Miracle-dz/UniFAR-FTUs huggingface dataset:
Nitrocatechol derivatives as inhibitors of catechol-O-methyltransferase.

Catechol-0-methyltransferase (EC 2.1.1.6; COMT) catalyses Sadenosylmethionine-dependent methylation of a variety of catechols and plays a role in terminating the activities of the catecholamine neurotransmitters dopamine and noradrenaline. Two isoenzymes, the soluble and membrane-bound forms (S-COMT and MB-COMT) are present in most tissues and although the former is more abundant, their different kinetic parameters suggest that the MB-form may play the dominant role in inactivating the catecholamines [I]. Studies on the inhibition of COMT have been extensive since specific and effective inhibitors could help elucidate the physiological role and properties of the enzyme. Furthermore, development of effective COMT inhibitors could be promising for therapeutic use both in Parkinson's disease and in diseases connected to an aberrant catecholamine metabolism. Early COMT inhibitors, e.g. tropolone, were not suitable for use in vivo (see review [2]). It was observed that catechol compounds with electron withdrawing substituents, particularly NO2 groups, greatly enhanced inhibitory activity [3] and this gave rise to a second generation of potent and selective COMT inhibitors [4,5]. Nitrocatechol was the key structure in the majority of these compounds (see Fig. 1) and these had inhibition constant (Ki) values in the nanomolar range [4,5]. The aims of this work were to study the efficacy of some nitrocatechol derivatives as inhibitors of both forms of COMT, especially the MB-form. Most previous studies have concentrated on the soluble enzyme and since the MB-form may be more important at low, physiological concentrations of substrate, it is possible that this form may have different affinities for inhibitors of the enzyme. Human S-COMT and MB-COMT cloned and expressed in Escherichiu coli [6] were used as enzyme sources. COMT activity was assayed with using a slight modification of a direct solvent-extraction assay which determined the amount of radioactive guaiacol formed 171. A series of fixed inhibitor concentrations was used (see Table l ) , while the concentration of catechol was varied between approximately half to several times the K, concentration for each form of the enzyme and meth~l [~H]labelled AdoMet was held at 390 pM. Representative doublereciprocal plots are also shown in Figs. 2 (a) and (b) for the inhibition of S-COMT and MB-COMT by 4,5-dinitrocatechol with respect to catechol. The Ki values were determined for the nitrocatechol derivatives by plotting slopes of the double reciprocal plots against inhibitor concentration and results for both forms of the enzyme are shown in Table 1.
A 183-Year History of Fire and Recent Fire Suppression Impacts in Select Pine and Oak Forest Stands of the Menominee Indian Reservation, Wisconsin

Abstract Due to the paucity of long-term fire chronologies in the upper Midwest, we studied basal cross-sections dating back to 1822 and the impacts of recent fire suppression in pine and oak stands on the Menominee Indian Reservation in northeast Wisconsin. A total of 93 fire events with a fire-return interval (FRI) of 5.9–17.7 y were recorded across all stands before fire suppression activities in 1935. After 1935, we recorded 29 fires. Most stands have only burned 0–3 times since 1935, and only four of 16 stands yielded enough fire years to calculate FRIs. Superposed Epoch Analysis (SEA) determined significantly lower Palmer Drought Severity Index (PDSI) values 1 y before individual fire years. Fire wounding occurred primarily in the dormant season and average tree diameter at time of wounding ranged from 7–30 cm. Current forest composition was dominated by white pine (Pinus strobus L.) and red maple (Acer rubrum L.) overstories, whereas seedlings and saplings were predominantly eastern hemlock (Tsuga canadensis (L). Carrière), witch-hazel (Hamamelis virginiana L.) and sugar maple (A. saccharum Marsh.). Tree species recorded on similar soils in 19th Century General Land Office surveys were mainly aspen (Populus), white pine and eastern hemlock. We conclude that the combination of logging and decreased fire occurrence over the past century resulted in a compositional shift from historic aspen, pine and oak forests towards later successional northern hardwoods.
Patterns of everyday technology use and activity involvement in mild cognitive impairment: a five-year follow-up study

ABSTRACT Objectives: The aims were to describe longitudinal patterns in terms of perceived ability to use everyday technology (ET) and involvement in everyday activities over five years in older adults with mild cognitive impairment (MCI), and to examine the predictive value of these patterns regarding diagnostic outcomes. Method: Thirty older adults diagnosed with MCI at inclusion, reported their perceived ability in using ET and involvement in everyday activities on seven occasions over five years. Individual longitudinal case plots and a pattern-oriented analysis were used to compare the participants' distribution in earlier identified stable/ascending, fluctuating and descending patterns of functioning (year 0–2). Fisher's exact test was used for testing the relation between pattern and diagnostic outcomes. Results: An initial descending pattern of functioning tended to continue; none of these participants later developed a more stable pattern. More congruent trajectories of change appeared over time. Pattern affinity years 0–2 and diagnostic outcome were significantly related (p = .05), with a dementia diagnosis being more likely for those initially displaying an early descending pattern Conclusion: These findings point to a need for early support focusing on the use of ET for persons with MCI who early after diagnosis descend in functioning.
Complement C5b-9 Membrane Attack Complex Increases Expression of Endoplasmic Reticulum Stress Proteins in Glomerular Epithelial Cells*

In the passive Heymann nephritis (PHN) model of membranous nephropathy, complement C5b-9 induces glomerular epithelial cell (GEC) injury, proteinuria, and activation of cytosolic phospholipase A2 (cPLA2). This study addresses the role of endoplasmic reticulum (ER) stress proteins (bip, grp94) in GEC injury. GEC that overexpress cPLA2 (produced by transfection) and “neo” GEC (which expresses cPLA2at a lower level) were incubated with complement (40 min), and leakage of constitutively expressed bip and grp94 from ER into cytosol was measured to monitor ER injury. Greater leakage of bip and grp94 occurred in complement-treated GEC that overexpress cPLA2, as compared with neo, implying that cPLA2 activation perturbed ER membrane integrity. After chronic incubation (4–24 h), C5b-9 increased bip and grp94 mRNAs and proteins, and the increases were dependent on cPLA2. Expression of bip-antisense mRNA reduced stimulated bip protein expression and enhanced complement-dependent GEC injury. Glomerular bip and grp94 proteins were up-regulated in proteinuric rats with PHN, as compared with normal control. Pretreatment of rats with tunicamycin or adriamycin, which increase ER stress protein expression, reduced proteinuria in PHN. Thus, C5b-9 injures the ER and enhances ER stress protein expression, in part, via activation of cPLA2. ER stress protein induction is a novel mechanism of protection from complement attack.
Long‐term outcome of acquired aplastic anaemia in children: comparison between immunosuppressive therapy and bone marrow transplantation

A total of 100 children under the age of 17 years with acquired aplastic anaemia (AA) were initially treated with immunosuppressive therapy (IST) (n = 63) or bone marrow transplantation (BMT) (n = 37) from an HLA‐matched family donor. The projected 10‐year survival rates were 55 ± 8% and 97 ± 3% respectively (P = 0·004). Because the IST group included 11 non‐responders who were salvaged by BMT from an HLA‐matched unrelated donor, we compared failure‐free survival (FFS) between the groups. The probability of FFS at 10 years was 97 ± 3% for the BMT group, compared with 40 ± 8% for the IST group (P = 0·0001). Seven patients evolved to myelodysplastic syndrome (MDS) with monosomy 7 and the estimated cumulative incidence of MDS 10 years after diagnosis was 20 ± 7% in the IST group. We compared the outcome of children treated with IST during the two consecutive periods of 1983–91 (group A, n = 40) and 1991–8 (group B, n = 23) to assess the impact of combined therapy with anti‐thymocyte globulin and cyclosporin. The probability of FFS at 7 years follow‐up was the same in the two groups (50 ± 8% vs. 40 ± 15%, P = 0·40). We recommend BMT as first‐line therapy in paediatric severe AA patients with an HLA‐matched family donor. Alternative donor BMT is recommended as salvage therapy in patients who relapse or do not respond to initial IST.
Platelet Counts and Postoperative Stroke After Coronary Artery Bypass Grafting Surgery

BACKGROUND: Declining platelet counts may reveal platelet activation and aggregation in a postoperative prothrombotic state. Therefore, we hypothesized that nadir platelet counts after on-pump coronary artery bypass grafting (CABG) surgery are associated with stroke. METHODS: We evaluated 6130 adult CABG surgery patients. Postoperative platelet counts were evaluated as continuous and categorical (mild versus moderate to severe) predictors of stroke. Extended Cox proportional hazard regression analysis with a time-varying covariate for daily minimum postoperative platelet count assessed the association of day-to-day variations in postoperative platelet count with time to stroke. Competing risks proportional hazard regression models examined associations between day-to-day variations in postoperative platelet counts with timing of stroke (early: 0–1 days; delayed: ≥2 days). RESULTS: Median (interquartile range) postoperative nadir platelet counts were 123.0 (98.0–155.0) × 109/L. The incidences of postoperative stroke were 1.09%, 1.50%, and 3.02% for platelet counts >150 × 109/L, 100 to 150 × 109/L, and <100 × 109/L, respectively. The risk for stroke increased by 12% on a given postoperative day for every 30 × 109/L decrease in platelet counts (adjusted hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.01–1.24; P= .0255). On a given day, patients with moderate to severe thrombocytopenia were almost twice as likely to develop stroke (adjusted HR, 1.89; 95% CI, 1.13–3.16; P= .0155) as patients with nadir platelet counts >150 × 109/L. Importantly, such thrombocytopenia, defined as a time-varying covariate, was significantly associated with delayed (≥2 days after surgery; adjusted HR, 2.83; 95% CI, 1.48–5.41; P= .0017) but not early postoperative stroke. CONCLUSIONS: Our findings suggest an independent association between moderate to severe postoperative thrombocytopenia and postoperative stroke, and timing of stroke after CABG surgery.
Clinical Value of Loss of Heterozygosity in Serum Microsatellite DNA of Patients With Gastrointestinal Stromal Tumors

Goals To study the role of loss of heterozygosity (LOH) in serum microsatellite DNA of patients with gastrointestinal stromal tumors (GIST). Background In GIST, tumor markers from peripheral blood are missing. Study Seventy-eight patients (59 GIST, 13 leiomyomas, 2 leiomyosarcomas, and 4 schwannomas) underwent resection at our institute between 1985 and 2006. Thirty-three preoperative sera (26 GIST and 7 non-GIST) and 62 postoperative sera (47 GIST and 15 non-GIST) were available and tested for alterations in 12 representative microsatellite loci on chromosomes 22, 17, 13, 9, and 3, using fluorescence-based automated capillary electrophoresis by ABI Prism. Survival was calculated with Kaplan-Meier plots. Results Seventeen out of 26 GIST patients had a positive preoperative serum LOH score (≥2 LOH, sensitivity 65.4%), and 6 out of 7 non-GIST patients had a negative score (≤1 LOH, specificity 85.7%, P=0.030, Fisher exact test). Serum LOH in GIST were strongly correlated with Fletcher risk groups (P=0.016, χ2 test). All metastasized GIST (7/7) showed ≥2 LOH preoperatively. Postoperative sensitivity and specificity of LOH analysis for prediction of relapse in 47 GIST was 75.0% and 64.1%, respectively. After a median observation time of 51.3 months (95% confidence interval, 39.4-61.4), LOH in serum significantly predicted overall survival (P=0.007, log-rank test). Conclusions LOH serum analysis in GIST may play a role as a noninvasive, differential diagnostic, prognostic, and monitoring marker in the clinical routine.
Luteinizing Hormone/Choriogonadotropin-Dependent, Cholera Toxin-Catalyzed Adenosine 5′-Diphosphate (ADP)-Ribosylation of the Long and Short Forms of Gsα and Pertussis Toxin-Catalyzed ADP-Ribosylation of Giα

Although it is well established that activated LH/human (h) CG receptor stimulates adenylyl cyclase activity (via the heterotrimeric stimulatory guanine nucleotide-binding protein, Gs) and in some cells stimulates phospholipase C activity, there is no evidence for a direct physical interaction between the LH/CG receptor and Gs or any other G protein(s). We conducted studies using cholera toxin (CTX) and pertussis toxin (PTX) to determine which Gα proteins were associated with the LH/CG receptor in ovarian follicular membranes. Since hormone-dependent, CTX-catalyzed ADP ribosylation (AR) constitutes evidence that a Gα protein is specifically associated with a receptor, CTX-catalyzed AR of membrane proteins was examined both in the presence and absence of guanine nucleotides to determine which G proteins exhibit hCG-dependent labeling by[ 32P]NAD. Results demonstrated the time- and hCG-dependent AR of both a 45-kDa protein and a 48/50-kDa doublet as well as a 40-kDa protein that was also sensitive to AR by .
A comparison of chromogenic substrates for horseradish peroxidase as a label in steroid enzyme immunoassay.

Six chromogenic substrates for horseradish peroxidase (HRP) as an enzyme label were compared with regard to the sensitivity obtainable with a testosterone enzyme immunoassay system. The chromogens tested were 2, 2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS), o-phenylenediamine (OPD), 5-aminosalicylic acid (5-AS), 3-amino-9-ethylcarbazole (AEC), 3, 3', 5, 5'-tetramethylbenzidine (TMB) and 3-methyl-2-benzothiazolinone hydrazone (MBTH); for comparison, a fluorimetric assay using 3-(p-hydroxyphenyl)propionic acid was also carried out. An HRP-labeled antigen was prepared by the N-succinimidyl ester method. The bound and free enzyme-labeled antigens were separated by a double antibody method. A dose-response curve with a satisfactory sensitivity was obtained in each system by the use of a minimum amount of the HRP label at an appropriate dilution of anti-testosterone antiserum (Ka=2×1010M-1). The amounts of testosterone needed to displace 50% of the bound label ranged from 9 to 150 pg. The sensitivity decreases in the order : TMB>OPD>ABTS>5-AS>MBTH>AEC. The assay using the non-mutagenic substrate, TMB, gave a high sensitivity, comparable to that of the fluorimetric method.
Disruption of the vastus medialis obliquus with medial knee ligament injuries

We reviewed the clinical records of 189 consecutive surgically treated acute ligamentous injuries of the me dial compartment of the knee to determine the preva lence of disruptions of the vastus medialis obliquus muscle and to document the results of simultaneous repair of the disruption. Forty knees (40 patients) dem onstrated a vastus medialis muscle disruption at the time of surgical repair for the medial ligamentous dis ruption. All were surgically corrected and the sites of tearing were documented. The vastus medialis obliquus muscle was ruptured from the adductor tubercle in 31 (78%) knees. Of these, the tibial collateral ligament was torn from its femoral attachment in 19 (61 %) knees and the meniscofemoral portion of the capsular ligament ligament was torn from its femoral attachment in 23 (74%) knees. The vastus medialis obliquus muscle was ruptured from the patella in seven (18%) knees and was ruptured interstitially in nine (23%) knees. Each of the 40 patients returned for objective, subjective, and functional follow-up evaluation (average, 39 months). At follow-up examination, 88% of the 40 knees were rated as good subjectively, 90% objectively, and 93% functionally. A high correlation exists between tears of the vastus medialis obliquus muscle from its femoral attachment and tears of the medial compartment liga ments from their respective femoral attachments. Sur gical repair of disruptions of the vastus medialis obli quus muscle at the time of primary repair of injury to the ligaments of the medial compartment of the knee can prevent subsequent disorder of the extensor mech anism and can produce an objectively, subjectively, and functionally stable knee.
Pre-ictal heart rate variability assessment of epileptic seizures by means of linear and non-linear analyses.

OBJECTIVE The purpose of the present study was to analyze the effects of epilepsy on the autonomic control of the heart in pre-ictal phase in order to find an algorithm of early detection of seizure onset. METHODS Overall 133 epileptic seizures were analyzed from 12 patients with epilepsy (seven males and five females; mean age 43.91 years, SD: 10.16) participated in this study. Single lead electrocardiogram recordings of epileptic patients were compiled. 240, 90-30, 30-10 and 5 minutes heart rate variability (HRV) signals of preseizure were chosen for analysis of heart rate. As HRV signals are non-stationary, a set of time and frequency domain features (Mean HR, Triangular Index, LF, HF, LF/HF) and nonlinear parameters (SD1, SD2 and SD2/SD1 indices derived from Poincare plots) extracted from HRV is analyzed. Statistical analysis was performed using paired sample t-test for comparisons of the segments and differences between pre-ictal segments were evaluated by Tukey tests. RESULTS There was slight tachycardia in segments near the seizure (30 minutes before: 85.3517 bpm, 5 minutes before: 119.3630.82 bpm, p=0.0207) which significantly differ from baseline in segments far from seizure (240 minutes before: 66.5211.7 bpm). Also there was significant increase in LF/HF ratio (30 minutes before: 1.10.22, 5 minutes before: 2.120.5, p=0.0332) and SD2/SD1 ratio (30 minutes before: 1.20.15, 5 minutes before: 2.030.55, p=0.0431) when compared to segments far from the seizure (240 minutes before: 0.780.24 and 0.780.14) respectively. Although there was about decrease of triangular index in segments near the seizure the percentage of decrease was not comparable to segments far from the seizure. CONCLUSION Significant changes of HRV parameters in pre-ictal (5 minutes before the seizure) are obviously higher in comparison to interictal baseline. Pre-ictal significant changes of HRV suggesting that this time can be considered as prediction time for designing an algorithm of early detection of seizure onset based on HRV.
Characteristics of nanofibers extracted from kenaf core

Cellulose nanofibers were isolated from kenaf core fibers by employing chemo-mechanical treatments. The morphologies and sizes of the fibers were explored with environmental scanning electron microscopy (ESEM) and transmission electron microscopy (TEM). The results of chemical analysis showed that the cellulose contents of the bleached pulp fibers and nanofibers increased from 46% to 92% and to 94%, respectively. Most of the produced nanofibers had diameters in the range of 20 to 25 nm, whereas kenaf nanofibers ranged in diameter diameters from 10 to 75 nm. Fourier transform infrared spectroscopy (FTIR) analysis revealed the removal of lignin and the majority of the hemicelluloses from the kenaf core fibers. The thermogravimetric analysis (TGA), which was carried out to evaluate the thermal properties of the fibers, demonstrated that the thermal stabilities of these fibers were increased by the chemo-mechanical treatments. The results of X-ray analysis confirmed that chemical and mechanical treatments can improve the crystallinity of fibers.
The ligament anatomy of the deltoid complex of the ankle: a qualitative and quantitative anatomical study.

BACKGROUND The deltoid ligament has both superficial and deep layers and consists of up to six ligamentous bands. The prevalence of the individual bands is variable, and no consensus as to which bands are constant or variable exists. Although other studies have looked at the variance in the deltoid anatomy, none have quantified the distance to relevant osseous landmarks. METHODS The deltoid ligaments from fourteen non-paired, fresh-frozen cadaveric specimens were isolated and the ligamentous bands were identified. The lengths, footprint areas, orientations, and distances from relevant osseous landmarks were measured with a three-dimensional coordinate measurement device. RESULTS In all specimens, the tibionavicular, tibiospring, and deep posterior tibiotalar ligaments were identified. Three additional bands were variable in our specimen cohort: the tibiocalcaneal, superficial posterior tibiotalar, and deep anterior tibiotalar ligaments. The deep posterior tibiotalar ligament was the largest band of the deltoid ligament. The origins from the distal center of the intercollicular groove were 16.1 mm (95% confidence interval, 14.7 to 17.5 mm) for the tibionavicular ligament, 13.1 mm (95% confidence interval, 11.1 to 15.1 mm) for the tibiospring ligament, and 7.6 mm (95% confidence interval, 6.7 to 8.5 mm) for the deep posterior tibiotalar ligament. Relevant to other pertinent osseous landmarks, the tibionavicular ligament inserted at 9.7 mm (95% confidence interval, 8.4 to 11.0 mm) from the tuberosity of the navicular, the tibiospring inserted at 35% (95% confidence interval, 33.4% to 36.6%) of the spring ligament's posteroanterior distance, and the deep posterior tibiotalar ligament inserted at 17.8 mm (95% confidence interval, 16.3 to 19.3 mm) from the posteromedial talar tubercle. CONCLUSIONS The tibionavicular, tibiospring, and deep posterior tibiotalar ligament bands were constant components of the deltoid ligament. The deep posterior tibiotalar ligament was the largest band of the deltoid ligament. CLINICAL RELEVANCE The anatomical data regarding the deltoid ligament bands in this study will help to guide anatomical placement of repairs and reconstructions for deltoid ligament injury or instability.
Mass movement within a slope streak on Mars

Slope streaks on Mars represent a currently active geological process. Various theories for slope streak formation have suggested that slope streaks form by disturbing only a thin surface veneer, or by staining of the surface, preserving pre‐existing topography within the streak. Theories also vary as to whether the formation mechanism requires the presence of water or another liquid. We present observations of a slope streak that reveal topographic mounds within the streak. These mounds do not continue outside the streak, and we suggest that they formed with, or immediately after, the slope streak. We use estimates of the total volume of mounds in this particular streak, compared with the estimated excavation volume, to extrapolate to a global sediment transport rate from slope streak formation. If this slope streak is typical, then this calculated rate is greater than estimates of the total volume of material transported by dust storms each year.
SNPs in human β‐defensin 1 gene (DEFB1): frequencies in a Mexican population and new PCR–RFLPs assays

Polymerase chain reaction–restriction fragment length polymorphism assays for two single nucleotide polymorphisms in the human β‐defensin 1 gene have been validated with real‐time PCR in 101 healthy individuals from western Mexico. Allele frequencies were 52.5% (692‐A) and 98.5% (1836‐A). These assays can be confidently used as a cheaper alternative genotyping method for these sites.