Miracle-dz/UniFAR-FTUs huggingface dataset:
Recombinant antibodies for cancer therapy

Background: Recombinant antibodies have evolved into successful therapeutics with 10 approved for cancer and more in the pipeline. Four of the top ten cancer therapy drugs are recombinant antibodies. Objectives: To survey the current state-of-the-art highlighting the reasons for this success and looking ahead to the next generation of antibody therapy. Methods: An analysis was carried out to identify preclinical and clinical examples and the underlying concepts and mechanisms that have shown how to design better therapies. Results/conclusions: Greater understanding of the molecular basis of cancer has led to improved antibodies and a greater selection of targets. Fine tuning of successful antibodies through modification of glycosylation, affinity, size and other parameters are paying dividends. Fc-engineering is likely to be predominant in the near future but conjugates, fragments and fusion proteins will continue to be developed and find their place in the arsenal of antibody therapeutics.
Loading, release and stability of epirubicin-loaded drug-eluting beads

Purpose The aim of this study was to determine the loading efficiency, physico-chemical stability and release of epirubicin-loaded DC Bead™ (Biocompatibles UK Ltd, a BTG International group company) (bead size 70–150 µm (=DC BeadM1™) and 100–300 µm) after loading with epirubicin solution (2 mg/ml) or reconstituted powder formulation (25 mg/ml) and controlled storage. Methods DC Bead™ were loaded with 76 mg epirubicin solution (Epimedac™, Medac GmbH) or 75 mg epirubicin powder formulation (Farmorubicin™, Pharmacia Pfizer GmbH) per 2 ml of beads. Drug loading efficiency and stability were determined by measuring the epirubicin concentration in the excess solution after predetermined intervals (maximum 24 h) and different agitation conditions. Syringes with loaded beads were stored protected from light at room temperature. At predetermined intervals the beads were transferred into 200 ml phosphate buffered solution (pH 7.2) as elution medium and stirred automatically for 2 h not followed or followed by addition of 200 ml of 20% sodium chloride (=NaCl) solution and stirred for another 2 h to analyse the drug release and integrity of the epirubicin-loaded beads. Elution experiments were performed and samples taken periodically over a four-week period (day 0, 7, 14 and 28). A reversed-phase high-performance liquid chromatography assay with ultraviolet detection was utilized to analyse the concentration and purity of epirubicin. Results The loading procedure for DC Bead™ with epirubicin drug solutions resulted in a loading percentage of 95–99% within 6 h dependent on the bead size, epirubicin concentration in the loading solution and loading conditions. Loading levels remained stable and no epirubicin degradation products were observed over the period of 28 days, while the loaded beads were stored light protected at room temperature. Release of epirubicin into 200 ml phosphate buffered solution elution medium and additionally followed by release into the admixture with 200 ml 20% NaCl solution amounted to 5% and about 20% of the loaded epirubicin, respectively. Integrity of loaded epirubicin was proven over 28 days. Conclusions Epirubicin can be loaded into DC Bead™ of different sizes using the epirubicin powder formulation (25 mg/ml) or epirubicin injection concentrate (2 mg/ml). Physico-chemical stability is maintained over a period of at least 28 days when stored light protected at room temperature. Elution of epirubicin is dependent on the volume and cation exchange capacity of the elution medium.
Psychometric evaluation of the Customary Drinking and Drug Use Record (CDDR): a measure of adolescent alcohol and drug involvement.

OBJECTIVE The present study was undertaken to assess the psychometric characteristics of the Customary Drinking and Drug Use Record (CDDR), an interviewer-administered questionnaire. The CDDR provides current (past 3 months) and lifetime measures of four alcohol- and other drug-related domains: level of involvement, withdrawal characteristics, psychological/behavioral dependence symptoms, and negative consequences. The present report describes the evaluation of the psychometric properties of the instrument with youth between the ages of 13 and 22 years who had markedly variable histories of involvement with alcohol and other psychoactive substances. METHOD The sample assessed was composed of 166 adolescents recruited from two inpatient substance abuse treatment programs and 115 adolescents recruited from the community. Of the 281 subjects, 150 were male. Follow-up interviews with each adolescent and a resource person were conducted 6, 12, 24 and 48 months after the initial assessment. RESULTS Reliability of the CDDR was assessed by examination of internal consistency, test-retest reliability and interrater reliability. Convergent, discriminant and construct validity were evaluated for each of the CDDR domains, and gender and ethnic differences on substance involvement were examined. The CDDR was found to be internally consistent and reliable over time and across interviewers for each major domain assessed. The findings supported the validity of the four domains of alcohol and other drug involvement assessed on the CDDR. CONCLUSIONS The present results demonstrated convergent validity of the CDDR, ability to differentiate abusing from nonabusing youth and strong diagnostic specificity when compared to other standard instruments. The solid psychometric characteristics of the CDDR support its use for both research and clinical purposes.
Traffic engineering in next-generation optical Networks

In this article traffic-engineering issues regarding network survivability, traffic grooming, impairment-aware routing, virtual-topology engineering, and coordination among multiple layers of network architecture will be reviewed for next-generation optical networks based on wavelength-division multiplexing (WDM). Due to the recent progress and development of WDM technology, increasing traffic demands can be readily accommodated in the next-generation optical networks. In spite of the huge amount of capacity (e.g., OC-192) provided by a WDM channel, enhanced network services and network performance improvement can only be achieved with efficient traffic-engineering mechanisms. The fault-tolerant function is essential in order to provide seamless services to users by protecting their traffic against failures in the optical network because many connections can be carried on a fiber. Because the capacity of a WDM channel is very large, its bandwidth may not be efficiently utilized by a single connection. Hence, low-rate user connections need to be efficiently aggregated through the traffic-grooming scheme. An intelligent routing algorithm is especially necessary in the optical network where signal impairments due to device imperfections might degrade the signal quality. In addition, the virtual network connectivity (topology) should be flexibly maintained such that dynamic changes to the traffic demands can be easily absorbed, which can be implemented by the virtual-topology engineering method in a WDM network. As the dominant usage of Internet protocol (IP) of the Internet is expected to reside directly above the WDM layer in the future network, the coordinated traffic-engineering scheme should be deliberately designed for the multi-layer network by judiciously choosing where to put many overlapping functions in the different network layers.
Granulocyte depletion attenuates sustained pulmonary hypertension and increased pulmonary vasoreactivity caused by continuous air embolization in sheep.

Chronic pulmonary hypertension can develop in diseases associated with acute or repeated inflammation in the lungs, e.g., adult respiratory distress syndrome, chronic bronchitis. Inflammation has also been associated with some animal models of chronic pulmonary hypertension. We have previously shown that 12 days of continuous air embolization into sheep results in the functional and structural changes of chronic pulmonary hypertension. To determine whether granulocytes contribute to these changes, five sheep were granulocyte-depleted with hydroxyurea immediately before and during air embolization (AIR-PMN) and were compared with sheep receiving air embolization (AIR only). Air embolization was discontinued briefly every 4 days for monitoring of pulmonary vascular pressures and assessment of pulmonary vasoreactivity to a bolus injection of PGH2-A. After 12 days of air embolization, the lungs were removed for structural studies. AIR-PMN sheep did not develop the sustained increase in pulmonary artery pressure seen in the AIR sheep (Day 12, AIR-PMN = 20 +/- 3 cm H2O; AIR = 29 +/- 2; mean +/- SE). Similarly, the increased pulmonary pressor response to PGH2-A seen in AIR sheep was not found in the AIR-PMN group. Structural studies of the barium-injected lungs of AIR-PMN sheep revealed a twofold increase in medial thickness of normally muscular arteries and a significant increase in the percent of muscular intraacinar arteries (similar to findings in lungs from AIR sheep). The number of barium-filled arteries was increased in AIR-PMN sheep when compared with that in AIR sheep, but the number was still less than in the control sheep. We conclude that granulocytes may contribute to the functional changes of chronic pulmonary hypertension after continuous air embolization in sheep, but they do not play a role in structural changes involving pulmonary arterial smooth muscle cells and their precursors. The present data also suggest that the reduction in peripheral arterial filling is the structural alteration that contributes most to the sustained rise in pulmonary artery pressure. The data further suggest that pulmonary hypertension after air embolization may have a vasoconstrictive component that is granulocyte-dependent.
Comparison of the Frequency Compensation Techniques for CMOS Two-Stage Miller OTAs

Several design options are nowadays available for the frequency compensation of CMOS two-stage transconductance operational amplifiers, from the traditional Miller approach employing a nulling resistor or a voltage buffer, to a current buffer or the more modern current amplifier. However, designers have no results on the frequency performance achievable that allow to consciously choose the best approach to meet the prescribed specifications efficiently. In this paper, a comparison among the possible Miller approaches is carried out by exploiting an analytical figure of merit that expresses a tradeoff between gain-bandwidth product, load capacitance, and total transconductance for a given value of phase margin. Interesting and useful results, even unexpected, are found. The accuracy of the comparison is also validated through simulations.
CD19 regulates the development of bleomycin-induced pulmonary fibrosis in a mouse model.

OBJECTIVE The contribution of CD19 and B lymphocytes to pulmonary fibrosis is controversial. The aim of this study was to address the role of CD19 during the development of pulmonary fibrosis. METHODS Mice lacking or overexpressing the B cell surface molecule CD19, which is known as a positive regulator of B cell activation, were used in a model of bleomycin-induced pulmonary fibrosis. Ten or sixteen days after intratracheal injection of bleomycin, lung sections from mice were evaluated by histologic analysis. Seven days after instillation, the total leukocyte count and the number of B cells in bronchoalveolar lavage fluid (BALF) were determined, using a hemocytometer and flow cytometry. Bleomycin was also administered into selectin-deficient or intercellular adhesion molecule 1-deficient mouse strains. The level of CXCR3 expression on B cells was determined by flow cytometry. RESULTS CD19 deficiency significantly reduced susceptibility to intratracheal bleomycin challenge on day 16, while CD19 overexpression augmented fibrosis even on day 10. Furthermore, the survival rate and number of B cells in BALF also correlated with CD19 expression levels. The accumulation of B cells in BALF was dependent on CD19 levels, whereas there was no association with the levels of selectins or intercellular adhesion molecule 1. Additionally, CXCR3 was up-regulated in BALF B cells, while it was rarely expressed on circulating B cells. Furthermore, CD19 signaling facilitated B cell CXCR3 up-regulation in response to stimulation in vitro. CONCLUSION These results suggest that CD19 signaling is associated with the development of pulmonary fibrosis by controlling B cell infiltration into lung tissue, which may be associated with CXCR3 up-regulation.
Postoperative treatment outcome in canine mammary tumors. Multivariate analysis of the prognostic value of pre- and postoperatively available information.

OBJECTIVE Mammary tumors belong to the most common canine neoplasias. Few data are available on postoperative outcome and independent prognostic value of variables including pre-operatively available parameters such as cytology. The aim of this study was to characterize outcome following surgery and identify independent prognostic factors in canine mammary tumors. MATERIAL AND METHODS Prospective study in which dogs with mammary tumors underwent surgical tumor removal followed by histopathologic examination of the neoplasias. Kaplan-Meier log rank analysis and multivariate regression analyses were used to evaluate survival, recurrence-free interval (RFI) and metastasis free interval (MFI) as well as independent influence of variables on outcome. RESULTS 134 dogs with mammary tumors were included. In 126 dogs without distant metastasis, overall survival duration was 1113 d; median RFI and MFI were not reached. Histologic grade showed independent influence on duration of RFI (p=0.040), MFI (p=0.007), and survival (p=0.029). Median survival in benign (n=98), grade 1 (n=10) and grade 2 (n=16) malignant tumors was 1319 d, 670 d, 406 d, respectively. Cytology exerted independent influence on the likelihood for recurrence (p=0.013), duration of RFI (p=0.026) and survival (p=0.030). CONCLUSION AND CLINICAL RELEVANCE Histologic grade was of independent prognostic significance for postoperative outcome in this population of dogs with mammary tumors. As a pre-operatively available parameter, cytology may also possess prognostic value in canine mammary neoplasias.
Laminar organization of epileptiform discharges in the rat entorhinal cortex in vitro

1 Interictal and ictal epileptiform discharges induced by 4‐aminopyridine (4AP, 50 μM) were studied in the rat lateral entorhinal cortex with field potential and intracellular recordings in an in vitro slice preparation. Both types of discharge disappeared in layer II, but continued to occur in layers IV‐VI after a knife cut separation was made at approximately 600 μm from the pia (n= 4 slices). 2 Interictal depolarizations recorded in layer IV‐VI cells (amplitude, 29.4 ± 8.6 mV; duration, 386 ± 177.4 ms, means ± s.d.; n= 17) were capped by action potential bursts, while smaller interictal depolarizations in layer II cells (amplitude, 11.7 ± 5.8 mV; duration, 192.6 ± 47.9 ms; n= 10) were associated with single action potentials and were terminated by a hyperpolarization. Ictal discharges were initiated by an interictal discharge; they were characterized by a depolarization of 31.5 ± 6.2 mV (n= 12) in layer IV‐VI and 11.6 ± 3.5 mV (n= 7) in layer II neurones. 3 Slow, presumptive Ca2+‐mediated spikes occurred in layer II (n= 4) and IV‐VI (n= 6) cells loaded with the Na+ channel blocker QX‐314 (50 mM). These events were synchronized with population spikes during interictal and ictal discharges, and were abolished by Ni2+ (1 mM, n= 4 cells) along with the 4AP‐induced synchronous activity. 4 The N‐methyl‐D‐aspartate (NMDA) receptor antagonist 3,3‐(2‐carboxypiperazine‐4‐yl)‐propyl‐1‐phosphonate (CPP, 10 μM) abolished ictal discharges and reduced interictal depolarizations in layer IV‐VI neurones (n= 4). The non‐NMDA receptor antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX, 10 μM) abolished both interictal and ictal activity (n= 4 cells). 5 These findings provide evidence for a role played by NMDA‐mediated mechanisms in the generation of epileptiform discharges in the entorhinal cortex. Lack of an NMDA‐mediated component along with presence of inhibition in layer II neurones results in attenuation of epileptiform activity at this site. Moreover Ca2+‐mediated spikes may contribute to the appearance of epileptiform discharges in this model.
How can high mobility channel materials boost or degrade performance in advanced CMOS

Big hopes are still placed in high mobility materials such as III–V compound semiconductors. The key new elements that may moderate this belief are: degradation of DIBL, subthreshold slope and gate capacitance due to larger dielectric constant and smaller density of states in III–V materials. We will show how DIBL plays directly on performance, especially in LP technologies. This effect is now for the first time taken into account along with all other degradation sources associated with III–V channels. As a result, the gain in performance turns out to be much smaller than the expected 2X, and even become negative. This analysis also shows in which applications and conditions, the III–V channels exhibit their strengths the best.
Cavisoma magnum (Cavisomidae), a unique Pacific acanthocephalan redescribed from an unusual host, Mugil cephalus (Mugilidae), in the Arabian Gulf, with notes on histopathology and metal analysis

Cavisoma magnum (Southwell, 1927) Van Cleave, 1931 was originally described from a sea bass, Serranus sp. and spotted surgeonfish, Ctenochaetus strigosus (Perciformes) off Sri Lanka before its more recent redescription from milkfish in the Philippines in 1995. These reports were based on only light infections of their host fishes. Of the few flathead grey mullets, Mugil cephalus (Mugilidae), that we examined in the Arabian Gulf, one fish was infected with 1,450 worms. One milkfish, Chanos chanos (Chanidae), from the same location in the Arabian Gulf, was also heavily infected with specimens of C. magnum. The descriptions of this unique large worm are revised and for the first time, we provide SEM images, new systematic observations, metal analysis of hooks showing extremely high levels of sulfur, and histopathology in the mullet intestinal tissue. Adjustments and corrections of previous descriptive accounts are made. The histopathology studies show extensive damage to the host intestinal tissue including epithelial necrosis, hemorrhaging and worm encapsulation. There is an extensive amount of host connective tissue surrounding the worm. Results of x-ray analysis displayed high levels of sulfur in proboscis hooks, especially at the tips and edges of these attachment structures.
Clinical impact of ultrathin colonoscopy for Crohn's disease patients with strictures

Mucosal healing is now the ideal treatment goal for patients with Crohn's disease (CD) and endoscopy is suitable for both visualizing the intestinal mucosa and optimizing treatment according to the objective endoscopic findings; however, passing through strictures with a conventional colonoscope is sometimes difficult. An ultrathin colonoscope (outer diameter 9.2 mm) has been developed for superior insertion performance.
Generational Wealth Accounts: Did Public and Private Inter-Generational Transfers Offset Each Other Over the Financial Crisis?

We develop Generational Wealth Accounts (GWA): the first set of balance sheets, broken down by generations, to include all human capital, tangible wealth, financial wealth, and transfer wealth, and the uses to which these resources are put. We then use them to measure the size, nature (public or private; capital or current) and direction of inter-generational transfers and assess the sustainability of public and private consumption plans. We confirm that public sector consumption in the UK is unsustainable but show that the private sector is close to balance. Aggregate consumption plans are therefore unsustainable. Although public sector finances worsened significantly over the crisis, the private sector balance improved and capital transfers to the young increased, more than fully offsetting this deterioration. We find that increases in house prices redistributed resources away from the young and towards the old but had little effect on overall sustainability.
Management of heparin-induced thrombocytopenia

Purpose of reviewThe purpose of this review is to summarize recent findings on heparin-induced thrombocytopenia (HIT), a prothrombotic disorder caused by platelet-activating IgG targeting platelet factor 4 (PF4)/polyanion complexes. Recent findingsHIT can explain unusual clinical events, including adrenal hemorrhages, arterial/intracardiac thrombosis, skin necrosis, anaphylactoid reactions, and disseminated intravascular coagulation. Sometimes, HIT begins/worsens after stopping heparin (‘delayed-onset’ HIT). Various HIT-mimicking disorders are recognized (e.g., acute disseminated intravascular coagulation/‘shock liver’ with limb ischemia). HIT has features of both B-cell and T-cell immune responses; uptake of PF4/heparin complexes into macrophages (‘macropinocytosis’) facilitates the anti-PF4/heparin immune response. Antibody-induced activation of monocytes and platelets via their Fc&ggr;IIA receptors triggers an intense procoagulant response. Sometimes, HIT antibodies recognize PF4 bound to (platelet-associated) chondroitin sulfate, explaining how HIT might occur without concurrent or recent heparin (delayed-onset HIT, ‘spontaneous HIT syndrome’). The molecular structure of HIT antigen(s) has been characterized, providing a rationale for future drug design to avoid HIT and improve its treatment. The poor correlation between partial thromboplastin time and plasma argatroban levels (risking subtherapeutic anticoagulation) and need for intravenous administration of argatroban have led to increasing ‘off-label’ treatment with fondaparinux or one of the direct oral anticoagulants. SummaryUnderstanding the molecular mechanisms and unusual clinical features of HIT will improve its management.
A case study about the use and evaluation of cyber deceptive methods against highly targeted attacks

Traditional defences such as intrusion detection systems, firewalls and antivirus software are not enough to prevent security breaches caused by highly targeted cyber threats. As many of these attacks go undetected, this paper shows the results of a case study which consists of implementation of a methodology that selects, maps, deploys, tests and monitors the deceptions for the purpose of early detection. Metrics are developed to validate the effectiveness of the deception implementation. Firstly, various deception mechanisms are mapped to the first three phases of the intrusion kill chain: reconnaissance, weaponization and delivery. Then, Red Teams were recruited to test the deceptions for two case scenarios. Applying metrics, it is shown that the deceptions in the case studies are effective in the detection of cyber threats before the target asset was exploited and successful in creating attacker confusion and uncertainty about the organization’s network topology, services and resources.