gebhart/patrepeval huggingface dataset:
An optical probe for detecting chondrocyte apoptosis in response to mechanical injury (2017)

Cartilage injury induced by acute excessive contact stress is common and mostly affects young adult. Although early detection of cartilage injury may prevent serious and lifelong arthritic complications, early detection and treatment is not possible due to the lack of a reliable detection method. Since chondrocyte injury and subsequent cell death are the early signs of cartilage injury, it is likely that cartilage cell apoptosis can be used to predict the extent of injury. To test this hypothesis, a near infrared probe was fabricated to have high affinity to apoptotic cells. In vitro tests show that this apoptosis probe has low toxicity, high specificity, and high affinity to apoptotic cells. In addition, there is a positive relationship between apoptotic cell numbers and fluorescence intensities. Using a mouse xiphoid injury model, we found significant accumulation of the apoptosis probes at the injured xiphoid cartilage site. There was also a positive correlation between probe accumulation and the number of apoptotic chondrocytes within the injured xiphoid cartilage, which was confirmed by TUNEL assay. The results support that the apoptosis probes may serve as a powerful tool to monitor the extent of mechanical force-induced cartilage injury in vivo.
Discovery of 2-Pyridinone Aminals: A Prodrug Strategy to Advance a Second Generation of HIV-1 Integrase Strand Transfer Inhibitors (2015)

The search for new molecular constructs that resemble the critical two-metal binding pharmacophore required for HIV integrase strand transfer inhibition represents a vibrant area of research within drug discovery. Here we present the discovery of a new class of HIV integrase strand transfer inhibitors based on the 2-pyridinone core of MK-0536. These efforts led to the identification of two lead compounds with excellent antiviral activity and preclinical pharmacokinetic profiles to support a once-daily human dose prediction. Dose escalating PK studies in dog revealed significant issues with limited oral absorption and required an innovative prodrug strategy to enhance the high-dose plasma exposures of the parent molecules.
A new ascosporogenous yeast genus: Yamadazyma gen.nov. (1989)

Volume: 35
Transport in isolated rat hepatocytes of the phospho-oligosaccharide that mimics insulin action. Effects of adrenalectomy and glucocorticoid treatment (1991)

The addition to intact cells of an inositol phospho-oligosaccharide (POS), which is the polar head-group of an insulin-sensitive glycosylphosphatidylinositol, mimics and may mediate some of the biological effects of this hormone. Here we report the existence of a POS transport system in hepatocytes. This POS transport system is specific and time- and dose-dependent. Insulin-resistance caused by dexamethasone administration to rats was accompanied by a decrease in the hepatocyte POS transport system. In contrast, bilateral adrenalectomy provoked a significant increase in the transport of POS. Both the temporal uptake of POS and the regulation of this process by conditions known to modify the sensitivity to insulin suggest that this novel transport system might be involved in the insulin signalling mechanism.
cAMP binding proteins in the rat cerebral cortex after administration of selective 5-HT and NE reuptake blockers with antidepressant activity. (1991)

This study was undertaken to evaluate the cyclic adenosine monophosphate (cAMP) binding proteins in the cerebral cortex of rat after short- and long-term administration with antidepressants. Prolonged treatment with different antidepressants that inhibit serotonin or norepinephrine uptake such as fluoxetine and the (+) enantiomer of oxaprotiline, respectively, was able to induce an increase in the photoactivated incorporation of 8-N3-[32P]cAMP into a protein band with apparent molecular weight of 52,000 in both soluble and crude microtubule fraction. On the contrary, chronic treatment with the (-) enantiomer of oxaprotiline, which does not affect monoamine uptake, failed to produce this effect. Moreover, no changes were observed after acute or in vitro addition of antidepressants, suggesting that modification in the cAMP binding may be related to adaptive changes elicited by prolonged antidepressants treatment. In conclusion, our studies indicate that the cAMP binding protein associated with the crude microtubule fraction could be an intracellular target for the action of antidepressant drugs.
Combined Influence of Gene-Specific Cord Blood Methylation and Maternal Smoking Habit on Birth Weight (2013)

Our data suggest that gene-specific methylation of cord DNA is associated with BWP and this methylation provides an additional effect on BWP to that of smoking during pregnancy.
Gene Transcription RNA Analysis Essential Techniques (1996)

Gene Transcription RNA Analysis Essential Techniques , Gene Transcription RNA Analysis Essential Techniques , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
Review and Fabrication of Nanochannels for Single Phase Liquid Flow (2005)

The topic of single phase liquid flow in submicron or nanochannels is a nascent field. There have only been a couple papers that have dealt with this area directly. The most probable reason for this is that currently most research in fluid mechanics or heat transfer is being focused on micron size channels. To help facilitate researchers to focus on this undeveloped area, this paper serves as a review for some of the micro-fabrication processes that will make it possible for engineers and scientists to study this field in greater detail.
Computer-based program for identifying medication orders requiring dosage modification based on renal function. (1991)

A computer-based program that enables staff pharmacists to quickly review medication orders written for renally impaired patients is described. Medication orders requiring dosage modification based on the renal function of the patients for whom they were written were being identified by a medical staff-approved pharmacist intervention program. However, staff pharmacists were unable to assess the orders easily and rapidly because of a lack of readily available patient data. In response, a computer-based intervention program was developed. Specific dosage guidelines for renally eliminated drugs in patients with renal dysfunction were entered into the pharmacy computer. An interface with the laboratory computer enables the pharmacy computer to access creatinine concentration or clearance values, perform calculations if necessary, and alert pharmacists to specific drug orders that may require modification. Such medication orders are flagged by the pharmacy computer during order entry. When a staff pharmacist judges that intervention is needed, he or she telephones the ordering physician or sends a note to the patient's nursing station. Over a two-month period, 1485 orders were identified as being potentially inappropriate. Physicians were contacted about 191 of the flagged orders, and they accepted the pharmacist's recommendation for 141 (74%) of these orders. The interventions resulted in a drug acquisition cost saving of $7082 over the two-month period. A computer-based program enabled staff pharmacists to easily and rapidly identify orders for renally eliminated agents that required modification, reduced the risk of adverse reactions, trimmed costs, and promoted the clinical dimension of pharmacy practice.
A Scorpion Probe–Based Real-Time PCR Assay for Detection of E. coli O157:H7 in Dairy Products (2009)

Methods for rapidly detecting Escherichia coli O157:H7, a high risk foodborne pathogen of considerable public health concern, are extremely important for monitoring of food safety. Conventional detection such as microbiological, biochemical, and immunological methods, including polymerase chain reactions (PCR), are time consuming and only qualitative. In this study, a rapid real-time PCR (RTi-PCR) method based on Scorpion probe technology targeting the eae gene of E. coli O157:H7 was developed and applied using spiked and naturally contaminated products. The assay was highly specific and did not show any cross-reactivity with any of the 15 nontargeted bacterial cultures. The assay was sensitive enough to detect 2 log colony-forming units (CFU)/mL of the target pathogen in pure broth culture and 3 log CFU/mL in spiked skim milk. When the assay was applied with 60 market dairy food samples, one sample each of raw milk, paneer, and ice cream, was found to be positive for E. coli O157:H7 with respective RTi-PCR counts of 6.7, 6.2, and 5.9 log CFU. The present study demonstrates the application of Scorpion probe technology for the detection of foodborne pathogens and reports the presence of E. coli O157:H7 in paneer, a very popular indigenous dairy product (soft cheese) in India, for the first time.
High mobility group A1 and cancer: potential biomarker and therapeutic target. (2012)

The High Mobility Group A1 (HMGA1, formerly HMG-I/Y) gene is highly expressed during embryogenesis and in virtually all aggressive human cancers studied to date, although its role in these settings is only beginning to emerge. Moreover, high levels of expression portend a poor prognosis in some tumors. Increasing evidence suggests that the HMGA1 protein functions as a master regulator with a critical role in normal development and tumor progression in diverse malignancies. These proteins contain AT-hook DNA binding domains that mediate binding to AT-rich regions of chromatin. After binding to DNA, HMGA1 alters DNA structure, and orchestrates the assembly of a transcriptional complex or "enhanceosome" to regulate gene expression. Previous studies indicate that HMGA1 participates in regulating fundamental cellular processes, including transcription, cell cycle progression, embryonic development, neoplastic transformation, differentiation, senescence, viral integration, and DNA repair by virtue of its ability to interact with other proteins, bind to DNA, and modulate gene expression. Recent studies also link HMGA1 expression to poor differentiation status and a refractory, stem cell-like state in aggressive cancers. Together, these findings suggest that HMGA1 could serve as a useful biomarker and therapeutic target in advanced malignancies. Here, we focus on prior studies implicating HMGA1 in the pathogenesis of refractory human tumors arising from diverse tissues and its potential role as a biomarker. We also review previous attempts to target HMGA1 pathways in cancer. Further study of HMGA1 promises to have a major impact on our ability to understand and treat cancer.
Surfactant protein D deficiency influences allergic immune responses (2004)

SP-D may be critical for the modulation of early stages of allergic inflammation in vivo.
Milzverlust und Replantation autologen Milzgewebes beim Erwachsenen (1993)

Der Milzverlust ist mit der permanenten Gefahr septischer Komplikationen verbunden. Auch wenn Erwachsene nur selten davon betroffen werden, sollte die Milz erhalten werden. Bei einer unvermeidbaren Splenektomie kann autologes Milzgewebe replantiert werden. Das Gewebe regeneriert und kann mit Einschränkungen zelluläre und humorale Funktionen übernehmen. Ein Gröβenwachstum ist nicht nachweisbar. Eine verminderte Durchblutung, die sich szintigrafisch belegen läβt, und eine gestörte Mikroarchitektur lassen die Replantate im Hinblick auf eine Phagozytose von Mikroorganismen bei Erwachsenen als funktionslos erscheinen.
5′-Cytosine-Phosphoguanine (CpG) Methylation Impacts the Activity of Natural and Engineered Meganucleases (2012)

In this study, we asked whether CpG methylation could influence the DNA binding affinity and activity of meganucleases used for genome engineering applications. A combination of biochemical and structural approaches enabled us to demonstrate that CpG methylation decreases I-CreI DNA binding affinity and inhibits its endonuclease activity in vitro. This inhibition depends on the position of the methylated cytosine within the DNA target and was almost total when it is located inside the central tetrabase. Crystal structures of I-CreI bound to methylated cognate target DNA suggested a molecular basis for such inhibition, although the precise mechanism still has to be specified. Finally, we demonstrated that the efficacy of engineered meganucleases can be diminished by CpG methylation of the targeted endogenous site, and we proposed a rational design of the meganuclease DNA binding domain to alleviate such an effect. We conclude that although activity and sequence specificity of engineered meganucleases are crucial parameters, target DNA epigenetic modifications need to be considered for successful gene editions.
Trimetazidine Reduces Renal Dysfunction by Limiting the Cold Ischemia/Reperfusion Injury in Autotransplanted Pig Kidneys (2000)

Ischemia/reperfusion injury leads to delayed graft function, which is a major problem in kidney transplantation. This study investigated the effects of adding trimetazidine (TMZ) to the perfusate of cold-stored kidneys on the function of reperfused autotransplanted pig kidney. The left kidney was removed and cold-flushed with Euro-Collins (EC), or University of Wisconsin (UW) solutions with or without 10(-6)M TMZ and stored for 48 h at 4 degrees C. The kidneys were then autotransplanted and the contralateral kidneys were removed. Several parameters were analyzed over the 14 d after transplantation. The survival rate was 57% in pigs transplanted with kidneys cold-flushed with UW and 43% for those flushed with EC solution; it was 100% for pigs having kidneys cold-flushed with TMZ-supplemented UW and EC solutions. The functions of the transplanted kidneys were also better preserved after cold flush with TMZ-supplemented solutions than with TMZ-free solutions. Creatinine clearance was higher and the urinary excretion of trimethylamine-N-oxide and dimethylamine, used as markers of renal medulla injury, were lower in animals transplanted with kidneys cold-flushed with TMZ-supplemented solutions than with TMZ-free solutions. The cytoprotective action of TMZ also reduced interstitial and peritubular inflammation and the numbers of infiltrating mononuclear CD45+and CD3+ T cells. These results indicate that the tissue damage due to ischemia/reperfusion injury may be prevented, at least in part, by adding TMZ to preservation solutions.
Synthesis, biological evaluation, and preliminary structure-activity considerations of a series of alkylphenols as intravenous anesthetic agents (1980)

Following our discovery of the intravenous (iv) anesthetic activity of 2,6-diethylphenol in mice, a series of alkylphenols was examined in this species and the most active analogues were further evaluated in rabbits. The synthesis of compounds which were not commercially available was accomplished by adaptations of standard ortho-alkylation procedures for phenols. Structure-activity relationships were found to be complex, but, in general, potency and kinetics appeared to be a function of both the lipophilic character and the degree of steric hindrance exerted by ortho substituents. The most interesting compounds were found in the 2,6-dialkyl series, and the greatest potency was associated with 2,6-di-sec-alkyl substitution. In particular, 2,6-diisopropylphenol (ICI 35 868) emerged as a candidate for further development and has subsequently been shown to be an effective iv anesthetic agent in man.
Altered Alveolar Surfactant Is an Early Marker of Acute Lung Injury in Septic Adult Sheep (1994)

The purpose of this study was to characterize changes in the endogenous surfactant system in adult sheep rendered septic via cecal ligation and perforation (CLP). Forty-eight hours after CLP, septic animals had significant increases in mean pulmonary artery pressure (PAP) (p < 0.01), cardiac index (CI) (p < 0.01), and arterial lactate (p < 0.05) values compared with their respective baseline values, while the same measurements in a sham-operated control group did not change significantly. The changes in the septic group were associated with significantly lower PaO2 (p < 0.05) and alveolar to arterial (A-a) oxygen gradient values (p < 0.01) at 48 h compared with baseline measurements. No changes in oxygenation occurred within the sham-operated group. Surfactant phospholipid (PL) composition and surface activity measurements of isolated alveolar surfactant aggregate forms were similar for the two groups at 48 h. However, the ratio of poorly functioning small aggregate forms (SA) to superior functioning large aggregates (LA) was significantly increased in the septic versus the sham-operated animals (p < 0.01). This was associated with significantly decreased surfactant protein A (SP-A), B (SP-B), and C (SP-C) levels in septic versus sham-operated animals (p < 0.05). We conclude that sepsis-associated lung injury resulted in altered alveolar surfactant aggregate forms. These changes, together with altered surfactant protein levels, may represent a very sensitive marker of acute lung injury in high-risk patients. Furthermore, these findings suggest that exogenous surfactant given at an early stage of lung injury may mitigate progressive lung dysfunction.
The Dengue Threat to the United States (2010)

Over the past 3 decades, dengue has spread rapidly and has emerged as one of the world's most common mosquitoborne viral diseases. Although often found in tropical and semitropical areas, dengue is capable of being transmitted in temperate climates as well. Dengue is currently endemic to Mexico, most other Latin American countries, and parts of the Caribbean, and it has the potential to become reestablished as an endemic disease in the United States. In fact, sustained transmission of dengue has occurred in Florida within the past year. Conditions exist in the U.S. that could facilitate sustained dengue transmission, including environmental factors, competent mosquito vectors, limited vector and dengue surveillance, increased domestic outdoor daytime activities in warmer months, and low public awareness of the disease. If dengue were to be reestablished in the U.S., it could have significant medical, public health, and economic consequences for the country. The impact of dengue as a public health threat could be lessened through enhanced awareness and reporting of cases, increased support for vector surveillance and control programs, and a greater focus on vaccine development.
Conformational changes in tertiary structure near the ligand binding site of an integrin I domain (1999)

For efficient ligand binding, integrins must be activated. Specifically, a conformational change has been proposed in a ligand binding domain present within some integrins, the inserted (I) domain [Lee, J., Bankston, L., Arnaout, M. & Liddington, R. C. (1995) Structure (London) 3, 1333-1340]. This proposal remains controversial, however, despite extensive crystal structure studies on the I domain [Lee, J., Bankston, L., Arnaout, M. & Liddington, R. C. (1995) Structure (London) 3, 1333-1340; Liddington, R. & Bankston, L. (1998) Structure (London) 6, 937-938; Qu, A. & Leahy, D. J. (1996) Structure (London) 4, 931-942; and Baldwin, E. T., Sarver, R. W., Bryant, G. L., Jr., Curry, K. A., Fairbanks, M. B., Finzel, B. C. , Garlick, R. L., Heinrikson, R. L., Horton, N. C. & Kelly, L. L. (1998) Structure (London) 6, 923-935]. By defining the residues present in the epitope of a mAb against the human Mac-1 integrin (alphaMbeta2, CD11b/CD18) that binds only the active receptor, we provide biochemical evidence that the I domain itself undergoes a conformational change with activation. This mAb, CBRM1/5, binds the I domain very close to the ligand binding site in a region that is widely exposed regardless of activation as judged by reactivity with other antibodies. The conformation of the epitope differs in two crystal forms of the I domain, previously suggested to represent active and inactive receptor. Our data suggests that conformational differences in the I domain are physiologically relevant and not merely a consequence of different crystal lattice interactions. We also demonstrate that the transition between the two conformational states depends on species-specific residues at the bottom of the I domain, which are proposed to be in an interface with another integrin domain, and that this transition correlates with functional activity.
The dynamics of the cat retinal X cell centre. (1987)

1. The dynamics of the centre mechanism of individual cat X retinal ganglion cells is investigated. The visual stimuli consist of temporal contrast modulation of stationary patterns. In order to study the response of the centre mechanism, patterns were either sine gratings of high spatial frequency or small circular spots positioned over the receptive-field centre. 2. Responses to contrast reversal are approximately linear. However, as the modulation depth of the stimulus increases, responses become more transient. Ganglion cell responses show this phenomenon at moderate contrasts (e.g. 0.1), which do not elicit discharges that approach the maximum firing rate of the ganglion cell. 3. A sequence of dynamical models are constructed from responses elicited by sum-of-sinusoids modulation of the spatial pattern. The first model is strictly linear. It consists of a series of low-pass filters and a single high-pass filter. The linear model predicts the approximate shape of the step response, but does not account for the change in shape of the response as a function of modulation depth. 4. The second model, a quasi-linear model, allows the 'linear' dynamics to vary slowly with a neural measure of contrast. The main effect of high contrast is a shorter time constant in the high-pass filter. This model accounts qualitatively for the increased transience of the response, but fails to predict the magnitude of the effect at higher modulation depths. 5. In the third model, the transfer characteristics of the centre response adjust rapidly as contrast changes. This intrinsically non-linear model provides excellent agreement with observed response to steps and more complex modulation patterns. 6. The non-linearity necessitated by a voltage-to-spikes transduction is analysed quantitatively. In most ganglion cells, a simple truncation at 0 impulses/s (and no saturation) explains the changes in apparent gain and mean firing rate that occur as modulation depth is increased. A non-linear voltage-to-spike transduction per se cannot account for the observed effect of contrast on dynamics. 7. The parameters of the dynamical model are measured for a population of twenty-seven X ganglion cells (nineteen on-centre and eight off-centre). The low-pass stage and the strength of the high-pass stage are relatively uniform across the population. The over-all gain and the dynamics of the high-pass stage vary substantially across the population, but show no consistent dependence on the on-off distinction or on retinal location. Some implications of this variability for retinal function are discussed.