gebhart/patrepeval huggingface dataset:
Schizophrenia: More dopamine, more D<sub>2</sub>receptors (2000)

Schizophrenia is a major therapeutic challenge of modern medicine, and one of the last frontiers of brain research. The illness is defined by delusions, hallucinations, disorganized behavior, and cognitive difficulties such as memory loss. It occurs in ≈1% of the world population and usually first appears in early adulthood. Although antipsychotic medications have dramatically improved the lives of patients with schizophrenia, the causes of the illness remain unknown.

Of the many contemporary theories of schizophrenia, the most enduring has been the dopamine hypothesis. As originally put by Van Rossum in 1967 (ref. 1, p. 321), “When the hypothesis of dopamine blockade by neuroleptic agents can be further substantiated, it may have fargoing consequences for the pathophysiology of schizophrenia. Overstimulation of dopamine receptors could be part of the aetiology … [emphasis added].” Indeed, this speculative sentence by Van Rossum foreshadows the title of the important work by Abi-Dargham et al . (2) in this issue of PNAS: “Increased baseline occupancy of D2 receptors by dopamine in schizophrenia.”

The discovery of the antipsychotic/dopamine receptor (3, 4), now commonly known as the dopamine D2 receptor, led to repeated confirmation that it is the primary site of action for all antipsychotics (3–5), including clozapine and quetiapine (6). All these drugs have different potencies at the receptor. The potency depends on the drug's dissociation constant at D2, which, in turn, relates to the rate of release of the drug from the D2 receptor. For example, the dopamine D2 receptor releases clozapine and quetiapine more rapidly than it does any of the other antipsychotic drugs (7, 8).

Given the tight correlation between the clinical potency and the D2-blocking action of the antipsychotic medications, dopamine overactivity could be the common denominator in the …
Skin stretch feedback for gaming environments (2012)

This paper presents the design and development of handheld gaming devices that provide a new form of touch feedback: skin stretch feedback. Our prior work showed 1-1.5 mm of skin stretch applied to the fingertips (or thumb tips) could provide direction cues with high accuracy. The direction of each cue corresponded to the direction of applied skin stretch. Haptic feedback via tactile skin stretch can be used to provide tactile gaming effects and directional information through the same interface used for game inputs. Tests conducted with devices that resemble modern game controllers indicated which grip style is preferred by users and how to present direction cues to achieve the highest recognition rates. The main contribution of this paper is to show an initial demonstration of the benefits of skin stretch feedback in a multimodal gaming scenario.
Eigenschaften und Verwendbarkeit des 10, 11‐Dihydro‐5<i>H</i>‐dibenzo[<i>a,d</i>]cyclohepten‐5‐yl‐Rests (= 5‐Dibenzosuberyl‐Rests) als neue Schutzgruppe für Amine, Aminosäuren, Alkohole, Thiole und Carbonsäuren (1976)

Properties and suitability of the 10,11‐dihydro‐5 H ‐dibenzo[ a, d ]cyclohepten‐5‐yl group (= 5‐dibenzosuberyl group) as a new protecting group for amines, amino‐acids, alcohols, thiols and carboxylic acids. The 10,11‐dihydro‐5 H ‐dibenzo[ a,d ]cyclohepten‐5‐yl group (5‐dibenzosuberyl group): magnified image has been found useful for protecting amines, alcohols, thiols, and carboxylic acids. Furthermore, the investigated 5‐amino compounds are extremely stable in strongly acidic media ( e. g. in hydrogen bromide) and still the amino group is easily cleaved under mild conditions, such as those used for N‐trityl compounds ( e.g. boiling in dilute acetic acid or catalytic hydrogenation). Hence this ring system could be a valuable and adaptable protecting group, especially in peptide chemistry.
Correction: Hyaluronsäuregele zur Druckregulierung in der Glaukomtherapie (2017)

Correction: Ophthalmologe 2017 10.1007/s00347-017-0602-z Sehr geehrter Leser, sehr geehrte Leserin, leider wurde der oben genannte Beitrag online zunächst mit fehlerhaftem deutschen Titel veröffentlicht. Wir bitten, den korrekten Titel Hyaluronsäuregele zur Druckregulierung in der Glaukomtherapie zu berücksichtigen und den Fehler zu entschuldigen. Die Redaktion
The Discovery of Dabigatran Etexilate (2013)

Thromboembolic disease is a major cause of mortality and morbidity in the developed world and is caused by an excessive stimulation of coagulation. Thrombin is a key serine protease in the coagulation cascade and numerous efforts have been made to develop safe and effective orally active direct thrombin inhibitors (DTIs). Current anticoagulant therapy includes the use of indirect thrombin inhibitors (e.g., heparins, low-molecular-weight-heparins) and vitamin K antagonists such as warfarin. However there are several caveats in the clinical use of these agents including narrow therapeutic window, parenteral delivery, and food- and drug-drug interactions. Dabigatran is a synthetic, reversible DTI with high affinity and specificity for its target binding both free and clot-bound thrombin, and offers a favorable pharmacokinetic profile. Large randomized clinical trials have demonstrated that dabigatran provides comparable or superior thromboprophylaxis in multiple thromboembolic disease indications compared to standard of care. This minireview will highlight the discovery and development of dabigatran, the first in a class of new oral anticoagulant agents to be licensed worldwide for the prevention of thromboembolism in the setting of orthopedic surgery and stroke prevent in atrial fibrillation.
Pharmacological Effects of Cisplatin Combination with Natural Products in Cancer Chemotherapy (2022)

Cisplatin and other platinum-based drugs, such as carboplatin, ormaplatin, and oxaliplatin, have been widely used to treat a multitude of human cancers. However, a considerable proportion of patients often relapse due to drug resistance and/or toxicity to multiple organs including the liver, kidneys, gastrointestinal tract, and the cardiovascular, hematologic, and nervous systems. In this study, we sought to provide a comprehensive review of the current state of the science highlighting the use of cisplatin in cancer therapy, with a special emphasis on its molecular mechanisms of action, and treatment modalities including the combination therapy with natural products. Hence, we searched the literature using various scientific databases., such as MEDLINE, PubMed, Google Scholar, and relevant sources, to collect and review relevant publications on cisplatin, natural products, combination therapy, uses in cancer treatment, modes of action, and therapeutic strategies. Our search results revealed that new strategic approaches for cancer treatment, including the combination therapy of cisplatin and natural products, have been evaluated with some degree of success. Scientific evidence from both in vitro and in vivo studies demonstrates that many medicinal plants contain bioactive compounds that are promising candidates for the treatment of human diseases, and therefore represent an excellent source for drug discovery. In preclinical studies, it has been demonstrated that natural products not only enhance the therapeutic activity of cisplatin but also attenuate its chemotherapy-induced toxicity. Many experimental studies have also reported that natural products exert their therapeutic action by triggering apoptosis through modulation of mitogen-activated protein kinase (MAPK) and p53 signal transduction pathways and enhancement of cisplatin chemosensitivity. Furthermore, natural products protect against cisplatin-induced organ toxicity by modulating several gene transcription factors and inducing cell death through apoptosis and/or necrosis. In addition, formulations of cisplatin with polymeric, lipid, inorganic, and carbon-based nano-drug delivery systems have been found to delay drug release, prolong half-life, and reduce systemic toxicity while other formulations, such as nanocapsules, nanogels, and hydrogels, have been reported to enhance cell penetration, target cancer cells, and inhibit tumor progression.
Placental glutathione S-transferase (GST-P) induction as a potential mechanism for the anti-carcinogenic effect of the coffee-specific components cafestol and kahweol (1996)

The coffee specific diterpenes cafestol and kahweol (C + K) have been reported to be anti-carcinogenic in several animal models. It has been postulated that this activity may be related to their ability to induce glutathione S-transferases (GSTs). We investigated the influence of a mixture of C + K, incorporated at various levels in the diet of Sprague-Dawley rats, on the expression of different hepatic GST iso-enzymes. Liver samples were examined using isoform-specific GST substrates and antibodies, and highly selective oligomers were employed to determine effects at the RNA level. A dose-dependent increase in general GST activity was observed in male and female animals following 28 or 90 days of treatment. A time-course study demonstrated that the maximal effect was observed within 5 days of treatment. Little or no effect was found on the activity of GST alpha and mu iso-enzymes. The most striking observation was a dose-dependent induction of placental glutathione S-transferase (GST-P) which could be demonstrated at the mRNA, protein and enzymatic levels. This effect was observed in both male and female rats. The maximal induction was attained within 5 days of treatment with C + K, remained elevated with continued treatment, but was reversible on withdrawal of treatment. Immunohistochemical examination of liver slices revealed a strong even distribution of GST-P expression throughout the acinus at the highest dose of C + K, while at lower doses the induction of GST-P occurred predominantly in periportal hepatocytes. There was no indication of the presence of preneoplastic foci and, furthermore, the effect of C + K on the GST-P was completely reversible. These findings indicate that the anticarcinogenic mechanism of C + K may involve a specific induction of GST-P and suggest a potential role for GST-P in detoxifying carcinogenic compounds.
AIRMobile: Accelerated Instant Replay for In-Meeting Review by Mobile Users (2011)

Videoconference participants attending from mobile devices often miss parts of meetings, either because they are running late to the meeting or because of network service interruptions. Thus, they may need to catch up on the content they missed. Asking other attendees for a recap is often disruptive. We present AIRMobile, an Accelerated Instant Replay system for mobile videoconferencing that enables mobile attendees to privately catch up on an ongoing meeting.
Central Nervous System–Active Medications and Risk for Falls in Older Women (2002)

Community-dwelling older women taking CNS-active medications, including those taking benzodiazepines, antidepressants, and anticonvulsants, are at increased risk of frequent falls. Minimizing use of these CNS-active medications may decrease risk of future falls. Our results suggest that fall risk in women taking benzodiazepines is at best marginally decreased by use of short-acting preparations. Similarly, our findings indicate that preferential use of selective serotonin-reuptake inhibitors is unlikely to reduce fall risk in older women taking antidepressants.
Characterization and sequence analysis of pilin from F-like plasmids (1985)

Conjugative pili are expressed by derepressed plasmids and initiate cell-to-cell contact during bacterial conjugation. They are also the site of attachment for pilus-specific phages (f1, f2, and QB). In this study, the number of pili per cell and their ability to retract in the presence of cyanide was estimated for 13 derepressed plasmids. Selected pilus types were further characterized for reactivity with anti-F and anti-ColB2 pilus antisera as well as two F pilus-specific monoclonal antibodies, one of which is specific for a sequence common to most F-like pilin types (JEL92) and one which is specific for the amino terminus of F pilin (JEL93). The pilin genes from eight of these plasmids were cloned and sequenced, and the results were compared with information on F, ColB2, and pED208 pilin. Six pilus groups were defined: I, was F-like [F, pED202(R386), ColV2-K94, and ColVBtrp]; IIA was ColB2-like in sequence but had a lowered sensitivity to f1 phage due to its decreased ability for pilus retraction [pED236(ColB2) and pED203(ColB4)]; IIB was ColB2-like but retained f1 sensitivity [pED200(R124) and pED207(R538-1)]; III contained R1-19, which had a ColB2-like amino terminus but had an additional lysine residue at its carboxy terminus which may affect its phage sensitivity pattern and its antigenicity; IV was R100-1-like [R100-1 and presumably pED241(R136) and pED204(R6)] which had a unique amino-terminal sequence combined with a carboxy terminus similar to that of F. pED208(Folac) formed group V, which was multipiliated and exhibited poor pilus retraction although it retained full sensitivity to f1 phage. The pED208 pilin gene could not be cloned at this time since it shared no homology with the pilin gene of the F plasmid.
High Performance Pigments (2001)

Preface. List of Contributors. PART 1. Introduction to Inorganic High Performance Pigments (Gunther Buxbaum). Bismuth Vanadates (hartmut Endriss). Cadmium Pigments (Paul Dunning). Cerium Pigments (Jean--Noel Berte). Complex Inorganic Color Pigments: An Overview (James White). Titanate Pigments: Colored Rutile, Priderite, and Pseudobrookite Structured Pigments (John Maloney). PART II. Special Effect Pigments (Gerhard Pfaff). Crystal Design of High Performance Pigments (Peter Erk). PART III. The Global Market for Organic High Performance Pigments (Fritz Brenzikofer). Benzimidazolone Pigments and Related Structures (Hans--Joachim Metz and Frank Morgenroth). Diketopyrrolopyrrole (DPP) Pigments (Olof Wallquist). Dioxazine Violet Pigments (Terence Chamberlain). Disazocondensation Pigments (Fritz Herren). Isoindoline Pigments (Volker Radtke, et al.). Isoindolinone Pigments (Abul Iqbal, et al.). Perylene Pigments (Michael Greene). Phthalocyanines -- High Performance Pigments with New Applications (Masao Tanaka). Quinacridone Pigments (Edward E. Jaffe). Quinophthalone Pigments (Volker Radtke). Thiazines, Oxazines and Other Novel High--Performance Pigments (Bansi L. Kaul). PART IV. Chemical and Physical Characterization of High Performance Pigments (Bansi L. Kaul). Regulatory Affairs for High Performance Pigments: North America (Harold F. Fitzpatrick and Glenn C. Merritt). Regulatory and Legislative Aspects of Relevance to High Performance Pigments: Europe (Eric Clarke and Herbert Motschi). Toxicology and Ecotoxicology Issues with High Performance Pigments (Hugh Smith). Appendix. Index.
Comparison of the low‐contrast detectability of two ultrasound systems using a grayscale phantom (2016)

The purpose of the present study was to evaluate the relevance of using a phantom to simulate a clinical situation where small low contrast objects are embedded in relatively homogeneous organs in order to discriminate between different ultrasound machines, taking into account human observer variability. One high-end and one general ultrasound machine using the same probe were included. Images containing 4 and 6.4-mm objects of four different contrasts were collected from a greyscale phantom at different depths. Six observers participated in a 4-alternative forced choice study based on 960 images. Variability was determined using bootstrapping. At four of sixteen depth/size/contrast combinations, the visual performance of the high-end machine was significantly higher. The results indicate that it is possible to use a greyscale phantom to discriminate between ultrasound machines in terms of their ability to reproduce clinically relevant low-contrast objects. However, the number of images and number of observers needed are larger than those usually used for constancy control, if the large uncertainties caused by human observer variability is to be taken correctly into account.
REVIEWS (1974)

The Editor welcomes carefully written reviews of worthwhile publications from the readers of M.A.N. Reviewers should follow the format of the following article, and should submit two clean copies, double‐spaced on white bond with ample margins. —CWK Drugs and Foods from Little–Known Plants: Notes in Harward University Herbia by Siri von Reis Altschul
On determining the most appropriate test cut-off value: the case of tests with continuous results (2016)

There are several criteria for determination of the most appropriate cut-off value in a diagnostic test with continuous results. Mostly based on receiver operating characteristic (ROC) analysis, there are various methods to determine the test cut-off value. The most common criteria are the point on ROC curve where the sensitivity and specificity of the test are equal; the point on the curve with minimum distance from the left-upper corner of the unit square; and the point where the Youden's index is maximum. There are also methods mainly based on Bayesian decision analysis. Herein, we show that a proposed method that maximizes the weighted number needed to misdiagnose, an index of diagnostic test effectiveness we previously proposed, is the most appropriate technique compared to the aforementioned ones. For determination of the cut-off value, we need to know the pretest probability of the disease of interest as well as the costs incurred by misdiagnosis. This means that even for a certain diagnostic test, the cut-off value is not universal and should be determined for each region and for each disease condition.
Efficient user-level file cache management on the Sun Vnode interface (2018)

Abstract: "In developing a distributed file system, there are several good reasons for implementing the client file cache manager as a user-level process. These include ease of implementation, increased portability, and minimal impact on kernel size. For reasons of compatibility it is also desirable to use a standard file intercept mechanism on the client. The Sun VFS/Vnode file system interface is such a standard. However, this interface is designed for kernel-based file systems, and a user-level cache manager that used the Vnode mechanism would pay a large performance penalty due to the high number of kernel to cache manager context switches per file system call.This paper describes our solution to the problem for the Coda file system. By using a relatively small amount of kernel code to cache critical information, we are able to retain the much larger and more complex components of the Coda cache manager in a user level process. The measurements of Coda presented here confirm the performance benefits of this strategy, and indicate the relative merits of caching different kinds of information in the kernel."
Therapeutic Plasma Exchange (1981)

I.- Dialysebehandlung heute - eine Bestandsaufnahme.- Diskussion.- II.- Technologische Aspekte zur Membranplasmapherese.- Diskussion.- Myasthenia gravis: Current State of Knowledge.- Discussion.- Die Plasmaaustausch-Behandlung bei Myasthenia gravis und anderen neuropsychiatrischen Erkrankungen.- Diskussion.- Plasmapheresis for Therapy in Patients with Metastasizing Solid Tumors.- Discussion.- Plasma Exchange in Hyperlipidemia.- Discussion.- Plasmapherese bei thyreotoxischer Krise.- Diskussion.- Plasmaaustausch bei Digitalis-Intoxikation.- Diskussion.- Plasmapheresis or Lymphapheresis in Rheumatoid Arthritis.- Discussion.- Plasma Filtration Detoxification on Hepatic Patients: Its Optimal Operating Conditions.- Discussion.- Plasma Exchange in Anti-GBM Disease.- Discussion.- Plasmaseparation in der Behandlung von rapid progressiven Glomerulonephritiden.- Diskussion.- Plasma Exchange in Immune Complex Rapid Progressive Glomerulonephritis.- Discussion.- Plasma Exchange in Renal Allograft Rejection.- Discussion.- Problems of Plasma Exchange Therapy.- Discussion.- III.- Topics in Therapeutic Plasma Exchange: A Classification of Published Work.
Vitronectin adsorption on surfaces visualized by tapping mode atomic force microscopy (2003)

Vitronectin (Vn) is an abundant glycoprotein present in plasma and the extracellular matrix of most tissue and is an important medium required for bone cells to attach and spread on biomaterial surfaces. Hence, Vn adsorption is an initial and key step in implantation. In this study, adsorption of Vn molecules on mica and oxidized titanium substrates in Milli-Q water (pH 5.6) and in simulated body fluid (SBF, pH 7.4) has been investigated using tapping mode atomic force microscopy. Conformation of the adsorbed proteins was determined from the images. The effect of adsorption time was investigated on mica surfaces. The protein first attaches to the surface, then immediately spreads out with different lateral dimensions of adsorbed protein and becomes aggregated. After 15 min of adsorption, globular Vn molecules form clusters of aggregates in extended chains on the mica surface. Globular Vn molecules appear flatter (i.e., oblate ellipsoids) and coalesce on the ridges of the uneven oxidized titanium surface. From cross-sectional analyses of the Vn images, it was found that the contact areas of Vn molecules associated with Ti surfaces are larger than those with mica surfaces. This suggests that the different surface properties of substrates contribute to this different conformation of adsorbed Vn molecules. The larger contact areas of Vn associated with Ti substrates indicates higher affinity for the biomaterial oxidized titanium surface than for mica. In SBF, Vn interacted weakly with the mica surfaces and Vn molecules were easily desorbed during the imaging process. On oxidized titanium substrates, after 3 h of incubation time in Vn-SBF solution, images can be obtained showing adsorbed Vn aggregates on the oxidized titanium surface. In this case, the protein colloids are strongly adherent, with increased lateral dimensions compared with the adsorption on mica.
Novel protein families in archaean genomes (1995)

In a quest for novel functions in archaea, all archaean hypothetical open reading frames (ORFs), as annotated in the Swiss-Prot protein sequence database, were used to search the latest databases for the identification of characterized homologues. Of the 95 hypothetical archaean ORFs, 25 were found to be homologous to another hypothetical archaean ORF, while 36 were homologous to non-archaean proteins, of which as many as 30 were homologous to a characterized protein family. Thus the level of sequence similarity in this set reaches 64%, while the level of function assignment is only 32%. Of the ORFs with predicted functions, 12 homologies are reported here for the first time and represent nine new functions and one gene duplication at an acetyl-coA synthetase locus. The novel functions include components of the transcriptional and translational apparatus, such as ribosomal proteins, modification enzymes and a translation initiation factor. In addition, new enzymes are identified in archaea, such as cobyric acid synthase, dCTP deaminase and the first archaean homologues of a new subclass of ATP binding proteins found in fungi. Finally, it is shown that the putative laminin receptor family of eukaryotes and an archaean homologue belong to the previously characterized ribosomal protein family S2 from eubacteria. From the present and previous work, the major implication is that archaea seem to have a mode of expression of genetic information rather similar to eukaryotes, while eubacteria may have proceeded into unique ways of transcription and translation. In addition, with the detection of proteins in various metabolic and genetic processes in archaea, we can further predict the presence of additional proteins involved in these processes.
Towards highly selective ethylene epoxidation catalysts using hydrogen peroxide and tungsten- or niobium-incorporated mesoporous silicate (KIT-6) (2014)

Nb- and W-KIT-6 materials display significant ethylene epoxidation activity with H<sub>2</sub>O<sub>2</sub> as the oxidant at mild temperatures that eliminate substrate burning.