Miracle-dz/UniFAR-FTUs huggingface dataset:
The Impact of Age on the Female Reproductive System

Evaluation of the female reproductive system in a general toxicity setting can be challenging for the toxicologic pathologist due to the cyclic nature of the estrous and menstrual cycles, timing of puberty and reproductive senescence, and species differences. Age in particular can have a significant impact on the histologic appearance of the female reproductive system and create challenges when trying to distinguish test article–related findings from normal developmental or senescent changes. This review describes the key physiologic and histologic features of immaturity, the transition through puberty, sexual maturity, and reproductive senescence in the female reproductive system, with an emphasis on practical applications for the toxicologic pathologist, and includes recommendations for distinguishing and documenting these developmental periods. Rats and cynomolgus monkeys are used as examples throughout with correlations to clinically observed end points to better aid the toxicologic pathologist in understanding how age may impact study interpretation.
Revisiting Chaos Theorem to Understand the Nature of miRNAs in Response to Drugs of Abuse

Just like Matryoshka dolls, biological systems follow a hierarchical order that is based on dynamic bidirectional communication among its components. In addition to the convoluted inter‐relationships, the complexity of each component spans several folds. Therefore, it becomes rather challenging to investigate phenotypes resulting from these networks as it requires the integration of reductionistic and holistic approaches. One dynamic system is the transcriptome which comprises a variety of RNA species. Some, like microRNAs, have recently received a lot of attention. miRNAs are very pleiotropic and have been considered as therapeutic and diagnostic candidates in the biomedical fields. In this review, we survey miRNA profiles in response to drugs of abuse (DA) using 118 studies. After providing a summary of miRNAs related to substance use disorders (SUD), general patterns of miRNA signatures are compared among studies for single or multiple drugs of abuse. Then, current challenges and drawbacks in the field are discussed. Finally, we provide support for considering miRNAs as a chaotic system in normal versus disrupted states particularly in SUD and propose an integrative approach for studying and analyzing miRNA data. J. Cell. Physiol. 230: 2857–2868, 2015. © 2015 Wiley Periodicals, Inc.
Identity Based Cryptography for Smart-grid Protection

The smart grid offers secure and intelligent energy distribution systems that delivers energy from suppliers to consumers based on two-way demand and response digital communication technologies to control appliances at consumers homes to save energy and increase reliability. The smart grid improves existing energy distribution systems with digital information management and advanced metering systems. Increased interconnectivity and automation over the grid systems presents new challenges for security and its management. Cryptographic key management involved multiple components of the Smart Grid such as: advanced metering infrastructure, demand response systems, home area networks (HANs), neighborhood area networks that connect the home to utility systems, supervisory control and data acquisition (SCADA) systems that control generation, transmission and distribution systems and plugin electric vehicles. Smart grid requires the design of a mutual authentication scheme and a key management protocol that keep the exchanges safe between the consumers and suppliers. This paper proposes efficient techniques that use the advantages of identity based cryptography to improve the resiliency against an insider or outsider attacker. We present how a hierarchical form of identity based cryptography is particularly in phase with the complex networks requirements such as the Smart grid ones. Key–Words: Cryptography, IBE, IBS, HIBE, Smart-grids
The spatial distribution of cold gas in hierarchical galaxy formation models

The distribution of cold gas in dark matter haloes is driven by key processes in galaxy formation: gas cooling, galaxy mergers, star formation and reheating of gas by supernovae. We compare the predictions of four different galaxy formation models for the spatial distribution of cold gas. We find that satellite galaxies make little contribution to the abundance or clustering strength of cold gas selected samples, and are far less important than they are in optically selected samples. The halo occupation distribution function of present-day central galaxies with cold gas mass >10^9 h^(−1) M_⊙ is peaked around a halo mass of ≈10^(11) h^(−1) M_⊙, a scale that is set by the AGN suppression of gas cooling. The model predictions for the projected correlation function are in good agreement with measurements from the H i Parkes All-Sky Survey. We compare the effective volume of possible surveys with the Square Kilometre Array with those expected for a redshift survey in the near-infrared. Future redshift surveys using neutral hydrogen emission will make possible measurements of the baryonic acoustic oscillations that are competitive with the most ambitious spectroscopic surveys planned in the near-infrared.
Photoplethysmogram (PPG) signal analysis and wavelet de-noising

The use of optical sensors is nowadays very common in the area of non-invasive diagnosis. This is mainly because of their salient features like, simple construction, low cost, easy to use, relatively inexpensive nature etc. Photoplethysmography (PPG) sensor is one among the wide variety of optical sensors available, and is used to measure the blood volumetric changes occurring in the various parts of the body. PPG signal contains rich source of information related to cardio-pulmonary system. But the major problem associated with the signal is the motion artifacts, causing corruption in the original PPG signal. The aim of this study is to know in deep about the different parameters of PPG signal. Peak and transition points of the pulse signal are determined as a part of pulse wave analysis. Wavelet transform is now commonly used in a wide variety of signal processing applications. In this work wavelet de-noising is used for removing AWGN from the PPG signal. Various mother wavelets are studied and the performance of them are evaluated based on the cross correlation with the original signal.
Di-Nucleotide Repeat Polymorphisms of the Insulin-Like Growth Factor-1 Gene and Their Association with IGF-1, Insulin-Like Growth Factor-Binding Protein-1 and Birth Size in a Sri-Lankan Cohort

Background: Insulin-like growth factor (IGF)-I is implicated in fetal growth. Ethnic variations of IGF-1 have also been suggested. Di-nucleotide repeat polymorphisms of the IGF-1 gene or their association with IGF-1 levels and birth size have not been studied in Sri Lankans. Objectives: To describe IGF-1 di-nucleotide repeat polymorphisms and their association with IGF-1 and IGF-binding protein (IGFBP)-1 levels and birth size in a cohort of Sri Lankans. Methods: A cross-sectional study on 200 mother-newborn pairs was carried out. Maternal and cord blood levels of IGF-1 and IGFBP-1 were measured by enzyme-linked immunosorbent assay. Three di-nucleotide repeat polymorphisms of the IGF-1 gene [cytosine-adenine (CA) repeats in the promoter and 3′ regions and intron 2 cytosine-thymine (CT) repeat] were studied using PCR amplification and fragment analysis. Results:Cord blood IGFBP-1 levels correlated negatively with birth weight (p < 0.01) and crown-heel length (p < 0.05). Wild-type alleles of the CA repeat polymorphisms differed from those reported in other populations. Newborn and maternal intron 2 CT repeat polymorphism showed a significant effect on birth weight (p < 0.01 and p < 0.001, respectively), crown-heel length (p < 0.01) and head circumference (p < 0.01 and p < 0.05, respectively). Promoter region CA repeat polymorphism and intron 2 CT repeat polymorphism in the newborns were significantly (p < 0.05) associated with cord blood IGF-1 levels. Almost all these effects were limited to primiparous pregnancies. Conclusions: In Sri Lankans intron 2 CT repeat polymorphism of the IGF-1 gene appears to be a significant contributor to IGF-1 levels and birth size in primiparous pregnancies.
Acarbose for the prevention of diabetes, hypertension, and cardiovascular disease in subjects with impaired glucose tolerance: the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) Trial.

OBJECTIVE To evaluate, in subjects with impaired glucose tolerance (IGT), the effect of acarbose on the incidence of diabetes, hypertension, and cardiovascular disease. METHODS The Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) Trial was an international, multicenter, double-blind, placebo-controlled, randomized investigation, undertaken in 9 participating countries from December 1995 through August 2001. Patients were randomly assigned to receive placebo (N = 715) or acarbose, 100 mg three times a day (N = 714), and underwent follow-up for a mean of 3.3 years. Sixty-one subjects (4%) were excluded from the study because they did not have IGT or had no postrandomization data; thus, 1,368 subjects remained for intent-to-treat analysis. The outcome measures were the development of diabetes based on a single oral glucose tolerance test, the development of hypertension ((3) 140/90 mm Hg), and the development of major cardiovascular events, including coronary heart disease, cardiovascular death, stroke, and peripheral vascular disease. RESULTS Two hundred eleven subjects in the acarbose-treated group and 130 in the placebo group discontinued treatment prematurely; however, they underwent follow-up for assessment of end points. Acarbose treatment resulted in a 25% relative risk reduction in the development of type 2 diabetes (hazards ratio [HR], 0.75; 95% confidence interval [CI], 0.63 to 0.90; P = 0.0015), in a 34% risk reduction in the development of new cases of hypertension (HR, 0.66; 95% CI, 0.49 to 0.89; P = 0.0059), and in a 49% risk reduction in the development of cardiovascular events (HR, 0.51; 95% CI, 0.28 to 0.95; P = 0.03). A post hoc cost-effectiveness analysis done from the Swedish perspective showed that acarbose treatment was likely to be cost-effective in the management of subjects with IGT. CONCLUSION The STOP-NIDDM Trial demonstrated that, in subjects with IGT, acarbose treatment was effective in reducing the risk of type 2 diabetes. It also suggested that it was associated with a reduction in hypertension and cardiovascular disease.
Clinical Ethics Consultants: Advocates for Both Patients and Clinicians

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Sonic hedgehog signaling coordinates the proliferation and differentiation of neural stem/progenitor cells by regulating cell cycle kinetics during development of the neocortex

Sonic hedgehog (Shh) acts as a morphogen in normal development of various vertebrate tissues and organs. Shh signaling is essential for patterning and cell‐fate specification, particularly in the central nervous system. Shh signaling plays different roles depending on its concentration, area, and timing of exposure. During the development of the neocortex, a low level of Shh is expressed in the neural stem/progenitor cells as well as in mature neurons in the dorsal telencephalon. Shh signaling in neocortex development has been shown to regulate cell cycle kinetics of radial glial cells and intermediate progenitor cells, thereby maintaining the proliferation, survival and differentiation of neurons in the neocortex. During the development of the telencephalon, endogenous Shh signaling is involved in the transition of slow‐cycling neural stem cells to fast‐cycling neural progenitor cells. It seems that high‐level Shh signaling in the ventral telencephalon is essential for ventral specification, while low‐level Shh signaling in the dorsal telencephalon plays important roles in the fine‐tuning of cell cycle kinetics. The Shh levels and multiple functions of Shh signaling are important for proper corticogenesis in the developing brain. The present paper discusses the roles of Shh signaling in the proliferation and differentiation of neural stem/progenitor cells.
A complete generalized solution to the inverse kinematics of robots

The kinematic transformation between task space and joint configuration coordinates is nonlinear and configuration dependent. A solution to the inverse kinematics is a vector of joint configuration coordinates that corresponds to a set of task space coordinates. For a class of robots closed form solutions always exist, but constraints on joint displacements cannot be systematically incorporated in the process of obtaining a solution. An iterative solution is presented that is suitable for any class of robots having rotary or prismatic joints, with any arbitrary number of degrees of freedom, including both standard and kinematically redundant robots. The solution can be obtained subject to specified constraints and based on certain performance criteria. The solution is based on a new rapidly convergent constrained nonlinear optimization algorithm which uses a modified Newton-Raphson technique for solving a system nonlinear equations. The algorithm is illustrated using as an example a kinematically redundant robot.
Manganese superoxide dismutase protects mitochondrial complex I against adriamycin-induced cardiomyopathy in transgenic mice.

Adriamycin (ADR) is a potent anticancer drug that causes severe cardiomyopathy. We have previously demonstrated that ADR-induced ultrastructural mitochondrial injury in the heart was attenuated in manganese superoxide dismutase (MnSOD) transgenic mice. To further investigate the biochemical mechanisms by which MnSOD protected mitochondria against ADR-induced damage, cardiac mitochondrial function and activities were evaluated. The results showed that ADR caused significant decrease in state 3 respiration and respiratory control ratio using both complex I and II substrates in nontransgenic mice. In transgenic mice, state 3 respiration for complex I substrates remained unaffected by ADR, but was reduced for complex II substrate. Complex I activity was significantly decreased in nontransgenic, but not in transgenic mice after ADR treatment, suggesting that mitochondrial complex I is sensitive to inactivation by superoxide radicals. The activities of complex II and mitochondrial creatine kinase were decreased by ADR in both nontransgenic and transgenic mice. These results support our previous observations on the protective role of MnSOD on the ultrastructural damage of the heart after ADR treatment and extend the understanding of its mechanisms in mitochondria.
Infection Process of the Hepatitis B Virus Depends on the Presence of a Defined Sequence in the Pre-S1 Domain

ABSTRACT During the life cycle of hepatitis B virus (HBV), the large envelope protein (L) plays a pivotal role. Indeed, this polypeptide is essential for viral assembly and probably for the infection process. By performing mutagenesis experiments, we have previously excluded a putative involvement of the pre-S2 domain of the L protein in viral infectivity. In the present study, we have evaluated the role of the pre-S1 region in HBV infection. For this purpose, 21 mutants of the L protein were created. The entire pre-S1 domain was covered by contiguous deletions of 5 amino acids. First, after transfection into HepG2 cells, the efficient expression of both glycosylated and unglycosylated L mutant proteins was verified. The secretion rate of envelope proteins was modified positively or negatively by deletions, indicating that the pre-S1 domain contains several regulating sequences able to influence the surface protein secretion. The ability of mutant proteins to support the production of virions was then studied. Only the four C-terminal deletions, covering the 17 amino acids suspected to interact with the cytoplasmic nucleocapsids, inhibited virion release. Finally, the presence of the modified pre-S1 domain at the external side of all secreted virions was confirmed, and their infectivity was assayed on normal human hepatocytes in primary culture. Only a short sequence including amino acids 78 to 87 tolerates internal deletions without affecting viral infectivity. These results confirm the involvement of the L protein in the infection step and demonstrate that the sequence between amino acids 3 and 77 is involved in this process.
The Use of Intravenous Atropine After a Saline Infusion in the Prevention of Spinal Anesthesia-Induced Hypotension in Elderly Patients

We investigated the efficacy of IV atropine for preventing spinal anesthesia-induced hypotension in elderly patients. Seventy-five patients undergoing transurethral prostate or bladder surgery were randomized to receive either placebo (n = 25), atropine 5 &mgr;g/kg (small-dose atropine, n = 25) or atropine 10 &mgr;g/kg (large-dose atropine, n = 25) after the induction of spinal anesthesia. All the patients received an IV infusion of 10 mL/kg 0 . 9% normal saline over 10 min before the induction of anesthesia. The systolic blood pressure decreased in all three groups after spinal anesthesia. There was a significant increase in the mean heart rate in both atropine groups as compared to the placebo group (placebo group: 78 bpm, 95% confidence interval [CI]: 76.6–78.5; small-dose atropine group: 86 bpm, 95% CI 83.9–88.8; large-dose atropine group: 97 bpm, 95% CI 94.5–100.3;P = 0.001). There was a significant decrease in the incidence of hypotension in patients who received atropine (placebo group: 76%, small-dose atropine group: 52%, large-dose atropine group: 40%, P = 0.03). The mean dose of ephedrine required was significantly decreased in the atropine groups (placebo group: 12.2 mg [sd= 10.5], small-dose atropine group: 7.4 mg [sd= 10.0], large-dose atropine group: 5.4 mg [sd= 8.7 mg], P = 0.048). The total amount of IV fluid and number of patients requiring metaraminol in addition to 30 mg of ephedrine were not significantly different among the three groups. Significant side effects, such as confusion, ST segment changes or angina were not detected in any of the patients. We conclude that IV atropine may be a useful supplement to the existing methods in preventing hypotension induced by spinal anesthesia. Implications IV atropine increases heart rate in a dose-dependent manner in elderly patients undergoing spinal anesthesia. It reduces the incidence of hypotension and the dose of ephedrine required. Small-dose atropine may be a useful supplement in preventing spinal anesthesia-induced hypotension in elderly patients.
A Study of the Mechanism of Inhibition of Fibrinolysis by Activated Thrombin-activable Fibrinolysis Inhibitor*

TAFI (thrombin-activable fibrinolysis inhibitor) is a recently described plasma zymogen that, when exposed to the thrombin-thrombomodulin complex, is converted by proteolysis at Arg92 to a basic carboxypeptidase that inhibits fibrinolysis (TAFIa). The studies described here were undertaken to elucidate the molecular basis for the inhibition of fibrinolysis. When TAFIa is included in a clot undergoing fibrinolysis induced by tissue plasminogen activator and plasminogen, the time to achieve lysis is prolonged, and free arginine and lysine are released over time. In addition, TAFIa prevents a 2.5-fold increase in the rate constant for plasminogen activation which occurs when fibrin is modified by plasmin in the early course of fibrin degradation. The effect is specific for the Glu- form of plasminogen. TAFIa prevents or at least attenuates positive feedback expressed through Lys-plasminogen formation during the process of fibrinolysis initiated by tissue plasminogen activator and plasminogen. TAFIa also inhibits plasmin activity in a clot and prolongs fibrinolysis initiated with plasmin. We conclude that TAFIa suppresses fibrinolysis by removing COOH-terminal lysine and arginine residues from fibrin, thereby reducing its cofactor functions in both plasminogen activation and the positive feedback conversion of Glu-plasminogen to Lys-plasminogen. At relatively elevated concentrations, it also directly inhibits plasmin.
Postnatal histochemical fiber type differentiation in normal and hypothyroid rat soleus muscle

We have analyzed the effect of 6‐propylthiouracil‐induced hypothyroidism on neonatal fiber type differentiation in the rat soleus muscle. Body weight, total soleus fiber number, histochemical fiber type differentiation, and morphometry were determined at 7, 14, 21, and 28 days. Neonatal hypothyroidism (1) inhibits the apparent ∼50% increase in soleus muscle fiber number occurring at 14–21 days, (2) blocks the transformation of type 2C to type 2A fibers occurring between 14 and 21 days, (3) preferentially inhibits the increase in type 2 fiber diameter, and (4) retards the development of sarcoplasmic reticulum. Immature muscle fibers reveal type 1 and type 2 fiber myosin adenosine triphosphatase (ATPase) differentiation at pH 10.3, which drops to pH 9.4 with maturation. No myosin ATPase differentiation was found at pH 9.4 in the hypothyroid animals, even at 28 days.
The Use of Antimicrobial Agents after Diagnosis of Viral Respiratory Tract Infections in Hospitalized Adults: Antibiotics or Anxiolytics?

Objective. Because extensive antibiotic use by inpatients has been associated with the development of multidrug-resistant organisms, we aimed to determine which variables were associated with the use of antibiotics after viral respiratory tract infection diagnosis among adult patients admitted to the hospital with respiratory symptoms. Methods. A retrospective cohort study was conducted at 2 affiliated urban hospitals in Pennsylvania. We identified all adult patients admitted to the hospital during the period from November 1, 2005, through August 1, 2007, with a viral assay positive for influenza A or B, parainfluenza, adenovirus, or respiratory syncytial virus. Among these patients, we identified those who received antibiotics after the diagnosis of viral RTL Data on demographics; comorbidities; and physical examination, laboratory, and radiographic findings were ascertained to identify risk factors for antimicrobial use among these patients. Results. A total of 196 hospitalized patients with positive viral assay results were included; 125 of 131 patients administered antibiotics continued to receive them after viral RTI diagnosis. Among 52 patients with an abnormal chest radiograph, 46 continued antibiotic therapy. An abnormal chest radiograph was independently associated with continued antibiotic use (adjusted odds ratio, 4.28 [95% confidence interval, 1.71-10.77]; P = .002). However, the majority of patients (79 of 125 [63%]) who continued antibiotic therapy had normal chest imaging findings. Eight patients (6%) who continued antibiotic therapy and no patients who stopped developed C. difficile infection (95% CI, 1.5-00; p = .05), but there was no significant difference in length of stay or mortality. Conclusions. Antibiotics are commonly used to treat hospitalized patients with known acute viral RTIs. Continued use is strongly associated with abnormal radiograph findings at admission. However, the reasons for continuation of antibiotics in the treatment of the majority of patients with normal radiographs are unclear and may represent inappropriate use.