gebhart/patrepeval huggingface dataset:
Characterization of a high‐affinity human antibody with a disulfide bridge in the third complementarity‐determining region of the heavy chain (2012)

Disulfide bridges are common in the antigen-binding site from sharks (new antigen receptor) and camels (single variable heavy-chain domain, VHH), in which they confer both structural diversity and domain stability. In human antibodies, cysteine residues in the third complementarity-determining region of the heavy chain (CDR-H3) are rare but naturally encoded in the IGHD germline genes. Here, by panning a phage display library designed based on human germline genes and synthetic CDR-H3 regions against a human cytokine, we identified an antibody (M3) containing two cysteine residues in the CDR-H3. It binds the cytokine with high affinity (0.4 nM), recognizes a unique epitope on the antigen, and has a distinct neutralization profile as compared with all other antibodies selected from the library. The two cysteine residues form a disulfide bridge as determined by mass spectrometric peptide mapping. Replacing the cysteines with alanines did not change the solubility and stability of the monoclonal antibody, but binding to the antigen was significantly impaired. Three-dimensional modeling and dynamic simulations were employed to explore how the disulfide bridge influences the conformation of CDR-H3 and binding to the antigen. On the basis of these results, we envision that designing human combinatorial antibody libraries to contain intra-CDR or inter-CDR disulfide bridges could lead to identification of human antibodies with unique binding profiles.
Imaging of small vessels using photoacoustics: An in vivo study (2004)

We show PA images of externalized blood vessels and demonstrate in vivo PA imaging of vasculature through layers of skin varying in thickness.
Suppression of TNF-α-Induced Apoptosis by NF-κB (1996)

Tumor necrosis factor alpha (TNF-alpha) signaling gives rise to a number of events, including activation of transcription factor NF-kappaB and programmed cell death (apoptosis). Previous studies of TNF-alpha signaling have suggested that these two events occur independently. The sensitivity and kinetics of TNF-alpha-induced apoptosis are shown to be enhanced in a number of cell types expressing a dominant-negative IkappaBalpha (IkappaBalphaM). These findings suggest that a negative feedback mechanism results from TNF-alpha signaling in which NF-kappaB activation suppresses the signals for cell death.
Protein Tyrosine Phosphatases (1993)

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
Receptor-mediated Immunoglobulin G Transport Across Mucosal Barriers in Adult Life (2002)

Mucosal secretions of the human gastrointestinal, respiratory, and genital tracts contain the immunoglobulins (Ig)G and secretory IgA (sIgA) that function together in host defense. Exactly how IgG crosses epithelial barriers to function in mucosal immunity remains unknown. Here, we test the idea that the MHC class I–related Fc-receptor, FcRn, transports IgG across the mucosal surface of the human and mouse lung from lumen to serosa. We find that bronchial epithelial cells of the human, nonhuman primate, and mouse, express FcRn in adult-life, and demonstrate FcRn-dependent absorption of a bioactive Fc-fusion protein across the respiratory epithelium of the mouse in vivo. Thus, IgG, like dimeric IgA, can cross epithelial barriers by receptor-mediated transcytosis in adult animals. These data show that mucosal surfaces that express FcRn reabsorb IgG and explain a mechanism by which IgG may act in immune surveillance to retrieve lumenal antigens for processing in the lamina propria or systemically.
Determination of the secondary structures of proteins by circular dichroism and optical rotatory dispersion (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDetermination of the secondary structures of proteins by circular dichroism and optical rotatory dispersionYee-Hsiung Chen, Jen Tsi Yang, and Hugo M. MartinezCite this: Biochemistry 1972, 11, 22, 4120–4131Publication Date (Print):October 1, 1972Publication History Published online1 May 2002Published inissue 1 October 1972https://pubs.acs.org/doi/10.1021/bi00772a015https://doi.org/10.1021/bi00772a015research-articleACS PublicationsRequest reuse permissionsArticle Views4201Altmetric-Citations1652LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
The complete nucleotide sequence for rabbit muscle aldolase A messenger RNA. (1984)

The complete nucleotide sequence of rabbit muscle aldolase mRNA has been determined from recombinant cDNA clones and from a primer-extended cDNA synthesis on the mRNA template. The sequence is composed of 1375 nucleotides, exclusive of the poly(A) tails. The 5'-untranslated region contains 62 bases including a potential ribosome-binding site. The 3'-untranslated region is 221 bases long. The remaining 1092 nucleotides are in an open reading frame coding for 364 amino acids. There is a single methionine residue preceding the NH2-terminal proline. The deduced amino acid sequence corrects a number of discrepancies between published structures as well as assignments previously missed. The sequences of the cloned cDNAs suggests there may be microheterogeneity in the messenger RNA population.
Sodium channelSCN1Aand epilepsy: Mutations and mechanisms (2010)

Mutations in a number of genes encoding voltage-gated sodium channels cause a variety of epilepsy syndromes in humans, including genetic (generalized) epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome (DS, severe myoclonic epilepsy of infancy). Most of these mutations are in the SCN1A gene, and all are dominantly inherited. Most of the mutations that cause DS result in loss of function, whereas all of the known mutations that cause GEFS+ are missense, presumably altering channel activity. Family members with the same GEFS+ mutation often display a wide range of seizure types and severities, and at least part of this variability likely results from variation in other genes. Many different biophysical effects of SCN1A-GEFS+ mutations have been observed in heterologous expression systems, consistent with both gain and loss of channel activity. However, results from mouse models suggest that the primary effect of both GEFS+ and DS mutations is to decrease the activity of GABAergic inhibitory neurons. Decreased activity of the inhibitory circuitry is thus likely to be a major factor contributing to seizure generation in patients with GEFS+ and DS, and may be a general consequence of SCN1A mutations.
PD-1 Blockade Boosts Radiofrequency Ablation–Elicited Adaptive Immune Responses against Tumor (2016)

The PD-L1-PD-1 axis plays a critical role in dampening RFA-induced antitumor immune responses, and this study provides a strong rationale for combining RFA and the PD-L1/PD-1 blockade in the clinical setting.
A highly conserved vascular permeability factor secreted by a variety of human and rodent tumor cell lines. (1986)

We have previously reported that rodent tumor cell lines secrete a potent vascular permeability factor with a molecular weight of 34,000-42,000 (Senger et al. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science (Wash. DC), 219: 983-985, 1983). This tumor-secreted vascular permeability factor (VPF) causes a rapid and completely reversible increase in microvascular permeability in the species (guinea pig or rat) from which the tumors were derived without causing mast cell degranulation or endothelial cell damage or exciting an inflammatory cell infiltrate. This VPF may be responsible, at least in part, for the increased permeability which is commonly displayed by solid and ascites tumor vessels. We have now examined 7 human tumor cell lines and have determined that 5 of them also secrete this same VPF. Antibody raised to guinea pig line 10 VPF neutralized more than 90% of the vascular permeability-increasing activity secreted by these 5 human tumor lines. Furthermore, VPFs from both guinea pig and human tumor sources bound to and were eluted similarly from immobilized heparin and comigrated identically on sodium dodecyl sulfate-polyacrylamide gels. Finally, 2 tumorigenic (in nude mice) human cell lines were found to secrete at least 14-fold more VPF than their directly matched, nontumorigenic counterparts, suggesting that elevated expression of this permeability factor may correlate with neoplastic transformation. These data suggest that a broad spectrum of tumor cells from several species, including humans, secretes a highly conserved molecule that enhances local vascular permeability and that this function may be important for tumor growth.
Interstitial fibrosis and growth factors. (2000)

Interstitial pulmonary fibrosis (IPF) is scarring of the lung caused by a variety of inhaled agents including mineral particles, organic dusts, and oxidant gases. The disease afflicts millions of individuals worldwide, and there are no effective therapeutic approaches. A major reason for this lack of useful treatments is that few of the molecular mechanisms of disease have been defined sufficiently to design appropriate targets for therapy. Our laboratory has focused on the molecular mechanisms through which three selected peptide growth factors could play a role in the development of IPF. Hundreds of growth factors and cytokines could be involved in the complex disease process. We are studying platelet-derived growth factor because it is the most potent mesenchymal cell mitogen yet described, transforming growth factor beta because it is a powerful inducer of extracellular matrix (scar tissue) components by mesenchymal cells, and tumor necrosis factor alpha because it is a pleiotropic cytokine that we and others have shown is essential for the development of IPF in animal models. This review describes some of the evidence from studies in humans, in animal models, and in vitro, that supports the growth factor hypothesis. The use of modern molecular and transgenic technologies could elucidate those targets that will allow effective therapeutic approaches.
The Cervical and Lumbar Vertebrae — An Anthropometric Model (1984)

An anthropometric model for human vertebrae in the mid-sagital plane is described, using parameters which were measured from lateral X-rays of the cervical and lumbar regions in normal, healthy men. The data was processed statistically and results are presented. The findings reported are new in the literature. They can be used in many ways, including modelling of the spine, and orthopaedics. Clinically significant parameters are the heights of the vertebral bodies and the intervertebral spacings. The relations between these parameters are presented and discussed.
Effect of polysilicon depletion on MOSFET I–V characteristics (1993)

MOSFET current (IDS) degradation as a function of polysilicon gate concentration (Np) and gate oxide thickness (tox) is demonstrated using measured and simulated results. It is found that as the oxide thickness and/or polysilicon gate concentration decrease, the I–V degradation becomes more pronounced. Experimental data show that as Np decreases from 1.6 × 1019 cm−3 to 5 × 1018 cm−3 for a device with tox ≃ 7 nm, the drain current IDS decreases approximately 14% at | VGS − VTH | = 2 V and | VDS | = 2.5 V. The measured data are in general agreement with the theoretical results based on a modified Pao–Sah model that takes into account the polysilicon depletion effect.
Haptic feedback design for a virtual button along force-displacement curves (2013)

In this paper, we present a haptic feedback method for a virtual button based on the force-displacement curves of a physical button. The original feature of the proposed method is that it provides haptic feedback, not only for the "click" sensation but also for the moving sensation before and after transition points in a force-displacement curve. The haptic feedback is by vibrotactile stimulations only and does not require a force feedback mechanism. We conducted user experiments to show that the resultant haptic feedback is realistic and distinctive. Participants were able to distinguish among six different virtual buttons, with 94.1% accuracy even in a noisy environment. In addition, participants were able to associate four virtual buttons with their physical counterparts, with a correct answer rate of 79.2%.
Vascular Remodeling in Response to Altered Blood Flow Is Mediated by Fibroblast Growth Factor-2 (1999)

Vascular structures adapt to changes in blood flow by adjusting their diameter accordingly. The factors mediating this process are only beginning to be identified. We have recently established a mouse model of arterial remodeling in which flow in the common carotid artery is interrupted by ligation of the vessel near the carotid bifurcation, resulting in a dramatic reduction in vessel diameter as a consequence of inward remodeling and intimal lesion formation. In the present study, we used this model to determine the role of fibroblast growth factor-2 (FGF-2) in the remodeling response by maintaining neutralizing serum levels of a mouse monoclonal antibody against FGF-2 for 4 weeks. Morphometric analysis revealed that intimal lesion formation was not affected by the antibody. However, lumen narrowing was significantly inhibited, resulting in a greater than 3-fold increase in lumen area in anti-FGF-2-treated animals compared with controls. Treatment with anti-FGF-2 antibody significantly inhibited the reduction in vessel diameter (inward remodeling) and shortening of the internal elastic lamina in the ligated vessel. In addition, anti-FGF-2 treatment also caused outward remodeling of the contralateral carotid artery. These findings identify FGF-2 as an important factor in vascular remodeling, and its effects are likely to be mediated by increasing vascular tone. The results are consistent with the recent observation of reduced vascular tone in the FGF-2-deficient mouse.
A Tunable Femtosecond Modelocked Semiconductor Laser for Applications in OTDM-Systems (1998)

In this paper, we describe the properties of an external cavity modelocked semiconductor laser with a tunability of wavelength, pulse width and repetition rate. This modelocked laser generates optical pulses with pulse widths down to 180 fs and with repetition rates up to 14 GHz in a 120 nm wavelength range near 1.55 mu m or 1.3 mu m. The generated pulses are close to the transform limit and are therefore suitable for very high speed communication systems. In addition to the tunability, this pulse source is a compact and mechanically stable device. We report on two applications of this pulse source in optical time division multiplexing experiments. In the first example the modelocked laser is used as an all-optical clock recovery. In the second example the modelocked laser was used to characterize an interferometric switch by pump-probe experiments.
Increased Survival with Enzalutamide in Prostate Cancer after Chemotherapy (2012)

Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy. (Funded by Medivation and Astellas Pharma Global Development; AFFIRM ClinicalTrials.gov number, NCT00974311.).
Systemic delivery of peptides and proteins across absorptive mucosae. (1996)

As therapeutic peptides and proteins become readily available through rapid advances in recombinant technology, and because rapid presystemic elimination renders them ineffective when administered orally, pharmaceutical scientists are faced with the challenge of delivering these macromolecules systemically; therefore, alternative routes of delivery need to be investigated. Transmucosal delivery through absorptive mucosae represents one of these alternatives. This route has the advantage of being noninvasive and of bypassing hepatogastrointestinal clearance. The absorptive mucosae that have been investigated for delivery of peptides and proteins include buccal, nasal, pulmonary, rectal, and vaginal. Nasal delivery has been studied extensively and has been the most successful--nasal sprays for buserelin, desmopressin, oxytocin, and calcitonin are already available commercially. In general, enzyme inhibitors and permeation enhancers need to be coadministered for successful delivery of these biopharmaceuticals. Classes of enhancers used for transmucosal delivery include bile salts, dihydrofusidates, cyclodextrins, surfactants, and chelating agents. Each of these agents exerts its enhancing effects by a different mechanism, and each has been associated with adverse effects. This article discusses the physiology of each of the mucosae used, the fundamentals of transmucosal delivery, and recent progress in systemic delivery of therapeutic peptides and proteins across each of the mucosae; in an effort to highlight principles of transmucosal delivery, it also discusses the transmucosal delivery of enkephalin, calcitonin, and insulin as case studies.
Untraceable electronic mail, return addresses, and digital pseudonyms (1981)

A technique based on public key cryptography is presented that allows an electronic mail system to hide who a participant communicates with as well as the content of the communication--in spite of an unsecured underlying telecommunication system. The technique does not require a universally trusted authority. One correspondent can remain anonymous to a second, while allowing the second to respond via an untraceble return address.
Reducing source-generated noise in shallow seismic data using linear and hyperbolic τ - p transformations (2001)

Abstract High-resolution seismic reflection data recorded at many locations on the earth are plagued by the overwhelming effects of direct, refracted, guided, and surface waves. These different components of source-generated noise may completely mask reflections at traveltimes &amp;lt; ∼50–100 ms. Conventional processing methods that include the time-consuming application of mute functions may lead to the misprocessing of source-generated noise (especially guided waves) as reflected events and/or the unintentional removal of important shallow reflections. We introduce a combined linear and hyperbolic τ-p processing scheme that results in the effective separation of reflections from source-generated noise. After applying linear moveout terms that adjust the direct, refracted, and guided arrivals to appear horizontal to subhorizontal, the reduced traveltime shot gathers are transformed into the linear τ-p domain. It is then straightforward to design a single τ-p filter that eliminates most of the source-generated noise throughout the entire data set. Following inverse linear τ-p transformation and removal of the linear moveout terms, the filtered shot gathers contain reflections and residual elements of the source-generated noise. Because summing along hyperbolas favors reflections, transforming the filtered shot gathers into the hyperbolic τ-p domain leads to significant enhancements in the S/N ratio. A simple rescaling of data values in the hyperbolic τ-p domain, which results in the loss of true amplitude information, increases further the relative strength of the reflected signals. Finally, inverse hyperbolic transformation yields shot gathers dominated by reflections. In tests of the combined τ-p processing scheme on a synthetic shot gather and on a complete shallow seismic reflection data set recorded in northern Switzerland, significant improvements in the quality of reflections in the prestacked data and on a fully processed section are readily apparent. According to the results of these tests, the new scheme works well for reflections originating from flat and dipping horizons.
Design of substrate-site-directed inhibitors of adenylate kinase and hexokinase. Effect of substrate substituents on affinity for the adenine nucleotide sites (1976)

Nineteen derivatives of adenosine 5'-phosphate (AMP) bearing acylaminomethyl, acetoxy, or alkylaminomethyl substituents on the phosphate-ribose bridge (5' and O-5' positions) of AMP together with 2',3'-O-ethylidene, 2',3',-O-isopropylidene, and 2',3'-di-O-acetyl derivatives of AMP have been synthesized. Their substrate and/or competitive inhibitor properties with pig rabbit muscle AMP kinases indicate that all the substituents except 2',3'-O-ethlidene with the pig enzyme permitted binding of AMP at its enzymic site. Determination of enzyme-inhibitor dissociation constants showed that several compounds with substituents on the ribose-phosphate bridge bind as well or better than AMP. The affinity is ascribed in part to interaction between substituents and a lipophilic region of the enzymes adjacent to the ribose-phosphate bridge in the enzyme-AMP complexes. The enzyme-inhibitor dissociation constants reveal a structural dissimilarity between the pig and rabbit enzymes in the vicinity of the lipophilic region. The substrate and inhibitor properties of eight ATP derivatives gave evidence that affinity of ATP for its substrate site on the AMP kinases is compatible with acetyl- or chloroacetylaminomethyl groups at the phosphate-ribose bridge or with 2',3'-O-ethylidene or isopropylidene residues. The yeast hexokinase-ATP complex tolerated an acetylaminomethyl group at C-5' or a benzoylaminomethyl group adjacent to O-5'. The present findings regarding substituent tolerance could be used in the design of adenine nucleotide site-directed irreversible inhibitors.
Identification of a Chromosome 18q Gene that Is Altered in Colorectal Cancers (1990)

Allelic deletions involving chromosome 18q occur in more than 70 percent of colorectal cancers. Such deletions are thought to signal the existence of a tumor suppressor gene in the affected region, but until now a candidate suppressor gene on this chromosomal arm had not been identified. A contiguous stretch of DNA comprising 370 kilobase pairs (kb) has now been cloned from a region of chromosome 18q suspected to reside near this gene. Potential exons in the 370-kb region were defined by human-rodent sequence identities, and the expression of potential exons was assessed by an "exon-connection" strategy based on the polymerase chain reaction. Expressed exons were used as probes for cDNA screening to obtain clones that encoded a portion of a gene termed DCC; this cDNA was encoded by at least eight exons within the 370-kb genomic region. The predicted amino acid sequence of the cDNA specified a protein with sequence similarity to neural cell adhesion molecules and other related cell surface glycoproteins. While the DCC gene was expressed in most normal tissues, including colonic mucosa, its expression was greatly reduced or absent in most colorectal carcinomas tested. Somatic mutations within the DCC gene observed in colorectal cancers included a homozygous deletion of the 5' end of the gene, a point mutation within one of the introns, and ten examples of DNA insertions within a 0.17-kb fragment immediately downstream of one of the exons. The DCC gene may play a role in the pathogenesis of human colorectal neoplasia, perhaps through alteration of the normal cell-cell interactions controlling growth.