BackgroundThe appropriateness of the laparoscopic approach for the resection of rectal cancer has... more BackgroundThe appropriateness of the laparoscopic approach for the resection of rectal cancer has been controversial, although it is well established in colon cancer. This is a phase II study of laparoscopic abdominoperineal resection (APR) in the treatment of lower rectal cancers.MethodsPatients with lower rectal adenocarcinoma located within 6 cm above the anal verge were recruited and subjected to laparoscopic APR. The surgical principle included en bloc resection with high ligation of inferior mesenteric vessels by no-touch isolation and total mesorectal excision. Details of the surgical procedures are presented in the video. The technical efficiency and outcome of this surgical approach were evaluated prospectively. This study was approved by the institutional review board of National Taiwan University Hospital (NTUH).ResultsA total of 22 patients were enrolled in the study from January 2003 to December 2004 under the ethical guidelines of clinical trials in NTUH. There were 12 females and 10 males, with an age distribution of 62.5 ± 10.4 years. The body mass index was 24.8 ± 4.0 kg/m2. Physical status (American Society of Anesthesiology classification) was class I in 12, class II in eight, and class III in two patients. Tumor size was 44.0 ± 12.0 mm in diameter. Two patients were in pathologic TNM stage I, 14 in stage II, and six in stage III. The operation time was 214.0 ± 28.4 min. Blood loss was 54.0 ± 14.0 ml. Because the tumor specimen was retrieved from a perineal wound, the five 5 to 12 mm working ports constituted the abdominal wound. There were no major complications. However, wound infection of port sites was detected in one patient. The patients had a quick convalescence, as evaluated by the length of postoperative ileus (48.0 ± 12.0 h), length of hospitalization (8.0 ± 2.0 days), and degree of postoperative pain (3.5 ± 0.5 visual analogue scale). Return to partial activity, full activity, and work was 2.0 ± 0.5, 4.0 ± 0.8, and 6.0 ± 0.5 weeks, respectively. The number of cleared lymph nodes was 14.0 ± 2.0. During follow-up (median, 18 months; range, 6–30), lung metastasis and local pelvic recurrence developed in one and two patients, respectively. Besides the expenses covered by the National Bureau of Health Insurance of Taiwan, the additional payment by patients undergoing laparoscopic procedures was NT $24,000 ± 3000 (1 U.S. dollar = 32 NT$).ConclusionsIn our clinical setting, laparoscopic APR can be performed with good technical efficiency, quick functional recovery, and mild disability. The short-term oncologic results of laparoscopic APR seem to be acceptable, but further long-term follow-up for these patients is mandatory to define the oncologic outcomes of this approach.
We describe a neural attention model with a learnable retinal sampling lattice. The model is trai... more We describe a neural attention model with a learnable retinal sampling lattice. The model is trained on a visual search task requiring the classification of an object embedded in a visual scene amidst background distractors using the smallest number of fixations. We explore the tiling properties that emerge in the model's retinal sampling lattice after training. Specifically, we show that this lattice resembles the eccentricity dependent sampling lattice of the primate retina, with a high resolution region in the fovea surrounded by a low resolution periphery. Furthermore, we find conditions where these emergent properties are amplified or eliminated providing clues to their function.
OBJECTIVES To evaluate outcomes of transcatheter mitral valve replacement (TMVR) with transfemora... more OBJECTIVES To evaluate outcomes of transcatheter mitral valve replacement (TMVR) with transfemoral access in patients at prohibitive or high surgical risk. BACKGROUND Prohibitive surgical risk may preclude MVR surgery in some patients. The investigational Intrepid TMVR system (Medtronic, Minneapolis, MN) has previously been evaluated using transapical access for delivery of a self-expanding bioprosthetic valve. METHODS This prospective, multi-center, non-randomized early feasibility study (EFS) evaluated safety and performance of the Intrepid valve using transfemoral/transseptal access in patients with moderate-severe/severe, symptomatic mitral regurgitation (MR) at high surgical risk. Candidacy was determined by heart teams with approval by a central screening committee. Echocardiographic data were evaluated by an independent core laboratory. Clinical events were adjudicated by a clinical events committee. RESULTS Fifteen patients were enrolled at 6 sites from Feb 2020-May 2021. Median age was 80 years and STS-PROM was 4.7%; 87% were male and 53% had prior sternotomy. Fourteen implants were successful. One patient converted to surgery during the index procedure. Patients stayed a median 5 days post-procedure. There were 6 (40%) access site bleeds and 11 (73%) iatrogenic ASD closures. At 30 days, there were no deaths, strokes, or reinterventions. All implanted patients had trace/no valvar or paravalvar MR and mean gradient was 4.7±1.8 mmHg. CONCLUSIONS Thirty-day results from the Intrepid transfemoral TMVR EFS demonstrate excellent valve function and no mortality or stroke. Additional patients and longer follow-up are needed to confirm these findings.
Proceedings of the National Academy of Sciences, 2019
Short linear peptide motifs that are intracellular ligands of folded proteins are a modular, inco... more Short linear peptide motifs that are intracellular ligands of folded proteins are a modular, incompletely understood molecular interaction language in signaling systems. Such motifs, which frequently occur in intrinsically disordered protein regions, often bind partner proteins with modest affinity and are difficult to study with conventional structural biology methods. We developed LiF-MS (ligand-footprinting mass spectrometry), a method to map peptide binding sites on folded protein domains that allows consideration of their dynamic disorder, and used it to analyze a set of D-motif peptide–mitogen-activated protein kinase (MAPK) associations to validate the approach and define unknown binding structures. LiF-MS peptide ligands carry a short-lived, indiscriminately reactive cleavable crosslinker that marks contacts close to ligand binding sites with high specificity. Each marked amino acid provides an independent constraint for a set of directed peptide–protein docking simulations,...
Unstructured peptides, or linear motifs, present a poorly understood molecular language within th... more Unstructured peptides, or linear motifs, present a poorly understood molecular language within the context of cellular signaling. These modular regions are often short, unstructured and interact weakly and transiently with folded target proteins. Thus, they are difficult to study with conventional structural biology methods. We present Ligand-Footprinting Mass Spectrometry, or LiF-MS, as a method of mapping the binding sites and dynamic disorder of these peptides on folded protein domains. LiF-MS uses a cleavable crosslinker to mark regions of a protein contacted by a bound linear motif. We demonstrate this method can detect both conformation ensembles and binding orientations of a linear motif in its binding pocket to amino-acid-level detail. Furthermore, marked amino acids can be used as constraints in peptide-protein docking simulations to improve model quality. In conclusion, LiF-MS proves a simple and novel method of elucidating peptide docking structural data not accessible by...
Ndr/Lats kinases bind Mob coactivator proteins to form complexes that are essential and deeply co... more Ndr/Lats kinases bind Mob coactivator proteins to form complexes that are essential and deeply conserved components of “Hippo” signaling pathways, which control cell proliferation and morphogenesis in eukaryotes. All Ndr/Lats kinases have a characteristic N-terminal region (NTR) that binds a specific Mob co-factor: Lats kinases associate with Mob1 proteins, and Ndr kinases associate with Mob2 proteins. To better understand the functional significance of Mob protein association with Ndr/Lats kinases and selective binding of Ndr and Lats to distinct Mob co-factors, we solved crystal structures of Saccharomyces cerevisiae Cbk1(NTR)-Mob2 and Dbf2(NTR)-Mob1 and experimentally assessed determinants of Mob cofactor binding and specificity. This significantly refines the previously determined structure of Cbk1 kinase bound to Mob2, presently the only crystallographic model of a full length Ndr/Lats kinase complexed with a Mob cofactor. Our analysis indicates that the Ndr/Lats NTR-Mob interf...
Transactions of the I.R.E. Professional Group on Electronic Computers, 1952
In the two years since the first digital differential analyzer was put in operation, it has been ... more In the two years since the first digital differential analyzer was put in operation, it has been the complexity of filling and operating such machines, rather than any difficulty in coding them for a problem, that has constituted the main impediment to convenience and efficiency in their use. In filling some hundred-odd binary digits, one at a time, for each integrator information, the possibility of error is great. For instance, let us look at the binary number
Hemophagocytic Lymphohistiocytosis (HLH) and Macrophage Activation Syndrome (MAS) are life-threat... more Hemophagocytic Lymphohistiocytosis (HLH) and Macrophage Activation Syndrome (MAS) are life-threatening hyperferritinemic systemic inflammatory disorders. Though profound cytotoxic impairment causes familial HLH (fHLH), the mechanisms driving non-fHLH and MAS are largely unknown. MAS occurs in patients with suspected rheumatic disease, but the mechanistic basis for its distinction is unclear. Recently, a syndrome of recurrent MAS with infantile enterocolitis caused by NLRC4 inflammasome hyperactivity highlighted the potential importance of Interleukin (IL)-18. We tested this association in hyperferritinemic and autoinflammatory patients, and found a dramatic correlation of MAS risk with chronic (sometimes lifelong) elevation of mature IL-18, particularly with IL-18 unbound by IL-18 Binding Protein, or Free IL-18. In a mouse engineered to carry a disease-causing germline NLRC4mutation, we observed inflammasome-dependent, chronic IL-18 elevation. Surprisingly, this NLRC4-induced system...
Proceedings of the thirteenth annual SIGCPR conference on -, 1975
... The current president of the Association for Computing Machinery, Jean Sammet, established an... more ... The current president of the Association for Computing Machinery, Jean Sammet, established an AC~ ad hoc committee in October 1974 for the purpose of ... Harris, Fred Computation Center University of Chicago 5735 University Avenue Chicago, IL 60637 312-763-8401 ...
Presented here is a new measurement of Rb = Gamma([ Z]0[/to]b/bar b)/Gamma([ Z]0[/to]hadrons) usi... more Presented here is a new measurement of Rb = Gamma([ Z]0[/to]b/bar b)/Gamma([ Z]0[/to]hadrons) using a self-calibrating double tag technique where the b selection is based on topological and kinematic reconstruction of the mass of the B-decay vertex. The measurement was performed using a sample of 72074 hadronic Z0 events out of the 150k hadronic Z0 decays collected with the SLD
Abstract : This chapter is devoted to a discussion of three topics: The discovery of the major et... more Abstract : This chapter is devoted to a discussion of three topics: The discovery of the major etiologic agents of rickettsial disease, their vectors, and mechanisms of transmission; The major technological developments that have facilitated the study, control, and treatment of rickettsiae and rickettsial diseases; and the evolution of the concept of rickettsia from a microbial entity which is neither a typical bacterium nor a typical virus to a well-characterized set of bacteria. Contents of Volume I include: Etiology; Rocky Mountain Spotted Fever (RMSF); Epidemic and Endemic Typhus Fevers; Trench Fever; Scrub Typhus; Q Fevers; Rickettsialpox; Staining Rickettsiae; Preantibiotic Chemotherapy; Early Vaccines; The Yolk Sac Revolution; Rickettsiae as Organisms and Rickettsial Physiology. Reprints.
BackgroundThe appropriateness of the laparoscopic approach for the resection of rectal cancer has... more BackgroundThe appropriateness of the laparoscopic approach for the resection of rectal cancer has been controversial, although it is well established in colon cancer. This is a phase II study of laparoscopic abdominoperineal resection (APR) in the treatment of lower rectal cancers.MethodsPatients with lower rectal adenocarcinoma located within 6 cm above the anal verge were recruited and subjected to laparoscopic APR. The surgical principle included en bloc resection with high ligation of inferior mesenteric vessels by no-touch isolation and total mesorectal excision. Details of the surgical procedures are presented in the video. The technical efficiency and outcome of this surgical approach were evaluated prospectively. This study was approved by the institutional review board of National Taiwan University Hospital (NTUH).ResultsA total of 22 patients were enrolled in the study from January 2003 to December 2004 under the ethical guidelines of clinical trials in NTUH. There were 12 females and 10 males, with an age distribution of 62.5 ± 10.4 years. The body mass index was 24.8 ± 4.0 kg/m2. Physical status (American Society of Anesthesiology classification) was class I in 12, class II in eight, and class III in two patients. Tumor size was 44.0 ± 12.0 mm in diameter. Two patients were in pathologic TNM stage I, 14 in stage II, and six in stage III. The operation time was 214.0 ± 28.4 min. Blood loss was 54.0 ± 14.0 ml. Because the tumor specimen was retrieved from a perineal wound, the five 5 to 12 mm working ports constituted the abdominal wound. There were no major complications. However, wound infection of port sites was detected in one patient. The patients had a quick convalescence, as evaluated by the length of postoperative ileus (48.0 ± 12.0 h), length of hospitalization (8.0 ± 2.0 days), and degree of postoperative pain (3.5 ± 0.5 visual analogue scale). Return to partial activity, full activity, and work was 2.0 ± 0.5, 4.0 ± 0.8, and 6.0 ± 0.5 weeks, respectively. The number of cleared lymph nodes was 14.0 ± 2.0. During follow-up (median, 18 months; range, 6–30), lung metastasis and local pelvic recurrence developed in one and two patients, respectively. Besides the expenses covered by the National Bureau of Health Insurance of Taiwan, the additional payment by patients undergoing laparoscopic procedures was NT $24,000 ± 3000 (1 U.S. dollar = 32 NT$).ConclusionsIn our clinical setting, laparoscopic APR can be performed with good technical efficiency, quick functional recovery, and mild disability. The short-term oncologic results of laparoscopic APR seem to be acceptable, but further long-term follow-up for these patients is mandatory to define the oncologic outcomes of this approach.
We describe a neural attention model with a learnable retinal sampling lattice. The model is trai... more We describe a neural attention model with a learnable retinal sampling lattice. The model is trained on a visual search task requiring the classification of an object embedded in a visual scene amidst background distractors using the smallest number of fixations. We explore the tiling properties that emerge in the model's retinal sampling lattice after training. Specifically, we show that this lattice resembles the eccentricity dependent sampling lattice of the primate retina, with a high resolution region in the fovea surrounded by a low resolution periphery. Furthermore, we find conditions where these emergent properties are amplified or eliminated providing clues to their function.
OBJECTIVES To evaluate outcomes of transcatheter mitral valve replacement (TMVR) with transfemora... more OBJECTIVES To evaluate outcomes of transcatheter mitral valve replacement (TMVR) with transfemoral access in patients at prohibitive or high surgical risk. BACKGROUND Prohibitive surgical risk may preclude MVR surgery in some patients. The investigational Intrepid TMVR system (Medtronic, Minneapolis, MN) has previously been evaluated using transapical access for delivery of a self-expanding bioprosthetic valve. METHODS This prospective, multi-center, non-randomized early feasibility study (EFS) evaluated safety and performance of the Intrepid valve using transfemoral/transseptal access in patients with moderate-severe/severe, symptomatic mitral regurgitation (MR) at high surgical risk. Candidacy was determined by heart teams with approval by a central screening committee. Echocardiographic data were evaluated by an independent core laboratory. Clinical events were adjudicated by a clinical events committee. RESULTS Fifteen patients were enrolled at 6 sites from Feb 2020-May 2021. Median age was 80 years and STS-PROM was 4.7%; 87% were male and 53% had prior sternotomy. Fourteen implants were successful. One patient converted to surgery during the index procedure. Patients stayed a median 5 days post-procedure. There were 6 (40%) access site bleeds and 11 (73%) iatrogenic ASD closures. At 30 days, there were no deaths, strokes, or reinterventions. All implanted patients had trace/no valvar or paravalvar MR and mean gradient was 4.7±1.8 mmHg. CONCLUSIONS Thirty-day results from the Intrepid transfemoral TMVR EFS demonstrate excellent valve function and no mortality or stroke. Additional patients and longer follow-up are needed to confirm these findings.
Proceedings of the National Academy of Sciences, 2019
Short linear peptide motifs that are intracellular ligands of folded proteins are a modular, inco... more Short linear peptide motifs that are intracellular ligands of folded proteins are a modular, incompletely understood molecular interaction language in signaling systems. Such motifs, which frequently occur in intrinsically disordered protein regions, often bind partner proteins with modest affinity and are difficult to study with conventional structural biology methods. We developed LiF-MS (ligand-footprinting mass spectrometry), a method to map peptide binding sites on folded protein domains that allows consideration of their dynamic disorder, and used it to analyze a set of D-motif peptide–mitogen-activated protein kinase (MAPK) associations to validate the approach and define unknown binding structures. LiF-MS peptide ligands carry a short-lived, indiscriminately reactive cleavable crosslinker that marks contacts close to ligand binding sites with high specificity. Each marked amino acid provides an independent constraint for a set of directed peptide–protein docking simulations,...
Unstructured peptides, or linear motifs, present a poorly understood molecular language within th... more Unstructured peptides, or linear motifs, present a poorly understood molecular language within the context of cellular signaling. These modular regions are often short, unstructured and interact weakly and transiently with folded target proteins. Thus, they are difficult to study with conventional structural biology methods. We present Ligand-Footprinting Mass Spectrometry, or LiF-MS, as a method of mapping the binding sites and dynamic disorder of these peptides on folded protein domains. LiF-MS uses a cleavable crosslinker to mark regions of a protein contacted by a bound linear motif. We demonstrate this method can detect both conformation ensembles and binding orientations of a linear motif in its binding pocket to amino-acid-level detail. Furthermore, marked amino acids can be used as constraints in peptide-protein docking simulations to improve model quality. In conclusion, LiF-MS proves a simple and novel method of elucidating peptide docking structural data not accessible by...
Ndr/Lats kinases bind Mob coactivator proteins to form complexes that are essential and deeply co... more Ndr/Lats kinases bind Mob coactivator proteins to form complexes that are essential and deeply conserved components of “Hippo” signaling pathways, which control cell proliferation and morphogenesis in eukaryotes. All Ndr/Lats kinases have a characteristic N-terminal region (NTR) that binds a specific Mob co-factor: Lats kinases associate with Mob1 proteins, and Ndr kinases associate with Mob2 proteins. To better understand the functional significance of Mob protein association with Ndr/Lats kinases and selective binding of Ndr and Lats to distinct Mob co-factors, we solved crystal structures of Saccharomyces cerevisiae Cbk1(NTR)-Mob2 and Dbf2(NTR)-Mob1 and experimentally assessed determinants of Mob cofactor binding and specificity. This significantly refines the previously determined structure of Cbk1 kinase bound to Mob2, presently the only crystallographic model of a full length Ndr/Lats kinase complexed with a Mob cofactor. Our analysis indicates that the Ndr/Lats NTR-Mob interf...
Transactions of the I.R.E. Professional Group on Electronic Computers, 1952
In the two years since the first digital differential analyzer was put in operation, it has been ... more In the two years since the first digital differential analyzer was put in operation, it has been the complexity of filling and operating such machines, rather than any difficulty in coding them for a problem, that has constituted the main impediment to convenience and efficiency in their use. In filling some hundred-odd binary digits, one at a time, for each integrator information, the possibility of error is great. For instance, let us look at the binary number
Hemophagocytic Lymphohistiocytosis (HLH) and Macrophage Activation Syndrome (MAS) are life-threat... more Hemophagocytic Lymphohistiocytosis (HLH) and Macrophage Activation Syndrome (MAS) are life-threatening hyperferritinemic systemic inflammatory disorders. Though profound cytotoxic impairment causes familial HLH (fHLH), the mechanisms driving non-fHLH and MAS are largely unknown. MAS occurs in patients with suspected rheumatic disease, but the mechanistic basis for its distinction is unclear. Recently, a syndrome of recurrent MAS with infantile enterocolitis caused by NLRC4 inflammasome hyperactivity highlighted the potential importance of Interleukin (IL)-18. We tested this association in hyperferritinemic and autoinflammatory patients, and found a dramatic correlation of MAS risk with chronic (sometimes lifelong) elevation of mature IL-18, particularly with IL-18 unbound by IL-18 Binding Protein, or Free IL-18. In a mouse engineered to carry a disease-causing germline NLRC4mutation, we observed inflammasome-dependent, chronic IL-18 elevation. Surprisingly, this NLRC4-induced system...
Proceedings of the thirteenth annual SIGCPR conference on -, 1975
... The current president of the Association for Computing Machinery, Jean Sammet, established an... more ... The current president of the Association for Computing Machinery, Jean Sammet, established an AC~ ad hoc committee in October 1974 for the purpose of ... Harris, Fred Computation Center University of Chicago 5735 University Avenue Chicago, IL 60637 312-763-8401 ...
Presented here is a new measurement of Rb = Gamma([ Z]0[/to]b/bar b)/Gamma([ Z]0[/to]hadrons) usi... more Presented here is a new measurement of Rb = Gamma([ Z]0[/to]b/bar b)/Gamma([ Z]0[/to]hadrons) using a self-calibrating double tag technique where the b selection is based on topological and kinematic reconstruction of the mass of the B-decay vertex. The measurement was performed using a sample of 72074 hadronic Z0 events out of the 150k hadronic Z0 decays collected with the SLD
Abstract : This chapter is devoted to a discussion of three topics: The discovery of the major et... more Abstract : This chapter is devoted to a discussion of three topics: The discovery of the major etiologic agents of rickettsial disease, their vectors, and mechanisms of transmission; The major technological developments that have facilitated the study, control, and treatment of rickettsiae and rickettsial diseases; and the evolution of the concept of rickettsia from a microbial entity which is neither a typical bacterium nor a typical virus to a well-characterized set of bacteria. Contents of Volume I include: Etiology; Rocky Mountain Spotted Fever (RMSF); Epidemic and Endemic Typhus Fevers; Trench Fever; Scrub Typhus; Q Fevers; Rickettsialpox; Staining Rickettsiae; Preantibiotic Chemotherapy; Early Vaccines; The Yolk Sac Revolution; Rickettsiae as Organisms and Rickettsial Physiology. Reprints.
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