Miracle-dz/UniFAR-FTUs huggingface dataset:
Radioisotope concentrator gene therapy using the sodium/iodide symporter gene.

We demonstrate a novel method of concentrating radiation for tumor imaging or killing. The rat sodium/iodide symporter gene (rNIS) was cloned into a retroviral vector for transfer into cancer cells to mimic the iodide uptake of thyroid follicular cells. In vitro iodide transport shows that the symporter functions similarly in rNIS-transduced tumor cells and rat thyroid follicular cells. rNIS-transduced and control nontransduced (NV) human A375 melanoma xenografts established in vivo in athymic nude mice were imaged using a gamma camera after i.p. injections of 123I. The rNIS-transduced human A375 melanoma tumors are visually distinguishable from and accumulate significantly more radionuclides than NV tumors. In vitro clonogenic assays confirm efficacy and clearly show that rNIS-transduced A375 human melanoma, BNL.1 ME murine transformed liver, CT26 murine colon carcinoma, and IGROV human ovarian carcinoma can be selectively killed by the induced accumulation of 131I. Thus, NIS-based gene therapy may have both diagnostic and therapeutic applications for cancer.
In vitro antiviral activity of SCH446211 (SCH6), a novel inhibitor of the hepatitis C virus NS3 serine protease.

BACKGROUND Current hepatitis C virus (HCV) therapies may cure approximately 60% of infections. They are often contraindicated or poorly tolerated, underscoring the need for safer and more effective drugs. A novel, alpha-ketoamide-derived, substrate-based inhibitor of the HCV serine protease (SCH446211) was developed. Compared with earlier reported inhibitors of similar chemical class, it has a P1'-P2' extension which provides extended interaction with the protease active site. The aim of this study was to evaluate the in vitro antiviral activity of SCH446211. METHODS Binding constant of SCH446211 to HCV NS3 protease was measured with the chromogenic substrate in vitro cleavage assay. Cell-based activity of SCH446211 was evaluated in replicon cells, which are Huh-7 hepatoma cells stably transfected with a subgenomic HCV RNA as reported previously. After 72 h of incubation with SCH446211, viral transcription and protein expression were measured by real-time RT-PCR (TaqMan), quantitative in situ hybridization, immunoblot and indirect immunofluorescence. RESULTS The binding constant of SCH446211 to HCV NS3 protease was 3.8 +/- 0.4 nM. HCV replication and protein expression were inhibited by SCH446211 in replicon cells as consistently shown by four techniques. In particular, based on quantitative real-time RT-PCR measurements, the IC50 and IC90 of SCH446211 were estimated to be 40 +/- 20 and 100 +/- 20 nM (n = 17), respectively. Long-term culture of replicon cells with SCH446211 reduced replicon RNA to <0.1 copy per cell. SCH446211 did not show cellular toxicity at concentrations up to 50 microM. CONCLUSIONS SCH446211 is a potent inhibitor of HCV protease in vitro. Its extended interaction with the HCV NS3 protease active site is associated with potent in vitro antiviral activity. This observation is potentially a useful guide for development of future potent inhibitors against HCV NS3 protease.
Ceftriaxone-Resistant Salmonella enterica Serotype Typhimurium Sequence Type 313 from Kenyan Patients Is Associated with the blaCTX-M-15 Gene on a Novel IncHI2 Plasmid

ABSTRACT Multidrug-resistant bacteria pose a major challenge to the clinical management of infections in resource-poor settings. Although nontyphoidal Salmonella (NTS) bacteria cause predominantly enteric self-limiting illness in developed countries, NTS is responsible for a huge burden of life-threatening bloodstream infections in sub-Saharan Africa. Here, we characterized nine S. Typhimurium isolates from an outbreak involving patients who initially failed to respond to ceftriaxone treatment at a referral hospital in Kenya. These Salmonella enterica serotype Typhimurium isolates were resistant to ampicillin, chloramphenicol, cefuroxime, ceftriaxone, aztreonam, cefepime, sulfamethoxazole-trimethoprim, and cefpodoxime. Resistance to β-lactams, including to ceftriaxone, was associated with carriage of a combination of blaCTX-M-15, blaOXA-1, and blaTEM-1 genes. The genes encoding resistance to heavy-metal ions were borne on the novel IncHI2 plasmid pKST313, which also carried a pair of class 1 integrons. All nine isolates formed a single clade within S. Typhimurium ST313, the major clone of an ongoing invasive NTS epidemic in the region. This emerging ceftriaxone-resistant clone may pose a major challenge in the management of invasive NTS in sub-Saharan Africa.
UDP-galactose transporter is required for Theiler's virus entry into mammalian cells.

Theiler's murine encephalomyelitis viruses (TMEV) are divided into two groups: high-neurovirulence strains, such as GDVII, cause fatal encephalitis, while low-neurovirulence strains, such as BeAn and DA, cause persistent infection and demyelination in mice. Cell surface sialic acid is bound by the low-neurovirulence DA and BeAn viruses, but not by the high-neurovirulence GDVII virus. We have identified a clone from a BHK-21 cell cDNA library that mediates TMEV entry and infection by viruses of both TMEV groups in a receptor-negative BHK-21 cell variant (R26). The sequence of this clone is 96.4% identical to the human UDP-galactose transporter (UGT), which belongs to a family of nucleotide-sugar transporter proteins involved in the biosynthesis of complex carbohydrate structures in the trans-Golgi network. UGT mRNA from R26 cells was found to have a 490-nucleotide deletion involving the C-terminal amino acids 255 to 392 and 81 nucleotides of the 3' noncoding region. These results suggest two possibilities by which UGT may mediate TMEV entry and infection. The most likely one relates to the transporter function of adding galactose to another receptor protein. This possibility suggests the requirement for a specific glycoprotein interaction for GDVII virus cell binding and entry, e.g., galactose for GDVII and sialic acid for BeAn. Alternatively, UGT might be a TMEV receptor itself, acting via UGT cycling to the cell surface.
Improve SMT Quality with Automatically Extracted Paraphrase Rules

We propose a novel approach to improve SMT via paraphrase rules which are automatically extracted from the bilingual training data. Without using extra paraphrase resources, we acquire the rules by comparing the source side of the parallel corpus with the target-to-source translations of the target side. Besides the word and phrase paraphrases, the acquired paraphrase rules mainly cover the structured paraphrases on the sentence level. These rules are employed to enrich the SMT inputs for translation quality improvement. The experimental results show that our proposed approach achieves significant improvements of 1.6~3.6 points of BLEU in the oral domain and 0.5~1 points in the news domain.
Key Estimation Using a Hidden Markov Model

A novel technique to estimate the predominant key in a musical excerpt is proposed. The key space is modelled by a 24-state Hidden Markov Model (HMM), where each state represents one of the 24 major and minor keys, and each observation represents a chord transition, or pair of consecutive chords. The use of chord transitions as the observations models a greater temporal dependency between consecutive chords than would observations of single chords. The key transition and chord emission probabilities are initialised using the results of perceptual tests in order to reflect the human expectation of harmonic relationships. HMM parameters are then trained on a per-song basis using handannotated chord symbols, before the model for each song is decoded to give the likelihood of each key at each time frame. Examples of the algorithm as a segmentation technique are given, and its capability to estimate the overall key of a song is evaluated using a data set of 110 Beatles songs, of which 91% were correctly classified. An extension to include operation from audio data instead of chord symbols is planned, which will enable application to general music retrieval purposes.
Harvesting and Preparing Drosophila Embryos for Electrophysiological Recording and Other Procedures

Drosophila is a premier genetic model for the study of both embryonic development and functional neuroscience. Traditionally, these fields are quite isolated from each other, with largely independent histories and scientific communities. However, the interface between these usually disparate fields is the developmental programs underlying acquisition of functional electrical signaling properties and differentiation of functional chemical synapses during the final phases of neural circuit formation. This interface is a critically important area for investigation. In Drosophila, these phases of functional development occur during a period of <8 hours (at 25°C) during the last third of embryogenesis. This late developmental period was long considered intractable to investigation owing to the deposition of a tough, impermeable epidermal cuticle. A breakthrough advance was the application of water-polymerizing surgical glue that can be locally applied to the cuticle to enable controlled dissection of late-stage embryos. With a dorsal longitudinal incision, the embryo can be laid flat, exposing the ventral nerve cord and body wall musculature to experimental investigation. This system has been heavily used to isolate and characterize genetic mutants that impair embryonic synapse formation, and thus reveal the molecular mechanisms governing the specification and differentiation of synapse connections and functional synaptic signaling properties.
Whole-exome sequencing characterizes the landscape of somatic mutations and copy number alterations in adrenocortical carcinoma.

CONTEXT Adrenocortical carcinoma (ACC) is a rare and lethal malignancy with a poorly defined etiology, and the molecular genetics of ACC are incompletely understood. OBJECTIVE To utilize whole-exome sequencing for genetic characterization of the underlying somatic mutations and copy number alterations present in ACC. DESIGN Screening for somatic mutation events and copy number alterations (CNAs) was performed by comparative analysis of tumors and matched normal samples from 41 patients with ACC. RESULTS In total, 966 nonsynonymous somatic mutations were detected, including 40 tumors with a mean of 16 mutations per sample and one tumor with 314 mutations. Somatic mutations in ACC-associated genes included TP53 (8/41 tumors, 19.5%) and CTNNB1 (4/41, 9.8%). Genes with potential disease-causing mutations included GNAS, NF2, and RB1, and recurrently mutated genes with unknown roles in tumorigenesis comprised CDC27, SCN7A, and SDK1. Recurrent CNAs included amplification at 5p15.33 including TERT (6/41, 14.6%) and homozygous deletion at 22q12.1 including the Wnt repressors ZNRF3 and KREMEN1 (4/41 9.8% and 3/41, 7.3%, respectively). Somatic mutations in ACC-established genes and recurrent ZNRF3 and TERT loci CNAs were mutually exclusive in the majority of cases. Moreover, gene ontology identified Wnt signaling as the most frequently mutated pathway in ACCs. CONCLUSIONS These findings highlight the importance of Wnt pathway dysregulation in ACC and corroborate the finding of homozygous deletion of Wnt repressors ZNRF3 and KREMEN1. Overall, mutations in either TP53 or CTNNB1 as well as focal CNAs at the ZNRF3 or TERT loci denote mutually exclusive events, suggesting separate mechanisms underlying the development of these tumors.
Interferon-Beta Therapy of Multiple Sclerosis Patients Improves the Responsiveness of T Cells for Immune Suppression by Regulatory T Cells

Multiple sclerosis (MS) is an inflammatory autoimmune disease characterized by imbalanced immune regulatory networks, and MS patient-derived T effector cells are inefficiently suppressed through regulatory T cells (Treg), a phenomenon known as Treg resistance. In the current study we investigated T cell function in MS patients before and after interferon-beta therapy. We compared cytokine profile, responsiveness for Treg-mediated suppression ex vivo and evaluated reactivity of T cells in vivo using a humanized mouse model. We found that CD4+ and CD8+ T cells of therapy-naive MS patients were resistant to Treg-mediated suppression. Treg resistance is associated with an augmented IL-6 production, enhanced IL-6 receptor expression, and increased PKB/c-Akt phosphorylation. These parameters as well as responsiveness of T cells to Treg-mediated suppression were restored after interferon-beta therapy of MS patients. Following transfer into immunodeficient mice, MS T cells induced a lethal graft versus host disease (GvHD) and in contrast to T cells of healthy volunteers, this aggressive T cell response could not be controlled by Treg, but was abolished by anti-IL-6 receptor antibodies. However, magnitude and lethality of GvHD induced by MS T cells was significantly decreased after interferon-beta therapy and the reaction was prevented by Treg activation in vivo. Our data reveals that interferon-beta therapy improves the immunoregulation of autoaggressive T effector cells in MS patients by changing the IL-6 signal transduction pathway, thus restoring their sensitivity to Treg-mediated suppression.
Use of metabolic monitors in a multidisciplinary Intensive Care Unit: A prospective pilot study of 20 patients

Introduction: Caloric intake of critically ill patients are usually calculated using predictive equations. Recent advances in gas exchange measurements have the potential to estimate energy expenditure at the bedside and at different time periods. Materials and Methods: Energy needs of critically ill patients were estimated over a period of 3 months using simplistic formula of 25 kcal/kg/day estimated energy expenditure (EEE), Harris–Benedict equation (HBE) (Basal energy expenditure [BEE]) and M-COVX™ metabolic monitor resting energy expenditure (REE) on day 4 of Intensive Care Unit (ICU) admission. Calculations based on HBE were taken as standard, and percentage errors (PE) were calculated for each patient for values derived from simplistic formula and metabolic monitor. Adequacy of nutritional intake in ICU was also assessed. Results: Metabolic monitor could be used in only 20/70 patients. The mean age of patients was 40 years, 65% were males, and average body mass index was 23.69 kg/m2. Intermittent intolerance to feeds was reported in 50%. Values of REE and EEE were greater than BEE in 70% of patients. A significant difference was reported in values of PE of ≤20% and ≥30%; P = 0.0003 and 0.0001, respectively estimated using REE and EEE. Conclusions: It is not feasible to use metabolic monitors in all patients. Variability in readings is large and further studies are needed to establish the validity of its measurements. Calculations using simplistic formulas are much closer to values obtained using HBE.
Connecdenn, A Novel DENN Domain-Containing Protein of Neuronal Clathrin-Coated Vesicles Functioning in Synaptic Vesicle Endocytosis

Clathrin-coated vesicles (CCVs) are responsible for the endocytosis of multiple cargo, including synaptic vesicle membranes. We now describe a new CCV protein, termed connecdenn, that contains an N-terminal DENN (differentially expressed in neoplastic versus normal cells) domain, a poorly characterized protein module found in multiple proteins of unrelated function and a C-terminal peptide motif domain harboring three distinct motifs for binding the α-ear of the clathrin adaptor protein 2 (AP-2). Connecdenn coimmunoprecipitates and partially colocalizes with AP-2, and nuclear magnetic resonance and peptide competition studies reveal that all three α-ear-binding motifs contribute to AP-2 interactions. In addition, connecdenn contains multiple Src homology 3 (SH3) domain-binding motifs and coimmunoprecipitates with the synaptic SH3 domain proteins intersectin and endophilin A1. Interestingly, connecdenn is enriched on neuronal CCVs and is present in the presynaptic compartment of neurons. Moreover, connecdenn has a uniquely stable association with CCV membranes because it resists extraction with Tris and high-salt buffers, unlike most other CCV proteins, but it is not detected on purified synaptic vesicles. Together, these observations suggest that connecdenn functions on the endocytic limb of the synaptic vesicle cycle. Accordingly, disruption of connecdenn interactions with its binding partners through overexpression of the C-terminal peptide motif domain or knock down of connecdenn through lentiviral delivery of small hairpin RNA both lead to defects in synaptic vesicle endocytosis in cultured hippocampal neurons. Thus, we identified connecdenn as a component of the endocytic machinery functioning in synaptic vesicle endocytosis, providing the first evidence of a role for a DENN domain-containing protein in endocytosis.
A hybrid language model for open-vocabulary Thai LVCSR

This paper investigates the use of a hybrid language model for open-vocabulary Thai LVCSR. Thai text is written without word boundary markers and the definition of word unit is often ambiguous due to the presence of compound words. Hence, to build open-vocabulary LVCSR, a very large lexicon is required to also handle word unit ambiguity. Pseudo-morpheme (PM), a syllable-like sub-word unit specifically designed for Thai is considered to be a more well-defined unit. To overcome the problem of out-of-vocabulary words and to also reduce the size of the lexicon, a hybrid language model which combines word and sub-word units is proposed. Words and sub-words frequently found in several domains constitute open-vocabulary for general domain Thai LVCSR. To verify our scheme, we run recognition experiments on data from various tasks including broadcast news transcription, dictation and mobile speech-to-speech translation. Open-vocabulary Thai LVCSR using the hybrid language model obviously reduces the out-of-vocabulary problem. The proposed model having a much smaller lexicon size achieves a comparable recognition error rate to a baseline system using a full-word lexicon.
Human adaptation to a miniature robot: Precursors of mutual adaptation

Mutual adaptation is an important phenomenon in human-human communications. Traditionally HRI research was more interested in investigating adaptation of the robot to the human using machine learning techniques but the possibility of utilizing the natural ability of humans to adapt to other humans and artifacts including robots is recently becoming increasingly attractive. This paper presents some of the results from an experiment conducted to investigate the interaction patterns and effectiveness of motion cues as a feedback modality between a human operator and a miniature robot in a confined collaborative navigation task. The results presented in this paper show evidence of human adaptation to the robot and moreover suggest that the adaptation rate is not constant or continuous in time but is discontinuous and nonlinear. The results also show evidence of a starting exploration stage before the adaptation with duration dependent on the expectations of the human regarding the capabilities of the robot in the given task. The paper investigates how to utilize these and related findings for building robots not only capable of adapting to human operators but can also help those operators adapt to them.
Assessment of Children

Course Description Child Assessment serves as an introductory graduate course to the principles and theories of the assessment of children. Throughout the semester you will be exposed to numerous theories of assessment and domains of assessment. Additionally, you will develop basic competency in many of these areas through experiential tasks (e.g., administering and scoring an intelligence test). There is no widely accepted “right” assessment; however, there are better and worse assessments for individuals and problems. At the end of the course, you should be prepared to continue honing your assessment skills in future iterations of your training. Please note that this syllabus is a tentative schedule of the course and may change as the semester progresses.
Altered processing of corollary discharge in thalamic lesion patients

Accumulating evidence suggests that thalamic nuclei relay corollary discharge information of saccadic eye movements, enabling the visual system to update the representation of visual space. The present study aimed to explore the effect of thalamic lesions in humans on updating‐related cortical processing. Event‐related potentials were recorded while four patients with impairments in using corollary discharge information and 12 healthy control subjects performed a saccadic double‐step task. In the experimental condition, which required the use of corollary discharge information, control subjects showed a pronounced positivity over the parietal cortex starting about 150 ms after first saccade onset, reflecting the updating process. In the patients, parietal processing related to updating was altered. Three patients showed evidence of reduced updating event‐related potential effects, consistent with a unilateral deficit in using corollary discharge information. In two patients, the event‐related potential topography differed significantly from the topography pattern observed in controls. Thalamic damage affects updating‐related processing, presumably due to insufficient transfer of saccade‐related information to parietal areas. This study thus provides further evidence for thalamic involvement in relaying corollary discharge information related to saccadic eye movements. Our data suggest that integration of corollary discharge and motor information occurs directly before the second saccade in a double‐step task.
Situational Action Theory

Der gegenstandliche Beitrag gibt eine deutschsprachige Einfuhrung in die Situational Action Theory. Diese Theorie will erklaren, warum Menschen Verhaltensregeln befolgen oder brechen. Kriminalitat als Ubertretung strafrechtlich geschutzter Verhaltensregeln ist vom Erklarungsanspruch mit erfasst. Im Wesentlichen wird argumentiert, dass eine Person-Umwelt-Interaktion einen Wahrnehmungs-Entscheidungs-Prozess initiiert, der dann das individuelle Handeln steuert. Moralischen Faktoren wird dabei ein groseres Einflussgewicht beigemessen als kontrollierenden Kraften.
Real-Time Reverse Transcription Loop-Mediated Isothermal Amplification for Rapid Detection of West Nile Virus

ABSTRACT A one-step, single tube, real-time accelerated reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for detecting the envelope gene of West Nile (WN) virus. The RT-LAMP assay is a novel method of gene amplification that amplifies nucleic acid with high specificity, efficiency, and rapidity under isothermal conditions with a set of six specially designed primers that recognize eight distinct sequences of the target. The whole procedure is very simple and rapid, and amplification can be obtained in less than 1 h by incubating all of the reagents in a single tube with reverse transcriptase and Bst DNA polymerase at 63°C. Detection of gene amplification could be accomplished by agarose gel electrophoresis, as well as by real-time monitoring in an inexpensive turbidimeter. When the sensitivity of the RT-LAMP assay was compared to that of conventional RT-PCR, it was found that the RT-LAMP assay demonstrated 10-fold higher sensitivity compared to RT-PCR, with a detection limit of 0.1 PFU of virus. By using real-time monitoring, 104 PFU of virus could be detected in as little as 17 min. The specificity of the RT-LAMP assay was validated by the absence of any cross-reaction with other, closely related, members of the Flavivirus group, followed by restriction digestion and nucleotide sequencing of the amplified product. These results indicate that the RT-LAMP assay is extremely rapid, cost-effective, highly sensitive, and specific and has potential usefulness for rapid, comprehensive WN virus surveillance along with virus isolation and/or serology.