gebhart/patrepeval huggingface dataset:
Effect of the three‐dimensional structure on the deamidation reaction of ribonuclease A (1999)

Kinetic data on the deamidation reaction of Asn67 in RNase A and of Asn3 in the two peptides Ac-Cys-Lys-Asn-Gly-Gln-Thr-Asn-Cys-NH2 and Ac-Cys(Me)-Lys-Asn-Gly-Gln-Thr-Asn-Cys(Me)-NH2, whose sequences are similar to that of the deamidation site in the enzyme, have been determined in a wide range of pH and buffer concentrations. The values of the observed rate constant (k) for the enzyme are markedly lower than those for the peptides. However, the k dependence on pH and buffers is similar for all three substrates, indicating a similar reaction mechanism. The lower k-values for the enzyme have been quantitatively related to the thermal stability and the three-dimensional structure of the enzyme.
Peripheral cannabinoid receptor, CB2, regulates bone mass (2006)

The endogenous cannabinoids bind to and activate two G protein-coupled receptors, the predominantly central cannabinoid receptor type 1 (CB1) and peripheral cannabinoid receptor type 2 (CB2). Whereas CB1 mediates the cannabinoid psychotropic, analgesic, and orectic effects, CB2 has been implicated recently in the regulation of liver fibrosis and atherosclerosis. Here we show that CB2-deficient mice have a markedly accelerated age-related trabecular bone loss and cortical expansion, although cortical thickness remains unaltered. These changes are reminiscent of human osteoporosis and may result from differential regulation of trabecular and cortical bone remodeling. The CB2(-/-) phenotype is also characterized by increased activity of trabecular osteoblasts (bone-forming cells), increased osteoclast (the bone-resorbing cell) number, and a markedly decreased number of diaphyseal osteoblast precursors. CB2 is expressed in osteoblasts, osteocytes, and osteoclasts. A CB2-specific agonist that does not have any psychotropic effects enhances endocortical osteoblast number and activity and restrains trabecular osteoclastogenesis, apparently by inhibiting proliferation of osteoclast precursors and receptor activator of NF-kappaB ligand expression in bone marrow-derived osteoblasts/stromal cells. The same agonist attenuates ovariectomy-induced bone loss and markedly stimulates cortical thickness through the respective suppression of osteoclast number and stimulation of endocortical bone formation. These results demonstrate that the endocannabinoid system is essential for the maintenance of normal bone mass by osteoblastic and osteoclastic CB2 signaling. Hence, CB2 offers a molecular target for the diagnosis and treatment of osteoporosis, the most prevalent degenerative disease in developed countries.
Maximum n-times Coverage for COVID-19 Vaccine Design (2021)

In the maximum $n$-times coverage problem, we are provided a set of elements, a weight for each element, and a set of overlays where each overlay specifies an element specific coverage of zero or more times. The goal is to select up to $k$ overlays such that the sum of the weights of elements that are covered at least $n$ times is maximized. We also define the min-cost $n$-times coverage problem where the objective is to select the minimum set of overlays such that the sum of the weights of elements that are covered at least $n$ times is at least $\tau$. We show that the $n$-times coverage objective is not submodular, and we present an efficient solution by sequential greedy optimization. We frame the design of a peptide vaccine for COVID-19 as maximum $n$-times coverage using machine learning defined candidate peptide sets, and show that our solution is superior to 29 other published COVID-19 peptide vaccine designs in predicted population coverage and the expected number of peptides displayed by each individual's HLA molecules.
The Effectiveness of Specific Collagen Peptides on Osteoarthritis in Dogs-Impact on Metabolic Processes in Canine Chondrocytes (2017)

In clinical trials over the past decade, the beneficial effect of orally administered collagen peptides in osteoarthritic dogs has been clearly demonstrated [1] [2] [3]. Although a statistically significant improvement in the lameness and vitality of dogs in general has been documented, the mode of action of the collagen peptide treatment is still under discussion. A previous study [3] indicated that the reduction in lameness and increased mobility in dogs after collagen peptide treatment were associated with a statistically significantly lowered plasma content of MMP-3, which is involved in collagen degradation. In addition, the content of the MMP-antagonist TIMP-1 increased slightly after collagen peptide supplementation, suggesting a direct impact on the cartilage metabolism, particularly on the decrease of extracellular matrix degradation. Based on these findings, the impact of specific collagen peptides (PETA-GILE?) on cartilage metabolism was tested in canine chondrocytes in the current investigation. In addition to the biosynthesis of various matrix molecules (type II collagen, aggrecan and elastin), the RNA profile of inflammatory cytokines and degenerative matrix molecules was investigated. The results showed clearly that the supplementation of specific collagen peptides reduced catabolic processes, as indicated by a statistically significant decrease in inflammatory cytokines and proteases in canine chondrocytes compared with untreated control experiments. In addition, a statistically significantly enhanced biosynthesis of type II collagen, elastin, and aggrecan was observed. Hence, the current data supports the suggested anti-inflammatory effect of specific collagen peptides, but also clearly demonstrates a pronounced stimulatory impact on matrix molecule synthesis. A combination of both observed effects might help to explain the previously reported clinical improvements after collagen peptide supplementation. Furthermore, the beneficial effect of the specific collagen peptides was also confirmed in case reports on osteoarthritic dogs that demonstrated decreased lameness and increased vitality in the affected animals after PETAGILE treatment.
Entropic Unfolding of DNA Molecules in Nanofluidic Channels (2008)

Single DNA molecules confined to nanoscale fluidic channels extend along the channel axis in order to minimize their conformational free energy. When such molecules are forced into a nanoscale fluidic channel under the application of an external electric field, monomers near the middle of the DNA molecule may enter first, resulting in a folded configuration with less entropy than an unfolded molecule. The increased free energy of a folded molecule results in two effects: an increase in extension factor per unit length for each segment of the molecule, and a spatially localized force that causes the molecule to spontaneously unfold. The ratio of this unfolding force to hydrodynamic friction per DNA contour length is measured in nanochannels with two different diameters.
A reassessment of the relationship between aroK- and aroL-encoded shikimate kinase enzymes of Escherichia coli (1995)

In the course of sequencing the aroK gene, a number of errors were found in the published sequence. The corrected sequence alters the length of the aroK coding region such that the AroK and AroL proteins are now of comparable length and the homology between them extends the entire length of the two enzymes.
Role of dehydropeptidase-I in the metabolism of glutathione and its conjugates in the rat kidney. (1987)

14C-N-Ethylmaleimide-S-cysteinylglycine was used to investigate the role of dehydropeptidase-I in the metabolism of glutathione conjugates. The dipeptide was rapidly hydrolyzed to 14C-N-ethylmaleimide-S-cysteine in isolated rat renal cells, and subsequently acetylated to 14C-N-ethylmaleimide-S-N-acetylcysteine. Cilastatin, a specific inhibitor of dehydropeptidase-I, strongly inhibited the hydrolysis of the dipeptide by the isolated cells. In rat kidney homogenates, the marked inhibitory effect of cilastatin was also observed on the hydrolysis of cystinyl-bis-glycine and leukotriene D4, which are dipeptide intermediates in the biotransformation of oxidized glutathione and endogenous glutathione conjugate, respectively. In contrast, the inhibitory effect of bestatin, a potent inhibitor of aminopeptidase-M, was much smaller than that of cilastatin on the hydrolysis of these dipeptides by the renal cells and homogenates. These results suggest that dehydropeptidase-I plays a more important role in the metabolism of glutathione and its conjugates than aminopeptidase-M does.
PaveMend as a Solution for Rapid Runway Repair (2002)

The paper first gives definition and historical perspective to the problem of Rapid Runway Repair (RRR), particularly its roots in the area of expedient runway construction. The differences in Cold War and post-Cold War RRR needs are also discussed. CeraTech, Inc.'s PaveMend is presented as a good solution for post-Cold War RRR needs, which are speed of the repair and durability of the repair. The homogeneous nature of PaveMend is illustrated by a photomicrograph, and the ability of PaveMend to be engineered to match the material to be repaired is discussed as a desirable quality. A manufacturer's specification sheet with independent, third-party lab results is presented, which illustrates the ability of PaveMend to mimic the properties of a typical runway which might need RRR in the post-Cold War era.
Estimating Actual Transpiration of Apple Trees Based on Infrared Thermometry (2014)

A method was developed based on the radiative properties and energy budget of a single apple leaf to calculate the actual transpiration (T) of apple trees. The model uses canopy temperature (Tc), air temperature (Ta) measured in the orchard, and other meteorological data from a local weather station as inputs. The model was applied to two scenarios, as follows: (1) well-watered, young Fuji apple trees in the 2007 and 2008 growing seasons; and (2) older apple trees, bearing little fruit in the 2013 growing season. Simulated transpiration rates at both scenarios were compared with Penman-Monteith (PM) model predictions corrected by regionally adjusted crop coefficients, i.e., values of ETc. In 2007 and 2008, a linear regression analysis of the relationship between daily mean transpiration (Tavg) and ETc revealed that they better agreed on warm and dry days (correlation coefficient R2=0.57, slope=1.16, and intercept=0.4) than during cold and humid periods (R2=0.48, slope=0.69, and intercept=2.3). Combining the results of the 2007 and 2008 seasons, Tavg and ETc presented a fairly good agreement, with the relationships R2, slope, and intercept of 0.77, 1.0, and 1.08, respectively. In 2013, the actual water use calculated by a soil water budget approach (ETWB) was considerably less than ETc while there was no significant difference between the total simulated transpiration (ΣTavg) and ETWB. In 2013, a linear regression analysis of the relationship between midday T (Tmid), Tavg, and midday stem water potential (Ψstem) showed they were highly correlated (Tmid, R2=0.85; Tavg, R2=0.87). The experiments presented varied results on the linear relationship between air vapor pressure deficit (Da) and Tavg from year to year. On the other hand, canopy and air temperature difference (ΔTm) was linearly related to Tavg in all of the seasons. According to the model for the actual transpiration (i.e., the T-model), the apple trees had an intense transpiration in the morning and then there was a decline around solar noon. The transpiration increased again late in the afternoon. Real-time estimations of water use using the T-model can provide a basis for a fully automated system of irrigating apple orchards.
A 4.6Tbits/s 3.6GHz single-cycle NoC router with a novel switch allocator in 65nm CMOS (2007)

As chip multiprocessors (CMPs) become the only viable way to scale up and utilize the abundant transistors made available in current microprocessors, the design of on-chip networks is becoming critically important. These networks face unique design constraints and are required to provide extremely fast and high bandwidth communication, yet meet tight power and area budgets. In this paper, we present a detailed design of our on-chip network router targeted at a 36-core shared-memory CMP system in 65nm technology. Our design targets an aggressive clock frequency of 3.6GHz, thus posing tough design challenges that led to several unique circuit and microarchitectural innovations and design choices, including a novel high throughput and low latency switch allocation mechanism, a non-speculative single-cycle router pipeline which uses advanced bundles to remove control setup overhead, a low-complexity virtual channel allocator and a dynamically-managed shared buffer design which uses prefetching to minimize critical path delay. Our router takes up 1.19mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> area and expends 551 mW power at 10% activity, delivering a single-cycle no-load latency at 3.6GHz clock frequency while achieving a peak switching data rate in excess of 4.6Tbits/s per router node.
Building and breeding molecules to spy on cells and tumors (2004)

Imaging of biochemical processes in living cells and organisms is essential for understanding how genes and gene products work together in space and time and in health and disease. Such imaging depends crucially on indicator molecules designed to maximize sensitivity and specificity. These molecules can be entirely synthetic, entirely genetically encoded macromolecules, or hybrid combinations, each approach having its own pros and cons. Recent examples from the author's laboratory include peptides whose uptake into cells is triggered by proteases typical of tumors, monomeric red fluorescent proteins and biarsenical-tetracysteine systems for determining the age and electron-microscopic location of proteins.
Superhydrophobic Fabrics Produced by Electrospinning and Chemical Vapor Deposition (2005)

A versatile method to produce superhydrophobic fabrics by combining electrospinning and initiated chemical vapor deposition (iCVD) is reported. In this study, poly(caprolactone) (PCL) was first electrospun and then coated with a thin layer of hydrophobic polymerized perfluoroalkyl ethyl methacrylate (PPFEMA) by iCVD. The hierarchical surface roughness inherent in the PCL electrospun mats and the extremely low surface free energy of the coating layer obtained by iCVD yields stable superhydrophobicity with a contact angle of 175° and a threshold sliding angle less than 2.5° for a 20 mg droplet. This PPFEMA-coated PCL mat was also shown to exhibit at least “grade 8” oleophobicity. Hydrophobicity was demonstrated to increase monotonically with a reduction in diameter among bead-free fibers and with the introduction of a high density of relatively small diameter beads. The systematic effect of fiber morphology on superhydrophobicity was also investigated theoretically and experimentally using both beaded and bead-free fibers with diameters ranging from 600 to 2200 nm.
Where Is Current Research on Blockchain Technology?—A Systematic Review (2016)

Blockchain is a decentralized transaction and data management technology developed first for Bitcoin cryptocurrency. The interest in Blockchain technology has been increasing since the idea was coined in 2008. The reason for the interest in Blockchain is its central attributes that provide security, anonymity and data integrity without any third party organization in control of the transactions, and therefore it creates interesting research areas, especially from the perspective of technical challenges and limitations. In this research, we have conducted a systematic mapping study with the goal of collecting all relevant research on Blockchain technology. Our objective is to understand the current research topics, challenges and future directions regarding Blockchain technology from the technical perspective. We have extracted 41 primary papers from scientific databases. The results show that focus in over 80% of the papers is on Bitcoin system and less than 20% deals with other Blockchain applications including e.g. smart contracts and licensing. The majority of research is focusing on revealing and improving limitations of Blockchain from privacy and security perspectives, but many of the proposed solutions lack concrete evaluation on their effectiveness. Many other Blockchain scalability related challenges including throughput and latency have been left unstudied. On the basis of this study, recommendations on future research directions are provided for researchers.
[A genetic method for exposing a given epitope at the surface of the bacterium Escherichia coli. Perspectives]. (1986)

We describe a genetic method leading to insertion of a defined epitope into certain sites of a protein. This method is applied to LamB, an outer membrane protein from Escherichia coli K12. It allowed us to construct an "exposition vector". The bacterial clone harboring this vector with its passenger exposes the epitope at its surface. We discuss briefly some of the perspectives which are opened by this approach concerning the study of structure and localization of proteins, the development of live vaccines and the direct cloning and exposure of unknown epitopes.
In vivogeneration of highly abundant sequence-specific oligonucleotides for antisense and triplex gene regulation (1994)

Antisense and triplex oligonucleotides continue to demonstrate potential as mediators of gene-specific repression of protein synthesis. However, inefficient and heterogeneous cellular uptake, intracellular sequestration, and rapid intracellular and extracellular degradation represent obstacles to their eventual clinical utility. Efficient cellular delivery of targeted ribozymes can present similar problems. In this report we describe a system for circumventing these obstacles and producing large quantities of short, sequence-specific RNA oligonucleotides for use in these gene regulation strategies. The oligonucleotides are generated from a vector containing promoter, capping, and termination sequences from the human small nuclear U6 gene, surrounding a synthetic sequence incorporating the oligonucleotide of interest. In vivo, these oligonucleotides are produced constitutively and without cell type specificity in levels up to 5 x 10(6) copies per cell, reach steady-state levels of expression within 9 hours post-transfection, and are still readily detectable 7 days post-transfection. In addition, these oligonucleotides are retained in the nucleus, obtain a 5' gamma-monomethyl phosphate cap, and have an intracellular half-life of approximately one hour. This expression vector provides a novel and efficient method of intracellular delivery of antisense or triplex RNA oligonucleotides (and/or ribozymes) for gene regulation, as well as a cost-effective means of comparing the biological activity arising from a variety of different potential oligonucleotide sequences.
How to hide the elephant- or the donkey- in the room: Practical privacy against statistical inference for large data (2013)

We propose a practical methodology to protect a user's private data, when he wishes to publicly release data that is correlated with his private data, in the hope of getting some utility. Our approach relies on a general statistical inference framework that captures the privacy threat under inference attacks, given utility constraints. Under this framework, data is distorted before it is released, according to a privacy-preserving probabilistic mapping. This mapping is obtained by solving a convex optimization problem, which minimizes information leakage under a distortion constraint. We address a practical challenge encountered when applying this theoretical framework to real world data: the optimization may become untractable and face scalability issues when data assumes values in large size alphabets, or is high dimensional. Our work makes two major contributions. We first reduce the optimization size by introducing a quantization step, and show how to generate privacy mappings under quantization. Second, we evaluate our method on a dataset showing correlations between political views and TV viewing habits, and demonstrate that good privacy properties can be achieved with limited distortion so as not to undermine the original purpose of the publicly released data, e.g. recommendations.
Intracellular calcium dependence of large dense-core vesicle exocytosis in the absence of synaptotagmin I (2001)

Synaptotagmin I is a synaptic vesicle-associated protein essential for synchronous neurotransmission. We investigated its impact on the intracellular Ca(2+)-dependence of large dense-core vesicle (LDCV) exocytosis by combining Ca(2+)-uncaging and membrane capacitance measurements in adrenal slices from mouse synaptotagmin I null mutants. Synaptotagmin I-deficient chromaffin cells displayed prolonged exocytic delays and slow, yet Ca(2+)-dependent fusion rates, resulting in strongly reduced LDCV release in response to short depolarizations. Vesicle recruitment, the shape of individual amperometric events, and endocytosis appeared unaffected. These findings demonstrate that synaptotagmin I is required for rapid, highly Ca(2+)-sensitive LDCV exocytosis and indicate that it regulates the equilibrium between a slowly releasable and a readily releasable state of the fusion machinery. Alternatively, synaptotagmin I could function as calcium sensor for the readily releasable pool, leading to the destabilization of the pool in its absence.
Regulation of c-Jun NH2-terminal Kinase ( Jnk) Gene Expression during T Cell Activation (2000)

The c-Jun NH(2)-terminal kinases (JNKs) are a group of mitogen-activated protein (MAP) kinases that participate in signal transduction events mediating specific cellular functions. Activation of JNK is regulated by phosphorylation in response to cellular stress and inflammatory cytokines. Here, we demonstrate that JNK is regulated by a second, novel mechanism. Induction of Jnk gene expression is required in specific tissues before activation of this signaling pathway. The in vivo and in vitro ligation of the T cell receptor (TCR) leads to induction of JNK gene and protein expression. TCR signals are sufficient to induce JNK expression, whereas JNK phosphorylation also requires CD28-mediated costimulatory signals. Therefore, both expression and activation contribute to the regulation of the JNK pathway to ensure proper control during the course of an immune response.
Classical and late-onset forms of congenital adrenal hyperplasia caused by 21-OH deficiency reveal different alterations in the C4/21-OH gene region. (1986)

Congenital adrenal hyperplasia (CAH) is due to defective adrenal cortisol biosynthesis. In most cases, deficiency of a P 450-C21 specific steroid hydroxylase impairing cortisol synthesis has been found. The disease is HLA-linked, and on clinical grounds it can be divided into two major forms, the classical and the non-classical type. Here, evidence is presented that the classical and the non-classical forms of CAH caused by 21-OH deficiency are due to different genetic alterations in the C4/21-OH gene region. In most cases of classical CAH associated with the HLA-Bw47 antigen, a specific and selective loss of the 21-OH B gene was observed with some interesting exceptions. Alterations in the 21-OH gene region in the non-classical forms of CAH, patients either HLA-B14; DR1 homo- or heterozygous, are different. Our data indicate the possibility of gene conversion events in this genomic region in non-classical CAH.