Miracle-dz/UniFAR-FTUs huggingface dataset:
Apolipoprotein E negatively regulates house dust mite-induced asthma via a low-density lipoprotein receptor-mediated pathway.

RATIONALE Distinct sets of corticosteroid-unresponsive genes modulate disease severity in asthma. OBJECTIVES To identify corticosteroid-unresponsive genes that provide new insights into disease pathogenesis and asthma therapeutics. METHODS Experimental murine asthma was induced by nasal administration of house dust mite for 5 days per week. Dexamethasone and apolipoprotein E (apo E) mimetic peptides were administered via osmotic minipumps. MEASUREMENTS AND MAIN RESULTS Genome-wide expression profiling of the lung transcriptome in a house dust mite-induced model of murine asthma identified increases in apo E mRNA levels that persisted despite corticosteroid treatment. House dust mite-challenged apo E⁻(/)⁻ mice displayed enhanced airway hyperreactivity and goblet cell hyperplasia, which could be rescued by administration of an apo E(130-149) mimetic peptide. Administration of the apo E(130-149) mimetic peptide to house dust mite-challenged apo E⁻(/)⁻ mice also inhibited eosinophilic airway inflammation, IgE production, and the expression of Th2 and Th17 cytokines. House dust mite-challenged low-density lipoprotein receptor (LDLR) knockout mice displayed a similar phenotype as apo E⁻(/)⁻ mice with enhanced airway hyperreactivity, goblet cell hyperplasia, and mucin gene expression, but could not be rescued by the apo E(130-149) mimetic peptide, consistent with a LDLR-dependent mechanism. CONCLUSIONS These findings for the first time identify an apo E-LDLR pathway as an endogenous negative regulator of airway hyperreactivity and goblet cell hyperplasia in asthma. Furthermore, our results demonstrate that strategies that activate the apo E-LDLR pathway, such as apo E mimetic peptides, might be developed into a novel treatment approach for patients with asthma.
Milp-hyperbox classification for structure-based drug design in the discovery of small molecule inhibitors of SIRTUIN6

Virtual screening of chemical libraries following experimental assays of drug candidates is a common procedure in structure-based drug discovery. However, virtual screening of chemical libraries with millions of compounds requires a lot of time for computing and data analysis. A priori classification of compounds in the libraries as low- and high-binding free energy sets decreases the number of compounds for virtual screening experiments. This classification also reduces the required computational time and resources. Data analysis is demanding since a compound can be described by more than one thousand attributes that make any data analysis very challenging. In this paper, we use the hyperbox classification method in combination with partial least squares regression to determine the most relevant molecular descriptors of the drug molecules for an efficient classification. The effectiveness of the approach is illustrated on a target protein, SIRT6. The results indicate that the proposed approach outperforms other approaches reported in the literature with 83.55% accuracy using six common molecular descriptors (SC-5, SP-6, SHBd, minHaaCH, maxwHBa, FMF). Additionally, the top 10 hit compounds are determined and reported as the candidate inhibitors of SIRT6 for which no inhibitors have so far been reported in the literature.
Immunohistochemical Detection of NPM1 Mutation in Acute Myeloid Leukemia and its Association With Cup-like Nuclear Morphology of Blasts

Blasts showing cup-like nuclei in acute myeloid leukemia (AML) have been identified in patients with nucleophosmin 1 gene (NPM1) mutation, that is, AML with cytoplasmic NPM (NPMc+ AML). We analyzed 100 consecutive cases of AML, and defined the cutoff percentages of cup-like blasts in peripheral blood and bone marrow aspirate smears that can predict NPMc+ AML. A lower cutoff level of ≥10% blasts in peripheral blood and ≥9% in bone marrow aspirate gave an excellent specificity for NPMc+ AML and a positive-predictive value of 90.9% and a negative-predictive value of 87.6% for NPMc+ AML. Cup-like nuclei were associated with higher total leukocyte count, higher blasts percentage, AML-M1 subtype, and human leukocyte antigen-DR region negativity. Our results suggest that cup-like nuclei represent an important morphologic clue that can predict NPMc+ AML and guide toward prioritizing the further workup of AML patients.
New repulsive potential functions with angle distributions for local path planning

This paper presents new repulsive potential functions (RPFs) for point robot path planning. In this scheme, the RPF for path planning has a different magnitude at each direction of a RPF based on the angle between a goal and an obstacle, unlike a conventional RPF in which the same magnitude at each direction is obtained. In doing so, the RPF attempts to overcome some of the typical problems that may arise with the conventional RPF. In particular, this paper presents a set of analyses for designing potential functions to avoid local minima for a number of representative scenarios. Specifically, the following cases are addressed: (i) a non-reachable goal problem (a case in which the potential of the goal is overwhelmed by the potential of an obstacle), (ii) an obstacle collision problem (a case in which the potential of the obstacle is overwhelmed by the potential of the goal) and (iii) a narrow passage problem (a case in which the potential of the goal is overwhelmed by the potential of two obstacles). The proposed RPF scheme eliminates the non-feasible area for the three cases by the help of an angle-varying magnitude between a goal and an obstacle. The example results show that the proposed RPF scheme can effectively construct a path-planning system with the capability of reaching a goal and avoiding obstacles despite possible local minima.
Characterizing Set Containments Involving Infinite Convex Constraints and Reverse-Convex Constraints

Dual characterizations of the containment of a closed convex set, defined by infinite convex constraints, in an arbitrary polyhedral set, in a reverse-convex set, defined by convex constraints, and in another convex set, defined by finite convex constraints, are given. A special case of these dual characterizations has played a key role in generating knowledge-based support vector machine classifiers which are powerful tools in data classification and mining. The conditions in these dual characterizations reduce to simple nonasymptotic conditions under Slater's constraint qualification.
The Polycystic Ovary Syndrome

This symposium in Clinical Obstetrics and Gynecology is devoted to evaluation of management of women with polycystic ovary syndrome (PCOS). As pointed out by Bradley Trivax and Ricardo Azziz in their chapter on diagnosis, PCOS is the most common endocrine abnormality among women in the reproductive age group, occurring in about 1 in 15 women. Thus, PCOS accounts for a significant proportion of visits to gynecologists, primary care physicians, and others who provide health care to women. This monograph is written to assist such providers in providing a contemporary, sophisticated approach to the evaluation and management of women with PCOS based on the best evidence in the literature. The very definition of PCOS has been a subject of heated debate over the past 2 decades. In the United States, the focus had been on a history of chronic anovulation combined with evidence of androgen excess. In Europe, it has been argued that the morphology of the ovaries on the basis of ultrasound assessment is important as well. In 2003, a consensus definition arose from a conference in Rotterdam that combined these viewpoints, as described by Trivax and Azziz. These authors provide an historical view and an up-to-date summary of the characteristics of women with PCOS, a comparison of the different criteria, a description of the epidemiology of the condition, and an approach to diagnosis. Because of substantial evidence regarding familial aggregation, a genetic basis for this condition is thought to be likely. It has become clear, however, that transmission of this disorder is complex and probably not attributable to a single gene locus. Marie Nam and Jerome Strauss review the literature on the genetics of PCOS. They report on linkage and association studies that point to over 50 candidate genes as a source of heritable predisposition, but also review the various factors that have hindered the efforts to attain clarity about the genetics of PCOS, including variable and broad definition, small sample sizes, low fecundity, and lack of a male phenotype.
Enteritis due to feline infectious peritonitis virus.

臨床・病理・血清学的にネコ伝染性腹膜炎(FIP)と診断され死亡したネコ4例および仔ネコの実験接種例14例について, 腸病変とウイルス抗原あるいはウイルス粒子の所在を検索した. 自然例2例および実験例12例が下痢を発した. 多くの病例の小腸・大腸粘膜は水腫性に肥厚し, 腸内容は水様～粘液状であった. 自然例3例および実験例12例の小腸・大腸病変は粘膜上皮の変性・剥離・増生を特徴とする比較的表在性の変化で, 固有層には浮腫, 少数の好中球お上び単核細胞浸潤がみられ, 隣接上皮細胞相互の癒合もしばしばみとめられた. しかし, 他の自然例1例および実験死亡例2例では, 小腸・大腸ともに炎症病変は激しく粘膜深部に及んでいた. これらの自然例および実験例の腸上皮細胞細胞質にはウイルス特異蛍光がみられ, 電顕ではコロナウイルス粒子が検出された. コロナウイルス粒子は自然例および実験例の糞便中にも検出された. 以上のことから, 腸病変部から排出されたウイルスが糞便を介して伝播する可能性が示唆された.
Penetration Disorder: Dyspareunia Exists on the Extension of Vaginismus

Thank you very much for giving me a chance to comment on new definitions and classifications (Basson et al., 2000). I am a certified clinical psychologist and have been engaged in sex therapy for more than 20 years. During this experience, I was sometimes embarrassed at the fact that a woman often is diagnosed as suffering from a different sexual dysfunction by many therapists, and therefore professionals cannot have discussions or conduct research. I think that this happens because of lack of proper diagnostic framework and classification. So I proposed a new definition and diagnosis of female sexual dysfunction at the 14th World Congress of Sexology at Hong Kong in 1999. Let me describe its points and comment on your report. I investigated 128 patients and got the results as follows. The groups consisted of 77 patients who could not endure vaginal penetration and who are suspected to have vaginismus = Group 1; 21 patients who could endure vaginal penetration with pain = Group 2; 30 patients who could have coitus but who avoided sexual communication = Group 3)
Influence of steep Trendelenburg position and CO(2) pneumoperitoneum on cardiovascular, cerebrovascular, and respiratory homeostasis during robotic prostatectomy.

BACKGROUND The steep (40 degrees ) Trendelenburg position optimizes surgical exposure during robotic prostatectomy. The goal of the current study was to investigate the combined effect of this position and CO(2) pneumoperitoneum on cardiovascular, cerebrovascular, and respiratory homeostasis during these procedures. METHODS Physiological data were recorded during the whole surgical procedure in 31 consecutive patients who underwent robotic endoscopic radical prostatectomy under general anaesthesia. Heart rate, mean arterial pressure, central venous pressure, Sp(o(2)), Pe'(co(2)), P(Plat), tidal volume, compliance, and minute ventilation were monitored and recorded. Arterial samples were obtained to determine the arterial-to-end-tidal CO(2) tension gradient. Continuous regional cerebral tissue oxygen saturation (Sct(o(2))) was determined by near-infrared spectroscopy. RESULTS Although patients were in the Trendelenburg position, all variables investigated remained within a clinically acceptable range. Cerebral perfusion pressure (CPP) decreased from 77 mm Hg at baseline to 71 mm Hg (P=0.07), and Sct(o(2)) increased from 70% to 73% (P<0.001). Pe'(co(2)) increased from 4.12 to 4.79 kPa (P<0.001) and the arterial-to-Pe'(co(2)) tension difference increased from 1.06 kPa in the normal position to a maximum of 1.41 kPa (P<0.001) after 2 h in the Trendelenburg position. CONCLUSIONS The combination of the prolonged steep Trendelenburg position and CO(2) pneumoperitoneum was well tolerated. Haemodynamic and pulmonary variables remained within safe limits. Regional cerebral oxygenation was well preserved and CPP remained within the limits between which cerebral blood flow is usually considered to be maintained by cerebral autoregulation.
Air pollution and children--an unhealthy mix.

Residents in urban areas may be worried about the air they breathe. In recent reports, air pollution has been linked to increased mortality, an increased risk of asthma, and decreased development of lung function in childhood. In this issue of the Journal, Kulkarni et al.1 investigate this last finding. The authors show that carbon particles, similar to those in ambient air, are present in the airway macrophages of children and that an increased level of carbon in the macrophages correlates with decreased lung function. Why should we care about lung function in children? The lungs develop steadily throughout childhood, with .
Amyloid Fibrils as Building Blocks for Natural and Artificial Functional Materials

Proteinaceous materials based on the amyloid core structure have recently been discovered at the origin of biological functionality in a remarkably diverse set of roles, and attention is increasingly turning towards such structures as the basis of artificial self‐assembling materials. These roles contrast markedly with the original picture of amyloid fibrils as inherently pathological structures. Here we outline the salient features of this class of functional materials, both in the context of the functional roles that have been revealed for amyloid fibrils in nature, as well as in relation to their potential as artificial materials. We discuss how amyloid materials exemplify the emergence of function from protein self‐assembly at multiple length scales. We focus on the connections between mesoscale structure and material function, and demonstrate how the natural examples of functional amyloids illuminate the potential applications for future artificial protein based materials.
A calibration with an adaptive data selection based on Bayes estimation for a successive stochastic approximation ADC system

A novel low-power high-precision analog-to-digital converter (ADC) called the successive stochastic approximation ADC (SSA-ADC) has been recently proposed, which has two kinds of outputs from a stochastic flash ADC (SF-ADC) and a successive approximation register ADC (SAR-ADC) modes, respectively. In this paper, we propose a software-level calibration and encoding based on the machine learning for the two outputs to generate an total output. In addition, from the practical viewpoint, we propose an incremental learning which selects additional data by keeping a balance between the uniform random and preferential selections based on the Bayesian estimation at each learning.
Evolution beyond LTE-advanced with Full Dimension MIMO

In this paper, we study the overall development of Full Dimension MIMO (FD-MIMO) technology in the context of next generation evolution towards B4G and 5G cellular systems. FD-MIMO relies on a large number of antennas placed in a 2-dimensional antenna array panel at base stations (BSs). Utilizing the 2-dimensional antenna array, FD-MIMO simultaneously transmits to a large number of mobile stations (MSs) effectively realizing high order multi-user MIMO (MU-MIMO) well beyond what is possible today. This paper discusses the research and standardization effort in 3GPP to incorporate the features and performance benefits of FD-MIMO in the next evolution of LTE standards. In order to demonstrate the potential performance benefits of FD-MIMO, system level evaluation results are provided using the 3GPP evaluation methodology. Evaluation results show that FD-MIMO can provide vast improvement over conventional LTE networks.
Predicting multimode chassis resonance of single or nested rectangular computer enclosures

Designing standardized six-sided computer enclosures that contain multiple types of active circuitry across several products, it is critical to predict and qualify excited cavity resonances against the expected harmonic spectrum generated by the active circuits. Moreover, if the enclosure or chassis is housed within another enclosure, it is also important to predict resonances of the larger housing enclosure. This paper presents a simplified method of quickly determining rectangular chassis enclosure resonances using simple multimode resonant cavity formula and no electromagnetic field solvers. Key resonance frequencies are assigned a risk category depending on number of modes excited, and effective ‘Q’ of each resonance frequency.
Phase II feasibility study of preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil for esophageal squamous cell carcinoma

The combination of docetaxel, cisplatin, and 5‐fluorouracil (DCF) as preoperative treatment for esophageal squamous cell carcinoma (ESCC) has not been investigated. We carried out a multicenter phase II feasibility study of preoperative chemotherapy with DCF for ESCC. Patients with clinical stage II/III ESCC (International Union Against Cancer TNM classification system, 6th edition) were eligible. Chemotherapy consisted of i.v. docetaxel (70–75 mg/m2) and cisplatin (70–75 mg/m2) on day 1, and continuous infusion of fluorouracil (750 mg/m2/day) on days 1–5. Antibiotic prophylaxis on days 5–15 was mandatory. This regimen was repeated every 3 weeks with a maximum of three cycles allowed. After completion of chemotherapy, esophagectomy with extended lymphadenectomy was carried out. The primary endpoint was the completion rate of protocol treatment. Forty‐two eligible patients were enrolled. During chemotherapy, the most common grade 3 or 4 toxicities were neutropenia (83%), anorexia (7%), and stomatitis (5%). Forty‐one (98%) patients underwent surgery. The completion rate of protocol treatment was 90.5% (38/42). No treatment‐related death was observed and the incidence of operative morbidity was tolerable. According to RECIST, the overall response rate after the completion of DCF was 64.3%. Pathological complete response was achieved in 17%. The estimated 2‐year progression‐free survival and overall survival were 74.5% and 88.0%, respectively. Although these data are preliminary, preoperative DCF was well tolerated. Antitumor activity was highly promising and warrants further investigation. This trial was registered with University Hospital Medical Information Network (no. UMIN000002396).
Temozolomide-based combination for advanced neuroendocrine neoplasms: a systematic review of the literature.

BACKGROUND In this systematic review, we explored the value of using temozolomide (TMZ)-based combinations for advanced neuroendocrine neoplasms (NENs). METHODS Database search were conducted using the terms 'NENs' and 'TMZ' and 'systemic therapy. ' Outcomes of interest included progression-free survival and overall survival, toxicities and tumor response. RESULTS In total, 16 trials including 348 patients were included. Median progression-free survival ranged from 6 to 31 months. The disease control rate ranged from 65 to 100%. Frequently reported grade 3/4 toxicities were leukopenia, lymphopenia and elevated transaminases. CONCLUSION The published clinical data suggest that TMZ-based combination with some anticancer agents (especially capecitabine) could be an effective treatment option for advanced low-intermediate grade NENs.
Update on the keratoconus genetics

Keratoconus (KC) is one of the leading causes for keratoplasty. While the genetic aetiology of more and more corneal dystrophies is revealed, KC falls behind. And it is not because of lack of effort. The diversity in the many published results from over two decades is discussed in relation to the present knowledge in molecular biology. Results that at first appear to be in conflict with each other make sense when placed in the right context. Ophthalmologists often refer to KC as a heterogeneous disease. This review demonstrates that it truly is a multifactorial disease. Despite the many attempts to reveal the aetiology of KC, the pathological mechanism(s) still remain to be solved.
In situ identification of bacteria in drinking water and adjoining biofilms by hybridization with 16S and 23S rRNA-directed fluorescent oligonucleotide probes

Free-water-phase and surface-associated microorganisms from drinking water were detected and roughly identified by hybridization with fluorescence-labeled oligonucleotide probes complementary to regions of 16S and 23S rRNA characteristic for the domains Bacteria, Archaea, and Eucarya and the beta and gamma subclasses of Proteobacteria. Samples of glass-attached biofilms and plankton were taken from a Robbins device installed in a water distribution system. More than 70% of the surface-associated cells and less than 40% of the planktonic cells visualized by 4',6-diamidino-2-phenylindole staining bound detectable amounts of rRNA-targeted probes. These findings are an indication for higher average rRNA content and consequently higher physiological activity of the attached microbial cells compared with the free-living cells. All detectable cells hybridized with the bacterial probe, whereas no Archaea and no Eucarya cells could be detected. Simultaneous hybridization with probes specific for the beta and gamma subclasses of Proteobacteria revealed that microcolonies already consisted of mixed populations in early stages with fewer than 50 cells. These observations provide further evidence that the coexistence and interaction of bacteria in drinking water biofilms may be an integral part of their growth and survival strategies.
Application of QSAR models in analysis of antibacterial activity of some benzimidazole derivatives against Sarcina lutea

In the present paper, a quantitative structure activity relationship (QSAR) has been carried out on a series of 2-methyl and 2-aminobenzimidazole derivatives to identify the lipophilicity requirements for their inhibitory activity against bacteria Sarcina lutea. The tested compounds displayed in vitro antibacterial activity and minimum inhibitory concentration (MIC) was determined for all compounds. The partition coefficients of the studied compounds were measured by the shake flask method (log P) and by theoretical calculation (Clog P). The relationships between lipophilicity descriptors and antibacterial activities were investigated and the mathematical models have been developed as a calibration models for predicting the inhibitory activity of this class of compounds. The models were validated by leave-one-out (LOO) technique as well as by the calculation of statistical parameters for the established models. Therefore, QSAR analysis reveals that lipophilicity descriptor govern the inhibitory activity of benzimidazoles studied against Sarcina lutea.
A genetic cluster of early onset Parkinson's disease in a Colombian population

We previously identified in two families with early onset Parkinson's Disease (PD) from the isolated population of Antioquia (Colombia), a parkin Cys212Tyr substitution caused by a G736A mutation. This mutation was subsequently observed in a Spanish family, suggesting that it could have been taken to Antioquia by Spanish immigrants. Here we screened for the G736A mutation in additional Antioquian early onset PD cases and used haplotype analysis to investigate the relationship between Spanish and Antioquian G736A chromosomes. We confirmed the occurrence of an extensive founder effect in Antioquia. Thirteen individuals (10 homozygotes) from seven nuclear families were identified with the G736A mutation. Genealogical investigations demonstrated the existence of shared ancestors between six of these families four to five generations ago and no evidence of Spanish ancestry during this period. A second parkin mutation (a duplication of exon 3), was detected in the three G736A heterozygote carriers. Haplotype data exclude a recent common ancestry between the Spanish and Antioquian patients studied here and is consistent with the introduction of the G736A mutation in Antioquia during early colonial times (about 16 generations ago). © 2006 Wiley‐Liss, Inc.