Miracle-dz/UniFAR-FTUs huggingface dataset:
The Na+/H+ exchanger and pH regulation in the heart

The mammalian Na+/H+ exchanger isoform 1 (NHE1) is an integral membrane protein ubiquitously expressed in mammalian cells. It is made up of two domains: a 500‐amino acid membrane domain that is responsible for transport and removes protons, and a regulatory intracellular cytosolic domain made up of 315 amino acids. NHE1 is the major isoform found in the myocardium where it plays an important role in the regulation of intracellular pH by exchanging one intracellular proton for one extracellular sodium. Although NHE1 normally fulfills this important physiological role, aberrant regulation and overactivation of NHE1 contribute to heart disease, including acute ischemia reperfusion damage and cardiac hypertrophy. This review summarizes past and current knowledge of the role and regulation of NHE1 in the myocardium. © 2014 IUBMB Life, 66(10):679–685, 2014
Regulation of Vacuolar pH and Its Modulation by Some Microbial Species

SUMMARY To survive within the host, pathogens such as Mycobacterium tuberculosis and Helicobacter pylori need to evade the immune response and find a protected niche where they are not exposed to microbicidal effectors. The pH of the microenvironment surrounding the pathogen plays a critical role in dictating the organism's fate. Specifically, the acidic pH of the endocytic organelles and phagosomes not only can affect bacterial growth directly but also promotes a variety of host microbicidal responses. The development of mechanisms to avoid or resist the acidic environment generated by host cells is therefore crucial to the survival of many pathogens. Here we review the processes that underlie the generation of organellar acidification and discuss strategies employed by pathogens to circumvent it, using M. tuberculosis and H. pylori as examples.
A HYBRID METHOD FOR PREDICTING STRONG GROUND MOTIONS AT BROAD-FREQUENCIES NEAR M 8 EARTHQAUKES IN SUBDUCTION ZONES

The near-field strong motions during the 1985 Michoacan earthquake (M8) are successfully simulated at broadband frequencies. For the simulation at low frequencies (0 to 1 Hz), the modified k-square model (Hisada, 1999) is used by considering the k-squared (wavenumbersquared) distributions of slip (Mendoza and Hartzell, 1989) and the incoherent rupture time. For modeling the slip velocity, the Kostrov-type function with fmax of 10 Hz is adopted. The simulated results reproduced well the observed long-period ground motions, including the rampfunction-like displacements with the permanent offsets, and the near-field directivity pulses in the velocities. On the other hand, for the simulation at high frequencies (0.5 to 10 Hz), the KamaeIrikura-Boore method (Kamae, et al, 1998) is used. The results reproduced well the observed accelerations including the directivity effects. Accordingly, the simulated Fourier spectra agree well with those observed at broadband frequencies (0 to 10 Hz). The source parameters of an M8 earthquake in a subduction zone can be easily applied to strong motion predictions in other areas using appropriate Green’s functions.
The Value of the Voting Right: A Study of the Milan Stock Exchange Experience

I study the large premium (82 percent) attributed to voting shares on the Milan Stock Exchange. The premium varies according to the ownership structure and the concentration of the voting rights, and it can be rationalized in the presence of enormous private benefits of control. A case study seems to indicate that in Italy private benefits of control can easily be worth more than 60 percent of the value of nonvoting equity. A tentative explanation for these findings is provided. Article published by Oxford University Press on behalf of the Society for Financial Studies in its journal, The Review of Financial Studies.
Methodology For Validating Software Metrics

A comprehensive metrics validation methodology is proposed that has six validity criteria, which support the quality functions assessment, control, and prediction, where quality functions are activities conducted by software organizations for the purpose of achieving project quality goals. Six criteria are defined and illustrated: association, consistency, discriminative power, tracking, predictability, and repeatability. The author shows that nonparametric statistical methods such as contingency tables play an important role in evaluating metrics against the validity criteria. Examples emphasizing the discriminative power validity criterion are presented. A metrics validation process is defined that integrates quality factors, metrics, and quality functions. >
Sensor/channel redundancy for sensor-to-actuator networked control systems

Nowadays, reliability is becoming more and more important in the design of Networked Control Systems (NCSs). Fault-tolerance is often used to increase system reliability. In this paper, Triple Modular Redundancy (TMR) and Parallel Redundancy Protocol (PRP) are both applied to a Sensor-to-Actuator architecture with 16 sensors, 4 Actuators and one Supervisor. Two of the 16 sensors as well as two of the 4 actuators are wireless while the rest of the nodes are wired. It is first shown that this NCS succeeds in meeting all control system requirements (zero packet loss and bounded end-to-end delay). Reliability models are then developed to help designers choose the appropriate mix of fault-tolerant techniques in order to maximize lifetime while at the same time minimizing the extra cost due to the added redundancy.
Depletion of TSG101 forms a mammalian `Class E' compartment: a multicisternal early endosome with multiple sorting defects

The early endosome comprises morphologically distinct regions specialised in sorting cargo receptors. A central question is whether receptors move through a predetermined structural pathway, or whether cargo selection contributes to the generation of endosome morphology and membrane flux. Here, we show that depletion of tumour susceptibility gene 101 impairs the selection of epidermal growth factor receptor away from recycling receptors within the limiting membrane of the early endosome. Consequently, epidermal growth factor receptor sorting to internal vesicles of the multivesicular body and cargo recycling to the cell surface or Golgi complex are inhibited. These defects are accompanied by disruption of bulk flow transport to the lysosome and profound structural rearrangement of the early endosome. The pattern of tubular and vacuolar domains is replaced by enlarged vacuoles, many of which are folded into multicisternal structures resembling the `Class E' compartments that define several Saccharomyces cerevisiae vacuolar protein sorting mutants. The cisternae are interleaved by a fine matrix but lack other surface elaborations, most notably clathrin.
Dynamic Harmonic Domain Modeling of Transients in Three-Phase Transmission Lines

This paper presents a traveling wave based transmission line model which includes harmonics in transient state. The line model is interfaced with a nonlinear load and both are simulated through the dynamic harmonic domain technique. This technique permits the user to follow step-by-step the harmonics of the propagating waveforms during transient conditions. An illustrative example involving a transmission line network with nonlinear loads is presented and the proposed model is compared with its time domain counterpart.
Periodic filters for performance enhancement of millimeter-wave microstrip antenna arrays

In this paper, periodic filters have been employed to enhance the performance of microstrip antenna arrays in automotive radar sensors. An isolation of more than 45 dB has been measured between transmit and receive antenna arrays formed on the same substrate with a separation distance of only 40 mm between them. The isolation enhancement obtained is more than 15 dB. Also a gain enhancement of about 2 dB has been observed due to employment of these periodic filters. Since these periodic filters consist of circular openings etched on the ground plane of the antenna, there is no additional cost or fabrication effort associated with this technique. These openings act as periodic stop band filters to suppress surface waves propagating between the antenna arrays. Measured and computed isolation values agree well.
Zur Eigengesetzlichkeit natürlicher Benutzeroberflächen

Seit mehr als 20 Jahren werden immer wieder die gleichen Argumente fur und gegen naturlichsprachliche Benutzeroberflachen (BNO) vorgetragen, die sich auf Teilaspekte beziehen und an vordergrundige Plausibilitaten appellieren. Sich erneut damit zu beschaftigen, scheint entbehrlich. Mehr Gewicht haben zwei Argumentationsrichtungen, die sich in den letzten Jahren immer deutlicher artikulierten, und m.E. entscheidend sind fur jede Beschaftigung mit naturlichsprachlichen BNO auser halb der engen Grenzen rein linguistisch orientierter Interessen: 1. Ausgangsthese: Die "Naturlichkeit" einer naturlichsprachlichen BNO liegt vor allem darin, das der Benutzer diesen Kommunikationsmodus bereits beherrscht. Der Benutzer soll sich bei der Mensch-Computer-Interaktion (MCI) genauso verhalten wie beim zwischenmenschlichen Dialog, wodurch neues Lernen entfallt. Diese postulierte Moglichkeit einer Gleichsetzung wird von einigen Autoren prinzipiell in Frage gestellt ([Winograd & Flores 1986], [Herrmann 1986], [Krambrich 1988]: MCI und zwischenmenschlicher Dialog basieren auf fundamental verschiedenen Voraussetzungen; eine die Vorteile zwischenmenschlicher Kommunikation erhaltende Ubertragung in die MCI scheint prinzipiell nicht moglich. Graphischen BNO ist der Vorzug zu geben. Abgeschwachtere Formen dieser Denkrichtung stellen naturlichsprachliche BNO nicht prinzipiell in Frage, sehen aber die Differenzen zum zwischenmenschlichen Dialog als entscheidend an (Eigengesetzlichkeiten, Subsetproblem, Computertalk, Mischformen).
Representation Techniques For Distributed Knowledge Models

Throughout geography, recent attention has been paid to the problems of formalizing knowledge structures. The impetus for this focus comes from many sources, not least the need to manage large information repositories and to extract understanding from complex datasets. There is a parallel need, however, to understand not just how knowledge is manifested within data, but how it is constructed from data, and from the cooperative investigation of researchers distributed across space and time. Achieving this understanding requires techniques that support knowledge sharing and the capture of that knowledge’s evolution. The research discussed here concerns the development of a model for representing geographic concepts as cooperatively constructed, experientially grounded, and semantically interoperable resources. This model is implemented in a Web environment for visual knowledge construction.
Packet splitting and adaptive modulation based on CSI of time domain for decode‐and‐forward cooperative OFDM systems in different channel model

Cooperative communications obtain the transmission and channel diversity gains by using the relay node. However, since cooperative communications transmit the redundancy signal to obtain the transmission diversity gain, the transmission rate is degraded. Moreover, since cooperative communications add the interference in the relay node, the diversity gain is also degraded. The packet splitting has been proposed based on the channel state information of the time domain to obtain the good system performance without the redundancy signal. Moreover, the adaptive modulation has been proposed to improve the transmission rate. In this paper, we propose the combination method with the packet splitting and the adaptive modulation based on the channel state information of the time domain to improve the bit error rate and throughput performances for decode‐and‐forward cooperative orthogonal frequency division multiplexing systems in the different channel model. From the computer simulation results, we determine the optimum weight and threshold for the proposed method. Moreover, the proposed method shows the good bit error rate and throughput performances.
CYTOCHROME P-450 3 A 4 : Regulation and Role in Drug Metabolism

Cytochrome P-450 (P-450) 3A4 is the most abundant P-450 expressed in human liver and small intestine. P-450 3A4 contributes to the metabolism of approximately half the drugs in use today, and variations in its catalytic activity are important in issues of bioavailability and drug-drug interactions. The gene is known to be inducible by barbiturates, glucocorticoids, and rifampicin in humans and in isolated hepatocytes, although the mechanism remains unclear. The 5′-untranslated region includes putative basal transcription element, hepatocyte nuclear factor, p53, AP-3, glucocorticoid regulatory element, pregnane X receptor, and estrogen receptor element sequences. Recently, the GRE element has been shown to act in a classic glucocorticoid response. Several issues remain to be resolved regarding the catalytic activity of the P-450 3A4 protein, including rate-limiting steps and the need for cytochrome b5, divalent cations, and acidic phospholipid systems for optimal activity. Another issue involves the basis of the homotropic and heterotropic cooperativity seen with the enzyme. The in vivo significance of these findings remains to be further established. In addition to more basic studies on P-450 3A4, several areas of practical interest to the pharmaceutical industry require development.
Splenic marginal metallophilic macrophages and marginal zone macrophages are the major interferon-alpha/beta producers in mice upon intravenous challenge with herpes simplex virus.

The interferon (IFN)-alpha/beta-producing cells (IPCs) are localized predominantly in the spleen, in particular in the marginal zones (MZ), in C57BL/6 mice injected intravenously (i.v.) with UV-inactivated herpes simplex virus (HSV). We defined the phenotype of these murine IPCs using simultaneous immunohistochemical labelling of intracellular IFN-alpha/beta and various surface antigens. We found that the IPCs in the MZ are not dendritic cells because they did not express major histocompatibility complex (MHC) class II and CD11c molecules. Furthermore, they did not express antigenic markers typical for T cells, B cells or red pulp macrophages. In contrast, the majority of IPCs were stained by the anti-sialoadhesin monoclonal antibody (MoAb) SER-4, which is specific for marginal metallophilic macrophages. In addition, a minor part of the IPCs with a more outward localization in the MZ were stained by a MoAb specific for MZ macrophages. We conclude that the massive IFN-alpha/beta production in the MZ of the spleen upon in vivo stimulation by HSV is mainly exerted by marginal metallophilic macrophages and to a lesser extent by MZ macrophages.
Trends in the incidence of cancers among HIV-infected persons and the impact of antiretroviral therapy: a 20-year cohort study

Objective:To describe trends in incidence rates of AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs) during the HIV epidemic and to evaluate predictors, including the impact of antiretroviral therapy, of cancer development. Design:Retrospective analysis of a multicenter, prospective natural history study including 4498 HIV-infected US military beneficiaries with 33 486 person-years of follow-up. Methods:Predictors evaluated included demographics, clinical data, time-updated CD4 cell counts, HIV viral loads, and antiretroviral history. Time periods were classified as early pre (1984–1990), late pre (1991–1995), early post (1996–2000), and late post (2001–2006) HAART eras. Cox proportional hazard models were used to evaluate the association of specific factors with cancer. Results:Ten percent of HIV-infected persons developed cancer. ADC rates increased between the early and late pre-HAART eras (7.6 and 14.2 cases per 1000 person-years) and have since declined from 5.4 to 2.7 in the early and late HAART eras, respectively (P < 0.001). Rates of NADCs have risen over the four periods (2.9, 2.8, 4.2, 6.7, P = 0.0004). During the late HAART era, 71% of cancers were NADCs. Predictors for ADCs included low CD4 cell count, noncancer AIDS diagnosis, and lack of HAART. NADCs were predicted by increasing age and white race (due to skin cancers). Conclusion:Although the rate of ADCs continues to fall, the rate of NADCs is rising and now accounts for the majority of cancers in HIV-infected persons. The development of NADCs is associated with increasing age among HIV patients. HAART use is protective for ADCs, but did not significantly impact NADCs.
Implementation of a “Lisp comprehension” macro

This paper describes a set of Lisp macros that enable the use of "list comprehensions" which are a very powerful notation that provides a very compact expression of common list operations see [2] for a full discussion. List comprehensions have been introduced by David Turner in KRC, where they were called ZF-expressions [7]. They have since been introduced in several other pure functional languages like SASL [8], Miranda1 [5] and Haskell [3].
Innate Immunity-Based Immunotherapy of Cancer

The immune system protects against invading pathogens and transformed cells, including cancer. Mammalian immune system is divided into two major categories, i.e., innate and adaptive immunity. Innate immunity consists of cellular and biochemical defense mechanisms that respond in the early phase after harmful events, such as encounters with microbes or transformed cells. The cellular components of innate immunity include dendritic cells (DCs), macrophages and monocytes, polynuclear cells (e.g. neutrophils and mast cells), natural killer (NK) cells, ┛├ T cells and natural killer T (NKT) cells. Adaptive immunity consists of T and B lymphocytes and their humoral mediators, including cytokines and antibodies, and achieves excellent antigen specificity by somatic rearrangement of the antigen receptor genes of each lymphocyte lineage; T cell receptor for T lymphocytes and immunoglobulin for B lymphocytes, respectively. Furthermore, another excellent characteristic of adaptive immunity is a “memory system” to maintain antigenspecific lymphocytes in a functionally quiescent or slowly cycling state for many years. The memory system enables host organisms to respond to the second and subsequent exposure to the same or related antigens in a more rapid and effective manner.
MicroRNAs and Cancer: A meeting summary of the eponymous Keystone Conference

This report summarizes the information presented at the 2009 Keystone Conference on MicroRNAs and Cancer, held in Keystone, Colorado, USA, June 10th to 15th 2009. Soon after microRNAs (miRNAs) emerged as an abundant new class of non-coding RNAs (ncRNAs), evidence started to mount supporting important roles for these regulatory RNAs in human health and disease. Mis-regulation of specific miRNA pathways has been linked to diverse cancers. The recent Keystone meeting highlighted progress in understanding the role of miRNAs in normal development and oncogenesis. Recurring themes included the complexities associated with miRNA biogenesis, target recognition, elucidation of genetic networks where miRNAs play pivotal roles often within feedback loops, and the promise of small RNAs as diagnostics and therapeutics in combating cancer.
Abrupt Decline in Kidney Function Before Initiating Hemodialysis and All-Cause Mortality: The Chronic Renal Insufficiency Cohort (CRIC) Study.

BACKGROUND It is not clear whether the pattern of kidney function decline in patients with chronic kidney disease (CKD) may relate to outcomes after reaching end-stage renal disease (ESRD). We hypothesize that an abrupt decline in kidney function prior to ESRD predicts early death after initiating maintenance hemodialysis therapy. STUDY DESIGN Prospective cohort study. SETTING & PARTICIPANTS The Chronic Renal Insufficiency Cohort (CRIC) Study enrolled men and women with mild to moderate CKD. For this study, we studied 661 individuals who developed chronic kidney failure that required hemodialysis therapy initiation. PREDICTORS The primary predictor was the presence of an abrupt decline in kidney function prior to ESRD. We incorporated annual estimated glomerular filtration rates (eGFRs) into a mixed-effects model to estimate patient-specific eGFRs at 3 months prior to initiation of hemodialysis therapy. Abrupt decline was defined as having an extrapolated eGFR≥30mL/min/1.73m(2) at that time point. OUTCOMES All-cause mortality within 1 year after initiating hemodialysis therapy. MEASUREMENTS Multivariable Cox proportional hazards. RESULTS Among 661 patients with CKD initiating hemodialysis therapy, 56 (8.5%) had an abrupt predialysis decline in kidney function and 69 died within 1 year after initiating hemodialysis therapy. After adjustment for demographics, cardiovascular disease, diabetes, and cancer, abrupt decline in kidney function was associated with a 3-fold higher risk for death within the first year of ESRD (adjusted HR, 3.09; 95% CI, 1.65-5.76). LIMITATIONS Relatively small number of outcomes; infrequent (yearly) eGFR determinations; lack of more granular clinical data. CONCLUSIONS Abrupt decline in kidney function prior to ESRD occurred in a significant minority of incident hemodialysis patients and predicted early death in ESRD.
The National Marrow Donor Program in 2006: constants and challenges

ob Graves was a giant of a man—both physically and in his catalytic role in the creation of the National Marrow Donor Program (NMDP). He worked tirelessly to create the NMDP, to secure its first federal dollars, and to lead the organization during its formative years. He also befriended many who were searching for unrelated marrow donors for loved ones in the pre-1990s wilderness that existed before the NMDP was fully operational. The history of the origins of the NMDP is chronicled in an article by McCullough and colleagues in this issue of TRANSFUSION. If Bob Graves were alive to see today’s NMDP, he would be understandably proud of its achievements in the 20 years since its legal creation. He would be especially proud of the way different scientific, medical, and public health constituencies involved in unrelated marrow recruitment, transplantation, and research have learned to work together for the public good. He also would be awed by the sheer numbers of transplants (marrow, peripheral blood progenitor cells [PBPC], and cord blood) facilitated annually by the NMDP, approaching 3000. Looking back over the past 15 years of the NMDP’s history, a number of things—both good and ill—have remained constant. Some of these constants have been keys to the organization’s success while others are refractory issues that spotlight the need for new approaches to the challenges of building on that success.
Factors associated with seizure freedom in the surgical resection of glioneuronal tumors

Purpose: Gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumors (DNETs) are low‐grade brain tumors of glioneuronal origin that commonly present with seizures. Achieving seizure control in patients with glioneuronal tumors remains underappreciated, as tumor‐related epilepsy significantly affects patients’ quality‐of‐life.