Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of topoisomerase I inhibition, DNA damage, and cytotoxicity of camptothecin derivatives presently in clinical trials.

BACKGROUND Camptothecins belong to a group of anticancer agents with a unique mechanism of action: poisoning of eukaryotic DNA topoisomerase I. Two camptothecin derivatives, topotecan (TPT) and CPT-11, are in clinical trials and their chemotherapeutic efficacy appears promising. PURPOSE Our aim was to compare simultaneously the molecular and cellular pharmacology of the various camptothecin derivatives that are presently in clinical trials. METHODS Cytotoxicity of drugs toward human colon carcinoma HT-29 cells was determined by colony-forming assays. DNA single-strand breaks (SSB) were measured by alkaline elution. Drug potency to induce topoisomerase 1-mediated DNA cleavage and the sequence selectivity of the breaks were determined by sequencing gel autoradiography. RESULTS SN-38 and CPT were more cytotoxic than 9-AC and TPT, and CPT-11 was almost inactive toward HT-29 cells. IC50 values were 8.8 nM for SN-38, 10 nM for CPT, 19 nM for 9-AC, 33 nM for TPT, and greater than 100 nM for CPT-11. In drug-induced DNA damage measured by alkaline elution drug concentrations producing 1000-rad-equivalents (C1000), values were 0.037 microM for SN-38, 0.051 microM for CPT, 0.085 microM for 9-AC, 0.28 microM for TPT, and greater than 1 microM for CPT-11. SN-38 remained the most potent compound in isolated nuclei, and CPT-11 was still inactive. The potency ranking was the same as in whole cells, and the C1000 values were 0.0025 microM for SN-38, 0.012 microM for CPT, 0.021 microM for 9-AC, 0.44 microM for TPT, and greater than 0.1 microM for CPT-11. Potency difference between SN-38 and the other compounds was greater in isolated nuclei than in whole cells. CONCLUSIONS Kinetics of the reversal of drug-induced SSB in isolated nuclei suggest that dissociation of SN-38 from cleavable complexes is much slower than that of CPT. Cleavage patterns of CPT and 9-AC were similar but differed from those of TPT and SN-38. Although in vitro analyses do not necessarily reflect chemotherapeutic efficacy, this study found that SN-38 is the most potent compound and that 9-AC and TPT are less active than CPT in this system. The effect of CPT-11 is minimal. Therefore, the clinical activity of CPT-11 may strongly depend on its hydrolysis to SN-38. Differences in DNA sequence selectivity and the stability of cleavable complexes induced by the drugs may also contribute to differences among CPT derivatives.
Fiscal Consistency and Federal District Spending in Congressional Elections

Theory: Conventional wisdom holds that legislators win votes by acquiring federal spending for constituents. Scholars have struggled, however, to support this belief empirically. This paper links federal district spending and pork with an explanation based on consistency: electoral performance hinges on legislators' fiscal consistency, i.e., whether their votes on federal spending are consistent with their credit claiming for pork flowing to their districts. Hypotheses: In districts receiving substantial pork, fiscally liberal incumbents perform better electorally than fiscal conservatives. In low-pork districts fiscal conservatives perform better. Methods: These hypotheses are tested using aggregate-level data from the 198490 United States House elections and individual-level data from the 1988 Senate Election Study. Results: The hypotheses are supported on the aggregate and individual levels. Fiscally consistent legislators receive more votes than fiscally inconsistent legislators.
Sexual Differentiation of the Neuroendocrine Mechanisms Regulating Mate Recognition in Mammals

When in breeding condition, male and female mammals seek out and mate with opposite‐sex conspecifics. The neural mechanisms controlling mate recognition and heterosexual partner preference are sexually differentiated by the perinatal actions of sex steroid hormones. Many mammalian species use odours to identify potential mates. Thus, sex differences in partner preference may actually reflect sex differences in how male and female mammals perceive socially relevant odours. Two olfactory systems have evolved in vertebrates that differ considerably in their anatomy and function. It is generally believed that the main olfactory system is used to detect a wide variety of volatile odours derived from food prey among many sources, whereas the accessory olfactory system has evolved to detect and process primarily nonvolatile odours shown to influence reproductive behaviours and neuroendocrine functions. Some recent results obtained in oestradiol‐deficient aromatase knockout (ArKO) mice that provide evidence for a developmental role of oestradiol in olfactory investigation of volatile body odours are discussed, suggesting that: (i) oestrogens contribute to the development of the main olfactory system and (ii) mate recognition is mediated by the main as opposed to the accessory olfactory system. Thus, sex differences in mate recognition and sexual partner preference may reflect sex differences in the perception of odours by the main olfactory system.
Glaucoma evolution in patients with diabetes.

UNLABELLED Glaucoma and diabetes are two chronic diseases with a long suspected pathogenic relationship. PURPOSE Screening for glaucoma in patients with diabetes. MATERIAL AND METHODS A retrospective study on 92 eyes from 46 patients with primitive open angle glaucoma (POAG) (normal and hypertensive) and intraocular hypertension (OHT) receiving medication and/or surgery associated with diabetes mellitus (DM) (type I, type II, mixed) is presented. Participants were divided into two groups as following: 16 eyes with glaucoma and diabetic retinopathy changes (group 1) and 76 eyes with glaucoma and without diabetic retinopathy changes (group 2). The following parameters were analysed: ocular pressure (Goldmann aplanotonometry), perimeter development (computerized perimetry) and fundus condition (absence, presence or progression of diabetic retinopathy). RESULTS In patients with glaucoma and diabetic retinopathy (8 patients) we found a mean difference between treated intraocular pressure (IOP) and IOP last untreated control of 4.95 mmHg; a depreciation of the MD by 4.18 dB and an average number of glaucoma medications used of 0.889 +/- 1.054. Predominant changes in proliferative diabetic retinopathy were mild. In patients with glaucoma in the absence of diabetic retinopathy, the average difference between untreated IOP and IOP under treatment at the last check-up was 1.63 mmHg, the MD depreciation was by 0.65 dB and the average number of glaucoma medications used was 0.795 +/- 0.978. CONCLUSIONS No statistically significant differences in terms of initial and final pressure were found. No statistically significant differences in the evolution of changes in perimeter between the two groups were observed. The presence of non-proliferating diabetic retinopathy influenced (only marginally statistically) the glaucomatous disease progression. Large comparative prospective studies are needed for the long-term follow up.
Current knowledge of tooth development: patterning and mineralization of the murine dentition

The integument forms a number of different types of mineralized element, including dermal denticles, scutes, ganoid scales, elasmoid scales, fin rays and osteoderms found in certain fish, reptiles, amphibians and xenarthran mammals. To this list can be added teeth, which are far more widely represented and studied than any of the other mineralized elements mentioned above, and as such can be thought of as a model mineralized system. In recent years the focus for studies on tooth development has been the mouse, with a wealth of genetic information accrued and the availability of cutting edge techniques. It is the mouse dentition that this review will concentrate on. The development of the tooth will be followed, looking at what controls the shape of the tooth and how signals from the mesenchyme and epithelium interact to lead to formation of a molar or incisor. The number of teeth generated will then be investigated, looking at how tooth germ number can be reduced or increased by apoptosis, fusion of tooth germs, creation of new tooth germs, and the generation of additional teeth from existing tooth germs. The development of mineralized tissue will then be detailed, looking at how the asymmetrical deposition of enamel is controlled in the mouse incisor. The continued importance of epithelial–mesenchymal interactions at these later stages of tooth development will also be discussed. Tooth anomalies and human disorders have been well covered by recent reviews, therefore in this paper we wish to present a classical review of current knowledge of tooth development, fitting together data from a large number of recent research papers to draw general conclusions about tooth development.
Dynamic Lognormal Shadowing Framework for the Performance Evaluation of Next Generation Cellular Systems

Performance evaluation tools for wireless cellular systems are very important for the establishment and testing of future internet applications. As the complexity of wireless networks keeps growing, wireless connectivity becomes the most critical requirement in a variety of applications (considered also complex and unfavorable from propagation point of view environments and paradigms). Nowadays, with the upcoming 5G cellular networks the development of realistic and more accurate channel model frameworks has become more important since new frequency bands are used and new architectures are employed. Large scale fading known also as shadowing, refers to the variations of the received signal mainly caused by obstructions that significantly affect the available signal power at a receiver’s position. Although the variability of shadowing is considered mostly spatial for a given propagation environment, moving obstructions may significantly impact the received signal’s strength, especially in dense environments, inducing thus a temporal variability even for the fixed users. In this paper, we present the case of lognormal shadowing, a novel engineering model based on stochastic differential equations that models not only the spatial correlation structure of shadowing but also its temporal dynamics. Based on the proposed spatio-temporal shadowing field we present a computationally efficient model for the dynamics of shadowing experienced by stationary or mobile users. We also present new analytical results for the average outage duration and hand-offs based on multi-dimensional level crossings. Numerical results are also presented for the validation of the model and some important conclusions are drawn.
d-Xylose Concentration-Dependent Hydrolase Expression Profiles and the Function of CreA and XlnR in Aspergillus niger

ABSTRACT Aspergillus niger is an important organism for the production of industrial enzymes such as hemicellulases and pectinases. The xylan-backbone monomer, d-xylose, is an inducing substance for the coordinate expression of a large number of polysaccharide-degrading enzymes. In this study, the responses of 22 genes to low (1 mM) and high (50 mM) d-xylose concentrations were investigated. These 22 genes encode enzymes that function as xylan backbone-degrading enzymes, accessory enzymes, cellulose-degrading enzymes, or enzymes involved in the pentose catabolic pathway in A. niger. Notably, genes encoding enzymes that have a similar function (e.g., xylan backbone degradation) respond in a similar manner to different concentrations of d-xylose. Although low d-xylose concentrations provoke the greatest change in transcript levels, in particular, for hemicellulase-encoding genes, transcript formation in the presence of high concentrations of d-xylose was also observed. Interestingly, a high d-xylose concentration is favorable for certain groups of genes. Furthermore, the repressing influence of CreA on the transcription and transcript levels of a subset of these genes was observed regardless of whether a low or high concentration of d-xylose was used. Interestingly, the decrease in transcript levels of certain genes on high d-xylose concentrations is not reflected by the transcript level of their activator, XlnR. Regardless of the d-xylose concentration applied and whether CreA was functional, xlnR was constitutively expressed at a low level.
Sexuality After Ovarian Cancer Therapy

Disturbances of sex life may significantly impair the quality of life and negatively affect the partnership of many women undergoing therapy for ovarian cancer. The problems may have different causes depending on the personal history, the development of female identity and the body self-image of affected women. Younger women are mostly concerned by the complete loss of ovarian function, while for postmenopausal women the loss of the remaining androgen activity of the postmenopausal ovary may play an important role. Importantly, 62% of patients complain of dyspareunia and 75% of orgasmic dysfunction after therapy for ovarian cancer. The significance of radical pelvic and para-aortal lymph node dissection with regard to sexual arousal disorders is not yet very clear. Physicians function as an important model when they talk about therapy-induced sexual dysfunction, thereby signalizing that they regard sexuality as a natural part of life. Physicians do not necessarily need special training to provide sexual therapy. An attitude of interest and an open mind with regard to the patients' sexual problems may give her or him the opportunity for further helpful interventions. Somatic or sexual impairments should not be equated with a general failure of the person. Addressing such problems in detail can avoid unnecessary suffering for patients. A local or systemic application of estrogens seems justifiable from an oncological point of view. Antidepressive therapy should be considered if necessary. For premenopausal patients with an early and highly differentiated carcinoma fertility-preserving surgery may be an option.
Integrating Palliative Care Into the PICU: A Report From the Improving Palliative Care in the ICU Advisory Board*

Objective: This review highlights benefits that patients, families and clinicians can expect to realize when palliative care is intentionally incorporated into the PICU. Data Sources: We searched the MEDLINE database from inception to January 2014 for English-language articles using the terms “palliative care” or “end of life care” or “supportive care” and “pediatric intensive care. ” We also hand-searched reference lists and author files and relevant tools on the Center to Advance Palliative Care website. Study Selection: Two authors (physicians with experience in pediatric intensive care and palliative care) made final selections. Data Extraction: We critically reviewed the existing data and tools to identify strategies for incorporating palliative care into the PICU. Data Synthesis: The Improving Palliative Care in the ICU Advisory Board used data and experience to address key questions relating to: pain and symptom management, enhancing quality of life, communication and decision-making, length of stay, sites of care, and grief and bereavement. Conclusions: Palliative care should begin at the time of a potentially life-limiting diagnosis and continue throughout the disease trajectory, regardless of the expected outcome. Although the PICU is often used for short term postoperative stabilization, PICU clinicians also care for many chronically ill children with complex underlying conditions and others receiving intensive care for prolonged periods. Integrating palliative care delivery into the PICU is rapidly becoming the standard for high quality care of critically ill children. Interdisciplinary ICU staff can take advantage of the growing resources for continuing education in pediatric palliative care principles and interventions.
Perkembangan Obligasi Syari’ah (Sukuk) di Indonesia: Analisis Peluang dan Tantangan

Sukuk is one of the instruments that provides opportunity for Muslim and non-Muslim investors to invest in Indonesia. Thus, the sukuk can be used to build the nation’s economy and create public welfare. However, the opportunity above is not without challenges and obstacles, one of them in a social context, the law of SBSN is very inclusive of market segments. The investors who buy State inaugural Sukuk are dominated by the conventional institutions. One of the strategic initiatives that need to be immediately executed in an effort to optimize the chances of developing sukuk is to socialize in order to provide insight to the general public about the existence of sukuk by involving many stakeholders such as practitioners, analysts, academics, and scholars in the fild of Islamic economics.
Root-end Filling Materials Alter Fibroblast Differentiation

Root-end filling materials are commonly used following endodontic surgical procedures; however, their effect on adjacent soft tissues is poorly understood. We predict that, due to the differences in their chemical composition, these materials will have profoundly different effects on the survival and differentiation of fibroblasts. Many of the root-end filling materials examined were initially cytotoxic to both PDL and gingival fibroblasts in co-culture experiments; however, this was reduced after the materials were washed in either mineral trioxide aggregate (MTA) or hybrid ionomere composite resin (HICR) for 2 wks. Additionally, PDL fibroblasts displayed enhanced proliferation on MTA and survival on amalgam when compared with gingival fibroblasts. MTA preferentially induced alkaline phosphatase expression and activity in both PDL and gingival fibroblasts. In contrast, HICR inhibited alkaline phosphatase expression and activity. In addition, MTA and HICR repressed pleiotrophin in PDL fibroblasts, while HICR repressed periostin in both fibroblasts. Thus, root-end filling materials differentially affect periodontal fibroblast differentiation. Abbreviations: mineral trioxide aggregate (MTA), zinc-oxide eugenol cement (ZOEC), hybrid ionomer composite resin (HICR), reverse-transcriptase polymerase chain-reaction (RT-PCR).
DyeCycle violet used for side population detection is a substrate of P‐glycoprotein

Cancer stem cells (CSC) are increasingly recognized as key target cells for cancer therapy because they are both tumorigenic and chemoresistant and, therefore, can give rise to recurrent disease. Side population (SP) sorting using an ultraviolet (UV) laser is an established method to isolate CSC based on ABC drug transporter‐dependent (e.g., ABCG2) Hoechst 33342 efflux. We here show that Vybrant® DyeCycle™ Violet (DCV), a DNA‐binding fluorophor allowing SP sorting using a non‐UV laser (such as violet laser), is transported via P‐glycoprotein (PgP). Because PgP might be particularly abundant in multidrug‐resistant cancer cells rather than bona fide CSC, investigators using DCV should be aware that this strategy might also detect PgP‐expressing non‐CSC. © 2012 International Society for Advancement of Cytometry
Synthesis of poly(Pro–Hyp–Gly)n by direct polycondensation of (Pro–Hyp–Gly)n, where n = 1, 5, and 10, and stability of the triple‐helical structure

Pro–Hyp–Gly is a characteristic amino acid sequence found in fibrous collagens, and (Pro–Hyp–Gly)10, which has been widely used as a collagen‐model peptide, forms a stable triple‐helical structure. Here, we synthesized polypeptides consisting of the Pro–Hyp–Gly sequence by direct polycondensation of (Pro–Hyp–Gly)n, where n = 1, 5, and 10, using 1‐hydroxybenzotriazole and 1‐ethyl‐3‐(3‐dimethyl‐aminopropyl)‐carbodiimide hydrochloride in both phosphate buffer (pH = 7.4) and dimethylsulfoxide (DMSO) solutions for 48 h at 20°C. The reaction of (Pro–Hyp–Gly)5 and (Pro–Hyp–Gly)10 in DMSO successfully gave polypeptides with molecular weights over 10,000, whereas low molecular weight products were obtained by reaction in phosphate buffer (pH = 7.4). In contrast, Pro–Hyp–Gly at a concentration of 50 mg/mL in phosphate buffer (pH = 7.4) gave polypeptides with molecular weights over 10,000. The Fourier transform infrared (FTIR) and 1H nuclear magnetic resonance (NMR) spectra of poly(Pro–Hyp–Gly)10 revealed that the polymerization of (Pro–Hyp–Gly)10 described in this report had no side reactions. Each polypeptide obtained shows a collagen‐like triple‐helical structure, and the triple‐helical structures of poly(Pro–Hyp–Gly) and poly(Pro–Hyp–Gly)10 were stable up to T = 80°C, which suggests that the high molecular weight promotes stability of the triple‐helical structure, in addition to the high Hyp content. Furthermore, transmission electron microscopy (TEM) observations show that poly(Pro–Hyp–Gly)10 aggregates to form nanofiber‐like structures about 10 nm in width, which suggests that a Pro–Hyp–Gly repeating sequence contains enough information for triple‐helix formation, and for subsequent nanofiber‐like structure formation. © 2005 Wiley Periodicals, Inc. Biopolymers 79: 163–172, 2005
Human pose recognition and tracking using RGB-D camera

In this work, we address the problem of human body pose recognition using RGB-D sensor, to perform user tracking by a mobile robot. User's skeleton joints orientations are used in this approach to compute torso joint orientation, which is necessary to distinguish the four poses: Face, Back, Right of Left. In addition, a face recognition method is used to re-identify user when lost from camera field of view. Experiments were carried out to validate proposed methods, and obtained results show that targeted user following can be achieved successfully.
Application of a model to analyze shoulder biomechanics in adult patients with spinal cord injury when walking with crutches in two different gait patterns.

BACKGROUND Specific biomechanical models have been developed to study gait using crutches. Clinical application of these models is needed in adult spinal cord injury (SCI) population walking with different patterns of gait with crutches to prevent overuse shoulder injuries. OBJECTIVE To apply a biomechanical model in a clinical environment to analyze shoulder in adult SCI patients walking with two different patterns of gait with crutches: two point reciprocal gait (RG) and swing-through gait (SG). METHODS Load cells were fixed to the distal ends and forearm cuffs of a pair of crutches. An active markers system was used for kinematics. Five cycles for each gait pattern were analyzed applying a biomechanical model of the upper limbs. Fifteen subjects with SCI were analyzed. RESULTS The flexo-extension range of motion was significantly greater when using SG (p < 0.01). Similarly, the superior, posterior and medial forces were significantly stronger for SG in all 3 directions. Flexion, adduction and internal rotation torques were also greater in SG (p < 0.01). CONCLUSIONS A biomechanical model was successfully applied to study shoulder biomechanics in adult patients with SCI walking with crutches in two different gait patterns. Greater loads exerted on the shoulder walking with SG were confirmed compared to RG.