gebhart/patrepeval huggingface dataset:
The sVEGFR1-i13 splice variant regulates a β1 integrin/VEGFR autocrine loop involved in the progression and the response to anti-angiogenic therapies of squamous cell lung carcinoma (2018)

Overall, these results reveal an unexpected pro-tumoural function of sVEGFR1-i13 in SQLC tumour cells, which contributes to their progression and escape from anti-angiogenic therapies. These data might help to understand why some SQLC patients do not respond to anti-angiogenic therapies.
Misdiagnosis of specific cytomegalovirus infection of the ileoanal pouch as refractory idiopathic chronic pouchitis (1999)

Specific cytomegalovirus infection of the ileal pouch-anal anastomosis may be misdiagnosed as idiopathic refractory chronic pouchitis. Cytomegalovirus must be excluded before immune modifier therapy or pouch excision in these patients.
Dn Symmetric Hamiltonian System: A Network of Coupled Gyroscopes as a Case Study (2013)

The evolution of a large class of biological, physical and engineering systems can be studied through both dynamical systems theory and Hamiltonian mechanics. The former theory, in particular its specialization to study systems with symmetry, is already well developed and has been used extensively on a wide variety of spatio-temporal systems. There are, however, fewer results on higher-dimensional Hamiltonian systems with symmetry. This lack of results has lead us to investigate the role of symmetry, in particular dihedral symmetry, on high-dimensional coupled Hamiltonian systems. As a representative example, we consider the model equations of a ring of vibratory gyroscopes. The equations are reformulated in a Hamiltonian structure and the corresponding normal forms are derived. Through a normal form analysis, we investigated the effects of various coupling schemes and unraveled the nature of the bifurcations that lead the ring of gyroscopes into and out of synchronization. The Hamiltonian approach is specially useful in investigating the collective behavior of small and large ring sizes and it can be readily extended to other symmetry-related systems.
Shaped Parallel-Plate Lens for Mechanical Wide-Angle Beam Steering (2021)

This article presents a parallel-plate lens beamformer for continuous wide-angle scanning. The design is based on a compact dual-lens system with extended scanning range and is optimized using a previously developed geometrical optics technique. Beam steering is accomplished with a mechanical feed system based on the noncontact characteristic of groove gap waveguides, offering large bandwidth, low profile, and mechanical ruggedness. The proposed concept is validated by an all-metal prototype of a <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$20.5\lambda $ </tex-math></inline-formula> lens operating in the uplink Ka-band allocated to satellite communications (27.5–31 GHz). Good agreement is obtained between the simulated and measured performances. The measured return loss is greater than 12 dB over the entire frequency band and beyond. High scanning performances are achieved over an angular range of ±50° (±14 beamwidths), with maximum scan losses in the order of 3 dB and good pattern stability over the entire band. The proposed solution is particularly suited for next-generation satellite terminals requiring compact broadband antennas with continuous beam-steering capability over a large angular range.
Top-Quality Planning: Finding Practically Useful Sets of Best Plans (2020)

The need for finding a set of plans rather than one has been motivated by a variety of planning applications. The problem is studied in the context of both diverse and top-k planning: while diverse planning focuses on the difference between pairs of plans, the focus of top-k planning is on the quality of each individual plan. Recent work in diverse planning introduced additionally restrictions on solution quality. Naturally, there are application domains where diversity plays the major role and domains where quality is the predominant feature. In both cases, however, the amount of produced plans is often an artificial constraint, and therefore the actual number has little meaning. Inspired by the recent work in diverse planning, we propose a new family of computational problems called top-quality planning, where solution validity is defined through plan quality bound rather than an arbitrary number of plans. Switching to bounding plan quality allows us to implicitly represent sets of plans. In particular, it makes it possible to represent sets of plans that correspond to valid plan reorderings with a single plan. We formally define the unordered top-quality planning computational problem and present the first planner for that problem. We empirically demonstrate the superior performance of our approach compared to a top-k planner-based baseline, ranging from 41% increase in coverage for finding all optimal plans to 69% increase in coverage for finding all plans of quality up to 120% of optimal plan cost. Finally, complementing the new approach by a complete procedure for generating all valid reorderings of a given plan, we derive a top-quality planner. We show the planner to be competitive with a top-k planner based baseline.
A Response to “Osgood-Schlatter Disease in an English Setter” (2013)

Correspondence to: Dr. Dirsko von Pfeil Veterinary Specialists of Alaska 3330 Fairbanks Street Anchorage 99503, Alaska United States Phone: +1 907 274 0645 E-mail: drvonpfeil.vsoa@ak.net Dear Doctors Stigen and Mikalsen, We appreciate your contribution to the intriguing subject of tibial tuberosity injuries (1). Indeed, the case you saw recently in the Norwegian School of Veterinary Science appears to be very similar to Osgood-Schlatter disease in people. As stated in our publication, at the time of its writing, no case similar to the one you describe was reported in the available veterinary literature (2). We sincerely appreciate you sharing this case with the veterinary community. Based on the provided history of your patient, it is most likely that this dog suffered from a type – III tibial tuberosity avulsion fracture when it was five-months old. Over time, fusion with malunion of the proximally displaced and avulsed tibial tuberosity to the proximal tibia occurred. It is interesting that you state that “The most obvious pain response was provoked by maximally extending the right stifle joint” as with Osgood-Schlatter disease or tibial tuberosity avulsion, pain can usually be localized at the insertion of the patellar ligament, and elicited upon flexion of the knee. It would be interesting to follow this case and, if indicated see if shockwave treatment or resection of the ununited ossicles may help to decrease discomfort. In case of treatment, histopathology of the ossified particles may also provide additional information. Again, thank you for your contribution and helping to increase the knowledge base on tibial tuberosity injuries. Sincerely, Dirsko J. F. von Pfeil1,2; Charles E. DeCamp2; Curtis W. Probst2; Loic M. Dejardin2 1Veterinary Specialists of Alaska, Anchorage, Alaska, USA; 2Department of Small Animal Clinical Sciences, Michigan State University, College of Veterinary Medicine, East Lansing, Michigan, USA
Modeling Approaches for Ligand-Based 3D Similarity (2010)

3D ligand-based similarity approaches are widely used in the early phases of drug discovery for tasks such as hit finding by virtual screening or compound design with quantitative structure-activity relationships. Here in we review widely used software for performing such tasks. Some techniques are based on relatively mature technology, shape-based similarity for instance. Typically, these methods remained in the realm of the expert user, the experienced modeler. However, advances in implementation and speed have improved usability and allow these methods to be applied to databases comprising millions of compounds. There are now many reports of such methods impacting drug-discovery projects. As such, the medicinal chemistry community has become the intended market for some of these new tools, yet they may consider the wide array and choice of approaches somewhat disconcerting. Each method has subtle differences and is better suited to certain tasks than others. In this article we review some of the widely used computational methods via application, provide straightforward background on the underlying theory and provide examples for the interested reader to pursue in more detail. In the new era of preclinical drug discovery there will be ever more pressure to move faster and more efficiently, and computational approaches based on 3D ligand similarity will play an increasing role in in this process.
Quantum Network Utility: A Framework for Benchmarking Quantum Networks (2022)

The absence of a common framework for benchmarking quantum networks is an obstacle to comparing the capabilities of different quantum networks. We propose a general framework for quantifying the performance of a quantum network, which is based on the value created by connecting users through quantum channels. In this framework, we define the quantum network utility metric $U_{QN}$ to capture the social and economic value of quantum networks. While the quantum network utility captures a variety of applications from secure communications to distributed sensing, we study the example of distributed quantum computing in detail. We hope that the adoption of the utility-based framework will serve as a foundation for guiding and assessing the development of new quantum network technologies and designs.
Anion−π Interactions in Bisadenine Derivatives:  A Combined Crystallographic and Theoretical Study (2007)

In this manuscript we report a high-level ab initio study of anion-pi interactions involving N9-methyl-adenine, N6-methyl-adenine, N9-methyl-hypoxanthine, a dimer of N9-methyl-adenine, and N9,N9'-trimethylene-bisadenine. DNA bases like adenine are electron-deficient arenes that are well suited for interacting favorably with anions. We demonstrate that these compounds are able to interact favorably with anions. N9-Methyl-adenine, N6-methyl-adenine, and the dimer of N9-methyl-adenine interact with the anion via the six-membered ring more strongly than adenine due to cooperativity effects between the noncovalent pi-pi and anion-pi interactions. This pattern, i.e., coexistence of pi-pi and anion-pi bonding, is observed experimentally in the solid state. Finally, we report the solid-state characterization of two new compounds N6,N6'-dimethylene-bisadenine hydrochloride and an outer-sphere complex of protonated N9,N9'-trimethylene-bishypoxanthine with zinc tetrachloride anion, that exhibit interesting anion-pi interactions. They are in strong agreement with high-level theoretical calculations.
SARM1 acts downstream of neuroinflammatory and necroptotic signaling to induce axon degeneration (2020)

Neuroinflammation and necroptosis are major contributors to neurodegenerative disease, and axon dysfunction and degeneration is often an initiating event. SARM1 is the central executioner of pathological axon degeneration. Here, we demonstrate functional and mechanistic links among these three pro-degenerative processes. In a neuroinflammatory model of glaucoma, TNF-α induces SARM1-dependent axon degeneration, oligodendrocyte loss, and subsequent retinal ganglion cell death. TNF-α also triggers SARM1-dependent axon degeneration in sensory neurons via a noncanonical necroptotic signaling mechanism. MLKL is the final executioner of canonical necroptosis; however, in axonal necroptosis, MLKL does not directly trigger degeneration. Instead, MLKL induces loss of the axon survival factors NMNAT2 and STMN2 to activate SARM1 NADase activity, which leads to calcium influx and axon degeneration. Hence, these findings define a specialized form of axonal necroptosis. The demonstration that neuroinflammatory signals and necroptosis can act locally in the axon to stimulate SARM1-dependent axon degeneration identifies a therapeutically targetable mechanism by which neuroinflammation can stimulate axon loss in neurodegenerative disease.
Dendritic Cells from Chronic Lymphocytic Leukemia Patients Are Normal Regardless of Ig V Gene Mutation Status (2004)

Patients with B-type chronic lymphocytic leukemia (B-CLL) segregate into 2 subgroups based on the mutational status of the immunoglobulin (Ig) V genes and the patients in these subgroups follow very different clinical courses. To examine whether dendritic cells (DCs) generated from CLL patients can be candidates for immune therapy, we compared the phenotypic and functional capacities of DCs generated from patients of the 2 CLL subgroups (normal age-matched subjects [normal-DCs]). Our data show that immature DCs from B-CLL patients (B-CLL-DCs) have the same capacity to take up antigen as those from normal controls. Furthermore, B-CLL-DCs generated from the 2 CLL subgroups up-regulated MHC-II, CD80, CD86, CD83, CD40, and CD54 and down-regulated CD206 in response to stimulation with a cocktail of cytokines (CyC) and secreted increased levels of tumor necrosis factor alpha, interleukin (IL)-8, IL-6, IL-12 (p70), and RANTES in a manner typical of mature normal-DCs. Interestingly, CD54 was significantly more up-regulated by CyC in B-CLL-DCs compared with normal-DCs. Except for CD54, no significant differences in surface molecule expression were observed between normal-DCs and B-CLL-DCs. B-CLL-DCs from both subgroups, including 6 patients with VH1-69, that usually fare poorly, presented tetanus toxoid to autologous T cells in vitro similar to normal- DCs. Our data show that DCs generated from the B-CLL subgroup with unmutated Ig V genes are functionally normal. These results are very promising for the use of DCs from patients with poor prognosis for immunotherapy.
Cement interdigitation and bone-cement interface after augmenting fractured vertebrae: A cadaveric study (2012)

Cavity-creating procedures reduce the cement interdigitation significantly and may accordingly reduce the effectiveness of the augmentation procedures.
Correlation Of Imaging Technologies: Methodologies. (2019)

Correlative technologies have been transforming the way researchers obtain information from their specimens based on the advantages of these different technologies that range between the millimeter and nanometer scales. Attempts to combine multidimensional data are often met with the challenge of overcoming nonideal sample conditions such as reduced fluorescence signal, poor specimen preservation, specimen deformation, or low specimen contrast, prompting the development and use of enhanced sample preparation procedures to overcome such challenges. Correlative light and electron microscopy (CLEM) can be done by means of transmission (TEM) and scanning (SEM) electron imaging (Figure
Structural Insights into Group II Intron Catalysis and Branch-Site Selection (2002)

Group II self-splicing introns catalyze autoexcision from precursor RNA transcripts by a mechanism strikingly similar to that of the spliceosome, an RNA-protein assembly responsible for splicing together the protein-coding parts of most eukaryotic pre-mRNAs. Splicing in both cases initiates via nucleophilic attack at the 5' splice site by the 2' OH of a conserved intron adenosine residue, creating a branched (lariat) intermediate. Here, we describe the crystal structure at 3.0 A resolution of a 70-nucleotide RNA containing the catalytically essential domains 5 and 6 of the yeast ai5gamma group II self-splicing intron, revealing an unexpected two-nucleotide bulged structure around the branch-point adenosine in domain 6.
The impact of the COVID-19 pandemic on the Management of Locally Advanced Primary/Recurrent Rectal Cancer (2020)

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Abstract 1965: Discovery of ZN-c3, a potent Wee-1 inhibitor with a differentiated pharmacologic and kinase selectivity profile (2021)

Abstract Genome instability initiated by DNA damage or DNA replication stress is a driver of tumor development. To ensure the accuracy of DNA replication, DNA damage response (DDR) mediated by various cell cycle checkpoints activate the DNA repair system. One such checkpoint system is the G2-M checkpoint which is involved in the repair and prevention of excessive DNA damage. A key regulator of the G2-M checkpoint is the Wee1 kinase which causes cell cycle arrest to prevent damaged cells from entering mitosis. Thus, inhibition of Wee1 should prevent G2-M checkpoint activation which would lead to unscheduled mitotic entry and induction of apoptosis. Small-molecule inhibitors of Wee1 are currently being tested in several tumor types. Preliminary results show promising clinical activity of AZD-1775, a potent inhibitor of Wee1, however, achieving an optimal dose and a schedule that is well-tolerated has been a challenge. Here, we describe the characterization of ZN-c3, a potent, selective and orally bioavailable small-molecule inhibitor of Wee1. ZN-c3 exhibits potent anti-proliferative activity across multiple tumor cell lines. Compared to AZD-1775, ZN-c3 has superior selectivity profile against a panel of kinases. In vivo, ZN-c3 induced tumor regression as a single agent in several tumor models including non-small cell lung cancer, ovarian cancer, and uterine sarcoma. In combination studies, ZN-c3 potentiates the antitumor efficacies of carboplatin and gemcitabine. The pharmacokinetic and efficacy profiles of ZN-c3 and AZD-1775 were compared in tumor xenograft models. ZN-c3 showed higher plasma and tumor exposure than AZD-1775, which correlated with more potent tumor growth inhibition than AZD-1775. In summary, ZN-c3, with its key differentiated pharmacologic and kinase selectivity profile, is a promising new generation of DDR inhibitor. ZN-c3 is currently in clinical development for the treatment of advanced solid cancers. Citation Format: Jiali Li, Brant Boren, Peter Q. Huang, Kevin D. Bunker, Fernando Doñate, Ahmed A. Samatar. Discovery of ZN-c3, a potent Wee-1 inhibitor with a differentiated pharmacologic and kinase selectivity profile [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1965.
Methylene Insertion Reactions of Samarium Carbenoids into Boron–Hydrogen and Phosphorus–Hydrogen Bonds (1996)

Abstract A samarium carbenoid, generated from diiodomethane and samarium metal, reacts with phosphine–boranes to afford phosphine–monomethylborane in good yields. The P–H bonds of secondary phosphine–boranes or secondary phosphine oxides are subjected to methylene insertion with the same carbenoid to give the corresponding P-methylated derivatives.
CHEMICAL RELEASE STUDIES. V. RECOMBINATION DURING RADIAL FREE EXPANSION OF A PLASMA SPHERE. (1961)

Abstract : Smith's analysis of ion-electron recombination in nozzle flow is adapted to radial free expansion of a plasma sphere. A 'peeling onion' model is developed; the plasma ball sheds outer layers from an undisturbed core until the center is reached. Each layer in turn serves as a steady state source for the expanding gas. A family of curves of the degree of ionization vs. reduced time for the retreating layers is obtained. The degree of ionization asymptotically approaches a quenched value, beta infinity (r). Evaluation of beta infinity (r) vs. the radii of the source layers indicates that the degree of ionization increases from the edges of the expanding plasma toward the center. The fraction of ions quenched is determined by integration over the volume elements. The recombination of iodine (in argon carrier) released by shattering glass spheres is suggested as an experimental test of the expansion model. (Author)
Restauraciones en túnel frente a restauraciones de clase II para lesiones proximales peqeñas. Comparación de la resistencia del diente (1995)

El enfasis creciente sobre la conservacion de las estructuras dentales ha llevado a los disenos de cavidades alternativas para las caries proximales precoces. Se han comparado in vitro la restauracion en tunel (que conserva la cresta marginal) y las restauraciones de composite conservadoras de clase II, con pruebas destructivas y no destructivas para valorar la restistencia del diente. Las restauraciones en tunel, que en general se consideran las mas conservadoras de las dos tecnicas, resultaron mas daninas, tal y como demuestra la rigidez, la resistencia a la fractura y la proximidad a la pulpa. 
(Quintessence Int 1993; 24: 93-98)
Overall survival in patients with metastatic or locally advanced pancreatic cancer following chemoradiation with novel combination of aldoxorubicin, N-803 IL-15 superagonist, and PDL1- NK cell therapy. (2023)

720 Background: Pancreatic cancer claimed an estimated 47,050 lives in the USA in 2020, with an expected median overall survival (OS) of 3 months in 3rd line. (Manax ASCO GI 2019), with no evidence of disease control in these late stage patients. We hypothesize that effective response against pancreatic cancer requires orchestration of both the innate and adaptive immune system to accomplish immunogenic cell death with survival benefit. Herein we report updated results of the fully enrolled cohort of a novel combination immunotherapy protocol of low-dose chemoradiation, cytokine-induced NK and T cell activation via N-803 (an IL-15 cytokine superagonist ), and allogeneic off-the-shelf PDL1-targeted high-affinity NK cell (PDL1 t-haNK) infusion. Methods: We report data from a multi-center study, on 83 3rd line or greater, subjects treated with low dose, chemo radiation Nab-paclitaxel (100 mg/ m2 IV), Gemcitabine (600 mg/m2 IV); Cyclophosphamide (50 mg PO BID) and low dose SBRT. This induction immuno-modulation therapy to induce DAMPs was followed with investigational agents activating the innate and adaptive systems: Aldoxorubicin (150 mg/m2 IV), N-803, an IL-15 superagonist (15 μg/kg SC) and PD-L1 t-haNK (~2 × 109cells/dose IV). Prophylactic G-CSF or EPO was not allowed. All treatments were administered on an outpatient basis. Results: As of submission, median follow-up is 4.9 months. Median age 62, M:F ratio 46:36. ECOG 0-1,97%. 74/83 (89%) reported at least 1 investigational product related AE (TRAE) with 63/83 (76%) reporting at least 1 TRA grade 3 or higher. The most common were anemia 41%, neutropenia 20%, thrombocytopenia 10%, all others &lt;10%. SAEs attributed to investigational agents were reported in 8/83 (10%) patients. Treatment is ongoing for 6 subjects (7%), with 17.1 months as the longest duration on therapy to date. Median OS is 5.7 months (95% CI: 4.9, 6.4) with 26/83 alive to date. Median PFS is 2.3 months (95% CI: 2.0, 3.6) and 37% of subjects achieving stable disease &gt;=8 weeks. Median OS in 3 rd line (N=38) is 6.3 months, Median OS in 4 th line or greater (N=40) is 5.0 months. Conclusions: Historical 3 month median OS in 3 rd line metastatic pancreatic cancer patients has been exceeded. A doubling of survival in 3 rd line is seen in QUILT 88 investigating a novel combination immunotherapy protocol of low-dose chemoradiation, N-803 and PDL1 t-haNK therapy. Updated data will be presented. Clinical trial information: NCT03563144 .