gebhart/patrepeval huggingface dataset:
Dynamic temperature-induced crystallization of proteins (1997)

This laboratory has designed a protein crystallization system which controls the supersaturation state of proteins via precise temperature changes. The system is coupled to lasers to monitor the aggregation state of the protein and to provide a mechanism for dynamic control of the crystallization process (DC/PCGT). This automated dynamic control process has resulted in systematic and predictable responses with regard to crystal size. However, in order to successfully use temperature-induced crystallization, it is necessary to understand, at least qualitatively, the dependence of protein solubility on temperature. These data are available for a limited number of proteins. We have therefore designed a multichambered thermal gradient device. This device uses microliter amounts of protein solutions and has been instrumental, not only as a means of screening protein solubility as a function of temperature, but in optimizing crystallizing conditions.
Decellularized Articular Cartilage Microparticles for Expansion of Mesenchymal Stem Cells and Zonal Regeneration of Articular Cartilage (2021)

Abstract Introduction The objective was to create multilayer cellular constructs using fetal or adult, decellularized articular cartilage in particulate form as microcarriers for expansion and fusion of mesenchymal stem cells (MSCs) to regenerate the stratified structure of articular cartilage. Methods Porous microparticles (CMPs) generated from decellularized fetal or adult bovine articular cartilage were used as microcarriers for expansion of human MSCs. The CMP expanded MSCs (CMP-MSCs) were used to generate injectable hydrogels or preformed multilayer constructs for articular cartilage regeneration. In the injectable approach, CMP-MSCs were suspended in alginate gel, crosslinked with calcium chloride, and incubated in chondrogenic medium to generate an injectable regenerative construct. In the preformed approach, fetal or adult CMP-MSCs were suspended in a culture medium, allowed to settle sequentially by the force of gravity, and fused by incubation in chondrogenic medium to generate multilayer cell sheets. The constructs were characterized with respect to compressive modulus, cellularity, and expression of chondrogenic markers. Results Human MSCs expanded on fetal or adult CMPs in basal medium maintained the expression of mesenchymal markers. The injectable CMP-MSCs hydrogels had significantly higher expression of chondrogenic markers and compressive modulus after four weeks incubation in chondrogenic medium compared to MSCs directly encapsulated in alginate gel; preformed CMP-MSCs cell sheets had significantly higher compressive modulus and expression of chondrogenic markers compared to MSCs in the pellet culture. Conclusion The preformed cell sheet approach is potentially useful for creating multilayer constructs by sequential gravitational settling of CMP-MSCs to mimic the stratified structure of articular cartilage. Insight, Innovation, Integration This work described a novel approach to recreate the zonal structure of articular cartilage. Human MSCs were expanded on porous microcarrier beads generated from decellularized fetal or adult bovine articular cartilage. The cell-seeded microbeads were fused by gravitational settling to form mono- or bi-layer cell sheets. The cell sheets were cultured in chondrogenic medium to regenerate the articular cartilage tissue. The in vitro regenerated tissue had higher compressive modulus and expression of chondrogenic markers compared to the MSC pellet culture.
Epithelial PD-L2 Expression Marks Barrett's Esophagus and Esophageal Adenocarcinoma (2015)

Esophageal adenocarcinoma is an increasingly common disease with a dismal 5-year survival rate of 10% to 15%. In the first systematic evaluation of the PD-1 pathway in esophageal adenocarcinoma, we identify expression of PD-L2 in cancer cells in 51.7% of esophageal adenocarcinomas. Epithelial PD-L1 was expressed on only 2% of cases, although PD-L1(+) immune cells were observed in 18% of esophageal adenocarcinomas. We also evaluated expression in the precursor lesion of esophageal adenocarcinoma, Barrett's esophagus, which emerges following gastric reflux-induced esophageal inflammation, and found PD-L2 expression in Barrett's esophagus but not in non-Barrett's esophagus esophagitis. Because the progression from squamous esophagitis to Barrett's esophagus is accompanied by a transition from a TH1 to TH2 immune response, we hypothesized that the TH2 cytokines IL4/IL13 could contribute to PD-L2 induction. We confirmed that these cytokines can augment PD-L2 expression in esophageal adenocarcinoma cell lines. These results suggest that the inflammatory environment in Barrett's esophagus and esophageal adenocarcinoma may contribute to the expression of PD-L2. Furthermore, the potential for PD-1 receptor blockade to be effective in esophageal adenocarcinomas with epithelial PD-L2 or immune cell PD-L1 expression should be evaluated in clinical trials.
Both Viral Transcription and Replication Are Reduced when the Rabies Virus Nucleoprotein Is Not Phosphorylated (2002)

Rabies virus nucleoprotein (N) plays vital roles in regulation of viral RNA transcription and replication by encapsidation of the nascent genomic RNA. Rabies virus N is phosphorylated, and previous studies demonstrated that mutation of the phosphorylated serine at position 389 to alanine resulted in reduction of viral transcription and/or replication of a rabies virus minigenome. In the present study, we mutated the serine (S) at position 389 to alanine (A), glycine (G), aspartic acid (D), asparagine (N), glutamic acid (E), and glutamine (Q) and examined the effects of these mutations on rabies virus transcription and replication in the minigenome. Furthermore, mutations from S to A, S to D, and S to E were also incorporated into the full-length infectious virus. Mutation of the serine to each of the other amino acids resulted in the synthesis of an unphosphorylated N and reduction of viral transcription and replication in the minigenome. Mutations from S to A and S to D also resulted in reduction of both viral transcription and replication in full-length infectious viruses. Growth curve studies indicated that production of the mutant virus with the S-to-A mutation (L16A) was as much as 10,000-fold less than that of the wild-type virus (L16). Northern blot hybridization with rabies virus gene probes revealed that the rates of viral transcription and replication were reduced by as much as 10-fold in the mutant viruses when the N was not phosphorylated. Interpretation of the data from the minigenome system and the full-length infectious virus indicates that phosphorylation of rabies virus N is necessary for replication. Further studies involving cycloheximide treatment of infected cells revealed that viral transcription was also reduced when the N was not phosphorylated. Taken together, these results provide definitive evidence that N phosphorylation plays an important role in the processes of rabies virus transcription and replication.
Co-supported tandem catalysts for production of linear low density polyethylene (2017)

A phenoxy-imine titanium trimerization catalyst and a silylene linked cyclopentadienyl-amido titanium polymn.\ncatalyst are co-immobilized on methylaluminoxane/silica particles to create a tandem catalytic system to generate linear low d. polyethylene (LLDPE) from an ethylene only feed. The 1-hexene incorporation into the polymer can be controlled by varying the ethylene pressure.
The synthesis and <i>in vitro</i> testing of a zinc-activated MRI contrast agent (2007)

Zinc(II) plays a vital role in normal cellular function as an essential component of numerous enzymes, transcription factors, and synaptic vesicles. While zinc can be linked to a variety of physiological processes, the mechanisms of its cellular actions are less discernible. Here, we have synthesized and tested a Zn(II)-activated magnetic resonance imaging (MRI) contrast agent in which the coordination geometry of the complex rearranges upon binding of Zn(II). In the absence of Zn(II) water is restricted from binding to a chelated Gd(III) ion by coordinating acetate arms resulting in a low relaxivity of 2.33 mM(-1) x s(-1) at 60 MHz. Upon addition of Zn(II) the relaxivity of the Gd(III)-Zn(II) complex increases to 5.07 mM(-1) x s(-1) and is consistent with one water molecule bound to Gd(III). These results were confirmed by nuclear magnetic relaxation dispersion analysis. There was no observed change in relaxivity of the Gd(III) complex when physiologically competing cations Ca(II) and Mg(II) were added. A competitive binding assay gave a dissociation constant of 2.38 x 10(-4) M for the Gd(III)-Zn(II) complex. In vitro magnetic resonance images confirm that Zn(II) concentrations as low as 100 microM can be detected by using this contrast agent.
An 850 nm pure near-infrared emitting iridium complex for solution-processed organic light-emitting diodes (2020)

The first example of an iridium(<sc>iii</sc>) emitter in pure near-infrared OLEDs with an emission peak at 850 nm and full emission over 700 nm.
Dual Alleviation of Acute and Neuropathic Pain by Fused Opioid Agonist-Neurokinin 1 Antagonist Peptidomimetics (2015)

Herein, the synthesis and biological evaluation of dual opioid agonists-neurokinin 1 receptor (NK1R) antagonists is described. In these multitarget ligands, the two pharmacophores do not overlap, and this allowed maintaining high NK1R affinity and antagonist potency in compounds 12 and 13. Although the fusion of the two ligands resulted in slightly diminished opioid agonism at the μ- and δ-opioid receptors (MOR and DOR, respectively), as compared to the opioid parent peptide, balanced MOR/DOR activities were obtained. Compared to morphine, compounds 12 and 13 produced more potent antinociceptive effects in both acute (tail-flick) and neuropathic pain models (von Frey and cold plate). Similarly to morphine, analgesic tolerance developed after repetitive administration of these compounds. To our delight, compound 12 did not produce cross-tolerance with morphine and high antihyperalgesic and antiallodynic effects could be reinstated after chronic administration of each of the two compounds.
ChemInform Abstract: Syntheses of FDA Approved HIV Protease Inhibitors (2002)

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.
Optical mapping near-eye three-dimensional display with correct focus cues (2017)

We present an optical mapping near-eye (OMNI) three-dimensional display method for wearable devices. By dividing a display screen into different subpanels and optically mapping them to various depths, we create a multiplane volumetric image with correct focus cues for depth perception. The resultant system can drive the eye's accommodation to the distance that is consistent with binocular stereopsis, thereby alleviating the vergence-accommodation conflict, the primary cause for eye fatigue and discomfort. Compared with the previous methods, the OMNI display offers prominent advantages in adaptability, image dynamic range, and refresh rate.
Dexamethasone Partially Rescues Ataxia Telangiectasia-mutated (ATM) Deficiency in Ataxia Telangiectasia by Promoting a Shortened Protein Variant Retaining Kinase Activity (2012)

Ataxia telangiectasia (AT) is a rare genetic disease, still incurable, resulting from biallelic mutations in the ataxia telangiectasia-mutated (ATM) gene. Recently, short term treatment with glucocorticoid analogues improved neurological symptoms characteristic of this syndrome. Nevertheless, the molecular mechanism involved in glucocorticoid action in AT patients is not yet known. Here we describe, for the first time in mammalian cells, a short direct repeat-mediated noncanonical splicing event induced by dexamethasone, which leads to the skipping of mutations upstream of nucleotide residue 8450 of ATM coding sequence. The resulting transcript provides an alternative ORF translated in a new ATM variant with the complete kinase domain. This miniATM variant was also highlighted in lymphoblastoid cell lines from AT patients and was shown to be likely active. In conclusion, dexamethasone treatment may partly restore ATM activity in ataxia telangiectasia cells by a new molecular mechanism that overcomes most of the mutations so far described within this gene.
Glycolipids as indicators of tumorigenesis (1978)

Hyperplastic liver nodules and hepatocellular carcinomas were induced in rats by oral administration of the carcinogen N-2-fluorenylacetamide. Neoplastic tissue was compared with control, fetal, neonatal, and precancerous liver tissues. The development of the tumors was slow, such that temporal changes in the biochemical and morphologic development of carcinogenesis could be identified. Ganglioside sialic acid levels were elevated in all but the most poorly differentiated tumors. Experiments to monitor individual enzymes suggested that the alterations in glycolipid composition were a direct effect of alterations in biosynthetic activities. The pattern during tumorigenesis was the inverse of that during normal development. Also, ganglioside patterns showed a progressive simplification from hyperplastic nodules to well-differentiated hepatomas and through two grades of poorly differentiated hepatomas. An increase in the activity of the branchpoint enzyme of ganglioside biosynthesis preceded both a decrease in the branchpoint enzyme of the disialoganglioside pathway and a marked increase in the galactosyltranferase of GM1 formation. The results indicate that ganglioside deletions are the end result of a cascade of events in the tumorigenic transformation. The onset of ganglioside deletions but not of the cascade per se may correlate with the onset of malignancy. Glycolipid levels are elevated early in certain surrounding tissues especially in the blood. In rats bearing transplantable hepatomas, serum levels of lipid-bound sialic acid were elevated 2.5-fold. Similar results were obtained with sera of mice bearing transplantable mammary carcinomas and of cancer patients. These findings provide new emphasis for gangliosides in both cancer detection and as regulatory signals for growth and multiplication of cells.
Local Inhibition of PERK Enhances Memory and Reverses Age-Related Deterioration of Cognitive and Neuronal Properties (2017)

Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is one of four known kinases that respond to cellular stress by deactivating the eukaryotic initiation factor 2 α (eIF2α) or other signal transduction cascades. Recently, both eIF2α and its kinases were found to play a role in normal and pathological brain function. Here, we show that reduction of either the amount or the activity of PERK, specifically in the CA1 region of the hippocampus in young adult male mice, enhances neuronal excitability and improves cognitive function. In addition, this manipulation rescues the age-dependent cellular phenotype of reduced excitability and memory decline. Specifically, the reduction of PERK expression in the CA1 region of the hippocampus of middle-aged male mice using a viral vector rejuvenates hippocampal function and improves hippocampal-dependent learning. These results delineate a mechanism for behavior and neuronal aging and position PERK as a promising therapeutic target for age-dependent brain malfunction.<b>SIGNIFICANCE STATEMENT</b> We found that local reduced protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) expression or activity in the hippocampus enhances neuronal excitability and cognitive function in young normal mice, that old CA1 pyramidal cells have reduced excitability and increased PERK expression that can be rescued by reducing PERK expression in the hippocampus, and that reducing PERK expression in the hippocampus of middle-aged mice enhances hippocampal-dependent learning and memory and restores it to normal performance levels of young mice. These findings uncover an entirely new biological link among PERK, neuronal intrinsic properties, aging, and cognitive function. Moreover, our findings propose a new way to fight mild cognitive impairment and aging-related cognitive deterioration.
Cover Picture:Transparent Zeolite–Polymer Hybrid Materials with Adaptable Properties (Adv. Funct. Mater. 14/2007) (2007)

Abstract On p. 2298, Gion Calzaferri and co‐workers of the University of Bern, Switzerland report on a new, simple preparation procedure for highly transparent zeolite‐polymer hybrid materials and polymer covered zeolite L monolayers. The thus‐obtained new transparent host–guest inorganic–organic hybrid materials offer fascinating novel possibilities for the development of optical devices such as lenses, special mirrors, filters, polarizer, grids, optical storage devices, and windows. We report here on a simple preparation procedure for highly transparent zeolite‐polymer hybrid materials and polymer covered zeolite L monolayers. Wrapping up zeolites containing, e.g., dye molecules as guest species with alkoxysilane derivatives results in an efficient dispersion of the nano particles into the organic liquid monomer. The following copolymerisation process leads to a hard, insoluble and transparent material containing zeolites. Optical properties such as colour, luminescence, refractive index or photochromism can be adapted by simply changing the type and amount of the guest in the zeolite crystals, while transparency is maintained.
Degradation Phenomena in Small-Molecule Organic Light-Emitting Devices (2004)

Studies of electroluminescence degradation mechanisms in small-molecule-based organic light-emitting devices (OLEDs) are reviewed. Luminescence degradation due to the growth of visible nonemissive defects, widely referred to as "dark spots", as well as device catastrophic failure phenomena are addressed briefly. A special emphasis is given to intrinsic degradation phenomena that cause the decrease in the electroluminescence efficiency of the OLEDs during operation. In the discussion of intrinsic degradation, some widely accepted models that have been proposed to explain the degradation behavior are introduced and reviewed in view of experimental observations. These models are (i) the morphological instability model, (ii) the unstable cationic AlQ3 model, (iii) the indium migration model, (iv) the mobile ionic impurities model, and (v) the immobile positive charge accumulation model.
Estimating word-stability during incremental speech recognition (2012)

Many speech user interfaces can be improved by incrementally displaying or interpreting a speech recognizer’s current best path as a user speaks. This gives rise to a problem of instability, whereby the best path may change frequently, particularly with respect to the words most recently spoken. Introducing a lag between the audio most recently processed and the portion of the best path shown to the user can lead to more usable incremental results. In the ideal case, the lag introduced would vary to recover exactly the longest stable prefix of the best path. In this paper, we introduce a framework for estimating a stability statistic for each word, and explore the tradeoff of stability and lag by thresholding stability statistics estimated using a variety of features.
Multibit correcting data interface for fault-tolerant systems (1993)

A fault-detecting, bidirectional data interface between uncoded data from one component, such as a processor, and coded data in the rest of the system is described. This interface is capable of correcting a single multibit symbol error or detecting the occurrence of two such errors. The device uses a shortened Reed-Solomon code, and two practical symbol sizes are considered; nibble (4-bit) errors are protected by a (40, 32) binary equivalent shortened code, and byte errors are covered by a (80, 64) binary-sized code. The Reed-Solomon codes have maximum protection levels, even when shortened, and allow simplifying the design options. A dual orthogonal basis used for the symbols' representations provides significant hardware savings. The interface unit achieves internal fault detection by comparing regenerated parity values in a totally self-checking equality checker. A fault-tolerant ultrareliable memory module is proposed and evaluated. An illustrative design is realized using a single desktop programmable gate array.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Electron Beam Block Exposure (1991)

A new exposure technique called block exposure was examined in order to increase the throughput of direct writing of memory LSI devices using an electron beam. With this technique, an electron beam is projected to a block of aperture patterns in the stencil mask to change the beam shape. Frequently used LSI pattern components are defined as blocks to be reused during the exposure. Patterns that are rarely used are exposed by using a variable-shape beam. With the demagnification ratio of one percent, masks are easy to fabricate and very reliable. The patterns with a 0.13-µm minimum feature size are well projected on a single-layer resist. With block exposure, any shape can be accurately transferred irrespective of the pattern shape or size. The throughput of about ten 8-in wafers per hour is estimated for several pattern layers of a 64-Mbit dynamic random-access memory (DRAM).
Wavelet decomposition of software entropy reveals symptoms of malicious code (2016)

Sophisticated malware authors can sneak hidden malicious contents into portable executable files, and this contents can be hard to detect, especially if encrypted or compressed. However, when an executable file switches between contents regimes (e.g., native, encrypted, compressed, text, and padding), there are corresponding shifts in the file’s representation as an entropy signal. In this paper, we develop a method for automatically quantifying the extent to which patterned variations in a file’s entropy signal make it “suspicious”. In Experiment 1, we use wavelet transforms to define a Suspiciously Structured Entropic Change Score (SSECS), a scalar feature that quantifies the suspiciousness of a file based on its distribution of entropic energy across multiple levels of spatial resolution. Based on this single feature, it was possible to raise predictive accuracy on a malware detection task from 50.0% to 68.7%, even though the single feature was applied to a heterogeneous corpus of malware discovered “in the wild”. In Experiment 2, we describe how wavelet-based decompositions of software entropy can be applied to a parasitic malware detection task involving large numbers of samples and features. By extracting only string and entropy features (with wavelet decompositions) from software samples, we are able to obtain almost 99% detection of parasitic malware with fewer than 1% false positives on good files. Moreover, the addition of wavelet-based features uniformly improved detection performance across plausible false positive rates, both in a strings-only model (e.g., from 80.90% to 82.97%) and a strings-plus-entropy model (e.g. from 92.10% to 94.74%, and from 98.63% to 98.90%). Overall, wavelet decomposition of software entropy can be useful for machine learning models for detecting malware based on extracting millions of features from executable files.