gebhart/patrepeval huggingface dataset:
Overview of Peptide and Protein Analysis by Mass Spectrometry (1996)

One goal of this introductory overview is to try and dispel the still widely held, but now mistaken, belief that mass spectrometry is beyond the technical resources of the typical laboratory or facility engaged in the structural characterization or synthesis of peptides and proteins. Over the last five years, mass spectrometers and associated data systems have become available that can be operated by anyone capable of running a modern amino acid analyzer or Edman sequencer, yet are powerful enough to handle the most demanding analyses that the peptide or protein investigator might require. The remaining goals of this article are to familiarize peptide and protein chemists with the types of mass spectrometers that are appropriate for the majority of their analytical needs, to describe the kinds of experiments that can be performed with these instruments on a routine basis, and to discuss the kinds of information that these experiments provide. The emphasis here is on established tools and techniques that can realistically be used for problem solving. As a result, many useful instruments and techniques employed by the trained mass spectroscopist are not discussed here, because they do not satisfy these criteria or are not yet widely available; however, a few of these are briefly mentioned at the end of the unit. The overview concludes with a tutorial discussion on the meaning and practical importance of a number of fundamental experimental and performance-related issues that have important implications for interpretation and use of mass spectral data, such as mass accuracy and resolution.
The antioxidant conundrum in cancer. (2003)

The health-related effects of interactions between reactive oxygen species (ROS) and dietary antioxidants and the consequences of dietary antioxidant supplementation on human health are by no means clear. Although ROS, normal byproducts of aerobic metabolism, are essential for various defense mechanisms in most cells, they can also cause oxidative damage to DNA, proteins, and lipids, resulting in enhanced disease risk. Dietary antioxidants (e.g., vitamin E, vitamin C, beta-carotene, and selenium), as well as endogenous antioxidant mechanisms, can help maintain an appropriate balance between the desirable and undesirable cellular effects of ROS. However, any health-related effects of interactions between dietary antioxidants and ROS likely depend on the health status of an individual and may also be influenced by genetic susceptibilities. Clinical studies of antioxidant supplementation and changes in either oxidative status, disease risk, or disease outcome have been carried out in healthy individuals, populations at risk for certain diseases, and patients undergoing disease therapy. The use of antioxidants during cancer therapy is currently a topic of heated debate because of an overall lack of clear research findings. Some data suggest antioxidants can ameliorate toxic side effects of therapy without affecting treatment efficacy, whereas other data suggest antioxidants interfere with radiotherapy or chemotherapy. Overall, examination of the evidence related to potential interactions between ROS and dietary antioxidants and effects on human health indicates that consuming dietary antioxidant supplements has pros and cons for any population and raises numerous questions, issues, and challenges that make this topic a fertile field for future research. Overall, current knowledge makes it premature to generalize and make specific recommendations about antioxidant usage for those at high risk for cancer or undergoing treatment.
KINETICS OF ACID DEMINERALIZATION IN HISTOLOGIC TECHNIQUE (1974)

The rate of progression of the demineralization front during acid demineralization is investigated for standardized elephant's ivory dentine specimens. A theoretical model for the penetration based upon a combined diffusion with reaction process is set up. It is demonstrated that the results are in accordance with the proposed model. For specimens of certain geometrical shapes (semi-infinite or plane sheet) the distance penetrated by the front is directly proportional to the square root of the time.
Semiconductor Surface Roughness: Dependence on Sign and Magnitude of Bulk Strain (1994)

Changes in surface roughness have been studied as a function of bulk compressive and tensile strains (biaxial in the plane of the sample surface) in thin films of compositionally uniform and dislocation-free ${\mathrm{Ge}}_{0.5}$${\mathrm{Si}}_{0.5}$. A pronounced surface roughness is observed only for films under compressive strains exceeding 1.4%. Molecular dynamics simulations show that this striking result has its origin in the strain-induced lowering of surface step free energies.
Heparin-induced thrombocytopenia (2013)

Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder caused by antibodies that recognize complexes of platelet factor 4 (PF4) and heparin. HIT is frequently considered in the differential diagnosis of thrombocytopenia occurring in patients on heparin therapy. HIT is a challenging diagnosis because of routine heparin use in hospitalized patients, the common occurrence of thrombocytopenia, and high rates of anti-PF4/heparin seroconversions in patients treated with heparin. Our diagnostic approach to HIT is presented here, underscoring critical elements of clinical and laboratory evaluation.
Apoptotic and antitumor activity of death receptor antibodies require inhibitory Fcγ receptor engagement (2012)

By virtue of their ability to induce apoptosis and regulate growth, differentiation, and cytokine responses, the tumor necrosis factor receptor (TNFR) superfamily members have emerged as attractive targets for anticancer therapeutics. Agonistic antibodies to apoptosis-inducing TNFRs, such as death receptor 5 (DR5), although displaying impressive activities against a variety of tumors in preclinical models, appear to be less active in clinical trials. We report that the in vivo apoptotic and antitumor activities of these antibodies have an absolute requirement for the coengagement of an inhibitory Fcγ receptor, FcγRIIB. Anti-DR5 antibodies of the type currently in clinical trials have weak FcγRIIB binding and thus are compromised in their proapoptotic and antitumor activities in both colon and breast carcinoma models. Enhancing FcγRIIB engagement increases apoptotic and antitumor potency. Our results demonstrate that Fc domain interactions are critical to the therapeutic activity of anti-DR5 antibodies and, together with previous reports on agonistic anti-CD40 antibodies, establish a common requirement for FcγRIIB coengagement for optimal biological effects of agonistic anti-TNFR antibodies.
Form of antigen dictates immunity: Irradiated cell vs. whole cell lysate vaccination (48.16) (2007)

Abstract The context in which antigen is perceived by the immune system dictates the quality of the ensuing immune response, which can range from tolerance to lasting immunity. In the current report we investigated the effects of vaccinating mice with antigen in two separate contexts, namely: Irradiated cells, or whole cell lysates. Using the MethA tumor model we observed that although a single vaccination with irradiated MethA cells leads to immunity in BALB/c mice, vaccination with the same cell equivalents of whole cell lysate does not. These results were surprising in light of the substantial body of literature demonstrating the immunostimulatory effects of cell lysates. We hypothesize that although each vaccination contains the same potential antigens, due to the different context in which they are delivered, the immune system will react to them differently. To test this we analyzed multiple characteristics of the immune response following vaccination with irradiated cells or whole cell lysates including: Tumor protection, the quantity and quality of an antigen specific T cell response, stability and persistence of antigen, and the effects of multiple vaccinations. We report dramatic differences between the two immunogens at each of the aspects tested. Our data suggests that although whole cell lysates contain antigen and the same potentially immunostimulatory components as irradiated cells, vaccinating mice with irradiated tumor cells leads to a much greater T cell response and tumor protection than does vaccinating with whole cell lysates.
Distributed Representations of Words and Phrases and their Compositionality (2013)

The recently introduced continuous Skip-gram model is an efficient method for learning high-quality distributed vector representations that capture a large number of precise syntactic and semantic word relationships. In this paper we present several extensions that improve both the quality of the vectors and the training speed. By subsampling of the frequent words we obtain significant speedup and also learn more regular word representations. We also describe a simple alternative to the hierarchical softmax called negative sampling. An inherent limitation of word representations is their indifference to word order and their inability to represent idiomatic phrases. For example, the meanings of "Canada" and "Air" cannot be easily combined to obtain "Air Canada". Motivated by this example, we present a simple method for finding phrases in text, and show that learning good vector representations for millions of phrases is possible.
Quantitative studies of inhibitors of ADP-ribosylation in vitro and in vivo (1989)

The ADP-ribosyl moiety of NAD+ is consumed in reactions catalyzed by three classes of enzymes: poly(ADP-ribose) polymerase, protein mono(ADP-ribosyl)transferases, and NAD+ glycohydrolases. In this study, we have evaluated the selectivity of compounds originally identified as inhibitors of poly(ADP-ribose) polymerase on members of the three classes of enzymes. The 50% inhibitory concentration (IC50) of more than 20 compounds was determined in vitro for both poly(ADP-ribose) polymerase and mono(ADP-ribosyl)transferase A in an assay containing 300 microM NAD+. Of the compounds tested, benzamide was the most potent inhibitor of poly(ADP-ribose) polymerase with an IC50 of 3.3 microM. The IC50 for benzamide for mono(ADP-ribosyl)transferase A was 4.1 mM, and similar values were observed for four additional cellular mono(ADP-ribosyl)transferases. The IC50 for NAD+ glycohydrolase for benzamide was approximately 40 mM. For seven of the best inhibitors, inhibition of poly(ADP-ribose) polymerase in intact C3H1OT1/2 cells was studied as a function of the inhibitor concentration of the culture medium, and the concentration for 50% inhibition (culture medium IC50) was determined. Culture medium IC50 values for benzamide and its derivatives were very similar to in vitro IC50 values. For other inhibitors, such as nicotinamide, 5-methyl-nicotinamide, and 5-bromodeoxyuridine, culture medium IC50 values were 3-5-fold higher than in vitro IC50 values. These results suggest that micromolar levels of the benzamides in the culture medium should allow selective inhibition of poly(ADP-ribose) metabolism in intact cells. Furthermore, comparative quantitative inhibition studies should prove useful for assigning the biological effects of these inhibitors as an effect on either poly(ADP-ribose) or mono(ADP-ribose) metabolism.
Control of Electrical Activity in Central Neurons by Modulating the Gating of Small Conductance Ca2+-activated K+ Channels (2001)

In most central neurons, action potentials are followed by an afterhyperpolarization (AHP) that controls firing pattern and excitability. The medium and slow components of the AHP have been ascribed to the activation of small conductance Ca(2+)-activated potassium (SK) channels. Cloned SK channels are heteromeric complexes of SK alpha-subunits and calmodulin. The channels are activated by Ca(2+) binding to calmodulin that induces conformational changes resulting in channel opening, and channel deactivation is the reverse process brought about by dissociation of Ca(2+) from calmodulin. Here we show that SK channel gating is effectively modulated by 1-ethyl-2-benzimidazolinone (EBIO). Application of EBIO to cloned SK channels shifts the Ca(2+) concentration-response relation into the lower nanomolar range and slows channel deactivation by almost 10-fold. In hippocampal CA1 neurons, EBIO increased both the medium and slow AHP, strongly reducing electrical activity. Moreover, EBIO suppressed the hyperexcitability induced by low Mg(2+) in cultured cortical neurons. These results underscore the importance of SK channels for shaping the electrical response patterns of central neurons and suggest that modulating SK channel gating is a potent mechanism for controlling excitability in the central nervous system.
Characterization of domains of herpes simplex virus type 1 glycoprotein E involved in Fc binding activity for immunoglobulin G aggregates (1994)

Herpes simplex virus type 1 glycoproteins gE and gI form receptors for the Fc domain of immunoglobulin G (IgG) which are expressed on the surface of infected cells and on the virion envelope and which protect the virus from immune attack. Glycoprotein gE-1 is a low-affinity Fc receptor (FcR) that binds IgG aggregates, while gE-1 and gI-1 form a complex which serves as a higher-affinity FcR capable of binding IgG monomers. In this study, we describe two approaches used to map an Fc binding domain on gE-1 for IgG aggregates. First, we constructed nine plasmids encoding gE-1/gD-1 fusions proteins, each containing a large gE-1 peptide inserted into the ectodomain of gD-1. Fusion proteins were tested for FcR activity with IgG-sensitized erythrocytes in a rosetting assay. Three of the fusion proteins containing overlapping gE-1 peptides demonstrated FcR activity; the smallest peptide that retained Fc binding activity includes gE-1 amino acids 183 to 402. These results indicate that an Fc binding domain is located between gE-1 amino acids 183 and 402. To more precisely map the Fc binding domain, we tested a panel of 21 gE-1 linker insertion mutants. Ten mutants with insertions between gE-1 amino acids 235 and 380 failed to bind IgG-sensitized erythrocytes, while each of the remaining mutants demonstrated wild-type Fc binding activity. Taken together, these results indicate that the region of gE-1 between amino acids 235 and 380 forms an FcR domain. A computer-assisted analysis of the amino acid sequence of gE-1 demonstrates an immunoglobulin-like domain contained within this region (residues 322 to 359) which shares homology with mammalian FcRs.
A new method for the preparation of metaphase chromosomes for flow analysis. (1981)

A new method for the preparation of metaphase chromosomes for flow analysis has been evaluated. It has been shown that this method, which involves detergent lysis of metaphase cells and polyamines to stabilize the DNA, yields lower coefficients of variation and background levels in the DNA histograms than is currently obtained by hexylene glycol based methods. A conventional flow cytometer (FACS-II) has been used to resolve the human karyotype into about 14 peaks after ethidium bromide staining and excitation with a relatively low level of illumination (0.4 W at 488 nm). Flow karyotypes have also been obtained from suspension cell lines, in particular from the mouse cell line, Friend 707/B10. The only disadvantage of this method is that the chromosomes are highly condensed and therefore banding studies on sorted chromosomes may not be possible.
Free-space optical interconnect using an FLC SLM for active beam steering and wave front correction (2004)

Free-space optical interconnects have a wide range of potential applications in the field of telecommunications, computing, and data storage. Of particular interest is their use at the printed circuit board-to-printed circuit board level to either augment or replace a conventional electronic backplane. Although it is possible to design a free-space interconnect capable of operating at data rates equal to, or greater than conventional electronic backplanes, acceptance of free-space technology has been slow due to the perceived difficulties in aligning the system, and in maintaining alignment during the operational cycle of a product. In this paper we describe the implementation of a free space optical interconnect that uses a programmable diffractive element for active beam steering in order to maintain the link between the two printed circuit boards. Moreover, by using a modal wave front sensor, the diffractive element corrects for static aberrations. These static aberrations, such as field curvature and coma, are due to intrinsic imperfections in the optical system related to the lenses used. In addition, aberrations introduced by misalignments can also be compensated for. The diffractive structure is displayed on a ferroelectric liquid crystal spatial light modulator. Simulations and theoretical discussions of the performance of the system are shown and analysed.
Molecular diversity in amino-terminal domains of human calpastatin by exon skipping. (1992)

Calpastatin, a specific inhibitor of calpain, consists of a unique N-terminal domain (domain L) and four repetitive calpain-inhibition domains (domains 1-4). Calpastatin cDNA of human was reported to have two deletions in domains L and 1, as compared with that of pig and rabbit. We isolated human calpastatin genomic DNA clones, and the sequence analysis revealed seven exons for domain L and five exons for domain 1. Those deletions in the human cDNA were retained in its genomic DNA as exons 3 and 11. By the reverse transcription polymerase chain reaction method, three calpastatin cDNAs, full-length domains L and 1, and two natural mutants with deletions in either exon 3 or in both exons 3 and 5, were cloned from human fibroblast WI-38 cell line mRNA. Domain L was found to be rich in basic amino acid residues, especially for exon 3, and its N-terminal half was highly conserved among species. The isoelectric points (pI) of domain L and domains 1-4 were calculated to be 10.27 and 4.26-4.90, respectively. Moreover, human tissues and cell lines displayed different patterns of reverse transcription polymerase chain reaction products in agarose gel electrophoresis. Therefore, alternative splicing is most likely the cause for the molecular diversity, and the multiple isoforms are implicated for specific physiological roles.
The Plankton-Climate Connection (1987)

For more than 31/2 billion years, the earth has provided the exact mix of water, gases and temperature that life, as we know it, requires for existence. Is this a fortuitous occurrence? Has life been riding around on a huge piece of rock that has luckily furnished suitable accommodation? Or has life taken part in the process, creating for itself a cozy environment that can support plankton, pandas and a panoply of other earthly organisms? These are the questions raised by a controversial theory called the Gaia hypothesis. Proposed in the early 1970s by British scientist James E. Lovelock, working with biologist Lynn Margulis of Boston University, the Gaia hypothesis states that life has regulated and stabilized the environment, keeping it within the narrow bounds that allow life to continue. And now, microscopic marine plants are floating into the Gaia debate. Evidence is emerging that these onecelled plants, called plankton, are at least partially responsible for setting the temperature of the earth. And the new findings are enhancing scientists' understanding of how life can influence the global climate. The discovery of a previously unknown plankton-climate connection is enough to raise the eyebrows of many scientists. But it's only part of the story
Galanin Modulation of Seizures and Seizure Modulation of Hippocampal Galanin in Animal Models of Status Epilepticus (1998)

We examined the role of hippocampal galanin in an animal model of status epilepticus (SE). Control rats showed abundant galanin-immunoreactive (Gal-IR) fibers in the dentate hilus, whereas no Gal-IR neurons were observed. Three hours after the onset of self-sustaining SE (SSSE), induced either by intermittent stimulation of the perforant path for 30 min (PPS) or by injection of lithium and pilocarpine, Gal-IR fibers disappeared in the hilus and remained absent for up to 1 week afterward. Twelve hours after the induction of SE by PPS or 3 hr after pilocarpine administration, Gal-IR neurons appeared in the hilus; these neurons increased in number after 1 d and gradually declined 3 and 7 d later. Galanin concentration in the hippocampus, measured by ELISA, significantly decreased on the plateau of SSSE and increased 24 hr after PPS. Galanin (0.05 nmol) injected into the hilus prevented the induction of SSSE, and 0.5 nmol of galanin stopped established SSSE. These effects were attenuated by galanin receptor antagonists (M35 > M40 >/= M15). 2-Ala-galanin (5 nmol), a putative agonist of galanin type 2 receptors, prevented but was unable to stop SSSE. M35 facilitated the development of SSSE when given before PPS. We suggest that hippocampal galanin acts as an endogenous anticonvulsant via galanin receptors. SE-induced galanin depletion in the hippocampus may contribute to the maintenance of seizure activity, whereas the increase of galanin concentration and the appearance of galanin-immunoreactive neurons may favor the cessation of SSSE. The seizure-protecting action of galanin SSSE opens new perspectives in the treatment of SE.
Prostate-specific antigen value as a marker in breast cancer. (2006)

The immunoexpression of prostate-specific antigen in breast cancers has been well established, but the role of this extra-prostate PSA appears to be a complex, poorly understood and of doubtful prognostic value. In this context, our aim was to evaluate PSA in breast carcinomas and to compare the results with several established prognostic markers of breast cancer: estrogen and progesterone receptors status, HER2/neu status, histological type of tumor, grade of differentiation, stage, tumor size, nodal and menopausal status. We have immunohistochemically assessed 53 breast carcinomas for PSA, ER, PR and oncoprotein HER2/neu status. The relationship between the clinical and histopathological markers was analyzed by chi-square test. In the present study PSA was expressed in 60.3% of cases, and we have found a significant correlation with the histological type and HER2/neu negative status in premenopausal women. No statistically significant difference was found between PSA positivity and menopausal status of the patients, nodal status, estrogen and progesterone receptors, HER2/neu status in postmenopausal patients, tumor size or histological grade. We conclude that in our study PSA can not be considered as a valuable independent prognostic factor in breast carcinoma. As long as the majorities of PSA positive carcinomas were small in size, early stage, better and moderately differentiated, HER2/neu negative and 70% of ER/PR positive carcinomas expressed PSA, it might be useful as a marker for a subset of breast cancers with better prognosis, which could respond to endocrine therapy, in correlation with other prognostic markers.
Transcriptional regulation of bone formation by the osteoblast-specific transcription factor Osx (2010)

Bone formation is a complex developmental process involving the differentiation of mesenchymal stem cells to osteoblasts. Osteoblast differentiation occurs through a multi-step molecular pathway regulated by different transcription factors and signaling proteins. Osx (also known as Sp7) is the only osteoblast-specific transcriptional factor identified so far which is required for osteoblast differentiation and bone formation. Osx knock-out mice lack bone completely and cartilage is normal. This opens a new window to the whole research field of bone formation. Osx inhibits Wnt pathway signaling, a possible mechanism for Osx to inhibit osteoblast proliferation. These reports demonstrate that Osx is the master gene that controls osteoblast lineage commitment and the subsequent osteoblast proliferation and differentiation. This review is to highlight recent progress in understanding the molecular mechanisms of transcriptional regulation of bone formation by Osx.