Miracle-dz/UniFAR-FTUs huggingface dataset:
The Combi-Targeting Concept: Dissection of the Binary Mechanism of Action of the Combi-Triazene SMA41 in Vitro and Antitumor Activity in Vivo

We have previously reported the synthesis of SMA41, a unimolecular combination of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) of the quinazoline class and a DNA-damaging monomethyltriazene termed “combimolecule”. Hydrolysis of 1-[4-(m-tolylamino)-6-quinazolinyl]-3-methyltriazene (SMA41) gives rise to an intact TKI [6-amino-4-(3-methylanilino)quinazoline; SMA52] capable of inhibiting epidermal growth factor (EGF)-induced EGFR autophosphorylation and a DNA-targeting methyldiazonium species. Herein, we showed that SMA41 blocked EGF-induced EGFR autophosphorylation by an irreversible mechanism, suggesting that it may covalently damage the receptor in these cells. More importantly, this was associated with significant inhibition of mitogen-activated protein kinase activation in A431 cells. In cells treated with [14C]SMA41, radio-high-performance liquid chromatography detection of both N7- and O6-methylguanine revealed an almost complete repair of the O6-methylguanine lesions and a greater tolerance of the N7-methylguanine adducts 24 h post-treatment. In contrast to temozolomide (a cyclic triazene used in the clinic) and the reversible inhibitor SMA52, SMA41 induced significant cell cycle arrest in S, G2, and M phases 24 h after a 2-h drug exposure. Furthermore, in vivo studies demonstrated that SMA41 was well tolerated. At 200 mg/kg, it showed approximately 2-fold greater antiproliferative activity than SMA52 in A431 cells implanted in immunocompromised SCID mice. These results suggest that the binary targeting properties of SMA41 are associated with a binary cascade of events in the cells that seem to culminate into significant growth inhibition in vitro and in vivo.
N-acetylglucosamine-Mediated Expression of nagA and nagB in Streptococcus pneumoniae

In this study, we have explored the transcriptomic response of Streptococcus pneumoniae D39 to N-acetylglucosamine (NAG). Transcriptome comparison of S. pneumoniae D39 wild-type grown in chemically defined medium (CDM) in the presence of 0.5% NAG to that grown in the presence of 0.5% glucose revealed elevated expression of many genes/operons, including nagA, nagB, manLMN, and nanP. We have further confirmed the NAG-dependent expression of nagA, nagB, manLMN, and nanP by β-galactosidase assays. nagA, nagB and glmS are putatively regulated by a transcriptional regulator NagR. We predicted the operator site of NagR (dre site) in PnagA, PnagB, and PglmS, which was further confirmed by mutating the predicted dre site in the respective promoters (nagA, nagB, and glmS). Growth comparison of ΔnagA, ΔnagB, and ΔglmS with the D39 wild-type demonstrates that nagA and nagB are essential for S. pneumoniae D39 to grow in the presence of NAG as a sole carbon source. Furthermore, deletion of ccpA shows that CcpA has no effect on the expression of nagA, nagB, and glmS in the presence of NAG in S. pneumoniae.
The variable relationship between the lower cranial nerves and jugular foramen tumors: implications for neural preservation.

Tumors involving the jugular foramen (JF) have a variable relationship to the neurovascular structures (jugular vein, cranial nerves IX-XI) that traverse this conduit through the skull base. The surgeon familiar with the site of origin, growth pattern, and geometry of each of the common lesions affecting this region with respect to surrounding nerves and vessels is at a considerable advantage when undertaking a function-sparing procedure. Anatomically, the JF has two vascular compartments that may be affected by tumor: the jugular bulb laterally and a passage for the inferior petrosal sinus medially. Tumors may also penetrate the JF along the fibro-osseous diaphragm, which divides these two vascular channels. The lower cranial nerves lie on either side of this partition, which is connected to the posterior cranial fossa via a curved, funnel-shaped cone of dura. Tumors that arise within or penetrate the JF lateral to this neural plane displace the nerves medially, a position favorable for their preservation during tumor extirpation. By contrast, medially positioned tumors displace the cranial nerves onto the lateral tumor surface, where they interpose between surgeon and tumor-an unfavorable location. Glomus tumors consistently arise in the lateral aspect of the JF, displacing the lower cranial nerves medially. This positioning accounts for the high rate of neural preservation in small and medium-size glomus tumors that have not invaded the foramen's central partition. Meningiomas that arise lateral to the JF (e.g., the posterior petrous surface, sigmoid sinus) favorably displace the lower cranial nerves medially. By contrast, tumors that originate medial to the JF (e.g., clivus, foramen magnum) are unfavorable, laterally displacing the multiple small rootlets that coalesce into cranial nerves IX-XI into a vulnerable location. Schwannomas arise within the neural plane and have a variable geometry that depends, in part, upon the nerve of origin. Theoretically, tumors that arise from the ninth nerve, which is located on the lateral surface of the neural plane, should be more favorable than those originating from the tenth or eleventh nerves, which lie on its deep surface. The propensity of these three tumor types toward thrombosis of the jugulosigmoid complex also carries important surgical implications. Because glomus tumors arise from the jugular bulb, the jugulosigmoid complex is nearly always occluded. In both meningiomas and schwannomas, however, the jugular system may occasionally remain patent. This is important to recognize through angiography and/or magnetic resonance venography, since sacrifice of a patent, dominant system risks intracerebral venous infarction.
Long Lines at Polling Stations? Observations from an Election Day Field Study

ABSTRACT This pilot study represents the first systematic attempt to determine how common lines are on Election Day, at what times of day lines are most likely to form, what are the bottlenecks in the voting process, and how long it takes an average citizen to cast his or her ballot. This study highlights the importance of evaluating polling station operations as a three-step process: arrival, check-in, and casting a ballot. We collected data during the 2008 presidential primary election in California, measuring the efficiency of the operational components of 30 polling stations across three counties. We found statistically significant, and meaningful, variation in the service rates of poll workers and voting technology. Our findings should better help election officials make critical decisions about the allocation of critical resources.
The performance of layered broadcast with superposition coding

In wireless broadcast system, where feedback is limited and channel state information is only available at the receiver side, layered broadcasting approach has been proposed to fully utilize the channel resources by providing different levels of service quality to users with different channel conditions. However, no upper bound has been given yet to show how the layered broadcast scheme will outperform the conventional broadcast (CB) scheme. In this paper, system average achievable rate (SAAR) is defined as the mean achievable rate of all users within the coverage. Based on continuum superposition coding (SC) with infinite layers, the upper bound of the SAAR of layered broadcasting is given by the derivation of the optimal power distribution function among the superposed layers. The results show that, by promoting the experience of stronger users (users with better channel conditions) without seriously degrading the performance of weaker users (users with worse channel conditions), layered broadcasting approach greatly increases the average system performance. Copyright © 2011 John Wiley & Sons, Ltd.
[Roles of cytochrome c, caspase-9, and caspase-3 in pentavalent vanadium-induced neuronal apoptosis].

OBJECTIVE To investigate the roles of cytochrome c (Cyt-c), caspase-9, and caspase-3 in pentavalent vanadium-induced neuronal apoptosis and to provide a basis for mechanism research. METHODS Neurons from rats aged 1-3 days were cultured and treated with vanadium pentoxide (V2O5) at 5, 10, or 20 mmol/L. Neuronal apoptosis was detected by TdT-mediated dUTP-biotin nick end labeling (TUNEL). The protein levels of Cyt-c, caspase-9, and caspase-3 were determined by Western blot. RESULTS Apoptosis bodies were detected in the nuclei of neurons by TUNEL. The number of neurons with apoptosis bodies increased with increasing dose of V2O5 The apoptosis index (AI) was significantly higher in the 10 and 20 mm/L exposure groups than in the control group (P < 0.05 or P < 0.01). Western blot showed that the protein expression levels of Cyt-c and caspase-3 significantly increased in the 5 mmol/L exposure group as compared with the control group (P < 0.05). In the 10 and 20 mmol/L exposure groups, the protein expression of Cyt-c, caspase-9, and caspase-3 all increased as compared with the control group (P < 0.01). Neuronal AI was positively correlated with Cyt-c, caspase-9, and caspase-3 (r = 0.954, P < 0.01; r = 0.938, P < 0.01; r = 0.943, P < 0.01). CONCLUSION Pentavalent vanadium may induce neuronal apoptosis. The protein expression of Cyt-c, caspase-9, and caspase-3 may play an important role in neuronal apoptosis induced by pentavalent vanadium.
Can bedside assessment reliably exclude aspiration following acute stroke?

OBJECTIVE To investigate the ability of a bedside swallowing assessment to reliably exclude aspiration following acute stroke. SUBJECTS Consecutive patients admitted within 24 h of stroke onset to two hospitals. METHODS A prospective study. Where possible, all patients had their ability to swallow assessed on the day of admission by both a doctor and a speech and language therapist using a standardized proforma. A videofluoroscopy examination was conducted within 3 days of admission. RESULTS 94 patients underwent videofluoroscopy; 20 (21%) were seen to be aspirating, although this was not detected at the bedside in 10. In 18 (22%) of the patients the speech and language therapist considered the swallow to be unsafe. In the medical assessment, 39 patients (41%) had an unsafe swallow. Bedside assessment by a speech and language therapist gave a sensitivity of 47%, a specificity of 86%, positive predictive value (PPV) of 50% and a negative predictive value (NPV) of 85% for the presence of aspiration. Multiple logistic regression was used to identify the optimum elements of the bedside assessments for predicting the presence of aspiration. A weak voluntary cough and any alteration in conscious level gave a sensitivity of 75%, specificity of 72%, PPV of 41% and NPV of 91% for aspiration. CONCLUSION Bedside assessment of swallowing lacks the necessary sensitivity to be used as a screening instrument in acute stroke, but there are concerns about the use of videofluoroscopy as a gold standard. The relative importance of aspiration and bedside assessment in predicting complications and outcome needs to be studied.
[Pregnancy in type 1 diabetes: insulin pump versus intensified conventional therapy].

OBJECTIVES To evaluate and compare the outcome of pregnancies in women with type 1 diabetes treated with continuous subcutaneous insulin pump or multiple insulin injections. PATIENTS AND METHODS Thirty-three patients treated with pump, 23 with multiple injections. Were mainly investigated: glycemic control (HbA1C), fetal outcome (congenital malformations, preterm delivery, perinatal mortality), rates of gestational hypertension and cesarean section. RESULTS HbA1C (1st, 2nd and 3rd trimester) with pump was not significantly different from that obtained with multiple injections (respectively, 7.5 +/- 1.24 vs 7.6 +/- 1.4; 6.34 +/- 0.6 vs 6.6 +/- 0.8; 6.6 +/- 0.7 vs 6.4 +/- 0.7). Fetal prognosis was also similar. The occurrence of gestational hypertension was linked to diabetic complications [OR 5,7, IC95% 1.24-25, p = 0.0025]. The rate of cesarean section (70% in women treated with pump) was influenced by diabetes duration. In planned pregnancy, independently of therapeutic device, HbA1C during organogenesis was better (6.9% +/- 0.78 vs 8.51 +/- 1.3, p < 0.0001) with no perinatal death and no major congenital malformation. DISCUSSION AND CONCLUSION Fetal prognosis is not overall significantly different with insulin pump compared with intensified conventional therapy. The initiation of insulin pump therapy should not be systematic. Instead, the benefits risks ratio must be assessed resulting in a tailored prescription according to individual needs. This therapeutic choice should be discussed before conception, as planned pregnancy is a main prognostic factor. Diabetes duration and complications remain key factors for the prognosis.
Clinical characteristics of α-pyrrolidinovalerophenone (α-PVP) poisoning

Abstract Context: α-Pyrrolidinovalerophenone (α-PVP) is a synthetic cathinone that has been abused in recent years. The clinical presentation of acute α-PVP poisoning has not been well characterized. Objective: To elucidate the clinical features of acute α-PVP poisoning. Materials and methods: This retrospective case series included eight subjects that visited our hospital emergency department (ED) between March 2012 and November 2014 and had analytically confirmed blood α-PVP levels. Data related to subject demographics, clinical history, laboratory findings, blood drug levels, and outcome were collected. Results: The median age of the eight study subjects was 27 (range; 21–63) years, and six were male. Drug preparations had been administered by rectal insertion (three subjects) or inhalation (five subjects). The time between drug exposure and presentation at the ED was 8.5 (1–24) h and blood α-PVP concentrations ranged from 1.0 to 52.5 ng/ml. Although psychiatric and neurological findings were reported before arrival at the ED in 5/8 and 7/8 subjects, respectively, these were only observed in 1/8 and 2/8 subjects, respectively, at the ED. Symptoms of high body temperature (3/8), tachycardia (5/8), hypertension (3/8), acid-base balance disorder (5/8), coagulopathy (4/6), blood creatinine phosphokinase >190 U/l (6/8), and a blood lactate level > 1.7 mmol/l (5/7) were observed. All subjects survived and were discharged. Conclusions: This retrospective case series showed that after acute exposure to α-PVP, transient neuropsychiatric findings were accompanied by more persistent sympathomimetic physical findings, disorders of acid-base balance and blood coagulation, high blood creatinine phosphokinase, and hyperlactacidemia.
Unsupervised adaptation for deep neural networks using Alternating Direction Method of Multipliers

In this paper, we continue our work on linear least squares based adaptation (LLS) for deep neural networks. We show that our previously proposed algorithm is a special case of an optimization algorithm called Alternating Direction Method of Multipliers (ADMM). We demonstrate that the adaptation algorithm can improve the performance on various deep neural networks including the bidirectional long short term memory (BLSTM). On the Switchboard subset of the Hub5 2000 evaluation set, we show that LLS adaptation can achieve 6 to 9% relative word error rate (WER) reduction, and improve our two-pass system to 7.5% WER. In this paper, we also analyze the factors that could contribute to the success of an adaptation algorithm. This helps us to understand under what circumstances, adaptation could improve the system performance.
GGAKE: GPU Based Genome Assembly Using K-Mer Extension

The genome assembly problem involves constructing the complete genome sequence from the reads generated by the sequencers. The Next Generation Sequencing (NGS) platforms produce a large number of short reads at a very low cost. Many assemblers have been developed to work with NGS reads. The assembly process is computation intensive and also requires a large amount of memory to store the reads. Numerous efforts are being made in recent times to parallelize the assembly process in order to reduce computation time. In this paper we present the design and development of a GPU based genome assembler (GGAKE). Our assembler works using the concept of k-mer extension. Prefix and suffix k-mers are spotted out of every read. Suffix k-mers are matched with prefix k-mers and extensions for every read are noted. Contigs are generated by extending the reads. We have implemented GGAKE on Nvidia's GPU using the CUDA programming model and benchmarked it on five bacterial genomes. Our results prove that at high coverage GGAKE is capable of producing good quality assembly in a small amount of time.
Generation of a Canine Anti-EGFR (ErbB-1) Antibody for Passive Immunotherapy in Dog Cancer Patients

Passive immunotherapy with monoclonal antibodies represents a cornerstone of human anticancer therapies, but has not been established in veterinary medicine yet. As the tumor-associated antigen EGFR (ErbB-1) is highly conserved between humans and dogs, and considering the effectiveness of the anti-EGFR antibody cetuximab in human clinical oncology, we present here a “caninized” version of this antibody, can225IgG, for comparative oncology studies. Variable region genes of 225, the murine precursor of cetuximab, were fused with canine constant heavy gamma and kappa chain genes, respectively, and transfected into Chinese hamster ovary (CHO) DUKX-B11 cells. Of note, 480 clones were screened and the best clones were selected according to productivity and highest specificity in EGFR-coated ELISA. Upon purification with Protein G, the recombinant cetuximab-like canine IgG was tested for integrity, correct assembly, and functionality. Specific binding to the surface of EGFR-overexpressing cells was assessed by flow cytometry and immunofluorescence; moreover, binding to canine mammary tissue was demonstrated by immunohistochemistry. In cell viability and proliferation assays, incubation with can225IgG led to significant tumor cell growth inhibition. Moreover, this antibody mediated significant tumor cell killing via phagocytosis in vitro. We thus present here, for the first time, the generation of a canine IgG antibody and its hypothetical structure. On the basis of its cetuximab-like binding site, on the one hand, and the expression of a 91% homologous EGFR molecule in canine cancer, on the other hand, this antibody may be a promising research compound to establish passive immunotherapy in dog patients with cancer. Mol Cancer Ther; 13(7); 1777–90. ©2014 AACR.
PATTERN OF KHAT ABUSE AND ACADEMIC PERFORMANCE AMONG SECONDARY SCHOOL AND COLLEGE STUDENTS IN JAZAN REGION, KINGDOM OF SAUDI ARABIA (KSA)

Background: Khat is a widely-abused psychoactive substance in East African countries, Yemen and Southwestern areas of the Kingdom of Saudia Arabia (KSA), especially in Jazan region. However, patterns of Khat consumption as well as its adverse consequences on academic work are not well studied. Objective: The study was conducted to assess the pattern of Khat abuse and its associated academic effect on Secondary School and College students in Jazan region, KSA. Methods: A cross-sectional study was conducted in May 2006, in Secondary Schools and Colleges in Jazan region, KSA. Students in each class were selected by systematic random sampling technique. Self-administered questionnaire was used for data collection. Data was processed and analyzed using the Statistical Package for Social Sciences (SPSS). Results: Most Khat sessions were conducted in homes (43.8%) and friend's houses (37.0%). The mean duration of a Khat session is 6.1 ±3.13 hours and 5.5% chew Khat for 12-18 hours. Most Khat sessions take place at the weekends (48.4%) usually after 8 p.m (69.8%). Conclusion: Most chewing sessions took place at weekends usually in social gatherings after 8 p.m. with an average duration of about 6 hours. Smoking and educational problems were more prevalent among Khat chewers. Strong preventive and control measures including early interventions and increase of awareness need to be implemented. Recreational alternatives for young people and families especially at weekends and holidays have to be found.
Cross-modal Interactions in Time and Space: Auditory Influence on Visual Attention in Hemispatial Neglect

Recent studies indicate that auditory tone presentation and auditory alerting can temporarily ameliorate visuospatial attention deficits in patients with unilateral neglect [Frassinetti, F. , Pavani, F. , & Ladavas, E. Acoustical vision of neglected stimuli: Interaction among spatially converging audiovisual inputs in neglect patients. Journal of Cognitive Neuroscience, 14, 6269, 2002; Robertson, I. H. , Mattingley, J. B. , Rorden, C. , & Driver, J. Phasic alerting of neglect patients overcomes their spatial deficit in visual awareness. Nature, 395, 169172, 1998]. The current study investigated proposed mechanisms of cross-modal interaction to determine conditions in which auditory stimulation affects spatial and nonspatially lateralized attention deficits in a patient with hemispatial neglect. In Experiment 1, a target was presented among related distracters (conjunction search) while a tone was presented either bilaterally or in a congruent or incongruent spatial location with respect to the visual target. Whereas the results suggest a benefit of both general alerting and cross-modal spatial integration on visual search efficiency, the most significant improvement occurred when the target and tone were both presented in contralesional space. In Experiment 2, the effect of auditory alerting on selective attention was examined in a rapid serial visual search procedure with visual targets embedded in a stream of distracters presented at central fixation. When two targets were presented without an alerting tone, the patient missed the second target for up to 1000 msec after the first target appeared (a finding known as the attentional blink [AB] and, on average, about 400500 msec in normals). An alerting tone presented at a fixed temporal location significantly reduced the AB in a tone-duration-dependent manner. Experiment 3 examined the effect of cross-modal space on selective attention in an AB paradigm in which T2 occurred randomly to the left or right of T1 with a spatially congruent or incongruent tone. Discrimination of T2 in contralesional space significantly improved when the tone was presented in the same location, and was impaired when the tone was presented on the ipsilesional side. The findings are discussed as they relate to cross-modal interactions and their influence on spatial and nonspatially lateralized attention deficits in neglect.