gebhart/patrepeval huggingface dataset:
Intercostal nerve transfer to restore upper extremity functions after brachial plexus injury. (1995)

We report the efficacy of intercostal nerve transfer to restore elbow flexion, shoulder functions, and hand functions. One hundred and twelve patients with loss of elbow flexion were treated with intercostal nerve transfer to the musculocutaneous nerve and 97 (87%) of them regained grade 3 or 4 elbow flexion. Seven patients with loss of shoulder functions were treated with combined intercostal nerve transfer to the axillary nerve and phrenic nerve transfer to the suprascapular nerve, and 4 (57%) of them regained more than 80 degrees abduction and 5 (71%) regained more than 50 degrees external rotation starting with the forearm against the chest. To restore hand functions, intercostal nerves were sutured to the radial nerve or one of its branches in 40 patients and to the median nerve in 10 patients. Motor recovery was poor in both nerve transfers, but protective sensation was regained in the fingers innervated by the median nerve in 9 (90%) of the 10 patients. We conclude that intercostal nerve transfer after brachial plexus injury was a useful procedure to restore elbow flexion and shoulder functions, and for restoring a protective sensation in the fingers.
Emergency material scheduling optimization model and algorithms: A review (2019)

In the emergency management of disruptions, efficient emergency material scheduling (EMS) is a key factor to save people's lives and reduce loss. Based on the literature of EMS and related areas in recent years, the research was summarized from two aspects of EMS optimization model and algorithms. It is concluded that the EMS optimization models mainly aim at the shortest time, shortest distance, minimum cost, maximum satisfaction and fairness, etc. The constraints usually include the quantity of supply depots, relief supply and vehicles, the types of commodities, the road network conditions, the budgets and the demand forecast of emergency materials. Multi-objective model is more complex and it usually considers more than one objective. To find the optimized solution, the multi-objective model with complex constraints needs more efficient algorithms. The existing algorithms, including mathematic algorithm and heuristic algorithm, have been categorized. For NP-hard (non-deterministic polynomial hard) problems, heuristic algorithms should be designed, which mainly include genetic algorithm (GA), ant colony optimization (ACO), particle swarm optimization (PSO), etc. Based on the characteristics of the optimization model and various algorithms, appropriate algorithm or tools should be chosen and designed to obtain the optimized solution of EMS model. Finally, the development trends of EMS optimization model and algorithm in the future are proposed.
Optical channel speeds for future transport networks (2011)

In this paper the history of channel speed development of optical transport networks, from a few MbI/s to beyond 100 GbI/s, is reviewed. A new channel type categorization, which divided various channel designs into only three basic channel types, has been proposed. Based on the new categorization distinguishable performances of the three types of channels are analyzed and the future direction of optical channel designs is predicted.
Human poly(ADP-ribose) glycohydrolase is expressed in alternative splice variants yielding isoforms that localize to different cell compartments (2004)

Poly(ADP-ribose) glycohydrolase (PARG) is the only protein known to catalyze hydrolysis of ADP-ribose (ADPR) polymers to free ADP-ribose. While numerous genes encode different poly(ADP-ribose) polymerases (PARPs) that all synthesize ADP-ribose polymer, only a single gene coding for PARG has been detected in mammalian cells. Here, we describe two splice variants of human PARG mRNA, which lead to expression of PARG isoforms of 102 kDa (hPARG102) and 99 kDa (hPARG99) in addition to the full-length PARG protein (hPARG111). These splice variants differ from hPARG111 by the lack of exon 1 (hPARG102) or exons 1 and 2 (hPARG99). They are generated by the utilization of ambiguous splice donor sites in the PARG gene 5' untranslated region. The hPARG111 isoform localizes to the nucleus, whereas hPARG102 and hPARG99 are cytoplasmic proteins. The nuclear targeting of hPARG111 is due to a nuclear localization signal (NLS) in exon 1 that was mapped to the amino acids (aa) (10)CTKRPRW(16). Immunocytochemistry, immunoblotting, and PARG enzyme activity measurements show that the cytoplasmic isoforms of PARG account for most of the PARG activity in cells in the absence and presence of genotoxic stress. The predominantly cytoplasmic location of cellular PARG is intriguing as most known cellular PARPs have a nuclear localization.
Phase I results of human endogenous retrovirus type-E (HERV-E) TCR transduced T-cells in patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC). (2023)

2549 Background: The CT-RCC HERV-E is expressed in the majority of ccRCC tumors with no expression in normal tissues. T-cells transduced to express a HERV-E TCR are cytotoxic to ccRCC &amp; mediate tumor regression of human ccRCC in a murine model. We developed a method to manufacture HERV-E TCR transduced T-cells (HERV-E TCR) for clinical development. Methods: We conducted a phase I dose-escalation trial (DL1:1x10 6 , DL2:5x10 6 , DL3:1x10 7 &amp; DL4:5x10 7 cells/kg) to evaluate the safety of adoptively infused HERV-E TCR in mccRCC pts. HERV-E TCR contain T-cells engineered to express an HLA-A*11 restricted HERV-E TCR and a truncated CD34 cassette for in vivo monitoring. Eligible HLA-A*11 pts had mccRCC, ECOG 0-1 &amp; prior antiangiogenic &amp; checkpoint inhibitors therapy unless contraindicated/unavailable. Cyclophosphamide &amp; fludarabine were given followed by HERV-E TCR infusion &amp; IL-2 administration. Results: 14 HLA-A*11+ pts (median age 56) were treated including 3 pts in each DLs 1-3 &amp; 5 pts in DL4. 86% had ≥ 3 prior treatment lines (range 1-7): 36% had high-dose IL2, 57% Ipilimumab-Nivolumab &amp; 50% ≥ 3 lines of anti-VEGFR therapy. Bone, liver &amp; brain metastases were present in 71%, 43%, and 14% of pts. All HERV-E TCR products met sterility, purity, and potency criteria for release and infusion (Table). No HERV-E TCR dose-limiting toxicities or treatment-related deaths occurred. Pts received a mean: 12 IL-2 doses (IQR 11-14). 57% pts had G3-4 febrile neutropenia &amp; 7% G3-4 capillary leak syndrome. 1 pt experienced G2 skin rash possibly related to HERV-E TCR. Best response included 7% pts with partial response &amp; 29% with stable disease ≥ 8 weeks. The mPFS: 62 days (IQR 31,90). At DL4, TCR transgene expression was detectable in PBMCs at a mean 6.3% (range (r) 0.02-25), 12.3% (r 0.01-61.2), 3.45% (r 0.00-13.7) &amp; 2.89% (r 0.00-11.5) on days 4, 7, 14, &amp; 21. HERV-E TCR were detected in the malignant pleural effusion of 1 pt. Conclusions: This is the first trial evaluating TCR-engineered T-cells targeting a human endogenous retrovirus in ccRCC. The manufacturing method utilized produced large numbers of highly purified CD8+ HERV-E reactive T-cells that were not associated with any dose limiting toxicities when given at doses up to 5x10 7 cells/kg. For pts in DL4, HERV-E TCR were observed to proliferate in vivo, traffic to a metastatic site, and induce tumor regression in one mccRCC pts. Clinical trial information: NCT03354390 . [Table: see text]
Combating Aging with the Colt Duty Cycle Equalizer (2010)

Bias temperature instability, hot-carrier injection, and gate-oxide wear out will cause severe lifetime degradation in the performance and the reliability of future CMOS devices. The design guard band to counter these negative effects will be too expensive, largely due to the worst-case behavior induced by the uneven utilization of devices on the chip. To mitigate these effects over a chip's lifetime, this paper proposes Colt, a simple yet holistic scheme to balance the utilization of devices in a processor by equalizing the duty cycle ratio of circuits'internal nodes and the usage frequency of devices. Colt relies on alternating true-and complement-mode operations to equalize the duty cycle ratio of signals (thus the utilization of devices) in most data path and storage devices. Colt also employs a pseudorandom indexing scheme to balance the usage of entries in storage structures that often exhibit highly uneven utilization of entries. Finally, an operand-swapping scheme equalizes utilization of the left and right operand data paths. The proposed mechanisms impose trivial overhead in area, complexity, power, and performance, while recapturing 27% of aging-induced performance degradation and improving meantime to failure by an estimated 40%.
PML-RARα Alleviates the Transcriptional Repression Mediated by Tumor Suppressor Rb (2001)

A fusion between the promyelocytic leukemia (PML) protein and the retinoic acid receptor-alpha (RARalpha) results in the transforming protein of acute promyelocytic leukemia, PML-RARalpha. PML has growth-suppressive properties and is localized within distinct nuclear structures referred to as nuclear bodies. PML participates in numerous cellular functions, including transcriptional activation, apoptosis, and transcriptional repression, whereas PML-RARalpha blocks these functions. However, the role played by PML-RARalpha in leukemogenesis remains unclear. Here we report that PML is required for transcriptional repression mediated by the tumor suppressor Rb. Rb interacts with the histone decaetylase (HDAC) complex containing co-repressors and represses the transcription of the E2F target genes. Overexpression of PML enhanced Rb-mediated repression. The degree of Rb-mediated repression was weakened by injecting anti-PML antibodies and was lower in Pml-deficient mouse embryonic fibroblasts. PML-RARalpha inhibited Rb-mediated repression, and two co-repressor-interacting sites on the PML-RARalpha molecule were required for this activity. Furthermore, PML-RARalpha blocked the interaction between Rb and HDAC. Thus, aberrant binding of PML-RARalpha to co-repressor-HDAC complexes may inhibit their association with Rb, resulting in the abrogation of Rb activity. Thus, the disruption of Rb-mediated repression may be a contributory factor in leukemogenesis.
Abstract 2925: WAVE3 is associated with chemoresistance in TNBC by activating tumor angiogenesis downstream of the STAT1/Hif-1α/VEGF-A signaling axis (2015)

Abstract Chemoresistance is the main cause of disease recurrence and eventual death of breast cancer patients, particularly those harboring triple-negative breast cancer (TNBC) tumors for which effective FDA-approved drugs currently do not exist. However, a recent study determined that TNBCs can be segregated into 6 genetically distinct subtypes that do in fact exhibit differential rates of pathological complete response (pCR) to standard-of-care chemotherapies. Interestingly, the mesenchymal and mesenchymal stem-like subtypes of TNBCs exhibit the lowest rates of pCR when treated with standard-of-care chemotherapies. WAVE3 is an actin-cytoskeleton remodeling protein, and recent studies have highlighted a potential role for WAVE3 in promoting tumor progression and metastasis in TNBC. However, whether WAVE3 activity is involved in the development of chemoresistance in TNBCs, remains unclear. Here we show that loss of WAVE3 expression resensitizes human TNBC cells to Doxorubicin and Docetaxel, as measured by increased apoptosis and cell death. We also show that WAVE3 knockdown in the chemotherapy-treated TNBC cells results in inhibition of STAT1 phosphorylation, as well as a significant decrease in expression levels of its downstream effector Hif-1α. Since Hif-1α is a major activator of VEGF-A production, and therefore, a stimulator of tumor angiogenesis, loss of Hif-1α in the WAVE3-knocdown cells resulted in the inhibition the chemotherapy-mediated VEGF-A secretion and the downstream activation of angiogenesis, a phenomenon that often accompanies chemoresistance. Our data identify a critical role of WAVE3 in sensitizing TNBC to chemotherapy by inhibiting the STAT1⌠Hif-1α⌠VEGF-A signaling axis, and support the possibility of WAVE3 inhibition as a promising approach for TNBC cancer therapy. Citation Format: Gangarao Davuluri, Edward F. Plow, William P. Schiemann, Khalid Sossey-Alaoui. WAVE3 is associated with chemoresistance in TNBC by activating tumor angiogenesis downstream of the STAT1/Hif-1α/VEGF-A signaling axis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2925. doi:10.1158/1538-7445.AM2015-2925
Tumor antigen CA125 suppresses antibody-dependent cellular cytotoxicity (ADCC) via direct antibody binding and suppressed Fc-γ receptor engagement (2017)

Cancers employ a number of mechanisms to evade host immune responses. Here we report the effects of tumor-shed antigen CA125/MUC16 on suppressing IgG1-mediated antibody-dependent cellular cytotoxicity (ADCC). This evidence stems from prespecified subgroup analysis of a Phase 3 clinical trial testing farletuzumab, a monoclonal antibody to folate receptor alpha, plus standard-of-care carboplatin-taxane chemotherapy in patients with recurrent platinum-sensitive ovarian cancer. Patients with low serum CA125 levels treated with farletuzumab demonstrated improvements in progression free survival (HR 0.49, <i>p</i> = 0.0028) and overall survival (HR 0.44, <i>p</i> = 0.0108) as compared to placebo. Farletuzumab's pharmacologic activity is mediated in part through ADCC. Here we show that CA125 inhibits ADCC by directly binding to farletuzumab that in turn perturbs Fc-γ receptor engagement on effector cells.
A 2′←5′-Adenylate Trimer With a Positively Charged 2′(3′)-Terminal 8-(4-Aminobunl)Aminoadenosine Residue: Synthesis, Conformation and RNase L Binding (1997)

Abstract An analogue of the 2-5A core trimer containing an 8-(4-aminobutyl)-aminoadenosine (1; A) residue at the 2′(3′)-terminus [2; (2′,5′)A2A∗] was synthesized. The conformation of (2′,5′)A2A∗ was studied by 1H, 13C-NMR, and CD spectroscopy. The (2′,5′)A2A∗ exhibits very low binding ability to the RNase L of mouse L cells, but slightly enhanced resistance to digestion by SVPD compared to the parent trimer.
The Induction of HIV Gag-Specific CD8+ T Cells in the Spleen and Gut-Associated Lymphoid Tissue by Parenteral or Mucosal Immunization with Recombinant Listeria monocytogenes HIV Gag (2003)

The induction of mucosal immunity is crucial in controlling viral replication during HIV infection. In this study we compare the ability of a recombinant Listeria monocytogenes that expresses and secretes the HIV Ag Gag to induce CD8(+) T cells against this Ag in the spleen, mesenteric lymph nodes, and Peyer's patches and the ability to provide effector Gag-specific CD8(+) T cells to the lamina propria after i.v., oral, or rectal administration of the vaccine. The levels of Ag-specific CD8(+)-activated T cells were measured ex vivo using intracellular cytokine staining for IFN-gamma and H-2K(d) Gag peptide tetramer staining. We found that all routes of immunization induced Gag-specific CD8(+) T cells in the spleen. After secondary infection, we observed substantial increases in splenic levels of CD8(+) T cells, and levels of Gag-specific cells were similar to those against listeriolysin O, the immunodominant Ag of L. monocytogenes. Both primary and secondary oral immunization resulted in abundant Gag-specific CD8(+)-activated T cells in the lamina propria that constituted approximately 35% of the CD8 compartment. However, significant levels of Gag and listeriolysin O-specific CD8(+) T cells were observed in mucosal lymphoid tissue only after two immunizations, perhaps because they had already entered the lamina propria compartment after a single immunization. In the context of HIV, a mucosally administered vaccine seems best calculated to prompt an immune response that is capable of preventing infection. The data presented in this report demonstrate that mucosally administered Listeria can prompt such a response and that booster doses can maintain this response.
Supplementary Figure 4 from Targeting TRAIL Death Receptor 4 with Trivalent DR4 Atrimer Complexes (2023)

&lt;p&gt;PDF file, 53K, TRAIL-receptor expression in SW620 and HCT15 cell lines. Western blot analysis of TRAIL receptors in SW620 and HCT15 cells.&lt;/p&gt;
30-Gb/s Optical Link Combining Heterogeneously Integrated III–V/Si Photonics With 32-nm CMOS Circuits (2014)

We present a silicon photonics optical link utilizing heterogeneously integrated photonic devices driven by low-power advanced 32-nm CMOS integrated circuits. The photonic components include a quantum-confined Stark effect electroabsorption modulator and an edge-coupled waveguide photodetector, both made of III-V material wafer bonded on silicon-on-insulator wafers. The photonic devices are wire bonded to the CMOS chips and mounted on a custom PCB card for testing. We demonstrate an error-free operation at data rates up to 30 Gb/s and transmission over 10 km at 25 Gb/s with no measured sensitivity penalty and a timing margin penalty of 0.2 UI.
Flow and Compaction During the Vacuum Assisted Resin Transfer Molding Process (2001)

The flow of an epoxy resin and compaction behavior of carbon fiber preform during vacuum- assisted resin transfer molding (VARTM) infiltration was measured using an instrumented tool. Composite panels were fabricated by the VARTM process using SAERTEX(R)2 multi-axial non- crimp carbon fiber fabric and the A.T.A.R.D. SI-ZG-5A epoxy resin. Resin pressure and preform thickness variation was measured during infiltration. The effects of the resin on the compaction behavior of the preform were measured. The local preform compaction during the infiltration is a combination of wetting and spring-back deformations. Flow front position computed by the 3DINFIL model was compared with the experimental data.
The conserved lysine of the catalytic domain of protein kinases is actively involved in the phosphotransfer reaction and not required for anchoring ATP. (1993)

The study of the various protein kinases reveals that, despite their considerably diversity, they have evolved from a common origin. Eleven conserved subdomains have been described that encompass the catalytic core of these enzymes. One of these conserved regions, subdomain II, contains an invariant lysine residue present in all known protein kinase catalytic domains. Two facts have suggested that this conserved lysine of subdomain II is essential for binding ATP: (i) several investigators have demonstrated that this residue is physically proximal to the ATP molecule, and (ii) conservative substitutions at this site render the kinase inactive. However, these results are also consistent with a functional role of the conserved lysine of subdomain II in orienting or facilitating the transfer of phosphate. To study in more detail the role of subdomain II, we have generated mutants of the protein-tyrosine kinase pp56lck that have single amino acid substitutions within the area surrounding the conserved residue Lys-273 in subdomain II. When compared with wild-type pp56lck, these mutants displayed profound reductions in their phosphotransfer efficiencies and small differences in their affinities for ATP. Further, the substitution of arginine for Lys-273 resulted in a mutant protein unable to transfer the gamma-phosphate of ATP but able to bind 8-azido-ATP with an efficiency similar to that of wild-type pp56lck. These results suggest that the region including Lys-273 of subdomain II is involved in the enzymatic process of phosphate transfer, rather than in anchoring ATP.
Degeneration of proprioceptive sensory nerve endings in mice harboring amyotrophic lateral sclerosis–causing mutations (2015)

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily targets the motor system. Although much is known about the effects of ALS on motor neurons and glial cells, little is known about its effect on proprioceptive sensory neurons. This study examines proprioceptive sensory neurons in mice harboring mutations associated with ALS, in SOD1(G93A) and TDP43(A315T) transgenic mice. In both transgenic lines, we found fewer proprioceptive sensory neurons containing fluorescently tagged cholera toxin in their soma five days after injecting this retrograde tracer into the tibialis anterior muscle. We asked whether this is due to neuronal loss or selective degeneration of peripheral nerve endings. We found no difference in the total number and size of proprioceptive sensory neuron soma between symptomatic SOD1(G93A) and control mice. However, analysis of proprioceptive nerve endings in muscles revealed early and significant alterations at Ia/II proprioceptive nerve endings in muscle spindles before the symptomatic phase of the disease. Although these changes occur alongside those at α-motor axons in SOD1(G93A) mice, Ia/II sensory nerve endings degenerate in the absence of obvious alterations in α-motor axons in TDP43(A315T) transgenic mice. We next asked whether proprioceptive nerve endings are similarly affected in the spinal cord and found that nerve endings terminating on α-motor neurons are affected during the symptomatic phase and after peripheral nerve endings begin to degenerate. Overall, we show that Ia/II proprioceptive sensory neurons are affected by ALS-causing mutations, with pathological changes starting at their peripheral nerve endings.
Optical Node with Passband Overlapped Filter and Impairment Aware Least Slot Count Path First Algorithm for Guardband-Less Elastic Optical Network (2017)

We propose a novel optical band-pass filter device and a dedicated optical path design algorithm to reduce guardband use in EON. Simulation and experimental results demonstrate twice the spectral efficiency of EON and applicability to actual networks.
Open-ended Learning in Symmetric Zero-sum Games (2019)

Zero-sum games such as chess and poker are, abstractly, functions that evaluate pairs of agents, for example labeling them `winner' and `loser'. If the game is approximately transitive, then self-play generates sequences of agents of increasing strength. However, nontransitive games, such as rock-paper-scissors, can exhibit strategic cycles, and there is no longer a clear objective -- we want agents to increase in strength, but against whom is unclear. In this paper, we introduce a geometric framework for formulating agent objectives in zero-sum games, in order to construct adaptive sequences of objectives that yield open-ended learning. The framework allows us to reason about population performance in nontransitive games, and enables the development of a new algorithm (rectified Nash response, PSRO_rN) that uses game-theoretic niching to construct diverse populations of effective agents, producing a stronger set of agents than existing algorithms. We apply PSRO_rN to two highly nontransitive resource allocation games and find that PSRO_rN consistently outperforms the existing alternatives.
Ovarian cancer chemokines may not be a significant barrier during whole tumor antigen dendritic-cell vaccine and adoptive T-cell immunotherapy (2015)

Tumor barriers preventing T-cell homing and engraftment should be neutralized during cancer immunotherapy. We recently discovered that ovarian cancer expresses quasi-universal chemokines that can support T-cell homing. Furthermore, T cells elicited by whole tumor antigen dendritic-cell vaccines express cognate chemokine receptors which are upregulated by CD3/CD28 costimulation.
ChemInform Abstract: Syntheses and Antifungal Activity of dl‐Griseofulvin and Its Congeners. Part 3. (1998)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.