gebhart/patrepeval huggingface dataset:
Relative noncovalent association constant between immunoglobulin H and L chains is unrelated to their expression or antigen-binding activity. (1987)

With H and L chains derived from the murine hybridoma and myeloma proteins NQ5-89.4, 93G7, AIDA10/3, AIDA10/16, HyHEL-10, HyHEL-9, HyHEL-8, HyHEL-5, XRPC25, J539, UPC10, 6684, and C101, the relationship between the relative affinity between H-L pairs, their antigen-binding characteristics, and the primary structure of their VH and VL domains was assessed. Using competitive chain reassociation assays in which two different L chains were allowed to compete for a limiting amount of an H chain, it was observed that different pairs of L chains tended to compete to the same degree regardless of which H chain was used as the limiting reagent and regardless of whether they were the autologous or heterologous L chain. In agreement with our previous results, it was also observed that when there was limited diversity between the Vk segments of the competing L chains, the relative competitive ability of an L chain was dictated by the nature of the first residue of the Jk segment, residue 96. However, when a high degree of diversity existed between the Vk segments of the competing L chains, the relative affinity was dictated by the V segment. It was further demonstrated that junctional diversity in the L chain may not necessarily be essential for antibody activity, determined using autologous and heterologous, noncovalently reassociated immunoglobulin molecules in antigen-binding assays. Combined with the results of the competitive reassociation assays, it was evident that no correlation between the competitive ability of these L chains existed or, by inference, the relative mutual affinity between different H-L pairs and their ability to form an antigen-binding site. These results were in agreement with the random rearrangement of VH and VL domain gene segments and argue against any restrictions in the expression of the full repertoire of immunoglobulin molecules due to combinatorial (H-L pairing) mechanisms.
Specific and Modular Binding Code for Cytosine Recognition in Pumilio/FBF (PUF) RNA-binding Domains (2011)

Pumilio/fem-3 mRNA-binding factor (PUF) proteins possess a recognition code for bases A, U, and G, allowing designed RNA sequence specificity of their modular Pumilio (PUM) repeats. However, recognition side chains in a PUM repeat for cytosine are unknown. Here we report identification of a cytosine-recognition code by screening random amino acid combinations at conserved RNA recognition positions using a yeast three-hybrid system. This C-recognition code is specific and modular as specificity can be transferred to different positions in the RNA recognition sequence. A crystal structure of a modified PUF domain reveals specific contacts between an arginine side chain and the cytosine base. We applied the C-recognition code to design PUF domains that recognize targets with multiple cytosines and to generate engineered splicing factors that modulate alternative splicing. Finally, we identified a divergent yeast PUF protein, Nop9p, that may recognize natural target RNAs with cytosine. This work deepens our understanding of natural PUF protein target recognition and expands the ability to engineer PUF domains to recognize any RNA sequence.
Inhibition of Tyrosine Kinase Activation Blocks the Down-Regulation of CXC Chemokine Receptor 4 by HIV-1 gp120 in CD4+ T Cells (1999)

Because the binding of HIV-1 envelope to CD4 initiates a configurational change in glycoprotein 120 (gp120), enabling it to interact with fusion coreceptors, we investigated how this process interferes with the expression and function of CXC chemokine receptor 4 (CXCR4) in CD4+ T lymphocytes. A recombinant gp120 (MN), after preincubation with CD4+ T lymphocytes, significantly inhibited the binding and chemotaxis of the cells in response to the CXCR4 ligand stromal cell-derived factor-1alpha (SDF-1alpha), accompanied by a markedly reduced surface expression of CXCR4. gp120, but not SDF-1alpha, induced rapid tyrosine phosphorylation of src-like kinase p56lck in CD4+ T cells, whereas both gp120 and SDF-1alpha caused phosphorylation of the CXCR4. The tyrosine kinase inhibitor herbimycin A abolished the phosphorylation of p56lck and CXCR4 induced by gp120 in association with maintenance of normal expression of cell surface CXCR4 and a migratory response to SDF-1alpha. Thus, a CD4-associated signaling molecule(s) including p56lck is activated by gp120 and is required for the down-regulation of CXCR4.
Empirical Closed Loop Modeling of a Suspension System Using Neural Network (1997)

A closed-loop system modeling of an active/semiactive suspension system has been accomplished through an artificial neural network. A 7DOF full model as a system's equation of motion has been derived and an output feedback linear quadratic regulator has been designed for control purpose. A training set of a sample data has been obtained through a computer simulation. A 7DOF full model with LQR controller simulated under several road conditions such as sinusoidal bumps and rectangular bumps. A general multilayer perceptron neural network is used for dynamic modeling and target outputs are fedback to the a layer. A backpropagation method is used as a training algorithm. Model validation of new dataset have been shown through computer simulations.
The phonics check, checks more than phonics (2018)

One of the most classic debates in reading development research is how children learn to read. There is extensive research on the processes in reading acquisition and the most effective ways to teach children how to read. Over 30 years of research, based on rigorously implemented methods, has consistently identified that effective reading instruction is underpinned by helping children to decode words using phonics (Castles et al. 2018).
Erenumab in chronic migraine with medication overuse (2019)

This study provides Class II evidence that erenumab reduces monthly migraine days at 3 months in patients with chronic migraine and medication overuse.
III. Physical One-Way Functions (2003)

How can we assign unique, tamper-resistant, and unforgeable identifiers to everyday objects at a very low cost? Physical One-Way Functions (POWFs) provide a novel approach to answering this question. POWFs can be obtained from the inherent threedimensional microstructure of a large class of physical systems known as mesoscopic systems. They are inexpensive to fabricate and prohibitively difficult to duplicate; they admit no compact mathematical representation and are intrinsically tamper-resistant. In this paper, we show how POWFs are obtained by using coherent scattering of visible laser radiation from inhomogeneous structures and experimentally demonstrate their properties. We also discuss potential attacks on POWFs and possible applications.
An New Avenue to Nonfouling Materials (2007)

Nonfouling materials are of great importance for numerous applications. A simple method is introduced to prepare nonfouling materials and surfaces (see figure) with unique properties from a variety of desirable functional groups. Materials with a uniform distribution of mixed charged groups at the nanometer scale, similar to zwitterionic materials, are excellent candidates for use as nonfouling materials.
Diterpene synthesis in Stevia rebaudiana: recruitment and up‐regulation of key enzymes from the gibberellin biosynthetic pathway (1999)

Stevia rebaudiana Bertoni leaves accumulate a mixture of at least eight different glycosides derived from the tetracyclic diterpene steviol. These natural products taste intensely sweet and have similar biosynthetic origins to those of gibberellic acid (GA). The initial steps leading to the formation of GA result from the two-step cyclization of geranylgeranyl diphosphate (GGDP) to (-)-kaurene via the action of two terpene cyclases (-)-copalyl diphosphate synthase (CPS) and (-)-kaurene synthase (KS). Steviol biosynthesis probably uses the same mechanism although the genes and enzymes from S. rebaudiana that are involved in the cyclization of GGDP have not been characterized. We have isolated both the CPS and KS genes from S. rebaudiana and found that recombinant CPS and KS were catalytically active, suggesting that the CPS and KS genes participate in steviol biosynthesis. The genes coding for CPS and KS are usually present in single copies in most plant species and their expression is normally low and limited to rapidly growing tissues. The KS gene has been duplicated in the S. rebaudiana genome and both the KS and CPS genes are highly expressed in mature leaves, a pattern opposite to that found with GA biosynthesis. This pattern may, at least in part, lead to temporal and spatial separation of GA and steviol biosynthesis and probably helps to prevent over-expression from interfering with normal GA metabolism. Our results show that CPS and KS are part of the steviol glycoside biosynthetic pathway and that Stevia rebaudiana has recruited two genes to secondary metabolism from a highly regulated pathway involved in hormone biosynthesis.
Direct gene transfer to mouse melanoma by intratumor injection of free DNA. (1996)

Long-term expression of a reporter gene has previously been reported in skeletal and cardiac muscles after direct injection of naked plasmid DNA. In this study, we have shown that the direct injection of free plasmid DNA into mouse melanoma BL6 solid tumor can also result in a high level of transfection. THe average amount of chloramphenicol acetyltransferase (CAT) expressed by injecting 30 micrograms plasmid DNA containing a CAT gene into a single BL6 tumor was 1.9 +/- 1.0 ng, which is comparable to that reported in the skeletal muscle. Cationic liposomes, Lipofectamine and DC-chol/DOPE, inhibited gene expression in a dose-dependent manner. Transgene expression by free DNA persisted for at least 10 days. The size of tumor did not seem to affect the gene expression, but proper choice of a diluent solution for DNA was an important factor. Genes driven by the CMV promoter were expressed much more efficiently than genes driven by the SV40 or T7 promoter. Optimal dosage of injected DNA was from 30 to 70 micrograms per tumor. Other mouse melanomas, human melanomas and cervical carcinomas are also able to express directly injected plasmid DNA, but the transfection efficiency is lower than the BL6 tumor. Direct injection of free plasmid DNA is a simple and effective approach and might be a potential method for cancer gene therapy.
Frequency analysis of atrial fibrillation from the surface electrocardiogram. (2004)

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Neither the natural history of AF nor its response to therapy are sufficiently predictable by clinical and echocardiographic parameters. Atrial fibrillatory frequency (or rate) can reliably be assessed from the surface electrocardiogram (ECG) using digital signal processing (filtering, subtraction of averaged QRST complexes, and power spectral analysis) and shows large inter-individual variability. This measurement correlates well with intraatrial cycle length, a parameter which appears to have primary importance in AF domestication and response to therapy. AF with a low fibrillatory rate is more likely to terminate spontaneously, and responds better to antiarrhythmic drugs or cardioversion while high rate AF is more often persistent and refractory to therapy. In conclusion, frequency analysis of AF seems to be useful for non-invasive assessment of electrical remodeling in AF and may subsequently be helpful for guiding AF therapy.
Nonlinear 3D projection printing of concave hydrogel microstructures for long-term multicellular spheroid and embryoid body culture (2015)

Long-term culture and monitoring of individual multicellular spheroids and embryoid bodies (EBs) remains a challenge for in vitro cell propagation. Here, we used a continuous 3D projection printing approach - with an important modification of nonlinear exposure - to generate concave hydrogel microstructures that permit spheroid growth and long-term maintenance, without the need for spheroid transfer. Breast cancer spheroids grown to 10 d in the concave structures showed hypoxic cores and signs of necrosis using immunofluorescent and histochemical staining, key features of the tumor microenvironment in vivo. EBs consisting of induced pluripotent stem cells (iPSCs) grown on the hydrogels demonstrated narrow size distribution and undifferentiated markers at 3 d, followed by signs of differentiation by the presence of cavities and staining of the three germ layers at 10 d. These findings demonstrate a new method for long-term (e.g. beyond spheroid formation at day 2, and with media exchange) 3D cell culture that should be able to assist in cancer spheroid studies as well as embryogenesis and patient-derived disease modeling with iPSC EBs.
CELL-SURFACE ANCHORING OF PROTEINS VIA GLYCOSYL-PHOSPHATIDYLINOSITOL STRUCTURES (1988)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Extended Depth of Focus and Aberration Control (2001)

Recent advances are presented in the use of a new paradigm for the design of imaging systems. The concept of wavefront coding is described, and several examples are given where previously unobtainable performance is obtained.
The case for partial indexes (1989)

Current data managers support secondary and/or primary indexes on columns of relations. In this paper we suggest the advantages that result from indexes which contain only some of the possible values in a column of a relation.
Bilateral high-frequency stimulation in the subthalamic nucleus for the treatment of Parkinson disease: correlation of therapeutic effect with anatomical electrode position (2002)

This observation makes blocking or activation of large fiber connections arising in the STN or running nearby more likely than electrical interference with cell bodies inside the STN. Anatomical correlates may be the pallidothalamic bundle (including Field H of Forel and the thalamic fascicle), the pallidosubthalamic tract, and/or the zona incerta.
Adipocyte extracellular matrix composition, dynamics and role in obesity (2010)

The central role of the adipose tissue in lipid metabolism places specific demands on the cell structure of adipocytes. The protein composition and dynamics of the extracellular matrix (ECM) is of crucial importance for the functioning of those cells. Adipogenesis is a bi-phasic process in which the ECM develops from a fibrillar to a laminar structure as cells move from the commitment phase to the growth phase characterized by storage of vast amounts of triglycerides. Mature adipocytes appear to spend a lot of energy on the maintenance of the ECM. ECM remodeling is mediated by a balanced complement of constructive and destructive enzymes together with their enhancers and inhibitors. ECM remodeling is an energy costing process regulated by insulin, by the energy metabolism, and by mechanical forces. In the obese, overgrowth of adipocytes may lead to instability of the ECM, possibly mediated by hypoxia.
Proton Transfers in the Photochemical Reaction Cycle of Proteorhodopsin (2002)

The spectral and photochemical properties of proteorhodopsin (PR) were determined to compare its proton transport steps to those of bacteriorhodopsin (BR). Static and time-resolved measurements on wild-type PR and several mutants were done in the visible and infrared (FTIR and FT-Raman). Assignment of the observed C=O stretch bands indicated that Asp-97 and Glu-108 serve as the proton acceptor and donor, respectively, to the retinal Schiff base, as do the residues at corresponding positions in BR, but there are numerous spectral and kinetic differences between the two proteins. There is no detectable dark-adaptation in PR, and the chromophore contains nearly entirely all-trans retinal. Because the pK(a) of Asp-97 is relatively high (7.1), the proton-transporting photocycle is produced only at alkaline pH. It contains at least seven transient states with decay times in the range from 10 micros to 200 ms, but the analysis reveals only three distinct spectral forms. The first is a red-shifted K-like state. Proton release does not occur during the very slow (several milliseconds) rise of the second, M-like, intermediate, consistent with lack of the residues facilitating extracellular proton release in BR. Proton uptake from the bulk, presumably on the cytoplasmic side, takes place prior to release (tau approximately 2 ms), and coincident with reprotonation of the retinal Schiff base. The intermediate produced by this process contains 13-cis retinal as does the N state of BR, but its absorption maximum is red-shifted relative to PR (like the O state of BR). The decay of this N-like state is coupled to reisomerization of the retinal to all-trans, and produces a state that is O-like in its C-C stretch bands, but has an absorption maximum apparently close to that of unphotolyzed PR.
High throughput assembly of spatially controlled 3D cell clusters on a micro/nanoplatform (2010)

Guided assembly of microscale tissue subunits (i.e. 3D cell clusters/aggregates) has found applications in cell therapy/tissue engineering, cell and developmental biology, and drug discovery. As cluster size and geometry are known to influence cellular responses, the ability to spatially control cluster formation in a high throughput manner could be advantageous for many biomedical applications. In this work, a micro- and nanofabricated platform was developed for this purpose, consisting of a soft-lithographically fabricated array of through-thickness microwells structurally bonded to a sheet of electrospun fibers. The microwells and fibers were manufactured from several polymers of biomedical interest. Human hepatocytes were used as model cells to demonstrate the ability of the platform to allow controlled cluster formation. In addition, the ability of the device to support studies on semi-controlled heterotypic interactions was demonstrated by co-culturing hepatocytes and fibroblasts. Preliminary experiments with other cells of interest (pancreatic cells, embryonic stem cells, and cardiomyocytes) were also conducted. Our platform possesses several advantages over previously developed microwell arrays: a more in vivo-like topographical stimulation of cells; better nutrient/waste exchange through the underlying nanofiber mat; and easy integration into standard two-chamber cell culture well systems.
Enhanced antitumor activity by combining an adenovirus harboring ING4 with cisplatin for hepatocarcinoma cells (2010)

The inhibitor of growth (ING) family proteins have been defined as candidate tumor suppressors. ING4 as a novel member of the ING family has potential tumor-suppressive effects. In this study, we explored the combined effect of adenovirus-mediated ING4 (Ad-ING4) gene transfer plus chemotherapy drug cisplatin (CDDP) on SMMC-7721 human hepatocarcinoma cells in vitro and in vivo, and its underlying mechanism. We demonstrated that Ad-ING4 plus CDDP induced synergistic growth inhibition, enhanced apoptosis, and had an additive effect on upregulation of Fas, Bax, Bak, cleaved Bid, cleaved caspase-8, caspase-9, caspase-3 and cleaved PARP, and on downregulation of Bcl-2 and Bcl-X(L) in SMMC-7721 hepatocarcinoma cells. Moreover, Ad-ING4 plus CDDP synergistically suppressed in vivo SMMC-7721 hepatocarcinoma subcutaneous (s.c.) xenografted tumor growth and reduced tumor vessel CD34 expression and microvessel density (MVD) in athymic nude mice. Most importantly, Ad-ING4 plus CDDP did not have overlapping toxicities in HL-7702 normal human liver cells and normal liver tissues of mice. The in vitro and in vivo enhanced antitumor effect elicited by Ad-ING4 plus CDDP was closely associated with the cooperative regulation of extrinsic and intrinsic apoptotic pathways and synergistic inhibition of tumor angiogenesis. Thus, our results indicate that Ad-ING4 plus CDDP is a potential combined treatment strategy for hepatocarcinoma.
QuipuNet: Convolutional Neural Network for Single-Molecule Nanopore Sensing (2018)

Nanopore sensing is a versatile technique for the analysis of molecules on the single-molecule level. However, extracting information from data with established algorithms usually requires time-consuming checks by an experienced researcher due to inherent variability of solid-state nanopores. Here, we develop a convolutional neural network (CNN) for the fully automated extraction of information from the time-series signals obtained by nanopore sensors. In our demonstration, we use a previously published data set on multiplexed single-molecule protein sensing. The neural network learns to classify translocation events with greater accuracy than previously possible, while also increasing the number of analyzable events by a factor of 5. Our results demonstrate that deep learning can achieve significant improvements in single molecule nanopore detection with potential applications in rapid diagnostics.
Catalysis of Thiol/Disulfide Exchange (2005)

Glutaredoxin (Grx) and protein-disulfide isomerase (PDI) are members of the thioredoxin superfamily of thiol/disulfide exchange catalysts. Thermodynamically, rat PDI is a 600-fold better oxidizing agent than Grx1 from Escherichia coli. Despite that, Grx1 is a surprisingly good protein oxidase. It catalyzes protein disulfide formation in a redox buffer with an initial velocity that is 30-fold faster than PDI. Catalysis of protein and peptide oxidation by the individual catalytic domains of PDI and by a Grx1-PDI chimera show that differences in active site chemistry are fundamental to their oxidase activity. Mutations in the active site cysteines reveal that Grx1 needs only one cysteine to catalyze rapid substrate oxidation, whereas PDI requires both cysteines. Grx1 is a good oxidase because of the high reactivity of a Grx1-glutathione mixed disulfide, and PDI is a good oxidase because of the high reactivity of the disulfide between the two active site cysteines. As a protein disulfide reductase, Grx1 is also superior to PDI. It catalyzes the reduction of nonnative disulfides in scrambled ribonuclease and protein-glutathione mixed disulfides 30-180 times faster than PDI. A multidomain structure is necessary for PDI to catalyze effective protein reduction; however, placing Grx1 into the PDI multidomain structure does not enhance its already high reductase activity. Grx1 and PDI have both found mechanisms to enhance active site reactivity toward proteins, particularly in the kinetically difficult direction: Grx1 by providing a reactive glutathione mixed disulfide to supplement its oxidase activity and PDI by utilizing its multidomain structure to supplement its reductase activity.
A critical point for random graphs with a given degree sequence (1995)

Abstract Given a sequence of nonnegative real numbers λ 0 , λ 1 … which sum to 1, we consider random graphs having approximately λ i n vertices of degree i. Essentially, we show that if Σ i(i ‐ 2)λ i &gt; 0, then such graphs almost surely have a giant component, while if Σ i ( i ‐ 2)λ. &lt; 0, then almost surely all components in such graphs are small. We can apply these results to G n,p ,G n.M , and other well‐known models of random graphs. There are also applications related to the chromatic number of sparse random graphs.