A disruptive alternative to semi-continuous multi-column chromatography processes

Protein purification to date is still dominated by expensive chromatography operations. Within the bioprocessing segment of the biopharmaceutical industry, enormous advances in upstream processing performance have moved the cost-reduction bottleneck to downstream processing (DSP). In an effort to reduce DSP costs, the industry is progressively turning to multi-column semi-continuous manufacturing techniques, adapted from neighbouring chemical processing industries. In the case of Affinity Chromatography, the primary theoretical advantage lies in alleviating particularly expensive bind/elute capture steps by allowing saturation of any given unit of resin with product feed while routing the partially depleted effluent flow-through material to follow-on unsaturated resin through the use of multiple columns in a sequence. The saturation better utilises the resin in each of its cycles allowing a reduction in per gram cost and improved time usage, and since saturation can achieve the full static binding capacity without being limited by a dynamic flow, this allows the system to flow faster, saving even more time. However, industrial adoption of these new techniques has been slow, owing to their significant increase in developmental and operational complexity and the capital expense of additional hardware requirements. In this presentation we will reveal and discuss processing factors that may significantly impact the true benefits in speed for multi-column processes, particularly relating to the necessary scheduling effects of aligning multiple synchronous columns, and to back pressure and column height effects that both slow the achievable productivity and mask true comparisons with traditional batch chromatography. We have found scenarios where these factors can combine to make semi-continuous multi-column processes significantly slower than equivalent batch processes, and the loss in productivity can, in some circumstances, cancel much of the cost savings on resin consumption. In an effort to understand, improve and simplify these semi-continuous processes, we internally developed a novel and potentially disruptive operational method that matches or exceeds the benefits of a semi-continuous process, without the complexity. Data from a prototype un-optimised version tested at pilot scale will show that significant performance gains can be achieved on standard chromatography equipment with minimal modification

Durability and generalization of attribution-based feedback following failure: Effects on expectations and behavioral persistence

Objective: This experiment investigated, following perceived failure, the immediate, long-term (i.e., durability), and cross-situational (i.e., generalization) effects of attribution-based feedback on expectations and behavioral persistence. Design: We used a 3×2 (Group×Time) experimental design over seven weeks with attributions, expectations of success, and persistence as dependent measures. Method: 49 novice participants were randomly assigned to one of three treatment (attributional feedback) groups: (a) functional (i.e., controllable and unstable); (b) dysfunctional (i.e., uncontrollable and stable); or (c) no feedback. Testing involved three sessions, in which participants completed a total of five trials across two performance tasks (golf-putting and dart-throwing). In order to track whether the attributional manipulation conducted within the context of the golf-putting task in Session 2 would generalize to a new situation, participants performed a dart-throwing task in Session 3, and their scores were compared with those recorded at baseline (in Session 1). Results: Analysis of pre- and post-intervention measures of attributions, expectations, and persistence revealed that the functional attributional feedback led to more personally controllable attributions following failure in a golf-putting task, together with increases in success expectations and persistence. In contrast, dysfunctional attributional feedback led to more personally uncontrollable and stable attributions following failure, together with lower success expectations and reduced persistence. These effects extended beyond the intervention period, were present up to four weeks post intervention, and were maintained even when participants performed a different (i.e., dart-throwing) task. Conclusions: The findings demonstrate that attributional feedback effects are durable over time and generalize across situations

Rapport de la campagne PROPPAC 04 à bord du N.O. Le Suroît (30 octobre au 26 novembre 1989)

La campagne PROPPAC 4, dont l'ORSTOM était maître d'oeuvre, s'est déroulée du 30 octobre au 26 novembre 1989 entre 20°S (nord de la Nouvelle-Calédonie) et 5°S le long de 165°E. L'objectif était de décrire en deux points fixes de 8 jours la variabilité à court terme des paramètres hydrologiques et planctoniques, leur répartition le long de la colonne d'eau, la distribution des différentes classes d'organismes et de mesurer l'intensité des flux : advection et mélanges, taux de sédimentation, production primaire et secondaire. Ces informations, recueillies dans deux situations oligotrophes considérées comme typiques, doivent permettre de compléter les données rudimentaires de biologie qui sont collectées au cours des stations de courte durée des radiales bi-annuelles SURTROPAC depuis 1984 et servir à la définition de la relation production-hydrologie dans le Pacifique occidental. La première station de 8 jours, dont la position a été choisie à l'issue d'une radiale préliminaire, était située à 7-8°S et caractérisée par une pycnocline profonde (75 m) et marquée, avec un maximum de chlorophylle vers 80-100 m. La seconde, située à 16°S, correspondrait à une structure hydrologique avec un faible gradient et des sels nutritifs vers 140 m, le maximum de chlorophylle se situant à 120-140 m. (Résumé d'auteur

Explaining the global distribution of peak-spectrum variability of sea surface height

Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 35 (2008): L14602, doi:10.1029/2008GL034312.A 14-year satellite observation of sea surface height (SSH) reveals an interesting pattern. Along any latitude, there is a frequency at which the SSH power spectrum peaks, regardless of which hemisphere or oceanic basin. This peak-spectrum frequency is nearly identical to the critical frequency at which the zonal energy propagation of Rossby waves becomes stagnant. The interior ocean adjusts to atmospheric forcing by radiating energy away through Rossby waves. There are two distinct groups of Rossby waves, long ones carry the energy to the west while short ones send the energy to the east. At the critical frequency, these two waves merge and their zonal energy propagation becomes stagnant. Consequently, the energy from atmospheric forcing may accumulate in the ocean interior, and thus result in a spectrum peak.This study is supported by China’s National Basic Research Priorities Programmer (2005CB422303 and 2007CB411804), the key project of the International Science and Technology Cooperation program of China (2006DFB21250), the Ministry of Education’s 111 Project (B07036), the Program for New Century Excellent Talents in University (NECT-07-0781), and the US National Science Foundation (OCE-0351055)

UNLV College of Education Multicultural & Diversity Newsletter

Each morning I wound my way up the steep hill along the deeply rutted dirt path, exchanging daily maaa\u27s with five bleating sheep and shouting out, ¡Hola! in response to the children who gleefully identified me as ¡Gringa! Women and children, colorful bowls of cooked maize balanced atop their heads, sauntered to and from Maria Elena\u27s where their maize would be ground; at home the dough would be shaped and flattened into tortillas, the mainstay of every meal in the small Guatemalan village of San Juan

Bragg- and Moving-glasses: a theory of disordered vortex lattices

We study periodic lattices, such as vortex lattices in type II superconductors in a random pinning potential. For the static case we review the prediction that the phase diagram of such systems consists of a topologically ordered Bragg glass phase, with quasi long range translational order, at low fields. This Bragg glass phase undergoes a transition at higher fields into another glassy phase, with dislocations, or a liquid. This proposition is compatible with a large number of experimental results on BSCCO or Thalium compounds. Further experimental consequences of our results and relevance to other systems will be discussed. When such vortex systems are driven by an external force, we show that, due to periodicity in the direction transverse to motion, the effects of static disorder persist even at large velocity. In $d=3$, at weak disorder, or large velocity the lattice forms a topologically ordered glass state, the ``moving Bragg glass'', an anisotropic version of the static Bragg glass. The lattice flows through well-defined, elastically coupled, static channels. We determine the roughness of the manifold of channels and the positional correlation functions. The channel structure also provides a natural starting point to study the influence of topological defects such as dislocations. In $d=2$ or at strong disorder the channels can decouple along the direction of motion leading to a ``smectic'' like flow. We also show that such a structure exhibits an effective transverse critical pinning force due to barriers to transverse motion, and discuss the experimental consequences of this effect.Comment: Proceedings of M2S-HTSC-V conference (Beijing, Feb 97) to be published in Physica C; 4 pages, 3 figures, uses espcrc2.st

Doping dependent charge order correlations in electron-doped cuprates

Understanding the interplay between charge order (CO) and other phenomena (e.g. pseudogap, antiferromagnetism, and superconductivity) is one of the central questions in the cuprate high-temperature superconductors. The discovery that similar forms of CO exist in both hole- and electron-doped cuprates opened a path to determine what subset of the CO phenomenology is universal to all the cuprates. Here, we use resonant x-ray scattering to measure the charge order correlations in electron-doped cuprates (La2-xCexCuO4 and Nd2-xCexCuO4) and their relationship to antiferromagnetism, pseudogap, and superconductivity. Detailed measurements of Nd2-xCexCuO4 show that CO is present in the x = 0.059 to 0.166 range, and that its doping dependent wavevector is consistent with the separation between straight segments of the Fermi surface. The CO onset temperature is highest between x = 0.106 and 0.166, but decreases at lower doping levels, indicating that it is not tied to the appearance of antiferromagnetic correlations or the pseudogap. Near optimal doping, where the CO wavevector is also consistent with a previously observed phonon anomaly, measurements of the CO below and above the superconducting transition temperature, or in a magnetic field, show that the CO is insensitive to superconductivity. Overall these findings indicate that, while verified in the electron-doped cuprates, material-dependent details determine whether the CO correlations acquire sufficient strength to compete for the ground state of the cuprates.Comment: Supplementary information available upon reques

Effectiveness of tapentadol prolonged release (PR) compared with oxycodone/naloxone PR for the management of severe chronic low back pain with a neuropathic component: a randomized, controlled, open‐label, phase 3b/4sStudy

[Abstract] OBJECTIVE: To evaluate the effectiveness of tapentadol prolonged release (PR) vs. oxycodone/naloxone PR in non-opioid-pretreated patients with severe chronic low back pain with a neuropathic pain component. METHODS: Eligible patients (average pain intensity [numerical rating scale-3 (NRS-3)] ≥6; painDETECT positive/unclear) were randomized to twice-daily tapentadol PR 50 mg or oxycodone/naloxone PR 10 mg/5 mg. After a 21-day titration (maximum twice-daily doses: tapentadol PR 250 mg, or oxycodone/naloxone PR 40 mg/20 mg plus oxycodone PR 10 mg), target doses were continued for 9 weeks. The primary effectiveness endpoint was the change in NRS-3 from baseline to final evaluation; the exact repeated confidence interval (RCI) for tapentadol PR minus oxycodone/naloxone PR was used to establish noninferiority (upper limit <1.3) and superiority (confirmatory analyses). RESULTS: For the primary effectiveness endpoint, tapentadol PR was noninferior to oxycodone/naloxone PR (97.5% RCI: [-1.820, -0.184]; P < 0.001). This exact RCI also yielded evidence of superiority for tapentadol PR vs. oxycodone/naloxone PR (significantly greater reduction in pain intensity; P = 0.003). Improvements (baseline to final evaluation) in painDETECT and Neuropathic Pain Symptom Inventory scores were significantly greater with tapentadol PR vs. oxycodone/naloxone PR (all P ≤ 0.005). CONCLUSIONS: The study was formally shown to be positive and demonstrated, in the primary effectiveness endpoint, the noninferiority for tapentadol PR vs. oxycodone/naloxone PR. The effectiveness of tapentadol PR was superior to that of oxycodone/naloxone PR by means of clinical relevance and statistical significance (confirmatory evidence of superiority). Tapentadol PR was associated with significantly greater improvements in neuropathic pain-related symptoms and global health status than oxycodone/naloxone PR and with a significantly better gastrointestinal tolerability profile. Tapentadol PR may be considered a first-line option for managing severe chronic low back pain with a neuropathic pain component