text{ }{\mathrm{fb}}^{\ensuremath{-}1}$. We observe the first significant signals in the $CP$ -even final states of the $D$ meson for both the suppressed ${B}^{\ensuremath{-}}\ensuremath{\rightarrow}D{K}^{\ensuremath{-}}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}$ and favored ${B}^{\ensuremath{-}}\ensuremath{\rightarrow}D{\ensuremath{\pi}}^{\ensuremath{-}}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}$ modes, as well as in the doubly Cabibbo suppressed $D\ensuremath{\rightarrow}{K}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}$ final state of the ${B}^{\ensuremath{-}}\ensuremath{\rightarrow}D{\ensuremath{\pi}}^{\ensuremath{-}}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}$ decay. Evidence for the suppressed decay ${B}^{\ensuremath{-}}\ensuremath{\rightarrow}D{K}^{\ensuremath{-}}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}$, with $D\ensuremath{\rightarrow}{K}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}$, is also presented. From the observed yields in the ${B}^{\ensuremath{-}}\ensuremath{\rightarrow}D{K}^{\ensuremath{-}}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}$, ${B}^{\ensuremath{-}}\ensuremath{\rightarrow}D{\ensuremath{\pi}}^{\ensuremath{-}}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}$ and their charge conjugate decay modes, the most probable value of the weak phase $\ensuremath{\gamma}$ corresponds to $\ensuremath{\gamma}=(7{4}_{\ensuremath{-}19}^{+20})\ifmmode^\circ\else\textdegree\fi{}$. This is one of the most precise single-measurement determinations of $\ensuremath{\gamma}$ to date.
The Checkpoint Kinase Inhibitor AZD7762 Potentiates Chemotherapy-Induced Apoptosis of p53 -Mutated Multiple Myeloma Cells (2012)

DNA cross-linking agents are frequently used in the treatment of multiple myeloma-generating lesions, which activate checkpoint kinase 1 (Chk1), a critical transducer of the DNA damage response. Chk1 activation promotes cell survival by regulating cell-cycle arrest and DNA repair following genotoxic stress. The ability of AZD7762, an ATP-competitive Chk1/2 inhibitor to increase the efficacy of the DNA-damaging agents bendamustine, melphalan, and doxorubicin was examined using four human myeloma cell lines, KMS-12-BM, KMS-12-PE, RPMI-8226, and U266B1. The in vitro activity of AZD7762 as monotherapy and combined with alkylating agents and the "novel" drug bortezomib was evaluated by studying its effects on cytotoxicity, signaling, and apoptotic pathways. The Chk1/2 inhibitor AZD7762 potentiated the antiproliferative effects of bendamustine, melphalan, and doxorubicin but not bortezomib in multiple myeloma cell lines that were p53-deficient. Increased γH2AX staining in cells treated with bendamustine or melphalan plus AZD7762 indicates a greater degree of DNA damage with combined therapy. Abrogation of the G(2)-M checkpoint by AZD7762 resulted in mitotic catastrophe with ensuing apoptosis evidenced by PARP and caspase-3 cleavage. In summary, the cytotoxic effects of bendamustine, melphalan and doxorubicin on p53-deficient multiple myeloma cell lines were enhanced by the coadministration of AZD7762. These data provide a rationale for testing these combinations in patients with relapsed and/or refractory multiple myeloma.
Supplemental Figure S1 from Obesity Contributes to Ovarian Cancer Metastatic Success through Increased Lipogenesis, Enhanced Vascularity, and Decreased Infiltration of M1 Macrophages (2023)

&lt;p&gt;Overview of experimental cohorts.&lt;/p&gt;
Increased Susceptibility to Infection Related to Extent of Burn Injury (1984)

A model of burn wound sepsis in which the mortality caused by infection was significantly greater after a 60% total body surface area (TBSA) burn than after a 30% TBSA burn was developed in the rat. In rats that sustained a 60% TBSA burn (30% partial plus 30% full thickness), the 30% TBSA partial-thickness burn that was inoculated with Pseudomonas aeruginosa strain 59-1244 developed invasive wound infection (greater 10(5) colony-forming units per gram of tissue). Infection did not develop in rats that had a 30% TBSA partial-thickness burn inoculated, without additional injury. The additional burn in the rats with a 60% TBSA burn seemed to affect the development of infection in the partial-thickness wound and the overall outcome by a mechanism other than by infection of the full-thickness wound itself. Autopsy confirmed that mortality was caused by sepsis.
Binding of hsp90-Associated Immunophilins to Cytoplasmic Dynein:  Direct Binding and in Vivo Evidence that the Peptidylprolyl Isomerase Domain Is a Dynein Interaction Domain (2002)

FKBP52 is a steroid receptor-associated immunophilin that binds via a tetratricopeptide repeat (TPR) domain to hsp90. FKBP52 has also been shown to interact either directly or indirectly via its peptidylprolyl isomerase (PPIase) domain with cytoplasmic dynein, a motor protein involved in retrograde transport of vesicles toward the nucleus. The functional role for the PPIase domain in receptor movement was demonstrated by showing that expression of the PPIase domain fragment of FKBP52 in 3T3 cells inhibits dexamethasone-dependent nuclear translocation of a green fluorescent protein-glucocorticoid receptor chimera. Here, we show that cytoplasmic dynein is co-immunoadsorbed with two other TPR domain proteins that bind hsp90 (the cyclophilin CyP-40 and the protein phosphatase PP5). Both proteins possess PPIase homology domains, and co-immunoadsorption of cytoplasmic dynein with each is blocked by the PPIase domain fragment of FKBP52. Using purified proteins, we show that FKBP52, PP5, and the PPIase domain fragment bind directly to the intermediate chain of cytoplasmic dynein. PP5 colocalizes with both cytoplasmic dynein and microtubules, and expression of the PPIase domain fragment of FKBP52 in 3T3 cells disrupts its cytoskeletal localization. We conclude that the PPIase domains of the hsp90-binding immunophilins interact directly with cytoplasmic dynein and that this interaction with the motor protein is responsible for the microtubular localization of PP5 in vivo.
ChemInform Abstract: Highly Enantioselective Organocatalytic Addition of Aldehydes to N‐(Phenylmethylene)benzamides: Asymmetric Synthesis of the Paclitaxel Side Chain and Its Analogues. (2009)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 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.
SCREEN FOR DOMINANT BEHAVIORAL MUTATIONS CAUSED BY GENOMIC INSERTION OF P-ELEMENT TRANSPOSONS INDROSOPHILA: AN EXAMINATION OF THE INTEGRATION OF VIRAL VECTOR SEQUENCES (2007)

Here we report the development of a high-throughput screen to assess dominant mutation rates caused by P-element transposition within the Drosophila genome that is suitable for assessing the undesirable effects of integrating foreign regulatory sequences (viral cargo) into a host genome. Three different behavioral paradigms were used: sensitivity to mechanical stress, response to heat stress, and ability to fly. The results, from our screen of 35,000 flies, indicate that mutations caused by the random insertion of transposons in Drosophila are more effective at disrupting flight than stress sensitivity. This approach was used to ascertain the frequency of deleterious dominant mutations caused by viral vectors utilized in gene therapy.
Real-time Emulation of MASQUE-based QUIC Proxying in LTE Networks using ns-3 (2023)

Tools for real-time emulation of mobile networks are valuable for researchers due to the high amount of time and resources it allows to save compared to carrying out measurements in live networks. In this paper we present the rationale, design and prototype implementation of a novel net device in the ns-3 open source network simulator that allows for end-to-end real-time emulation of LTE networks with real endpoints. We then show the performance evaluation of a QUIC proxy built on MASQUE using our emulated LTE setup. Our results confirm the intended behavior of the implementation, however, we also show the limitations of the real-time capabilities of ns-3.
Association Between Active Wegener's Granulomatosis and Anticytoplasmic Antibodies (1989)

Autoantibodies reacting with the cytoplasm of granulocytes and monocytes (anticytoplasmic antibodies [ACPAs]) were found in 42 of 45 patients with active Wegener's granulomatosis (WG) (sensitivity, 93%). Specificity was tested in selected groups of patients with closely related diseases. Of 58 patients without a diagnosis of WG, 2 had ACPAs (specificity, 97%). The significance of ACPA titration for assessing or predicting disease activity was evaluated in a 16-month prospective study of 35 patients with WG. Seventeen relapses were observed and all were preceded by a significant rise of the ACPA titer. Anticytoplasmic antibodies are a specific and sensitive marker for active WG; a rising titer is a sensitive marker for the development of a relapse.
Quercetin Inhibits Lef1 and Resensitizes Docetaxel-Resistant Breast Cancer Cells (2020)

Drug resistance is a major problem for breast cancer patients. Docetaxel is an anti-mitotic agent that serves as first line of treatment in metastatic breast cancer, however it is susceptible to cellular drug resistance. Drug-resistant cells are able to spread during treatment, leading to treatment failure and eventually metastasis, which remains the main cause for cancer-associated death. In previous studies, we used single-cell technologies and identified a set of genes that exhibit increased expression in drug-resistant cells, and they are mainly regulated by Lef1. Furthermore, upregulating Lef1 in parental cells caused them to become drug resistant. Therefore, we hypothesized that inhibiting Lef1 could resensitize cells to docetaxel. Here, we confirmed that Lef1 inhibition, especially on treatment with the small molecule quercetin, decreased the expression of Lef1 and resensitized cells to docetaxel. Our results demonstrate that Lef1 inhibition also downregulated ABCG2, Vim, and Cav1 expression and equally decreased Smad-dependent TGF-β signaling pathway activation. Likewise, these two molecules worked in a synergetic manner, greatly reducing the viability of drug-resistant cells. Prior studies in phase I clinical trials have already shown that quercetin can be safely administered to patients. Therefore, the use of quercetin as an adjuvant treatment in addition to docetaxel for the treatment of breast cancer may be a promising therapeutic approach.
ChemInform Abstract: Aqueous Dye‐Sensitized Solar Cells (2015)

Abstract Review: efforts towards the realization of an artificial photosynthetic system able to convert sunlight into electricity using water as solvent; 328 refs.
Novel Chimeras of Botulinum Neurotoxins A and E Unveil Contributions from the Binding, Translocation, and Protease Domains to Their Functional Characteristics (2008)

Hyperexcitability disorders of cholinergically innervated muscles are treatable with botulinum neurotoxin (BoNT) A. The seven serotypes (A-G) potently block neurotransmission by binding to presynaptic receptors, undergoing endocytosis, transferring to the cytosol, and inactivating proteins essential for vesicle fusion. Although BoNT/A and BoNT/E cleave SNAP-25, albeit at distinct sites, BoNT/E blocks neurotransmission faster and more potently. To identify the domains responsible for these characteristics, the C-terminal heavy chain portions of BoNT/A and BoNT/E were exchanged to create chimeras AE and EA. After high yield expression in Escherichia coli, these single chain chimeras were purified by two-step chromatography and activated by conversion to disulfide-linked dichains. In vitro, each entered neurons, cleaved SNAP-25, and blocked neuromuscular transmission while causing flaccid paralysis in vivo. Acidification-dependent translocation of the light chain to the cytosol occurred more rapidly for BoNT/E and EA than for BoNT/A and AE because the latter pair remained susceptible for longer to inhibitors of the vesicular proton pump, and BoNT/A proved less sensitive. The receptor-binding and protease domains do not seem to be responsible for the speeds of intoxication; rather the N-terminal halves of their heavy chains are implicated, with dissimilar rates of cytosolic transfer of the light chains being due to differences in pH sensitivity. AE produced the most persistent muscle weakening and therefore has therapeutic potential. Thus, proof of principle is provided for tailoring the pharmacological properties of these toxins by protein engineering.
Relating Temperature-Dependent Aging Rate to Cathode Materials in Commercial 18650 Li-Ion Battery (2017)

Temperature plays an important role in battery aging rate. Previous reports 1-3 of commercial batteries with different cathode materials revealed the relationship between aging rate and cycling temperature ( between 25 o C and 70 o C ) can be described by Arrhenius plot. In other words, battery aging rate increases with increasing cycling temperature within range from 25 o C to 70 o C. While most Li-ion batteries suffer significant capacity loss when cycled at elevated temperatures, previous report 4 has suggested that high temperature abuse testing had nearly no effect on aging rate of commercial 18650 NCA-based batteries, an effect not reported for batteries with LiCoO 2 or other common chemistries. We have investigated this effect further and reported that long-term constant current cycle testing of commercial 18650 NCA–based batteries at elevated temperature showed less capacity loss than control testing performed at room temperature, as shown in figure 1. Furthermore, the batteries cycled at room temperature exhibited excessive SEI formation on anode surface whereas there was much less SEI formation in the elevated temperature testing. Mechanisms such as excessive lithium plating have been put forward as a possible cause 4 , though this would not explain why NCA-based batteries outperform batteries based on other similar cathode chemistries. We will present several possible hypotheses that describe this aging mechanism with a focus on understanding the relationship between SEI formation on the anode and cathode surface chemistry. Reference: 1. Ramadass, P.; Haran, B.; White, R.; Popov, B. N., Capacity fade of Sony 18650 cells cycled at elevated temperatures Part I. Cycling performance. J Power Sources 2002, 112 (2), 606-613. 2. Situ, W. F.; Yang, X. Q.; Li, X. X.; Zhang, G. Q.; Rao, M. M.; Wei, C.; Huang, Z., Effect of high temperature environment on the performance of LiNi0.5Co0.2Mn0.3O2 battery. Int J Heat Mass Tran 2017, 104 , 743-748. 3. Waldmann, T.; Wilka, M.; Kasper, M.; Fleischhammer, M.; Wohlfahrt-Mehrens, M., Temperature dependent ageing mechanisms in Lithium-ion batteries - A Post-Mortem study. J Power Sources 2014, 262 , 129-135. 4. Waldmann, T.; Kasper, M.; Wohlfahrt-Mehrens, M., Optimization of Charging Strategy by Prevention of Lithium Deposition on Anodes in high-energy Lithium-ion Batteries – Electrochemical Experiments. Electrochim Acta 2015, 178 , 525-532. Figure 1
Strain-induced lateral confinement of excitons in semiconductor quantum wells (1989)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text J. M. Worlock and K. Kash, "Strain-induced lateral confinement of excitons in semiconductor quantum wells," Optics News 15(12), 25-26 (1989) Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Structural Properties of Kerogens with Different Maturities (2020)

The thermogenic transformation of kerogen into hydrocarbons accompanies the development of a pore network within the kerogen that serves as gas storage locations both in pore space and surface area for adsorbed gas within the source rock. Therefore, the successful recovery of gas from these rocks depends on the accessible surface area, surface properties, and interconnectivity of the pore system. These parameters can be difficult to determine because of the nanoscale of the structures within the rock. This study seeks to investigate the pore structure, surface heterogeneity, and composition of recovered kerogens isolated from source rocks with progressively increasing thermogenic maturities. Prompt gamma-ray activation analysis (PGAA), nitrogen and methane volumetric gas sorption, and small-angle neutron scattering (SANS) are combined to explore the relationship between the chemical composition, pore structure, surface roughness, surface heterogeneity, and maturity. PGAA results indicate that higher mature kerogens have lower hydrogen/carbon ratio. Nitrogen gas adsorption indicates that the pore volume and accessible specific surface area are higher for more mature kerogens. The methane isosteric heat at different methane uptake in the kerogens is determined by methane isotherms and shows that approximately two types of binding sites are present in low mature kerogens while the binding sites are relatively homogeneous in the most mature kerogen. The hysteresis effect of the structure during the adsorption and desorption process at different CD<sub>4</sub> gas pressures are studied. An extended generalized Porod's scattering law method (GPSLM) is further developed here to analyze kerogens with fractal surfaces. This extended GPSLM quantifies the surface heterogeneity of the kerogens with a fractal surface and shows that kerogen with high maturity is chemically more homogeneous, consistent with the results from methane isosteric heat. SANS analysis also suggests a pronounced surface roughness in the more mature kerogens. A microporous region circling around the nanopores, which contributes to high surface roughness and methane storage, is shown to develop with maturity.
Average firing rate rather than temporal pattern determines metabolic cost of activity in thalamocortical relay neurons (2019)

Thalamocortical (TC) relay cells exhibit different temporal patterns of activity, including tonic mode and burst mode, to transmit sensory information to the cortex. Our aim was to quantify the metabolic cost of different temporal patterns of neural activity across a range of average firing rates. We used a biophysically-realistic model of a TC relay neuron to simulate tonic and burst patterns of firing. We calculated the metabolic cost by converting the calculated ion fluxes into the demand for ATP to maintain homeostasis of intracellular ion concentrations. Most energy was expended on reversing Na<sup>+</sup> entry during action potentials and pumping Ca<sup>2+</sup> out of the cell. Average firing rate determined the ATP cost across firing patterns by controlling the overall number of spikes. Varying intraburst frequency or spike number in each burst influenced the metabolic cost by altering the interactions of inward and outward currents on multiple timescales, but temporal pattern contributed substantially less to the metabolic demand of neural activity as compared to average firing rate. These predictions should be considered when interpreting findings of functional imaging studies that rely of estimates of neuronal metabolic demand, e.g., functional magnetic resonance imaging.