Miracle-dz/UniFAR-FTUs huggingface dataset:
Ginseng and vaginal bleeding.

To the Editor. — Ginseng has been reported to produce a physiological estrogenlike effect on the vaginal mucosa, mastalgia with diffuse mammary nodularity in postmenopausal women, and, experimentally, stimulation of corticotropin secretion and altered RNA hepatic metabolism. After bilateral oophorectomy, Punnonen and Lukola 1 observed a notable vaginal effect in a patient ingesting an unstated amount of Rumanian ginseng only two weeks per month. A 72-year-old woman experienced vaginal bleeding and a moderate estrogen effect after ingesting one tablet daily of a Swiss-Austrian geriatric formula containing 200 mg of ginseng of an unspecified source (Geriatric Pharmaton, Bernardgass, Austria). Physicians should be alerted to a possible vaginal bleeding action of ginseng in postmenopausal women.
SPEECH ENCODING IN THE AUDITORY NERVE: IMPLICATIONS FOR COCHLEAR IMPLANTS a

Discussions of stimulus encoding for cochlear prostheses have focused on replacement of peripheral auditory processing by at least a crude simulation of the function of the normal system. ’** The ultimate goal of the prosthesis is to provide the central nervous system with information adequate for the perception of speech. An understanding of the normal encoding of speech in the auditory nerve is therefore fundamental to the development of a simulation-type prosthesis or even to the evaluation of the potential for success of such devices. In this paper we shall review some recent studies of speech encoding in the auditory nerve. In particular, we shall consider representations of speech spectra in terms of average discharge rates of fiber responses and in terms of temporal (phase-locked) properties of the discharge patterns. As we will emphasize, we cannot at this point rule out either representation as the one actually used by the normal auditory system. We will, however, discuss the relationship of both average rate and temporal encoding to stimulation strategies for cochlear implants.
CD8+ chronic lymphocytic leukemia: an extensive characterization of a bizarre hybrid neoplasia

Atypical chronic lymphocytic leukemia (CLL) expressing the CD8 antigen have a frequency of less than 0.5% of all cases, however, they are not yet been fully characterized. Herein a CD8+ CLL case was extensively studied. Besides the classical CLL antigen expression, an unusual presence of surface markers such as CD11c, CD56, and CD154 was observed. Moreover, gene expression of chemokine receptors belonging to the CCR family were clearly evidenced as well as mRNA for both, Th1 and Th2 cytokines. Likewise, granzyme A, B and perforin gene expression, cytotoxic T cell or NK enzymes were found. The intricate profile of membrane molecules and gene expression suggest that it could be favorable, rather than deletereous, for the maintainance of the neoplastic process.
aprABC: a Mycobacterium tuberculosis complex‐specific locus that modulates pH‐driven adaptation to the macrophage phagosome

Following phagocytosis by macrophages, Mycobacterium tuberculosis (Mtb) senses the intracellular environment and remodels its gene expression for growth in the phagosome. We have identified an acid and phagosome regulated (aprABC) locus that is unique to the Mtb complex and whose gene expression is induced during growth in acidic environments in vitro and in macrophages. Using the aprA promoter, we generated a strain that exhibits high levels of inducible fluorescence in response to growth in acidic medium in vitro and in macrophages. aprABC expression is dependent on the two‐component regulator phoPR, linking phoPR signalling to pH sensing. Deletion of the aprABC locus causes defects in gene expression that impact aggregation, intracellular growth, and the relative levels of storage and cell wall lipids. We propose a model where phoPR senses the acidic pH of the phagosome and induces aprABC expression to fine‐tune processes unique for intracellular adaptation of Mtb complex bacteria.
Children with Minimal Sensorineural Hearing Loss: Prevalence, Educational Performance, and Functional Status

Objective: This study was designed to determine the prevalence of minimal sensorineural hearing loss (MSHL) in school‐age children and to assess the relationship of MSHL to educational performance and functional status. Design: To determine prevalence, a single‐staged sampling frame of all schools in the district was created for 3rd, 6th, and 9th grades. Schools were selected with probability proportional to size in each grade group. The final study sample was 1218 children. To assess the association of MSHL with educational performance, children identified with MSHL were assigned as cases into a subsequent case‐control study. Scores of the Comprehensive Test of Basic Skills (4th Edition) (CTBS/4) then were compared between children with MSHL and children with normal hearing. School teachers completed the Screening Instrument for Targeting Education Risk (SIFTER) and the Revised Behavior Problem Checklist for a subsample of children with MSHL and their normally hearing counterparts. Finally, data on grade retention for a sample of children with MSHL were obtained from school records and compared with school district norm data. To assess the relationship between MSHL and functional status, test scores of all children with MSHL and all children with normal hearing in grades 6 and 9 were compared on the COOP Adolescent Chart Method (COOP), a screening tool for functional status. Results: MSHL was exhibited by 5.4% of the study sample. The prevalence of all types of hearing impairment was 11.3%. Third grade children with MSHL exhibited significantly lower scores than normally hearing controls on a series of subtests of the CTBS/4; however, no differences were noted at the 6th and 9th grade levels. The SIFTER results revealed that children with MSHL scored poorer on the communication subtest than normal‐hearing controls. Thirty‐seven percent of the children with MSHL failed at least one grade. Finally, children with MSHL exhibited significantly greater dysfunction than children with normal hearing on several subtests of the COOP including behavior, energy, stress, social support, and self‐esteem. Conclusions: The prevalence of hearing loss in the schools almost doubles when children with MSHL are included. This large, education‐based study shows clinically important associations between MSHL and school behavior and performance. Children with MSHL experienced more difficulty than normally hearing children on a series of educational and functional test measures. Although additional research is necessary, results suggest the need for audiologists, speech‐language pathologists, and educators to evaluate carefully our identification and management approaches with this population. Better efforts to manage these children could result in meaningful improvement in their educational progress and psychosocial well‐being.
Recrudescence of Plasmodium falciparum malaria in a primigravid woman with anaemia as the only sign of disease

Correspondence: S. Odolini, University Division of Infectious and Tropical Diseases, University of Brescia, Piazza Spedali Civili, 1, Brescia 25123, Italy. E-mail: silvia.odolini@gmail.com follow-up. Th e patient was born in Burkina Faso, she stayed in Italy for the last 7 years but she had a 2-month stay in Burkina Faso in August and September 2011, during the 1st trimester of pregnancy, without taking any anti-malarial chemoprophylaxis. She returned to Italy on 2 October 2011 and a worsening anaemia was found. On admission, the patient was in good general condition; she was alert and oriented without fever (36.9 ° C) and with a blood pressure of 100/70 mmHg. Physical examination was normal without rash, scleral icterus or lymphadenopathy. Laboratory investigations (Table I) showed severe anaemia (haemoglobin Hb: 7.8 g/dl) with a low red cell count (RBC 2,650,000/cells/ μ l) and normal white and platelet cell counts (WBC 6,300/cells/ μ l, PLT 252,000/cells/ μ l) but mildhyper-LDH (LDH 293 U/l) and higher levels of serum iron (319 μ g/dl) were found. Malaria had been missed in the initial diff erential diagnosis but, 24 hours aft er admission, by direct microscopy examination of peripheral blood cells, haemoparasites were noted within red blood cells. Th e rapid antigen detection test was positive, while PCR was not carried out. Th e patient was referred to our University Division of Infectious and Tropical Diseases on 3 March 2012. Th ick and thin blood fi lms revealed P. falciparum trophozoites with a parasitaemia of 0.05%. Th e patient received mefl oquine 750 mg per os as initial dose, followed by 500 mg and 250 mg given, respectively, 12 and 24 h aft er initial dose. No other treatment options suitable in pregnancy, with the exception of quinine, were at that time available in Italy. She was blood transfused, since pregnant, on 4 March, with a signifi cant improvement of haemoglobin levels, and on 5 March, she was discharged in good clinical condition. Fever was not reported during the hospitalisation and an obstetric evaluation showed normal fetal conditions. Haemoglobin levels were stable in further laboratory investigations.
Localization of Rate-Limiting Defect for Glucose Disposal in Skeletal Muscle of Insulin-Resistant Type I Diabetic Patients

We searched for metabolic crossover points in muscle glucose metabolite profiles during maintenance of matched glucose fluxes across forearm muscle in insulin-resistant type I (insulin-dependent) diabetic patients and nondiabetic subjects. To classify subjects as insulin sensitive or insulin resistant, whole-body and forearm glucose disposal, oxidative and nonoxidative glucose disposal (indirect calorimetry), and glycogen synthesis (muscle glycogen content in needle biopsies) were measured under euglycemic conditions at two insulin concentrations. Wholebody and forearm muscle glucose disposal were significantly reduced in diabetic patients compared with control subjects. The reduction in total glucose disposal was due to similar relative reductions in oxidative and nonoxidative glucose disposal, pointing toward rate limitation early in glucose metabolism. The defect in nonoxidative glucose disposal was at least partly due to a defect in muscle glycogen synthesis, because muscle glycogen content failed to increase in response to an increase in the plasma insulin concentration in the diabetic patients. The mostinsulin-resistant type 1 diabetic patients were restudied under conditions where, by glucose mass action, whole-body glucose disposal was forced to be similar to that in the control subjects. Matching glucose fluxes in the two groups resulted in similar rates of forearm and whole-body oxidative and nonoxidative glucose disposal and muscle glycogen synthesis, but it did not result in accumulation of free intracellular glucose, glucose-6-phosphate, glucose-1-phosphate, fructose-6-phosphate, or lactate in muscle. These data imply that the rate-limiting defect for glucose disposal in skeletal muscle of type I diabetic patients is at the level of glucose transport.
An adaptive hybrid ant colony optimization algorithm for solving Capacitated Vehicle Routing

Ant Colony Algorithm has certain advantages in solving Capacitated Vehicle Routing Problem (CVRP), but there are still easy to fall into local optimum, the search speed etc. To overcome these problems this paper presents an adaptive hybrid Ant colony optimization algorithm for solving Capacitated Vehicle Routing Problem. The adaptive hybrid ant colony optimization algorithm uses genetic algorithms to adjust pheromone matrix algorithm, and designs an adaptive pheromone evaporation rate adjustment strategies, and uses local search strategies to reduce the amount of calculation. Experiment on Some classic problems shows that the presented algorithm for solving the Capacitated Vehicle Routing Problem is effective and has better performance.
Reactivated Triton-Extracted Models of Paramecium: Modification of Ciliary Movement by Calcium Ions

Triton-extracted models of Paramecium were reactivated to swim in solutions of adenosine triphosphate and magnesium ions. The cilia beat in the normal direction (toward the rear) when the calcium ion concentration was less than 10-6M, and they beat in the "reversed" direction (toward the front) when calcium ion concentration was raised above 10-6M. These results support the proposal that ciliary reversal, hence backward swimming, of live paramecia is mediated by an increased cytoplasmic calcium concentration around the ciliary system by calcium-dependent membrane responses to external stimuli.
Assay Interference by Aggregation

Aggregation is a common mechanism of compound-mediated assay interference encountered in high-throughput screening (HTS) and follow-up experiments. Compounds that form aggregates in situ can nonspecifically perturb biomolecules in biochemical and cell-based assays. Nonspecific bioactivity from aggregation can waste significant resources when unaccounted for in assay design and readout interpretation. This chapter describes two general principles: (a) experimental considerations to mitigate the impact of aggregation in bioassays, and (b) counter-screens and other strategies to identify aggregation among bioactive test compounds. This content should be useful for those performing bioassays utilizing small-molecules, including HTS and follow-up assays, chemical biology, and molecular pharmacology. 1 Novartis Institutes for Biomedical Research, Cambridge, MA, USA. 2 National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA. 3 National Human Genome Research Institute, Bethesda, MD, USA. 4 Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA; Email: jdahlin@bwh.harvard. edu. Corresponding author. NLM Citation: Auld DS, Inglese J, Dahlin JL. Assay Interference by Aggregation. 2017 Jul 26. In: Sittampalam GS, Coussens NP, Brimacombe K, et al., editors. Assay Guidance Manual [Internet]. Bethesda (MD): Eli Lilly & Company and the National Center for Advancing Translational
Antibiotics Improve Survival in Sepsis Independent of Injury Severity but do not Change Mortality in Mice with Markedly Elevated Interleukin 6 Levels

Genetically identical mice have a heterogeneous response to antibiotic therapy in sepsis, with only a subset deriving therapeutic benefit. We sought to determine whether the severity of a septic insult correlates with the survival benefit conferred by antibiotics. We also sought to determine whether antibiotics given 12 h after injury alter survival in animals predicted to die based upon high interleukin (IL)-6 levels drawn 6 h earlier. Adult male ND4 mice (n = 363) were subjected to double-puncture cecal ligation and puncture (CLP) with a 19-, 21-, or 23-gauge needle. Animals were randomized to receive imipenem or 0.9% NaCl every 12 h after CLP for 5 days. Ten-day survival was 16%, 26%, and 52%, respectively, for untreated animals. Antibiotics decreased the absolute risk of death 17% to 23% regardless of injury severity. In a separate cohort, mice (n = 37) were subjected to single or double-puncture CLP with a 21-gauge needle. IL-6 levels were assayed 6 h postoperatively and mice were followed for survival. Levels greater than 14,000 pg/mL were identified as predicting a 100% mortality (7/7 animals dead). A third set of mice (n = 94) then underwent double-puncture CLP with either 21-, 23-, or 25-gauge needle and had IL-6 levels measured in a similar fashion. Animals were randomized to receive imipenem or 0.9% NaCl beginning 12 h postoperatively (6 h after IL-6 levels were drawn) and continued for 5 days or until death. Although antibiotics decreased mortality overall, all animals with IL-6 levels greater than 14,000 pg/mL (n = 13) died, regardless of whether they received antibiotics or the gauge of needle used. These results indicate that antibiotics improve outcome in murine sepsis, regardless of injury severity. Furthermore, there is a threshold IL-6 level that can be identified 6 h after sepsis above which animals are destined to die, and antibiotic treatment does not alter their outcome.
Data mining techniques and its effect in customer relationship management

Data mining technology helps in extracting hidden knowledge from the data. It has been researched extensively over a considerable time period. In this paper, the authors look at developments in the area of data mining for the years 2007 to 2012, focusing mainly on customer relationship management, association rule mining, data mining algorithms and application areas relating to data mining. Data mining offers a wide range of tools and techniques which are used across all sectors of business and industry. This paper refers to a number of sources, including online data, international journal articles, conference proceedings, white papers, books and abstracts. Of the 861 research papers reviewed, around 83 are referenced in this paper. The articles listed here are having relevance with a research domain timeline with their purpose. This review is intended to provide a base framework for academics, customer-centric corporate entities and researchers who use data mining techniques and tools.
Optimization of protein expression systems for modern drug discovery

The expression of high levels of stable and functional proteins remains a bottleneck in many scientific endeavors, including the determination of structures in a high-throughput fashion or the screening for novel active compounds in modern drug discovery. Recently, numerous developments have been made to improve the production of soluble and active proteins in heterologous expression systems. These include modifications to the expression constructs, the introduction of new and/or improved pro- and eukaryotic expression systems, and the development of improved cell-free protein synthesis systems. The introduction of robotics has enabled a massive parallelization of expression experiments, thereby vastly increasing the throughput and, hopefully, the output of such experiments. In addition, the big challenges of recombinant overexpression of membrane and secreted proteins are tackled, and some new methods are reviewed.
Rho-associated Kinase of Chicken Gizzard Smooth Muscle*

Rho-associated kinase (Rho-kinase) from chicken gizzard smooth muscle was purified to apparent homogeneity (160 kDa on SDS-polyacrylamide gel electrophoresis) and identified as the ROKα isoform. Several substrates were phosphorylated. Rates with myosin phosphatase target subunit 1 (MYPT1), myosin, and the 20-kDa myosin light chain were higher than other substrates. Thiophosphorylation of MYPT1 inhibited myosin phosphatase activity. Phosphorylation of myosin at serine 19 increased actin-activated Mg+-ATPase activity, i.e. similar to myosin light chain kinase. Myosin phosphorylation was increased at higher ionic strengths, possibly by formation of 6 S myosin. Phosphorylation of the isolated light chain and myosin phosphatase was decreased by increasing ionic strength. Rho-kinase was stimulated 1.5–2-fold by guanosine 5′-O-3-(thio)triphosphate·RhoA, whereas limited tryptic hydrolysis caused a 5–6-fold activation, independent of RhoA. Several kinase inhibitors were screened and most effective were Y-27632, staurosporine, and H-89. Several lipids caused slight activation of Rho-kinase, but arachidonic acid (30–50 μm) induced a 5–6-fold activation, independent of RhoA. These results suggest that Rho-kinase of smooth muscle may be involved in the contractile process via phosphorylation of MYPT1 and myosin. Activation by arachidonic acid presents a possible regulatory mechanism for Rho-kinase.
IRAK1 Serves as a Novel Regulator Essential for Lipopolysaccharide-induced Interleukin-10 Gene Expression*♦

Being one of the key kinases downstream of Toll-like receptors, IRAK1 has initially thought to be responsible for NFκB activation. Yet IRAK1 knock-out mice still exhibit NFκB activation upon lipopolysaccharide (LPS) challenge, suggesting that IRAK1 may play other un-characterized function. In this report, we show that IRAK1 is mainly involved in Stat3 activation and subsequent interleukin-10 (IL-10) gene expression. Splenocytes from IRAK1-deficient mice fail to exhibit LPS-induced Stat3 serine phosphorylation and IL-10 gene expression yet still maintain normal IL-1β gene expression upon LPS challenge. Mechanistically, we observe that IRAK1 modification upon LPS challenge leads to its modification, nuclear distribution, and interaction with Stat3. IRAK1 can directly use Stat3 as a substrate and cause Stat3 serine 727 phosphorylation. In addition, nuclear IRAK1 binds directly with IL-10 promoter in vivo upon LPS treatment. Atherosclerosis patients usually have elevated serum IL-10 levels. We document here that IRAK1 is constitutively modified and localized in the nucleus in the peripheral blood mononuclear cells from atherosclerosis patients. These observations reveal the mechanism for the novel role of IRAK1 in the complex Toll-like receptor signaling network and indicate that IRAK1 regulation may be intimately linked with the pathogenesis and/or resolution of atherosclerosis.
Evaluation of measurement uncertainty with the principles of entropy optimization

A measurement process has imperfections that give rise to uncertainty in each measurement result. Statistical tools give the assessment of uncertainties associated to the results only if all the relevant quantities involved in the process are interpreted or regarded as random variables. In other terms all the sources of uncertainty are characterized by probability distribution functions, the form of which is assumed to either be known from measurements or unknown and so conjectured. Entropy is an information measure associated with the probability distribution of any random variable, so that it plays an important role in the metrological activity. In this paper the author introduces two basic entropy optimization principles: the Jaynespsilas principle of maximum entropy and the Kulbackpsilas principle of minimum cross-entropy (minimum directed divergence) and discusses the methods to approach the optimal solution of those entropic forms in some specific measurements models.
Differences in processing efficiency of response selection between skilled and sub-skilled kendo players

本研究では, 熟練・準熟練群の大学生の剣道選手における反応選択の処理効率の熟練差を検討した. ここでは, 被験者の技知識を確認して実験条件を設定した. そして, その条件に対する運動技能の獲得度合と, 反応選択の処理効率を検討する2実験課題を実施した. まず, 技能確認実験では熟練差はなく, 条件の低・中難度に対する両群の運動技能の獲得が概ね確認された. 反応選択実験では, 技知識の活用頻度, 時間効率, 技能発揮において熟練差が認められた. 熟練群の思考内容と技知識の繁用は, 予測による能動的な反応選択を多用することを示していた. また, その知識の繁用は, 環境に存在する干渉への耐性を頑健にするように処理機能を向上させる. 一方, 準熟練群は, 処理機能が干渉に対して脆弱であるために技知識を活用することができず, 受動的な反応選択を強いられると考えられた. この採用する処理様相の能動性・受動性と処理機能の頑健性・脆弱性の相違が, 反応選択における時間効率と技能発揮の処理効率の熟練差をもたらしていた. すなわち, 剣道では, 技知識を活用した予測による能動的な反応選択が重要であることが示された. 競技実践者は, 有効な技知識を獲得し, 反応選択でこれを多用する中で, 知識の洗練と処理機能の強化を図るべきである.
Brain morphometry volume in autistic spectrum disorder: a magnetic resonance imaging study of adults

Background Several prior reports have found that some young children with autism spectrum disorder [ASD; including autism and Asperger's syndrome and pervasive developmental disorder – not otherwise specified (PDD-NOS)] have a significant increase in head size and brain weight. However, the findings from older children and adults with ASD are inconsistent. This may reflect the relatively small sample sizes that were studied, clinical heterogeneity, or age-related brain differences. Method Hence, we measured head size (intracranial volume), and the bulk volume of ventricular and peripheral cerebrospinal fluid (CSF), lobar brain, and cerebellum in 114 people with ASD and 60 controls aged between 18 and 58 years. The ASD sample included 80 people with Asperger's syndrome, 28 with autism and six with PDD-NOS. Results There was no significant between-group difference in head and/or lobar brain matter volume. However, compared with controls, each ASD subgroup had a significantly smaller cerebellar volume, and a significantly larger volume of peripheral CSF. Conclusions Within ASD adults, the bulk volume of cerebellum is reduced irrespective of diagnostic subcategory. Also the significant increase in peripheral CSF may reflect differences in cortical maturation and/or ageing.