Law in the Cultivation of Hope

In recent years scholars have begun to question the longstanding dichotomization of (legal) reason and the passions, and have offered significant understanding of the connection of law and the emotions. Much of this work, however, has been done within a fairly narrow ambit. This Article seeks to broaden this scholarship in two ways. First, it points to an unexplored relation between law and the emotions: the role of law in cultivating the emergence of emotions. And second, it moves beyond the negative emotions, and directs attention to positive emotions and their interplay with the law outside the criminal context. Following these two new directions, the Article focuses on the role of law in the cultivation of hope. It suggests a role for law that has not been explored before: facilitating the emergence of positive emotions, and thus empowering law’s beneficiaries. The Article first uncovers the structure of hope as an emotion, and identifies the necessary qualities for developing individual hopes: the ability to imagine new possibilities not encompassed by one’s present condition; a sense of agency sufficient to envision oneself pursuing distant objectives; and adequate resources that enable bringing such goals about. After characterizing individual hope, the Article turns to a less-discussed possibility: the active, external effort to cultivate hope in people whose deprivation prevents them from envisioning and pursuing alternative futures for themselves. A profile of a beneficial effort to cultivate hope in others is then developed, drawing on the narrative of the award-winning documentary film “Born into Brothels”. This original profile reflects five elements that are central to such an effort: communicating recognition and vision; introducing an activity that allows for individuation; providing resources; supporting agency; and fostering solidarity. However, given the systematic character of the social problems that give rise to despair, individual efforts at cultivation may not suffice and institutional interventions, including those secured by law, may be indispensable. This Part concludes by discussing the perils entailed in such an enterprise. Finally the Article applies its analysis to the cultivation of hope through law. It explores the example of Project Head Start, which was enacted as a core component of the War on Poverty. For decades the Project has served to engage poor children and their families in new opportunities for personal and collective growth. Remarkably, this study finds many of the characteristics of a successful cultivation of hope in certain features of the Project that are required or facilitated by law: the involvement of parents in the operation of the Project\u27s local centers, and the strong solidarity that has emerged among parents, and between parents and Project staff. It further illustrates how some of the predicted risks of cultivating hope have materialized in this context, while others have not. The Article concludes by calling for further investigation of the promising notion that, by drawing on its capacity to cultivate positive emotions, the law may play an empowering role in the lives of individuals and groups

Heterotrophic and Autotrophic Contribution to Dinitrogen Fixation in the Gulf of Aqaba

We evaluated the seasonal contribution of heterotrophic and autotrophic diazotrophy to the total dinitrogen (N2) fixation in the photic zone of a pelagic station in the northern Gulf of Aqaba, Red Sea. N2 fixation rates were highest during a Trichodesmium bloom in winter (0.7 nmol N l-1 d-1), decreased 7-fold 1 wk later throughout the upper 200 m (~0.1 nmol N l-1) d-1), and were significantly coupled with both primary and bacterial productivity. N2 fixation rates were generally higher in the upper 200 m (~0.4 nmol N l-1) d-1)) during the thermally stratified summer and were correlated solely with bacterial productivity. Experimental enrichment of seawater by phosphorus (P) enhanced bacterial productivity and N2 fixation rates during both seasons by 3- to 5-fold. Moreover, during the stratified season, experimental amendments to seawater applying a combination of the photosynthetic inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea and a mixture of amino acids increased both bacterial productivity and N2 fixation rates. Our findings from the northern Gulf of Aqaba indicate that in the photic zone, a shift occurs in the diazotrophic community from phototrophic and heterotrophic populations in winter, including the cyanobacteria Trichodesmium, to predominantly heterotrophic diazotrophs in summer. These heterotrophic diazotrophs may be both carbon and P limited as illustrated by their response to additions of P and amino acids

Current Developments of Clinical Sequencing and the Clinical Utility of Polygenic Risk Scores in Inflammatory Diseases

In this mini-review, we highlight selected research by the Deutsche Forschungsgemeinschaft (DFG) Cluster of Excellence "Precision Medicine in Chronic Inflammation" focusing on clinical sequencing and the clinical utility of polygenic risk scores as well as its implication on precision medicine in the field of the inflammatory diseases inflammatory bowel disease, atopic dermatitis and coronary artery disease. Additionally, we highlight current developments and discuss challenges to be faced in the future. Exemplary, we point to residual challenges in detecting disease-relevant variants resulting from difficulties in the interpretation of candidate variants and their potential interactions. While polygenic risk scores represent promising tools for the stratification of patient groups, currently, polygenic risk scores are not accurate enough for clinical setting. Precision medicine, incorporating additional data from genomics, transcriptomics and proteomics experiments, may enable the identification of distinct disease pathogeneses. In the future, data-intensive biomedical innovation will hopefully lead to improved patient stratification for personalized medicine

Determinants of translation efficiency and accuracy

A given protein sequence can be encoded by an astronomical number of alternative nucleotide sequences. Recent research has revealed that this flexibility provides evolution with multiple ways to tune the efficiency and fidelity of protein translation and folding

Nonlinear harmonic generation and devices in doubly-resonant Kerr cavities

We describea theoretical analysis of the nonlinear dynamics of third-harmonic generation ($\omega\to3\omega$) via Kerr (\chithree) nonlinearities in a resonant cavity with resonances at both $\omega$ and $3\omega$. Such a doubly resonant cavity greatly reduces the required power for efficient harmonic generation, by a factor of $\sim V/Q^2$ where $V$ is the modal volume and $Q$ is the lifetime, and can even exhibit 100% harmonic conversion efficiency at a critical input power. However, we show that it also exhibits a rich variety of nonlinear dynamics, such as multistable solutions and long-period limit cycles.We describe how to compensate for self/cross-phase modulation (which otherwise shifts the cavity frequencies out of resonance), and how to excite the different stable solutions (and especially the high-efficiency solutions) by specially modulated input pulses.Comment: 12 pages, 12 figure

The Three Pillars of Machine Programming

In this position paper, we describe our vision of the future of machine programming through a categorical examination of three pillars of research. Those pillars are:(i) intention,(ii) invention, and (iii) adaptation. Intention emphasizes advancements in the human-to-computer and computer-to-machine-learning interfaces. Invention emphasizes the creation or refinement of algorithms or core hardware and software building blocks through machine learning (ML). Adaptation emphasizes advances in the use of ML-based constructs to autonomously evolve software

The Best and Worst of Contracts Decisions: An Anthology

Five hundred years ago, the common law of contract was without substance. It was form-procedure. Plaintiffs picked a form of action, and common law judges made sure someone besides themselves answered all the hard questions; the parties, a jury, or a ritual determined the winner and the remedy. Judges ran a switch on a conflicts-resolution railway. Thomas More, when Chancellor of England (1529-33), urged judges to lay tracks and control the trains. The problem, he said, was that the judges, by the verdict of the jury[,] cast off all quarrels from themselves. The judges soon assumed greater authority, taking responsibility for the law\u27s substance. The consideration requirement was in place by 1539, and judges afterwards imposed doctrine upon doctrine. Over centuries, they created the common law of contract. That law is now mature, more or less, meaning that judges have tools to fix what they want to fix, and feel free to do so. The law they created-the common law of contract-is a remarkable intellectual and political achievement

An electronic health record (EHR) log analysis shows limited clinician engagement with unsolicited genetic test results

How clinicians utilize medically actionable genomic information, displayed in the electronic health record (EHR), in medical decision-making remains unknown. Participating sites of the Electronic Medical Records and Genomics (eMERGE) Network have invested resources into EHR integration efforts to enable the display of genetic testing data across heterogeneous EHR systems. To assess clinicians' engagement with unsolicited EHR-integrated genetic test results of eMERGE participants within a large tertiary care academic medical center, we analyzed automatically generated EHR access log data. We found that clinicians viewed only 1% of all the eMERGE genetic test results integrated in the EHR. Using a cluster analysis, we also identified different user traits associated with varying degrees of engagement with the EHR-integrated genomic data. These data contribute important empirical knowledge about clinicians limited and brief engagements with unsolicited EHR-integrated genetic test results of eMERGE participants. Appreciation for user-specific roles provide additional context for why certain users were more or less engaged with the unsolicited results. This study highlights opportunities to use EHR log data as a performance metric to more precisely inform ongoing EHR-integration efforts and decisions about the allocation of informatics resources in genomic research

Id1 Interacts and Stabilizes the Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) in Nasopharyngeal Epithelial Cells

The EBV-encoded latent membrane protein 1 (LMP1) functions as a constitutive active form of tumor necrosis factor receptor (TNFR) and activates multiple downstream signaling pathways similar to CD40 signaling in a ligand-independent manner. LMP1 expression in EBV-infected cells has been postulated to play an important role in pathogenesis of nasopharyngeal carcinoma. However, variable levels of LMP1 expression were detected in nasopharyngeal carcinoma. At present, the regulation of LMP1 levels in nasopharyngeal carcinoma is poorly understood. Here we show that LMP1 mRNAs are transcribed in an EBV-positive nasopharyngeal carcinoma (NPC) cell line (C666-1) and other EBV-negative nasopharyngeal carcinoma cells stably re-infected with EBV. The protein levels of LMP1 could readily be detected after incubation with proteasome inhibitor, MG132 suggesting that LMP1 protein is rapidly degraded via proteasome-mediated proteolysis. Interestingly, we observed that Id1 overexpression could stabilize LMP1 protein in EBV-infected cells. In contrary, Id1 knockdown significantly reduced LMP1 levels in cells. Co-immunoprecipitation studies revealed that Id1 interacts with LMP1 by binding to the CTAR1 domain of LMP1. N-terminal region of Id1 is required for the interaction with LMP1. Furthermore, binding of Id1 to LMP1 suppressed polyubiquitination of LMP1 and may be involved in stabilization of LMP1 in EBV-infected nasopharyngeal epithelial cells

Daratumumab, lenalidomide, and dexamethasone in relapsed/refractory myeloma: a cytogenetic subgroup analysis of POLLUX

High cytogenetic risk abnormalities confer poor outcomes in multiple myeloma patients. In POLLUX, daratumumab/lenalidomide/dexamethasone (D-Rd) demonstrated significant clinical benefit versus lenalidomide/dexamethasone (Rd) in relapsed/refractory multiple myeloma (RRMM) patients. We report an updated subgroup analysis of POLLUX based on cytogenetic risk. The cytogenetic risk was determined using fluorescence in situ hybridization/karyotyping; patients with high cytogenetic risk had t(4;14), t(14;16), or del17p abnormalities. Minimal residual disease (MRD; 10–5) was assessed via the clonoSEQ® assay V2.0. 569 patients were randomized (D-Rd, n = 286; Rd, n = 283); 35 (12%) patients per group had high cytogenetic risk. After a median follow-up of 44.3 months, D-Rd prolonged progression-free survival (PFS) versus Rd in standard cytogenetic risk (median: not estimable vs 18.6 months; hazard ratio [HR], 0.43; P < 0.0001) and high cytogenetic risk (median: 26.8 vs 8.3 months; HR, 0.34; P = 0.0035) patients. Responses with D-Rd were deep, including higher MRD negativity and sustained MRD-negativity rates versus Rd, regardless of cytogenetic risk. PFS on subsequent line of therapy was improved with D-Rd versus Rd in both cytogenetic risk subgroups. The safety profile of D-Rd by cytogenetic risk was consistent with the overall population. These findings demonstrate the improved efficacy of daratumumab plus standard of care versus standard of care in RRMM, regardless of cytogenetic risk