gebhart/patrepeval huggingface dataset:
Atomistic Description of Electron Beam Damage in Nitrogen-Doped Graphene and Single-Walled Carbon Nanotubes (2012)

By combining ab initio simulations with state-of-the-art electron microscopy and electron energy loss spectroscopy, we study the mechanism of electron beam damage in nitrogen-doped graphene and carbon nanotubes. Our results show that the incorporation of nitrogen atoms results in noticeable knock-on damage in these structures already at an acceleration voltage of 80 kV, at which essentially no damage is created in pristine structures at corresponding doses. Contrary to an early estimate predicting rapid destruction via sputtering of the nitrogen atoms, in the case of substitutional doping, damage is initiated by displacement of carbon atoms neighboring the nitrogen dopant, leading to the conversion of substitutional dopant sites into pyridinic ones. Although such events are relatively rare at 80 kV, they become significant at higher voltages typically used in electron energy loss spectroscopy studies. Correspondingly, we measured an energy loss spectrum time series at 100 kV that provides direct evidence for such conversions in nitrogen-doped single-walled carbon nanotubes, in excellent agreement with our theoretical prediction. Besides providing an improved understanding of the irradiation stability of these structures, we show that structural changes cannot be neglected in their characterization employing high-energy electrons.
High expression of the cGMP‐specific phosphodiesterase, PDE9A, in sickle cell disease (SCD) and the effects of its inhibition in erythroid cells and SCD neutrophils (2008)

Modulation of intracellular cyclic guanosine monophosphate (cGMP) may characterize a therapeutic target for sickle cell disease (SCD); cGMP-dependent signalling may be important for erythroid foetal haemoglobin induction and exert anti-inflammatory functions in leucocytes. As the inhibition of phosphodiesterases (PDEs), which regulate intracellular cGMP, can result in tissue-specific elevation of cGMP, we studied the gene expressions of cGMP-specific PDEs (-1A, -5A and -9A) in the reticulocytes and neutrophils of healthy controls, steady-state SCD patients and SCD patients on hydroxycarbamide therapy (SCDHC). PDE9A gene expression was found in numerous cell types; however, high expression was found in neutrophils, reticulocytes, CD34(+)-derived erythroid cells and K562 erythroleukaemic cells, indicating a high haematopoietic cell expression. PDE9A gene expression was, however, significantly higher in the reticulocytes and neutrophils of SCD individuals, compared to control cells; Western blotting confirmed the production of PDE9A protein in SCD neutrophils and K562 cells. Inhibition of PDE9A enzyme with the specific inhibitor, BAY73-6691, significantly increased production of the gamma-globin gene (HBG) in K562 cells and reversed the increased adhesive properties of SCD neutrophils. Since elevation of haematopoietic intracellular cGMP may be beneficial in SCD, the relatively limited tissue distribution of PDE9A suggests that it could represent a novel drug target worthy of further study.
Troponin I Inhibitory Peptide (96−115) Has an Extended Conformation When Bound to Skeletal Muscle Troponin C (1999)

We have utilized CD and NMR spectroscopy to study the conformation of the troponin I (TnI) inhibitory peptide [TnI(96-115)] free in solution and when bound to troponin C (TnC). Analysis of the CD spectrum of the free peptide in aqueous solution indicates it is only approximately 3% helix. Upon complex formation with TnC, there is no change in total helix content compared to the sum of the free components. The NMR data support a predominantly extended conformation for the free peptide. TnI(96-115) bound to TnC was selectively observed by NMR using deuterated TnC (dTnC). For the 1:1 ratio of TnI(96-115) to dTnC used, 95% of the peptide was bound to dTnC. The chemical shifts of the TnC-bound peptide resonances are similar to those of the free peptide, indicating that the change in peptide conformation as a consequence of binding to TnC is small. For the TnC-bound TnI(96-115) peptide, the ratios of sequential Halpha-HN to intraresidue HN-Halpha NOE cross-peak volumes support a predominantly extended conformation, possibly kinked at Gly104. The results presented here are in agreement with sequence analysis predictions for TnI(96-115) as a free peptide or within the intact TnI sequence. The predominantly extended structure for the 96-115 inhibitory sequence segment of TnI with a kink at Gly104 may facilitate its binding alternately to actin or TnC in response to the Ca2+ signals that control thick and thin filament interactions during the contractile cycle.
Michael E. Miller (2017)

Michael E. Miller, 57, died on April 9 in Shutesbury, Mass. “In his field, Michael was a key figure in bioremediation and a mentor to many, and was admired and adored by all. He was likewise highly respected and beloved as a dancer and organizer for gender-role-free dance and Balkan dance, an LGBT and other progressive political activist, and a professional-grade chef, amateur botanist, naturalist, and astronomer. The number of people who mourn his loss is nearly innumerable.”—Robert E. Seletsky, husband Most recent title: principal environmental chemist, CDM Smith Education: B.S., chemistry, Swarthmore College, 1981; Ph.D., physical chemistry, Cornell University, 1986 Survivor: husband, Robert E. Seletsky; sister, Beth Miller Coimbra To recognize your late loved one or colleague, submit obituary information at cenm.ag/obits.
Language support for lightweight transactions (2003)

Concurrent programming is notoriously difficult. Current abstractions are intricate and make it hard to design computer systems that are reliable and scalable. We argue that these problems can be addressed by moving to a declarative style of concurrency control in which programmers directly indicate the safety properties that they require. In our scheme the programmer demarks sections of code which execute within lightweight software-based transactions that commit atomically and exactly once. These transactions can update shared data, instantiate objects, invoke library features and so on. They can also block, waiting for arbitrary boolean conditions to become true. Transactions which do not access the same shared memory locations can commit concurrently. Furthermore, in general, no performance penalty is incurred for memory accesses outside transactions.We present a detailed design of this proposal along with an implementation and evaluation. We argue that the resulting system ( i ) is easier for mainstream programmers to use, ( ii ) prevents lock-based priority-inversion and deadlock problems and ( iii ) can offer performance advantages.
Sensible Organizations: Technology and Methodology for Automatically Measuring Organizational Behavior (2008)

We present the design, implementation, and deployment of a wearable computing platform for measuring and analyzing human behavior in organizational settings. We propose the use of wearable electronic badges capable of automatically measuring the amount of face-to-face interaction, conversational time, physical proximity to other people, and physical activity levels in order to capture individual and collective patterns of behavior. Our goal is to be able to understand how patterns of behavior shape individuals and organizations. By using on-body sensors in large groups of people for extended periods of time in naturalistic settings, we have been able to identify, measure, and quantify social interactions, group behavior, and organizational dynamics. We deployed this wearable computing platform in a group of 22 employees working in a real organization over a period of one month. Using these automatic measurements, we were able to predict employees' self-assessments of job satisfaction and their own perceptions of group interaction quality by combining data collected with our platform and e-mail communication data. In particular, the total amount of communication was predictive of both of these assessments, and betweenness in the social network exhibited a high negative correlation with group interaction satisfaction. We also found that physical proximity and e-mail exchange had a negative correlation of r = -0.55 (p 0.01), which has far-reaching implications for past and future research on social networks.
Nucleotide sequence and structure of the human apolipoprotein E gene. (1985)

The gene for human apolipoprotein E (apo-E) was selected from a library of cloned genomic DNA by screening with a specific cDNA hybridization probe, and its structure was characterized. The complete nucleotide sequence of the gene as well as 856 nucleotides of the 5' flanking region and 629 nucleotides of the 3' flanking region were determined. Analysis of the sequence showed that the mRNA-encoding region of the apo-E gene consists of four exons separated by three introns. In comparison to the structure of the mRNA, the introns are located in the 5' noncoding region, in the codon for glycine at position -4 of the signal peptide region, and in the codon for arginine at position +61 of the mature protein. The overall lengths of the apo-E gene and its corresponding mRNA are 3597 and 1163 nucleotides, respectively; a mature plasma protein of 299 amino acids is produced by this gene. Examination of the 5' terminus of the gene by S1 nuclease mapping shows apparent multiple transcription initiation sites. The proximal 5' flanking region contains a "TATA box" element as well as two nearby inverted repeat elements. In addition, there are four Alu family sequences associated with the apo-E gene: an Alu sequence located near each end of the gene and two Alu sequences located in the second intron. This knowledge of the structure permits a molecular approach to characterizing the regulation of the apo-E gene.
Structure of the murine erythropoietin receptor complex. Characterization of the erythropoietin cross-linked proteins. (1991)

The structure of the murine erythropoietin receptor was studied using antibodies against the intracellular part of the cloned erythropoietin receptor chain. These antibodies precipitated erythropoietin-receptor complexes from Triton X-100-solubilized cells. When the complexes were cross-linked by disuccinimidyl suberate, the 85- and 100-kDa erythropoietin-cross-linked proteins previously described were immunoprecipitated. However, these proteins were not precipitated when the complexes were denatured and reduced before immunoprecipitation. Using 1-ethyl 3-(3-dimethylaminopropyl)carbodiimide, we observed erythropoietin cross-linking with a protein of 66 kDa in addition to the 100- and 85-kDa proteins. Only the 66-kDa erythropoietin-cross-linked protein was immunoprecipitated by anti-receptor antibodies after denaturation and reduction of the complex. Thus, our results suggest that the 85- and 100-kDa proteins previously evidenced by cross-linking are associated with the cloned chain of the receptor to form a multimeric complex but these proteins seem immunologically unrelated to the cloned chain. We observed that reducing the length of molecules able to cross-link amino groups decreased the efficiency of cross-linking with the 100-kDa protein and only the 85-kDa protein was cross-linked with erythropoietin using 1,5-difluoro-2,4-dinitrobenzene. These results suggest that the 85- and 100-kDa proteins occupate slightly different positions relative to the erythropoietin molecule bound to the receptor.
Reversal of Neurological Defects in a Mouse Model of Rett Syndrome (2007)

Rett syndrome is an autism spectrum disorder caused by mosaic expression of mutant copies of the X-linked MECP2 gene in neurons. However, neurons do not die, which suggests that this is not a neurodegenerative disorder. An important question for future therapeutic approaches to this and related disorders concerns phenotypic reversibility. Can viable but defective neurons be repaired, or is the damage done during development without normal MeCP2 irrevocable? Using a mouse model, we demonstrate robust phenotypic reversal, as activation of MeCP2 expression leads to striking loss of advanced neurological symptoms in both immature and mature adult animals.
Gene therapy for vascular proliferative disorders. (1996)

Despite major advances in interventional techniques in recent years, restenosis remains an important late complication of percutaneous revascularization procedures. Vascular smooth muscle cell proliferation after arterial injury plays an important role in the pathogenesis of restenosis. Major progress has been made recently in elucidating the cellular and molecular mechanisms underlying this proliferative response. This in turn has led to the development of novel, gene-based approaches for the treatment and prevention of restenosis as well as other vascular proliferative disorders. Included among these are somatic gene therapy the ability to introduce and express recombinant genes in non-germ-line cells of a recipient organism in vivo. This article reviews specific genetic approaches that have recently been developed for the treatment of vascular proliferative disorders such as restenosis, focusing on the use of adenovirus-mediated arterial gene transfer strategies designed to suppress the vascular smooth muscle cell proliferative response associated with these diseases.
Targeting the EGFR Pathway for Cancer Therapy (2006)

Clinical studies have shown that HER-2/Neu is over-expressed in up to one-third of patients with a variety of cancers, including B-cell acute lymphoblastic leukemia (B-ALL), breast cancer and lung cancer, and that these patients are frequently resistant to conventional chemo-therapies. Additionally, in most patients with multiple myeloma, the malignant cells over-express a number of epidermal growth factor receptors (EGFR)s and their ligands, HB-EGF and amphiregulin, thus this growth-factor family may be an important aspect in the patho-biology of this disease. These and other, related findings have provided the rationale for the targeting of the components of the EGFR signaling pathways for cancer therapy. Below we discuss various aspects of EGFR-targeted therapies mainly in hematologic malignancies, lung cancer and breast cancer. Beside novel therapeutic approaches, we also discuss specific side effects associated with the therapeutic inhibition of components of the EGFR-pathways. Alongside small inhibitors, such as Lapatinib (Tykerb, GW572016), Gefitinib (Iressa, ZD1839), and Erlotinib (Tarceva, OSI-774), a significant part of the review is also dedicated to therapeutic antibodies (e.g.: Trastuzumab/Herceptin, Pertuzumab/Omnitarg/rhuMab-2C4, Cetuximab/Erbitux/IMC-C225, Panitumumab/Abenix/ABX-EGF, and also ZD6474). In addition, we summarize, both current therapy development driven by antibody-based targeting of the EGFR-dependent signaling pathways, and furthermore, we provide a background on the history and the development of therapeutic antibodies.
Cloning of a species-specific antigen of Mycobacterium bovis (1988)

A DNA library from a virulent strain of Mycobacterium bovis was constructed in the expression vector lambda gt11, and the library was probed with antisera to M. bovis. Clones expressing M. bovis antigens were isolated and characterized by using M. bovis-specific monoclonal antibodies that recognize a 22,000-molecular-weight protein (MPB70). MPB70 is a major protein antigen of the vaccine strain of M. bovis BCG and of virulent M. bovis, the causative agent of bovine tuberculosis. Of 32 clones selected by using polyclonal affinity-purified anti-M. bovis sera, 5 were recognized by the anti-MPB-70 monoclonal antibodies, and one monoclonal antibody, SB10, recognized all 5 clones. Characterization of these clones showed that one clone containing a 253-base-pair insert expressed a polypeptide bound by all of the MPB70-specific monoclonal antibodies. Western blots (immunoblots) showed that this cloned protein was recognized by sera from M. bovis-infected cattle, although not all cattle with bovine tuberculosis produced antibodies reactive to this clone. DNA sequencing of the clone showed that it coded for 84 amino acids from positions 17 to 114 of the 161-amino-acid protein, with a 16-peptide deletion between positions 79 and 94. Apart from this deletion, there were seven other variations between the cloned sequence and that deduced from M. bovis BCG MPB70.
High frequency of EBV association with non‐random abnormalities of the chromosome region 1q21‐25 in aids‐related Burkitt's lymphoma‐derived cell lines (1995)

Chromosome 1q abnormalities represent the second most frequent cytogenetic lesion of Burkitt lymphoma (BL) and acute lymphoblastic leukemia (ALL)-L3. The most frequent change is partial duplication of the long arm of chromosome 1, involving variable bands but consistently including 1q23. Among AIDS-related BL similar chromosome 1q abnormalities have also been found. We have now characterized in detail the chromosome 1q abnormalities of 4 AIDS-BL cell lines and compared them to other molecular features of the tumor clone, namely infection by Epstein Barr virus (EBV). Immunophenotypic characteristics were also assessed by conventional in situ immunocytochemical and flow cytometric procedures. The B-cell origin of all cell lines was demonstrated by the expression of B-cell-restricted markers (e.g., CD19). Analysis of Ig light chains confirmed their monoclonal nature. The t(8;14) was present in 3 of the 4 lines, whereas variant translocation t(8;22) was detected in the remaining cell line. Additional chromosomal changes were found in all cases, with chromosome 1 being involved in all. Structural changes encompassed in each case the 1q21-25 bands, in either duplication or partial trisomy. EBER ISH studies identified EBV association in 3 of the 4 AIDS-BL cell lines in contrast to previous studies of BL of immunocompetent individuals. Our findings of a high frequency of chromosome 1q abnormalities in EBV-infected AIDS-related BL cell lines demonstrate that such chromosomal abnormality and EBV positivity are not mutually exclusive and are possibly independent factors, whereas their close association in AIDS may be related to the immunodeficiency.
A Two-Step Compressed Spectrum Sensing Scheme for Wideband Cognitive Radios (2010)

For cognitive radios (CRs), compressive sampling (CS) techniques have been utilized for spectrum sensing in order to alleviate the high signal acquisition costs in the wideband regime. Given the desired sensing performance, the fundamental limit on the sampling rates is determined by the actual sparsity order S <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">nz</sub> of the signal spectrum, which can be considerably lower than the Nyquist sampling rate. However, S <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">nz</sub> is time-varying and hence unknown a priori for a dynamic CR network, and is typically available in the form of its statistical upper bound S <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">max</sub> . When the practical sampling rate is chosen according to S <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">max</sub> in lieu of S <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">nz</sub> , this rate is unnecessarily high for accurate spectrum sensing and hence wasteful of the sensing resources. To circumvent this problem, this paper develops a two-step compressed spectrum sensing (TS-CSS) scheme for efficient wideband sensing. The first step quickly estimates the actual sparsity order of the wide spectrum of interest using a small number of samples, and the second step adjusts the total number of samples collected according to the estimated signal sparsity order. By doing so, the overall sampling rate is minimized adaptively. The cornerstone of this work is the fact that the number of measurements required for estimating the signal sparsity order is (much) smaller than that for reconstructing the sparse signal itself. The gap between these two numbers is delineated in this paper in closed form, which offers valuable design guideline. Validated by simulations, the proposed TS-CSS scheme achieves the desired sensing performance at considerably reduced sensing costs, using a lowered average sampling rate compared with traditional one-step compressive sampling schemes.
Clarks Flour Mill and Water Race Maheno, North Otago (2000)

This paper describes the strengthening and upgrading carried out by David G. Cox for the Historic Places Trust on the Maheno Flour Mill. Flour Mills were an important part of the local economy and were common throughout the East Coast of the South Island of New Zealand in the 1800's. They represented the interface between industry and agriculture and required considerable venture capital to set up. Flour Mills were large buildings from 4 to 6 stories high with machinery generally driven by water power to grind the wheat for flour or the oats for oatmeal. The Historic Places Trust bought the Maheno Mill in 1977 as an example of the larger country waterpowered flour mills that were once so common. The mill is a 4 story structure with load bearing walls of local Oamaru limestone and timber floors. The mill race comes from the Kakanui River and originally drove an overshot water wheel. The building was in serious disrepair when bought by the Historic Places Trust and David G. Cox, a structural engineer experienced in providing structural strength to historic buildings, was commissioned to carry out the repairs. This involved strengthening the limestone walls by placing a reinforced concrete shear wall inside the limestone facing and providing floor bracing lo make the structure capable of resisting seismic loads. The paper describes the innovative means of providing structural strength without changing the appearance of the building.
Homing endonucleases: structural and functional insight into the catalysts of intron/intein mobility (2001)

Homing endonucleases confer mobility to their host intervening sequence, either an intron or intein, by catalyzing a highly specific double-strand break in a cognate allele lacking the intervening sequence. These proteins are characterized by their ability to bind long DNA target sites (14-40 bp) and their tolerance of minor sequence changes in these sites. A wealth of biochemical and structural data has been generated for these enzymes over the past few years. Herein we review our current understanding of homing endonucleases, including their diversity and evolution, DNA-binding and catalytic mechanisms, and attempts to engineer them to bind novel DNA substrates.
Resistance to Tomato Spotted Wilt Virus Infection in Transgenic Tobacco Expressing the Viral Nucleocapsid Gene (1992)

A recombinant plasmid containing the entire tomato spotted with virus (TSWV) nucleocapsid gene, with the exception of nucleotide encoding three N-terminal amino acids, was isolated by screening a complementary DNA library, prepared against random primed viral RNA, using a specific monoclonal antibody. The insert contained in plasmid pTSW1 was repaired and amplified by polymerase chain reaction, and the complete nucleocapsid protein gene was introduced into Nicotiana tabacum 'Samsun' by leaf disk transformation using Agrobacterium tumefaciens. Transgenic plants expressing the viral nucleocapsid protein were resistant to subsequent infection following mechanical inoculation with TSWV as indicated by a lack of systemic symptoms and little or no systemic accumulation of virus as determined by double antibody sandwich enzyme-liked immunosorbent assay. These results further extend the applicability of coat protein-mediated resistance, as previously demonstrated for a number of simple plant viruses composed of a positive-sense RNA genome encapsidated with a single species of coat protein, to a membrane-encapsidated, multi-component, negative-sense RNA virus.