gebhart/patrepeval huggingface dataset:
Susceptibility contrast imaging of cerebral blood volume: Human experience (1991)

Magnetic resonance (MR) can offer a unique window on the structure/function relationships in the brain, by utilizing the established link between tissue function, metabolism, and hemodynamics. This report focuses on recent applications of MR-based cerebral blood volume (CBV) imaging in humans. Our methodology uses high-speed "single-shot" or echo planar imaging techniques, which provide the necessary temporal resolution for mapping the rapid cerebral transit of contrast agents. These MR CBV mapping techniques have been used to study normal human brain task activation and in the clinical study of patients with brain tumors. In the latter, positron emission tomography imaging was used for functional metabolic and CBV correlation. Susceptibility contrast CBV imaging should allow us to improve our understanding of the relationship between the detailed physiology and morphology of the microvascular bed and functional attributes of the brain. These techniques can be applied to understanding fundamental questions of cognitive neuroscience and can aid in improving diagnostic sensitivity and specificity in various neuropathologies.
Feasibility studies for simultaneous immunochemical multianalyte drug assay by capillary electrophoresis with laser-induced fluorescence (1994)

We present a method for the simultaneous quantification of multiple drug analytes in urine, based on combining immunochemical binding with capillary electrophoretic separation. Two fluorescent drug-cyanine (Cy) dye conjugates were prepared as competing species for the immunoassay. Morphine was derivatized with Cy5 (lambda max = 652 nm, epsilon = 215,000 mol-1cm-1 L), phencyclidine (PCP) with Cy5.5 (lambda max = 675 nm, epsilon = 200,000 mol-1cm-1L). The high-efficiency resolving power of the capillary electrophoresis system (20 microns x 27 cm column) separated the individual labeled drugs, and the antigen-antibody complexes were detected by laser-induced fluorescence (laser: 10 mW He-Ne at 632.8 nm) with Cy5 diacid as internal standard. Simultaneous competitive immunoassay of morphine and PCP in urine showed that the free labeled-drug peak areas were proportional to the concentrations of the drug species present in the urine sample. This immunoassay can be performed routinely and reproducibly in < 5 min with analytical detection limits of 4 nmol/L for PCP and 40 nmol/L for morphine.
Theory of a Wide-Gap Emitter for Transistors (1957)

In order to obtain a high current amplification factor, it is important in transistors that the ratio of the injected minority carrier current over the total emitter current, γ, be close to unity, or that the quantity 1-γ, called the injection deficit, be as small as possible. It is shown that the injection deficit of an emitter can be decreased by several orders of magnitude if the emitter has a higher band gap than the base region. This effect can be utilized either in addition to the commonly used high emitter doping in order to eliminate the alpha falloff with current, or to decrease the high emitter doping in order to obtain a lower emitter capacitance. Decreasing the emitter capacitance in high-frequency transistors may be utilized either to extend their frequency range or to increase their power capabilities by increasing the area.
Molecular mechanisms of resistance to antifolates, a review. (1995)

Methotrexate (MTX) is a clinically important antifolate that has been used in combination with other chemotherapeutic agents in the treatment of malignancies including acute lymphocytic leukemia, osteosarcoma, carcinomas of the breast, head and neck, choriocarcinoma and non-Hodgkin's lymphoma. The primary target of MTX is the enzyme dihydrofolate reductase (DHFR) which catalyzes the reduction of folate and 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate. Understanding of MTX action has revealed how cells acquire resistance to this drug. The four known mechanisms of MTX resistance are a decrease in the uptake of the drug, a decrease in the retention of the drug due to defective polyglutamylation or an increase in polyglutamate breakdown, an increase in the enzyme activity and a decrease in the binding of MTX to DHFR. The molecular basis for some of these mechanisms has been elucidated in MTX resistant cell lines; in particular the occurrence of gene amplification resulting in increased DHFR and point mutations resulting in altered DHFR with reduced affinity for MTX. Cloning of the human folylpolyglutamate synthase gene and the reduced folate transport gene have been reported recently and should facilitate the identification of the molecular basis of these resistant phenotypes. DHFR protein has been shown to regulate its synthesis by exerting an inhibitory influence on its own translation. Addition of MTX relieves this inhibition thus providing a possible molecular explanation for the rapid rise in DHFR activity noted in some cells after MTX administration. Alterations in genes involved in regulating the cell cycle such as cyclin D1 and the retinoblastoma (Rb) gene have also been shown to influence cellular response to MTX. Overexpression of cyclin D1 in HT1080, a human fibrosarcoma cell line, results in decreased MTX sensitivity. The molecular basis of this observation is under investigation. Abnormalities in the Rb gene may also have profound effects on MTX sensitivity. Rb interacts with the family of transcription factors called E2F reducing transcription of genes that contain E2F binding sites in the promoter regions e.g. DHFR. When Rb is deleted or rendered nonfunctional levels of "free" or unbound E2F are high resulting in enhanced transcription of genes such as DHFR. This results in increased DHFR protein and may lead to MTX resistance. As the knowledge regarding mechanisms of resistance increases newer approaches to circumvent such resistance or to target resistant cells can be undertaken.
Single‐molecule genomics (2009)

The term 'single-molecule genomics' (SMG) describes a group of molecular methods in which single molecules are detected or sequenced. The focus on the analysis of individual molecules distinguishes these techniques from more traditional methods, in which template DNA is cloned or PCR-amplified prior to analysis. Although technically challenging, the analysis of single molecules has the potential to play a major role in the delivery of truly personalized medicine. The two main subgroups of SMG methods are single-molecule digital PCR and single-molecule sequencing. Single-molecule PCR has a number of advantages over competing technologies, including improved detection of rare genetic variants and more precise analysis of copy-number variation, and is more easily adapted to the often small amount of material that is available in clinical samples. Single-molecule sequencing refers to a number of different methods that are mainly still in development but have the potential to make a huge impact on personalized medicine in the future.
Immunological distinction between acetylcholine receptor and the alpha-bungarotoxin-binding component on sympathetic neurons. (1977)

Clone PC12 of a rat sympathetic neuron cell line binds alpha-bungarotoxin and exhibits carbamoylcholine-stimulated uptake of sodium ions. Concentrations of alpha-bungarotoxin that saturate the alpha-bungarotoxin-binding site have no effect on agonist-stimulated sodium uptake. Conversely, antibodies against eel acetylcholine receptor block the agonist-induced sodium flux but fail to recognize the alpha-bungarotoxin-binding component. Detergent extracts of the PC12 clone inhibit the ability of antibody to eel acetylcholine receptor to recognize 125I-alpha-bungarotoxin-acetylcholine receptor complexes derived from muscle. These results distinguish between a ganglionic nicotinic acetylcholine receptor and an alpha-bungarotoxin-binding component on these cells, and provide evidence for antigenic similarities between muscle acetylcholine receptor and ganglionic acetylcholine receptor.
Liposomal stabilization of camptothecin's lactone ring (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLiposomal stabilization of camptothecin's lactone ringThomas G. Burke, Alfred E. Staubus, A. K. Mishra, and Henryk MalakCite this: J. Am. Chem. Soc. 1992, 114, 21, 8318–8319Publication Date (Print):October 1, 1992Publication History Published online1 May 2002Published inissue 1 October 1992https://pubs.acs.org/doi/10.1021/ja00047a069https://doi.org/10.1021/ja00047a069research-articleACS PublicationsRequest reuse permissionsArticle Views401Altmetric-Citations72LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Methamphetamine abuse. (2007)

Methamphetamine is a stimulant commonly abused in many parts of the United States. Most methamphetamine users are white men 18 to 25 years of age, but the highest usage rates have been found in native Hawaiians, persons of more than one race, Native Americans, and men who have sex with men. Methamphetamine use produces a rapid, pleasurable rush followed by euphoria, heightened attention, and increased energy. Possible adverse effects include myocardial infarction, stroke, seizures, rhabdomyolysis, cardiomyopathy, psychosis, and death. Chronic methamphetamine use is associated with neurologic and psychiatric symptoms and changes in physical appearance. High-risk sexual activity and transmission of human immunodeficiency virus are also associated with methamphetamine use. Use of methamphetamine in women who are pregnant can cause placental abruption, intrauterine growth retardation, and preterm birth, and there can be adverse consequences in children exposed to the drug. Treatment of methamphetamine intoxication is primarily supportive. Treatment of methamphetamine abuse is behavioral; cognitive behavior therapy, contingency management, and the Matrix Model may be effective. Pharmacologic treatments are under investigation.
Synthesis and thermal properties of poly(cycloalkyl methacrylate)s bearing bridged‐ and fused‐ring structures (1993)

Abstract Radical polymerizations of some cycloalkyl methacrylates bearing bridged‐ and fused‐ring structures, i.e., bornyl methacrylate (BoMA), isobornyl methacrylate (IBoMA), 2‐decahydronaphthyl methacrylate (DNMA), and 3‐tetracyclo [4.4.0 2,5 .1 7,10 ] dodecyl methacrylate (TCDMA), were carried out. The radical polymerization reactivities of these monomers depended on the structure of the cycloalkyl ester groups in the following order: TCDMA &gt; BoMA &gt; DNMA &gt; CHMA &gt; IBoMA &gt; MMA, where CHMA and MMA are cyclohexyl and methyl methacrylates, respectively. The propagation and termination rate constants of these monomers were evaluated from the polymer radical concentration determined by electron spin resonance spectroscopy. The solubilities and microstructures of the resulting polymers were examined. Thermal properties, i.e., glass transition temperatures and decomposition behaviors, of the polymers were also investigated and related to the structures of the polymer side chain. © 1993 John Wiley &amp; Sons, Inc.
E.E. Cummings (2003)

Provides critical analysis from several viewpoints of such poems as All in green went my love riding, Memorabilia, and somewhere i have never traveled..
Promising Advances in the Management of Adrenal Insufficiency (2013)

Adrenal insufficiency is a rare disease that is difficult for patients to live with due to the lifelong requirement of steroid therapy and the ever-present risk of adrenal crisis. This article discusses the diagnosis of adrenal insufficiency, prevalence and prevention for adrenal crisis, and recent advances in the treatment of Addison's disease.
Expression of two conserved leptospiral antigens in Escherichia coli (1989)

The genes encoding two protein antigens of Leptospira interrogans serovar pomona were cloned and expressed in Escherichia coli. Rabbit antisera raised against the cloned proteins, designated p12 and p20, were used to identify the antigens in Western blots of disrupted leptospiral cells. The proteins p12 and p20 were conserved within the genus Leptospira and were not detected in Leptonema illini. Although both proteins were present in leptospiral outer envelope preparations they did not elicit the production of agglutinating or opsonising antibodies.
Overexpression of the regulator of G-protein signaling 5 reduces the survival rate and enhances the radiation response of human lung cancer cells (2015)

Regulator of G protein signaling 5 (RGS5) belongs to the R4 subfamily of RGS proteins, a family of GTPase activating proteins, which is dynamically regulated in various biological processes including blood pressure regulation, smooth muscle cell pathology, fat metabolism and tumor angiogenesis. Low-expression of RGS5 was reported to be associated with tumor progression in lung cancer. In the present study, we examined the potential roles of RGS5 in human lung cancer cells by overexpressing RGS5 in the cancer cells and further explored the underlying molecular mechanisms. The RGS5 gene was cloned and transfected into the human lung cancer cell lines A549 and Calu-3. The cells were tested for apoptosis with flow cytometry, for viability with MTT, for mobility and adhesion capacity. The radiosensitization effect of RGS5 was measured by a colony formation assay. The mechanisms of RGS5 functioning was also investigated by detection of protein expression with western blot analysis, including PARP, caspase 3 and 9, bax, bcl2, Rock1, Rock2, CDC42, phospho-p53 (Serine 15) and p53. The present study demonstrated that RGS5 overexpression remarkably induced apoptosis in human lung cancer cells, which was suggested to be through mitochondrial mechanisms. Overexpression of RGS5 resulted in significantly lower adhesion and migration abilities of the lung cancer cells (P<0.01). Furthermore, overexpression of RGS5 sensitized the lung cancer cells to radiation. In conclusion, the present study showed that RGS5 played an inhibitory role in human lung cancer cells through induction of apoptosis. Furthermore, RGS5 enhanced the cytotoxic effect of radiation in the human lung cancer cells. Our results indicated that RGS5 may be a potential target for cancer therapy.
Structure-Activity Relationships of a Series of Echinocandins and the Discovery of CD101, a Highly Stable and Soluble Echinocandin with Distinctive Pharmacokinetic Properties (2016)

Echinocandins are a first-line therapy for candidemia and invasive candidiasis. They are generally safe with few drug interactions, but the stability and pharmacokinetic properties of currently approved echinocandins are such that each was developed for daily intravenous infusion. We sought to discover a novel echinocandin with properties that would enable more flexible dosing regimens, alternate routes of delivery, and expanded utility. Derivatives of known echinocandin scaffolds were generated, and an iterative process of design and screening led to the discovery of CD101, a novel echinocandin that has since demonstrated improved chemical stability and pharmacokinetics. Here, we report the structure-activity relationships (including preclinical efficacy and pharmacokinetic data) for the series of echinocandin analogs from which CD101 was selected. In a mouse model of disseminated candidiasis, the test compounds displayed clear dose responses and were generally associated with lower fungal burdens than that of anidulafungin. Single-dose pharmacokinetic studies in beagle dogs revealed a wide disparity in the half-lives and volumes of distribution, with one compound (now known as CD101) displaying a half-life that is nearly 5-fold longer than that of anidulafungin (53.1 h versus 11.6 h, respectively). In vitro activity data against panels of Candida spp. and Aspergillus spp. demonstrated that CD101 behaved similarly to approved echinocandins in terms of potency and spectrum of activity, suggesting that the improved efficacy observed in vivo for CD101 is a result of features beyond the antifungal potency inherent to the molecule. Factors that potentially contribute to the improved in vivo efficacy of CD101 are discussed.
Generation of the Brucella melitensis ORFeome Version 1.1: Figure 1 (2004)

The bacteria of the Brucella genus are responsible for a worldwide zoonosis called brucellosis. They belong to the alpha-proteobacteria group, as many other bacteria that live in close association with a eukaryotic host. Importantly, the Brucellae are mainly intracellular pathogens, and the molecular mechanisms of their virulence are still poorly understood. Using the complete genome sequence of Brucella melitensis, we generated a database of protein-coding open reading frames (ORFs) and constructed an ORFeome library of 3091 Gateway Entry clones, each containing a defined ORF. This first version of the Brucella ORFeome (v1.1) provides the coding sequences in a user-friendly format amenable to high-throughput functional genomic and proteomic experiments, as the ORFs are conveniently transferable from the Entry clones to various Expression vectors by recombinational cloning. The cloning of the Brucella ORFeome v1.1 should help to provide a better understanding of the molecular mechanisms of virulence, including the identification of bacterial protein-protein interactions, but also interactions between bacterial effectors and their host's targets.
A Method for Permanent Transvenous Left Ventricular Pacing (1998)

LV-based pacing has recently been reported to be of benefit in patients with severe cardiac failure and left bundle branch block. LV permanent pacing has been reported using epicardial leads but the surgical mortality is excessive. A transvenous approach is now favored. In this regard, cannulation of the coronary sinus and of one of its tributaries using only the permanent electrode is feasible but technically challenging. We describe a "long guiding sheath" method using catheterization, and a long radiopaque and peelable sheath. Once the coronary sinus is cannulated with the electrophysiological catheter, the long sheath is advanced to the mid-part of the coronary sinus. The permanent pacing electrode is then placed through the sheath and into a tributary of the coronary sinus. This method has been attempted in 10 patients and was successful in 8, with an average lead insertion time of 21 +/- 5.5 minutes and an average fluoroscopic time of 11 +/- 5.5 minutes. In conclusion, although transvenous left ventricular pacing remains a challenge, the "long guiding sheath" approach appears to facilitate this procedure with both a high success rate and an acceptable procedure time.
Flexible and Stretchable Strain Sensing Actuator for Wearable Soft Robotic Applications (2016)

Despite the emergence of flexible and stretchable actuators, few possess sensing capabilities. Here, we present a facile method of integrating a flexible pneumatic actuator with stretchable strain sensor to form a soft sensorized actuator. The elastomeric actuator comprises a microchannel connected to a controlled air source to achieve bending. The strain sensor comprises a thin layer of screen‐printed silver nanoparticles on an elastomeric substrate to achieve its stretchability and flexibility while maintaining excellent conductivity at ≈8 Ω sq –1 . By printing a mesh network of conductive structures, our strain sensor is able to detect deformations beyond 20% with a high gauge factor beyond 50 000. The integration of a pneumatic soft actuator with our sensing element enables the measurement of the extent of actuator bending. To demonstrate its potential as a rehabilitation sensing actuator, we fit the sensorized actuator in a glove to further analyze finger kinematics. With this, we are able to detect irregular movement patterns in real time and assess finger stiffness or dexterity.
Bortezomib Causes ER Stress-related Death of Acute Promyelocytic Leukemia Cells Through Excessive Accumulation of PML-RARA. (2015)

UbcH8 may have a utility as a biomarker of treatment response to bortezomib in patients with APL. Furthermore, bortezomib impairs the UPS that controls normal protein homeostasis by causing excessive accumulation of PML-RARA augmenting ER stress and leading to APL cell death. The study provides a rationale for incorporating proteasome inhibitors in the treatment of diseases expressing aberrant proteins. Furthermore, monitoring of UPS-related enzymes might have use in predicting the treatment response to proteasome inhibitors and in assessing their therapeutic effects.
Estimating the Impact of Electric Vehicle Smart Charging on Distribution Transformer Aging (2012)

This paper describes a method for estimating the impact of plug-in electric vehicle (PEV) charging on overhead distribution transformers, based on detailed travel demand data and under several different schemes for mitigating overloads by shifting PEV charging times (smart charging). The paper also presents a new smart charging algorithm that manages PEV charging based on estimated transformer temperatures. We simulated the varied behavior of drivers from the 2009 National Household Transportation Survey, and transformer temperatures based an IEEE standard dynamic thermal model. Results are shown for Monte Carlo simulation of a 25 kVA overhead distribution transformer, with ambient temperature data from hot and cold climate locations, for uncontrolled and several smart-charging scenarios. These results illustrate the substantial impact of ambient temperatures on distribution transformer aging, and indicate that temperature-based smart charging can dramatically reduce both the mean and variance in transformer aging without substantially reducing the frequency with which PEVs obtain a full charge. Finally, the results indicate that simple smart charging schemes, such as delaying charging until after midnight can actually increase, rather than decrease, transformer aging.
Botulinum Toxin Treatment of Spasmodic Torticollis (1992)

We reviewed the efficacy and adverse effects of repeated botulinum toxin injections into hyperactive neck muscles of 107 successive patients with spasmodic torticollis. They received 510 injection treatments over a median period of 15 months (range 3-42 months). One patient failed to benefit at all, but 101 (95%) patients reported considerable (moderate or excellent) benefit from at least one treatment. On a global subjective response rating, 93% of 429 treatments resulted in some improvement and 76% in moderate or excellent improvement. Pain reduction followed 89% of 190 treatments with moderate or excellent reduction after 66%. Median duration of benefit was 9 weeks. All torticollis types responded equally well and injections into two (or more) involved neck muscles were more effective than injection into a single muscle. The most frequent adverse effect was dysphagia, occurring after 44% of all treatments, but this was severe after only 2%. Antibodies to botulinum toxin were detected in the serum of three out of the five patients in whom loss of treatment efficacy occurred. We conclude that botulinum toxin treatment is the most effective available therapy for spasmodic torticollis and practical advice is provided for anyone wishing to set up the technique.