Miracle-dz/UniFAR-FTUs huggingface dataset:
Fabs-in-tandem immunoglobulin is a novel and versatile bispecific design for engaging multiple therapeutic targets

ABSTRACT In recent years, the development of bispecific antibody (bsAb) has become a major trend in the biopharmaceutical industry. By simultaneously engaging 2 molcular targets, bsAbs show unique mechanisms of action that could lead to clinical benefits unattainable by conventional monoclonal antibodies. Various bsAb generation formats have been described, and several are being investigated in clinical development. However, some bsAb constructs have proven to be problematic due to their unfavorable physicochemical and pharmacokinetic properties, as well as poor manufacturing efficiencies. We describe here a new bispecific design, Fabs-in-tandem immunoglobulin (FIT-Ig), in which 2 antigen-binding fragments are fused directly in a crisscross orientation without any mutations or use of peptide linkers. This unique design provides a symmetric IgG-like bispecific molecule with correct association of 2 sets of VH/VL pairs. We show that FIT-Ig molecules exhibit favorable drug-like properties, in vitro and in vivo functions, as well as manufacturing efficiency for commercial development.
A new range-sensor based globally convergent navigation algorithm for mobile robots

We present TangentBug, a new range-sensor based navigation algorithm for two degrees-of-freedom mobile robots. The algorithm combines local reactive planning with globally convergent behaviour. For the local planning, TangentBug uses the range data to compute a locally shortest path based on a novel structure, termed the local tangent graph (LTG). The robot uses the LTG for choosing the locally optimal direction while moving towards the target. The robot also uses the LTG in its other motion mode, where it follows an obstacle boundary. In this mode the robot uses the LTG for making local short-cuts and testing a leaving condition which allows the robot to resume its motion towards the target. We analyze the convergence and performance properties of TangentBug. We also present simulation results, showing that TangentBug consistently performs better than the classical VisBug algorithm. Moreover, TangentBug produces paths that in simple environments approach the globally optimal path as the sensor's maximal detection range increases.
Transmission of hepatitis B virus among heart transplant recipients during endomyocardial biopsy procedures.

BACKGROUND The unexpected conversion to HBsAg seropositivity of three cardiac allograft recipients prompted us to conduct a multidisciplinary study to identify the source, transmission mode, and extent of the hepatitis B virus (HBV) infection among the 256 cardiac allograft recipients of our hospital. METHODS All recipients were retrospectively screened for serum markers of HBV infection. A selected genomic region defining subtypes of the viruses involved was amplified and sequenced. An epidemiologic case-control study for possible risk factors was conducted to identify the mode of transmission. RESULTS Eighteen additional HBV-infected patients were identified, none of whom had shown symptoms of HBV infection. The involvement of one virus (subtype ayw 3) was shown in 20 of the 21 HBV-infected patients. This virus is found in less than 10% of HBV-infected individuals in The Netherlands. The demonstration of a common source of infection, combined with results of the epidemiologic study, identified posttransplantation endomyocardial biopsy procedures as the most likely mode of transmission. However, we also found evidence of secondary virus transmission by cardiac catheterization procedures to nonallograft recipients. CONCLUSIONS The immunosuppressive therapy practiced in these patients to prevent allograft rejection may have not only facilitated virus transmission by causing high levels of viremia but also left the spreading of HBV undetected by causing a subclinical course of the infection. These findings stress the necessity of strict hygienic precautions during intravascular diagnostic procedures and indicate that vaccination against and routine monitoring for certain bloodborne infections in cardiac allograft recipients should be considered.
Structure of the Q237W mutant of HhaI DNA methyltransferase: an insight into protein-protein interactions

Abstract We have determined the structure of a mutant (Q237W) of HhaI DNA methyltransferase, complexed with the methyl-donor product AdoHcy. The Q237W mutant proteins were crystallized in the monoclinic space group C2 with two molecules in the crystallographic asymmetric unit. Protein-protein interface calculations in the crystal lattices suggest that the dimer interface has the specific characteristics for homodimer protein-protein interactions, while the two active sites are spatially independent on the outer surface of the dimer. The solution behavior suggests the formation of HhaI dimers as well. The same HhaI dimer interface is also observed in the previously characterized binary (M.HhaIAdoMet) and ternary (M.HhaIDNAAdoHcy) complex structures, crystallized in different space groups. The dimer is characterized either by a noncrystallographic two-fold symmetry or a crystallographic symmetry. The dimer interface involves three segments: the aminoterminal residues 28, the carboxyterminal residues 313327, and the linker (amino acids 179184) between the two functional domains the catalytic methylation domain and the DNA target recognition domain. Both the amino- and carboxy-terminal segments are part of the methylation domain. We also examined proteinprotein interactions of other structurally characterized DNA MTases, which are often found as a 2-fold related dimer with the largest dimer interface area for the group-β MTases. A possible evolutionary link between the Type I and Type II restriction-modification systems is discussed.
Analytically bounding data cache behavior for real-time systems

This dissertation presents data cache analysis techniques that make it feasible to predict data cache behavior and to bound the worst-case execution time for a large class of real-time programs. Data Caches are an increasingly important architectural feature in most modern computer systems. They help bridge the gap between processor speeds and memory access times. One inherent difficulty of using data caches in a real-time system is the unpredictability of memory accesses, which makes it difficult to calculate worst-case execution times of real-time tasks. This dissertation presents an analytical framework that characterizes data cache behavior in the context of independent, periodic tasks with deadlines less than or equal to their periods, executing on a single, in-order processor. The framework presented has three major components. (1) The first component analytically derives data cache reference patterns for all scalar and non-scalar references in a task. Using these, it produces a safe and tight upper bound on the worst-case execution time of the task without considering interference from other tasks. (2) The second component calculates the worst-case execution time and response time of a task in the context of a multi-task, prioritized, preemptive environment. This component calculates Data-Cache Related Preemption Delay for tasks assuming that all tasks in the system are completely preemptive. (3) In the third component, tasks are allowed to have critical sections in which they access shared resources. In this context, two analysis techniques are presented. In the first one, a task executing in a critical section is not allowed to be preempted by any other task. In the second one, the framework incorporates Resource Sharing Policies to arbitrate accesses to shared resources, thereby improving responsiveness of high-priority tasks that do not use a particular resource. In all the components presented in this dissertation, a direct-mapped data cache is assumed. Experimental results demonstrate the value of all the analysis techniques described above in the context of data cache usage in a hard real-time system.
Monitoring urban transformation in the old city of Shanghai and its former foreign settlements from 1985 to 2014

In this paper, we monitored the urban morphology of the old city of Shanghai and its former foreign concessions from 1985 to 2014. Based on a time-series of Landsat 5, 7 and 8 images, this study used Iteratively Reweighted Multivariate Alteration Detection (IRMAD) analysis to detect land-use modifications from traditional urban pattern to new constructions. Results show that urban transformation mainly started in 1995 and perpetuate at an average rate of 88 ha per year. It also brings out that about 55% of the old urban pattern was modified in 2014. A detailed interpretation highlights the development of modern high-rise buildings, roads and subway networks, green infrastructures but also the conservation of protected historical buildings.
An MC-SS Platform for Short-Range Communications in the Personal Network Context

Wireless personal area networks (WPANs) have gained interest in the last few years, and several air interfaces have been proposed to cover WPAN applications. A multicarrier spread spectrum (MC-SS) air interface specified to achieve 130 Mbps in typical WPAN channels is presented in this paper. It operates in the 5.2 GHz ISM band and achieves a spectral efficiency of 3.25 . Besides the robustness of the MC-SS approach, this air interface yields to reasonable implementation complexity. This paper focuses on the hardware design and prototype of this MC-SS air interface. The prototype includes RF, baseband, and IEEE802.15. 3 compliant medium access control (MAC) features. Implementation aspects are carefully analyzed for each part of the prototype, and key hardware design issues and solutions are presented. Hardware complexity and implementation loss are compared to theoretical expectations, as well as flexibility is discussed. Measurement results are provided for a real condition of operations.
Extracranial Internal Carotid Artery Occlusion: The Role of Common Carotid Artery Volume Flow

Background and Purpose. Quantitative measurement of blood flow volume in the common carotid artery (CCA) is now possible using the color velocity imaging quantification (CVI‐Q) ultrasound technique. The aim of this study was to evaluate the cerebral hemodynamic effects of unilateral internal carotid artery (ICA) occlusion on CCA blood flow volumes (FVs) using CVI‐Q. Methods. Records of ultrasound studies in our neurosonology laboratory were retrospectively reviewed to identify patients with unilateral ICA occlusions who at a minimum received both a routine color duplex carotid ultrasound examination and quantitative measurement of FV in the CCA, bilaterally, using the CVI‐Q method. A total of 71 patients met criteria and were included in the cohort. A side to side comparison was performed for FV, peak systolic velocities (PSV), end‐diastolic velocities (EDV), and resistance indices (RIs) in the CCA. Results correlated with any other available data such as flow direction in the ophthalmic artery and the presence of intracranial collateralization. Results. The FV, PSV, and EDV were significantly reduced, and the RI was significantly increased in the CCA on the side of the occlusion. A subgroup analysis in patients who also had an examination of the ophthalmic (n= 61) and the intracranial arteries of the Circle of Willis (n= 50), showed significantly higher FV in the CCA on the side of the occlusion if there was also reversed flow in the ophthalmic artery on the side of the occlusion (344 ± 144 ml/min versus 169 ± 53 ml/min). Conclusion. Quantitative FV measurement using CVI‐Q ultrasound can identify clear alterations in volume flow, collateral pathways, and cerebral hemodynamics in patients with unilateral ICA occlusion. It is a complementary tool, providing additional objective information about the cerebral hemodynamic effects of ICA occlusion that goes beyond what is available using routine flow velocity data.
Rolling-circle replication of mitochondrial DNA in the higher plant Chenopodium album (L.)

The mitochondrial genomes of higher plants are larger and more complex than those of all other groups of organisms. We have studied the in vivo replication of chromosomal and plasmid mitochondrial DNAs prepared from a suspension culture and whole plants of the dicotyledonous higher plant Chenopodium album (L.). Electron microscopic studies revealed sigma-shaped, linear, and open circular molecules (subgenomic circles) of variable size as well as a minicircular plasmid of 1.3 kb (mp1). The distribution of single-stranded mitochondrial DNA in the sigma structures and the detection of entirely single-stranded molecules indicate a rolling-circle type of replication of plasmid mp1 and subgenomic circles. About half of the sigma-like molecules had tails exceeding the lengths of the corresponding circle, suggesting the formation of concatemers. Two replication origins (nicking sites) could be identified on mpl by electron microscopy and by a new approach based on the mapping of restriction fragments representing the identical 5' ends of the tails of sigma-like molecules. These data provide, for the first time, evidence for a rolling-circle mode of replication in the mitochondria of higher plants.
Origin and Course of the Dorsomedial Cutaneous Nerve to the Great Toe

The purpose of this study was to describe the course of the dorsomedial cutaneous nerve (DMCN) to the great toe. The DMCN is a branch of the medial dorsal cutaneous nerve, which originates from the superficial peroneal nerve. Injury to the DMCN may result in a painful neuroma. Identifying and protecting the DMCN to the great toe during surgical procedures near these areas may decrease the rate of painful neuroma formation.
RNA Polymerase II CTD Modifications: How Many Tales From a Single Tail

Eukaryote's RNA polymerases II (RNAPII) have the feature to contain, at the carbossi‐terminal region of their largest subunit Rpb1, a unique CTD domain. Rpb1‐CTD is composed of an increasing number of repetitions of the Y1S2P3T4S5P6S7 heptad that goes in parallel with the developmental level of organisms. Because of its composition, the CTD domain has a huge structural plasticity; virtually all the residues can be subjected to post‐translational modifications and the two prolines can either be in cis or trans conformations. In light of these features, it is reasonable to think that different specific nuances of CTD modification and interacting factors take place not only on different gene promoters but also during different stages of the transcription cycle and reasonably might have a role even if the polymerase is on or off the DNA template. Rpb1‐CTD domain is involved not only in regulating transcriptional rates, but also in all co‐transcriptional processes, such as pre‐mRNA processing, splicing, cleavage, and export. Moreover, recent studies highlight a role of CTD in DNA replication and in maintenance of genomic stability and specific CTD‐modifications have been related to different CTD functions. In this paper, we examine results from the most recent CTD‐related literature and give an overview of the general function of Rpb1‐CTD in transcription, transcription‐related and non transcription‐related processes in which it has been recently shown to be involved in. J. Cell. Physiol. 229: 538–544, 2014. © 2013 Wiley Periodicals, Inc.
Thrombin Regulates Intracellular cAMP Concentration in Human Platelets through Phosphorylation / Activation of PDE 3 A

Thrombin-induced cAMP reduction potentates several steps in platelet activation, including Ca mobilization, cytoskeletal reorganization, and fibrinogen receptor conformation. We now reinvestigate the signaling pathways by which intracellular cAMP content is controlled following platelet activation by thrombin. When washed human platelets were stimulated with thrombin, cAMP-dependent phosphodiesterase (PDE3A) activity was significantly increased. A non-selective PDE inhibitor, 3-Isobutyl1-methylxanthine (IBMX), and the PDE3 selective inhibitors milrinone and cilostazol each suppressed thrombin-induced cAMP-dependent PDE responses, but not two different PDE2 inhibitors. Selective inhibition of PDE3A resulted in reversal of thrombin-induced cAMP reduction indicating that thrombin activated PDE3A. In synergy with inhibition of adenylate cyclase by thrombin, activated PDE3A accelerates cAMP hydrolysis and maximally reduces the cAMP content. Thrombin-induced PDE3A activation was diminished concomitantly with dephosphorylation of PDE3A by proteinphosphatase 1 (PP1). An Akt inhibitor blocked PDE3A activation and constrained thrombin-induced cAMP reduction. A P2Y12 inhibitor also reduced thrombin-induced cAMP reduction. The combination of both reversed cAMP decrease by thrombin. Thrombin-mediated phosphorylated PDE3A was isolated by liquid chromatography, detected by a mAb against Akt-phosphorylated substrate, and verified by immunoprecipitation study. The predominant isoform phosphorylated by Akt was the 136 kDa species. We suggest that activation/phosphorylation of PDE3A via Akt signaling pathway participates in regulating cAMP during thrombin activation of platelets. For personal use only. on October 28, 2017. by guest www.bloodjournal. org From
Design and analysis of a reconfigurable robotic gripper for limp material handling

Discusses the design and modeling fundamentals of a multiple degree of freedom reconfigurable robotic gripper system (RGS), designed to reliably automate the process of limp material handling without causing distortion, deformation and/or folding. The reconfigurable gripper design draws upon the authors' (2000) previously reported work on the flat surfaced, fixed-dimensions gripper system. The design of the reconfigurable gripper system consists of four arms in a cross-bar configuration, with a flat surfaced, fixed dimensions, suction based gripper unit mounted on each of the arms. In the paper, the kinematic and dynamic performances of the reconfigurable robotic gripper system are analyzed and then validated using 1-DEAS software.
Sequential extraction of components of multicomponent PPS signals

A procedure for parameter estimation of multicomponent polynomial phase signals is presented. This scheme, while restricted to high SNRs, has the advantage of being extremely simple. It is also insensitive to the equal-coefficient identifiability problem of the HAF (high-order ambiguity function) based methods. It poses, however, some restrictions on the component amplitudes. Its performance in noise is investigated, and confirmed with several examples.
A Generic Curriculum Model for Computing Degree Programs

The current literature shows the existing curriculum models are unable to meet the needs of the today’s dynamic & complex education as the society is more open, diverse, multidimensional, fluid and more problematical. A generic curriculum model is proposed for all types of computer degree programs. The proposed model defines five meta-processes, a flexible structure for hidden and formal curriculum, and innovative ideas for branding and capstone project. Taking a futuristic approach and keeping an eye on the emerging needs of today’s knowledge driven society, the proposed model aims to transform students into valuable plug-n-play knowledge workers equipped with up-to-date knowledge, marketable skills, valuable competencies, unique expertise, globally compatible dispositions and culturally and professionally acceptable values. Through introducing competencies, expertise and dispositions among threshold standards we have given a new starting point for curriculum experts to extend the virtual boundaries of teaching-learning environment from classrooms to work-place environments. The proposed model not only meets the existing needs of the core computing disciplines but also accommodate the implications of newly emerging disciplines. Its flexible structure allows both institutions and faculty to decorate it according to their
Diversity of Prophages in Dominant Staphylococcus aureus Clonal Lineages

ABSTRACT Temperate bacteriophages play an important role in the pathogenicity of Staphylococcus aureus, for instance, by mediating the horizontal gene transfer of virulence factors. Here we established a classification scheme for staphylococcal prophages of the major Siphoviridae family based on integrase gene polymorphism. Seventy-one published genome sequences of staphylococcal phages were clustered into distinct integrase groups which were related to the chromosomal integration site and to the encoded virulence gene content. Analysis of three marker modules (lysogeny, tail, and lysis) for phage functional units revealed that these phages exhibit different degrees of genome mosaicism. The prevalence of prophages in a representative S. aureus strain collection consisting of 386 isolates of diverse origin was determined. By linking the phage content to dominant S. aureus clonal complexes we could show that the distribution of bacteriophages varied remarkably between lineages, indicating restriction-based barriers. A comparison of colonizing and invasive S. aureus strain populations revealed that hlb-converting phages were significantly more frequent in colonizing strains.
Submucous diathermy of the inferior turbinates in chronic hypertrophic rhinitis

Summary Twenty patients, 10 allergic and 10 non-allergic, with chronic hypertrophic rhinitis and presenting mainly with bilateral nasal obstruction were subjected to sub-mucosal diathermy of their inferior turbinates. There was significant post-operative improvement clinically, histopathologically and histochemically in the non-allergic group, while the improvement was less obvious in the allergic cases. The post-operative clinical improvement as regards rhinorrhea and sneezing was not as marked as that for nasal obstruction. Evaluation of the results showed that sub-mucous diathermy of inferior turbinates is a good line of treatment for cases of chronic hypertrophic rhinitis, with better results in the non-allergic group of patients.
The conserved amino‐terminal domain of hSRP1 alpha is essential for nuclear protein import.

Nuclear proteins are targeted through the nuclear pore complex (NPC) in an energy‐dependent reaction. The import reaction is mediated by nuclear localization sequences (NLS) in the substrate which are recognized by heterodimeric cytoplasmic receptors. hSRP1 alpha is an NLS‐binding subunit of the human NLS receptor complex and is complexed in vivo with a second subunit of 97 kDa (p97). We show here that a short amino‐terminal domain in hSRP1 alpha is necessary and sufficient for its interaction with p97. This domain is conserved in other SRP1‐like proteins and its fusion to a cytoplasmic reporter protein is sufficient to promote complete nuclear import, circumventing the usual requirement for an NLS receptor interaction. The same amino‐terminal domain inhibits import of NLS‐containing proteins when added to an in vitro nuclear transport assay. While full‐length hSRP alpha is able to leave the nucleus, the amino‐terminal domain alone is not sufficient to promote exit. We conclude that hSRP1 alpha functions as an adaptor to tether NLS‐containing substrates to the protein import machinery.