Miracle-dz/UniFAR-FTUs huggingface dataset:
Poly(ADP-ribose) polymerase-1 inhibition reverses temozolomide resistance in a DNA mismatch repair–deficient malignant glioma xenograft

Temozolomide is a DNA-methylating agent used in the treatment of malignant gliomas. In this study, we have examined if inhibition of poly(ADP-ribose) polymerase (PARP) could increase the cytotoxicity of temozolomide, particularly in cells deficient in DNA mismatch repair. Athymic mice, transplanted with mismatch repair–proficient [D-245 MG] or deficient [D-245 MG (PR)] xenografts, were treated with a combination of temozolomide and the PARP inhibitor, INO-1001. For the tumors deficient in mismatch repair, the most effective dose of INO-1001 was found to be 150 mg/kg, given i.p. thrice at 4-hour intervals with the first injection in combination with 262.5 mg/kg temozolomide (0.75 LD10). This dose of temozolomide by itself induced no partial regressions and a 4-day growth delay. In two separate experiments, the combination therapy increased the growth delay by 21.6 and 9.7 days with partial regressions observed in four of eight and three of nine mice, respectively. The addition of INO-1001 had a more modest, yet statistically significant, increase in tumor growth delay in the mismatch repair–proficient xenografts. In these experiments, mice were treated with a lower amount of temozolomide (88 mg/kg), which resulted in growth delays of 43.1 and 39.2 days. When the temozolomide treatment was in combination with 200 mg/kg INO-1001, there was an increase in growth delay to 48.9 and 45.7 days, respectively. These results suggest that inhibition of PARP may increase the efficacy of temozolomide in the treatment of malignant gliomas, particularly in tumors deficient in DNA mismatch repair.
A Cytoplasmic Dynein Heavy Chain Is Required for Oscillatory Nuclear Movement of Meiotic Prophase and Efficient Meiotic Recombination in Fission Yeast

Meiotic recombination requires pairing of homologous chromosomes, the mechanisms of which remain largely unknown. When pairing occurs during meiotic prophase in fission yeast, the nucleus oscillates between the cell poles driven by astral microtubules. During these oscillations, the telomeres are clustered at the spindle pole body (SPB), located at the leading edge of the moving nucleus and the rest of each chromosome dangles behind. Here, we show that the oscillatory nuclear movement of meiotic prophase is dependent on cytoplasmic dynein. We have cloned the gene encoding a cytoplasmic dynein heavy chain of fission yeast. Most of the cells disrupted for the gene show no gross defect during mitosis and complete meiosis to form four viable spores, but they lack the nuclear movements of meiotic prophase. Thus, the dynein heavy chain is required for these oscillatory movements. Consistent with its essential role in such nuclear movement, dynein heavy chain tagged with green fluorescent protein (GFP) is localized at astral microtubules and the SPB during the movements. In dynein-disrupted cells, meiotic recombination is significantly reduced, indicating that the dynein function is also required for efficient meiotic recombination. In accordance with the reduced recombination, which leads to reduced crossing over, chromosome missegregation is increased in the mutant. Moreover, both the formation of a single cluster of centromeres and the colocalization of homologous regions on a pair of homologous chromosomes are significantly inhibited in the mutant. These results strongly suggest that the dynein-driven nuclear movements of meiotic prophase are necessary for efficient pairing of homologous chromosomes in fission yeast, which in turn promotes efficient meiotic recombination.
A Distributed and Cooperative Approach to Botnet Detection Using Gossip Protocol

Bots, in recent times, have posed a major threat to enterprise networks. With the distributed nature of the way in which botnets operate, the problems faced by enterprises have become acute. A bot is a program that operates as an agent for a user and runs automated tasks over the internet, at a much higher rate than would be possible for a human alone. A collection of bots in a network, used for malicious purposes, is referred to as a botnet. In this paper we suggested a distributed, co-operative approach towards detecting botnets is a given network which is inspired by the gossip protocol. Each node in a given network runs a standalone agent that computes a suspicion value for that node after regular intervals. Each node in the network exchanges its suspicion values with every other node in the network at regular intervals. The use of gossip protocol ensures that if a node in the network is compromised, all other nodes in the network are informed about it as soon as possible. Each node also ensures that at any instance, by means of the gossip protocol, it maintains the latest suspicion values of all the other nodes in the network.
Recombinant VP4 of Human Rhinovirus Induces Permeability in Model Membranes

ABSTRACT In common with all nonenveloped viruses, the mechanism of picornavirus membrane penetration during cell entry is poorly understood. The small, myristylated capsid protein VP4 has been implicated in this process. Here we show that recombinant VP4 of human rhinovirus 16 has the ability to associate with and induce membrane permeability in otherwise intact liposomes. This provides further evidence that VP4 plays a key role in picornavirus cell entry.
How are migrant employees manages? An integrated analysis

I integrate theories of acculturation, statistical discrimination and social distance with social identity theory to propose a comprehensive theoretical framework that accounts for the differential managerial treatment of social groups. I develop and apply this framework to study the extent to which migrant employees are managed differently than native employees are and to unpack differentials in managerial treatment between specific migrant groups. Hallmark of the framework is that it considers group membership as well as traits of the social group to which an employee belongs and the fluidity of group boundaries. I predict that migrants receive different managerial treatment than natives do but that this difference diminishes with acculturation. I further predict that the level of economic development of migrants’ home country and home-host country (dis)similarities explain differentials in managerial treatment between migrant groups. In a sample comprising up to 13,628 migrants from more than 160 home countries and focusing on job autonomy as a key feature of how employees are managed or supervised, I find strong empirical support for these predictions. This paper helps understand the mechanisms and factors that bias employers to make suboptimal use of human capital resources drawn from a crossculturally diverse workforce.
The Protein Phosphatase 2A Inhibitor LB100 Sensitizes Ovarian Carcinoma Cells to Cisplatin-Mediated Cytotoxicity

Despite early positive response to platinum-based chemotherapy, the majority of ovarian carcinomas develop resistance and progress to fatal disease. Protein phosphatase 2A (PP2A) is a ubiquitous phosphatase involved in the regulation of DNA-damage response (DDR) and cell-cycle checkpoint pathways. Recent studies have shown that LB100, a small-molecule inhibitor of PP2A, sensitizes cancer cells to radiation-mediated DNA damage. We hypothesized that LB100 could sensitize ovarian cancer cells to cisplatin treatment. We performed in vitro studies in SKOV-3, OVCAR-8, and PEO1, -4, and -6 ovarian cancer lines to assess cytotoxicity potentiation, cell-death mechanism(s), cell-cycle regulation, and DDR signaling. In vivo studies were conducted in an intraperitoneal metastatic mouse model using SKOV-3/f-Luc cells. LB100 sensitized ovarian carcinoma lines to cisplatin-mediated cell death. Sensitization via LB100 was mediated by abrogation of cell-cycle arrest induced by cisplatin. Loss of the cisplatin-induced checkpoint correlated with decreased Wee1 expression, increased cdc2 activation, and increased mitotic entry (p-histone H3). LB100 also induced constitutive hyperphosphorylation of DDR proteins (BRCA1, Chk2, and γH2AX), altered the chronology and persistence of JNK activation, and modulated the expression of 14-3-3 binding sites. In vivo, cisplatin sensitization via LB100 significantly enhanced tumor growth inhibition and prevented disease progression after treatment cessation. Our results suggest that LB100 sensitizes ovarian cancer cells to cisplatin in vitro and in vivo by modulation of the DDR pathway and cell-cycle checkpoint abrogation. Mol Cancer Ther; 14(1); 90–100. ©2014 AACR.
Drosophila CENP-A Mutations Cause a BubR1- Dependent Early Mitotic Delay without Normal Localization of Kinetochore Components

The centromere/kinetochore complex plays an essential role in cell and organismal viability by ensuring chromosome movements during mitosis and meiosis. The kinetochore also mediates the spindle attachment checkpoint (SAC), which delays anaphase initiation until all chromosomes have achieved bipolar attachment of kinetochores to the mitotic spindle. CENP-A proteins are centromere-specific chromatin components that provide both a structural and a functional foundation for kinetochore formation. Here we show that cells in Drosophila embryos homozygous for null mutations in CENP-A (CID) display an early mitotic delay. This mitotic delay is not suppressed by inactivation of the DNA damage checkpoint and is unlikely to be the result of DNA damage. Surprisingly, mutation of the SAC component BUBR1 partially suppresses this mitotic delay. Furthermore, cid mutants retain an intact SAC response to spindle disruption despite the inability of many kinetochore proteins, including SAC components, to target to kinetochores. We propose that SAC components are able to monitor spindle assembly and inhibit cell cycle progression in the absence of sustained kinetochore localization.
Transgenic and Knock‐out Mice: Models of Neurological Disease

Besides providing useful model systems for basic science, studies based on modification of the mammalian germ line are changing our understanding of pathogenetic principles. In this article, we review the most popular techniques for generating specific germ line mutations in vivo and discuss the impact of various transgenic models on the study of neurodegenerative diseases.
Recognizing Faces --- An Approach Based on Gabor Wavelets

As a hot research topic over the last 25 years, face recognition still seems to be a difficult and largely problem. Distortions caused by variations in illumination, expression and pose are the main challenges to be dealt with by researchers in this field. Efficient recognition algorithms, robust against such distortions, are the main motivations of this research. Based on a detailed review on the background and wide applications of Gabor wavelet, this powerful and biologically driven mathematical tool is adopted to extract features for face recognition. The features contain important local frequency information and have been proven to be robust against commonly encountered distortions. To reduce the computation and memory cost caused by the large feature dimension, a novel boosting based algorithm is proposed and successfully applied to eliminate redundant features. The selected features are further enhanced by kernel subspace methods to handle the nonlinear face variations. The efficiency and robustness of the proposed algorithm is extensively tested using the ORL, FERET and BANCA databases. To normalize the scale and orientation of face images, a generalized symmetry measure based algorithm is proposed for automatic eye location. Without the requirement of a training process, the method is simple, fast and fully tested using thousands of images from the BioID and BANCA databases. An automatic user identification system, consisting of detection, recognition and user management modules, has been developed. The system can effectively detect faces from real video streams, identify them and retrieve corresponding user information from the application database. Different detection and recognition algorithms can also be easily integrated into the framework.
Anomalous Beam Pattern with Diffraction Grating on the End Surface of Hollow Optical Fiber

We fabricated 1-D diffraction grating on the end surface of cleaved hollow optical fibers with a direct inscribing method using femtosecond laser pulses, and measured the beam shape patterns in near and far fields. We confirmed near and far fields beam patterns generated by diffraction grating and ring shaped core.
Capt: Concurrent assignment and planning of trajectories for multiple robots

In this paper, we consider the problem of concurrent assignment and planning of trajectories (which we denote Capt) for a team of robots. This problem involves simultaneously addressing two challenges: (1) the combinatorially complex problem of finding a suitable assignment of robots to goal locations, and (2) the generation of collision-free, time parameterized trajectories for every robot. We consider the Capt problem for unlabeled (interchangeable) robots and propose algorithmic solutions to two variations of the Capt problem. The first algorithm, c-Capt, is a provably correct, complete, centralized algorithm which guarantees collision-free optimal solutions to the Capt problem in an obstacle-free environment. To achieve these strong claims, c-Capt exploits the synergy obtained by combining the two subproblems of assignment and trajectory generation to provide computationally tractable solutions for large numbers of robots. We then propose a decentralized solution to the Capt problem through d-Capt, a decentralized algorithm that provides suboptimal results compared to c-Capt. We illustrate the algorithms and resulting performance through simulation and experimentation.
Battle Scars? The Puzzling Decline in Employment and Rise in Disability Receipt among Vietnam Era Veterans

Using Current Population Survey and US Army administrative data, we document that between 2000 and 2010, the employment rate of Vietnam era veterans fell markedly relative to non-veterans of the same cohorts while simultaneously their enrollment increased steeply in the Veterans Disability Compensation (DC) program, which provides healthcare and transfer payments to veterans with service-connected disabilities. Thirty percent of Vietnam era Army veterans enrolled in DC in 2006 received benefits for Post-Traumatic Stress Disorder, with median annual payments of $25,500. The declining employment and rising transfer payments to Vietnam era veterans underscore the long-term private and public costs of wartime service, potentially stemming from both adverse health consequences and policies that have expanded benefits eligibility.
Exercise Training Restores Baroreflex Sensitivity in Never-Treated Hypertensive Patients

The effects of exercise training on baroreflex control of sympathetic nerve activity in human hypertension are unknown. We hypothesized that exercise training would improve baroreflex control of muscle sympathetic nerve activity (MSNA) and heart rate (HR) in patients with hypertension and that exercise training would reduce MSNA and blood pressure (BP) in hypertensive patients. Twenty never-treated hypertensive patients were randomly divided into 2 groups: exercise-trained (n=11; age: 46±2 years) and untrained (n=9; age: 42±2 years) patients. An age-matched normotensive exercise-trained group (n=12; age: 42±2 years) was also studied. Baroreflex control of MSNA (microneurography) and HR (ECG) was assessed by stepwise intravenous infusions of phenylephrine and sodium nitroprusside and analyzed by linear regression. BP was monitored on a beat-to-beat basis. Exercise training consisted of three 60-minute exercise sessions per week for 4 months. Under baseline conditions (before training), BP and MSNA were similar between hypertensive groups but significantly increased when compared with the normotensive group. Baroreflex control of MSNA and HR was similar between hypertensive groups but significantly decreased when compared with the normotensive group. In hypertensive patients, exercise training significantly reduced BP (P<0.01) and MSNA (P<0.01) levels and significantly increased baroreflex control of MSNA and HR during increases (P<0.01 and P<0.03, respectively) and decreases (P<0.01 and P<0.03, respectively) in BP. The baseline (preintervention) difference in baroreflex sensitivity between hypertensive patients and normotensive individuals was no longer observed after exercise training. No significant changes were found in untrained hypertensive patients. In conclusion, exercise training restores the baroreflex control of MSNA and HR in hypertensive patients. In addition, exercise training normalizes MSNA and decreases BP levels in these patients.
FINDING A PATH IN THE SUSTAINABILITY JUNGLE. A FRAMEWORK FOR CORPORATE ACTION

Collective concerns about sustainable development and proposals about how to achieve sustainability have produced a confusing body of terminology that is more like a jungle of issues than a framework to enable focused action. Businesses, in particular, with their global reach, influence, capabilities and supposed deep pockets, are expected to contribute more towards sustainability; and yet the lack of clear definitions has left a vacuum of corporate guidance. Corporate Social Responsibility (CSR) has become a synonym for corporate action towards sustainability, but companies continue to struggle to understand how to deal with this issue. This paper looks at some important drivers that link the overall discussion of sustainability with the business world. It presents a framework for corporate action that facilitates a practical approach grounded in existing market realities. By separating social responsiveness (social compliance) from social responsibility (CSR), it provides a two-phase approach that gives priority to credibly implementing social compliance without missing opportunities for leadership and excellence. The importance of social compliance in legitimizing, strengthening and building trust in market regulatory institutions is emphasized. It is argued that experimenting with unfocused CSR often is a zero-sum game for society, and that CSR without an explicit social compliance framework lacks credibility. From the basis of a convincingly implemented social compliance framework, corporations may express their social responsibility as a voluntary measure and create social value more directly, without compromising their ability to create economic value. Because of the urgency and need for prioritization to achieve sustainable development it is proposed that corporations shift their CSR focus towards developing countries. Three models that have been identified as opportunities for corporations to contribute to this goal are discussed.
HIV-Care Outcome in Saudi Arabia; a Longitudinal Cohort

Background Clinical characteristics of HIV-1 infection in people inhabiting Western, Sub-Saharan African, and South-East Asian countries are well recognized. However, very little information is available with regard to HIV-1 infection and treatment outcome in MENA countries including the Gulf Cooperation Council (GCC) states. Methods Clinical, demographic and epidemiologic characteristics of 602 HIV-1 infected patients followed in the adult Infectious Diseases Clinic of King Faisal Specialist Hospital and Research Centre, in Riyadh, Kingdom of Saudi Arabia a tertiary referral center were longitudinally collected from 1989 to 2010. Results Of the 602 HIV-1 infected patients in this observation period, 70% were male. The major mode of HIV-1 transmission was heterosexual contact (55%). At diagnosis, opportunistic infections were found in 49% of patients, most commonly being pneumocysitis. AIDS associated neoplasia was also noted in 6% of patients. A hundred and forty-seven patients (24%) died from the cohort by the end of the observation period. The mortality rate peaked in 1992 at 90 deaths per 1000 person-year, whereas the mortality rate gradually decreased to <1% from 1993-2010. In 2010, 71% of the patients were receiving highly active retroviral therapy. Conclusions These data describe the clinical characteristic of HIV-1-infected patients at a major tertiary referral hospital in KSA over a 20-year period. Initiation of antiretroviral therapy resulted in a significant reduction in both morbidity and mortality. Future studies are needed in the design and implementation of targeted treatment and prevention strategies for HIV-1 infection in KSA.
Web application for recognition of mathematical formulas

We present a system for on-line mathematical formulas recognition. The main principles of the method we applied for recognition are explained. It is based on the structural construction paradigm and utilizes a sort of twodimensional grammars called coordinate grammars. Grammar productions are used to model spatial relationships among mathematical symbols. The system itself has been developed as a web application in HTML5. We give details on its client-server architecture and user interface. We also discuss advantages of the chosen approach.
Vectors and Spatial Patterns of Angiostrongylus cantonensis in Selected Rice-Farming Villages of Muñoz, Nueva Ecija, Philippines

In the Philippines, rats and snails abound in agricultural areas as pests and source of food for some of the local people which poses risks of parasite transmission to humans such as Angiostrongylus cantonensis. This study was conducted to determine the extent of A. cantonensis infection among rats and snails collected from rice-farming villages of Muñoz, Nueva Ecija. A total of 209 rats, 781 freshwater snails, and 120 terrestrial snails were collected for the study. Heart and lungs of rats and snail tissues were examined and subjected to artificial digestion for parasite collection. Adult worms from rats were identified using SSU rDNA gene. Seven nematode sequences obtained matched A. cantonensis. Results revealed that 31% of the rats examined were positive with A. cantonensis. Rattus norvegicus and R. tanezumi showed prevalence of 46% and 29%, respectively. Furthermore, only Pomacea canaliculata (2%) and Melanoides maculata (1%) were found to be positive for A. cantonensis among the snails collected. Analysis of host distribution showed overlapping habitats of rats and snails as well as residential and agricultural areas indicating risks to public health. This study presents a possible route of human infection for A. cantonensis through handling and consumption of P. canaliculata and M. maculata or crops contaminated by these snails.