gebhart/patrepeval huggingface dataset:
Generation and Characterization of Human Monoclonal scFv Antibodies against Helicobacter pylori Antigens (2002)

Infection with Helicobacter pylori is chronic despite a vigorous cellular and humoral immune response and causes severe pathology in some patients. In this study, phage display was used as a new approach in order to investigate the role of the host's humoral immune response in the pathogenesis of H. pylori gastritis. Human monoclonal single-chain Fv (scFv) antibody fragments against H. pylori cell lysate and the H. pylori urease were isolated from an immune phage display library, constructed from peripheral blood lymphocytes of an H. pylori-infected patient. After affinity selection, 23% of the clones tested showed binding activity against a lysate of the H. pylori Sydney strain in enzyme-linked immunosorbent assay (ELISA) and 9% bound the H. pylori urease. Further characterization by PCR-fingerprint analysis and sequencing revealed that two closely related H. pylori binders and one antiurease scFv could be isolated. The selected scFvs were highly specific as analyzed by ELISA and immunoblots using various bacterial lysates and recombinant proteins. Analysis of the humoral immune response following H. pylori infection using human monoclonal antibodies might contribute to a better understanding of the pathogenesis of the disease. Moreover, using immune phage display libraries, it might be possible for relevant epitopes of H. pylori antigens to be determined, which might be of use for vaccine development.
High-Flux Solar-Driven Thermochemical Dissociation of CO 2 and H 2 O Using Nonstoichiometric Ceria (2010)

Because solar energy is available in large excess relative to current rates of energy consumption, effective conversion of this renewable yet intermittent resource into a transportable and dispatchable chemical fuel may ensure the goal of a sustainable energy future. However, low conversion efficiencies, particularly with CO(2) reduction, as well as utilization of precious materials have limited the practical generation of solar fuels. By using a solar cavity-receiver reactor, we combined the oxygen uptake and release capacity of cerium oxide and facile catalysis at elevated temperatures to thermochemically dissociate CO(2) and H(2)O, yielding CO and H(2), respectively. Stable and rapid generation of fuel was demonstrated over 500 cycles. Solar-to-fuel efficiencies of 0.7 to 0.8% were achieved and shown to be largely limited by the system scale and design rather than by chemistry.
Neonatal AAV delivery of alpha-synuclein induces pathology in the adult mouse brain (2017)

Abnormal accumulation of alpha-synuclein (αsyn) is a pathological hallmark of Lewy body related disorders such as Parkinson's disease and Dementia with Lewy body disease. During the past two decades, a myriad of animal models have been developed to mimic pathological features of synucleinopathies by over-expressing human αsyn. Although different strategies have been used, most models have little or no reliable and predictive phenotype. Novel animal models are a valuable tool for understanding neuronal pathology and to facilitate development of new therapeutics for these diseases. Here, we report the development and characterization of a novel model in which mice rapidly express wild-type αsyn via somatic brain transgenesis mediated by adeno-associated virus (AAV). At 1, 3, and 6 months of age following intracerebroventricular (ICV) injection, mice were subjected to a battery of behavioral tests followed by pathological analyses of the brains. Remarkably, significant levels of αsyn expression are detected throughout the brain as early as 1 month old, including olfactory bulb, hippocampus, thalamic regions and midbrain. Immunostaining with a phospho-αsyn (pS129) specific antibody reveals abundant pS129 expression in specific regions. Also, pathologic αsyn is detected using the disease specific antibody 5G4. However, this model did not recapitulate behavioral phenotypes characteristic of rodent models of synucleinopathies. In fact no deficits in motor function or cognition were observed at 3 or 6 months of age. Taken together, these findings show that transduction of neonatal mouse with AAV-αsyn can successfully lead to rapid, whole brain transduction of wild-type human αsyn, but increased levels of wildtype αsyn do not induce behavior changes at an early time point (6 months), despite pathological changes in several neurons populations as early as 1 month.
The strategic use of antiestrogens to control the development and growth of breast cancer. (1992)

Tamoxifen has become the endocrine treatment of choice for all stages of breast cancer. Its low incidence of side effects and proven survival advantage observed during adjuvant therapy in postmenopausal women with node-positive disease has encouraged the use of long-term treatment for patients to benefit fully from therapy. The drug has an appropriate level of estrogen-like effects that could be beneficial to maintain bone density and prevent development of coronary heart disease by lowering circulating cholesterol. These effects might be useful in all patients with estrogen receptor-positive breast cancer who currently are receiving no therapy. This antiestrogenic agent could be effective therapy to deter recurrence, and the estrogen-like side effects support the physiologic processes of the patient as hormone-replacement therapy. In the laboratory, a tamoxifen-stimulated breast cancer model has been described in vivo. This form of drug resistance may occur in patients after long-term or indefinite adjuvant therapy. Novel pure antiestrogenic drugs have been discovered that soon will become available as second-line therapy after tamoxifen failure. In addition, tamoxifen is being evaluated in the United Kingdom as chemosuppressive therapy to prevent the development of breast cancer in high-risk women. A similar clinical evaluation is underway in the United States.
Immunogenicity and Safety of a Multicomponent Meningococcal Serogroup B Vaccine and a Quadrivalent Meningococcal CRM 197 Conjugate Vaccine against Serogroups A, C, W-135, and Y in Adults Who Are at Increased Risk for Occupational Exposure to Meningococcal Isolates (2010)

Laboratory staff who work with meningococcal isolates are at increased risk for developing invasive disease relative to the general population. This was the first study of laboratory workers who received both a conjugate vaccine against meningococcal serogroups A, C, W-135, and Y (Men ACWY-CRM, Menveo) and an investigational multicomponent vaccine against serogroup B containing factor H binding protein, neisserial adhesin A, Neisseria heparin binding antigen, and New Zealand strain outer membrane vesicles (4CMenB). Healthy adults (18 to 50 years of age) received three doses of 4CMenB at baseline, 2 months, and 6 months followed by a single dose of MenACWY-CRM 1 month later. Immunogenicity was assessed via serum bactericidal assay using human complement (hSBA) at 1 month postvaccination; solicited reactogenicity and adverse events were monitored. Fifty-four participants enrolled. Bactericidal immune responses were evident after each dose of 4CMenB, as assessed by hSBA geometric mean titers and percentages of subjects with hSBA titers of ≥4 against the test strains or a 4-fold rise in titer over baseline. At 1 month postvaccination, most MenACWY-CRM recipients had hSBA titers of ≥8 against serogroups A, C, W-135, and Y. Few participants discontinued due to an adverse event or vaccine reaction. Rates of solicited reactions were lower after MenACWY-CRM than after 4CMenB administration. Sequential administration of 4CMenB and MenACWY-CRM provided robust evidence of an immune response against serogroups A, B, C, W-135, and Y in laboratory workers routinely exposed to meningococcal isolates.
The basic residues of placenta growth factor type 2 retrieve sequestered angiogenic factors into a soluble form: implications for tumor angiogenesis. (1998)

Placenta growth factor type 1 (PIGF-1) can be synthesized by neoplastic cells in an alternative form (PIGF-2) by the addition of basic amino acids to its classic sequence. Here we show that the basic residues of PIGF-2 compete for the binding of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) to heparan sulfate proteoglycans of the cell surface and extracellular matrix. In doing so, PIGF-2 basic sequences inhibit the sequestering of VEGF and bFGF and maintain them in a highly diffusible form, thus enhancing their angiogenic effect. In agreement with these in vitro data, the presence of PIGF-2 transcripts in tumors correlates with their blood vessel number. These results suggest a mechanism by which growth factor isoforms produced by neoplastic cells enhance the formation of new blood vessels supporting tumor growth and progression.
The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. (1998)

The Mini-International Neuropsychiatric Interview (M.I.N.I.) is a short structured diagnostic interview, developed jointly by psychiatrists and clinicians in the United States and Europe, for DSM-IV and ICD-10 psychiatric disorders. With an administration time of approximately 15 minutes, it was designed to meet the need for a short but accurate structured psychiatric interview for multicenter clinical trials and epidemiology studies and to be used as a first step in outcome tracking in nonresearch clinical settings. The authors describe the development of the M.I.N.I. and its family of interviews: the M.I.N.I.-Screen, the M.I.N.I.-Plus, and the M.I.N.I.-Kid. They report on validation of the M.I.N.I. in relation to the Structured Clinical Interview for DSM-III-R, Patient Version, the Composite International Diagnostic Interview, and expert professional opinion, and they comment on potential applications for this interview.
Improved quality factor spiral inductors on GaAs substrates (1999)

We present test data for several spiral inductors with improved quality factors fabricated on GaAs substrates. It has been shown experimentally that the quality factor of spiral inductors can be increased by reducing magnetically induced currents and by narrowing the line width of the inner turns similar to the one reported for silicon micromachined inductor. Using this technique, we observed about 22% improvement in the quality factor of spiral inductors as compared to standard spiral inductors having constant line width.
Estrogen Receptor Expression in Benign Breast Epithelium and Breast Cancer Risk (1998)

The overexpression of estrogen receptors in normal breast epithelium may augment estrogen sensitivity and hence the risk of breast cancer.
Putrescine Breakdown in the Yeast Candida boidinii: Subcellular Location of Some of the Enzymes Involved and Properties of Two Acetamidoaldehyde Dehydrogenases (1987)

SUMMARY: Two acetamidoaldehyde dehydrogenases were identified in Candida boidinii grown on putrescine as sole nitrogen source with glucose as carbon source. One of them, enzyme A, although present when cells were grown on ammonium or l-lysine, increased in activity when cells were grown on putrescine or spermidine. The other, enzyme B, was absent when the putrescine was replaced by l-lysine or ammonium, but was present if the nitrogen source was spermidine or acetylputrescine. Both dehydrogenases were active with NAD+ or NADP+ as electron acceptor. Apparent K m values for 3-acetamidopropionaldehyde and 4-acetamidobutyr-aldehyde were respectively 0·83 mM and 0·041 mM for enzyme A and 0·077 mM and 0·015 mM for enzyme B. Enzyme A was competitively inhibited by chloral hydrate with a K i of 0·6 mM, whiile enzyme B was unaffected. Both enzymes were slightly (20%) stimulated by 50 mM-KCl. Although both enzymes catalysed the oxidation of a range of aldehyde substrates, and are thus both general aldehyde dehydrogenases, it is suggested that acetamidoaldehyde dehydrogenase B is more probably specifically involved in putrescine degradation. Subcellular fractionation of spheroplast lysates showed that enzyme B was cytosolic, remaining unsedimented at 100000 g, while enzyme A co-sedimented with mitochondrial marker enzymes in a sucrose density gradient. It was also shown that acetamidoalkanoate deacetylase and acetylputrescine oxidase activities, two other key enzymes in the breakdown of putrescine and spermidine, were respectively cytosolic and peroxisomal in their location in the cell.
Targeting Signal Transduction Pathways in Metastatic Breast Cancer: A Comprehensive Review (2010)

Greater understanding of the underlying etiology and biology of breast cancer is enabling the clinical development of targeted therapies for metastatic breast cancer (MBC). Following the successful introduction of trastuzumab, the first human epidermal growth factor receptor (HER) biologically targeted therapy to become widely used in MBC patients, other agents have been developed. Novel agents include monoclonal antibodies such as pertuzumab, which bind to receptors on the cell surface, and tyrosine kinase inhibitors (TKIs) such as lapatinib, which target intracellular pathways such as that of the epidermal growth factor receptor. There is also growing clinical experience with antiangiogenic agents, particularly in combination with chemotherapy. These include the monoclonal antibody bevacizumab, which targets vascular endothelial growth factor receptor, and multitargeted TKIs with antiangiogenic and antiproliferative activities, such as sunitinib. Combination treatment with multiple agents targeting both the HER family and angiogenic pathways (e.g., trastuzumab plus bevacizumab) is also showing activity in the clinical setting. Despite recent advances, there are unanswered questions regarding the management of MBC with targeted agents. Future studies are necessary to determine the optimal combinations, doses, and schedules required to maximize clinical activity while minimizing toxicity. Despite the temptation to use a targeted agent in all patients, identification of patient subgroups most likely to benefit must be a key goal and will be critical to the successful future use of these treatments. The aim of this review is to summarize some of the key signaling pathways involved in tumor progression and some of the novel therapies that are in development for MBC.
Elevated Serum Insulin-Like Growth Factor Binding Protein-2 as a Prognostic Marker in Patients with Ovarian Cancer (2004)

In ovarian cancer IGFBP-2 is elevated at diagnosis, and corresponds to stage and histology with patients in the highest tertile of IGFBP-2 more likely to relapse and have a poorer outlook. Identification of these patients at diagnosis may allow more individualized, aggressive adjuvant treatment and follow-up, and IGFBP-2 may therefore be an important additional prognostic marker in this disease.
Association of Pseudomonas cepacia with chronic granulomatous disease (1975)

Pseudomonas cepacia was recovered from a number of infected sites in three patients with chronic granulomatous disease of childhood. The organisms were identified on the basis of their oxidative utilization of a variety of carbohydrates and their positive beta-galactosidase and oxidase activities. They were resistant to most antimicrobial agents and moderately susceptible to chloramphenicol. Peripheral blood leukocytes isolated from two siblings with chronic granulomatous disease, including one of the patients in this series, failed to kill P. cepacia in vitro. Prolonged prophylactic and antimicrobial therapy may well have played a significant role in the colonization and infection of these patients with P. cepacia.
Terminology of metal–organic frameworks and coordination polymers (IUPAC Recommendations 2013) (2013)

A set of terms, definitions, and recommendations is provided for use in the classification of coordination polymers, networks, and metal–organic frameworks (MOFs). A hierarchical terminology is recommended in which the most general term is coordination polymer. Coordination networks are a subset of coordination polymers and MOFs a further subset of coordination networks. One of the criteria an MOF needs to fulfill is that it contains potential voids, but no physical measurements of porosity or other properties are demanded per se. The use of topology and topology descriptors to enhance the description of crystal structures of MOFs and 3D-coordination polymers is furthermore strongly recommended.
Apoptosis is promoted by the dsRNA‐activated factor (DRAF1) during viral infection independent of the action of interferon or p53 (2001)

An apoptotic cellular defense mechanism is triggered in response to viral dsRNA generated during the course of infection by many DNA and RNA viruses. We demonstrate that apoptosis induced by dsRNA or a paramyxovirus is independent of the action of interferon as it can proceed in a variety of cell lines and primary cells deficient in an interferon response. Initiation of apoptosis appears to be triggered by activation of a cellular transcription factor, the dsRNA-activated factor (DRAF1). DRAF1 is composed of interferon regulatory factor 3 (IRF-3) and the transcriptional coactivators CREB binding protein (CBP) or p300. We find that activation of IRF-3 in the absence of viral infection stimulates apoptosis. In addition, a negative interfering mutant blocks both target gene induction and apoptosis, demonstrating a requirement for gene expression by IRF-3/DRAF1 to promote apoptosis. IRF-3/DRAF1 target gene expression is also induced in response to a distinct apoptotic stimulus, the DNA damaging agent etoposide. The activity of the p53 tumor suppressor does not appear to be required for IRF-3/DRAF1-mediated apoptosis.
Pathologic changes secondary to radiation (1986)

Abstract In order to be effective in the treatment of disease, especially neoplastic disease, radiation necessarily needs to be given in large doses. When treating tumors with high radiosensitivity in tissue of relatively low radiosensitivity, few complications of therapy occur. Frequently, however, the differential of sensitivity to radiation between the neoplasm and normal tissues exposed is small and the incidence of radiation injury to normal tissues becomes significant. Nowhere is this more apparent than in treatment of neoplasms during which the alimentary canal is heavily radiated. The following discussion will describe the pathologic changes that occur in the various units of the exposed alimentary tract and in various components of those units during and especially months or years after radiation therapy. The usual rapid and effective regeneration of the rapid‐renewal cell system after injury will be noted. The serious delayed manifestations of injury to the fibrovascular tissues with resulting delayed complications of ulcerations, stenoses, fistula formation, and obstructing adhesions will be emphasized. Brief discussions of several other organ systems injured by radiation will be presented . The development of second neoplasms as a result of radiation will be briefly mentioned and discussed from three standpoints: very low levels, low levels, and high levels of radiation .
Enhanced Performance of GaN-Based Vertical Light-Emitting Diodes with Circular Protrusions Surmounted by Hexagonal Cones and Indium–Zinc Oxide Current Spreading Layer (2011)

The performance of vertically structured GaN-based light-emitting diodes (VLEDs) with an efficient surface roughening scheme that uses KrF laser irradiation, chemical wet etching, and an indium–zinc oxide (IZO) transparent conductive layer atop the n-GaN surface is investigated. The GaN surface, with circular protrusions and hexagonal cones, gives photons multiple opportunities to find escape cones, and the IZO film acts as a current spreading layer. The fabricated VLEDs with the proposed surface roughening scheme exhibited 79.3 and 65.1% increases in light output power at 350 and 750 mA, respectively, and showed a relatively low forward voltage compared to that of regular VLEDs.
Minocycline Delays Death of Retinal Ganglion Cells in Experimental Glaucoma and After Optic Nerve Transection (2006)

The safety record of minocycline and its ability to penetrate the blood-brain barrier suggest that this drug is a promising neuroprotective drug for optic nerve injuries.
Substance abuse and managed care (1993)

Substance abuse by the late 1980s had already become a prominent, out-of-control sector of health care. Some of the reasons for this crisis, as well as more recent changes in this specialty field, are explicated in this chapter.
The Role of Cytokine in the Lupus Nephritis (2011)

Lupus nephritis (LN) is a major clinical manifestation of systemic lupus erythematosus (SLE). Although numerous abnormalities of immune system have been proposed, cytokine overexpression plays an essential role in the pathogenesis of LN. In the initial phase of the disease, the immune deposits and/or autoantibodies induce cytokine production in renal resident cells, leading to further inflammatory cytokine/chemokine expression and leukocyte infiltration and activation. Then, infiltrate leukocytes, such as macrophages (Mφ) and dendritic cells (DCs), secrete a variety of cytokines and activate naïve T cells, leading the cytokine profile towards T helper (Th)1, Th2, and/or Th17. Recent studies revealed these inflammatory processes in experimental animal models as well as human LN. The cytokine targeted intervention may have the therapeutic potentials for LN. This paper focuses on the expression of cytokine and its functional role in the pathogenesis of LN.
A 28-kDa protein from Mycobacterium leprae is a target of the human antibody response in lepromatous leprosy. (1988)

The gene for a 28-kDa Mycobacterium leprae protein Ag, a major target of antibodies from patients with lepromatous leprosy, was cloned from a lambda-gt11-M. leprae DNA expression library and sequenced. Antibodies to this protein were detected in the serum of the majority of 15 individual lepromatous patients that were tested. The predicted amino acid sequence of the 28-kDa protein suggests that it is localized to the bacterial plasma membrane or cell wall.
Use of Capsular Polysaccharide–Tetanus Toxoid Conjugate Vaccine for Type II Group BStreptococcusin Healthy Women (2000)

An estimated 15% of invasive group B streptococcal (GBS) disease is caused by type II capsular polysaccharide (II CPS). In developing a pentavalent vaccine for the prevention of GBS infections, individual GBS CPSs have been coupled to tetanus toxoid (TT) to prepare vaccines with enhanced immunogenicity. Type II GBS (GBS II) vaccine was created by direct, covalent coupling of II CPS to TT by reductive amination. In 2 clinical trials, 75 healthy nonpregnant women 18-45 years old were randomized to receive II CPS-TT (II-TT) conjugate (dose range, 3.6-57 microg of CPS component) or uncoupled II CPS vaccine. Both vaccines were well tolerated. II CPS-specific IgG serum concentrations (as well as IgM and IgA) peaked 2 weeks after immunization, being significantly higher in recipients of conjugated vaccine than in recipients of uncoupled CPS. Immunological responses to conjugate were dose dependent and correlated with opsonophagocytosis in vitro. These results support inclusion of II-TT conjugate when preparing a multivalent GBS vaccine.
Rational Design and Binding Mode Duality of MDM2–p53 Inhibitors (2013)

Structural analysis of both the MDM2-p53 protein-protein interaction and several small molecules bound to MDM2 led to the design and synthesis of tetrasubstituted morpholinone 10, an MDM2 inhibitor with a biochemical IC50 of 1.0 μM. The cocrystal structure of 10 with MDM2 inspired two independent optimization strategies and resulted in the discovery of morpholinones 16 and 27 possessing distinct binding modes. Both analogues were potent MDM2 inhibitors in biochemical and cellular assays, and morpholinone 27 (IC50 = 0.10 μM) also displayed suitable PK profile for in vivo animal experiments. A pharmacodynamic (PD) experiment in mice implanted with human SJSA-1 tumors showed p21(WAF1) mRNA induction (2.7-fold over vehicle) upon oral dosing of 27 at 300 mg/kg.