gebhart/patrepeval huggingface dataset:
Understanding the Mechanism of Gelation and Stimuli-Responsive Nature of a Class of Metallo-Supramolecular Gels (2006)

Utilizing metal-ligand binding as the driving force for self-assembly of a ditopic ligand, which consists of a 2,6-bis-(1'-methylbenzimidazolyl)-4-oxypyridine moiety attached to either end of a penta(ethylene glycol) core, in the presence of a transition metal ion (Zn(II)) and a lanthanide metal ion (La(III)), we have achieved formation of stimuli-responsive metallo-supramolecular gels. We describe herein a series of experimental studies, including optical and confocal microscopy, dynamic light scattering, wide-angle X-ray diffraction, and rheology, to explore the properties of such gels, as well as the nature of the gelation mechanism. Morphological and X-ray diffraction observations suggest gelation occurs via the flocculation of semicrystalline colloidal particles, which results in the gels exhibiting pronounced yielding and thixotropic behavior. Application of mechanical stress results in a decrease in the particle size, which is accompanied by an increase in gel strength after removal of the stress. Moreover, studies show that the presence of lanthanide(III) perchlorate increases the mechano-responsiveness of the gels, as a consequence of reduced crystallinity of the colloidal particles, presumably due to the different coordination ability of lanthanide(III) and zinc(II), which changes the nature of the self-assembly in these materials.
Targeting of cells expressing wild‐type EGFR and type‐III mutant EGFR (EGFRvIII) by anti‐EGFR MAb ICR62: A two‐pronged attack for tumour therapy (2003)

With a view to their use in cancer therapy, we have produced rat monoclonal antibodies (MAbs) directed against 5 distinct epitopes (A-E) on the external domain of the wild-type human EGF receptor (EGFR). Here, we have investigated the relative binding and anti-tumour activity of our anti-EGFR MAbs against HC2 20d2/c cells, which have been engineered to overexpress the type-III mutated form of the human EGFR (EGFRvIII). We found that anti-EGFR MAbs that are the most effective antagonists of EGFR ligands (e.g., ICR16, ICR62 and ICR80) also bind to cells that overexpress the EGFRvIII. Although these antibodies are potent inhibitors of the growth of cells which express wild-type EGFR, they did not directly inhibit the growth in vitro of EGFRvIII expressing HC2 20d2/c cells, or the constitutive tyrosine kinase activity of this receptor. However, in the presence of human peripheral blood mononuclear cells (PBMC), the rat IgG2b MAb ICR62 induced strong antibody-dependent cell-mediated cytotoxicity (ADCC) against HC2 20d2/c cells in culture. Interestingly, MAb ICR62 also inhibited very effectively experimental lung metastases of HC2 20d2/c cells in athymic nude mice. Our results suggest that anti-EGFR MAb ICR62, which binds to the EGFRvIII, may have potential in the treatment of tumors which overexpress the EGFRvIII via immunological mechanisms such as ADCC. Since tumours that are EGFRvIII positive may also overexpress the wild-type EGFR, the use of anti-EGFR MAbs that target both wild-type and mutant receptors may have advantages over those that target only1form.
In vivo Cytotoxicity of Type I CD20 Antibodies Critically Depends on Fc Receptor ITAM Signaling (2010)

Antibody-Fc receptor (FcR) interactions play an important role in the mechanism of action of most therapeutic antibodies against cancer. Effector cell activation through FcR triggering may induce tumor cell killing via antibody-dependent cellular cytotoxicity (ADCC). Reciprocally, FcR cross-linking of antibody may lead to the induction of apoptotic signaling in tumor cells. The relative importance of these bisecting pathways to in vivo antibody activity is unknown. To unravel these roles, we developed a novel mouse model with normal FcR expression but in which FcR signaling was inactivated by mutation of the associated gamma-chain. Transgenic mice showed similar immune complex binding compared with wild-type mice. In contrast, ADCC of cells expressing frequently used cancer targets, such as CD20, epidermal growth factor receptor, Her2, and gp75, was abrogated. Using the therapeutic CD20 antibodies ofatumumab and rituximab, we show that FcR cross-linking of antibody-antigen immune complexes in the absence of gamma-chain signaling is insufficient for their therapeutic activity in vivo. ADCC therefore represents an essential mechanism of action for immunotherapy of lymphoid tumors.
CRYSTALSenhancements: dealing with hydrogen atoms in refinement (2010)

Because they scatter X-rays weakly, H atoms are often abused or neglected during structure refinement. The reasons why the H atoms should be included in the refinement and some of the consequences of mistreatment are discussed along with selected real examples demonstrating some of the features for hydrogen treatment that can be found in the software suite CRYSTALS .
Ex Vivo Gene Trasfer for Hemophilia A That Enhances Safety and Results in Sustained In Vivo Factor VIII Expression from Lentivirally-Engineered Endothelial Progenitors. (2006)

Abstract Hemophilia is an excellent candidate disorder for the use of gene therapy as a treatment modality. However, significant obstacles have been encountered with systemic delivery of viral vectors that have prevented sustained expression of the therapeutic protein. Investigation of alternative gene therapy strategies for hemophilia that enhance safety and facilitate long-term, therapeutic levels of the transgene product is imperative. In this study, we evaluated an ex vivo gene therapy strategy for hemophilia A. Circulating endothelial cell progenitors (blood outgrowth endothelial cells - BOECs) were isolated from canine and mouse blood and transduced with a third generation self-inactivating lentiviral vector encoding the canine FVIII transgene under the transcriptional control of either the CMV promoter or an endothelial cell-specific regulatory element. Transduced BOECs were injected either intravenously (IV) or subcutaneously mixed with Matrigel (SC+Matrigel) into NOD/SCID mice. Canine FVIII antigen levels were assayed at weekly intervals using an Asserachrom VIII:Ag ELISA that detects canine FVIII against a background of normal murine FVIII levels in the NOD/SCID mice. The mean FVIII antigen levels in mice injected with BOECs at 3 weeks following treatment were 37.5 mU/mL and 105.8mU/mL, for IV and SC+Matrigel administration, respectively. These FVIII antigen levels were sustained up to 12 weeks at therapeutic levels (21.3mU/mL and 21.7mU/mL, for IV and SC+Matrigel administration respectively). To evaluate if the observed loss of FVIII expression by 12 weeks post-treatment resulted from transcriptional silencing of the viral promoter, the CMV promoter was replaced with the endothelial cell-specific thrombomodulin (TM) promoter and transduced BOECs were implanted SC with Matrigel. In contrast to results from the CMV-regulated transgene, sustained therapeutic levels of FVIII have been documented for the duration of the study with the TM-regulated construct (34.3 mU/mL at 3 weeks and 22.5 mU/mL at 20 weeks) Immunostaining at 18 weeks after SC implantation of the transduced BOECs, shows that these cells still express FVIII and von Willebrand Factor. Biodistribution analysis by flow cytometry and quantitative PCR demonstrated that SC-implanted BOECs were retained inside the scaffold and were not detected at any other anatomic site. These results indicate that genetically-modified endothelial progenitors implanted in a SC scaffold can provide sustained therapeutic levels of FVIII and are a promising safe delivery vehicle for gene therapy of hemophilia. Currently, these engineered cells have been implanted into immunocompetant mice and FVIII levels are being assessed.
Efficient initialization and crash recovery for log-based file systems over flash memory (2006)

While flash memory has been widely adopted for storage systems for various embedded systems, issues on performance and reliability have started receiving growing attention in recent years. How to provide efficient roll back and quick mounting for flash-memory file systems has become important research topics in recent years, in addition to the work on effective garbage collection and superb run-time performance. Such an observation motivates our work on the investigation of efficient initialization and crash recovery of flash-memory file systems based on log structures. A methodology is proposed for the acceleration of mounting and crash recovery for log-based file systems. A system prototype based on a well-known flash-memory file system YAFFS was implemented with performance evaluation. The experimental results show that the proposed methodology can reduce the mounting time significantly, regardless of whether the file system is properly unmounted.
Comparison of the Ocular Hypotensive Effect of Brimonidine, Dorzolamide, Latanoprost, or Artificial Tears Added to Timolol in Glaucomatous Monkey Eyes (2000)

The addition of brimonidine, dorzolamide, or latanoprost to timolol caused similar additional reductions of IOP in glaucomatous monkey eyes.
PP.27.20 (2015)

Objective: Uric acid (UA) may induce growth of cardiomyocytes and interstitial fibrosis in animal models. However, clinical studies that investigated the relationship between UA and cardiac and carotid remodelling showed conflicting results. So we evaluated the relationship between UA levels and morphofunctional biventricular and carotid parameters in a cohort of mild hypertensive untreated patients. Design and method: We enrolled 152 consecutive non-smoking patients, without known cardiovascular diseases, gout or diabetes, never treated with antihypertensive drugs: 88 subjects had newly diagnosed hypertension (BP > 130 and/or 80 mmHg during ABPM), 64 normotensive subjects matched for age, sex and body mass index. All patients underwent: blood tests with evaluation of acid uric levels and renal function parameters, echocardiography with left (LV) and right ventricle (RV) morphofunctional evaluation, carotid ultrasonography. Results: UA levels were higher in hypertensive patients (5.3 ± 1.4 vs 4.6 ± 1.2 mg/dL, p 0.003). Renal function was in normal range and similar in the two groups. Univariate analysis showed a relationship between UA and: LV mass (r 0.212, p 0.009), midwall fractional shortening (r -0.183 p 0.02), relative wall thickness (r 0.199 p 0.01), right ventricle wall thickness (r 0.303 p 0.001), RV E’ (r -0.256 p 0.002), RV E/E’ (r 0.176 p 0.03), carotid intima-media thickness (r 0.176 p 0.03). We found no correlation between UA and diastolic LV function parameters. Conclusions: In a cohort of mild hypertensive untreated patients, uric acid levels correlate with morphofunctional biventricular and carotid parameters. Our results may underline a role of uric acid in the onset of morphofunctional biventricular and carotid remodelling. New prospectives studies are needed to confirm these data.
Heart Failure Decreases Nerve Activity in the Right Atrial Ganglionated Plexus (2011)

The RAGP-NA is essential for the vagal nerve to counterbalance the SG in sinus rate control. In HF, RAGP denervation and decreased RAGP-NA contribute to the sinus node dysfunction.
Binding studies and photoaffinity labeling identify two classes of phenycyclidine receptors in rat brain (1987)

Binding and photoaffinity labeling experiments were employed in order to differentiate 1-(1-phenylcyclohexyl)piperidine (PCP) receptor sites in rat brain. Two classes of PCP receptors were characterized and localized: one class binds [3H]-N-[1-(2-thienyl)cyclohexyl]piperidine [( 3H]TCP) with high affinity (Kd = 10-15 nM) and the other binds the ligand with a relatively low affinity (Kd = 80-100 nM). The two classes of sites have different patterns of distribution. Forebrain regions are characterized by high-affinity sites (hippocampus greater than frontal cortex greater than thalamus greater than olfactory bulb greater than hypothalamus), but some parts (e.g., hippocampus, hypothalamus) contain low-affinity sites as well. In the cerebellum only low-affinity sites were detected. Binding sites for [3H]PCP and for its photolabile analogue [3H]azido-PCP showed a regional distribution similar to that of the [3H]TCP sites. The neuroleptic drug haloperidol did not block binding to either the high- or the low-affinity [3H]TCP sites, whereas Ca2+ inhibited binding to both. Photoaffinity labeling of the PCP receptors with [3H]AZ-PCP indicated that five specifically labeled polypeptides of these receptors (Mr 90,000, 62,000, 49,000, 40,000, and 33,000) are unevenly distributed in the rat brain. Two of the stereoselectively labeled polypeptides (Mr 90,000 and 33,000) appear to be associated with the high- and low-affinity [3H]TCP-binding sites; the density of the Mr 90,000 polypeptide in various brain regions correlates well with the localization of the high-affinity sites, whereas the density of the Mr 33,000 polypeptide correlates best with the distribution of the low-affinity sites.(ABSTRACT TRUNCATED AT 250 WORDS)
Transplant Rejection (1993)

In this review, we summarize the cellular and molecular events in the rejection of transplanted allografts, as well as the rationale for the evolving techniques to suppress such rejection. Allogenic major histocompatibility complex antigens expressed on the allograft and/or on the "passenger leukocytes" within the graft are the major antigenic stimuli recognized as being foreign by receptors of CD4+/T helper cells of the host. Host macrophages provide a second signal, interleukin (IL) 1, essential to the activation of T helper cells. Subsequent production of IL-2 by T helper cells leads to activation and proliferation of cytotoxic T cells and lymphokine-activated killer cells and the release of IL-4 and IL-6. In addition, IL-2 promotes release of interferon gamma as well as tumor necrosis factor and other proinflammatory cytokines. Therapeutic options to "downregulate" this cascade have gradually evolved from global nonspecific immunosuppressive techniques (total body irradiation, antilymphocyte serum) to increasingly specific modalities currently being studied, including monoclonal antibodies against the IL-2 receptor (thus targeting only vigorously proliferating T cells), antibodies against specific cytokines (interferon gamma, tumor necrosis factor), and now "designer" antibody-toxin conjugate molecules that deliver toxins to selected receptor targets. Finally, work continues toward inducing preoperative antigen-specific (graft) tolerance, including utilization of gene transfection techniques to transfect donor major histocompatibility complex antigens to recipients before surgery, which has been shown to prolong murine cardiac allografts, perhaps by priming specific suppressor cells. Further understanding of the initiation of, and subsequent events in, transplantation rejection will lead to increasingly effective prolongation of graft survival while minimizing adverse effects on the host.
Current concepts and novel targets in advanced pancreatic cancer (2012)

Pancreatic cancer remains one of the most aggressive tumours with a 5-year survival rate of less than 5%. The dismal prognosis of this tumour entity that is associated with a high degree of drug resistance has not changed over the past decades. Since 1997, gemcitabine-based regimens have been the therapy of choice for advanced pancreatic cancer. Recently, however, new combination chemotherapy regimens achieved a significant survival benefit compared to gemcitabine-based therapies. In addition, novel approaches to improve drug delivery are currently being developed, and new drugs targeting signalling pathways both within the tumour cells and the tumour microenvironment are undergoing preclinical and clinical validation. Furthermore, efforts are being made to identify predictive markers for individualised treatment approaches based on molecular tumour characteristics. This review provides an overview on current and emerging concepts as well as novel targets for systemic treatment of advanced pancreatic cancer. Combination therapies incorporating drugs directed against these new targets may open new avenues for improving the efficacy of current treatment approaches and overcoming the devastating prognosis of pancreatic cancer patients.
Interpretation of Oligonucleotide Mass Spectra for Determination of Sequence Using Electrospray Ionization and Tandem Mass Spectrometry (1996)

Procedures are described for interpretation of mass spectra from collision-induced dissociation of polycharged oligonucleotides produced by electrospray ionization. The method is intended for rapid sequencing of oligonucleotides of completely unknown structure at approximately the 15-mer level and below, from DNA or RNA. Identification of sequence-relevant ions that are produced from extensive fragmentation in the quadrupole collision cell are based primarily on (1) recognition of 3'- and 5'- terminal residues as initial steps in mass ladder propagation, (2) alignment of overlapping nucleotide chains that have been constructed independently from each terminus, and (3) use of experimentally measured molecular mass in rejection of incorrect sequence candidates. Algorithms for sequence derivation are embodied in a computer program that requires < 2s for execution. The interpretation procedures are demonstrated for sequence location of simple forms of modification in the base and sugar. The potential for direct sequencing of components of mixtures is shown using an unresolved fraction of unknown oligonucleotides from ribosomal RNA.
T Cell Retargeting with MHC Class I-Restricted Antibodies: The CD28 Costimulatory Domain Enhances Antigen-Specific Cytotoxicity and Cytokine Production (2005)

T cells require both primary and costimulatory signals for optimal activation. The primary Ag-specific signal is delivered by engagement of the TCR. The second Ag-independent costimulatory signal is mediated by engagement of the T cell surface costimulatory molecule CD28 with its target cell ligand B7. However, many tumor cells do not express these costimulatory molecules. We previously constructed phage display derived F(AB), G8, and Hyb3, Ab-based receptors with identical specificity but distinct affinities for HLA-A1/MAGE-A1, i.e., "TCR-like" specificity. These chimeric receptors comprised the FcepsilonRI-gamma signaling element. We analyzed whether linking the CD28 costimulation structure to it (gamma + CD28) could affect the levels of MHC-restricted cytolysis and/or cytokine production. Human scFv-G8(POS) T lymphocytes comprising the gamma + CD28 vs the gamma signaling element alone produced substantially more IL-2, TNF-alpha, and IFN-gamma in response to HLA-A1/MAGE-A1(POS) melanoma cells. Also a drastic increase in cytolytic capacity of scFv-G8(POS) T cells, equipped with gamma + CD28 vs the gamma-chain alone was observed.
Allocating Uncertain and Unresponsive Resources: An Experimental Approach (1989)

We identify an important class of economic problems that arise naturally in several applications: the allocation of multiple resources when there are uncertainties in demand or supply, unresponsive supplies (no inventories and fixed capacities), and significant demand indivisibilities (rigidities). Examples of such problems include: scheduling job shops, airports, or supercomputers; zero-inventory planning; and the allocation and pricing of NASA's planned Space Station. Using experimental methods, we show that the two most common organizations used to deal with this problem, markets and administrative procedures, can perform at very low efficiencies (60-65% efficiency in a seemingly robust example). Thus, there is a need to design new mechanisms that more efficiently allocate resources in these environments. We develop and analyze two mechanisms that arise naturally from auctions used to allocate single-dimensional goods. These new mechanisms involve computer-assisted coordination made possible by the existence of networked computers. Both mechanisms significantly improve on the performance of administrative and market procedures.
A randomized trial of adding fluoxetine to a naltrexone treatment programme for heroin addicts (1998)

The study showed that the combination of fluoxetine and naltrexone produced significantly greater retention than in patients given only naltrexone. Placebo-controlled trials are warranted to assess how far this reflects a specific pharmacological effect.
Bounds and constructions for ternary constant-composition codes (2002)

The problem of determining the maximum size of a ternary code is considered, under the restriction that each symbol should appear a given number of times in each codeword. Upper and lower bounds on the size of such codes under the Hamming metric are discussed, where the lower bounds follow from constructions of good codes. Some of the results are obtained by explicitly finding codes by computer search. A table of exact values and best known bounds on the maximum size for codes of length at most 10 is presented.
Amino acid sequence of mammalian elongation factor 2 deduced from the cDNA sequence: homology with GTP-binding proteins. (1986)

Complementary DNA clones, pHEW1 and pRE2, coding for hamster and rat polypeptide chain elongation factor 2 (EF-2), respectively, were isolated and sequenced. It was shown that the cDNA insert in pHEW1 contains a 2574-base-pair open reading frame coding for an 857-amino acid polypeptide with Mr 95,192, excluding the initiation methionine. Comparative studies of sequence homology among EF-2 and several GTP-binding proteins show that five regions in the amino-terminal position of EF-2, corresponding to about 160 amino acids, show homology with GTP-binding proteins, including protein synthesis elongation and initiation factors, mammalian ras proteins, and transducin. The carboxyl-terminal half of EF-2 contains several regions that have 34-75% homology with bacterial elongation factor G. These results suggest that the amino-terminal region of EF-2 participates in the GTP-binding and GTPase activity whereas the carboxyl-terminal region interacts with ribosomes. Finally, the sequence provides direct evidence that diphthamide (2-[3-carboxy-amido-3-(trimethylammonio)propyl]histidine), the site of ADP-ribosylation by diphtheria toxin, is produced by post-translational modification of a histidine residue in the primary translational product.
Isolation and sequencing of the gene coding for an antigenic 34-kilodalton protein of Mycobacterium paratuberculosis (1993)

The gene coding for an antigenic 34-kDa protein of Mycobacterium paratuberculosis was isolated and sequenced. The 897-bp open reading frame coded for a novel protein containing specific B epitopes. The occurrence of well-defined hydrophobic and hydrophilic portions suggests the wall location of the protein.