Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase I Clinical and Pharmacological Study of Thymidine ( NSC 21548 ) and cis-Diamminedichloroplatinum ( II ) in Patients with Advanced Cancer 1

Studies in cell culture systems have demonstrated synergistic cytotoxicity of thymidine and its in vivo metabolite thymine with cisplatin. We have conducted a Phase I trial to assess the toxic effects and tolerable doses of thymidine plus cisplatin in patients with advanced cancer. Twenty such patients were treated with varying doses of thymidine infused continuously during Days 1-5 of a 28-day cycle. Cisplatin at a dose of 100 mg/m2 was administered on Day 3 of the cycle. Using this schedule, the maximally tolerated dose of thymidine was 60 g/nr/day. Hematological toxicity was dose limiting with median granulocyte and platelet nadirs of 1,500/mm3 and 55,000/mm3, respectively. Central nervous system and gastrointestinal toxicity was also prominent. Plasma and urine thymidine and thymine concentrations were determined using a high-performance liquid chromatography assay. At the maximally tolerated thymidine dose, steady state plasma thymidine concentrations approached or exceeded 1 HIMin all patients, and thymine levels of 12 HIMwere achievable. These concentrations approach those demonstrated to produce synergistic cytotoxicity with cisplatin in vitro. Further pharmacokinetic analysis re vealed that there is a progressive fall in thymidine plasma clearance with increasing dose and that cisplatin administration is followed by a signif icant fall in plasma thymidine clearance. No clear-cut relationships between platelet nadir and thymidine pharmacokinetics could be found, although nonlinear regression analysis did reveal a significant correlation between steady-state plasma thymidine concentration and platelet nadir. The recommended thymidine dose for Phase II trials of this combination is 60 n/nr/day jn patients with little or no prior therapy.
Discourse Structure in the TRAINS Project

In a natural dialog, a considerable proportion of the utterances actually relate to the maintenance of the dialog itself rather than to furthering the task or goals motivating the conversation. For example, many utterances serve to acknowledge, clarify, correct a previous utterance rather than pursue some goal in the domain. In addition, natural dialog is full of false starts, ungrammatical sentences and other complexities not found in in written language. This paper describes our recent efforts to define and construct a model of discourse interaction that handle dialogs that are rich in these natural dialog-related phenomena.
Partial deafness cochlear implantation at the University of Kansas: techniques and outcomes.

BACKGROUND One of the most significant recent advances in cochlear implantation is the implantation of patients with residual hearing. These patients have a downsloping sensorineural hearing loss with poor speech discrimination and perform poorly with standard amplification. Studies using a variety of different electrode designs have demonstrated that it is possible to implant an inner ear and preserve residual hearing. Initial studies have demonstrated that a combination of residual acoustic hearing in the low frequencies with electrical stimulation in the mid- to high frequencies resulted in superior hearing performance in background noise. PURPOSE The objective of this study was to determine the effect of electrode insertion depth on hearing preservation. STUDY SAMPLE Eighteen patients with mild to severe hearing loss in the low frequencies combined with poor word recognition were recruited for the study. INTERVENTION Cochlear implantation. DATA COLLECTION AND ANALYSIS Pre- and postoperative hearing test, Hearing in Noise Test, and consonant-nucleus-consonant testing. Data analysis was performed with Kruskal Wallis and Mann-Whitney testing. RESULTS In our study of 18 patients implanted with a Med-El PulsarCI100 we demonstrated the ability to preserve residual hearing with implant insertion depths ranging from 20 to 28 mm, giving us the possibility of near complete cochlear frequency coverage with an implant array while preserving residual hearing. These patients performed well both in quiet and in 10 dB signal-to-noise ratio conditions. CONCLUSION Hearing preservation was achievable even with deep implant insertion. Patients performed well in combined acoustic and electric conditions.
Treatment of Painful Heel Syndrome With Shock Waves

In a prospective clinical study, the effectiveness of shock waves on painful heel syndrome in 80 patients (20 men and 60 women) with an average age of 48 years was investigated. Six patients had bilateral treatments. Each treatment consisted of 1000 impulses of shock waves at 14 kV. A 100-point scoring system (70 points for pain and 30 points for function) was used for evaluation. The intensity of pain was measured with a visual analog scale from 0 to 10. The overall results were no complaints in 20.6%, significantly better in 52.9%, slightly better in 17.6%, and unchanged in 8.8% of 64 patients (68 heels) with 12 weeks followup; no complaints in 59.3%, significantly better in 27.7%, slightly better in 13% of 52 patients (54 heels) with 6 months followup. None of patients’ symptoms became worse. Seventeen patients (18 heels) who did not respond favorably to the first treatment had significantly better results after a second treatment. There were no device-related problems, and no systemic or local complications. Shock wave treatment is a new modality of therapy that is safe and effective in the treatment of patients with painful heel syndrome.
Silent cerebral infarction in a community-based autopsy series in Japan. The Hisayama Study.

BACKGROUND AND PURPOSE The purpose of this study was to assess the prevalence and characteristics of silent cerebral infarction in a population-based consecutive autopsy series of residents of Hisayama, Kyushu, Japan. METHODS Autopsy records, cerebral pathological findings, and clinical charts of 966 Hisayama residents recorded during the 26 years from 1961 to 1987 were examined (autopsy rate, 82.4%). The subjects were divided into three groups: those with both clinically apparent strokes and pathologically verified cerebral infarcts (stroke group), those having pathological evidence of cerebral infarction in the brain but without clinical stroke episodes (silent infarction group), and those with neither infarction nor stroke episode (noninfarction group). Risk factors and brain pathology in the three groups were compared. RESULTS Silent cerebral infarction was found in 12.9% of the 966 subjects who had undergone autopsy, and its frequency increased with age. The subjects with silent infarcts were older, had higher systolic or diastolic blood pressure, and had atrial fibrillation more frequently than subjects in the noninfarction group. There were no significant differences in the locations of infarcts between the stroke and silent infarction groups, although infarcts tended to be located in the deeper area of the brain in the latter. The number and size of infarcts were smaller in the silent infarction group than in the stroke group. CONCLUSIONS Diastolic blood pressure and atrial fibrillation appear to be strong predictors of silent cerebral infarction in the Japanese general population. Stroke becomes clinically apparent as infarct volume increases.
Simultaneous Quantitative Detection of Relevant Biomarkers in Breast Cancer by Quantitative Real-Time PCR

The assessment of ERα, PgR and HER2 status is routinely performed today to determine the endocrine responsiveness of breast cancer samples. Such determination is usually accomplished by means of immunohistochemistry and in case of HER2 amplification by means of fluorescent in situ hybridization (FISH). The analysis of these markers can be improved by simultaneous measurements using quantitative real-time PCR (Qrt-PCR). In this study we compared Qrt-PCR results for the assessment of mRNA levels of ERα, PgR, and the members of the human epidermal growth factor receptor family, HER1, HER2, HER3 and HER4. The results were obtained in two independent laboratories using two different methods, SYBR Green I and TaqMan probes, and different primers. By linear regression we demonstrated a good concordance for all six markers. The quantitative mRNA expression levels of ERα, PgR and HER2 also strongly correlated with the respective quantitative protein expression levels prospectively detected by EIA in both laboratories. In addition, HER2 mRNA expression levels correlated well with gene amplification detected by FISH in the same biopsies. Our results indicate that both Qrt-PCR methods were robust and sensitive tools for routine diagnostics and consistent with standard methodologies. The developed simultaneous assessment of several biomarkers is fast and labor effective and allows optimization of the clinical decision-making process in breast cancer tissue and/or core biopsies.
A Blocker Filtering Technique for SAW-Less Wireless Receivers

An active filtering technique to remove the out-of-band blockers in wireless receivers is presented. The circuit employs a feed-forward filtering path to produce an arbitrarily narrow frequency response in the low-noise amplifier (LNA), eliminating the need for an external surface acoustic wave (SAW) filter at the receiver front-end. The required notch filtering in the feed-forward path is realized through a receiver translational loop, driven by the same local oscillator (LO) signals used in the main receiver. For the proof of concept, a prototype amplifier in 65 nm standard CMOS, intended for Global System for Mobile Communication (GSM) applications, is implemented. When the filtering is enabled, the amplifier 3-dB bandwidth reduces from 220 MHz to about 4.5 MHz, and a stop-band rejection of over 21 dB is achieved.
Disease-related Risk of Vertebral Fracture During Glucocorticoid Treatment of Collagen Vascular Diseases

To the Editor: Collagen vascular diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren’s syndrome (SS), systemic sclerosis (SSc)/mixed connective tissue disease (MCTD), polymyositis/dermatomyositis (PM/DM), and microscopic polyangiitis, are chronic and sometimes involve multiple organs, and are thus occasionally life-threatening. Immunosuppressive treatment with longterm high-dose glucocorticoids is necessary, but the treatment causes a high incidence of osteoporosis1,2,3. Recently, we demonstrated that patients treated with longterm high-dose glucocorticoids have a high risk of symptomatic vertebral fractures in collagen vascular diseases, based on the analysis of the Chiba-Shimoshizu Rheumatic Cohort4,5. The chronic and systemic inflammation in patients with RA and SLE has been recognized as causing secondary osteoporosis independently of glucocorticoids6, and many studies demonstrated that patients with RA have lower bone mineral density (BMD) and an increased risk of fracture7,8,9. However, it was not known whether there is a disease-specific or disease-related risk of osteoporotic fracture under glucocorticoid treatment among the collagen vascular diseases. We investigated the disease-specific or disease-related risk for osteoporotic symptomatic vertebral fracture by focusing on women treated with high-dose glucocorticoids for the long term for collagen vascular diseases, subanalyzing a cohort at Shimoshizu National Hospital in Japan. The study subjects were newly treated with an initial dose of > 20 mg/day prednisolone (PSL) equivalent for at least 6 months without prior prophylactic treatment with bisphosphonate, hormone replacement therapy, or selective estrogen receptor modulator to prevent bone loss. We defined glucocorticoid dose increase as the reintroduction of ≥ 20 mg/day of glucocorticoid (PSL equivalent) due to increased disease activity in patients whose doses were once tapered to < 20 mg/day. Symptomatic vertebral fracture was defined as vertebral deformity that was confirmed … Address correspondence to Dr. I. Tatsuno, Department of Clinical Cell Biology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan. E-mail: ichiro-tatsuno{at}faculty.chiba-u.jp
Coxsackievirus A6: a new emerging pathogen causing hand, foot and mouth disease outbreaks worldwide

Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the predominant pathogens causing outbreaks of hand, foot and mouth disease (HFMD) worldwide. Other human enterovirus A (HEV-A) serotypes tend to cause only sporadic HFMD cases. However, since a HFMD caused by coxsackievirus A6 broke out in Finland in 2008, CA6 has been identified as the responsible pathogen for a series of HFMD outbreaks in Europe, North America and Asia. Because of the severity of the clinical manifestations and the underestimated public health burden, the epidemic of CA6-associated HFMD presents a new challenge to the control of HFMD. This article reviewed the epidemic characteristics, molecular epidemiology, clinical features and laboratory diagnosis of CA6 infection. The genetic evolution of CA6 strains associated with HFMD was also analyzed. It indicated that the development of a multivalent vaccine combining EV71, CA16 and CA6 is an urgent necessity to control HFMD.
Confocal laser scanning microscopy to study formation and properties of polyelectrolyte nanocapsules derived from CdCO3 templates

Three‐dimensional confocal laser scanning microscopy (CLSM) was used as an essential investigation method to obtain information about the formation and morphological characteristics of nanocapsules. Nanocapsules are built by layer‐by‐layer deposition of alternatively charged polyelectrolytes on templates forming nanostructured hollow shells. CLSM is unique in allowing for monitoring of the core dissolution process in real time and for studying nanocapsule functioning in hydrated conditions within a three‐dimensional and temporal framework. Since we are also interested in the identification of other possible templates, we briefly report on the use of yeast cells as biocolloidal cores monitored by means of two‐photon microscopy. Here we focus our attention on the use of CdCO3 crystals as template candidates for the preparation of stable capsules. Both cubic and spherical CdCO3 cores have been produced. Cubic cores exhibit higher monodispersity and smaller size compared to spherical ones. Capsules templated on these cores have a higher surface‐to‐volume ratio that is valuable for applications related to drug delivery, functional properties of the shells and adsorption of proteins, and other biologically relevant molecules. Microsc. Res. Tech. 59:536–541, 2002. © 2002 Wiley‐Liss, Inc.
Night-Time Vehicle Sensing in Far Infrared Image with Deep Learning

The use of night vision systems in vehicles is becoming increasingly common. Several approaches using infrared sensors have been proposed in the literature to detect vehicles in far infrared (FIR) images. However, these systems still have low vehicle detection rates and performance could be improved. This paper presents a novel method to detect vehicles using a far infrared automotive sensor. Firstly, vehicle candidates are generated using a constant threshold from the infrared frame. Contours are then generated by using a local adaptive threshold based on maximum distance, which decreases the number of processing regions for classification and reduces the false positive rate. Finally, vehicle candidates are verified using a deep belief network (DBN) based classifier. The detection rate is 93.9% which is achieved on a database of 5000 images and video streams. This result is approximately a 2.5% improvement on previously reported methods and the false detection rate is also the lowest among them.
Speech-driven lip motion generation for tele-operated humanoid robots

In order to tele-operate the lip motion of a humanoid robot (such as android) from the utterances of the operator, we developed a speech-driven lip motion generation method. The proposed method is based on the rotation of the vowel space, given by the first and second formants, around the center vowel, and a mapping to the lip opening degrees. The method requires the calibration of only one parameter for speaker normalization, so that no other training of models is required. In a pilot experiment, the proposed audio-based method was perceived as more natural than vision-based approaches, regardless of the language.
Effects of pH and Magnetic Material on Immunomagnetic Separation of Cryptosporidium Oocysts from Concentrated Water Samples

ABSTRACT In this study, we examined the effect that magnetic materials and pH have on the recoveries of Cryptosporidium oocysts by immunomagnetic separation (IMS). We determined that particles that were concentrated on a magnet during bead separation have no influence on oocyst recovery; however, removal of these particles did influence pH values. The optimal pH of the IMS was determined to be 7.0. The numbers of oocysts recovered from deionized water at pH 7.0 were 26.3% higher than those recovered from samples that were not at optimal pH. The results indicate that the buffers in the IMS kit did not adequately maintain an optimum pH in some water samples. By adjusting the pH of concentrated environmental water samples to 7.0, recoveries of oocysts increased by 26.4% compared to recoveries from samples where the pH was not adjusted.
Brain Amyloid-Beta Fragment Signatures in Pathological Ageing and Alzheimer's Disease by Hybrid Immunoprecipitation Mass Spectrometry

Background: Senile plaques in Alzheimer's disease (AD) are composed of amyloid-β (Aβ), especially N-truncated forms including Aβ4-42. These are thought to be neurotoxic. However, individuals may live for decades with biomarker evidence of cerebral β-amyloidosis (positive amyloid PET imaging and/or low cerebrospinal fluid levels of the 42 amino acid form of Aβ) without cognitive impairment. This condition may be termed pathological ageing (PA). Objective: To investigate whether there is a difference in the cerebral Aβ fragment pattern in brain specimens from non-demented (PA) and demented (AD) individuals expressing the full neuropathological triad of AD (senile plaques, neurofibrillary tangles and neurodegeneration). Methods: We extracted Aβ using formic acid and hybrid (6E10 and 4G8) immunoprecipitation from fresh-frozen temporal cortex tissue of 6 elderly individuals (mean age ± SD: 89 ± 3.5 years) with PA and 10 patients with AD (mean age ± SD: 72 ± 8.5 years). The full spectrum of Aβ peptides was determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Results: AD patients had generally more N-terminally truncated and pyroglutamate-modified Aβ than PA patients, whereas PA patients had on average more Aβ1-40 than AD patients. Conclusion: Senile plaques in AD may have an Aβ fragment composition distinct from PA with more N-terminally and pyroglutamate-modified Aβ peptides that may be linked to neurotoxicity.
Pseudomonas aeruginosa High-Level Resistance to Polymyxins and Other Antimicrobial Peptides Requires cprA, a Gene That Is Disrupted in the PAO1 Strain

ABSTRACT The arn locus, found in many Gram-negative bacterial pathogens, mediates resistance to polymyxins and other cationic antimicrobial peptides through 4-amino-l-arabinose modification of the lipid A moiety of lipopolysaccharide. In Pseudomonas aeruginosa, several two-component regulatory systems (TCSs) control the arn locus, which is necessary but not sufficient for these resistance phenotypes. A previous transposon mutagenesis screen to identify additional polymyxin resistance genes that these systems regulate implicated an open reading frame designated PA1559 in the genome of the P. aeruginosa PAO1 strain. Resequencing of this chromosomal region and bioinformatics analysis for a variety of P. aeruginosa strains revealed that in the sequenced PAO1 strain, a guanine deletion at the end of PA1559 results in a frameshift and truncation of a full-length open reading frame that also encompasses PA1560 in non-PAO1 strains, such as P. aeruginosa PAK. Deletion analysis in the PAK strain showed that this full-length open reading frame, designated cprA, is necessary for polymyxin resistance conferred by activating mutations in the PhoPQ, PmrAB, and CprRS TCSs. The cprA gene was also required for PmrAB-mediated resistance to other cationic antimicrobial peptides in the PAK strain. Repair of the mutated cprA allele in the PAO1 strain restored polymyxin resistance conferred by an activating TCS mutation. The deletion of cprA did not affect the arn-mediated lipid A modification, indicating that the CprA protein is necessary for a different aspect of polymyxin resistance. This protein has a domain structure with a strong similarity to the extended short-chain dehydrogenase/reductase family that comprises isomerases, lyases, and oxidoreductases. These results suggest a new avenue through which to pursue targeted inhibition of polymyxin resistance.
Factors regulating the rat insulin-like growth factor-binding protein-1 response to octreotide.

Insulin-like growth factor-binding protein-1 (IGFBP-1) production is increased by somatostatin and its analogues. In order to determine the time course and identify possible mechanisms of this increase in vivo we administered octreotide to rats and determined IGFBP-1 concentrations by RIA. After 60 min of anaesthesia, the mean baseline IGFBP-1 concentrations were 166 (95% confidence interval 123 to 225) ng/ml and increased in saline-infused animals to 729 (488 to 1086) ng/ml after 180 min. IGFBP-1 was stimulated transiently in response to octreotide, with circulating IGFBP-1 concentrations peaking at 1605 (1220 to 2111) ng/ml at 105 min during a continuous infusion of octreotide (100 micrograms/kg per h). In conscious chronically cannulated rats, baseline IGFBP-1 concentrations were 22 (18 to 28) ng/ml, 8-fold less than in the anaesthetised state, and were stimulated in the short term after administration of an octreotide bolus (100 micrograms/kg s.c.) to reach 88 (62 to 126) ng/ml at 60 min. A similar response was seen after i.v. administration to conscious rats. Intravenous bolus of octreotide (100 micrograms/kg) in rats anaesthetised for 3 h resulted in an increase in IGFBP-1 to peak at 1556 (1268 to 1910) ng/ml at 60 min. The IGFBP-1 response to octreotide was diminished in high-fat fed hyperinsulinaemic rats. The pattern of disappearance of iodinated IGFBP-1 from the circulation was not influenced by octreotide. The changes in GH, insulin and glucose concentrations alone did not sufficiently account for the patterns of response observed. We conclude that, in rats, octreotide stimulates IGFBP-1 acutely and this response is potentiated by factors related to anaesthesia.
Two new polyhydroxysterols produced by Fusarium solani, an endophytic fungus from Chloranthus multistachys

Abstract A highly antagonistic endophytic fungus, designated strain CL39, was originated from the leaves of Chloranthus multistachys collected in Wulong of Chongqing municipality of China in November 2015. The strain was identified as Fusarium solani based on morphological characteristics, 5.8S gene and internal transcribed spacer sequence analysis. Two new compounds, 2β, 9α-dihydroxy-5α-methoxyergosta-7, 22-diene (1), 2β, 6β-dihydroxy-5α-methoxyergosta-7, 22-diene (2) have been isolated from the culture broth of the strain. Structures of the new compounds were elucidated by detailed analysis of their spectroscopic data aided by the comparison with reported data of related derivatives, and found to belong to the polyhydroxylated steroids with a hydroxyl at C-2 instead of C-3, a rare structure among the steroids. The extract of this strain and all isolated compounds were evaluated for their antagonistic activities.