gebhart/patrepeval huggingface dataset:
The trade-off between regularity and stability in Tikhonov regularization (1997)

When deriving rates of convergence for the approximations generated by the application of Tikhonov regularization to illâposed operator equations, assumptions must be made about the nature of the stabilization (i.e., the choice of the seminorm in the Tikhonov regularization) and the regularity of the least squares solutions which one looks for. In fact, it is clear from works of Hegland, Engl and Neubauer and Natterer that, in terms of the rate of convergence, there is a tradeâoff between stabilization and regularity. It is this matter which is examined in this paper by means of the bestâpossible worstâerror estimates. The results of this paper provide better estimates than those of Engl and Neubauer, and also include and extend the best possible rate derived by Natterer. The paper concludes with an application of these results to firstâkind integral equations with smooth kernels.
Contacts between DNA gyrase and its binding site on DNA: features of symmetry and asymmetry revealed by protection from nucleases. (1981)

DNA gyrase supercoils DNA by passing one DNA segment through another by means of a reversible double-strand break at specific DNA sites. We determined the nucleotide sequence of two highly preferred gyrase binding sites and analyzed the grip of gyrase on the DNA by using protection from nuclease attack. The DNA-breakage site of gyrase was centered in about 50 base pairs (bp) of DNA that was completely protected from DNase I and flanked by DNA regions cut at average intervals of 9.9 bases. The same pattern of protection from DNase I was observed with topoisomerase II', an enzyme that shares structural homology with gyrase. The gyrase site of DNA breakage was off-center in the 140 bp of DNA protected from exonuclease III digestion. ATP or inhibitors of gyrase had little specific effect on DNase I protection. On addition of a nonhydrolyzable analogue of ATP, previously stable barriers to exonuclease III were invaded and new barriers appeared. We discuss a detailed model uniting these results with previous data on gyrase structure and mechanism.
Enhanced T-Cell Immunogenicity and Protective Efficacy of a Human Immunodeficiency Virus Type 1 Vaccine Regimen Consisting of Consecutive Priming with DNA and Boosting with Recombinant Fowlpox Virus (1998)

The induction of human immunodeficiency virus (HIV)-specific T-cell responses is widely seen as critical to the development of effective immunity to HIV type 1 (HIV-1). Plasmid DNA and recombinant fowlpox virus (rFPV) vaccines are among the most promising safe HIV-1 vaccine candidates. However, the immunity induced by either vaccine alone may be insufficient to provide durable protection against HIV-1 infection. We evaluated a consecutive immunization strategy involving priming with DNA and boosting with rFPV vaccines encoding common HIV-1 antigens. In mice, this approach induced greater HIV-1-specific immunity than either vector alone and protected mice from challenge with a recombinant vaccinia virus expressing HIV-1 antigens. In macaques, a dramatic boosting effect on DNA vaccine-primed HIV-1-specific helper and cytotoxic T-lymphocyte responses, but a decline in HIV-1 antibody titers, was observed following rFPV immunization. The vaccine regimen protected macaques from an intravenous HIV-1 challenge, with the resistance most likely mediated by T-cell responses. These studies suggest a safe strategy for the enhanced generation of T-cell-mediated protective immunity to HIV-1.
Genetics of Chromosomally Mediated Intermediate Resistance to Ceftriaxone and Cefixime in Neisseria gonorrhoeae (2009)

All strains of Neisseria gonorrhoeae with reduced susceptibility to ceftriaxone and cefixime (cephalosporin-intermediate-resistant [Ceph(i)] strains) contain a mosaic penA allele encoding penicillin-binding protein 2 (PBP 2) with nearly 60 amino acid differences compared to the sequence of wild-type PBP 2, together with a set of resistance determinants (i.e., mtrR, penB, and/or ponA1) that are required for high-level penicillin resistance. To define the individual contributions of these determinants to reduced susceptibility to ceftriaxone and cefixime, we created isogenic strains containing the mosaic penA allele from the Ceph(i) strain 35/02 (penA35) together with one or more of the other resistance determinants and determined the MICs of penicillin G, ceftriaxone, and cefixime. The majority of cefixime resistance is conferred by the penA35 allele, with only a small contribution coming from mtrR and penB, whereas ceftriaxone resistance is nearly equally dependent upon mtrR and penB. Unlike high-level penicillin resistance, the ponA1 allele does not appear to be important for Ceph(i). A strain containing all four determinants has increased resistance to ceftriaxone and cefixime but not to the levels that the donor Ceph(i) strain does, suggesting that Ceph(i) strains, similar to high-level-penicillin-resistant strains, contain an additional unknown determinant that is required to reach donor levels of resistance. Our data also suggest that the original Ceph(i) strains arose from the transformation of penA genes from commensal Neisseria species into a penicillin-resistant strain already harboring mtrR, penB, ponA1, and the unknown gene(s) involved in high-level penicillin resistance.
Transmembrane folding of the human erythrocyte anion exchanger (AE1, Band 3) determined by scanning and insertional N-glycosylation mutagenesis (1999)

The human erythrocyte anion exchanger (AE1, Band 3) contains up to 14 transmembrane segments, with a single site of N-glycosylation at Asn642 in extracellular (EC) loop 4. Scanning and insertional N-glycosylation mutagenesis were used to determine the folding pattern of AE1 in the membrane. Full-length AE1, when expressed in transfected human embryonic kidney (HEK)-293 or COS-7 cells, retained a high-mannose oligosaccharide structure. Scanning N-glycosylation mutagenesis of EC loop 4 showed that N-glycosylation acceptor sites (Asn-Xaa-Ser/Thr) spaced 12 residues from the ends of adjacent transmembrane segments could be N-glycosylated. An acceptor site introduced at position 743 in intracellular (IC) loop 5 that could be N-glycosylated in a cell-free translation system was not N-glycosylated in transfected cells. Mutations designed to disrupt the folding of this loop enhanced the level of N-glycosylation at Asn743 in vitro. The results suggest that this loop might be transiently exposed to the lumen of the endoplasmic reticulum during biosynthesis but normally folds rapidly, precluding N-glycosylation. EC loop 4 insertions into positions 428, 484, 754 and 854 in EC loops 1, 2, 6 and 7 respectively were efficiently N-glycosylated, showing that these regions were extracellular. EC loop 4 insertions into positions 731 or 785 were poorly N-glycosylated, which was inconsistent with an extracellular disposition for these regions of AE1. Insertion of EC loop 4 into positions 599 and 820 in IC loops 3 and 6 respectively were not N-glycosylated in cells, which was consistent with a cytosolic disposition for these loops. Inhibitor-affinity chromatography with 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonate (SITS)-Affi-Gel was used to assess whether the AE1 mutants were in a native state. Mutants with insertions at positions 428, 484, 599, 731 and 785 showed impaired inhibitor binding, whereas insertions at positions 754, 820 and 854 retained binding. The results indicate that the folding of the C-terminal region of AE1 is more complex than originally proposed and that this region of the transporter might have a dynamic aspect.
ChemInform Abstract: Synthesis of (.+‐.)‐Ambrox from (E)‐Nerolidol and β‐Ionone via Allylic Alcohol (2,3) Sigmatropic Rearrangement. (1996)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Functional characterization of the mammalian mRNA decapping enzyme hDcp2 (2003)

Regulation of decapping is a critical determinant of mRNA stability. We recently identified hDcp2 as a human decapping enzyme with intrinsic decapping activity. This activity is specific to N(7)-methylated guanosine containing RNA. The hDcp2 enzyme does not function on the cap structure alone and is not sensitive to competition by cap analog, suggesting that hDcp2 requires the RNA for cap recognition. We now demonstrate that hDcp2 is an RNA-binding protein and its recognition and hydrolysis of the cap substrate is dependent on an initial interaction with the RNA moiety. A biochemical characterization of hDcp2 revealed that a 163 amino acid region containing two evolutionarily conserved regions, the Nudix fold hydrolase domain and the adjacent Box B region contained methyl-cap-specific hydrolysis activity. Maximum decapping activity for wild-type as well as truncation mutants of hDcp2 required Mn(2+) as a divalent cation. The demonstration that hDcp2 is an RNA-binding protein with an RNA-dependent decapping activity will now provide new approaches to identify specific mRNAs that are regulated by this decapping enzyme as well as provide novel avenues to control mRNA decapping and turnover by influencing the RNA-binding property of hDcp2.
Silicide and Schottky barrier formation in the Ti-Si and the Ti-SiOx -Si systems (1982)

Silicide and Schottky barrier formation has been characterized for Ti deposited on the Si(100) surface, both with and without surface oxides present. Reactions were carried out in ultrahigh vacuum, while observing electronic and chemical changes with ultraviolet photoemission spectroscopy and Auger electron spectroscopy. Ti deposited on Si shows a sharp interface, no change in Fermi level position, and no silicide formation until heated to 400–500 °C. Ti deposited on thin oxides (&amp;lt;20 Å) frees silicon at the interface and reacts through the oxide to form a silicide when heated to 400–500 °C. Ti deposited on thick thermal oxides also frees Si, but no further reaction occurs until heated to 700–900 °C, at which point TiOx forms near the surface. This differing behavior of thin and thick oxides is shown to be consistent with bulk thermodynamic data.
The occurrence of monocytoid B-lymphocytes in autoimmune disorders. (1993)

Occurrence of monocytoid B-lymphocytes (MBL) in extranodal organs in various inflammatory diseases was examined. MBL were present in 5 (11.4%) of 44 patients with Graves' disease, 11 (36.7%) of 30 with Hashimoto's thyroiditis, 1 (8.3%) of 12 with lymphoid follicular hyperplasia (LFH) of stomach, 1 (10%) of 10 with cutaneous LFH, and 0 of 5 with LFH of lung. The MBL presented as irregularly shaped nodular collections of cells, directly surrounding secondary follicles. Immunohistochemistry revealed a B-cell nature of these cells which expressed the following antigens; CD3-, CD 15-, CD45RA+, CD45Ro-, CDw 75+, CD74+, Mx-PanB+, MB-1+, EMA-. There were no immunoglobulin light chain restriction among infiltrating lymphoid cells. MBL in 2 of 18 cases showed positive reaction for CD43. The patients with MBL were older than those without MBL in each organ site, though the difference was not statistically significant. These findings showed that the MBL could appear in nonlymphoid organs affected by long-standing inflammation. High frequency of the appearance of the MBL in Hashimoto's thyroiditis suggest that MBL proliferation correlates with an impaired immune status.
Interaction between the Corticotropin-Releasing Factor System and Hypocretins (Orexins): A Novel Circuit Mediating Stress Response (2004)

The hypothalamic neuropeptides hypocretins (orexins) play a crucial role in the stability of arousal and alertness. We tested whether the hypocretinergic system is a critical component of the stress response activated by the corticotropin-releasing factor (CRF). Our results show that CRF-immunoreactive terminals make direct contact with hypocretin-expressing neurons in the lateral hypothalamus and that numerous hypocretinergic neurons express the CRF-R1/2 receptors. We also demonstrate that application of CRF to hypothalamic slices containing identified hypocretin neurons depolarizes membrane potential and increases firing rate in a subpopulation of hypocretinergic cells. CRF-induced depolarization was tetrodotoxin insensitive and was blocked by the peptidergic CRF-R1 antagonist astressin. Moreover, activation of hypocretinergic neurons in response to acute stress was severely impaired in CRF-R1 knock-out mice. Together, our data provide evidence of a direct neuroanatomical and physiological input from CRF peptidergic system onto hypocretin neurons. We propose that, after stressor stimuli, CRF stimulates the release of hypocretins and that this circuit contributes to activation and maintenance of arousal associated with the stress response.
Complex seismic trace analysis (1979)

Abstract The conventional seismic trace can be viewed as the real component of a complex trace which can be uniquely calculated under usual conditions. The complex trace permits the unique separation of envelope amplitude and phase information and the calculation of instantaneous frequency. These and other quantities can be displayed in a color-encoded manner which helps an interpreter see their interrelationship and spatial changes. The significance of color patterns and their geological interpretation is illustrated by examples of seismic data from three areas.
Differential expression of cardiac ANP and BNP in a rabbit model of progressive left ventricular dysfunction (2001)

The current studies demonstrate differential activation of atrial and LV ANP and BNP under normal conditions and during the progression to heart failure and provide a molecular basis for the superiority of BNP as marker of LV dysfunction and CHF.
An empirical approach to grouping and segmentation (2002)

This thesis presents a novel dataset of 12,000 segmentations of 1,000 natural images by 30 human subjects. The subjects marked the locations of objects in the images, providing ground truth data for learning grouping cues and benchmarking grouping algorithms. We feel that the data-driven approach is critical for two reasons: (1) the data reflects "ecological statistics" that the human visual system has evolved to exploit, and (2) innovations in computational vision should be evaluated quantitatively. &lt;p&gt;We develop a battery of segmentation comparison measures that we use both to validate the consistency of the human data and to provide approaches for evaluating grouping algorithms. In conjunction with the segmentation dataset, the various measures provide "micro-benchmarks" for boundary detection algorithms and pixel affinity functions, as well a benchmark for complete segmentation algorithms. Using these performance measures, we can systematically improve grouping algorithms with the human ground truth as our goal. &lt;p&gt;Starting at the lowest level, we present local boundary models based on brightness, color, and texture cues, where the cues are individually optimized with respect to the dataset and then combined in a statistically optimal manner with classifiers. The resulting detector is shown to significantly outperform prior state-of-the-art algorithms. Next, we learn from data how to combine the boundary model with patch-based features in a pixel affinity model to settle long-standing debates in computer vision with empirical results: (1) brightness boundaries are more informative than patches, and vice versa for color; (2) texture boundaries and patches are the two most powerful cues; (3) proximity is not a useful cue for grouping, it is simply a result of the process; and (4) both boundary-based and region-based approaches provide significant independent information for grouping
Identifying Relationships among Genomic Disease Regions: Predicting Genes at Pathogenic SNP Associations and Rare Deletions (2009)

Translating a set of disease regions into insight about pathogenic mechanisms requires not only the ability to identify the key disease genes within them, but also the biological relationships among those key genes. Here we describe a statistical method, Gene Relationships Among Implicated Loci (GRAIL), that takes a list of disease regions and automatically assesses the degree of relatedness of implicated genes using 250,000 PubMed abstracts. We first evaluated GRAIL by assessing its ability to identify subsets of highly related genes in common pathways from validated lipid and height SNP associations from recent genome-wide studies. We then tested GRAIL, by assessing its ability to separate true disease regions from many false positive disease regions in two separate practical applications in human genetics. First, we took 74 nominally associated Crohn's disease SNPs and applied GRAIL to identify a subset of 13 SNPs with highly related genes. Of these, ten convincingly validated in follow-up genotyping; genotyping results for the remaining three were inconclusive. Next, we applied GRAIL to 165 rare deletion events seen in schizophrenia cases (less than one-third of which are contributing to disease risk). We demonstrate that GRAIL is able to identify a subset of 16 deletions containing highly related genes; many of these genes are expressed in the central nervous system and play a role in neuronal synapses. GRAIL offers a statistically robust approach to identifying functionally related genes from across multiple disease regions--that likely represent key disease pathways. An online version of this method is available for public use (http://www.broad.mit.edu/mpg/grail/).
Interferon Alfa-2b Antibodies and Clinical Resistance in a Patient with Hairy Cell Leukemia (1989)

A patient with hairy cell leukemia is described who, during the course of treatment of his disease with interferon αb, developed antibodies to the drug. Coincident with antibody development, clinical resistance to the effect of alfa interferon was noted Despite an increasing dose of interferon, no signs of disease response were noted and the patient required a change in therapy to deoxycoformycin. Although similar findings have been described in patients treated with interferon alfa-2a, this is the first report of clinical resistance associated with neutralizing antibody formation in a hairy cell leukemia patient treated with interferon alfa-2b.
The Emergence of Universal Immune Receptor T Cell Therapy for Cancer (2019)

Chimeric antigen receptor (CAR) T cells have shown great success in the treatment of CD19+ hematological malignancies, leading to their recent approval by the FDA as a new cancer treatment modality. However, their broad use is limited since a CAR targets a single tumor associated antigen (TAA), which is not effective against tumors with heterogeneous TAA expression or emerging antigen loss variants. Further, stably engineered CAR T cells can continually and uncontrollably proliferate and activate in response to antigen, potentially causing fatal on-target off-tumor toxicity, cytokine release syndrome, or neurotoxicity without a method of control or elimination. To address these issues, our lab and others have developed various universal immune receptors (UIRs) that allow for targeting of multiple TAAs by T cells expressing a single receptor. UIRs function through the binding of an extracellular adapter domain which acts as a bridge between intracellular T cell signaling domains and a soluble tumor antigen targeting ligand (TL). The dissociation of TAA targeting and T cell signaling confers many advantages over standard CAR therapy, such as dose control of T cell effector function, the ability to simultaneously or sequentially target multiple TAAs, and control of immunologic synapse geometry. There are currently four unique UIR platform types: ADCC-mediating Fc-binding immune receptors, bispecific protein engaging immune receptors, natural binding partner immune receptors, and anti-tag CARs. These UIRs all allow for potential benefits over standard CARs, but also bring unique engineering challenges that will have to be addressed to achieve maximal efficacy and safety in the clinic. Still, UIRs present an exciting new avenue for adoptive T cell transfer therapies and could lead to their expanded use in areas which current CAR therapies have failed. Here we review the development of each UIR platform and their unique functional benefits, and detail the potential hurdles that may need to be overcome for continued clinical translation.
ANTI-IDIOTYPIC AND NON-ANTI-INDIOTYPIC ANTIBODIES TO OKT3 ARISING DESPITE INTENSE IMMUNOSUPPRESSION (1986)

The frequency, timing, and specificity of the humoral antibody response to a murine monoclonal antibody (OKT3, IgG2a) were measured in 21 consecutive renal allograft recipients. These patients received i.v. OKT3, 1-5 mg/day for 10-20 days as treatment for acute graft rejection. Maintenance immunosuppression consisted of azathioprine and corticosteroids. Using three different assays, an antibody response was detected in 75% of the 20 patients with adequate samples. The ELISA assay of the overall IgM and IgG reactivity to OKT3 revealed that IgM anti-OKT3 appeared in 65% and IgG anti-OKT3 in 50% of the patients, reaching a peak 20-33 days after the last dose of OKT3. The IgM preceeded the IgG in most cases (P less than 0.02) and in 8 cases was detected during therapy. One patient had high levels of IgM anti-OKT3 before therapy, yet responded normally to OKT3. Interference with the therapeutic effectiveness was evident in one patient who developed IgG antibodies during therapy. His serum blocked the binding of F-OKT3 to normal lymphocytes in the presence of normal BALB/c serum. The blocking assay, done by flow cytometry, measured anti-idiotypic (Id) reactivity since the sera did not affect the binding of OKT8 (another IgG2a) or anti-Leu4 (another anti-T3), and the blocking activity remained after affinity absorption with normal mouse IgG. Using this assay, 60% of the patients made an anti-Id response. One made only anti-Id, and several had anti-Id at times when other reactivities were undetectable. Antibodies to non-idiotypic, presumably isotypic, determinants represented on OKT8 occurred in only 44%, while other reactivity (OKT4; IgG2bK) was less common (12%) and weaker. While no adverse allergic reactions occurred in this group of patients, the anti-Id antibodies, which are a prominent feature of the immune response to this and probably other monoclonal antibodies, can block their therapeutic effectiveness and can arise despite intense immunosuppression. This response may require the use of different idiotypes for prolonged or repeated courses of therapy and may be the major obstacle to the use of human monoclonal antibodies.
An efficient on-demand routing approach with directional flooding for wireless mesh networks (2010)

Current on-demand ad-hoc routing protocols are not appropriate for wireless mesh networks (WMNs), because flooding-based route discovery is both redundant and expensive in terms of control message overhead. In this paper, we propose an efficient on-demand routing approach with directional flooding (DF), which is suitable for the WMNs with limited mobility. In the route discovery process to reach a gateway, our DF scheme can reduce the number of route request (RREQ) packets broadcast by using a restricted directional flooding technique. Simulation results show that ad hoc on-demand distance vector (AODV) with DF (AODV-DF) can significantly reduce routing overhead by RREQ packets and enhance overall performance compared with the original AODV.