Miracle-dz/UniFAR-FTUs huggingface dataset:
Early Events in Mycobacterium tuberculosis Infection in Cynomolgus Macaques

ABSTRACT Little is known regarding the early events of infection of humans with Mycobacterium tuberculosis. The cynomolgus macaque is a useful model of tuberculosis, with strong similarities to human tuberculosis. In this study, eight cynomolgus macaques were infected bronchoscopically with low-dose M. tuberculosis; clinical, immunologic, microbiologic, and pathologic events were assessed 3 to 6 weeks postinfection. Gross pathological abnormalities were observed as early as 3 weeks, including Ghon complex formation by 5 weeks postinfection. Caseous granulomas were observed in the lung as early as 4 weeks postinfection. Only caseous granulomas were observed in the lungs at these early time points, reflecting a rigorous initial response. T-cell activation (CD29 and CD69) and chemokine receptor (CXCR3 and CCR5) expression appeared localized to different anatomic sites. Activation markers were increased on cells from airways and only at modest levels on cells in peripheral blood. The priming of mycobacterium-specific T cells, characterized by the production of gamma interferon occurred slowly, with responses seen only after 4 weeks of infection. These responses were observed from T lymphocytes in blood, airways, and hilar lymph node, with responses predominantly localized to the site of infection. From these studies, we conclude that immune responses to M. tuberculosis are relatively slow in the local and peripheral compartments and that necrosis occurs surprisingly quickly during granuloma formation.
Conservation of genes encoding components of a type IV pilus assembly/two‐step protein export pathway in Neisseria gonorrhoeae

Three gonococcal genes have been identified which encode proteins with substantial similarities to known components of the type IV pilus biogenesis pathway in Pseudomonas aeruginosa. Two of the genes were identified based on their hybridization with a DNA probe derived from the pilB gene of P. aeruginosa under conditions of reduced stringency. The product of the gonococcal pilF gene is most closely related to the pilus assembly protein PilB of P. aeruginosa while the product of the gonococcal pilT gene is most similar to the PilT protein of P. aeruginosa which is involved in pilus‐associated twitching motility and colony morphology. The products of both of these genes display canonical nucleoside triphosphate binding sites and are predicted to be to cytoplasmically localized based on their overall hydrophilicity. The gonococcal pilD gene, identified by virtue of its linkage to the pilF gene, is homologous to a family of prepilin leader peptidase genes. When expressed in Escherichia coli, the gonococcal PilD protein functions to process gonococcal prepilin in a manner consistent with its being gonococcal prepilin peptidase. These results suggest that Neisseria gonorrhoeae is capable of expressing many of the essential elements of a highly conserved protein translocation system and that these gene products are probably involved in pilus biogenesis.
An empirical study on gamma shadow fading based localization

In this paper, we propose a maximum likelihood estimator for received signal strength (RSS) based indoor localization systems by exploiting gamma shadow fading model. In order to investigate the validity of proposed method in a realistic environment, we develop a testbed based on Wi-Fi technology. Through experimental analyses, we first demonstrate the gamma distribution is a good fit to lognormal distribution, and both of them can sufficiently accurately characterize the empirical RSS observations. Then, we observe that gamma distribution is worth investigating for indoor localization compared to lognormal model because it provides superior accuracy. We further analyze the impacts of uncertainties of considered distributions' parameters on the localization performance via simulations.
Early Identification and Intervention in Depressive Disorders: Towards a Clinical Staging Model

Background: Depressive disorders are common and associated risks include the onset of secondary disorders, substance use disorders, impairment in social and occupational functioning, and an increase in suicidality. As the onset often occurs in youth, there is a clear imperative for early identification and intervention to ameliorate, if not prevent, associated distress. Methods: An extensive search of relevant databases and an ancestry search was undertaken. Results: There is a limited but growing body of literature on this topic that is discussed in relation to a clinical staging model, which may prove to be a useful framework for identifying where an individual lies along the continuum of the course of a depressive illness thus allowing interventions to be matched for that stage. The identification of a subsyndromal and prodromal stage of depressive disorders provides early intervention opportunities. Conclusions: It is argued that a clinical staging heuristic may increase the number of those treated early, which may in turn delay or prevent onset, reduce severity, or prevent progression in the course of depressive disorders.
A Feasibility Pilot Trial of Individualized Homeopathic Treatment of Fatigue in Children Receiving Chemotherapy

Background. Fatigue is a major problem in children with cancer. The objective was to examine the feasibility of performing a clinical trial of homeopathic treatment for fatigue in children receiving chemotherapy. Materials. This was a single-institution, open-label, pilot study. Children 2 to 18 years old, diagnosed with cancer, and receiving chemotherapy were eligible. Participants were given individualized homeopathic treatment for a maximum of 14 days. In-home or clinic assessments were conducted up to 3 times weekly. Feasibility was defined as the ability to recruit and administer homeopathy to 10 participants within 1 year. Fatigue was measured using the Symptom Distress Scale daily and the PedsQL Multidimensional Fatigue Module weekly. Results. Between April 2012 and April 2014, 155 potential participants were identified. There were 45 eligible and contacted patients; 36 declined participation, 30 because they were not interested; 9 agreed to participate, but 1 participant withdrew prior to treatment initiation. Median length of homeopathic treatment was 10.5 (range = 6 to 14) days. All parents found homeopathic treatment to be easy or very easy to follow. Conclusions. Trials of individualized homeopathy for fatigue reduction in pediatric cancer are not feasible in this context; lack of interest was a primary reason. Alternative approaches to evaluating homeopathy efficacy are needed.
Analysis of RNase P Protein (rnpA) Expression in Bacillus subtilis Utilizing Strains with Suppressible rnpA Expression

ABSTRACT Bacterial RNase P is composed of an RNA subunit and a single protein subunit (encoded by the rnpB and rnpA genes, respectively). We constructed Bacillus subtilis mutant strains that conditionally express the RNase P protein under control of the xylose promoter (P xyl ). In one strain (d7), rnpA expression was efficiently repressed in the absence of the inducer xylose, leading to cell growth arrest. Growth could be restored by a second functional rnpA allele. This is the first RNase P protein knockdown strain, providing the first direct proof that the rnpA gene is essential in B. subtilis and, by inference, in other bacteria. We further show (i) that, in the wild-type context, rnpA expression is attenuated by transcriptional polarity and (ii) that translation of rnpA mRNA in B. subtilis can be initiated at two alternative start codons. His-tagged RNase P protein variants are functional in vivo and permit purification of in vivo-assembled holoenzymes by affinity chromatography. Simultaneous expression of plasmid-encoded RNase P RNA and His-tagged protein increased RNase P holoenzyme yields. Massive overproduction of RNase P protein in strain d7 is compatible with cell viability.
Quality improvement: getting to how.

Intense enthusiasm for public reporting of health care performance continues unabated. Dating from when Relman (1988) first observed that the third revolution in medicine was the age of accountability, the demands of multiple stakeholders, including consumers, have resulted in using evidence about the relationship between health care inputs and outcomes to develop and implement standardized performance measures. Since that time standardized public reports of clinical performance and patients' experiences of care have been developed and implemented widely. At this writing several additional initiatives have begun or are on the horizon: mandatory reporting of nursing home performance, voluntary reporting for hospital performance, and products of the National Quality Forum's consensus development process. The Agency for Healthcare Research and Quality (AHRQ) and the Department of Health and Human Services will publish annual reports on the quality of health care and disparities in health care starting in 2003.
Impulse activity evokes precocious sprouting of nociceptive nerves into denervated skin.

We have studied the sprouting of intact high-threshold mechanosensory nerves into adjacent denervated trunk skin in adult rats behaviorally, histologically, and electrophysiologically. In the anesthetized animal, stimulation of high-threshold endings in back skin by localized pinching elicits a bilateral reflex excitation of the underlying skeletal muscle, the cutaneous trunci muscle (CTM), visible as a twitch-like puckering of the skin. The reflex was also evoked by electrical excitation of A delta and of C fibers in the dorsal cutaneous nerves (DCNs), with characteristic latencies of 7-20 msec and 40-60 msec, respectively; excitation of low-threshold (A alpha) fibers was ineffective. After cutting selected DCNs, the deprived skin became insensible, but pinch responsiveness gradually recovered over the following 2 weeks. Regeneration of cut axons was not responsible for this recovery; when neighboring intact DCNs were cut, however, all responses were abolished in the recovered skin that had been initially denervated. By 3-5 days after denervation, axons in the dermis were all histologically absent or degenerating; when pinch sensitivity was restored to such skin, silver-stainable axons reappeared in the formerly empty Schwann tubes. During the work we noticed that the periodic examination by pinching, used to follow the time course of recovery of function in individual animals, led to an earlier development of this recovery than in animals that were examined only once at a specified time after denervation. This apparent acceleration in the redevelopment of pinch sensitivity was correlated with the appearance of axons in the recovered skin, and was shown to be due to the impulse activity evoked in the remaining nerves by the periodic pinching; it did not occur when the nerves were blocked by tetrodotoxin (TTX), and it was mimicked by a brief (10-min) period of electrical excitation of the A delta fibers in a remaining nerve carried out at the time when the denervation of skin was done. The time course of the phenomenon suggested that the principal effect of the impulses was to shorten the latency to the onset of sprouting in the activated A delta axons; that is, they induced precocious sprouting. The impulses needed to be conducted centrally for the effect to occur, and precocious sprouting failed to occur if the impulses were allowed to proceed only distally toward the skin. It seems that a brief conditioning burst of impulses in A delta axons sensitizes the neurons to the influence of a sprouting stimulus that appears when skin is denervated. (ABSTRACT TRUNCATED AT 400 WORDS)
The role of low intensity pulsed ultrasound therapy in the management of acute fractures: a systematic review.

BACKGROUND The aim of this study was to review the evidence regarding the use of low intensity pulsed ultrasound (LIPUS) in the management of acute long bone fractures. METHODS Systematic review of Medline, Embase, and CINAHL databases. Further published studies were retrieved by hand searching bibliographies of relevant articles. Retrieved studies were limited to English-language studies published since 1956. Retrieved studies were excluded from review using the following criteria: case reports, exclusively pathologic fractures, treatment of therapeutic osteotomies and arthrodesis, initiation of ultrasound therapy after the first month following injury, no reporting of assessment of time to fracture healing, cellular studies, and nonclinical articles. Studies were reviewed independently by two reviewers using the CONSORT score. No statistical analysis was performed as the data from the studies were not suitable for pooled analysis. RESULTS Seven randomized controlled trials and two meta-analyses were retrieved using the search strategy. CONCLUSION The literature supports the use of LIPUS in the treatment of acute fractures treated with plaster immobilization.
Mechanisms promoting tree species co‐existence: Experimental evidence with saplings of subtropical forest ecosystems of China

Questions The maintenance of a diverse sapling pool is of particular importance for the regeneration and persistance of species-rich forest ecosystems. However, the mechanisms of co-existence of saplings have rarely been studied experimentally. Do species richness, species composition, species identity and stand density affect the co-existence, growth patterns and crown architecture of tree saplings? Location Jiangxi Province, southeast China. Methods In a field experiment, we manipulated the local neighbourhood of saplings of four early-successional subtropical species (Schima superba, Elaeocarpus decipiens, Quercus serrata and Castanea henryi) with regard to species richness (one, two and four species), species composition (monocultures, six-two-species combinations and one-four-species combination) and stand density (low, intermediate and high). We tested for treatment effects and impact of species identity on growth variables, biomass allocation, crown architectural traits and branch demography. Results Species richness was a poor predictor of all response variables, but enhanced pruning and branch turnover. In contrast, species composition proved to be of great importance for growth, biomass allocation, crown architecture and branch demography. Local neighbourhood interactions of saplings were characterized by complementary or facilitative, as well as by competitive mechanisms. Intra-specific competition was higher than inter-specific competition for two species (C. henryi, Q. serrata) depending on the respective species combination. To a high degree, the competitive ability of species can be explained by species identity. Competition for light likely played a major role in our experiment, as evidenced by the strong response of crown architecture and branch demography to the manipulated predictor variables. Conclusions Effects of species composition and species identity on growth rates and crown architecture variables of tree saplings point to niche separation as a mechanism of species co-existence, while effects of species richness were not yet prominent at the sapling life stage.
Research of real options optimization investment under asymmetry information

The real options are enlargement of the financial options. Its essence is object item investment and policy decision of management. In this paper real options investor and value function of operator are described. The optimization investment policy decision of the real options has been analyzed under different information conditions. The operator of real options hides the item value information under asymmetry information. It is a principal_agent problem having the converse selection. This paper designed that objective function is taken at the biggest mathematical expectation value of investment profit. The optimization control of the state equation is taken at the investment and quantity discount. Using maximal principle the found solution scheme of the real options optimization investment and the quantity discount has been derived. Finally, the emulation experiment in the real options optimization investment was made. The analysis result of real options in the item investment problem is verified.
Cross‐sectional study of the susceptibility of Candida isolates to antifungal drugs and in vitro–in vivo correlation in HIV‐infected patients

Objectives:To investigate (1) the frequency of clinical resistance to oral polyenes or azole treatment for oral candidiasis, (2) the frequency of resistant in vitro Candida strains, (3) the relationship between the susceptibilities of in vitro Candida species and in vivo status in HIV patients.Design:Prospective cross-sectional study.Setting:Tertiary care clinic at Bocage Hospital, Dijon, France.Patients:HIV-infected patients with and without oral candidiasis.Interventions:Clinical examination, oral swab for mycologic investigations.Main outcome measures:Clinical diagnosis of oral candidiasis, identification of the antifungal treatment given within the previous month, identification of Candida species, antimycogramm and determination of the minimal inhibitory concentration (MIC) for fluconazole, and measurement of T-helper cell count.Results:Within a 2-month period, 154 HIV-infected patients were studied: 46 heterosexuals, 51 intravenous drug users (IVDU), 52 homosexuals and five blood transfusion recipients. The percentages of patients with oral candidiasis were: 41, 80, 44 and 20%, respectively (P<0.05); the mean T-helper cell counts were 200, 135, 210 and 238×106/l cells, respectively (P <0.05). Twenty-two patients (14.3%) had received recent azole treatment and 29 (18.8%) recent oral polyene treatment. Among the 84 patients with and the 70 patients without oral candidiasis, 78 and 28 Candida strains were isolated, respectively. Although Candida albicans represented the majority of Candida species (88 strains, 83%), the non-albicans strains were isolated more frequently in patients who had received recent antifungal treatment. No strains were resistant to ketoconazole, miconazole or econazole; however, six (5.6%), 16 (15%) and 10 (9.5%) were intermediately susceptible to the three drugs, respectively. Twelve (1 3.6%) of the 88 C. albicans, five of the six C. (Torulopsis) glabrata, one of the five C. tropicalis and all three C. krusei strains were resistant to fluconazole. These resistant strains were separated as follows: 41.1% of C. albicans strains resistant to fluconazole were isolated from patients who had received recent azole therapy, 1 7.6% from patients who received recent oral polyene, and 3.7% from patients who had not received any recent antifungal treatment (P= 0.004). The mean MIC of these three categories of isolates were 3.6, 1.6 and 0.6mg/l, respectively (P=0.06). Conclusions:Oral candidiasis and fluconazole-resistant Candida isolates are more frequently found in IVDU. Treatments using azoles select non-albicans strains and are associated with decreased susceptibilities of C. albicans strains to fluconazole in particular. These findings show that prolonged azole treatment in severely immunocompromised patients should be avoided.
Modulation of TNF‐α expression in bone marrow macrophages: Involvement of vitamin D response element

The calcium‐regulating hormone, 1,25(OH)2D3, induces tumor necrosis factor‐α (TNF‐α) synthesis and release from bone marrow macrophages (BMMs). To investigate the mechanism of this regulation, we have examined the effects of 1,25(OH)2D3 on the cytokine message. 1,25(OH)2D3 increased TNF‐α mRNA abundance in a dose‐ and time‐dependent manner. The combined treatment of BMMs with LPS and 1,25(OH)2D3 resulted in a synergistic increase of TNF‐α. The steroid also increased the expression of CD14 (LPS receptor). Vitamin D receptors (VDRs) mediate 1,25(OH)2D3 genomic effects by forming homodimers or heterodimers with retinoic acid receptors (RARs) or retinoic X receptors (RXRs). The RXR ligand, 9‐cis retinoic acid (9cRA), reduced TNF‐α mRNA abundance in BMMs, but increased CD14 mRNA levels. 1,25(OH)2D3 or LPS did not affect TNF‐α transcript stability. 9cRA, however, caused TNF‐α mRNA destabilization. Next, we searched for potential vitamin D response elements (VDREs) in the promoter region (1.2 kb) of the TNF‐α gene, and identified six such sequences. Using electrophoresis mobility shift assay (EMSA) we identified one of those sequences (−1008 to −994) as a likely candidate to be a VDRE (tnfVDRE). The binding of tnfVDRE to BMM‐derived nuclear extract was increased following cell treatment with 1,25(OH)2D3. No induction was observed with 9cRA treatment, but the retinoid enhanced the activity of 1,25(OH)2D3 when added together. Previously characterized VDREs (mouse osteopontin and rat osteocalcin) competed effectively with tnfVDRE, demonstrating the nature of the TNF‐α‐derived sequence as a VDRE. We observed super‐shift and block‐shift of the complex in the presence of either anti‐VDR or anti‐RXR antibodies. Our data suggest that 1,25(OH)2D3 increases TNF‐α transcript abundance in BMMs via a transcriptional mechanism; 9cRA decreases TNF‐α mRNA by destabilizing the transcript, and possibly also by forming transcriptionally inactive complex with 1,25(OH)2D3 on the tnfVDRE. The receptor complex interacting with tnfVDRE found in the promoter of the cytokine gene is probably composed of VDR‐RXR heterodimer. J. Cell. Biochem. 88: 986–998, 2003. © 2003 Wiley‐Liss, Inc.
Effect of Thymine Glycol on Transcription Elongation by T7 RNA Polymerase and Mammalian RNA Polymerase II*

Thymine glycols are formed in DNA by exposure to ionizing radiation or oxidative stress. Although these lesions are repaired by the base excision repair pathway, they have been shown also to be subject to transcription-coupled repair. A current model for transcription-coupled repair proposes that RNA polymerase II arrested at a DNA lesion provides a signal for recruitment of the repair enzymes to the lesion site. Here we report the effect of thymine glycol on transcription elongation by T7 RNA polymerase and RNA polymerase II from rat liver. DNA substrates containing a single thymine glycol located either in the transcribed or nontranscribed strand were used to carry out in vitro transcription. We found that thymine glycol in the transcribed strand blocked transcription elongation by T7 RNA polymerase ∼50% of the time but did not block RNA polymerase II. Thymine glycol in the nontranscribed strand did not affect transcription by either polymerase. These results suggest that arrest of RNA polymerase elongation by thymine glycol is not necessary for transcription-coupled repair of this lesion. Additional factors that recognize and bind thymine glycol in DNA may be required to ensure RNA polymerase arrest and the initiation of transcription-coupled repairin vivo.
A Case-Control Study of Pesticides and Fetal Death Due to Congenital Anomalies

We examined the association between late fetal death due to congenital anomalies (73 cases, 611 controls) and maternal residential proximity to pesticide applications in ten California counties. A statewide database of all applications of restricted pesticides was linked to maternal address to determine daily exposure status. We examined five pesticide chemical classes. The odds ratios from logistic regression models, adjusted for maternal age and county, showed a consistent pattern with respect to timing of exposure; the largest risks for fetal death due to congenital anomalies were from pesticide exposure during the 3rd–8th weeks of pregnancy. For exposure either in the square mile of the maternal residence or in one of the adjacent 8 square miles, odds ratios ranged from 1.4 (95% confidence interval = 0.8–2.4) for phosphates, carbamates, and endocrine disruptors to 2.2 (95% confidence interval = 1.3–3.9) for halogenated hydrocarbons. Similar odds ratios were observed when a more restrictive definition of nonexposure (not exposed to any of the five pesticide classes during the 3rd–8th weeks of pregnancy) was used. The odds ratios for all pesticide classes increased when exposure occurred within the same square mile of maternal residence.