gebhart/patrepeval huggingface dataset:
Rational Design of Nonlinear Optical Materials Based on 2D Coordination Networks (2001)

Zinc(II) and cadmium(II) coordination networks with m-pyridinecarboxylate bridging ligands, Zn(nicotinate)2, 1, Cd(nicotinate)2, 2, Cd{3-[2-(4-pyridyl)ethenyl]benzoate}2, 3, Zn4{3-[2-(4-pyridyl)ethenyl]benzoate}8·{3-[2-(4-pyridyl)ethenyl]benzoic acid}·(H2O), 4, Zn{4-[2-(3-pyridyl)ethenyl]benzoate}2·H2O, 5, and Zn{5-[2-(3-pyridyl)ethenyl]thiophene-2-carboxylate}2, 6, have been synthesized under hydro(solvo)thermal conditions. With the exception of 5, these compounds adopt 2D grid structures. The use of unsymmetrical bent m-pyridinecarboxylate ligands leads to the formation of intrinsically acentric 2D grids which provide an interesting structural motif for the rational synthesis of polar solids. Compounds 1 and 3−5 are non-centrosymmetric and show significant powder second harmonic generation efficiencies. Compound 2 adopts a centrosymmetric structure due to the presence of a μ2,η3-carboxylate bridge, while compound 6 adopts a centrosymmetric structure due to the presence of 2-fold interpenetration. The present work illustrates the potential of rational synthesis of nonlinear-optical-active acentric solids by exploiting the propensity of the formation of 2D coordination networks based on bent linking groups. Crystal data for 1: tetragonal space group P43212, a = 7.709(1) Å, b = 7.709(1) Å, c = 20.327 Å, and Z = 8. Crystal data for 2: monoclinic space group P21/n, a = 10.055(1) Å, b = 10.219(1) Å, c = 12.733(1) Å, β = 105.169(2)o, and Z = 4. Crystal data for 3: orthorhombic space group Fdd2, a = 20.622(1) Å, b = 36.426(1) Å, c = 6.241(1) Å, and Z = 8. Crystal data for 4: monoclinic space group Cc, a = 21.875(2) Å, b = 15.158(1) Å, c = 32.863(2) Å, β = 102.997(1), and Z = 4. Crystal data for 5: orthorhombic space group P21212, a = 7.625(1) Å, b = 25.430(2) Å, c = 5.863(1) Å, and Z = 4. Crystal data for 6: orthorhombic space group Pcca, a = 17.150(2) Å, b = 9.966(1) Å, c = 12.108(2) Å, and Z = 8.
Rationale for clinical use of immunotoxins in cancer and autoimmune disease. (1991)

Immunotoxins constructed by conjugating monoclonal antibodies to plant and bacterial toxin molecules are being evaluated clinically for the treatment of cancer and as immunosuppressive agents in treating autoimmune diseases. Immunoconjugates constructed with ricin A-chain and in certain indications, whole ricin have been most extensively investigated. The experience with these immunotoxins has highlighted issues to be dealt with in order to improve therapeutic efficacy. Immunotoxins containing ricin A-chain conjugated to monoclonal antibody reacting with the CD5 molecule on T lymphocytes has proved most efficacious in treating acute graft versus host disease (aGvHD) in patients receiving bone marrow transplants as part of a regimen of high dose chemotherapy in leukaemias and lymphomas. This involved immunotoxin used after the onset of a GvHD or prophylactically to reduce the development of the condition. Immunotoxin treatment of leukaemias and lymphomas is also showing promise with clinical responses being observed. In comparison, treatment of solid cancers such as colorectal cancer and malignant melanoma has not yet proved effective. Factors to be resolved in order to improve treatment include better pharmacokinetic properties of immunotoxins, improved tumour penetration and the use of antibody cocktails to accommodate antigenic heterogeneity of tumours.
Defective dimerization of von Willebrand factor subunits due to a Cys-> Arg mutation in type IID von Willebrand disease. (1996)

The same heterozygous T -> C transition at nt 8567 of the von Willebrand factor (vWF) transcript was found in two unrelated patients with type III) von Willebrand disease, with no other apparent abnormality. In one family, both alleles were normal in the parents and one sister; thus, the mutation originated de novo in the proposita. The second patient also had asymptomatic parents who, however, were not available for study. The structural consequences of the identified mutation, resulting in the CyS2010 -> Arg substitution, were evaluated by expression of the vWF carboxyl-terminal domain containing residues 1366-2050. Insect cells infected with recombinant baculovirus expressing normal vWF sequence secreted a disulfide linked dimeric molecule with an apparent molecular mass of 150 kDa before reduction, yielding a single band of 80 kDa after disulfide bond reduction. In contrast, cells expressing the mutant fragment secreted a monomeric molecule of apparent molecular mass of 80 kDa, which remained unchanged after reduction. We conclude that CyS2010 is essential for normal dimerization of vWF subunits through disulfide bonding of carboxyl-terminal domains and that a heterozygous mutation in the corresponding codon is responsible for defective multimer formation in type III) von Willebrand disease.
Pomalidomide Cyclophosphamide and Prednisone (PCP) Treatment for Relapsed/Refractory Multiple Myeloma (2012)

Abstract Abstract 446 Background: The outcome of myeloma (MM) patients who are no longer responding to thalidomide, lenalidomide or bortezomib is poor, with a median event-free survival of 5 months and median overall survival (OS) of 9 months (Kumar SK et al, Leukemia 2012). The newer immunomodulatory drug pomalidomide, has shown significant activity in these clinical conditions. Aims: We assessed dosing, efficacy and safety of pomalidomide-cyclophosphamide-prednisone (PCP) in MM patients relapsed/refractory to lenalidomide. Methods: Pomalidomide was administered in doses ranging from 1 to 2.5 mg/day on days 1–28, cyclophosphamide at 50 mg every other day on days 1–28 and prednisone at 50 mg every other day on days 1–28 for 6 cycles, followed by maintenance therapy with pomalidomide-prednisone. Thromboprophylaxis with aspirin 100 mg/day or low-molecular weight heparin was recommended at physician's discretion. Results: The maximum tolerated dose (MTD) of pomalidomide was defined as 2.5 mg/day. Fifty-two patients were enrolled at the MTD and evaluated after completing at least 1 PCP cycle. Median age was 69 years (range 41–83). The median time from diagnosis to enrolment was 55 months (range 15–203). Best responses to PCP included 6% of complete response (CR), 19% of at least very good partial response (VGPR), 54% of at least partial response (PR) and 75% of at least minimal response (MR). Time to PR was rapid (median 1.8 months). After a median follow-up of 11 months (range 1–18), 1-year progression-free survival (PFS) and OS rates were 52% and 78%, respectively. PFS was not significantly different in patients with high-risk cytogenetic compared with patients with standard-risk disease and in patients younger or older than 75 years. Toxicities were primarily hematologic and included grade 4 neutropenia (13%) and thrombocytopenia (4%). At least grade 3 non-hematologic toxicities included infections (8%), rash (6%) and neurologic (6%). Thromboembolism occurred in 1 patient. Four patients discontinued treatment for toxicity (2 infections, 1 neurologic and 1 hepatic toxicity). Conclusions: PCP induced high response rates and prolonged PFS after prior exposure to lenalidomide and bortezomib (Table), without adding significant toxicity. PCP could be considered a valuable salvage option for pre-treated MM patients. Disclosures: Palumbo: Celgene: Consultancy, Honoraria. Larocca:Celgene: Honoraria. Sciacca:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Guglielmelli:Celgene: Honoraria. Giuliani:Celgene: Research Funding. Boccadoro:Celgene: Consultancy, Honoraria.
A randomized trial of fluorouracil and folinic acid in patients with metastatic colorectal carcinoma. (1988)

We determined the therapeutic effect of fluorouracil (5-FU) in combination with folinic acid (FA) in patients with measurable recurrent or metastatic carcinoma of the colon or rectum by comparing it to standard 5-FU therapy in a prospective randomized controlled trial. Patients were randomized to receive either FA, 200 mg/m2/d for five consecutive days, or nothing. All patients received 5-FU, 370 mg/m2/d for five days on the first course, with subsequent dose modifications to maintain equal toxicity in the two arms. One hundred thirty patients were entered on trial and only five were excluded from the analysis because they did not meet the eligibility criteria or they refused therapy after randomization. The two treatment arms were balanced for 11 clinical characteristics. Patients were evaluated for response at the end of every two treatment courses and toxicity after every course of therapy. Median follow-up was 1.45 years. Dose-limiting toxicity was mucositis and diarrhea on this treatment schedule, although neutropenia was apparent. The response rate was 33% (21 of 63 patients) in the 5-FU and FA arm and was 7% (four of 61 patients) in the 5-FU arm (P less than .0005). Time to disease progression was significantly different in the combination arm as compared with the single-agent arm (P = .023). Overall survival was significantly longer for patients treated with 5-FU and FA as compared with those receiving 5-FU alone (P = .05). The median survival was 12.6 months for patients receiving the combination, and 9.6 months for those receiving 5-FU alone. Our results indicate that the combination of 5-FU and FA is effective treatment for patients with metastatic or recurrent carcinoma of the rectum and colon who have not received prior chemotherapy.
Evaluation of Outcomes With Citalopram for Depression Using Measurement-Based Care in STAR*D: Implications for Clinical Practice (2006)

The response and remission rates in this highly generalizable sample with substantial axis I and axis III comorbidity closely resemble those seen in 8-week efficacy trials. The systematic use of easily implemented measurement-based care procedures may have assisted in achieving these results.
Biochemical properties of glutamate synthase of salt-tolerantBradyrhizobiumsp. strain WR1001 (1986)

Accumulation of high levels of intracellular glutamate was a common response of a variety of bacteria to osmotic stress. We characterized the NADPH-dependent glutamate synthase (GOGAT) in Bradyrhizobium sp. strain WR1001. This enzyme had a pH optimum in the region of 8.3, as compared to 7.6 for most other Rhizobium strains reported in the literature. The enzyme was not inhibited by the end product, glutamate, in the range 50–200 mM.
CRISPR-spacer integration reporter plasmids reveal distinct genuine acquisition specificities among CRISPR-Cas I-E variants ofEscherichia coli (2013)

Prokaryotes immunize themselves against transmissible genetic elements by the integration (acquisition) in clustered regularly interspaced short palindromic repeats (CRISPR) loci of spacers homologous to invader nucleic acids, defined as protospacers. Following acquisition, mono-spacer CRISPR RNAs (termed crRNAs) guide CRISPR-associated (Cas) proteins to degrade (interference) protospacers flanked by an adjacent motif in extrachomosomal DNA. During acquisition, selection of spacer-precursors adjoining the protospacer motif and proper orientation of the integrated fragment with respect to the leader (sequence leading transcription of the flanking CRISPR array) grant efficient interference by at least some CRISPR-Cas systems. This adaptive stage of the CRISPR action is poorly characterized, mainly due to the lack of appropriate genetic strategies to address its study and, at least in Escherichia coli, the need of Cas overproduction for insertion detection. In this work, we describe the development and application in Escherichia coli strains of an interference-independent assay based on engineered selectable CRISPR-spacer integration reporter plasmids. By using this tool without the constraint of interference or cas overexpression, we confirmed fundamental aspects of this process such as the critical requirement of Cas1 and Cas2 and the identity of the CTT protospacer motif for the E. coli K12 system. In addition, we defined the CWT motif for a non-K12 CRISPR-Cas variant, and obtained data supporting the implication of the leader in spacer orientation, the preferred acquisition from plasmids harboring cas genes and the occurrence of a sequential cleavage at the insertion site by a ruler mechanism.
Fabrication of silicon nanostructures with a scanning tunneling microscope (1993)

A technique is presented for fabricating Si nanostructures with a scanning tunneling microscope operated in air. The process involves the direct chemical modification of a H-passivated Si(100) surface and a subsequent liquid etch. The chemically modified portions of the surface can withstand a deep (≳100 nm) liquid etch of the unmodified regions with no etch degradation of the modified surface. At a write speed of 1–10 μm/s, large-area (50 μm×50 μm) patterns with lateral feature sizes ∼25 nm are reliably fabricated.
Computer-Aided Design of Catalysts (2020)

Introduction, E. Robert Becker and Carmo J. Pereira Microkinetic Analysis and Catalytic Reaction Synthesis for Methane Partial Oxidation, Ma.-Guadalupe Cadenas-Galindo, Luis M. Aparicio, Dale F. Rudd, and James A. Dumesic Catalyst-Based Descriptions of Catalytic Cracking Chemistry, David T. Allen, Pradeep Marathe, and Robert H. Harding Molecular Simulation of Kinetic Interactions in Complex Mixtures, Matthew Neurock, Scott M. Stark, and Michael T. Klein Simulation Techniques for the Characterization of Structural and Transport Properties of Catalyst Pellets, Sebastian C. Reyes and Enrique Iglesia Optimal Distribution of Catalyst in Pellets, Asterios Gavriildis, Arvind Varma, and Massimo Morbidelli Reaction-Transport Selectivity Models and the Design of Fischer-Tropsch Catalysts, Enrique Iglesia, Sebastian C. Reyes, and Stuart L. Soled Catalytic Converter Modeling for Automotive Emission Control, Se H. Oh Design of Monolithic Catalysts for Improved Transient Performance, Kyriacos Zygourakis Modeling of Polymerization Processes, Kyu-Yong Choi Impact of Wetting on Catalyst Performance in Multiphase Reactions Systems, Michael P. Harold Catalytic Membrane Reactors, Theodore T. Tsotsis, Althea M. Champagnie, Ronald G. Minet, and Paul K. T. Liu Some Aspects of Modeling in Petroleum Processing, Ajit V. Sapre and James R. Katzer
Implementation of Adjoint Solution for Optimal Control of Smart Wells (2005)

Abstract Practical production optimization problems typically involve large, highly complex reservoir models, thousands of unknowns and many nonlinear constraints, which makes the numerical calculation of gradients for the optimization process impractical. This work explores a new algorithm for production optimization using optimal control theory. The approach is to use the underlying simulator as the forward model and its adjoint for the calculation of gradients. Direct coding of the adjoint model is, however, complex and time consuming, and the code is dependent on the forward model in the sense that it must be updated whenever the forward model is modified. We investigate an adjoint procedure that avoids these limitations. For a fully implicit forward model and specific forms of the cost function and nonlinear constraints, all information necessary for the adjoint run is calculated and stored during the forward run itself. The adjoint run then requires only the appropriate assembling of this information to calculate the gradients. This makes the adjoint code essentially independent of the forward model and also leads to enhanced efficiency, as no calculations are repeated. Further, we present an efficient approach for handling nonlinear constraints that also allows us to readily apply commercial constrained optimization packages. The forward model used in this work is the General Purpose Research Simulator (GPRS), a highly flexible compositional/black oil research simulator developed at Stanford University. Through two examples, we demonstrate that the linkage proposed here provides a practical strategy for optimal control within a general-purpose reservoir simulator. These examples illustrate production optimization with conventional wells as well as with smart wells, in which well segments can be controlled individually.
An overexpression of fibroblast growth factor (FGF) and FGF receptor 4 in a severe clinical phenotype of facioscapulohumeral muscular dystrophy (2000)

We evaluated the expression of a select panel of growth factors and their receptors, including fibroblast growth factor 1 (FGF-1), fibroblast growth factor 2 (FGF-2), platelet-derived growth factor (PDGF), FGF receptor 1 (FGF-R1), FGF receptor 3 (FGF-R3), FGF receptor 4 (FGF-R4), PDGF receptor alpha (PDGF-Ralpha), PDGF receptor beta (PDGF-Rbeta), and heparan sulfate proteoglycan (HSPG), in muscle biopsy specimens from nine facioscapulohumeral muscular dystrophy (FSHD) patients using immunohistochemistry. Two cases of Duchenne-type muscular dystrophy (DMD), two of Becker-type muscular dystrophy (BMD), and one of limb-girdle-type muscular dystrophy (LGMD) were also investigated. Widespread immunostaining for FGF-1 and FGF-2 on the sarcolemma and overexpression of FGF-R4 in endomysial and perimysial connective tissue were seen in one patient with a severe clinical phenotype of FSHD who had respiratory failure. Standard histochemistry in this patient revealed marked interstitial fibrosis and lobulated fibers. The overexpression of FGF and FGF-R4 in this severe FSHD case may be associated with the muscle fibrosis and disease severity.
Methicillin-Resistant Staphylococcus aureus (MRSA) Detection: Comparison of Two Molecular Methods (IDI-MRSA PCR Assay and GenoType MRSA Direct PCR Assay) with Three Selective MRSA Agars (MRSA ID, MRSA Select , and CHROMagar MRSA) for Use with Infection-Control Swabs (2007)

Methicillin-resistant Staphylococcus aureus (MRSA) is an increasing problem. Rapid detection of MRSA-colonized patients has the potential to limit spread of the organism. We evaluated the sensitivities and specificities of MRSA detection by two molecular methods (IDI-MRSA PCR assay and GenoType MRSA Direct PCR assay) and three selective MRSA agars (MRSA ID, MRSASelect, and CHROMagar MRSA), using 205 (101 nasal, 52 groin, and 52 axillary samples) samples from consecutive known MRSA-infected and/or -colonized patients. All detection methods had higher MRSA detection rates for nasal swabs than for axillary and groin swabs. Detection of MRSA by IDI-MRSA was the most sensitive method, independent of the site (94% for nasal samples, 80% for nonnasal samples, and 90% overall). The sensitivities of the GenoType MRSA Direct assay and the MRSA ID, MRSASelect, and CHROMagar MRSA agars with nasal swabs were 70%, 72%, 68%, and 75%, respectively. All detection methods had high specificities (95 to 99%), independent of the swab site. Extended incubation for a further 24 h with selective MRSA agars increased the detection of MRSA, with a corresponding decline in specificity secondary to a significant increase in false-positive results. There was a noticeable difference in test performance of the GenoType MRSA Direct assay in detection of MRSA (28/38 samples [74%]) compared with detection of nonmultiresistant MRSA (17/31 samples [55%]) (susceptible to two or more non-beta-lactam antibiotics). This was not observed with selective MRSA agar plates or IDI-MRSA. Although it is more expensive, in addition to rapid turnaround times of 2 to 4 h, IDI-MRSA offers greater detection of MRSA colonization, independent of the swab site, than do conventional selective agars and GenoType MRSA Direct.
Ovarian Response to Follicle-Stimulating Hormone (FSH) Stimulation Depends on the FSH Receptor Genotype* (2000)

Because the ovarian response to FSH stimulation in assisted reproduction is variable, ranging from hyporesponse to hyperresponse, with the possible complication of ovarian hyperstimulation, it would be of great benefit to predict the response of the patients to FSH. To date, no clear-cut predictors of ovarian responsiveness to FSH have been identified. In this study, we investigated the role of two distinct FSH receptor (FSHR) variants, Thr307/Asn680 and Ala307/Ser680, in the response to FSH in women undergoing controlled ovarian stimulation. The FSHR polymorphism at position 680 was analyzed by restriction-fragment-length polymorphism in 161 ovulatory women below the age of 40 yr. With reference to the couple, infertility has been diagnosed as being attributable to male causes (76%), tubal factor (11%), or both (13%). The distribution was 29% for the Asn/Asn, 45% for the Asn/Ser, and 26% for the Ser/Ser FSHR variant. Peak estradiol levels, number of preovulatory follicles, and number of retrieved oocytes were similar in the 3 groups. However, basal FSH levels were significantly different among the 3 groups (6.4 +/- 0.4 IU/L, 7.9 +/- 0.3 IU/L, and 8.3 +/- 0.6 IU/L for the Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively, P < 0.01). The number of FSH ampoules required for successful stimulation was significantly different among the 3 groups (31.8 +/- 2.4, 40.7 +/- 2.3, and 46.8 +/- 5.0 for the Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively, P < 0.05). According to multiple linear regression analysis, the number of ampoules needed could be predicted from a linear combination of both the type of polymorphism and basal FSH levels (P < 0.001). These clinical findings demonstrate that the ovarian response to FSH stimulation depends on the FSHR genotype.
Cocurrent downflow circulating fluidized bed (downer) reactors — A state of the art review (1995)

Abstract In the last decade, cocurrent downflow circulating fluidized bed reactors, called “downer” reactors, have been proposed as an alternative to upflow circulating fluidized bed, or “riser”, reactors. In this paper, published results on downer studies are summarized and future directions of research are recommended. Downer reactors are shown to have several distinct advantages over upflow circulating fluidized bed reactors and can potentially be used in many industrial processes, mainly due to a more uniform gas and solids flow structure compared with risers.
Genome editing for scalable production of alloantigen‐free lentiviral vectors for in vivo gene therapy (2017)

Lentiviral vectors (LV) are powerful and versatile vehicles for gene therapy. However, their complex biological composition challenges large-scale manufacturing and raises concerns for <i>in vivo</i> applications, because particle components and contaminants may trigger immune responses. Here, we show that producer cell-derived polymorphic class-I major histocompatibility complexes (MHC-I) are incorporated into the LV surface and trigger allogeneic T-cell responses. By disrupting the beta-2 microglobulin gene in producer cells, we obtained MHC-free LV with substantially reduced immunogenicity. We introduce this targeted editing into a novel stable LV packaging cell line, carrying single-copy inducible vector components, which can be reproducibly converted into high-yield LV producers upon site-specific integration of the LV genome of interest. These LV efficiently transfer genes into relevant targets and are more resistant to complement-mediated inactivation, because of reduced content of the vesicular stomatitis virus envelope glycoprotein G compared to vectors produced by transient transfection. Altogether, these advances support scalable manufacturing of alloantigen-free LV with higher purity and increased complement resistance that are better suited for <i>in vivo</i> gene therapy.