HEDGE FUND DUE DILIGENCE: A SOURCE OF ALPHA IN A HEDGE FUND PORTFOLIO STRATEGY

Due diligence is an important source of alpha in a well designed hedge fund portfolio strategy. It is generally understood that the high returns possible in investing in hedge funds are somewhat offset by the relative lack of transparency on operational issues. The performance of a diversified hedge fund portfolio can be enhanced by excluding those funds likely to do poorly – or fail – due to operational risk concerns. However, effective due diligence is an expensive concern. This implies that there is a strong competitive advantage to those funds of funds sufficiently large to absorb this fixed and necessary cost. The consequent economies of scale that we document in funds of funds are quite substantial and support the proposition that due diligence is a source of alpha in hedge fund investment

FPGA Implementation of a Fixed Latency Scheme in a Signal Packet Router for the Upgrade of ATLAS Forward Muon Trigger Electronics

We propose a new fixed latency scheme for Xilinx gigabit transceivers that will be used in the upgrade of the ATLAS forward muon spectrometer at the Large Hadron Collider. The fixed latency scheme is implemented in a 4.8 Gbps link between a frontend data serializer ASIC and a packet router. To achieve fixed latency, we use IO delay and dedicated carry in resources in a Xilinx FPGA, while minimally relying on the embedded features of the FPGA transceivers. The scheme is protocol independent and can be adapted to FPGA from other vendors with similar resources. This paper presents a detailed implementation of the fixed latency scheme, as well as simulations of the real environment in the ATLAS forward muon region.Comment: 8 pages, 8 figures, accepted by IEEE - Transactions on Nuclear Scienc

HEDGE FUND DUE DILIGENCE: A SOURCE OF ALPHA IN A HEDGE FUND PORTFOLIO STRATEGY

Due diligence is an important source of alpha in a well designed hedge fund portfolio strategy. It is generally understood that the high returns possible in investing in hedge funds are somewhat offset by the relative lack of transparency on operational issues. The performance of a diversified hedge fund portfolio can be enhanced by excluding those funds likely to do poorly – or fail – due to operational risk concerns. However, effective due diligence is an expensive concern. This implies that there is a strong competitive advantage to those funds of funds sufficiently large to absorb this fixed and necessary cost. The consequent economies of scale that we document in funds of funds are quite substantial and support the proposition that due diligence is a source of alpha in hedge fund investment

Gapless spin-excitations in the superconducting state of a quasi-one-dimensional spin-triplet superconductor

Majorana zero modes form as intrinsic defects in an odd-orbital one-dimensional superconductor thus motivating the search for such materials in the pursuit of Majorana physics. Here, we present combined experimental results and first principles calculations which suggest that quasi-one-dimensional K$_2$Cr$_3$As$_3$ may be such a superconductor. Using inelastic neutron scattering we probe the dynamic spin-susceptibilities of K$_2$Cr$_3$As$_3$ and K$_2$Mo$_3$As$_3$ and show the presence of antiferromagnetic spin-fluctuations in both compounds. Below the superconducting transition, these fluctuations gap in K$_2$Mo$_3$As$_3$ but not in K$_2$Cr$_3$As$_3$. Using first principles calculations, we show that these fluctuations likely arise from nesting on one dimensional features of the Fermi surface. Considering these results we propose that while K$_2$Mo$_3$As$_3$ is a conventional superconductor, K$_2$Cr$_3$As$_3$ is likely a spin-triplet, and consequently, topological superconductor.Comment: 8 pages, 4 figure

Morphology of the medial collateral ligament of the knee

<p>Abstract</p> <p>Background</p> <p>Quantitative knowledge on the anatomy of the medial collateral ligament (MCL) is important for treatment of MCL injury and for MCL release during total knee arthroplasty (TKA). The objective of this study was to quantitatively determine the morphology of the MCL of human knees.</p> <p>Methods</p> <p>10 cadaveric human knees were dissected to investigate the MCL anatomy. The specimens were fixed in full extension and this position was maintained during the dissection and morphometric measurements. The outlines of the insertion sites of the superficial MCL (sMCL) and deep MCL (dMCL) were digitized using a 3D digitizing system.</p> <p>Results</p> <p>The insertion areas of the superficial MCL (sMCL) were 348.6 ± 42.8 mm²and 79.7 ± 17.6 mm²on the tibia and femur, respectively. The insertion areas of the deep MCL (dMCL) were 63.6 ± 13.4 mm²and 71.9 ± 14.8 mm²on the tibia and femur, respectively. The distances from the centroids of the tibial and femoral insertions of the sMCL to the tibial and femoral joint line were 62.4 ± 5.5 mm and 31.1 ± 4.6 mm, respectively. The distances from the centroids of dMCL in the tibial insertion and the femoral insertion to the tibial and femoral joint line were 6.5 ± 1.3 mm and 20.5 ± 4.2 mm, respectively. The distal portion of the dMCL (meniscotibial ligament - MTL) was approximately 1.7 times wider than the proximal portion of the dMCL (meniscofemoral ligament - MFL), whereas the MFL was approximately 3 times longer than the MTL.</p> <p>Conclusions</p> <p>The morphologic data on the MCL may provide useful information for improving treatments of MCL-related pathology and performing MCL release during TKA.</p

Inhibition of chemotherapy resistant breast cancer stem cells by a ROR1 specific antibody.

Breast cancers enduring treatment with chemotherapy may be enriched for cancer stem cells or tumor-initiating cells, which have an enhanced capacity for self-renewal, tumor initiation, and/or metastasis. Breast cancer cells that express the type I tyrosine kinaselike orphan receptor ROR1 also may have such features. Here we find that the expression of ROR1 increased in breast cancer cells following treatment with chemotherapy, which also enhanced expression of genes induced by the activation of Rho-GTPases, Hippo-YAP/TAZ, or B lymphoma Mo-MLV insertion region 1 homolog (BMI1). Expression of ROR1 also enhanced the capacity of breast cancer cells to invade Matrigel, form spheroids, engraft in Rag2-/-[Formula: see text] mice, or survive treatment with paclitaxel. Treatment of mice bearing breast cancer patient-derived xenografts (PDXs) with the humanized anti-ROR1 monoclonal antibody cirmtuzumab repressed expression of genes associated with breast cancer stemness, reduced activation of Rho-GTPases, Hippo-YAP/TAZ, or BMI1, and impaired the capacity of breast cancer PDXs to metastasize or reengraft Rag2-/-[Formula: see text] mice. Finally, treatment of PDX-bearing mice with cirmtuzumab and paclitaxel was more effective than treatment with either alone in eradicating breast cancer PDXs. These results indicate that targeting ROR1 may improve the response to chemotherapy of patients with breast cancer

BCG hydrogel promotes CTSS-mediated antigen processing and presentation, thereby suppressing metastasis and prolonging survival in melanoma.

BACKGROUND The use of intralesional Mycobacterium bovis BCG (intralesional live BCG) for the treatment of metastatic melanoma resulted in regression of directly injected, and occasionally of distal lesions. However, intralesional-BCG is less effective in patients with visceral metastases and did not significantly improve overall survival. METHODS We generated a novel BCG lysate and developed it into a thermosensitive PLGA-PEG-PLGA hydrogel (BCG hydrogel), which was injected adjacent to the tumor to assess its antitumor effect in syngeneic tumor models (B16F10, MC38). The effect of BCG hydrogel treatment on contralateral tumors, lung metastases, and survival was assessed to evaluate systemic long-term efficacy. Gene expression profiles of tumor-infiltrating immune cells and of tumor-draining lymph nodes from BCG hydrogel-treated mice were analyzed by single-cell RNA sequencing (scRNA-seq) and CD8+ T cell receptor (TCR) repertoire diversity was assessed by TCR-sequencing. To confirm the mechanistic findings, RNA-seq data of biopsies obtained from in-transit cutaneous metastases of patients with melanoma who had received intralesional-BCG therapy were analyzed. RESULTS Here, we show that BCG lysate exhibits enhanced antitumor efficacy compared to live mycobacteria and promotes a proinflammatory tumor microenvironment and M1 macrophage (MΦ) polarization in vivo. The underlying mechanisms of BCG lysate-mediated tumor immunity are dependent on MΦ and dendritic cells (DCs). BCG hydrogel treatment induced systemic immunity in melanoma-bearing mice with suppression of lung metastases and improved survival. Furthermore, BCG hydrogel promoted cathepsin S (CTSS) activity in MΦ and DCs, resulting in enhanced antigen processing and presentation of tumor-associated antigens. Finally, BCG hydrogel treatment was associated with increased frequencies of melanoma-reactive CD8+ T cells. In human patients with melanoma, intralesional-BCG treatment was associated with enhanced M1 MΦ, mature DC, antigen processing and presentation, as well as with increased CTSS expression which positively correlated with patient survival. CONCLUSIONS These findings provide mechanistic insights as well as rationale for the clinical translation of BCG hydrogel as cancer immunotherapy to overcome the current limitations of immunotherapies for the treatment of patients with melanoma