Legal Obstacles to Private Enforcement of Competition Law

Private enforcement of competition law serves many important goals, including deterrence of future anti-competitive harms and correction of past harms. This article sheds light on several potential legal obstacles to such enforcement which could prevent it from achieving its goals. The examples mainly build upon the experience of different jurisdictions with private litigation. It also suggests some possible solutions for dealing with or limiting such obstacles. As Europe is in the early stages of applying its Damages Directive and creating a private competition law enforcement regime, recognising – and possibly avoiding – obstacles to efficient private enforcement is both timely and important

A fluorophore attached to nicotinic acetylcholine receptor beta M2 detects productive binding of agonist to the alpha delta site

To study conformational transitions at the muscle nicotinic acetylcholine (ACh) receptor (nAChR), a rhodamine fluorophore was tethered to a Cys side chain introduced at the beta-19' position in the M2 region of the nAChR expressed in Xenopus oocytes. This procedure led to only minor changes in receptor function. During agonist application, fluorescence increased by (Delta-F/F) approximate to 10%, and the emission peak shifted to lower wavelengths, indicating a more hydrophobic environment for the fluorophore. The dose-response relations for Delta-F agreed well with those for epibatidine-induced currents, but were shifted approximate to 100-fold to the left of those for ACh-induced currents. Because (i) epibatidine binds more tightly to the alpha-gamma-binding site than to the alpha-delta site and (ii) ACh binds with reverse-site selectivity, these data suggest that Delta-F monitors an event linked to binding specifically at the alpha-delta-subunit interface. In experiments with flash-applied agonists, the earliest detectable Delta-F occurs within milliseconds, i.e., during activation. At low [ACh] (less than or equal to 10 muM), a phase of Delta-F occurs with the same time constant as desensitization, presumably monitoring an increased population of agonist-bound receptors. However, recovery from Delta-F is complete before the slowest phase of recovery from desensitization (time constant approximate to 250 s), showing that one or more desensitized states have fluorescence like that of the resting channel. That conformational transitions at the alpha-delta-binding site are not tightly coupled to channel activation suggests that sequential rather than fully concerted transitions occur during receptor gating. Thus, time-resolved fluorescence changes provide a powerful probe of nAChR conformational changes

Noise sensitivity of an atomic velocity sensor

We use Bloch oscillations to accelerate coherently Rubidium atoms. The variation of the velocity induced by this acceleration is an integer number times the recoil velocity due to the absorption of one photon. The measurement of the velocity variation is achieved using two velocity selective Raman pi-pulses: the first pulse transfers atoms from the hyperfine state 5S1/2 |F=2, mF=0> to 5S1/2, |F=1, mF = 0> into a narrow velocity class. After the acceleration of this selected atomic slice, we apply the second Raman pulse to bring the resonant atoms back to the initial state 5S1/2, |F=2, mF = 0>. The populations in (F=1 and F=2) are measured separately by using a one-dimensional time-of-flight technique. To plot the final velocity distribution we repeat this procedure by scanning the Raman beam frequency of the second pulse. This two pi-pulses system constitutes then a velocity sensor. Any noise in the relative phase shift of the Raman beams induces an error in the measured velocity. In this paper we present a theoretical and an experimental analysis of this velocity sensor, which take into account the phase fluctuations during the Raman pulses

Predicting Fracture in the Proximal Humerus using Phase Field Models

Proximal humerus impacted fractures are of clinical concern in the elderly population. Prediction of such fractures by CT-based finite element methods encounters several major obstacles such as heterogeneous mechanical properties and fracture due to compressive strains. We herein propose to investigate a variation of the phase field method (PFM) embedded into the finite cell method (FCM) to simulate impacted humeral fractures in fresh frozen human humeri. The force-strain response, failure loads and the fracture path are compared to experimental observations for validation purposes. The PFM (by means of the regularization parameter $l_0$) is first calibrated by one experiment and thereafter used for the prediction of the mechanical response of two other human fresh frozen humeri. All humeri are fractured at the surgical neck and strains are monitored by Digital Image Correlation (DIC). Experimental strains in the elastic regime are reproduced with good agreement ($R^2 = 0.726$), similarly to the validated finite element method [9]. The failure pattern and fracture evolution at the surgical neck predicted by the PFM mimic extremely well the experimental observations for all three humeri. The maximum relative error in the computed failure loads is $3.8\%$. To the best of our knowledge this is the first method that can predict well the experimental compressive failure pattern as well as the force-strain relationship in proximal humerus fractures

Dipole and Bloch oscillations of cold atoms in a parabolic lattice

The paper studies the dynamics of a Bose-Einstein condensate loaded into a 1D parabolic optical lattice, and excited by a sudden shift of the lattice center. Depending on the magnitude of the initial shift, the condensate undergoes either dipole or Bloch oscillations. The effects of dephasing and of atom-atom interactions on these oscillations are discussed.Comment: 3 pages, to appear in proceeding of LPHYS'05 conference (July 4-8, 2005, Kyoto, Japan

A phase II study of retifanlimab (INCMGA00012) in patients with squamous carcinoma of the anal canal who have progressed following platinum-based chemotherapy (POD1UM-202)

PD-L1 inhibitor; Anal cancer; RetifanlimabInhibidor de PD-L1; Cáncer anal; RetifanlimabInhibidor de PD-L1; Càncer anal; RetifanlimabBackground Locally advanced or metastatic squamous carcinoma of the anal canal (SCAC) has poor prognosis following platinum-based chemotherapy. Retifanlimab (INCMGA00012), a humanized monoclonal antibody targeting programmed death protein-1 (PD-1), demonstrated clinical activity across a range of solid tumors in clinical trials. We present results from POD1UM-202 (NCT03597295), an open-label, single-arm, multicenter, phase II study evaluating retifanlimab in patients with previously treated advanced or metastatic SCAC. Patients and methods Patients ≥18 years of age had measurable disease and had progressed following, or were ineligible for, platinum-based therapy. Retifanlimab 500 mg was administered intravenously every 4 weeks. The primary endpoint was overall response rate (ORR) by independent central review. Secondary endpoints were duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results Overall, 94 patients were enrolled. At a median follow-up of 7.1 months (range, 0.9-19.4 months), ORR was 13.8% [95% confidence interval (CI) 7.6% to 22.5%], with one complete response (1.1%) and 12 partial responses (12.8%). Responses were observed regardless of human immunodeficiency virus or human papillomavirus status, programmed death ligand 1 (PD-L1) expression, or liver metastases. Stable disease was observed in 33 patients (35.1%) for a DCR of 48.9% (95% CI 38.5% to 59.5%). Median DOR was 9.5 months (range, 5.6 months-not estimable). Median (95% CI) PFS and OS were 2.3 (1.9-3.6) and 10.1 (7.9-not estimable) months, respectively. Retifanlimab safety in this population was consistent with previous experience for the PD-(L)1 inhibitor class. Conclusions Retifanlimab demonstrated clinically meaningful and durable antitumor activity, and an acceptable safety profile in patients with previously treated locally advanced or metastatic SCAC who have progressed on or are intolerant to platinum-based chemotherapy.This work was supported by Incyte Corporation (Wilmington, DE, USA) (no grant number)

Microstructured blood vessel surrogates reveal structural tropism of motile malaria parasites

Plasmodium sporozoites, the highly motile forms of the malaria parasite, are transmitted naturally by mosquitoes and traverse the skin to find, associate with, and enter blood capillaries. Research aimed at understanding how sporozoites select blood vessels is hampered by the lack of a suitable experimental system. Arrays of uniform cylindrical pillars can be used to study small cells moving in controlled environments. Here, an array system displaying a variety of pillars with different diameters and shapes is developed in order to investigate how Plasmodium sporozoites associate to the pillars as blood vessel surrogates. Investigating the association of sporozoites to pillars in arrays displaying pillars of different diameters reveals that the crescent-shaped parasites prefer to associate with and migrate around pillars with a similar curvature. This suggests that after transmission by a mosquito, malaria parasites may use a structural tropism to recognize blood capillaries in the dermis in order to gain access to the blood stream

An optical lattice on an atom chip

Optical dipole traps and atom chips are two very powerful tools for the quantum manipulation of neutral atoms. We demonstrate that both methods can be combined by creating an optical lattice potential on an atom chip. A red-detuned laser beam is retro-reflected using the atom chip surface as a high-quality mirror, generating a vertical array of purely optical oblate traps. We load thermal atoms from the chip into the lattice and observe cooling into the two-dimensional regime where the thermal energy is smaller than a quantum of transverse excitation. Using a chip-generated Bose-Einstein condensate, we demonstrate coherent Bloch oscillations in the lattice.Comment: 3 pages, 2 figure