gebhart/patrepeval huggingface dataset:
Exploding vs. imploding headache in migraine prophylaxis with Botulinum Toxin A (2006)

Migraine headache is routinely managed using medications that abort attacks as they occur. An alternative approach to migraine management is based on prophylactic medications that reduce attack frequency. One approach has been based on local intramuscular injections of Botulinum Toxin Type A (BTX-A). Here, we explored for neurological markers that might distinguish migraine patients who benefit from BTX-A treatment (100 units divided into 21 injections sites across pericranial and neck muscles). Responders and non-responders to BTX-A treatment were compared prospectively (n=27) and retrospectively (n=36) for a host of neurological symptoms associated with their migraine. Data pooled from all 63 patients are summarized below. The number of migraine days per month dropped from 16.0+/-1.7 before BTX-A to 0.8+/-0.3 after BTX-A (down 95.3+/-1.0%) in 39 responders, and remained unchanged (11.3+/-1.9 vs. 11.7+/-1.8) in 24 non-responders. The prevalence of aura, photophobia, phonophobia, osmophobia, nausea, and throbbing was similar between responders and non-responders. However, the two groups offered different accounts of their pain. Among non-responders, 92% described a buildup of pressure inside their head (exploding headache). Among responders, 74% perceived their head to be crushed, clamped or stubbed by external forces (imploding headache), and 13% attested to an eye-popping pain (ocular headache). The finding that exploding headache was impervious to extracranial BTX-A injections is consistent with the prevailing view that migraine pain is mediated by intracranial innervation. The amenability of imploding and ocular headaches to BTX-A treatment suggests that these types of migraine pain involve extracranial innervation as well.
Expression of a foreign epitope on the surface of the adenovirus hexon (1994)

To present short protein sequences to the host immune system a foreign epitope has been expressed on the surface of the adenovirus virion as part of the hexon. As the trimeric hexon constitutes 240 out of the 252 capsomers of the virus, the foreign epitope is repeated 720 times on the virion surface. An eight amino acid sequence from the major antigenic site in the VP1 capsid protein of poliovirus type 3 was engineered into two regions of the adenovirus type 2 hexon. The two loop regions chosen to accommodate the foreign sequences are exposed on the surface of the virion, show sequence variation between serotypes and are the sites of interaction with neutralizing antibodies. Virus with substitutions in loop I had wild-type growth characteristics, whereas virus with substitutions in loop II grew poorly. Adenoviruses with poliovirus sequences in loop I were recognized and efficiently neutralized by antisera specific for the poliovirus sequence; an antiserum raised against the adenovirus with the poliovirus insert specifically recognized the VP1 capsid protein of poliovirus type 3. It is therefore feasible to alter the surface properties of the adenovirus virion and in doing so to manipulate the immune response to this virus.
Purification and binding properties of human platelet factor four. (1976)

Methods are described for the purification of a heparin-neutralizing protein from human platelets. The protein, obtained by conventional or affinity chromatographic techniques, is homogeneous by disc and sodium dodecyl sulfate gel electrophoresis, immunoelectrophoresis, and gel electrofocusing and can be obtained in a final yield of 75%. The protein has a subunit molecular weight of 9600, an isoelectric point at pH 7.6, and 18% basic and 22% acidic amino acid residues. The purified heparin-neutralizing protein forms dissociable complexes with heparin as measured by electrophoretic and Millipore filtration techniques employing [3H]heparin. The ability of a series of sulfated glycosaminoglycans to displace [3H]heparin from the binding protein was compared. The mole ratios required were: heparin less than heparan sulfate less than dermatan sulfate less than chondroitin 6-sulfate less than chondroitin 4-sulfate. Although the degree of sulfation of the aminoglycans correlated with the ability to displace [3H]heparin, the conformation fo the carboxyl group of the uronic acid and the location of the sulfate groups on the amino sugar also influenced the affinity for the protein. Evidence is also presented that binding to aminoglycans occurs via ionic interactions between lysine residues on the protein and negatively charged groups on the aminoglycan. Chemical modification of lysines by guanidination decreased heparin-neutralizing and binding activity, while modification of arginine residues had no effect. Heparin could prevent lysine modification when specifically bound to the heparin-neutralizing protein, but did not prevent lysine modification of other proteins.
Phosphorylation of Tyrosine 992, 1068, and 1086 Is Required for Conformational Change of the Human Epidermal Growth Factor Receptor C-Terminal Tail (1999)

We reported previously that a conformation-specific antibody, Ab P2, to a 16-amino acid peptide (Glu-Gly-Tyr-Lys-Lys-Lys-Tyr-Gln-Gln-Val-Asp-Glu-Glu-Phe-Leu-Arg) of the cytoplasmic domain of the beta-type platelet-derived growth factor receptor also recognizes the epidermal growth factor (EGF) receptor. Although the antibody is not directed to phosphotyrosine, it recognizes in immunoprecipitation the activated and hence phosphorylated form of both receptors. In P2 peptide, there are two tripeptide sequences, Asp-Glu-Glu and Tyr-Gln-Gln, that are also present in the EGF receptor. Our present studies using either EGF receptor C-terminal deletion mutants or point mutations (Tyr-->Phe) and our previous studies on antibody inhibition by P2-derived peptides suggest that Gln-Gln in combination with Asp-Glu-Glu forms a high-affinity complex with Ab P2 and that such complex formation is dependent on tyrosine phosphorylation. Of the five phosphate acceptor sites in the EGF receptor, clustered in the extreme C-terminal tail, phosphorylation of three tyrosine residues (992, 1068, and 1086) located between Asp-Glu-Glu and Gln-Gln is necessary for Ab P2 binding. In contrast, the acceptor sites Tyr 1173 and 1148 play no role in the conformation change. Asp-Glu-Glu and Gln-Gln are located 169 amino acids apart, and it is highly likely that the interactions among three negatively charged phosphotyrosine residues in the receptor C terminus may result in the bending of the peptide chain in such a way that these two peptides come close to each other to form an antibody-binding site. Such a possibility is also supported by our finding that receptor dephosphorylation results in complete loss of Ab P2-binding activity. In conclusion, we have identified a domain within the cytoplasmic part of the EGF receptor whose conformation is altered by receptor phosphorylation; furthermore, we have identified the tyrosine residues that positively regulate this conformation.
The annual report to the nation on the status of cancer, 1973-1997, with a special section on colorectal cancer (2000)

The continuing declines in overall cancer incidence and death rates are encouraging. However, a few of the top ten incidence or mortality cancer sites continued to increase or remained level. For many cancer sites, whites had lower incidence and mortality rates than blacks but higher rates than Hispanics, Asian and Pacific Islanders, and American Indians/Alaska Natives. The variations in colorectal cancer incidence and death rates by race/ethnicity, gender, age, and geographic area may be related to differences in risk factors, demographic characteristics, screening, and medical practice. New efforts currently are underway to increase awareness of screening benefits and treatment for colorectal cancer.
Viral Nanoparticles Donning a Paramagnetic Coat:  Conjugation of MRI Contrast Agents to the MS2 Capsid (2006)

A nanoparticle magnetic resonance imaging (MRI) contrast agent was developed by conjugation of more than 500 gadolinium chelate groups onto a viral capsid. The high density of paramagnetic centers and slow tumbling rate of modified MS2 capsids provided enhanced T1 relaxivities up to 7200 mM-1s-1 per particle. A bimodal imaging agent was generated by sequential conjugation of fluorescein and Gd3+ chelate. These results illustrate the potential for engineering natural protein assemblies to address bionanotechnology applications.
Molecular cloning of a house dust mite allergen with common antibody binding specificities with multiple components in mite extracts (1993)

Plaque radio-immuno assay has been used to isolate an IgE-binding clone from a lambda gt11 library of Dermatophagoides pteronyssinus cDNA. The clone HD6 contained DNA encoding a 215 residue protein which contained a predicted 17 amino acid residue leader sequence, no cysteines and a single N-glycosylation site. The 198 residue mature protein would have a predicted MW of 22,177 D. No homologues were found in searches of the data banks. Sera from 14/38 allergic children reacted strongly with the polypeptide produced by the clone (37%). Skin tests showed reactivity in 16/30 (53%) allergic patients and 0/10 of controls. Affinity purification of rabbit antibodies with the clone showed that antibodies to the polypeptide had specificities to multiple products in mite extracts corresponding to components of Mr 29, 27 and 24 K by Western blotting. Absorption studies of IgE in allergic serum indicated further entities at 13 and 11.5 kD. It is proposed to name this allergen Der p VII.
The Human Endogenous Retrovirus Envelope Glycoprotein, Syncytin-1, Regulates Neuroinflammation and Its Receptor Expression in Multiple Sclerosis: A Role for Endoplasmic Reticulum Chaperones in Astrocytes (2007)

Retroviral envelopes are pathogenic glycoproteins which cause neuroinflammation, neurodegeneration, and endoplasmic reticulum stress responses. The human endogenous retrovirus (HERV-W) envelope protein, Syncytin-1, is highly expressed in CNS glia of individuals with multiple sclerosis (MS). In this study, we investigated the mechanisms by which Syncytin-1 mediated neuroimmune activation and oligodendrocytes damage. In brain tissue from individuals with MS, ASCT1, a receptor for Syncytin-1 and a neutral amino acid transporter, was selectively suppressed in astrocytes (p < 0.05). Syncytin-1 induced the expression of the endoplasmic reticulum stress sensor, old astrocyte specifically induced substance (OASIS), in cultured astrocytes, similar to findings in MS brains. Overexpression of OASIS in astrocytes increased inducible NO synthase expression but concurrently down-regulated ASCT1 (p < 0.01). Treatment of astrocytes with a NO donor enhanced expression of early growth response 1, with an ensuing reduction in ASCT1 expression (p < 0.05). Small-interfering RNA molecules targeting Syncytin-1 selectively down-regulated its expression, preventing the suppression of ASCT1 and the release of oligodendrocyte cytotoxins by astrocytes. A Syncytin-1-transgenic mouse expressing Syncytin-1 under the glial fibrillary acidic protein promoter demonstrated neuroinflammation, ASCT1 suppression, and diminished levels of myelin proteins in the corpus callosum, consistent with observations in CNS tissues from MS patients together with neurobehavioral abnormalities compared with wild-type littermates (p < 0.05). Thus, Syncytin-1 initiated an OASIS-mediated suppression of ASCT1 in astrocytes through the induction of inducible NO synthase with ensuing oligodendrocyte injury. These studies provide new insights into the role of HERV-mediated neuroinflammation and its contribution to an autoimmune disease.
Effect of base sequence on the DNA cross-linking properties of pyrrolobenzodiazepine (PBD) dimers (2011)

Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimers are synthetic sequence-selective DNA minor-groove cross-linking agents that possess two electrophilic imine moieties (or their equivalent) capable of forming covalent aminal linkages with guanine C2-NH(2) functionalities. The PBD dimer SJG-136, which has a C8-O-(CH(2))(3)-O-C8'' central linker joining the two PBD moieties, is currently undergoing phase II clinical trials and current research is focused on developing analogues of SJG-136 with different linker lengths and substitution patterns. Using a reversed-phase ion pair HPLC/MS method to evaluate interaction with oligonucleotides of varying length and sequence, we recently reported (JACS, 2009, 131, 13 756) that SJG-136 can form three different types of adducts: inter- and intrastrand cross-linked adducts, and mono-alkylated adducts. These studies have now been extended to include PBD dimers with a longer central linker (C8-O-(CH(2))(5)-O-C8'), demonstrating that the type and distribution of adducts appear to depend on (i) the length of the C8/C8'-linker connecting the two PBD units, (ii) the positioning of the two reactive guanine bases on the same or opposite strands, and (iii) their separation (i.e. the number of base pairs, usually ATs, between them). Based on these data, a set of rules are emerging that can be used to predict the DNA-interaction behaviour of a PBD dimer of particular C8-C8' linker length towards a given DNA sequence. These observations suggest that it may be possible to design PBD dimers to target specific DNA sequences.
Functional organization of microtubule-associated protein tau. Identification of regions which affect microtubule growth, nucleation, and bundle formation in vitro. (1993)

Tau protein is a microtubule-associated protein that is almost exclusively expressed in the brain and is enriched in the axon. Determination of tau's sequence has revealed three to four tandem repeats that have been shown to constitute the microtubule binding site. In order to study the functional organization of tau, we prepared a series of truncated tau fragments using an Escherichia coli expression system. We assayed each fragment's activity in promoting growth of microtubules and in nucleating free microtubules. We found that tau's ability to nucleate microtubules requires the presence of additional sequence amino-terminal to that required for growth. We demonstrate that tau's carboxyl and amino termini differentially affect microtubule growth and nucleation. Finally, we show that in vitro microtubule bundle formation occurs when tubulin is assembled in the presence of an amino- and carboxyl-terminally truncated tau protein, whereas almost no bundling is observed in the presence of full-length tau or tau fragments that contain the amino terminus in addition to the repeat domain. We conclude that although the presence of the repeat domain promotes the growth of microtubules, the structural requirements for nucleation activity are more stringent. The differentiation between the growth promoting and nucleation activities on the structural level makes it possible for the two activities to be differentially regulated in vivo.
Expression and characterization of human apolipoprotein A-I in Chinese hamster ovary cells. (1987)

We produced human apolipoprotein A-I (apoA-I) in Chinese hamster ovary (CHO) cells. The CHO cells were transfected with an expression plasmid which placed the human apoA-I gene under the direction of the human metallothionein II gene promoter. Isolation of a clonal cell line resulted in high level expression of apoA-I. Greater than 30% of total protein secreted by these CHO cells was apoA-I, which enabled us to purify apoA-I with a single step purification scheme. As a result, large quantities of apoA-I can be produced and isolated without having to rely on plasma sources. Structural characterization of the recombinant apoA-I showed it to be identical to authentic apoA-I from human serum high density lipoprotein. Furthermore, we demonstrated approximately equal to 90% of the apoA-I secreted by CHO cells is processed, mature protein. A portion of the secreted recombinant apoA-I was associated with lipid and floated at a density approximately equal to 1.10 g/ml. Additional analysis identified the presence of five isoforms of apoA-I in the CHO cell conditioned medium. Processing and post-translational modification of the recombinant apoA-I occurred in the CHO cell cultures in the absence of serum components. We conclude that the human apoA-I produced by CHO cells is identical to circulating, mature apoA-I in humans and that recombinant mammalian expression offers an opportunity to investigate apoA-I processing.
Transforming growth factor β1 modulates angiotensin induced calcium influx in vascular smooth muscle (1995)

The modulatory effects of transforming growth factor beta 1 (TGF beta 1) on the angiotensin II (Ang II)-induced increase in cytosolic free calcium concentration ([Ca2+]i) were investigated in vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). [Ca2+]i in VSMC was measured using the fluorescent dye fura-2. When TGF beta 1 was applied 30s prior to Ang II, the Ang II-induced [Ca2+]i increase was significantly enhanced in VSMC from SHR (P < 0.05 compared to control), whereas after the preincubation with TGF beta 1 for 30 min, the Ang II-induced [Ca2+]i increase was significantly reduced in VSMC from both strains. Using the manganese-quenching technique, it was confirmed that short-term exposure to TGF beta 1 enhanced the Ang II-induced trans-plasma-membrane calcium influx in SHR. The inhibition of protein kinase C by calphostin C abolished the stimulatory effect of TGF beta 1 on the Ang II-induced [Ca2+]i increase. It is concluded that TGF beta 1 modulates the Ang II-induced calcium handling in VSMC.
Convex optimization problems (2004)

Convex optimization problems arise frequently in many different fields. This book provides a comprehensive introduction to the subject, and shows in detail how such problems can be solved numerically with great efficiency. The book begins with the basic elements of convex sets and functions, and then describes various classes of convex optimization problems. Duality and approximation techniques are then covered, as are statistical estimation techniques. Various geometrical problems are then presented, and there is detailed discussion of unconstrained and constrained minimization problems, and interior-point methods. The focus of the book is on recognizing convex optimization problems and then finding the most appropriate technique for solving them. It contains many worked examples and homework exercises and will appeal to students, researchers and practitioners in fields such as engineering, computer science, mathematics, statistics, finance and economics.
The Biology of Skin Grafts (1993)

We suggest that skin grafts may work not only as tissue replacement but as pharmacologic agents that provide a stimulus for healing. We believe that, someday, it may be possible to augment the stimulatory properties of donor skin to speed healing of the recipient wound.
Pseudomonas aeruginosaIncreases Formation of Multidrug-Tolerant Persister Cells in Response to Quorum-Sensing Signaling Molecules (2010)

Bacterial persister cells constitute a small portion of a culture which is tolerant to killing by lethal doses of bactericidal antibiotics. These phenotypic variants are formed in numerous bacterial species, including those with clinical relevance like the opportunistic pathogen Pseudomonas aeruginosa. Although persisters are believed to contribute to difficulties in the treatment of many infectious diseases, the underlying mechanisms affecting persister formation are not well understood. Here we show that even though P. aeruginosa cultures have a significantly smaller fraction of multidrug-tolerant persister cells than cultures of Escherichia coli or Staphylococcus aureus, they can increase persister numbers in response to quorum-sensing-related signaling molecules. The phenazine pyocyanin (and the closely related molecule paraquat) and the acyl-homoserine lactone 3-OC12-HSL significantly increased the persister numbers in logarithmic P. aeruginosa PAO1 or PA14 cultures but not in E. coli or S. aureus cultures.
Immobilization of Amine-modified Oligonucleotides on Bifunctional Polymer Brushes Synthesized by Surface-initiated Polymerization (2012)

Polymer brushes on solid substrates formed by surfaceinitiated polymerization can tailor the substrates' surface properties, allowing for example, the functionalization of glass surfaces for the construction of DNA microarrays used in the diagnosis of diseases and the study of genomics. Glass surfaces are often functionalized by the formation of self-assembled monolayers (SAMs) of silanes containing functional groups, such as amine, alcohol, or carboxylic acid, at their terminal ends. However, silanization is difficult to control for the formation of high-quality SAMs, resulting in poorly reproducible surface functionalization. Therefore polymer brushes, which can be grown as highdensity brushes in a controllable manner, have been studied for the surface functionalization of glass substrates. For example, polymer brushes based on polyethylene glycol methacrylate (PEGMA) have been used for surface coatings because they can limit the nonspecific adsorption of biomolecules onto the surfaces. Here, we report the synthesis of a bifunctional polymer brush by surface-initiated polymerization and its application in the immobilization of oligonucleotides. The polymer brush possessed two functional moieties, bio-inert polyethylene glycol (PEG) and bio-reactive aldehyde groups, which respectively provided effective resistance to biofouling and high binding ability for the specific immobilization of amine-modified oligonucleotides. The surface-initiated polymerization of the bifunctional polymer brush is outlined in Scheme 1. 2-Bromo-2-methylN-(3-triethoxysilylpropyl)-propionamide (BTPAm) was synthesized by a synthetic procedure reported previously (Supporting Information, Figure S1) and a SAM of BTPAm was formed by immersing a freshly cleaned and O2 plasmatreated glass substrate in a toluene solution of BTPAm (0.3 w/v %) with subsequent curing at different temperatures. The resulting SAM was confirmed by the appearance of peaks characteristic of NH-CO at 1650 cm, N-H bending at 1530 cm, and Si-O stretching at 1112-1026 cm in the ATR-FTIR spectrum of the BTPAm initiator film (Figure 1, spectrum b) compared with the spectrum of bare surface (Figure 1, spectrum a). The surface-tethered BTPAm presented a terminal bromoisobutyrate moiety, which allowed surface-initiated atom transfer radical polymerization (SIATRP) on the glass substrates. SI-ATRP can provide control over chain length and surface density of polymers under ambient conditions. The surface-initiated polymerization was then conducted in an oxygen-free environment using CuBr/Tris[2-(dimethylamino)ethyl]amine (Me6TREN) cata-
A mixed-cation lead mixed-halide perovskite absorber for tandem solar cells (2016)

Metal halide perovskite photovoltaic cells could potentially boost the efficiency of commercial silicon photovoltaic modules from ∼20 toward 30% when used in tandem architectures. An optimum perovskite cell optical band gap of ~1.75 electron volts (eV) can be achieved by varying halide composition, but to date, such materials have had poor photostability and thermal stability. Here we present a highly crystalline and compositionally photostable material, [HC(NH2)2](0.83)Cs(0.17)Pb(I(0.6)Br(0.4))3, with an optical band gap of ~1.74 eV, and we fabricated perovskite cells that reached open-circuit voltages of 1.2 volts and power conversion efficiency of over 17% on small areas and 14.7% on 0.715 cm(2) cells. By combining these perovskite cells with a 19%-efficient silicon cell, we demonstrated the feasibility of achieving >25%-efficient four-terminal tandem cells.