Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Phosphate in a Multistep Enzymatic Reaction: Reactions of the Substrate and Intermediate in Pieces

Several mechanistically unrelated enzymes utilize the binding energy of their substrate’s nonreacting phosphoryl group to accelerate catalysis. Evidence for the involvement of the phosphodianion in transition state formation has come from reactions of the substrate in pieces, in which reaction of a truncated substrate lacking its phosphorylmethyl group is activated by inorganic phosphite. What has remained unknown until now is how the phosphodianion group influences the reaction energetics at different points along the reaction coordinate. 1-Deoxy-d-xylulose-5-phosphate (DXP) reductoisomerase (DXR), which catalyzes the isomerization of DXP to 2-C-methyl-d-erythrose 4-phosphate (MEsP) and subsequent NADPH-dependent reduction, presents a unique opportunity to address this concern. Previously, we have reported the effect of covalently linked phosphate on the energetics of DXP turnover. Through the use of chemically synthesized MEsP and its phosphate-truncated analogue, 2-C-methyl-d-glyceraldehyde, the current study revealed a loss of 6.1 kcal/mol of kinetic barrier stabilization upon truncation, of which 4.4 kcal/mol was regained in the presence of phosphite dianion. The activating effect of phosphite was accompanied by apparent tightening of its interactions within the active site at the intermediate stage of the reaction, suggesting a role of the phosphodianion in disfavoring intermediate release and in modulation of the on-enzyme isomerization equilibrium. The results of kinetic isotope effect and structural studies indicate rate limitation by physical steps when the covalent linkage is severed. These striking differences in the energetics of the natural reaction and the reactions in pieces provide a deeper insight into the contribution of enzyme–phosphodianion interactions to the reaction coordinate.
Two years of Finnish Telestroke

Background: Official guidelines on stroke promote the use of telemedicine via bidirectional videoconferencing equipment, which provides a valid and reliable means of facilitating thrombolysis delivery to patients in distant or rural hospitals. Methods: The present prospective cohort study describes the characteristics and 3-month outcome of the thrombolysis patients treated in 5 community hospitals served by the Helsinki University Central Hospital (HUCH) in a telestroke network during 2007 to 2009. The characteristics and outcome of telestroke thrombolysis patients are compared with consecutive thrombolysis patients (n = 985) treated at HUCH. Results: A total of 106 consecutive telestroke consultations in 2 years led to IV thrombolysis in 61 patients (57.5%). The median NIH Stroke Scale score was 10 (range 3–26), onset to treatment time 120 minutes (interquartile range [IQR] 49), length of consultation 25 minutes (IQR 18) if the consultation led to thrombolysis and 15 minutes (IQR 10) if not (p = 0.032). The rate of symptomatic intracranial bleedings was 6.7% (4/60) according to the National Institute of Neurological Disorders and Stroke definition. Half (28/57) of the thrombolysis patients with complete follow-up data had a favorable outcome (modified Rankin Scale [mRS] 0–2) and a third (17/57) had an excellent recovery (mRS 0–1). Thus the patients treated with thrombolysis based on teleconsultation had similar outcome with those treated at HUCH (mRS 0–2: 49.1% vs 58.1%, p = 0.214 and mRS 0–1: 17/57 [29.4%] vs 352/957 [36.8%], p = 0.289). Conclusions: A special feature of the Finnish pilot is the high percentage of consultations leading to thrombolytic treatment with features and results very similar to on-site thrombolysis at the neurologic emergency room of HUCH.
Density and Refractive Index Studies of Dental Hard Tissues

There is no published material on density distribution of dry deciduous enamel and dentin. No density values on moist deciduous enamel are available, however Deakins, Boyd and Drain (1) have shown a density distribution for 51 moist blocks of deciduous dentin. They found an approximately normal distribution around the mean density of 1.91. Their values were on samples which included water and protein in the tubules and some cementum. Black (2) gave a value of 2.08 for moist dentin from one deciduous root. The recent development of the method for separation of tooth tissues (3) into samples of known density limits provides an opportunity for measurement of these fundamental properties of deciduous enamel and dentin. In the work reported herewith all of the enamel and all of the dentin from several teeth were pooled, dried, powdered and separated into fractions of known density limits. Density distribution curves were obtained and mean densities calculated for the dry tissues studied.
Megakaryopoiesis in vitro in myelodysplastic syndromor and development es and acute myeloid leukaemia: effect of pegylated recombinant human megakaryocyte growth and development factor in combination with other growth factors

Pegylated recombinant human megakaryocyte growth and development factor (PEG‐rHuMGDF) can stimulate megakaryopoiesis in vitro in some myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) patients. We assessed PEG‐rHuMGDF combined with granulocyte colony‐stimulating factor (G‐CSF), granulocyte–macrophage CSF (GM‐CSF), interleukin 3 (IL‐3), IL6, stem cell factor (SCF) or erythropoietin in 40 MDS, 33 AML and 16 normal bone marrow samples. CD61‐positive cells in suspension cultures increased with PEG‐rHuMGDF alone in 20/25 RA + RAS, 11/14 RAEB + RAEBt and 29/33 AML cases. Further increases when IL‐3 and/or SCF were added to PEG‐rHuMGDF occurred in 14/20 RA + RAS, 8/13 RAEB + RAEBt and 18/26 AML cases. CFU‐Mk growth was poor overall, but could be enhanced by PEG‐rHuMGDF combinations in some patients. Stimulation of megakaryopoiesis by PEG‐rHuMGDF can be augmented by IL‐3 and SCF in many MDS and AML patients.
Serum adipocyte fatty acid–binding protein associated with ischemic stroke and early death

Objective: Adipocyte fatty acid–binding protein (A-FABP) is an adipokine shown to have adverse metabolic and proinflammatory effects, and contributes to atherosclerosis in mice. However, its role in cardiovascular diseases in humans remains to be established. In this case-control study, we investigated the association of serum A-FABP with ischemic stroke, and examined its association with early mortality. Methods: Serum A-FABP was measured, using ELISA, in 306 subjects with acute ischemic stroke and 306 age-, sex-, and body mass index–matched controls. All controls were free of cardiovascular diseases. Serum A-FABP was also measured in another 60 ischemic stroke subjects who died within 3 months of acute stroke. Results: Serum A-FABP was higher in subjects with ischemic stroke as compared to controls (19.6 ng/mL [14.3–28.4 ng/mL] vs 15.2 ng/mL [10.6–23.6 ng/mL] in men and 32.4 ng/mL [24.5–45.7 ng/mL] vs 22.0 ng/mL [14.3–34.0 ng/mL] in women, stroke vs control, p < 0.001). On logistic regression analyses with the model including hypertension, diabetes, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, lipid-lowering treatment, smoking, and A-FABP, serum A-FABP was independently associated with stroke (odds ratio 2.10, 95% confidence interval 1.50–2.94, p < 0.001), and the associations of A-FABP with ischemic stroke were additive to conventional risk factors, as demonstrated on likelihood ratio tests (p < 0.001). Furthermore, high serum A-FABP was associated with increased 3-month mortality in ischemic stroke subjects (odds ratio 2.65, 95% confidence interval 1.18–5.96, p = 0.018), independent of age and NIH Stroke Scale score. Conclusions: Serum A-FABP was significantly associated with ischemic stroke in our case-control study, and may serve as a useful prognostic indicator for early mortality.
Discovery of incednine as a potent modulator of the anti-apoptotic function of Bcl-xL from microbial origin.

Anti-apoptotic oncoproteins Bcl-2 and Bcl-xL are overexpressed in many cancers and play a crucial role in cancer initiation, progression, and resistance to chemotherapy. Therefore, the discovery of a functional inhibitor for these proteins and improved understanding of the molecular mechanisms of these proteins will be an aid to novel anti-tumor therapies. Here, using chemical−genetic cell-based screening, we have discovered a chemically and biologically unique substance, incednine, as a novel functional modulator of Bcl-2/Bcl-xL from the fermentation broth of Streptomyces sp. ML693-90F3. This compound was isolated as a HCl salt by solvent extraction and using centrifugal liquid−liquid partition chromatography. Its structure was elucidated by spectroscopic analysis, X-ray crystallographic analysis, and computational studies. Incednine has a molecular formula, C42H63N3O8, and consists of a novel skeletal structure, enol-ether amide in a 24-membered macrolactam core, with two aminosugars. Bcl-xL-overexpress.
Interleukin-7 receptor alpha gene polymorphism influences multiple sclerosis risk in Asians

A recent genome-wide survey identified non–human leukocyte antigen ( HLA ) genes that are related to multiple sclerosis (MS). Among these, an association of a single nucleotide polymorphism (SNP), rs6897932, in the interleukin-7 receptor α gene ( IL-7RA ) with MS susceptibility has been widely replicated in Caucasians.1,–,3 The SNP located in the transmembrane domain of IL-7Rα is nonsynonymous and functional: the MS-susceptible CC allele increases levels of the soluble form of IL-7Rα via exon skipping, and decreases the expression of membrane-bound IL-7Rα, thereby causing decreased IL-7/IL-7R signaling.1,–,3 IL-7/IL-7R signaling induces thymic production of FOXP3+ regulatory T cells, which efficiently ameliorate experimental autoimmune encephalomyelitis,4 an animal model of MS. Thus, the rs6897932 polymorphism of the IL-7RA gene may confer MS susceptibility through decreased production of FOXP3+ regulatory T cells due to downregulated IL-7/IL-7R signaling. This polymorphism has never been reported in either MS or neuromyelitis optica (NMO) in Asians. Therefore, in the present cross-sectional study, we investigated the association of the IL-7RA SNP rs6897932 with non-NMO MS and NMO in the Japanese. ### Methods. All patients with NMO fulfilled the 2006 Wingerchuk5 criteria for NMO, while those with NMO spectrum disorders who did not completely meet the criteria were excluded. All non-NMO patients with MS satisfied …
A multicenter assessment of cervical cord atrophy among MS clinical phenotypes

Objective: In this multicenter study, a new semiautomatic method for segmenting the cervical cord from C2 to C5 was used to investigate the correlation between cord atrophy and clinical disability in a large sample of patients with multiple sclerosis (MS). Methods: T2 and 3-dimensional T1-weighted cervical cord scans and dual-echo brain scans were acquired from 143 healthy controls, 22 patients with clinically isolated syndromes (CIS), 101 patients with relapsing-remitting MS (RRMS), 79 patients with secondary progressive MS (SPMS), 58 patients with benign MS (BMS), and 75 patients with primary progressive MS (PPMS) in 3 European centers. Normalized cervical cord cross-sectional area (CSAn) was measured by an active surface cord model. Between-group comparisons were performed using linear mixed-effect models. A nonparametric kernel estimator was used to obtain smoothed plots of CSA along the cervical cord. Results: Cord CSAn was significantly lower in PPMS vs healthy controls, BMS vs RRMS, SPMS vs BMS, and RRMS. From C2 to C5, a net separation and definition of the plots of patients with BMS, PPMS, and SPMS was seen with respect to those of the other study groups. CSAn was correlated with Expanded Disability Status Scale (r = −0.49, p < 0.0001), with a differential effect among disease clinical phenotypes: no association in either CIS or in BMS; association in RRMS (r = −0.30, p = 0.001), SPMS (r = −0.34, p = 0.001), and PPMS (r = −0.27, p = 0.01). Conclusions: Cervical cord atrophy provides a relevant and useful marker for the characterization of clinical heterogeneity of patients with MS. The stability of this measure among different centers supports its use as potential outcome measure to monitor disease progression in multicenter trials.
Trajectories of brain and hippocampal atrophy in FTD with mutations in MAPT or GRN

Objective: To use multiple serial MRI to assess rates and trajectories of brain and hippocampal atrophy in subjects with frontotemporal dementia (FTD) with progranulin (GRN) or microtubule-associated protein tau (MAPT) gene mutations. Methods: In this case-control study, we identified 8 subjects with mutations in GRN and 12 subjects with mutations in MAPT who had at least 2 serial MRIs. Serial MRIs were registered to baseline MRI for each subject using 9 df registration and rate of whole brain atrophy was calculated using the boundary-shift integral. Hippocampal volume was measured using Freesurfer. Mixed effects linear regression models were used to model volume change over time in both groups after adjusting for head size, age at baseline, and disease duration at baseline. Results: The annual rate of whole brain atrophy in the MAPT subjects was 2.4% per year (95% confidence interval [CI] 1.9–2.8). The GRN subjects showed a higher rate of whole brain atrophy at 3.5% per year (95% CI 2.8–4.2; p = 0.01). Rates of hippocampal atrophy were not different across the groups (MAPT = 7.8% [95% CI 3.9–12], GRN = 6.5% [95% CI 1.7–11], p = 0.66). Rates of whole brain atrophy in GRN, and hippocampal atrophy in MAPT, were associated with age, with older subjects showing slower rates of atrophy (p = 0.01 and p < 0.001). Conclusions: Subjects with FTD with GRN mutations have a faster rate of whole brain atrophy than subjects with FTD with MAPT mutations, with similar rates of hippocampal atrophy. Rates of atrophy in both groups were associated with age. These findings are important for future treatment trials in FTD that use rates of atrophy as an outcome measure.
The health condition in the Sami population of Sweden, 1961–2002: causes of death and incidences of cancer and cardiovascular diseases

Abstract Introduction. The sami people are the natives of northern Scandinavia and the Kola Peninsula. The knowledge about the health and living conditions of the Swedish Sami is exremely limited, which contrasts with the large amount of detailed information on health, demographic and socio-economic issues available for other circumpolar native populations.
A survey of major constraints limiting commercial poultry production in and around Gombe metropolis

In a survey of major constraints limiting commercial poultry production in Gombe metropolis, 2,121 poultry cases were presented at the Gombe State Veterinary Clinic between January 1995 and December 2004. Out of the total number of cases presented, Newcastle disease (ND) accounted for 14.66%, chronic respiratory disease (CRD) 12.31%, fowl typhoid (FT) 12.02%, coccidiosis 10.81%, fowl pox (FP) 10.33%, fowl cholera (FC) 8.63%, nutritional disorders 8.49%, ectoparasitism 7.49% while helminthosis accounted for 7.07%. Based on the analysis of 110 questionnaires administered to poultry farmers, ND was found to be the most prevalent accounting for 19.1% of the total, FP accounted for 15.7%, and helminthosis accounted for 2.2%. The results suggest that infectious, non-infectious, and parasitic diseases constituted the major constraints to successful commercial poultry production in Gombe State. Keywords : Poultry production, constraints, Gombe State, Nigeria. Nigerian Veterinary Journal Vol. 27 (2) 2006: pp. 75-78
Analysis of Sociodemographic and Clinical Factors Associated with Hospitalized Stroke Patients of Bangladesh

A hospital based cross sectional study was carried out to analyze prevalence of risk factors for stroke in hospitalized patient in a medical college hospital. 100 patients were chosen using purposive sampling technique. Highest incidence of stroke was between the 6th and 7th decade. Patients came from both urban (54%) and rural (46%) areas and most of them belong to the low-income group (47%). In occupational category; service holder (28%) and retired person (21%) were the highest groups. Most of the study subjects were literate (63%). CT scan study revealed that the incidence of ischaemic stroke was 61% and haemorrhagic stroke 39%. Analysis indicated hypertension as major risk factor for stroke (63%) and major portion of the patients (42.85%) were on irregular or no treatment. Twenty four percent of the patients had heart diseases and out of 24 patients 45.83% were suffering from ischaemic heart disease. The present study detected diabetes in 21% patients. Fifty three percent of the study subjects were smoker, 39% patients had habit of betelnut chewing. Out of 26 female patients, only 23% had history of using oral contraceptives. Majority of the patients were sedentary workers (46%). Thirty seven percent of the stroke patients were obese. Among the stroke patients 9% had previous history of stroke and 3% had TIA respectively. Most of the patients (21%) were awake while they suffered from stroke and the time of occurrence was mostly in the afternoon (46%). This study found that hypertension, cigarette smoking, ischaemic heart disease and diabetes mellitus are the major risk factors prevalent in our community while other risk factors demand further study.
Heart rate variability in patients after cardiac valve surgery

The aim of study was to analyze heart rate variability (HRV) after different cardiac valve surgery procedures and the prognostic values of these findings. This study included 101 consecutive patients who underwent surgical implantation for an artificial valve. The mean age of the patients was 62 ± 10 years. An aortic valve was implanted in 65 patients. A mitral valve was implanted in 36 patients. HRV was analyzed from 24 hours Holter electrocardiographic (ECG) records. The time from the operation to the recording of Holter ECG and measuring HRV was 3.8 ± 1.4 months. After discharged from stationary cardiac rehabilitation, all involved patients were contacted to provide data on their health in the follow-up period (33 ± 21 months). A total of 46 patients with an implanted artificial valve had decreased overall HRV or standard deviation of all normal R-R intervals (SDNN) < 93 ms. Patients with an implanted artificial mitral valve had a shorter RR interval (817 ± 122 vs. 863 ± 122ms, p=0.03) and lower values of total power (1166 ± 1888 vs. 2802 ± 3601 ms2, p<0.001) compared to patients with an implanted artificial aortic valve. The results of study show that several months after cardiac surgery, almost half of the patients with an implanted artificial valve have decreased HRV. However, postoperative decreased HRV in those patients have no importance in long-term prediction of mortality rate.
A New Floating Memristance Simulator Circuit Based on Second Generation Current Conveyor

In this paper, a new floating analog memristance simulator circuit based on second generation current conveyors and passive elements is proposed. Theoretical derivations are presented which decribe the circuit characteristics. The hardware of proposed simulator circuit is built using commercially available components. Theoretical derivations are validated with PSPICE simulation and experimental results. Performance of circuit was tested with simple example circuits. All results show that proposed simulator circuit provides frequency dependent pinched hysteresis loop and nonvolatility features. Exciting frequency, minimum and maximum memristance values and memristance range can be adjustable with simple passive element values. Simulator circuit has a frequency range of 1Hz to 40kHz.
Home Modification Assessments: Clinical Utility and Treatment Context

ABSTRACT Occupational therapists need effective assessments to help evaluate the physical, social, and psychological aspects of the home environment when planning home modification interventions. Assessment tools need to have a client-centered focus, emphasis on occupation or occupational performance, comprehensive evaluation of the environment, strong psychometric properties, and clinical utility. When selecting an assessment tool, occupational therapists also need to take into an account the type of home modification interventions that they will be able to complete in a given treatment context. Because of the unique needs of each home modification intervention, there is no one-fits-all assessment; the best tool will depend on the context of care. This paper details six assessment tools for use in three different contexts of care.
A Time-Interleaved Statistically-Driven Two-Step Flash ADC for High-Speed Wireline Applications

This paper presents a statistically-driven two-step flash sub-analog-to-digital converter (ADC) to construct the high-speed time-interleaved ADC in wireline communication applications. The comparators in the flash sub-ADC are divided into the large probability first stage and the small probability second stage to take advantage of the nonuniform probability distribution of the input signal. At the first step of operation, the large probability first stage is activated while the small probability second stage is suspended. If the input signal is beyond the input range of the first stage, the segment selection signal will trigger proper segment in the second stage. Feed-forward equalization is proposed to manipulate the probability distribution of the ADC input signal. A possible implementation of the proposed ADC as well as the modulation and equalization scheme is presented to comply with the IEEE 802.3ap 10G Ethernet standard. In the case of a PAM-4 pseudorandom signal, the proposed solution achieves 66% reduction on the average number of activated comparators compared to a conventional flash ADC.
Ketoconazole revisited: a preoperative or postoperative treatment in Cushing's disease.

CONTEXT Although transsphenoidal surgery remains the first-line treatment in Cushing's disease (CD), recurrence is observed in about 20% of cases. Adjunctive treatments each have specific drawbacks. Despite its inhibitory effects on steroidogenesis, the antifungal drug ketoconazole was only evaluated in series with few patients and/or short-term follow-up. OBJECTIVE Analysis of long-term hormonal effects and tolerance of ketoconazole in CD. DESIGN A total of 38 patients were retrospectively studied with a mean follow-up of 23 months (6-72). SETTING All patients were treated at the same Department of Endocrinology in Marseille, France. PATIENTS The 38 patients with CD, of whom 17 had previous transsphenoidal surgery. INTERVENTION Ketoconazole was begun at 200-400 mg/day and titrated up to 1200 mg/day until biochemical remission. MAIN OUTCOME MEASURES Patients were considered controlled if 24-h urinary free cortisol was normalized. RESULTS Five patients stopped ketoconazole during the first week because of clinical or biological intolerance. On an intention to treat basis, 45% of the patients were controlled as were 51% of those treated long term. Initial hormonal levels were not statistically different between patients controlled or uncontrolled. Ketoconazole was similarly efficacious as a primary or postoperative treatment. Among 15 patients without visible adenoma at initial evaluation, subsequent follow-up allowed identification of the lesion in five cases. No adrenal insufficiency was observed. Adverse effects were rare in patients treated long term. CONCLUSIONS Ketoconazole is a safe and efficacious treatment in CD, particularly in patients for whom surgery is contraindicated, or delayed because of the absence of image of adenoma on magnetic resonance imaging.