gebhart/patrepeval huggingface dataset:
Nanopatterns with Biological Functions (2006)

Both curiosity and a desire for efficiency have advanced our ability to manipulate materials with great precision on the micrometer and, more recently, on the nanometer scale. Certainly, the semiconductor and integrated circuit industry has put the pressure on scientist and engineers to develop better and faster nanofabrication techniques. Furthermore, our curiosity as to how life works, and how it can be improved from a medical perspective, stands to gain a great deal from advances in nanotechnology. Novel nanofabrication techniques are opening up the possibilities for mimicking the inherently nano-world of the cell, i.e., the nanotopographies of the extracellular matrix (ECM) and the nanochemistry presented on both the cell membrane and the ECM. In addition, biosensing applications that rely on fabrication of high-density, precision arrays, e.g., DNA or gene chips and protein arrays, will gain significantly in efficiency and, thus, in usefulness once it becomes possible to fabricate heterogeneous nanoarrays. Clearly, continued advances in nanotechnology are desired and required for advances in biotechnology. In this review, we describe the leading techniques for generating nanopatterns with biological function including parallel techniques such as extreme ultraviolet interference lithography (EUV-IL), soft-lithographic techniques (e.g., replica molding (RM) and microcontact printing (muCP)), nanoimprint lithography (NIL), nanosphere lithography (NSL) (e.g., colloid lithography or colloidal block-copolymer micelle lithography) and the nanostencil technique, in addition to direct-writing techniques including e-beam lithography (EBL), focused ion-beam lithography (FIBL) and dip-pen nanolithography (DPN). Details on how the patterns are generated, how biological function is imparted to the nanopatterns, and examples of how these surfaces can and are being used for biological applications will be presented. This review further illustrates the rapid pace by which advances are being made in the field of nanobiotechnology, owing to an increasing number of research endeavors, for an ever increasing number of applications.
Clinical significance of the bicuspid aortic valve (2000)

The association of bicuspid aortic valve with aortic stenosis, aortic regurgitation, and infective endocarditis has been known for almost 150 years and with dissection of the aorta for 75 years. 1 These complications are mentioned only briefly in cardiology textbooks 3 and a standard work on medical insurance underwriting 4 implies that it is usually a benign lesion: when diagnosed at routine medical examination and if the valve is functionally normal, insurance is oVered at ordinary rates. The authors also state "If there is no stenosis by age 20 years (defined as a peak gradient of less than 40 mm Hg) and only trivial insuYciency, there is an excellent chance that significant haemodynamic change will not develop before age 70." However, on the basis of published reports by this age the majority of patients will have died or developed serious symptoms requiring surgical intervention. This review summarises the major studies that provide information on the incidence, pathology, and natural history of the bicuspid aortic valve. Clinical diagnosis of this condition was unsatisfactory before the widespread use of cross sectional echocardiography approximately 15 years ago. Most of the information in this paper therefore comes from large necropsy series and from reports on patients who have undergone aortic valve replacement. It has to be accepted that conclusions based on these reports may be inaccurate, because of nonuniformity of diagnostic criteria and varying age range, source/selection of patients studied, and study objectives.
A three‐dimensional statistical approach to improved image quality for multislice helical CT (2007)

Multislice helical computed tomography scanning offers the advantages of faster acquisition and wide organ coverage for routine clinical diagnostic purposes. However, image reconstruction is faced with the challenges of three-dimensional cone-beam geometry, data completeness issues, and low dosage. Of all available reconstruction methods, statistical iterative reconstruction (IR) techniques appear particularly promising since they provide the flexibility of accurate physical noise modeling and geometric system description. In this paper, we present the application of Bayesian iterative algorithms to real 3D multislice helical data to demonstrate significant image quality improvement over conventional techniques. We also introduce a novel prior distribution designed to provide flexibility in its parameters to fine-tune image quality. Specifically, enhanced image resolution and lower noise have been achieved, concurrently with the reduction of helical cone-beam artifacts, as demonstrated by phantom studies. Clinical results also illustrate the capabilities of the algorithm on real patient data. Although computational load remains a significant challenge for practical development, superior image quality combined with advancements in computing technology make IR techniques a legitimate candidate for future clinical applications.
Oxidative Stress and Autophagy (2006)

Organisms respond to oxidative injury by orchestrating a stress response to prevent further damage. An increase in the intracellular levels of antioxidant agents, and at the same time the removal of already damaged components, are both part of the oxidative stress response. Lysosomes have been classically considered one of the main targets of the reactive oxygen species. In fact, the destabilization of the lysosomal membrane during oxidizing conditions promotes the leakage of the enzymes contained in these organelles and contributes to cellular damage. However, recent evidence supports a protective role of the lysosomal system, which can eliminate altered intracellular components through autophagy, at least in the first stages of oxidative injury. Consequently, activation of the main intracellular proteolytic systems, the ubiquitin/proteasome, and also the lysosomal/autophagic system occurs during the oxidative stress response. The opposing roles for the lysosomal system under oxidizing conditions are discussed in this review.
Age-DependentNeisseria meningitidisSerogroup C Class-Specific Antibody Concentrations and Bactericidal Titers in Sera from Young Children from Montana Immunized with a Licensed Polysaccharide Vaccine (1998)

Neisseria meningitidis serogroup C bactericidal titers and class-specific enzyme-linked immunosorbent assay (ELISA) antibody concentrations were measured in sera from 173 children (1 to 5 years old) before and 6 weeks and 7 months following vaccination with a quadrivalent (A/C/Y/W-135) polysaccharide vaccine. The immune responses of the children were compared with those of 40 adults 6 weeks postvaccination. Both bactericidal titers and ELISA antibody concentrations were significantly higher in the adults than in the children (P < 0.05). In addition, the ratio of immunoglobulin G (IgG) to IgM was higher in the children than in the adults. With an ELISA total antibody concentration of >/=2 microg/ml used as a measure of seroconversion, >/=84% of the individuals from each age group responded to the serogroup C polysaccharide. However, with a >/=4-fold-increase in bactericidal titer used, only 18% of 1-year-olds, 32% of 2-year-olds, and 50 to 60% of 3-, 4-, and 5-year-olds seroconverted. The ELISA results suggest that >50% of all children retained >/=2 microg of total antibody per ml at 7 months postimmunization. However, the bactericidal titers suggest that <10% of children <4 years old retained a >/=4-fold increase at 7 months following vaccination. Of particular note, 59 of 79 sera (75%) from the 1- and 2-year-olds had high ELISA antibody concentrations (2 to 20 microg/ml) with no associated bactericidal titer (<1:8). Discordant results between bactericidal titers and ELISA antibody concentrations were not explained by the presence of IgA blocking antibody or relative levels of IgG and IgM. The bactericidal results show age-dependent differences in the production and retention of antibody in young children immunized with serogroup C polysaccharide; these differences are not evident with the ELISA data.
Clinical Trials in Head Injury (2002)

Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate significant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research.
Point Substitution in the Central Hydrophobic Cluster of a Human β-Amyloid Congener Disrupts Peptide Folding and Abolishes Plaque Competence (1996)

Alzheimer's disease (AD) is pathologically characterized by the presence of numerous insoluble amyloid plaques in the brain composed primarily of a 40-43 amino acid peptide, the human beta-amyloid peptide (A beta). The process of A beta deposition can be modeled in vitro by deposition of physiological concentrations of radiolabeled A beta onto preexisting amyloid in preparations of unfixed AD cerebral cortex. Using this model system, it has been shown that A beta deposition is biochemically distinct from A beta aggregation and occurs readily at physiological A beta concentrations, but which regions and conformations of A beta are essential to A beta deposition is poorly understood. We report here that an active congener, A beta (10-35)-NH2, displays time dependence, pH-activity profile, and kinetic order of deposition similar to A beta (1-40), and is sufficiently soluble for NMR spectroscopy in water under conditions where it actively deposits. To examine the importance of the central hydrophobic cluster of A beta (LVFFA, residues 17-21) for in vitro A beta deposition, an A beta (10-35)-NH2 analog with a single point substitution (F19T) in this region was synthesized and examined. Unlike A beta (10-35)-NH2, the F19T analog was plaque growth incompetent, and NMR analysis indicated that the mutant peptide was significantly less folded than wild-type A beta. These results support previous studies suggesting that the plaque competence of A beta correlates with peptide folding. Since compounds that alter A beta folding may reduce amyloid deposition, the central hydrophobic cluster of A beta will be a tempting target for structure-based drug design when high-resolution structural information becomes available.
Effects of storage time of red blood cell transfusions on the prognosis of coronary artery bypass graft patients (2006)

In these analyses, pertaining to 2732 CABG patients, no justification could be found for use of a particular maximum storage time for RBC transfusions in patients undergoing CABG surgery.
Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. (2000)

We provide evidence that cyclooxygenase (COX)-2-derived prostaglandins contribute to tumor growth by inducing newly formed blood vessels (neoangiogenesis) that sustain tumor cell viability and growth. COX-2 is expressed within human tumor neovasculature as well as in neoplastic cells present in human colon, breast, prostate, and lung cancer biopsy tissue. COX-1 is broadly distributed in normal, as well as in neoplastic, tissues. The contribution of COX-2 to human tumor growth was indicated by the ability of celecoxib, an agent that inhibits the COX-2 enzyme, to suppress growth of lung and colon tumors implanted into recipient mice. Mechanistically, celecoxib demonstrated a potent antiangiogenic activity. In a rat model of angiogenesis, we observe that corneal blood vessel formation is suppressed by celecoxib, but not by a COX-1 inhibitor. These and other data indicate that COX-2 and COX-2-derived prostaglandins may play a major role in development of cancer through numerous biochemical mechanisms, including stimulation of tumor cell growth and neovascularization. The ability of celecoxib to block angiogenesis and suppress tumor growth suggests a novel application of this anti-inflammatory drug in the treatment of human cancer.
Hyperhomocysteinaemia and endothelial dysfunction in young patients with peripheral arterial occlusive disease (1995)

Hyperhomocysteinaemia, defined as an abnormally high plasma homocysteine concentration after an oral methionine load, is common in young (< or = 50 years) patients with peripheral arterial occlusive disease. It is thought to predispose to atherosclerosis by injuring the vascular endothelium. Treatment with pyridoxine and/or folic acid may lower plasma homocysteine levels. In mildly hyperhomocysteinaemic patients with peripheral arterial occlusive disease, we studied the effect of daily treatment with pyridoxine (250 mg) plus folic acid (5 mg) on homocysteine metabolism (i.e. plasma concentrations in the fasting state and after methionine loading, in 48 patients) and on endothelial function (in 18 patients). Endothelial function was estimated as the plasma concentrations of the endothelium-derived proteins, von Willebrand factor (vWF), thrombomodulin (TM), and tissue-type plasminogen activator (tPA). At baseline, fasting homocysteine levels were above normal in 24 of the 48 patients (50%); post-load levels, by definition, were above normal in 100% of patients. After 12 weeks of treatment, fasting and post-load levels were normal in 98 and 100% of patients, respectively. Endothelial function was assessed in 18 patients who completed 1 year of treatment. At baseline, median vWF (235%) and TM (57.1 ng mL-1) levels were above normal. At follow-up, vWF levels had decreased to 170% (P = 0.01) and TM levels had decreased to 49 ng mL-1 (P = 0.04). tPA levels were normal at baseline and did not change. Endothelial dysfunction is present in young patients with peripheral arterial occlusive disease and hyperhomocysteinaemia. Pyridoxine plus folic acid treatment normalizes homocysteine metabolism in virtually all patients, and appears to ameliorate endothelial dysfunction.
Mapatumumab, a Fully Human Agonistic Monoclonal Antibody That Targets TRAIL-R1, in Combination with Gemcitabine and Cisplatin: a Phase I Study (2009)

Mapatumumab in combination with gemcitabine and cisplatin is safe and well tolerated at doses up to 30 mg/kg. Further studies on this combination are warranted.
Standardization of two immunological HbA1c routine assays according to the new IFCC reference method. (2003)

The measurement of HbA1c is meanwhile well established as the most important parameter in clinical chemistry for monitoring the long term metabolic control of diabetic patients. However, the comparability of HbA1c values obtained by different methods in different laboratories and different countries is limited since there was no internationally agreed reference method available. Additionally the % HbA1c values, based on the most common DCCT values are too high due to well known non specificity of the DCCT standardization protocol. Recently a new reference method for the determination of HbA1c was developed and has been approved by the IFCC as the future basis for the worldwide standardization of HbA1c routine assays. The two routine methods from Roche Diagnostics (both based on the immunoturbidimetric determination of the stable glucose adduct to the N-terminal group of the hemoglobin beta chain, Roche-Hitachi/Tina-quant [a] and COBAS INTEGRA) are directly standardized against this new reference method. Both routine methods are based on a two step approach: in a first step the total Hb is quantified by a colorimetric method and in a second step the stable glucose adduct to the N-terminal group of the hemoglobin beta chain is quantified by immunoturbidity (HbA1c mass). Consequently, first the standardization of the total Hb assay was reconfirmed by method comparisons against the cyanomethemoglobin reference method. Second, the standardization of the HbA1c mass was done by running method comparisons against the new IFCC reference method. The resulting new calibrator values for HbA1c [mass] and total Hb [mass] allow a direct estimation of % HbA1c according to IFCC just by calculating the HbA1c [mass]/total Hb [mass] ratio. Good linear correlations were obtained when comparing the routine methods against the new IFCC reference, indicating the high specificity of these immunological approaches. The following correlations are obtained: Hitachi / Tina-quant [a] (Y) versus IFCC reference method (X): Y = -0.031 + 1.009 x X; r = 0.995. COBAS INTEGRA (Y) versus IFCC reference method (X): Y = -0.156 + 1.006 x X; r = 0.997. Hitachi / Tina-quant [a] (Y) versus Integra (X); (both standardized according to IFCC): Y = 0.057 + 1.003 x X; r = 0.997. The HbA1c values obtained with this new IFCC standardization are significantly lower than the well known DCCT values. Due to the specificity of the immunological approach which is very close to the analyte as defined by the IFCC reference method, no further corrections of the obtained % HbA1c values are necessary. A slope/intercept correction formula is derived which allows the transformation of IFCC values into the DCCT numbers if requested.
A New Strategy for Smoking Cessation: Characterization of a Bacterial Enzyme for the Degradation of Nicotine (2015)

Smoking is the leading cause of preventable diseases; thus, effective smoking cessation aids are crucial for reducing the prevalence of cigarette smoking and smoking-related illnesses. In our current campaign we offer a nicotine-degrading enzyme from Pseudomonas putida, NicA2, a flavin-containing protein. To explore its potential, a kinetic evaluation of the enzyme was conducted, which included determination of K(m), k(cat), buffer/serum half-life, and thermostability. Additionally, the catabolism profile of NicA2 was elucidated to assess the potential toxicity of the nicotine-derived products. In characterizing the enzyme, a favorable biochemical profile of the enzyme was discovered, making NicA2 a prospective therapeutic candidate. This approach provides a new avenue for the field of nicotine addiction therapy.
Photoelectrochemical devices for solar water splitting – materials and challenges (2017)

It is widely accepted within the community that to achieve a sustainable society with an energy mix primarily based on solar energy we need an efficient strategy to convert and store sunlight into chemical fuels. A photoelectrochemical (PEC) device would therefore play a key role in offering the possibility of carbon-neutral solar fuel production through artificial photosynthesis. The past five years have seen a surge in the development of promising semiconductor materials. In addition, low-cost earth-abundant co-catalysts are ubiquitous in their employment in water splitting cells due to the sluggish kinetics of the oxygen evolution reaction (OER). This review commences with a fundamental understanding of semiconductor properties and charge transfer processes in a PEC device. We then describe various configurations of PEC devices, including single light-absorber cells and multi light-absorber devices (PEC, PV-PEC and PV/electrolyser tandem cell). Recent progress on both photoelectrode materials (light absorbers) and electrocatalysts is summarized, and important factors which dominate photoelectrode performance, including light absorption, charge separation and transport, surface chemical reaction rate and the stability of the photoanode, are discussed. Controlling semiconductor properties is the primary concern in developing materials for solar water splitting. Accordingly, strategies to address the challenges for materials development in this area, such as the adoption of smart architectures, innovative device configuration design, co-catalyst loading, and surface protection layer deposition, are outlined throughout the text, to deliver a highly efficient and stable PEC device for water splitting.
Smoothened Mutation Confers Resistance to a Hedgehog Pathway Inhibitor in Medulloblastoma (2009)

The Hedgehog (Hh) signaling pathway is inappropriately activated in certain human cancers, including medulloblastoma, an aggressive brain tumor. GDC-0449, a drug that inhibits Hh signaling by targeting the serpentine receptor Smoothened (SMO), has produced promising anti-tumor responses in early clinical studies of cancers driven by mutations in this pathway. To evaluate the mechanism of resistance in a medulloblastoma patient who had relapsed after an initial response to GDC-0449, we determined the mutational status of Hh signaling genes in the tumor after disease progression. We identified an amino acid substitution at a conserved aspartic acid residue of SMO that had no effect on Hh signaling but disrupted the ability of GDC-0449 to bind SMO and suppress this pathway. A mutation altering the same amino acid also arose in a GDC-0449-resistant mouse model of medulloblastoma. These findings show that acquired mutations in a serpentine receptor with features of a G protein-coupled receptor can serve as a mechanism of drug resistance in human cancer.
Use of artificial neural networks in evaluating prognostic factors determining the response to dendritic cells pulsed with PSMA peptides in prostate cancer patients (2000)

ANN analysis emphasizes the importance of level of DC infusion, immune parameters, cytokines, and markers such as PSMA in determining the response to PSMA peptide immunotherapy. The criteria of response were judged to be correct in 86% of metastatic patients and 83% of locally recurrent patients evaluated in this study.
Pharmacology for Post-Traumatic Stress Disorder Related to Childhood Sexual Abuse: A Literature Review (2002)

The literature on pharmacotherapy for PTSD in general and childhood trauma and PTSD in particular is small and inconsistent, but we need to be aware of any and all advances.
Evaluation of a Rapid Gram Stain Interpretation Method for Diagnosis of Bacterial Vaginosis (2006)

A simple Gram stain evaluation for the diagnosis of bacterial vaginosis was assessed in comparison to Nugent's method. The sensitivity (90%), specificity (94%), positive and negative predictive values (90% and 94%), and good interobserver agreement obtained indicate that the test method can be performed reliably in the routine clinical microbiology laboratory.