Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

The results of treatment in 1,086 general paralytics the majority of whom were followed for more than five years

Paresis strikes most frequently during life's most productive years. It is seen approximately three times as frequently in males as females, and over twice as frequently in whites as in Negroes. The usual incubation period is 10 to 24 years after infection. The simple dementing type of psychosis is more frequent than all other types combined. In the absence of previous treatment the spinal fluid complement fixation reaction is always positive and the spinal fluid cell count is almost always elevated. The blood serologic test may, rarely, be negative.Penicillin prevents paresis. None of the present group of 1,086 patients had received penicillin for early syphilis. Paresis has not been observed to develop following the penicillin treatment of asymptomatic neurosyphilis.The present study cannot be said to reflect the effect of penicillin alone, but only the effect of penicillin with or without fever therapy on a mixed group of paretics, a small but undetermined number of whom already had a process perhaps wholly or partly arrested by other types of therapy before penicillin was given.The trend in recent years in the United States has been toward the treatment of paresis with penicillin alone. The possible additive effects of fever therapy are not sufficient to justify its use in any significant number of patients. The early diagnosis and prompt penicillin treatment of incipient paresis result in clinical remission and ability to work in more than 80 per cent of patients and will prevent practically all deaths from neurosyphilis. Even the severe or institutionalized patient has one chance out of three of improvement and rehabilitation for work. In contrast to the dire prognosis of untreated paresis only 9 per cent of penicillin-treated paretics are dead of paresis 10 years after treatment. Even so, the penicillin-treated paretic has nearly four times the death rate of his or her nonsyphilitic age, race, or sex counterpart.The effects of treatment upon the individual signs and symptoms of paresis are in general strikingly beneficent. In the majority of cases, however, abnormalities of speech, insight, calculation, judgment, and general information do not entirely disappear.Repository penicillin is quite as suitable as aqueous penicillin. Although the minimal effective dose is unknown, the present study suggests that 6 million units is probably ample.In general, more than one course of penicillin is of no demonstrable additional value. Absence of clinical improvement, persistently abnormal spinal fluid protein level, or persistently positive spinal fluid complement fixation reaction are not indications for re-treatment. Re-treatment with penicillin is indicated under the following circumstances: an initial course of therapy of less than 6 million units, temporary clinical improvement following an initial course with subsequent clinical progression, or spinal fluid cell count of 5 or more after the first post-treatment year. The essentially identical probability of death in patients who receive one course and patients who receive more than one course of treatment is strong evidence against the value of routinely repeated courses of penicillin in the treatment of general paralysis.Herxheimer reactions, notably exacerbation of the paretic psychosis or convulsive seizures, occur more frequently in the presence of spinal fluid pleocytosis than in its absence. The Herxheimer reaction does not appear to cause long-term damage.Skilled neuropsychiatric examination affords definite prognostic data as to the probability of improvement in psychosis, rehabilitation for work, and to a certain extent as to death itself. Progression and death due to neurosyphilis occurred almost altogether in patients with "severe" pretreatment psychosis. Post-treatment psychiatric hospitalization was directly proportional, and clinical improvement and rehabilitation for work inversely proportional to the severity of pretreatment psychosis. Type of psychosis was of less importance prognostically. The shorter the duration of psychosis at the time of treatment the more frequent was clinical improvement and rehabilitation for work. The presence at the time of treatment of incontinence, inability to perform simple acts of personal toilet, and of convulsions afforded a particularly poor prognosis for longevity.Work status at the time of treatment was of great prognostic import, and of perhaps equal significance was the length of time which had elapsed since the patient had been able to work at his usual occupation.Age, race, and sex were relatively unimportant factors in prognosis.Pretreatment pleocytosis indicates an active inflammatory process more susceptible of improvement by treatment, but in a minority of patients leaving behind sufficient brain damage to nullify any real clinical effect. The absence of pleocytosis indicated a relatively static process less susceptible of improvement. Pretreatment spinal fluid protein levels were of less prognostic import. Persistent cell counts of 11 or more were for practical purposes not encountered after penicillin treatment. Clinical progression did, however, occur significantly more frequently with persistent cell counts of 5 to 10 than with cell counts of 4 or less. Persistent spinal fluid protein elevation was relatively frequent but of no prognostic import.Considering the fact that as the incidence of syphilis itself decreases, dementia paralytica is becoming something of a neuropsychiatric rarity, the data which I have presented are perhaps of more historical interest than practical importance. They are, however, a dramatic illustration of the progress of medicine in four decades. A disease which was uniformly fatal within a few short years prior to Wagner von Jauregg's 1917 discovery of the efficacy of malaria therapy has now become curable in some, and partially remediable in many, by virtue of brief treatment with penicillin. The credit for this accomplishment is shared by your country through Fleming and Florey, and my own through Mahoney. Most of it belongs to Britain. May our future scientific and friendly brotherhood prove as profitable!Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32493/3/0000580.pd

Genomic Profiling of Biliary Tract Cancer Cell Lines Reveals Molecular Subtypes and Actionable Drug Targets

Biliary tract cancers (BTCs) currently have no approved targeted therapies. Although genomic profiling of primary BTCs has identified multiple potential drug targets, accurate models are needed for their evaluation. Genomic profiling of 22 BTC cell lines revealed they harbor similar mutational signatures, recurrently mutated genes, and genomic alterations to primary tumors. Transcriptomic profiling identified two major subtypes, enriched for epithelial and mesenchymal genes, which were also evident in patient-derived organoids and primary tumors. Interrogating these models revealed multiple mechanisms of MAPK signaling activation in BTC, including co-occurrence of low-activity BRAF and MEK mutations with receptor tyrosine kinase overexpression. Finally, BTC cell lines with altered ERBB2 or FGFRs were exquisitely sensitive to specific targeted agents, whereas surprisingly, IDH1-mutant lines did not respond to IDH1 inhibitors in vitro. These findings establish BTC cell lines as robust models of primary disease, reveal specific molecular disease subsets, and highlight specific molecular vulnerabilities in these cancers