gebhart/patrepeval huggingface dataset:
Site-Specific Attachment of Functionalized Poly(ethylene glycol) to the Amino Terminus of Proteins (1996)

A convenient method for the construction of site-specifically modified poly(ethylene glycol)-protein conjugates is described. This method relies on the ability to generate a reactive carbonyl group in place of the terminal amino group. If the protein has N-terminal serine or threonine, this can be done by very mild periodate oxidation and generates a glyoxylyl group. A method less restricted by the nature of the N-terminal residue, but which requires somewhat harsher conditions, is metal-catalyzed transamination, which gives a keto group. The N-terminal-introduced reactive carbonyl group specifically reacts, under mild acidic conditions, with an aminooxy-functionalized poly(ethylene glycol) to form a stable oxime bond. Using polymers of different size and shape (linear or multibranched), various conjugates of IL-8, G-CSF, and IL-1ra were constructed and further characterized with respect to their biological activity and pharmacokinetic behavior in rats. Unlike most previous methods, this approach places a single PEG chain at a defined site on the protein. It should therefore be more likely to conserve biological activity when the latter depends on interaction with another macromolecule (unlike enzymic activity which often survives multiple PEGylation).
A low-noise high-gain transimpedance amplifier with high dynamic range in 0.13&#x00EC;m CMOS (2012)

This paper designed a low-noise high-gain tran simpedance amplifier with high dynamic range. The input stage of TIA uses an individual power supply to accommodate the level of the photodiode(PD). Then the signal is transmitted to the subsequent circuit by a level shifting circuit. The TIA adopts DCrestore to stabilize work points, and uses a MOS working in the linear region to reduce the effective input signal to realize high dynamic range. Key noise components are optimized to reduce the input referred current noise. This TIA was validated in 0.13 urn CMOS. The simulation results show the -3dB bandwidth is 1.8GHz, the maximum gain is 82.27dB Ω, the input referred noise is 125nA, and the measure current ranges 5uA ~2mA.
High-power Yb-doped photonic bandgap fiber amplifier at 1150-1200 nm (2009)

Ytterbium-doped solid-core photonic bandgap fiber amplifiers operating at the long-wavelength edge of the ytterbium gain band are reported. The low-loss bandgap transmission window is formed in the very low gain region, whilst outside the bandgap, large attenuation inhibits the exponential growth of amplified spontaneous emission in the huge-gain 1030-1100 nm region. Hence parasitic-lasing-free, high-power amplification with a marked efficiency is enabled. A 32 W output at 1156 nm with a 66% slope efficiency and 30 W output at 1178 nm with a 58% slope efficiency were successfully obtained. To our knowledge, these are the highest output powers generating from active photonic bandgap fibers, as well as from ytterbium-doped fiber lasers at these wavelengths.
Biophysical Properties and Slow Voltage-Dependent Inactivation of a Sustained Sodium Current in Entorhinal Cortex Layer-II Principal Neurons (1999)

The functional and biophysical properties of a sustained, or "persistent," Na(+) current (I(NaP)) responsible for the generation of subthreshold oscillatory activity in entorhinal cortex layer-II principal neurons (the "stellate cells") were investigated with whole-cell, patch-clamp experiments. Both acutely dissociated cells and slices derived from adult rat entorhinal cortex were used. I(NaP), activated by either slow voltage ramps or long-lasting depolarizing pulses, was prominent in both isolated and, especially, in situ neurons. The analysis of the gating properties of the transient Na(+) current (I(NaT)) in the same neurons revealed that the resulting time-independent "window" current (I(NaTW)) had both amplitude and voltage dependence not compatible with those of the observed I(NaP), thus implying the existence of an alternative mechanism of persistent Na(+)-current generation. The tetrodotoxin-sensitive Na(+) currents evoked by slow voltage ramps decreased in amplitude with decreasing ramp slopes, thus suggesting that a time-dependent inactivation was taking place during ramp depolarizations. When ramps were preceded by increasingly positive, long-lasting voltage prepulses, I(NaP) was progressively, and eventually completely, inactivated. The V(1/2) of I(NaP) steady state inactivation was approximately -49 mV. The time dependence of the development of the inactivation was also studied by varying the duration of the inactivating prepulse: time constants ranging from approximately 6.8 to approximately 2.6 s, depending on the voltage level, were revealed. Moreover, the activation and inactivation properties of I(NaP) were such as to generate, within a relatively broad membrane-voltage range, a really persistent window current (I(NaPW)). Significantly, I(NaPW) was maximal at about the same voltage level at which subthreshold oscillations are expressed by the stellate cells. Indeed, at -50 mV, the I(NaPW) was shown to contribute to >80% of the persistent Na(+) current that sustains the subthreshold oscillations, whereas only the remaining part can be attributed to a classical Hodgkin-Huxley I(NaTW). Finally, the single-channel bases of I(NaP) slow inactivation and I(NaPW) generation were investigated in cell-attached experiments. Both phenomena were found to be underlain by repetitive, relatively prolonged late channel openings that appeared to undergo inactivation in a nearly irreversible manner at high depolarization levels (-10 mV), but not at more negative potentials (-40 mV).
The cloning and characterization of the arom gene of Pneumocystis carinii (1993)

The arom gene, encoding a single polypeptide that catalyses five consecutive steps of the pre-chorismate aromatic amino acid biosynthetic pathway, has been cloned from the opportunistic pathogen Pneumocystis carinii. There is a single open reading frame of 4788 bp which includes an intron of 45 bp that does not introduce a stop codon into the sequence. Thus, the derived amino acid sequence consists of 1581 residues, which is highly homologous to all fungal AROM proteins studied to date. These data support the view that P. carinii is a fungus and imply that its aromatic amino acid biosynthesis is conventionally organized.
Biologic features of HIV-2. An update. (1991)

The history serology and epidemiology of the new human T-lymphocyte retrovirus HIV-2 are reviewed. This relative of HIV-1 the cause of AIDS was discovered in Senegal in 1985. Sera from persons harboring HIV-2 have antibodies more closely resembling those against SIV the primate immunodeficiency virus than HIV-1. HIV-2 shares 40% of its genome with HIV-1 binds to the same lymphocyte CD4 receptor and binds by a similar viral envelope glycoprotein gp120. In contrast to HIV-1 HIV-2 replicates more slowly and demonstrates less cell killing and syncytial cell formation than HIV-1. People with HIV-2 react positively to about 80% of the early ELISA tests for HIV-1. Many HIV-1 positive patients have high antibody titers to some of the shared antigens. In some countries e.g. Burkina Faso and Ivory Coast significant proportions of sera react to both HIV-1 and HIV-2 tests and are called reactors. To tell whether a person is really infected with both viruses the definitive diagnosis would be virus isolation or polymerase chain reaction studies. ElISA tests are being designed to distinguish both viruses. There are at least 4 patterns of dual infection according to prevalence of each HIV type. Generally HIV-2 is endemic in West Africa and less common in the former Portuguese colonies Mozambique an Angola while HIV-2 is prevalent in East Central Africa. HIV-2 is spreading to other countries by travellers. There is very little information on the natural history of HIV-2 infection. No large case-control or prospective population-based studies are available. HIV-2 infection is transmitted by the same routes as HIV-1 except the perinatal transmission rate is low. Rates of ARC and AIDS-like disease are believed to be low and the prevalence in the population predominantly in older adults suggests that HIV-2 has been endemic in West Africa for at least 18 years.
Optimization of metabolic stability as a goal of modern drug design (2001)

Abstract Metabolism and other pharmacokinetic (PK) studies have always played a critical role in helping to optimize the bioavailability and duration of action of new drugs thereby increasing their success rate. With the advent of automated combinatorial synthesis, high‐throughput pharmacological testing, and the ability to create extensive databases in the past decade, drug discovery has undergone an amazing evolution. With the increased throughput of drug discovery, metabolism and other PK studies have evolved to keep pace. Often called “early ADME” studies, these studies are characterized by parallel processing and higher throughput than before. This article focuses on a particular class of early ADME (absorption, distribution mechanism, and excretion) studies known as “metabolic stability” studies. The theoretical basis for metabolic stability and its relationship to the concept of metabolic intrinsic clearance is briefly presented. Some key relationships between structure and metabolism are summarized. Several case studies from recent medicinal chemistry literature are reviewed to exemplify how metabolic stability studies influenced drug design and led to improvements in bioavailability and half‐life. Finally, future trends in drug metabolism and analytical chemistry and how they may influence metabolic stability studies are reviewed. © 2001 John Wiley &amp; Sons, Inc. Med Res Rev, 21, No. 5, 412–449, 2001
WDM EDFA gain characterization with a reduced set of saturating channels (1996)

The advent of EDFA-based dense WDM places demanding optical source requirements for EDFA characterization. An iterative method is proposed here, based on a homogeneous amplifier model, to calculate the required signal conditions for WDM testing with a reduced set of saturating channels and a broad-band noise probe. EDFA gain measurements demonstrating this reduced-source technique agree to within 0.2 dB to those obtained with a four-channel WDM system operating near 1.55 μm.
Isolation and characterization of a variant dihydrofolate reductase cDNA from methotrexate-resistant murine L5178Y cells (1990)

Dihydrofolate reductase (DHFR) cDNA sequences were isolated from a methotrexate-resistant mouse L5178Y cell line previously shown to contain methotrexate-resistant dihydrofolate reductase enzyme activity. Specifically-primed reverse transcription products were amplified using the polymerase chain reaction and then cloned into a mammalian expression plasmid. Candidate clones were identified by restriction analysis and then functionally tested by transfection into mouse 3T3 fibroblasts, selecting for methotrexate-resistant colonies. Sequence analysis of the cDNA clones demonstrated the substitution of tryptophan (TGG) in place of the wild-type phenylalanine (TTC) at codon 31. Sequencing of PCR-amplified genomic DNA extracted from the drug-resistant L5178Y cells confirmed the tryptophan codon at position 31. Transfection of mammalian tissue culture cells with expression plasmids containing the trp31 DHFR sequence resulted in substantial methotrexate-resistant colony formation. Recombinant trp31 DHFR enzyme activity expressed in stably-transfected Chinese hamster ovary cells was approximately 20-fold less sensitive to methotrexate inhibition than wild-type mouse DHFR enzyme activity. We conclude that the cloned Trp31 DHFR sequence encodes an enzyme substantially resistant to methotrexate which confers a drug-resistance phenotype to cells in which it is expressed.
Tumor iNOS predicts poor survival for stage III melanoma patients (2006)

Inducible nitric oxide synthase (iNOS) produces nitric oxide, which has growth promoting activity in melanoma. A preliminary study of tumors from patients with Stage III melanoma who had received neo-adjuvant therapy revealed an association of tumor iNOS expression with shortened survival. The objective of the present study was to determine whether iNOS expression in tumors of newly diagnosed, untreated Stage III patients is predictive of survival. iNOS expression was examined by immunohistochemistry in tumors from 132 patients. The staining was evaluated for percentage of positive cells (Number score) and the intensity of staining (Intensity score). The association of iNOS expression with overall and disease-specific survival was tested in univariate and multivariate Cox proportional hazards regression models that included other known prognostic factors. Results of the univariate analysis demonstrated that the presence of iNOS in a patient's tumor, whether graded on the basis of Number or Intensity score, was associated with a significant increase in the hazard ratio of death from melanoma. These findings were corroborated by median survival data estimated from Kaplan Meier analysis. In the multivariate model including iNOS number or intensity, gender, age, number of lymph nodes, macroscopic disease and in-transit disease, only iNOS expression predicted survival. We conclude that a significant association exists between tumor iNOS expression and shortened survival in untreated Stage III melanoma patients. The ability of iNOS to predict outcomes for these patients may be independent of other known prognostic factors, providing a new molecular marker with significant potential for clinical utility.
Multiparameter measurements of thin films using beam-profile reflectometry (1993)

Beam-profile reflectometry is a new technique for measuring the thickness and optical constants of dielectric, semiconducting, and thin metal films. The technique consists of measuring the intensity profile of a highly focused beam reflected from the sample. By using a linearly polarized light source and a tightly focussed beam, the S- and P-polarization reflectivities of the film are simultaneously obtained over a wide range of angles. The focusing also provides a submicrometer spot, thus allowing these measurements to be performed in very small geometries. How the information present in the reflectivity profiles can reveal information about as many as three unknown film parameters simultaneously is described, and results from film samples for which the multiparameter fitting capability was essential to the success of the measurement are also presented.
Automatic gazetteer enrichment with user-geocoded data (2013)

Geographical knowledge resources or gazetteers that are enriched with local information have the potential to add geographic precision to information retrieval. We have identified sources of novel local gazetteer entries in crowd-sourced OpenStreetMap and Wikimapia geotags that include geo-coordinates. We created a fuzzy match algorithm using machine learning (SVM) that checks both for approximate spelling and approximate geocoding in order to find duplicates between the crowd-sourced tags and the gazetteer in effort to absorb those tags that are novel. For each crowd-sourced tag, our algorithm generates candidate matches from the gazetteer and then ranks those candidates based on word form or geographical relations between each tag and gazetteer candidate. We compared a baseline of edit distance for candidate ranking to an SVM-trained candidate ranking model on a city level location tag match task. Experiment results show that the SVM greatly outperforms the baseline.
Gabapentin Increases Slow‐wave Sleep in Normal Adults (2002)

GBP appears to be less disruptive to sleep than are some of the older AEDs. These findings may underlie the drug's therapeutic effect in the treatment of disorders associated with sleep disruption.
Electrically tunable superhydrophobic nanostructured surfaces (2005)

In this work, we discuss dynamic electrical control of the wetting behavior of liquids on nanostructured surfaces spanning the entire possible range from superhydrophobic behavior to nearly complete wetting. It is demonstrated that a droplet of liquid can be reversibly switched between the superhydrophobic “rolling ball” state and the hydrophilic immobile droplet state by the application of electrical voltage and current. The nature of the transition mechanism is studied both experimentally and theoretically. The reported results provide novel methods of manipulating liquids at microscale.
Brain-derived neurotrophic factor: role in depression and suicide (2009)

Depression and suicidal behavior have recently been shown to be associated with disturbances in structural and synaptic plasticity. Brain-derived neurotrophic factor (BDNF), one of the major neurotrophic factors, plays an important role in the maintenance and survival of neurons and in synaptic plasticity. Several lines of evidence suggest that BDNF is involved in depression, such that the expression of BDNF is decreased in depressed patients. In addition, antidepressants up-regulate the expression of BDNF. This has led to the proposal of the "neurotrophin hypothesis of depression". Increasing evidence demonstrates that suicidal behavior is also associated with lower expression of BDNF, which may be independent from depression. Recent genetic studies also support a link of BDNF to depression/suicidal behavior. Not only BDNF, but abnormalities in its cognate receptor tropomycin receptor kinase B (TrkB) and its splice variant (TrkB.T1) have also been reported in depressed/suicidal patients. It has been suggested that epigenetic modulation of the Bdnf and Trkb genes may contribute to their altered expression and functioning. More recently, impairment in the functioning of pan75 neurotrophin receptor has been reported in suicide brain specimens. pan75 neurotrophin receptor is a low-affinity neurotrophin receptor that, when expressed in conjunction with low availability of neurotropins/Trks, induces apoptosis. Overall, these studies suggest the possibility that BDNF and its mediated signaling may participate in the pathophysiology of depression and suicidal behavior. This review focuses on the critical evidence demonstrating the involvement of BDNF in depression and suicide.
Coronary Hyperreactivity to Adrenergic Stimulation and Increased Nocturnal Vagal Tone Trigger Coronary Vasospasm (1998)

The relationship between autonomic nervous system activity (ANA) and coronary vasoreactivity during transient myocardial ischemia was determined in patients with vasospastic angina (VA). ANA was measured by power spectral analysis of heart rate variability and humoral factors following intravenous infusion of insulin in 24 patients with VA and 6 control patients. Nine (38%) of the VA patients had significant ST segment depression (STD), and 4 of these patients had symptomatic STD. The frequency of anginal episodes in the 9 patients with VA and STD was significantly greater than that in the 15 VA patients without STD (3.4 +/- 3.1 vs 0.5 +/- 0.8 episodes/week, p < 0.05). The increase in the LF/HF ratio 30 min after insulin injection in patients with STD was significantly greater than that in patients without STD (34 +/- 31% vs 4 +/- 34%, p < 0.05). All of the patients with VA and STD had significant coronary vasospasm in response to the infusion of < or = 20 micrograms of acetylcholine, higher levels of nocturnal parasympathetic activity, and greater norepinephrine production in response to insulin stimulation than the VA patients without STD. These findings suggest that increased vagal tone and hyperreactivity to adrenergic stimulation may trigger vasospasm in patients with VA.
Discovery and Characterization of 4‘-(2-Furyl)-N-pyridin-3-yl-4,5‘-bipyrimidin-2‘-amine (LAS38096), a Potent, Selective, and Efficacious A2BAdenosine Receptor Antagonist (2007)

A novel series of N-heteroaryl 4'-(2-furyl)-4,5'-bipyrimidin-2'-amines has been identified as potent and selective A(2B) adenosine receptor antagonists. In particular, compound 5 showed high affinity for the A(2B) receptor (Ki = 17 nM), good selectivity (IC(50): A(1) > 1000 nM, A(2A) > 2500 nM, A3 > 1000 nM), displayed a favorable pharmacokinetic profile in preclinical species, and showed efficacy in functional in vitro models.
Disease modifying and anti-nociceptive effects of the bisphosphonate, zoledronic acid in a model of bone cancer pain (2002)

Inoculation of syngeneic MRMT-1 mammary tumour cells into one tibia of female rats produced tumour growth within the bone associated with a reduction in bone mineral density (BMD) and bone mineral content (BMC), severe radiological signs of bone destruction, together with the development of behavioural mechanical allodynia and hyperalgesia. Histological and radiological examination showed that chronic treatment with the bisphosphonate, zoledronic acid (30 microg/kg, s.c.), for 19 days significantly inhibited tumour proliferation and preserved the cortical and trabecular bone structure. In addition, BMD and BMC were preserved and a dramatic reduction of tartrate resistant acid phosphatase-positive polykaryocytes (osteoclasts) was observed. In behavioural tests, chronic treatment with zoledronic acid but not the significantly less effective bisphosphonate, pamidronate, or the selective COX-2 inhibitor, celebrex, attenuated mechanical allodynia and hyperalgesia in the affected hind paw. Zoledronic acid also attenuated mechanical hyperalgesia associated with chronic peripheral neuropathy and inflammation in the rat. In contrast, pamidronate or clodronate did not have any anti-hyperalgesic effect on mechanical hyperalgesia in the neuropathic and inflammatory pain models. We conclude that zoledronic acid, in addition to, or independent from, its anti-metastatic and bone preserving therapeutic effects, is an anti-nociceptive agent in a rat model of metastatic cancer pain. This unique property of zoledronic acid amongst the bisphosphonate class of compounds could make this drug a preferred choice for the treatment of painful bone metastases in the clinic.
Rhodopsin and Porphyropsin Fields In the Adult Bullfrog Retina (1971)

Though it had been supposed earlier that the bullfrog undergoes a virtually complete metamorphosis of visual systems from vitamin A(2) and porphyropsin in the tadpole to vitamin A(1) and rhodopsin in the adult, the present observations show that the retina of the adult frog may contain as much as 30-40% porphyropsin, all of it segregated in the dorsal zone. The most dorsal quarter of the adult retina may contain 81-89% porphyropsin mixed with a minor amount of rhodopsin; the ventral half contains only rhodopsin. Further, the dorsal zone contains a two to three times higher concentration of visual pigments than the ventral retina. The pigment epithelium underlying the retina contains a corresponding distribution of vitamins A(1) and A(2), predominantly vitamin A(2) in the dorsal pigment epithelium, exclusively vitamin A(1) in the ventral zone. The retina accepts whatever vitamin A the pigment epithelium provides it with, and turns it into the corresponding visual pigment. Thus, a piece of light-adapted dorsal retina laid back on ventral pigment epithelium regenerates rhodopsin, whereas a piece of light-adapted ventral retina laid back on dorsal pigment epithelium regenerates predominantly porphyropsin. Vitamin A(2) must be made from vitamin A(1), by dehydrogenation at the 3,4-bond in the ring. This conversion must occur in the pigment epithelium, presumably through the action of a vitamin A-3,4-dehydrogenase. The essential change at metamorphosis is to make much less of this dehydrogenase, and to sequester it in the dorsal pigment epithelium. Some adult bullfrogs, perhaps characteristically taken in the summer, contain very little porphyropsin-only perhaps 5%-still sequestered in the dorsal retina. The gradient of light over the retinal surface has little if any effect on this distribution. The greater density of visual pigments in the dorsal retina, and perhaps also-although this is less clear-the presence of porphyropsin in this zone, has some ecological importance in increasing the retinal sensitivity to the dimmer and, on occasion, redder light received from below.